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Clinical Toxicology

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https://www.readbyqxmd.com/read/28448027/dry-powder-and-nebulized-aerosol-inhalation-of-pharmaceuticals-delivered-to-mice-using-a-nose-only-exposure-system
#1
Jonathan E Phillips, Xuxia Zhang, James A Johnston
Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease...
April 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446067/the-chemical-disruption-of-human-metabolism
#2
Stephen J Genuis, Edmond Kyrillos
BACKGROUND: Recent evidence highlights the reality of unprecedented human exposure to toxic chemical agents found throughout our environment - in our food and water supply, in the air we breathe, in the products we apply to our skin, in the medical and dental materials placed into our bodies, and even within the confines of the womb. With biomonitoring confirming the widespread bioaccumulation of myriad toxicants among population groups, expanding research continues to explore the pathobiological impact of these agents on human metabolism...
April 26, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28443181/development-of-a-test-method-for-the-evaluation-of-dna-damage-in-mouse-spermatogonial-stem-cells
#3
Hye Lyun Jeon, Jung-Sun Yi, Tae Sung Kim, Youkyung Oh, Hye Jeong Lee, Minseong Lee, Jin Seok Bang, Kinarm Ko, Il Young Ahn, Kyungyuk Ko, Joohwan Kim, Hye-Kyung Park, Jong Kwon Lee, Soo Jung Sohn
Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage...
April 2017: Toxicological Research
https://www.readbyqxmd.com/read/28442326/inhaled-efficacious-dose-translation-from-rodent-to-human-a-retrospective-analysis-of-clinical-standards-for-respiratory-diseases
#4
REVIEW
J E Phillips
Clinical pharmacologists and toxicologists are often faced with predicting equivalent dosages for humans from biological observations in laboratory animals. Allometric scaling has been used extensively as the basis for extrapolation of drug dosage that might be expected to produce the equivalent biological effects. Allometry is the study of size and its consequences and it is based on the anatomical, physiological, and biochemical similarities between animals. In this review, retrospective analyses have been performed based on data reported in the literature in an attempt to determine the utility of allometric scaling for human dose projections from pre-clinical data for compounds that are delivered by inhalation...
April 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28440681/discovery-and-preclinical-development-of-dasabuvir-for-the-treatment-of-hepatitis-c-infection
#5
Mohamed El Kassas, Tamer Elbaz, Enas Hafez, Mohamed Naguib Wifi, Gamal Esmat
Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families...
April 25, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28437889/safety-of-sucrose-esters-from-physalis-peruviana-l-in-a-28-day-repeated-dose-study-in-mice
#6
Yanet C Ocampo, Daneiva C Caro, David E Rivera, Luis A Franco
Although extracts and consumed foods from Physalis species contain sucrose esters from their glandular trichomes, there is no experimental data available on their toxicological effects. As peruvioses A and B isolated from Physalis peruviana L. calyces have proved to be effective anti-inflammatory and immunomodulatory compounds, this work aimed to investigate their sub-acute toxicity study and genotoxicity. For this, CD-1(ICR) mice were treated intraperitoneally with peruvioses at doses of 2.5, 5, and 10mg/kg/day for 28 consecutive days, to simulate therapeutic and over-therapeutic dosage levels...
April 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28435095/application-of-advanced-preclinical-models-and-methods-in-anesthetic-neurotoxicity-research
#7
REVIEW
Cheng Wang, Xuan Zhang, Fang Liu
Recently, there has been increasing concern regarding the potential of anesthetics to disturb the long-term function of the central nervous system (CNS). The field of anesthesia-related toxicology, therefore, has engaged multiple scientific disciplines and utilized a variety of pre-clinical research models in an attempt to identify the basic characteristics of the anesthetic agents that may produce acute and/or chronic adverse effects on the CNS. This review discusses how the application of advanced research approaches and models, such as the nonhuman primate, neural stem cell-derived organotypic slice cultures and/or organs-on-chips systems, can serve as translational models of infantile anesthetic exposure...
April 20, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#8
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28433587/pharmacokinetic-and-toxicology-comparator-testing-of-biosimilar-drugs-assessing-need
#9
Paul Baldrick
A key element in the development of a biosimilar molecule is the comparability of the biological activity/nonclinical similarity to the innovator drug. Although some regulatory guidelines are encouraging little or no in vivo testing, currently a common practice is to perform at least one toxicology and/or one pharmacokinetic (PK) study to assess if any different findings occur for in-life, clinical pathology and histopathological parameters or in exposure. An exercise was performed in which the results of such testing were evaluated...
