Pharmacological /S1 Issn 1734-1140 Reports

67 VOL. 67 Supplement 1 2015 VOL. 67 Supplement 1 2015 PHARMACOLOGICAL /S1 ISSN 1734-1140 REPORTS

CONTENTS REPORTS PHARMACOLOGICAL

Special Issue: XIX International Congress of the Polish Pharmacological Society

Guest Editors: D. Malinowski, B. Gawron´ska-Szklarz Special Issue: XIX International Congress of the Polish Pharmacological Society 1 Editorial H.M. Droz´dzik Guest Editors: D. Malinowski, B. Gawron´ska-Szklarz 2 Abstracts – XIX Congress PTF 46 Author index

Vol PHARMACOLOGICAL . . 67 / S1 (

2015 REPORTS ) ) 1 – 48 Special Issue Issue Special ELSEVIER

INSTITUTE OF PHARMACOLOGY POLISH ACADEMY OF SCIENCES ScienceDirect KRAKÓW (POLAND) PHARMACOLOGICAL REPORTS

CONTENTS Vol. 67, Supplement 1 Special Issue: XIX International Congress of the Polish Pharmacological Society

Guest Editors: D. Malinowski, B. Gawrońska-Szklarz

1 Editorial H.M. Droździk 2 Abstracts – XIX Congress PTF 46 Author index

Editor-in-Chief Władysław Lason´

Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St Louis PHARMACOLOGICAL REPORTS

CONTENTS Vol. 67, Supplement 1 Special Issue: XIX International Congress of the Polish Pharmacological Society

Guest Editors: D. Malinowski, B. Gawrońska-Szklarz

1 Editorial H.M. Droździk 2 Abstracts – XIX Congress PTF 46 Author index

Editor-in-Chief Władysław Lason´

Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia • San Diego • St Louis Aims and scope Pharmacological Reports publishes papers concerning all aspects of basic and clinical pharmacology, dealing with the action of drugs at the cellular and molecular level, and papers on the relationship between molecular structure and biological activity. Studies of plant extracts are not suitable for Pharmacological Reports. We only publish reports on compounds with well-defined chemical structures. The language of all publications is English. PHARMACOLOGICAL REPORTS © 2015, Institute of Pharmacology Polish Academy of Sciences Published by Elsevier Sp. z o.o. All rights reserved Official journal of Institute of Pharmacology, Polish Academy of Sciences. This journal and the individual contributions contained in it are protected under copyright by Elsevier Sp. z.o.o., and the following terms and conditions apply to their use: Editor-in-Chief: Władysław Lason´ Photocopying Single photocopies of single articles may be made for personal use as allowed by national copyright laws. Permission of the Publisher [email protected] and payment of a fee is required for all other photocopying, including multiple or systematic copying, copying for advertising Deputy Editor: Graz˙ yna Skuza or promotional purposes, resale, and all forms of document delivery. Special rates are available for educational institutions that wish [email protected] to make photocopies for non-proﬁt educational classroom use. For information on how to seek permission visit www.elsevier.com/permissions or call: (+44) 1865 843830 (UK)/(+1) 215 239 3804 Managing Editor: Beata Kreiner (USA), [email protected]

Derivative works Subscribers may reproduce tables of contents or prepare lists of articles including abstracts for internal circulation within their Co-Editors: institutions. Permission of the Publisher is required for resale or distribution outside the institution. Permission of the Publisher is Jacek Bojarski required for all other derivative works, including compilations and translations. Stefan Chłopicki Electronic storage or usage Władysława Daniel Permission of the Publisher is required to store or use electronically any material contained in this journal, including any article or part Małgorzata Filip of an article. Except as outlined above, no part of this publication may be reproduced, stored in a retrieval system or transmitted in any Jolanta Jaworek form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior writ en permission of the Publisher. Irena Nalepa Address permissions requests to: Elsevier Rights Department, at the telephone numbers and e-mail address noted above. Barbara Przewłocka Notice No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Because of rapid advances in the medical sciences, in particular, independent veriﬁcation of diagnoses and drug dosages should be ADVISORY BOARD made. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. Chairman: Peter Jenner (London) The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Krzysztof We˛dzony (Kraków) Joseph Knoll (Budapest) Author enquiries Vice-chairman: Wojciech Kostowski (Warszawa) For enquiries relating to the submission of articles (including electronic submission) please visit this journal’s homepage at Edmund Przegalin´ski (Kraków) Solomon Z. Langer (Paris) http://www.elsevier.com/locate/pharep. For detailed instructions on the preparation of electronic artwork, please visit http://www. Vice-chairman: Pavel Mareš (Prague) elsevier.com/artworkinstructions. Contact details for questions arising after acceptance of an article, especially those relating to proofs, Andrzej Pilc (Kraków) Jerzy Z. Nowak (Łódz´) will be provided by the publisher. You can track accepted articles at http://www.elsevier.com/trackarticle. You can also check our Members: Adam Płaz´nik (Warszawa) Author FAQs at http://www.elsevier.com/authorFAQ and/or contact Customer Support via http://support. elsevier.com Journal of Lembit Allikmets (Tartu) Giorgio Racagni (Milan) Applied Biomedicine proceeds entirely online at www.ees.elsevier.com/pharep. There is an online tutorial for authors and online Włodzimierz Buczko (Białystok) Klaus Starke (Freiburg) support for technical problems or questions via Elsevier’s Author Support team (authorsupport@ elsevier.com). Aldona Dembin´ska-Kiec´ (Kraków) Jerzy Vetulani (Kraków) Manfred Göthert (Bonn) Peter Waldmeier (Basel) The Instructions to Authors can be found on the journal’s website Ryszard Gryglewski (Kraków) Paul Willner (Swansea) http://www.elsevier.com/journals/pharmacological-reports/1734-1140/guide-for-authors

Publication information: Pharmacological Reports ISSN ISSN: 1734-1140. For 2015 Volume 67 is scheduled for publication.

Subscription prices are available upon request from the Publisher or from the Elsevier Customer Service Department nearest you or Publication of this journal is supported by funds of the Ministry of Science and Higher Education and by grant “Index Plus” from this journal’s website (http://www.elsevier.com/locate/pharep). Further information is available on this journal and other Elsevier ------products through Elsevier’s website (http://www.elsevier.com). Subscriptions are accepted on a prepaid basis only and are entered on Indexed in: Biological Abstracts / BIOSIS, Chemical Abstracts, Excerpta Medica / EMBASE, a calendar year basis. Issues are sent by standard mail (surface within Europe, air delivery outside Europe). Priority rates are available International Pharmaceutical Abstracts / IPA, Polish Medical Bibliography / GBL, upon request. Claims for missing issues should be made within six months of the date of dispatch. Index Medicus / MEDLINE, Index Copernicus, Biotechnology Abstracts, Scopus Impact factor (ISI 2014) = 1.928 Orders, claims, and journal enquiries: please contact the Elsevier Customer Service Department nearest you: Poland: Elsevier Sp. z o.o., ul. Migdałowa 4/59, 02-796 Warszawa, Poland. tel.: (+48) 22 546 3827, (+48) 510 134 282, fax.: (+48) 22 546 3821, www.elsevier.com, email: [email protected] Address St. Louis: Elsevier Customer Service Department, 3251 Riverport Lane, Maryland Heights, MO 63043, USA; phone: (800) 6542452 [toll Institute of Pharmacology, Polish Academy of Sciences, free within the USA]; (+1) (314) 4478871 [outside the USA]; fax: (+1) (314) 4478029; e-mail: [email protected] Sme˛tna 12, 31-343 Kraków, Poland Oxford: Elsevier Customer Service Department, The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK; phone: (+44) (1865) phone: 48 (12) 662-32-37 843434; fax: (+44) (1865) 843970; e-mail: [email protected] fax: 48 (12) 637-45-00 e-mail: [email protected] Tokyo: Elsevier Customer Service Department, 4F Higashi-Azabu, 1-Chome Bldg, 1-9-15 Higashi-Azabu, Minato-ku, Tokyo 106-0044, Japan; phone: (+81) (3) 5561 5037; fax: (+81) (3) 5561 5047; e-mail: [email protected] Singapore: Elsevier Customer Service Department, 3 Killiney Road, #08-01 Winsland House I, Singapore 239519; phone: (+65) 63490222; fax: (+65) 67331510; e-mail: [email protected] Advertsing informaton: Advertsing orders and enquiries can be sent to: Elsevier Sp. z o.o., ul. Migdałowa 4/59, 02-796 Warszawa, Poland, e-mail: [email protected], tel.: (+48) 519 796 821 Aims and scope Pharmacological Reports publishes papers concerning all aspects of basic and clinical pharmacology, dealing with the action of drugs at the cellular and molecular level, and papers on the relationship between molecular structure and biological activity. Studies of plant extracts are not suitable for Pharmacological Reports. We only publish reports on compounds with well-defined chemical structures. The language of all publications is English. PHARMACOLOGICAL REPORTS © 2015, Institute of Pharmacology Polish Academy of Sciences Published by Elsevier Sp. z o.o. All rights reserved Official journal of Institute of Pharmacology, Polish Academy of Sciences. This journal and the individual contributions contained in it are protected under copyright by Elsevier Sp. z.o.o., and the following terms and conditions apply to their use: Editor-in-Chief: Władysław Lason´ Photocopying Single photocopies of single articles may be made for personal use as allowed by national copyright laws. Permission of the Publisher [email protected] and payment of a fee is required for all other photocopying, including multiple or systematic copying, copying for advertising Deputy Editor: Graz˙ yna Skuza or promotional purposes, resale, and all forms of document delivery. Special rates are available for educational institutions that wish [email protected] to make photocopies for non-proﬁt educational classroom use. For information on how to seek permission visit www.elsevier.com/permissions or call: (+44) 1865 843830 (UK)/(+1) 215 239 3804 Managing Editor: Beata Kreiner (USA), [email protected]

Publication information: Pharmacological Reports ISSN ISSN: 1734-1140. For 2015 Volume 67 is scheduled for publication.

Publishing Editor Subscription and Distribution Manager Marketing & Promotion Manager th Joanna Lewczuk Jacek Sołtyk Anna Grzeszczyk 50 Anniversary of the Polish Pharmacological Society [email protected] [email protected] [email protected] +48 515 082 585,+ 48 22 546 38 24 +48 22 546 38 27,+ 48 510 134 282 +48 546 38 40, + 48 515 090 174 17 th – 19th SEPTEMBER 2015 The Guide for Authors is available at http://www.elsevier.com/journals/pharmacological-reports/1734-1140/guide- for-authors S´WINOUJS´CIE, POLAND

Guide for Authors: – All articles are subject to double blind peer review – Disclosure any actual or potential conflict of interest (any financial, personal or other relationships with other people or organizations), ethics and funding should be provided in separate files attached to the article (Acknowledgement) – Upon acceptance of an article, authors will be asked to transfer copyright to the owner of the journal – Submission of an article implies that the work described has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder – A statement that all authors have approved the final article should be true and included in the disclosure (authors are obliged to provide details about authors’ contribution) Authors are requested to submit their manuscripts at http://ees.elsevier.com/pharep. There are online tutorials for authors and reviewers available at http://support.elsevier.com/app/epsupport Submission checklist Ensure that the following items are present: One author has been designated as the corresponding author with contact details: • E-mail address • Full postal address • Phone numbers All necessary files have been uploaded, and contain: • Abstract (structured for original papers/short communications or unstructured for reviews). • Keywords • All figure captions • All tables (including title, description, footnotes) Further considerations • Manuscript has been ‘spell-checked’ and ‘grammar-checked’. Authors who are not native English speakers are requested to attach a certificate/statement confirming that professional language editing has been performed • Paper does not exceed word limits (See Guide for Authors for the word count for each article type) • Text and tables submitted in editable format (Word, LaTex) • Each table, figure, photograph, or illustration included as a separate file • All symbols converted correctly in the pdf file • References are in the correct format for this journal • All references mentioned in the Reference list are cited in the text, and vice versa • Permission has been obtained for use of copyrighted material from other sources (including the Web) • Color figures are clearly marked as being intended for color reproduction on the Web (free of charge) and in print, or to be reproduced in color on the Web (free of charge) and in black-and-white in print • If only color on the Web is required, black-and-white versions of the figures are also supplied for printing purposes For any further information on please visit our customer support site at http://support.elsevier.com

Please consult the Guide for Authors for further details of any item.

The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Publisher Elsevier Sp. z o.o., Migdałowa 4/59 02-796 Warsaw, Poland Tel. +48 22 546 38 20 Fax. +48 22 546 38 21 Director of Journals Publishing Publishing Manager Advertising Pharma Solutions XIX INTERNATIONAL CONGRESS Ewa Kittel-Prejs Agnieszka Pawłowska Mariusz Radzio [email protected] [email protected] +48 519 796 821 OF THE POLISH PHARMACOLOGICAL SOCIETY

Please consult the Guide for Authors for further details of any item.

The paper used in this publication meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Pharmacological Reports 67S (2015) 1

Contents lists available at ScienceDirect ORGANIZING COMMITTEE President: Barbara Gawron´ska-Szklarz, Szczecin Pharmacological Reports Vice President: Monika Białecka, Szczecin Secretary: Stefania Juz´wiak, Szczecin journal homepage: www.elsevier.com/locate/pharep Members: Wanda Górnik, Szczecin Maria Kałdon´ska, Szczecin Danuta Kosik-Bogacka, Szczecin Mateusz Kurzawski, Szczecin Joanna Łapczuk, Szczecin Anna Machoy-Mokrzyn´ska, Szczecin Editorial Damian Malinowski, Szczecin Magdalena Peruz˙ yn´ska, Szczecin Joanna Wagner, Szczecin Dear Friends and Colleagues, discussed during the congress involve: progress in epilepsy and antiepileptic drugs, glutamate metabotropic receptors in CNS We have a great pleasure and honor to host you at the XIX disorders, neurotoxicity and neuroprotection as well as safety and SCIENTIFIC COMMITTEE International Congress of the Polish Pharmacological Society and optimization of pharmacotherapy. celebrate the 50th anniversary of the Polish Pharmacological President: Marek Droz´dzik, Szczecin The congress venue is located in the Baltic See holiday resort Society. S´winoujsćie, which offers a leisure time after scientific meetings. Vice President: Barbara Gawron´ska-Szklarz, Szczecin The congress gathers top Polish pharmacologists, and its high You can enjoy picturesque sunsets, beach walks or spent time in Members: Lucyna Antkiewicz-Michaluk, Kraków scientific level is also guaranteed by the attendance of many cafeterias close to the pier. internationally recognized experts in basic and clinical pharma- We look forward to welcome you in S´winoujsćie. Włodzimierz Buczko, Białystok cology. The congress is an excellent opportunity to exchange ideas Prof. dr hab. Marek Droz´dzik Stanisław Jerzy Czuczwar, Lublin and to establish new scientific contacts, listen to the state of the art Anna Jabłecka, Poznan´ lectures and participate in symposia. The main scientific aspects President of the Polish Pharmacological Society Małgorzata Kajta, Kraków Marek Kowalczyk, Warszawa Władysław Lason´, Kraków Bogusław Okopien´, Katowice Andrzej Pilc, Kraków Adam Płazńik, Warszawa Anna Wiela-Hojen´ska, Wrocław

The abstracts of communications presented at the Congress are printed without alterations from the manuscripts submitted by the authors, who bear the full responsibility for their essential content.

http://dx.doi.org/10.1016/j.pharep.2015.06.011 1734-1140/� 2015 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences. Pharmacological Reports 67S (2015) 1

The abstracts of communications presented at the Congress are printed without alterations from the manuscripts submitted by the authors, who bear the full responsibility for their essential content.

Honorary Lecture (sponsored by the British Pharmacological receptors are also able to activate ion channels (particularly Contents lists available at ScienceDirect Society) TRPV1) and nuclear hormone receptors (particularly PPARs). The endocannabinoids are not only subject to hydrolysis by cognate The endocannabinoid system as a nexus of enzymes favouring either amide or ester analogues, but may also Pharmacological Reports signalling complexity be transformed by oxidative metabolism to entities with distinct Steve Alexander molecular targets. In addition, the cognate hydrolytic enzymes journal homepage: www.elsevier.com/locate/pharep may be inhibited by agents targeting eicosanoid turnover, the School of Biomedical Sciences, University of Nottingham, United Kingdom NSAIDs. Signalling at the cannabinoid receptors is further complicated by recent evidence for orphan GPCR acting as The established pattern, now over 20 years old, of cannabinoid ‘‘cannabinoid receptor-like receptors’’, as well as the phenomena receptor signalling has the CB1 receptor expressed chiefly on of agonist bias, and positive and negative allosteric modulators. neurones and the CB2 receptor expressed chiefly on immune cells, Abstracts – XIX Congress PTF This complexity, combined with the difficulties in measuring both of which are activated by THC, the major psychoactive changes in ‘available’ endocannabinoid levels in heterogeneous ingredient from the Cannabis plant. Endocannabinoids are tissues like the CNS over timescales consistent with functional endogenous fatty acid derivatives, divided into amide and ester effects, ensures that the endocannabinoid system is likely to allow Opening Lecture analogues, which produce many of the same effects as THC upon us at least another 20 years of intense analysis. The origins of the Polish Pharmacological Society Abstract not submitted. administration in vivo. In recent years, it has become clear that there is a challenging complexity of signalling associated with the Edmund Przegalin´ ski http://dx.doi.org/10.1016/j.pharep.2015.06.014 http://dx.doi.org/10.1016/j.pharep.2015.06.013 endocannabinoid system. Thus, ligands active at cannabinoid Honorary Member of Polish Pharmacological Society, Polish Academy of Sciences, Krako´w, Poland

1734-1140/ Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 3

1734-1140/ 4 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 5

Plenary Lectures (intestinal tract, liver, organ barriers) are major variables for Symposia PBN during SE resulted in aggravation of emotional impairment bioavailability in the micro-compartment of drug action. and epilepsy. Caffeine and other methylxanthine derivatives – Progress in Epilepsy and Antiepileptic Drugs Therefore, data on regional expression of transporter protein Are they dangerous to patients with epilepsy? along the human gastrointestinal tract as measured by real-time Ambiguous effects of neuroprotective treatment Supported by grant P304/12/G069 of the Czech Science Foundation. 1,2 Stanisław J. Czuczwar RT-PCR and targeted proteomics (LC–MS/MS) and on absorption of with free radical scavenger N-tert-butyl-alfa- 240 ml water used for swallowing drug dosage forms will be phenylnitrone (PBN) on outcome of status http://dx.doi.org/10.1016/j.pharep.2015.06.018 1 Department of Pathophysiology, Medical University, Lublin, Poland presented. In that context, methods are discussed to evaluate the epilepticus and their mechanisms 2 Department of Physiopathology, Institute of Rural Health, Lublin, physiological condition on the site of disintegration in man by Poland Hana Kubova´, Jaroslava Folbergrova´, Pavel Maresˇ magnetic-marker-monitoring and MRI-imaging. The functional Drug-resistant epilepsy from the clinical point of meaning for absorption of probe drugs will be discussed Institute of Physiology, Czech Academy of Sciences, Prague, Czech view In spite of many antiepileptic drugs (AEDs) available, still ca 30% considering the properties of drug dosage forms, transporter Republic Barbara Błaszczyk of patients with epilepsy are not sufficiently controlled for seizure mediated ‘‘absorption windows’’ or influence by organ diseases. activity. A possibility exists that AED-resistance may be, in some Department of Health Sciences at Economics, Law and Medical Finally, data from drug interaction studies with enzyme inducers Neuroprotection represents a widely explored treatment instances, related to methylxanthine derivatives (theophylline, Sciences, Kielce, Specialized Neurological Office, Kielce, Poland and modulators of multidrug transporters as well as data from option for many central nervous system (CNS) disorders and aims caffeine) simultaneously administered or ingested with antiepi- pharmacokinetic studies in healthy subjects selected for functional to prevent or slow disease progression and secondary injuries by leptic treatment. Theophylline is prescribed for the management of relevant polymorphisms are presented to conclude on the clinical preventing or limiting the neuronal loss. Even though neuro- Most of patients with epilepsy respond to treatment with asthma or chronic pulmonary obstructive disease and caffeine is relevance of in vitro evidence. protection is usually defined as the ability to safe neurons from monotherapy: 47% of patients are seizure-free with first antiepi- present in a variety of drugs (appetite stimulants, antiviral drugs, injury or degeneration, the main aim of neuroprotective treatment leptic drug (AED), another 13% achieve seizure freedom with analgesics), being also the most consumed psychoactivator. second monotherapy. The objective of a treatment is to obtain http://dx.doi.org/10.1016/j.pharep.2015.06.016 is to preserve functional abilities of the CNS or at least to Experimental studies clearly indicate that both methylxanthine minimize the extend of functional alterations over a long term seizure freedom without adverse effects. Practical tenets for derivatives, administered acutely, significantly reduced the period. However, experimental studies on neuroprotective achieving successful monotherapy in new-onset epilepsy include anticonvulsant activity of most conventional and newer antiepi- Pathomechanisms of xenobiotic action in the effects of various drugs or treatment strategies often evaluate the following: select an efficacious AED for the specific seizure leptic drugs against maximal electroshock-induced seizures in nervous system only limited number of functional parameters for limited time type; choose an AED with tolerable adverse effect and toxicity mice. Caffeine was also evaluated chronically in this regard and its profile; titrate the AED slowly to the desired dose. Małgorzata Kajta after the therapy cessation. negative activity upon AEDs was even intensified. Interestingly, Using various experimental models, several common mecha- Other considerations when selecting an AED: whilst acute methylxanthines did not impair the protective action Department of Experimental Neuroendocrinology, Institute of Phar- nisms behind neurodegeneration which include oxidative stress, of carbamazepine against maximal electroshock in mice, chronic macology, Polish Academy of Sciences, Krako´w, Poland mitochondrial dysfunction, excitotoxicity and/or inflammatory 1. Patient factors: seizure type and syndrome, age, gender, caffeine did. Some newer AEDs, lamotrigine, oxcarbazepine, and changes were identified and tested as possible therapeutic targets. pregnancy potential, comorbidities, comedications, lifestyle tiagabine were not affected by either acute or chronic caffeine. There is a growing body of evidence that environmental organic Previously, we examined neuroprotective effects of free radical 2. AED characteristics: spectrum and efficacy, mechanism of Clinical data generally agree with the results of animal studies, pollutants may affect neural development and increase the scavenger PBN in several models of neurodegeneration in action, indications (eg. monotherapy, children etc), tolerabili- indicating that ingestion of caffeine may increase seizure frequency of nervous system disorders. These pollutants include immature rats. Present study analyzed long term effects of ty/safety (neuropsychological implications), dosing frequency, frequency in patients with epilepsy. Importantly, when ingestion dioxins, polychlorinated biphenyls (PCBs), pesticides, brominated neuroprotective treatment with free radical scavenger during titration complexity, simplicity of use, drug-drug interaction of caffeine is stopped then the seizure frequency returns to flame retardants, plasticizers, personal care products and drugs. LiCl/pilocarpine status epilepticus (SE) and its functional con- profile, teratogenic potential (pregnancy registries), availability, baseline. Summing up, the available experimental and clinical data Because many of the chemicals alter the hormone-dependent sequences in juvenile animals. SE was induced in 25-day-old (P25) cost, reimbursement. strongly argues against the therapeutic use of methylxanthine processes and disrupt functioning of endocrine glands, they have rats and PBN was administered in a total dose of 200 mg/kg (two derivatives or ingestion of caffeine in patients with epilepsy. been classified as Endocrine Disrupting Chemicals (EDCs). Interest- times 100 mg/kg). Three months after SE, cognitive abilities and When the first AED monotherapy is ineffective these patients ingly, even relatively low concentrations of them have been emotional state were assessed in behavioral tests, spontaneous need further evaluation for: possible misdiagnosis, insufficient http://dx.doi.org/10.1016/j.pharep.2015.06.015 reported to cause long-term alterations in functioning of neural video/EEG was monitored for 5 consecutive days and then dosage/nonadherence, signs of treatment-resistant epilepsy. Ther- transmission, formation of neural networks, and methylation of extension of the damage to temporal structures was evaluated apeutic triage in epilepsy care: monotherapy with AED1, alterna- using morphometry and stereological cell count. tive monotherapy, polytherapy, vagus nerve stimulation, drug The route of drugs to their place of action – specific gene regions in the young brain. Epidemiological data PBN treatment partially improved learning abilities in MWM study, epilepsy surgery. AED polytherapy has more potential to Meaning and clinical implications of drug showed associations between exposure to environmental pollu- but resulted in increased aggressiveness. Performance in MWM improve seizure control and possibly achieve higher rates of transporters (Sponsored by Federation of tants and increased risk of neuropsychiatric disorders such as negatively correlated with the hippocampal volume. Video/EEG seizure freedom than monotherapy alone. European Pharmacology Societies) autism, attention deficit and hyperactivity disorder, learning disabilities, aggressiveness and depression. Exposures to pesticides monitoring demonstrated the significant increase of seizure However: Werner Siegmund and PCBs have also been associated with neural degenerations, frequency and duration in PBN animals. Time spent seizing per 1. Extent to which AED combinations in practice provide superior Department of Clinical Pharmacology, University Medicine of involving Parkinson’s and Alzheimer’s diseases. EDCs are known to 24 h was 9.3 times higher in PBN-group than in controls. In seizure control appears variable between different add-on Greifswald, Greifswald, Germany act via several classes of receptors, e.g. estrogen receptors (ERs), contrast, histopathological evaluation revealed significant de- glucocorticoid and mineralocorticoid receptors (GR and MR), crease of neuronal loss in the hilus of the hippocampus and studies. peroxisome proliferator-activated receptor g (PPARg), retinoic X hippocampal atrophy. To analyze mechanisms responsible for 2. Adverse effects and pharmacokinetic interactions may be Many drugs are substrates of drug metabolizing enzymes and/ receptors (RXRs), pregnane X receptor (PXR), constitutive andros- epilepsy worsening, we look for association between seizure associated with memory complaints, depression, fatigue etc. or multidrug transport proteins such as P-glycoprotein (P-gp), tane receptor (CAR), and aryl hydrocarbon receptor (AhR). severity and various morphological parameters including markers 3. Other drawbacks include difficulties in determining individual MRP2 or OATPs. Affinity to clinically relevant transporter proteins However, the best documented receptor mechanisms of EDC of adult hippocampal neurogenesis. Seizure severity was not drug actions, more complex dosage regimens, poorer treatment (wild-type and genetic variants) involved in cellular drug uptake actions on neural tissue are these related to ERs and AhR. associated with the hippocampal damage. On the contrary, we compliance, and increased treatment costs. and efflux can be thoroughly quantified in vitro using validated in found numerous misplaced Prox-1 positive cells in the hilus of the vitro cell models and transport assays. Evaluation of the functional Acknowledgment: Supported by the statutory funds from the Insti- dentate gyrus in both control and PBN animals and number of http://dx.doi.org/10.1016/j.pharep.2015.06.019 meaning of transporters proteins for absorption and distribution in tute of Pharmacology PAS in Krakow, Poland. these cells positively correlated with severity of epilepsy. Number vivo, however, remains difficult because of the complexity of of Prox-1 cells was however not affected by neuroprotective processes involved in drug absorption. Pharmaceutic-technological treatment. Using double labeling immunohistochemistry, we miRNA in models of acquired epilepsy factors and the physiological condition along the ‘‘first pass route’’ http://dx.doi.org/10.1016/j.pharep.2015.06.017 identified significantly more numerous subpopulation of hilar Katarzyna Lukasiuk neurons (NeuN positive) expressing Prox-1 in PBN treated animals. Nencki Institute of Experimental Biology, Polish Academy of Sciences, The number of Prox-1/NeuN positive neurons positively correlated Warszawa, Poland with seizure severity. Seizure severity however had no effects on cognitive or emotional functions. Our data demonstrate contradictory effects of neuroprotec- It is estimated that approximately 50 million people worldwide tive treatment on functional outcome of SE in juvenile rats. In and 6 million in Europe alone have active epilepsy. In many cases, contrast to protection of cognitive functions administration of epilepsy develops as the result of a brain damaging insult that 6 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 7 initiates cascades of events, called epileptogenesis (latency Our data speaking in favor of the role of adenosinergic system in group III mGlu receptors’ signaling in visceral pain processing is Centre, Grant no. 2012/6/ 06/A/NZ7/00014 (MAESTRO) given to period), after which recurrent spontaneous seizures occur. arrest of seizures are in agreement with conclusions of During and still largely unknown. And yet, visceral pain is associated with a A. Pilc. Epileptogenic insult causes a number of changes that lead to the Spencer (1992) – they demonstrated an action of adenosinergic wide variety of chronic functional disorders including irritable remodeling of neuronal circuits and subsequent seizures, which system in the arrest of seizures as well as in postictal refractoriness bowel syndrome and painful bladder syndrome. Interestingly, http://dx.doi.org/10.1016/j.pharep.2015.06.024 are undrilled by changes in the transcriptome to distinguish in human epileptic hippocampal tissue. stress has recently been shown as one of the most significant risk metabolic pathways affected by epileptic processes. Mechanisms factors increasing the prevalence of these disorders and exacer- of the regulation of gene expression in epileptogenesis are not well The studies were supported by a grant No. P304/12/G069 of the Grant bating the severity of pain symptoms. We utilised the Wistar Kyoto Alterations in brain mGluR5 and D2 receptor described. Recently the role of epigenetic mechanisms including Agency of the Czech Republic. (WKY) rat strain, as a model of stress-sensitive visceral hypersen- density during MDMA abstinence in different miRNA, have been proposed. miRNAs are small (20–24 bp), non- sitivity, to investigate the involvement of group III mGlu receptors living conditions in rats coding RNAs that regulate the expression of target genes by http://dx.doi.org/10.1016/j.pharep.2015.06.021 in stress-associated visceral pain disorders. WKY rats are known to Małgorzata Frankowska 1,*, 2 1 binding to the 30-untranslated regions (UTR) of target mRNAs and display a stress-hyper-responsive phenotype along with innate Lucyna Pomierny-Chamioło , Joanna Miszkiel , by this have a role in the regulation and fine-tuning of gene Glutamate Metabotropic Receptors and CNS Disorders hypersensitivity to noxious colon and urinary bladder distension Bartosz Pomierny 2, Małgorzata Filip 1,2 expression. In our study we have investigated changes in the as compared to stress-resilient Sprague Dawley rats. Here we show 1 expression levels of miRNAs and the expression of their potential Chemical Biology at Lundbeck: Enhancing CNS that WKY rats exhibit an altered pattern of group III mGlu Laboratory of Drug Addiction Pharmacology, Institute of Pharma- mRNA targets in the hippocampal dentate gyrus of rats subjected drug discovery research receptors expression in certain regions of brain limbic system, cology, Polish Academy of Sciences, Krako´w, Poland 2 to epileptogenesis in the amygdala stimulation model of the Dario Doller which are tightly associated with emotional processes including Department of Toxicology, Faculty of Pharmacy, Jagiellonian temporal lobe epilepsy. We found that there are ensembles of visceral pain. Moreover, WKY rats display a profound up- University, Medical College, Krako´w, Poland Chemical Biology, Lundbeck Research, Paramus, NJ, USA miRNAs that change expression levels over time. Analysis of the regulation of mGlu7 receptors’ expression on the periphery, *Corresponding author. mRNA expression from the same animals revealed that the namely in bladder tissue, while pharmacological inhibition of this expression of several mRNAs that are potential targets for miRNA Greater emphasis is being placed on the stringent selection, receptor effectively reduces visceral hypersensitivity in the MDMA (3,4-methylenedioxymethylamphetamine; ecstacy) is a with altered expression level is regulated in the expected direction. validation and interrogation of targets to maximize success rates animals. Altogether, these data suggest that altered group III psychostimulant currently considered as most popular drug of The functional characterization of miRNAs and their potential in clinical trials and deliver much needed therapies to patients. In mGlu receptor signaling may be one of the mechanisms underlying abuse in Europe. Accumulative evidence suggests that the mRNA targets indicate that miRNA can participate in several response to this challenge, Chemical Biology is emerging as a vital visceral hypersensitivity in stress-prone individuals. To this end, dopamine and glutaminergic transmission and the corresponding molecular events that occur in epileptic tissue, including immune component to providing adequate confidence before launching pharmacological modulation of these receptors might be an dopamine D2 (D2R) and glutamate mGlu5 (mGluR5) receptors are response and neuronal plasticity. Localization of the expression of full discovery programs. The use of well-qualified chemical tools attractive approach for the management of stress-induced visceral involved in MDMA-evoked seeking and relapse behaviors. top miRNAs indicated their neuronal function. Complex changes in in combination with disease-relevant biological systems provides pain. The aim of study was to uncover the role of D2R and mGluR5 in the expression of miRNAs suggest an important role for miRNA in a powerful approach to creating mechanistic knowledge key to craving-related brain neuroadaptations in the rats exposed to the decisions made during drug discovery programs. Such MDMA. With using the titrated receptor antagonists [cH]raclopride the molecular mechanisms of epilepsy. http://dx.doi.org/10.1016/j.pharep.2015.06.023 systematic interrogation of biological pathways with novel probe and [cH]MPEP, several binding assays were performed to evaluate compounds should enhance preclinical validation of target D R and mGluR densities in the neural circuitry of rats trained to http://dx.doi.org/10.1016/j.pharep.2015.06.020 2 5 biology, and lead to a more efficient paradigm for the develop- The mechanism of antipsychotic-like action of self-administer MDMA (0.5 mg/kg/infusion; FR5) that were ment of novel medicines. the mGlu receptor activators: Focus on subsequently assigned to live in either isolation conditions (home Role of adenosinergic modulatory system in To highlight the value of Chemical Biology in modern drug GABAergic signaling cage; HC), or exposed to experimental cage (EC) or exposed to ictogenesis discovery research, we present our efforts in the area of Glutamate Joanna M. Wieron´ ska 1,*, Monika Wozńiak 1, enriched environment (EE) during a period of forced abstinence. To Biology. Glutamate is a major neurotransmitter in mammal brain, 2 1 Pavel Maresˇ, Hana Kubova´ Francine Acher , Andrzej Pilc create control groups, a ‘yoked’ procedure was employed. acting through a network of ion channels, GPCRs and transporters. EC resulted in a significant decrease in density of D2R in the 1 Department of Developmental Epileptology, Institute of Physiology, The study of the pharmacological effects of positive allosteric Institute of Pharmacology, Polish Academy of Sciences, Krako´w, hippocampus (by 29%) and an increase in the nucleus accumbens Czech Academy of Sciences, Prague, Czech Republic modulators (PAMs) of metabotropic glutamate receptors (mGluRs) Poland (23%) of rats previously self-administered MDMA, while ‘yoked’ 2 has received significant attention in the last decade of drug Universite´ Paris Descartes, Paris, France MDMA animals displayed opposite results with a significant One of the potent inhibitory modulatory systems in mammali- discovery. The potential of these compounds to provide new *Corresponding author. increase in the hippocampus (28%) and decreases in the nucleus an brain is an adenosinergic system. There are two types of therapies for major CNS diseases (AD, PD, MS) contrasts with the accumbens and dorsal striatum (by 20–24%). Abstinence in EE metabotropic adenosine receptors in the brain – ubiquitous challenges associated with optimizing the chemical matter for The GABAergic/glutamatergic imbalance in the brain is thought resulted in a significant rise (by 16–27%) in D2R in the limbic inhibitory A1 and less important excitatory A2A localized mainly PAMs. We will discuss our efforts in the Chemical Biology of to be one of the main causes that leads to development of structures (the prefrontal cortex, nucleus accumbens and hippo- in basal ganglia. Suppression of epileptic phenomena may be mGluR4 potentiation, which led to the discovery of ligands with schizophrenia. Therefore it seems that the pharmacological campus) in rats with history of MDMA self-administration. MDMA mediated by inhibitory A1 receptors and this action might be distinct properties and enhanced our target understanding. manipulations within those two systems may restore the ‘yoked’ animals resulted in ca. 40% increase in the hippocampus in studied by means of specific agonists (e.g. CCPA) or antagonists homeostasis in the brain, thus exerting antipsychotic efficacy. receptor density. In the brains of rats self-administered MDMA and (e.g. DPCPX). http://dx.doi.org/10.1016/j.pharep.2015.06.022 Both glutamatergic and GABAergic compounds were shown to MDMA ‘yoked’ controls housed in HC, a significant increase (by 33 c Two models of epileptic seizures were used in our study: possess antipsychotic-like effects in animal models of positive, and 127%) in [ H]raclopride binding to D2R in the nucleus convulsions induced by systemic administration of pentylenetet- Group III mGlu receptors in the brain and negative and cognitive symptoms of schizophrenia. However, the accumbens and prefrontal cortex was found. Moreover, MDMA razol (100 mg/kg sc as 100% convulsant dose and 60 mg/kg sc as a periphery: Implications for visceral pain interesting thing is, that the compounds may complement each- self-administration and subsequent HC isolation produced subthreshold dose) and epileptic after discharges elicited by others action, and as a result the sub effective doses of two or more increases in D2R density in the dorsal striatum (by 85%), with Anna V. Golubeva 1,*, Rachel D. Moloney 1, electrical stimulation of sensorimotor cortex in rats. Animals of drugs can be administered at the same time to achieve therapeutic decreased in MDMA ‘yoked’ animals (by 36%). Timothy G. Dinan 1,2, John F. Cryan 1,3 various ages were tested, majority of experiments was performed effect. This could decrease the risk of inducing the unwanted EC evoked a significant decrease (>25%) in density of mGluR5 in in 12- and 25-day-old rat pups. 1 Alimentary Pharmabiotic Centre, University College Cork, Cork, adverse effects. the prefrontal cortex of rats previously exposured to MDMA. CCPA was found to suppress PTZ-induced seizures whereas Ireland In our research we investigated, if the parallel administration of Neither EE nor HC induced significant changes in mGluR5 in rat DPCPX potentiated these seizures. This potentiation was especially 2 Department of Psychiatry, University College Cork, Cork, Ireland GABAB positive allosteric modulators together with metabotropic repeated treated with history MDMA. expressed if various doses of DPCPX (0.5–5 mg/kg ip) were 3 Department of Anatomy & Neuroscience, University College Cork, glutamate receptors ligands in a sub effective doses induced Since EE and EC reduce relapse to MDMA on the behavioural combined with a subconvulsant dose of pentetrazol in both basic Cork, Ireland antipsychotic-like effects in animal models of schizophrenia. We level, the present observations seem to indicate the importance of age groups. *Corresponding author. showed that the concomitant administration of mGlu5 and GABAB accumbal D2R and mGluR5 interaction and may refer them as Cortical epileptic after discharges were suppressed by an PAMs is effective in the models of negative and cognitive, but not molecular targets to control drug seeking and relapse. agonist CCPA in a dose-related manner and they were extremely There is growing awareness that group III metabotropic positive symptoms, while the co-administration of GABAB-mGlu4 This study was supported by the grant no. 2011/03/D/NZ7/06295 by prolonged by DPCPX. Twelve-day-old rats pups exhibited up to glutamate receptors, which are broadly expressed throughout activators exerts positive effect in the models of positive the NCN (Krako´ w, Poland) and by the statutory activity of Institute of seventeen fold prolongation of after discharges. In agreement with the nociceptive pathways of the central and peripheral nervous symptoms, only. Pharmacology PAS. the effect on mechanisms ending seizures postictal refracteriness systems, modulate the perception of pain of different modalities, Acknowledgements: The study was supported by the Statutory in 25-day-old rats was partly blocked by the antagonist DPCPX. including inflammatory and neuropathic pain. However, the role of Funds of the Polish Academy of Science and by the National Science http://dx.doi.org/10.1016/j.pharep.2015.06.025 6 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 7 initiates cascades of events, called epileptogenesis (latency Our data speaking in favor of the role of adenosinergic system in group III mGlu receptors’ signaling in visceral pain processing is Centre, Grant no. 2012/6/ 06/A/NZ7/00014 (MAESTRO) given to period), after which recurrent spontaneous seizures occur. arrest of seizures are in agreement with conclusions of During and still largely unknown. And yet, visceral pain is associated with a A. Pilc. Epileptogenic insult causes a number of changes that lead to the Spencer (1992) – they demonstrated an action of adenosinergic wide variety of chronic functional disorders including irritable remodeling of neuronal circuits and subsequent seizures, which system in the arrest of seizures as well as in postictal refractoriness bowel syndrome and painful bladder syndrome. Interestingly, http://dx.doi.org/10.1016/j.pharep.2015.06.024 are undrilled by changes in the transcriptome to distinguish in human epileptic hippocampal tissue. stress has recently been shown as one of the most significant risk metabolic pathways affected by epileptic processes. Mechanisms factors increasing the prevalence of these disorders and exacer- of the regulation of gene expression in epileptogenesis are not well The studies were supported by a grant No. P304/12/G069 of the Grant bating the severity of pain symptoms. We utilised the Wistar Kyoto Alterations in brain mGluR5 and D2 receptor described. Recently the role of epigenetic mechanisms including Agency of the Czech Republic. (WKY) rat strain, as a model of stress-sensitive visceral hypersen- density during MDMA abstinence in different miRNA, have been proposed. miRNAs are small (20–24 bp), non- sitivity, to investigate the involvement of group III mGlu receptors living conditions in rats coding RNAs that regulate the expression of target genes by http://dx.doi.org/10.1016/j.pharep.2015.06.021 in stress-associated visceral pain disorders. WKY rats are known to Małgorzata Frankowska 1,*, 2 1 binding to the 30-untranslated regions (UTR) of target mRNAs and display a stress-hyper-responsive phenotype along with innate Lucyna Pomierny-Chamioło , Joanna Miszkiel , by this have a role in the regulation and fine-tuning of gene Glutamate Metabotropic Receptors and CNS Disorders hypersensitivity to noxious colon and urinary bladder distension Bartosz Pomierny 2, Małgorzata Filip 1,2 expression. In our study we have investigated changes in the as compared to stress-resilient Sprague Dawley rats. Here we show 1 expression levels of miRNAs and the expression of their potential Chemical Biology at Lundbeck: Enhancing CNS that WKY rats exhibit an altered pattern of group III mGlu Laboratory of Drug Addiction Pharmacology, Institute of Pharma- mRNA targets in the hippocampal dentate gyrus of rats subjected drug discovery research receptors expression in certain regions of brain limbic system, cology, Polish Academy of Sciences, Krako´w, Poland 2 to epileptogenesis in the amygdala stimulation model of the Dario Doller which are tightly associated with emotional processes including Department of Toxicology, Faculty of Pharmacy, Jagiellonian temporal lobe epilepsy. We found that there are ensembles of visceral pain. Moreover, WKY rats display a profound up- University, Medical College, Krako´w, Poland Chemical Biology, Lundbeck Research, Paramus, NJ, USA miRNAs that change expression levels over time. Analysis of the regulation of mGlu7 receptors’ expression on the periphery, *Corresponding author. mRNA expression from the same animals revealed that the namely in bladder tissue, while pharmacological inhibition of this expression of several mRNAs that are potential targets for miRNA Greater emphasis is being placed on the stringent selection, receptor effectively reduces visceral hypersensitivity in the MDMA (3,4-methylenedioxymethylamphetamine; ecstacy) is a with altered expression level is regulated in the expected direction. validation and interrogation of targets to maximize success rates animals. Altogether, these data suggest that altered group III psychostimulant currently considered as most popular drug of The functional characterization of miRNAs and their potential in clinical trials and deliver much needed therapies to patients. In mGlu receptor signaling may be one of the mechanisms underlying abuse in Europe. Accumulative evidence suggests that the mRNA targets indicate that miRNA can participate in several response to this challenge, Chemical Biology is emerging as a vital visceral hypersensitivity in stress-prone individuals. To this end, dopamine and glutaminergic transmission and the corresponding molecular events that occur in epileptic tissue, including immune component to providing adequate confidence before launching pharmacological modulation of these receptors might be an dopamine D2 (D2R) and glutamate mGlu5 (mGluR5) receptors are response and neuronal plasticity. Localization of the expression of full discovery programs. The use of well-qualified chemical tools attractive approach for the management of stress-induced visceral involved in MDMA-evoked seeking and relapse behaviors. top miRNAs indicated their neuronal function. Complex changes in in combination with disease-relevant biological systems provides pain. The aim of study was to uncover the role of D2R and mGluR5 in the expression of miRNAs suggest an important role for miRNA in a powerful approach to creating mechanistic knowledge key to craving-related brain neuroadaptations in the rats exposed to the decisions made during drug discovery programs. Such MDMA. With using the titrated receptor antagonists [cH]raclopride the molecular mechanisms of epilepsy. http://dx.doi.org/10.1016/j.pharep.2015.06.023 systematic interrogation of biological pathways with novel probe and [cH]MPEP, several binding assays were performed to evaluate compounds should enhance preclinical validation of target D R and mGluR densities in the neural circuitry of rats trained to http://dx.doi.org/10.1016/j.pharep.2015.06.020 2 5 biology, and lead to a more efficient paradigm for the develop- The mechanism of antipsychotic-like action of self-administer MDMA (0.5 mg/kg/infusion; FR5) that were ment of novel medicines. the mGlu receptor activators: Focus on subsequently assigned to live in either isolation conditions (home Role of adenosinergic modulatory system in To highlight the value of Chemical Biology in modern drug GABAergic signaling cage; HC), or exposed to experimental cage (EC) or exposed to ictogenesis discovery research, we present our efforts in the area of Glutamate Joanna M. Wieron´ ska 1,*, Monika Wozńiak 1, enriched environment (EE) during a period of forced abstinence. To Biology. Glutamate is a major neurotransmitter in mammal brain, 2 1 Pavel Maresˇ, Hana Kubova´ Francine Acher , Andrzej Pilc create control groups, a ‘yoked’ procedure was employed. acting through a network of ion channels, GPCRs and transporters. EC resulted in a significant decrease in density of D2R in the 1 Department of Developmental Epileptology, Institute of Physiology, The study of the pharmacological effects of positive allosteric Institute of Pharmacology, Polish Academy of Sciences, Krako´w, hippocampus (by 29%) and an increase in the nucleus accumbens Czech Academy of Sciences, Prague, Czech Republic modulators (PAMs) of metabotropic glutamate receptors (mGluRs) Poland (23%) of rats previously self-administered MDMA, while ‘yoked’ 2 has received significant attention in the last decade of drug Universite´ Paris Descartes, Paris, France MDMA animals displayed opposite results with a significant One of the potent inhibitory modulatory systems in mammali- discovery. The potential of these compounds to provide new *Corresponding author. increase in the hippocampus (28%) and decreases in the nucleus an brain is an adenosinergic system. There are two types of therapies for major CNS diseases (AD, PD, MS) contrasts with the accumbens and dorsal striatum (by 20–24%). Abstinence in EE metabotropic adenosine receptors in the brain – ubiquitous challenges associated with optimizing the chemical matter for The GABAergic/glutamatergic imbalance in the brain is thought resulted in a significant rise (by 16–27%) in D2R in the limbic inhibitory A1 and less important excitatory A2A localized mainly PAMs. We will discuss our efforts in the Chemical Biology of to be one of the main causes that leads to development of structures (the prefrontal cortex, nucleus accumbens and hippo- in basal ganglia. Suppression of epileptic phenomena may be mGluR4 potentiation, which led to the discovery of ligands with schizophrenia. Therefore it seems that the pharmacological campus) in rats with history of MDMA self-administration. MDMA mediated by inhibitory A1 receptors and this action might be distinct properties and enhanced our target understanding. manipulations within those two systems may restore the ‘yoked’ animals resulted in ca. 40% increase in the hippocampus in studied by means of specific agonists (e.g. CCPA) or antagonists homeostasis in the brain, thus exerting antipsychotic efficacy. receptor density. In the brains of rats self-administered MDMA and (e.g. DPCPX). http://dx.doi.org/10.1016/j.pharep.2015.06.022 Both glutamatergic and GABAergic compounds were shown to MDMA ‘yoked’ controls housed in HC, a significant increase (by 33 c Two models of epileptic seizures were used in our study: possess antipsychotic-like effects in animal models of positive, and 127%) in [ H]raclopride binding to D2R in the nucleus convulsions induced by systemic administration of pentylenetet- Group III mGlu receptors in the brain and negative and cognitive symptoms of schizophrenia. However, the accumbens and prefrontal cortex was found. Moreover, MDMA razol (100 mg/kg sc as 100% convulsant dose and 60 mg/kg sc as a periphery: Implications for visceral pain interesting thing is, that the compounds may complement each- self-administration and subsequent HC isolation produced subthreshold dose) and epileptic after discharges elicited by others action, and as a result the sub effective doses of two or more increases in D2R density in the dorsal striatum (by 85%), with Anna V. Golubeva 1,*, Rachel D. Moloney 1, electrical stimulation of sensorimotor cortex in rats. Animals of drugs can be administered at the same time to achieve therapeutic decreased in MDMA ‘yoked’ animals (by 36%). Timothy G. Dinan 1,2, John F. Cryan 1,3 various ages were tested, majority of experiments was performed effect. This could decrease the risk of inducing the unwanted EC evoked a significant decrease (>25%) in density of mGluR5 in in 12- and 25-day-old rat pups. 1 Alimentary Pharmabiotic Centre, University College Cork, Cork, adverse effects. the prefrontal cortex of rats previously exposured to MDMA. CCPA was found to suppress PTZ-induced seizures whereas Ireland In our research we investigated, if the parallel administration of Neither EE nor HC induced significant changes in mGluR5 in rat DPCPX potentiated these seizures. This potentiation was especially 2 Department of Psychiatry, University College Cork, Cork, Ireland GABAB positive allosteric modulators together with metabotropic repeated treated with history MDMA. expressed if various doses of DPCPX (0.5–5 mg/kg ip) were 3 Department of Anatomy & Neuroscience, University College Cork, glutamate receptors ligands in a sub effective doses induced Since EE and EC reduce relapse to MDMA on the behavioural combined with a subconvulsant dose of pentetrazol in both basic Cork, Ireland antipsychotic-like effects in animal models of schizophrenia. We level, the present observations seem to indicate the importance of age groups. *Corresponding author. showed that the concomitant administration of mGlu5 and GABAB accumbal D2R and mGluR5 interaction and may refer them as Cortical epileptic after discharges were suppressed by an PAMs is effective in the models of negative and cognitive, but not molecular targets to control drug seeking and relapse. agonist CCPA in a dose-related manner and they were extremely There is growing awareness that group III metabotropic positive symptoms, while the co-administration of GABAB-mGlu4 This study was supported by the grant no. 2011/03/D/NZ7/06295 by prolonged by DPCPX. Twelve-day-old rats pups exhibited up to glutamate receptors, which are broadly expressed throughout activators exerts positive effect in the models of positive the NCN (Krako´ w, Poland) and by the statutory activity of Institute of seventeen fold prolongation of after discharges. In agreement with the nociceptive pathways of the central and peripheral nervous symptoms, only. Pharmacology PAS. the effect on mechanisms ending seizures postictal refracteriness systems, modulate the perception of pain of different modalities, Acknowledgements: The study was supported by the Statutory in 25-day-old rats was partly blocked by the antagonist DPCPX. including inflammatory and neuropathic pain. However, the role of Funds of the Polish Academy of Science and by the National Science http://dx.doi.org/10.1016/j.pharep.2015.06.025 8 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 9

