小儿急性中毒143例分析

本研究拟通过观察谷氨酰胺合成酶（GS）、谷氨酰胺酶（PAG）、琥珀酸脱氢酶（SDH）和Na^＋-K^＋-ATPase活性的改变,探讨地卓西平（MK-801）和牛磺酸对锰致大鼠兴奋性毒性的影响。将大鼠按体重随机分成4组,第1组为对照组,皮下注射0．9％的氯化钠;第2组为单纯染锰组,皮下注射0．9％的氯化钠;第3、4组为预处理干预组,分别皮下注射0．3μmnol／kg的MK-801和1mmol／kg的牛磺酸,皮下注射2h后,第1组腹腔注射0．9％的氯化钠,第2-4组腹腔注射200μmol／kg的氯化锰,染锰25d,MK-801和牛磺酸隔日注射一次,共预处理13次。最后一次染毒后24h处死大鼠,切取大脑皮质和纹状体。测定大脑皮质SDH、Na^＋-K^＋-ATPase的活性;测定脑纹状体GS、PAG的活性。结果显示单纯染锰组与对照组比较,纹状体GS、脑皮质SDH和Na^＋-K^＋-ATPase的活性明显降低（P〈0．01）,纹状体PAG的活性升高。MK-801预处理干预组与单纯染锰组比较,纹状体GS和脑皮质Na^＋-K^＋-ATPase的活性明显升高,脑皮质SDH的活性升高,纹状体PAG的活性降低;牛磺酸预处理干预组纹状体CS和脑皮质SDH的活性明显升高,脑皮质的Na^＋．K^＋-ATPase活性升高。提示MK-801和牛磺酸对锰所致兴奋性毒性均有不同程变的拮抗作用。     

正交法改进牛磺酸颗粒制粒工艺

目的：改进牛磺酸颗粒的制粒工艺，提高收率。方法：采用正交法对工艺进行优化。结果：改进后的工艺，制粒收率由原工艺的81．8％提高到94．5％。结论：改进后的牛磺酸颗粒制粒工艺收率和生产效率明显提高，工艺可行。     

Effects of systemic and regional taurine on skeletal muscle function following ischaemia-reperfusion injury.

INTRODUCTION: Tissues subjected to prolonged ischaemia are paradoxically further damaged when their perfusion is restored. The mechanisms underlying this ischaemia-reperfusion injury are complex, but oxidative attack is a central feature. Among the therapeutic agents used to attenuate ischaemia-reperfusion injury, endogenous agents such as taurine which form part of the native defence mechanism against oxidative damage are of particular interest. METHODS: Using a model of hindlimb ischaemia-reperfusion injury in the rat, taurine solution was administered either into the operated hindlimb, into the systemic circulation, or both. Contraction strengths of gastrocnemius biopsies from the operated and contralateral (control) hindlimbs of each animal were measured. RESULTS: Fast twitch strength was impaired significantly by ischaemia-reperfusion injury, and taurine injected into the operated limb conferred partial protection. A similar trend was observed for tetany, but protection by taurine was not statistically significant for tetanic contraction strength. CONCLUSION: Preservation of fast twitch strength following ischaemia-reperfusion injury by administration of taurine before ischaemia has clinical potential. However, delivery to the affected tissues during ischaemia presents technical difficulties.     

牛磺酸对肝微粒体膜的保护作用研究

以四氯化碳（ＣＣｌ４，１０ｍｍｏｌ．Ｌ＾－１）与分离的大鼠肝微粒体共同温育（３７℃，１０，２０，３０，６０，１２０分钟），预先或同时加入牛磺酸（Ｔａｕｒｉｎｅ，Ｔａｕ），观察其对肝微粒体膜的保护作用，结果表明，ＣＣｌ４引起孵育体系中外源性加入的还原型谷胱甘肽（ＧＳＨ）、微粒体膜蛋白巯基（Ｐ－ＳＨ）含量降低，膜脂流动性（ＬＦＵ）降低，Ｔａｕ对此均有罗明显的保护作用；在用Ｔａｕ预孵育的实验体系中，Ｔａ     

Contralateral Circling Behaviour Induced by Intranigral Injection of Taurine in Rats

Abstract A study was made of the effect of unilateral injection of taurine into the substantia nigra on the behaviour of rats. Taurine (10–200 μg) induced a dose-dependent contralateral circling behaviour. The maximum intensity of circling after doses of 100–200 μg of taurine was reached within 10 min. and the circling lasted for about 4–5 hrs. There was neither ipsilateral circling nor stereotyped behaviour. Intranigral injection of isethionic acid, a metabolite of taurine, induced weak ipsilateral circling of short duration. Pretreatment with bicuculline (3 mg/kg intraperitoneally) or strychnine (0.25 mg/kg intraperitoneally) significantly inhibited the taurine-induced circling. A dose of 1 mg/kg but not of 0.5 mg/kg of haloperidol (subcutaneously) significantly decreased the intensity of the taurine-induced circling. Pretreatment with atropine (10 mg/kg intraperitoneally) had no significant effect on the circling behaviour. Besides the dopaminergic nigrostriatal pathway, the non-dopaminergic nigral output pathways also seem to be involved in the taurine-induced circling behaviour. The results show that taurine may play some role in the function of the substantia nigra.     

Suppression of conditioned drinking by taurine and related compounds.

