Relative Mortality from Overdose Ofantidepressants
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Virulence and Transcriptome Profile of Multidrug-Resistant Escherichia Coli from Chicken Received: 3 April 2017 Hafiz I.Hussain 1, Zahid Iqbal1,4, Mohamed N
www.nature.com/scientificreports OPEN Virulence and transcriptome profile of multidrug-resistant Escherichia coli from chicken Received: 3 April 2017 Hafiz I.Hussain 1, Zahid Iqbal1,4, Mohamed N. Seleem3, Deyu Huang2, Adeel Sattar2, Haihong Accepted: 3 July 2017 Hao1 & Zonghui Yuan1,2 Published: xx xx xxxx Numerous studies have examined the prevalence of pathogenic Escherichia coli in poultry and poultry products; however, limited data are available regarding their resistance- and virulence-associated gene expression profiles. This study was designed to examine the resistance and virulence of poultryE. coli strains in vitro and in vivo via antibiotic susceptibility, biofilm formation and adhesion, and invasion and intracellular survivability assays in Caco-2 and Raw 264.7 cell lines as well as the determination of the median lethal dose in two-day old chickens. A clinical pathogenic multidrug-resistant isolate, E. coli 381, isolated from broilers, was found to be highly virulent in cell culture and 1000-fold more virulent in a chicken model than other strains; accordingly, the isolate was subsequently selected for transcriptome analysis. The comparative gene expression profile of MDRE. coli 381 and the reference human strain E. coli ATCC 25922 was completed with Illumina HiSeq. 2500 transcriptome analysis. Differential gene expression analysis indicates that there are multiple pathways involved in the resistance and virulence of this highly virulent strain. The results garnered from this study provide critical information about the highly virulent MDR E. coli strain of poultry origin and warrant further investigation due to its significant threat to public health. Escherichia coli is a Gram-negative bacterium that displays a wide range of genomic diversity. -
Oecd Guideline for the Testing of Chemicals
Draft November 2009 OECD GUIDELINE FOR THE TESTING OF CHEMICALS PROPOSAL FOR A NEW TEST GUIDELINE 223 Avian Acute Oral Toxicity Test INTRODUCTION 1. This test guideline describes procedures designed to estimate the acute oral toxicity of substances to birds, and it provides three testing options: (1) limit dose test, (2) LD50-slope test, and (3) LD50-only test. The LD50-slope and LD50-only options are sequential testing procedures. The test method selected will depend on whether or not a definitive median dose (LD50) and slope of the dose-response curve are both needed. Sequential testing procedures target the placement of doses and match the precision of the endpoint with the precision required. These sequential procedures were designed to minimise the numbers of birds used. A computer programme is available to aid the placement of doses and estimate the LD50, slope and confidence limits. 2. Development of this test guideline began at the SETAC/OECD Workgroup on avian toxicity testing following a workshop held in Pensacola, Florida, United States, in 1994 (1) with subsequent open SETAC and closed OECD Expert Group meetings in Europe and the United States to develop and optimise the sequential testing design. The sequential testing design has been developed with extensive statistical validation (2). INITIAL CONSIDERATIONS 3. The information required by different hazard assessment schemes may vary considerably. To satisfy these various needs, the following three tests are described: Limit dose test – This is the preferred test when toxicity is expected to be low and lethality is unlikely at the limit dose. The limit dose must be adequate for assessment purposes, and it is usually 2000 mg/kg-bwt. -
Toxicological Profile for Radon