b+ b+ Cocaine-induced dysregulation in metabotropic demonstrated that (1) serotonin receptor (5-HT-R) antagonists Ca concentration (Ca i) and cytotoxicity were studied in Acknowledgements: This project was financed by the statutory glutamate receptors expression in rat brain areas acutely attenuate dopamine (DA) D1-R supersensitivity in rats primary cultures of rat cerebellar granule cells (CGC). CGC were founds of the Institute of Pharmacology PAS, Krako´ w, Poland and Lucyna Pomierny-Chamioło 1,*, lesioned as neonates with 6-hydroxydopamine (n6-OHDA); (2) acutely challenged with 7.5, 10 or 25 mM TBBPA, accumulation by grant 2012/07/B/NZ7/01149. 2 1,2 45 b+ Małgorzata Frankowska , Małgorzata Filip neonatal lesioning of 5-HT nerves chronically attenuates D1-R of Ca was measured, Ca i and changes in plasma membrane supersensitization in n6-OHDA-lesioned rats; and (3) enhances the potential were evaluated with fluorescent probes. CGC survival 1 http://dx.doi.org/10.1016/j.pharep.2015.06.030 Department of Toxicology, Faculty of Pharmacy, Jagiellonian ability of intrastriatal amphetamine to evoke dopamine release; (4) was assessed after 24 h using propidium iodide staining. Effects University, Medical College, Krako´w, Poland 3 small adulthood 5-HT lesions in n6-OHDA-lesioned rats produce D2- of TBBPA on binding of the H-labeled MK-801, glutamate and 2 Molecular Mechanisms of Xenobiotic – Induced Effects Laboratory of Drug Addiction Pharmacology, Institute of Pharma- R supersensitivity and an increase in exploratory locomotor activity glycine to isolated rat brain cortical membranes were also cology, Polish Academy of Sciences, Krako´w, Poland (a model of hyperactivity) which (5) is attenuated by both studied. The antagonists, 0.5 mM MK-801 and 2.5 mM bastadin Risk related to exposure to environmental *Corresponding author. amphetamine and a 5-HT-R agonist; (6) 5-HT-R antagonists but 12 co-administered with 200 mM ryanodine were used to inhibit pollutants not D1-R antagonists attenuate spontaneous vacuous chewing NMDARs and RyRs, respectively. TBBPA concentration-depen- 45 b+ Anna K. Wo´ jtowicz Impairment of control evoked by cocaine begins in the brain movements (VCMs) in rats in which haloperidol-induced tardive dently increased Ca uptake and Ca i in CGC, depolarized the areas processing reward as nucleus accumbens, but the long-term dyskinesia was produced. These findings demonstrate that 5-HT and cells and reduced their viability. MK-801 specifically and Department of Animal Biotechnology, Animal Sciences Faculty, drug intake disturbs whole brain leading to memory and learning DA neuronal systems each act in part as a redundant system to the completely prevented TBBPA-induced 45Ca uptake. Both, MK- University of Agriculture, Krako´w, Poland disturbances, dysfunction of emotions, executive control or other, but in certain instances each functions as an opposing system 801 and bastadin 12 with ryanodine partially inhibited rise in b+ cognitive disorders. Recent findings have highlighted a role of to the other. The fine tuning among neurotransmitter systems in Ca i and decreased TBBPA toxicity. Combination of NMDAR and Development of new technologies lead to the release into the glutamate transmission and metabotropic glutamate receptors brain likely serves to hone neuronal responses in a manner that RyR inhibitors completely prevented TBBPA-induced increases environment many man-made pollutants. Their sources are mainly b+ (mGluRs) in mediating cocaine use disorder. Genetic deletion or optimizes responses to the environment. in Ca i and partially reduced cytotoxicity. TBBPA had no industry, agriculture, car exhaust fumes, personal care products as 3 pharmacological blockade of mGluR5 and stimulation of mGluR2/3 significant effect on [ H]glycine binding to brain membranes, well as pharmaceutics. They access living organisms with food and 3 3 or mGluR7 inhibit cocaine self-administration and cocaine- http://dx.doi.org/10.1016/j.pharep.2015.06.027 inhibited [ H]glutamate binding, and potentiated [ H]MK-801 water, via respiration and skin absorption. These compounds often induced reinstatement in rats and squirrel monkeys [for review binding which was suppressed by ligands of the poliamine site. accumulate in human tissues and may participate in etiology of b+ see Pomierny-Chamioło et al., Pharm Ther, 2014]. Thus, TBBPA induces in CGC Ca release via destabilized RyRs, various disorders. Many studies indicated a strong correlation Neurotoxicity of fluorine b+ Our study revealed that cocaine self-administration evokes a and independently NMDAR-mediated Ca influx, resulting from between enhanced level of environmental pollutants and in- Dariusz Chlubek significant elevation in the mGluR5 receptor protein expression its multisite action on the NMDAR complex and also from CGC creased frequency of developmental malformations, reproductive and binding in the dorsal striatum with a parallel fall in mGluR2/3 Department of Biochemistry and Medical Chemistry, Pomeranian depolarization. Both these effects participate in TBBPA-evoked and metabolic disorders, neurobehavioral impairments, immuno- b+ receptor affinity in the nucleus accumbens and prefrontal cortex. Medical University, Szczecin, Poland increases in Ca i and cytotoxicity. logical abnormalities and tumors. In addition, effects of the The most prominent changes in the mGluRs and glutamate pollutants may unravel even in the next generations. Environ- transmission are reported during withdrawal from chronic cocaine Supported by NCN grant 2012/05/B/N27/03225. Fluorine is a gas that does not occur in its free state in nature. mental contaminants may affect cellular processes by DNA treatment. After extinction training in the prefrontal cortex we Being highly reactive, fluorine easily interacts with other elements damage, mutations, alterations in gene expression, interference observed a decrease in mGluR5 receptor and a rise in the affinity of http://dx.doi.org/10.1016/j.pharep.2015.06.029 forming a variety of inorganic and organic compounds. A part of with enzymes, reactive oxygen species formation etc. Furthermore, mGluR2/3 receptors. Interestingly, in rats following cocaine self- these compounds is toxic, while others have been used in certain certain xenobiotics are metabolized and transformed to even more administration and yoked cocaine delivery in the nucleus prophylactic actions (sodium monofluorophosphate, aminofluor- toxic products than the parent compound. Some environmental accumbens and hippocampus an elevation in mGluR5 was New perspectives for therapeutic use of ide), and even in the treatment (fluorouracil, fluoroquinolones). contaminants are able to mimic actions of endogenous hormones, detected, while in the dorsal striatum the increased was observed endogenous neuroprotective amine, 1MeTIQ: Functioning in the environment, the living organisms are thus they are included in Endocrine Disrupting Chemicals (EDCs). only in rats with non-contingent cocaine administration. Behavioral and biochemical studies continuously exposed to larger or smaller doses of fluorides, EDCs may disrupt synthesis, secretion and metabolism of Reinstatement of cocaine seeking behavior evoked an impor- which means they are forced to metabolize them. In case of chronic Agnieszka Wa˛sik, Lucyna Antkiewicz-Michaluk hormones which could result in disregulation of physiological tant reduction in mGluR5 receptor density in the hippocampus exposure even to relatively low doses of fluoride, the symptoms of processes and organism homeostasis. restricted to animals self-administered cocaine while mGluR2/3 Department of Neurochemistry, Institute of Pharmacology, Polish poisoning may occur, which is called fluorosis. The main symptoms were left unchanges. Academy of Sciences, Krako´w, Poland Supported by NCN grant 2012/07/B/NZ4/00238. of this disease are associated with the accumulation of fluoride in We observed changes in mGluRs protein expression, receptor bone and/or teeth, however the significant effects of intoxication density and their affinity seem to be brain region specific and 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an en- http://dx.doi.org/10.1016/j.pharep.2015.06.031 may also concern soft tissues, especially the kidney, liver and brain. dependent of the manner of cocaine administration. These dogenous substance which is present in human and mammalian Fluoride passes through the blood-brain barrier, penetrating the molecular analyses extend previous pharmacological observation brain. This substance presents whole palette of clinically respective structures of the central nervous system, particularly the Neurodevelopmental effects of nonylphenol and provide more neuroanatomical background for understanding advantageous effects within brain as: neuroprotective, antiad- hippocampus, cortex and cerebellum. The effects of fluoride in these Ewa Litwa *, Joanna Rzemieniec, Agnieszka Wnuk, cocaine use disorder. dictive and monoamine oxidase (MAO)-inhibiting properties. structures may include the neurodegenerative changes, the dys- Władysław Lason´ , Małgorzata Kajta Depression is connected with many disturbances in monoamin- function of receptors and disturbed metabolism of neurotransmit- ergic transmission, and 1MeTIQ significantly affects monoamines Department of Experimental Neuroendocrinology, Institute of Phar- http://dx.doi.org/10.1016/j.pharep.2015.06.026 ters, leading to the development of clinical symptoms, of which the metabolism in the mammalian brain recently, we investigated macology, Polish Academy of Sciences, Krako´w, Poland cognitive impairment and lowered intelligence quotient (IQ) scores antidepressant potential of 1MeTIQ in the experimental model of *Corresponding author. are the most frequently mentioned. The latter concern in particular Neurotoxicity and Neuroprotection depression. Both behavioral and biochemical tests confirmed children living in areas contaminated by emissions of fluorine antidepressant properties of 1MeTIQ: in forced swimming test Nonylphenol belongs to alkylophenols and is widely used as a Monoaminergic system interactions in compounds or consuming artificially fluoridated drinking water. (FST) 1MeTIQ decreased the immobility time with potency component of the plastics, paints and agricultural chemicals. Most neurotoxicity similar to classical antidepressants: imipramine or desipramine. of nonylphenol metabolites accumulate in adipose tissue, liver and 1, 1 http://dx.doi.org/10.1016/j.pharep.2015.06.028 Richard M. Kostrzewa *, John P. Kostrzewa , Neurochemical ex vivo study have shown that acute administra- brain in much higher concentrations than in other tissues. It has 2 Ryszard Brus tion of 1MeTIQ increase the concentration of dopamine, been postulated that hormonal disturbances and exposure to Mechanisms of calcium imbalance in serotonin and noradrenaline in the rat brain. In vivo microdialysis xenobiotics during pregnancy or perinataly may cause strong and 1 Department of Biomedical Sciences, Quillen College of Medicine, East tetrabromobisphenol A-induced neurotoxicity study demonstrated that 1MeTIQ (25 mg/kg) given concomitant- persistent developmental abnormalities of the nervous system, Tennessee State University, Johnson City, TN, USA Jerzy W. Łazarewicz *, Dominik Diamandakis, ly with imipramine (15 mg/kg) produced a long-lasting increase concomitantly with increased ratio of attention deficit and 2 Department of Nurse, High School of Strategic Planning, Da˛browa Elz˙ bieta Ziemin´ ska, Elz˙ bieta Salin´ ska of the monoamines concentrations in the extracellular area: hyperactivity disorder as well as learning and cognitive deficits Go´rnicza, Poland dopamine (up to 300%; p < 0.01), noradrenaline (about 900%; in children. Therefore, the scope of our studies is a detrimental *Corresponding author. Department of Neurochemistry, Mossakowski Medical Research p < 0.01), and serotonin (approx. 400%; p < 0.01). Additionally, effect of nonylphenol on developing nervous system. We Centre, Polish Academy of Sciences, Warszawa, Poland 1MeTIQ reduced oxidative stress by blocking the MAO activity. demonstrated, that nonylphenol induced the loss of mitochondrial A series of studies focused on the inter-relationship between *Corresponding author. The received results suggest that 1MeTIQ as an endogenous membrane potential, apoptotic nuclei fragmentation and neuronal monoaminergic systems in brain, highlights their modulatory neuroprotective compound can be promising and safe antide- cell death. It also activated caspase-3, -8 and -9, but not calpains influence on one another; and uncovers their respective effects on The roles of ryanodine and NMDA receptors (NMDARs & RyRs) in pressant in the clinic. [Litwa et al., J Steroid Biochem Mol Biol, 2014]. The effects of alternate receptor sensitivity status. In vivo studies in rats have tetrabromobisphenol A (TBBPA)-evoked increases in intracellular 10 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 11 nonylphenol were mediated by xenobiotic receptors RXRa, PXR Molecular mechanism of neurotoxic action of hippocampal cells subjected to glutamic acid or hypoxia. Daidzein Pharmacogenetics in transplantion the pesticide DDT metabolite and CAR, and were correlated with the developmental stage of and raloxifene bind to estrogen receptors with SERMs properties, Mateusz Kurzawski neuronal cells in in vitro culture. Prenatal exposure to nonylphenol Agnieszka Wnuk *, Joanna Rzemieniec, Ewa Litwa, whereas DIM is representative of SAhRMs. Treatment with diminished spontaneous apoptosis and enhanced vulnerability of Władysław Lason´ , Małgorzata Kajta glutamic acid (1 mM, 6 h) or oxygen deprivation (5% CO2/95% Department of Experimental and Clinical Pharmacology, Pomeranian neuronal cells to NP-induced apoptosis. Furthermore, prenatal N2, 18 h) caused apoptosis and neurotoxicity in mouse cell Medical University, Szczecin, Poland exposure to nonylphenol caused cognitive impairments in mouse Department of Experimental Neuroendocrinology, Institute of Phar- cultures. Daidzein, raloxifene, and DIM (1.10 mM) inhibited the offspring, as detected via Novel Object Recognition test. Our study macology, Polish Academy of Sciences, Krako´w, Poland glutamate/hypoxia-induced loss of mitochondrial membrane Allogenic solid organ transplantation has become a routine demonstrated that prolonged prenatal exposure to nonylphenol *Corresponding author. potential, caspase-3 activity, and lactate dehydrogenase release. procedure in patients with end stage organ diseases. However, increased the vulnerability of hippocampal cells to toxicity and In siRNA ERb-/GPR30-transfected cells, daidzein did not inhibit the successful maintenance of graft function usually cannot be apoptosis. It also affected the xenobiotic receptors both at the Dichlorodiphenyldichloroethylene (DDE) is a primary environ- glutamate-induced effects. Similarly, in the hippocampal neurons achieved without administration of immunosuppressive drugs. genome and protein levels. In global context, studying the effects of mental and metabolic degradation product of the pesticide DDT. It with silenced expression of Era, raloxifene lost its anti-hypoxic Immunosuppressants represent drugs of narrow therapeutic nonylphenol should be of particular importance, especially in is a toxic compound belonging to organochlorines and has never capacity. Furthermore, in the cells transfected with siRNA AhR/ index, hence, drug levels must be kept within therapeutic range, respect to neural development and the risk of the next exposure to been commercially produced. However, parental DDT is still used ARNT, DIM was no longer protective. Our data point to strong which is absolutely crucial for graft function preservation. Drug this endocrine disrupting chemical. in some developing countries for disease-vector control of malaria. neuroprotective potential of SERM and SAhRM in the hippocampal and its metabolite concentrations depend on efficiency of patient DDT and DDE remain in the environment because they are cells undergoing excitotoxicity and hypoxia. They also provide individual metabolism, and, in case of immunosuppressive agents, This work was supported by the Polish National Center of Science, resistant to degradation and bioaccumulate in the food chain. DDE evidence for a key role of ER/AhR/ARNT signaling pathways in many enzymes and transporters involved in their metabolism and grant no. 2011/01/N/NZ4/04950. is a highly fat-soluble compound that accumulates in the fatty neuroprotection mediated by daidzein, raloxifene, and DIM, which distribution are encoded by highly polymorphic genes. Therefore, a tissues of animals and humans. Increasing evidence suggests that may contribute to development of new therapeutic strategies. large part of interindividual variability in drug dosage and http://dx.doi.org/10.1016/j.pharep.2015.06.032 the presence of DDE in the environment induces brain damage at response is of genetic, hereditary nature. Recently, many studies This work was supported by The National Science Centre, Poland doses much lower than those affecting adult brain, leading to were undertaken to investigate the relationship between genetic abnormal fetal neurodevelopmental processes. A recent epidemi- grant No. 2011/01/N/NZ3/04786. Joanna Rzemieniec and Agnieszka Impact of triclosan on apoptotic processes in factors, immunosuppressive agents’ pharmacokinetics and thera- ological study showed that DDE prenatal exposure has a long-term Wnuk are holders of scholarship from the KNOW sponsored by neuronal cells py outcome. Those studies include, among others, a classic effect and is negatively associated with neural development, Ministry of Science and Higher Education, Republic of Poland. pharmacogenetic example, thiopurine S-methyltransferase (TPMT) Konrad A. Szychowski *, Agnieszka M. Sitarz, cognitive skills and also has been related to increased risk for deficiency in relation to toxicity of azathioprine, an impact of Anna K. Wo´ jtowicz autism and ADHD-like behaviours [Torres-Sańchez; Environ http://dx.doi.org/10.1016/j.pharep.2015.06.035 CYP3A4/CYP3A5 genetic variants on pharmacokinetics of calci- Department of Animal Biotechnology, Animal Sciences Faculty, Health Perspect, 2013]. Nevertheless, data on the effects of DDE neurin inhibitors, or influence of UGT1A9 polymorphism on course University of Agriculture, Krako´w, Poland on the nervous system are scarce. Especially little is known about Safety and Opimization of Pharmacotherapy of treatment with mycophenolic acid. This presentation sum- *Corresponding author. the impact of DDE on individual receptors that are strongly marizes the recent state of knowledge in the field of pharmaco- associated with brain development. The aim of this study was to Optimization of antibiotic therapy genetics related to solid organ transplantation (including studies reveal the molecular mechanisms of DDE-induced apoptosis Anna Wiela-Hojen´ ska *, Magdalena Hurkacz, Triclosan (TCS) is a commonly used antimicrobial agent added performed in the Polish population), trying to settle whether during early stages of neural development with particular Krystyna Głowacka to personal care and sanitizing products. Recent studies have genetic testing for polymorphic variants of xenobiotic-metaboliz- emphasis on nuclear receptors that act as transcription factors. demonstrated that TCS in concentrations detected in the human ing enzymes, transport proteins or drug targets could be used for This work improves perspectives for understanding the impact of Department of Clinical Pharmacology, Wrocław Medical University, body activated Fas-dependent extrinsic apoptotic signaling making immunosuppressive therapy more efficient and safe. DDE on neurodevelopmental processes that may have far-reaching Wrocław, Poland pathway in mouse neurons in vitro [Szychowski et al., Neurosci- * implications evident in the mature nervous system. Given that Corresponding author. ence, 2015]. The aryl hydrocarbon receptor (AhR) is involved in the http://dx.doi.org/10.1016/j.pharep.2015.06.037 neurodevelopmental and neurodegenerative processes are accom- cell response to the numerous xenobiotics. This receptor regulates panied by apoptosis, knowledge about the effects of DDE in Contemporary antimicrobial therapy should be directed by expression of genes which control growth, differentiation, neuronal cells may contribute to understanding its deleterious objective criteria which allow for maximal effectiveness of Pharmacovigilance in Poland – Present and metabolism and apoptotic process of the neurons. The aim of apoptotic actions. In addition, these studies characterize the treatment with minimal side effects. The major problem with future the present study was to investigate the role of AhR, CYP1A1, prenatal vulnerability of neuronal cells to DDE and contribute to its significant clinical implication is the fact that under-dosing of Daria Schetz 1,2, Ivan Kocic´ 3 CYP1B1 and NMDA receptor in the cytotoxic and apoptotic effects antibiotics appears common. Therapeutic concentrations are possible withdrawal or controlled use in industry. 1 of TCS in mouse neocortical neurons. Cultures were prepared from frequently not achieved, leading to multiple bacterial resistance, Department of Clinical Toxicology, Medical University of Gdansk, Swiss mouse embryos on day 15/16 of gestation. The cells were which is associated with increased patient mortality, length of Gdan´sk, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.034 2 cultured in Neurobasal medium with B27 and glutamine. After inpatient stay, extended drug courses exposing the patient to Pomeranian Centre of Toxicology, Gdan´sk, Poland 3 exposure to TCS expression of AhR, CYP1A1, CYP1B1 and NMDA potentially toxic side effects. Typical pharmacokinetic parameters Department of Pharmacology, Medical University of Gdansk, Gdan´sk, receptor subunits were measured. To verify the involvement of Neuroprotective effects of phytoestrogens and Poland (Cl, Vd, t0,5, AUC, Cmax) do not adequately describe the altered PK/PD AhR in TCS mechanism of action, the AhR siRNA was used. After selective modulators of nuclear receptors properties, especially in critically ill patients. In recent years, the silencing procedure and exposure to AhR agonist, antagonist or Joanna Rzemieniec *, Ewa Litwa, Agnieszka Wnuk, efficacy of antibiotics has been improved through the use of three Rational use of medicines is highly important for every society, TCS, the release of the lactate dehydrogenase (LDH) and caspase-3 Władysław Lason´ , Małgorzata Kajta basic markers such: Cmax/MIC for antibiotics with pronounced not only with respect to the public finance but also to safety of activity in cells were measured. Preliminary data demonstrated concentration-dependent killing (aminoglycosides, fluoroquino- pharmacotherapy. Evidence based medicine (EBM) and pharma- that TCS enhanced expression of the AhR, CYP1B1 and altered the Department of Experimental Neuroendocrinology, Institute of Phar- lones, daptomycin), AUC/MIC for antibiotics with weak concen- covigilance (PHV) are the fundamental strategies for improvement expression of NMDA receptor subunits. Additionally, in the macology, Polish Academy of Sciences, Krako´w, Poland tration-dependent effects, but with prolonged persistent effects in this field, however implementation of the principals of EBM and presence of agonist as well as TCS the increase in neuronal *Corresponding author. (glycopeptides, fluoroquinolones, azithromycin, tigecycline), and PHV in practice is extremely difficult. Poland has one of the lowest apoptosis and LDH release into the culture medium were observed. T>MIC for antibiotics with a weak or no concentration dependency rate of adverse drug effects reporting in European Union. The main In neurons undergoing silencing procedure, in the presence of Hypoxia in adults and neonates may lead to stroke or cerebral (b-lactams, carbapenems, clarithromycin, erythromycin, linezo- reason is lack of properly functioning regional adverse drug agonist no significant changes in cytotoxicity or induction of palsy which could result in seizures, cognitive deficits and lid). Moreover antibiotics are the most irrationally prescribed drug reactions monitoring centers, that should identify the hazard-risk apoptosis were observed. Moreover, the cytotoxic and proapopto- neurodevelopmental abnormalities. However, there are no effec- class. So implementation of special guidelines for the hospital associated with pharmaceutical products. In Pomeranian province tic effects of TCS were partially reduced after silencing procedure. tive, neuroprotective therapies against stroke or perinatal asphyx- scenario and strict adherence should be ensured to promote their such regional center was created in 2012, and thereafter adverse In summary, the presented study demonstrated that TCS enhanced ia. Scientists are still searching for novel strategies to cure neuronal rational use. The spontaneous reporting of the adverse reactions to drug reporting is significantly higher. The center is involved in expression of AhR and CYP1B1 and altered expression pattern of degeneration induced by hypoxic/ischemic events. This kind of antibiotics is very important for identification of threats in local prevention campaigns at the local level. Based on experience of NMDA receptor subunits. application involves the use of selective receptor modulators, such population. Close collaboration between physicians, pharmacists, Department of Pharmacology, MUG in Pomerania Province such as selective estrogen receptor modulators (SERMs) and selective Supported by NCN Grant 2014/13/N/NZ4/04809. clinical pharmacologists, clinical pharmacists, microbiologists and information strategy contributes to increase awareness by aryl hydrocarbon receptor modulators (SAhRMs). In the present patients results in improved quality of antibiotic therapy. providing current information about drug-related issues. The best study, we evaluated the neuroprotective capacity of daidzein, example of this is three-fold increase in adverse drug reactions http://dx.doi.org/10.1016/j.pharep.2015.06.033 raloxifene and 3,3’-diindolylmethane (DIM) in mouse primary http://dx.doi.org/10.1016/j.pharep.2015.06.036 reporting in Pomerania province after the publication of our first 10 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 11 nonylphenol were mediated by xenobiotic receptors RXRa, PXR Molecular mechanism of neurotoxic action of hippocampal cells subjected to glutamic acid or hypoxia. Daidzein Pharmacogenetics in transplantion the pesticide DDT metabolite and CAR, and were correlated with the developmental stage of and raloxifene bind to estrogen receptors with SERMs properties, Mateusz Kurzawski neuronal cells in in vitro culture. Prenatal exposure to nonylphenol Agnieszka Wnuk *, Joanna Rzemieniec, Ewa Litwa, whereas DIM is representative of SAhRMs. Treatment with diminished spontaneous apoptosis and enhanced vulnerability of Władysław Lason´ , Małgorzata Kajta glutamic acid (1 mM, 6 h) or oxygen deprivation (5% CO2/95% Department of Experimental and Clinical Pharmacology, Pomeranian neuronal cells to NP-induced apoptosis. Furthermore, prenatal N2, 18 h) caused apoptosis and neurotoxicity in mouse cell Medical University, Szczecin, Poland exposure to nonylphenol caused cognitive impairments in mouse Department of Experimental Neuroendocrinology, Institute of Phar- cultures. Daidzein, raloxifene, and DIM (1.10 mM) inhibited the offspring, as detected via Novel Object Recognition test. Our study macology, Polish Academy of Sciences, Krako´w, Poland glutamate/hypoxia-induced loss of mitochondrial membrane Allogenic solid organ transplantation has become a routine demonstrated that prolonged prenatal exposure to nonylphenol *Corresponding author. potential, caspase-3 activity, and lactate dehydrogenase release. procedure in patients with end stage organ diseases. However, increased the vulnerability of hippocampal cells to toxicity and In siRNA ERb-/GPR30-transfected cells, daidzein did not inhibit the successful maintenance of graft function usually cannot be apoptosis. It also affected the xenobiotic receptors both at the Dichlorodiphenyldichloroethylene (DDE) is a primary environ- glutamate-induced effects. Similarly, in the hippocampal neurons achieved without administration of immunosuppressive drugs. genome and protein levels. In global context, studying the effects of mental and metabolic degradation product of the pesticide DDT. It with silenced expression of Era, raloxifene lost its anti-hypoxic Immunosuppressants represent drugs of narrow therapeutic nonylphenol should be of particular importance, especially in is a toxic compound belonging to organochlorines and has never capacity. Furthermore, in the cells transfected with siRNA AhR/ index, hence, drug levels must be kept within therapeutic range, respect to neural development and the risk of the next exposure to been commercially produced. However, parental DDT is still used ARNT, DIM was no longer protective. Our data point to strong which is absolutely crucial for graft function preservation. Drug this endocrine disrupting chemical. in some developing countries for disease-vector control of malaria. neuroprotective potential of SERM and SAhRM in the hippocampal and its metabolite concentrations depend on efficiency of patient DDT and DDE remain in the environment because they are cells undergoing excitotoxicity and hypoxia. They also provide individual metabolism, and, in case of immunosuppressive agents, This work was supported by the Polish National Center of Science, resistant to degradation and bioaccumulate in the food chain. DDE evidence for a key role of ER/AhR/ARNT signaling pathways in many enzymes and transporters involved in their metabolism and grant no. 2011/01/N/NZ4/04950. is a highly fat-soluble compound that accumulates in the fatty neuroprotection mediated by daidzein, raloxifene, and DIM, which distribution are encoded by highly polymorphic genes. Therefore, a tissues of animals and humans. Increasing evidence suggests that may contribute to development of new therapeutic strategies. large part of interindividual variability in drug dosage and http://dx.doi.org/10.1016/j.pharep.2015.06.032 the presence of DDE in the environment induces brain damage at response is of genetic, hereditary nature. Recently, many studies This work was supported by The National Science Centre, Poland doses much lower than those affecting adult brain, leading to were undertaken to investigate the relationship between genetic abnormal fetal neurodevelopmental processes. A recent epidemi- grant No. 2011/01/N/NZ3/04786. Joanna Rzemieniec and Agnieszka Impact of triclosan on apoptotic processes in factors, immunosuppressive agents’ pharmacokinetics and thera- ological study showed that DDE prenatal exposure has a long-term Wnuk are holders of scholarship from the KNOW sponsored by neuronal cells py outcome. Those studies include, among others, a classic effect and is negatively associated with neural development, Ministry of Science and Higher Education, Republic of Poland. pharmacogenetic example, thiopurine S-methyltransferase (TPMT) Konrad A. Szychowski *, Agnieszka M. Sitarz, cognitive skills and also has been related to increased risk for deficiency in relation to toxicity of azathioprine, an impact of Anna K. Wo´ jtowicz autism and ADHD-like behaviours [Torres-Sańchez; Environ http://dx.doi.org/10.1016/j.pharep.2015.06.035 CYP3A4/CYP3A5 genetic variants on pharmacokinetics of calci- Department of Animal Biotechnology, Animal Sciences Faculty, Health Perspect, 2013]. Nevertheless, data on the effects of DDE neurin inhibitors, or influence of UGT1A9 polymorphism on course University of Agriculture, Krako´w, Poland on the nervous system are scarce. Especially little is known about Safety and Opimization of Pharmacotherapy of treatment with mycophenolic acid. This presentation sum- *Corresponding author. the impact of DDE on individual receptors that are strongly marizes the recent state of knowledge in the field of pharmaco- associated with brain development. The aim of this study was to Optimization of antibiotic therapy genetics related to solid organ transplantation (including studies reveal the molecular mechanisms of DDE-induced apoptosis Anna Wiela-Hojen´ ska *, Magdalena Hurkacz, Triclosan (TCS) is a commonly used antimicrobial agent added performed in the Polish population), trying to settle whether during early stages of neural development with particular Krystyna Głowacka to personal care and sanitizing products. Recent studies have genetic testing for polymorphic variants of xenobiotic-metaboliz- emphasis on nuclear receptors that act as transcription factors. demonstrated that TCS in concentrations detected in the human ing enzymes, transport proteins or drug targets could be used for This work improves perspectives for understanding the impact of Department of Clinical Pharmacology, Wrocław Medical University, body activated Fas-dependent extrinsic apoptotic signaling making immunosuppressive therapy more efficient and safe. DDE on neurodevelopmental processes that may have far-reaching Wrocław, Poland pathway in mouse neurons in vitro [Szychowski et al., Neurosci- * implications evident in the mature nervous system. Given that Corresponding author. ence, 2015]. The aryl hydrocarbon receptor (AhR) is involved in the http://dx.doi.org/10.1016/j.pharep.2015.06.037 neurodevelopmental and neurodegenerative processes are accom- cell response to the numerous xenobiotics. This receptor regulates panied by apoptosis, knowledge about the effects of DDE in Contemporary antimicrobial therapy should be directed by expression of genes which control growth, differentiation, neuronal cells may contribute to understanding its deleterious objective criteria which allow for maximal effectiveness of Pharmacovigilance in Poland – Present and metabolism and apoptotic process of the neurons. The aim of apoptotic actions. In addition, these studies characterize the treatment with minimal side effects. The major problem with future the present study was to investigate the role of AhR, CYP1A1, prenatal vulnerability of neuronal cells to DDE and contribute to its significant clinical implication is the fact that under-dosing of Daria Schetz 1,2, Ivan Kocic´ 3 CYP1B1 and NMDA receptor in the cytotoxic and apoptotic effects antibiotics appears common. Therapeutic concentrations are possible withdrawal or controlled use in industry. 1 of TCS in mouse neocortical neurons. Cultures were prepared from frequently not achieved, leading to multiple bacterial resistance, Department of Clinical Toxicology, Medical University of Gdansk, Swiss mouse embryos on day 15/16 of gestation. The cells were which is associated with increased patient mortality, length of Gdan´sk, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.034 2 cultured in Neurobasal medium with B27 and glutamine. After inpatient stay, extended drug courses exposing the patient to Pomeranian Centre of Toxicology, Gdan´sk, Poland 3 exposure to TCS expression of AhR, CYP1A1, CYP1B1 and NMDA potentially toxic side effects. Typical pharmacokinetic parameters Department of Pharmacology, Medical University of Gdansk, Gdan´sk, receptor subunits were measured. To verify the involvement of Neuroprotective effects of phytoestrogens and Poland (Cl, Vd, t0,5, AUC, Cmax) do not adequately describe the altered PK/PD AhR in TCS mechanism of action, the AhR siRNA was used. After selective modulators of nuclear receptors properties, especially in critically ill patients. In recent years, the silencing procedure and exposure to AhR agonist, antagonist or Joanna Rzemieniec *, Ewa Litwa, Agnieszka Wnuk, efficacy of antibiotics has been improved through the use of three Rational use of medicines is highly important for every society, TCS, the release of the lactate dehydrogenase (LDH) and caspase-3 Władysław Lason´ , Małgorzata Kajta basic markers such: Cmax/MIC for antibiotics with pronounced not only with respect to the public finance but also to safety of activity in cells were measured. Preliminary data demonstrated concentration-dependent killing (aminoglycosides, fluoroquino- pharmacotherapy. Evidence based medicine (EBM) and pharma- that TCS enhanced expression of the AhR, CYP1B1 and altered the Department of Experimental Neuroendocrinology, Institute of Phar- lones, daptomycin), AUC/MIC for antibiotics with weak concen- covigilance (PHV) are the fundamental strategies for improvement expression of NMDA receptor subunits. Additionally, in the macology, Polish Academy of Sciences, Krako´w, Poland tration-dependent effects, but with prolonged persistent effects in this field, however implementation of the principals of EBM and presence of agonist as well as TCS the increase in neuronal *Corresponding author. (glycopeptides, fluoroquinolones, azithromycin, tigecycline), and PHV in practice is extremely difficult. Poland has one of the lowest apoptosis and LDH release into the culture medium were observed. T>MIC for antibiotics with a weak or no concentration dependency rate of adverse drug effects reporting in European Union. The main In neurons undergoing silencing procedure, in the presence of Hypoxia in adults and neonates may lead to stroke or cerebral (b-lactams, carbapenems, clarithromycin, erythromycin, linezo- reason is lack of properly functioning regional adverse drug agonist no significant changes in cytotoxicity or induction of palsy which could result in seizures, cognitive deficits and lid). Moreover antibiotics are the most irrationally prescribed drug reactions monitoring centers, that should identify the hazard-risk apoptosis were observed. Moreover, the cytotoxic and proapopto- neurodevelopmental abnormalities. However, there are no effec- class. So implementation of special guidelines for the hospital associated with pharmaceutical products. In Pomeranian province tic effects of TCS were partially reduced after silencing procedure. tive, neuroprotective therapies against stroke or perinatal asphyx- scenario and strict adherence should be ensured to promote their such regional center was created in 2012, and thereafter adverse In summary, the presented study demonstrated that TCS enhanced ia. Scientists are still searching for novel strategies to cure neuronal rational use. The spontaneous reporting of the adverse reactions to drug reporting is significantly higher. The center is involved in expression of AhR and CYP1B1 and altered expression pattern of degeneration induced by hypoxic/ischemic events. This kind of antibiotics is very important for identification of threats in local prevention campaigns at the local level. Based on experience of NMDA receptor subunits. application involves the use of selective receptor modulators, such population. Close collaboration between physicians, pharmacists, Department of Pharmacology, MUG in Pomerania Province such as selective estrogen receptor modulators (SERMs) and selective Supported by NCN Grant 2014/13/N/NZ4/04809. clinical pharmacologists, clinical pharmacists, microbiologists and information strategy contributes to increase awareness by aryl hydrocarbon receptor modulators (SAhRMs). In the present patients results in improved quality of antibiotic therapy. providing current information about drug-related issues. The best study, we evaluated the neuroprotective capacity of daidzein, example of this is three-fold increase in adverse drug reactions http://dx.doi.org/10.1016/j.pharep.2015.06.033 raloxifene and 3,3’-diindolylmethane (DIM) in mouse primary http://dx.doi.org/10.1016/j.pharep.2015.06.036 reporting in Pomerania province after the publication of our first 12 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 13 number of newsletter ‘‘The Safe Pharmacotherapy’’ which showed Concluding, the genetic polymorphism of drugs biotransforma- Oral Presentations (1 mg/kg, ip), an inductor of memory impairments was adminis- the important role of adverse drug reaction reporting. tion is clinically significant from the point of view of the tered 0.5 h later. In both assays the results obtained for GT-94- effectiveness and safety of hypertension pharmacotherapy. The effects of metabotropic glutamate receptor treated mice were compared to those of vehicle- or vehicle and 5 (mGluR5) positive allosteric modulator (PAM), http://dx.doi.org/10.1016/j.pharep.2015.06.038 scopolamine-treated mice. In the MWM paradigm mice were http://dx.doi.org/10.1016/j.pharep.2015.06.039 CDPPB, on learning and memory impaired by swimming in the water-filled pool trying to find an underwater chronic ethanol treatment in rats platform. The whole procedure lasted six days and the escape Clinical significance of CYP450 polymorphism Marta Marszalek-Grabska, Jolanta H. Kotlinska latency time to platform was measured. In the two-day RAWM on the efficacy and safety of treatment of The safety of NSAIDs in geriatric population – mice were swimming in the eight-arm maze in the pool trying to hypertension Analysis of Regional Centre for Monitoring Department of Pharmacology and Pharmacodynamics, Medical find the platform located in one of the arms. The parameter 1 2 Adverse Drug Reactions in Poznan (ROMDNL) University, Lublin, Poland Anna Wojtczak , Mariola Rychlik-Sych , analysed in the RAWM was a number of errors (entries to an arm 2 2 1 1 Małgorzata Baran´ ska , Jadwiga Skre˛tkowicz Anna Jabłecka , Katarzyna Korzeniowska , with no platform). Based on the results, in the MWM GT94-treated 1 2 Artur Cies´lewicz , Agnieszka Gaczkowska , Aims: Ethanol addiction is a severe disorder with many mice found the platform in the significantly shorter time (p < 0.05) 1 Department of Internal Medicine and Diabetology, Medical Univer- 2 2 Olga Pustkowska , Adrianna Maria Borowicz , consequences including impairment in spatial learning and than mice from scopolamine-treated control group. In the RAWM sity of Lodz, Ło´dz´, Poland Mariola Pawlaczyk 2 memory. Glutamate is involved in learning and memory processes, 2 mice that were administered GT94 made statistically significantly Department of Pharmacogenetics, Medical University of Lodz, Ło´dz´, and chronic ethanol administration induces up-regulation of 1 Department of Clinical Pharmacology, Poznan University of Medical less errors (p < 0.05) as compared to the scopolamine-treated Poland glutamate neurotransmission. PAM mGluR5, CDPPB, potentiates Sciences, Poznan´, Poland control group. mGlu5 receptor function and can facilitate learning in spatial tasks. 2 Department of Geriatric Medicine and Gerontology, Poznan Univer- The essence of pharmacogenetic studies is to provide a The aim of the present study was to investigate, whether CDPPB, This work was supported by the National Science Centre grant sity of Medical Sciences, Poznan´, Poland scientific explanation for personal differences in the process of enhances learning and memory processes impaired by chronic number DEC-2012/05/B/NZ7/02705. drugs metabolism. Genes encoding the cytochrome P450 ethanol treatment in the Barnes maze test. The aging of the society makes the elderly main consumers of enzymes are characterized by genetic polymorphism. The Methods: Experiments were performed in male Wistar rats. http://dx.doi.org/10.1016/j.pharep.2015.06.042 changes in enzymes activity caused by gene polymorphism drugs. Older people frequently react differently to drugs than Ethanol was administered intragastrically, once a day, at the dose may affect the pharmacokinetics, biotransformation, and of young ones, what can be derived from changes in pharmacokinet- of 5 g/kg (50%, w/v) for 5 days. Following 2 days of ethanol From antiarrhythmics to anticonvulsants: course drug concentration. These modifications in drug metabo- ics and/or pharmacodynamics. One of the drug groups most withdrawal, rats were trained in the Barnes maze for 3 consecutive ADD424042, a Disopyramide derivative, is a non- lism due to genetic factors can cause side effects or reduce the frequently used by the elderly are NSAIDs (non-steroid anti- days. CDPPB (30 mg/kg) was administered intraperitoneally, cardiotoxic ion channel blocker with broad- therapeutic effects. Data obtained from the meta-analysis of large inflammatory drugs) – mostly to alleviate acute and chronic pain 20 min prior to each of 3 daily training sessions. During each spectrum anticonvulsant activity groups of patients suggest that more than 40% of adverse events typical for arthritis and other musculoskeletal system diseases. training session errors and latency to locate the escape hole were were noted due to lack of dose modification based on the genotype However, due to the inhibition of prostaglandin synthesis the use measured for 3 min. Final test was conducted 24 h after the last Marcin Ufnal 1, Marek Kro´ l 2, Piotr Podsadni 2, of the patient. of NSAIDs is associated with the risk of adverse effects concerning training session. Animals were retested 7 days after the final test to Bartłomiej Szulczyk 2, Jadwiga Turło 2, Many commonly used drugs in the treatment of hypertension gastrointestinal tract, kidneys and cardiovascular system. assess memory retention. Adrian Drapala 1, Maciej Dawidowski 2 are extensively metabolized in the liver and they undergo The aim of the study was the assessment of safety of NSAIDs use Results: Our results demonstrated that CDPPB (30 mg/kg, ip) 1 Department of Experimental Physiology and Pathophysiology, oxidation by isoenzymes of cytochrome P450. The most notable in the group of 202 older patients (>65 years old) receiving reversed memory impairment in the Barnes maze test induced by Laboratory of Centre for Preclinical Research, Medical University of differences are in response to b-blockers, diuretics, ACE inhibitors hospital or outpatient treatment. Adverse effects associated with ethanol administration. Treatment with CDPPB decreased latency Warsaw, Warszawa, Poland and angiotensin receptor blockers (ARBs). The relationship gastrointestinal tract were reported by 56 patients. In addition to and errors in locating the escape hole, as compared to ethanol- 2 Department of Drug Technology and Pharmaceutical Biotechnology, between genotypes and the occurrence of adverse effects from arbitrary increase of drugs’ dose by the patients (due to lack of treated rats. Ethanol-treated animals retested 7 days after the final Medical University of Warsaw, Warszawa, Poland antihypertensive medications was the subject of many studies. As desired effect) a significant problem is off-the-count purchase of test, exhibited memory impairment compared to saline-treated well, the results of our study demonstrated that the genotype of various pharmaceutical forms of the same drug (68% of respon- rats. CYP2D6 (one of isoenzymes of cytochrome P450) remains a major dents). Pain treatment in patients with NSAIDs contraindicated Conclusions: These results suggest that CDPPB improved Epilepsy and cardiac arrhythmias share common character- determinant of the metoprolol plasma concentrations. The high was carried out using paracetamol and tramadol. memory deficits induced by ethanol administration and empha- istics, i.e. abnormal electrophysiological activity of neurons and plasma concentration of antihypertensive drugs may exposing size the importance of mGlu5 receptors in learning and memory cardiomyocytes, respectively. Disopyramide is a 1a class anti- patients to side effects. http://dx.doi.org/10.1016/j.pharep.2015.06.040 processes. arrhythmic agent. Currently, indications for Disopyramide treatment are limited to life-threatening ventricular tachycardia as it may cause the worsening of pre-existing arrhythmias or produce http://dx.doi.org/10.1016/j.pharep.2015.06.041 ventricular fibrillation. To our knowledge there have been no reports of anticonvulsant activity of Disopyramide, likely due to its Novel gamma-aminobutyric acid reuptake cardiotoxicity. We evaluated the effects of ADD424042, a inhibitor improves spatial learning and memory Disopyramide derivative, in a battery of in vivo rodent models of in Morris water maze and radial arm water maze epilepsy and checked its effects on electric activity of the heart and tests arterial blood pressure (BP) in rats. ADD424042 was evaluated in Adrian Podkowa 1, Kinga Sałat 1, Anna Furgała 1, the in vivo rodent models of epilepsy within the Anticonvulsant Szczepan Mogilski 1, Paula Zare˛ba 2, Screening Program (ASP) of The National Institute of Neurological Katarzyna Kulig 2, Barbara Filipek 1 Disorders and Stroke (NINDS), Bethesda, USA. The compound showed a broad spectrum activity across most of the widely used 1 Department of Pharmacodynamics, Faculty of Pharmacy, Jagiello- ‘classical’ animal models (MES, scMET, ivMET, scBIC, scPIC, Frings nian University, Krako´w, Poland AGS). In addition, it showed activity in models of pharmacorestant 2 Department of Physicochemical Drug Analysis, Faculty of Pharmacy, seizures (6 Hz, corneally kindled mice, hippocampal and amygda- Jagiellonian University, Krako´w, Poland la-kindled rat). Importantly, we showed that unlike parent Disopyramide, ADD424042 possessed none, or very small cardi- Gamma-aminobutyric acid plays an important role in forma- otoxic effect. We have found that the compound had no effect on tion of memory. The aim of this study was to investigate an impact QT and corrected QT intervals, at a dose which was 15 times higher

of GT94, an inhibitor of the GABA reuptake, on memory and than ED50 for the anticonvulsant effect in the MES model learning processes in C57BL/6 mice. For this purpose, two generalized tonic hind limb seizures. In contrast, equimolar and experiments were performed, Morris water maze (MWM) and twice lower doses of Disopyramide caused a significant prolongation radial arm water maze (RAWM). The examined compound of QT and corrected QT. Furthermore, the rats treated with was intraperitoneally (ip) administered at the dose of 30 mg/kg ADD424042 showed no other apparent changes in ECG recording 1 h before the acquisition trial, and scopolamine hydrochloride and BP, whereas rats treated with equimolar doses of Disopyramide 14 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 15 showed significant disturbances in ECG recording and changes in BP. sensory context and physiological state as during the encoding The optimization of local application of 3 Centre for Prophylaxis and Treatment of Infectious Diseases and Drug Collectively, these results suggested that ADD424042 has a clinical phase. The aim of this study was to evaluate if modulation of gentamicin for treatment of biofilm-related Addiction, Wroclaw Healthcare Centre, Poland potential in design of novel compounds for treatment of refractory protein kinase/phosphatase activities influences morphine- and osteomyelitis – Results of microbiological epilepsy. ethanol-induced state-dependent memory, including cross state- evaluation in vitro The aim of this work was to estimate the influence of C3435T dependent memory between morphine, ethanol and nicotine. Adam Feliks Junka 1, Beata Ma˛czyn´ ska 1, mutation in ABCB1 gene on the risk, the course of heroin addiction http://dx.doi.org/10.1016/j.pharep.2015.06.043 Experiments were conducted on male Swiss mice. To assess Anna Secewicz 1, Danuta Smutnicka 1, and the effectiveness of methadone substitution therapy. ABCB1 memory function passive avoidance test was used. The apparatus Patrycja Szymczyk 2, Marzenna Bartoszewicz 1 polymorphism was estimated in 108 heroin dependent individua- consists of two compartments: an illuminated one and a dark part, ls. The control group consisted of 60 healthy volunteers. DNA was Toxicity of the kynurenine pathway elements to 1 equipped with the energized grid floor. The test is based on the Department of Pharmaceutical Microbiology, Medical University of isolated from leukocytes of peripheral blood. The ABCB1 genotype the early life stages of zebrafish (Daniorerio) association formed between an aversive stimulus (a foot shock) Wroclaw, Wrocław, Poland was analyzed by polymerase chain reaction amplification and 1 1 2 Michał Majewski , Piotr Jakubowski , and a specific environmental context. Morphine (10.0 mg/kg sc) Centre for Advanced Manufacturing Technology, Wroclaw University restriction fragment length polymorphism (PCR-RFLP) techniques 2 2 Piotr Podlasz , Natalia Kasica , and ethanol (1.0 g/kg ip) triggered state-dependent memory and of Technology, Wrocław, Poland for C3435T mutation. For the statistical calculation the Kolmo- 1 Marta Pugaczewska cross state-dependent memory with an additional account of gorov–Smirnov Test and Yates’ chi-square Test were used. nicotine (0.1 mg/kg sc). FK-506 – a phosphatase inhibitor (1.0 and The biofilm is community of microorganisms embedded within 1 Department of Pharmacology and Toxicology, Faculty of Medical In our study we have not observed any statistically significant 5.0 mg/kg ip) and SL-327 – a kinase inhibitor (3.0 and 10.0 mg/kg extracellular matrix and displaying high resistance to antimicro- Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland predominance of the main mutation at the ABCB1 3435 locus ip) were used in order to estimate involvement of protein kinase/ bial measures. Biofilm may develop on virtually every surface of 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, among heroin addicted individuals compared to healthy ones. phosphatase activities in cognitive effects of used psychoactive human body, including bones. One potential approach to biofilm- University of Warmia and Mazury in Olsztyn, Olsztyn, Poland The time of addiction and heroin bout (defined as continuous drugs. The results suggest that protein kinase/phosphatase balance related bone infections is application of effective topical delivery everyday heroin use) were a statistically significantly (p < 0.05) is involved in morphine- and ethanol-induced state-dependent system for ensuring high local antibiotic concentrations at the site longer in the heterozygous (17.4 9.9 years and 77.1 63.1 Tryptophan metabolites, the substances which are intensive- � � learning. of infection. The aim of the presented experiment was to evaluate months) and mutation (17.8 9.6 years and 84.9 50.5 months) ly metabolized in animals and humans, were tested for lethality, � � in vitro concentrations of antibiotic gentamycin efficient against genotype in comparison to wild-type genotype (11.4 2.8 years and hatching, heart-beat and teratogenicity in a 3-day assay using � http://dx.doi.org/10.1016/j.pharep.2015.06.045 biofilm formed by different nosocomial pathogens on hydroxyap- 21.6 10.9 months). In addition, the study found that the zebrafish embryos and for lethality in 5 day old larval forms. 3- � atite. The high local concentrations of gentamicin applied were prevalence of brown sugar rather than ‘‘Polish heroin’’ dependence Hydroxykynurenine (3-OH-Kyn) and 3-hydroxyanthranilic acid achieved by use of gentamycin sponge and their efficacy was (domestic product from poppy straw or juice, usually shows higher (3-OH-AA) are known because of their neurotoxic properties Extract from root of Pueraria lobata inhibits an compared with efficacy of gentamycin’s concentrations possible to contents of heroine than brown sugar) in the group of 3435CC (62.5% through oxygen radical generation; whereas, quinolinic acid acute alcohol tolerance in high-preferring obtain during systemic antibiotic therapy. The nosocomial strains vs. 37.5%) were higher than in the group of 3435CT (28.5% vs. 71.5%) (QUIN) toxicity is a result of an NMDA receptor agonist. On (WHP) and low-preferring (WLP) alcohol- used were: Staphylococcus aureus (n = 10), Pseudomonas aeruginosa and 3435TT (33.3% vs. 66.7%) genotype. No difference in the doses of the other hand, kynurenic acid (KYNA) works as a neuropro- drinking rats (n = 10), Klebsiella pneumoniae (n = 10). Minimal Inhibitory Con- brown sugar and ‘‘Polish heroin’’ was seen between the investigated tectant and an AMPA, NMDA and kainate glutamate receptor Przemysław Ł. Mikołajczak 1,2, Michał Szulc 1, centration (MIC) of gentamycin against these strains in biofilm groups. The percentage of patients with opioid dependency rather antagonist. Ewa Kamin´ ska 1, Wanda Dyr 3, form was 4–512 mg/L, which classify them all as ‘‘resistant’’ than multiple drug use was statistically significantly (p = 0.03) In the present study, zebrafish embryos and 5dpf larvae were Edyta Wyszogrodzka 3, Agnieszka Gryszczyn´ ska 2, according to binding EUCAST guidelines. Contrary, high ratio of lower in the 3435CC (12.5% vs. 87.5%) than in 3435CT (63.6% vs. used as a model to investigate the developmental toxicities of a Teresa Bobkiewicz-Kozłowska 1 biofilm eradication (90–100%) was achieved, when the sponge was 36.4%) and 3435TT (40% vs. 60%) genotype group. As a consequence nine kynurenines, namely, QUIN, kynurenic acid, kynurenine (L- 1 Department of Pharmacology, Poznan´ University of Medical Sciences, applied, what is related with significantly higher concentrations of of deeper heroin addiction higher prevalence of HIV and HCV kyn), 3-OH-Kyn, 3-OH-AA, anthranilic acid (AA), xanthurenic acid Poznan´, Poland antibiotic released (ca. 2000 mg/L). The obtained results show infection in the heterozygous (40.9% and 95.5%) and mutation (50.0% (XA), picolinic acid (PA) and nicotinic acid (NA). The half lethal 2 Department of Pharmacology and Phytochemistry, Institute of insufficiency of systemic antibiotic therapy in treatment of and 90.0%) groups rather than in the patients with wild-type (12.5% and concentration (LC50) values indicated that the rank order of Natural Fibres and Medicinal Plants, Poznan´, Poland bacterial biofilm and the necessity of application of high, local 75.0%) genotype. Moreover, our findings indicate statistically signifi- toxicities of the kynurenines were QUIN > AA > KYNA > XA > 3- 3 Department of Pharmacology and Physiology of the Nervous System, concentration of these antimicrobials at the site of infection. cantly (p = 0.01) overrepresentation of occasional alcohol users and OH-Kyn > NA > 3-OH-AA > PA. LC50 was higher in 5 dpf larvae in Institute of Psychiatry and Neurology, Warszawa, Poland frequency of collapse due to heroin overdose among the group with comparison to 24, 48 and 72 hpf embryos. The kynurenine http://dx.doi.org/10.1016/j.pharep.2015.06.047 3435CC genotype (87.5% and 5.25 3.2 collapse) rather than in the exposure resulted in a variety of developmental lesions in the � group with 3435CT (27.3% and 3.0 2.1 collapse) and 3435TT (50.0% embryos/larvae, such as a delay in time to hatch or accelerated The aim of this study was to examine the ability of extract from � and 2.6 2.1 collapse). We have not observed any statistically hatching, pericardial edema, malformation of head and growth root of Pueraria lobata (kudzu) and its isoflavonoids (puerarin and Genetic polymorphism and the risk of drug � significant differences in the doses and concentrations of methadone retardation. These data suggest that QUIN, AA, and KYNA are more daidzin) to inhibit the development of acute ethanol tolerance. dependence and methadone substitution between the group of 3435CC, 3435CT and 3435TT. potent toxicants than others, and indicate that further research of The experiments were performed on male Warsaw High therapy success Preferring (WHP) and Warsaw Low Preferring (WLP) rats treated These results can indicate that C3435T mutation in ABCB1 gene their toxicities is required. Łukasz Łapin´ ski 1,3, Jacek Ga˛siorowski 2,3, with kudzu (500 mg/kg, po), puerarin (150 mg/kg, po) or daidzin does not increase the risk of heroin addiction development, the Krystyna Głowacka 1 (40 mg/kg, po) once a day for 8 consecutive days 60 min before course of methadone therapy but may have negative effects on its http://dx.doi.org/10.1016/j.pharep.2015.06.044 course. ethanol injection. For development of alcohol tolerance the rats 1 Department of Clinical Pharmacology, Wrocław, Poland were injected with ethanol in a dose of 3.0 g/kg (ip)dailyfor8 2 Department of Infectious Diseases, Hepatology and Acquired Impact of balance between protein kinase and consecutive days and 30, 60 and 90 min after alcohol adminis- Immune Deficiencies, Wroclaw Medical University, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.048 phosphatase activities on state-dependent tration a hypothermia testing procedure was used. Moreover, on memory of psychoactive drugs in passive 8th day a sleep time period produced by ethanol was measured. It avoidance task in mice was found that WHP and WLP rats differ in their hypothermic Agnieszka Michalak, Graz˙ yna Biała effect of alcohol, since both on the 1st and 8th day of the experiment WLP animals showed a stronger lowering of rectal Department of Pharmacology and Pharmacodynamics, Medical temperature. In both group of rats a tolerance to the hypothermic University of Lublin, Lublin, Poland effect especially after 60 and 90 min was observed. Kudzu and the isoflavonoids blocked the acute alcohol tolerance especially Neuroplasticity plays a great role in memory formation as well after 90 min from administration of ethanol in WHP and WLP as addiction development. Phosphorylation provokes structural animals, whereas the compounds did not affect the sleep time and functional changes in synapses, hence mediates this specific period of rats. However, more study is needed for understanding ability of the brain to be remodeled. Psychoactive drugs may kudzu’s mechanism involved in the development of alcohol produce a very specific type of memory called state-dependent tolerance. memory. It is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same http://dx.doi.org/10.1016/j.pharep.2015.06.046 14 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 15 showed significant disturbances in ECG recording and changes in BP. sensory context and physiological state as during the encoding The optimization of local application of 3 Centre for Prophylaxis and Treatment of Infectious Diseases and Drug Collectively, these results suggested that ADD424042 has a clinical phase. The aim of this study was to evaluate if modulation of gentamicin for treatment of biofilm-related Addiction, Wroclaw Healthcare Centre, Poland potential in design of novel compounds for treatment of refractory protein kinase/phosphatase activities influences morphine- and osteomyelitis – Results of microbiological epilepsy. ethanol-induced state-dependent memory, including cross state- evaluation in vitro The aim of this work was to estimate the influence of C3435T dependent memory between morphine, ethanol and nicotine. Adam Feliks Junka 1, Beata Ma˛czyn´ ska 1, mutation in ABCB1 gene on the risk, the course of heroin addiction http://dx.doi.org/10.1016/j.pharep.2015.06.043 Experiments were conducted on male Swiss mice. To assess Anna Secewicz 1, Danuta Smutnicka 1, and the effectiveness of methadone substitution therapy. ABCB1 memory function passive avoidance test was used. The apparatus Patrycja Szymczyk 2, Marzenna Bartoszewicz 1 polymorphism was estimated in 108 heroin dependent individua- consists of two compartments: an illuminated one and a dark part, ls. The control group consisted of 60 healthy volunteers. DNA was Toxicity of the kynurenine pathway elements to 1 equipped with the energized grid floor. The test is based on the Department of Pharmaceutical Microbiology, Medical University of isolated from leukocytes of peripheral blood. The ABCB1 genotype the early life stages of zebrafish (Daniorerio) association formed between an aversive stimulus (a foot shock) Wroclaw, Wrocław, Poland was analyzed by polymerase chain reaction amplification and 1 1 2 Michał Majewski , Piotr Jakubowski , and a specific environmental context. Morphine (10.0 mg/kg sc) Centre for Advanced Manufacturing Technology, Wroclaw University restriction fragment length polymorphism (PCR-RFLP) techniques 2 2 Piotr Podlasz , Natalia Kasica , and ethanol (1.0 g/kg ip) triggered state-dependent memory and of Technology, Wrocław, Poland for C3435T mutation. For the statistical calculation the Kolmo- 1 Marta Pugaczewska cross state-dependent memory with an additional account of gorov–Smirnov Test and Yates’ chi-square Test were used. nicotine (0.1 mg/kg sc). FK-506 – a phosphatase inhibitor (1.0 and The biofilm is community of microorganisms embedded within 1 Department of Pharmacology and Toxicology, Faculty of Medical In our study we have not observed any statistically significant 5.0 mg/kg ip) and SL-327 – a kinase inhibitor (3.0 and 10.0 mg/kg extracellular matrix and displaying high resistance to antimicro- Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland predominance of the main mutation at the ABCB1 3435 locus ip) were used in order to estimate involvement of protein kinase/ bial measures. Biofilm may develop on virtually every surface of 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, among heroin addicted individuals compared to healthy ones. phosphatase activities in cognitive effects of used psychoactive human body, including bones. One potential approach to biofilm- University of Warmia and Mazury in Olsztyn, Olsztyn, Poland The time of addiction and heroin bout (defined as continuous drugs. The results suggest that protein kinase/phosphatase balance related bone infections is application of effective topical delivery everyday heroin use) were a statistically significantly (p < 0.05) is involved in morphine- and ethanol-induced state-dependent system for ensuring high local antibiotic concentrations at the site longer in the heterozygous (17.4 9.9 years and 77.1 63.1 Tryptophan metabolites, the substances which are intensive- � � learning. of infection. The aim of the presented experiment was to evaluate months) and mutation (17.8 9.6 years and 84.9 50.5 months) ly metabolized in animals and humans, were tested for lethality, � � in vitro concentrations of antibiotic gentamycin efficient against genotype in comparison to wild-type genotype (11.4 2.8 years and hatching, heart-beat and teratogenicity in a 3-day assay using � http://dx.doi.org/10.1016/j.pharep.2015.06.045 biofilm formed by different nosocomial pathogens on hydroxyap- 21.6 10.9 months). In addition, the study found that the zebrafish embryos and for lethality in 5 day old larval forms. 3- � atite. The high local concentrations of gentamicin applied were prevalence of brown sugar rather than ‘‘Polish heroin’’ dependence Hydroxykynurenine (3-OH-Kyn) and 3-hydroxyanthranilic acid achieved by use of gentamycin sponge and their efficacy was (domestic product from poppy straw or juice, usually shows higher (3-OH-AA) are known because of their neurotoxic properties Extract from root of Pueraria lobata inhibits an compared with efficacy of gentamycin’s concentrations possible to contents of heroine than brown sugar) in the group of 3435CC (62.5% through oxygen radical generation; whereas, quinolinic acid acute alcohol tolerance in high-preferring obtain during systemic antibiotic therapy. The nosocomial strains vs. 37.5%) were higher than in the group of 3435CT (28.5% vs. 71.5%) (QUIN) toxicity is a result of an NMDA receptor agonist. On (WHP) and low-preferring (WLP) alcohol- used were: Staphylococcus aureus (n = 10), Pseudomonas aeruginosa and 3435TT (33.3% vs. 66.7%) genotype. No difference in the doses of the other hand, kynurenic acid (KYNA) works as a neuropro- drinking rats (n = 10), Klebsiella pneumoniae (n = 10). Minimal Inhibitory Con- brown sugar and ‘‘Polish heroin’’ was seen between the investigated tectant and an AMPA, NMDA and kainate glutamate receptor Przemysław Ł. Mikołajczak 1,2, Michał Szulc 1, centration (MIC) of gentamycin against these strains in biofilm groups. The percentage of patients with opioid dependency rather antagonist. Ewa Kamin´ ska 1, Wanda Dyr 3, form was 4–512 mg/L, which classify them all as ‘‘resistant’’ than multiple drug use was statistically significantly (p = 0.03) In the present study, zebrafish embryos and 5dpf larvae were Edyta Wyszogrodzka 3, Agnieszka Gryszczyn´ ska 2, according to binding EUCAST guidelines. Contrary, high ratio of lower in the 3435CC (12.5% vs. 87.5%) than in 3435CT (63.6% vs. used as a model to investigate the developmental toxicities of a Teresa Bobkiewicz-Kozłowska 1 biofilm eradication (90–100%) was achieved, when the sponge was 36.4%) and 3435TT (40% vs. 60%) genotype group. As a consequence nine kynurenines, namely, QUIN, kynurenic acid, kynurenine (L- 1 Department of Pharmacology, Poznan´ University of Medical Sciences, applied, what is related with significantly higher concentrations of of deeper heroin addiction higher prevalence of HIV and HCV kyn), 3-OH-Kyn, 3-OH-AA, anthranilic acid (AA), xanthurenic acid Poznan´, Poland antibiotic released (ca. 2000 mg/L). The obtained results show infection in the heterozygous (40.9% and 95.5%) and mutation (50.0% (XA), picolinic acid (PA) and nicotinic acid (NA). The half lethal 2 Department of Pharmacology and Phytochemistry, Institute of insufficiency of systemic antibiotic therapy in treatment of and 90.0%) groups rather than in the patients with wild-type (12.5% and concentration (LC50) values indicated that the rank order of Natural Fibres and Medicinal Plants, Poznan´, Poland bacterial biofilm and the necessity of application of high, local 75.0%) genotype. Moreover, our findings indicate statistically signifi- toxicities of the kynurenines were QUIN > AA > KYNA > XA > 3- 3 Department of Pharmacology and Physiology of the Nervous System, concentration of these antimicrobials at the site of infection. cantly (p = 0.01) overrepresentation of occasional alcohol users and OH-Kyn > NA > 3-OH-AA > PA. LC50 was higher in 5 dpf larvae in Institute of Psychiatry and Neurology, Warszawa, Poland frequency of collapse due to heroin overdose among the group with comparison to 24, 48 and 72 hpf embryos. The kynurenine http://dx.doi.org/10.1016/j.pharep.2015.06.047 3435CC genotype (87.5% and 5.25 3.2 collapse) rather than in the exposure resulted in a variety of developmental lesions in the � group with 3435CT (27.3% and 3.0 2.1 collapse) and 3435TT (50.0% embryos/larvae, such as a delay in time to hatch or accelerated The aim of this study was to examine the ability of extract from � and 2.6 2.1 collapse). We have not observed any statistically hatching, pericardial edema, malformation of head and growth root of Pueraria lobata (kudzu) and its isoflavonoids (puerarin and Genetic polymorphism and the risk of drug � significant differences in the doses and concentrations of methadone retardation. These data suggest that QUIN, AA, and KYNA are more daidzin) to inhibit the development of acute ethanol tolerance. dependence and methadone substitution between the group of 3435CC, 3435CT and 3435TT. potent toxicants than others, and indicate that further research of The experiments were performed on male Warsaw High therapy success Preferring (WHP) and Warsaw Low Preferring (WLP) rats treated These results can indicate that C3435T mutation in ABCB1 gene their toxicities is required. Łukasz Łapin´ ski 1,3, Jacek Ga˛siorowski 2,3, with kudzu (500 mg/kg, po), puerarin (150 mg/kg, po) or daidzin does not increase the risk of heroin addiction development, the Krystyna Głowacka 1 (40 mg/kg, po) once a day for 8 consecutive days 60 min before course of methadone therapy but may have negative effects on its http://dx.doi.org/10.1016/j.pharep.2015.06.044 course. ethanol injection. For development of alcohol tolerance the rats 1 Department of Clinical Pharmacology, Wrocław, Poland were injected with ethanol in a dose of 3.0 g/kg (ip)dailyfor8 2 Department of Infectious Diseases, Hepatology and Acquired Impact of balance between protein kinase and consecutive days and 30, 60 and 90 min after alcohol adminis- Immune Deficiencies, Wroclaw Medical University, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.048 phosphatase activities on state-dependent tration a hypothermia testing procedure was used. Moreover, on memory of psychoactive drugs in passive 8th day a sleep time period produced by ethanol was measured. It avoidance task in mice was found that WHP and WLP rats differ in their hypothermic Agnieszka Michalak, Graz˙ yna Biała effect of alcohol, since both on the 1st and 8th day of the experiment WLP animals showed a stronger lowering of rectal Department of Pharmacology and Pharmacodynamics, Medical temperature. In both group of rats a tolerance to the hypothermic University of Lublin, Lublin, Poland effect especially after 60 and 90 min was observed. Kudzu and the isoflavonoids blocked the acute alcohol tolerance especially Neuroplasticity plays a great role in memory formation as well after 90 min from administration of ethanol in WHP and WLP as addiction development. Phosphorylation provokes structural animals, whereas the compounds did not affect the sleep time and functional changes in synapses, hence mediates this specific period of rats. However, more study is needed for understanding ability of the brain to be remodeled. Psychoactive drugs may kudzu’s mechanism involved in the development of alcohol produce a very specific type of memory called state-dependent tolerance. memory. It is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same http://dx.doi.org/10.1016/j.pharep.2015.06.046 16 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 17

