维胺酯2种给药方案治疗寻常痤疮44例

目的 :观察维胺酯不同剂量治疗痤疮的疗效和安全性 ,探索有效治疗方案。方法 :将 4 4例中、重度寻常痤疮病人分为 2组 ,A组 2 4例 ,总疗程 6mo ,分别在mo 1～ 2按 1mg·kg- 1·d- 1;在mo 3～ 4按 2 5mg ,qd ;在mo 5～ 6按 2 5mg ,qod的剂量口服。B组 2 0例 ,5 0mg ,tid ,总疗程 6wk。结果 :2组总累积量A组为 (6 14 3±s 5 71)mg ,B组为 6 30 0mg ;治疗后临床评分分别为 (7.7± 1.7)分vs(7.7±1.6 )分 ;基本痊愈率分别为 5 4%vs 5 0 % ,差异均无显著意义 (P >0 .0 5 )。日剂量分别为 (0 .5 3±0 .0 3)mg·kg- 1·d- 1vs (2 .4± 0 .3)mg·kg- 1·d- 1、不良反应率为 8%vs 4 0 % ;复发率 12 %vs4 5 % ,差异均有显著意义 (P <0 .0 5或P <0 .0 1)。结论 :应用维胺酯低剂量长疗程治疗寻常痤疮 ,疗效好 ,安全性高 ,复发率低。     

4种非甾体抗炎药治疗类风湿关节炎的成本-效果分析

目的 :探讨 4种口服非甾体抗炎药治疗类风湿性关节炎 6mo的成本和效果。方法 :4 6 1例病人随机分成 4组 ,双氯芬酸组 131例 ,服用双氯芬酸 75～ 10 0mg·d- 1,萘丁美酮组 131例 ,服用萘丁美酮 10 0 0mg·d- 1,美洛昔康组 14 4例 ,服用美洛昔康 15mg·d- 1,塞来昔布组 5 5例 ,服用塞来昔布 2 0 0mg·d- 1,疗程均为 6mo。运用成本 -效果分析对 4组病人进行分析评价。结果 :双氯芬酸、萘丁美酮、美洛昔康、塞来昔布 4组完成疗程病例数分别为12 5 ,12 7,139和 5 5例。在疗程结束时 ,4组间疗效无显著差异 (P >0 .0 5 ) ,塞来昔布组不良反应率明显低于其他 3组 (P <0 .0 1)。 4组总成本分别为(14 0 0±s 32 6 ) ,(15 31± 36 ) ,(2 0 18± 5 2 7) ,(32 2 5±76 7)元 ;成本 -效果比为 (2 0 4 1± 6 12 ) ,(2 5 6 0±6 81) ,(2 985± 70 6 ) ,(4 6 6 7± 1389)元·例 - 1;经敏感度分析后的成本 -效果比为 (1896± 4 5 5 ) ,(2 36 6±6 38) ,(2 6 6 9± 5 89) ,(3978± 96 3)元·例 - 1。结论 :双氯芬酸为治疗类风湿性关节炎的较佳方案 ,在经济许可的情况下 ,偏重考虑药物安全性 ,塞来昔布也是一个较佳选择。     

环孢素软胶囊在肾移植病人中的应用

目的 :观察环孢素软胶囊 (以下简称环孢素 )应用于肾移植病人的疗效和不良反应。方法 :2 4例入选的肾移植病人 ,男性 15例 ,女性 9例 ,年龄34a±s 6a(18～ 6 5a)。给予环孢素 +硫唑嘌呤 +泼尼松三联用药 ,其中环孢素起始剂量 8mg·kg- 1·d- 1,以后依血浓度 ,肝、肾功能调整给药量 ,硫唑嘌呤为 50～ 70mg·d- 1,泼尼松于术后d3给 80mg·d- 1,以后递减至维持量。所有病人使用环孢素 ,时间最长为 15mo ,观察随访期 12mo± 2mo。结果 :2 4例中仅出现 2例不典型急性排斥反应 ,2例ALT轻度升高 ,8例出现震颤 ,2例出现齿龈增生 ,5例多毛。结论 :环孢素软胶囊对肾移植病人具有免疫抑制作用 ,肝毒性小。     

文拉法辛治疗抑郁症74例

目的 :观察文拉法辛治疗抑郁症的疗效。方法 :抑郁症 74例 (男性 30例 ,女性 4 4例 ,年龄 36a±s 3a ,病程 2 5mo± 3mo)采用文拉法辛 10 0mg± 2 5mg(50～ 2 50mg·d- 1) po ,疗程 6wk。另外采用马普替林治疗同类病人 72例 (男性 2 9例 ,女性4 3例 ,年龄 36a± 6a ,病程 2 4mo± 4mo)用量 115mg± 15mg(75～ 150mg·d- 1) po ,疗程 6wk。结果 :文拉法辛组显效率为 78% ,马普替林组显效率为 75% ,2组疗效差异无显著意义 (P >0 .0 5) ,文拉法辛组不良反应较马普替林组小。结论 :文拉法辛治疗抑郁症疗效良好 ,起效快 ,不良反应轻微。     

非线性混合效应模型法估算癫(间)患者苯妥英群体药物动力学参数

目的 应用非线性混合效应模型法(NONMEM),估算癫癇患者苯妥英群体药物动力学参数,考察各因素对最大消除速率常数Vm(mg·d-1)及米氏常数Km(mg·L-1)的影响。方法 回顾性搜集56例门诊及住院癫癇患者服用苯妥英钠日剂量和血药浓度数据96对,并运行SAS程序进行计算。结果 患者的性别、年龄、体重、合并用药等对药物动力学参数均无显著性影响,Vm=(522.40±10.25)mg·d-1(513.14～630.63 mg·d-1),Km=(11.05±9.62)mg·L-1(1.90～34.83 mg·L-1)。血药浓度预测值与实测值相关性良好。结论 用非线性混合效应模型法估算癫癇患者苯妥英群体药物动力学参数方法可靠,值得推广。     

利培酮治疗首发精神分裂症的临床观察

目的观察利培酮治疗首发精神分裂症患者的情况.方法选取88例首发并住院的精神分裂症患者,进行开放性临床治疗观察,服用利培酮从1mg·d-1开始,逐渐增加到治疗量3～6mg·d-1,疗程为12周.用CGI,BPRS,TESS等工具评估疗效及不良反应.结果利培酮治疗首发精神分裂症的有效率是92.4%,治疗的平均剂量是(3.77±1.03) mg·d-1,不良反应少见.结论利培酮治疗首发精神分裂症患者安全、可靠.     

