DOCSLIB.ORG

Effect of the Nutritional Supplement Alanerv on the Serum PON1 Activity in Post-Acute Stroke Patients

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Effect of the Nutritional Supplement Alanerv on the Serum PON1 Activity in Post-Acute Stroke Patients Pharmacological Reports Copyright © 2013 2013, 65, 743750 by Institute of Pharmacology ISSN 1734-1140 Polish Academy of Sciences Shortcommunication EffectofthenutritionalsupplementALAnerv® ontheserumPON1activityinpost-acutestroke patients BogdanN.Manolescu1,MihaiBerteanu2,DeliaCintezã2 1 DepartmentofOrganicChemistry”C.Nenitescu”,FacultyofAppliedChemistryandScienceofMaterials, PolytechnicUniversityofBucharest,011061,Bucharest,Romania 2 DepartmentofRehabilitationandPhysicalMedicine,FacultyofMedicine,UniversityofMedicineandPharmacy ”CarolDavila”,020022,Bucharest,Romania Correspondence: BogdanN.Manolescu,e-mail:[email protected] Abstract: Background: Paraoxonase-1 (PON1) is one of the HDL-associated proteins which contributes to the antioxidant properties of these lipoproteins. The aim of this pilot study was to evaluate the effect of the nutritional supplement ALAnerv® on serum PON1 activity inpost-acutestrokepatientsundergoingrehabilitation. Methods: We enrolled 28 post-acute stroke patients and randomly divided them into (–) ALA or (+) ALA study groups. All the pa- tients underwent the same rehabilitation program and received comparable standard medications. Moreover, (+) ALA patients re- ceived ALAnerv® for two weeks (2 pills/day). The serum PON1 activity was assessed on blood samples taken at the admission and at the discharge moments, respectively. We used paraoxon (paraoxonase activity, PONA), phenyl acetate (arylesterase activity, ARYLA) and dihydrocoumarin (lactonase activity, LACTA) as substrates, the latter activity being regarded as physiologically rele- vant.A controlgroupof14apparentlyhealthysubjectswasalsocreated. Results: In the (+) ALA group, LACTAsignificantly increased during the study period (17.6 ± 3.2 vs. 27.6 ± 3.5, p = 0.002). Moreo- ver, the percentage of LACTAvariation between (–) ALA and (+) ALA groups during the study was also statistically different (–11.7 ±6.9% vs. +95.1±29.7%,p < 0.0001). Conclusions: These preliminary results suggest that ALAnerv® could contribute to the improvement of the physiologically relevant LACTA of PON1 in post-acute stroke patients, enabling this enzyme to contribute to the redox correction. Also, this study raises the questionabouttheeffectofalongertreatmentperiodovertheotherenzymaticactivitiesofserumPON1. Keywords: post-acutestroke,paraoxonase,lactonase,rehabilitation,lipoicacid,ALAnerv® Abbreviations: BI – Barthel index, DHLA – dihydrolipoic Introduction acid, GPx – glutathione peroxidase, HDL – high density lipo- protein particles, HDL-C – HDL cholesterol, LA – lipoic acid, LCAT – lecithine:cholesterol acyltransferase, Lp-PLA2 – Serum paraoxonase 1 (PON1) (EC 3.1.8.1), para- lipoprotein-associated phospholipase A2, PAF-AH – platelet oxonase 2 (PON2) and paraoxonase 3 (PON3) form activating factor acetylhydrolase, PL – phospholipids, PON1 – a family of enzymes which are essentially lactonases paraoxonase 1, PON2 – paraoxonase 2, PON3 – paraoxonase 3, TAG – triacylglycerol(s), TC – total cholesterol, VLDL – with a broad spectrum of substrate specificities [11, 31]. verylowdensitylipoproteinparticles PON1 is synthesized by the liver and secreted into the Pharmacological Reports, 2013, 65, 743750 743 blood where it becomes associated mainly with high The present pilot study was aimed to investigate density lipoproteins (HDL) and to a lesser extent with the influence of the ALAnerv® nutritional supplement very low density lipoproteins (VLDL) and postpran- on the activity of serum PON1 in post-acute stroke dial chylomicrons [16]. PON1 acts on several physio- patients undergoing rehabilitation. Because of the logically relevant lactones, including drugs (i.e., spi- PON1’s sensitivity to oxidative stress, we speculated ronolactones, lovastatin, mevastatin, and simvastatin), that using a nutritional supplement that contains lipoic homocysteine thiolactone and the N-acyl-homoserine acid (LA), a redox active compound, could contribute lactones produced by some Gram-negative pathogenic to the correction of serum PON1 activity in post-acute bacteria (i.e., Pseudomonas aeruginosa) [4, 8, 22]. Be- stroke patients. It is documented the ability of LA to side the lactonase activity, PON1 also hydrolyzes or- participate in thiol/disulfide exchange reactions with ganophosphorus compounds (i.e., paraoxon, chlorpyri- other biomolecules, making thus possible the correc- fos, diazoxon) and phenyl acetate; namely it exhibits tionoftheredoxstatus[18,19,25,28]. paraoxonase and arylesterase activities [11]. PON1, alongside with lecithine:cholesterol acyl- transferase (LCAT), lipoprotein-associated phospholi- pase A2 (Lp-PLA2), platelet activating factor acetyl- MaterialsandMethods hydrolase (PAF-AH), and glutathione peroxidase (GPx), is responsible for the antioxidant, anti- inflammatory and antiatherogenic properties of HDL Studypopulationanddesign [24]. These properties of PON1 could be explained through different mechanisms: (i) lactonization of The study population comprised 28 post-acute stroke oxidized fatty acids from lipoprotein phospholipids patients which were enrolled and randomly divided in with the subsequent hydrolysis (lactonase activity) of (–) ALA and (+) ALA study groups. The inclusion the corresponding lactones, (ii) reduction of choles- criterion for both groups was the diagnostic of an teryl ester hydroperoxides through a peroxidase like ischemic or hemorrhagic stroke in the previous 90 activity, and (iii) stimulation of the cholesterol efflux days before the enrollment. Cancer, chronic renal fail- from macrophages [1, 2, 33, 36]. The aforementioned ure, chronic inflammatory, autoimmune and hemato- oxidized compounds are important mediators of the logical disorders, smoking and chronic alcohol con- inflammatory response leading to initiation and devel- sumption were pathological conditions used as exclu- opmentoftheatherogenesisphenomena[37]. sion criteria. Patients who were under treatment with In a specific population, there is a great variability vitamins and anti-inflammatory drugs during the two of both PON1 catalytic activity (40–50 fold) and con- months preceding the beginning of the study were centration (13–15 fold) [32]. A major factor responsi- also excluded as well as patients with previous cere- ble for this situation is the existence of approximately brovascular events (cerebral hemorrhage, hemorrha- 200 single nucleotide polymorphisms (SNPs) of gicinfarct,transientischemicattack). which L55M and Q192R, found in the coding region All patients were hospitalized for a period of two of PON1 gene, are the most investigated [9]. Other weeks and underwent a standard rehabilitation pro- factors responsible for the variability include (i) the gram, receiving comparable medication. Moreover, ® qualitative and quantitative lipid composition of the patients from (+) ALA group received ALAnerv diet, (ii) consumption of dietary antioxidants (i.e., vi- (2pills/day)duringthehospitalizationperiod. tamins C and E, quercetin, resveratrol, gallic and ella- The serum PON1 activity using different substrates gic acids etc.), and (iii) use of different drugs (i.e., (paraoxon, phenyl acetate, and dihydrocoumarin) was statins, fibrates, probucol, ezetimibe, aspirin, rosigli- evaluated in blood samples taken from (–) ALA and tazoneetc.)[9,13]. (+) ALA groups and from a third group of 14 appar- PON1 is very sensitive to oxidative stress and it is ently healthy volunteers (Controls), matching for age well documented that different pathological condi- and sex distribution. These subjects were recruited tions (cardio- and cerebrovascular diseases, diabetes from persons presented for routine medical control. mellitus, obesity etc.) are associated with a redox im- None had a previous cerebrovascular event (cerebral balance characterized by low levels of PON1 activity hemorrhage, hemorrhagic infarct, transient ischemic [6,28,35]. attack). 