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Toxicologic Pathology

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https://www.readbyqxmd.com/read/27895265/gut-homeostasis-microbial-dysbiosis-and-opioids
#1
Fuyuan Wang, Sabita Roy
Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics...
November 28, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27895264/sex-differences-in-human-and-animal-toxicology-toxicokinetics
#2
Michael Gochfeld
Sex, the states of being female or male, potentially interacts with all xenobiotic exposures, both inadvertent and deliberate, and influences their toxicokinetics (TK), toxicodynamics, and outcomes. Sex differences occur in behavior, exposure, anatomy, physiology, biochemistry, and genetics, accounting for female-male differences in responses to environmental chemicals, diet, and pharmaceuticals, including adverse drug reactions (ADRs). Often viewed as an annoying confounder, researchers have studied only one sex, adjusted for sex, or ignored it...
November 28, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27879438/a-comparison-of-rodent-and-nonrodent-laryngeal-and-tracheal-bifurcation-sensitivities-in-inhalation-toxicity-studies-and-their-relevance-for-human-exposure
#3
Vasanthi Mowat, David J Alexander, Andrew M Pilling
In inhalation toxicity studies, drug-induced lesions are frequently reported in the larynx and sometimes at the tracheal bifurcation (carina) in the rat, but less so in the dog or monkey, bringing into question the relevance of these rodent findings for humans. The rat larynx is widely considered to be more sensitive than that of the dog and monkey in its response to inhaled xenobiotics, although we could find no published data to support this. In this review, data from 52 inhalation studies involving rodent and nonrodent species were collated and reviewed...
November 22, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27879437/book-review-atlas-of-histology-of-the-juvenile-rat
#4
Susan A Elmore
No abstract text is available yet for this article.
November 22, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27879436/cytological-bone-marrow-cell-differential-counts-and-morphologic-findings-in-healthy-cynomolgus-monkeys-macaca-fascicularis-from-nonclinical-toxicology-studies
#5
Caitlyn M Carter, Laura C Cregar, Adam D Aulbach
Cytological bone marrow evaluation is utilized in nonclinical toxicology studies to characterize hematopoietic effects when the combined interpretation of histologic and complete blood count data does not yield sufficient information. Results from cytological bone marrow examination should be interpreted in the context of variability observed in concurrent control animals with consideration of cytologist experience and historical/published data. Cytological bone marrow differential counts and cellular morphologic findings from 130 (66 male, 64 female) healthy control cynomolgus monkeys from nonclinical toxicology studies were retrospectively analyzed...
November 22, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27879435/identification-of-mhc-haplotypes-associated-with-drug-induced-hypersensitivity-reactions-in-cynomolgus-monkeys
#6
Hong Wu, Jessica Whritenour, Jonathan C Sanford, Christopher Houle, Karissa K Adkins
Drug-induced hypersensitivity reactions can significantly impact drug development and use. Studies to understand risk factors for drug-induced hypersensitivity reactions have identified genetic association with specific human leukocyte antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can occur in nonhuman primates; however, association between drug-induced hypersensitivity reactions and major histocompatibility complex (MHC) alleles has not been described. In this study, tissue samples were collected from 62 cynomolgus monkeys from preclinical studies in which 9 animals had evidence of drug-induced hypersensitivity reactions...
November 22, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27856969/impact-of-age-on-the-male-reproductive-system-from-the-pathologist-s-perspective
#7
Catherine A Picut, Amera K Remick
Age, and in particular young age, can significantly impact the response to toxicants in animals and can greatly influence the interpretation of tissue changes by the toxicologic pathologist. Although this applies to multiple organ systems, the current review focuses on the male reproductive system. When performing microscopic evaluation of male reproductive organs, the toxicologic pathologist must be aware of the dynamic changes in histomorphology, predominantly driven by timed hormonal alterations, at various life stages...
