山羊肝精口服液的研制与早中期白内障的防治

山羊肝精口服液是经多年临床经验及反复研究所得的成果,剂型恰当,工艺合理,质量可控,稳定性好。药效学试验说明,本制剂具有健壮身体,抗疲劳的功能。毒理学试验与临床观察说明山羊肝精口服液具有安全性。     

某部军事训练伤前瞻性流行病学研究

目的：了解军事训练伤的发生规律与特点。方法：采用前瞻性流行病学研究方法,对某部１９９７年３月至２月的军事训练伤进行调查。结果：该部军事训练伤的年度发生率为３０．０４％,上半年训练伤的发生率明显高于下半年,训练伤的发生率随年龄增加而逐渐下降,不同单位训练伤的发生率不同。在训练伤病例中以关节扭伤所占比例最大（３３．２１％）,受伤部位以肘,腿,踝和腕部为主,受伤课目以战术训练和５公里越野跑等所占比例高（     

烟草凝集物对家兔胚泡乳酸脱氢酶及过氧化脂质的影响

为探讨吸烟对胚泡发育的影响,观察了烟草凝集物对孕７天兔胚泡的过氧化脂质和乳酸脱氢酶的影响,结果表明,体外培养４ｈ时ＬＰＯ水平比２ｈ显示升高,４ｈＬＤＨ与２ｈＬＤＨ相比差异不显著。ＬＤＨ活力与ＣＳＣ剂量不相关,但ＬＰＯ有随ＣＳＣ剂量增加上升的趋势,其ｒ值接近Ｐ＝０．０５的显著性水平。提示ＣＳＣ有促进脂质过氧化反应的趋势。     

改良的巩膜隧道小切口不缝合白内障超声乳化人工晶体植入术

目的： 评价改良的巩膜隧道切口不缝合白内障超声乳化技术的疗效。方法： 对９１ 例老年性白内障行超声乳化并植入光学部为６ｍ ｍ 的 Ｐ Ｍ Ｍ Ａ 人工晶体, 外切口距角膜缘０５～１０ｍ ｍ , 内切口位于角膜缘内 ２０ｍ ｍ 的透明角膜处。结果： 术后一周内裸眼视力高于 ０５ 者达 ９３％ 。术前及术后一天、一周、一月、三月的角膜散光值分别为 ０７９±０２９ Ｄ、１１９±０５８ Ｄ、１０８±０４８ Ｄ、１０６±０５６ Ｄ和 １０７±０６３ Ｄ。结论： 改良的巩膜隧道切口不缝合超声乳化技术, 术后早期获得良好的裸眼视力, 角膜散光小, 可植入 Ｐ Ｍ Ｍ Ａ 人工晶体, 降低手术费用。     

Structure-based design of selective inhibitors of dihydrofolate reductase: synthesis and antiparasitic activity of 2, 4-diaminopteridine analogues with a bridged diarylamine side chain