744 Pharmacological Reports, 2013, 65, 743750 ® EffectofALAnerv onserumPON1inpost-acutestroke Bogdan N. Manolescu et al. From the patients belonging to the (–) ALA and (+) All the reagents were purchased from Sigma- ALA groups, two blood samples were taken, at the Aldrich (St Louis, MO, USA): O,O-diethyl-O-(4- begining of the hospitalization and at the discharge, nitrophenyl) phosphate (paraoxon), phenyl acetate, respectively; one blood sample was taken from each dihydrocoumarin, anhydrous CaCl2, Tris, Tris-HCl. subjectbelongingtotheControlsgroup. The spectrophotometric assays were performed using The BI scale was used to evaluate the patients’ abil- a Shimadzu UV-VIS mini 1240 spectrophotometer ity to perform basic activities of daily living (ADLs) (ShimadzuCorporation,Kyoto,Japan). [26]. This scale can be used to determine a baseline The lipid profile was obtained by assessing TC, level of functioning and to monitor the improvement TAG and PL with commercially available kits (Spin- inADLsoverthetime. react, Spain). Total lipids were evaluated with a phos- The ethics review boards of the National Institute phovanilline reagent-based method, according to the of Rehabilitation, Physical Medicine and Balneocli- manufacturer instructions (Spinreact, Spain). HDL-C matology and “Elias” Emergency Hospital approved was evaluated after precipitation with phosphotung- the protocol of this study (1289/10.06.2009). In- stic acid and MgCl2 (Spinreact, Spain). The Friede- formed consent was obtained from all the subjects en- wald formula was used for the estimation of the rolled in the study or from their relatives. The medica- LDL-Cconcentration. tionusedbyallthesubjectswasrecorded.
Load more

Recommended publications
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • The Differential Effects of Statins on the Metastatic Behaviour of Prostate Cancer
    British Journal of Cancer (2012) 106, 1689–1696 & 2012 Cancer Research UK All rights reserved 0007 – 0920/12 www.bjcancer.com The differential effects of statins on the metastatic behaviour of prostate cancer *,1 1 1 2,3 2,3 2,4 1,2,4 M Brown , C Hart , T Tawadros , V Ramani , V Sangar , M Lau and N Clarke 1 Genito Urinary Cancer Research Group, University of Manchester, Paterson Institute for Cancer Research, Manchester Academic Health Science Centre, 2 The Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK; Department of Urology, The Christie NHS Foundation 3 Trust, Wilmslow Road, Manchester M20 4BX, UK; Department of Urology, University Hospital of South Manchester NHS Trust, Manchester M23 9LT, 4 UK; Department of Urology, Salford Royal NHS Foundation Trust, Stott Lane, Manchester M6 8HD, UK BACKGROUND: Although statins do not affect the incidence of prostate cancer (CaP), usage reduces the risk of clinical progression and mortality. Although statins are known to downregulate the mevalonate pathway, the mechanism by which statins reduce CaP progression is unknown. METHODS: Bone marrow stroma (BMS) was isolated with ethical approval from consenting patients undergoing surgery for non- malignant disease. PC-3 binding, invasion and colony formation within BMS was assessed by standardised in vitro co-culture assays in the presence of different statins. RESULTS: Statins act directly on PC-3 cells with atorvastatin, mevastatin, simvastatin (1 mM) and rosuvastatin (5 mM), but not pravastatin, significantly reducing invasion towards BMS by an average of 66.68% (range 53.93–77.04%; Po0.05) and significantly reducing both 2 2 number (76.2±8.29 vs 122.9±2.48; P ¼ 0.0055) and size (0.2±0.0058 mm vs 0.27±0.012 mm ; P ¼ 0.0019) of colonies formed within BMS.