April 20, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#10
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28428958/debromoaplysiatoxin-as-the-causative-agent-of-dermatitis-in-a-dog-after-exposure-to-freshwater-in-california
#11
Birgit Puschner, Adrienne C Bautista, Chris Wong
Contamination of recreational waters with cyanobacterial toxins continues to increase and presents a risk to animals and humans. Although cases of acute hepato- and neurotoxicoses in dogs following cyanotoxin exposure exist, no reports of skin-related reactions in dogs exist. A 5-year-old female spayed 34 kg Bracco Italiano was initially presented for rapid onset of severe pruritus and urticaria. Marked excoriation and erythema were noted over the chest and neck, while urticaria was noted in the inguinal regions and ventral abdomen...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28426096/managing-the-sequence-specificity-of-antisense-oligonucleotides-in-drug-discovery
#12
Peter H Hagedorn, Bo R Hansen, Troels Koch, Morten Lindow
All drugs perturb the expression of many genes in the cells that are exposed to them. These gene expression changes can be divided into effects resulting from engaging the intended target and effects resulting from engaging unintended targets. For antisense oligonucleotides, developments in bioinformatics algorithms, and the quality of sequence databases, allow oligonucleotide sequences to be analyzed computationally, in terms of the predictability of their interactions with intended and unintended RNA targets...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28424823/-coma-in-the-emergency-room
#13
M Braun, C J Ploner, T Lindner, M Möckel, W U Schmidt
Coma of unknown origin (CUO) is a frequent unspecific emergency symptom associated with a high mortality. A fast diagnostic work-up is essential given the wide spectrum of underlying diagnoses that are made up of approximately 50% primary central nervous system (CNS) pathologies and approximately 50% extracerebral, almost exclusively internal medical causes. Despite the high mortality associated with this symptom, there are currently no generally accepted management guidelines for adult patients presenting with CUO...
April 19, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28421968/chronic-toxicology-studies-of-basal-insulin-peglispro-in-rats-and-dogs-a-novel-pegylated-insulin-lispro-analog-with-a-prolonged-duration-of-action
#14
Richard A Byrd, Jamie L Blackbourne, Mary Pat Knadler, Albert E Schultze, John L Vahle
Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because chronic parenteral administration of PEGylated proteins to animals has sometimes resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc) injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with systemic toxicities or other changes, including vacuolation of tissue macrophages, renal tubular cells, and ependymal cells...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28421846/clinical-toxicology-past-and-future
#15
Steven A Seifert
No abstract text is available yet for this article.
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28421121/availability-pharmaceutics-security-pharmacokinetics-and-pharmacological-activities-of-patchouli-alcohol
#16
REVIEW
Guanying Hu, Cheng Peng, Xiaofang Xie, Sanyin Zhang, Xiaoyu Cao
Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28417172/simultaneous-determination-of-multiclass-pesticide-residues-in-human-plasma-using-a-mini-quechers-method
#17
Anshuman Srivastava, Satyajeet Rai, Ashish Kumar Sonker, Kajal Karsauliya, Chandra Prabha Pandey, Sheelendra Pratap Singh
Blood is one of the most assessable matrices for the determination of pesticide residue exposure in humans. Effective sample preparation/cleanup of biological samples is very important in the development of a sensitive, reproducible, and robust method. In the present study, a simple, cost-effective, and rapid gas chromatography-tandem mass spectrometry method has been developed and validated for simultaneous analysis of 31 multiclass (organophosphates, organochlorines, and synthetic pyrethroids) pesticide residues in human plasma by means of a mini QuEChERS (quick, easy, cheap, effective, rugged, and safe) method...
April 17, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28417026/cardiovascular-complications-of-acute-amphetamine-abuse-cross-sectional-study
#18
Elham Bazmi, Farinaz Mousavi, Leila Giahchin, Tahmineh Mokhtari, Behnam Behnoush
OBJECTIVES: This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. METHODS: This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded...
February 2017: Sultan Qaboos University Medical Journal
https://www.readbyqxmd.com/read/28416568/pharmacological-and-toxicological-properties-of-the-potent-oral-%C3%AE-secretase-modulator-bpn-15606
#19
Steven L Wagner, Kevin D Rynearson, Steven K Duddy, Can Zhang, Phuong D Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B Klee, Corinne M Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H Lin, Doo Y Kim, William C Mobley, Robert A Rissman, Rudolph E Tanzi
Alzheimer's disease is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42 amino acid amyloid β peptide, as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance are postulated to initiate and drive the AD pathological process. We initially introduced a novel class of bridged aromatics referred to as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides...
April 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28416413/evaluation-of-the-physiotel%C3%A2-digital-m11-cardiovascular-telemetry-implant-in-socially-housed-cynomolgus-monkeys-up-to-16weeks-after-surgery
#20
Ninette K Andersen, Olivier Meyer, Alys Bradley, Nils Dragsted, Anders B Lassen, Ingrid Sjögren, Julie M Larsen, Warren Harvey, Rastislav Bator, Aileen Milne
INTRODUCTION: The novel PhysioTel™ Digital M11 telemetry implant was evaluated in socially housed monkeys with respect to both safety pharmacological cardiovascular (arterial blood pressure (BP), heart rate (HR) and electrocardiogram (ECG)) and toxicological (clinical pathology and histopathology) endpoints. METHODS: Telemetry and clinical pathology data were obtained repeatedly up to 16weeks after surgery in four female cynomolgus monkeys, followed by necropsy...
April 14, 2017: Journal of Pharmacological and Toxicological Methods
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