石杉碱甲类似物的研究Ⅲ．N－甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲（１）是从中草药石杉属植物千层塔（ＬｙｃｏｐｏｄｉｕｍｓｅｒｒａｔｕｍＴｈｕｎｂ．）中分得的一种高效可逆的乙酰胆碱酯酶抑制剂，临床试验证实它对早老性痴呆症有显著疗效。本文报道Ｎ－甲基吡啶酮石杉碱甲类似物２和３的合成。２－甲氧基－５－甲氧羰基－１１－亚甲基－５，９－甲撑环辛－７－烯并吡啶（９）在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮１０，再用甲醇钠和碘甲烷甲基化得Ｎ－甲基吡啶酮１１，１１经碱性水解，Ｃｕｒｔｉｕｓ重排和氨基的脱保护得Ｎ－甲基吡啶酮石杉碱甲类似物２。通过类似的途径从中间体２－甲氧基－５－甲氧羰基－７－甲基－１１－酮－５，９－甲撑环辛－７－烯并吡啶（１４）合成了类似物３。类似物２和３的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Mounting and calibration of stairs on piezoelectric force platforms

To calculate the centre of pressure using piezoelectric force plates mounted on pads, no net tensile stresses may be imposed on the surface of the plate. This condition is violated when stairs are attached to the plates, unless the plates are preloaded. Typical shear forces encountered when climbing stairs were used to determine required preloads of approximately 16.4 N/cm step height. Vertical and horizontal loads were applied at known locations on the steps, and points of application were calculated. Deviations were within ± 3 mm. The effect of point of application inaccuracy on calculated joint moments is considerable. A 2 cm medial shift in the point of application resulted in calculated peak knee abduction/adduction moment errors of 35%.     

The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes

Indoleamine 2,3-dioxygenase (IDO), a flavin-dependent enzyme that catalyzes the conversion of tryptophan to kynurenine, is induced in peripheral blood mononuclear cells by interferon-gamma (IFN gamma). Interleukin-4 (IL-4) is a cytokine that modulates the functional properties of monocytes/macrophages, and we investigated the effects of IL-4 on IDO. We showed that IL-4 inhibited the induction of IDO mRNA and IDO activity by IFN gamma in human monocytes. The inhibitory effect was evident with as little as 2 U/mL of IL-4. These results provide the first evidence that a cytokine can provide a negative signal for IDO expression and that IL-4 can influence the catabolism of tryptophan.