Attenuation of delta opioid receptor-mediated signaling by kainic acid in neural cells: involvement of protein kinase C and intracellular Ca2+.

The potential modulation of opioid receptor signaling by kainic acid (KA) has been investigated in neuroblastoma x glioma NG 108-15 hybrid cells and neuroblastoma SK-N-SH cells. Acute incubation of KA significantly attenuated delta opioid receptor (DOR) signaling induced by the DOR agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE), as measured by activation of G proteins and inhibition of cAMP accumulation. The attenuation by KA was time- and dose-dependent and could be blocked by antagonists of kainate/AMPA receptors, suggesting possible mediation through kainate/AMPA receptors. KA attenuation of DPDPE-stimulated G protein activation was reversed by inhibitors of protein kinase C or by removal of both extracellular Ca2+ and intracellular Ca2+. In contrast, NMDA attenuation of DPDPE-stimulated G protein activation was independent of intracellular Ca2+, indicating that different mechanism(s) may underlie the modulation effect of KA and NMDA. This notion was further supported by the results that KA did not alter nociceptin/orphanin FQ-stimulated G protein activation in NG 108-15 cells but NMDA did. In addition, pretreatment of NG 108-15 cells with antagonists of kainate/AMPA receptors blocked the acute desensitization of DOR signaling. These data provide evidence that KA may be involved in the modulation of opioid receptor signal transduction.     

Three new taxane diterpenoids from seeds of the Chinese yew, Taxus yunnanensis and T. chinensis var. mairei

Three new taxane diterpenoids were isolated from the seeds of the Chinese yew, Taxus yunnanensis Cheng et L. K. Fu and T. chinensis var. mairei Cheng et L. K. Fu. The structures were established as 1beta,10beta-dihydroxy-9alpha,13alpha-diacetoxy-5alpha-(3'-dimethylamino-3'-phenyl)-propionyloxytaxa-4(20),11-diene, 5alpha-hydroxy-9alpha,100,13alpha-triacetoxy-11(15-->1)abeotaxa-4(20),11-di-ene, and 5alpha,13alpha-dihydroxy-9alpha,10beta-diacetoxy-11 (15-->1 )abeo-taxa-4(20),11-diene on the basis of 1D, 2D NMR, and mass spectral analysis.     

Mechanism, structure-activity studies, and potential applications of glutathione S-transferase-catalyzed cleavage of sulfonamides.

The mechanism of sulfonamide cleavage of PNU-109112, a potent HIV-1 protease inhibitor, by glutathione-S-transferase (GST) was investigated in the presence of reduced GSH. GST-catalyzed sulfonamide cleavage takes place via the nucleophilic attack of GSH on the pyridine moiety of the substrate with formation of the GS-para-CN-pyridinyl conjugate, the corresponding amine, and sulfur dioxide. Structure activity studies with a variety of sulfonamides indicate that an electrophilic center alpha to the sulfonyl group is required for cleavage. Substituents that withdraw electron density from the carbon atom alpha- to the sulfonyl group facilitate nucleophilic attack by the GS(-) thiolate bound to GST. The rate of sulfonamide cleavage is markedly affected by the nature of the electrophilic group; replacement of para-CN by para-CF(3) on the pyridine ring of PNU-109112 confers stability against sulfonamide cleavage. On the other hand, stability of sulfonamides is less dependent on the nature of the amine moiety. These principles can be applied to the synthesis of sulfonamides, labile toward cellular GST, that may serve as prodrugs for release of bioactive amines. Tumors are particularly attractive targets for these sulfonamide prodrugs as GST expression is significantly up-regulated in many cancer cells. Another potential application could be in organic synthesis, where protection of amines as the corresponding activated sulfonamides can be reversed by GST/GSH under mild conditions.     

Important role of endothelium-derived hyperpolarizing factor in shear stress--induced endothelium-dependent relaxations in the rat mesenteric artery.

Shear stress is one of the most important stimulators for the release of endothelium-derived relaxing factors. Although shear stress-induced release of nitric oxide (NO) has been extensively investigated, it remains to be elucidated whether endothelium-derived hyperpolarizing factor (EDHF) contributes to the endothelium-dependent relaxations to shear stress. This study was designed to address this point in the isolated rat mesenteric artery. Large mesenteric arteries (400-500 microm) and resistance mesenteric arteries (150-250 microm) of the rat were precontracted with phenylephrine (at 80 mm Hg of perfusion pressure), and the changes in vessel diameter in response to variable flow (0-300 microl/min) were continuously examined. The relative contributions of vasodilator prostaglandins, NO, and EDHF were analyzed by the inhibitory effects of indomethacin (10(-5) M), N(G)-nitro-L-arginine (L-NNA, 10(-4) M), and KCl (40 mM), respectively. The shear stress-induced relaxations were totally endothelium dependent in both-sized blood vessels, and the contribution of NO was more prominent in large arteries than in resistance arteries, whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large- and intermediate-conductance Ca2+ -activated K channels) and apamin (an inhibitor of small-conductance Ca2+ -activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. These results indicate that EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, where K channels, especially calcium-activated K channels, appear to be involved.     

