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Toxicologic Pathology

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https://www.readbyqxmd.com/read/29448902/the-altmetric-attention-score-what-does-it-mean-and-why-should-i-care
#1
Susan A Elmore
No abstract text is available yet for this article.
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29400254/histomorphologic-analysis-of-the-late-term-rat-fetus-and-placenta
#2
Phanie L Charest, Vanessa Vrolyk, Pauline Herst, Maryse Lessard, Deborah M Sloboda, Mathieu Dalvai, Julius Haruna, Janice L Bailey, Marie-Odile Benoit-Biancamano
Histological examination of the rat placenta and fetus is uncommon. Toxicological studies mainly rely on gross examination of the fetus and on fetal and placental weights. These are often insufficient to assess the fetal and placental toxicity of xenobiotics. The small size of the fetus makes its dissection labor-intensive. Thus, our objective was to develop a simple and accurate technique to evaluate the rat fetus and placenta. Sprague-Dawley rat fetuses at gestational day 19.5 ( n = 18) and their placentas ( n = 32) were fixed in formalin...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29390940/metastasis-to-the-f344-rat-pancreas-from-lung-cancer-induced-by-4-methylnitrosamino-1-3-pyridyl-1-butanone-and-enantiomers-of-its-metabolite-4-methylnitrosamino-1-3-pyridyl-1-butanol-constituents-of-tobacco-products
#3
Ramesh C Kovi, Charles S Johnson, Silvia Balbo, Stephen S Hecht, M Gerard O'Sullivan
Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused by tobacco products. NNK and racemic NNAL are reported to induce lung and pancreatic tumors in rats. The carcinogenicity in Fischer 344 rats of NNK, NNAL, and its enantiomers ( R)-NNAL and ( S)-NNAL has been studied recently, and all test compounds induced significant numbers of lung tumors...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29382273/conflict-of-interest-in-journal-peer-review
#4
David B Resnik, Susan A Elmore
No abstract text is available yet for this article.
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29378501/comparative-proteomic-analysis-of-liver-steatosis-and-fibrosis-after-oral-hepatotoxicant-administration-in-sprague-dawley-rats
#5
B Claire McDyre, Mohamed Diwan M AbdulHameed, Matthew G Permenter, William E Dennis, Christine E Baer, Jason M Koontz, Molly H Boyle, Anders Wallqvist, John A Lewis, Danielle L Ippolito
The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29334850/an-immunopathological-evaluation-of-the-porcine-cholecyst-matrix-as-a-muscle-repair-graft-in-a-male-rat-abdominal-wall-defect-model
#6
Dhanush Krishna Balakrishnan-Nair, Narayanan Divakaran Nair, Syam Kunnekkattu Venugopal, Vijayan Narayana Das, Sisilamma George, Mammen John Abraham, Saji Eassow, Malcolm Ronald Alison, Anoop Sainulabdeen, Thapasimuthu Vijayamma Anilkumar
With the increasing use of animal-based biomaterials for regenerative medical applications, the need for their safety assessment is paramount. A porcine cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect model. Host tissue-scaffold interface samples were collected 2, 8, and 16 weeks postimplantation and evaluated by histopathology, immunohistochemistry, and electron microscopy. The nature of the tissue reaction was compared with those induced by a jejunum-derived scaffold (JDS) prepared by the same method and a commercial-grade small intestinal submucosa (CSIS) scaffold...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29310530/unc569-induced-morphological-changes-in-pigment-epithelia-and-photoreceptor-cells-in-the-retina-through-mertk-inhibition-in-mice
#7
Ayako Sayama, Keiko Okado, Koichi Nakamura, Tatsuya Kawaguchi, Takuma Iguchi, Toshihiko Makino, Koichi Yabe, Kiyonori Kai, Kazuhiko Mori
Mer proto-oncogene tyrosine kinase (MerTK), which is expressed in the retinal pigment epithelium (RPE), regulates phagocytosis of shed photoreceptor outer segments (POS). To investigate the effects of drug-induced MerTK inhibition on the retina, UNC569, a specific MerTK inhibitor, was orally administered to male mice at a concentration of 60, 100, or 150 mg/kg for up to 14 days. Furthermore, MerTK inhibition in the retinal tissue sample was examined using a phosphorylation assay following a single dose of UNC569 at 100 mg/kg...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29233079/a-diagnostic-approach-for-rodent-progressive-cardiomyopathy-and-like-lesions-in-toxicology-studies-up-to-28-days-in-the-sprague-dawley-rat-part-2-of-2
#8
James R Hailey, Beverly E Maleeff, Heath C Thomas, Gail Pearse, Jan C Klapwijk, Patrizia G Cristofori, Brian Berridge, Carie L Kimbrough, George A Parker, Daniel Morton, Susan Elmore, Jerry F Hardisty, Noel O Dybdal, David A Rehagen, James D Fikes, Martin Lamb, Kathleen Biddle, Bernard S Buetow, Vinicius Carreira, Abraham Nyska, Niraj K Tripathi, Heather C Workman, Jean-Guy Bienvenu, Ingrid Brees, James R Turk, Rick R Adler
To test the diagnostic approach described in part 1 of this article, 2 exercises were completed by pathologists from multiple companies/agencies. Pathologist's examination of whole slide image (WSI) heart sections from rats using personal diagnostic approaches (exercise #1) corroborated conclusions from study #1. Using the diagnostic approach described in part 1, these pathologists examined the same WSI heart sections (exercise #2) to determine whether that approach increased consistency of diagnosis of rodent progressive cardiomyopathy (PCM) lesions...
