No abstract

This study was conducted to characterize spontaneous testicular and epididymal microscopic findings in eighty control beagle dogs from toxicity studies. Hypospermatogenesis, characterized by randomly scattered missing spermatids and/or spermatocytes within seminiferous tubules, was observed in 75% of dogs six to seven months of age and declined to fewer than 10% in dogs over eleven months of age. Atrophy/hypoplasia of seminiferous tubules, characterized by subcapsular triangular clusters of tubules containing no germ cells, was observed in 25 to 40% of dogs under twelve months old, decreasing with age to 14 to 17% in dogs twelve to thirty-six months old. Retained spermatids, multinucleate giant cells, intracytoplasmic vacuoles (presumably in Sertoli cells), and swollen spermatocytes were common findings of minimal severity. Six-and seven-month-old dogs had lower testicular weights, less filling of the epididymal tails with sperm, and a two-fold higher incidence of abnormal epididymal content compared to dogs more than eight months of age. Most male beagles were histologically sexually mature by eight to nine months of age. This study confirms published reports that dogs at least ten months of age at necropsy usually are adequate for routine microscopic evaluation of the testes. If evaluation of spermatogenesis is critical, the incidental findings can be minimized by using males over twelve months of age.

Abdominal ultrasound examinations of 20 dogs with confirmed leptospirosis were reviewed retrospectively for renal abnormalities. Three dogs had a normal ultrasound examination. The remaining 17 dogs had sonographic abnormalities of the kidneys. These abnormalities, seen either alone or in combination, included renalmegaly (n=10), pyelectasia (n=9), increased cortical echogenicity (n=15), perinephric effusion (n=5), and a medullary band of increased echogenicity (n=6). At our institution, the medullary band of increased echogenicity has only been seen in dogs with leptospirosis and may therefore be a specific sonographic sign for this disease.

An 8-year-old female spayed Cocker Spaniel mix breed dog was presented with generalized erythroderma, scaling and alopecia. Radiographs of the thorax demonstrated a discrete lung mass which was aspirated using ultrasound guidance and cytological analysis revealed large abnormal lymphocytes. Similar cells were observed in the peripheral blood and in skin biopsies. The cells in the skin biopsies were epidermotropic, indicative of an uncommon cutaneous lymphoma termed cutaneous T cell lymphoma (CTCL), sometimes also called mycosis fungoides. Immunohistochemical staining of a skin biopsy was positive for the CD3 antigen demonstrating that the lymphocyte infiltrate was of a T-cell lineage. The presence of neoplastic lymphocytes in the epidermis and peripheral blood indicate that this is a rare variant of Cutaneous Epidermotropic Lymphoma (CEL) called Sézary syndrome based on nomenclature used in the human literature. An unusual feature of this dog, not seen in previous cases, was the presence of a discrete neoplastic lung mass.

Peroxisomal proliferator-activated receptor (PPAR)-␣ is a ligand-activated transcriptional factor that regulates genes involved in lipid metabolism and energy homeostasis. PPAR-␣ activators, including fibrates, have been used to treat dyslipidemia for several decades. In contrast to their known effects on lipids, the pharmacological consequences of PPAR-␣ activation on cardiac metabolism and function are not well understood. Therefore, we evaluated the role that PPAR-␣ receptors play in the heart. Our studies demonstrate that activation of PPAR-␣ receptors using a selective PPAR-␣ ligand results in cardiomyocyte necrosis in mice. Studies in PPAR-␣-deficient mice demonstrated that cardiomyocyte necrosis is a consequence of the activation of PPAR-␣ receptors. Cardiac fatty acyl-CoA oxidase mRNA levels increased at doses in which cardiac damage was observed and temporally preceded cardiomyocyte degeneration, suggesting that peroxisomal ␤-oxidation correlates with the appearance of microscopic injury and cardiac injury biomarkers. Increased myocardial oxidative stress was evident in mice treated with the PPAR-␣ agonists coinciding with increased peroxisomal biomarkers of fatty acid oxidation. These findings suggest that activation of PPAR-␣ leads to increased cardiac fatty acid oxidation and subsequent accumulation of oxidative stress intermediates resulting in cardiomyocyte necrosis. (Am J

The immunosuppressive effect of experimental Boophilus microplus infestation on bovine peripheral blood lymphocytes (PBL) and on host antibody production to a protein antigen (ovalbumin) was examined. Boophilus microplus infestation caused a marginal decrease in the percentage of T lymphocytes in PBL, which was observed in both lightly (5000 larvae) and heavily (40,000 larvae) infested cattle, and began at the second infestation and continued until the end of the fourth infestation. The percentage of B lymphocytes in heavily tick-infested cattle was less than that in non-infested control cattle after the fourth infestation. The response of PBL from tick-infested cattle to phytohemagglutinin (PHA) was always less than that of tick-free cattle after the second infestation. No noteworthy differences were detected between the three stages of tick infestation, that is, 1 week before the peak of adult engorgement, the middle of the peak and 1 week after all ticks had dropped. Boophilus microplus saliva (100 microliters ml-1) suppressed 47% of the response of bovine PBL to PHA in vitro. This suppressive effect of saliva may contribute to the lower responsiveness of PBL from tick-infested cattle. Antibody production by tick-infested cattle was examined during the third and fourth heavy tick infestation. Tick-infested cattle showed a diminished response against ovalbumin after the second immunization. The immunosuppressive effects of tick infestation may play an important role in tick survival or in the transmission of tick-borne diseases in the field.

Simian retrovirus (SRV) type D is a common cause of simian acquired immunodeficiency syndrome (SAIDS)

Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and metabolism of the test substance to help assess human risk.