Posters arterial disease of lower limbs, stage II in Fontaine scale. Before the IL6 S174G>C gene polymorphism in psoriasis: analysis was performed with the use of PCR/RFLP method. The beginning of the study every participant underwent laboratory tests Focus on treatment efficacy obtained results allow to determine the correlation between the The effects of tiagabine on lipopolysaccharide which assured that the results of complete blood count, glucose, 1 2 pharmacological response and genetic variants of MDR1 poly- (LPS)-induced proinflammatory cytokine Monika Białecka , Roksana Ostasz , electrolytes, urea, creatinine and C-reactive protein were within 1 3 morphisms. release from primary rat microglial cell cultures Mateusz Kurzawski , Adam Klimowicz , limits. Furthermore, they collected precise clinical history in order to 3 2 Honorata Fabian´ czyk , Piotr Bojko , This study was supported by the National Science Centre, Grant No. Dariusz Andrzejczak, Agata Woldan-Tambor, 4 4 exclude patients for whom use of this amino acid is contraindicated. Violetta Dziedziejko , Krzysztof Safranow , Jolanta B. Zawilska L 1 UMO-2011/03/B/NZ7/06550. Participants were obtaining 6 g of -arginine and 20 mg simvastatin Marek Droz´dzik daily. The safety of this supplementation was confirmed throughout Department of Pharmacodynamics, Medical University of Ło´dz´, Ło´dz´, supplementation. None of the patients experienced adverse events 1 Department of Experimental and Clinical Pharmacology, Pomeranian http://dx.doi.org/10.1016/j.pharep.2015.06.053 Poland excluding its participation in the study. Registered adverse effects Medical University, Szczecin, Poland 2 concern gastrointestinal tract (23%). Additional beneficial effects Aesthetic Dermatology Center ‘‘Hippocrates’’, Szczecin, Poland The association of MTHFR, MTR, MTRR and CSE Inflammation could be a hallmark of several central nervous 3 were: improving potency (4 men) and improvement warmth upper Department of Dermatology, Division of Dermatopharmacology, expression with development of hypertension in system diseases including depression, schizophrenia and neuro- and lower extremities (12 patients). Pomeranian Medical University, Szczecin, Poland Caucasian population degenerative diseases. Several studies have brought new discov- 4 Department of Biochemistry and Medical Chemistry, Pomeranian 1,2 2 eries linking inflammatory process with epilepsy and Anna Bogacz , Małgorzata Go´ rska-Paukszta , http://dx.doi.org/10.1016/j.pharep.2015.06.050 Medical University, Szczecin, Poland 2,3 2 epileptogenesis. Increased levels of proinflammatory cytokines Marcin Oz˙ arowski , Aleksandra Kowalska , 2,4 were demonstrated both in animal models of epilepsy/seizures Bogusław Czerny , Interleukin-6 (IL-6) is implicated in the pathogenesis of 2,5 and many clinical studies in patients with epilepsy. Experimental The effect of antidepressant drugs on the Agnieszka Seremak-Mrozikiewicz psoriasis as well as in its treatment efficacy. The aim of this study studies also indicate a proconvulsive action of interleukin (IL)-1b, fractalkine and IGF-1 levels in brain of of 406 psoriasis patients and 203 healthy controls was to evaluate 1 Department of Clinical Pharmacy and Biopharmacy, University of IL-6 and tumor necrosis factor (TNF)-a. On the other hand, it is prenatally stressed adult rats – Link to the association between the IL6 174G>C (rs1800795) polymor- Medical Sciences, Poznan´, Poland suggested that antiepileptic drugs could modulate immune system depression � phism and psoriasis susceptibility, as well as treatment efficacy. 2 Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland activity. Therefore the aim of the present study was to investigate Agnieszka Basta-Kaim, Monika Les´kiewicz, The frequency of genotype GG (33.7% vs. 20.7%; p = 0.00022; 3 Department of Pharmaceutical Botany and Plant Biotechnology, whether tiagabine could affect the lipopolysaccharide (LPS)- Joanna S´lusarczyk, Ewa Trojan, Katarzyna Głombik, OR = 0.51, 95% confidence interval 0.34–0.76) and of allele G University of Medical Sciences, Poznan´, Poland induced release of TNF-a, IL-1b and IL-6 from primary rat Joanna Sowa, Władysław Lason´ (56.2% vs. 46.8%; p = 0.0023) was significantly higher in the psoriasis 4 Department of General Pharmacology and Pharmacoeconomics, microglial cell cultures. Levels of the proinflammatory cytokines Department of Experimental Neuroendocrinology, Institute of Phar- group compared to controls. No polymorphism variants were Pomeranian Medical University, Szczecin, Poland were measured in supernatants of the primary rat microglial cell 5 macology, Polish Academy of Sciences, Krako´w, Poland associated with better response to topical or combined topical/ Division of Perinatology and Women’s Diseases, Poznan University of culture with a commercially available enzyme-linked immuno- narrow-band ultraviolet B (NB-UVB) treatment. We conclude that Medical Sciences, Poznan´, Poland sorbent assay kits. Additionally, the effect of the drug on microglial the IL6 174G>C polymorphism can be a marker of susceptibility to cell viability was measured (MTT test). Tiagabine (1, 10, 100 mg/ The aim of the present study was to examine whether prenatal � psoriasis, with an almost 2-fold increased risk of the disease in Recently, studies have shown that both polymorphisms and ml; 24 h) caused a statistically significant reduction of LPS- stress influence fractalkine and IGF-1 levels in the frontal cortex of individuals carrying the GG genotype; however, it was not associated changes of expression in genes encoding enzymes involved in the stimulated release of IL-1b, IL-6, TNF-a from primary rat adult offspring. Furthermore the influence of chronic treatment of with treatment response to topical and/or NB-UVB therapy. methionine and homocysteine metabolism (MHM), such as microglial cells in a concentration-dependent manner. The drug imipramine, fluoxetine and tianeptine on the levels of these methylenetetrahydrofolate, reductase (MTHFR), methionine at a concentration of 100 mg/ml caused a slight, but significant proteins was studied. http://dx.doi.org/10.1016/j.pharep.2015.06.052 synthase (MTR), methionine synthase reductase (MTRR) and decrease in microglial cell viability after 24 h incubation. The Pregnant Sprague-Dawley rats were subjected to stress sessions cystathionine gamma-lyase (CSE) may play a key role in the observed effect on proinflammatory cytokines could be regarded from 14th day of pregnancy until the delivery. At 3 months of age, the development of hypertension. The aim of the study was to as additional and beneficial property of tiagabine. control and the prenatally stressed male rats were tested for The importance of G2677T/A and C3435T MDR1 determine the expression level of MTHFR, MTR, MTRR and CSE behavioral changes in the two-bottle sucrose preference test and gene polymorphisms in the individualization of genes in the development of hypertension in Caucasian population Supported by the grant from the Medical University of Ło´ dz´ (503/3- forced swim test. Next, chronic administration of imipramine or therapy in patients after kidney transplantation 011-01/503-01; 502-03/3-011-01/502-34-007; 503/3-011-01/503- tianeptine was conducted. Animals were killed by rapid decapitation using real-time PCR method. The control group consisted of 74 Anna Bogacz 1,2, Joanna Bartkowiak-Wieczorek 1, 06-300). The authors wish to thank Dr. M. Namiecin´ ska (IMB PAS) 24 h after the last treatment and the frontal cortices were rapidly healthy patients and 90 patients with diagnosed hypertension. The Maciej Kotowski 3, Bogusław Machalin´ ski 3, dissected out and stored at 80 8C. Levels of IGF-1 and fractalkine expression level of MTHFR gene showed no statistically significant for her valuable feedback on microglial cell isolation. � Aleksandra Kowalska 2, Bogusław Czerny 2,4 were determined in tissue homogenates by ELISA assays. Behavioral difference between study groups. An increase of mRNA level was verification of the animal model revealed that prenatally stressed 1 observed for MTR and CTH while a decrease of expression was http://dx.doi.org/10.1016/j.pharep.2015.06.049 Laboratory of Experimental Pharmacogenetics, Department of male rats consumed significantly less sweetened water than their Clinical Pharmacy and Biopharmacy, University of Medical Sciences, noted for MTRR in women with hypertension compared to control control counterparts, thus revealing anhedonic behavior. Moreover Poznan´, Poland group. Our results suggest that the elevated RNA expression of Safety of 60-day L-arginine supplementation of 2 prenatally stressed rats exhibit not only an increase in immobility Department of Stem Cells and Regenerative Medicine, Institute of MTR in placenta of preeclamptic patients is probably results of a patients with peripheral arterial disease of lower time but also a decrease in swimming and climbing behavior in the Natural Fibres and Medicinal Plants, Plewiska, Poland potential compensation mechanism of the MHM while elevated limbs 3 modified Porsolt test. Imipramine or tianeptine administration Department of General Pathology, Pomeranian Medical University, CSE expression indicates that homocysteine may be eliminated Natasza Balcer-Dymel, Katarzyna Korzeniowska, reversed behavioral deficits. In biochemical studies a significant Szczecin, Poland through the alternate transsulfuration pathway. Artur Cies´lewicz, Anna Jabłecka reduction in the amount of IGF-1 protein and fractalkine concentra- 4 Department of General Pharmacology and Pharmacoeconomics, tion in the frontal cortex of stressed animals has been found. Pomeranian Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.054 Department of Clinical Pharmacology, Poznan University of Medical Furthermore chronic administration of tianeptine normalize frac- Sciences, Poznan´, Poland talkine and IGF-1 level in prenatally stressed animals. In conclusion Kidney transplantation is the treatment target of irreversible IP562083 a novel mGluR7 negative allosteric our results clearly indicate that prenatal stress causes long-lasting renal failure. The application of immunosuppressive drugs affect modulator L-Arginine (2-amino-5-guanidino-pentanoic acid) is a condi- behavioral alterations. Reduction of fractalkine and IGF-1 levels the improvement of organ transplants, but they can lead to adverse ´ 1 1 tionally essential, proteinogenic amino acid that is a natural observed in this study may be one of the causes of behavioral Piotr Branski , Grzegorz Burnat , reactions especially to nephrotoxicity associated with the devel- 2 2 constituent of dietary proteins. It may play an important role in the changes in our model. Since beneficial effect of tianeptine, at least in Anna Stankiewicz , Ryszard Bugno , opment of chronic transplant dysfunction, acute rejection and 2 2 treatment of cardiovascular disease due to its antiatherogenic, part, may result from potentiation of proteins analyzed so, it can be Maria Paluchowska , Katarzyna Kaczorowska , increased mortality of patients. Therefore, it is still looking for the 1 2 1 anti-ischemic, antiplatelet, and antithrombotic properties. It has Barbara Chrusćicka , Andrzej Bojarski , Andrzej Pilc postulated that a better understanding of IGF-1 and fractalkine optimal dosage regimen of immunosuppressive drugs in patients been promoted as a growth stimulant and as a treatment for interactions can contribute to improved efficiency of antidepressant after kidney transplantation. The reason of interindividual 1 Department of Neurobiology Institute of Pharmacology PAS, Krako´w, erectile dysfunction in men. treatment. variability may be intestinal P-glycoprotein (P-gp) encoding the Poland The aim of the study was to assess the safety of L-arginine multidrug resistance gene (MDR1) which may affect significantly 2 Department of Medicinal Chemistry, Institute of Pharmacology PAS, supplementation for sixty days in patients with lipid dysregulation This work was supported by the National Science Centre, Poland grant the pharmacokinetics and pharmacodynamics of tacrolimus. The Krako´w, Poland and with peripheral arterial disease of lower limbs. One hundred no. 2013/09/B/NZ7/04096 and by the statutory funds of PAS. aim of the study was to evaluate the correlation between patients (62 men and 38 women) were included into this trial. All therapeutic effect of tacrolimus and C3435T and G2677T/A Background: Glutamate neurotransmission is controlled by patients were above 55 years old and suffered from peripheral http://dx.doi.org/10.1016/j.pharep.2015.06.051 polymorphisms for MDR1 gene involved in drug transport. Genetic negative feedback loop by mGlu7 receptor which has been 16 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 17

Posters arterial disease of lower limbs, stage II in Fontaine scale. Before the IL6 S174G>C gene polymorphism in psoriasis: analysis was performed with the use of PCR/RFLP method. The beginning of the study every participant underwent laboratory tests Focus on treatment efficacy obtained results allow to determine the correlation between the The effects of tiagabine on lipopolysaccharide which assured that the results of complete blood count, glucose, 1 2 pharmacological response and genetic variants of MDR1 poly- (LPS)-induced proinflammatory cytokine Monika Białecka , Roksana Ostasz , electrolytes, urea, creatinine and C-reactive protein were within 1 3 morphisms. release from primary rat microglial cell cultures Mateusz Kurzawski , Adam Klimowicz , limits. Furthermore, they collected precise clinical history in order to 3 2 Honorata Fabian´ czyk , Piotr Bojko , This study was supported by the National Science Centre, Grant No. Dariusz Andrzejczak, Agata Woldan-Tambor, 4 4 exclude patients for whom use of this amino acid is contraindicated. Violetta Dziedziejko , Krzysztof Safranow , Jolanta B. Zawilska L 1 UMO-2011/03/B/NZ7/06550. Participants were obtaining 6 g of -arginine and 20 mg simvastatin Marek Droz´dzik daily. The safety of this supplementation was confirmed throughout Department of Pharmacodynamics, Medical University of Ło´dz´, Ło´dz´, supplementation. None of the patients experienced adverse events 1 Department of Experimental and Clinical Pharmacology, Pomeranian http://dx.doi.org/10.1016/j.pharep.2015.06.053 Poland excluding its participation in the study. Registered adverse effects Medical University, Szczecin, Poland 2 concern gastrointestinal tract (23%). Additional beneficial effects Aesthetic Dermatology Center ‘‘Hippocrates’’, Szczecin, Poland The association of MTHFR, MTR, MTRR and CSE Inflammation could be a hallmark of several central nervous 3 were: improving potency (4 men) and improvement warmth upper Department of Dermatology, Division of Dermatopharmacology, expression with development of hypertension in system diseases including depression, schizophrenia and neuro- and lower extremities (12 patients). Pomeranian Medical University, Szczecin, Poland Caucasian population degenerative diseases. Several studies have brought new discov- 4 Department of Biochemistry and Medical Chemistry, Pomeranian 1,2 2 eries linking inflammatory process with epilepsy and Anna Bogacz , Małgorzata Go´ rska-Paukszta , http://dx.doi.org/10.1016/j.pharep.2015.06.050 Medical University, Szczecin, Poland 2,3 2 epileptogenesis. Increased levels of proinflammatory cytokines Marcin Oz˙ arowski , Aleksandra Kowalska , 2,4 were demonstrated both in animal models of epilepsy/seizures Bogusław Czerny , Interleukin-6 (IL-6) is implicated in the pathogenesis of 2,5 and many clinical studies in patients with epilepsy. Experimental The effect of antidepressant drugs on the Agnieszka Seremak-Mrozikiewicz psoriasis as well as in its treatment efficacy. The aim of this study studies also indicate a proconvulsive action of interleukin (IL)-1b, fractalkine and IGF-1 levels in brain of of 406 psoriasis patients and 203 healthy controls was to evaluate 1 Department of Clinical Pharmacy and Biopharmacy, University of IL-6 and tumor necrosis factor (TNF)-a. On the other hand, it is prenatally stressed adult rats – Link to the association between the IL6 174G>C (rs1800795) polymor- Medical Sciences, Poznan´, Poland suggested that antiepileptic drugs could modulate immune system depression � phism and psoriasis susceptibility, as well as treatment efficacy. 2 Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland activity. Therefore the aim of the present study was to investigate Agnieszka Basta-Kaim, Monika Les´kiewicz, The frequency of genotype GG (33.7% vs. 20.7%; p = 0.00022; 3 Department of Pharmaceutical Botany and Plant Biotechnology, whether tiagabine could affect the lipopolysaccharide (LPS)- Joanna S´lusarczyk, Ewa Trojan, Katarzyna Głombik, OR = 0.51, 95% confidence interval 0.34–0.76) and of allele G University of Medical Sciences, Poznan´, Poland induced release of TNF-a, IL-1b and IL-6 from primary rat Joanna Sowa, Władysław Lason´ (56.2% vs. 46.8%; p = 0.0023) was significantly higher in the psoriasis 4 Department of General Pharmacology and Pharmacoeconomics, microglial cell cultures. Levels of the proinflammatory cytokines Department of Experimental Neuroendocrinology, Institute of Phar- group compared to controls. No polymorphism variants were Pomeranian Medical University, Szczecin, Poland were measured in supernatants of the primary rat microglial cell 5 macology, Polish Academy of Sciences, Krako´w, Poland associated with better response to topical or combined topical/ Division of Perinatology and Women’s Diseases, Poznan University of culture with a commercially available enzyme-linked immuno- narrow-band ultraviolet B (NB-UVB) treatment. We conclude that Medical Sciences, Poznan´, Poland sorbent assay kits. Additionally, the effect of the drug on microglial the IL6 174G>C polymorphism can be a marker of susceptibility to cell viability was measured (MTT test). Tiagabine (1, 10, 100 mg/ The aim of the present study was to examine whether prenatal � psoriasis, with an almost 2-fold increased risk of the disease in Recently, studies have shown that both polymorphisms and ml; 24 h) caused a statistically significant reduction of LPS- stress influence fractalkine and IGF-1 levels in the frontal cortex of individuals carrying the GG genotype; however, it was not associated changes of expression in genes encoding enzymes involved in the stimulated release of IL-1b, IL-6, TNF-a from primary rat adult offspring. Furthermore the influence of chronic treatment of with treatment response to topical and/or NB-UVB therapy. methionine and homocysteine metabolism (MHM), such as microglial cells in a concentration-dependent manner. The drug imipramine, fluoxetine and tianeptine on the levels of these methylenetetrahydrofolate, reductase (MTHFR), methionine at a concentration of 100 mg/ml caused a slight, but significant proteins was studied. http://dx.doi.org/10.1016/j.pharep.2015.06.052 synthase (MTR), methionine synthase reductase (MTRR) and decrease in microglial cell viability after 24 h incubation. The Pregnant Sprague-Dawley rats were subjected to stress sessions cystathionine gamma-lyase (CSE) may play a key role in the observed effect on proinflammatory cytokines could be regarded from 14th day of pregnancy until the delivery. At 3 months of age, the development of hypertension. The aim of the study was to as additional and beneficial property of tiagabine. control and the prenatally stressed male rats were tested for The importance of G2677T/A and C3435T MDR1 determine the expression level of MTHFR, MTR, MTRR and CSE behavioral changes in the two-bottle sucrose preference test and gene polymorphisms in the individualization of genes in the development of hypertension in Caucasian population Supported by the grant from the Medical University of Ło´ dz´ (503/3- forced swim test. Next, chronic administration of imipramine or therapy in patients after kidney transplantation 011-01/503-01; 502-03/3-011-01/502-34-007; 503/3-011-01/503- tianeptine was conducted. Animals were killed by rapid decapitation using real-time PCR method. The control group consisted of 74 Anna Bogacz 1,2, Joanna Bartkowiak-Wieczorek 1, 06-300). The authors wish to thank Dr. M. Namiecin´ ska (IMB PAS) 24 h after the last treatment and the frontal cortices were rapidly healthy patients and 90 patients with diagnosed hypertension. The Maciej Kotowski 3, Bogusław Machalin´ ski 3, dissected out and stored at 80 8C. Levels of IGF-1 and fractalkine expression level of MTHFR gene showed no statistically significant for her valuable feedback on microglial cell isolation. � Aleksandra Kowalska 2, Bogusław Czerny 2,4 were determined in tissue homogenates by ELISA assays. Behavioral difference between study groups. An increase of mRNA level was verification of the animal model revealed that prenatally stressed 1 observed for MTR and CTH while a decrease of expression was http://dx.doi.org/10.1016/j.pharep.2015.06.049 Laboratory of Experimental Pharmacogenetics, Department of male rats consumed significantly less sweetened water than their Clinical Pharmacy and Biopharmacy, University of Medical Sciences, noted for MTRR in women with hypertension compared to control control counterparts, thus revealing anhedonic behavior. Moreover Poznan´, Poland group. Our results suggest that the elevated RNA expression of Safety of 60-day L-arginine supplementation of 2 prenatally stressed rats exhibit not only an increase in immobility Department of Stem Cells and Regenerative Medicine, Institute of MTR in placenta of preeclamptic patients is probably results of a patients with peripheral arterial disease of lower time but also a decrease in swimming and climbing behavior in the Natural Fibres and Medicinal Plants, Plewiska, Poland potential compensation mechanism of the MHM while elevated limbs 3 modified Porsolt test. Imipramine or tianeptine administration Department of General Pathology, Pomeranian Medical University, CSE expression indicates that homocysteine may be eliminated Natasza Balcer-Dymel, Katarzyna Korzeniowska, reversed behavioral deficits. In biochemical studies a significant Szczecin, Poland through the alternate transsulfuration pathway. Artur Cies´lewicz, Anna Jabłecka reduction in the amount of IGF-1 protein and fractalkine concentra- 4 Department of General Pharmacology and Pharmacoeconomics, tion in the frontal cortex of stressed animals has been found. Pomeranian Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.054 Department of Clinical Pharmacology, Poznan University of Medical Furthermore chronic administration of tianeptine normalize frac- Sciences, Poznan´, Poland talkine and IGF-1 level in prenatally stressed animals. In conclusion Kidney transplantation is the treatment target of irreversible IP562083 a novel mGluR7 negative allosteric our results clearly indicate that prenatal stress causes long-lasting renal failure. The application of immunosuppressive drugs affect modulator L-Arginine (2-amino-5-guanidino-pentanoic acid) is a condi- behavioral alterations. Reduction of fractalkine and IGF-1 levels the improvement of organ transplants, but they can lead to adverse ´ 1 1 tionally essential, proteinogenic amino acid that is a natural observed in this study may be one of the causes of behavioral Piotr Branski , Grzegorz Burnat , reactions especially to nephrotoxicity associated with the devel- 2 2 constituent of dietary proteins. It may play an important role in the changes in our model. Since beneficial effect of tianeptine, at least in Anna Stankiewicz , Ryszard Bugno , opment of chronic transplant dysfunction, acute rejection and 2 2 treatment of cardiovascular disease due to its antiatherogenic, part, may result from potentiation of proteins analyzed so, it can be Maria Paluchowska , Katarzyna Kaczorowska , increased mortality of patients. Therefore, it is still looking for the 1 2 1 anti-ischemic, antiplatelet, and antithrombotic properties. It has Barbara Chrusćicka , Andrzej Bojarski , Andrzej Pilc postulated that a better understanding of IGF-1 and fractalkine optimal dosage regimen of immunosuppressive drugs in patients been promoted as a growth stimulant and as a treatment for interactions can contribute to improved efficiency of antidepressant after kidney transplantation. The reason of interindividual 1 Department of Neurobiology Institute of Pharmacology PAS, Krako´w, erectile dysfunction in men. treatment. variability may be intestinal P-glycoprotein (P-gp) encoding the Poland The aim of the study was to assess the safety of L-arginine multidrug resistance gene (MDR1) which may affect significantly 2 Department of Medicinal Chemistry, Institute of Pharmacology PAS, supplementation for sixty days in patients with lipid dysregulation This work was supported by the National Science Centre, Poland grant the pharmacokinetics and pharmacodynamics of tacrolimus. The Krako´w, Poland and with peripheral arterial disease of lower limbs. One hundred no. 2013/09/B/NZ7/04096 and by the statutory funds of PAS. aim of the study was to evaluate the correlation between patients (62 men and 38 women) were included into this trial. All therapeutic effect of tacrolimus and C3435T and G2677T/A Background: Glutamate neurotransmission is controlled by patients were above 55 years old and suffered from peripheral http://dx.doi.org/10.1016/j.pharep.2015.06.051 polymorphisms for MDR1 gene involved in drug transport. Genetic negative feedback loop by mGlu7 receptor which has been 18 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 19

/ localized to presynaptic terminals. In a knock-out mice (mGluR7� �) lidene)camphor (4-MBC) and benzophenones derivatives. So far Angiotensin II receptor blockers and on cell mediated immune response, (ii) to evaluate the role of where this mechanism is impaired, we could observe spontaneous there are no studies on the effects of these compounds on the angiotensin converting enzyme inhibitors melatonin in coordinating these potential GD-induced immune seizures. This implicated risk of seizure after inhibition of mGluR7 viability of neurons, most susceptible to damage brain cells. In the modulate central formation of kynurenic acid in alterations. The studies were performed on maternal generation activity. However, modulation of mGluR7 activity could be present study, we investigate the effect of OMC and 4-MBC on cells rat cortical slices (F0) and on first filial generation (F1) of male and female offspring beneficial. In 2010 has been developed MMPIP, first negative viability and caspase-3 activity in human neuroblastoma cell line Iwona Chmiel-Perzyn´ ska 1, Adam Perzyn´ ski 2, of Wistar albino rats. Low clinically asymptomatic concentrations allosteric modulator (NAM) which proportional to glutamate (SH-SY5Y cells). It has been found that OMC present in medium for Bartosz Olajossy 3, Ewa M. Urban´ ska 4 of GD were administered in a repeated dose by subcutaneous 4 5 concentration decrease mGlu7 receptor activity. MMPIP alleviates 72 h in concentrations 10� and 10� M increased lactate injections (sc). Animals were exposed to a five injections that have pain and normalizes affective and cognitive behavior in neuropathic dehydrogenase release (LDH) and decreased 3-[4,5-dimethylthia- 1 Department of Experimental and Clinical Pharmacology, Medical been performed every four days, first in pregnancy and subse- mice. Another mGluR7 NAM, ADX71743 showed anxiolytic zol-2-yl]2,5-diphenyl tetrazolium bromide (MTT) reduction. OMC University of Lublin, Poland quently during the lactation period. The procedure of intoxication properties in the rodent test. Therefore, we need novel agents with present in medium for 24 h did not show cytotoxic effect. 4-MBC 2 II Department of Psychiatry and Psychiatry Rehabilitation, Medical was initiated on day 11 of pregnancy and terminated at day 10 NAM properties for mGlu7 receptor to evaluate if the inhibition of increased level of LDH and decreased MTT reduction in concen- University of Lublin, Poland after delivery. A single daily dose received by the animal was 0, 2 of 4 3 the receptor would produce anxiolytic-like activity. trations 10� M present in medium for 24 and 72 h. Determining Department of Cardiology, Cardinal Wyszynski Hospital of Lublin the LD50 value. Melatonin at pharmacological dose was given sc for

Aim: Identification novel chemical scaffold possessing mGlu7 the effect of test compounds on the caspase-3 activity, the Voivodeship, Poland 21 consecutive days beginning from the day directly preceding negative allosteric modulation activity by interaction with executive enzyme in process of apoptosis, it was found that OMC 4 Laboratory of Cellular and Molecular Pharmacology, Department of intoxication and continuing until the end of its term. Six months 7 transmembrane region of mGlu7 receptor. enhanced activity of this enzyme at concentration of 10� M, Experimental and Clinical Pharmacology, Medical University of Lublin, after the end of poisoning the animals were euthanized for Methods: Human GRM7 was cloned into genome of HEK-293 whereas 4-MBC was already operating at a concentration of Poland evaluation of mRNA levels for selected cytokines (IL-1b, IL-2, IL-4, 8 cells contained T-Rex expression system (Invitrogen). Expression 10� M. The obtained results demonstrated, that the tested filters IL-6, Il-10, TNFa and IFN-g) in the hypothalamus. To determine the of the receptor was analyzed by means of qRT-PCR and Western at high concentrations exert cytotoxic effect, whilst the proapop- The renin–angiotensin–aldosteron (RAA) system plays an level of gene expression, Real-time PCR with SYBR Green dye was blot in both: cells before and after stable transfection with GRM7. totic effects exhibited even at low concentrations. These com- essential role in regulation of blood pressure and may contribute applied. The obtained results show that GD modulates immune The screening study and activity of potential NAM was determined pounds may be important factors involved in pathogenesis of to local inflammatory processes and target-organ damage in reaction; intoxication of rats with GD resulted in significant using forskolin-induced cAMP accumulation, in a HEK-293 T-Rex neurodegenerative diseases, however, such conclusion must be various tissues, including central nervous system (CNS). Kynurenic reduction of transcript levels for the majority of analyzed cell line stably expressing mGlu7 or mock transfected HEK-293 T- confirmed in in vivo studies. acid (KYNA) is tryptophan metabolite formed in the brain and in cytokines, except mRNA of IL-1b, whose expression significantly Rex cell line. For the functional characterization of mGlu7 we the periphery, known to block ionotropic glutamate receptors and increased in F0 females and in males of their F1 offspring. In the F1 measured level of cyclic AMP (cAMP) by cAMP dynamic2 (CisBio) http://dx.doi.org/10.1016/j.pharep.2015.06.056 a7 nicotinic receptors, and to act as ligands of G protein-coupled female, there was no significant influence of GD on the IL-1b kit according to manufacture instructions. The concentration GPR35 receptors and human aryl hydrocarbon (AHR) receptors. transcript level. It has also been demonstrated for the first time the response curves were fitted using the non-linear regression The aim of this study was to assess the effect of angiotensin regulatory effect of melatonin on GD-induced cytokine distur- analysis program, GraphPad Prism (GraphPad Software). All liquid Evaluation of pharmacists’ opinion and converting enzyme inhibitors (ACE-I) and angiotensin receptor bances. This preliminary study would suggest the potential handling operations were performed using EVO 2000 system knowledge regarding generic medicinal antagonists (ARBs) on KYNA synthesis in vitro. KYNA was produced protective value of melatonin to enhance immune functions in (Tecan). products in Poland de novo in rat cortical slices and quantified fluorometrically, using an impaired immunity induced by GD poisoning. Results: Via in vitro screening of compound collection we have HPLC method. Grzegorz Cessak 1,2, Marta Da˛browska 2, identified chemical scaffold possessing mGluR potential NAM ARBs, losartan and telmisartan (50–250 mM) decreased forma- 7 Ewa Bałkowiec-Iskra 1,2 http://dx.doi.org/10.1016/j.pharep.2015.06.059 activity and IP562083 was obtained by successive chemical tion of KYNA to 75–60% of control (p < 0.05). Studied ACE-I modification. IP562083 inhibited LSP4-2022 or L-Glu induced 1 The Office for Registration of Medicinal Products, Medical Devices inhibited KYNA synthesis only at higher concentrations i.e. Analysis of vitamin D receptor polymorphism activation of mGlu7 receptor with IC50 value 3.5 mM. The maximal and Biocidal Product, Warszawa, Poland captopril at 500–1000 mM (80–70% of control, p < 0.05) and and its relation to mineral bone density in the response of LSP4-2022 and L-Glu were reduced in the presence of 2 Department of Experimental and Clinical Pharmacology, Medical ramipril at 1000 mM (82% of control, p < 0.05). The action of pathogenesis of osteoporosis IP562083. University of Warsaw, Warszawa, Poland ramipril was biphasic and, at 50–100 mM, the drug slightly 1,2 3 Conclusions: We have now identified, and characterized new increased KYNA production (to 120 and 124% of control, p < 0.05). Bogusław Czerny , Dariusz Boron´ , Anna Bogacz 1,4, Karolina Dziekan 1, potential mGlu7 NAM. Introduction of rules that enabled registration of generic The above data suggest novel aspect of action of drugs Aleksandra Kowalska 1, Radosław Kujawski 1, medicinal products constituted one of the major breakthroughs modulating RAA system associated with changes in brain synthesis Acknowledgments: This study is supported by project PBS1/B7/8/ Agnieszka Seremak-Mrozikiewicz 1,5, in pharmacotherapy. Generic drugs currently available on the of KYNA. 2012 financed by The National Centre for Research and Development. Adam Kamin´ ski 1, Izabela Uzar 2 market meet the criteria of bioequivalence that have been agreed Supported by grants from Medical University of Lublin, DS 450/14 and upon by registration agencies all over the world. They allow 1 Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.055 450/15. treatment that is as effective and safe, as the one achieved with 2 Department of General Pharmacology and Pharmacoeconomics, their reference products. Lower prices of generic drugs are due Pomeranian Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.058 Effects of 2-ethyl-hexyl-4-trimethoxycinnamate only to the reduced costs of obtaining the marketing authoriza- 3 Department of Histology and Embryology, Medical University of (OMC) and 3-(4-methylbenzylidene)camphor (4- tion, and these drugs meet the same quality requirements as the Silesia, Zabrze, Poland MBC) on cell viability in human neuroblastoma reference products. However, some cases of lack of therapeutic Assessment of melatonin’s ability to regulate 4 Department of Clinical Pharmacy and Biopharmacy, University of SH-SY5Y cell line equivalence may be found in the literature. As in Poland immune response in the hypothalamus of Medical Sciences, Poznan´, Poland Z˙ aneta Broniowska, Bogusława Budziszewska pharmacists are allowed to switch between reference and soman-poisoned rat; long-term effects 5 Division of Perinatology and Women’s Diseases, Poznan University of generic drugs the aim of our study was to evaluate pharmacists’ Magdalena Ciechanowska 1, Magdalena Łapot 1, Medical Sciences, Poznan´, Poland Department of Biochemical Toxicology, Chair of Toxicology, Faculty perception, views and knowledge regarding generic medicines. Marek Brytan 1, Edyta Paruszewska 1, of Pharmacy, Jagiellonian University Collegium Medicum, Krako´w, We also explored their perception of safety, quality and efficacy Małgorzata Paluch 1, Franciszek Przekop 2, Osteoporosis is a chronic, metabolic bone disease characterized Poland of generic drugs. The questionnaire, consisting of 16 questions Mirosław Mikicin 3, Marek Kowalczyk 1,3 by a decrease in bone mineral density and abnormalities in was sent to Polish pharmacists. We show, that pharmacists are microarchitecture leading to increased susceptibility to fracture. 1 UV filters are increasingly used in personal care product to aware of law aspects of approval and marketing authorization for The General Karol Kaczkowski Military Institute of Hygiene and This disease is determined by many factors, among which genetic protect human skin from the damaging effects of sunlight. There generic medicinal product in Poland. Moreover, they are familiar Epidemiology, Department of Pharmacology and Toxicology, Wars- factors play the important role. The aim of our study was to are two group of UV filters: physical filters and organic compounds with various aspects and limitations of reference-generic zawa, Poland evaluate the frequency of 283G>A (rs1544410) polymorphism of 2 which absorb UV-light. UV filters are added to consumer sunscreen products switch. In conclusion, our comprehensive analysis of The Kielanowski Institute of Animal Physiology and Nutrition, Polish the vitamin D receptor (VDR) gene and its relation to the clinical products in a concentration of 10%, but remain essentially pharmacists role allows to have a broad picture of actions that Academy of Sciences, Department of Neuroendocrinology, Jabłonna, parameters in postmenopausal women. The study consisted of 800 unidentified in technical products. Most of organic compounds have been made in the area of generic drug safety monitoring in Poland women at the postmenopausal (505) and reproductive (295) age 3 are highly lipophilic and can therefore bioaccumulate in humans Poland. Jozef Pilsudski University of Physical Education in Warsaw, from Caucasian population. The postmenopausal group included and environment. Exposure of human body is significant and Warszawa, Poland women with osteoporosis and osteopenia and healthy patients. still growing. Most common substances in cosmetics products are: http://dx.doi.org/10.1016/j.pharep.2015.06.057 Analysis of polymorphism was performed by real-time PCR using 2-ethyl-hexyl-4-trimethoxycinnamate (OMC), 3-(4-methylbenzy- The aim of the present study was (i) to determine whether HybProbe probes while BMD was measured by dual-energy X-ray perinatal exposure to soman (GD) exerted an adverse distant effect absorptiometry (DEXA) method. The obtained results showed 18 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 19

Aim: Identification novel chemical scaffold possessing mGlu7 the effect of test compounds on the caspase-3 activity, the Voivodeship, Poland 21 consecutive days beginning from the day directly preceding negative allosteric modulation activity by interaction with executive enzyme in process of apoptosis, it was found that OMC 4 Laboratory of Cellular and Molecular Pharmacology, Department of intoxication and continuing until the end of its term. Six months 7 transmembrane region of mGlu7 receptor. enhanced activity of this enzyme at concentration of 10� M, Experimental and Clinical Pharmacology, Medical University of Lublin, after the end of poisoning the animals were euthanized for Methods: Human GRM7 was cloned into genome of HEK-293 whereas 4-MBC was already operating at a concentration of Poland evaluation of mRNA levels for selected cytokines (IL-1b, IL-2, IL-4, 8 cells contained T-Rex expression system (Invitrogen). Expression 10� M. The obtained results demonstrated, that the tested filters IL-6, Il-10, TNFa and IFN-g) in the hypothalamus. To determine the of the receptor was analyzed by means of qRT-PCR and Western at high concentrations exert cytotoxic effect, whilst the proapop- The renin–angiotensin–aldosteron (RAA) system plays an level of gene expression, Real-time PCR with SYBR Green dye was blot in both: cells before and after stable transfection with GRM7. totic effects exhibited even at low concentrations. These com- essential role in regulation of blood pressure and may contribute applied. The obtained results show that GD modulates immune The screening study and activity of potential NAM was determined pounds may be important factors involved in pathogenesis of to local inflammatory processes and target-organ damage in reaction; intoxication of rats with GD resulted in significant using forskolin-induced cAMP accumulation, in a HEK-293 T-Rex neurodegenerative diseases, however, such conclusion must be various tissues, including central nervous system (CNS). Kynurenic reduction of transcript levels for the majority of analyzed cell line stably expressing mGlu7 or mock transfected HEK-293 T- confirmed in in vivo studies. acid (KYNA) is tryptophan metabolite formed in the brain and in cytokines, except mRNA of IL-1b, whose expression significantly Rex cell line. For the functional characterization of mGlu7 we the periphery, known to block ionotropic glutamate receptors and increased in F0 females and in males of their F1 offspring. In the F1 measured level of cyclic AMP (cAMP) by cAMP dynamic2 (CisBio) http://dx.doi.org/10.1016/j.pharep.2015.06.056 a7 nicotinic receptors, and to act as ligands of G protein-coupled female, there was no significant influence of GD on the IL-1b kit according to manufacture instructions. The concentration GPR35 receptors and human aryl hydrocarbon (AHR) receptors. transcript level. It has also been demonstrated for the first time the response curves were fitted using the non-linear regression The aim of this study was to assess the effect of angiotensin regulatory effect of melatonin on GD-induced cytokine distur- analysis program, GraphPad Prism (GraphPad Software). All liquid Evaluation of pharmacists’ opinion and converting enzyme inhibitors (ACE-I) and angiotensin receptor bances. This preliminary study would suggest the potential handling operations were performed using EVO 2000 system knowledge regarding generic medicinal antagonists (ARBs) on KYNA synthesis in vitro. KYNA was produced protective value of melatonin to enhance immune functions in (Tecan). products in Poland de novo in rat cortical slices and quantified fluorometrically, using an impaired immunity induced by GD poisoning. Results: Via in vitro screening of compound collection we have HPLC method. Grzegorz Cessak 1,2, Marta Da˛browska 2, identified chemical scaffold possessing mGluR potential NAM ARBs, losartan and telmisartan (50–250 mM) decreased forma- 7 Ewa Bałkowiec-Iskra 1,2 http://dx.doi.org/10.1016/j.pharep.2015.06.059 activity and IP562083 was obtained by successive chemical tion of KYNA to 75–60% of control (p < 0.05). Studied ACE-I modification. IP562083 inhibited LSP4-2022 or L-Glu induced 1 The Office for Registration of Medicinal Products, Medical Devices inhibited KYNA synthesis only at higher concentrations i.e. Analysis of vitamin D receptor polymorphism activation of mGlu7 receptor with IC50 value 3.5 mM. The maximal and Biocidal Product, Warszawa, Poland captopril at 500–1000 mM (80–70% of control, p < 0.05) and and its relation to mineral bone density in the response of LSP4-2022 and L-Glu were reduced in the presence of 2 Department of Experimental and Clinical Pharmacology, Medical ramipril at 1000 mM (82% of control, p < 0.05). The action of pathogenesis of osteoporosis IP562083. University of Warsaw, Warszawa, Poland ramipril was biphasic and, at 50–100 mM, the drug slightly 1,2 3 Conclusions: We have now identified, and characterized new increased KYNA production (to 120 and 124% of control, p < 0.05). Bogusław Czerny , Dariusz Boron´ , Anna Bogacz 1,4, Karolina Dziekan 1, potential mGlu7 NAM. Introduction of rules that enabled registration of generic The above data suggest novel aspect of action of drugs Aleksandra Kowalska 1, Radosław Kujawski 1, medicinal products constituted one of the major breakthroughs modulating RAA system associated with changes in brain synthesis Acknowledgments: This study is supported by project PBS1/B7/8/ Agnieszka Seremak-Mrozikiewicz 1,5, in pharmacotherapy. Generic drugs currently available on the of KYNA. 2012 financed by The National Centre for Research and Development. Adam Kamin´ ski 1, Izabela Uzar 2 market meet the criteria of bioequivalence that have been agreed Supported by grants from Medical University of Lublin, DS 450/14 and upon by registration agencies all over the world. They allow 1 Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.055 450/15. treatment that is as effective and safe, as the one achieved with 2 Department of General Pharmacology and Pharmacoeconomics, their reference products. Lower prices of generic drugs are due Pomeranian Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.058 Effects of 2-ethyl-hexyl-4-trimethoxycinnamate only to the reduced costs of obtaining the marketing authoriza- 3 Department of Histology and Embryology, Medical University of (OMC) and 3-(4-methylbenzylidene)camphor (4- tion, and these drugs meet the same quality requirements as the Silesia, Zabrze, Poland MBC) on cell viability in human neuroblastoma reference products. However, some cases of lack of therapeutic Assessment of melatonin’s ability to regulate 4 Department of Clinical Pharmacy and Biopharmacy, University of SH-SY5Y cell line equivalence may be found in the literature. As in Poland immune response in the hypothalamus of Medical Sciences, Poznan´, Poland Z˙ aneta Broniowska, Bogusława Budziszewska pharmacists are allowed to switch between reference and soman-poisoned rat; long-term effects 5 Division of Perinatology and Women’s Diseases, Poznan University of generic drugs the aim of our study was to evaluate pharmacists’ Magdalena Ciechanowska 1, Magdalena Łapot 1, Medical Sciences, Poznan´, Poland Department of Biochemical Toxicology, Chair of Toxicology, Faculty perception, views and knowledge regarding generic medicines. Marek Brytan 1, Edyta Paruszewska 1, of Pharmacy, Jagiellonian University Collegium Medicum, Krako´w, We also explored their perception of safety, quality and efficacy Małgorzata Paluch 1, Franciszek Przekop 2, Osteoporosis is a chronic, metabolic bone disease characterized Poland of generic drugs. The questionnaire, consisting of 16 questions Mirosław Mikicin 3, Marek Kowalczyk 1,3 by a decrease in bone mineral density and abnormalities in was sent to Polish pharmacists. We show, that pharmacists are microarchitecture leading to increased susceptibility to fracture. 1 UV filters are increasingly used in personal care product to aware of law aspects of approval and marketing authorization for The General Karol Kaczkowski Military Institute of Hygiene and This disease is determined by many factors, among which genetic protect human skin from the damaging effects of sunlight. There generic medicinal product in Poland. Moreover, they are familiar Epidemiology, Department of Pharmacology and Toxicology, Wars- factors play the important role. The aim of our study was to are two group of UV filters: physical filters and organic compounds with various aspects and limitations of reference-generic zawa, Poland evaluate the frequency of 283G>A (rs1544410) polymorphism of 2 which absorb UV-light. UV filters are added to consumer sunscreen products switch. In conclusion, our comprehensive analysis of The Kielanowski Institute of Animal Physiology and Nutrition, Polish the vitamin D receptor (VDR) gene and its relation to the clinical products in a concentration of 10%, but remain essentially pharmacists role allows to have a broad picture of actions that Academy of Sciences, Department of Neuroendocrinology, Jabłonna, parameters in postmenopausal women. The study consisted of 800 unidentified in technical products. Most of organic compounds have been made in the area of generic drug safety monitoring in Poland women at the postmenopausal (505) and reproductive (295) age 3 are highly lipophilic and can therefore bioaccumulate in humans Poland. Jozef Pilsudski University of Physical Education in Warsaw, from Caucasian population. The postmenopausal group included and environment. Exposure of human body is significant and Warszawa, Poland women with osteoporosis and osteopenia and healthy patients. still growing. Most common substances in cosmetics products are: http://dx.doi.org/10.1016/j.pharep.2015.06.057 Analysis of polymorphism was performed by real-time PCR using 2-ethyl-hexyl-4-trimethoxycinnamate (OMC), 3-(4-methylbenzy- The aim of the present study was (i) to determine whether HybProbe probes while BMD was measured by dual-energy X-ray perinatal exposure to soman (GD) exerted an adverse distant effect absorptiometry (DEXA) method. The obtained results showed 20 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 21 correlation between 283G>A polymorphism of VDR gene and the BU226 on isolated rat heart atria. Otherwise the attempt was made Expression of drug metabolizing enzymes along examine the effect of ALA on two indicators of early atherosclero- BMD scores for the lumbar vertebrae in women with osteopenia to explain the engagement of I2-imidazoline receptor and, the human gastrointestinal tract sis: mRNA TGF-b expression in tissues and on cEC concentration in and osteoporosis. Moreover, vitamin D receptor polymorphism probably, of KATP channels involvement in those effects. Marek Droz´dzik 1, Jette Peters 2, Joanna Lapczuk 1, peripheral blood of rats with diabetes. The investigation was also correlated with reduced BMD values. In conclusion, polymor- The inotropic and chronotropic responses of each imidazoline Marek Ostrowski 3, Sierk Haenisch 4, performed on 28 male Wistar rats with induced diabetes and on 15 phism (rs1544410) of VDR gene has been proved to be the genetic agent were measured alone and in the presence of antagonists: Werner Siegmund 2, Stefan Oswald 2 non-diabetic animals. ALA or placebo were administered into the factor of postmenopausal osteoporosis. idazoxan (I2-imidazoline receptor) and yohimbine (alpha2-adren- stomach once daily within 8 weeks to all of examined animals. ergic receptor). PNU37883 or glibenclamide – the antagonists of 1 Department of Experimental and Clinical Pharmacology, Pomeranian TGF-b mRNA expression in aorta and in myocardium was assayed http://dx.doi.org/10.1016/j.pharep.2015.06.060 KATP channels were also used. Medical University, Szczecin, Poland by real-time PCR and cEC count was measured using flow Metrazoline, BU224, BU239 and BU226 elicited positive 2 Department of Clinical Pharmacology, University of Greifswald, cytometry techniques. It was found that TGF-b mRNA expression

chronotropic activities on heart atria (Emax = 115.2 2.5%, Greifswald, Germany in myocardium in ALA-treated rats with diabetes is lower than in Evaluation of the effects of dietary antioxidant � 3 114.7 2.8%, 108.1 3.0% and 105.1 1.7% of the control, respec- Department of General and Transplantation Surgery, Pomeranian placebo-treated rats with diabetes and similar to the control non- in animal model of dexamethasone-induced � � � tively). Idazoxan stronger than yohimbine diminished those effects so Medical University, Szczecin, Poland diabetic group. TGF-b mRNA expression in aorta of ALA-treated neurotoxicity – A preliminary study 4 the engagement of I2-imidazoline receptors in chronotropic effect of Institute of Experimental and Clinical Pharmacology, University of rats with diabetes was higher than in placebo-treated rats with Zofia Danilczuk the compounds studied could be postulated. Moreover PNU37883 as Kiel, Kiel, Germany diabetes and in comparison to non-diabetic animals. The well as glibenclamide abolished chronotropic activity of BU226 so the percentage of cEC in peripheral blood observed in ALA-treated Department of Experimental and Clinical Pharmacology, Medical engagement of K channels in chronotropic effects of imidazolines rats was similar to non-diabetic group and significantly lower than University of Lublin, Lublin, Poland ATP The oral absorption of many drugs is highly influenced by could not be excluded. BU239 and BU224 exerted distinct positive intestinal biotransformation. To characterize or even predict the in placebo-treated animals with diabetes. It could be concluded inotropic effects on heart atria (Emax = 119.4 3.5% and 119.2 4.7% impact of intestinal drug processing, the knowledge of intestinal that ALA could be the helpful agent in prevention of diabetes- Glucocorticoids (GCs) and other preparations, e.g. dexametha- � � of the control, respectively), but only BU224 activity was markedly expression levels of enzymes is an essential prerequisite. Therefore, related atherosclerosis development. sone (DEX – a synthetic GCs receptor agonist) are often used antagonized by idazoxan, which confirms the involvement of I2- the aim of this study was to comprehensively analyse the expression therapeutically for their potent anti-inflammatory and immuno- imidazoline receptors in that effect. of clinically relevant phase I and II enzymes, and nuclear receptors http://dx.doi.org/10.1016/j.pharep.2015.06.065 suppressive properties in the different diseases. Chronic stress or along the entire human gastrointestinal tract. Intestinal tissue was prolonged exposure to high levels of GCs induces neuropathologi- http://dx.doi.org/10.1016/j.pharep.2015.06.062 collected from 8 organ donors (age: 24–56). In each case 10 samples cal alterations, which are frequently associated with cognitive Effect of choline salicylate DPCM and DPAE in from the entire gut (duodenum: 1, jejunum: 2, ileum: 3, colon: 4) deficits, such as the impairment of memory and learning. Brain guinea pigs were taken, and mRNA expression of 12 genes of metabolizing injury, caused by ischemic or hemorrhagic stroke or trauma, may ACPT-I, a group III mGlu receptor agonist, 1 2 enzymes (CYPs: 8, phase II enzymes: 4) were measured using Wojciech Dziewiszek , Wojciech Michalski , lead to the increased production of reactive oxygen species (ROS) reduces infarction and behavioral deficit in 1 3 custom-made TaqMan1 low density arrays. Gene expression was Adam Szela˛g , Marek Bochnia and, in effect, to tissue damage via several different cellular normotensive and spontaneously hypertensive normalized to five house-keeping genes and analyzed using the 1 molecular pathways. Many authors suggested the neuroprotective rats subjected to transient focal cerebral Department of Pharmacology, Wrocław Medical University, Wroc- DDCt-method. Intestinal expression of CYP2C9, CYP2D6, SULT1A, effect of antioxidant agent. ischemia ław, Poland UGT1A and UGT2B7 increased from duodenum to jejunum and was 2 The purpose of this study was to investigate the effect of Helena Domin 1, Łukasz Przykaza 2, Wrocław University of Technology, Institute of Telecommunications, the highest in distal jejunum but markedly lower in ileum and colon. antioxidant agent such as: spirulina (blue-green algae) in animal Ewa Kozniewska 2,3, Paweł Boguszewski 4, Teleinformatics and Acoustics, Wrocław, Poland CYP3A4/5 was predominately found in the upper intestine. The 3 model of dexamethasone-induced neurotoxicity. The experiments Maria S´miałowska 1 Department of Otolaryngology, Faculty of Dentistry, Wrocław intestinal expression rang order of drug metabolizing enzymes was were carried out on male Albino Swiss mice (25–30 g). Spirulina Medical University, Wrocław, Poland 1 as follows: CYP3A4 > CYP2C9 > CYP2C19 > CYP2D6 = CYP3A5 = was administered ip (0.5 g and 1.0 g/kg/day) 4 h before DEX Institute of Pharmacology, PAS, Krako´w, Poland 2 CYP2B6, CYP2C8. In all intestinal regions, SULT1A, UGT1A, CYP3A4 (16 mg/kg/day) for 14 days. The long-term memory acquisition, Mossakowski Medical Research Centre PAS, Warszawa, Poland The aim of work was an assessment of the effect of choline 3 and CYP2C9 were the most prominent genes. The intestinal motor performance, as well as body weight and lethality were Medical University of Warsaw, Warszawa, Poland salicylate i.m. application on the distortion product of cochlear 4 distribution of the expression of SULT1A and UGT1A enzymes and evaluated 14 days after the drugs administration. The results of our Nencki Institute of Experimental Biology PAS, Warszawa, Poland microphonics (DPCM) and acoustic otoemission (DPOAEThe UGT2B7 was as follows: duodenum < jejunum > ileum > colon, study have shown that DEX evoked deterioration of all parameters ototoxicity study of choline salicylate (ChS) was performed in 6 whereas for UGT2B15 there was stable but significantly lower in behavioral tests. In mice treated with DEX, spirulina improved Our earlier studies showed that ACPT-I [(1S,3R,4S)-1-amino- guinea pigs. Choline salicylate was administered intramuscularly expression along GI tract. There is a substantial expression gradient parameters of behavioral tests in a higher dose and increased cyclopentane-1,2,4-tricarboxylic acid], a blood–brain-barrier per- in the dose 200 mg/kg. CM and DPOAE were received using the new for several enzymes along the human alimentary tract, which may reduction of body weight in mice subjected to DEX. meable agonist of group III metabotropic glutamate receptors homodyne method before and 60 min after each medicine explain regio-selective differences in intestinal drug metabolism. Although the preliminary study suggests protective effect of (mGluR) was neuroprotective against kainate-induced excitotoxi- application. Biopotentials were examined under ketamine/xyla- spirulina in this experimental model, it should be confirmed in city in vitro and in vivo. The aim of the present study was to assess zine anesthesia. Measurements were carried out for five fixed further research. neuroprotective potential of ACPT-I in vivo in normotensive http://dx.doi.org/10.1016/j.pharep.2015.06.064 intermodulation frequencies f3: 1321, 1875, 2671, 3142 and (Sprague Dawley) and spontaneously hypertensive (SHR) rats 5342 Hz. Each of the five frequencies was obtained for 4 different after transient middle cerebral artery occlusion (MCAO). Since the http://dx.doi.org/10.1016/j.pharep.2015.06.061 The effect of alpha-lipoic acid (ALA) on early ratios k = f2/f1 = 1.20, 1.25, 1.30, 1.35. The following two tone evaluation of functional outcome after ischemia is a key stages of atherosclerosis in rats with diabetes intensity combinations were used: 50 dB, 60 dB and 55 dB, 65 dB. component in improving the clinical relevance of experimental Marzena Dworacka 1, Hanna Winiarska 1, The measurements were reregistered continuously with the Metrazoline, BU224, BU226 and BU239 act on stroke studies, we analyzed not only the brain infarction volume Anna Wesołowska 1, Saule Iskakova 2, computer system. The effect of the choline salicylate both on isolated rat heart atria via I2-imidazoline but also the motor function of rats subjected to MCAO and after Yergen Kurmambayev 2, Galina Chukanova 2, the DPCM and DPOAE level and the phase of these signals were receptors. Are the ATP-sensitive potassium treatment with ACPT-I. Transient focal cerebral ischemia was Bartosz Frycz 3, Paweł P. Jagodzin´ ski 3, investigated. The results show that the DPOAE signal on some (KATP) channels also involved? induced by the occlusion of the right MCA for 90 min. Morpholog- Grzegorz Dworacki 4 frequencies was increased. In addition, by analyzing the phase Justyna Długoke˛cka, Sylwia Szynaka, ical and behavioral analysis was performed 72 h after MCAO/ behavior, was observed the change its course and the reduction of Karolina Wojtalik, Antoni Nasal, reperfusion. We demonstrated that both in normotensive and SHR 1 Department of Pharmacology Poznan University of Medical Sciences, the phase signal stability DPCM and DPOAE. Aleksandra Radwan´ ska, Roman Kaliszan rats ACPT-I (30 mg/kg) injected intraperitoneally either 30 min Poznan´, Poland after starting MCAO or 30 min after beginning of reperfusion, not 2 Department of Pharmacology Marat Ospanov University of Medical Department of Biopharmaceutics and Pharmacodynamics, Medical http://dx.doi.org/10.1016/j.pharep.2015.06.066 only diminished the infarction volume but also improved gait Sciences, Aktobe, Kazakhstan University, Gdan´sk, Poland parameters (Catwalk analysis) and mobility in an open field test. In 3 Department of Biochemistry and Molecular Biology, Poznan´ conclusion, the obtained results indicate that ACPT-I may be not University of Medical Sciences, Poznan´, Poland Differential skeletal effects of trigonelline, an The cardiotropic effects of imidazolines result mostly from their only neuroprotective against ischemic neuronal damage but also 4 Department of Clinical Immunology, Poznan´ University of Medical alkaloid present in coffee, in streptozotocin- and interaction with imidazoline/alpha2-adrenergic receptors. The diminishes postischemic functional deficits. Sciences, Poznan´, Poland streptozotocin/nicotinamide-treated rats possible participation of the KATP channels in above described Joanna Folwarczna 1, Aleksandra Janas 1, tropic activities of imidazolines is still unclear. The aim of the study The study was supported by grant No. N N401 091037 from MS&HE. 1 1 ´ 1 Recently the efficacy of alpha-lipoic acid (ALA) on atheroscle- Maria Pytlik , Urszula Cegieła , Leszek Sliwin´ ski , was to determine the chrono- and inotropic effects of selective I2- 2 ˇ 2 rosis was suggested, by showing that ALA modulates multiple Zora Krivosˇı´kova´ , Korne´lia Stefı´kova´ , imidazoline receptor ligands: metrazoline, BU224, BU239 and http://dx.doi.org/10.1016/j.pharep.2015.06.063 2 pathogenic aspects of atherosclerosis. The aim of the study was to Martin Gajdosˇ 20 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 21 correlation between 283G>A polymorphism of VDR gene and the BU226 on isolated rat heart atria. Otherwise the attempt was made Expression of drug metabolizing enzymes along examine the effect of ALA on two indicators of early atherosclero- BMD scores for the lumbar vertebrae in women with osteopenia to explain the engagement of I2-imidazoline receptor and, the human gastrointestinal tract sis: mRNA TGF-b expression in tissues and on cEC concentration in and osteoporosis. Moreover, vitamin D receptor polymorphism probably, of KATP channels involvement in those effects. Marek Droz´dzik 1, Jette Peters 2, Joanna Lapczuk 1, peripheral blood of rats with diabetes. The investigation was also correlated with reduced BMD values. In conclusion, polymor- The inotropic and chronotropic responses of each imidazoline Marek Ostrowski 3, Sierk Haenisch 4, performed on 28 male Wistar rats with induced diabetes and on 15 phism (rs1544410) of VDR gene has been proved to be the genetic agent were measured alone and in the presence of antagonists: Werner Siegmund 2, Stefan Oswald 2 non-diabetic animals. ALA or placebo were administered into the factor of postmenopausal osteoporosis. idazoxan (I2-imidazoline receptor) and yohimbine (alpha2-adren- stomach once daily within 8 weeks to all of examined animals. ergic receptor). PNU37883 or glibenclamide – the antagonists of 1 Department of Experimental and Clinical Pharmacology, Pomeranian TGF-b mRNA expression in aorta and in myocardium was assayed http://dx.doi.org/10.1016/j.pharep.2015.06.060 KATP channels were also used. Medical University, Szczecin, Poland by real-time PCR and cEC count was measured using flow Metrazoline, BU224, BU239 and BU226 elicited positive 2 Department of Clinical Pharmacology, University of Greifswald, cytometry techniques. It was found that TGF-b mRNA expression chronotropic activities on heart atria (Emax = 115.2 2.5%, Greifswald, Germany in myocardium in ALA-treated rats with diabetes is lower than in Evaluation of the effects of dietary antioxidant � 3 114.7 2.8%, 108.1 3.0% and 105.1 1.7% of the control, respec- Department of General and Transplantation Surgery, Pomeranian placebo-treated rats with diabetes and similar to the control non- in animal model of dexamethasone-induced � � � tively). Idazoxan stronger than yohimbine diminished those effects so Medical University, Szczecin, Poland diabetic group. TGF-b mRNA expression in aorta of ALA-treated neurotoxicity – A preliminary study 4 the engagement of I2-imidazoline receptors in chronotropic effect of Institute of Experimental and Clinical Pharmacology, University of rats with diabetes was higher than in placebo-treated rats with Zofia Danilczuk the compounds studied could be postulated. Moreover PNU37883 as Kiel, Kiel, Germany diabetes and in comparison to non-diabetic animals. The well as glibenclamide abolished chronotropic activity of BU226 so the percentage of cEC in peripheral blood observed in ALA-treated Department of Experimental and Clinical Pharmacology, Medical engagement of K channels in chronotropic effects of imidazolines rats was similar to non-diabetic group and significantly lower than University of Lublin, Lublin, Poland ATP The oral absorption of many drugs is highly influenced by could not be excluded. BU239 and BU224 exerted distinct positive intestinal biotransformation. To characterize or even predict the in placebo-treated animals with diabetes. It could be concluded inotropic effects on heart atria (Emax = 119.4 3.5% and 119.2 4.7% impact of intestinal drug processing, the knowledge of intestinal that ALA could be the helpful agent in prevention of diabetes- Glucocorticoids (GCs) and other preparations, e.g. dexametha- � � of the control, respectively), but only BU224 activity was markedly expression levels of enzymes is an essential prerequisite. Therefore, related atherosclerosis development. sone (DEX – a synthetic GCs receptor agonist) are often used antagonized by idazoxan, which confirms the involvement of I2- the aim of this study was to comprehensively analyse the expression therapeutically for their potent anti-inflammatory and immuno- imidazoline receptors in that effect. of clinically relevant phase I and II enzymes, and nuclear receptors http://dx.doi.org/10.1016/j.pharep.2015.06.065 suppressive properties in the different diseases. Chronic stress or along the entire human gastrointestinal tract. Intestinal tissue was prolonged exposure to high levels of GCs induces neuropathologi- http://dx.doi.org/10.1016/j.pharep.2015.06.062 collected from 8 organ donors (age: 24–56). In each case 10 samples cal alterations, which are frequently associated with cognitive Effect of choline salicylate DPCM and DPAE in from the entire gut (duodenum: 1, jejunum: 2, ileum: 3, colon: 4) deficits, such as the impairment of memory and learning. Brain guinea pigs were taken, and mRNA expression of 12 genes of metabolizing injury, caused by ischemic or hemorrhagic stroke or trauma, may ACPT-I, a group III mGlu receptor agonist, 1 2 enzymes (CYPs: 8, phase II enzymes: 4) were measured using Wojciech Dziewiszek , Wojciech Michalski , lead to the increased production of reactive oxygen species (ROS) reduces infarction and behavioral deficit in 1 3 custom-made TaqMan1 low density arrays. Gene expression was Adam Szela˛g , Marek Bochnia and, in effect, to tissue damage via several different cellular normotensive and spontaneously hypertensive normalized to five house-keeping genes and analyzed using the 1 molecular pathways. Many authors suggested the neuroprotective rats subjected to transient focal cerebral Department of Pharmacology, Wrocław Medical University, Wroc- DDCt-method. Intestinal expression of CYP2C9, CYP2D6, SULT1A, effect of antioxidant agent. ischemia ław, Poland UGT1A and UGT2B7 increased from duodenum to jejunum and was 2 The purpose of this study was to investigate the effect of Helena Domin 1, Łukasz Przykaza 2, Wrocław University of Technology, Institute of Telecommunications, the highest in distal jejunum but markedly lower in ileum and colon. antioxidant agent such as: spirulina (blue-green algae) in animal Ewa Kozniewska 2,3, Paweł Boguszewski 4, Teleinformatics and Acoustics, Wrocław, Poland CYP3A4/5 was predominately found in the upper intestine. The 3 model of dexamethasone-induced neurotoxicity. The experiments Maria S´miałowska 1 Department of Otolaryngology, Faculty of Dentistry, Wrocław intestinal expression rang order of drug metabolizing enzymes was were carried out on male Albino Swiss mice (25–30 g). Spirulina Medical University, Wrocław, Poland 1 as follows: CYP3A4 > CYP2C9 > CYP2C19 > CYP2D6 = CYP3A5 = was administered ip (0.5 g and 1.0 g/kg/day) 4 h before DEX Institute of Pharmacology, PAS, Krako´w, Poland 2 CYP2B6, CYP2C8. In all intestinal regions, SULT1A, UGT1A, CYP3A4 (16 mg/kg/day) for 14 days. The long-term memory acquisition, Mossakowski Medical Research Centre PAS, Warszawa, Poland The aim of work was an assessment of the effect of choline 3 and CYP2C9 were the most prominent genes. The intestinal motor performance, as well as body weight and lethality were Medical University of Warsaw, Warszawa, Poland salicylate i.m. application on the distortion product of cochlear 4 distribution of the expression of SULT1A and UGT1A enzymes and evaluated 14 days after the drugs administration. The results of our Nencki Institute of Experimental Biology PAS, Warszawa, Poland microphonics (DPCM) and acoustic otoemission (DPOAEThe UGT2B7 was as follows: duodenum < jejunum > ileum > colon, study have shown that DEX evoked deterioration of all parameters ototoxicity study of choline salicylate (ChS) was performed in 6 whereas for UGT2B15 there was stable but significantly lower in behavioral tests. In mice treated with DEX, spirulina improved Our earlier studies showed that ACPT-I [(1S,3R,4S)-1-amino- guinea pigs. Choline salicylate was administered intramuscularly expression along GI tract. There is a substantial expression gradient parameters of behavioral tests in a higher dose and increased cyclopentane-1,2,4-tricarboxylic acid], a blood–brain-barrier per- in the dose 200 mg/kg. CM and DPOAE were received using the new for several enzymes along the human alimentary tract, which may reduction of body weight in mice subjected to DEX. meable agonist of group III metabotropic glutamate receptors homodyne method before and 60 min after each medicine explain regio-selective differences in intestinal drug metabolism. Although the preliminary study suggests protective effect of (mGluR) was neuroprotective against kainate-induced excitotoxi- application. Biopotentials were examined under ketamine/xyla- spirulina in this experimental model, it should be confirmed in city in vitro and in vivo. The aim of the present study was to assess zine anesthesia. Measurements were carried out for five fixed further research. neuroprotective potential of ACPT-I in vivo in normotensive http://dx.doi.org/10.1016/j.pharep.2015.06.064 intermodulation frequencies f3: 1321, 1875, 2671, 3142 and (Sprague Dawley) and spontaneously hypertensive (SHR) rats 5342 Hz. Each of the five frequencies was obtained for 4 different after transient middle cerebral artery occlusion (MCAO). Since the http://dx.doi.org/10.1016/j.pharep.2015.06.061 The effect of alpha-lipoic acid (ALA) on early ratios k = f2/f1 = 1.20, 1.25, 1.30, 1.35. The following two tone evaluation of functional outcome after ischemia is a key stages of atherosclerosis in rats with diabetes intensity combinations were used: 50 dB, 60 dB and 55 dB, 65 dB. component in improving the clinical relevance of experimental Marzena Dworacka 1, Hanna Winiarska 1, The measurements were reregistered continuously with the Metrazoline, BU224, BU226 and BU239 act on stroke studies, we analyzed not only the brain infarction volume Anna Wesołowska 1, Saule Iskakova 2, computer system. The effect of the choline salicylate both on isolated rat heart atria via I2-imidazoline but also the motor function of rats subjected to MCAO and after Yergen Kurmambayev 2, Galina Chukanova 2, the DPCM and DPOAE level and the phase of these signals were receptors. Are the ATP-sensitive potassium treatment with ACPT-I. Transient focal cerebral ischemia was Bartosz Frycz 3, Paweł P. Jagodzin´ ski 3, investigated. The results show that the DPOAE signal on some (KATP) channels also involved? induced by the occlusion of the right MCA for 90 min. Morpholog- Grzegorz Dworacki 4 frequencies was increased. In addition, by analyzing the phase Justyna Długoke˛cka, Sylwia Szynaka, ical and behavioral analysis was performed 72 h after MCAO/ behavior, was observed the change its course and the reduction of Karolina Wojtalik, Antoni Nasal, reperfusion. We demonstrated that both in normotensive and SHR 1 Department of Pharmacology Poznan University of Medical Sciences, the phase signal stability DPCM and DPOAE. Aleksandra Radwan´ ska, Roman Kaliszan rats ACPT-I (30 mg/kg) injected intraperitoneally either 30 min Poznan´, Poland after starting MCAO or 30 min after beginning of reperfusion, not 2 Department of Pharmacology Marat Ospanov University of Medical Department of Biopharmaceutics and Pharmacodynamics, Medical http://dx.doi.org/10.1016/j.pharep.2015.06.066 only diminished the infarction volume but also improved gait Sciences, Aktobe, Kazakhstan University, Gdan´sk, Poland parameters (Catwalk analysis) and mobility in an open field test. In 3 Department of Biochemistry and Molecular Biology, Poznan´ conclusion, the obtained results indicate that ACPT-I may be not University of Medical Sciences, Poznan´, Poland Differential skeletal effects of trigonelline, an The cardiotropic effects of imidazolines result mostly from their only neuroprotective against ischemic neuronal damage but also 4 Department of Clinical Immunology, Poznan´ University of Medical alkaloid present in coffee, in streptozotocin- and interaction with imidazoline/alpha2-adrenergic receptors. The diminishes postischemic functional deficits. Sciences, Poznan´, Poland streptozotocin/nicotinamide-treated rats possible participation of the KATP channels in above described Joanna Folwarczna 1, Aleksandra Janas 1, tropic activities of imidazolines is still unclear. The aim of the study The study was supported by grant No. N N401 091037 from MS&HE. 1 1 ´ 1 Recently the efficacy of alpha-lipoic acid (ALA) on atheroscle- Maria Pytlik , Urszula Cegieła , Leszek Sliwin´ ski , was to determine the chrono- and inotropic effects of selective I2- 2 ˇ 2 rosis was suggested, by showing that ALA modulates multiple Zora Krivosˇı´kova´ , Korne´lia Stefı´kova´ , imidazoline receptor ligands: metrazoline, BU224, BU239 and http://dx.doi.org/10.1016/j.pharep.2015.06.063 2 pathogenic aspects of atherosclerosis. The aim of the study was to Martin Gajdosˇ 22 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 23

