卡维地洛对慢性心力衰竭心功能的影响

目的　探讨卡维地洛对慢性心力衰竭患者心功能的影响。方法 :将 6 0例慢性心力衰竭患者双盲随机分为两组 ,卡维地洛组 (A组 ) 30例 ,美托洛尔组 (B且 ,对照组 ) 30例。两组病人基础临床特征相似 ,应用彩色超声心动图测量病人治疗前、后 6个月射血分数 (EF)左室短轴缩短分数 (FS)及左心室腔径容积变化 ,并观察患者的 NYHA心动能、血压的变化。结果　治疗 6个月后 ,A组的 EF和 FS比 B组明显增高。 (EF:0 .4 6± 0 .2 3%比 0 .39± 0 .18% ,P<0 .0 1) (FS:2 5 .0± 1.6 4 %比 2 2 .3± 1.36 % ,P<0 .0 1)左室舒张末径 (L VDd)和左室收缩末径 (L VDs)均比治疗前缩短分别为 (L VDd:5 0 .0± 0 .76 m m比 37.0± 0 .34mm) (L VDs:5 3.0± 0 .4 7mm比 4 0 .0± 0 .15 mm) ,P均 <0 .0 1。左室舒张末期容积 (L VEDV)和左室收缩末期容积 (L VESV)均比治疗前缩小分别为 [10 4± 0 .15 ) ml比 (31.15±0 .77) ml和 (119± 0 .19) ml比 (34.17± 0 .6 7) ml,均 P<0 .0 1],治疗 6个月后两组患者的 NYHA心功能分级改善。治疗期间 ,卡维地洛组无心衰恶化 ,美托洛尔组有 2例因心衰恶化住院。结论　卡维地洛与美托洛尔对慢性心力衰竭均有较好的疗效 ,前者更优于后者。     

氨氯地平在心衰治疗中对肿瘤坏死因子-α、白细胞介素-1,6的作用

目的 :探讨氨氯地平在心力衰竭 (心衰 )治疗中对细胞因子的作用。方法 :选择扩张型心肌病和缺血性心脏病心衰病人共 6 0例 ,随机分成常规组与氨氯地平组。常规组给予常规抗心衰治疗 ,氨氯地平组在常规治疗基础上加用氨氯地平 5mg ,po ,qd。同时建立正常组。检测肿瘤坏死因子 α(TNF α)、白细胞介素 1(IL 1)、白细胞介素 6 (IL 6 )。结果 :IL 1,IL 6 ,TNF α在心衰病人中分别达 (30±s 13) ,(99± 4 3)和 (2 4± 5 )ng·L- 1,较正常人[(6 .1± 1.7) ,(2 9± 8) ,(16± 5 )ng·L- 1]明显增高(P <0 .0 1)。治疗 6wk后 ,氨氯地平组病人较常规组IL 6 ,TNF α明显降低 ,分别为 (45± 2 4 )和 (17±5 ) ,(6 0± 31)和 (2 0± 4 )ng·L- 1(P <0 .0 1)。结论 :氨氯地平治疗心衰的作用之一可能在于降低细胞因子如IL 6和TNF α的水平     

卡介菌多糖核酸治疗充血性心力衰竭

目的 :研究卡介菌多糖核酸 (BCG PSN)对慢性充血性心力衰竭 (心衰 )病人免疫机能、心衰治疗周期及住院医疗费用的影响。方法 :5 9例心衰病人 ,常规抗感染、强心、利尿、扩血管等治疗 ,分BCG PSN组与常规组。BCG PSN组在常规治疗基础上给BCG PSN 1mg ,im ,qod× 2 6d。观察 2组T淋巴细胞CD4 /CD8,IgG ,IgA ,IgM及C3,住院费用及心衰缓解时间。另有 36例健康人作为对照。结果 :心衰病人IgG及C3升高 ,T细胞亚群CD4 /CD8下降 ;BCG PSN组较常规组治疗后IgG[(14 .2± 2 .4 ) g·L- 1vs (16 .3± 2 .4 ) g·L- 1,P <0 .0 5 ]和CD8[(30±5 ) %vs (38± 6 ) % ,P <0 .0 1]降低更明显 ,IgM[(3.0± 0 .6 ) g·L- 1vs (2 .1± 0 .5 ) g·L- 1,P <0 .0 1]及CD4 [(46± 6 ) %vs(38± 5 ) % ,P <0 .0 1]升高更明显 ;BCG PSN组较常规组心衰改善所需时间缩短 [(6± 3)dvs (8.4± 2 .6 )d ,P <0 .0 1],住院总药费有所降低。结论 :BCG PSN可提高心衰病人的免疫功能 ,加快心衰改善 ,住院费用降低     

