Differential Effects of Anionic,Cationic, Nonionic,and Physiologic Surfactants on the Dissociation, α-Chymotryptic Degradation,and Enteral Absorption of Insulin Hexamers

Various surfactants were investigated to compare their effects on insulin dissociation, -chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate procine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of -chymotrypsin (0.5 µM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/ proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1–5 mM. However, extensive charge–charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An -chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the -chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min. The results further emphasize the importance of the degree of insulin aggregation on its enteral transport.     

Ba2+ differentially inhibits the Rb+ efflux promoting and the vasorelaxant effects of levcromakalim and minoxidil sulfate in rat isolated aorta

The K⁺ channel openers activate ATP-sensitive K⁺ channels (K_ATP) in vascular smooth muscle and induce relaxation. In this study, the relationship between these two effects was examined in rings of rat aorta using levcromakalim and minoxidil sulfate as the openers and Ba²⁺ as the K⁺ channel blocker; K⁺ channel opening was assessed by determining the rate constant of ⁸⁶Rb⁺ efflux from the preparation.Ba²⁺ inhibited the ⁸⁶Rb⁺ efflux stimulated by levcromakalim in a noncompetitive manner with an IC₅₀ value of 29 M and a Hill-coefficient of 1.2. At concentrations > 300 M, Ba²⁺ increased the tension of rat aortic rings concentration-dependently. Levcromakalim relaxed contractions to Ba²⁺ (0.5 and 1 mM) with potencies similar to those determined against KCl (25 mM) or noradrenaline as spasmogens (EC₅₀ values 15–40 nM). The vasorelaxant effect against Ba²⁺ was inhibited by the K_ATP channel blockers, glibenclamide and tedisamil, and abolished in depolarizing medium (55 mM KCl). At 3 mM Ba²⁺, levcromakalim was still able to transiently induce complete relaxation; however, within 1 h oscillations in tension developed, leading to a stable level of only 15% relaxation. A similar level of relaxation was achieved against 10 mM Ba²⁺ whereas the combination of 0.5 mM Ba²⁺ and 3 M tedisamil blocked the relaxant effect of levcromakalim completely. With minoxidil sulfate as the K_ATP channel opener the results of the ⁸⁶Rb⁺ efflux and tension experiments were similar to those obtained with levcromakalim.It is concluded that Ba²⁺ is more potent in inhibiting the K⁺ channel opening than the vasorelaxant effects of the openers. On the basis of the ⁸⁶Rb⁺ efflux experiments it is estimated that at least 97% of the channels opened by the activators can be blocked without major effects on vasorelaxation suggesting a dissociation between the two effects. However, if the block is pushed to extremes ( 99.95%) the vasorelaxant effect of the openers is also abolished suggesting a link between both effects. This paradoxon remains to be solved.     

十二烷基硫酸钠在天然水体中的降解作用

本文研究了十二烷基硫酸钠在天然水体中的降解作用,结果表明十二烷基硫酸钠在天然水体中的降解主要依赖于微生物的降解。微生物最适降解条件为ｐＨ６．５～９．４和３６℃左右。降解作用随温度升高（４～３６．５℃）和微生物浓度增大而加快,用十二烷基硫酸钠预先驯化微...     

镁对脑缺血早期脑组织中谷氨酸及一氧化氮含量的影响

为研究镁在脑缺血早期对神经元保护作用的机制,用电凝法建立大鼠大脑中动脉缺血模型,在造模前给大鼠注射２０ｇ／Ｌ硫酸镁,观察镁对脑组织中谷氨酸（Ｇｌｕ）及一氧化氮（ＮＯ）含量的影响。结果显示,高浓度镁可明显降低脑缺血皮质中Ｇｌｕ、ＮＯ含量,在缺血组Ｇｌｕ、ＮＯ的峰值浓度分别为９．８７、４４．９７ｎｍｏｌ／ｇ,而在加镁组两者浓度分别为７．６８、３３．９２ｎｍｏｌ／ｇ。提示：镁对脑缺血早期神经元的保护作用与其降低脑组织中Ｇｌｕ及ＮＯ含量有关。     