1 Department of Pharmacology, School of Pharmacy with the Division 1.41 to 5.08 pmol KYNA/g tissue (p < 0.001). Valproate did not Effect of prolonged stress on NO synthases and epilepsy is overexpression of p-glycoprotein (p-gp) in blood–brain of Laboratory Medicine, Medical University of Silesia, Katowice, influence TRP and KYN level in brain cortex. IL-1b levels in brain structures and HPA axis barrier. This protein is responsible for efflux of numerous Poland Our data suggest, that valproate administration may enhance activity xenobiotics, including AEDs and thus may decrease concentration 2 Department of Clinical and Experimental Pharmacotherapy, Medical KYNA synthesis in the brain. It can be suggested that elevated Anna Ga˛dek-Michalska, Joanna Tadeusz, of this drugs in a brain and thus compromise therapy. Faculty, Slovak Medical University, Bratislava, Slovakia content of KYNA may contribute to antiepileptic and other central Paulina Rachwalska, Jan Bugajski Zebrafish, a vertebrate with complementary advantages to effects of valproate. rodents, has been recently widely used in laboratories of both basic Diabetes leads to development of osteoporosis. Streptozotocin Department of Physiology, Institute of Pharmacology, Polish Academy medical studies and clinical research. Combining the complexity of Acknowledgements: Supported by the grant from Medical Universi- (STZ) in a single dose induces experimental type 1 diabetes, of Sciences, Krako´w, Poland animal studies and in vitro high throughput screening, the ty of Lublin, No DS 457/2015. Paulina Fonderska and Łukasz Pyzio are whereas administration of nicotinamide (NA) 15 min earlier dose- zebrafish has proven to be a powerful tool for target identification, dependently protects against the STZ action. Trigonelline is an students in the Department of Experimental and Clinical Pharmacol- The aim of this study was to determine the effect of prior disease modelling and drug development. alkaloid with potential antidiabetic activity. The aim of the study ogy, Medical University in Lublin. repeated restraint stress (RS) on a single restraint-induced changes In our study, effects of p-gp inhibitors ritonavir and tariquidar was to investigate effects of trigonelline on diabetes-induced in IL-1b and nitric oxide synthase (NOS) levels in prefrontal cortex on the efficacy of levetiracetam in PTZ epilepsy model in 7 dpf disorders in the rat skeletal system. http://dx.doi.org/10.1016/j.pharep.2015.06.068 (PFC), hippocampus, hypothalamus and plasma and assess if these zebrafish larvae were investigated. After 24 h pretreatment period Effects of trigonelline (50 mg/kg po daily for 4 weeks) were alterations may influence HPA axis responses. Experiments were with levetiracetam and p-gp inhibitors larvae were deposited into investigated in 3-month-old female Wistar rats, which, 2 weeks performed on male Wistar rats. The first group consisted of control multiwell plate and then treated with 10 mM pentylenetetrazole before the start of trigonelline administration, received STZ Association of genetic variability with the non-stressed animals. In the second group, animals were subjected solution for epilepsy induction. Plate was then recorded by means (60 mg/kg ip) alone or STZ after NA (230 mg/kg ip). Serum bone antiplatelet effect of clopidogrel and to single restraint stress (RS) for 10 min. In the third group, the of camcorder and fish movement was tracked and then locomotion turnover markers, mineral density (BMD) and mechanical proper- concentration of inactive clopidogrel metabolite animals were restrained for 10 min twice a day repeatedly for 3, 7 parameters were analyzed. Results indicate that simultaneous use ties were studied. in patients after percutaneous coronary and 14 consecutive days and decapitated 24 h after the last of levetiracetam and p-gp inhibitors significantly changes move- STZ induced diabetes, with significant decreases in BMD and intervention (PCI) restraint. The fourth group consisted of prior repeatedly restrained ment patterns in 7 dpf larvae suggesting possible use in epilepsy worsening of cancellous bone mechanical properties (the tibial Barbara Gawron´ ska-Szklarz 1, Anna Czerkawska 1, rats (for 3, 7 and 14 days), which were subjected to 10 min restraint treatment. metaphysis). STZ after NA induced hyperglycemia lasting first 2 Urszula Adamiak-Giera 1, Szymon Ole˛dzki 2, stress 24 h after the last restraint period and rapidly decapitated 0, weeks of the experiment only; slight worsening of cancellous bone Mateusz Kurzawski 1, Maria Kałdon´ ska 1, 1, 2 and 3 h later. IL-1b, ACTH and corticosterone levels were http://dx.doi.org/10.1016/j.pharep.2015.06.071 mechanical properties and a decrease in vertebral BMD were Maria Jastrze˛bska 3, Krzysztof Safranow 4, determined in plasma using commercially available kits. IL-1b, demonstrated. Trigonelline tended to worsen bone mechanical Zdzisława Kornacewicz-Jach 2 neuronal nitric oxide synthase (nNOS) and inducible nitric oxide Antidepressant- and anxiolytic-like effects of properties and did not affect BMD in the diabetic rats. In NA/STZ- synthase (iNOS) levels in the above mentioned brain structures 1 ‘‘biased’’ 5-HT receptor agonists F15599 and treated rats, trigonelline significantly increased BMD and tended to Department of Pharmacology, Pomeranian Medical University, samples were analyzed by western blot procedure. The present 1A F13714 in rats improve cancellous bone strength. Szczecin, Poland results indicate time-related similarities in the potent alterations 2 1 1 In conclusion, trigonelline favorably affected the skeletal Department of Cardiolog, Pomeranian Medical University, Szczecin, in IL-1b levels in brain structures, and pituitary-adrenal hormones. Magdalena Jastrze˛bska-Wie˛sek , Anna Partyka , 1 ´ 2 system only in the non-diabetic (NA/STZ-treated) rats. A tendency Poland Single restraint for 10 min significantly decreases iNOS levels in Anna Wasik , Joanna Sniecikowska , 3 3 1 to worsen some skeletal parameters in the diabetic rats indicates Department of Laboratory Diagnostics and Molecular Medicine, PFC and hypothalamus. Repeated RS for 3 days most strongly Adrian Newman-Tancredi , Anna Wesołowska Pomeranian Medical University, Szczecin, Poland that, in certain conditions, trigonelline may damage bone. enhances iNOS level induced by single RS, which was gradually 1 4 Department of Clinical Pharmacy, Jagiellonian University Medical Department of Biochemistry and Medical Chemistry, Pomeranian reduced by prior RS for 7 and 14 days. Parallel but much weaker Medical University, Szczecin, Poland College, Krako´w, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.067 changes appear with nNOS level. In brain structures, changes in 2 Department of Pharmaceutical Chemistry, Jagiellonian University NOS levels induced by single RS are enhanced or reduced by prior Medical College, Krako´w, Poland The objective of this study was to investigate the contribution restraint, depending on brain structure and the period of prior 3 Effect of long-term administration of valproate Neurolixis Inc, San Diego, CA, USA of genetic polymorphism of CYP2C19, CYP3A4/5, ABCB1 and PON1 stress. Changes in the rapid and strong ACTH and corticosterone on tryptophan, kynurenine and kynurenic acid genes to the plasma concentrations of inactive metabolite of secretion, induced by a single restraint or preceded by repeated RS, content in rat brain cortex The 5-HT receptors have drawn attention as a target for clopidogrel and pharmacodynamic effect of clopidogrel in Polish do not seem to be directly correlated with alterations of IL-1b and 1A pharmacotherapy for variety CNS disorders. 5-HT receptors are Paulina Fonderska, Łukasz Pyzio, Izabela Zakrocka, patients. A total of 209 (149 M, 60 F) patients with CAD NOS levels in brain structures. 1A Waldemar A. Turski, Tomasz Kocki undergoing PCI who received dual antiplatelet therapy (clopido- expressed as both 5-HT1A autoreceptors, located in the raphe grel plus aspirin) were enrolled in this study. Whole blood for Acknowledgments: This research was supported by grant: POIG nucleus, and post-synaptic 5-HT1A heteroreceptors, located in Chair and Department of Experimental and Clinical Pharmacology, genotyping was taken before PCI. Each individual was genotyped 01.01.02-12-004/09-00 financed by European Regional Development various brain regions, i.e. cortex, hypothalamus and septum/ Medical University of Lublin, Lublin, Poland for SNPs marking CYP2C19, CYP3A4/5, ABCB1 and PON1 variant Fund as well as by the statutory funds from the Institute of Pharma- hippocampus. Activation of these serotonin receptors, in the different brain regions, exerts different effects. 5-HT receptor alleles. The allelic discrimination TaqMan real-time PCR assays cology, Polish Academy of Sciences. 1A Kynurenines are the metabolites of tryptophan formed along were used for detection. Concentration of clopidogrel inactive agonists have been investigated to function as antidepressants and kynurenine pathway. Among neuroactive kynurenines the role of anxiolytics. Furthermore, they are used as add-ons to atypical metabolite in plasma was determined in steady state 1–3.5 h http://dx.doi.org/10.1016/j.pharep.2015.06.070 kynurenic acid (KYNA) is well established. KYNA was shown to (mean 2 h) after clopidogrel administration. At the same time 1 antipsychotics, and also to ameliorate female sexual dysfunction display potent neuroprotective and anticonvulsive properties and sample of whole blood was taken to determine ADP-induced and Parkinson’s disease. Compounds F15599 and F13714 have its impaired production was implicated in the pathogenesis of platelet aggregation. Clopidogrel inactive metabolite concentra- P-glycoprotein inhibitors modulate been developed as two ‘‘biased’’ 5-HT1A receptor agonists. It has epilepsy and neurodegenerative disorders. Moreover, its anti- tion in plasma was determined by a HPLC method. ADP-induced levetiracetam effects in zebrafish epilepsy model been demonstrated that F15599 preferentially activates post- inflammatory and antioxidant properties were suggested. KYNA is platelet aggregation was assessed with multiple electrode Piotr Jakubowski 1, Michał Majewski 1, synaptic 5-HT1A heteroreceptors over raphe-located autorecep- synthesized mainly within astrocytes by kynurenine aminotrans- platelet aggregometry using a Muliplate analyzer. Mann–Whit- Piotr Podlasz 2, Anna Jakimiuk 3, Natalia Kasica 2 tors, and F13714 exerts an opposite pharmacological profile with ferases (KAT I and II) from its bioprecursor, kynurenine (KYN). ney test was used to analyze associations of the quantitative more pronounced activity at raphe-located autoreceptors, and only 1 Department of Pharmacology and Toxicology, Faculty of Medical In the present study the influence of long-term administration variables with CYP2C19, CYP3A4/5, ABCB1 and PON1 genotypes. modest activation at post-synaptic heteroreceptors. The aim of this Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland of antiepileptic drug valproate on the synthesis of tryptophan General linear model was used to find independent predictors of study was to examine antidepressant- and anxiolytic-like effects of 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, (TRP), and its metabolites: KYN and KYNA in the brain cortex was clopidogrel metabolite concentration. Presence of CYP2C19*2 F15599 and F13714, administered orally 30 min before tests to University of Warmia and Mazury in Olsztyn, Olsztyn, Poland evaluated. allele was associated with higher ADP-induced platelet aggrega- rats. The antidepressant-like effect was investigated in the forced 3 Department of Pathophysiology, Forensic Veterinary and Adminis- Adult male Wistar rats were administered valproate (400 mg/ tion and presence of ABCB1 2677A allele was associated with swim test while anxiolytic-like activity was assessed in the conflict tration, Faculty of Veterinary Medicine, University of Warmia and kg, ip) for 14 days. Brain cortex was collected 24 h after the last lower clopidogrel metabolite concentration. There was no drinking Vogel and the elevated plus maze tests in rats. It would be Mazury in Olsztyn, Olsztyn, Poland injection of a drug and the level of TRP, KYN and KYNA were significant association between ADP-induced platelet aggrega- interesting if any differences in pharmacological activity would be assessed. TRP, KYN and KYNA were quantified using HPLC system tion and clopidogrel metabolite concentration. observed for these ‘‘biased’’ 5-HT1A receptor agonists. with UV–Vis and fluorometric detectors. Epilepsy is one of the most common neurological diseases with It was found that long-term administration of valproate 50–60 million people affected worldwide. Unfortunately, only 70% Supported by JU MC funds: K/ZDS/004121. http://dx.doi.org/10.1016/j.pharep.2015.06.069 significantly increased content of KYNA in brain cortex from of patients are effectively treated with currently available antiepileptic drugs (AEDs). One of the leading hypothesis for refractory http://dx.doi.org/10.1016/j.pharep.2015.06.072 22 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 23

1 Department of Pharmacology, School of Pharmacy with the Division 1.41 to 5.08 pmol KYNA/g tissue (p < 0.001). Valproate did not Effect of prolonged stress on NO synthases and epilepsy is overexpression of p-glycoprotein (p-gp) in blood–brain of Laboratory Medicine, Medical University of Silesia, Katowice, influence TRP and KYN level in brain cortex. IL-1b levels in brain structures and HPA axis barrier. This protein is responsible for efflux of numerous Poland Our data suggest, that valproate administration may enhance activity xenobiotics, including AEDs and thus may decrease concentration 2 Department of Clinical and Experimental Pharmacotherapy, Medical KYNA synthesis in the brain. It can be suggested that elevated Anna Ga˛dek-Michalska, Joanna Tadeusz, of this drugs in a brain and thus compromise therapy. Faculty, Slovak Medical University, Bratislava, Slovakia content of KYNA may contribute to antiepileptic and other central Paulina Rachwalska, Jan Bugajski Zebrafish, a vertebrate with complementary advantages to effects of valproate. rodents, has been recently widely used in laboratories of both basic Diabetes leads to development of osteoporosis. Streptozotocin Department of Physiology, Institute of Pharmacology, Polish Academy medical studies and clinical research. Combining the complexity of Acknowledgements: Supported by the grant from Medical Universi- (STZ) in a single dose induces experimental type 1 diabetes, of Sciences, Krako´w, Poland animal studies and in vitro high throughput screening, the ty of Lublin, No DS 457/2015. Paulina Fonderska and Łukasz Pyzio are whereas administration of nicotinamide (NA) 15 min earlier dose- zebrafish has proven to be a powerful tool for target identification, dependently protects against the STZ action. Trigonelline is an students in the Department of Experimental and Clinical Pharmacol- The aim of this study was to determine the effect of prior disease modelling and drug development. alkaloid with potential antidiabetic activity. The aim of the study ogy, Medical University in Lublin. repeated restraint stress (RS) on a single restraint-induced changes In our study, effects of p-gp inhibitors ritonavir and tariquidar was to investigate effects of trigonelline on diabetes-induced in IL-1b and nitric oxide synthase (NOS) levels in prefrontal cortex on the efficacy of levetiracetam in PTZ epilepsy model in 7 dpf disorders in the rat skeletal system. http://dx.doi.org/10.1016/j.pharep.2015.06.068 (PFC), hippocampus, hypothalamus and plasma and assess if these zebrafish larvae were investigated. After 24 h pretreatment period Effects of trigonelline (50 mg/kg po daily for 4 weeks) were alterations may influence HPA axis responses. Experiments were with levetiracetam and p-gp inhibitors larvae were deposited into investigated in 3-month-old female Wistar rats, which, 2 weeks performed on male Wistar rats. The first group consisted of control multiwell plate and then treated with 10 mM pentylenetetrazole before the start of trigonelline administration, received STZ Association of genetic variability with the non-stressed animals. In the second group, animals were subjected solution for epilepsy induction. Plate was then recorded by means (60 mg/kg ip) alone or STZ after NA (230 mg/kg ip). Serum bone antiplatelet effect of clopidogrel and to single restraint stress (RS) for 10 min. In the third group, the of camcorder and fish movement was tracked and then locomotion turnover markers, mineral density (BMD) and mechanical proper- concentration of inactive clopidogrel metabolite animals were restrained for 10 min twice a day repeatedly for 3, 7 parameters were analyzed. Results indicate that simultaneous use ties were studied. in patients after percutaneous coronary and 14 consecutive days and decapitated 24 h after the last of levetiracetam and p-gp inhibitors significantly changes move- STZ induced diabetes, with significant decreases in BMD and intervention (PCI) restraint. The fourth group consisted of prior repeatedly restrained ment patterns in 7 dpf larvae suggesting possible use in epilepsy worsening of cancellous bone mechanical properties (the tibial Barbara Gawron´ ska-Szklarz 1, Anna Czerkawska 1, rats (for 3, 7 and 14 days), which were subjected to 10 min restraint treatment. metaphysis). STZ after NA induced hyperglycemia lasting first 2 Urszula Adamiak-Giera 1, Szymon Ole˛dzki 2, stress 24 h after the last restraint period and rapidly decapitated 0, weeks of the experiment only; slight worsening of cancellous bone Mateusz Kurzawski 1, Maria Kałdon´ ska 1, 1, 2 and 3 h later. IL-1b, ACTH and corticosterone levels were http://dx.doi.org/10.1016/j.pharep.2015.06.071 mechanical properties and a decrease in vertebral BMD were Maria Jastrze˛bska 3, Krzysztof Safranow 4, determined in plasma using commercially available kits. IL-1b, demonstrated. Trigonelline tended to worsen bone mechanical Zdzisława Kornacewicz-Jach 2 neuronal nitric oxide synthase (nNOS) and inducible nitric oxide Antidepressant- and anxiolytic-like effects of properties and did not affect BMD in the diabetic rats. In NA/STZ- synthase (iNOS) levels in the above mentioned brain structures 1 ‘‘biased’’ 5-HT receptor agonists F15599 and treated rats, trigonelline significantly increased BMD and tended to Department of Pharmacology, Pomeranian Medical University, samples were analyzed by western blot procedure. The present 1A F13714 in rats improve cancellous bone strength. Szczecin, Poland results indicate time-related similarities in the potent alterations 2 1 1 In conclusion, trigonelline favorably affected the skeletal Department of Cardiolog, Pomeranian Medical University, Szczecin, in IL-1b levels in brain structures, and pituitary-adrenal hormones. Magdalena Jastrze˛bska-Wie˛sek , Anna Partyka , 1 ´ 2 system only in the non-diabetic (NA/STZ-treated) rats. A tendency Poland Single restraint for 10 min significantly decreases iNOS levels in Anna Wasik , Joanna Sniecikowska , 3 3 1 to worsen some skeletal parameters in the diabetic rats indicates Department of Laboratory Diagnostics and Molecular Medicine, PFC and hypothalamus. Repeated RS for 3 days most strongly Adrian Newman-Tancredi , Anna Wesołowska Pomeranian Medical University, Szczecin, Poland that, in certain conditions, trigonelline may damage bone. enhances iNOS level induced by single RS, which was gradually 1 4 Department of Clinical Pharmacy, Jagiellonian University Medical Department of Biochemistry and Medical Chemistry, Pomeranian reduced by prior RS for 7 and 14 days. Parallel but much weaker Medical University, Szczecin, Poland College, Krako´w, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.067 changes appear with nNOS level. In brain structures, changes in 2 Department of Pharmaceutical Chemistry, Jagiellonian University NOS levels induced by single RS are enhanced or reduced by prior Medical College, Krako´w, Poland The objective of this study was to investigate the contribution restraint, depending on brain structure and the period of prior 3 Effect of long-term administration of valproate Neurolixis Inc, San Diego, CA, USA of genetic polymorphism of CYP2C19, CYP3A4/5, ABCB1 and PON1 stress. Changes in the rapid and strong ACTH and corticosterone on tryptophan, kynurenine and kynurenic acid genes to the plasma concentrations of inactive metabolite of secretion, induced by a single restraint or preceded by repeated RS, content in rat brain cortex The 5-HT receptors have drawn attention as a target for clopidogrel and pharmacodynamic effect of clopidogrel in Polish do not seem to be directly correlated with alterations of IL-1b and 1A pharmacotherapy for variety CNS disorders. 5-HT receptors are Paulina Fonderska, Łukasz Pyzio, Izabela Zakrocka, patients. A total of 209 (149 M, 60 F) patients with CAD NOS levels in brain structures. 1A Waldemar A. Turski, Tomasz Kocki undergoing PCI who received dual antiplatelet therapy (clopido- expressed as both 5-HT1A autoreceptors, located in the raphe grel plus aspirin) were enrolled in this study. Whole blood for Acknowledgments: This research was supported by grant: POIG nucleus, and post-synaptic 5-HT1A heteroreceptors, located in Chair and Department of Experimental and Clinical Pharmacology, genotyping was taken before PCI. Each individual was genotyped 01.01.02-12-004/09-00 financed by European Regional Development various brain regions, i.e. cortex, hypothalamus and septum/ Medical University of Lublin, Lublin, Poland for SNPs marking CYP2C19, CYP3A4/5, ABCB1 and PON1 variant Fund as well as by the statutory funds from the Institute of Pharma- hippocampus. Activation of these serotonin receptors, in the different brain regions, exerts different effects. 5-HT receptor alleles. The allelic discrimination TaqMan real-time PCR assays cology, Polish Academy of Sciences. 1A Kynurenines are the metabolites of tryptophan formed along were used for detection. Concentration of clopidogrel inactive agonists have been investigated to function as antidepressants and kynurenine pathway. Among neuroactive kynurenines the role of anxiolytics. Furthermore, they are used as add-ons to atypical metabolite in plasma was determined in steady state 1–3.5 h http://dx.doi.org/10.1016/j.pharep.2015.06.070 kynurenic acid (KYNA) is well established. KYNA was shown to (mean 2 h) after clopidogrel administration. At the same time 1 antipsychotics, and also to ameliorate female sexual dysfunction display potent neuroprotective and anticonvulsive properties and sample of whole blood was taken to determine ADP-induced and Parkinson’s disease. Compounds F15599 and F13714 have its impaired production was implicated in the pathogenesis of platelet aggregation. Clopidogrel inactive metabolite concentra- P-glycoprotein inhibitors modulate been developed as two ‘‘biased’’ 5-HT1A receptor agonists. It has epilepsy and neurodegenerative disorders. Moreover, its anti- tion in plasma was determined by a HPLC method. ADP-induced levetiracetam effects in zebrafish epilepsy model been demonstrated that F15599 preferentially activates post- inflammatory and antioxidant properties were suggested. KYNA is platelet aggregation was assessed with multiple electrode Piotr Jakubowski 1, Michał Majewski 1, synaptic 5-HT1A heteroreceptors over raphe-located autorecep- synthesized mainly within astrocytes by kynurenine aminotrans- platelet aggregometry using a Muliplate analyzer. Mann–Whit- Piotr Podlasz 2, Anna Jakimiuk 3, Natalia Kasica 2 tors, and F13714 exerts an opposite pharmacological profile with ferases (KAT I and II) from its bioprecursor, kynurenine (KYN). ney test was used to analyze associations of the quantitative more pronounced activity at raphe-located autoreceptors, and only 1 Department of Pharmacology and Toxicology, Faculty of Medical In the present study the influence of long-term administration variables with CYP2C19, CYP3A4/5, ABCB1 and PON1 genotypes. modest activation at post-synaptic heteroreceptors. The aim of this Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland of antiepileptic drug valproate on the synthesis of tryptophan General linear model was used to find independent predictors of study was to examine antidepressant- and anxiolytic-like effects of 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, (TRP), and its metabolites: KYN and KYNA in the brain cortex was clopidogrel metabolite concentration. Presence of CYP2C19*2 F15599 and F13714, administered orally 30 min before tests to University of Warmia and Mazury in Olsztyn, Olsztyn, Poland evaluated. allele was associated with higher ADP-induced platelet aggrega- rats. The antidepressant-like effect was investigated in the forced 3 Department of Pathophysiology, Forensic Veterinary and Adminis- Adult male Wistar rats were administered valproate (400 mg/ tion and presence of ABCB1 2677A allele was associated with swim test while anxiolytic-like activity was assessed in the conflict tration, Faculty of Veterinary Medicine, University of Warmia and kg, ip) for 14 days. Brain cortex was collected 24 h after the last lower clopidogrel metabolite concentration. There was no drinking Vogel and the elevated plus maze tests in rats. It would be Mazury in Olsztyn, Olsztyn, Poland injection of a drug and the level of TRP, KYN and KYNA were significant association between ADP-induced platelet aggrega- interesting if any differences in pharmacological activity would be assessed. TRP, KYN and KYNA were quantified using HPLC system tion and clopidogrel metabolite concentration. observed for these ‘‘biased’’ 5-HT1A receptor agonists. with UV–Vis and fluorometric detectors. Epilepsy is one of the most common neurological diseases with It was found that long-term administration of valproate 50–60 million people affected worldwide. Unfortunately, only 70% Supported by JU MC funds: K/ZDS/004121. http://dx.doi.org/10.1016/j.pharep.2015.06.069 significantly increased content of KYNA in brain cortex from of patients are effectively treated with currently available antiepileptic drugs (AEDs). One of the leading hypothesis for refractory http://dx.doi.org/10.1016/j.pharep.2015.06.072 24 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 25

Effect of trigonelline on oxidative stress markers nuclear factor–kB ligand) and OPG (osteoprotegerin) belonging to The results of the study may pave a way towards deeper coordination in the chimney test in mice. The anticonvulsant in lenses of rats with streptozotocin-induced the RANK/RANKL/OPG signaling pathway, are a cause of osteopo- understanding of the mechanism of action of antipsychotic drugs. activity of PGB in mice was determined in the mouse MES model by type 1 diabetes rosis. The aim of study was to investigate the distribution of denoting median effective potencies (ED50 values) of the drug Ilona Kaczmarczyk-Sedlak 1, Maria Zych 1, genotypes of OPG, RANK and RANKL polymorphisms and to http://dx.doi.org/10.1016/j.pharep.2015.06.075 administered either alone or in combination with ACEA (2.5 mg/kg, Joanna Folwarczna 2, Weronika Wojnar 1, analyze their relationship with bone parameters in postmeno- ip). Acute neurotoxicity of PGB manifesting in form of impairment 1 1 1 pausal women. Our results showed a higher frequency of AG of motor coordination in mice was assessed in the chimney test by Sławomir Dudek , Anna Bon´ ka , Lech Sedlak Isobolographic analysis of interactions for genotype and mutated G allele of the 163A>G polymorphism in calculating median toxic potencies (TD values) of PGB adminis- � selected three-drug combinations of 50 1 Department of Pharmacognosy and Phytochemistry, Medical Uni- OPG gene in women with osteoporosis. Analysis of the frequency of tered either alone or in combination with ACEA (2.5 mg/kg, ip). antiepileptic drugs in the maximal versity of Silesia, Katowice, Poland genotypes and alleles of RANK and RANKL polymorphisms showed Protective indices (PI values), as quotients of TD and ED values, electroshock-induced seizure test in mice 50 50 2 Department of Pharmacology, School of Pharmacy with the Division no statistically significant differences between study groups. were calculated either for PGB administered alone or in combination 1 1 of Laboratory Medicine, Medical University of Silesia, Katowice, However, the TT genotype and T allele of 643C>T polymorphism Maria W. Kondrat-Wro´ bel , Jan Wro´ bel , with ACEA. Results indicates that ACEA (2.5 mg/kg, ip) significantly � 2 3 Poland appeared more frequent in the group with osteoporosis and Mirosław Zagaja , Magdalena Florek-Łuszczki , enhanced the anticonvulsant action of PGB (p < 0.05) in the mouse 1,3 osteopenia compared to healthy women. These results suggest a Jarogniew J. Łuszczki MES model and simultaneously, it had no impact on the acute One of the major causes of cataract is oxidative stress induced participation of 163A>G polymorphism in osteoporosis devel- 1 neurotoxic effects of the antiepileptic drug in the chimney test in � Department of Pathophysiology Medical University, Lublin, Poland by increased level of reactive oxygen species (ROS), which occurs, opment. Moreover, the RANKL 643C>T polymorphism can have a 2 mice. The PI value for the combination of PGB with ACEA was 1.96 � Isobolographic Analysis Laboratory, Lublin, Poland among others, in diabetes mellitus (DM). Proper antioxidant significant influence on body weight and BMI in postmenopausal 3 Department of Public Health, Institute of Rural Health, Lublin, Poland and increased from that for PGB administered alone, which activity of the organism should be maintained to prevent the women with osteoporosis. amounted to 1.16. In conclusion, the simultaneous activation of cannabinoid CB receptors by the highly potent CB receptor agonist oxidative stress. An alkaloid trigonelline (TRG), occuring in The aim of this study was to isobolographically characterize 1 1 ACEA and blockade of voltage-gated calcium channels by PGB seems fenugreek and coffee seeds is considered as a potential hypogly- http://dx.doi.org/10.1016/j.pharep.2015.06.074 types of interactions for 3 selected three-drug combinations of to be synergistic from preclinical point of view. cemic compound. The aim of the study was to examine the effect of various antiepileptic drugs (lacosamide + topiramate + valproate, TRG on oxidative stress markers in lenses of rats with streptozo- Short- and long-term effect of clozapine on the lacosamide + oxcarbazepine + valproate and lacosamide + oxcarba- tocin-induced type 1 diabetes. http://dx.doi.org/10.1016/j.pharep.2015.06.077 mRNA expression of the genes encoding ErbB4- zepine + topiramate) in the maximal electroshock-induced seizure The study was conducted on female Wistar rats, divided into 3 PI3K pathway: A pilot study (MES) test in mice. Tonic hindlimb extension (seizure activity) was groups: I-control, II-DM, III-DM+TRG (50 mg/kg po; 4 weeks). The 1 2 evoked in albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s Effects of xanthotoxin on the anticonvulsant diabetes was induced by singular administration of streptozotocin Michał S. Karbownik , Janusz Szemraj , 1 3 stimulus duration) delivered via auricular electrodes. Type I action of various second-generation (60 mg/kg ip), and administration of TRG started 2 weeks Edward Kowalczyk , Tadeusz Pietras isobolographic analysis for the studied antiepileptic drugs (admin- antiepileptic drugs in the maximal afterwards. After 4 weeks, the rats were sacrificed, lenses were 1 Department of Pharmacology and Toxicology, Medical University of istered intraperitoneally for a fixed drug dose ratio of 1:1:1) was electroshock-induced seizure test in mice collected and homogenated in PBS. In 10% (w/v) homogenates, the Lodz, Ło´dz´, Poland used. Potential concurrent adverse-effect profiles of interactions of 1 2 activity of superoxide dismutase (SOD), catalase (CAT), glutathione 2 Maria W. Kondrat-Wro´ bel , Mirosław Zagaja , Department of Medical Biochemistry, Medical University of Lodz, three-drug combinations of the antiepileptic drugs were evaluated 3 1 peroxidase (GPx) and levels of glutathione (GSH) and thiobarbi- Magdalena Florek-Łuszczki , Daniel Pyrka , Ło´dz´, Poland in the chimney (motor performance), passive avoidance (long-term 1 4 turic acid reactive substances (TBARS) were determined. 3 Jan Wro´ bel , Krystyna Skalicka-Wozńiak , Department of Pneumology and Allergology, Medical University of memory), and grip-strength (muscular strength) tests. Results 5 1,2 Michał Glen´ sk , Jarogniew J. Łuszczki In lenses of DM rats, in comparison with the control rats, a Lodz, Ło´dz´, Poland indicates that the three-drug combinations of lacosamide + topir- statistically significant decrease of GSH and an increase of TBARS amate + valproate, lacosamide + oxcarbazepine + valproate and 1 Department of Pathophysiology, Medical University, Lublin, Poland along with a statistically insignificant decrease of CAT and 2 Introduction: The mechanism of clozapine’s unprecedented lacosamide + oxcarbazepine + topiramate (at the fixed drug dose Isobolographic Analysis Laboratory, Lublin, Poland increases of SOD and GPx were observed. Administration of TRG 3 therapeutic efficacy in the treatment of schizophrenia has not yet ratio of 1:1:1) exerted synergistic interaction with respect to their Department of Public Health, Institute of Rural Health, Lublin, Poland to DM rats resulted in statistically significant increases of GSH, CAT 4 been fully elucidated. Recently, it was reported that mRNA anticonvulsant activity in the mouse MES model. None of the studied Department of Pharmacognosy with Medicinal Plant Unit, Medical and GPx, and a decrease of TRABS, as well as an insignificant expression of neuregulin 1-downstream molecules encoded by three-drug combinations was associated with any concurrent University, Lublin, Poland increase of SOD as compared to DM control rats. 5 PIK3CD and PIK3R3 was increased in schizophrenia patients and adverse effects with regards to motor coordination, long-term Department of Pharmacognosy, Medical University, Wrocław, Poland In conclusion, TRG may prevent the development of cataract in associated with ERBB4 risk genotype. Pharmacological inhibition of memory or muscular strength. In conclusions, synergistic anti- type 1 diabetes in rats. p110d, a protein product of PIK3CD, was found to produce convulsant activity of the examined three-drug combinations The aim of this study was to evaluate the effects of xanthotoxin antipsychotic-like effect, and haloperidol was observed to decrease (lacosamide + topiramate + valproate, lacosamide + oxcarbazepine (8-methoxypsolaren – a naturally occurring coumarin) on the http://dx.doi.org/10.1016/j.pharep.2015.06.073 PIK3CD mRNA expression in an animal model [Law et al., Proc Natl + valproate and lacosamide + oxcarbazepine + topiramate) in the anticonvulsant potency of four second-generation antiepileptic Acad Sci U S A, 2012]. mouse MES model, could offer the patients with drug resistant drug (lamotrigine, oxcarbazepine, pregabalin and topiramate) The importance of gene polymorphisms in Aim of the study: The aim of the study was to examine if epilepsy some favorable triple therapy regimens, if the results from against maximal electroshock-induced tonic seizures (MES) in RANKL/RANK/OPG pathway in etiology of clozapine affects mRNA expression of ERBB4, PIK3CD, and PIK3R3 in this study would be translated into clinical settings. mice. Tonic hindlimb extension (seizure activity) was evoked in postmenopausal osteoporosis a cell line model in 24-h and 96-h incubation time periods. albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus http://dx.doi.org/10.1016/j.pharep.2015.06.076 Adam Kamin´ ski 1, Karolina Dziekan 1, Materials and methods: U-87MG human glioblastoma cell line duration) delivered via ear-clip electrodes. Potential concurrent Hubert Wolski 2, Radosław Kujawski 1, was used as an experimental model. Quantitative polymerase adverse-effect profiles of interactions between xanthotoxin and 1,3 1,4 chain reaction was used to examine the mRNA expression of the the second-generation antiepileptic drugs were evaluated in the Anna Bogacz , Marcin Oz˙ arowski , Influence of arachidonyl-20-chloroethylamide Bogusław Czerny 1,5, Małgorzata Go´ rska-Paukszta 1, genes. (ACEA) on the anticonvulsant and acute chimney test (motor performance). Results indicates that xantho- Agnieszka Seremak-Mrozikiewicz 1,2 Results: Clozapine produced no statistically significant changes neurotoxic effects of pregabalin in mice toxin administered intraperitoneally (100 mg/kg) significantly in mRNA expression of ERBB4. In 24-h culture no statistically enhanced the anticonvulsant potency of pregabalin and topir- Maria W. Kondrat-Wro´ bel 1, Mirosław Zagaja 2, 1 Institute of Natural Fibres and Medicinal Plants, Plewiska, Poland significant changes in mRNA expression of PIK3CD were observed, amate (p < 0.001) and oxcarbazepine (p < 0.01), but not that of Marta Andres-Mach 2, Magdalena M. Krysa 1, 2 Division of Perinatology and Women’s Diseases, Poznan University of however, in 96-h culture clozapine reduced PIK3CD mRNA lamotrigine in the mouse MES model. Xanthotoxin (50 mg/kg) Piotr L. Jaworski 1, Magdalena Florek-Łuszczki 3, Medical Sciences, Poznan´, Poland expression in 1 mM to 0.67 (p = 0.02), in 5 mM to 0.73 (p = 0.04), significantly potentiated the anticonvulsant potency of pregabalin Jarogniew J. Łuszczki 1,2 3 Department of Clinical Pharmacy and Biopharmacy, University of and in 20 mM to 0.56 (p = 0.001) of a baseline, respectively. In 24-h (p < 0.05) and topiramate (p < 0.001) and had no impact on the Medical Sciences, Poznan´, Poland culture no statistically significant changes in mRNA expression of 1 Department of Pathophysiology, Medical University, Lublin, Poland anticonvulsant potency of oxcarbazepine in the mouse MES model. 4 Department of Pharmaceutical Botany and Plant Biotechnology, PIK3R3 were observed, however, in 96-h culture clozapine reduced 2 Isobolographic Analysis Laboratory, Lublin, Poland None of the combinations of xanthotoxin (100 mg/kg) with University of Medical Sciences, Poznan´, Poland PIK3R3 mRNA expression in 20 mM to 0.63 (p = 0.02) of a baseline. 3 Department of Public Health, Institute of Rural Health, Lublin, Poland lamotrigine, oxcarbazepine and topiramate were associated with 5 Department of General Pharmacology and Pharmacoeconomics, Conclusions: Clozapine seems to decrease the mRNA expression any concurrent adverse effects with regards to motor coordination. Pomeranian Medical University, Szczecin, Poland of PIK3CD, and in high concentrations also PIK3R3, the genes The aim of this study was to determine the influence of In contrast, the combination of xanthotoxin (100 mg/kg) with recently found to be involved in schizophrenia ErbB4-PI3K pregabalin significantly impaired motor coordination in mice arachidonyl-20-chloroethylamide (ACEA – a highly potent canna- susceptibility pathway, but probably only in 96-h culture. The (p < 0.01), as compared to vehicle-treated animals. In conclusions, Studies have shown that disorders of bone metabolism which is binoid CB1 receptor agonist) on the anticonvulsant activity of regulated by three tumor necrosis factors, such as RANK (receptor results for clozapine are similar with that of haloperidol tested pregabalin (PGB – a second-generation antiepileptic drug) in the xanthotoxin (a naturally occurring coumarin) enhanced the activator of nuclear factor kappa B), RANKL (receptor activator of in an animal model by Law et al. [Proc Natl Acad Sci U S A, 2012]. maximal electroshock-induced seizure (MES) test and on motor anticonvulsant action of oxcarbazepine and topiramate in the 26 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 27 mouse MES model. The utmost caution is required when 1 Department of Clinical Pharmacology, Poznan University of Medical audiogenic seizure response. The doses of saturated fatty acids that 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- combining xanthotoxin with pregabalin due to the acute adverse Sciences, Poznan´, Poland did not influence locomotor activity in the open field test also did gy, Warszawa, Poland effects (impairment of motor coordination) that might appear. 2 Clinical Hospital of Przemienienia Pan´skiego in Poznan´, Poznan´, not alter sleep duration after intraperitoneal alcohol administra- 2 Department of Experimental and Clinical Pharmacology, Medical Xanthotoxin as a component of supplementary diet would Poland tion. Saturated fatty acids and EtOH increased corticosterone University of Warsaw, Warszawa, Poland contribute to seizure suppression in epileptic patients inadequate- concentration in the serum when administered separately and also 3 Department of Experimental and Clinical Pharmacology, Faculty of ly medicated with second-generation antiepileptic drugs, if the A major problem in both health and economic terms is the issue when administered together. The above-described changes were Biology and Earth Sciences, Jagiellonian University in Krakow, Krako´w, results from this study could be translated into clinical settings. of polypharmacy and polypragmasia. There is no standard significant when compared with controls. Biochemical data are, on Poland definition concerning polypragmasia. Polypharmacy is most the other hand, diverse and very difficult to interpret. http://dx.doi.org/10.1016/j.pharep.2015.06.078 commonly defined as receiving at least 5 drugs. Polypragmasia Conclusion: Presented data suggest that saturated fatty acids This study assessed behaviour as measured by positive is sometimes referred as uptake by the patient at least one drug for reduce spontaneous alcohol intake and severity of the withdrawal reinforcement-related 50 kHz calls in rats with different fear which there is no indication or more drugs than is clinically syndrome, they do not however influence the impact of a single conditioned response strength, i.e., low (LR) and high anxiety (HR) Effect of 2-methyl-6-(phenylethynyl)pyridine indicated. Such an approach in the case of older people is dose of alcohol. The biochemical mechanism of those actions is yet rats after amphetamine injection in two injection protocol (TIPS). hydrochloride (MPEP) on the anticonvulsant sometimes limited due to occurring multidisease. The study to be further studied. The results showed that the first dose of amphetamine evoked action of lamotrigine, oxcarbazepine, pregabalin presents the analysis of 120 case records of patients hospitalized in similar behavioural effects in frequency-modulated (FM 50-kHz and topiramate in the maximal electroshock- http://dx.doi.org/10.1016/j.pharep.2015.06.081 2014 in 15 wards of the Hospital of Przemienienia Pan´ skiego in calls) in the LR and HR rats. The second injection of amphetamine induced seizure test in mice Poznan´ (anesthesia, chemotherapy, surgery, gynecology, oncology, resulted in stronger FM 50-kHz calls in LR compared with HR rats. 1 ˙ 2 Maria W. Kondrat-Wro´ bel , Dorota Zo´ łkowska , hematology, cardiology, palliative medicine, ophthalmology, Peripheral inflammation affects function of The biochemical data (ex vivo) showed that LR rats had increased 1,3 Jarogniew J. Łuszczki pulmonological). 36 were randomly selected stories, 52 stories trigeminal neurons in mice basal levels of dopamine in the amygdala and increased homo- 1 Department of Pathophysiology, Medical University, Lublin, Poland of patients whose pharmacotherapy consisted of 5 and more drugs Olga Kuzawin´ ska, Krzysztof Lis, vanilic acid (HVA), dopamine’s main metabolite in the cortex and 2 Department of Neurology, School of Medicine, University of and 32 stories of patients over 80 years of age. Tomasz Grygorowicz, Agnieszka Cudna, amygdala. Moreover, the in vivo (microdialysis) study showed that California, Davis, Sacramento, CA, USA That assessment concerned the validity of used drugs and the Marta Da˛browska, Dagmara Mirowska-Guzel, the LR rats had increased HVA concentrations in the basolateral 3 Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, prevalence of: polypharmacy, adverse effects and drug interac- Ewa Bałkowiec-Iskra amygdala, in response to an aversive context. The data suggest that Poland tions. Analysis confirmed the validity of therapy. The use of HR and LR rats have different reactivity of the reward pathways. It appropriate treatment fit to patients’ health status and concurrent Department of Experimental and Clinical Pharmacology, Medical is supposed that the differences in the activity in the amygdala- disease, helped to avoid clinically significant drug interactions and University of Warsaw, Warszawa, Poland cortex circuitry may be one of the biological factors that underlie The aim of this study was to evaluate the effects of 2-methyl-6- serious adverse effects. Registered adverse reactions were quickly individual differences in the response to fear stimuli and the (phenylethynyl)pyridine hydrochloride (MPEP – a potent and diagnosed allowing for their effective treatment. Our previous studies showed that inflammatory reaction in the rewarding effects of amphetamine. highly selective non-competitive antagonist at the mGlu5 receptor area of trigeminal ganglion (TG) nociceptive endings affects subtype and a positive allosteric modulator at mGlu4 receptors) on neurochemical properties of TG, causing increase in concentration This study was supported by the Grant No. UMO-2011/03/B/N4/ http://dx.doi.org/10.1016/j.pharep.2015.06.080 the anticonvulsant potency of four second-generation antiepileptic of both brain-derived neurotrophic factor (BDNF) and calcitonin 02385 Institute of Psychiatry and Neurology in Warsaw, Poland drug (lamotrigine [LTG], oxcarbazepine [OXC], pregabalin [PGB] gene-related peptide (CGRP). In the present study, we have and from the National Science Centre, Poland. and topiramate [TPM]) against maximal electroshock-induced Ketogenic diet suppresses spontaneous ethyl employed CFA-induced TG inflammation model to begun investi- tonic seizures (MES) in mice. Tonic hindlimb extension (seizure alcohol intake and reduces withdrawal gating the underlying molecular mechanisms of the inflammation- http://dx.doi.org/10.1016/j.pharep.2015.06.083 activity) was evoked in albino Swiss mice by a current (25 mA, syndrome in rats induced changes in trigeminal neurons properties. 500 V, 50 Hz, 0.2 s stimulus duration) delivered via ear-clip 1 2 Paweł Krza˛sćik , Wanda Dyr , A model of orofacial inflammation was obtained by local ip 2 2 Expression of drug transporters along the electrodes. MPEP was administered intraperitoneally ( ) in Edyta Wyszogrodzka , Danuta Turzyn´ ska , injection of CFA to the mice left whisker pad. Pain reaction was increasing doses of 0.5–2.0 mg/kg, so as to determine its influence 2 2 human gastrointestinal tract Alicja Sobolewska , Anna Sko´ rzewska , assessed every day by von-Frey filaments. Seven and 14 days after 1 2 3 on the threshold for electroconvulsions in mice. The antiepileptic Jerzy Walkowiak 2, Małgorzata Zajda 1, CFA injection mice were euthanized. Both TG were removed for Joanna Łapczuk , Jette Peters , Marek Ostrowski , drugs (LTG, OXC, PGB and TPM) were administered ip either alone 1,2 2 2 Adam Płazńik quantitative PCR analysis of differences in concentration and Werner Siegmund , Stefan Oswald , or in combination with MPEP in increasing doses so as to expression of BDNF, CGRP and selected proinflammatory cyto- Marek Droz´dzik 1 1 determine their median effective doses (ED50 values) in the MES Department of Experimental and Clinical Pharmacology, Medical kines, separately in the left and the right TG, both in male and 1 test. Results indicate that MPEP in doses of 1.5 and 2 mg/kg University, Warszawa, Poland female mice. Immunostaining using primary antibodies against Department of Experimental and Clinical Pharmacology, Pomeranian significantly elevated (p < 0.05 and p < 0.001) the threshold for 2 Department of Pharmacology and Physiology of the Nervous System, Medical University, Szczecin, Poland BDNF and TRPV1 and then with secondary antibodies conjugated 2 electroconvulsions in mice. MPEP administered ip at a dose of 1 mg/ Institute Psychiatry and Neurology, Warszawa, Poland with Alexa Fluor was performed after perfusion with 250 ml of 4% Department of Clinical Pharmacology, University of Greifswald, kg significantly enhanced the anticonvulsant potency of pregabalin Greifswald, Germany paraformaldehyde. Trigeminal ganglion were removed from the 3 and topiramate (p < 0.05), but not that of lamotrigine or oxcarba- Objective: In the present study we analyzed the influence of orally sculls, crioprotected and cut on the 20 microm sections. Department of General and Transplantation Surgery, Pomeranian zepine in the mouse MES model. In contrast, MPEP at a dose of administered basic ingredients of the ketogenic diet – saturated Our results indicate that response of TG to peripheral Medical University, Szczecin, Poland 0.5 mg/kg had no impact on the anticonvulsant potency of all the fatty acids: octanoic acid and decanonic acid (a mixture propor- inflammatory reaction is gender-dependent, what may explain studied antiepileptic drugs in the mouse MES model. In conclusions, tioned 89:11) on the influence of ethyl alcohol (EtOH) in rats. differences in frequency and severity of trigeminal nerve – Intestinal expression and function of transporter proteins are MPEP as the potent and highly selective non-competitive antagonist Methods: 1. Influence of saturated fatty acids on spontaneous associated disorders observed between women and men. crucial determinants of the oral absorption of many drugs. of mGlu5 and the positive allosteric modulator of mGlu4 receptors intake of alcohol and sacharosis in rats with high alcohol TG neurons in female mice showed increased expression of However, expression profile of drug transporters is not homoge- potentiated the anticonvulsant action of PGB and TPM in the mouse preference (WHP). CGRPa, this neuropeptide may act as the main mediator of nous along the GI tract, which might be the reason for site- MES model. The inhibition of mGlu5 receptors by MPEP in the brain 2. Influence of saturated fatty acids on audiogenic seizure trigeminal signaling during migraine. dependent absorption of several drugs. The aim of this study was to might contribute to the reduction of seizures in experimental response (ASR) in EtOH withdrawal in rats. comprehensively analyse the expression of clinically relevant This project has been supported by the Polish National Science Center, animals receiving PGB and TPM. 3. Influence of saturated fatty acids on duration of sleep induced transporter proteins along the human gastrointestinal tract. based on the Decision No. DEC-2012/05/B/NZ4/02385. by intraperitoneal alcohol administration. Intestinal tissue was obtained from eight organ donors, with no 4. Influence of saturated fatty acids on the open field test. documented gastrointestinal diseases. From each donor samples http://dx.doi.org/10.1016/j.pharep.2015.06.079 http://dx.doi.org/10.1016/j.pharep.2015.06.082 5. Analysis of influence of saturated fatty acids on corticoste- from the duodenum, jejunum, ileum and colon (ascending, rone plasma concentration in rats. transverse, descending and sigmoid) were taken. The quantitative Analysis of medical records of patients 6. Analysis of influence of saturated fatty acids on NA, DA, 5-HT Rewarding effect of amphetamine on 50 kHz expression of 27 transporter genes (ABC: 6, SLC: 21) was performed hospitalized in the Clinical Hospital of TM and their metabolites’ concentrations as well as concentrations of USV is stronger in the ‘low’ anxiety rats in 7900HT Real Time PCR System using predesigned TaqMan low Przemienienia Pan´ skiego in Poznan taurin, glutamine, glycine, alanine, aspargic acetate, glutaminergic 1 1 density array cards and the gene expression was calculated as the 1 1 Małgorzata Lehner , Ewa Taracha , Katarzyna Korzeniowska , Ewa Kaz´mierczk , acetate and GABA in frontal cortex, striatum, hippocampus and 1 2 relative expression to the endogenous control 18S rRNA (DCT 1 1 Ewelina Kaniuga , Aleksandra Wisłowska-Stanek , Iwona Andrys-Wawrzyniak , Iwona Smolarek , PVN tissue homogenates. 3 1 method). All ABC transporters included into analysis could be 1 1 2 Jacek Wro´ bel , Alicja Sobolewska , Artur Cies´lewicz , Anna Jabłecka , Hanna Gracz , Results: Saturated fatty acids dose-dependently suppressed 1 1 detected in all intestinal regions. The expression of ABCB1, ABCC2, 2 2 Danuta Turzyn´ ska , Anna Sko´ rzewska , Anna Głowacka , Jolanta Nagadowska spontaneous alcohol intake by WHP rats. They also suppressed Adam Płazńik 1,2 and ABCG2 increased from duodenum to jejunum (significant for 26 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 27 mouse MES model. The utmost caution is required when 1 Department of Clinical Pharmacology, Poznan University of Medical audiogenic seizure response. The doses of saturated fatty acids that 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- combining xanthotoxin with pregabalin due to the acute adverse Sciences, Poznan´, Poland did not influence locomotor activity in the open field test also did gy, Warszawa, Poland effects (impairment of motor coordination) that might appear. 2 Clinical Hospital of Przemienienia Pan´skiego in Poznan´, Poznan´, not alter sleep duration after intraperitoneal alcohol administra- 2 Department of Experimental and Clinical Pharmacology, Medical Xanthotoxin as a component of supplementary diet would Poland tion. Saturated fatty acids and EtOH increased corticosterone University of Warsaw, Warszawa, Poland contribute to seizure suppression in epileptic patients inadequate- concentration in the serum when administered separately and also 3 Department of Experimental and Clinical Pharmacology, Faculty of ly medicated with second-generation antiepileptic drugs, if the A major problem in both health and economic terms is the issue when administered together. The above-described changes were Biology and Earth Sciences, Jagiellonian University in Krakow, Krako´w, results from this study could be translated into clinical settings. of polypharmacy and polypragmasia. There is no standard significant when compared with controls. Biochemical data are, on Poland definition concerning polypragmasia. Polypharmacy is most the other hand, diverse and very difficult to interpret. http://dx.doi.org/10.1016/j.pharep.2015.06.078 commonly defined as receiving at least 5 drugs. Polypragmasia Conclusion: Presented data suggest that saturated fatty acids This study assessed behaviour as measured by positive is sometimes referred as uptake by the patient at least one drug for reduce spontaneous alcohol intake and severity of the withdrawal reinforcement-related 50 kHz calls in rats with different fear which there is no indication or more drugs than is clinically syndrome, they do not however influence the impact of a single conditioned response strength, i.e., low (LR) and high anxiety (HR) Effect of 2-methyl-6-(phenylethynyl)pyridine indicated. Such an approach in the case of older people is dose of alcohol. The biochemical mechanism of those actions is yet rats after amphetamine injection in two injection protocol (TIPS). hydrochloride (MPEP) on the anticonvulsant sometimes limited due to occurring multidisease. The study to be further studied. The results showed that the first dose of amphetamine evoked action of lamotrigine, oxcarbazepine, pregabalin presents the analysis of 120 case records of patients hospitalized in similar behavioural effects in frequency-modulated (FM 50-kHz and topiramate in the maximal electroshock- http://dx.doi.org/10.1016/j.pharep.2015.06.081 2014 in 15 wards of the Hospital of Przemienienia Pan´ skiego in calls) in the LR and HR rats. The second injection of amphetamine induced seizure test in mice Poznan´ (anesthesia, chemotherapy, surgery, gynecology, oncology, resulted in stronger FM 50-kHz calls in LR compared with HR rats. 1 ˙ 2 Maria W. Kondrat-Wro´ bel , Dorota Zo´ łkowska , hematology, cardiology, palliative medicine, ophthalmology, Peripheral inflammation affects function of The biochemical data (ex vivo) showed that LR rats had increased 1,3 Jarogniew J. Łuszczki pulmonological). 36 were randomly selected stories, 52 stories trigeminal neurons in mice basal levels of dopamine in the amygdala and increased homo- 1 Department of Pathophysiology, Medical University, Lublin, Poland of patients whose pharmacotherapy consisted of 5 and more drugs Olga Kuzawin´ ska, Krzysztof Lis, vanilic acid (HVA), dopamine’s main metabolite in the cortex and 2 Department of Neurology, School of Medicine, University of and 32 stories of patients over 80 years of age. Tomasz Grygorowicz, Agnieszka Cudna, amygdala. Moreover, the in vivo (microdialysis) study showed that California, Davis, Sacramento, CA, USA That assessment concerned the validity of used drugs and the Marta Da˛browska, Dagmara Mirowska-Guzel, the LR rats had increased HVA concentrations in the basolateral 3 Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, prevalence of: polypharmacy, adverse effects and drug interac- Ewa Bałkowiec-Iskra amygdala, in response to an aversive context. The data suggest that Poland tions. Analysis confirmed the validity of therapy. The use of HR and LR rats have different reactivity of the reward pathways. It appropriate treatment fit to patients’ health status and concurrent Department of Experimental and Clinical Pharmacology, Medical is supposed that the differences in the activity in the amygdala- disease, helped to avoid clinically significant drug interactions and University of Warsaw, Warszawa, Poland cortex circuitry may be one of the biological factors that underlie The aim of this study was to evaluate the effects of 2-methyl-6- serious adverse effects. Registered adverse reactions were quickly individual differences in the response to fear stimuli and the (phenylethynyl)pyridine hydrochloride (MPEP – a potent and diagnosed allowing for their effective treatment. Our previous studies showed that inflammatory reaction in the rewarding effects of amphetamine. highly selective non-competitive antagonist at the mGlu5 receptor area of trigeminal ganglion (TG) nociceptive endings affects subtype and a positive allosteric modulator at mGlu4 receptors) on neurochemical properties of TG, causing increase in concentration This study was supported by the Grant No. UMO-2011/03/B/N4/ http://dx.doi.org/10.1016/j.pharep.2015.06.080 the anticonvulsant potency of four second-generation antiepileptic of both brain-derived neurotrophic factor (BDNF) and calcitonin 02385 Institute of Psychiatry and Neurology in Warsaw, Poland drug (lamotrigine [LTG], oxcarbazepine [OXC], pregabalin [PGB] gene-related peptide (CGRP). In the present study, we have and from the National Science Centre, Poland. and topiramate [TPM]) against maximal electroshock-induced Ketogenic diet suppresses spontaneous ethyl employed CFA-induced TG inflammation model to begun investi- tonic seizures (MES) in mice. Tonic hindlimb extension (seizure alcohol intake and reduces withdrawal gating the underlying molecular mechanisms of the inflammation- http://dx.doi.org/10.1016/j.pharep.2015.06.083 activity) was evoked in albino Swiss mice by a current (25 mA, syndrome in rats induced changes in trigeminal neurons properties. 500 V, 50 Hz, 0.2 s stimulus duration) delivered via ear-clip 1 2 Paweł Krza˛sćik , Wanda Dyr , A model of orofacial inflammation was obtained by local ip 2 2 Expression of drug transporters along the electrodes. MPEP was administered intraperitoneally ( ) in Edyta Wyszogrodzka , Danuta Turzyn´ ska , injection of CFA to the mice left whisker pad. Pain reaction was increasing doses of 0.5–2.0 mg/kg, so as to determine its influence 2 2 human gastrointestinal tract Alicja Sobolewska , Anna Sko´ rzewska , assessed every day by von-Frey filaments. Seven and 14 days after 1 2 3 on the threshold for electroconvulsions in mice. The antiepileptic Jerzy Walkowiak 2, Małgorzata Zajda 1, CFA injection mice were euthanized. Both TG were removed for Joanna Łapczuk , Jette Peters , Marek Ostrowski , drugs (LTG, OXC, PGB and TPM) were administered ip either alone 1,2 2 2 Adam Płazńik quantitative PCR analysis of differences in concentration and Werner Siegmund , Stefan Oswald , or in combination with MPEP in increasing doses so as to expression of BDNF, CGRP and selected proinflammatory cyto- Marek Droz´dzik 1 1 determine their median effective doses (ED50 values) in the MES Department of Experimental and Clinical Pharmacology, Medical kines, separately in the left and the right TG, both in male and 1 test. Results indicate that MPEP in doses of 1.5 and 2 mg/kg University, Warszawa, Poland female mice. Immunostaining using primary antibodies against Department of Experimental and Clinical Pharmacology, Pomeranian significantly elevated (p < 0.05 and p < 0.001) the threshold for 2 Department of Pharmacology and Physiology of the Nervous System, Medical University, Szczecin, Poland BDNF and TRPV1 and then with secondary antibodies conjugated 2 electroconvulsions in mice. MPEP administered ip at a dose of 1 mg/ Institute Psychiatry and Neurology, Warszawa, Poland with Alexa Fluor was performed after perfusion with 250 ml of 4% Department of Clinical Pharmacology, University of Greifswald, kg significantly enhanced the anticonvulsant potency of pregabalin Greifswald, Germany paraformaldehyde. Trigeminal ganglion were removed from the 3 and topiramate (p < 0.05), but not that of lamotrigine or oxcarba- Objective: In the present study we analyzed the influence of orally sculls, crioprotected and cut on the 20 microm sections. Department of General and Transplantation Surgery, Pomeranian zepine in the mouse MES model. In contrast, MPEP at a dose of administered basic ingredients of the ketogenic diet – saturated Our results indicate that response of TG to peripheral Medical University, Szczecin, Poland 0.5 mg/kg had no impact on the anticonvulsant potency of all the fatty acids: octanoic acid and decanonic acid (a mixture propor- inflammatory reaction is gender-dependent, what may explain studied antiepileptic drugs in the mouse MES model. In conclusions, tioned 89:11) on the influence of ethyl alcohol (EtOH) in rats. differences in frequency and severity of trigeminal nerve – Intestinal expression and function of transporter proteins are MPEP as the potent and highly selective non-competitive antagonist Methods: 1. Influence of saturated fatty acids on spontaneous associated disorders observed between women and men. crucial determinants of the oral absorption of many drugs. of mGlu5 and the positive allosteric modulator of mGlu4 receptors intake of alcohol and sacharosis in rats with high alcohol TG neurons in female mice showed increased expression of However, expression profile of drug transporters is not homoge- potentiated the anticonvulsant action of PGB and TPM in the mouse preference (WHP). CGRPa, this neuropeptide may act as the main mediator of nous along the GI tract, which might be the reason for site- MES model. The inhibition of mGlu5 receptors by MPEP in the brain 2. Influence of saturated fatty acids on audiogenic seizure trigeminal signaling during migraine. dependent absorption of several drugs. The aim of this study was to might contribute to the reduction of seizures in experimental response (ASR) in EtOH withdrawal in rats. comprehensively analyse the expression of clinically relevant This project has been supported by the Polish National Science Center, animals receiving PGB and TPM. 3. Influence of saturated fatty acids on duration of sleep induced transporter proteins along the human gastrointestinal tract. based on the Decision No. DEC-2012/05/B/NZ4/02385. by intraperitoneal alcohol administration. Intestinal tissue was obtained from eight organ donors, with no 4. Influence of saturated fatty acids on the open field test. documented gastrointestinal diseases. From each donor samples http://dx.doi.org/10.1016/j.pharep.2015.06.079 http://dx.doi.org/10.1016/j.pharep.2015.06.082 5. Analysis of influence of saturated fatty acids on corticoste- from the duodenum, jejunum, ileum and colon (ascending, rone plasma concentration in rats. transverse, descending and sigmoid) were taken. The quantitative Analysis of medical records of patients 6. Analysis of influence of saturated fatty acids on NA, DA, 5-HT Rewarding effect of amphetamine on 50 kHz expression of 27 transporter genes (ABC: 6, SLC: 21) was performed hospitalized in the Clinical Hospital of TM and their metabolites’ concentrations as well as concentrations of USV is stronger in the ‘low’ anxiety rats in 7900HT Real Time PCR System using predesigned TaqMan low Przemienienia Pan´ skiego in Poznan taurin, glutamine, glycine, alanine, aspargic acetate, glutaminergic 1 1 density array cards and the gene expression was calculated as the 1 1 Małgorzata Lehner , Ewa Taracha , Katarzyna Korzeniowska , Ewa Kaz´mierczk , acetate and GABA in frontal cortex, striatum, hippocampus and 1 2 relative expression to the endogenous control 18S rRNA (DCT 1 1 Ewelina Kaniuga , Aleksandra Wisłowska-Stanek , Iwona Andrys-Wawrzyniak , Iwona Smolarek , PVN tissue homogenates. 3 1 method). All ABC transporters included into analysis could be 1 1 2 Jacek Wro´ bel , Alicja Sobolewska , Artur Cies´lewicz , Anna Jabłecka , Hanna Gracz , Results: Saturated fatty acids dose-dependently suppressed 1 1 detected in all intestinal regions. The expression of ABCB1, ABCC2, 2 2 Danuta Turzyn´ ska , Anna Sko´ rzewska , Anna Głowacka , Jolanta Nagadowska spontaneous alcohol intake by WHP rats. They also suppressed Adam Płazńik 1,2 and ABCG2 increased from duodenum to jejunum (significant for 28 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 29

