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The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics from the 1940S and up to 1960 Exemplified by a Small Pharmaceutical Player
The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player Leisner, Jørgen J. Published in: Frontiers in Microbiology DOI: 10.3389/fmicb.2020.00976 Publication date: 2020 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): Leisner, J. J. (2020). The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player. Frontiers in Microbiology, 11, [976]. https://doi.org/10.3389/fmicb.2020.00976 Download date: 29. Sep. 2021 fmicb-11-00976 June 10, 2020 Time: 21:55 # 1 REVIEW published: 12 June 2020 doi: 10.3389/fmicb.2020.00976 The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player Jørgen J. Leisner* Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark The 1940s and 1950s witnessed a diverse search for not just natural product antibiotics but also for synthetic and semisynthetic compounds. This review revisits this epoch, using the research by a Danish pharmaceutical company, LEO Pharma, as an example. LEO adopted a strategy searching for synthetic antibiotics toward specific bacterial Edited by: Rustam Aminov, pathogens, in particular Mycobacterium tuberculosis, leading to the discovery of a University of Aberdeen, new derivative of a known drug. Work on penicillin during and after WWII lead to the United Kingdom development of associated salts/esters and a search for new natural product antibiotics. -
Survey of Tiamulin+Oxytetracyclinein Control of CRD Complex Due to La Sota Vaccine in Broiler Chickens
Available online a t www.scholarsresearchlibrary.com Scholars Research Library European Journal of Zoological Research, 2013, 2 (4): 45-49 (http://scholarsresearchlibrary.com/archive.html) ISSN: 2278–7356 Survey of Tiamulin+Oxytetracyclinein control of CRD complex due to La Sota vaccine in broiler chickens Adel Feizi Department of Clinical Sciences, Tabriz Branch, Islamic Azad University, Tabriz, Iran _____________________________________________________________________________________________ ABSTRACT Mycoplasma gallisepticum (MG) is one of the most important diseases of poultry industry in Iran and all over the world. Mortality, poor weight gain and increasing of feed conversion ratio (FCR) were seen in MG infected flocks. Several drugs are used for prevention and control of MG, the purpose of this study was to investigateoxytetracycline + Tiamulinefficacy on MG, and its role on broilers performance.In this study, 240 Ross 308 broilers divided in 2 groups. In one of the groups, oxytetracycline + Tiamulinwere used in days 21 to 30 following La Sota vaccination for controlling vaccination reaction and in the secondgroup, placebo was used and that group mentioned as a control group. Gross lesions, mortality, and growth parameters include body weight gain,feed intake and FCR were calculated in all groups weekly after 21 st day.Results showed that in treatment groups mortality percent was significantly (p<0.05) lower than control group and pericarditis, perihepatitis and airsacculitis was sever in control groups in comparison to antibiotic treated groups. Also body weight and FCR was significantly were different between control group and oxytetracycline + Tiamulin group (p<0.05).It can be concluded that usage of these antibiotics simultaneously could prevent vaccination reaction due to La Sota vaccine and also following MG complications, economical losses in poultry and finally it can be improve broilers performance Key words: Vaccination Reaction, Mycoplasma Gallisepticum, Oxytetracycline, Tiamulin, Ross 308. -
Partners in Practice
