Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.

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Background. Telomeric deletions contribute to genetic instability and may represent an important mechanism of carcinogenesis. Amplification of the c‐erbB‐2 gene has been demonstrated in breast carcinoma. The clinical significance of telomeric deletions and c‐erbB‐2 gene amplification therefore was studied in patients with breast disorders. Methods. The Southern blot analysis was used to measure telomeric length as well as the c‐erbB‐2 gene amplification of breast carcinomas, adjacent normal breast tissues, fibroadenomas, and cases of gynecomastia. Results. Significant reductions in telomeric length and concentration were observed in all breast tissues when compared to placental DNA. Mean telomeric lengths were lowest in carcinomas and fibroadenomas. There were no significant differences, however, in the telomeric lengths among tissues from patients with breast carcinomas, fibroadenomas, or gynecomastia. The degree of telomeric deletion correlated significantly with histologic grade and was most notable in Grade 3 (scirrhous) breast carcinoma. The extent of telomeric deletion reflects the histologic aggressiveness of breast carcinoma, and telomeric reduction already can be seen in the adjacent normal breast tissues from patients with breast cancer. c‐erbB‐2 gene amplification was observed in 26.8% of the patients with breast carcinoma. c‐erbB‐2 gene amplification was not observed, however, in patients with fibroadenomas or gynecomastia. The degree of telomeric deletion did not correlate with c‐erbB‐2 gene amplification, tumor size, clinical stage, steroid receptors, or prognosis. Telomeric length was shorter in lymph node‐negative tumors than in lymph node‐positive tumors. Conclusions. These findings indicate that a shorter telomere length reflects growth advantage in breast cancer tissue, and telomeric reduction may promote cancer progression. Cancer 1994; 73:2978–84.

Maternal adrenocortical function was studied by measuring plasma cortisol and urinary free cortisol during gestation.

Adult male Wistar rats were subjected to acute and chronic immobilization stress. Changes in plasma levels of LH, FSH and testosterone and in the content of testicular inhibin and testosterone were studied. Plasma LH levels decreased significantly in response to both acute and chronic stress. Significant decreases in plasma testosterone content were also observed after chronic stress. In contrast, plasma FSH and testicular bioassayable inhibin content did not change after acute or chronic stress. These findings indicate that in male rats immobilization stress induced a dissociation in LH and FSH responses, and decreased testosterone while inhibin remained unaffected.