高血压心功能不全患者血清尿酸水平变化及氯沙坦对其影响

目的 :探讨原发性高血压 (EH)心功能不全患者血清尿酸 (UA)水平的变化及氯沙坦 (Los)对其影响。方法 :比较EH60例不同心功能状态下尿酸浓度 ,同时将60例患者分为Los组和Enalapril(Ena)组两组 ,每组30例 ,Los组给50Los50mg1日1次 ;Ena组Ena10mg1日1次。疗程4周 ,观察治疗前后UA变化。结果 :(1)EH心功能I、Ⅱ、Ⅲ、Ⅳ级的UA分别为 (4 8±1 4) ,(5 2±1 2) ,(7 5±2 0) ,(9 2±2 3)mg/dl,心功能Ⅳ级者明显高于Ⅲ级患者 (P<0 01)。 (2)Los组治疗前后UA分别为(7 6±2 4) ,(5 5±1 9)mg/dl(P<0 01) ,Ena组治疗前后分别为 (7 3±3 1) ,(6 2±2 0)mg/dl(P<0 05)。两组治疗后比较有显著差异 (P<0 05 ,t=2 08)。结论 :EH心功能不全患者UA随着心功能不全加重而明显升高。Los在改善心功能同时 ,还具有降尿酸作用。可取得最有效的心血管保护效益     

曲美他嗪对心脏病患者心室重塑和心功能的影响

目的　探讨曲美他嗪 (trimetazidine ,TMZ)对缺血性心脏病心力衰竭患者心室重塑和心功能的影响。方法　缺血性心脏病心力衰竭患者 78例 ,左室射血分数≤ 4 0 % ,心功能 (NYHA)Ⅱ～Ⅳ级 ,常规治疗基础上随机分为TMZ组 (n =4 0 )和对照组 (n =38)。治疗 6个月 ,观察曲美他嗪对心室重塑和心功能的影响。结果经过 6个月治疗 ,TMZ治疗组症状和心功能改善 ,与对照组比较左室收缩末容积下降 [(15 9 2± 4 6 7)mlvs(179 8± 4 8 5 )ml,P <0 0 5 ],左室收缩末内径减小 [32 7± 4 1)mmvs (39 5± 3 9)mm ,P <0 0 5 ],左室射血分数显著提高 [(4 8 6± 9 5 ) %vs (35 .2± 8.7) % ,P <0 0 1];与基线比较左室舒张末容积下降 (P <0 0 5 ) ,左室舒张末内径减小 (P <0 0 5 ) ,但两组间尚无统计学差异。结论　在心力衰竭标准治疗基础上 ,应用TMZ能显著改善缺血性心脏病心力衰竭患者心室重构重塑和心功能     

心力衰竭患者血浆可溶性Fas水平测定及其临床意义

目的探讨心力衰竭 (CHF)患者细胞凋亡抑制物血浆可溶性Fas(sFas)水平检测的临床意义 ,以及与NYHA心功能分级、血浆TNF α、AII浓度的关系。方法心力衰竭患者 4 2例 ,健康对照组 2 9例 ,同时检测血浆sFas、TNF α、AII等指标。结果心衰患者血浆sFas水平升高 ,与对照组比较差异有显著意义 (P <0 0 5 ) ,对照组为 6 17± 2 0 1ng ml,心衰组为 16 5 5± 9 4ng ml;心功能Ⅱ级组为10 76± 5 32ng ml,Ⅲ级组为 13 11± 4 4 2ng ml,Ⅳ级组为 2 4 0 2± 10 6 7ng ml,显示血浆sFas水平随患者心衰加重而显著增高 ;同时心衰患者血浆TNF α、AII浓度亦升高 ,但与sFas无相关性。结论心衰病人血浆sFas水平升高 ,因而推测在心衰的发病机理中sFas可能起了重要作用     