December 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29233078/book-review-pathology-for-toxicologists-principles-and-practices-of-laboratory-animal-pathology-for-study-personnel-mcinnes-e-ed-2017-pathology-for-toxicologists-principles-and-practices-of-laboratory-animal-pathology-for-study-personnel-wiley-blackwell-hoboken
#9
https://www.readbyqxmd.com/read/29233077/new-technologies-real-time-telepathology-systems-novel-cost-effective-tools-for-real-time-consultation-and-data-sharing
#10
Gabriel Siegel, Dan Regelman, Robert Maronpot, Moti Rosenstock, Abraham Nyska
Real-time telepathology for use in investigative and regulated preclinical toxicology studies is now feasible. Newly developed microscope-integrated telepathology systems enable geographically remote stakeholders to view the live histopathology slide as seen by the study pathologist within the microscope. Simultaneous online viewing and dialog between study pathologist and remote colleagues is an efficient and cost-effective means for consultation, pathology working groups, and peer review, facilitating good science and economic benefits by enabling more timely and informed clinical decisions...
December 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29162012/meeting-report-tissue-based-image-analysis
#11
Chandra Saravanan, Vanessa Schumacher, Danielle Brown, Robert Dunstan, Jean-Rene Galarneau, Marielle Odin, Sasmita Mishra
Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29162011/skeletal-muscle-injury-biomarkers-assay-qualification-efforts-and-translation-to-the-clinic
#12
Richard A Goldstein
Skeletal muscle (SKM) injury or myopathy results in structural or functional defects in SKMs that can be caused by variety of factors such as (1) genetic, (2) drug-induced, (3) disease progression (cachexia), or (4) aging (sarcopenia). Creatine kinase (CK) and aspartate transaminase (AST) activity assays have been routinely used as SKM injury biomarkers, but they lack sensitivity and tissue specificity. In collaboration with the Predictive Safety Testing Consortium, we evaluated the diagnostic performance of a muscle injury biomarker panel (MIP) compared to CK and AST and their correlation with the histology scores across 34 different rat studies...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29105581/wnt-mediated-modulation-of-bone-metabolism-implications-for-wnt-targeting-to-treat-extraskeletal-disorders
#13
Whitney A Bullock, Alexander G Robling
The WNT-signaling pathway is involved in cellular and tissue functions that control such diverse processes as body axis patterning, cellular proliferation, differentiation, and life span. The long list of molecules that can participate or modify WNT signaling makes this pathway one of the most complex in cell biology. In bone tissues, WNT signaling is required for proper skeletal development, and human mutations in various components of the cascade revealed insights into pharmacologic targeting that can be harnessed to improve skeletal health...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29096595/pleiotropic-actions-of-fgf23
#14
Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29046115/bone-and-the-immune-system
#15
M Neale Weitzmann
Osteoporosis increases fracture risk, a cause of crippling morbidity and mortality. The immunoskeletal interface (ISI) is a centralization of cell and cytokine effectors shared between skeletal and immune systems. Consequently, the immune system mediates powerful effects on bone turnover. Physiologically, B cells secrete osteoprotegerin (OPG), a potent anti-osteoclastogenic factor that preserves bone mass. However, activated T cells and B cells secrete pro-osteoclastogenic factors including receptor activator of Nuclear factor-kappaB (NF-kB) ligand (RANKL), Interleukin (IL)-17A, and tumor necrosis factor (TNF)-α promoting bone loss in inflammatory states such as rheumatoid arthritis...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29046139/immunohistochemical-characterization-of-sarcomas-in-trp53-haploinsufficient-mice
#16
M P Jokinen, D L Morgan, H C Price, R A Herbert, T Saddler, D Dixon
The use of immunohistochemical (IHC) staining in determining and/or confirming the cellular origin of poorly differentiated sarcomas was evaluated in this study. Sarcomatous neoplasms were evaluated in a research study conducted in 2 strains of p53+/- haploinsufficient mice. The most common neoplasms were undifferentiated sarcomas, followed by osteosarcomas and rhabdomyosarcomas (RMSs). The RMSs were poorly differentiated and appeared similar to the pleomorphic, or adult type, RMS of humans. All sarcomas stained positive by IHC for the mesenchymal cell intermediate filament vimentin...