RADON 205 10. GLOSSARY Some terms in this glossary are generic and may not be used in this profile. Absorbed Dose, Chemical—The amount of a substance that is either absorbed into the body or placed in contact with the skin. For oral or inhalation routes, this is normally the product of the intake quantity and the uptake fraction divided by the body weight and, if appropriate, the time, expressed as mg/kg for a single intake or mg/kg/day for multiple intakes. For dermal exposure, this is the amount of material applied to the skin, and is normally divided by the body mass and expressed as mg/kg. Absorbed Dose, Radiation—The mean energy imparted to the irradiated medium, per unit mass, by ionizing radiation. Units: rad (rad), gray (Gy). Absorbed Fraction—A term used in internal dosimetry. It is that fraction of the photon energy (emitted within a specified volume of material) which is absorbed by the volume. The absorbed fraction depends on the source distribution, the photon energy, and the size, shape and composition of the volume. Absorption—The process by which a chemical penetrates the exchange boundaries of an organism after contact, or the process by which radiation imparts some or all of its energy to any material through which it passes. Self-Absorption—Absorption of radiation (emitted by radioactive atoms) by the material in which the atoms are located; in particular, the absorption of radiation within a sample being assayed. Absorption Coefficient—Fractional absorption of the energy of an unscattered beam of x- or gamma- radiation per unit thickness (linear absorption coefficient), per unit mass (mass absorption coefficient), or per atom (atomic absorption coefficient) of absorber, due to transfer of energy to the absorber. -
Fatal Toxicity of Antidepressant Drugs in Overdose
BRITISH MEDICAL JOURNAL VOLUME 295 24 OCTOBER 1987 1021 Br Med J (Clin Res Ed): first published as 10.1136/bmj.295.6605.1021 on 24 October 1987. Downloaded from PAPERS AND SHORT REPORTS Fatal toxicity of antidepressant drugs in overdose SIMON CASSIDY, JOHN HENRY Abstract dangerous in overdose, thus meriting investigation of their toxic properties and closer consideration of the circumstances in which A fatal toxicity index (deaths per million National Health Service they are prescribed. Recommendations may thus be made that prescriptions) was calculated for antidepressant drugs on sale might reduce the number offatalities. during the years 1975-84 in England, Wales, and Scotland. The We used national mortality statistics and prescription data tricyclic drugs introduced before 1970 had a higher index than the to compile fatal toxicity indices for the currently available anti- mean for all the drugs studied (p<0-001). In this group the depressant drugs to assess the comparative safety of the different toxicity ofamitriptyline, dibenzepin, desipramine, and dothiepin antidepressant drugs from an epidemiological standpoint. Owing to was significantly higher, while that ofclomipramine, imipramine, the nature of the disease these drugs are particularly likely to be iprindole, protriptyline, and trimipramine was lower. The mono- taken in overdose and often cause death. amine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p<0-001). Ofthese newer drugs, maprotiline had a fatal toxicity index similar to that Sources ofinformation and methods of the older tricyclic antidepressants, while the other newly The statistical sources used list drugs under their generic and proprietary http://www.bmj.com/ introduced drugs had lower toxicity indices, with those for names. -
Method of Rough Estimation of Median Lethal Dose (Ld50)
b Meta olis g m & ru D T o f x o i Journal of Drug Metabolism and l c a o n l o r Saganuwan, J Drug Metab Toxicol 2015, 6:3 g u y o J Toxicology DOI: 10.4172/2157-7609.1000180 ISSN: 2157-7609 Research Article Open Access Arithmetic-Geometric-Harmonic (AGH) Method of Rough Estimation of Median Lethal Dose (Ld50) Using Up – and – Down Procedure *Saganuwan Alhaji Saganuwan Department of Veterinary Physiology, Pharmacology and Biochemistry, College Of Veterinary Medicine, University Of Agriculture, P.M.B. 2373, Makurdi, Benue State, Nigeria *Corresponding author: Saganuwan Alhaji Saganuwan, Department of Veterinary Physiology, Pharmacology and Biochemistry, College Of Veterinary Medicine, University Of Agriculture, P.M.B. 2373, Makurdi, Benue State, Nigeria, Tel: +2348027444269; E-mail: [email protected] Received date: April 6,2015; Accepted date: April 29,2015; Published date: May 6,2015 Copyright: © 2015 Saganuwan SA . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Earlier methods adopted for the estimation of median lethal dose (LD50) used many animals (40 – 100). But for the up – and – down procedure, 5 – 15 animals can be used, the number I still consider high. So this paper seeks to adopt arithmetic, geometric and harmonic (AGH) mean for rough estimation of median lethal dose (LD50) using up – and – down procedure by using 2 – 6 animals that may likely give 1 – 3 reversals. The administrated doses should be summed up and the mean, standard deviation (STD) and standard error of mean (SEM) should be determined. -
(LC50) of Pathogenic Microorganisms and Their Antigens in Vaccine Development Saganuwan Alhaji Saganuwan*
Saganuwan BMC Res Notes (2020) 13:289 https://doi.org/10.1186/s13104-020-05126-x BMC Research Notes RESEARCH NOTE Open Access Application of median lethal concentration (LC50) of pathogenic microorganisms and their antigens in vaccine development Saganuwan Alhaji Saganuwan* Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modifed arithmetical formula of Reed and Muench has been integrated with other formulas and used to deter- mine bacterial colony forming unit/viral concentration, virulence and immunogenicity. Results: Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aerugi- nosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fsh, New Castle Disease virus in chicken, Sheep Pox virus, Foot-and-Mouth Disease virus and Hepatitis A virus in vitro, respectively. The LC 50s for the pathogens using diferent routes of administrations are 1.93 103(sheep poxvirus) and 1.75 1010 for Staphylococcus × × aureus (ATCC29213) in rat, respectively. Titer index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. 3 11 Hence, parasite inoculum of 10 to 10 may be used as basis for determination of LC50 and median bacterial concen- trations (BC50).Pathogenic -
Interpretation of Postmortem Toxicology Results
INTERPRETATION OF POSTMORTEM TOXICOLOGY RESULTS Pharmacogenetics and Drug-Alcohol Interaction Anna Koski Department of Forensic Medicine University of Helsinki Finland ACADEMIC DISSERTATION To be publicly discussed, with the permission of the Medical Faculty of the University of Helsinki, in the auditorium of the Department of Forensic Medicine on September 23rd 2005, at 12 noon. Helsinki 2005 SUPERVISORS Professor Antti Sajantila Department of Forensic Medicine University of Helsinki Helsinki, Finland Docent Ilkka Ojanperä Department of Forensic Medicine University of Helsinki Helsinki, Finland REVIEWERS Docent Eero Mervaala Institute of Biomedicine University of Helsinki Helsinki, Finland Docent Kari Poikolainen Finnish Foundation for Alcohol Studies National Research and Development Centre for Welfare and Health Helsinki, Finland OPPONENT Professor Jørg Mørland Division of Forensic Toxicology and Drug Abuse Norwegian Institute of Public Health Oslo, Norway ISBN 952-91-9214-2 (paperback) ISBN 952-10-2662-6 (pdf) http://ethesis.helsinki.fi Helsinki University Printing House Helsinki 2005 Obtaining a quantitative result is not the endpoint of the analytical process. Irving Sunshine CONTENTS ABBREVIATIONS......................................................................................................................... 6 LIST OF ORIGINAL PUBLICATIONS .............................................................................................. 7 ABSTRACT................................................................................................................................. -
High Degree of Acute Toxicity
