Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.

We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20-22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain <200 mg/dL, whereas after IK Tx, three animals required minimal doses of insulin (1-3 U/day) and one animal was insulin free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression.

Cardiorespiratory fitness, physical activity patterns and coronary risk factors in preadolescent boys.

The relationships between cardiorespiratory fitness, daily physical activity, and selected coronary artery disease (CAD) risk factors were evaluated in a sample of 91 preadolescent boys. Cardiorespiratory fitness was assessed (VO2max). Physical activity level was assessed using daytime heart rate telemetry. CAD risk factors included total cholesterol, fasting triglycerides, HDL-cholesterol, LDL-cholesterol, fasting blood glucose, systolic and diastolic blood pressures, and body fat content. The mean value of VO2max exhibited significant negative relationship with body fat percent (r = -0.55). Controlling the effects of age, body mass index and body fat percent resulted in a significant inverse relationship between physical activity and systolic (r = -0.29) and diastolic (r = -0.28) blood pressures. Analysis of data by quartiles revealed significant differences only in body fat percent across fitness categories, while no significant differences were detected in the other CAD risk factors. However, higher HDL-cholesterol and lower triglycerides levels were observed in those boys with higher levels of physical activity. It was concluded that except with body fatness, cardiorespiratory fitness is not strongly associated with lower CAD risk factors, while physical activity level was significantly associated with lower blood pressure level but not with the other CAD risk factors.