ADRENALS: Spring 2012 What you won’t find in a textbook Partners in Practice Dr Sue Foster BVSc, MVetClinStud, FACVSc Vetnostics Small Animal Medical Consultant ➤ Cutaneous Mycobacterial Disease in Dogs and Cats: Part 2 PART 4b: UCCr and CALP ➤ The Most Difficult and Frustrating Diagnoses As part 4 of this series looks at diagnostic tests, we can’t Corticosteroid-induced alkaline phosphatase escape some statistics. So, some very simplistic explanations (c-ALP) relative to hyperA are as follows: ➤ Adrenals: Part 4b Increased serum ALP, the most common routine laboratory Sensitivity: the likelihood that the test will detect hyperA abnormality in hyperA is due mainly to the induction Specificity: the chance that a positive test is truly hyperA of a specific ALP isoenzyme by glucocorticoids. The corticosteroid-induced isoenzyme of ALP can be measured Then, there are predictive values which take into account by electrophoretic separation, heat inactivation or more the prevalence or likelihood of a disease in addition to usually in commercial laboratories, by levamisole-inhibition. sensitivity and specificity. The levamisole inhibition explains why c-ALP is sometimes referred to as l-ALP but this terminology can be confusing Positive predictive value (PPV): the chance of a positive as sometimes l-ALP is used to describe the liver isoenzyme; result being indicative of hyperA in dogs with signs of it is also referred to as CAP (corticosteroid-induced ALP) or hyperA (e.g. Can we confidently diagnose hyperA when we SIAP (steroid-induced alkaline phosphatase). get a “positive” result?) The sensitivity of c-ALP has been reported to be 0.81-0.95.7-9 Negative predictive value (NPV): the likelihood that a Specificity is poor (0.18-0.44)7-9 and PPV in one study was negative results eliminates the possibility of hyperA in dogs as low as 21.4%7 thus this test cannot be recommended as with signs of hyperA (e.g. -
Data on Before and After the Traceability System of Veterinary Antimicrobial Prescriptions in Small Animals at the University Veterinary Teaching Hospital of Naples
animals Article Data on before and after the Traceability System of Veterinary Antimicrobial Prescriptions in Small Animals at the University Veterinary Teaching Hospital of Naples Claudia Chirollo , Francesca Paola Nocera , Diego Piantedosi, Gerardo Fatone , Giovanni Della Valle, Luisa De Martino * and Laura Cortese Department of Veterinary Medicine and Animal Productions, University of Naples, “Federico II”, Via Delpino 1, 80137 Naples, Italy; [email protected] (C.C.); [email protected] (F.P.N.); [email protected] (D.P.); [email protected] (G.F.); [email protected] (G.D.V.); [email protected] (L.C.) * Correspondence: [email protected]; Tel.: +39-081-253-6180 Simple Summary: Veterinary electronic prescription (VEP) is mandatory by law, dated 20 November 2017, No. 167 (European Law 2017) Article 3, and has been implemented in Italy since April 2019. In this study, the consumption of antimicrobials before and after the mandatory use of VEP was analyzed at the Italian University Veterinary Teaching Hospital of Naples in order to understand how the traceability of antimicrobials influences veterinary prescriptions. The applicability and utility of VEP may present an effective surveillance strategy able to limit both the improper use of Citation: Chirollo, C.; Nocera, F.P.; antimicrobials and the spread of multidrug-resistant pathogens, which have become a worrying Piantedosi, D.; Fatone, G.; Della Valle, threat both in veterinary and human medicine. G.; De Martino, L.; Cortese, L. Data on before and after the Traceability Abstract: Over recent decades, antimicrobial resistance has been considered one of the most relevant System of Veterinary Antimicrobial issues of public health. -
NARMS – EB 2000 Veterinary Isolates Fig. 18. Resistance Among Salmonella Serotypes for Isolates from Cattle*
NARMS – EB 2000 Veterinary Isolates Fig. 18. Resistance Among Salmonella Serotypes for Isolates from Cattle* S. typhimurium (n=332)** S. montevideo (n=330) Amikacin 0.00% Amikacin 0.00% Amox-Clav 14.46% Amox-Clav 0.61% Ampicillin 66.87% Ampicillin 0.61% Apramycin 1.20% Apramycin 0.00% Cefoxitin 10.54% Cefoxitin 0.61% Ceftiofur 12.65% Ceftiofur 0.61% Ceftriaxone 0.00% Ceftriaxone 0.00% Cephalothin 13.25% Cephalothin 0.61% Chloramphenicol 39.46% Chloramphenicol 0.91% Ciprofloxacin 0.00% Ciprofloxacin 0.00% Gentamicin 3.31% Gentamicin 0.30% Kanamycin 38.86% Kanamycin 0.00% Nalidixic Acid 0.00% Nalidixic Acid 0.00% Streptomycin 66.57% Streptomycin 1.52% Sulfamethoxazole 66.87% Sulfamethoxazole 1.21% Tetracycline 66.57% Tetracycline 2.12% Trimeth-Sulfa 5.42% Trimeth-Sulfa 0.30% 0% 10% 20% 30% 40% 50% 60% 70% 80% 0% 1% 1% 2% 2% 3% **including copenhagen S. anatum (n=292) S. newport (n=185) Amikacin 0.00% Amikacin 0.00% Amox-Clav 1.71% Amox-Clav 80.00% Ampicillin 2.40% Ampicillin 80.54% Apramycin 0.00% Apramycin 0.00% Cefoxitin 1.37% Cefoxitin 77.84% Ceftiofur 1.37% Ceftiofur 80.00% Ceftriaxone 0.00% Ceftriaxone 2.16% Cephalothin 2.05% Cephalothin 77.84% Chloramphenicol 1.71% Chloramphenicol 81.62% Ciprofloxacin 0.00% Ciprofloxacin 0.00% Gentamicin 0.68% Gentamicin 7.57% Kanamycin 1.71% Kanamycin 7.57% Nalidixic Acid 0.34% Nalidixic Acid 0.00% Streptomycin 2.05% Streptomycin 82.70% Sulfamethoxazole 2.05% Sulfamethoxazole 74.05% Tetracycline 35.96% Tetracycline 83.24% Trimeth-Sulfa 0.34% Trimeth-Sulfa 25.41% 0% 5% 10% 15% 20% 25% 30% 35% 40% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% *all sources NARMS – EB 2000 Veterinary Isolates Fig. -
