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Clinical Toxicology

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https://www.readbyqxmd.com/read/29219051/development-and-uses-of-offline-and-web-searchable-metabolism-databases-the-case-of-benzo-a-pyrene
#1
Slobodan P Rendic, F Peter Guengerich
The paper presents development and use of offline and Web-searchable human and other species metabolism databases. A search of the databases presented will produce basic information on metabolic reactions or transporter systems published on specific drug or other chemical, kinetic values, as well as structure of the metabolites. In addition, searching enables comparison of the data between different species models. The data cover time the period until 2008, and the current Web-searchable database [19] is updated quarterly each year and over the period until October 2017...
December 7, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29217158/evidence-based-traditional-anti-diarrheal-medicinal-plants-and-their-phytocompounds
#2
REVIEW
Pooja Rawat, Pawan Kumar Singh, Vipin Kumar
Traditional medicines are an integral component of alternative health care systems used by millions of the people worldwide. Traditionally used herbals are multi-constituent medications, safety and efficacy of which is based on experiences of the practitioners, whereas modern drugs are single molecules, rigorously tested, structurally optimized and toxicologically cleared. Plants are being recognized as potential source of drug discovery and more than 80% of modern drugs are derived directly from natural sources (plants, microbes, cells etc...
December 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29216524/multiple-fatalities-in-the-north-of-england-associated-with-synthetic-fentanyl-analogue-exposure-detection-and-quantitation-a-case-series-from-early-2017
#3
Laura Hikin, Paul R Smith, Eleanor Ringland, Simon Hudson, Stephen R Morley
BACKGROUND: Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). METHODS: Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry...
November 29, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29214921/heteropterys-tomentosa-a-juss-toxicological-and-adaptogenic-effects-in-experimental-models
#4
Géssica Alves Fraga, Sikiru Olaitan Balogun, Emilly Della Pascqua, Ruberlei Godinho de Oliveira, Guilherme Botelho, Eduarda Pavan, Thiago da Rosa Lima, Eudes Thiago Pereira Avila, Clarissa de Medeiros Amorim Krueger, Valdir Cechinel Filho, Amílcar Sabino Damazo, Domingos Tabajara de Oliveira Martins, Fabrício Azevedo Voltarelli
BACKGROUND: The constant pursuit of improved athletic performance characterizes high-performance sport and the use of medicinal plants as dietary supplements is becoming widespread among athletes to enhance long-term endurance performance. AIM: The present study evaluated the toxicity of Heteropterys tomentosa (HEHt) and its acute adaptogenic effects. METHODS: The in vitro safety profile was evaluated on CHO-k1 cells using the alamar Blue assay, at concentrations ranging from 3...
December 2017: Nutrition and Health
https://www.readbyqxmd.com/read/29214146/micrornas-and-toxicology-a-love-marriage
#5
REVIEW
Elisabeth Schraml, Matthias Hackl, Johannes Grillari
With the dawn of personalized medicine, secreted microRNAs (miRNAs) have come into the very focus of biomarker development for various diseases. MiRNAs fulfil key requirements of diagnostic tools such as i) non or minimally invasive accessibility, ii) robust, standardized and non-expensive quantitative analysis, iii) rapid turnaround of the test result and iv) most importantly because they provide a comprehensive snapshot of the ongoing physiologic processes in cells and tissues that package and release miRNAs into cell-free space...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/29209455/acute-and-13-week-subchronic-toxicological-evaluations-of-turanose-in-mice
#6
Joo-Yeon Chung, Jihye Lee, Daeyeon Lee, Eunju Kim, Jae-Ho Shin, Pu Reum Seok, Sang-Ho Yoo, Yuri Kim
BACKGROUND/OBJECTIVES: Turanose, α-D-glucosyl-(1→3)-α-D-fructose, is a sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose, acute and subchronic oral toxicity studies were conducted with ICR mice. MATERIALS AND METHODS: For the acute oral toxicity study, turanose was administered as a single oral dose [10 g/kg body weight (b.w.)]. In the subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg b.w. doses of turanose daily for 13 weeks...