August 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29046138/usefulness-of-simultaneous-measurement-of-plasma-steroids-including-precursors-for-the-evaluation-of-drug-effects-on-adrenal-steroidogenesis-in-rats
#17
Tomoaki Tochitani, Akihito Yamashita, Izumi Matsumoto, Mami Kouchi, Yuta Fujii, Izuru Miyawaki, Toru Yamada, Kiyoko Bando
The aim of this study was to evaluate the usefulness of simultaneous measurement of plasma steroids, including precursors, for the evaluation of drug effects on adrenal steroidogenesis in vivo. Plasma concentrations of corticosterone and its precursors were examined in rats dosed with compounds that affect adrenal steroidogenesis via different modes of action as well as the relationships of the changes with blood chemistry and adrenal histopathology. Male rats were dosed with tricresyl phosphate, aminoglutethimide, trilostane (TRL), metyrapone (MET), ketoconazole (KET), or mifepristone for 7 days...
August 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28830301/induction-of-severe-chronic-hyperplastic-candidiasis-in-rat-by-opportunistic-infection-of-c-albicans-through-combination-of-diabetes-and-intermittent-prednisolone-administration
#18
Yui Terayama, Tetsuro Matsuura, Kiyokazu Ozaki
Chronic hyperplastic candidiasis progresses from squamous cell hyperplasia to squamous cell carcinoma (SCC); however, the oncogenic mechanism remains unclear. In the present study, we attempted to induce opportunistic Candida albicans infection and establish chronic hyperplastic candidiasis in rats by combining diabetic condition and prednisolone administration, followed by analysis of the inflammatory cells involved in the disease progression. Female Wistar Bunn/Kobori (WBN/Kob) rats were divided into 3 groups: alloxan-induced diabetic rats (A group) along with diabetic (AP group) and nondiabetic (P group) rats intermittently treated with prednisolone...
August 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28830332/hypersensitivity-reactions-to-obinutuzumab-in-cynomolgus-monkeys-and-relevance-to-humans
#19
Elisabeth Husar, Maria Solonets, Olaf Kuhlmann, Eginhard Schick, Hanna Piper-Lepoutre, Thomas Singer, Gaurav Tyagi
Obinutuzumab (GA101, Gazyva™, Gazyvaro®, F. Hoffmann-La Roche AG, Basel, Switzerland) is a humanized, glycoengineered type II antibody targeted against CD20. The preclinical safety evaluation required to support clinical development and marketing authorization of obinutuzumab included repeat-dose toxicity studies in cynomolgus monkeys for up to 6-month dosing with a 9-month recovery period. Results from those studies showed decreases in circulating B cells and corresponding B-cell depletion in lymphoid tissues, consistent with the desired pharmacology of obinutuzumab...
July 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28830331/vascular-imaging-of-matrix-metalloproteinase-activity-as-an-informative-preclinical-biomarker-of-drug-induced-vascular-injury
#20
Raymond J Gonzalez, Shu-An Lin, Bohumil Bednar, Brett Connolly, Lisa LaFranco-Scheuch, Gebre M Mesfin, Thomas Philip, Shetal Patel, Timothy Johnson, Frank D Sistare, Warren E Glaab
Lack of biomarkers specific to and either predictive or diagnostic of drug-induced vascular injury (DIVI) continues to be a major obstacle during drug development. Biomarkers derived from physiologic responses to vessel injury, such as inflammation and vascular remodeling, could make good candidates; however, they characteristically lack specificity for vasculature. We evaluated whether vascular remodeling-associated protease activity, as well as changes to vessel permeability resulting from DIVI, could be visualized ex vivo in affected vessels, thereby allowing for visual monitoring of the pathology to address specificity...
July 2017: Toxicologic Pathology
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