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Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg-1, 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle—regulated by both diet and CB1 receptor activity—through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD. [ABSTRACT FROM AUTHOR]

In this study, we developed a quantitative method with digital image analysis to evaluate the degree of gingival overgrowth (GO). and compared GO in kidney transplant patients treated with cyclosporin A (CsA) (n=21) or CsA-nifedipine (n=8) and a group of healthy controls (n=30). The method was reproducible and reliable. Our findings showed significant differences in papillary and gingival surface between controls and transplant patients treated with GO inducers. Gingival overgrowth index also differed significantly between controls and each patient group (p<0.01, Kruskal-Wallis test). The administration of the calcium channel blocker nifedipine potentiated the adverse effect of CsA: comparison of the morphometric findings revealed significant differences between patients treated with CsA alone and CsA 1 nifedipine in papillary area, dental area, and GO index (p<0.01, Mann-Whitney U-test). We conclude that the method of image analysis we developed is useful in assessing the degree of GO. [ABSTRACT FROM AUTHOR]