ABCB1 and ABCC2), where all mentioned transporters reached their 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- IL-17A and IL-17F gene polymorphism are not the important factors Materials and methods: 24 male Wistar rats receiving normal highest expression levels and decreased significantly in ileum and gy, Warszawa, Poland associated with susceptibility and some clinical parameters of RA in a diet were used in the experiment. On Day 1 rats were divided colon. In all intestinal segments, ABCC3 was the most abundant 2 Department of Experimental and Clinical Pharmacology, Centre for Polish population. randomly in two groups: ABC transporter. As for the analyzed SLC transporters no mRNA Preclinical Research and Technology CePT, Medical University of expression could be observed for OATP1A2, OATP1B1 and OATP1B3 Warsaw, Warszawa, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.087 1. Group P – rats receiving pantoprazole (3 mg/kg) along the entire GI tract, whereas OATP4C1, MATE 1/2, OCT1, OCTN1, 2. Group C (control group) – rats receiving saline solution PEPT2 revealed very low expression level. The expression of PEPT1, The effects of a ketogenic diet in controlling seizure activity The effect of testosterone and endurance OST / , OATP2B1 significantly increase from duodenum to Saline solution and pantoprazole were given intraperitoneally a b have been proven in many studies, although its mechanism of training on signaling pathways in the rat spinal jejunum, whereas the expression of OST and PEPT1 were found once daily for 84 days. On Day 85 blood samples were collected. a action has not been clearly established. The aim of this study was cord to be significantly decreased from jejunum to colon. In conclusion, to investigate the influence of octanoic and decanoic fatty acids Serum calcium and phosphate levels were assessed in certified Andrzej Małecki 1,*, Katarzyna Nierwin´ ska 1, each segment of gastrointestinal tract is characterized by different (FA), the main components in the medium-chain triglyceride laboratory. Anna Pudełko 2, Jo´ zef Langfort 1, Marta Nowacka 1 gene expression pattern of drug transporters. However, the highest diet, on the metabolism of TRP, the activity of the kynurenic Results: Serum calcium level was significantly decreased in level of mRNA of the analyzed genes was found in jejunum. pathway and the concentrations of monoamines and amino 1 rats receiving pantoprazole comparing to control group (9.6250 The Jerzy Kukuczka Academy of Physical Education in Katowice, � acids, including branched amino acids (BCAA) and aromatic 0.5463 mg/dl vs. 10.1545 0.3778 mg/dl, p = 0.014). No significant Katowice, Poland � http://dx.doi.org/10.1016/j.pharep.2015.06.084 amino acids (AAA). The acute effects of FA on the sedation index 2 Department of Pharmacology, Medical University of Silesia, Kato- difference in serum phosphate levels between analyzed groups was and hippocampal electrical after-discharge threshold were also detected (4.9083 0.7154 mg/dl in group P vs. 5.0636 1.2118 mg/ wice, Poland � � assessed. dl in group C, p > 0.05). No significant differences between analyzed Association of catechol-O-methyltransferase *Corresponding author. [email protected] We observed that intra-gastric administration of FA led to groups in age and body weight on Day 85 were detected. gene variability with pain sensitivity in patients increases in the brain levels of TRP and in the central and Summary: Long-term therapy with pantoprazole may lead to after hip replacement We have estimated the impact of two doses of testosterone on peripheral concentration of kynurenic acid, as well as to decrease in serum calcium level. 1 the signaling pathways in rat spinal cord and BDNF, VEGF and heat Anna Machoy-Mokrzyn´ ska , significant changes in the brain and plasma concentrations of 1 1 shock protein (Hsp70) in the rat spinal cord. Zuzanna Starzyn´ ska-Sadura , Monika Białecka , BCAA and AAA. We found that the administration of FA clearly http://dx.doi.org/10.1016/j.pharep.2015.06.089 1 2 Adult male Wistar rats were trained using a motor-driven Mateusz Kurzawski , Krzysztof Safranow , increased the seizure threshold and induced sedation. Further- 3 1 treadmill for 6 weeks (40–60 min 5 times a week) and/or were Andrzej Bohatyrewicz , Marek Droz´dzik more, we have demonstrated that blocking TRP passage into the treated (6 wks) with two doses of testosterone (i.m.; 8 mg/kg or Impact of carvedilol on ADMA–DDAH pathway 1 brain, abolishes these effects of FA but had no similar effect on the Department of Pharmacology, Pomeranian Medical University, 80 mg/kg body weight). Spinal cords were collected 48 hours after and IL1-beta level after single dose formation of ketone bodies. Given that FA are major components Szczecin, Poland the last training cycle and stored at 80 8C. Proteins employed in cyclophosphamide administration in rat model � 2 Department of Biochemistry and Medical Chemistry, Szczecin, Poland of a ketogenic diet, it is suggested that the anticonvulsant effects signaling pathways (p-Akt, PKC, pERK1/2, p-p38) as well as BDNF, Anna Merwid-La˛d *, Małgorzata Trocha, 3 Department of Orthopaedics, Traumatology and Musculoskeletal of a ketogenic diet may be partly dependent on changes in TRP VEGF-A, VEGF-C and HSP70 levels were measured using Western Ewa Chlebda-Sieragowska, Marta Szandruk, Oncology, Pomeranian Medical University, Szczecin, Poland metabolism. blot method in whole tissue lysates of spinal cord. Beata Nowak, Tomasz Sozan´ ski, Some of the effects of the endurance training and testosterone The study was supported by Grant No. 2014/13/B/NZ7/02277 from Małgorzata Piesńiewska, Adam Szela˛g may be associated with increased signal transmission associated The aim of this study was to determine association between the National Science Centre, Poland. genetic polymorphism of the COMT gene and pain perception. with nitric oxide and protein kinase systems. Endurance training, Department of Pharmacology, Wroclaw Medical University, Wrocław, Genetic polymorphisms of catechol-O-methyltransferase (COMT) testosterone (8 mg/kg) and their combination increased VEGF-A Poland http://dx.doi.org/10.1016/j.pharep.2015.06.086 (rs4680:A > G – Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C and decreased VEGF-C levels. The higher dose of testosterone *Corresponding author. > G) and pain sensitivity after hip replacement due to coxarthrosis reduced both isoforms of VEGF. Endurance training could only were studied. The postoperative pain intensity was measured by IL-17A and IL-17F gene polymorphisms in partially offset the adverse effects of high doses of testosterone. Cyclophosphamide-induced (CPX) tissue damages are con- VAS – Visual Analogue Scale after 6 weeks as well as 6 and 12 patients with rheumatoid arthritis Training used separately did not affect the amount of BDNF in nected to the induction of oxidative stress and proinflammatory months following the orthopedic surgery genomic DNA was Damian Malinowski 1, Violetta Dziedziejko 2, spinal cord tissue homogenates. The higher dose of testosterone cytokines in tissues. This may influence ADMA level and DDAH extracted from whole blood samples. The SNPs (single nucleotide Krzysztof Safranow 2, Andrzej Pawlik 1 used alone and combined with endurance training led to decrease activity. Carvedilol is considered as strong antioxidant. The aim of polymorphism) within the COMT gene were evaluated using in BDNF protein. Obtained results suggest, that excessive supply this study was to check impact of carvedilol on CPX-induced 1 Taqman genotyping assays. Haplotypes were classified in accord- Department of Pharmacokinetics and Therapeutic Drug Monitoring, of testosterone may cause undesirable influence on the spinal changes in ADMA/DDAH pathway and IL1-beta concentration. ing to COMT activity: A_C_C_G – low, A_T_C_A – medium and Pomeranian Medical University, Szczecin, Poland cord. Male rats were given single intraperitoneal dose of 200 mg/kg of 2 G_C_G_G – high activity. Analysis of associations between COMT Department of Biochemistry and Medical Chemistry, Pomeranian cyclophosphamide. Carvedilol was given once daily at a dose of genotypes and clinical outcomes was performed by means of Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.088 2 mg/kg by gastric tube a day before, at the day and one day after Mann–Whitney U test. General linear model was used for CPX injection. Intraperitoneal injections of mesna (200 mg/kg) multivariate analysis. Carriers of the following variants: rs6269 Rheumatoid arthritis (RA) is a chronic inflammatory disease Influence of pantoprazole, a proton-pump were done 20 min before, 4 and 8 h after CPX administration, G, rs4818 G, rs4633 C, as well as carriers of the high activity COMT associated with the destruction of affected joints. Numerous inhibitor, on serum calcium and phosphate divided into 20%, 40% and 40% doses, respectively. Rats in haplotype (G_C_G_G) declared lower pain intensity after 12 cytokines play the important role in the RA pathogenesis, which levels in rats experimental groups received as follows: C – normal saline, X – months from hip replacement when compared to non-carriers. initiate and maintenance the inflammatory response in joints. CPX, MX – CPX + mesna, VX – CPX + carvedilol, MVX – CPX + mes- Agnieszka Matuszewska *, Beata Nowak, The results of this study indicate that polymorphism of the COMT Interleukin-17 plays important role in the pathogenesis of RA. The na + carvedilol. Levels of ADMA in serum and IL1-beta in kidney Anna Merwid-La˛d, Marta Szandruk, gene may play a role in the mechanism of pain perception. We aim of this study was to examine the associations between were measured using ELISA kit. DDAH activity was determined Joanna Kwiatkowska, Małgorzata Piesńiewska, conclude that haplotype accountable for high metabolic activity of polymorphisms in the IL-17A and IL-17F genes and RA. Previous spectrophotometrically in liver. Serum ADMA level was signifi- Adam Szela˛g COMT enzyme was correlated with lower pain sensitivity in reports have linked IL-17 to the pathogenesis of RA. We examined cantly increased in X group in comparison to the control. This patents after hip replacement. 422 patients (340 female, 82 male, mean age 57.5 12.4 years) action of CPX was significantly reversed only in groups receiving � Department of Pharmacology, Medical University, Wrocław, Poland with rheumatoid arthritis diagnosed according to the criteria of *Corresponding author. mesna (MX and MVX), but not in the group receiving carvedilol http://dx.doi.org/10.1016/j.pharep.2015.06.085 American College of Rheumatology/European League against Rheu- alone. DDAH activity was comparable in all studied groups and any matism and 338 subjects as a control group. Single nucleotide Background: Proton-pump inhibitors (PPIs) belong to wildly significant differences were noticed. In VX group kidney concen- polymorphism (SNP) in the IL-17A (rs2275913) and IL-17F (rs763780, used drugs. Epidemiological studies revealed, that long-term tration of IL1-beta was significantly lower than in all other groups. The interaction between fatty acids and rs11465553, rs2397084) genes was genotyped using TaqMan therapy with PPIs increases risk of vertebral and hip fractures [Yu IL1-beta level was decreased also in MVX group and in comparison tryptophan in the efficacy of a ketogenic diet in genotyping assays from Life Technologies Genomic. There were no EW et al., Am J Med, 2011]. Maintaining proper bone mass depends to the control group the difference was on significance border controlling seizure activity significant differences in distribution of IL-17A and IL-17F genotypes among others on calcium-phosphate homeostasis. (p = 0.057). In conclusion only mesna decreases ADMA, but only Piotr Maciejak 1,2, Janusz Szyndler 2, and alleles between RA patients and control group. There were no Aims: The aim of the study was top evaluate influence of carvedilol decreases IL1-beta level, what requires further studies. Danuta Turzyn´ ska 1, Alicja Sobolewska 1, significant associations between IL-17A and IL-17F genotypes and age pantoprazole, a proton-pump inhibitor, on serum calcium and Karolina Kołosowska 2, Paweł Krza˛sćik 2, of disease diagnosis rheumatoid factor, erosive disease as well as phosphate levels in rats. http://dx.doi.org/10.1016/j.pharep.2015.06.090 Adam Płazńik 1,2 extra-articular manifestations. The results of this study suggest, that 28 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 29

ABCB1 and ABCC2), where all mentioned transporters reached their 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- IL-17A and IL-17F gene polymorphism are not the important factors Materials and methods: 24 male Wistar rats receiving normal highest expression levels and decreased significantly in ileum and gy, Warszawa, Poland associated with susceptibility and some clinical parameters of RA in a diet were used in the experiment. On Day 1 rats were divided colon. In all intestinal segments, ABCC3 was the most abundant 2 Department of Experimental and Clinical Pharmacology, Centre for Polish population. randomly in two groups: ABC transporter. As for the analyzed SLC transporters no mRNA Preclinical Research and Technology CePT, Medical University of expression could be observed for OATP1A2, OATP1B1 and OATP1B3 Warsaw, Warszawa, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.087 1. Group P – rats receiving pantoprazole (3 mg/kg) along the entire GI tract, whereas OATP4C1, MATE 1/2, OCT1, OCTN1, 2. Group C (control group) – rats receiving saline solution PEPT2 revealed very low expression level. The expression of PEPT1, The effects of a ketogenic diet in controlling seizure activity The effect of testosterone and endurance OST / , OATP2B1 significantly increase from duodenum to Saline solution and pantoprazole were given intraperitoneally a b have been proven in many studies, although its mechanism of training on signaling pathways in the rat spinal jejunum, whereas the expression of OST and PEPT1 were found once daily for 84 days. On Day 85 blood samples were collected. a action has not been clearly established. The aim of this study was cord to be significantly decreased from jejunum to colon. In conclusion, to investigate the influence of octanoic and decanoic fatty acids Serum calcium and phosphate levels were assessed in certified Andrzej Małecki 1,*, Katarzyna Nierwin´ ska 1, each segment of gastrointestinal tract is characterized by different (FA), the main components in the medium-chain triglyceride laboratory. Anna Pudełko 2, Jo´ zef Langfort 1, Marta Nowacka 1 gene expression pattern of drug transporters. However, the highest diet, on the metabolism of TRP, the activity of the kynurenic Results: Serum calcium level was significantly decreased in level of mRNA of the analyzed genes was found in jejunum. pathway and the concentrations of monoamines and amino 1 rats receiving pantoprazole comparing to control group (9.6250 The Jerzy Kukuczka Academy of Physical Education in Katowice, � acids, including branched amino acids (BCAA) and aromatic 0.5463 mg/dl vs. 10.1545 0.3778 mg/dl, p = 0.014). No significant Katowice, Poland � http://dx.doi.org/10.1016/j.pharep.2015.06.084 amino acids (AAA). The acute effects of FA on the sedation index 2 Department of Pharmacology, Medical University of Silesia, Kato- difference in serum phosphate levels between analyzed groups was and hippocampal electrical after-discharge threshold were also detected (4.9083 0.7154 mg/dl in group P vs. 5.0636 1.2118 mg/ wice, Poland � � assessed. dl in group C, p > 0.05). No significant differences between analyzed Association of catechol-O-methyltransferase *Corresponding author. [email protected] We observed that intra-gastric administration of FA led to groups in age and body weight on Day 85 were detected. gene variability with pain sensitivity in patients increases in the brain levels of TRP and in the central and Summary: Long-term therapy with pantoprazole may lead to after hip replacement We have estimated the impact of two doses of testosterone on peripheral concentration of kynurenic acid, as well as to decrease in serum calcium level. 1 the signaling pathways in rat spinal cord and BDNF, VEGF and heat Anna Machoy-Mokrzyn´ ska , significant changes in the brain and plasma concentrations of 1 1 shock protein (Hsp70) in the rat spinal cord. Zuzanna Starzyn´ ska-Sadura , Monika Białecka , BCAA and AAA. We found that the administration of FA clearly http://dx.doi.org/10.1016/j.pharep.2015.06.089 1 2 Adult male Wistar rats were trained using a motor-driven Mateusz Kurzawski , Krzysztof Safranow , increased the seizure threshold and induced sedation. Further- 3 1 treadmill for 6 weeks (40–60 min 5 times a week) and/or were Andrzej Bohatyrewicz , Marek Droz´dzik more, we have demonstrated that blocking TRP passage into the treated (6 wks) with two doses of testosterone (i.m.; 8 mg/kg or Impact of carvedilol on ADMA–DDAH pathway 1 brain, abolishes these effects of FA but had no similar effect on the Department of Pharmacology, Pomeranian Medical University, 80 mg/kg body weight). Spinal cords were collected 48 hours after and IL1-beta level after single dose formation of ketone bodies. Given that FA are major components Szczecin, Poland the last training cycle and stored at 80 8C. Proteins employed in cyclophosphamide administration in rat model � 2 Department of Biochemistry and Medical Chemistry, Szczecin, Poland of a ketogenic diet, it is suggested that the anticonvulsant effects signaling pathways (p-Akt, PKC, pERK1/2, p-p38) as well as BDNF, Anna Merwid-La˛d *, Małgorzata Trocha, 3 Department of Orthopaedics, Traumatology and Musculoskeletal of a ketogenic diet may be partly dependent on changes in TRP VEGF-A, VEGF-C and HSP70 levels were measured using Western Ewa Chlebda-Sieragowska, Marta Szandruk, Oncology, Pomeranian Medical University, Szczecin, Poland metabolism. blot method in whole tissue lysates of spinal cord. Beata Nowak, Tomasz Sozan´ ski, Some of the effects of the endurance training and testosterone The study was supported by Grant No. 2014/13/B/NZ7/02277 from Małgorzata Piesńiewska, Adam Szela˛g may be associated with increased signal transmission associated The aim of this study was to determine association between the National Science Centre, Poland. genetic polymorphism of the COMT gene and pain perception. with nitric oxide and protein kinase systems. Endurance training, Department of Pharmacology, Wroclaw Medical University, Wrocław, Genetic polymorphisms of catechol-O-methyltransferase (COMT) testosterone (8 mg/kg) and their combination increased VEGF-A Poland http://dx.doi.org/10.1016/j.pharep.2015.06.086 (rs4680:A > G – Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C and decreased VEGF-C levels. The higher dose of testosterone *Corresponding author. > G) and pain sensitivity after hip replacement due to coxarthrosis reduced both isoforms of VEGF. Endurance training could only were studied. The postoperative pain intensity was measured by IL-17A and IL-17F gene polymorphisms in partially offset the adverse effects of high doses of testosterone. Cyclophosphamide-induced (CPX) tissue damages are con- VAS – Visual Analogue Scale after 6 weeks as well as 6 and 12 patients with rheumatoid arthritis Training used separately did not affect the amount of BDNF in nected to the induction of oxidative stress and proinflammatory months following the orthopedic surgery genomic DNA was Damian Malinowski 1, Violetta Dziedziejko 2, spinal cord tissue homogenates. The higher dose of testosterone cytokines in tissues. This may influence ADMA level and DDAH extracted from whole blood samples. The SNPs (single nucleotide Krzysztof Safranow 2, Andrzej Pawlik 1 used alone and combined with endurance training led to decrease activity. Carvedilol is considered as strong antioxidant. The aim of polymorphism) within the COMT gene were evaluated using in BDNF protein. Obtained results suggest, that excessive supply this study was to check impact of carvedilol on CPX-induced 1 Taqman genotyping assays. Haplotypes were classified in accord- Department of Pharmacokinetics and Therapeutic Drug Monitoring, of testosterone may cause undesirable influence on the spinal changes in ADMA/DDAH pathway and IL1-beta concentration. ing to COMT activity: A_C_C_G – low, A_T_C_A – medium and Pomeranian Medical University, Szczecin, Poland cord. Male rats were given single intraperitoneal dose of 200 mg/kg of 2 G_C_G_G – high activity. Analysis of associations between COMT Department of Biochemistry and Medical Chemistry, Pomeranian cyclophosphamide. Carvedilol was given once daily at a dose of genotypes and clinical outcomes was performed by means of Medical University, Szczecin, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.088 2 mg/kg by gastric tube a day before, at the day and one day after Mann–Whitney U test. General linear model was used for CPX injection. Intraperitoneal injections of mesna (200 mg/kg) multivariate analysis. Carriers of the following variants: rs6269 Rheumatoid arthritis (RA) is a chronic inflammatory disease Influence of pantoprazole, a proton-pump were done 20 min before, 4 and 8 h after CPX administration, G, rs4818 G, rs4633 C, as well as carriers of the high activity COMT associated with the destruction of affected joints. Numerous inhibitor, on serum calcium and phosphate divided into 20%, 40% and 40% doses, respectively. Rats in haplotype (G_C_G_G) declared lower pain intensity after 12 cytokines play the important role in the RA pathogenesis, which levels in rats experimental groups received as follows: C – normal saline, X – months from hip replacement when compared to non-carriers. initiate and maintenance the inflammatory response in joints. CPX, MX – CPX + mesna, VX – CPX + carvedilol, MVX – CPX + mes- Agnieszka Matuszewska *, Beata Nowak, The results of this study indicate that polymorphism of the COMT Interleukin-17 plays important role in the pathogenesis of RA. The na + carvedilol. Levels of ADMA in serum and IL1-beta in kidney Anna Merwid-La˛d, Marta Szandruk, gene may play a role in the mechanism of pain perception. We aim of this study was to examine the associations between were measured using ELISA kit. DDAH activity was determined Joanna Kwiatkowska, Małgorzata Piesńiewska, conclude that haplotype accountable for high metabolic activity of polymorphisms in the IL-17A and IL-17F genes and RA. Previous spectrophotometrically in liver. Serum ADMA level was signifi- Adam Szela˛g COMT enzyme was correlated with lower pain sensitivity in reports have linked IL-17 to the pathogenesis of RA. We examined cantly increased in X group in comparison to the control. This patents after hip replacement. 422 patients (340 female, 82 male, mean age 57.5 12.4 years) action of CPX was significantly reversed only in groups receiving � Department of Pharmacology, Medical University, Wrocław, Poland with rheumatoid arthritis diagnosed according to the criteria of *Corresponding author. mesna (MX and MVX), but not in the group receiving carvedilol http://dx.doi.org/10.1016/j.pharep.2015.06.085 American College of Rheumatology/European League against Rheu- alone. DDAH activity was comparable in all studied groups and any matism and 338 subjects as a control group. Single nucleotide Background: Proton-pump inhibitors (PPIs) belong to wildly significant differences were noticed. In VX group kidney concen- polymorphism (SNP) in the IL-17A (rs2275913) and IL-17F (rs763780, used drugs. Epidemiological studies revealed, that long-term tration of IL1-beta was significantly lower than in all other groups. The interaction between fatty acids and rs11465553, rs2397084) genes was genotyped using TaqMan therapy with PPIs increases risk of vertebral and hip fractures [Yu IL1-beta level was decreased also in MVX group and in comparison tryptophan in the efficacy of a ketogenic diet in genotyping assays from Life Technologies Genomic. There were no EW et al., Am J Med, 2011]. Maintaining proper bone mass depends to the control group the difference was on significance border controlling seizure activity significant differences in distribution of IL-17A and IL-17F genotypes among others on calcium-phosphate homeostasis. (p = 0.057). In conclusion only mesna decreases ADMA, but only Piotr Maciejak 1,2, Janusz Szyndler 2, and alleles between RA patients and control group. There were no Aims: The aim of the study was top evaluate influence of carvedilol decreases IL1-beta level, what requires further studies. Danuta Turzyn´ ska 1, Alicja Sobolewska 1, significant associations between IL-17A and IL-17F genotypes and age pantoprazole, a proton-pump inhibitor, on serum calcium and Karolina Kołosowska 2, Paweł Krza˛sćik 2, of disease diagnosis rheumatoid factor, erosive disease as well as phosphate levels in rats. http://dx.doi.org/10.1016/j.pharep.2015.06.090 Adam Płazńik 1,2 extra-articular manifestations. The results of this study suggest, that 30 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 31

uroselective a1A-blockers against cancellous potential of focal application of penicillin-G in rats. A question arises studied antidepressants protected against the LPS. Tianeptine ław, Poland bone disorders induced by androgen deficiency whether the orexin 1 receptor antagonist may affect the anticon- induced the stronger effects on the BDNF mRNA expression than 2 Division of Pathomorphology and Oncological Cytology, Wroclaw in rats vulsant efficacy of a number of antiepileptic drugs (AEDs). desipramine or fluoxetine. In conclusion, our results suggest that Medical University, Wrocław, Poland 3 Rafał Miozga *, Urszula Cegieła, Joanna Folwarczna, Experiments were conducted on male Swiss mice (20–24 g of chronic stress and inflammation induce deleterious alterations Department of Epizootiology and Clinic of Birds and Exotic Animals, Szymon Piskorz weight) and seizure activity was induced by maximal electroshock leading to the remarkable reduction of BDNF expression and The Faculty of Veterinary Medicine, Wroclaw University of Environ- (alternating current of 25 mA, stimulus duration of 0.2 s) delivered antidepressants reverse this effect successfully. ment, Wrocław, Poland Department of Pharmacology, Medical University of Silesia, Katowice, via ear electrodes. All drugs were given ip. Neurotoxic effects of AEDs *Corresponding author. Sosnowiec, Poland combined with SB334867 were evaluated in the chimney test and http://dx.doi.org/10.1016/j.pharep.2015.06.093 *Corresponding author. passive avoidance task. SB334867 (0.625–1.25 mg/kg) did not affect Kaempferol is a natural flavonoid isolated from Cuscute chinesis, the seizure threshold. When given at 1.25 mg/kg, SB334867 Influence of kaempferol on bone mineral density herb used in Chinese medicine among others to ameliorate Uroselective a1A-blockers and finasteride are the primary drugs significantly impaired the anticonvulsant potential of two newer in rats with ovariectomy-induced osteoporosis symptoms of menopause. The aim of the study was to assess used for the pharmacotherapy of benign prostatic hyperplasia, AEDs, lamotrigine and oxcarbazepine, increasing their ED50s from influence of kaempferol on endometrium hypotrophy and weight Beata Nowak 1,*, Agnieszka Matuszewska 1, which, like osteoporosis, develops with ageing in men. The aim of 3.6 to 7.1 and from 17.0 to 22.2 mg/kg, respectively. At 0.625 mg/kg, gain in rats with ovariectomy-induced hypogonadism. 18 female Wojciech Dziewiszek 1, Diana Je˛drzejuk 2, the study was to investigate the effect of a combination therapy the orexin 1 receptor antagonist was ineffective as regards these Wistar rats, divided in three groups (‘‘sham’’ operated group Ewa Sadanowicz 2, Marcin Landwo´ jtowicz 2, (finasteride with tamsulosin or silodosin) on bone remodeling in AEDs. Conventional AEDs, carbamazepine or valproate and the (SHAM), ovariectomized control group (OVX-C) and ovariecomized Tomasz Piasecki 3, Marta Szandruk 1, rats with androgen deficiency induced by orchidectomy. newer AED, topiramate, were not affected by SB334867 (1.25 mg/ group receiving kaempfrol (OVX-K)) were used in the experiment. Anna Merwid-La˛d 1, Małgorzata Trocha 1, Three-month-old Wistar rats were orchidectomized (ORX) or kg). Neurotoxic potential of lamotrigine was elevated by SB334867 ‘‘Sham’’ operation and ovariectomy were performed on Day 1. After Joanna Kwiatkowska 1, Adam Szela˛g 1 sham-operated, and, after 7 days, divided into 6 groups (n = 10): (1.25 mg/kg) whilst that of oxcarbazepine was not modified, as 8 weeks (since Day 57), time needed to induce metabolic changes sham-operated control rats, ORX control rats, ORX rats receiving: evaluated in the chimney test (motor coordination). SB334867 1 Department of Pharmacology, Wroclaw Medical University, Wroc- due to hypogonadism, kaempferol (OVX-K) and saline solution tamsulosin, silodosin, finasteride and tamsulosin, or finasteride (1.25 mg/kg) in combination with lamotrigine or oxcarbazepine, did ław, Poland (SHAM and OVX-C) were administrated by gastric tube for the and silodosin. Tamsulosin (0.1 mg/kg), silodosin (0.3 mg/kg) and not influence the performance of mice in the passive avoidance task 2 Department of Endocrinology, Diabetology and Isotopes Therapy, following 8 weeks (till Day 112). On Day 1 there was no significant finasteride (1 mg/kg) were administered by a gastric tube once (long-term memory). The results indicate that the anticonvulsant Wroclaw Medical University, Wrocław, Poland difference in body weight between groups. On Day 56 we observed daily, for 9 weeks (6 days a week). Bone mass and mineral mass, activity and neurotoxic potential of some AEDs may be associated 3 Department of Epizootiology and Clinic of Birds and Exotic Animals, increased weight gain in ovariectomized animals comparing to calcium and phosphorus content in the bone mineral, histomor- with orexin 1 receptor-mediated events. The Faculty of Veterinary Medicine, Wroclaw University of Environ- ‘‘sham’’ operated ones (61.3 22.4% vs. 33.6 12.5%, p = 0.021). � � phometric parameters and mechanical properties of compact and During the following 8 weeks we observed normalization of weight Supported by Grant no. DS. 475/15. ment, Wrocław, Poland cancellous bone were determined 10 weeks after ORX or sham *Corresponding author. gain in kaempferol treated animals (2.0 2.4%) comparing to ‘‘sham’’ � operation. operated (3.1 3.2%, p > 0.05) and ovariectomized control http://dx.doi.org/10.1016/j.pharep.2015.06.092 � Orchidectomy-induced androgen deficiency intensified the (7.8 3.1%, p = 0.007) groups. On Day 112 we observed significant Kaempferol is a natural flavonoid isolated from Cuscute chinesis, � resorption of cancellous and compact bone, resulting in significant herb used in Chinese medicine among others in osteoporosis uterine hypotrophy in ovariectomized animals (OVX-C: Chronic stress enhanced vulnerability of BDNF decreases in the mass of bone mineral, calcium and phosphorus treatment. The aim of the study was to assess influence of kaempferol 1021 128 mm, p < 0.001; OVX-K: 1271 103 mm, p < 0.001) to inflammation in the rat olfactory bulbs – � � content, the cortical bone growth and transverse cross-section on bone mineral density (BMD) in rats with ovariectomy-induced compering to ‘‘sham’’ operated ones (2644 245 mm). However, in Protective effect of antidepressants � surface, width of trabeculae in the epiphysis and metaphysis of the osteoporis. 30 female 3-month-old Wistar rats, divided in four OVX-K group uterine hypotrophy was significantly less profound than 1,2, 3 femur, as well as significant worsening of mechanical properties of Marta Nowacka *, Monika Paul-Samojedny , groups (Baseline control (BC), ‘‘sham’’ operated group (SHAM), in OVX-C group (OVX-K vs. OVX-C p = 0.014). Analysis of perime- 2 2 the tibial metaphysis and femoral diaphysis. The use of tamsulosin Anna M. Bielecka , Ewa Obuchowicz ovariectomized control group (OVX-C), ovariecomized group trium, myometrium, and endometrium thickness revealed that or silodosin counteracted the effects induced by androgen receiving kaempfrol (OVX-K), and ovariecomized group receiving differences between groups were mainly dependent on endometrium 1 Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy deficiency in cancellous and compact bone. The preventive effect alendronate (OVX-A)) were used in the experiment. ‘‘Sham’’ thickness. Beneficial influence of kaempferol on weight gain and Kukuczka Academy of Physical Education, Katowice, Poland of silodosin was stronger than that of tamsulosin, and finasteride operation and ovariectomy were performed on Day 1. After 8 weeks endometrium hypotrophy in ovariectomiazed rats supports its utility 2 Department of Pharmacology, School of Medicine, Medical University weakened the effects of both drugs in trabecular bone. (since Day 57), time needed to induce metabolic changes due to in ameliorating at least some menopausal symptoms. of Silesia, Katowice, Poland hypogonadism, kaempferol (OVX-K), alendronate (OVX-A) and 3 Department of Medical Genetics, Faculty of Pharmacy, Medical http://dx.doi.org/10.1016/j.pharep.2015.06.091 saline solution (SHAM and OVX-C) were administrated by gastric http://dx.doi.org/10.1016/j.pharep.2015.06.095 University of Silesia, Sosnowiec, Poland tube for the following 8 weeks (till Day 112). We observed significant *Corresponding author. decrease in femur index, defined as femur index femur Influence of SB334867, an orexin 1 receptor ¼ Comparison of the animal models of mass=body weightx 100%, in all ovariectomized groups (OVX-C: antagonist, on the anticonvulsant activity of It was suggested, that neuroinflamation as well as neurotrophic schizophrenia induced by prenatal stress or 0.3487 0.0209%, p = 0.02; OVX-K: 0.3515 0.0242%, p = 0.01; OVX- some conventional and novel antiepileptic factors are involved in the response to stress in brain. With respect � � methylazoxymethanol acetate administration A: 0.3496 0.0233%, p = 0.04) compering to SHAM group (0.3981 drugs against maximal electroshock-induced to psychiatric disorders recently obtained data indicate the � * 0.0329%). However BMD was significantly decreased only in OVX-C Elz˙ bieta Nowakowska , Piotr Ratajczak, seizures in mice significance of disturbed neurogenesis in brain areas other than � group (0.2458 0.0078 g/cm3 vs. 0.2327 0.0055 g/cm3, p = 0.04). In Krzysztof Kus Barbara Miziak 1,*, Maria Kondrat-Wrobel 1, the hippocampus. Olfactory bulb is one of the prominent post- � � all groups apart from OVX-C we observed age-related increase in BMD, Magdalena Chrosćin´ ska-Krawczyk 1,2, developmental neurogenesis areas in the adult mammalian brain Department of Pharmacoeconomics and Social Pharmacy, Poznan when compared to BC (BC: 0.2213 0.0109%; BC vs. OVX-C p > 0.05) Ewa Jasin´ ska 1, Ewa Krzewicka 1, Artur Romaniuk 1, [Lledo et al., Nat Rev Neurosci, 2006]. The aim of this study was to � University of Medical Sciences, Poznan´, Poland comparing to BC. No differences between analyzed groups in serum Łukasz Pyzia 1, Stanisław J. Czuczwar 1,3 investigate the influence of antidepressants given chronically on *Corresponding author. calcium and serum phosphate levels were detected. Beneficial influence the lipopolysaccharide (LPS) effect on BDNF in olfactory bulbs of 1 Department of Pathophysiology, Medical University, Lublin, Poland of kaempferol on bone mineral density in rats with ovariectomy- female rats subjected to chronic stress. Female Sprague-Dawley The aim of study was to find whether spatial memory 2 Department of Pediatrics, Endocrinology and Neurology, Medical induced osteoporosis needs further research. rats (200 20 g) were subjected to 4-week social instability stress impairment and disruption in locomotor activity were found in University, Lublin, Poland � [Herzog et al., Neurosci., 2009]. Desipramine (10 mg/kg), fluoxetine prenatally stressed group of rats (PSG) and methylazoxymethanol 3 Department of Physiopathology, Institute of Rural Health, Lublin, http://dx.doi.org/10.1016/j.pharep.2015.06.094 (5 mg/kg), tianeptine (10 mg/kg) or saline was administered ip once acetate-treated group of rats (MAMG). In addition we examined Poland daily. On the last day of experiment, LPS (1 mg/kg, ip) or saline were PSG and MAMG in course of basal plasma corticosterone (CORT) *Corresponding author. injected to rats being at the same phase of estrus cycle. Six hours later Influence of kaempferol on endometrium and level and brain-derived neurothropic factor (BDNF) level in the rats were decapitated and the olfactory bulbs were immediately weight gain in rats with ovariectomy-induced hippocampus (HIP) and prefrontal cortex (PFC). Orexin is apparently involved in some processes – metabolism, isolated. QRT-PCR experiments were performed using TaqMan Gene hypogonadism Animal models of schizophrenia were studied in the Morris feeding, memory, sleep-wake cycle or nociception. Recently, an Expression Assays with ABI PRISM 7700 Sequence Detection System. Beata Nowak 1,*, Agnieszka Matuszewska 1, Water Maze (MWM – spatial memory) and locomotor activity test. association between orexin-mediated events and seizure activity has The BDNF concentration was measured with a conventional ELISA Wojciech Dziewiszek 1, Przemysław Kowalski 2, CORT level was measured using ELISA Kit ADI-900-097 while BDNF been postulated. Blockade of orexin 1 receptors by N-(2-methyl-6- assay. In the olfactory bulbs of LPS-treated rats subjected to chronic Tomasz Piasecki 3, Marta Szandruk 1, levels were assessed using ELISA Chemikine TM BDNF kit. benzoxazolyl)-N0-1,5-naphthyridin-4-yl urea (SB334867) resulted stress BDNF mRNA expression was decreased, but BDNF levels Anna Merwid-La˛d 1, Małgorzata Trocha 1, MWM results indicate that statistically significant increase in in an anticonvulsant effect against pentylenetetrazol-induced showed only such tendency in comparison to the stressed group. We Joanna Kwiatkowska 1, Adam Szela˛g 1 the number of escape latencies (spatial memory deterioration) was 30 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 31