December 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/29207768/controversies-in-serotonin-syndrome-diagnosis-and-management-a-review
#7
REVIEW
Mohd Faisal Uddin, Richard Alweis, Syed Raza Shah, Noman Lateef, Waqas Shahnawaz, Rohan Kumar Ochani, Amin Muhammad Dharani, Syed Arbab Shah
Over the past few years, Serotonin Syndrome (SS) has become a significant clinical concern. Over the last decade, United States saw a surge in antidepressant use. SS characteristically presents as the triad of altered mental status, autonomic dysfunction and neuromuscular excitation. Symptoms vary from patient to patient with mild cases presenting with subacute symptoms and severe cases progressing rapidly to death. Due to the protean manifestations of the syndrome along with non-specific prodromal, SS can easily be misdiagnosed if not carefully assessed...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29205207/therapeutic-targeting-of-membrane-associated-grp78-in-leukemia-and-lymphoma-preclinical-efficacy-in-vitro-and-formal-toxicity-study-of-bmtp-78-in-rodents-and-primates
#8
D I Staquicini, S D'Angelo, F Ferrara, K Karjalainen, G Sharma, T L Smith, C A Tarleton, D E Jaalouk, A Kuniyasu, W B Baze, B K Chaffee, P W Hanley, K F Barnhart, E Koivunen, S Marchiò, R L Sidman, J E Cortes, H M Kantarjian, W Arap, R Pasqualini
Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing class of agents...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29202828/calculation-of-the-disease-burden-associated-with-environmental-chemical-exposures-application-of-toxicological-information-in-health-economic-estimation
#9
REVIEW
Philippe Grandjean, Martine Bellanger
Calculation of costs and the Burden of Disease (BoD) is useful in developing resource allocation and prioritization strategies in public and environmental health. While useful, the Disability-Adjusted Life Year (DALY) metric disregards subclinical dysfunctions, adheres to stringent causal criteria, and is hampered by gaps in environmental exposure data, especially from industrializing countries. For these reasons, a recently calculated environmental BoD of 5.18% of the total DALYs is likely underestimated. We combined and extended cost calculations for exposures to environmental chemicals, including neurotoxicants, air pollution, and endocrine disrupting chemicals, where sufficient data were available to determine dose-dependent adverse effects...
December 5, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/29202623/nonclinical-development-of-anx005-a-humanized-anti-c1q-antibody-for-treatment-of-autoimmune-and-neurodegenerative-diseases
#10
Janice A Lansita, Kirsten M Mease, Haiyan Qiu, Ted Yednock, Sethu Sankaranarayanan, Susan Kramer
ANX005 is a humanized immunoglobulin G4 recombinant antibody against C1q that inhibits its function as the initiating molecule of the classical complement cascade. The safety and tolerability of ANX005 are currently being evaluated in a phase I trial in healthy volunteers ( www.clinicaltrials.gov Identifier: NCT03010046). Inhibition of C1q can be applied therapeutically in a broad spectrum of diseases, including acute antibody-mediated autoimmune disease, such as Guillain-Barré syndrome (GBS), and in chronic diseases of the central nervous system involving complement-mediated neurodegeneration, such as Alzheimer's disease (AD)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29196879/the-feasibility-of-physiologically-based-pharmacokinetic-modeling-in-forensic-medicine-illustrated-by-the-example-of-morphine
#11
Nadine Schaefer, Daniel Moj, Thorsten Lehr, Peter H Schmidt, Frank Ramsthaler
In forensic medicine, expert opinion is often required concerning dose and time of intake of a substance, especially in the context of fatal intoxications. In the present case, a 98-year-old man died 4 days after admission to a hospital due to a femur neck fracture following a domestic fall in his retirement home. As he had obtained high morphine doses in the context of palliative therapy and a confusion of his supplemental magnesium tablets with a diuretic by the care retirement home was suspected by the relatives, a comprehensive postmortem examination was performed...
December 1, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29189171/inappropriate-sinus-tachycardia
#12
Mohammed Ruzieh, Abdelmoniem Moustafa, Ebrahim Sabbagh, Ebrahim Sabbagh, Saima Karim
Definition and diagnosis: Inappropriate Sinus Tachycardia (IST) is a clinical syndrome characterized by a sinus heart rate inexplicably higher than one hundred beats per minute at rest that is associated with symptoms like palpitations, dyspnea or dizziness in the absence of primary causes of tachycardia. The diagnosis requires exclusion of other causes of tachycardia including medications/substances (such as anti-cholinergic, beta-blocker withdrawal, caffeine, and alcohol) or medical conditions (such as panic attacks, pulmonary embolism, fever, hyperthyroidism, hypovolemia, anemia, and pain)...
November 29, 2017: Current Cardiology Reviews
https://www.readbyqxmd.com/read/29189143/retrospective-demonstration-of-25i-nbome-acute-poisoning-using-hair-analysis
#13
Alice Ameline, Audrey Farrugia, Jean-Sebastien Raul, Pascal Kintz
BACKGROUND: The abuse of new psychoactive substances or NPS has been dramatically increasing all around the world since the late 2000s and has become a serious public health problem. NPS are a challenge for the worldwide forensic community due to the difficulties to accurately document the cases. The N-benzylmethoxy (NBOMe) group is a new class of hallucinogenic designer drugs and has gained importance in the recent years. 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine) is an analog of the 2C series of psychedelic phenethylamine drugs that contain an N-methoxybenzyl substituent, which significantly affects their pharmacological activities...