Appendix I High Degree of Acute Toxicity Criteria Toxic Highly Toxic Oral LD 50 50-500 mg/kg <50 mg/kg (albino rats) Skin Contact LD 50 200-1000 mg/kg <200 mg/kg (albino rabbits, 24 hour) Inhalation LD 50 200-2000 ppm/air <200 ppm/air (albino rats, one hour) High degree of acute toxicity are chemicals that are considered highly toxic or toxic chemicals which may be fatal or cause damage to target organs as a result of a single exposure or exposures of short duration. Toxic: (a) A chemical that has a median lethal dose (LD50) of more than 50 milligrams per kilogram but not more than 500 milligrams per kilogram of body weight when administered orally to albino rats weighing between 200 and 300 grams each. (b) A chemical that has a median lethal dose (LD50) of more than 200 milligrams per kilogram but not more than 1,000 milligrams per kilogram of body weight when administered by continuous contact for 24 hours (or less if death occurs within 24 hours) with the bare skin of albino rabbits weighing between two and three kilograms each. (c) A chemical that has a median lethal concentration (LC50) in air of more than 200 parts per million but not more than 2,000 parts per million by volume of gas or vapor, or more than two milligrams per liter but not more than 20 milligrams per liter of mist, fume, or dust, when administered by continuous inhalation for one hour (or less if death occurs within one hour) to albino rats weighing between 200 and 300 grams each. -
Copper Influences the Antibacterial Outcomes of a Β-Lactamase-Activated Prochelator Against Drug-Resistant Bacteria
Article Cite This: ACS Infect. Dis. XXXX, XXX, XXX−XXX pubs.acs.org/journal/aidcbc Copper Influences the Antibacterial Outcomes of a β‑Lactamase- Activated Prochelator against Drug-Resistant Bacteria † † † ‡ Jacqueline M. Zaengle-Barone, Abigail C. Jackson, David M. Besse, Bradford Becken, ‡ § ∥ † Mehreen Arshad, Patrick C. Seed, , and Katherine J. Franz*, † Department of Chemistry, Duke University, 124 Science Drive, Durham, North Carolina 27708, United States ‡ Department of Pediatrics, Duke University, Durham, North Carolina 27710, United States § Ann and Robert H. Lurie Children’s Hospital and Stanley Manne Children’s Research Institute, 225 E. Chicago Avenue, Chicago, Illinois 60611, United States ∥ Department of Microbiology and Immunology, Northwestern University, 300 E. Superior Street, Chicago, Illinois 60611, United States *S Supporting Information ABSTRACT: The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum anti- biotics, necessitates the development of new antimicrobials targeted against pathogenic organisms. Here, we explore the antibacterial outcomes and mode of action of a prochelator that exploits the production of β-lactamase enzymes by drug- resistant bacteria to convert a nontoxic compound into a metal-binding antimicrobial agent directly within the microenvironment of pathogenic organisms. Compound PcephPT (phenylacetamido-cephem-pyrithione) contains a cephalosporin core linked to 2-mercaptopyridine N-oxide (pyrithione) via one of its metal-chelating atoms, which minimizes its preactivation interaction with metal ions and its cytotoxicity. Spectroscopic and chromatographic assays indicate that PcephPT releases pyrithione in the presence of β-lactamase-producing bacteria. The prochelator shows enhanced antibacterial activity against strains expressing β-lactamases, with bactericidal efficacy improved by the presence of low-micromolar copper in the growth medium. -
Cyclic Antidepressant Drugs SI Conversion: [AUQ: Dr
834 II: THERAPEUTIC DRUGS 127. Spiker DG, Pugh DD. Combining tricyclic and monoamine oxidase inhibi- 145. Chambost M, Liron L, Peillon D, et al. [Serotonin syndrome during fluoxetine tor antidepressants. Arch Gen Psychiatry 1976;33(7):828–830. poisoning in a patient taking moclobemide.] Can J Anaesth 2000;47(3):246– 128. Peebles-Brown AE. Hyperpyrexia following psychotropic drug overdose. 250. Anaesthesia 1985;40(11):1097–1099. 146. Myrenfors PG, Eriksson T, Sandsted CS, et al. Moclobemide overdose. J 129. Tuck JR, Punell G. Uptake of (3H)5-hydroxytryptamine and (3H)noradrenaline Intern Med 1993;233(2):113–115. by slices of rat brain incubated in plasma from patients treated with chlorimi- 147. Pounder DJ, Jones GR. Post-mortem drug redistribution––a toxicological pramine, imipramine or amitriptyline. J Pharm Pharmacol 1973;25(7):573–574. nightmare. Forensic Sci Int 1990;45(3):253–263. 130. Gillman PK. Successful treatment of serotonin syndrome with chlorproma- 148. Lichtenwalner MR, Tully RG, Cohn RD, et al. Two fatalities involving zine. Med J Aust 1996;165(6):345–346. phenelzine. J Anal Toxicol 1995;19(4):265–266. 131. Graham PM. Successful treatment of the toxic serotonin syndrome with 149. Yonemitsu K, Pounder DJ. Postmortem changes in blood tranylcypromine chlorpromazine. Med J Aust 1997;166(3):166–167. concentration: competing redistribution and degradation effects. Forensic 132. Tackley RM, Tregaskis B. Fatal disseminated intravascular coagulation fol- Sci Int 1993;59(2):177–184. lowing a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia 150. Baselt RC, Shaskan E, Gross EM. Tranylcypromine concentrations and 1987;42(7):760–763. -