Simultaneous Determination of Amoxicillin and Clavulanic Acid in Pharmaceutical Preparations by Capillary Zone Electrophoresis
Brazilian Journal of Pharmaceutical Sciences vol. 52, n. 2, apr./jun., 2016 Article http://dx.doi.org/10.1590/S1984-82502016000200006 Simultaneous determination of amoxicillin and clavulanic acid in pharmaceutical preparations by capillary zone electrophoresis Gabriel Hancu1,*, Anamaria Neacşu1, Lajos Attila Papp1, Adriana Ciurba2 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, TîrguMureş, Romania, 2Department of PharmaceuticalTechnology, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most β-lactamase producing isolates susceptible to the drug. A fast, simple and efficient capillary electrophoresis method was developed for the simultaneous determination of amoxicillin and clavulanic acid from complex mixtures. Using a 25 mM sodium tetraborate as background electrolyte at a pH of 9.30, + 25 kV applied voltage, 25 °C system temperature, UV determination at 230 nm; we succeeded in simultaneous separation of amoxicillin and clavulanic acid in approximately 2 minutes. The analytical performance of the method was evaluated in terms of reproducibility, precision, accuracy, and linearity. The optimized analytical method was applied for the determination of the two analytes from combined commercial pharmaceutical preparations. This CE method is fast, inexpensive, efficient, and environmentally friendly when compared with the more frequently used high performance liquid chromatography methods described in the literature. Uniterms: Amoxicillin/determination. Clavulanic acid/determination. Capillary electrophoresis/ quantitative analysis. Antibacterials/quantitative analysis. O ácido clavulânico acentua o espectro antibacteriano de amoxicilina, tornando a maioria dos isolados produtores de β-lactamase sensíveis ao fármaco. Desenvolveu-se um método rápido, simples e eficiente de electroforese capilar (EC) para a determinação simultânea de amoxicilina e de ácido clavulânico a partir de misturas complexas. -
Antibiotics Acting on the Translational Machinery
Cell Science at a Glance 1391 Antibiotics acting on ribosomal factors, and recent structural Initiation studies of the ribosome (Ban et al., 2000; Prokaryotic protein synthesis starts with the translational Harms et al., 2001; Nissen et al., 2000; the formation of an initiation complex machinery Schlünzen et al., 2000; Wimberly et al., comprising the mRNA, initiator tRNA fMet 1, 1 2000; Yusupov et al., 2001) and (fMet-tRNA ), three initiation factors Jörg M. Harms *, Heike Bartels , complexes of ribosomes with inhibitors (IFs) and the 30S subunit. IF3 binding Frank Schlünzen1 and Ada (Brodersen et al., 2000; Pioletti et al., prevents association of the two Yonath1,2 2001; Schlünzen et al., 2001; Hansen et ribosomal subunits, verifies codon- 1Max-Planck Arbeitsgruppe Ribosomenstruktur, al., 2002; Bashan et al., 2003; Schlünzen anticodon complementarity and appears Notkestr. 85, 22607 Hamburg, Germany 2Department of Structural Biology, Weizmann et al., 2003) are now revealing the to regulate positioning of the mRNA. Institute, 76100 Rehovot, Israel mechanisms underlying their inhibitory IF1 blocks the acceptor site (A-site) to *Author for correspondence (e-mail: activity. prevent premature binding of the A-site [email protected]) tRNA. After binding of fMet-tRNAfMet, IF3 is released; this triggers hydrolysis Journal of Cell Science 116, 1391-1393 Responsibility for the various steps of © 2003 The Company of Biologists Ltd polypeptide synthesis is divided among of IF2-bound GTP, and IF2 and IF1 are doi:10.1242/jcs.00365 released (the exact sequence of events is the two ribosomal subunits (30S and not known). The 50S subunit then joins 50S). The 30S subunit ensures fidelity of Despite the appearance of bacterial the 30S initiation complex, forming the strains resistant to all clinical antibiotics, decoding by establishing accurate 70S ribosome. -
Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks
processes Review Tetracycline and Sulfonamide Antibiotics in Soils: Presence, Fate and Environmental Risks Manuel Conde-Cid 1, Avelino Núñez-Delgado 2 , María José Fernández-Sanjurjo 2 , Esperanza Álvarez-Rodríguez 2, David Fernández-Calviño 1,* and Manuel Arias-Estévez 1 1 Soil Science and Agricultural Chemistry, Faculty Sciences, University Vigo, 32004 Ourense, Spain; [email protected] (M.C.-C.); [email protected] (M.A.-E.) 2 Department Soil Science and Agricultural Chemistry, Engineering Polytechnic School, University Santiago de Compostela, 27002 Lugo, Spain; [email protected] (A.N.-D.); [email protected] (M.J.F.-S.); [email protected] (E.Á.-R.) * Correspondence: [email protected] Received: 30 October 2020; Accepted: 13 November 2020; Published: 17 November 2020 Abstract: Veterinary antibiotics are widely used worldwide to treat and prevent infectious diseases, as well as (in countries where allowed) to promote growth and improve feeding efficiency of food-producing animals in livestock activities. Among the different antibiotic classes, tetracyclines and sulfonamides are two of the most used for veterinary proposals. Due to the fact that these compounds are poorly absorbed in the gut of animals, a significant proportion (up to ~90%) of them are excreted unchanged, thus reaching the environment mainly through the application of manures and slurries as fertilizers in agricultural fields. Once in the soil, antibiotics are subjected to a series of physicochemical and biological processes, which depend both on the antibiotic nature and soil characteristics. Adsorption/desorption to soil particles and degradation are the main processes that will affect the persistence, bioavailability, and environmental fate of these pollutants, thus determining their potential impacts and risks on human and ecological health. -
Pharmacology
FORM UPDATED | 04/07/20 Pharmacology 865-974-5646 Diagnostic Laboratory Service For lab Date Received: # of Samples Received: vetmed.tennessee.edu/vmc/dls use only Institution/Practice: ASSAYS CURRENTLY AVAILABLE Veterinarian: Aciclovir Gabapentin Address: Amoxicillin Galliprant Bromide Ganciclovir Bupivacaine Hydromorphone Butorphanol Itraconazole & Hydroxyitraconazole Carboplatin Ivermectin Phone: Caffeine Ketamine & Norketamine Fax: Carprofen Ketoprofen Carvedilol Lidocaine & metabolites Type of Sample: Ceftiofur Meloxicam No. of Samples: Ceftiofur Equivalents Midazolam & Hydroxmidazolam Cefovecin Metronidazole Date &Time Dosed: Chloramphenicol Moxidectin Citrate (urine only) Omeprazole Date & Time Collected: Deracoxib Oxalate (urine only) Dosage Amount: Diazepam and Nordiazepam Oxytetracycline Famciclovir/Penciclovir Piroxicam Dosage Formulation: Fenbendazole Praziquantil Route: Fentanyl Prednisolone Firocoxib Propofol Sample Identification Info: Flunixin Robenacoxib Species: Canine Feline Equine Fluconazole Terbinafine Other:__________________________________________________________ Fluoroquinolones: Thiafentanil Medication History (All medications the animal is currently on or has recently received): Ciprofloxacin Tramadol and metabolites Enrofloxacin M1, M2, M4, & M5 Fleroxacin Uric Acid Marbofloxacin Valciclovir Moxifloxacin Voriconazole Furosemide Requested Assay: If you are interested in drugs not listed, contact the laboratory with questions about assay development and cost. Ship Samples to: UTCVM Pharmacology Laboratory 2407 -
A Diverse Intrinsic Antibiotic Resistome from a Cave Bacterium
ARTICLE Received 5 Jul 2016 | Accepted 1 Nov 2016 | Published 8 Dec 2016 DOI: 10.1038/ncomms13803 OPEN A diverse intrinsic antibiotic resistome from a cave bacterium Andrew C. Pawlowski1, Wenliang Wang1, Kalinka Koteva1, Hazel A. Barton2, Andrew G. McArthur1 & Gerard D. Wright1 Antibiotic resistance is ancient and widespread in environmental bacteria. These are there- fore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus. 1 Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1. 2 Department of Biology, University of Akron, Akron, Ohio 44325, USA. Correspondence and requests for materials should be addressed to G.D.W. (email: [email protected]). NATURE COMMUNICATIONS | 7:13803 | DOI: 10.1038/ncomms13803 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/ncomms13803 nderstanding the evolution and origins of antibiotic rhizophila (formerly identified as Micrococcus luteus) resistance genes is vital to predicting, preventing and (Supplementary Tables 1 and 2). -