November 29, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29188519/subretinal-and-intravitreal-retinal-injections-in-monkeys
#14
Daniyar Dauletbekov, K Ulrich Bartz-Schmidt, M Dominik Fischer
Ocular anatomy and physiology in cynomolgus monkeys (Macacca fascicularis) are very similar to that found in the human visual system. Therefore and despite significant ethical and economical implications, these animals constitute an excellent model system for toxicology and biodistribution studies in the development of new and meaningful treatment strategies for ocular disorders. The methods for delivery of investigational new drugs (INDs) to the ocular tissue are virtually identical to the methods used in clinical practice...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29186446/validation-of-the-i-stat%C3%A2-1-analyzer-for-postmortem-vitreous-humor-electrolytes-and-glucose-analysis
#15
Laura R Monzon, Sue Pearring, Caitlin Miller, Jay R Vargas
The analytical value of vitreous humor as a specimen in postmortem forensic toxicology has been known for some time. Numerous medical examiner laboratories outsource the analysis of this important specimen for electrolyte and glucose measurements. This can be both time-consuming and costly. The utility of the i-STAT®1 medical device to measure electrolytes and glucose in whole blood samples has been demonstrated for over two decades in a clinical setting through single-use disposable cartridges that introduce samples to the i-STAT®1...
November 24, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29186019/bioaccumulation-and-toxicity-of-carbon-nanoparticles-suspension-injection-in-intravenously-exposed-mice
#16
Ping Xie, Sheng-Tao Yang, Tiantian He, Shengnan Yang, Xiao-Hai Tang
Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29185815/2016-annual-report-of-the-american-association-of-poison-control-centers-national-poison-data-system-npds-34th-annual-report
#17
David D Gummin, James B Mowry, Daniel A Spyker, Daniel E Brooks, Michael O Fraser, William Banner
INTRODUCTION: This is the 34th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2016, 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 9.50 [7.33, 14.6] (median [25%, 75%]) min, facilitating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS...
December 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/29183241/alcohol-involvement-in-suicide-and-self-harm
#18
Celine Larkin, Eve Griffin, Paul Corcoran, Carmel McAuliffe, Ivan J Perry, Ella Arensman
BACKGROUND: Alcohol misuse and alcohol consumption are significant risk factors for suicidal behavior. AIMS: This study sought to identify factors associated with alcohol consumption in cases of suicide and nonfatal self-harm presentations. METHOD: Suicide cases in Cork, Ireland, from September 2008 to June 2012 were identified through the Suicide Support and Information System. Emergency department presentations of self-harm in the years 2007-2013 were obtained from the National Self-Harm Registry Ireland...
November 29, 2017: Crisis
https://www.readbyqxmd.com/read/29182526/immunohistochemical-analysis-of-rat-renal-tumours-caused-by-ochratoxin-a
#19
Diana Herman, Peter Mantle
Experimental renal cancer caused by ochratoxin A (OTA) in rats was first defined in the US National Toxicology Program (1989) and raised questions about any aetiological role in human urinary tract tumours. A review of histopathology in several rat kidney tumours from dietary OTA in recently described London studies, augmented by clinical immunohistochemistry for the first time for this mycotoxin, establishes their renal tubular cell origin. It had been assumed that the toxin might cause the human urothelial tumours associated with Balkan endemic nephropathy, but the present study could not support this...
November 28, 2017: Toxins
https://www.readbyqxmd.com/read/29181640/impact-of-gut-microbiota-on-drug-metabolism-an-update-for-safe-and-effective-use-of-drugs
#20
REVIEW
Keumhan Noh, You Ra Kang, Mahesh Raj Nepal, Rajina Shakya, Mi Jeong Kang, Wonku Kang, Sangkyu Lee, Hye Gwang Jeong, Tae Cheon Jeong
The intestinal mucosa and liver have long been considered as the main sites of drug metabolism, and the contribution of gut microbiota to drug metabolism has been under-estimated. However, it is now generally accepted that the gut microbiota plays an important role in drug metabolism prior to drug absorption or during enterohepatic circulation via various microbial enzymatic reactions in the intestine. Moreover, some drugs are metabolized by gut microbiota to specific metabolite(s) that cannot be formed in the liver...
November 27, 2017: Archives of Pharmacal Research
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