硫酸奈替米星注射液与硫酸丁胺卡那注射液临床疗效及安全性的比较

为评价硫酸奈替米星的临床疗效及安全性,在１７０例急性细菌感染性病人中作多中心临床研究。结果显示：硫酸奈替米星的有效率（９５．３％）显著高于对照药硫酸丁胺卡那的有效率（８４．１％）,试验组病人咳痰和腰痛症状的平均下降显著高于对照组;硫酸奈替米星治疗后细菌清除率达９７．２％;２组病人不良反应发生率均为４．８％,对照组中有２例（３．２％）出现耳鸣、１例（１．６％）听力减退,但试验组病人用药后未发现听力异常。结论：硫酸奈替米星临床疗效优于硫酸丁胺卡那且较少耳毒性。     

色甘胺醇气雾剂的高效液相色谱测定法

目的： 建立高效液相色谱法同时测定色甘胺醇气雾剂中的２ 个有效成分色甘酸钠和硫酸沙丁胺醇。方法： 采用Ｃ１８ 色谱柱, 以０－０２ ｍｏｌ·Ｌ－ １ 醋酸铵（ 用冰醋酸调节ｐＨ 为６－０ ±０－１） － 甲醇（１００∶３０） 为流动相, 检测波长为２２７ ｎｍ－ 结果： 色甘酸钠和硫酸沙丁胺醇的平均回收率（ ｎ ＝ ５）分别为９９－１２ ％ 和９９－９８ ％ ; 精密度（ ＲＳＤ） 分别为１－１ ％ 和１－０ ％ 。结论： 该测定方法简便快速     

Ultracytochemical studies of the blood-meningeal barrier (BMB) in rat spinal cord

Summary Alkaline phosphatase(AP),5-nucleotidase(5N) and nucleoside diphosphatase (NDPase) activities were studied by cytochemical methods applied to light and electron microscopy in the microvasculature of spinal cord leptomeningeal strips of normal and protamine sulfate (PS) treated rats. The increased permeability to intravenously injected horseradish peroxidase was observed in some segments of microvessels of PS treated rats. Enhanced formation of plasmalemmal pits and deep invaginations, formation of numerous pinocytic vesicles and the appearance of channel-like structures in the cytoplasm of endothelial cells were the most striking ultrastructural evidence of increased permeability of the affected microvessels. All of these structures also showed activity of AP, and to lesser extent, of NDPase; 5N activity was mainly associated with the delimiting membranes of pinocytic vesicles. Our data present evidence that a shift of enzymatic activity from luminal to abluminal surface of affected endothelial cells results from membrane flow accompanying increased transport activity via formation of pinocytic vesicles and channel-like structures.Supported in part by a grant from NINCDS No. 17271-01Visiting scientist from the Neurological Institute of the University of Vienna, Vienna, Austria     

Collagen shields and intraocular drug delivery: concentration of gentamicin in the aqueous and vitreous of a rabbit eye after lensectomy and vitrectomy

Five albino New Zealand rabbits underwent bilateral lensectomy and vitrectomy. All left eyes were fitted with a collagen shield that had been soaked for 5 min in 2.0 mL of gentamicin solution (40 mg/mL for IV use). Right eyes were treated with fortified gentamicin drops (13.6 mg/mL) every 30 min for 12 hrs. Aqueous and vitreous specimens were obtained at the following time intervals: 1, 2, 4, 8, 12 and 24 hrs.We found the gentamicin concentrations to be higher in the aqueous of all eyes treated with fortified gentamicin drops. Only those eyes treated with fortified gentamicin drops attained a therapeutic drug level (4g–9g/mL) in the aqueous. Therapeutic drug levels were not attained in the vitreous of either treatment group.