螺内酯对慢性心力衰竭患者心功能及血清脑利钠肽水平的影响

目的 :观察螺内酯对慢性心力衰竭患者心功能及血清脑利钠肽 (BNP)水平的影响。方法 :心衰患者 4 2例 ,心功能 (NYHA)分级为Ⅱ～Ⅳ级 ,均接受利尿剂、洋地黄、血管转换酶抑制剂类药物治疗 ,随机分为 2组 :螺内酯组 2 1例 ,在上述治疗基础上每日给予螺内酯 2 0mg ;对照组 2 1例 ,除不给予螺内酯外 ,余处理与治疗组相同。动态观察心衰患者治疗前和治疗后 1个月NYHA分级变化和采用酶联免疫吸附法测定心衰患者治疗前和治疗后 3个月血清BNP 32浓度。同时使用超声心动图测定左心室射血分数和左心室舒张末期内径。结果 :螺内酯组和对照组治疗 1个月后临床综合疗效总有效率分别为85 .7%和 76 .2 % (P <0 .0 5 ) ,显效率分别为 6 1.9%和 4 2 .9% (P <0 .0 5 )。两组患者治疗 1个月后 ,NY HA分级均有所改善 ,但螺内酯组治疗后改善显著(P <0 .0 5 )。治疗后螺内酯组患者左心室射血分数显著升高 (P <0 .0 5 ) ,左心室舒张末期内径显著降低 (P <0 .0 5 )。治疗后 2组血清BNP水平均显著下降 (P <0 .0 5 ) ,但螺内酯组对照组下降更显著 (P <0 .0 1)。螺内酯组治疗前后血清BNP水平降低值与左心室射血分数增加呈负相关 (r =- 0 .4 2 ,P <0 .0 5 ) ,而与左心室舒张末期内径缩小呈正相关 (r =0 .6 0 ,P <0 .0 5 )。结论 :螺     

贝那普利对风心病心力衰竭患者的治疗作用

贝目的　观察贝那普利对风心病心力衰竭患者的治疗效果。方法　本组 5 2例 ,年龄 2 3～ 67岁 ,体重 45～ 68公斤 ;风湿性主动脉瓣病变 17例 ,二尖瓣病变 35例。心功能Ⅲ级 31例 ,Ⅳ级 2 1例。每日口服贝那普利 (洛汀新 ) 10 32± 2 5 6( 2 5～ 2 0 )mg ,同时继续应用洋地黄及利尿剂。结果　应用贝那普利 2周后心功能提高Ⅲ级者 6例 ,Ⅱ级者 17例 ,Ⅰ级者 2 8例 ,无效 1例。左心室射血数明显增加 (P <0 0 1) ,心胸比率明显缩小 (P <0 0 5 ) ,无严重不良反应。结论　贝那普利用于治疗风心病心力衰竭患者是安全、有效的。     

内皮素和降钙素基因相关肽与扩张型心肌病的相关性

为探讨血浆内皮素 (ET)和降钙素基因相关肽 (GGRP)与扩张型心肌病 (DCM )的相关性 ,应用放射免疫分析法测定DCM治疗前后的ET和CGRP水平。结果 ,DCM组ET治疗前 ( 91 .2±2 2 .52 )ng/L ,治疗后为 ( 71 .2 1± 2 4 .64)ng/L均显著高于对照组 ( P <0 .0 1 .P <0 .0 5) ,CGRP水平治疗前为 ( 1 36.82± 2 1 .36)ng/L ,高于对照组的 ( 1 0 8.2 6± 1 3.2 8)ng/L(P <0 .0 1 ) ,治疗后为 ( 1 1 4 .54±1 7.2 6)ng/L ,差异不显著 ( P >0 .0 5)。结果提示 ,ET及CGRP水平与DCM病情相关 ,检测DCM患者ET及CGRP水平有助于判断病情。     

米力农合并小剂量地高辛治疗心梗后心衰临床观察

目的 :观察米力农合并小剂量地高辛治疗心梗后心力衰竭患者的临床疗效。方法 :选择 80例心梗后心力衰竭患者分别用米力农合并小剂量地高辛和一般治疗对照研究。以 10日为一疗程。治疗前后观察心功能指标及肝、肾功能等变化 ,用t检验。结果 :米力农组总有效率 82 .5 % ,治后CO 5 .88± 0 .96(L·min 1 ) ,CI 3 .5 8± 0 .2 4(L·min 1 ·m 2 ) ,EF 5 5± 14 (% )均明显优于对照组 (P<0 .0 5 )。结论 :米力农合并小剂量地高辛治疗心梗后心力衰竭安全有效。     

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.     

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.     

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.