Finasteride reduces the preventive effect of seizures in rats. Also, orexin A and B enhanced the convulsive did not observe any significant effect of stress or LPS alone. All the 1 Department of Pharmacology, Wroclaw Medical University, Wroc- uroselective a1A-blockers against cancellous potential of focal application of penicillin-G in rats. A question arises studied antidepressants protected against the LPS. Tianeptine ław, Poland bone disorders induced by androgen deficiency whether the orexin 1 receptor antagonist may affect the anticon- induced the stronger effects on the BDNF mRNA expression than 2 Division of Pathomorphology and Oncological Cytology, Wroclaw in rats vulsant efficacy of a number of antiepileptic drugs (AEDs). desipramine or fluoxetine. In conclusion, our results suggest that Medical University, Wrocław, Poland 3 Rafał Miozga *, Urszula Cegieła, Joanna Folwarczna, Experiments were conducted on male Swiss mice (20–24 g of chronic stress and inflammation induce deleterious alterations Department of Epizootiology and Clinic of Birds and Exotic Animals, Szymon Piskorz weight) and seizure activity was induced by maximal electroshock leading to the remarkable reduction of BDNF expression and The Faculty of Veterinary Medicine, Wroclaw University of Environ- (alternating current of 25 mA, stimulus duration of 0.2 s) delivered antidepressants reverse this effect successfully. ment, Wrocław, Poland Department of Pharmacology, Medical University of Silesia, Katowice, via ear electrodes. All drugs were given ip. Neurotoxic effects of AEDs *Corresponding author. Sosnowiec, Poland combined with SB334867 were evaluated in the chimney test and http://dx.doi.org/10.1016/j.pharep.2015.06.093 *Corresponding author. passive avoidance task. SB334867 (0.625–1.25 mg/kg) did not affect Kaempferol is a natural flavonoid isolated from Cuscute chinesis, the seizure threshold. When given at 1.25 mg/kg, SB334867 Influence of kaempferol on bone mineral density herb used in Chinese medicine among others to ameliorate Uroselective a1A-blockers and finasteride are the primary drugs significantly impaired the anticonvulsant potential of two newer in rats with ovariectomy-induced osteoporosis symptoms of menopause. The aim of the study was to assess used for the pharmacotherapy of benign prostatic hyperplasia, AEDs, lamotrigine and oxcarbazepine, increasing their ED50s from influence of kaempferol on endometrium hypotrophy and weight Beata Nowak 1,*, Agnieszka Matuszewska 1, which, like osteoporosis, develops with ageing in men. The aim of 3.6 to 7.1 and from 17.0 to 22.2 mg/kg, respectively. At 0.625 mg/kg, gain in rats with ovariectomy-induced hypogonadism. 18 female Wojciech Dziewiszek 1, Diana Je˛drzejuk 2, the study was to investigate the effect of a combination therapy the orexin 1 receptor antagonist was ineffective as regards these Wistar rats, divided in three groups (‘‘sham’’ operated group Ewa Sadanowicz 2, Marcin Landwo´ jtowicz 2, (finasteride with tamsulosin or silodosin) on bone remodeling in AEDs. Conventional AEDs, carbamazepine or valproate and the (SHAM), ovariectomized control group (OVX-C) and ovariecomized Tomasz Piasecki 3, Marta Szandruk 1, rats with androgen deficiency induced by orchidectomy. newer AED, topiramate, were not affected by SB334867 (1.25 mg/ group receiving kaempfrol (OVX-K)) were used in the experiment. Anna Merwid-La˛d 1, Małgorzata Trocha 1, Three-month-old Wistar rats were orchidectomized (ORX) or kg). Neurotoxic potential of lamotrigine was elevated by SB334867 ‘‘Sham’’ operation and ovariectomy were performed on Day 1. After Joanna Kwiatkowska 1, Adam Szela˛g 1 sham-operated, and, after 7 days, divided into 6 groups (n = 10): (1.25 mg/kg) whilst that of oxcarbazepine was not modified, as 8 weeks (since Day 57), time needed to induce metabolic changes sham-operated control rats, ORX control rats, ORX rats receiving: evaluated in the chimney test (motor coordination). SB334867 1 Department of Pharmacology, Wroclaw Medical University, Wroc- due to hypogonadism, kaempferol (OVX-K) and saline solution tamsulosin, silodosin, finasteride and tamsulosin, or finasteride (1.25 mg/kg) in combination with lamotrigine or oxcarbazepine, did ław, Poland (SHAM and OVX-C) were administrated by gastric tube for the and silodosin. Tamsulosin (0.1 mg/kg), silodosin (0.3 mg/kg) and not influence the performance of mice in the passive avoidance task 2 Department of Endocrinology, Diabetology and Isotopes Therapy, following 8 weeks (till Day 112). On Day 1 there was no significant finasteride (1 mg/kg) were administered by a gastric tube once (long-term memory). The results indicate that the anticonvulsant Wroclaw Medical University, Wrocław, Poland difference in body weight between groups. On Day 56 we observed daily, for 9 weeks (6 days a week). Bone mass and mineral mass, activity and neurotoxic potential of some AEDs may be associated 3 Department of Epizootiology and Clinic of Birds and Exotic Animals, increased weight gain in ovariectomized animals comparing to calcium and phosphorus content in the bone mineral, histomor- with orexin 1 receptor-mediated events. The Faculty of Veterinary Medicine, Wroclaw University of Environ- ‘‘sham’’ operated ones (61.3 22.4% vs. 33.6 12.5%, p = 0.021). � � phometric parameters and mechanical properties of compact and During the following 8 weeks we observed normalization of weight Supported by Grant no. DS. 475/15. ment, Wrocław, Poland cancellous bone were determined 10 weeks after ORX or sham *Corresponding author. gain in kaempferol treated animals (2.0 2.4%) comparing to ‘‘sham’’ � operation. operated (3.1 3.2%, p > 0.05) and ovariectomized control http://dx.doi.org/10.1016/j.pharep.2015.06.092 � Orchidectomy-induced androgen deficiency intensified the (7.8 3.1%, p = 0.007) groups. On Day 112 we observed significant Kaempferol is a natural flavonoid isolated from Cuscute chinesis, � resorption of cancellous and compact bone, resulting in significant herb used in Chinese medicine among others in osteoporosis uterine hypotrophy in ovariectomized animals (OVX-C: Chronic stress enhanced vulnerability of BDNF decreases in the mass of bone mineral, calcium and phosphorus treatment. The aim of the study was to assess influence of kaempferol 1021 128 mm, p < 0.001; OVX-K: 1271 103 mm, p < 0.001) to inflammation in the rat olfactory bulbs – � � content, the cortical bone growth and transverse cross-section on bone mineral density (BMD) in rats with ovariectomy-induced compering to ‘‘sham’’ operated ones (2644 245 mm). However, in Protective effect of antidepressants � surface, width of trabeculae in the epiphysis and metaphysis of the osteoporis. 30 female 3-month-old Wistar rats, divided in four OVX-K group uterine hypotrophy was significantly less profound than 1,2, 3 femur, as well as significant worsening of mechanical properties of Marta Nowacka *, Monika Paul-Samojedny , groups (Baseline control (BC), ‘‘sham’’ operated group (SHAM), in OVX-C group (OVX-K vs. OVX-C p = 0.014). Analysis of perime- 2 2 the tibial metaphysis and femoral diaphysis. The use of tamsulosin Anna M. Bielecka , Ewa Obuchowicz ovariectomized control group (OVX-C), ovariecomized group trium, myometrium, and endometrium thickness revealed that or silodosin counteracted the effects induced by androgen receiving kaempfrol (OVX-K), and ovariecomized group receiving differences between groups were mainly dependent on endometrium 1 Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy deficiency in cancellous and compact bone. The preventive effect alendronate (OVX-A)) were used in the experiment. ‘‘Sham’’ thickness. Beneficial influence of kaempferol on weight gain and Kukuczka Academy of Physical Education, Katowice, Poland of silodosin was stronger than that of tamsulosin, and finasteride operation and ovariectomy were performed on Day 1. After 8 weeks endometrium hypotrophy in ovariectomiazed rats supports its utility 2 Department of Pharmacology, School of Medicine, Medical University weakened the effects of both drugs in trabecular bone. (since Day 57), time needed to induce metabolic changes due to in ameliorating at least some menopausal symptoms. of Silesia, Katowice, Poland hypogonadism, kaempferol (OVX-K), alendronate (OVX-A) and 3 Department of Medical Genetics, Faculty of Pharmacy, Medical http://dx.doi.org/10.1016/j.pharep.2015.06.091 saline solution (SHAM and OVX-C) were administrated by gastric http://dx.doi.org/10.1016/j.pharep.2015.06.095 University of Silesia, Sosnowiec, Poland tube for the following 8 weeks (till Day 112). We observed significant *Corresponding author. decrease in femur index, defined as femur index femur Influence of SB334867, an orexin 1 receptor ¼ Comparison of the animal models of mass=body weightx 100%, in all ovariectomized groups (OVX-C: antagonist, on the anticonvulsant activity of It was suggested, that neuroinflamation as well as neurotrophic schizophrenia induced by prenatal stress or 0.3487 0.0209%, p = 0.02; OVX-K: 0.3515 0.0242%, p = 0.01; OVX- some conventional and novel antiepileptic factors are involved in the response to stress in brain. With respect � � methylazoxymethanol acetate administration A: 0.3496 0.0233%, p = 0.04) compering to SHAM group (0.3981 drugs against maximal electroshock-induced to psychiatric disorders recently obtained data indicate the � * 0.0329%). However BMD was significantly decreased only in OVX-C Elz˙ bieta Nowakowska , Piotr Ratajczak, seizures in mice significance of disturbed neurogenesis in brain areas other than � group (0.2458 0.0078 g/cm3 vs. 0.2327 0.0055 g/cm3, p = 0.04). In Krzysztof Kus Barbara Miziak 1,*, Maria Kondrat-Wrobel 1, the hippocampus. Olfactory bulb is one of the prominent post- � � all groups apart from OVX-C we observed age-related increase in BMD, Magdalena Chrosćin´ ska-Krawczyk 1,2, developmental neurogenesis areas in the adult mammalian brain Department of Pharmacoeconomics and Social Pharmacy, Poznan when compared to BC (BC: 0.2213 0.0109%; BC vs. OVX-C p > 0.05) Ewa Jasin´ ska 1, Ewa Krzewicka 1, Artur Romaniuk 1, [Lledo et al., Nat Rev Neurosci, 2006]. The aim of this study was to � University of Medical Sciences, Poznan´, Poland comparing to BC. No differences between analyzed groups in serum Łukasz Pyzia 1, Stanisław J. Czuczwar 1,3 investigate the influence of antidepressants given chronically on *Corresponding author. calcium and serum phosphate levels were detected. Beneficial influence the lipopolysaccharide (LPS) effect on BDNF in olfactory bulbs of 1 Department of Pathophysiology, Medical University, Lublin, Poland of kaempferol on bone mineral density in rats with ovariectomy- female rats subjected to chronic stress. Female Sprague-Dawley The aim of study was to find whether spatial memory 2 Department of Pediatrics, Endocrinology and Neurology, Medical induced osteoporosis needs further research. rats (200 20 g) were subjected to 4-week social instability stress impairment and disruption in locomotor activity were found in University, Lublin, Poland � [Herzog et al., Neurosci., 2009]. Desipramine (10 mg/kg), fluoxetine prenatally stressed group of rats (PSG) and methylazoxymethanol 3 Department of Physiopathology, Institute of Rural Health, Lublin, http://dx.doi.org/10.1016/j.pharep.2015.06.094 (5 mg/kg), tianeptine (10 mg/kg) or saline was administered ip once acetate-treated group of rats (MAMG). In addition we examined Poland daily. On the last day of experiment, LPS (1 mg/kg, ip) or saline were PSG and MAMG in course of basal plasma corticosterone (CORT) *Corresponding author. injected to rats being at the same phase of estrus cycle. Six hours later Influence of kaempferol on endometrium and level and brain-derived neurothropic factor (BDNF) level in the rats were decapitated and the olfactory bulbs were immediately weight gain in rats with ovariectomy-induced hippocampus (HIP) and prefrontal cortex (PFC). Orexin is apparently involved in some processes – metabolism, isolated. QRT-PCR experiments were performed using TaqMan Gene hypogonadism Animal models of schizophrenia were studied in the Morris feeding, memory, sleep-wake cycle or nociception. Recently, an Expression Assays with ABI PRISM 7700 Sequence Detection System. Beata Nowak 1,*, Agnieszka Matuszewska 1, Water Maze (MWM – spatial memory) and locomotor activity test. association between orexin-mediated events and seizure activity has The BDNF concentration was measured with a conventional ELISA Wojciech Dziewiszek 1, Przemysław Kowalski 2, CORT level was measured using ELISA Kit ADI-900-097 while BDNF been postulated. Blockade of orexin 1 receptors by N-(2-methyl-6- assay. In the olfactory bulbs of LPS-treated rats subjected to chronic Tomasz Piasecki 3, Marta Szandruk 1, levels were assessed using ELISA Chemikine TM BDNF kit. benzoxazolyl)-N0-1,5-naphthyridin-4-yl urea (SB334867) resulted stress BDNF mRNA expression was decreased, but BDNF levels Anna Merwid-La˛d 1, Małgorzata Trocha 1, MWM results indicate that statistically significant increase in in an anticonvulsant effect against pentylenetetrazol-induced showed only such tendency in comparison to the stressed group. We Joanna Kwiatkowska 1, Adam Szela˛g 1 the number of escape latencies (spatial memory deterioration) was 32 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 33 observed in PSG (1 and 7 days) and MAMG (1, 7, 14 and 21 days). In Anxiolytic-like properties of asenapine and comparison with carbon nanomaterials silica nanoflakes are anxiety behaviour and decreases memory disturbances. Adminis- turn both PSG and MAMG showed the increase in locomotor lurasidone in the rat models of anxiety characterized by better solubility and surface functionality. tration of metyrapone alleviates the depressive effect induced by activity. Biochemical studies indicate that CORT level was Anna Partyka 1,*, Anna Wasik 1, Małgorzata Piejko 1, Moreover, mesoporous structure of silica layer allows for effective stress, which suggests influence of glycocorticosteroids and the increase in PSG and MAMG (evidence of properly performed Marcin Kołaczkowski 2, Anna Wesołowska 1 drug transport. In the first step biocompatibility (WST1 assay) of hypothalamus-pituitary-adrenals axis in anhedonia caused by animal model of schizophrenia). Moreover decrease of BDNF level the silica nanoflakes with the use of two different dispersants (PEG, stress. The results presented here can contribute to development in the HIP and PFC was observed in PSG and MAMG which 1 Department of Clinical Pharmacy, Jagiellonian University Medical PBS) was evaluated. Results of the WST1 assay suggested that silica of more effective pharmacotherapy for anxiety, depression and correlate with impaired spatial memory and locomotor activity College, Krako´w, Poland nanoflakes functionalized with PEG demonstrated better biocom- cognitive processes in the contemporary environment exposed to observed in rats. 2 Department of Medicinal Chemistry, Jagiellonian University Medical patibility than PBS functionalized structures. The PEGylated silica everyday stress stimuli and addictions. In both animal models of schizophrenia behavioral and College, Krako´w, Poland nanomaterials showed significant cytotoxicity only at the highest biochemical changes in the examined offspring were observed. *Corresponding author. tested concentration (100 mg/ml), with 70% of cellular viability. http://dx.doi.org/10.1016/j.pharep.2015.06.100 As the HIP is structure which participate in spatial memory LDH test (lactate dehydrogenase viability test) confirmed biocom- process, the decrease in BDNF observed in the study could be Common accompaniments of schizophrenia condition are patibility of these structures. Antitumor activity of some new thymidine related to spatial memory deterioration found in PSG and MAMG. depression and anxiety [Buckley, Schizophr Bull, 2009]. The In order to define the cellular uptake, the nanostructures were dimers derivatives Moreover decrease level of BDNF observed in PFC could correlate second-generation of antipsychotics seem to be a new option labelled with fluorescent dye Alexa647, and confocal microscopy 1, 2 with increase locomotor activity of rats. Animal models of for the treatment of depressive/anxiety symptoms in schizophre- images were carried out. The cell imaging revealed efficient cell Anita Pin´ ska *, Dagmara Baraniak , 1 schizophrenia seem to be an important tool to understand the nia. Lurasidone and asenapine are the antipsychotic drugs which internalization of silica nanoflakes, with predominant cytosolic Piotr Ruszkowski key theories related to the disorder and can be used to assess have been recently introduced to the market [Ishibashi, J distribution both in fibroblasts as well as in cancer cells A375 1 Department of Pharmacology, Faculty of Pharmacy, Poznan efficacy of new drugs as well as create a new directions of Pharmacol Exp Ther, 2010; Schatzberg, Nemeroff, Textbook of (melanoma cell line) and MCF7 (breast cancer cell line). University of Medical Sciences, Poznan´, Poland research. Psychopharmacology, 2009]. Their antidepressant-like activity in In the next step, the cytotoxicity of silica-MTX (methotrexate) 2 Institute of Bioorganic Chemistry Polish Academy of Sciences, the rat forced swim test has been reported recently [Kołaczkowski, nanoflakes complex in reference to the free drug (MTX) was Poznan´, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.096 Naunyn Schmiedebergs Arch Pharmacol, 2014]. In the present evaluated. WST1 assay showed similar toxicity of both tested drug *Corresponding author. study we examined their anxiolytic-like properties in two well- delivery modalities. The cytotoxicity of MTX-nanoflakes ranged establish anxiety rat models: elevated plus maze (EPM) and Vogel from 78% to 23% against A375 and MCF7, respectively. Free MTX Effect of acute peripheral IL-1b administration Introduction: Antimetabolites are one of the largest groups of conflict drinking test. produced similar effects, i.e. mortality rate of 70% and 14% in A375 on BDNF mRNA expression in the rat brain drugs used in the treatment of cancer, this group consists of Asenapine (0.1–1 mg/kg) at a dose of 1 mg/kg significantly and MCF7 cells. structures nucleoside analogues which, due to a structural similarity to increased the percentage of time spent in the open arms, but The results proved that mesoporous silica nanoflakes are 1, 1,2 natural metabolites, may competitively participate in important Ewa Obuchowicz *, Marta M. Nowacka , simultaneously at doses of 0.3 and 1 mg/kg decreased the number promising, effective drug nanocarriers. These findings may provide 3 1 cell processes. Nucleoside analogues by incorporation into nucleic Monika Paul-Samojedny , Anna M. Bielecka of entries into the open arms without affecting the percentage of helpful information for designing efficient drug delivery system. acids, inhibit their synthesis, interfere with the normal cell 1 the open arms entries. Lurasidone did not change significantly the Department of Pharmacology, School of Medicine in Katowice, The authors are grateful for financial support from the Fundation for functions which can lead to apoptosis. This study is an in vitro parameters measured in the EPM. In the Vogel test asenapina Medical University of Silesia, Katowice, Poland analysis of compounds derived from nucleoside analogues. Dimers administered at a dose of 1 mg/kg and lurasidone at a dose of Polish Science within the FOCUS Programme (F4/2010/P/2013). 2 Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy consisting of thymidine and AZT, AddFU, 5FdU linked by a 1,2,3- 10 mg/kg substantially increased the number of shocks accepted Kukuczka Academy of Physical Education, Katowice, Poland triazole linker were analyzed against cancer cell lines using by rats and the number of licks. http://dx.doi.org/10.1016/j.pharep.2015.06.099 3 Department of Medical Genetics, Faculty of Pharmacy in Sosnowiec, sulforhodamine in vitro screening test. Screening of potential antipsychotics for anxiolytic-like prop- Medical University of Silesia, Katowice, Poland Results and discussion: Compounds 18b, 19a and 19b presented erties is considered to be an important part of modern drug *Corresponding author. Assessment of the influence of nicotine on the highest activity with the lowest IC50 values. For KB cell line the development. Our data suggest that asenapina and lurasidone anxiety effects, depressive behaviour and results were respectively: 8.2 mg/ml, 7.0 mg/ml, 6.0 mg/ml, and for revealed anxiolytic-like effects in EPM and/or in Vogel conflict Various medical conditions are associated with an activation of cognitive processes induced by prolonged stress the HeLa cell line were: 7.0 mg/ml, 6.4 mg/ml, 6.0 mg/ml. The drinking test in rats. peripheral cell-mediated immune, inflammatory, oxidative and in mice compound 20a with IC50 presented the lowest activity for cell lines KB – 40.3 mg/ml and HeLa – 45.0 mg/ml. The obtained results allow nitrosative stress pathways characterized, among the others, by an Supported by Funds for Statutory Activity of Jagiellonian University Karolina Pe˛kała *, Barbara Budzyn´ ska, us to conclude that the antitumor activity of our test compounds is enhanced levels of pro-inflammatory cytokines [Maes et al, Medical College, Krako´ w, Poland (K/ZDS/004121). Graz˙ yna Biała Neuroendocrinol Lett, 2011]. The present study was designed to related to the chemical structure of thymidine dimers. We can also assess the influence of an increased IL-1b levels at the periphery on http://dx.doi.org/10.1016/j.pharep.2015.06.098 Department of Pharmacology and Pharmacodynamics, Medical conclude that the hydrophobic TBDMS substituent at the 5th brain derived neurotrophic factor (BDNF) mRNA expression in University of Lublin, Lublin, Poland position of one of the thymidine molecules provides the highest female and male rats and BDNF mRNA in females exposed to *Corresponding author. activity. The activity of the compounds is also likely influenced by Mesoporous silica nanoflakes – chronic social instability stress (CSIS) for 29–30 days. CSIS the length of the inter-nucleoside linker and the presence of Biocompatibility, cellular uptake and drug paradigm is known to be more stressful for females than males. Nicotine, as the main component of tobacco smoke, acting halogen atoms. transport Male rats or female rats in the estrus phase were given an ip through central mechanisms, exerts influence on mood and Conclusions: Lack of previous scientific publications about 1, 1 injection of recombinant rat IL-1b (50 mg/kg; R&D System) or Magdalena Peruz˙ ynska *, Mariola Zbroja , emotional tension, and also contributes to physical and mental antitumor activity of the thymidine dimers, clearly shows a need 1 1 sterile, non-pyrogenic 0.9% saline (2 ml/kg) 4 h before decapita- Klaudia We˛grzynowska , Klaudia Trzeciak , dependence. Additionally, it was demonstrated in some experimen- for further research. There is a possibility for a new modification of 1 2 tion. The BDNF mRNA was determined by the qRT-PCR in the Sylwia Szela˛g , Dorota Rogin´ ska , tal animal models that chronic and acute stress may aggravate both thymidine dimers that could lead to potential new anticancer drugs. 2 3 pituitary, hypothalamus, hippocampus and amygdala. In females, a Bogusław Machalin´ ski , Krzysztof Cendrowski , behavioural as well as neuronal effects caused by administration of 1 3 tendency towards a reduction in the expression of BDNF mRNA Mateusz Kurzawski , Ewa Mijowska , nicotine. Taking into account frequent concomitance of nicotine http://dx.doi.org/10.1016/j.pharep.2015.06.101 1 especially in the pituitary gland and hypothalamus was observed. Marek Droz´dzik abuse and stress accompanying daily life we aimed our research at In male rats, IL-1b induced the stronger effect on the studied 1 Department of Experimental & Clinical Pharmacology, Szczecin, assessment of behavioural effects accompanying single and Effects of the African plum (Pygenum africanum) growth factor in the limbic structures, particularly in the Poland prolonged administration of nicotine in combination with chronic bark extract on bone mechanical properties in amygdala. In females previously exposed to CSIS procedure, IL- 2 Department of General Pathology, Pomeranian Medical University, mild unpredictable stress (CMUS) in experimental animal models. rats 1b significantly decreased the number of BDNF mRNA copies as The level of anxiety was examined in the elevated plus maze test Szczecin, Poland Szymon Piskorz *, Urszula Cegieła, compared to its effect in the non-stressed rats. The results indicate 3 (EPM), depressive effects in the forced swim test (FST) and cognitive Institute of Chemical and Environment Engineering, West Pomera- Aleksandra Janas, Rafał Miozga the differences between female and male rats in the response of nian University of Technology, Szczecin, Poland processes in the passive avoidance test (PA). Additionally, the effect BDNF to the enhanced peripheral level of IL-1b and suggest that *Corresponding author. of metyrapone – a compound inhibiting synthesis of corticosterone Department of Pharmacology, Medical University of Silesia, Katowice, especially under stress condition the peripheral IL-1b over- was described. In the conducted examinations the mice were Sosnowiec, Poland expression may influence the CNS function. submitted to the procedure of CMUS for 4 weeks, 2 h per day (e.g., Mesoporous silica nanoflakes are new promising silica nano- *Corresponding author. wet litter or the lack of it, tilting the cage by 458, limitation of water materials. The studied materials were synthesized on graphene or food, an electric sound signal) (90 dB). It was found that single and http://dx.doi.org/10.1016/j.pharep.2015.06.097 sheets core, that after silica coverage was burned out. In The extract of the bark of African plum (Pygenum africanum) prolonged administration of nicotine reverses depressive and is used in the prophylaxis and treatment (adjunctively to 32 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 33 observed in PSG (1 and 7 days) and MAMG (1, 7, 14 and 21 days). In Anxiolytic-like properties of asenapine and comparison with carbon nanomaterials silica nanoflakes are anxiety behaviour and decreases memory disturbances. Adminis- turn both PSG and MAMG showed the increase in locomotor lurasidone in the rat models of anxiety characterized by better solubility and surface functionality. tration of metyrapone alleviates the depressive effect induced by activity. Biochemical studies indicate that CORT level was Anna Partyka 1,*, Anna Wasik 1, Małgorzata Piejko 1, Moreover, mesoporous structure of silica layer allows for effective stress, which suggests influence of glycocorticosteroids and the increase in PSG and MAMG (evidence of properly performed Marcin Kołaczkowski 2, Anna Wesołowska 1 drug transport. In the first step biocompatibility (WST1 assay) of hypothalamus-pituitary-adrenals axis in anhedonia caused by animal model of schizophrenia). Moreover decrease of BDNF level the silica nanoflakes with the use of two different dispersants (PEG, stress. The results presented here can contribute to development in the HIP and PFC was observed in PSG and MAMG which 1 Department of Clinical Pharmacy, Jagiellonian University Medical PBS) was evaluated. Results of the WST1 assay suggested that silica of more effective pharmacotherapy for anxiety, depression and correlate with impaired spatial memory and locomotor activity College, Krako´w, Poland nanoflakes functionalized with PEG demonstrated better biocom- cognitive processes in the contemporary environment exposed to observed in rats. 2 Department of Medicinal Chemistry, Jagiellonian University Medical patibility than PBS functionalized structures. The PEGylated silica everyday stress stimuli and addictions. In both animal models of schizophrenia behavioral and College, Krako´w, Poland nanomaterials showed significant cytotoxicity only at the highest biochemical changes in the examined offspring were observed. *Corresponding author. tested concentration (100 mg/ml), with 70% of cellular viability. http://dx.doi.org/10.1016/j.pharep.2015.06.100 As the HIP is structure which participate in spatial memory LDH test (lactate dehydrogenase viability test) confirmed biocom- process, the decrease in BDNF observed in the study could be Common accompaniments of schizophrenia condition are patibility of these structures. Antitumor activity of some new thymidine related to spatial memory deterioration found in PSG and MAMG. depression and anxiety [Buckley, Schizophr Bull, 2009]. The In order to define the cellular uptake, the nanostructures were dimers derivatives Moreover decrease level of BDNF observed in PFC could correlate second-generation of antipsychotics seem to be a new option labelled with fluorescent dye Alexa647, and confocal microscopy 1, 2 with increase locomotor activity of rats. Animal models of for the treatment of depressive/anxiety symptoms in schizophre- images were carried out. The cell imaging revealed efficient cell Anita Pin´ ska *, Dagmara Baraniak , 1 schizophrenia seem to be an important tool to understand the nia. Lurasidone and asenapine are the antipsychotic drugs which internalization of silica nanoflakes, with predominant cytosolic Piotr Ruszkowski key theories related to the disorder and can be used to assess have been recently introduced to the market [Ishibashi, J distribution both in fibroblasts as well as in cancer cells A375 1 Department of Pharmacology, Faculty of Pharmacy, Poznan efficacy of new drugs as well as create a new directions of Pharmacol Exp Ther, 2010; Schatzberg, Nemeroff, Textbook of (melanoma cell line) and MCF7 (breast cancer cell line). University of Medical Sciences, Poznan´, Poland research. Psychopharmacology, 2009]. Their antidepressant-like activity in In the next step, the cytotoxicity of silica-MTX (methotrexate) 2 Institute of Bioorganic Chemistry Polish Academy of Sciences, the rat forced swim test has been reported recently [Kołaczkowski, nanoflakes complex in reference to the free drug (MTX) was Poznan´, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.096 Naunyn Schmiedebergs Arch Pharmacol, 2014]. In the present evaluated. WST1 assay showed similar toxicity of both tested drug *Corresponding author. study we examined their anxiolytic-like properties in two well- delivery modalities. The cytotoxicity of MTX-nanoflakes ranged establish anxiety rat models: elevated plus maze (EPM) and Vogel from 78% to 23% against A375 and MCF7, respectively. Free MTX Effect of acute peripheral IL-1b administration Introduction: Antimetabolites are one of the largest groups of conflict drinking test. produced similar effects, i.e. mortality rate of 70% and 14% in A375 on BDNF mRNA expression in the rat brain drugs used in the treatment of cancer, this group consists of Asenapine (0.1–1 mg/kg) at a dose of 1 mg/kg significantly and MCF7 cells. structures nucleoside analogues which, due to a structural similarity to increased the percentage of time spent in the open arms, but The results proved that mesoporous silica nanoflakes are 1, 1,2 natural metabolites, may competitively participate in important Ewa Obuchowicz *, Marta M. Nowacka , simultaneously at doses of 0.3 and 1 mg/kg decreased the number promising, effective drug nanocarriers. These findings may provide 3 1 cell processes. Nucleoside analogues by incorporation into nucleic Monika Paul-Samojedny , Anna M. Bielecka of entries into the open arms without affecting the percentage of helpful information for designing efficient drug delivery system. acids, inhibit their synthesis, interfere with the normal cell 1 the open arms entries. Lurasidone did not change significantly the Department of Pharmacology, School of Medicine in Katowice, The authors are grateful for financial support from the Fundation for functions which can lead to apoptosis. This study is an in vitro parameters measured in the EPM. In the Vogel test asenapina Medical University of Silesia, Katowice, Poland analysis of compounds derived from nucleoside analogues. Dimers administered at a dose of 1 mg/kg and lurasidone at a dose of Polish Science within the FOCUS Programme (F4/2010/P/2013). 2 Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy consisting of thymidine and AZT, AddFU, 5FdU linked by a 1,2,3- 10 mg/kg substantially increased the number of shocks accepted Kukuczka Academy of Physical Education, Katowice, Poland triazole linker were analyzed against cancer cell lines using by rats and the number of licks. http://dx.doi.org/10.1016/j.pharep.2015.06.099 3 Department of Medical Genetics, Faculty of Pharmacy in Sosnowiec, sulforhodamine in vitro screening test. Screening of potential antipsychotics for anxiolytic-like prop- Medical University of Silesia, Katowice, Poland Results and discussion: Compounds 18b, 19a and 19b presented erties is considered to be an important part of modern drug *Corresponding author. Assessment of the influence of nicotine on the highest activity with the lowest IC50 values. For KB cell line the development. Our data suggest that asenapina and lurasidone anxiety effects, depressive behaviour and results were respectively: 8.2 mg/ml, 7.0 mg/ml, 6.0 mg/ml, and for revealed anxiolytic-like effects in EPM and/or in Vogel conflict Various medical conditions are associated with an activation of cognitive processes induced by prolonged stress the HeLa cell line were: 7.0 mg/ml, 6.4 mg/ml, 6.0 mg/ml. The drinking test in rats. peripheral cell-mediated immune, inflammatory, oxidative and in mice compound 20a with IC50 presented the lowest activity for cell lines KB – 40.3 mg/ml and HeLa – 45.0 mg/ml. The obtained results allow nitrosative stress pathways characterized, among the others, by an Supported by Funds for Statutory Activity of Jagiellonian University Karolina Pe˛kała *, Barbara Budzyn´ ska, us to conclude that the antitumor activity of our test compounds is enhanced levels of pro-inflammatory cytokines [Maes et al, Medical College, Krako´ w, Poland (K/ZDS/004121). Graz˙ yna Biała Neuroendocrinol Lett, 2011]. The present study was designed to related to the chemical structure of thymidine dimers. We can also assess the influence of an increased IL-1b levels at the periphery on http://dx.doi.org/10.1016/j.pharep.2015.06.098 Department of Pharmacology and Pharmacodynamics, Medical conclude that the hydrophobic TBDMS substituent at the 5th brain derived neurotrophic factor (BDNF) mRNA expression in University of Lublin, Lublin, Poland position of one of the thymidine molecules provides the highest female and male rats and BDNF mRNA in females exposed to *Corresponding author. activity. The activity of the compounds is also likely influenced by Mesoporous silica nanoflakes – chronic social instability stress (CSIS) for 29–30 days. CSIS the length of the inter-nucleoside linker and the presence of Biocompatibility, cellular uptake and drug paradigm is known to be more stressful for females than males. Nicotine, as the main component of tobacco smoke, acting halogen atoms. transport Male rats or female rats in the estrus phase were given an ip through central mechanisms, exerts influence on mood and Conclusions: Lack of previous scientific publications about 1, 1 injection of recombinant rat IL-1b (50 mg/kg; R&D System) or Magdalena Peruz˙ ynska *, Mariola Zbroja , emotional tension, and also contributes to physical and mental antitumor activity of the thymidine dimers, clearly shows a need 1 1 sterile, non-pyrogenic 0.9% saline (2 ml/kg) 4 h before decapita- Klaudia We˛grzynowska , Klaudia Trzeciak , dependence. Additionally, it was demonstrated in some experimen- for further research. There is a possibility for a new modification of 1 2 tion. The BDNF mRNA was determined by the qRT-PCR in the Sylwia Szela˛g , Dorota Rogin´ ska , tal animal models that chronic and acute stress may aggravate both thymidine dimers that could lead to potential new anticancer drugs. 2 3 pituitary, hypothalamus, hippocampus and amygdala. In females, a Bogusław Machalin´ ski , Krzysztof Cendrowski , behavioural as well as neuronal effects caused by administration of 1 3 tendency towards a reduction in the expression of BDNF mRNA Mateusz Kurzawski , Ewa Mijowska , nicotine. Taking into account frequent concomitance of nicotine http://dx.doi.org/10.1016/j.pharep.2015.06.101 1 especially in the pituitary gland and hypothalamus was observed. Marek Droz´dzik abuse and stress accompanying daily life we aimed our research at In male rats, IL-1b induced the stronger effect on the studied 1 Department of Experimental & Clinical Pharmacology, Szczecin, assessment of behavioural effects accompanying single and Effects of the African plum (Pygenum africanum) growth factor in the limbic structures, particularly in the Poland prolonged administration of nicotine in combination with chronic bark extract on bone mechanical properties in amygdala. In females previously exposed to CSIS procedure, IL- 2 Department of General Pathology, Pomeranian Medical University, mild unpredictable stress (CMUS) in experimental animal models. rats 1b significantly decreased the number of BDNF mRNA copies as The level of anxiety was examined in the elevated plus maze test Szczecin, Poland Szymon Piskorz *, Urszula Cegieła, compared to its effect in the non-stressed rats. The results indicate 3 (EPM), depressive effects in the forced swim test (FST) and cognitive Institute of Chemical and Environment Engineering, West Pomera- Aleksandra Janas, Rafał Miozga the differences between female and male rats in the response of nian University of Technology, Szczecin, Poland processes in the passive avoidance test (PA). Additionally, the effect BDNF to the enhanced peripheral level of IL-1b and suggest that *Corresponding author. of metyrapone – a compound inhibiting synthesis of corticosterone Department of Pharmacology, Medical University of Silesia, Katowice, especially under stress condition the peripheral IL-1b over- was described. In the conducted examinations the mice were Sosnowiec, Poland expression may influence the CNS function. submitted to the procedure of CMUS for 4 weeks, 2 h per day (e.g., Mesoporous silica nanoflakes are new promising silica nano- *Corresponding author. wet litter or the lack of it, tilting the cage by 458, limitation of water materials. The studied materials were synthesized on graphene or food, an electric sound signal) (90 dB). It was found that single and http://dx.doi.org/10.1016/j.pharep.2015.06.097 sheets core, that after silica coverage was burned out. In The extract of the bark of African plum (Pygenum africanum) prolonged administration of nicotine reverses depressive and is used in the prophylaxis and treatment (adjunctively to 34 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 35