    [Show full text]
  • Critical Impact of Drug-Drug Interactions Via Intestinal CYP3A in the Risk Assessment of Weak Perpetrators Using Physiologically Based Pharmacokinetic Models
    DMD Fast Forward. Published on January 29, 2020 as DOI: 10.1124/dmd.119.089599 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 89599 Title page Critical impact of drug-drug interactions via intestinal CYP3A in the risk assessment of weak perpetrators using physiologically based pharmacokinetic models Makiko Yamada, Shin-ichi Inoue, Daisuke Sugiyama, Yumi Nishiya, Tomoko Ishizuka, Akiko Watanabe, Downloaded from Kengo Watanabe, Shinji Yamashita, Nobuaki Watanabe Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan dmd.aspetjournals.org (M.Y., S.I., D.S., Y.N., T.I., A.W., K.W., N.W.) and Faculty of Pharmaceutical Sciences, Setsunan University (S.Y.) at ASPET Journals on October 1, 2021 1 DMD Fast Forward. Published on January 29, 2020 as DOI: 10.1124/dmd.119.089599 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 89599 Running title page Running title: PBPK modeling of weak perpetrators via intestinal CYP3A *Corresponding author: Makiko Yamada, Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Phone: +81-3-3492- Downloaded from 3131; Fax: +81-3-5436-8567. E-mail: [email protected] Number of text pages: 28 Number of tables: 3 dmd.aspetjournals.org Number of figures: 5 Number of references: 23 Number of words in the Abstract: 245 at ASPET Journals on October 1, 2021 Number of words in the Introduction: 706 Number of words in the Discussion: 1483 Abbreviations: ACAT, Advanced Compartmental Absorption and Transit; AUC, area under the curve; AUCR, AUC ratio; CYP3A, cytochrome P450 3A; DDI, drug-drug interaction; FDA, Food and Drug Administration; Fg, intestinal availability; FPE, first pass effect; GMFE, geometric mean fold error ; LC- MS/MS, liquid chromatography-tandem mass spectrometry; PBPK, physiologically based pharmacokinetic; TDI, time-dependent inhibition.
    [Show full text]
  • Pharmaceutical and Veterinary Compounds and Metabolites
    PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES High quality reference materials for analytical testing of pharmaceutical and veterinary compounds and metabolites. lgcstandards.com/drehrenstorfer [email protected] LGC Quality | ISO 17034 | ISO/IEC 17025 | ISO 9001 PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES What you need to know Pharmaceutical and veterinary medicines are essential for To facilitate the fair trade of food, and to ensure a consistent human and animal welfare, but their use can leave residues and evidence-based approach to consumer protection across in both the food chain and the environment. In a 2019 survey the globe, the Codex Alimentarius Commission (“Codex”) was of EU member states, the European Food Safety Authority established in 1963. Codex is a joint agency of the FAO (Food (EFSA) found that the number one food safety concern was and Agriculture Office of the United Nations) and the WHO the misuse of antibiotics, hormones and steroids in farm (World Health Organisation). It is responsible for producing animals. This is, in part, related to the issue of growing antibiotic and maintaining the Codex Alimentarius: a compendium of resistance in humans as a result of their potential overuse in standards, guidelines and codes of practice relating to food animals. This level of concern and increasing awareness of safety. The legal framework for the authorisation, distribution the risks associated with veterinary residues entering the food and control of Veterinary Medicinal Products (VMPs) varies chain has led to many regulatory bodies increasing surveillance from country to country, but certain common principles activities for pharmaceutical and veterinary residues in food and apply which are described in the Codex guidelines.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • Activation of C-Jun N-Terminal Kinase Is Required for Mevastatin-Induced
