Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Toxicol Pathol ; 45(2): 260-266, 2017 02.
Article in English | MEDLINE | ID: mdl-28056663

ABSTRACT

There is limited direction in the literature or regulatory guidance on determination of adversity for clinical pathology (CP) biomarkers in preclinical safety studies. Toxicologic clinical pathologists representing the American Society for Veterinary Clinical Pathology-Regulatory Affairs Committee and Society of Toxicologic Pathology-Clinical Pathology Interest Group identified principles, overall approach, and unique considerations for assessing adversity in CP data interpretation to provide a consensus opinion. Emphasized is the need for pathophysiologic context and a weight-of-evidence approach. Most CP biomarkers do not have the potential to be adverse in isolation, regardless of magnitude of change. Rather, they quantify or describe the impact of effects, provide adjunct or supportive information regarding a process or pathogenesis, and provide translational biomarkers of effect. Most often, CP changes are part of a constellation of findings that collectively are adverse. Thus, most CP changes must be interpreted in conjunction with other study findings and require contextual and integrative interpretation. Exceptions include critical CP changes without correlates that indicate a health risk in the tested species. Overall, CP changes should not be interpreted in isolation and their adversity is best addressed with an integrated approach.


Subject(s)
Biomarkers/analysis , Drug-Related Side Effects and Adverse Reactions/diagnosis , Guidelines as Topic , Pathology, Clinical/standards , Pathology, Veterinary/standards , Toxicity Tests/standards , Animals , Drug-Related Side Effects and Adverse Reactions/veterinary , Humans , No-Observed-Adverse-Effect Level , Quality Control , Risk Assessment , Toxicity Tests/veterinary
2.
Toxicol Pathol ; 45(2): 267-274, 2017 02.
Article in English | MEDLINE | ID: mdl-27879436

ABSTRACT

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. Myeloid to erythroid (M:E) ratios and the percentage of total cells for each cell type were determined from differential cell count data. M:E ratios ranged from 0.6:1 to 2.3:1. Percentages of total granulocytic cells, total erythroid cells, and lymphocytes ranged from 26.6% to 60.6%, 25.7% to 52.2%, and 5.5% to 40.4%, respectively. Monocytes, plasma cells, mast cells, and mitotic figures were typically <1% of total cells. Notable morphologic findings included occasional giant neutrophilic metamyelocytes and band neutrophils, ring-shaped band neutrophil nuclei, metarubricyte nuclear blebbing and binucleation, multiple or nonfused megakaryocyte nuclei, and emperipolesis. These results represent cytological bone marrow findings from healthy control cynomolgus monkeys utilized in nonclinical toxicology studies and provide insight into expected background variability.


Subject(s)
Bone Marrow Cells/drug effects , Bone Marrow Cells/pathology , Bone Marrow Examination , Guidelines as Topic , Macaca fascicularis , Toxicity Tests/methods , Animals , Blood Cell Count , Bone Marrow Examination/veterinary , Female , Male , Sex Characteristics , Specimen Handling/veterinary , Toxicity Tests/veterinary
4.
Vet Clin Pathol ; 41(4): 502-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23121408

ABSTRACT

A 1-year-old female Boer goat was presented with a 1-day history of pigmenturia, anorexia, and shivering. Anemia was not present initially, but progressive hemolytic anemia developed subsequently and was characterized by the finding of Heinz bodies in both intact RBCs and in ghost cells and the presence of atypical fusiform RBCs. Plasma biochemical analysis revealed increased activities of aspartate aminotransferase and gamma-glutamyltransferase, hyperbilirubinemia, and azotemia. Histopathologic examination of a liver biopsy revealed necrosis of individual hepatocytes and intracytoplasmic rhodamine-positive granules, consistent with copper. Copper concentration in ante-mortem hepatic tissue was increased, and a diagnosis of copper toxicosis was made. Despite supportive therapy, the goat continued to decline and was euthanized. Necropsy findings included hepatic necrosis and hemoglobinuric nephrosis. Freshly collected specimens of liver and kidney had markedly increased copper concentrations. The mineral composition of the water, grass hay, and goat chow was evaluated, and toxins and significant mineral imbalances were not found. The underlying cause of the hepatic accumulation and subsequent release of copper remains unclear in this goat. Recently, Boer goats have been recognized as being prone to copper toxicosis and may be more susceptible than other breeds; similar to sheep, Boer goats may experience a hemolytic crisis secondary to copper toxicosis.


Subject(s)
Anemia, Hemolytic/veterinary , Chemical and Drug Induced Liver Injury/veterinary , Copper/poisoning , Goat Diseases/chemically induced , Goat Diseases/diagnosis , Heinz Bodies/ultrastructure , Anemia, Hemolytic/chemically induced , Animals , Biopsy , Blood Chemical Analysis/veterinary , Chemical and Drug Induced Liver Injury/diagnosis , Copper/analysis , Diagnosis, Differential , Euthanasia, Animal , Fatal Outcome , Female , Goats , Hematologic Tests/veterinary , Hemoglobinuria/chemically induced , Hemoglobinuria/veterinary , Hemolysis , Urinalysis/veterinary
SELECTION OF CITATIONS
SEARCH DETAIL
...