Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR) have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). Previous reports from our laboratory on streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax) and affinity (Kd) of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors

Two isoperimetric inequalities for the Sobolev constant

In this note we prove two isoperimetric inequalities for the sharp constant in the Sobolev embedding and its associated extremal function. The first such inequality is a variation on the classical Schwarz Lemma from complex analysis, similar to recent inequalities of Burckel, Marshall, Minda, Poggi-Corradini, and Ransford, while the second generalises an isoperimetric inequality for the first eigenfunction of the Laplacian due to Payne and Rayner.Comment: 11 page

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve Comparison of stentless versus stented bioprostheses

AbstractOBJECTIVESThe objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise.BACKGROUNDStentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise.METHODSThirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test. Valve effective orifice area and mean transvalvular pressure gradient at rest and during peak exercise were successfully measured using Doppler echocardiography in 30 of the 38 patients.RESULTSAt peak exercise, the mean gradient increased significantly less in stentless than in stented bioprostheses (+5 ± 3 vs. +12 ± 8 mm Hg; p = 0.002) despite similar increases in mean flow rates (+137 ± 58 vs. +125 ± 65 ml/s; p = 0.58); valve area also increased but with no significant difference between groups. Despite this hemodynamic difference, exercise capacity was not significantly different, but left ventricular (LV) mass and function were closer to normal in stentless bioprostheses. Overall, there was a strong inverse relation between the mean gradient during peak exercise and the indexed valve area at rest (r = 0.90).CONCLUSIONSHemodynamics during exercise are better in stentless than stented bioprostheses due to the larger resting indexed valve area of stentless bioprostheses. This is associated with beneficial effects with regard to LV mass and function. The relation found between the resting indexed valve area and the gradient during exercise can be used to project the hemodynamic behavior of these bioprostheses at the time of operation. It should thus be useful to select the optimal prosthesis given the patient’s body surface area and level of physical activity