Butriptyline Hydrochloride and Imipramine Hydrochloride in the Treatment of Non -Psychotic Depression
27 April 1974 S.-A. MEDIESE TYDSKRIF 873 Butriptyline Hydrochloride and Imipramine Hydrochloride in the Treatment of Non -Psychotic Depression A DOUBLE-BLIND TRIAL B. LEVINSON SUMMARY and reactive depression, anxiolysis and enuresis control in paediatrics, endogenous depression and involutional A comparison between butriptyline hydrochloride and melancholia, and the post-suicide syndrome.' The dosage one of the most widely-used tricyclic antidepressants, utilised by the investigators on their adult patients varied imipramine hydrochloride, was undertaken in 28 patients from 25 to 50 mg of butriptyline hydrochloride 3 - 4 suffering from non-psychotic depression in a double times per day. blind trial. Three criteria-side-effects, depression and The accurate assessment of psychiatric trials is fraught anxiety-were observed at each visit. The scoring system with difficulty. The terminology used is frequently mis representing degree of change from one visit to the other leading and often only applicable to separate and specific ranged from - 2 to +10, higher values indicating better schools of psychological thought. The patients themselves reactions to the drug. For each patient, the changes in supply the investigator with a subjective impression which individual criteria were accumulated up to the patient's has to be objectively documented into a statistically last visit. The number of patient observations per pair meaningful format. If the psychiatric investigator writes at weekly or fortnightly intervals varied between 2 and down impressions such as good, worse, mild deterioration, 5. Butriptyline hydrochloride was superior to imipramine etc., these subjective descriptive impressions pertain to hydrochloride in accumulated change on all three criteria, his assessment of the patient on that specific day only, the difference being statistically significant at the 99% hence uniformity is lost. -
Median Lethal Dose (LD50) Estimation of Β-Cyfluthrin in Male and Female Swiss Albino Mice
International Journal of Scientific and Research Publications, Volume 5, Issue 8, August 2015 1 ISSN 2250-3153 Median lethal dose (LD50) estimation of β-cyfluthrin in male and female Swiss albino mice # # Neelu Kanwar Rajawat , Rajbala Verma , Inderpal Soni Environmental Toxicology Lab, Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur 302004 India # Equal contribution Abstract- Present study was undertaken to determine the median documented in rats but satisfactory data related to LD50 in mice lethal dose (LD50) of β-cyfluthrin (β-cyf), a synthetic (type II) is not available. Moreover there is a difference in LD50 of β-cyf pyrethroid pesticide in male and female Swiss albino mice. The in male and female animals and also with different vehicles. Thus calculation of LD 50 is an initial screening step in the assessment an attempt was made to determine the acute oral LD50 of β-cyf in and evaluation of the toxic characteristic of a chemical substance. male and female Swiss albino mice using corn oil as vehicle. The selected single doses of β-cyfluthrin based on the pilot study were 200, 225, 250, 275 and 300 mg/kg b.wt. for male and 350, 375, 400, 425 and 450 mg/kg b.wt. for female animals. Pesticide II. MATERIALS AND METHODS was dissolved in corn oil and administered orally to different groups of male and female mice, consisting of 10 animals in each group. Signs of toxicity and possible death of animals were Test chemicals β-cyf (CAS No. 68359-37-5) was purchased from Sigma- monitored upto 96 h to calculate the median lethal dose (LD50) of β-cyf.