磺胺噻二嗪硫酮衍生物的合成及其抑菌活性

利用药物化学骈合原理设计并合成了一系列新的３，５－二取代１，３，５－噻二嗪－２－硫酮类化合物，其结构经红外光谱，紫外光谱及元素分析证实，抑菌活性试验显示了良好的抑菌活性。     

Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.

Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease.     

Hemophilia A: genetic prediction and linkage studies in all available families in Finland

RFLP studies were done in 82 (75%) of all known hemophilia A families in the Finnish population (approximately 5 million). Two intragenic RFLPs (Bc1I/F8A, XbaI/p482.6) and two extragenic markers (TaqI/St14, Bg1II/DX13) were used. Among 263 females at risk, carriership could be evaluated with an intragenic marker in 47% and with an extragenic marker in 26%. In 27% of the females, carriership could be neither excluded nor confirmed; 68% of these females were relatives of an isolated patient. Eight recombinations between the factor VIII gene (F8C) and DXS52 (lod 25.02 at theta max 0.06), eight recombinations between F8C and DXS15 (lod 21.91 at theta max 0.05), and two recombinations between DXS52 and DXS15 (lod 33.56 at theta max 0.01) were found. Using multipoint linkage analysis, the most likely order of loci supported by the data was: F8C-DXS15-DXS52-DXS134. RFLP segregation analysis provides a highly useful method of carrier detection and prenatal diagnosis of hemophilia A, but its limitations must be carefully taken into account.     

移植肾彩色多普勒血流超声与肾穿刺活检的对照研究

将彩色多普勒血流超声与移植肾活检结果相对照。评价无创性ＣＤＦＩ对移植肾排异反应的诊断价值。结果：不同病理状态下移植肾的阻力指数有所不同。急性排异和慢性排异反应组的ＲＩ值明显高于正常组。两次肾活检提示由急性排异转为慢性排异反应的同一患者，ＣＤＦＩ的动态观察显示，ＲＩ值明显增高。     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Disposition of leucovorin and its metabolites in dietary folic acid-deplete mice – comparison between tumor, liver and plasma

Purpose: A comprehensive pharmacokinetic study of leucovorin (5-formyltetrahydrofolate, 5-HCO-FH₄) and its metabolites was conducted in plasma, liver and implanted tumor tissue from mice maintained on a low folic acid diet. While it has been previously demonstrated that the antitumor activity of fluorouracil (FU) can be potentiated by 5-HCO-FH₄, the optimum time for administration of FU after 5-HCO-FH₄, to maximally elevate the active folate metabolite methylenetetrahydrofolate in tumor has not been established. Human plasma studies have defined the pharmacokinetics of circulating 5-HCO-FH₄ and its metabolites, but comparison with human tumor accumulation has not been practicable because of sampling difficulties. As an alternative, a mouse model system, based on low dietary folic acid, was used to evaluate plasma, liver and implanted tumor reduced folates after administration of 5-HCO-FH₄.Methods: Plasma and tissue samples were collected from folate-deplete mice over a 12-h period after intraperitoneal administration of 90 mg/kg [R, S ] 5-HCO-FH₄. Reduced folates were evaluated using a ternary complex assay. Results: The time at which max‐imal accumulation of parent compound and all metabolites, except 5-methyltetrahydrofolate (5-CH₃FH₄), occurred in tumor was the same as in plasma. Alternatively, peak liver accumulation was delayed relative to plasma for all folates except 5-CH₃FH₄. Conclusions: The results suggest that mouse plasma accumulation of reduced folates, with the exception of 5-CH₃FH₄, can predict tumor accumulation. Hence, evaluation of human plasma folate accumulation may potentially provide a means to improve the timing of the administration of FU relative to 5-HCO-FH₄ to achieve a superior therapeutic outcome. Received: 24 July 1996 / Accepted: 29 October 1996     

Prevalence of Hepatitis A, B, and C markers in school children of a rural area of Crete, Greece

Objective: To determine the prevalence of hepatitis A, B, and C markers in children who were attending junior and senior high schools in a high risk area in rural Crete, Greece. Methods: Three-hundred and thirty-four children who attended the three junior schools and one senior high school in the Agios Vassilios province of Southern Crete were invited to participate in the study. Three hundred and four of them were tested for hepatitis A, B, and C markers. Hepatitis B (HBV) markers (HBsAg and anti-HBc) as well as hepatitis A (anti-HAV) and hepatitis (anti-HCV) antibodies were tested with commercial enzyme-linked immunosorbent assay kits. Results: Six of the 304 children (1.97%) were found to be positive for anti-HAV, 1 (0.33%) to HBsAg, 7 (2.30%) to anti-HBc and none were found positive for anti-HCV. No significant differences were seen between the prevalence of anti-HAV antibodies in males (2%) and females (1.95%), and of anti-HBc antibodies in males (3.33%) and females (1.30%). Conclusions: The very low prevalence of anti-HAV is obviously due to the improved conditions of hygiene and it raises the question of the possible emergence of this disease at an older age and therefore appropriate preventative strategies should be considered. The low endemicity of hepatitis B in Crete in contrast to other areas of Greece also calls for a vaccination policy probably during adolescence. The absence of hepatitis C markers in the children in contrast to the observed higher prevalence of HCV-infected people in the adult population in the same rural area raises questions regarding possible sources of transmission of hepatitis C during the preceding years.     

骨盆骨折槽型固定器的研制及临床应用——附62例临床分析

为解决骨盆不稳定性骨折固定难，易产生并发症的难题，结合骨盆的特征进行研究，设计出一种新型骨盆骨折固定器，经62例骨盆不稳定性骨折的治疗观察，随访6个月～2年零6个月，治疗前后X线检查及临床疗效评定：治愈50例，好转12例，认为该固定器设计合理，操作简便，固定牢靠，有加压、撑开、纠正旋转等多项功能结合干一体，仅通过四枚4mm螺纹针，穿入髂骨的髂前上棘处，是一种治疗骨盆不稳定性骨折比较新颖和理想的外固定器。     

远节指末端离断伤两种治疗方法的回顾性分析

①目的 旨在比较分析原位缝合与贯穿植入随意血管神经束加原位缝合治疗远节指末端离断伤的疗效及优缺点，更有针对性地为临床提供一种有效的治疗方法。②方法 对临床两种治疗方法的29例加以回顾性总结、比较分析，获得详细相关数据资料，并对数据资料进行统计学的分析和处理。③结果 原位缝合治疗远节指末端离断伤的总有效率远低于贯穿植入随意血管神经束加原位缝合法。④结论 贯穿植入随意血管神经束原位缝合治疗远节指末端离断伤，是一种比较理想的方法，值得临床推广使用。     

以宗四维牵引为主治疗腰椎间盘突出症163例报告

目的观察以宗四维牵引和熏腰蒸气疗法治疗腰椎间盘突出症的临床疗效。方法应用仰卧纵轴骨盆牵引，俯卧骨盆牵引同时外展患肢牵引，仰卧屈曲双下肢悬吊牵引，俯卧过伸双下肢悬吊牵引，根据患者椎曲的改变类型辩证施治；牵引后进行熏腰蒸气治疗。结果腰椎间盘突出症治疗有效率为93％，无效率7％。