Intermittent treatment with parathyroid hormone (PTH) increases bone mass in experimental animals and humans. In vitro studies have suggested that the anabolic effect of PTH may be mediated by local growth factors. However, the relevance of these findings to in vivo situations remains unclear. In this study, we examined a time course of daily s.c. injections of hPTH(1-34) on the skeletal concentration of insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor (TGF-.3) in the proximal tail vertebrae of male rats. PTH caused a time and dose-dependent increase in the bone mineral density of the lumbar spine. This anabolic effect on bone mass was accompanied by progressive increases in bone matrix-associated IGF-I and TGF-fl1. Increases in IGF-I and TGF-1i1 became apparent after four and eight weeks of PTH treatment respectively and persisted through week 12. PTH had no effect on circulating IGF-I, suggesting that the increase of bone matrix IGF-I was due to the local effect of PTH on bone tissue directly rather than to an increase of circulating IGF-I. These data are consistent with the hypothesis that IGF-I and TGF-f81 may play a role as local mediators of the anabolic effects of PTH on bone metabolism. (J. Clin. Invest. 1995. 96:767-774.)
The racemic compound carvedilol possesses two complementary pharmacological effects, vasodilation and beta-blockade. The R- and S-enantiomers of carvedilol and the racemate were investigated with respect to the beta-blocking, vasodilating, and hypotensive actions. In agreement with results obtained with other beta-blockers, only the S-enantiomer of carvedilol exerts beta-blocking effects. In contrast, no substantial difference between the enantiomers could be seen with respect to alpha-blockade. The greater hypotensive activity of S-carvedilol may be attributed to beta-blockade, which inhibits counter-regulatory mechanisms provoked by vasodilation. From these results it is concluded that there is a rationale for using carvedilol as the racemate. Using the S-enantiomer would lead to relatively strong beta-blockade with only a weak vasodilating effect. The R-enantiomer alone would act only as a hypotensive agent without beta-blockade.
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