奥美沙坦酯与缬沙坦治疗中度原发性高血压临床研究

目的比较奥美沙坦酯和缬沙坦治疗中度原发性高血压的疗效和安全性。方法入选482例中度原发性高血压患者,按照1∶1随机分组,分别接受奥美沙坦酯20～40 mg/d或缬沙坦80～160 mg/d治疗,共8周。观察并比较其降压效果。结果治疗4周后,奥美沙坦酯组SeDBP平均下降了(10.58±6.82)mmHg,缬沙坦组下降了(9.38±7.16)mmHg;两组比较,P=0.004。奥美沙坦组与缬沙坦组分别有60%、61.74%的患者剂量加倍,加量有效率分别为52.22%、51.85%;治疗8周后,两组SeDBP平均下降(15.72±6.03)mmHg及(14.12±6.79)mmHg;治疗4周后,两组的药物不良反应发生率分别为3.33%、7.5%(P>0.05)。结论口服奥美沙坦酯胶囊20～40 mg/d,1次/d,能保持24 h平稳降压,8周总有效率为79.65%;与缬沙坦80～160 mg/d的降压疗效相近。而两组药物不良反应发生率差异无统计学意义。     

奥美沙坦酯与缬沙坦治疗中度原发性高血压临床研究

目的对奥美沙坦酯与缬沙坦治疗中度原发性高血压临床进行研究,把奥美沙坦酯、缬沙坦分成两组,对治疗原发性高血压效果和安全性进行比较。方法随机抽取本院500例原发性高血压患者,用6周的时间,采取人数比例1：1方法分别对奥美沙坦酯、缬沙坦两组以30～60mg／d、80～160mg／d进行治疗。对其治疗的效果进行观察。结果治疗2周后,奥美沙坦酯平均降低原发性高血压患者（10．22±6．33）mmHg,缬沙坦平均降低原发性高血压患者为（9．23±7．33）mmHg;两组实验的效果较为明显,结果测得几率P=0．004,说明差异具有统计学意义。奥美沙坦组和缬沙坦组分别有58％、63％的患者需要加倍,加量有效率不是很明显,分别为50．03％、51．22％;在治疗5周后,奥美沙坦酯、缬沙坦两组治疗原发性高血压,血压平均下降到（15．324±5．03）mmHg、（13．124±5．75）mmHg。结论奥美沙坦酯胶囊的口服量控制在30～60mg／d,次数控制1d,效果是24h血压稳定,缬沙坦80～160mg／d的降压效果与奥美沙坦酯降压效果较近。     

高剂量坎地沙坦西酯16mg治疗轻中度原发性高血压65例临床观察

目的:评价16 mg坎地沙坦西酯治疗轻中度原发性高血压患者的有效性和安全性.方法:采用随机、双盲、平行对照的研究方法,入选患者65例,随机接受坎地沙坦西酯16 mg·d-1(n=33)或8 mg·d-1(n=32)治疗,共8周,并对其中的37例患者于治疗前后进行24 h动态血压监测.结果:治疗8周末,16 mg组和8 mg组的收缩压分别下降(10.9±11.5)mmHg和(11.5±15.1)mmHg,舒张压分别下降(12.9±11.3)mmHg和(10.5±7.8)mmHg;两组的降压总有效率分别为70%和61.3%.动态血压监测显示,16 mg组和8 mg组的收缩压谷峰比值分别为73%和47%,舒张压为65%和47%.两组的不良事件发生率无统计学差异.结论:高剂量坎地沙坦西酯16 mg·d-1治疗轻中度原发性高血压安全有效,患者耐受性好.     

奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性

目的评价奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性。方法随机、双盲、双模拟、阳性药物(氯沙坦钾)平行对照。40例轻中度原发性高血压患者随机分为奥美沙坦酯或氯沙坦钾组,均治疗8周,观察两组治疗前后的血压、心率、心电图和血、尿常规等实验室检查结果的变化。结果奥美沙坦酯组与氯沙坦钾组比较,患者平均坐位收缩压和舒张压的降低程度均有显著性差异,分别为(18.9±8.7)mmHg和(12.6±7.6)mmHg(P<0.01);(13.8±3.5)mmHg和(11.7±3.3)mmHg(P<0.05)。治疗前后两组血压降低幅度均有显著差异,心率无明显变化。奥美沙坦酯和氯沙坦钾组降压显效率分别为63.2%和57.9%,总有效率分别为84.2%和68.4%,组间无显著差异。两组共出现3例头晕,实验室检查无异常改变。结论奥美沙坦酯治疗轻中度原发性高血压的疗效良好,不良反应发生率低。     

奥美沙坦酯与吲哒帕胺联合治疗原发性高血压的疗效及安全性研究

目的观察奥美沙坦酯与吲哒帕胺联合治疗原发性高血压的疗效及安全性。方法将160名原发性高血压患者随机分为奥美沙坦酯组与贝那普利组,每组各80例,患者每天早晨分别顿服奥美沙坦酯2．5mg和吲哒帕胺2．5mg,或贝那普利10mg和吲哒帕胺2．5mg,疗程为8周,观察治疗前后临床疗效及不良反应发生情况。结果治疗后两组患者血压有明显下降,奥美沙坦酯组收缩压与舒张压分别从治疗前（168．9±4．1）mmHg、（100．4±7．2）mmHg降至（125．9±8．9）mmHg、（80．9±6．6）mmHg（P〈0．05）,8周后有效率达92．5％;贝那普利组收缩压与舒张压分别从治疗前（170．4±15．1）mmHg、（102．9±7．7）mmHg降至（128．9±8．2）mmHg、（81．4±9．1）mmHg（P〈0．05）,8周后有效率达90．o％。两组患者均未发生严重不良事件,安全性指标无异常。结论联用奥美沙坦酯与吲哒帕胺治疗原发性高血压安全有效,副作用少,是高血压治疗联合用药的理想组合,可推荐临床应用。     