甲氯芬酯对吡拉西坦的体内药物动力学的影响

目的测定复方吡拉西坦粉针剂中主要成分吡拉西坦在大鼠体内的药物动力学 ,并考察粉针剂中另一成分甲氯芬酯对吡拉西坦药物动力学的影响及不同剂量吡拉西坦在大鼠体内药物动力学的差异。方法采用RP- HPLC法分别测定了大鼠静脉注射不同剂量吡拉西坦单方和复方吡拉西坦粉针剂后的血药质量浓度 ,计算其药物动力学参数。结果静脉注射吡拉西坦高、中、低剂量组(15 0、10 0、5 0mg·kg-1)及复方吡拉西坦粉针剂 (10 0mg·kg-1)在大鼠体内过程均符合双隔室模型。静脉注射剂量为 10 0mg·kg-1复方吡拉西坦粉针剂时 ,其主要的药物动力学参数t1/ 2 β、AUC分别是 (16 0 . 4± 2 5 . 8)min、(15 6. 6 6 1± 1785 . 4 )min·mg·L-1,与相同剂量的吡拉西坦单方药药物动力学参数没有显著性差异。结论吡拉西坦甲氯芬酯粉针剂中的另一个成分甲氯芬酯不影响主药吡拉西坦的药物动力学。吡拉西坦的大鼠体内药物动力学具有线性药物动力学特征。     

托吡酯与丙戊酸钠缓释片治疗难治性癫痫疗效比较

目的 :比较托吡酯与丙戊酸钠缓释片治疗难治性癫痫的疗效。方法 :托吡酯组 39例 ,丙戊酸钠组 4 1例 ,托吡酯成人及儿童剂量在约 2mo中逐渐增至 2 0 0mg·d- 1及 4mg·kg·d- 1左右 ,po ,bid。丙戊酸钠缓释片成人剂量 0 .5～ 1.0 g·d- 1,儿童剂量逐增至总量 15～ 30mg·kg·d- 1,为每日清晨或早晨、中午 2次服用。治疗 4mo及 6mo后评定疗效。结果 :托吡酯组治疗 6mo的继发性全身发作 ,简单及复杂性部分发作有效例数优于丙戊酸钠组 ,4例在加药期快时出现疲劳、嗜睡、注意力不集中等。丙戊酸钠组 1例发生骨髓造血功能严重低下。结论 :托吡酯治疗难治性癫痫简单及复杂部分性发作伴或不伴继发性全身发作疗效优于丙戊酸钠 ,无骨髓抑制 ,也无肝、肾功能损伤     

吡拉西坦和维生素E增强抗心绞痛药治疗老年心绞痛的效果

吡拉西坦(piracetam)是抗缺氧和改善脑代谢药,维生素E是抗氧化药,为研究这两种药物和抗心绞痛药伍用治疗老年心绞痛的效果,观察了稳定型心绞痛病人140例,年龄60～83岁,平均66.7岁。病人分3组,第1组50例,为对照组,施行传统疗法,用硝酸异山梨醇酯(40～60mg·d-1),硝苯地平(30～60mg·d-1),普萘洛尔(120～160mg·d-1)治疗,疗程4～6周。第2组50例,传统疗法并用吡拉西坦,头10d用量为4.4～5.2g·d-1(2.4～3.2g·d-1,分3～4次口服,2g·d-1静注),随后3～5周只口服2.4～3.2g·d-1。第3组40例,治疗和第2组相同之外,加用维生素E0.2g·d-1。治疗前、后…     

去甲泽拉木醛的免疫抑制作用

目的 :观察去甲泽拉木醛 (T 96)体外免疫抑制及抑制大鼠移植肾排斥的作用强度。方法 :( 1)体外培养BALB/C小鼠脾细胞 ,加有丝分裂原ConA刺激 ,并分别加不同浓度的T 96,用MTT法测定脾细胞的母细胞化情况。 ( 2 )行原位大鼠肾移植并分组 ,分别给予不同剂量的T 96,观察肾移植大鼠的生存期。结果 :T 960 .5mg·L- 1能显著抑制小鼠脾细胞的母细胞化作用 ,与对照组比较P <0 .0 1。T 9610mg·kg- 1·d- 1,2 0mg·kg- 1·d- 1分别延长肾移植大鼠生存期至 ( 14.8±s 1.0 )d和 ( 18.0± 1.5 )d ,与对照组 ( 6.9± 0 .6)d比较差异有非常显著意义 (P <0 .0 1)。T 9610mg·kg- 1·d- 1与泼尼松 10mg·kg- 1·d- 1联合应用延长肾移植大鼠生存期至 ( 32± 6)d。结论 :T 96有强烈抑制小鼠脾细胞母细胞化的作用 ,且有抑制大鼠移植肾的排斥作用 ,抑制作用随剂量加大而增强 ,与泼尼松联合应用 ,更能延长肾移植大鼠的存活时间。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.