November 16, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27879439/interpreting-and-integrating-clinical-and-anatomic-pathology-results-pulling-it-all-together
#8
Lila Ramaiah, Mary Jane Hinrichs, Elizabeth V Skuba, William O Iverson, Daniela Ennulat
The continuing education course on integrating clinical and anatomical pathology data was designed to communicate the importance of using a weight of evidence approach to interpret safety findings in toxicology studies. This approach is necessary, as neither clinical nor anatomic pathology data can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study end points were reviewed...
November 13, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27834287/naphthoquine-induced-central-nervous-system-and-hepatic-vasculocentric-toxicity-in-the-beagle-dog
#9
Jean-Rene Galarneau, Emily K Meseck, Robert L Hall, Wenkui Li, Margaret L Weaver
Naphthoquine phosphate (NP) was considered as a partner drug with a promising antimalarial drug candidate. Here we report unexpected adverse clinical signs and microscopic findings in a canine pilot toxicology study with NP. Male and female dogs were dosed daily by oral gavage with NP at 2, 10, or 50 mg/kg/day for a maximum of 14 days. NP was not tolerated at ≥10 mg/kg/day; several animals were sacrificed in moribund condition and marked neurological clinical signs were noted at 50 mg/kg/day. The main microscopic observation was central nervous system vasculocentric inflammation (mainly lymphocytes and macrophages) in the white and gray matter of various regions of the brain at ≥2 mg/kg/day and at lower incidence in the spinal cord at ≥10 mg/kg/day...
November 9, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27821709/proceedings-of-the-2016-national-toxicology-program-satellite-symposium
#10
Susan A Elmore, Vivian S Chen, Schantel Hayes-Bouknight, Jessica S Hoane, Kyathanahalli Janardhan, Linda H Kooistra, Thomas Nolte, Kathleen A Szabo, Gabrielle A Willson, Jeffrey C Wolf, David E Malarkey
The 2016 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in San Diego, CA, at the Society of Toxicologic Pathology's (STP) 35th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks, along with select images that were used by the audience for voting and discussion. Some lesions and topics covered during the symposium included malignant glioma and histiocytic sarcoma in the rodent brain; a new statistical method designed for histopathology data evaluation; uterine stromal/glandular polyp in a rat; malignant plasma cell tumor in a mouse brain; Schwann cell proliferative lesions in rat hearts; axillary schwannoma in a cat; necrosis and granulomatous inflammation in a rat brain; adenoma/carcinoma in a rat adrenal gland; hepatocyte maturation defect and liver/spleen hematopoietic defects in an embryonic mouse; distinguishing malignant glioma, malignant mixed glioma, and malignant oligodendroglioma in the rat; comparison of mammary gland whole mounts and histopathology from mice; and discussion of the International Harmonization of Nomenclature and Diagnostic Criteria collaborations...
November 7, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27815490/a-brief-overview-of-the-stp-35th-annual-symposium-on-the-basis-and-relevance-of-variation-in-toxicologic-responses
#11
Armando R Irizarry, Kathryn E Gropp, Darlene Dixon
The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolation to humans problematic. This brief overview summarizes speaker presentations from each session which describes important factors that may impact the interpretation of nonclinical discovery and developmental toxicity studies...
November 4, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27815489/translating-mouse-models-immune-variation-and-efficacy-testing
#12
Rani S Sellers
Mice and humans branched from a common ancestor approximately 80 million years ago. Despite this, mice are routinely utilized as animal models of human disease and in drug development because they are inexpensive, easy to handle, and relatively straightforward to genetically manipulate. While this has led to breakthroughs in the understanding of genotype-phenotype relationships and in the identification of therapeutic targets, translation of beneficial responses to therapeutics from mice to humans has not always been successful...
November 4, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27803290/deciphering-sources-of-variability-in-clinical-pathology-it-s-not-just-about-the-numbers
#13
Niraj K Tripathi, Nancy E Everds, A Eric Schultze, Armando R Irizarry, Robert L Hall, Anne Provencher, Adam Aulbach
The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals...
