Toxicologic pathology
-
Toxicologic pathology · Dec 2015
ReviewMouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical Approaches, Pathologic Features, and Common Measurements.
Acute respiratory distress syndrome (ARDS) is a severe pulmonary reaction requiring hospitalization, which is incited by many causes, including bacterial and viral pneumonia as well as near drowning, aspiration of gastric contents, pancreatitis, intravenous drug use, and abdominal trauma. In humans, ARDS is very well defined by a list of clinical parameters. However, until recently no consensus was available regarding the criteria of ARDS that should be evident in an experimental animal model. ⋯ Murine ARDS models typically are defined by such features as pulmonary edema and leukocyte infiltration in cytological preparations of bronchoalveolar lavage fluid and/or lung sections. Common pathophysiological indicators of ARDS in mice include impaired pulmonary gas exchange and histological evidence of inflammatory infiltrates into the lung. Thus, morphological endpoints remain a vital component of data sets assembled from animal ARDS models.
-
Toxicologic pathology · Dec 2015
Utilizing Whole Slide Images for Pathology Peer Review and Working Groups.
This article describes the results of comparisons of digitally scanned whole slide images (WSIs) and glass microscope slides for diagnosis of tissues under peer review by the National Toxicology Program. Findings in this article were developed as a result of the data collected from 6 pathology working groups (PWGs), 1 pathology peer review, and survey comments from over 25 participating pathologists. For each PWG, 6-14 pathologists examined 10-143 tissues per study from 6- and 9-month perinatal studies and 2-year carcinogenicity studies. ⋯ The intra- and interobserver diagnostic variation did not appear to influence the conclusions of any study. Based upon user opinions collected from surveys, WSIs may be less optimal than glass slides for evaluation of subtle lesions, large complex lesions, small lesions in a large section of tissue, and foci of altered hepatocytes. These results indicate that, although there may be some limitations, the use of WSIs can effectively accomplish the objectives of a conventional glass slide review and definitely serves as a useful adjunct to the conduct of PWGs.
-
Toxicologic pathology · Oct 2015
GuidelineScientific and Regulatory Policy Committee Review: Review of the Organisation for Economic Co-operation and Development (OECD) Guidance on the GLP Requirements for Peer Review of Histopathology.
In 2014, the Organisation for Economic Co-operation and Development (OECD) issued guidance no. 16, Guidance on the GLP Requirements for Peer Review of Histopathology. The stated purpose of the guidance document is "to provide guidance to pathologists, test facility management, study directors and quality assurance personnel on how the peer review of histopathology should be planned, managed, documented, and reported in order to meet Good Laboratory Practice (GLP) expectations and requirements." On behalf of and in collaboration with the global societies of toxicologic pathology, the Society of Toxicologic Pathology initiated a review of OECD guidance no. 16. The objectives of this review are to provide a unified interpretation of the guidance, to recommend compliant processes for organizations to implement, and to avoid inconsistent process adaptations across the industry. This review of the guidance document is the product of a global collaboration with other societies of toxicologic pathology and provides a section-by-section international consensus view and interpretation of the OECD guidance on peer review.
-
Regenerative biology/tissue engineering offers potential solutions for the repair and augmentation of diseased tissues and organs. Tissue engineering technology platforms currently under development for organ regeneration may function in part by recapitulating key mechanistic and signaling pathways associated with embryonic organogenesis. Temporal observations of observed morphological outcomes from the regeneration of tubular organs provide insights into the mechanisms of action associated with the activation of regenerative pathways in preclinical animal models and humans. ⋯ These results provide the foundation for a regenerative technology applicable to hollow organs of the gastrointestinal (GI) tract including esophagus and small intestine. Factors affecting the efficacy of observed regenerative outcomes within the GI tract include the roles of vascularization, innervations, and mesenchymal signaling. These will be discussed in the context of an overall mechanism of adult regeneration potentially applicable by the tissue engineering and regenerative medicine industry for continued development of hollow neo-organ products.
-
Toxicologic pathology · Jan 2014
Consensus diagnoses and mode of action for the formation of gastric tumors in rats treated with the chloroacetanilide herbicides alachlor and butachlor.
A panel of pathologists (Panel) was formed to evaluate the pathogenesis and human relevance of tumors that developed in the fundic region of rat stomachs in carcinogenicity and mechanistic studies with alachlor and butachlor. The Panel evaluated stomach sections stained with hematoxylin and eosin, neuron-specific enolase, and chromogranin A to determine the presence and relative proportion of enterochromaffin-like (ECL) cells in the tumors and concluded all tumors were derived from ECL cells. Biochemical and pathological data demonstrated the tumor formation involved a nongenotoxic threshold mode of action (MOA) initially characterized by profound atrophy of the glandular fundic mucosa that affected gastric glands, but not surface epithelium. ⋯ The mucosal atrophy, together with the increased gastrin, stimulated cell growth in one or more ECL cell populations, resulting in neoplasia. ECL cell autocrine and paracrine effects led to dedifferentiation of ECL cell tumors. The Panel concluded the tumors develop via a threshold-dependent nongenotoxic MOA, under conditions not relevant to humans.