Mice were conditioned to respond for water reinforcements on a FR-5 schedule. Taurine, injected intraperitoneally at doses of 9.0, 13.8, and 21.3 mmole/kg 30 min prior to the experimental session, produced a dose-related decrease in both the initial response rate and total number of reinforcements received by mice deprived of water for 24 hr. The structural analogues of taurine (aminomethanesulfonic acid, 3-aminopropanesulfonic acid, beta-alanine, cysteamine, and glycine) also produced a hypodipsia. Doses of taurine which produced depression of responding for water reinforcements were used which produced no suppression of spontaneous motor activity, rotarod performance, Sidman avoidance, or shuttle-box avoidance. After intraperitoneal injection, the concentration of taurine increased in the hypothalamus and medulla, but not in other brain areas. We suggest that taurine might be acting by specifically depressing areas of the hypothalamus which stimulate drinking.     

Taurine and hypotaurine transport by a single system in cultured neuroblastoma cells

The kinetics of mutual inhibition of taurine and hypotaurine uptake were studied using neuroblastoma C1300 cells as neuronal model. Hypotaurine and GABA inhibited taurine uptake competitively, increasing the apparent K_m. High-affinity uptake of hypotaurine was completely abolished and the low-affinity component competitively inhibited by taurine. GABA affected noncompetitively low-affinity hypotaurine uptake, whereas the effect on high-affinity uptake was competitive, with an increase in the apparent K_m. All structural analogues tested inhibited taurine and hypotaurine uptakes similarly. The most potent inhibitors were β-alanine and 2-guanidinoethanesulphonic acid. The mutual inhibition and similar specificity profiles of taurine and hypotaurine uptakes showed that these amino acids employ a single transport system in neuroblastoma cells. Competitive inhibition by GABA of the high-affinity uptake of taurine and hypotaurine further suggests that also GABA uses the same carrier system.     

Effect of electrical stimulation on the influx and efflux of taurine in brain slices of newborn and adult rats

Summary Brain slices from adult and newborn rats were incubated with [³⁵S]taurine in Krebs-Ringer bicarbonate medium at pH 7.4. In both age groups electrical stimulation increased the oxygen consumption of the slices. The influx of taurine only increased in slices from adult rats. The influx conformed to Michaelis-Menten kinetics. In slices from adult rat V_max increased and apparent K_m remained unchanged during electrical stimulation. Both K_m and V_max were greater in adult than in newborn rats. The efflux of taurine from slices depended on the intracellular concentration of taurine and was not measurably influenced by electrical stimulation.     

Effects of Taurine and Taurine Analogues on the Phosphorylation of a 44 kDa Protein Present in a Mitochondrial Subfraction of the Rat Heart: Partial Characterization of the 44 kDa Phosphoprotein

Recent studies suggest that taurine (2-aminoethanesulfonic acid) is involved in the regulation of protein phosphorylation in excitable tissues such as the retina, brain and heart. In order to determine the structural requirements for the effect of taurine on the phosphorylation of a 44 kDa protein(s), a series of taurine analogues were tested in an in vitro assay using a subcellular mitochondrial fraction of rat heart. Inhibitors of the phosphorylation of the 44 kDa protein include taurine and close structural analogues of taurine such as aminoethylhydrogen sulfate and α-sulfo-β-alanine. Secondary amines with the taurine structure partially locked into a saturated 5-membered ring such as (±) piperidine-3-sulfonic acid and 1,2,3,4-tetrahydroquinoline-8-sulfonic acid also possess inhibitory activity. Sulfone analogues of taurine such as 2-aminoethylmethylsulfone, a non-restricted taurine analogue with maximal conformational flexibility about its amino and sulfone moieties, and (±) 3-aminotetrahydrothiopyran-1.1-dioxide, an analogue containing the sulfone moiety in a six-membered ring structure, were found to be more potent inhibitors of phosphorylation than taurine despite the fact that the sulfone moiety is neither an isosteric nor isoelectronic substitution for the sulfonic acid moiety. The results of this study indicate that the inhibition of the phosphorylation of the 44 kDa protein in a rat heart mitochondrial fraction is relatively specific for the taurine structure. Two analogues of taurine with unsaturated rings containing a primary sulfonic acid and a secondary amine, pyridine-3-sulfonic acid and quinoline-8-sulfonic acid, were observed to be stimulators of the phosphorylation of the 44 kDa protein. In addition, 2-aminobenzenesulfonic acid also stimulated phosphorylation. Phase separation experiments with Triton X-114 suggest that the 44 kDa phosphoprotein is a soluble protein and not an integral membrane protein of the mitochondria. Phosphate incorporation into specific amino acids was determined by two-dimensional electrophoresis on celluloses plates and was found exclusively in the serine residues.     

Taurine allosterically inhibits binding of [S]-t-Butylbicyclophosphorothionate (TBPS) to rat brain synaptic membranes

The modulatory effects of taurine on [³⁵S]-t-Butylbicyclophosphorothionate (TBPS) binding to rat brain synaptic membranes were evaluated and compared with that of GABA. Taurine allosterically inhibited TBPS binding by interacting with a bicuculline-sensitive site, similar to GABA. Taurine was as effective as GABA but less potent. The potency of taurine inhibition of TBPS binding varied among brain regions with cerebellum > olfactory bulb > cortex, similar to that of GABA. Inhibition of TBPS binding to cortical membranes measured under nonequilibrium conditions yielded a dynamic biphasic inhibition curve that was similarly shaped for GABA and taurine. The effect of taurine on TBPS binding was pharmacologically specific in that β-alanine and guanadinoethanesulfonate were as effective as taurine, while hypotaurine and -aminoethylhydrogen sulfate were only partially effective at high concentrations, and isethionic acid was without effect. Taurine, similar to GABA enhanced the effects of pentobarbital on TBPS binding when present at concentrations that were otherwise ineffective on their own. The results of these studies support the notion that taurine interacts with the GABA recognition site of the GABA_A receptor complex.