促皮质素对甲醛引起大鼠脊髓内生长抑素的影响

目的：研究促皮质素（Ｃｏｒ）对甲醛引起大鼠脊髓内生长抑素及其合成的影响,方法：采用免疫组织化学,免疫组织化学双重染色法和原位杂交技术。结果：足底注射甲醛使大鼠脊髓背角内ＦＬＩ,ＳｏｍＬＩ,Ｓｏｍ－ＬＩ／ＦＬＩ和ＰＰＳ－ｍＲＮＡ神经元数均对较对照组显著增多,单独ｉｐＣｏｒ对脊髓背角ＦＬＩ和Ｓｏｍ－ＬＩ无明显影响。但是,ｉｐＣｏｒ显著抑制甲醛引起的背角内ＦＬＩ,Ｓｏｍ－ＬＩ,Ｓｏｍ－ＬＩ／ＦＬＩ和ＰＰ     

国产生长激素治疗生长激素缺乏症的疗效观察

了解国产人生长激素（ｈＧＨ）的治疗效果。方法：对１５例未经生长激素治疗的生长激素缺乏症（ＧＨＤ）病人（均经精氨酸和可乐宁两项生长激素激发试验明确诊断,生长激素峰值均小于 １０ μｇ／Ｌ）应用国产分泌型基因重组人生长激素（ｒｈＧＨ）进行治疗,剂量为０．１ｕ／（ｋｇ·ｄ）睡前脐周皮下注射,治疗时间６个月。结果：１５例ＧＨＤ病人６个月身高平均增长（６．３４±０．９４）ｃｍ,生长速度由治疗前的（３．３３±０．４９）ｃｍ／年增加到治疗后的（１２．６８±１．８６）ｃｍ／年。结论：国产人生长激素治疗效果达到国外同类产品水平,而价格仅为进口产品的１／６左右。可安全有效地用于治疗ＧＨＤ身材矮小病人。     

平阳霉素联合地塞米松治疗颌面部大面积海绵状血管瘤

目的：观察平阳霉素（ＰＹＭ）联合地塞米松（ＤＸＭ）治疗颌面部大面积海绵状血管瘤的临床疗效和不良反应。方法：对９例临床确诊的颌面部范围６ｃｍ×７ｃｍ～１０ｃｍ×１２ｃｍ之间的大面积海绵状血管瘤,采用每周１次多点多方向瘤腔内注射药物,比较治疗前后患者的反应和肿瘤的形成变化。结果：全部病例肿瘤消失,无明显不良反应,经８个月～４６个月观察,临床治愈率为１００％。结论：ＰＹＭ联合ＤＸＭ能够治愈颌面部大面积海绵状血管瘤,具有完整保存组织正常形态和功能的特点,克服了单独使用ＰＹＭ带来的不良反应,提示两药在治疗上有协同作用。     

1991年我国8省已婚妇女婚姻状况分析

利用１９９１年我国与美国北卡罗莱纳大学人口中心合作项目＂中国经济、人口和营养健康状况调查＂的调查资料,对中国辽宁、江苏、山东、河南、湖北、湖南、广西、贵州共８个省的４２８８名５０岁以下的已婚妇女的婚姻状况进行了统计分析。结果表明：１９９１年８省城、乡妇女在婚比为８７．７１％,离婚和分居比为０．４４％,丧偶比为１０．３０％。妇女已婚比２０岁以下为０．９０％,２０～３０岁为６６．９２％,３０岁以上为９７．７７％。１９９１年８省妇女平均初婚年龄为２３．７０岁,普通生育率达１．９０３％,生育１胎的比例为４６．９２％,生育２胎或２胎以上者占３２．６３％和２０．４４％,男女性别比１．１１：１。从计划生育指标来看,城、乡妇女晚婚率为４６．６６％,总节育率为６３．４１％,绝育率达２４．９７％,避孕率为３１．８９％。城、乡主要使用的节育措施为绝育术和避孕环,各占４９．７１％和４４．４９％,而使用避孕套节育的只占１．００％,药物避孕占３．３６％。总的看来,８省妇女的婚姻较稳定,平均初婚年龄逐年推迟,普通生育率水平较低。计划生育工作成效显著,但某些地区仍存在早婚早育和多胎生育的现象。     

对99例髋臼骨折内固定治疗的分析

从1972年11月到1994年3月,401例髋臼骨折病人中的99例经手术治疗并获随访,包括30例双柱骨折,13例横骨折伴后壁骨折,9例后壁骨折,9例后柱骨折,9例前往骨折伴前壁骨折,13例T形骨折和16例横骨折.平均随访时间为7年(2～14).外科手术入路的选择,后入路53次,髂腹股沟入路23次,延长的髂股骨入路11次,放射状入路9次和结合性入路6次.复位情况用X线平片来评判,解剖复位的有59例(59.6%),接近解剖复位(<2mm的错位)的有19例(19.2%).总结果用Harris Hip Score来评判,优秀的有53例(53.5%),良好的有25例(25.3%),一般的有14例(14.1%),差的有7例(7%).并发症中,有10例(53%)为感染,7例(37%)为静脉栓塞.这些结果表明,对于错位严重的髋臼骨折,切开复位内固定是一种可以选择的治疗方法.     

山蒟醇提取物的抗血小板聚集作用?

以山蒟醇提取物在兔的体内和体外-体内进行抗血小板聚集实验。结果表明山蒟醇提取物可抑制由血小板活化因子和花生四烯酸所致的血小板聚集,对2者所致的血小板聚集（体外试验）的IC_（50）。分别为40． 34、345． 46 mg／L。静脉注射山蒟醇提取物30 mg／kg,15 min后产生的抗血小板聚集作用最明显,其对血小板活化因子和花生四烯酸所致的血小板聚集（体内-体外试验）的抑制率分别为82．75％和33．34％;血小板聚集的持续时间分别为60、30 min。这表明山蒟醇提取物对血小板活化因子作用有一定的选择性。