journal
MENU ▼
Read by QxMD icon Read
search

Toxicologic Pathology

journal
https://www.readbyqxmd.com/read/29162012/meeting-report-tissue-based-image-analysis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28830330/ultrastructural-alterations-in-thyrocytes-of-zebrafish-danio-rerio-after-exposure-to-propylthiouracil-and-perchlorate
#11
Florian Schmidt, Raoul Wolf, Lisa Baumann, Thomas Braunbeck
Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorate (PER; 0-5,000 µg/L) for 5 weeks in a modified early life-stage test. None of the treatments caused significant mortality (no observed effect concentrations for survival ≥50 mg/L [PTU] and ≥5,000 µg/L [PER])...
July 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28618975/a-black-cohosh-extract-causes-hematologic-and-biochemical-changes-consistent-with-a-functional-cobalamin-deficiency-in-female-b6c3f1-n-mice
#12
Michelle C Cora, William Gwinn, Ralph Wilson, Debra King, Suramya Waidyanatha, Grace E Kissling, Sukhdev S Brar, Dorian Olivera, Chad Blystone, Greg Travlos
Black cohosh rhizome, available as a dietary supplement, is most commonly marketed as a remedy for dysmenorrhea and menopausal symptoms. A previous subchronic toxicity study of black cohosh dried ethanolic extract (BCE) in female mice revealed a dose-dependent ineffective erythropoiesis with a macrocytosis consistent with the condition known as megaloblastic anemia. The purpose of this study was to investigate potential mechanisms by which BCE induces these particular hematological changes. B6C3F1/N female mice (32/group) were exposed by gavage to vehicle or 1,000 mg/kg BCE for 92 days...
July 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28641507/the-acvp-stp-coalition-for-veterinary-pathology-fellows-celebrates-32-new-training-positions
#13
Gary Cockerell, Cory Brayton, Anne Barger, Brad Bolon
Since its creation in 2004, the Coalition for Veterinary Pathology Fellows, a partnership between the American College of Veterinary Pathologists and the Society of Toxicologic Pathology, has established 32 new training positions backed by US$7.4 million in financial support from private sponsors.
June 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28641506/regulatory-forum-opinion-piece-imaging-applications-in-toxicologic-pathology-recommendations-for-use-in-regulated-nonclinical-toxicity-studies
#14
Robert R Maronpot, Abraham Nyska, Sean P Troth, Kathleen Gabrielson, Polina Sysa-Shah, Vyacheslav Kalchenko, Yuri Kuznetsov, Alon Harmelin, Yael S Schiffenbauer, David Bonnel, Jonathan Stauber, Yuval Ramot
Available imaging systems for use in preclinical toxicology studies increasingly show utility as important tools in the toxicologic pathologist's armamentarium, permit longitudinal evaluation of functional and morphological changes in tissues, and provide important information such as organ and lesion volume not obtained by conventional toxicology study parameters. Representative examples of practical imaging applications in toxicology research and preclinical studies are presented for ultrasound, positron emission tomography/single-photon emission computed tomography, optical, magnetic resonance imaging, and matrix-assisted laser desorption ionization-imaging mass spectrometry imaging...
June 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28641505/in-utero-exposure-to-di-n-butyl-phthalate-induces-morphological-and-biochemical-changes-in-rats-postpuberty
#15
Yuya Okayama, Shin Wakui, Michael F Wempe, Mitsuru Sugiyama, Masaya Motohashi, Tomoko Mutou, Hiroyuki Takahashi, Eisuke Kume, Hiroshi Ikegami
Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels...
June 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28421969/dystrophic-mineralization-of-costal-cartilage-in-hartley-guinea-pigs
#16
Alexandria M Schauer, Adrienne Schucker, Cathy S Carlson
Hartley guinea pigs are widely used animal models of disease, particularly in studies of osteoarthritis. The purpose of this study was to investigate lesions in the costal cartilage from 16 male, 5- to 6-month-old Hartley guinea pigs. Routine histological sections from the costal cartilage and costochondral junction (longitudinal and cross sections) and sternum (for evaluation of bone marrow) were examined. All 16 (100%) animals had histological lesions involving the costal cartilage that included matrix degeneration and mineralization, reduced cellularity, and evidence of chondrocyte necrosis...
April 2017: Toxicologic Pathology
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
#17
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/28421967/lung-tumor-induction-by-26-week-dermal-application-of-1-2-dichloroethane-in-cb6f1-tg-rash2-mice
#18
Mayuko Suguro, Takamasa Numano, Mayumi Kawabe, Yuko Doi, Norio Imai, Yukinori Mera, Seiko Tamano
Short-term alternatives to traditional 2-year carcinogenic studies in rodents are being actively pursued. Recently, a 26-week short-term carcinogenicity study using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the evaluation of chemical carcinogenesis. However, an acceptable short-term carcinogenic study model for dermally applied products is still lacking. To investigate the suitability of using the rasH2 mouse to test carcinogenic potential, 1,2-dichloroethane (1,2-DCE) was dermally applied to rasH2 mice: 1,2-DCE is a known carcinogen that causes lung bronchiolo-alveolar adenomas and adenocarcinomas when administered topically, orally, or by inhalation exposure; 1,2-DCE at a dose level of 126 mg/mouse in 200 μl acetone or acetone alone (vehicle control) was applied to the dorsal skin of 10 mice of each sex 3 times a week for 26 weeks...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28421966/regulatory-forum-review-utility-of-in-vitro-secondary-pharmacology-data-to-assess-risk-of-drug-induced-valvular-heart-disease-in-humans-regulatory-considerations
#19
REVIEW
Thomas Papoian, Gowraganahalli Jagadeesh, Muriel Saulnier, Natalie Simpson, Arippa Ravindran, Baichun Yang, Adebayo A Laniyonu, Imran Khan, Ana Szarfman
Drug-induced valvular heart disease (VHD) is a serious side effect linked to long-term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B) agonists. Safety assessment for off-target pharmacodynamic activity is a common approach used to screen drugs for this undesired property. Such studies include in vitro assays to determine whether the drug is a 5-HT2B agonist, a necessary pharmacological property for development of VHD. Measures of in vitro binding affinity (IC50, Ki) or cellular functional activity (EC50) are often compared to maximum therapeutic free plasma drug levels ( fCmax) from which safety margins (SMs) can be derived...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28351296/regulatory-forum-opinion-piece-use-and-utility-of-animal-models-of-disease-for-nonclinical-safety-assessment-a-pharmaceutical-industry-survey
#20
Sherry J Morgan, Jessica Couch, Peggy Guzzie-Peck, Douglas A Keller, Ray Kemper, Monicah A Otieno, Robert J Schulingkamp, Thomas W Jones
An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies...
April 2017: Toxicologic Pathology
journal
journal
27666
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"