pharmacotherapy) of benign prostatic hyperplasia. The aim of the mRNA expression of all studied neuronal markers in cellular extracts Converging lines of evidence suggest that the pharmacological neuronal cultures of hippocampal origin were better protected present study was to investigate the effect of the extract of the bark prepared from the cultures exposed to the drug for 6–72 h. The antagonism of mGlu5 receptor with the negative allosteric against OGD insult than cortical neurons. Astrocyte cultures were of African plum on bone mechanical properties in rats with the nestin expression was the highest. These data confirm that the modulators, including MPEP, MTEP and GRN-529 exerts both the most resistant to ischemia mimicking condition and the presence of androgens and with androgen deficiency induced by microglial cells are important target for imipramine. anxiolytic- and antidepressant-like effects in several behavioural protective effects of the antidepressants were weaker than those orchidectomy. models of anxiety and depression. The present study was aimed at observed in the neuronal cultures. Three-month-old Wistar rats were orchidectomized (ORX) or http://dx.doi.org/10.1016/j.pharep.2015.06.103 investigating whether mGlu5 NAM, ADX48621 reveals anxiolytic- sham-operated (Sham), and, after 7 days, divided into 6 groups like and antidepressant-like properties in animal models of anxiety http://dx.doi.org/10.1016/j.pharep.2015.06.106 (n = 10): sham-operated control rats, sham-operated rats receiving (the elevated plus maze test (EPM), the stress-induced hyperther- Beneficial effects of concomitant administration the African plum barkextract (25 or 50 mg/kg), ORX control rats, ORX mia test (SIH) in mice) and depression (the forced swim test (FST) of bupropion and a pan-caspase inhibitor in Study on the mechanism of mydriatic activity of rats receiving the African plum bark extract (25 or 50 mg/kg). The in rats and mice and in the tail suspension test (TST) in mice). mice with experimental sepsis imidazoline derivatives dexmedetomidine, extract was administered by a gastric tube once daily, for 7 weeks (6 ADX48621 was administered per os 30 min before the experiment, 1, 1 marsanidine and 7-methylmarsanidine in rats – days a week). Mechanical properties of the tibial metaphysis and Krzysztof Pociecha *, Elz˙ bieta Wyska , at the doses of 3–50 mg/kg. 2 3 3 Are alpha2D-adrenoceptors engaged? femoral diaphysis and neck, and mass of bone and bone mineral, Monika Papiez˙ , Jacek Mlynarski , Sebastian Bas´ , In the EPM, ADX48621 at the dose of 50 mg/kg significantly 3 1, 1 were determined 8 weeks after ORX or sham operation. Marta Woyciechowska increased both the time spent in open arms and the number of Joanna Raczak-Gutknecht *, Teresa Fra˛ckowiak , Antoni Nasal 1, Anita Kornicka 2, Androgen deficiency induced by orchidectomy significantly 1 Department of Pharmacokinetics and Physical Pharmacy, Faculty of entries to open arms in CD-1 mice, which indicated anxiolytic-like Franciszek Sa˛czewski 2, Paweł Kowalski 1, reduced the mass of bone and bone mineral, causing significant Pharmacy, Jagiellonian University Medical College, Krako´w, Poland activity. Using the same strain of mice we also found that Roman Kaliszan 1 worsening of mechanical properties of the tibial metaphysis and 2 Department of Cytobiology, Faculty of Pharmacy, Jagiellonian ADX48621 (50 mg/kg) reduced the SIH response, thus confirming the femoral neck and diaphysis. anxiolytic potential of the drug. In the FST in rats the statistically University Medical College, Krako´w, Poland 1 Department of Biopharmaceutics and Pharmacodynamics, Medical The effect of the African plum bark extract on bone was 3 significant decrease in the immobility time was observed at the Faculty of Chemistry, Jagiellonian University, Krako´w, Poland University, Gdan´sk, Poland dependent on the level of androgens. Administration of the extract doses of 10 and 30 mg/kg of ADX48621. Additionally, dipraglurant *Corresponding author. 2 Department of Chemical Technology of Drugs, Medical University, counteracted the changes induced by androgen deficiency in (10 mg/kg) increased the swimming time parameter in this test. Gdan´sk, Poland orchidectomized rats, preventing the worsening of the mechanical Antidepressant-like effect was also noticed in the FST in CD-1 mice It is well known that apoptosis contributes significantly to the *Corresponding author. properties of the tibial metaphysis and femoral neck, and reduced when ADX48621 was administered at the doses of 30 and 50 mg/kg. pathophysiology of sepsis. Bupropion is an antidepressant drug that the unfavorable impact of orchidectomy on mechanical properties No effects of ADX48621 were observed in the TST in C57BL/6J mice. revealed an immunomodulatory activity in LPS-induced model of The imidazoline derivatives applicated to the circulatory of the femoral diaphysis. However, in rats with the presence of The examined compound did not affect the basal locomotor sepsis. The aim of the study was to examine the effects of bupropion system of laboratory animals (rats, cats and mice) are able to androgens, it did not significantly affect the mechanical properties activity in mice. The obtained results provided an evidence that the given separately and together with a pan-caspase inhibitor (Z-VAD- evoke pupillary dilation. Stimulation of postsynaptic a2-adreno- of the examined bones. selective mGlu5 receptor NAM, dipraglurant is a promising FMK) on serum TNF-a levels and markers of apoptosis in mice with ceptors within the Edinger-Westphal nucleus in the brain is therapeutic target for the treatment of anxiety and depression. sepsis induced by cecal ligation and puncture (CLP). The animals assumed to be responsible for this effect, while the I1-imidazoline http://dx.doi.org/10.1016/j.pharep.2015.06.102 were divided into 5 groups (n = 5): a sham-operated group (I), a http://dx.doi.org/10.1016/j.pharep.2015.06.105 receptors seem to be not involved. In our studies the mydriatic group with sepsis receiving an appropriate volume of vehicle (II), effect evoked by imidazoline-like agents: dexmedetomidine, Imipramine enhances expression of some 50 mg/kg bupropion ip (III), 1 mg/kg Z-VAD-FMK iv (IV), or both marsanidine, and 7-methylmarsanidine were compared. Effect of desipramine, fluoxetine and neuronal markers in glia cells in the rat primary compounds simultaneously (V) 1 h before CLP. The mice were The compounds studied were administered to anaesthetized tranylcypromine on viability and apoptosis of mixed glial culture sacrificed 24 h post-surgery and blood and thymi were collected. Wistar rats intravenously in cumulative doses. Pupil diameter was The level of apoptosis was determined using flow cytometry rat primary neuronal and astrocytic cell cultures measured by using stereoscopic microscope. All the compounds Marta Plato 1,*, Anna M. Bielecka 1, Joanna Orchel 2, (annexin V and iodium propide staining of thymocytes) and a subjected to oxygen-glucose deprivation in vitro exerted marked mydriatic activity. Among the agents studied Ewa Obuchowicz 1 fluorometric method (caspase 3 activity kit), whereas serum TNF-a Anna Pudełko *, Anna M. Bielecka, dexmedetomidine has the highest affinity to alpha2-adrenoceptors 1 Department of Pharmacology, School of Medicine in Katowice, levels were measured using ELISA. Mean percentages of annexin Ewa Obuchowicz (ED50 = 1.17 mg/kg). The corresponding ED50 values for 7-methyl- Medical University of Silesia, Katowice, Poland positive cells in groups I–V were: 5.7 4.4 (I), 34.0 17.9 (II), marsanidine and marsanidine were: 6.27 mg/kg and 53.7 mg/kg � � School of Medicine in Katowice, Medical University of Silesia in 2 Department of Molecular Biology, Faculty of Pharmacy in Sosnowiec, 20.2 7.1 (III), 26.2 11.1 (IV), and 15.3 2.6 (V), whereas mean respectively. Preliminary expariments with AGN 192403 regarded � � � Katowice, Department of Pharmacology, Katowice, Poland Medical University of Silesia, Katowice, Poland caspase activities (expressed in relative fluorescence units) in thymi as selective I1-imidazoline receptor antagonist seem to confirm the *Corresponding author. *Corresponding author. were: 10.2 0.1 (I), 89.7 54.1 (II), 32.2 28.1 (III), 29.7 20.3 (IV), hypothesis that involvement of these receptors in mydriatic effects � � � � and 13.3 4 (V). The mean serum TNF-a concentrations were not of imidazolines is marginal, if any. RX 821002 – a selective alpha2D- � According to the latest hypothesis the increase in the prolifera- affected by Z-VAD-FMK (155.0 214.6 vs. 142.1 218.5 pg/ml). adrenergic receptor antagonist caused parallel shift to the right of Imipramine, the oldest tricyclic antidepressant is recommended � � tion of neural precursors in adult hippocampus is considered to be Administration of bupropion significantly decreased levels of this the dose effects curves obtained for the agents studied. It may to use as a drug of second choice in therapy of endogenous involved in the mechanism of action of antidepressants. The changes cytokine both in the absence and presence of Z-VAD-FMK (18.4 8.6 suggest that this subtype of alpha2-adrenoceptor is engaged in depression and illness-associated depression and in therapy of � in neurogenesis are only seen after chronic, but not acute, treatment and 32.8 28.2 pg/ml, respectively). In conclusion, bupropion not only mydriatic effects of imidazoline derivatives. neuropathic pain. This drug is also frequently applied in pharmaco- � with antidepressant drugs. Moreover, several data suggest that significantly decreased serum TNF-a levels and apoptosis in thymi of logical studies as a reference antidepressant. The results of our antidepressant drugs may act indirectly via influence on glial cell mice with sepsis but also enhanced the anti-apoptotic effect of Z-VAD- earlier study shown that imipramine induced transformation of function (e.g. release of neurotrophins). http://dx.doi.org/10.1016/j.pharep.2015.06.107 FMK. Thus, this compound combination seems to be a promising microglial cells in the rat primary mixed glial culture into cells with The aim of the study was to evaluate and compare the effects of neuron-like phenotype [Obuchowicz et al., Pharmacol Rep, 2014]. alternative to the existing treatments of experimental sepsis. antidepressants, representatives of the distinct classes, on cell Evaluation of pharmacological interactions of Therefore, the present study was designed to check the effect of viability (MTT) and intensity of apoptosis (Hoechst 33342 dye) in the new imidazoline derivatives marsanidine and 7- imipramine on expression of some selected neuronal markers in the http://dx.doi.org/10.1016/j.pharep.2015.06.104 primary cultures of rat cortical neurons and astrocytes as well as methylmarsanidine with alpha2-adrenergic primary mixed glial culture. Experiments were performed on rat hippocampal neurons exposed to oxygen-glucose deprivation (OGD) receptors using rat mydriasis model primary mixed glial cell cultures in standard conditions (37 C, 95% 8 Potential anxiolytic- and antidepressant-like in vitro. OGD model is recognized cell damaging and pro-apoptotic 1, 1 air, 5% CO ). On day 13, the culture medium was replaced with a Joanna Raczak-Gutknecht *, Teresa Fra˛ckowiak , 2 activity of Dipraglurant (ADX48621), the novel stimulus applied to test protective effects of drugs and chemicals. 1 1 2 medium containing additionally imipramine in a concentration of Antoni Nasal , Paweł Kowalski , Anita Kornicka , negative allosteric modulator (NAM) of the Desipramine (tricyclic antidepressant drug, TAD), fluoxetine 2 1 Franciszek Sa˛czewski , Roman Kaliszan 10 mM. Total RNA was extracted from cells after 6, 12, 24, 48, 72 h metabotropic glutamate 5 (mGlu5) receptor (selective serotonin re-uptake inhibitor, SSRI) and tranylcypromine and 7 days incubation with imipramine using Trizol reagent 1 Karolina Podkowa 1,*, Agnieszka (non-selective MAO inhibitor) were added to the culture medium Department of Biopharmaceutics and Pharmacodynamics, Medical (Invitrogen) according to Chomczynski’s method (Chomczynski, Pałucha-Poniewiera 1, Sonia Poli 2, Andrzej Pilc 1 (concentration range 0.1–10 mM) and the cells were subjected to University, Gdan´sk, Poland 1993). The expression of neuronal markers such as: nestin, 2 OGD (3% O2, without glucose and trophic factors in medium) for 24 h. Department of Chemical Technology of Drugs, Medical University, 1 neurofilament (NF-200) and synaptophysine was analysed by Department of Neurobiology, Institute of Pharmacology Polish Antidepressants produced concentration-dependent protective Gdan´sk, Poland qRT-PCR assay (LightCykler 480, Roche). The expression of this Academy of Sciences, Krako´w, Poland effects on primary cultures exposed to OGD and reduced the *Corresponding author. 2 markers were estimated against a constitutive expression level of Addex Pharmaceuticals SA, 14 Chemin des Aulx, CH-1228, Plan Les number of apoptotic cells. The beneficial effects of the studied the house-keeping gene GAPDH (Glyceraldehyde 3-phosphate Ouates, Geneva, Switzerland drugs were found when the cell cultures were exposed to OGD and Firstly was postulated that central circulatory and mydriatic dehydrogenase). It has been found that imipramine increased *Corresponding author. the lower drug concentration (0.1 mM and 1 mM). Moreover, the effects of clonidine-like drugs are mediated exclusively via 34 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 35 pharmacotherapy) of benign prostatic hyperplasia. The aim of the mRNA expression of all studied neuronal markers in cellular extracts Converging lines of evidence suggest that the pharmacological neuronal cultures of hippocampal origin were better protected present study was to investigate the effect of the extract of the bark prepared from the cultures exposed to the drug for 6–72 h. The antagonism of mGlu5 receptor with the negative allosteric against OGD insult than cortical neurons. Astrocyte cultures were of African plum on bone mechanical properties in rats with the nestin expression was the highest. These data confirm that the modulators, including MPEP, MTEP and GRN-529 exerts both the most resistant to ischemia mimicking condition and the presence of androgens and with androgen deficiency induced by microglial cells are important target for imipramine. anxiolytic- and antidepressant-like effects in several behavioural protective effects of the antidepressants were weaker than those orchidectomy. models of anxiety and depression. The present study was aimed at observed in the neuronal cultures. Three-month-old Wistar rats were orchidectomized (ORX) or http://dx.doi.org/10.1016/j.pharep.2015.06.103 investigating whether mGlu5 NAM, ADX48621 reveals anxiolytic- sham-operated (Sham), and, after 7 days, divided into 6 groups like and antidepressant-like properties in animal models of anxiety http://dx.doi.org/10.1016/j.pharep.2015.06.106 (n = 10): sham-operated control rats, sham-operated rats receiving (the elevated plus maze test (EPM), the stress-induced hyperther- Beneficial effects of concomitant administration the African plum barkextract (25 or 50 mg/kg), ORX control rats, ORX mia test (SIH) in mice) and depression (the forced swim test (FST) of bupropion and a pan-caspase inhibitor in Study on the mechanism of mydriatic activity of rats receiving the African plum bark extract (25 or 50 mg/kg). The in rats and mice and in the tail suspension test (TST) in mice). mice with experimental sepsis imidazoline derivatives dexmedetomidine, extract was administered by a gastric tube once daily, for 7 weeks (6 ADX48621 was administered per os 30 min before the experiment, 1, 1 marsanidine and 7-methylmarsanidine in rats – days a week). Mechanical properties of the tibial metaphysis and Krzysztof Pociecha *, Elz˙ bieta Wyska , at the doses of 3–50 mg/kg. 2 3 3 Are alpha2D-adrenoceptors engaged? femoral diaphysis and neck, and mass of bone and bone mineral, Monika Papiez˙ , Jacek Mlynarski , Sebastian Bas´ , In the EPM, ADX48621 at the dose of 50 mg/kg significantly 3 1, 1 were determined 8 weeks after ORX or sham operation. Marta Woyciechowska increased both the time spent in open arms and the number of Joanna Raczak-Gutknecht *, Teresa Fra˛ckowiak , Antoni Nasal 1, Anita Kornicka 2, Androgen deficiency induced by orchidectomy significantly 1 Department of Pharmacokinetics and Physical Pharmacy, Faculty of entries to open arms in CD-1 mice, which indicated anxiolytic-like Franciszek Sa˛czewski 2, Paweł Kowalski 1, reduced the mass of bone and bone mineral, causing significant Pharmacy, Jagiellonian University Medical College, Krako´w, Poland activity. Using the same strain of mice we also found that Roman Kaliszan 1 worsening of mechanical properties of the tibial metaphysis and 2 Department of Cytobiology, Faculty of Pharmacy, Jagiellonian ADX48621 (50 mg/kg) reduced the SIH response, thus confirming the femoral neck and diaphysis. anxiolytic potential of the drug. In the FST in rats the statistically University Medical College, Krako´w, Poland 1 Department of Biopharmaceutics and Pharmacodynamics, Medical The effect of the African plum bark extract on bone was 3 significant decrease in the immobility time was observed at the Faculty of Chemistry, Jagiellonian University, Krako´w, Poland University, Gdan´sk, Poland dependent on the level of androgens. Administration of the extract doses of 10 and 30 mg/kg of ADX48621. Additionally, dipraglurant *Corresponding author. 2 Department of Chemical Technology of Drugs, Medical University, counteracted the changes induced by androgen deficiency in (10 mg/kg) increased the swimming time parameter in this test. Gdan´sk, Poland orchidectomized rats, preventing the worsening of the mechanical Antidepressant-like effect was also noticed in the FST in CD-1 mice It is well known that apoptosis contributes significantly to the *Corresponding author. properties of the tibial metaphysis and femoral neck, and reduced when ADX48621 was administered at the doses of 30 and 50 mg/kg. pathophysiology of sepsis. Bupropion is an antidepressant drug that the unfavorable impact of orchidectomy on mechanical properties No effects of ADX48621 were observed in the TST in C57BL/6J mice. revealed an immunomodulatory activity in LPS-induced model of The imidazoline derivatives applicated to the circulatory of the femoral diaphysis. However, in rats with the presence of The examined compound did not affect the basal locomotor sepsis. The aim of the study was to examine the effects of bupropion system of laboratory animals (rats, cats and mice) are able to androgens, it did not significantly affect the mechanical properties activity in mice. The obtained results provided an evidence that the given separately and together with a pan-caspase inhibitor (Z-VAD- evoke pupillary dilation. Stimulation of postsynaptic a2-adreno- of the examined bones. selective mGlu5 receptor NAM, dipraglurant is a promising FMK) on serum TNF-a levels and markers of apoptosis in mice with ceptors within the Edinger-Westphal nucleus in the brain is therapeutic target for the treatment of anxiety and depression. sepsis induced by cecal ligation and puncture (CLP). The animals assumed to be responsible for this effect, while the I1-imidazoline http://dx.doi.org/10.1016/j.pharep.2015.06.102 were divided into 5 groups (n = 5): a sham-operated group (I), a http://dx.doi.org/10.1016/j.pharep.2015.06.105 receptors seem to be not involved. In our studies the mydriatic group with sepsis receiving an appropriate volume of vehicle (II), effect evoked by imidazoline-like agents: dexmedetomidine, Imipramine enhances expression of some 50 mg/kg bupropion ip (III), 1 mg/kg Z-VAD-FMK iv (IV), or both marsanidine, and 7-methylmarsanidine were compared. Effect of desipramine, fluoxetine and neuronal markers in glia cells in the rat primary compounds simultaneously (V) 1 h before CLP. The mice were The compounds studied were administered to anaesthetized tranylcypromine on viability and apoptosis of mixed glial culture sacrificed 24 h post-surgery and blood and thymi were collected. Wistar rats intravenously in cumulative doses. Pupil diameter was The level of apoptosis was determined using flow cytometry rat primary neuronal and astrocytic cell cultures measured by using stereoscopic microscope. All the compounds Marta Plato 1,*, Anna M. Bielecka 1, Joanna Orchel 2, (annexin V and iodium propide staining of thymocytes) and a subjected to oxygen-glucose deprivation in vitro exerted marked mydriatic activity. Among the agents studied Ewa Obuchowicz 1 fluorometric method (caspase 3 activity kit), whereas serum TNF-a Anna Pudełko *, Anna M. Bielecka, dexmedetomidine has the highest affinity to alpha2-adrenoceptors 1 Department of Pharmacology, School of Medicine in Katowice, levels were measured using ELISA. Mean percentages of annexin Ewa Obuchowicz (ED50 = 1.17 mg/kg). The corresponding ED50 values for 7-methyl- Medical University of Silesia, Katowice, Poland positive cells in groups I–V were: 5.7 4.4 (I), 34.0 17.9 (II), marsanidine and marsanidine were: 6.27 mg/kg and 53.7 mg/kg � � School of Medicine in Katowice, Medical University of Silesia in 2 Department of Molecular Biology, Faculty of Pharmacy in Sosnowiec, 20.2 7.1 (III), 26.2 11.1 (IV), and 15.3 2.6 (V), whereas mean respectively. Preliminary expariments with AGN 192403 regarded � � � Katowice, Department of Pharmacology, Katowice, Poland Medical University of Silesia, Katowice, Poland caspase activities (expressed in relative fluorescence units) in thymi as selective I1-imidazoline receptor antagonist seem to confirm the *Corresponding author. *Corresponding author. were: 10.2 0.1 (I), 89.7 54.1 (II), 32.2 28.1 (III), 29.7 20.3 (IV), hypothesis that involvement of these receptors in mydriatic effects � � � � and 13.3 4 (V). The mean serum TNF-a concentrations were not of imidazolines is marginal, if any. RX 821002 – a selective alpha2D- � According to the latest hypothesis the increase in the prolifera- affected by Z-VAD-FMK (155.0 214.6 vs. 142.1 218.5 pg/ml). adrenergic receptor antagonist caused parallel shift to the right of Imipramine, the oldest tricyclic antidepressant is recommended � � tion of neural precursors in adult hippocampus is considered to be Administration of bupropion significantly decreased levels of this the dose effects curves obtained for the agents studied. It may to use as a drug of second choice in therapy of endogenous involved in the mechanism of action of antidepressants. The changes cytokine both in the absence and presence of Z-VAD-FMK (18.4 8.6 suggest that this subtype of alpha2-adrenoceptor is engaged in depression and illness-associated depression and in therapy of � in neurogenesis are only seen after chronic, but not acute, treatment and 32.8 28.2 pg/ml, respectively). In conclusion, bupropion not only mydriatic effects of imidazoline derivatives. neuropathic pain. This drug is also frequently applied in pharmaco- � with antidepressant drugs. Moreover, several data suggest that significantly decreased serum TNF-a levels and apoptosis in thymi of logical studies as a reference antidepressant. The results of our antidepressant drugs may act indirectly via influence on glial cell mice with sepsis but also enhanced the anti-apoptotic effect of Z-VAD- earlier study shown that imipramine induced transformation of function (e.g. release of neurotrophins). http://dx.doi.org/10.1016/j.pharep.2015.06.107 FMK. Thus, this compound combination seems to be a promising microglial cells in the rat primary mixed glial culture into cells with The aim of the study was to evaluate and compare the effects of neuron-like phenotype [Obuchowicz et al., Pharmacol Rep, 2014]. alternative to the existing treatments of experimental sepsis. antidepressants, representatives of the distinct classes, on cell Evaluation of pharmacological interactions of Therefore, the present study was designed to check the effect of viability (MTT) and intensity of apoptosis (Hoechst 33342 dye) in the new imidazoline derivatives marsanidine and 7- imipramine on expression of some selected neuronal markers in the http://dx.doi.org/10.1016/j.pharep.2015.06.104 primary cultures of rat cortical neurons and astrocytes as well as methylmarsanidine with alpha2-adrenergic primary mixed glial culture. Experiments were performed on rat hippocampal neurons exposed to oxygen-glucose deprivation (OGD) receptors using rat mydriasis model primary mixed glial cell cultures in standard conditions (37 C, 95% 8 Potential anxiolytic- and antidepressant-like in vitro. OGD model is recognized cell damaging and pro-apoptotic 1, 1 air, 5% CO ). On day 13, the culture medium was replaced with a Joanna Raczak-Gutknecht *, Teresa Fra˛ckowiak , 2 activity of Dipraglurant (ADX48621), the novel stimulus applied to test protective effects of drugs and chemicals. 1 1 2 medium containing additionally imipramine in a concentration of Antoni Nasal , Paweł Kowalski , Anita Kornicka , negative allosteric modulator (NAM) of the Desipramine (tricyclic antidepressant drug, TAD), fluoxetine 2 1 Franciszek Sa˛czewski , Roman Kaliszan 10 mM. Total RNA was extracted from cells after 6, 12, 24, 48, 72 h metabotropic glutamate 5 (mGlu5) receptor (selective serotonin re-uptake inhibitor, SSRI) and tranylcypromine and 7 days incubation with imipramine using Trizol reagent 1 Karolina Podkowa 1,*, Agnieszka (non-selective MAO inhibitor) were added to the culture medium Department of Biopharmaceutics and Pharmacodynamics, Medical (Invitrogen) according to Chomczynski’s method (Chomczynski, Pałucha-Poniewiera 1, Sonia Poli 2, Andrzej Pilc 1 (concentration range 0.1–10 mM) and the cells were subjected to University, Gdan´sk, Poland 1993). The expression of neuronal markers such as: nestin, 2 OGD (3% O2, without glucose and trophic factors in medium) for 24 h. Department of Chemical Technology of Drugs, Medical University, 1 neurofilament (NF-200) and synaptophysine was analysed by Department of Neurobiology, Institute of Pharmacology Polish Antidepressants produced concentration-dependent protective Gdan´sk, Poland qRT-PCR assay (LightCykler 480, Roche). The expression of this Academy of Sciences, Krako´w, Poland effects on primary cultures exposed to OGD and reduced the *Corresponding author. 2 markers were estimated against a constitutive expression level of Addex Pharmaceuticals SA, 14 Chemin des Aulx, CH-1228, Plan Les number of apoptotic cells. The beneficial effects of the studied the house-keeping gene GAPDH (Glyceraldehyde 3-phosphate Ouates, Geneva, Switzerland drugs were found when the cell cultures were exposed to OGD and Firstly was postulated that central circulatory and mydriatic dehydrogenase). It has been found that imipramine increased *Corresponding author. the lower drug concentration (0.1 mM and 1 mM). Moreover, the effects of clonidine-like drugs are mediated exclusively via 36 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 37 alfa2-adrenoceptor stimulation, however it has been discovered in the Scale of Adverse Effects and of duration of the illness on the (e.g. risperidone, RIS) to the ongoing treatment with antidepres- Depletion of peripheral macrophages influences later that imidazoline compounds exhibit also a high affinity to probability of remission was found. sants ADs, especially with selective serotonin reuptake inhibitors antidepressive action of electroconvulsive shock imidazoline receptors. The in vivo rat mydriasis model allows to The results require further confirmation in the clinical trial (SSRI) on the therapy of drug-resistant depression. Furthermore, (ECS) in the Porsolt’s test and alters MIF and obtain more details about the interactions between alpha2- applying in the larger group of patients. some earlier studies indicated a low level of the serum brain- BDNF expression in rat brain adrenoceptors and imidazoline derivatives (the potency, receptor derived neurotrophic factor (BDNF) in patients with major The study was partly funded by the NCN no. 2012/07/B/NZ7/04375. Adam Roman *, Justyna Kus´mierczyk, Marta affinity and agonistic/antagonistic properties) than in vitro studies. depressive disorders compared to control subjects. In addition, Kowalska, Ewa Trojan, Irena Nalepa The aim of the study was to evaluate the pharmacological they also demonstrated that treatment with ADs increased serum interactions of newly synthesized imidazoline ligands: marsani- http://dx.doi.org/10.1016/j.pharep.2015.06.109 BDNF concentration in depressed patients up to the level described Department of Brain Biochemistry, Institute of Pharmacology Polish dine and 7-methylmarsanidine with alpha2-adrenergic receptors in healthy controls. Thus, in the present study we investigated the Academy of Sciences, Krako´w, Poland localized in the brain. Both compounds showed significant affinity Anxiolytic-like effect of Aripiprazole and effect of repeated administration (once daily for14 day) of the SSRI *Corresponding author. to alpha2-adrenoceptors in rat brain radioligand studies (Ki values Olanzapine observed in prenatally stressed rats escitalopram (ESC) and a low dose of RIS, given separately or were 14.05 nM and 53.5 nM, respectively) [Sa˛czewski, J Med Chem, exposed to the ethyl alcohol jointly, on the BDNF mRNA and BDNF or p-CREB protein levels in The aim of the present study was to assess the effect of 2008]. Additionally yohimbine – a selective alpha2-adrenoceptor the hippocampus and prefrontal cortex of male Wistar rats. ESC depletion of peripheral macrophages on antidepressive action of Piotr Ratajczak *, Krzysztof Kus, antagonist was used in the experiments. The drug was adminis- (2.5, 5 and 10 mg/kg) was given repeatedly, separately or jointly ECS and on expression of selected markers in hippocampi of male Elz˙ bieta Nowakowska tered iv. to the rats at the dose 1.5 mg/kg prior to the cumulative with RIS (0.05 or 0.1 mg/kg). The tissue for biochemical assays was Wistar rats subjected to Porsolt’s test. Depletion was achieved by doses of the imidazolines studied. The results obtained confirmed Department of Pharmacoeconomics and Social Pharmacy, Poznan dissected 24 h after the last dose of ESC and RIS. The obtained twice intraperitoneal injections of clodronate encapsulated in the potent mydriatic activities of the compounds studied. University of Medical Sciences, Poznan´, Poland results showed that repeated treatment with ESC at a dose of liposomes. ECS was administered through ear clips once a day for Maximum mydriatic effects (Emax) of marsanidine and 7-methyl- *Corresponding author. 10 mg/kg only (but not with RIS in either dose used) significantly 10 consecutive days (70 mA, 100 pulses/s, 0.5 s) starting from the marsanidine were 3.76 mm and 3.45 mm, respectively and were elevated expression of mRNA and BDNF protein levels in the next day after second dose of liposomes. Antidepressive action was comparable to the model imidazoline drug – clonidine The aim of study was to find whether anxiety-like behavior was hippocampus. Co-administration with ESC (2.5 or 5 mg/kg) and RIS assessed by the Porsolt’s test 24 h after the last treatment. The rats (Emax = 3.61 mm). Yohimbine caused parallel shift to the right of found in prenatally stressed rats (animal model of schizophrenia) induced a more potent increase in BDNF mRNA expression in the were sacrificed one day after Porsolt’s test. The hippocampi were the dose-effect curves obtained for both compounds which and whether single and chronic administration of aripiprazole ARI hippocampus or prefrontal cortex and in the p-CREB protein level dissected and mRNA expression of selected markers: macrophage confirms the engagement of alpha2-adrenoceptor in the pupil (1.5 mg/kg ip) and olanzapine OLA (0.5 mg/kg ip) modify those only in the prefrontal cortex compared to either drugs given alone. migration inhibitory factor (MIF), cyklooksygenase-2 (COX-2), dilation mechanism of imidazolines studied. effect. We also determine whether ethyl alcohol exposure The obtained results suggest that the enhancement of BDNF gene transforming growth factor-b (TGF-b) and brain derived neuro- influence on the anxiolytic effect of drugs. expression may be essential for the therapeutic effect of co- trophic factor (BDNF) was measured with real-time PCR using http://dx.doi.org/10.1016/j.pharep.2015.06.108 The anxiolytic effects of ARI and OLA were determined in two treatment with ESC and a low dose RIS in drug-resistant depressed TaqMan gene expression assay. The results were standardized compartment exploratory test and were conducted on the NSCG patients. using HPRT as a reference gene. The depletion of macrophages led (non-stressed control group), PSG (prenatally stressed group), to shortening of the immobility time in Porsolt’s test and thus Therapeutic drug monitoring of depression – This study was financially supported by grant POIG. 01.01.02-12-004/ NSAG (non-stressed alcohol group) and PSAG (prenatally stressed modulated the antidepressive effect of ECS. Application of ECS Amplification by magnesium ions 09-00 and partly by statutory funds of the Institute of Pharmacology, alcohol group). decreased MIF expression only in rats depleted of macrophages 1,4, PAS, Krako´ w. Maria Radziwon´ -Zaleska *, Results indicate that treatment of both ARI and OLA produced a and increased COX-2 expression regardless of presence of 4 Beata Ryszewska-Pokrasńiewicz , statistically significant increase in the number of entries in the macrophages. Elimination of macrophages decreased BDNF 1,4 4 Michał Skalski , Jakub Skrzeszewski , white compartment (evidence of an anxiolytic effect) observed in http://dx.doi.org/10.1016/j.pharep.2015.06.111 expression regardless of ECS application. There were no changes 1,4 3,2 Ewa Drozdowicz , Gabriel Nowak , the NSCG (1, 7 and 21 days) and PSG (1, 7, 14 and 21 days) rats. In in expression of TGF-b. Our results showed that elimination of 3,2 5 Andrzej Pilc , Ewa Bałkowiec-Iskra turn study of the NSAG and PSAG indicate that only ARI showed an Therapeutic equivalence of psychotropic drugs peripheral macrophages may disturb ECS-driven homing of the anxiolytic effects (in both groups) – evidence of ARI anxiolytic cells into central nervous system and may participate in changes of 1 Chair of Psychiatry, Medical University of Warsaw, Warszawa, Konrad Rokita 1,3,*, Grzegorz Cessak 1,2, efficacy in ethanol exposed conditions. MIF and BDNF expression observed in the present study. Thus, Poland Marta Da˛browska 1, Ewa Bałkowiec-Iskra 1,2,3 Results indicate that ARI and OLA showed an anxiolytic effect in macrophages may play an important role not only in pathome- 2 Jagiellonian University Medical College, Krako´w, Poland both NSCG and PSG rats while after ethyl alcohol exposure only ARI 1 Department of Experimental and Clinical Pharmacology, Medical chanisms of depression but also in therapeutic action of ECS, both 3 Institiute of Pharmacology, Polish Academy of Science, Krako´w, demonstrated that effect. Anxiolytic effect of ARI in the ethanol University of Warsaw, Warszawa, Poland at behavioral and biochemical level. Poland exposed rats was probably related to the drug mechanism of action 2 The Office for Registration of Medicinal Products, Medical Devices 4 Nowowiejski Hospital, Warszawa, Poland This work was supported in part by grant no. POIG.01.01.02-12-004/ – ARI acts as partial agonist of the 5-HT1A receptors which was and Biocidal Products, Warszawa, Poland 5 Department of Experimental and Clinical Pharmacology, Medical 09 co-financed by the European Regional Development Fund and by previously reported [Savitz J, Prog Neurobiol, 2009] to be possibly 3 Nowowiejski City Hospital, Warszawa, Poland University of Warsaw, Warszawa, Poland . involved in the expression of anxiety-like behavior. Considering *Corresponding author. statutory funds of Institute of Pharmacology PAS *Corresponding author. the above, it seems justified to conduct further studies aimed at ARI effectiveness as well as searching new efficient methods of Introduction to the market of generic drugs has increased http://dx.doi.org/10.1016/j.pharep.2015.06.113 The aim of the study is to revise a hypothesis whether the pharmacotherapy for patients diagnosed with schizophrenia and access to modern therapies and enabled significant reduction of inhibition of the NMDA receptor by magnesium ions intensifies abusing ethyl alcohol. their cost, leading to containment of public expenditures on drug and accelerates antidepressant effect of the fluoxetine. Significance of the genetic polymorphism of reimbursement. The assessment of bioequivalence of reference CYP2D6 in patients with bullous pemphigoid The research was conducted in the Clinical Wards of the Chair of http://dx.doi.org/10.1016/j.pharep.2015.06.110 and generic drugs is based on the assumption that two different 1, 1 Psychiatry, 34 patients who were on the fluoxetine therapy due to Mariola Rychlik-Sych *, Małgorzata Baran´ ska , drug products are equivalent when their rate and extent of 1 1 a depression episode were included in the trial. The trial was Anna Wojtczak , Jadwiga Skre˛tkowicz , absorption do not show significant differences when administered 2 2 conducted on the double blind methodology with supplementa- Repeated co-treatment with escitalopram and Agnieszka Z˙ ebrowska , Elz˙ bieta Waszczykowska at the same dose under similar experimental conditions. However, tion of either magnesium ions or placebo. During an 8 week risperidone induces brain-derived neurotrophic despite regulatory declaration, switching from reference to generic 1 Department of Pharmacogenetics, Chair of Biopharmacy, Medical observation, using the psychometric scales, the clinical status of factor gene expression in rats drugs is often associated with concerns of healthcare providers University of Lodz, Ło´dz´, Poland the patients was assessed. Additionally, the levels of fluoxetine and 1,2, 1 Zofia Rogo´ z˙ *, Katarzyna Kamin´ ska , about decreased treatment effectiveness or occurrence of adverse 2 Department of Dermatology and Venereology, Chair of Dermatology magnesium in blood were controlled and the pharmaco-EEG was 1 Magdalena Sowa-Kuc´ma drug reactions. The aim of the present research was to and Venereology, Medical University of Lodz, Ło´dz´, Poland conducted. 1 retrospectively study therapeutic equivalence of selected refer- *Corresponding author. During all stages of the therapy there were no significant Institute of Pharmacology, Polish Academy of Sciences, Krako´w, ence and generic psychotropic drugs in patients treated in differences between patients treated with fluoxetine/magnesium Poland 2 Nowowiejski Hospital. In our preliminary data we show, that no ions and patients treated with fluoxetine/placebo, concerning Institute of Cosmetology, The Podhale State Higher Vocational School, Bullous pemphigoid (BP) belong to the group of autoimmune significant differences in clinical outcome was observed in patients neither the efficacy of the treatment nor its safety. There were no Nowy Targ, Poland diseases. Pathogenesis of autoimmune diseases is connected with after the switch. It indicates, that bioequivalent drugs are also statistically significant differences in the pharmaco-EEG profile in *Corresponding author. influence of environmental factors with individual dependence therapeutically equivalent and can be used interchangeably. both groups. among others on detoxification enzymes. Currently, the role of In the multidimensional statistical analysis of the whole Several clinical studies have recently suggested a beneficial cytochrome P-450 and its isoenzymes have been considered investigated group, a significant influence of the output values effect of the addition of a low dose of an atypical antipsychotic drug http://dx.doi.org/10.1016/j.pharep.2015.06.112 significant both in regulating drug metabolism and determining 36 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 37 alfa2-adrenoceptor stimulation, however it has been discovered in the Scale of Adverse Effects and of duration of the illness on the (e.g. risperidone, RIS) to the ongoing treatment with antidepres- Depletion of peripheral macrophages influences later that imidazoline compounds exhibit also a high affinity to probability of remission was found. sants ADs, especially with selective serotonin reuptake inhibitors antidepressive action of electroconvulsive shock imidazoline receptors. The in vivo rat mydriasis model allows to The results require further confirmation in the clinical trial (SSRI) on the therapy of drug-resistant depression. Furthermore, (ECS) in the Porsolt’s test and alters MIF and obtain more details about the interactions between alpha2- applying in the larger group of patients. some earlier studies indicated a low level of the serum brain- BDNF expression in rat brain adrenoceptors and imidazoline derivatives (the potency, receptor derived neurotrophic factor (BDNF) in patients with major The study was partly funded by the NCN no. 2012/07/B/NZ7/04375. Adam Roman *, Justyna Kus´mierczyk, Marta affinity and agonistic/antagonistic properties) than in vitro studies. depressive disorders compared to control subjects. In addition, Kowalska, Ewa Trojan, Irena Nalepa The aim of the study was to evaluate the pharmacological they also demonstrated that treatment with ADs increased serum interactions of newly synthesized imidazoline ligands: marsani- http://dx.doi.org/10.1016/j.pharep.2015.06.109 BDNF concentration in depressed patients up to the level described Department of Brain Biochemistry, Institute of Pharmacology Polish dine and 7-methylmarsanidine with alpha2-adrenergic receptors in healthy controls. Thus, in the present study we investigated the Academy of Sciences, Krako´w, Poland localized in the brain. Both compounds showed significant affinity Anxiolytic-like effect of Aripiprazole and effect of repeated administration (once daily for14 day) of the SSRI *Corresponding author. to alpha2-adrenoceptors in rat brain radioligand studies (Ki values Olanzapine observed in prenatally stressed rats escitalopram (ESC) and a low dose of RIS, given separately or were 14.05 nM and 53.5 nM, respectively) [Sa˛czewski, J Med Chem, exposed to the ethyl alcohol jointly, on the BDNF mRNA and BDNF or p-CREB protein levels in The aim of the present study was to assess the effect of 2008]. Additionally yohimbine – a selective alpha2-adrenoceptor the hippocampus and prefrontal cortex of male Wistar rats. ESC depletion of peripheral macrophages on antidepressive action of Piotr Ratajczak *, Krzysztof Kus, antagonist was used in the experiments. The drug was adminis- (2.5, 5 and 10 mg/kg) was given repeatedly, separately or jointly ECS and on expression of selected markers in hippocampi of male Elz˙ bieta Nowakowska tered iv. to the rats at the dose 1.5 mg/kg prior to the cumulative with RIS (0.05 or 0.1 mg/kg). The tissue for biochemical assays was Wistar rats subjected to Porsolt’s test. Depletion was achieved by doses of the imidazolines studied. The results obtained confirmed Department of Pharmacoeconomics and Social Pharmacy, Poznan dissected 24 h after the last dose of ESC and RIS. The obtained twice intraperitoneal injections of clodronate encapsulated in the potent mydriatic activities of the compounds studied. University of Medical Sciences, Poznan´, Poland results showed that repeated treatment with ESC at a dose of liposomes. ECS was administered through ear clips once a day for Maximum mydriatic effects (Emax) of marsanidine and 7-methyl- *Corresponding author. 10 mg/kg only (but not with RIS in either dose used) significantly 10 consecutive days (70 mA, 100 pulses/s, 0.5 s) starting from the marsanidine were 3.76 mm and 3.45 mm, respectively and were elevated expression of mRNA and BDNF protein levels in the next day after second dose of liposomes. Antidepressive action was comparable to the model imidazoline drug – clonidine The aim of study was to find whether anxiety-like behavior was hippocampus. Co-administration with ESC (2.5 or 5 mg/kg) and RIS assessed by the Porsolt’s test 24 h after the last treatment. The rats (Emax = 3.61 mm). Yohimbine caused parallel shift to the right of found in prenatally stressed rats (animal model of schizophrenia) induced a more potent increase in BDNF mRNA expression in the were sacrificed one day after Porsolt’s test. The hippocampi were the dose-effect curves obtained for both compounds which and whether single and chronic administration of aripiprazole ARI hippocampus or prefrontal cortex and in the p-CREB protein level dissected and mRNA expression of selected markers: macrophage confirms the engagement of alpha2-adrenoceptor in the pupil (1.5 mg/kg ip) and olanzapine OLA (0.5 mg/kg ip) modify those only in the prefrontal cortex compared to either drugs given alone. migration inhibitory factor (MIF), cyklooksygenase-2 (COX-2), dilation mechanism of imidazolines studied. effect. We also determine whether ethyl alcohol exposure The obtained results suggest that the enhancement of BDNF gene transforming growth factor-b (TGF-b) and brain derived neuro- influence on the anxiolytic effect of drugs. expression may be essential for the therapeutic effect of co- trophic factor (BDNF) was measured with real-time PCR using http://dx.doi.org/10.1016/j.pharep.2015.06.108 The anxiolytic effects of ARI and OLA were determined in two treatment with ESC and a low dose RIS in drug-resistant depressed TaqMan gene expression assay. The results were standardized compartment exploratory test and were conducted on the NSCG patients. using HPRT as a reference gene. The depletion of macrophages led (non-stressed control group), PSG (prenatally stressed group), to shortening of the immobility time in Porsolt’s test and thus Therapeutic drug monitoring of depression – This study was financially supported by grant POIG. 01.01.02-12-004/ NSAG (non-stressed alcohol group) and PSAG (prenatally stressed modulated the antidepressive effect of ECS. Application of ECS Amplification by magnesium ions 09-00 and partly by statutory funds of the Institute of Pharmacology, alcohol group). decreased MIF expression only in rats depleted of macrophages 1,4, PAS, Krako´ w. Maria Radziwon´ -Zaleska *, Results indicate that treatment of both ARI and OLA produced a and increased COX-2 expression regardless of presence of 4 Beata Ryszewska-Pokrasńiewicz , statistically significant increase in the number of entries in the macrophages. Elimination of macrophages decreased BDNF 1,4 4 Michał Skalski , Jakub Skrzeszewski , white compartment (evidence of an anxiolytic effect) observed in http://dx.doi.org/10.1016/j.pharep.2015.06.111 expression regardless of ECS application. There were no changes 1,4 3,2 Ewa Drozdowicz , Gabriel Nowak , the NSCG (1, 7 and 21 days) and PSG (1, 7, 14 and 21 days) rats. In in expression of TGF-b. Our results showed that elimination of 3,2 5 Andrzej Pilc , Ewa Bałkowiec-Iskra turn study of the NSAG and PSAG indicate that only ARI showed an Therapeutic equivalence of psychotropic drugs peripheral macrophages may disturb ECS-driven homing of the anxiolytic effects (in both groups) – evidence of ARI anxiolytic cells into central nervous system and may participate in changes of 1 Chair of Psychiatry, Medical University of Warsaw, Warszawa, Konrad Rokita 1,3,*, Grzegorz Cessak 1,2, efficacy in ethanol exposed conditions. MIF and BDNF expression observed in the present study. Thus, Poland Marta Da˛browska 1, Ewa Bałkowiec-Iskra 1,2,3 Results indicate that ARI and OLA showed an anxiolytic effect in macrophages may play an important role not only in pathome- 2 Jagiellonian University Medical College, Krako´w, Poland both NSCG and PSG rats while after ethyl alcohol exposure only ARI 1 Department of Experimental and Clinical Pharmacology, Medical chanisms of depression but also in therapeutic action of ECS, both 3 Institiute of Pharmacology, Polish Academy of Science, Krako´w, demonstrated that effect. Anxiolytic effect of ARI in the ethanol University of Warsaw, Warszawa, Poland at behavioral and biochemical level. Poland exposed rats was probably related to the drug mechanism of action 2 The Office for Registration of Medicinal Products, Medical Devices 4 Nowowiejski Hospital, Warszawa, Poland This work was supported in part by grant no. POIG.01.01.02-12-004/ – ARI acts as partial agonist of the 5-HT1A receptors which was and Biocidal Products, Warszawa, Poland 5 Department of Experimental and Clinical Pharmacology, Medical 09 co-financed by the European Regional Development Fund and by previously reported [Savitz J, Prog Neurobiol, 2009] to be possibly 3 Nowowiejski City Hospital, Warszawa, Poland University of Warsaw, Warszawa, Poland . involved in the expression of anxiety-like behavior. Considering *Corresponding author. statutory funds of Institute of Pharmacology PAS *Corresponding author. the above, it seems justified to conduct further studies aimed at ARI effectiveness as well as searching new efficient methods of Introduction to the market of generic drugs has increased http://dx.doi.org/10.1016/j.pharep.2015.06.113 The aim of the study is to revise a hypothesis whether the pharmacotherapy for patients diagnosed with schizophrenia and access to modern therapies and enabled significant reduction of inhibition of the NMDA receptor by magnesium ions intensifies abusing ethyl alcohol. their cost, leading to containment of public expenditures on drug and accelerates antidepressant effect of the fluoxetine. Significance of the genetic polymorphism of reimbursement. The assessment of bioequivalence of reference CYP2D6 in patients with bullous pemphigoid The research was conducted in the Clinical Wards of the Chair of http://dx.doi.org/10.1016/j.pharep.2015.06.110 and generic drugs is based on the assumption that two different 1, 1 Psychiatry, 34 patients who were on the fluoxetine therapy due to Mariola Rychlik-Sych *, Małgorzata Baran´ ska , drug products are equivalent when their rate and extent of 1 1 a depression episode were included in the trial. The trial was Anna Wojtczak , Jadwiga Skre˛tkowicz , absorption do not show significant differences when administered 2 2 conducted on the double blind methodology with supplementa- Repeated co-treatment with escitalopram and Agnieszka Z˙ ebrowska , Elz˙ bieta Waszczykowska at the same dose under similar experimental conditions. However, tion of either magnesium ions or placebo. During an 8 week risperidone induces brain-derived neurotrophic despite regulatory declaration, switching from reference to generic 1 Department of Pharmacogenetics, Chair of Biopharmacy, Medical observation, using the psychometric scales, the clinical status of factor gene expression in rats drugs is often associated with concerns of healthcare providers University of Lodz, Ło´dz´, Poland the patients was assessed. Additionally, the levels of fluoxetine and 1,2, 1 Zofia Rogo´ z˙ *, Katarzyna Kamin´ ska , about decreased treatment effectiveness or occurrence of adverse 2 Department of Dermatology and Venereology, Chair of Dermatology magnesium in blood were controlled and the pharmaco-EEG was 1 Magdalena Sowa-Kuc´ma drug reactions. The aim of the present research was to and Venereology, Medical University of Lodz, Ło´dz´, Poland conducted. 1 retrospectively study therapeutic equivalence of selected refer- *Corresponding author. During all stages of the therapy there were no significant Institute of Pharmacology, Polish Academy of Sciences, Krako´w, ence and generic psychotropic drugs in patients treated in differences between patients treated with fluoxetine/magnesium Poland 2 Nowowiejski Hospital. In our preliminary data we show, that no ions and patients treated with fluoxetine/placebo, concerning Institute of Cosmetology, The Podhale State Higher Vocational School, Bullous pemphigoid (BP) belong to the group of autoimmune significant differences in clinical outcome was observed in patients neither the efficacy of the treatment nor its safety. There were no Nowy Targ, Poland diseases. Pathogenesis of autoimmune diseases is connected with after the switch. It indicates, that bioequivalent drugs are also statistically significant differences in the pharmaco-EEG profile in *Corresponding author. influence of environmental factors with individual dependence therapeutically equivalent and can be used interchangeably. both groups. among others on detoxification enzymes. Currently, the role of In the multidimensional statistical analysis of the whole Several clinical studies have recently suggested a beneficial cytochrome P-450 and its isoenzymes have been considered investigated group, a significant influence of the output values effect of the addition of a low dose of an atypical antipsychotic drug http://dx.doi.org/10.1016/j.pharep.2015.06.112 significant both in regulating drug metabolism and determining 38 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 39 other functions of the organism, such as immunological response for paroxetine. The reversion of the sensitivity of the TS patients 2. Treatment is recommended and effective only in the early stages good affinity and selectivity [Berardi et al., J Med Chem, 2005]. The and responsibility for activation of toxic substances. One of the towards higher paroxetine-induced growth inhibition of PMBCs of the disease. aim of the present study was to find out whether PB190 produces best-known and clinically relevant isoenzymes of cytochrome P- may indicate that the PBMC sensitivity for paroxetine reflects a 3. Basic treatment methods supported by alternative medicine some anxiolytic-like effects in the elevated plus maze model in rats 450 with genetic variability is CYP2D6. In a population, carriers of state marker of depression. gives much better results. and four plate test in mice. DTG (di-o-tolyloguanidine), a widely genotypes and alleles responsible for extensive or poor metabo- 4. Patients are not familiar of the Lyme disease treatment methods. used sigma receptor agonist, was applied as a reference compound. lism occur. Extensive metabolism may result in an accelerated http://dx.doi.org/10.1016/j.pharep.2015.06.115 Rats (male Wistar) were injected intraperitoneally (ip) with PB190 activation or detoxification of xenobiotics whereas poor metabo- http://dx.doi.org/10.1016/j.pharep.2015.06.117 or DTG (1, 5 and 10 mg/kg) 30 min before the test. Both PB190 and lism may be associated with accumulation of toxic compounds or DTG (10 mg/kg), increased the number of entries and the time Assessment of generic psychotropic drugs their metabolites. spent in the open arms in the elevated plus maze. In the four plate therapy costs in Poland The influence of chronic corticosterone Analyses of polymorphism in CYP2D6 involved in the metabo- test in mice (male C57BL/6J), PB190 did not modify the number of 1,2, 2,3 administration on rat fear responses and lism of xenobiotics may contribute to expanding our knowledge in Katarzyna Sejbuk-Rozbicka *, Bartosz Łoza , punished crossings, while DTG (5 mg/kg ip) increased them by ca. 1,2 1,2,4 amygdala activity in the high- and low- anxiety terms of BP pathogenesis. Marta Da˛browska , Grzegorz Cessak , 55%. Diazepam (2 mg/kg), used as a positive control, increased the 1,2 1,2 rats: The effect of midazolam The aim of the study was to find out whether there was any Konrad Rokita , Dagmara Mirowska-Guzel , number of punished crossings to the extent similar to DTG. Though 1,2,4 1, 1 relationship between the CYP2D6 gene polymorphism and the Ewa Bałkowiec-Iskra Anna Sko´ rzewska *, Małgorzata Lehner , PB190 was without effect in the four plate test in mice, this fact Aleksandra Wisłowska-Stanek 2, development of bullous pemphigoid (BP). 1 Department of Experimental and Clinical Pharmacology, Medical may be due to its sedative character (it decreased locomotor Danuta Turzyn´ ska 1, Alicja Sobolewska 1, The study included 221 subjects, 71 patients with bullous University of Warsaw, Warszawa, Poland activity in all doses used in this study). The results suggest that the Paweł Krza˛sćik 2, Adam Płazńik 1,2 pemphigoid and 150 healthy volunteers constituting a control 2 Agency for Health Technology Assessment, Warszawa, Poland sigma1 receptor agonists may have an anxiolytic potential but group. The identification of CYP2D6 (CYP2D6*1, CYP2D6*3, 3 further study is required for confirmation of this possibility. Department of Psychiatry, Physiotherapy Division, Medical Univer- 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- CYP2D6*4) gene alleles was performed using the PCR-RFLP method. sity of Warsaw, Warszawa, Poland gy, Warszawa, Poland Acknowledgments. The study was supported by statutory activity of A higher frequency of the CYP2D6*3/CYP2D6*4 genotype was 4 Office for Registration of Medicinal Products, Medical Devices and 2 Department of Experimental and Clinical Pharmacology, Medical observed in patients with bullous pemphigoid BP (p = 0.0033) than the Institute of Pharmacology, Polish Academy of Sciences. The Biocidal Products, Warszawa, Poland University, Warszawa, Poland in controls. The relative risk of developing BP expressed with the authors wish to express their thanks to Dr. Carmen Abate for a kind *Corresponding author. *Corresponding author. odds ratio (OR) was nearly 4-time higher in subjects in whom the donation of PB190. presence of the CYP2D6*3 allele was detected (OR = 3.8; Provision of cost-effective drug treatment is of particular p = 0.0234). The aim of this study was to examine the changes in rat importance in patients with psychiatric diseases. Most of the http://dx.doi.org/10.1016/j.pharep.2015.06.119 The study results may imply the impact of the CYP2D6 gene emotional behavior and to determine differences in the amygdala therapies in question requires life-long treatment and consists of polymorphism (A2637 deletion) on a higher prevalence of bullous activity in low- (LR) and high-anxiety (HR) rats after the repeated more than one medicine. Introduction of generic drugs is one of the Effect of simvastatin on pharmacokinetics of pemphigoid. corticosterone administration (CORT) and acute midazolam (MID) major strategies for reducing contribution of costs of medications to injection. The animals were divided into LR and HR groups based diazepam in rats total healthcare costs. The primary evidence required both by FDA on the duration of their conditioned freezing in a contextual fear Wojciech Słupski *, Maria Rutkowska http://dx.doi.org/10.1016/j.pharep.2015.06.114 and EMA for marketing approval of a new generic drug is acceptable test (CFT). Repeated CORT increased anxiety-like behavior in the bioequivalence between the generic drug product and its corre- open field and reduced body weight in both the LR and HR groups. Department of Pharmacology, Wroclaw Medical University, Wrocław, Sensitivity to paroxetine-induced inhibition of sponding reference product. The price of the generic drug is Moreover, in the HR group, CORT increased freezing duration in the Poland lymphocyte growth in depressed patients as estimated to be 25% lower comparing with the reference product. CFT test, expression of c-Fos in the lateral (LA) and central (CeA) *Corresponding author. state marker of depression In the present study a comprehensive cost analysis of a two- amygdala and decreased alpha-2 subunit of GABA-A receptor year psychotropic drug treatment in one of high reference Polish Szymon Rzezńiczek 1,*, Małgorzata Obuchowicz 1, density in the CeA. The MID attenuated the neophobia and The aim of this study was to examine the effect of chronic (4 psychiatric hospitals has been performed. The total real costs have Wojciech Datka 2, Marcin Siwek 2, conditioned fear responses, decreased c-Fos expression in the LA weeks) orally administered simvastatin on the pharmacokinetics been compared with predictable costs of treatment with reference Dominika Dudek 2, Katarzyna Kmiotek 2, and CeA, and increased alpha-2 subunit density in CeA only in the of diazepam in rats. products if used instead of the available generic drugs. Our study Andrzej Pilc 1 HR group. These studies have shown that the HR rats are more Male Wistar Han rats were divided into two groups (n = 10). The due to the comprehensive analysis of both the availability and susceptible to the anxiogenic effects of CORT, which are associated first one received simvastatin (20 mg/kg) and the second one vehicle 1 Department of Neurobiology, Institute of Pharmacology PAS, costs of psychotropic medicinal products in Poland. with attenuation of GABAergic control over the amygdala output (1% Tween 80). After 4 weeks, 1 h after the administration of vehicle Krako´w, Poland controlling emotional responses. The current data may help to or simvastatin, both groups were given diazepam (10 mg/kg). For 2 Department of Affective Disorders, Chair of Psychiatry, Jagiellonian http://dx.doi.org/10.1016/j.pharep.2015.06.116 better understand the neurobiological mechanisms responsible for analysis of diazepam pharmacokinetics, blood samples (0.2 ml) University Medical College, Krako´w, Poland individual differences in psychopathological processes induced by were obtained from tail vein before and 0.5, 1, 2, 4, 6 h after * Corresponding author. Lyme disease (Borreliosis) treatment – repeated administration of high doses of glucocorticoids associat- diazepam administration. Serum concentrations of diazepam and its Questionaire study ed with chronic stress or affective pathology. metabolites (desmethyldiazepam, temazepam) were measured by Selective serotonin reuptake inhibitors (SSRIs) used as a first- high performance liquid chromatography (HPLC). Paulina Skałka *, Dariusz Boron´ , Halina Brus, line treatment are effective in less than 70% of depressive patients. The study was supported by Grant No. 2012/05/B/NZ7/02460 from Simvastatin (20 mg/kg) significantly reduced the AUC of Ryszard Brus Since the slow onset of action of the SSRIs is a great problem in the the National Science Centre, Poland. diazepam by 51.6% and its metabolite – temazepam by 54.6%. therapy of depression, there is a need to find the biomarkers of Department of Nursing, High School of Strategic Planning, Da˛browa Cmax of diazepam was also significantly decreased but other sensitivity for antidepressants. Expression of serotonin transporter Go´rnicza, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.118 pharmacokinetic parameters of diazepam and its metabolites like in human lymphocytes as well as an influence of the SSRIs on these *Corresponding author. t1/2 and Tmax did not undergo significant changes due to the co- cells, shown in the previous studies, indicated a possible linkage Anxiolytic-like effect of the sigma receptor administration of simvastatin. between growth inhibition of lymphocytes and molecular Lyme disease (Borreliosis) is the multisystem disease which ligands, PB190 and DTG Diminished bioavailability of diazepam by the co-administra- mechanism involving SERT. The aim of our study was to test tion of simvastatin can be caused by inhibition of cytochrome P450 attacks many organs such as nervous and skeletal system, heart Graz˙ yna Skuza *, Zofia Rogo´ z˙ whether paroxetine-induced growth inhibition of peripheral blood muscle and skin. Presented study concern clinical model, enzymes and/or P-glycoprotein. mononuclear cells (PBMCs) varies in major depression disorder epidemiology and treatment methods of Lyme disease (recom- Department of Pharmacology, Institute of Pharmacology, Polish (MDD) patients vs. control. We studied reaction of PBMCs obtained mended treatment scheme and unconventional methods as well). Academy of Sciences, Krako´w, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.120 from 66 MDD patients and 24 healthy volunteers for paroxetine. In the study and anonymous questionnaire was used. Questions *Corresponding author. The patients population consisted of 33 treatment-sensitive concern effectiveness and rating of diagnostics methods, analysis Influence of simvastatin on the anxiolytic effect patients (TS) – first diagnosed and 33 treatment resistance (TR) of the most common complications during Borrelia burgdorferi The sigma receptors are regarded as unique binding sites, of diazepam in the elevated plus maze test in rats patients. Blood from TS patients was collected 3 times during the distinct from opiate and PCP receptors, implicated in higher brain infection treatment. The study was performed in Małopolskie Wojciech Słupski *, Maria Rutkowska therapy (before treatment – TS I, after 4 weeks – TS II and after 7 region in 2012/2013. Data based on surveys refilled by patients. functions. Sigma receptor ligands have been proposed to be useful weeks – TS III). PBMCs were cultured with several concentrations Following conclusion from presented study once can withdraw: for treatment of several diseases, including depression and anxiety Department of Pharmacology, Wroclaw Medical University, Wrocław, of the drug. There were significant differences between the healthy [Fishback et al., Pharmacol Ther, 2010; Skuza, Curr Pharm Des, Poland vs. TS I and healthy vs. TR in terms of the growth inhibition levels 1. Effective methods of Lyme disease diagnosis doesn’t exist. 2012]. PB190 was claimed to be a sigma1 receptor agonist with a *Corresponding author. 38 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 39 other functions of the organism, such as immunological response for paroxetine. The reversion of the sensitivity of the TS patients 2. Treatment is recommended and effective only in the early stages good affinity and selectivity [Berardi et al., J Med Chem, 2005]. The and responsibility for activation of toxic substances. One of the towards higher paroxetine-induced growth inhibition of PMBCs of the disease. aim of the present study was to find out whether PB190 produces best-known and clinically relevant isoenzymes of cytochrome P- may indicate that the PBMC sensitivity for paroxetine reflects a 3. Basic treatment methods supported by alternative medicine some anxiolytic-like effects in the elevated plus maze model in rats 450 with genetic variability is CYP2D6. In a population, carriers of state marker of depression. gives much better results. and four plate test in mice. DTG (di-o-tolyloguanidine), a widely genotypes and alleles responsible for extensive or poor metabo- 4. Patients are not familiar of the Lyme disease treatment methods. used sigma receptor agonist, was applied as a reference compound. lism occur. Extensive metabolism may result in an accelerated http://dx.doi.org/10.1016/j.pharep.2015.06.115 Rats (male Wistar) were injected intraperitoneally (ip) with PB190 activation or detoxification of xenobiotics whereas poor metabo- http://dx.doi.org/10.1016/j.pharep.2015.06.117 or DTG (1, 5 and 10 mg/kg) 30 min before the test. Both PB190 and lism may be associated with accumulation of toxic compounds or DTG (10 mg/kg), increased the number of entries and the time Assessment of generic psychotropic drugs their metabolites. spent in the open arms in the elevated plus maze. In the four plate therapy costs in Poland The influence of chronic corticosterone Analyses of polymorphism in CYP2D6 involved in the metabo- test in mice (male C57BL/6J), PB190 did not modify the number of 1,2, 2,3 administration on rat fear responses and lism of xenobiotics may contribute to expanding our knowledge in Katarzyna Sejbuk-Rozbicka *, Bartosz Łoza , punished crossings, while DTG (5 mg/kg ip) increased them by ca. 1,2 1,2,4 amygdala activity in the high- and low- anxiety terms of BP pathogenesis. Marta Da˛browska , Grzegorz Cessak , 55%. Diazepam (2 mg/kg), used as a positive control, increased the 1,2 1,2 rats: The effect of midazolam The aim of the study was to find out whether there was any Konrad Rokita , Dagmara Mirowska-Guzel , number of punished crossings to the extent similar to DTG. Though 1,2,4 1, 1 relationship between the CYP2D6 gene polymorphism and the Ewa Bałkowiec-Iskra Anna Sko´ rzewska *, Małgorzata Lehner , PB190 was without effect in the four plate test in mice, this fact Aleksandra Wisłowska-Stanek 2, development of bullous pemphigoid (BP). 1 Department of Experimental and Clinical Pharmacology, Medical may be due to its sedative character (it decreased locomotor Danuta Turzyn´ ska 1, Alicja Sobolewska 1, The study included 221 subjects, 71 patients with bullous University of Warsaw, Warszawa, Poland activity in all doses used in this study). The results suggest that the Paweł Krza˛sćik 2, Adam Płazńik 1,2 pemphigoid and 150 healthy volunteers constituting a control 2 Agency for Health Technology Assessment, Warszawa, Poland sigma1 receptor agonists may have an anxiolytic potential but group. The identification of CYP2D6 (CYP2D6*1, CYP2D6*3, 3 further study is required for confirmation of this possibility. Department of Psychiatry, Physiotherapy Division, Medical Univer- 1 Department of Neurochemistry, Institute of Psychiatry and Neurolo- CYP2D6*4) gene alleles was performed using the PCR-RFLP method. sity of Warsaw, Warszawa, Poland gy, Warszawa, Poland Acknowledgments. The study was supported by statutory activity of A higher frequency of the CYP2D6*3/CYP2D6*4 genotype was 4 Office for Registration of Medicinal Products, Medical Devices and 2 Department of Experimental and Clinical Pharmacology, Medical observed in patients with bullous pemphigoid BP (p = 0.0033) than the Institute of Pharmacology, Polish Academy of Sciences. The Biocidal Products, Warszawa, Poland University, Warszawa, Poland in controls. The relative risk of developing BP expressed with the authors wish to express their thanks to Dr. Carmen Abate for a kind *Corresponding author. *Corresponding author. odds ratio (OR) was nearly 4-time higher in subjects in whom the donation of PB190. presence of the CYP2D6*3 allele was detected (OR = 3.8; Provision of cost-effective drug treatment is of particular p = 0.0234). The aim of this study was to examine the changes in rat importance in patients with psychiatric diseases. Most of the http://dx.doi.org/10.1016/j.pharep.2015.06.119 The study results may imply the impact of the CYP2D6 gene emotional behavior and to determine differences in the amygdala therapies in question requires life-long treatment and consists of polymorphism (A2637 deletion) on a higher prevalence of bullous activity in low- (LR) and high-anxiety (HR) rats after the repeated more than one medicine. Introduction of generic drugs is one of the Effect of simvastatin on pharmacokinetics of pemphigoid. corticosterone administration (CORT) and acute midazolam (MID) major strategies for reducing contribution of costs of medications to injection. The animals were divided into LR and HR groups based diazepam in rats total healthcare costs. The primary evidence required both by FDA on the duration of their conditioned freezing in a contextual fear Wojciech Słupski *, Maria Rutkowska http://dx.doi.org/10.1016/j.pharep.2015.06.114 and EMA for marketing approval of a new generic drug is acceptable test (CFT). Repeated CORT increased anxiety-like behavior in the bioequivalence between the generic drug product and its corre- open field and reduced body weight in both the LR and HR groups. Department of Pharmacology, Wroclaw Medical University, Wrocław, Sensitivity to paroxetine-induced inhibition of sponding reference product. The price of the generic drug is Moreover, in the HR group, CORT increased freezing duration in the Poland lymphocyte growth in depressed patients as estimated to be 25% lower comparing with the reference product. CFT test, expression of c-Fos in the lateral (LA) and central (CeA) *Corresponding author. state marker of depression In the present study a comprehensive cost analysis of a two- amygdala and decreased alpha-2 subunit of GABA-A receptor year psychotropic drug treatment in one of high reference Polish Szymon Rzezńiczek 1,*, Małgorzata Obuchowicz 1, density in the CeA. The MID attenuated the neophobia and The aim of this study was to examine the effect of chronic (4 psychiatric hospitals has been performed. The total real costs have Wojciech Datka 2, Marcin Siwek 2, conditioned fear responses, decreased c-Fos expression in the LA weeks) orally administered simvastatin on the pharmacokinetics been compared with predictable costs of treatment with reference Dominika Dudek 2, Katarzyna Kmiotek 2, and CeA, and increased alpha-2 subunit density in CeA only in the of diazepam in rats. products if used instead of the available generic drugs. Our study Andrzej Pilc 1 HR group. These studies have shown that the HR rats are more Male Wistar Han rats were divided into two groups (n = 10). The due to the comprehensive analysis of both the availability and susceptible to the anxiogenic effects of CORT, which are associated first one received simvastatin (20 mg/kg) and the second one vehicle 1 Department of Neurobiology, Institute of Pharmacology PAS, costs of psychotropic medicinal products in Poland. with attenuation of GABAergic control over the amygdala output (1% Tween 80). After 4 weeks, 1 h after the administration of vehicle Krako´w, Poland controlling emotional responses. The current data may help to or simvastatin, both groups were given diazepam (10 mg/kg). For 2 Department of Affective Disorders, Chair of Psychiatry, Jagiellonian http://dx.doi.org/10.1016/j.pharep.2015.06.116 better understand the neurobiological mechanisms responsible for analysis of diazepam pharmacokinetics, blood samples (0.2 ml) University Medical College, Krako´w, Poland individual differences in psychopathological processes induced by were obtained from tail vein before and 0.5, 1, 2, 4, 6 h after * Corresponding author. Lyme disease (Borreliosis) treatment – repeated administration of high doses of glucocorticoids associat- diazepam administration. Serum concentrations of diazepam and its Questionaire study ed with chronic stress or affective pathology. metabolites (desmethyldiazepam, temazepam) were measured by Selective serotonin reuptake inhibitors (SSRIs) used as a first- high performance liquid chromatography (HPLC). Paulina Skałka *, Dariusz Boron´ , Halina Brus, line treatment are effective in less than 70% of depressive patients. The study was supported by Grant No. 2012/05/B/NZ7/02460 from Simvastatin (20 mg/kg) significantly reduced the AUC of Ryszard Brus Since the slow onset of action of the SSRIs is a great problem in the the National Science Centre, Poland. diazepam by 51.6% and its metabolite – temazepam by 54.6%. therapy of depression, there is a need to find the biomarkers of Department of Nursing, High School of Strategic Planning, Da˛browa Cmax of diazepam was also significantly decreased but other sensitivity for antidepressants. Expression of serotonin transporter Go´rnicza, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.118 pharmacokinetic parameters of diazepam and its metabolites like in human lymphocytes as well as an influence of the SSRIs on these *Corresponding author. t1/2 and Tmax did not undergo significant changes due to the co- cells, shown in the previous studies, indicated a possible linkage Anxiolytic-like effect of the sigma receptor administration of simvastatin. between growth inhibition of lymphocytes and molecular Lyme disease (Borreliosis) is the multisystem disease which ligands, PB190 and DTG Diminished bioavailability of diazepam by the co-administra- mechanism involving SERT. The aim of our study was to test tion of simvastatin can be caused by inhibition of cytochrome P450 attacks many organs such as nervous and skeletal system, heart Graz˙ yna Skuza *, Zofia Rogo´ z˙ whether paroxetine-induced growth inhibition of peripheral blood muscle and skin. Presented study concern clinical model, enzymes and/or P-glycoprotein. mononuclear cells (PBMCs) varies in major depression disorder epidemiology and treatment methods of Lyme disease (recom- Department of Pharmacology, Institute of Pharmacology, Polish (MDD) patients vs. control. We studied reaction of PBMCs obtained mended treatment scheme and unconventional methods as well). Academy of Sciences, Krako´w, Poland http://dx.doi.org/10.1016/j.pharep.2015.06.120 from 66 MDD patients and 24 healthy volunteers for paroxetine. In the study and anonymous questionnaire was used. Questions *Corresponding author. The patients population consisted of 33 treatment-sensitive concern effectiveness and rating of diagnostics methods, analysis Influence of simvastatin on the anxiolytic effect patients (TS) – first diagnosed and 33 treatment resistance (TR) of the most common complications during Borrelia burgdorferi The sigma receptors are regarded as unique binding sites, of diazepam in the elevated plus maze test in rats patients. Blood from TS patients was collected 3 times during the distinct from opiate and PCP receptors, implicated in higher brain infection treatment. The study was performed in Małopolskie Wojciech Słupski *, Maria Rutkowska therapy (before treatment – TS I, after 4 weeks – TS II and after 7 region in 2012/2013. Data based on surveys refilled by patients. functions. Sigma receptor ligands have been proposed to be useful weeks – TS III). PBMCs were cultured with several concentrations Following conclusion from presented study once can withdraw: for treatment of several diseases, including depression and anxiety Department of Pharmacology, Wroclaw Medical University, Wrocław, of the drug. There were significant differences between the healthy [Fishback et al., Pharmacol Ther, 2010; Skuza, Curr Pharm Des, Poland vs. TS I and healthy vs. TR in terms of the growth inhibition levels 1. Effective methods of Lyme disease diagnosis doesn’t exist. 2012]. PB190 was claimed to be a sigma1 receptor agonist with a *Corresponding author. 40 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 41

This study was conducted to evaluate possible interaction of supplement; results of the present study indicate the need for an inflammatory component such as inflammatory bowel diseases ferin at the dose of 10 and 30 and 100 mg/kg and TNBS simvastatin with anxiolytic effect of diazepam. cautiousness. (IBD). The two major IBD subtypes are ulcerative colitis and administration, MDA concentration in intestinal tissues was Anxiety-like behavior of chronically administered simvastatin Crohn’s disease. This paper is a continuation of earlier study and lower compared to the colitis group (p < 0.001). Only after and its combined effect with diazepam in single dose were http://dx.doi.org/10.1016/j.pharep.2015.06.122 will explain whether the anti-inflammatory action of mangiferin is mangiferin at the dose of 100 mg/kg and TNBS administration investigated in the elevated plus maze test (EPM). The effect of associated with the NF-kB signaling pathway. The aim of current SOD activity in intestinal tissues was greater compared to the drugs on locomotor activity of rats was examined in the open field The protective effects of loganic acid and study was to assess the effect of mangiferin on NF-kB expression in colitis group (p < 0.05). It was shown that mangiferin exert test. anthocyanins from cornelian cherry fruits on experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid protective action on TNBS-induced changes in antioxidants state Simvastatin (2.5, 5, 10, 20 mg/kg) was administered orally once atherosclerosis risk factors in (TNBS) in rats. After an adaptation period rats were divided into in rat large intestine. a day for 6 weeks before the test. Diazepam (2.5, 5, 10, 20 mg/kg) hypercholesterolemic rabbits treatment groups as follows: the control group receiving alone or in combination with simvastatin was administered orally intragastrically distilled water and once saline per rectum, the Tomasz Sozan´ ski 1,*, Alicja Z. Kucharska 2, http://dx.doi.org/10.1016/j.pharep.2015.06.125 60 min before the test session. The trial sessions lasted 5 min and colitis group receiving intragastrically distilled water and once Dorota Szumny 1, Antoni Szumny 3, Jan Magdalan 1, behavioral parameters were measured using video-tracking rectally TNBS solution (50 mg/kg dissolved in ethanol) and 3 Małgorzata Trocha 1, Anna Merwid-La˛d 1, Novel approach to reduce intraocular pressure system. Simvastatin 2.5, 5 and 10 mg/kg did not affect significantly examination groups receiving intragastrically mangiferin (10 or 30 Tomasz Piasecki 4, Narcyz Pio´ recki 5,6, Adam Szela˛g 1 using natural compounds from Cornus mas parameters used to evaluate the anxiety reaction in EPM. The or 100 mg/kg) and a single rectal administration of TNBS solution. 1,2, 1 highest dose of simvastatin (20 mg/kg) exerted anxiogenic effect. 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Distilled water and mangiferin were given for 16 days; saline and Dorota Szumny *, Tomasz Sozan´ ski , 3 1 Simvastatin 10 and 20 mg/kg abolished anxiolytic effect of ław, Poland TNBS solution were given at 15th day of the experiment. The Alicja Kucharska , Wojciech Dziewiszek , 4,5 1 diazepam 5 and 10 mg/kg. Only simvastatin 20 mg/kg and the 2 Department of Fruit, Vegetable and Cereals Technology, Wroclaw experiment was terminated on the 17th day. The large intestine Narcyz Pio´ recki , Ewa Chlebda-Sieragowska , 1 1 6 co-administration of diazepam 10 mg/kg and simvastatin 20 mg/ University of Environmental and Life Sciences, Wrocław, Poland was isolated and prepared for immunohistochemical examination Jan Magdalan , Adam Szela˛g , Antoni Szumny kg resulted in a decrease of animal locomotor activity in EPM. 3 of NF-kB expression. Results of our preliminary studies indicated Department of Chemistry, Wroclaw University of Environmental and 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Simvastatin 20 mg/kg given alone and all diazepam combinations that the expression of NF-kB in the colitis group was greater Life Science, Wrocław, Poland ław, Poland with simvastatin reduced locomotor activity of rats in the open 4 compared to the control group (23.733 vs. 1.571, p < 0.001). Upon Department of Epizootiology and Clinic of Birds and Exotic Animals, 2 Ophthalmology Clinic, Uniwersytecki Szpital Kliniczny, Wrocław, field test. Results from this experiment suggest that simvastatin treatment with mangiferin at the dose of 30 mg/kg and 100 mg/kg Wroclaw University of Environmental and Life Sciences, Wrocław, Poland reduces the anxiolytic effect of diazepam. This is probably caused the expression of NF-kB was significantly decreased (10.080, Poland 3 Department of Fruit and Vegetables Technology, Wroclaw University by the pharmacodynamic or/and pharmacokinetic interaction 5 p < 0.05 and 3.286, p < 0.001, respectively). Administration of Bolestraszyce Arboretum and Institute of Physiography, Przemys´l, of Environmental and Life Sciences, Wrocław, Poland between these two drugs. mangiferin at the dose 10 mg/kg did not decrease NF-kB Poland 4 Arboretum and Institute of Physiography in Bolestraszyce, Poland 6 expression (p = NS). Department of Tourism & Recreation, University of Rzeszow, 5 Department of Turism & Recreation, University of Rzeszo´w, Rzeszo´w, http://dx.doi.org/10.1016/j.pharep.2015.06.121 Rzeszo´w, Poland Poland *Corresponding author. http://dx.doi.org/10.1016/j.pharep.2015.06.124 6 Department of Chemistry, Wroclaw University of Environmental and Life Science, Wrocław, Poland Potential unfavorable effect of curcumin on the The aim of the study was to compare effects of main compounds skeletal system Impact of mangiferin on selected parameters of *Corresponding author. of cornelian cherry fruits – iridoid loganic acid and mixture of Patrycja Sołtysiak *, Maria Pytlik, Urszula Cegieła, anthocyanins – on lipid levels, oxido-redox state and proinflam- oxidative stress in TNBS-induced colitis in rats Aleksandra Janas, Joanna Folwarczna matory cytokines in a model of diet-induced hypercholesterolemic Marta Szandruk *, Adam Szela˛g Glaucoma is one of the most common diseases of old age in rabbits. modern societies. It is an optic nerve neuropathy, which leads to Department of Pharmacology, School of Pharmacy with the Division of Department of Pharmacology, Wroclaw Medical University, Wrocław, Forty rabbits were divided into four groups. For 60 consecutive irreversible blindness. It is very often connected with increased Laboratory Medicine, Medical University of Silesia, Katowice, Poland Poland days the animals in the group P were supplied with standard feed. intraocular pressure (IOP) and disturbances in blood flow in the *Corresponding author. *Corresponding author. Groups CH, CH + LA, and CH + ANT were given the same feed +1% eye globe. Although there are a few group of antiglaucoma cholesterol. Once daily, the rabbits orally ingested the following medicine groups the number of chemical compounds that can Numerous health-promoting properties have been attributed to substances: groups P and CH – normal saline, group CH + LA – Mangiferin – polyphenol isolated from Belamcanda chinensis decrease IOP and increase blood flow is still limited, the up-to-date curcumin. Many of curcumin targets, especially NF-kB signaling in loganic acid at a dose of 20 mg/kg. b.w., and group CH+ANT rhizome – show antioxidant properties, which are interesting for investigation of new molecules is important. osteoclastic cells and Wnt signaling in osteoblastic cells, take part mixture of anthocyanins at a dose of 10 mg/kg b.w. the treatment of inflammatory pathologies associated with The aim of this study was check the usefulness of loganic acid in in bone metabolism regulation. There are no data on the skeletal It was shown that either loganic acid or mixture of anthocyanins oxidative stress in humans, such as inflammatory bowel disease glaucoma treating. The chemical composition of the dried effects of curcumin in humans, and data from experimental studies had positive impact on dyslipidemia caused by cholesterol-rich diet, (IBD). The aim of this study was to evaluate the intestinal Cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich are inconsistent. The aim of the present study was to investigate although effects caused by anthocyanins were more pronounced. antioxidant effect of mangiferin in the trinitrobenzenesulphonic fraction was investigated. Loganic acid (50%) and pelargonidin-3- the effect of curcumin on bone mechanical properties in normal Loganic acid showed significant anti-inflammatory effects decreas- acid (TNBS) model of rat colitis. After adaptation period, eighty galactoside (7%) were found as the main components. Among the male rats. ing TNF-a and IL-6 activity in serum. Anthocyanins exerted no male Wistar rats were randomly divided into 8 groups: rats other constituents, iridoid compound cornuside and the anthoc- The experiments were carried out on 4-month-old rats male considerable effects on investigated cytokines. Both loganic acid and receiving distilled water i.g. and once saline p.r. (control group), yans cyanidin 3-O-galactoside, cyanidin 3-O-robinobioside and Wistar rats, divided into 3 groups: I – Control rats, II – Curcumin anthocyanins proved positive effects on oxido-redox state in liver. rats receiving mangiferin at the doses 10 or 30 or 100 mg/kg i.g. pelargonidin 3-O-robinobioside were quantified in the fraction. In (10 mg/kg po daily), III – Curcumin (100 mg/kg po daily). After 4 and once saline p.r., rats receiving distilled water i.g. and once an animal model (New Zealand rabbits), the influence of loganic weeks of curcumin administration, serum bone turnover markers, http://dx.doi.org/10.1016/j.pharep.2015.06.123 TNBS solution p.r. (colitis group), groups receiving mangiferin at acid and the polyphenolic fraction isolated from Cornelian cherry bone mass and geometrical parameters, and bone mechanical the doses 10 or 30 or 100 mg/kg i.g. and a single administration of fruit was investigated. properties were determined. TNBS solution p.r. Distilled water and mangiferin were given for We found a strong IOP–hypotensive effect for a 0.7% solution of Effect of mangiferin on NF-kB expression in Curcumin at the lower dose induced statistically significant 10 consecutive days by gastric gavage; saline and TNBS solution loganic acid, which could be compared with the widely in experimental colitis induced by worsening of mechanical properties of the tibial metaphysis were given by rectal catheter at 15th day of experiment. The ophthalmology used timolol. About a 25% decrease in IOP was trinitrobenzenesulfonic acid in rats (cancellous bone), decreasing the values of the yield point load, experiment was terminated on the 17th day. Determination of observed within the first 3 h of use. Our data, obtained in an animal 1, 1 stress, displacement and accumulated energy. After administration Marta Szandruk *, Beata Nowak , malondialdehyde (MDA) concentration and superoxide dismut- model, directly suggest that loganic acid could be further used in 1 2 of curcumin at the higher dose, displacement and energy for the Agnieszka Matuszewska , Anna Czarny , ase (SOD) activity were performed in large intestinal tissues the adjunct therapy of glaucoma in patients with increased IOP. It 2 1 maximum load point significantly increased. There were no Ewa Zaczyn´ ska , Adam Szela˛g homogenates using colorimetric methods. MDA concentration in could also be beneficial for the intensification of vascular flows in significant curcumin effects on the mechanical properties of the rat large intestine increased (1.813 vs. 1.155, p < 0.001) and SOD diabetic and hypertensive retinopathy or other conditions of ocular 1 Department of Pharmacology, Wroclaw Medical University, Wroc- femoral diaphysis (compact bone) and neck (compact and activity decreased (10.78 vs. 16.55, p < 0.001) in the colitis group blood vessels (e.g. venous thrombosis or arterial embolism). ław, Poland cancellous bone), as well as bone mass, geometric parameters, compared to the control group. Mangiferin at the dose 10 mg/kg Further investigation is needed. 2 Institute of Immunology and Experimental Therapy, Polish Academy and serum turnover markers. decreased MDA concentration in comparison to the control of Sciences, Wrocław, Poland In conclusion, curcumin may induce unfavorable effects on group (0.850 vs. 1.155, p < 0.05). Upon treatment with mangi- *Corresponding author. http://dx.doi.org/10.1016/j.pharep.2015.06.126 the skeletal system. The differential effects of the lower and higher doses indicate that the mechanism of its action on bone is The nuclear transcription factor NF-kB has a crucial role in the complex. Curcumin is broadly promoted as a safe dietary pathogenesis of several human disorders, particularly those with 40 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 41

