Kazuyuki Kitamura

Hepatic changes in the acute phase of streptozotocin (SZ)-induced diabetes in mice.

We have reported the streptozotocin (SZ)-induced hepatic lesions in the subacute phase (4 to 12 weeks after the treatment), which are characterized by appearance of oncocytic hepatocytes, cytomegalic hepatocytes and bile duct hyperplasia. In this study, we focused on the acute phase (6 to 48 hours after the treatment) of the SZ-induced hepatic lesions of mice to clarify the onset of the hepatic alterations, especially before the induction of hyperglycemia. Livers were taken from 8-week-old Crj:CD-1 (ICR) male mice at 6, 12, 24, 36 and 48 hours after the 200 mg/kg b.w. of SZ-injection. SZ-induced hyperglycemia was noted at 36 and 48 hours after the treatment, but the hepatic changes including lipid peroxidation, mitochondrial swelling, peroxisome proliferation and inhibition of hepatocyte proliferation occurred before the elevation of the serum glucose levels. The present findings indicate the direct effects of SZ on hepatocytes rather than the secondary effects of diabetes, and certain correlations between the hepatocytic changes in the acute phase and those in the subacute one. In addition, ulcer and submucosal edema of the gallbladder were observed at 36 or 48 hours after the SZ-treatment, which can be a novel finding in SZ-treated animal.

Hematological and morphological investigation of thrombogenic mechanisms in the lungs of phenylhydrazine-treated rats.

Abnormality in hematological condition including hemolytic disorders has been suggested one of the risk factor of pulmonary thrombosis. We previously reported that phenylhydrazine (PHZ) could induce acute thrombosis in the rat lung. In this study, time-related hematological and histopathological changes were evaluated in PHZ-treated rats to reveal the pathogenesis of pulmonary thrombosis in hemolytic condition. Male Sprague-Dawley rats were administered PHZ at 40 mg/kg/day daily for up to 4 days (n=6). At 24 h after the last administration (i.e. on days 1, 2, 3, or 4), animals were euthanized and samples were subjected to hematology, light microscopy, and electron microscopy. PHZ-treated rats developed severe anemia on day 1 or later. On day 2 and after, congestion in the alveolar septa corresponding to accumulation of deformed/ghost erythrocytes in the alveolar capillaries was observed, which was the earliest change that preceded thrombus formation. Focal fibrin deposition in the alveolar septa was noted on day 3 and it expanded widely by day 4, while endothelial injury were minimally noted just on day 4. These congestive/thrombotic changes were predominant in the pulmonary capillaries. Changes in hemostatic parameters were noted only on day 4; which were prolonged prothrombin time and activated partial thromboplastin time, greatly increased plasma thrombin-antithrombin complex levels with statistical significance, and slightly decreased fibrinogen levels. In conclusion, the trigger of acute pulmonary thrombosis in PHZ-treated rats was considered to be regional stasis resulting from blockage caused by the deformed erythrocytes, and subsequent systemic hemostatic disruption.

Spontaneous amphophilic focus in the liver of a young Sprague-Dawley rat

Altered hepatocellular focus was histopathologically observed in the liver of a 6-week-old Sprague-Dawley rat. The hepatocytes within this lesion had diffusely eosinophilic cytoplasm with scattered basophilia and slightly enlarged nuclei with prominent nucleoli. Based on these cytological characteristics, the lesion of these hepatocytes was classified as an amphophilic focus. This is the first report to describe spontaneous amphophilic focus in a young rat.