    678 Preclinical report Activation of c-Jun N-terminal kinase is required for mevastatin-induced apoptosis of salivary adenoid cystic carcinoma cells Shan Zhanga, Xiao-Ling Wangb, Ye-Hua Gana and Sheng-Lin Lia Statins are inhibitors of 3-hydroxy-3-methylglutaryl mevastatin-induced JNK phosphorylation, but not coenzyme A reductase, originally developed for lowering p38 phosphorylation, and further decreased cholesterol. Statins also have pleiotropic effects, mevastatin-induced phosphorylation of ERK1/2. independent of cholesterol-lowering effects, including Taken together, the results suggest that the JNK induction of apoptosis in various cell lines. However, pathway was required for mevastatin-induced cell growth the mechanism underlying statin-induced apoptosis is inhibition and apoptosis in SACC cells. Statins could be still not fully understood. This study aims to explore the potential anticancer agents for SACC chemotherapy. proapoptotic effects and underlying mechanisms of statins Anti-Cancer Drugs 21:678–686 c 2010 Wolters Kluwer on human salivary adenoid cystic carcinoma (SACC). Health | Lippincott Williams & Wilkins. Exposure of SACC cells to mevastatin resulted in cell Anti-Cancer Drugs 2010, 21:678–686 growth inhibition and apoptosis in a dose-dependent manner, accompanied by the release of cytochrome Keywords: apoptosis, cell growth inhibition, mitogen-activated protein kinases, salivary adenoid cystic carcinoma, statin c and cleavage of caspase-3. A remarkable decrease in phosphorylation of extracellular signal-regulated kinase aCentral Laboratory and bDepartment of Preventive Dentistry, Peking University 1/2 (ERK1/2) and increase in phosphorylation of c-Jun School and Hospital of Stomatology, Zhongguancun Nandajie, Haidian District, N-terminal kinase (JNK) and p38 mitogen-activated kinase Beijing, PR China were observed.
    [Show full text]
  • The Prince and the Pauper. a Tale of Anticancer Targeted Agents
    Molecular Cancer BioMed Central Review Open Access The prince and the pauper. A tale of anticancer targeted agents Alfonso Dueñas-González*1,3, Patricia García-López1, Luis Alonso Herrera1, Jose Luis Medina-Franco2, Aurora González-Fierro1 and Myrna Candelaria1 Address: 1Unidad de Investigacion Biomédica en Cáncer, Instituto de Investigaciones Biomedicas, UNAM/Instituto Nacional de Cancerologia, Mexico City, Mexico, 2Torrey Pines Institute for Molecular Studies. 5775 Old Dixie Highway, Fort Pierce, Florida 34946, USA and 3Dirección de Investigación, Unidad de Investigacion Biomédica en Cáncer, Av. San Fernando 22, Tlalpan, 14080 México, D.F., México Email: Alfonso Dueñas-González* - [email protected]; Patricia García-López - [email protected]; Luis Alonso Herrera - [email protected]; Jose Luis Medina-Franco - [email protected]; Aurora González- Fierro - [email protected]; Myrna Candelaria - [email protected] * Corresponding author Published: 23 October 2008 Received: 27 June 2008 Accepted: 23 October 2008 Molecular Cancer 2008, 7:82 doi:10.1186/1476-4598-7-82 This article is available from: http://www.molecular-cancer.com/content/7/1/82 © 2008 Dueñas-González et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras.