This study was conducted to evaluate possible interaction of supplement; results of the present study indicate the need for an inflammatory component such as inflammatory bowel diseases ferin at the dose of 10 and 30 and 100 mg/kg and TNBS simvastatin with anxiolytic effect of diazepam. cautiousness. (IBD). The two major IBD subtypes are ulcerative colitis and administration, MDA concentration in intestinal tissues was Anxiety-like behavior of chronically administered simvastatin Crohn’s disease. This paper is a continuation of earlier study and lower compared to the colitis group (p < 0.001). Only after and its combined effect with diazepam in single dose were http://dx.doi.org/10.1016/j.pharep.2015.06.122 will explain whether the anti-inflammatory action of mangiferin is mangiferin at the dose of 100 mg/kg and TNBS administration investigated in the elevated plus maze test (EPM). The effect of associated with the NF-kB signaling pathway. The aim of current SOD activity in intestinal tissues was greater compared to the drugs on locomotor activity of rats was examined in the open field The protective effects of loganic acid and study was to assess the effect of mangiferin on NF-kB expression in colitis group (p < 0.05). It was shown that mangiferin exert test. anthocyanins from cornelian cherry fruits on experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid protective action on TNBS-induced changes in antioxidants state Simvastatin (2.5, 5, 10, 20 mg/kg) was administered orally once atherosclerosis risk factors in (TNBS) in rats. After an adaptation period rats were divided into in rat large intestine. a day for 6 weeks before the test. Diazepam (2.5, 5, 10, 20 mg/kg) hypercholesterolemic rabbits treatment groups as follows: the control group receiving alone or in combination with simvastatin was administered orally intragastrically distilled water and once saline per rectum, the Tomasz Sozan´ ski 1,*, Alicja Z. Kucharska 2, http://dx.doi.org/10.1016/j.pharep.2015.06.125 60 min before the test session. The trial sessions lasted 5 min and colitis group receiving intragastrically distilled water and once Dorota Szumny 1, Antoni Szumny 3, Jan Magdalan 1, behavioral parameters were measured using video-tracking rectally TNBS solution (50 mg/kg dissolved in ethanol) and 3 Małgorzata Trocha 1, Anna Merwid-La˛d 1, Novel approach to reduce intraocular pressure system. Simvastatin 2.5, 5 and 10 mg/kg did not affect significantly examination groups receiving intragastrically mangiferin (10 or 30 Tomasz Piasecki 4, Narcyz Pio´ recki 5,6, Adam Szela˛g 1 using natural compounds from Cornus mas parameters used to evaluate the anxiety reaction in EPM. The or 100 mg/kg) and a single rectal administration of TNBS solution. 1,2, 1 highest dose of simvastatin (20 mg/kg) exerted anxiogenic effect. 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Distilled water and mangiferin were given for 16 days; saline and Dorota Szumny *, Tomasz Sozan´ ski , 3 1 Simvastatin 10 and 20 mg/kg abolished anxiolytic effect of ław, Poland TNBS solution were given at 15th day of the experiment. The Alicja Kucharska , Wojciech Dziewiszek , 4,5 1 diazepam 5 and 10 mg/kg. Only simvastatin 20 mg/kg and the 2 Department of Fruit, Vegetable and Cereals Technology, Wroclaw experiment was terminated on the 17th day. The large intestine Narcyz Pio´ recki , Ewa Chlebda-Sieragowska , 1 1 6 co-administration of diazepam 10 mg/kg and simvastatin 20 mg/ University of Environmental and Life Sciences, Wrocław, Poland was isolated and prepared for immunohistochemical examination Jan Magdalan , Adam Szela˛g , Antoni Szumny kg resulted in a decrease of animal locomotor activity in EPM. 3 of NF-kB expression. Results of our preliminary studies indicated Department of Chemistry, Wroclaw University of Environmental and 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Simvastatin 20 mg/kg given alone and all diazepam combinations that the expression of NF-kB in the colitis group was greater Life Science, Wrocław, Poland ław, Poland with simvastatin reduced locomotor activity of rats in the open 4 compared to the control group (23.733 vs. 1.571, p < 0.001). Upon Department of Epizootiology and Clinic of Birds and Exotic Animals, 2 Ophthalmology Clinic, Uniwersytecki Szpital Kliniczny, Wrocław, field test. Results from this experiment suggest that simvastatin treatment with mangiferin at the dose of 30 mg/kg and 100 mg/kg Wroclaw University of Environmental and Life Sciences, Wrocław, Poland reduces the anxiolytic effect of diazepam. This is probably caused the expression of NF-kB was significantly decreased (10.080, Poland 3 Department of Fruit and Vegetables Technology, Wroclaw University by the pharmacodynamic or/and pharmacokinetic interaction 5 p < 0.05 and 3.286, p < 0.001, respectively). Administration of Bolestraszyce Arboretum and Institute of Physiography, Przemys´l, of Environmental and Life Sciences, Wrocław, Poland between these two drugs. mangiferin at the dose 10 mg/kg did not decrease NF-kB Poland 4 Arboretum and Institute of Physiography in Bolestraszyce, Poland 6 expression (p = NS). Department of Tourism & Recreation, University of Rzeszow, 5 Department of Turism & Recreation, University of Rzeszo´w, Rzeszo´w, http://dx.doi.org/10.1016/j.pharep.2015.06.121 Rzeszo´w, Poland Poland *Corresponding author. http://dx.doi.org/10.1016/j.pharep.2015.06.124 6 Department of Chemistry, Wroclaw University of Environmental and Life Science, Wrocław, Poland Potential unfavorable effect of curcumin on the The aim of the study was to compare effects of main compounds skeletal system Impact of mangiferin on selected parameters of *Corresponding author. of cornelian cherry fruits – iridoid loganic acid and mixture of Patrycja Sołtysiak *, Maria Pytlik, Urszula Cegieła, anthocyanins – on lipid levels, oxido-redox state and proinflam- oxidative stress in TNBS-induced colitis in rats Aleksandra Janas, Joanna Folwarczna matory cytokines in a model of diet-induced hypercholesterolemic Marta Szandruk *, Adam Szela˛g Glaucoma is one of the most common diseases of old age in rabbits. modern societies. It is an optic nerve neuropathy, which leads to Department of Pharmacology, School of Pharmacy with the Division of Department of Pharmacology, Wroclaw Medical University, Wrocław, Forty rabbits were divided into four groups. For 60 consecutive irreversible blindness. It is very often connected with increased Laboratory Medicine, Medical University of Silesia, Katowice, Poland Poland days the animals in the group P were supplied with standard feed. intraocular pressure (IOP) and disturbances in blood flow in the *Corresponding author. *Corresponding author. Groups CH, CH + LA, and CH + ANT were given the same feed +1% eye globe. Although there are a few group of antiglaucoma cholesterol. Once daily, the rabbits orally ingested the following medicine groups the number of chemical compounds that can Numerous health-promoting properties have been attributed to substances: groups P and CH – normal saline, group CH + LA – Mangiferin – polyphenol isolated from Belamcanda chinensis decrease IOP and increase blood flow is still limited, the up-to-date curcumin. Many of curcumin targets, especially NF-kB signaling in loganic acid at a dose of 20 mg/kg. b.w., and group CH+ANT rhizome – show antioxidant properties, which are interesting for investigation of new molecules is important. osteoclastic cells and Wnt signaling in osteoblastic cells, take part mixture of anthocyanins at a dose of 10 mg/kg b.w. the treatment of inflammatory pathologies associated with The aim of this study was check the usefulness of loganic acid in in bone metabolism regulation. There are no data on the skeletal It was shown that either loganic acid or mixture of anthocyanins oxidative stress in humans, such as inflammatory bowel disease glaucoma treating. The chemical composition of the dried effects of curcumin in humans, and data from experimental studies had positive impact on dyslipidemia caused by cholesterol-rich diet, (IBD). The aim of this study was to evaluate the intestinal Cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich are inconsistent. The aim of the present study was to investigate although effects caused by anthocyanins were more pronounced. antioxidant effect of mangiferin in the trinitrobenzenesulphonic fraction was investigated. Loganic acid (50%) and pelargonidin-3- the effect of curcumin on bone mechanical properties in normal Loganic acid showed significant anti-inflammatory effects decreas- acid (TNBS) model of rat colitis. After adaptation period, eighty galactoside (7%) were found as the main components. Among the male rats. ing TNF-a and IL-6 activity in serum. Anthocyanins exerted no male Wistar rats were randomly divided into 8 groups: rats other constituents, iridoid compound cornuside and the anthoc- The experiments were carried out on 4-month-old rats male considerable effects on investigated cytokines. Both loganic acid and receiving distilled water i.g. and once saline p.r. (control group), yans cyanidin 3-O-galactoside, cyanidin 3-O-robinobioside and Wistar rats, divided into 3 groups: I – Control rats, II – Curcumin anthocyanins proved positive effects on oxido-redox state in liver. rats receiving mangiferin at the doses 10 or 30 or 100 mg/kg i.g. pelargonidin 3-O-robinobioside were quantified in the fraction. In (10 mg/kg po daily), III – Curcumin (100 mg/kg po daily). After 4 and once saline p.r., rats receiving distilled water i.g. and once an animal model (New Zealand rabbits), the influence of loganic weeks of curcumin administration, serum bone turnover markers, http://dx.doi.org/10.1016/j.pharep.2015.06.123 TNBS solution p.r. (colitis group), groups receiving mangiferin at acid and the polyphenolic fraction isolated from Cornelian cherry bone mass and geometrical parameters, and bone mechanical the doses 10 or 30 or 100 mg/kg i.g. and a single administration of fruit was investigated. properties were determined. TNBS solution p.r. Distilled water and mangiferin were given for We found a strong IOP–hypotensive effect for a 0.7% solution of Effect of mangiferin on NF-kB expression in Curcumin at the lower dose induced statistically significant 10 consecutive days by gastric gavage; saline and TNBS solution loganic acid, which could be compared with the widely in experimental colitis induced by worsening of mechanical properties of the tibial metaphysis were given by rectal catheter at 15th day of experiment. The ophthalmology used timolol. About a 25% decrease in IOP was trinitrobenzenesulfonic acid in rats (cancellous bone), decreasing the values of the yield point load, experiment was terminated on the 17th day. Determination of observed within the first 3 h of use. Our data, obtained in an animal 1, 1 stress, displacement and accumulated energy. After administration Marta Szandruk *, Beata Nowak , malondialdehyde (MDA) concentration and superoxide dismut- model, directly suggest that loganic acid could be further used in 1 2 of curcumin at the higher dose, displacement and energy for the Agnieszka Matuszewska , Anna Czarny , ase (SOD) activity were performed in large intestinal tissues the adjunct therapy of glaucoma in patients with increased IOP. It 2 1 maximum load point significantly increased. There were no Ewa Zaczyn´ ska , Adam Szela˛g homogenates using colorimetric methods. MDA concentration in could also be beneficial for the intensification of vascular flows in significant curcumin effects on the mechanical properties of the rat large intestine increased (1.813 vs. 1.155, p < 0.001) and SOD diabetic and hypertensive retinopathy or other conditions of ocular 1 Department of Pharmacology, Wroclaw Medical University, Wroc- femoral diaphysis (compact bone) and neck (compact and activity decreased (10.78 vs. 16.55, p < 0.001) in the colitis group blood vessels (e.g. venous thrombosis or arterial embolism). ław, Poland cancellous bone), as well as bone mass, geometric parameters, compared to the control group. Mangiferin at the dose 10 mg/kg Further investigation is needed. 2 Institute of Immunology and Experimental Therapy, Polish Academy and serum turnover markers. decreased MDA concentration in comparison to the control of Sciences, Wrocław, Poland In conclusion, curcumin may induce unfavorable effects on group (0.850 vs. 1.155, p < 0.05). Upon treatment with mangi- *Corresponding author. http://dx.doi.org/10.1016/j.pharep.2015.06.126 the skeletal system. The differential effects of the lower and higher doses indicate that the mechanism of its action on bone is The nuclear transcription factor NF-kB has a crucial role in the complex. Curcumin is broadly promoted as a safe dietary pathogenesis of several human disorders, particularly those with 42 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 43

than in CIR. In 4 h of reperfusion ADMA was significantly higher in glycaemia, total daily glycemic variability index and HOMAIR Endocarditis (IE) is an infection in valvular endocardium. It During ischemia/reperfusion (IR) changes in the activity of groups underwent IR (CIR and SIR). In 24 h of reperfusion levels of index were significantly lower in DAPA-treated rats than in occurs 2.4–11.6 per 100,000 person-years and still has a high enzymes responsible for synthesis and degradation of NO are all examined parameters were restored. Obtained results may placebo-treated rats with stimulated glucose excursions. It could mortality rate, i.e. 20%. The cause of IE may be rheumatoic heart important. Protein arginine methyltransferase (PRMT) is responsi- suggest no protective properties of sitagliptin on rat livers injured be stated than, that DAPA reduces peripheral insulin resistance disease, bicuspid aortic valve, presence of a prosthetic cardiac valve, ble for protein methylation and formation of ADMA (inhibitor of NO by IR. and glycaemic variability. cardiac implantable electronic device infection of a permanent synthesis), and dimethylarginine dimethylaminohydrolase (DDAH) pacemaker or implantable cardioverter-defibrillator. IE often occurs is ADMA-metabolizing enzyme. We evaluated effect of IR and http://dx.doi.org/10.1016/j.pharep.2015.06.128 http://dx.doi.org/10.1016/j.pharep.2015.06.131 as comorbid to other diseases such as diabetes, kidney failure, tooth antidiabetic drug – sitagliptin (the dipeptidyl peptidase-4 (DPP-4) decay, blood infections (bacteremia, fungemia, viremia). In recent inhibitor) on DDAH activity and DDAH1 and PRMT1 mRNA Trimethylamine N-oxide, a bacterial metabolite, years there has been a significant change in the etiological factors expression rat liver. Rats received sitagliptin (5 mg/kg) (groups S0 Changes in the CRF expression after chronic with pharmacotherapeutic potential in lifestyle causing IE. In the past, dominant organisms are streptococci, but in and SIR) or saline solution (groups C0 and CIR) intragastrically for 14 restraint stress in high (HR) and low (LR) anxiety diseases the last decade – staphylococci raise more difficulties in diagnostics days. In groups CIR and SIR 70% of liver ischemia (left lateral and rats 1,* 2 and treatment. As a result of adherence of staphylococci to damaged median lobes) was achieved by occluding the branches of the portal Marcin Ufnal , Radoslaw Jazwiec , Aleksandra Wisłowska-Stanek 1,*, Małgorzata 2 1 1 endothelium and formulation of bacterial biofilm, there are quality- vein and hepatic artery using a microvascular clip. After 60 min. of Michal Dadlez , Adrian Drapala , Mariusz Sikora , Lehner 2, Anna Sko´ rzewska 2, Paweł Krza˛sćik 1, 1 phenotypic changes requiring increase in using of glycopeptide ischemia, the clip was removed to allow reperfusion for 24 h. After IR Janusz Skrzypecki Adam Płazńik 1,2 antibiotics. One of approved and well documented drug therapy, DDAH activity was measured in liver homogenates. DDAH1 and 1 Department of Experimental Physiology and Pathophysiology, both targeted and empirical one, is vancomycin. In this study we 1 PRMT1 mRNA were quantified by real-time PCR in liver tissue Department of Experimental and Clinical Pharmacology, Medical Laboratory of Centre for Preclinical Research, The Medical University decided to estimate, in the course of stewardshipment, clinical samples. Activity of DDAH was significantly lower in CIR compared University of Warsaw, Warszawa, Poland of Warsaw, Warszawa, Poland effects of treatment IE with a higher dose of vancomycin than is 2 to C0 but in drug-treated groups it was significantly increased in SIR 2 Department of Neurochemistry, Institute of Psychiatry and Neurolo- Mass Spectrometry Laboratory, Institute of Biochemistry and recommended by ESC, i.e. 32–34 mg/kg/24 h. Due to its narrow compared to S0. PRMT1 mRNA expression was significantly higher gy, Warszawa, Poland Biophysics, Polish Academy of Sciences, Warszawa, Poland therapeutic window, monitoring of a therapy has been used. The in CIR and SIR compared to C0 and S0, respectively. In conclusion *Corresponding author. *Corresponding author. comparisons in concentrations of vancomycin in plasma of patients influence of IR on DDAH activity and PRMT1 mRNA expression was with a diagnosis of IE after mitral or aortic valve replacement noticed. Protective action of sitagliptin was suggested by changes in The aim of our study was to investigate the influence of chronic Recent clinical studies show a positive correlation between an indicate that there did not occur perivalvular leakage within 4 and 6 DDAH activity. Drug administration has no impact on PRMT1 and restraint stress (5 weeks, 3 h/daily) on behavior and CRF elevated plasma level of Trimethylamine N-oxide (TMAO), a gut weeks after a valve replacement, as well as there was no vegetation DDAH1 mRNA expression. (corticoliberin) expression in the brain structures of rats selected bacteria metabolite, and myocardial infarction, stroke, diabetes or other septic complications. The final results were confirmed by for high and low anxiety (the freezing response was used as a and colorectal cancer. Blood TMAO increases after ingesting transthoracic or transesophageal echocardiography. http://dx.doi.org/10.1016/j.pharep.2015.06.127 discriminating variable). We found that in high anxiety rats, dietary L-carnitine and phosphatidylcholine, both abundant in Study supported by JU MC K/ZDS/004121. chronic restraint induced symptoms of anhedonia (i.e. it red meat. Therefore, TMAO has been suggested to be a causative decreased consumption of 1% solution of sucrose) and learned Influence of sitagliptin on arginine (Arg) and its link between unhealthy diet and some of lifestyle diseases. On the helplessness (an increased immobility in the Porsolt test) http://dx.doi.org/10.1016/j.pharep.2015.06.130 derivatives – Asymmetric and symmetric other hand, it has been well-established that TMAO protects compared to low anxiety rats and HR control group. These dimethylarginine (ADMA, SDMA) in rat liver normal protein folding counteracting the effects of urea, osmotic behavioral changes were accompanied by a decreased expression subjected to ischemia/reperfusion (IR) and hydrostatic pressures and heat. We did the study to establish Dapagliflozin decreases glycaemic variability of CRF in the paraventricular nucleus of the hypothalamus (pPVN) Małgorzata Trocha 1,*, Anna Merwid-La˛d 1, TMAO rat model for lifestyle diseases. Sprague Dawley rats were and peripheral insulin resistance in rats with and dentate gyrus of the hippocampus (DG) compared to low Tomasz Sozan´ ski 1, Dorota Nowak 1, fed standard laboratory chow. We implanted rats with telemetric diabetes anxiety restraint rats and to HR control group. The present result 1 2 transmitters (DSI) and continuous recordings of motor activity and Małgorzata Piesńiewska , Jerzy Wisńiewski , Hanna Winiarska 1,*, Anna Wesołowska 1, suggest that in high anxiety rats chronic restraint stress 2 2 hemodynamic parameters for 7 days before and 28 days during Mariusz Fleszar , Joanna Piechowicz , Saule Iskakova 2, Gulmira Zharmankhanova 2, attenuated the CRF expression in pPVN and DG, probably due 3 1 osmotic minipump driven infusion of either: saline or TMAO were Tomasz Piasecki , Adam Szela˛g Olzhas Urazayev 3, Agnieszka Stelmaszyk 1, to action of a negative hormonal feedback mechanism, thus performed. After the experiments plasma was collected for 1 modulating the stress response and inducing depressive-like 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Marzena Dworacka evaluation of TMAO concentration and basic biochemical test. symptoms. ław, Poland Plasma concentration of TMAO in control rats was 35.8 ng/ 1 Department of Pharmacology Poznan University of Medical Sciences, 2 Department of Medical Biochemistry, Wroclaw Medical University, mL 2.5 (means SE), which is about 10 times lower than that Poznan´, Poland This study was supported by the research grant UMO-2012/05/B/ � � Wrocław, Poland reported in humans. Chronic infusion of TMAO increased its plasma 2 Department of Pharmacology Marat Ospanov University of Medical NZ7/02460 from National Science Centre, Krako´ w, Poland. 3 Department of Epizootiology and Clinic of Bird and Exotic Animals, concentration to 4.7 mg/mL 0.5, with no effect on well-being of rats Sciences, Aktobe, Kazakhstan � Wrocław University of Environmental and Life Sciences, Wrocław, 3 i.e. rats’ motor activity and body weight. We found no significant Department of Oncology Marat Ospanov University of Medical http://dx.doi.org/10.1016/j.pharep.2015.06.132 Poland differences in hemodynamic parameters between rats infused with Sciences, Aktobe, Kazakhstan *Corresponding author. saline and TMAO. In conclusion, a four week 100-fold increase in *Corresponding author. 42 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 43

Impact of ischemia/reperfusion (IR) and Ischemia/reperfusion (IR) is considered to be the main cause of blood TMAO level has no negative effect on rat’s body weight, motor Large postprandial swings in blood glucose could result in sitagliptin administration on dimethylarginine cell damage in liver. Asymmetric dimethylarginine (ADMA) – an activity or hemodynamic parameters. It may be hypothesized that decrements of insulin sensitivity.Therefore, more attention has dimethylaminohydrolase (DDAH) activity and inhibitor of eNOS, is released from the ischemic organ during the accumulation of TMAO in the course of life-style diseases is either a been paid recently on glucose fluctuations and on its control protein arginine methyltransferase (PRMT) and reperfusion period. We evaluated effect of antidiabetic drug – lurking variable or that an accumulation of TMAO reflects the provided by anti-diabetic agents. Dapagliflozin (DAPA) is a novel DDAH1 mRNA expression in rat liver sitagliptin (the dipeptidyl peptidase-4 (DPP-4) inhibitor) on adaptation of cells to disturbing factors involved in etiology of the inhibitor of renal sodium-glucose cotransporter 2. The aim of our Małgorzata Trocha 1,*, Anna Merwid-La˛d 1, arginine (Arg) and its derivatives (ADMA, SDMA) level in rat liver diseases. If the latter is true, TMAO and other gut bacteria metabolites study was to estimate the effect of DAPA on glucose variability- Tomasz Sozan´ ski 1, Ewa Chlebda 1, Dorota Nowak 1, underwent IR. Rats received sitagliptin (5 mg/kg) (groups S0 and may have a therapeutic potential in lifestyle diseases. related insulin resistance. The investigation was performed on 44 Piotr Dzie˛giel 2, Małgorzata Piesńiewska 1, SIR) or saline solution (groups C0 and CIR) intragastrically for 14 male Wistar rats with induced diabetes (diabetes mellitus type 2 – Agnieszka Gomułkiewicz 2, Tomasz Piasecki 3, days. In groups CIR and SIR 70% of liver ischemia (left lateral and http://dx.doi.org/10.1016/j.pharep.2015.06.129 related model) and on 15 non-diabetic animals. In two groups Adam Szela˛g 1 median lobes) was achieved by occluding the branches of the with diabetes (DAPA-treated and placebo-treated) glucose portal vein and hepatic artery. After 60 min. of ischemia, the clip excursions were stimulated. DAPA (1 mg/kg) or placebo were 1 Effect of slow-long infusions of vancomycin in Department of Pharmacology, Wroclaw Medical University, Wroc- was removed to allow reperfusion for 24 h. Arg, ADMA and SDMA administered into the stomach once daily within 8 weeks to all of patients with mitral or aortic valve replacement ław, Poland were estimated just before ischemia and during reperfusion (0.5; 4 examined animals. The following parameters were estimated: a 2 1, 2 Department of Histology and Embryology, Wroclaw Medical and 24 h). After sitagliptin administration, no significant differ- Anna Wesołowska *, Łukasz Hon´ do concentration of glucose (fasting and postprandial), HbA1c, serum University, Wrocław, Poland ences in ADMA0, Arg0, SDMA0, and the A/A0 (Arg/ADMA) ratio insulin concentration. Insulin resistance was assessed based on 1 Department of Clinical Pharmacy, Jagiellonian University Medical 3 Department of Epizootiology and Clinic of Bird and Exotic Animals, were found between the groups. In 30 min and in 4 h of reperfusion HOMA index. The comparison of these parameters between rats College, Krako´w, Poland IR Wroclaw University of Environmental and Life Sciences, Wrocław, in CIR and SIR Arg and A/A levels were significantly decreased with diabetes and with or without glucose excursions documen- 2 Hospital of John Paul II, Krako´w, Poland Poland compared to C and S, respectively. Additionally, in 30 min of ted that glucose variability is related to increased insulin *Corresponding author. *Corresponding author. reperfusion concentration of Arg was significantly lower in SIR resistance. It was also found glucose excursions that postprandial than in CIR. In 4 h of reperfusion ADMA was significantly higher in glycaemia, total daily glycemic variability index and HOMAIR Endocarditis (IE) is an infection in valvular endocardium. It During ischemia/reperfusion (IR) changes in the activity of groups underwent IR (CIR and SIR). In 24 h of reperfusion levels of index were significantly lower in DAPA-treated rats than in occurs 2.4–11.6 per 100,000 person-years and still has a high enzymes responsible for synthesis and degradation of NO are all examined parameters were restored. Obtained results may placebo-treated rats with stimulated glucose excursions. It could mortality rate, i.e. 20%. The cause of IE may be rheumatoic heart important. Protein arginine methyltransferase (PRMT) is responsi- suggest no protective properties of sitagliptin on rat livers injured be stated than, that DAPA reduces peripheral insulin resistance disease, bicuspid aortic valve, presence of a prosthetic cardiac valve, ble for protein methylation and formation of ADMA (inhibitor of NO by IR. and glycaemic variability. cardiac implantable electronic device infection of a permanent synthesis), and dimethylarginine dimethylaminohydrolase (DDAH) pacemaker or implantable cardioverter-defibrillator. IE often occurs is ADMA-metabolizing enzyme. We evaluated effect of IR and http://dx.doi.org/10.1016/j.pharep.2015.06.128 http://dx.doi.org/10.1016/j.pharep.2015.06.131 as comorbid to other diseases such as diabetes, kidney failure, tooth antidiabetic drug – sitagliptin (the dipeptidyl peptidase-4 (DPP-4) decay, blood infections (bacteremia, fungemia, viremia). In recent inhibitor) on DDAH activity and DDAH1 and PRMT1 mRNA Trimethylamine N-oxide, a bacterial metabolite, years there has been a significant change in the etiological factors expression rat liver. Rats received sitagliptin (5 mg/kg) (groups S0 Changes in the CRF expression after chronic with pharmacotherapeutic potential in lifestyle causing IE. In the past, dominant organisms are streptococci, but in and SIR) or saline solution (groups C0 and CIR) intragastrically for 14 restraint stress in high (HR) and low (LR) anxiety diseases the last decade – staphylococci raise more difficulties in diagnostics days. In groups CIR and SIR 70% of liver ischemia (left lateral and rats 1,* 2 and treatment. As a result of adherence of staphylococci to damaged median lobes) was achieved by occluding the branches of the portal Marcin Ufnal , Radoslaw Jazwiec , Aleksandra Wisłowska-Stanek 1,*, Małgorzata 2 1 1 endothelium and formulation of bacterial biofilm, there are quality- vein and hepatic artery using a microvascular clip. After 60 min. of Michal Dadlez , Adrian Drapala , Mariusz Sikora , Lehner 2, Anna Sko´ rzewska 2, Paweł Krza˛sćik 1, 1 phenotypic changes requiring increase in using of glycopeptide ischemia, the clip was removed to allow reperfusion for 24 h. After IR Janusz Skrzypecki Adam Płazńik 1,2 antibiotics. One of approved and well documented drug therapy, DDAH activity was measured in liver homogenates. DDAH1 and 1 Department of Experimental Physiology and Pathophysiology, both targeted and empirical one, is vancomycin. In this study we 1 PRMT1 mRNA were quantified by real-time PCR in liver tissue Department of Experimental and Clinical Pharmacology, Medical Laboratory of Centre for Preclinical Research, The Medical University decided to estimate, in the course of stewardshipment, clinical samples. Activity of DDAH was significantly lower in CIR compared University of Warsaw, Warszawa, Poland of Warsaw, Warszawa, Poland effects of treatment IE with a higher dose of vancomycin than is 2 to C0 but in drug-treated groups it was significantly increased in SIR 2 Department of Neurochemistry, Institute of Psychiatry and Neurolo- Mass Spectrometry Laboratory, Institute of Biochemistry and recommended by ESC, i.e. 32–34 mg/kg/24 h. Due to its narrow compared to S0. PRMT1 mRNA expression was significantly higher gy, Warszawa, Poland Biophysics, Polish Academy of Sciences, Warszawa, Poland therapeutic window, monitoring of a therapy has been used. The in CIR and SIR compared to C0 and S0, respectively. In conclusion *Corresponding author. *Corresponding author. comparisons in concentrations of vancomycin in plasma of patients influence of IR on DDAH activity and PRMT1 mRNA expression was with a diagnosis of IE after mitral or aortic valve replacement noticed. Protective action of sitagliptin was suggested by changes in The aim of our study was to investigate the influence of chronic Recent clinical studies show a positive correlation between an indicate that there did not occur perivalvular leakage within 4 and 6 DDAH activity. Drug administration has no impact on PRMT1 and restraint stress (5 weeks, 3 h/daily) on behavior and CRF elevated plasma level of Trimethylamine N-oxide (TMAO), a gut weeks after a valve replacement, as well as there was no vegetation DDAH1 mRNA expression. (corticoliberin) expression in the brain structures of rats selected bacteria metabolite, and myocardial infarction, stroke, diabetes or other septic complications. The final results were confirmed by for high and low anxiety (the freezing response was used as a and colorectal cancer. Blood TMAO increases after ingesting transthoracic or transesophageal echocardiography. http://dx.doi.org/10.1016/j.pharep.2015.06.127 discriminating variable). We found that in high anxiety rats, dietary L-carnitine and phosphatidylcholine, both abundant in Study supported by JU MC K/ZDS/004121. chronic restraint induced symptoms of anhedonia (i.e. it red meat. Therefore, TMAO has been suggested to be a causative decreased consumption of 1% solution of sucrose) and learned Influence of sitagliptin on arginine (Arg) and its link between unhealthy diet and some of lifestyle diseases. On the helplessness (an increased immobility in the Porsolt test) http://dx.doi.org/10.1016/j.pharep.2015.06.130 derivatives – Asymmetric and symmetric other hand, it has been well-established that TMAO protects compared to low anxiety rats and HR control group. These dimethylarginine (ADMA, SDMA) in rat liver normal protein folding counteracting the effects of urea, osmotic behavioral changes were accompanied by a decreased expression subjected to ischemia/reperfusion (IR) and hydrostatic pressures and heat. We did the study to establish Dapagliflozin decreases glycaemic variability of CRF in the paraventricular nucleus of the hypothalamus (pPVN) Małgorzata Trocha 1,*, Anna Merwid-La˛d 1, TMAO rat model for lifestyle diseases. Sprague Dawley rats were and peripheral insulin resistance in rats with and dentate gyrus of the hippocampus (DG) compared to low Tomasz Sozan´ ski 1, Dorota Nowak 1, fed standard laboratory chow. We implanted rats with telemetric diabetes anxiety restraint rats and to HR control group. The present result 1 2 transmitters (DSI) and continuous recordings of motor activity and Małgorzata Piesńiewska , Jerzy Wisńiewski , Hanna Winiarska 1,*, Anna Wesołowska 1, suggest that in high anxiety rats chronic restraint stress 2 2 hemodynamic parameters for 7 days before and 28 days during Mariusz Fleszar , Joanna Piechowicz , Saule Iskakova 2, Gulmira Zharmankhanova 2, attenuated the CRF expression in pPVN and DG, probably due 3 1 osmotic minipump driven infusion of either: saline or TMAO were Tomasz Piasecki , Adam Szela˛g Olzhas Urazayev 3, Agnieszka Stelmaszyk 1, to action of a negative hormonal feedback mechanism, thus performed. After the experiments plasma was collected for 1 modulating the stress response and inducing depressive-like 1 Department of Pharmacology, Wroclaw Medical University, Wroc- Marzena Dworacka evaluation of TMAO concentration and basic biochemical test. symptoms. ław, Poland Plasma concentration of TMAO in control rats was 35.8 ng/ 1 Department of Pharmacology Poznan University of Medical Sciences, 2 Department of Medical Biochemistry, Wroclaw Medical University, mL 2.5 (means SE), which is about 10 times lower than that Poznan´, Poland This study was supported by the research grant UMO-2012/05/B/ � � Wrocław, Poland reported in humans. Chronic infusion of TMAO increased its plasma 2 Department of Pharmacology Marat Ospanov University of Medical NZ7/02460 from National Science Centre, Krako´ w, Poland. 3 Department of Epizootiology and Clinic of Bird and Exotic Animals, concentration to 4.7 mg/mL 0.5, with no effect on well-being of rats Sciences, Aktobe, Kazakhstan � Wrocław University of Environmental and Life Sciences, Wrocław, 3 i.e. rats’ motor activity and body weight. We found no significant Department of Oncology Marat Ospanov University of Medical http://dx.doi.org/10.1016/j.pharep.2015.06.132 Poland differences in hemodynamic parameters between rats infused with Sciences, Aktobe, Kazakhstan *Corresponding author. saline and TMAO. In conclusion, a four week 100-fold increase in *Corresponding author. 44 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 45

Modified swim test as a model of depressive-like In cortical slices irbesartan at the concentration of 0.5 and 1 mM Predictors of endothelial function in women A pharmaco-EEG assessment of the effect of negative symptoms of schizophrenia: GABAergic decreased KYNA synthesis to 66% (p < 0.001) and 42% (p < 0.001) with gestational diabetes mellitus requiring retigabine on alcohol use disorder course in and serotonergic signaling of control value, respectively. antidiabetic agents rabbits Monika Wozńiak *, Joanna Wieron´ ska, The activity of KAT I was inhibited by irbesartan at the AgnieszkaZawiejska 1,*, Ewa Wender-Ozegowska 1, Ewa Zwierzyn´ ska *, Bogusława Pietrzak Marcin Marciniak, Andrzej Pilc concentration of 0.1, 0.5 and 1 mM to 76% (p < 0.05); 58% Magdalena Borowska 2, Przemysław Mikołajczak 2, Department of Pharmacodynamics, Medical University, Ło´dz´, Poland (p < 0.05); 44% (p < 0.01) of control value, respectively. The activity Teresa Bobkiewicz-Kozłowska 2, Jacek Bra˛zert 1 Institute of Pharmacology, Polish Academy of Sciences, Krako´w, Poland of KAT II was diminished by irbesartan at the concentration of 0.5 and *Corresponding author. *Corresponding author. 1 mM to 45% (p < 0.05) and 25% (p < 0.01) of control, respectively. 1 Department of Obstetrics and Women’s Diseases, Poznan University Our data suggest that irbesartan may reduce KYNA synthesis in of Medical Sciences, Poznan´, Poland The new generation of antiepileptic drugs is characterized by 2 Modified forced swim test was proposed as an animal model of the brain. Department of Pharmacology, Poznan University of Medical Sciences, multidirectional mechanisms of action which influence signal negative symptoms of schizophrenia. Repeated MK-801 treatment Poznan´, Poland transmission also involved in the pathogenesis of alcohol use Supported by the grant from National Science Centre (NCN) PRELU- (13 days, 0.4 mg/kg dose) significantly increased immobility in the *Corresponding author. disorder (AUD). Therefore, current experimental and clinical DIUM 4 No. UMO-2012/07/N/NZ4/02088. forced swim test without affecting spontaneous locomotor research are focused on their possible use in addiction therapy. activity. Until now it was used predominantly to establish the Gestational diabetes mellitus is a perinatal complication of Individual studies in this research area are focused on new AEDs, putative antipsychotic activity of novel compounds. However, the http://dx.doi.org/10.1016/j.pharep.2015.06.134 increasing prevalence. However, limited data is available on such as retigabine. The aim of the study was to assess the effect of neurochemical mechanisms which may underlie behavioural endothelial function and its impact on fetomaternal status in this retigabine on quantitative changes in the bioelectric activity of changes observed in this model are not well understood. In our rapidly growing population. Aim of our study was to investigate the brain in rabbits receiving chronic ethanol. This work is a Systematic review of venous thromboembolism present studies we decided to investigate this subject focusing on whether any maternal metabolic characteristic is associated with continuation of our earlier study [Zwierzyn´ ska et al., Am J Drug in antipsychotics-exposed patients GABAergic and serotonergic neurotransmission, the important maternal endothelial function measured as serum concentrations of Alcohol Abuse, 2015]. Rabbits with electrodes implanted into the 1,2, 1,2 factors in a pathophysiology of schizophrenia. In the first part of Anna Zaremba *, Katarzyna Sejbuk-Rozbicka , sVCAM-1, hs-CRP, visfatin and adiponectin. Material and method: following brain structures: the midbrain reticular formation, the 3 1,4 our research the behavioural activity of the GABAergic and Bartosz Łoza , Grzegorz Cessak , data was taken from a cohort of pregnant women with gestational hippocampus and the frontal cortex were used. Retigabine was 1,5 1 serotonergic agents was investigated. All of the compounds Konrad Rokita , Dagmara Mirowska-Guzel , diabetes mellitus treated with diet plus insulin or diet plus administered po repeatedly at a dose of 5 mg/kg/day for the 6- 1,4,5 shortened the increased immobility time in investigated doses: Ewa Bałkowiec-Iskra metformin. Each participant was sampled upon referral to the week experimental period with ethanol ad libitum and the 2- (RS)-8-OH-DPAT (5-HT agonist) at 0.01 and 0.025 mg/kg doses, academic unit and then at least once in the third trimester. week abstinence period. The EEG was recorded after each week of 1A 1 Department of Experimental and Clinical Pharmacology, Medical or GABA activators SKF at 0.025–0.05 mg/kg and rac-BHFF at 2.5– Characteristic of the study group: age: 33.5 6.0 years, gestational the study. Ethanol-induced changes were observed in all studied B University of Warsaw, Warszawa, Poland � 10 mg/kg doses. In the second part of our studies mRNA age at GDM diagnosis: 25.6 4.2 weeks, gestational age at referral: structures as soon as 2 weeks of ethanol administration and they 2 Agency for Health Technology Assessment, Warszawa, Poland � expression and protein level for 5-HT receptors, and for 29.1 3.3 weeks, BMI at baseline: 32.1 6.0 kg/m2, average daily demonstrated the inhibitory effect of ethanol on the brain 1A 3 Department of Psychiatry, Physiotherapy Division, Medical Univer- � � GAD65 and GAD67 enzymes were measured in the cortex and glycemia at baseline: 6.1 0.7 mmol/dL, HbA at baseline: 5.7 0.7%; structures. During the abstinence period, the changes had a sity of Warsaw, Warszawa, Poland � 1c � hippocampus, with the use of RT- PCR and Western blot. The level proportion of nulliparous women: 64.1%, average gestational age at different character and significant neuronal hyperactivity was 4 Office for Registration of Medicinal Products, Medical Devices and of mRNA for GAD65 and GAD67 enzymes was lowered in the delivery: 38.4 1.4 weeks. Results: maternal BMI was a significant observed. Retigabine co-administered with ethanol decreased Biocidal Products, Warszawa, Poland � hippocampus after chronic MK-801 administration. The protein predictor for hs-CRP and adiponectin. Maternal LDL and total changes in the EEG recordings during both the periods of 5 Nowowiejski Hospital, Warszawa, Poland level of GAD65 enzymes was decreased in the hippocampus. The cholesterol was a significant predictor for adiponectin. However, these alcoholization and abstinence, and this effect concerned primarily *Corresponding author. chronic administration of MK-801 induced the significant associations explained only a small proportion of the variability in the the hippocampus. These results indicated that retigabine 2 increase of 5-HT1A receptors level both in prefrontal cortex and dependent parameters (R < 0.1). Also, significant but weak correla- decreases the sensitivity of the hippocampus to ethanol and this hippocampus. Our research support the hypothesis that the Many studies suggest an association between the use of tions were found between sVCAM-1 and hs-CRP (Rho = -0.319, modulatory effect may be significant in the development of antipsychotic medicines (APs) and occurrence of venous throm- changes of GABA and/or 5-HT1A receptors level may contribute to p=0.003), visfatin (Rho = -0.247, p=0.022) and adiponectin alcohol addiction. the pathophysiology of schizophrenia. boembolism (VTE). Thromboembolism is often associated with a (Rho = 0.278, p=0.001). No associations between maternal glycemic significant risk of disability or death, and also plays a role in control and markers of endothelial function was found in that cohort. http://dx.doi.org/10.1016/j.pharep.2015.06.137 significantly increasing treatment costs. Despite many years of http://dx.doi.org/10.1016/j.pharep.2015.06.133 Conclusions: in late pregnancy, only maternal BMI and lipids seem to be research on the association between the use of APs and VTE, associated with endothelial function in women with well-controlled specific pathogenetic mechanisms have not been identified. In the gestational diabetes mellitus. Effect of irbesartan on kynurenic acid present study we searched available electronic medical databases (MEDLINE, PubMed, EMBASE) using a comprehensive search production and activity of kynurenine http://dx.doi.org/10.1016/j.pharep.2015.06.136 aminotransferases in rat brain cortex strategy. All steps were performed by at least 2 analysts in compliance with current Cochrane Handbook for Systematic * Izabela Zakrocka , Waldemar A. Turski, Reviews of Interventions. The primary outcome measure of this ´ Ewa M. Urbanska, Tomasz Kocki systematic review was the occurrence of VTE (both DVT and/or PE) Department of Experimental and Clinical Pharmacology, Medical in patients exposed to AP drugs. Based on the identified reports it University of Lublin, Poland has been determined that the main risk factors for VTE are *Corresponding author. duration of treatment and patient-related factors, such as gender, age, body mass or physical activity. Current data does not allow identifying prothrombotic potential for individual APs. All Kynurenic acid (KYNA) is an endogenous brain constituent that patients treated with APs should be assessed with regard to the inhibits all three ionotropic excitatory amino acid (EAA) receptors. risk of thromboembolic complications and, if needed, appropriate Cerebral synthesis of KYNA from its bioprecursor L-kynurenine is prevention methods (most of all including elimination of catalyzed by kynurenine aminotransferases (KAT I and KAT II) modifiable risk factors) should be implemented. Moreover, localized preferentially within astrocytes. The possible role of patients should be educated about symptoms suggesting VTE. KYNA in regulation of blood pressure has been postulated. Recent Each patient with suspected VTE should be diagnosed and treated experimental data indicated that KYNA administered intrathecally immediately. or into the rostral ventrolateral medulla decreased arterial blood pressure. Irbesartan is known to cross the blood–brain barrier. It is an active angiotensin II type 1 receptor (AT1) antagonist. http://dx.doi.org/10.1016/j.pharep.2015.06.135 In this study the influence of irbesartan, an AT1 – receptor antagonist on the brain production of KYNA was investigated. 44 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45 45

Modified swim test as a model of depressive-like In cortical slices irbesartan at the concentration of 0.5 and 1 mM Predictors of endothelial function in women A pharmaco-EEG assessment of the effect of negative symptoms of schizophrenia: GABAergic decreased KYNA synthesis to 66% (p < 0.001) and 42% (p < 0.001) with gestational diabetes mellitus requiring retigabine on alcohol use disorder course in and serotonergic signaling of control value, respectively. antidiabetic agents rabbits Monika Wozńiak *, Joanna Wieron´ ska, The activity of KAT I was inhibited by irbesartan at the AgnieszkaZawiejska 1,*, Ewa Wender-Ozegowska 1, Ewa Zwierzyn´ ska *, Bogusława Pietrzak Marcin Marciniak, Andrzej Pilc concentration of 0.1, 0.5 and 1 mM to 76% (p < 0.05); 58% Magdalena Borowska 2, Przemysław Mikołajczak 2, Department of Pharmacodynamics, Medical University, Ło´dz´, Poland (p < 0.05); 44% (p < 0.01) of control value, respectively. The activity Teresa Bobkiewicz-Kozłowska 2, Jacek Bra˛zert 1 Institute of Pharmacology, Polish Academy of Sciences, Krako´w, Poland of KAT II was diminished by irbesartan at the concentration of 0.5 and *Corresponding author. *Corresponding author. 1 mM to 45% (p < 0.05) and 25% (p < 0.01) of control, respectively. 1 Department of Obstetrics and Women’s Diseases, Poznan University Our data suggest that irbesartan may reduce KYNA synthesis in of Medical Sciences, Poznan´, Poland The new generation of antiepileptic drugs is characterized by 2 Modified forced swim test was proposed as an animal model of the brain. Department of Pharmacology, Poznan University of Medical Sciences, multidirectional mechanisms of action which influence signal negative symptoms of schizophrenia. Repeated MK-801 treatment Poznan´, Poland transmission also involved in the pathogenesis of alcohol use Supported by the grant from National Science Centre (NCN) PRELU- (13 days, 0.4 mg/kg dose) significantly increased immobility in the *Corresponding author. disorder (AUD). Therefore, current experimental and clinical DIUM 4 No. UMO-2012/07/N/NZ4/02088. forced swim test without affecting spontaneous locomotor research are focused on their possible use in addiction therapy. activity. Until now it was used predominantly to establish the Gestational diabetes mellitus is a perinatal complication of Individual studies in this research area are focused on new AEDs, putative antipsychotic activity of novel compounds. However, the http://dx.doi.org/10.1016/j.pharep.2015.06.134 increasing prevalence. However, limited data is available on such as retigabine. The aim of the study was to assess the effect of neurochemical mechanisms which may underlie behavioural endothelial function and its impact on fetomaternal status in this retigabine on quantitative changes in the bioelectric activity of changes observed in this model are not well understood. In our rapidly growing population. Aim of our study was to investigate the brain in rabbits receiving chronic ethanol. This work is a Systematic review of venous thromboembolism present studies we decided to investigate this subject focusing on whether any maternal metabolic characteristic is associated with continuation of our earlier study [Zwierzyn´ ska et al., Am J Drug in antipsychotics-exposed patients GABAergic and serotonergic neurotransmission, the important maternal endothelial function measured as serum concentrations of Alcohol Abuse, 2015]. Rabbits with electrodes implanted into the 1,2, 1,2 factors in a pathophysiology of schizophrenia. In the first part of Anna Zaremba *, Katarzyna Sejbuk-Rozbicka , sVCAM-1, hs-CRP, visfatin and adiponectin. Material and method: following brain structures: the midbrain reticular formation, the 3 1,4 our research the behavioural activity of the GABAergic and Bartosz Łoza , Grzegorz Cessak , data was taken from a cohort of pregnant women with gestational hippocampus and the frontal cortex were used. Retigabine was 1,5 1 serotonergic agents was investigated. All of the compounds Konrad Rokita , Dagmara Mirowska-Guzel , diabetes mellitus treated with diet plus insulin or diet plus administered po repeatedly at a dose of 5 mg/kg/day for the 6- 1,4,5 shortened the increased immobility time in investigated doses: Ewa Bałkowiec-Iskra metformin. Each participant was sampled upon referral to the week experimental period with ethanol ad libitum and the 2- (RS)-8-OH-DPAT (5-HT agonist) at 0.01 and 0.025 mg/kg doses, academic unit and then at least once in the third trimester. week abstinence period. The EEG was recorded after each week of 1A 1 Department of Experimental and Clinical Pharmacology, Medical or GABA activators SKF at 0.025–0.05 mg/kg and rac-BHFF at 2.5– Characteristic of the study group: age: 33.5 6.0 years, gestational the study. Ethanol-induced changes were observed in all studied B University of Warsaw, Warszawa, Poland � 10 mg/kg doses. In the second part of our studies mRNA age at GDM diagnosis: 25.6 4.2 weeks, gestational age at referral: structures as soon as 2 weeks of ethanol administration and they 2 Agency for Health Technology Assessment, Warszawa, Poland � expression and protein level for 5-HT receptors, and for 29.1 3.3 weeks, BMI at baseline: 32.1 6.0 kg/m2, average daily demonstrated the inhibitory effect of ethanol on the brain 1A 3 Department of Psychiatry, Physiotherapy Division, Medical Univer- � � GAD65 and GAD67 enzymes were measured in the cortex and glycemia at baseline: 6.1 0.7 mmol/dL, HbA at baseline: 5.7 0.7%; structures. During the abstinence period, the changes had a sity of Warsaw, Warszawa, Poland � 1c � hippocampus, with the use of RT- PCR and Western blot. The level proportion of nulliparous women: 64.1%, average gestational age at different character and significant neuronal hyperactivity was 4 Office for Registration of Medicinal Products, Medical Devices and of mRNA for GAD65 and GAD67 enzymes was lowered in the delivery: 38.4 1.4 weeks. Results: maternal BMI was a significant observed. Retigabine co-administered with ethanol decreased Biocidal Products, Warszawa, Poland � hippocampus after chronic MK-801 administration. The protein predictor for hs-CRP and adiponectin. Maternal LDL and total changes in the EEG recordings during both the periods of 5 Nowowiejski Hospital, Warszawa, Poland level of GAD65 enzymes was decreased in the hippocampus. The cholesterol was a significant predictor for adiponectin. However, these alcoholization and abstinence, and this effect concerned primarily *Corresponding author. chronic administration of MK-801 induced the significant associations explained only a small proportion of the variability in the the hippocampus. These results indicated that retigabine 2 increase of 5-HT1A receptors level both in prefrontal cortex and dependent parameters (R < 0.1). Also, significant but weak correla- decreases the sensitivity of the hippocampus to ethanol and this hippocampus. Our research support the hypothesis that the Many studies suggest an association between the use of tions were found between sVCAM-1 and hs-CRP (Rho = -0.319, modulatory effect may be significant in the development of antipsychotic medicines (APs) and occurrence of venous throm- changes of GABA and/or 5-HT1A receptors level may contribute to p=0.003), visfatin (Rho = -0.247, p=0.022) and adiponectin alcohol addiction. the pathophysiology of schizophrenia. boembolism (VTE). Thromboembolism is often associated with a (Rho = 0.278, p=0.001). No associations between maternal glycemic significant risk of disability or death, and also plays a role in control and markers of endothelial function was found in that cohort. http://dx.doi.org/10.1016/j.pharep.2015.06.137 significantly increasing treatment costs. Despite many years of http://dx.doi.org/10.1016/j.pharep.2015.06.133 Conclusions: in late pregnancy, only maternal BMI and lipids seem to be research on the association between the use of APs and VTE, associated with endothelial function in women with well-controlled specific pathogenetic mechanisms have not been identified. In the gestational diabetes mellitus. Effect of irbesartan on kynurenic acid present study we searched available electronic medical databases (MEDLINE, PubMed, EMBASE) using a comprehensive search production and activity of kynurenine http://dx.doi.org/10.1016/j.pharep.2015.06.136 aminotransferases in rat brain cortex strategy. All steps were performed by at least 2 analysts in compliance with current Cochrane Handbook for Systematic * Izabela Zakrocka , Waldemar A. Turski, Reviews of Interventions. The primary outcome measure of this ´ Ewa M. Urbanska, Tomasz Kocki systematic review was the occurrence of VTE (both DVT and/or PE) Department of Experimental and Clinical Pharmacology, Medical in patients exposed to AP drugs. Based on the identified reports it University of Lublin, Poland has been determined that the main risk factors for VTE are *Corresponding author. duration of treatment and patient-related factors, such as gender, age, body mass or physical activity. Current data does not allow identifying prothrombotic potential for individual APs. All Kynurenic acid (KYNA) is an endogenous brain constituent that patients treated with APs should be assessed with regard to the inhibits all three ionotropic excitatory amino acid (EAA) receptors. risk of thromboembolic complications and, if needed, appropriate Cerebral synthesis of KYNA from its bioprecursor L-kynurenine is prevention methods (most of all including elimination of catalyzed by kynurenine aminotransferases (KAT I and KAT II) modifiable risk factors) should be implemented. Moreover, localized preferentially within astrocytes. The possible role of patients should be educated about symptoms suggesting VTE. KYNA in regulation of blood pressure has been postulated. Recent Each patient with suspected VTE should be diagnosed and treated experimental data indicated that KYNA administered intrathecally immediately. or into the rostral ventrolateral medulla decreased arterial blood pressure. Irbesartan is known to cross the blood–brain barrier. It is an active angiotensin II type 1 receptor (AT1) antagonist. http://dx.doi.org/10.1016/j.pharep.2015.06.135 In this study the influence of irbesartan, an AT1 – receptor antagonist on the brain production of KYNA was investigated. Pharmacological Reports 67 (2015) 46–48 Author index 47

Contents lists available at ScienceDirect Kostrzewa, J.P., 8 Nagadowska, J., 26 Radziwon´-Zaleska, M., 36 Kostrzewa, R.M., 8 Nalepa, I., 37 Ratajczak, P., 31, 36 Kotlinska, J.H., 13 Nasal, A., 20, 35 Rogin´ska, D., 32 Pharmacological Reports Kotowski, M., 17 Newman-Tancredi, A., 23 Rogóz˙ , Z., 36, 39 Kowalczyk, E., 24 Nierwin´ska, K., 29 Rokita, K., 37, 38, 44 journal homepage: www.elsevier.com/locate/pharep Kowalczyk, M., 19 Nowacka, M., 29, 30 Roman, A., 37 Kowalska, A., 17, 19 Nowacka, M.M., 32 Romaniuk, A., 30 Kowalska, M., 37 Nowak, B., 29, 31, 40 Ruszkowski, P., 33 Kowalski, P., 31, 35 Nowak, D., 42 Rutkowska, M., 39 Kozniewska, E., 20 Nowak, G., 36 Rychlik-Sych, M., 12, 37 Krivosˇíková, Z., 21 Nowakowska, E., 31, 36 Ryszewska-Pokrasńiewicz, B., 36 Author index Król, M., 13 Obuchowicz, E., 30, 32, 34, 35 Rzemieniec, J., 9, 10 Krysa, M.M., 25 Obuchowicz, M., 38 Rzezńiczek, S., 38 Krza˛sćik, P., 26, 28, 39, 43 Olajossy, B., 19 S´liwin´ski, L., 21 Krzewicka, E., 30 Ole˛ dzki, S., 22 S´lusarczyk, J., 16 Kubová, H., 5, 6 Orchel, J., 34 Sńiecikowska, J., 23 Kucharska, A., 41 Ostasz, R., 17 Sadanowicz, E., 31 Acher, F., 7 Chrusćicka, B., 17 Glen´sk, M., 25 Kucharska, A.Z., 40 Ostrowski, M., 21, 27 Safranow, K., 17, 22, 28 Adamiak-Giera, U., 22 Chukanova, G., 21 Głombik, K., 16 Kujawski, R., 19, 24 Oswald, S., 21, 27 Sałat, K., 13 Alexander, S., 3 Ciechanowska, M., 19 Głowacka, A., 11, 26 Kulig, K., 13 Oz˙ arowski, M., 17, 24 Salin´ska, E., 8 Andres-Mach, M., 25 Cies´lewicz, A., 12, 16, 26 Głowacka, K., 15 Kurmambayev, Y., 21 Pe˛ kała, K., 33 Sa˛ czewski, F., 35 Andrys-Wawrzyniak, I., 26 Cryan, J.F., 6 Golubeva, A.V., 6 Kurzawski, M., 11, 17, 22, 28, 32 Paluch, M., 19 Sˇtefíková, K., 21 Andrzejczak, D., 16 Cudna, A., 27 Gomułkiewicz, A., 42 Kus, K., 31, 36 Palucha-Poniewiera, A., 34 Schetz, D., 11 Antkiewicz-Michaluk, L., 9 Czarny, A., 40 Górska-Paukszta, M., 17, 24 Kus´mierczyk, J., 37 Paluchowska, M., 17 Secewicz, A., 15 Balcer-Dymel, N., 16 Czerkawska, A., 22 Gracz, H., 26 Kuzawin´ska, O., 27 Papiez˙, M., 34 Sedlak, L., 24 Bałkowiec-Iskra, E., 18, 27, 36, 37, 38, 44 Czerny, B., 17, 19, 24 Grygorowicz, T., 27 Kwiatkowska, J., 29, 31 Partyka, A., 23, 32 Sejbuk-Rozbicka, K., 38, 44 Baran´ska, M., 12, 37 Czuczwar, S.J., 4, 30 Gryszczyn´ska, A., 14 Landwójtowicz, M., 31 Paruszewska, E., 19 Seremak-Mrozikiewicz, A., 17, 19, 24 Baraniak, D., 33 Dadlez, M., 42 Haenisch, S., 21 Langfort, J., 29 Paul-Samojedny, M., 30, 32 Siegmund, W., 4, 21, 27 Bartkowiak-Wieczorek, J., 17 Danilczuk, Z., 20 Hon´do, Ł., 43 Łapczuk, J., 21, 27 Pawlaczyk, M., 12 Sikora, M., 42 Bartoszewicz, M., 15 Da˛ browska, M., 18, 27, 37, 38 Hurkacz, M., 11 Łapin´ski, Ł., 15 Pawlik, A., 28 Sitarz, A.M., 10 Bas´, S., 34 Datka, W., 38 Iskakova, S., 21, 43 Łapot, M., 19 Peruz˙ ynska, M., 32 Siwek, M., 38 Basta-Kaim, A., 16 Dawidowski, M., 13 Jabłecka, A., 12, 16, 26 Lason´, W., 9, 10, 16 Perzyn´ski, A., 19 Skalicka-Wozńiak, K., 25 Biała, G., 14, 33 Diamandakis, D., 8 Jagodzin´ski, P.P., 21 Łazarewicz, J.W., 8 Peters, J., 21, 27 Skałka, P., 38 Białecka, M., 17, 28 Dinan, T.G., 6 Jakimiuk, A., 23 Lehner, M., 27, 39, 43 Piasecki, T., 31, 40, 42 Skalski, M., 36 Bielecka, A.M., 30, 32, 34, 35 Długoke˛cka, J., 20 Jakubowski, P., 14, 23 Les´kiewicz, M., 16 Piechowicz, J., 42 Skórzewska, A., 26, 27, 39, 43 Błaszczyk, B., 5 Doller, D., 6 Janas, A., 21, 33, 40 Lis, K., 27 Piejko, M., 32 Skre˛ tkowicz, J., 12, 37 Bobkiewicz-Kozłowska, T., 14, 45 Domin, H., 20 Jasin´ska, E., 30 Litwa, E., 9, 10 Piesńiewska, M., 29, 42 Skrzeszewski, J., 36 Bochnia, M., 21 Drapala, A., 13, 42 Jastrze˛ bska, M., 22 Łoza, B., 38, 44 Pietras, T., 24 Skrzypecki, J., 42 Bogacz, A., 17, 19, 24 Droz´dzik, M., 17, 21, 27, 28, 32 Jastrze˛ bska-Wie˛ sek, M., 23 Lukasiuk, K., 5 Pietrzak, B., 45 Skuza, G., 39 Boguszewski, P., 20 Drozdowicz, E., 36 Jaworski, P.L., 25 Łuszczki, J.J., 25, 26 Pilc, A., 7, 17, 34, 36, 38, 44 Słupski, W., 39 Bohatyrewicz, A., 28 Dudek, D., 38 Jazwiec, R., 42 Machalin´ski, B., 17, 32 Pin´ska, A., 33 S´miałowska, M., 20 Bojarski, A., 17 Dudek, S., 24 Je˛ drzejuk, D., 31 Machoy-Mokrzyn´ska, A., 28 Piórecki, N., 40, 41 Smolarek, I., 26 Bojko, P., 17 Dworacka, M., 21, 43 Junka, A.F., 15 Maciejak, P., 28 Piskorz, S., 30, 33 Smutnicka, D., 15 Bon´ka, A., 24 Dworacki, G., 21 Kaczmarczyk-Sedlak, I., 24 Magdalan, J., 40, 41 Płazńik, A., 26, 27, 28, 39, 43 Sobolewska, A., 26, 27, 28, 39 Boron´, D., 19, 38 Dyr, W., 14, 26 Kaczorowska, K., 17 Majewski, M., 14, 23 Plato, M., 34 Sołtysiak, P., 40 Borowicz, A.M., 12 Dziedziejko, V., 17, 28 Kajta, M., 4, 9, 10 Małecki, A., 29 Pociecha, K., 34 Sowa, J., 16 Borowska, M., 44 Dziekan, K., 19, 24 Kałdon´ska, M., 22 Malinowski, D., 28 Podkowa, A., 13 Sowa-Kuc´ma, M., 36 Bran´ski, P., 17 Dzie˛ giel, P., 42 Kaliszan, R., 20, 35 Ma˛ czyn´ska, B., 15 Podkowa, K., 34 Sozan´ski, T., 29, 40, 41, 42 Bra˛ zert, J., 45 Dziewiszek, W., 21, 31, 41 Kamin´ska, E., 14 Marciniak, M., 44 Podlasz, P., 14, 23 Stankiewicz, A., 17 Broniowska, Z˙ ., 18 Fabianćzyk, H., 17 Kamin´ska, K., 36 Maresˇ, P., 5, 6 Podsadni, P., 13 Starzyn´ska-Sadura, Z., 28 Brus, H., 38 Filip, M., 7, 8 Kamin´ski, A., 19, 24 Marszalek-Grabska, M., 13 Poli, S., 34 Stelmaszyk, A., 43 Brus, R., 8, 38 Filipek, B., 13 Kaniuga, E., 27 Matuszewska, A., 29, 30, 31, 40 Pomierny, B., 7 Szandruk, M., 29, 31, 40, 41 Brytan, M., 19 Fleszar, M., 42 Karbownik, M.S., 24 Merwid-La˛ d, A., 29, 31, 40, 42 Pomierny-Chamioło, L., 7, 8 Szela˛ g, A., 21, 29, 31, 40, 41, 42 Budziszewska, B., 18 Florek-Łuszczki, M., 25 Kasica, N., 14, 23 Michalak, A., 14 Przegalin´ski, E., 2 Szela˛ g, S., 32 Budzyn´ska, B., 33 Folbergrová, J., 5 Kaz´mierczk, E., 26 Michalski, W., 21 Przekop, F., 19 Szemraj, J., 24 Bugajski, J., 23 Folwarczna, J., 21, 24, 30, 40 Klimowicz, A., 17 Mijowska, E., 32 Przykaza, Ł., 20 Szulc, M., 14 Bugno, R., 17 Fonderska, P., 22 Kmiotek, K., 38 Mikicin, M., 19 Pudełko, A., 29, 35 Szulczyk, B., 13 Burnat, G., 17 Frankowska, M., 7, 8 Kocic´, I., 11 Mikolajczak, P., 45 Pugaczewska, M., 14 Szumny, A., 40, 41 Cegieła, U., 21, 30, 33, 40 Fra˛ ckowiak, T., 35 Kocki, T., 22, 44 Mikołajczak, P.Ł., 14 Pustkowska, O., 12 Szumny, D., 40, 41 Cendrowski, K., 32 Frycz, B., 21 Kołaczkowski, M., 32 Miozga, R., 30, 33 Pyrka, D., 25 Szychowski, K.A., 10 Cessak, G., 18, 37, 38, 44 Furgała, A., 13 Kołosowska, K., 28 Mirowska-Guzel, D., 27, 38, 44 Pytlik, M., 21, 40 Szymczyk, P., 15 Chlebda, E., 42 Gaczkowska, A., 12 Kondrat-Wróbel, M., 25, 30 Miszkiel, J., 7 Pyzia, Ł., 30 Szynaka, S., 20 Chlebda-Sieragowska, E., 29, 41 Gajdosˇ, M., 21 Kondrat-Wróbel, M.W., 25, 26 Miziak, B., 30 Pyzio, Ł., 22 Szyndler, J., 28 Chlubek, D., 8 Ga˛ dek-Michalska, A., 23 Kornacewicz-Jach, Z., 22 Mlynarski, J., 34 Rachwalska, P., 23 Tadeusz, J., 23 Chmiel-Perzyn´ska, I., 19 Ga˛ siorowski, J., 15 Kornicka, A., 35 Mogilski, S., 13 Raczak-Gutknecht, J., 35 Taracha, E., 27 Chrosćin´ska-Krawczyk, M., 30 Gawron´ska-Szklarz, B., 22 Korzeniowska, K., 12, 16, 26 Moloney, R.D., 6 Radwan´ska, A., 20 Trocha, M., 29, 31, 40, 42 http://dx.doi.org/10.1016/S1734-40(15)00262-5 Pharmacological Reports 67 (2015) 46–48 Author index 47

Trojan, E., 16, 37 Wieron´ska, J., 44 Zaczyn´ska, E., 40 Trzeciak, K., 32 Wieron´ska, J.M., 7 Zagaja, M., 24, 25 Turło, J., 13 Winiarska, H., 21, 43 Zajda, M., 26 Turski, W.A., 22, 44 Wisńiewski, J., 42 Zakrocka, I., 22, 44 Turzyn´ska, D., 26, 27, 28, 39 Wisłowska-Stanek, A., 27, 39, 43 Zaremba, A., 44 Ufnal, M., 13. 42 Wnuk, A., 9, 10 Zare˛ ba, P., 13 Urazayev, O., 43 Wojnar, W., 24 Zawiejska, A., 45 Urban´ska, E.M., 19, 44 Wojtalik, K., 20 Zawilska, J.B., 16 Uzar, I., 19 Wojtczak, A., 12, 37 Zbroja, M., 32 Walkowiak, J., 26 Wójtowicz, A.K., 9, 10 Z˙ ebrowska, A., 37 Wa˛ sik, A., 9 Woldan-Tambor, A., 16 Zharmankhanova, G., 43 Wasik, A., 23, 32 Wolski, H., 24 Ziemin´ska, E., 8 Waszczykowska, E., 37 Woyciechowska, M., 34 Z˙ ółkowska, D., 26 Wender-Ozegowska, E., 45 Wozńiak, M., 7, 44 Zwierzyn´ska, E., 45 We˛ grzynowska, K., 32 Wróbel, J., 25, 27 Zych, M., 24 Wesołowska, A., 21, 23, 32, 43 Wyska, E., 34 Wiela-Hojen´ska, A., 11 Wyszogrodzka, E., 14, 26 48 Author index 67 VOL. 67 Supplement 1 2015 VOL. 67 Supplement 1 2015 PHARMACOLOGICAL /S1 ISSN 1734-1140 Trojan, E., 16, 37 Wieron´ska, J., 44 Zaczyn´ska, E., 40 REPORTS Trzeciak, K., 32 Wieron´ska, J.M., 7 Zagaja, M., 24, 25 Turło, J., 13 Winiarska, H., 21, 43 Zajda, M., 26 Turski, W.A., 22, 44 Wisńiewski, J., 42 Zakrocka, I., 22, 44 Turzyn´ska, D., 26, 27, 28, 39 Wisłowska-Stanek, A., 27, 39, 43 Zaremba, A., 44 CONTENTS REPORTS PHARMACOLOGICAL Ufnal, M., 13. 42 Wnuk, A., 9, 10 Zare˛ ba, P., 13 Urazayev, O., 43 Wojnar, W., 24 Zawiejska, A., 45 Urban´ska, E.M., 19, 44 Wojtalik, K., 20 Zawilska, J.B., 16 Special Issue: XIX International Congress of the Polish Pharmacological Society Uzar, I., 19 Wojtczak, A., 12, 37 Zbroja, M., 32 Walkowiak, J., 26 Wójtowicz, A.K., 9, 10 Z˙ ebrowska, A., 37 Guest Editors: D. Malinowski, B. Gawron´ska-Szklarz Special Issue: Wa˛ sik, A., 9 Woldan-Tambor, A., 16 Zharmankhanova, G., 43 XIX International Congress of the Polish Pharmacological Society Wasik, A., 23, 32 Wolski, H., 24 Ziemin´ska, E., 8 Waszczykowska, E., 37 Woyciechowska, M., 34 Z˙ ółkowska, D., 26 1 Editorial Wender-Ozegowska, E., 45 Wozńiak, M., 7, 44 Zwierzyn´ska, E., 45 H.M. Droz´dzik Guest Editors: D. Malinowski, B. Gawron´ska-Szklarz We˛ grzynowska, K., 32 Wróbel, J., 25, 27 Zych, M., 24 2 Abstracts – XIX Congress PTF Wesołowska, A., 21, 23, 32, 43 Wyska, E., 34 46 Author index Wiela-Hojen´ska, A., 11 Wyszogrodzka, E., 14, 26

Vol PHARMACOLOGICAL . . 67 / S1 (

2015 REPORTS ) ) 1 – 48 Special Issue Issue Special ELSEVIER

INSTITUTE OF PHARMACOLOGY POLISH ACADEMY OF SCIENCES ScienceDirect KRAKÓW (POLAND)