奥美沙坦酯治疗原发性高血压的疗效和安全性

目的：评价奥美沙坦酯治疗原发性高血压的疗效和安全性。方法：选择轻、中度高血压患者64例，随机分为奥美沙坦酯治疗组（n=34例）和缬沙坦对照组（n=30例），每日1次口服奥美沙坦酯20mg或缬沙坦80mg，2周后如舒张压≥90mmHg，则剂量加倍，进行8周的临床观察。结果：两组患者血压均得到明显降低（P〈0．01），奥关沙坦酯组，总有效率88．2％；缬沙坦组总有效率86．7％。两组比较无统计学差异（P〉0．05）。结论：奥美沙坦酯治疗原发性高血压疗效显著，与进口同类药缬沙坦相当，不良反应少，安全有效。     

奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的对比

目的比较奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪在治疗原发性高血压中的降压疗效。方法 80例原发性高血压患者随机分为奥美沙坦-氨氯地平组和奥美沙坦-氢氯噻嗪组,每组40例。奥美沙坦-氨氯地平组给予奥美沙坦酯20 mg和氨氯地平5 mg,口服,qd;奥美沙坦-氢氯噻嗪组给予奥美沙坦酯20 mg和氢氯噻嗪12.5 mg,口服,qd;疗程均为8周。观察患者24 h动态血压变化情况、血压昼夜波动节律,检测治疗前后实验室指标并记录不良反应发生情况。结果两组患者治疗后白昼、夜间平均收缩压和舒张压均降低(P<0.05),两组降低幅度无显著差异(P>0.05)。奥美沙坦-氨氯地平组治疗后白昼、夜间收缩压和舒张压变异均低于奥美沙坦-氢氯噻嗪组(P<0.05)。奥美沙坦-氨氯地平组血压昼夜节律异常逆转率为79%(11/14),高于奥美沙坦-氢氯噻嗪组(25%,4/16,P<0.05)。两组实验室指标均无明显变化。两组均无明显不良反应发生。结论奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的降压效果相当,但前者在降低血压变异性、改善高血压患者血压昼夜节律变化方面效果更佳,具有平稳降压的作用。     

氯沙坦和缬沙坦治疗原发性高血压合并高尿酸血症的疗效比较

目的观察比较氯沙坦和缬沙坦治疗原发性高血压合并高尿酸血症的降压和降尿酸作用。方法 60例原发性高血压伴高尿酸血症患者随机分为氯沙坦组和缬沙坦组,每组30例,分别服用氯沙坦50 mg·d-1和缬沙坦80 mg·d-1,4周后血压控制不佳者分别增加剂量至100 mg·d-1和160 mg·d-1,疗程8周。观察2组的血压和血尿酸变化。结果氯沙坦组和缬沙坦组均有良好的降压效果,降压疗效相似。氯沙坦组治疗后血尿酸水平与治疗前相比显著降低(P<0.05);缬沙坦组治疗前后血尿酸水平相比,差异无统计学意义。结论原发性高血压合并高尿酸血症者氯沙坦为首选降压药。     

奥美沙坦酯片治疗轻、中度原发性高血压的疗效和安全性

目的观察奥美沙坦酯片治疗轻、中度原发性高血压的疗效和安全性。方法61例轻、中度原发性高血压患者随机分为奥美沙坦酯组(n=30)和氯沙坦组(n=31),治疗8wk,观察2组治疗前后的血压、心率、心电图和血、尿实验室检查的变化。结果奥美沙坦酯组与氯沙坦组比较,坐位收缩压和舒张压降低程度都有显著差异,分别为(132±13 vs 139±13)mmHg(P<0.01)和(85±9 vs 87±9)mmHg(P<0.05)。奥美沙坦酯组降压有效率为83%;每日1次服用奥美沙坦酯作用可持续24h,药物降低收缩压和舒张压的谷峰比值均>50%。2组药物不良反应发生分别为1例和3例,2组比较无显著差别。结论奥美沙坦酯治疗轻、中度原发性高血压患者,能24h平稳降压,谷峰比满意,且耐受性较好。     

国产坎地沙坦酯治疗原发性高血压的随机双盲临床试验

目的:评价国产坎地沙坦酯治疗轻、中度高血压的疗效和安全性.方法:采用多中心随机双盲、双模拟、阳性药物平行对照试验设计,对217例高血压病患者随机给予坎地沙坦酯片(n=107,4～8mg*d-1)或对照药厄贝沙坦片(n=110,150～300mg*d-1);4周后血压未正常者加用氢氯噻(12.5mg*d-1),疗程8周.结果:试验组和对照组的单药治疗总有效率分别为72.4%和73.1%,两组间比较差异无显著性(P>0.05);联合用药后分别为93.3%和94.4%.平均坐位血压试验组由(155.6±10.9)/(98.6±4.9)mmHg降(130.2±10.0)/(82.7±5.7)mmHg,对照组由(152.6±10.3)/(98.4±4.1)mmHg降至(129.1±8.0)/(82.8±5.1)mmHg,两组间比较差异无显著性(P>0.05).两组不良反应发生率相似(12.3%和13.1%).结论:国产坎地沙坦酯治疗高血压安全有效,其降压效果和不良反应与厄贝沙坦相似.     

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.

     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。