    [Show full text]
  • Effects of Statins on Renin–Angiotensin System
    Journal of Cardiovascular Development and Disease Review Effects of Statins on Renin–Angiotensin System Nasim Kiaie 1,†, Armita Mahdavi Gorabi 1,†, Željko Reiner 2, Tannaz Jamialahmadi 3,4, Massimiliano Ruscica 5 and Amirhossein Sahebkar 6,7,8,9,* 1 Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran 1411713138, Iran; [email protected] (N.K.); [email protected] (A.M.G.) 2 Department of Internal Diseases, School of Medicine, University Hospital Center Zagreb, Zagreb University, 10000 Zagreb, Croatia; [email protected] 3 Quchan Branch, Department of Food Science and Technology, Islamic Azad University, Quchan 9479176135, Iran; [email protected] 4 Department of Nutrition, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran 5 Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; [email protected] 6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran 7 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran 8 School of Medicine, The University of Western Australia, Perth 6009, Australia 9 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran * Correspondence: [email protected] or [email protected] † Equally contributed. Abstract: Statins, a class of drugs for lowering serum LDL-cholesterol, have attracted attention because of their wide range of pleiotropic effects. An important but often neglected effect of statins is their role in the renin–angiotensin system (RAS) pathway. This pathway plays an integral role in the progression of several diseases including hypertension, heart failure, and renal disease.
    [Show full text]
  • Contemporary Medical Therapy for Polycystic Ovary Syndrome
    International Journal of Gynecology and Obstetrics (2006) 95, 236–241 www.elsevier.com/locate/ijgo REVIEW ARTICLE Contemporary medical therapy for polycystic ovary syndrome M.S.M. Lanham, D.I. Lebovic, S.E. Domino ⁎ Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA Received 19 July 2006; received in revised form 6 August 2006; accepted 9 August 2006 KEYWORDS Abstract Polycystic ovary syndrome is a multi-system endocrinopathy with long- Polycystic ovaries; term metabolic and cardiovascular health consequences. Patients typically present Insulin resistance; due to symptoms of irregular menstruation, hair growth, or infertility; however, Insulin sensitizing recent management options are aimed at further treating underlying glucose–insulin medicines abnormalities as well as androgen excess for proactive control of symptoms. By a 2003 international consensus conference, diagnosis is made by two out of three criteria: chronic oligoovulation or anovulation after excluding secondary causes, clinical or biochemical evidence of hyperandrogenism (but not necessarily hirsutism due to inter-patient variability in hair follicle sensitivity), and radiological evidence of polycystic ovaries. Traditional medical treatment options include oral contraceptive pills, cyclic progestins, ovulation induction, and anti-androgenic medications (aldosterone antagonist, 5α-reductase antagonist, and follicle ornithine decarbox- ylase inhibitor). Recent pharmacotherapies include insulin-sensitizing medications metformin and two thiazolidinediones (rosiglitazone/Avandia® and pioglitazone/ Actos®), a CYP19 aromatase inhibitor (letrozole/Femara®), and statins to potentially lower testosterone levels. © 2006 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 1. Definition peasant woman, married, moderately plump, infer- tile, with ovaries larger than normal, like doves' eggs, Perhaps the earliest text on polycystic ovary syndrome lumpy, shiny and whitish” in 1721 [1].
    [Show full text]
  • Cowden Syndrome and Pten Promoter Regulation
    COWDEN SYNDROME AND PTEN PROMOTER REGULATION DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Rosemary Elaine Teresi ***** The Ohio State University 2008 Dissertation Committee: Professor Allen Yates, Advisor Approved by Professor Charis Eng, Co-Advisor Professor Ching-Shih Chen _________________________________ Professor Denis Guttridge Advisor Integrated Biomedical Sciences Professor Matthew Ringel Graduate Program Professor Kristin Waite ABSTRACT Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome ten) are associated with the multi-hamartomatous disorder Cowden syndrome (CS). We show here that the PPARγ agonist Rosiglitazone, along with Lovastatin, Simvastatin, Pravastatin and Fluvastatin can induce PTEN expression by inducing PTEN transcription. Additionally, we observed, for the first time, that upregulation of SREBP protein, known to induce PPARγ expression, can increase PTEN expression. Our results indicate that Rosiglitazone, and SREBP utilizes PPARγ’s transcriptional activity to induce PTEN transcription, while the statins signal through PPARγ’s protein activity to upregulate PTEN expression. Studing the full-length PTEN identified a region between -854 and -791 that binds an as yet unidentified transcription factor, through which the statins induce PTEN expression. We examined the downstream effect of five PTEN promoter variants (-861G/T, - 853C/G, -834C/T, -798G/C, and -764G/A) that are not within any known cis-acting regulatory elements. We demonstrated that protein binding to the PTEN promoter (-893 to -755) was not altered in the five variants, when compared to the wild-type (WT) promoter. However, three of the variants (-861G/T, -853C/G, and -764G/A) demonstrated ~50% decrease in luciferase activity compared to the WT construct.
