Patterns of use of sildenafil among commercially insured adults in the United States: 1998-2002.

Sildenafil is increasingly being marketed to younger healthcare consumers. The purpose of this study was to profile sildenafil use in commercially insured, adult beneficiaries. Annual ambulatory prescription claims data from 1998 to 2002, for a nationwide, random sample of over 5 million life-years of commercially insured adults (aged > or =18 y), were examined retrospectively. The overall prevalence of sildenafil use increased from 0.8% (1998) to 1.4% (2002), an 84% increase. While the growth in use slowed in older males, use became more pronounced in younger males and females and decreased in older females. The fastest growing segment of users was found to be males aged 18-45 y. The proportion of users who had two or more claims for a medication that is suspected of inducing erectile dysfunction (ED) and/or a marker for a suspected ED-inducing disease decreased over the study period. Our findings suggest that use may increase among younger male and female patients and those without an underlying etiologic reason for use.

Vitamin E blocks the cytotoxic effect of gamma-linolenic acid when administered as late as the time of onset of cell death--insight into the mechanism of fatty acid induced cytotoxicity.

Certain polyunsaturated fatty acids can selectively kill tumor cell lines while causing little to no harm to normal cell lines. However, the mechanism of this cytotoxicity is only partially understood. Antioxidants such as vitamin E have been shown to be capable of completely blocking the cytotoxic response when administered concomitantly with the fatty acid. We report here that when vitamin E was added as late as 6 days following fatty acid treatment, at a time point when the process of cell death was well underway, any further development of cell death was blocked. This implies that the mechanism of fatty acid induced cytotoxicity does not involve a gradual compromising of the cell over the 5-7 day time course of cell death. Instead, the event triggering cell death is an oxidative phenomenon occurring over a short time span of minutes or hours, not days, and is completely blocked by vitamin E.

Stress modulates cholesterol-induced changes in plasma and liver fatty acid composition in rats fed n-6 fatty acid-rich oils.

The effects of dietary cholesterol (CH) and isolation stress on fatty acid compositions of plasma and liver cholesteryl ester and phospholipids were compared in growing rats fed an 18:2n-6 or an 18:3n-6 enriched semisynthetic diet for 2 weeks. Stress, CH-feeding, and dietary fats had no significant effects on plasma CH level, but CH-feeding alone elevated the liver CH concentrations. CH-feeding also modulated the liver polyunsaturated fatty acid compositions, i.e., increasing 18:2n-6 levels, and reducing 20:4n-6 levels, indicating an inhibition of the enzymes, delta-6 and delta-5-desaturases. The extent of these changes was less in rats fed 18:3n-6 than in those fed 18:2n-6. Stress, which alone had no significant effects on plasma and liver fatty acid compositions, attenuated the CH-induced changes of fatty acid levels.

Effect of essential fatty acid depletion on tissue phospholipid fatty acids in spontaneously hypertensive and normotensive rats.

Weanling male spontaneously hypertensive (SHR) and normotensive (WKY) rats were maintained on a fat-free semisynthetic diet and killed at various intervals. The effects of fat-depletion on the appearance of essential fatty acid (EFA) deficiency symptoms, the progressive changes of major fatty acids in plasma, liver, heart, and kidney phospholipids (PL), and in skin total lipids were compared between these two strains. After five weeks on the diet, the slower growth and the appearance of EFA deficiency symptoms became evident in SHR. In general, fat-depletion reduced the levels of n-6 fatty acids, whereas it increased those of 20:3n-9. However, the fat-depletion induced reduction of 18:2n-6 in heart PL and 20:4n-6 in kidney, while the elevation of 20:3n-9 in plasma, heart, and kidney PL were greater in WKY than in SHR. As a result, the elevation of biochemical EFA deficiency index--20:3n-9/20:4n-6 ratio--was greater in WKY than in SHR. In comparison with WKY, the concentrations of liver triacylglycerols and the weights of adipose tissues in SHR were reduced to a greater extent, indicating an active catabolism of triacylglycerols in SHR. This study suggests that the earlier appearance of morphological symptoms of EFA deficiency in SHR was not associated with the reducing n-6 EFA levels or with an elevation of triene/tetraene ratio, but possibly to a reduced supply of n-6 EFA for skin prostaglandin synthesis.

The effect of dietary n-6 and n-3 polyunsaturated fatty acids on blood pressure and tissue fatty acid composition in spontaneously hypertensive rats.

Effects of dietary n-6 and n-3 fatty acids (FAs) on blood pressure (BP) and tissue phospholipid (PL) FA composition in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were compared. Male weanling SHR and WKY were fed a fat-free semisynthetic diet supplemented with 10% (w/w) fats containing (a) 78% 18:2n-6 (LA-rich), (b) 20% LA and 55% 18:3n-3 (LN-rich), or (c) 11% LA and 3% LN (CON) for seven weeks. Dietary fats did not affect the BP elevation, but significantly altered the FA composition of brain, adrenal gland, renal medulla and cortex PL in SHR. The LA-rich diet increased n-6 FA while it reduced n-3 FA levels. The levels of 20:4n-6 were not significantly different between animals fed the LA-rich and the CON diets. LN-rich diet increased the levels of n-3 FAs, while it reduced those of n-6 FAs. However, the extent of change was significantly less in SHR than in WKY. In all dietary groups, SHR, as compared to WKY, had a relatively higher level of the 2 series prostaglandin (PG) precursor, 20:4n-6, and a relatively lower level of the 1 and 3 series PG precursors, 20:3n-6 and 20:5n-3. The possibility that the unbalanced eicosanoid FA precursor levels might contribute to the development of hypertension in this animal model is discussed.