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Actions of NCX, PMCA and SERCA on Short-Term Facilitation and Maintenance of Transmission in Nerve Terminals~!2010-03-10~!2010-08-23~!2010-09-08~!

Residual Ca 2+ can accumulate in the nerve terminal during repetitive stimulation; thus, the basis for short-term facilitation (STF). The plasmalemmal Na + /Ca 2+ exchanger (NCX), the Ca 2+ -ATPase (PMCA) and the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA) on the endoplasmic reticulum are three important Ca 2+ regulatory processes in controlling (Ca 2+ )i. The role of these (Ca 2+ )i regulators in the development and maintenance of STF was addressed at the neuromuscular junction. When the NCX is compromised by reduced (Na + )o, the EPSP amplitudes decrease, but with KB-R7943 (a reverse blocker of NCX) the amplitude increases. Compromising the PMCA with pH 8.8 produces an increase in EPSP amplitudes, but treatments with carboxyeosin (a blocker of PMCA) produced mixed results. Blocking the SERCA increases EPSP amplitudes. Facilitation was only slighted altered in some conditions with these manipulations. The results support the view that release is not saturated during a plateau phase of STF since the terminal is able to reach a new plateau with higher stimulation frequency or an altered (Ca 2+ )i. Multiple approaches in compromising the NCX and PMCA are presented. These findings are significant because there is a rapid alteration in transmission when compromising Ca 2+ extrusion mechanisms during STF.

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Grape Seed Procyanidins Improve Diabetic Symptoms in Mice with Streptozotocin-Induced Diabetes

Grape seed procyanidins (GSPCs) are bioflavonoid polymers that have been shown to have health benefits. We assessed the antidiabetic effect of GSPC in mice. Mice with streptozotocin(STZ)-induced diabetes were orally or intrape- ritoneally administered saline or 40-100 mg GSPC/kg BW daily for 7-10 d. We monitored body weight, blood glucose levels, amounts of food and water consumed, and amounts of urine and feces excreted. On the final day, we analyzed plasma chemistry and found that GSPC, but not structurally related monomers (e.g., catechin and epicatechin), reduced the glucose levels, food and water intake, and urine and feces excreted, all of which had increased due to STZ administra- tion. This suggests a procyanidin-dependent effect of grape seed polyphenols on diabetes. Oral administration of GSPC was less effective within 9 d than was intraperitoneal administration of GSPC, suggesting that the effect is route- dependent. The decrease in diabetic blood glucose levels was reversible; when GSPC administration was stopped, glucose levels rose. However, although pretreatment with GSPC for 7 d did not completely prevent STZ-induced diabetic effects, it rapidly reduced them. Treatment with GSPC reduced fasting glucose levels and improved glucose tolerance in STZ- treated mice, in addition to decreasing STZ-stimulated levels of plasma triglyceride and cholesterol, creatinine, uric acid, and alkaline phosphatase activity. Moreover, GSPC suppressed the reduction in pancreatic islets and the decrease in plasma insulin hormone levels caused by STZ. Our findings indicate that GSPC improves hyperglycemia, polydipsia, polyuria, and polyphagia in mice with STZ-induced diabetes.

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Radiobiological Study of Retinal Microvessel Proliferation in Diabetic-like Rat Model

Progressive evolution of retinal vascular in diabetic retinopathy leads to blindness in up to 8,000 patients yearly. The major purpose of this investigation was to determine proton radiation dose response of the eye's retinal vascu- lature in the hypergalactosemia induced rat model of diabetic-like retinopathy and gain insight of possible role of proton radiotherapy in controlling diabetic retinopathy. A single dose range of proton radiation (8, 14, and 20 Gy) was delivered to one eye of each rat at 4 months following induction of hypergalactosemia. The opposite eye of each rat, which was not irradiated, showed normal progression of retinopathy. Stereologic techniques were used to quantify tissue parameters in situ in a retinal digest preparation that allowed unobstructed access to the vasculature. 15 months following 50% galactose diet, characteristic histopathological lesions of retinopathy such as capillary endothelial cell proliferation, capillary clo- sure, capillary microaneurysms, pericyte loss developed in non-irradiated eyes. The endothelial cell densities for rat re- ceiving 50% galactose diet were significantly higher than that of control (p<0.05). Proton irradiation inhibited significant endothelial cell proliferation at dose from 14Gy to 20Gy (p<0.05), yet not diminished pericyte loss at current dose sched- ule. These findings indicated beneficial effects of proton radiation on hypergalactosemia induced diabetic-like retinopa- thy. Our study should have an impact on further studies to optimize radiation treatment strategies for diabetic retinopathy.

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