The reason for the 3-to 4-h delay between a rise in plasma free fatty acid (FFA) levels and the development of insulin resistance remains unknown. In the current study, we have tested the hypothesis that the delay may be caused by the need for plasma FFAs to first enter muscle cells and to be re-esterified there before causing insulin resistance. To this end, we have determined intramyocellular triglyceride (IMCL-TG) content with proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy in healthy volunteers before and 4 h after lowering of plasma FFAs (with euglycemic-hyperinsulinemic clamping) or after increasing plasma FFAs (with lipid plus heparin infusions). Increasing plasma FFAs (from 516 to 1,207 mol/l or from 464 to 1,857 mol/l, respectively) was associated with acute increases in IMCL-TG from 100 to 109 ؎ 5% (P < 0.05) or to 133 ؎ 11% (P < 0.01), respectively, and with a significant increase in insulin resistance (P < 0.05 after 3.5 h). Lowering of plasma FFAs from 560 to 41 mol/l was associated with a tendency for IMCL-TG to decrease (from 100 to 95 ؎ 3%). Changes in plasma FFAs correlated linearly with IMCL-TG (r ؍ 0.74, P < 0.003). The demonstration that acute changes in plasma FFAs were accompanied by corresponding changes in IMCL-TG and with the development of insulin resistance, taken together with previous reports of a close correlation between IMCL-TG and insulin resistance, supported the notion that accumulation of IMCL-TG is a step in the development of FFA-induced insulin resistance.
The past decade saw rises in heterosexual transmission of HIV and i.v. drug use, especially in the population aged >50 years. The CDC reports that the incidence of new HIV infection is stabilizing in men aged 30-39 years and even falling in men aged 20-29 years. Gonorrhea is well known to increase infectivity for HIV and other STDs. Although the rates of gonorrhea infection fell throughout the early 1990s, they increased by 9% between 1997 and 1999. The number of sildenafil prescriptions has increased by almost 80% over the last few years. Although there may be multiple contributory factors for these findings, to our knowledge this is the first paper in the urologic literature to examine such trends in the older male population, especially in the light of newly available medications for erectile dysfunction.
Evaluation and management of gunshot wounds to the penis may potentially be complex. Retrograde urethrogram should be performed in all cases except the most insignificant and superficial wounds. We describe our technique of penile exploration and artificial erection, noting excellent results in patients for whom follow-up is available. Additional studies are needed to prospectively evaluate techniques for management of gunshot urethral injuries.
Aims: Previous studies have shown increased density of M 2 receptors in hypertrophied rat bladders that possess an M 2 contractile phenotype. The aim of the current study is to determine whether human bladders with an M 2 contractile phenotype also have a greater density of bladder M 2 receptors. Materials and Methods: Human bladders were obtained from 24 di¡erent organ transplant donors. Darifenacin and methoctramine a⁄nity was determined by the rightward shift of cumulative carbachol concentration contractile response curves for each bladder. Radioligand binding and immunoprecipitation was used to quantify M 2 and M 3 subtypes in isolated detrusor muscle and urothelium. In addition, pig bladder muscle and urothelial receptors were quanti¢ed for comparison. Results: In the human urothelium total, M 2 and M 3 muscarinic receptor density is signi¢cantly negatively correlated with the a⁄nity of darifenacin for inhibition of contraction of the detrusor muscle. In the detrusor muscle there is no correlation between receptor density and darifenacin a⁄nity for inhibition of contraction. Muscarinic receptor density is greater in the muscle than in the urothelium in human bladders whereas in the pig bladder the density is greater in the urothelium than in the muscle. Conclusions: The greater density of urothelial muscarinic receptors in human bladders with lower darifenacin a⁄nity, indicative of a greater contribution of M 2 receptors to the contractile response, points towards a possible role of the urothelium in controlling M 2 mediated contractile phenotype. In comparison between human and pig bladders, the distribution of muscarinic receptor subtypes in the muscle and urothelium are quite di¡erent.
Brain activity changes as well as the areas of activation after treatment of lower urinary tract symptoms in patients with an anticholinergic medication or placebo are different in the 2 groups. Whether this finding represents action at the central nervous system or the bladder level is not known.
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