    [Show full text]
  • Review Calm the Raging Hormone
    Review Calm the raging hormone - A new therapeutic strategy involving progesterone-signaling for hemorrhagic CCMs Jun Zhang, Johnathan S. Abou-Fadel Departments of Molecular & Translational Medicine (MTM), Texas Tech University Health Science Center El Paso (TTUHSCEP), El Paso, TX 79905, USA. Correspondence to: Dr. Jun Zhang, Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, 5001 El Paso Drive, El Paso, El Paso, TX 79905, USA. E-mail: [email protected] How to cite this article: Zhang J, Abou-Fadel JS. Calm the raging hormone - A new therapeutic strategy involving progesterone-signaling for hemorrhagic CCMs. Vessel Plus 2021;5:[Accept]. http://dx.doi.org/10.20517/2574-1209.2021.64 Received: 15 Apr 2021 Revised: 12 Jun 2021 Accepted: 24 Jun 2021 First online: 5 Jul 2021 Abstract Cerebral cavernous malformations (CCMs), one of the most common vascular malformations, are characterized by abnormally dilated intracranial microvascular capillaries resulting in increased susceptibility to hemorrhagic stroke. As an autosomal dominant disorder with incomplete penetrance, the majority of CCMs gene mutation carriers are largely asymptomatic but when symptoms occur, the disease has typically reached the stage of focal hemorrhage with irreversible brain damage, while the molecular “trigger” initiating the occurrence of CCM pathology remain elusive. Currently, the invasive neurosurgery removal of CCM lesions is the only option for the treatment, despite the recurrence of the worse symptoms
    [Show full text]
  • Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential As Chemotherapeutic Targets
    molecules Review Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential as Chemotherapeutic Targets 1, 1, 1, 1,2 Ignasi B. Verdaguer y, Camila A. Zafra y, Marcell Crispim y, Rodrigo A.C. Sussmann , Emília A. Kimura 1 and Alejandro M. Katzin 1,* 1 Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508000, Brazil; [email protected] (I.B.V.); [email protected] (C.A.Z.); [email protected] (M.C.); [email protected] (R.A.C.S.); [email protected] (E.A.K.) 2 Centro de Formação em Ciências Ambientais, Universidade Federal do Sul da Bahia, Porto Seguro 45810-000 Bahia, Brazil * Correspondence: [email protected]; Tel.: +55-11-3091-7330; Fax: +5511-3091-7417 These authors contributed equally to this work. y Received: 5 August 2019; Accepted: 1 October 2019; Published: 16 October 2019 Abstract: Human parasitic protozoa cause a large number of diseases worldwide and, for some of these diseases, there are no effective treatments to date, and drug resistance has been observed. For these reasons, the discovery of new etiological treatments is necessary. In this sense, parasitic metabolic pathways that are absent in vertebrate hosts would be interesting research candidates for the identification of new drug targets. Most likely due to the protozoa variability, uncertain phylogenetic origin, endosymbiotic events, and evolutionary pressure for adaptation to adverse environments, a surprising variety of prenylquinones can be found within these organisms. These compounds are involved in essential metabolic reactions in organisms, for example, prevention of lipoperoxidation, participation in the mitochondrial respiratory chain or as enzymatic cofactors.
    [Show full text]