As part of a larger search for potent as well as selective inhibitors of dihydrofolate reductase (DHFR) enzymes from opportunistic pathogens found in patients with AIDS and other immune disorders, N-[(2,4-diaminopteridin-6-yl)methyl]dibenz[b,f]azepine (4a) and the corresponding dihydrodibenz[b,f]azepine, dihydroacridine, phenoxazine, phenothiazine, carbazole, and diphenylamine analogues were synthesized from 2, 4-diamino-6-(bromomethyl)pteridine in 50-75% yield by reaction with the sodium salts of the amines in dry tetrahydrofuran at room temperature. The products were tested for the ability to inhibit DHFR from Pneumocystis carinii (pcDHFR), Toxoplasma gondii (tgDHFR), Mycobacterium avium (maDHFR), and rat liver (rlDHFR). The member of the series with the best combination of potency and species selectivity was 4a, with IC(50) values against the four enzymes of 0. 21, 0.043, 0.012, and 4.4 microM, respectively. The dihydroacridine, phenothiazine, and carbazole analogues were also potent, but nonselective. Of the compounds tested, 4a was the only one to successfully combine the potency of trimetrexate with the selectivity of trimethoprim. Molecular docking simulations using published 3D structural coordinates for the crystalline ternary complexes of pcDHFR and hDHFR suggested a possible structural interpretation for the binding selectivity of 4a and the lack of selectivity of the other compounds. According to this model, 4a is selective because of a unique propensity of the seven-membered ring in the dibenz[b,f]azepine moiety to adopt a puckered orientation that allows it to fit more comfortably into the active site of the P. carinii enzyme than into the active site of the human enzyme. Compound 4a was also evaluated for the ability to be taken up into, and retard the growth of, P. carinii and T. gondii in culture. The IC(50) of 4a against P. carinii trophozoites after 7 days of continuous drug treatment was 1.9 microM as compared with previously observed IC(50) values of >340 microM for trimethoprim and 0.27 microM for trimetrexate. In an assay involving [(3)H]uracil incorporation into the nuclear DNA of T. gondii tachyzoites as the surrogate endpoint for growth, the IC(50) of 4a after 5 h of drug exposure was 0.077 microM. The favorable combination of potency and enzyme selectivity shown by 4a suggests that this novel structure may be an interesting lead for structure-activity optimization.     

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.     

Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.     

脊柱内固定对邻近运动节段的影响

为研究脊柱内固定对邻近关节突关节的影响,应用成年山羊20只,随机分长节段、短节段固定组和对照组,进行3个月、6个月的光镜、扫描电镜及透射电镜观察。结果发现近头侧2个邻近脊椎的关节突关节都出现了退变。长节段固定后邻近关节突关节早期就出现了较严重的退变,而短节段固定后其退变程度较轻。研究认为内固定后邻近运动节段的高应力环境是其关节突关节退变的主要因素,并有可能导致邻近运动节段的不稳定。     

阿芙唑嗪及多沙唑嗪十二指肠给药及对猫尿道压的选择性作用

目的观察不同给药途径对芙唑嗪（Ａｌｆ）和多沙唑嗪（Ｄｏｘ）降尿道反压的选择性作用。方法 电刺激麻醉猫腹下神经以长高尿道压,比较十二指肠和静脉两种途径给药时,Ａｌｆ和Ｄｏｘ降低平均动脉血压（ＭＢＰ）及尿道压（ＵＰ）的作用。结果：相同电刺激条件（１０Ｈｚ,２５Ｖ）Ａｌｆ肠道给药与静脉给经时ＥＤ２０（ＢＰ）／ＥＤ５０（ＵＰ）比值为１０．９：４．３;Ｄｏｘ两种给药途径的比值为３．１：２．１,Ａｌｆ十二指肠     

ACE基因多态性及循环中酶活性与EHT的关系及赖诺普利对其疗效的观察

对１１０例原发性高血压（ＥＨＴ）患者和１６３例正常对照者取血测定其血管紧张素转换酶（ＡＣＥ）基因Ｉ与 Ｄ多态性及循环中酶活性。高血压组Ｄ等位基因频率高于对照组,分别为 ０．５１８　２和０．４３２ ５（Ｐ＜０．０５）。两组中ＡＣＥ活性均存在ＤＤ＞ＩＤ＞Ⅱ。高血压组及对照组ＩＤ型ＡＣＥ活性分别为３１４．１±６７．９４和２５８．３５±６４．１１（Ｐ＜０．０１）,Ⅱ型分别为２５９．６８±６９．６８和２２０．８８±６２．８５（Ｐ＜０．０５）。高血压组应用赖诺普利后各基因型患者血压均有明显下降,降压幅度ＤＤ＞ＩＤ＞Ⅱ。结果显示ＡＣＥ基因多态性与原发性高血压有密切关系,ＤＤ型有高易患性。ＡＣＥ活性受基因型控制,ＤＤ型活性最高。应用赖诺普利后各基因型血压均有下降,降压幅度 ＤＤ＞ ＩＤ＞ Ⅱ。 ＤＤ型可作为ＡＣＥ抑制剂应用的最佳指征。