November 1, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27770110/the-microbiome-modulator-of-pharmacological-and-toxicological-exposures-and-responses
#14
Ellen K Silbergeld
The microbiome is increasingly recognized as a critical component in human development, health, and disease. Its relevance to toxicology and pharmacology involves challenges to current concepts related to absorption, metabolism, gene:environment, and pathways of response. Framing testable hypotheses for experimental and epidemiological studies will require attention to study designs, biosampling, data analysis, and attention to confounders.
October 21, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27770109/the-application-of-paraphenylenediamine-staining-for-assessment-of-phospholipidosis
#15
Norimitsu Shirai, Frank J Geoly, Walter F Bobrowski, Carlin Okerberg
Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies in cells exposed to xenobiotics. Demonstration of the lamellar bodies by transmission electron microscopy (TEM) is the hallmark for a definitive diagnosis of phospholipidosis. However, the preparation of tissue samples for TEM and their ultrastructural evaluation are technically challenging and time consuming. Paraphenylenediamine (PPD) is essentially a fat stain, and the staining mechanism is based upon the osmication of unsaturated lipids...
October 21, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27770108/histological-development-of-male-reproductive-organs-in-microminipigs
#16
Akihisa Kangawa, Masayoshi Otake, Satoko Enya, Toshinori Yoshida, Masatoshi Shibata
Microminipigs are becoming increasingly attractive alternatives for various experimental applications, such as general toxicology studies, owing to their manageable size. However, there are limited studies on the male reproductive organs of microminipigs, particularly on the histological aspects of sexual maturity. To clarify the development of male reproductive organs, 35 male microminipigs, aged 0 to 12 months, were used in this study. Histological and histomorphological evaluation was performed based on spermatogenic development, measurement of tubular structure in testes and epididymides, and histological progress of accessory glands...
October 21, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27770107/is-it-adverse-nonadverse-adaptive-or-artifact
#17
Arun R Pandiri, Roy L Kerlin, Peter C Mann, Nancy E Everds, Alok K Sharma, L Peyton Myers, Thomas J Steinbach
One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA...
October 21, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27753639/impact-of-the-genetics-and-source-of-preclinical-safety-animal-models-on-study-design-results-and-interpretation
#18
Karyn Colman
It has been long established that not only the species but also the strain and supplier of rodents used in preclinical safety studies can have a significant impact on the outcome of studies due to variability in their genetic background and thus spontaneous pathologic findings. In addition, local husbandry, housing, and other environmental conditions may have effects on the development and expression of comorbidities, particularly in longer-term or chronic studies. More recently, similar effects related to the source, including genetic and environmental variability, have been recognized in cynomolgus macaques (Macaca fascicularis)...
October 17, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27753638/the-impact-of-age-on-the-female-reproductive-system-a-pathologist-s-perspective
#19
Justin D Vidal
Evaluation of the female reproductive system in a general toxicity setting can be challenging for the toxicologic pathologist due to the cyclic nature of the estrous and menstrual cycles, timing of puberty and reproductive senescence, and species differences. Age in particular can have a significant impact on the histologic appearance of the female reproductive system and create challenges when trying to distinguish test article-related findings from normal developmental or senescent changes. This review describes the key physiologic and histologic features of immaturity, the transition through puberty, sexual maturity, and reproductive senescence in the female reproductive system, with an emphasis on practical applications for the toxicologic pathologist, and includes recommendations for distinguishing and documenting these developmental periods...
October 17, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27753637/acute-toxicity-of-vildagliptin-differences-in-sensitivity-between-cynomolgus-monkeys-of-asian-or-mauritian-origin
#20
Peter Hoffmann, Lori Martin, Michael Keselica, Diane Gunson, Elizabeth Skuba, Dan Lapadula, Michael Hayes, Phil Bentley, Steve Busch
This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances...
October 17, 2016: Toxicologic Pathology
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