Biomedical subjects

Yasuhiro Yoshikawa

Publications and source records attributed to Yasuhiro Yoshikawa.

76 records · Page 5Linked to original sources

PubMed2002

The effect of probucol on atherosclerosis in streptozotocin-induced diabetic-hyperlipidemic APA hamsters in different stages of atherosclerosis.

We investigated the effect of probucol (PB) on atherosclerosis in streptozotocin (SZ)-induced diabetic-hyperlipidemic APA hamsters in three different stages, the early, middle and late stages of atherosclerosis. Male APA hamsters were injected intraperitoneally with SZ or vehicle alone (citrate buffer; CB) as a control at the age of 8 weeks. At 6 weeks after injection (WAI) of SZ or CB (the early stage), 14 WAI (the middle stage) and 26 WAI (the late stage), animals were assigned to PB treated- or non-treated groups (CBPB, SZPB, CB, SZ). After 8 weeks of PB administration with diet, the aorta was taken from each animal for assessment of atheromatous lesions and blood samples were subjected to serum biochemical analysis and the measurement of blood lipid peroxide (LPO). In the middle stage, PB treatment significantly decreased serum total cholesterol level, slightly decreased LPO, and also tended to reduce the lesion area, although no statistical difference was seen. There was no marked effect of PB treatment in the early and late stages. These findings suggest that single use of PB has little effect on atherosclerosis of a hyperglycemia-hyperlipidemia animal model.

Animals↗

PubMed2002

Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia.

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller. The islets had hardly any insulin-immunoreactive cells and consisted of cells stained by anti-glucagon and somatostatin antibodies. One, three and six months after SZ-injection, a small number of cells with vacuolative changes, which were positive for PAS staining, were observed in most islets and the vacuolated cells were stained mainly by anti-insulin antibody. In addition, a number of PCNA-positive cells were observed, especially in the periphery of the vacuolated cells, while TUNEL-positive cells were not detected. This data suggests that beta-cells proliferating as a result of the replication of the resident beta-cells in islets had fallen into degeneration and necrosis by a stress, such as the glycogen deposition in hyperglycemia and hyperlipidemia. Consequently, secretion of insulin was maintained at low levels, which allowed the hamsters to live without insulin therapy in the diabetic condition for over 6 months.

Animals↗

PubMed2002

Safe and efficient methods of autologous hematopoietic stem cell transplantation for biomedical research in cynomolgus monkeys.

We have established safe and efficient methods for autologous hematopoietic stem cell (HSC) transplantation in cynomolgus monkeys (Macaca fascicularis) that include regimens of supportive care to ensure survival during hematopoietic reconstitution following otherwise lethal total body irradiation. Eleven young adult cynomolgus monkeys were studied. Bone marrow was aspirated from the ilium and/or tuber ischiae after administration of recombinant human stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). Using the immunomagnetic selection method, CD34+ cells were then isolated (90 to 95% pure) as a fraction containing HSCs. Just prior to transplantation, the animals received myeloablative total body irradiation-500 to 550 cGy daily for two days. The monkeys re-infused with CD34+ cells developed moderate to severe myelosuppression, with some animals requiring intravenous hyperalimentation, antibiotic administration, and blood transfusion. Hematopoiesis was restored in all animals after transplantation. It took 12 days, on average, until the peripheral white blood cell count reached more than 1,000 cells/microl. Up to two years after transplantation, signs of radiation-induced pneumonitis or other radiation-related disorders were not evident at the aforementioned dose of irradiation. This transplantation model will be useful for testing new approaches using HSCs for therapy of many diseases and will offer unique insights into the biology of these cells.

Animals↗

PubMedDate not supplied

Amelioration of the beta-cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments.

BACKGROUND: In our recent report, probucol treatment ameliorated glucose intolerance and increased the insulin-positive area in the pancreas of streptozotocin (SZ)-induced diabetic APA hamsters. The data suggested that the beneficial effects of probucol treatment on beta-cell function might result from its additive effect as an antioxidant. Here, we examined the antioxidant effects on the beta-cell function in SZ-induced diabetic APA hamsters treated with three different agents, N-acetyl-L-cysteine (NAC), aminoguanidine (AG) and pyridoxamine (PM). METHODS: The control (CB group) and diabetic (SZ group) hamsters were treated with NAC, AG or PM for four weeks from several days after SZ injection. RESULTS: Non-fasting plasma glucose and glycoalbumin levels were significantly reduced in SZ animals by NAC or PM treatment. Glucose tolerance test revealed that fasting plasma glucose levels of SZNAC and SZPM animals were low, similar to the corresponding control animals. Thirty minutes after glucose injection, amelioration in the plasma glucose levels of SZNAC and SZPM animals was observed. Immunohistochemistry revealed that the pancreata of SZNAC, SZAG and SZPM animals showed significantly higher percentages of insulin-positive area than those of non-treated SZ animals. The plasma 8OHdG and malondialdehyde plus 4-hydroxy-2-nonenal (4HNE) levels were significantly decreased especially in SZNAC and SZPM animals. 4HNE-positive cells stained by anti-4HNE antibody were reduced in the islets of each agent-treated animal. SZNAC and SZPM animals showed significantly increased beta-cell proliferation determined by insulin and BrdU double staining. All SZ groups treated with NAC, AG or PM had the high expression levels of Reg and INGAP, which are known to be expressed in regenerating islets. CONCLUSIONS: These data suggest that NAC and PM treatment of SZ-injected diabetic hamsters reduces oxidative stress and restores beta-cell function, but that AG treatment has little beneficial effect on the diabetic conditions of SZ-injected hamsters.

Acetylcysteine↗