A Sensitive Method for Direct Analysis of Impurities in Apramycin and Other Aminoglycoside Antibiotics Using Charged Aerosol
- SO4 A Sensitive Method for Direct Analysis of Impurities in Apramycin and Other Aminoglycoside Antibiotics Using Charged Aerosol Detection Zhen Long1, Qi Zhang2, Yan Jin1, Lina Liang1, Bruce Bailey2, Ian Acworth2, Deepali Mohindra3 1 2 3 Thermo Fisher Scientific, Shanghai, China, Thermo Fisher Scientific, Chelmsford, MA, USA and Thermo Fisher Scientific, Sunnyvale, CA, USA Comparison of CAD and ELSD Detection Analysis of Other Aminoglycoside Antibiotics Overview Results Purpose: To develop a sensitive non-derivatization method for impurity assessment of Sample pre-treatment with SPE This method has also been applied to impurity analysis of an additional eleven apramycin sulfate and other aminoglycoside antibiotics. Sample pre-treatment with SPE SPE Column: Dionex OnGuard II A CAD and ELSD are both nebulization-based universal detection technologies. aminoglycoside antibiotics, including neomycin, gentamicin, kanamycin, streptomycin, Comparison between CAD and ELSD under the same chromatographic conditions tobramycin, amikacin, etimicin, netilmicin, sisomicin, ribostamycin and paromomycin. Methods: A 30min gradient method using hydrophilic interaction liquid chromatography Sample solvent: 80% 5mM ammonium formate, 20% acetonitrile Sulfate is a major interference for apramycin impurity assessment with a HILIC method. demonstrated that CAD is much more sensitive than ELSD. As shown in the Figure 5 shows impurity analysis of kenamycin, etimicin, ribostamycin and paromomycin with charged aerosol detection (HILIC-CAD) was developed for direct analysis of Sample: 220.6 mg/mL in 2 mL sample solvent Without sample cleanup, some early eluting impurities were found to be masked under chromatograms in Figure 4 and data summarized in Table 1, 16 impurities (S/N >3) were using the HILIC-CAD method. -
Antibiotic Use Guidelines for Companion Animal Practice (2Nd Edition) Iii
ii Antibiotic Use Guidelines for Companion Animal Practice (2nd edition) iii Antibiotic Use Guidelines for Companion Animal Practice, 2nd edition Publisher: Companion Animal Group, Danish Veterinary Association, Peter Bangs Vej 30, 2000 Frederiksberg Authors of the guidelines: Lisbeth Rem Jessen (University of Copenhagen) Peter Damborg (University of Copenhagen) Anette Spohr (Evidensia Faxe Animal Hospital) Sandra Goericke-Pesch (University of Veterinary Medicine, Hannover) Rebecca Langhorn (University of Copenhagen) Geoffrey Houser (University of Copenhagen) Jakob Willesen (University of Copenhagen) Mette Schjærff (University of Copenhagen) Thomas Eriksen (University of Copenhagen) Tina Møller Sørensen (University of Copenhagen) Vibeke Frøkjær Jensen (DTU-VET) Flemming Obling (Greve) Luca Guardabassi (University of Copenhagen) Reproduction of extracts from these guidelines is only permitted in accordance with the agreement between the Ministry of Education and Copy-Dan. Danish copyright law restricts all other use without written permission of the publisher. Exception is granted for short excerpts for review purposes. iv Foreword The first edition of the Antibiotic Use Guidelines for Companion Animal Practice was published in autumn of 2012. The aim of the guidelines was to prevent increased antibiotic resistance. A questionnaire circulated to Danish veterinarians in 2015 (Jessen et al., DVT 10, 2016) indicated that the guidelines were well received, and particularly that active users had followed the recommendations. Despite a positive reception and the results of this survey, the actual quantity of antibiotics used is probably a better indicator of the effect of the first guidelines. Chapter two of these updated guidelines therefore details the pattern of developments in antibiotic use, as reported in DANMAP 2016 (www.danmap.org).