莫索尼定治疗难治性高血压

目的 :评价莫索尼定对难治性高血压的疗效及安全性。方法 :6 8例难治性高血压病人 ,男性38例 ,女性 30例 ,年龄 (5 4±s 14 )a ,在原有用药基础上加用莫索尼定 0 .2mg ,po ,qd ;若 2wk以上血压≥ 18.7/ 12kPa ,剂量增至 0 .4mg ,po ,qd ;于治疗前后进行 2 4h动态血压监测。结果 :治疗后偶测血压 [SBP和DBP分别为 (2 1.6± 1.6 )kPavs(18.1± 1.1)kPa ,(13.3± 0 .9)kPavs (11.3±0 .4 )kPa]及 2 4h动态血压均较治疗前明显降低(P <0 .0 5 ) ;不良反应轻微。结论 :莫索尼定治疗难治性高血压降压疗效确切 ,不良反应轻微     

伊贝沙坦与双氢克尿噻联合治疗高血压临床观察

目的　对伊贝沙坦 (Irb)与小剂量双氢克尿噻 (HCT)联合治疗原发性高血压的疗效、安全性进行临床评价。方法　 5 7例轻、中度原发性高血压患者经 2周安慰剂后 ,服用Irb 15 0mg ,每天 1次。 2周末坐位收缩压 (SBP)≥ 18.6kPa(140mmHg)、舒张压(DBP)≥ 12kPa(90mmHg)者加服HCT 12 .5mg ,每天 1次。继续服用 2周后 ,仍坐位SBP≥ 18.6kPa、DBP≥ 12kPa者 ,Irb加量至3 0 0mg,每天 1次 ,继续服用 4周。分别观察安慰剂期末和服药 8周末的 2 4h动态血压监测 (ABPM)值和实验室检查值的变化。结果　治疗 8周后坐位SBP和DBP分别下降 2 1.9%、17.1% ,降压有效率 98%。ABPM 2 4h平均血压、白昼夜间平均血压均明显下降 (P <0 .0 1) ,动态血压负荷值小于 40 %。无咳嗽等不良反应发生。结论　Irb与小剂量HCT合用可提高血压控制率 ,减少药物副作用 ,耐受性好     

厄贝沙坦治疗原发性高血压病人的疗效和安全性

目的 :评价国产厄贝沙坦对轻、中度原发性高血压病人的降压疗效和安全性。方法 :多中心、随机、双盲、双模拟设计。轻、中度原发性高血压病人 2 16例 ,经 2wk安慰剂导入期后 ,分成 2组 ,分别服厄贝沙坦 15 0mg加氯沙坦模拟药片 1片或氯沙坦 5 0mg加厄贝沙坦模拟药片 2片 ,qd。 4wk后如血压≥ 18.7/12kPa则将剂量加倍 ,共 8wk。另有 2 0例病人开放服厄贝沙坦。结果 :治疗 8wk后 ,厄贝沙坦组和氯沙坦组总有效率为 81.9%和77.0 %。收缩压下降 (2 .9±s 1.9)kPa和 (2 .6±2 .0 )kPa ,舒张压下降 (1.8± 1.1)kPa和 (1.8± 1.2 )kPa ,治疗前后差异均有非常显著意义 (P <0 .0 1) ,组间比较差异无显著意义 (P >0 .0 5 ) ;不良反应 2组分别为 8.7%和 8.9% ,无一例停药 ;开放组 2 4h动态血压监测T/P比值SBP 6 2 % ,DBP 5 6 %。结论 :厄贝沙坦是有效且不良反应少的长效降压药物     

西尼地平治疗轻、中度原发性高血压病人的疗效和安全性

目的 :观察西尼地平治疗轻、中度原发性高血压病人的降压疗效和安全性。方法 :采用随机、双盲、平行对照试验设计。经过 2wk安慰剂洗脱后 ,筛选轻、中度高血压病病人 4 8例。分为A组 2 4例 ,给西尼地平 5mg加苯磺酸氨氯地平模拟片 ,po ,qd ;B组 2 4例 ,为苯磺酸氨氯地平 5mg加西尼地平模拟片 ,po ,qd。 4wk末如达目标血压 (坐位舒张压≤ 12kPa) ,继续服用至 8wk末 ,否则剂量加倍服用至 8wk末。结果 :2组总有效率分别为 75 %和 83% ,2组收缩压降低幅度分别为 (0 .2 6±s 0 .16 )kPa和 (0 .31± 0 .16 )kPa ,舒张压降低幅度分别为 (0 .2 1± 0 .11)kPa和 (0 .2 4± 0 .0 8)kPa(均P <0 .0 1)。不良反应 2组无显著差异。结论 :西尼地平治疗对轻、中度原发性高血压病人有效、安全     

厄贝沙坦治疗轻、中度高血压病

目的 :评价国产厄贝沙坦对轻、中度原发性高血压的降压疗效及安全性。方法 :为双盲对照试验。轻、中度原发性高血压病人 40例 (男性 3 2例女性 8例 ,年龄 49a±s 1 0a)随机分为厄贝沙坦组和缬沙坦组各 2 0例 ,分别给予厄贝沙坦 1 5 0mg ,po,qd或缬沙坦 80mg ,po,qd ;2wk后按血压决定维持原剂量或厄贝沙坦增加到 3 0 0mg ,po,qd或缬沙坦增加为 1 60mg,po,qd;总疗程 4wk。结果 :厄贝沙坦治疗 4wk末的总有效率为 75 % ,收缩压下降 (2 .7± 1 .8)kPa,舒张压下降 (1 .5± 0 .8)kPa均P <0 .0 1 ;不良反应的发生率为 5 %。结论 :国产厄贝沙坦治疗轻、中度原发性高血压的短期疗效明显 ,每日服药 1次 ,疗效持久、稳定     

氯沙坦与氨氯地平的降压疗效及对左室肥厚逆转作用的比较

目的 :评价并比较氯沙坦及氨氯地平的降压疗效及对左室肥厚的逆转作用。方法 :12 0例高血压病伴左室肥厚病人随机分为 2组。氯沙坦组6 0例 ,给氯沙坦 2 5～ 50mg ,po ,qm。氨氯地平组6 0例 ,给氨氯地平 5～ 10mg ,po ,qm ;疗程均为 2 4wk。结果 :治疗 2 4wk后 ,氯沙坦组SBP和DBP下降差值分别为 (3.4± 1.7)kPa和 (2 .7± 0 .7)kPa ,氨氯地平组为 (3.2± 1.5)kPa和 (2 .2± 0 .9)kPa(均P<0 .0 1)。组间比较 ,氯沙坦组除偶测血压SBP外 ,DBP和 2 4h动态血压均较氨氯地平组下降显著 (P<0 .0 1)。2组室间隔厚度、左心室后壁厚度、左室心肌重量指数较治疗前显著改善 (P <0 .0 1)。结论 :氯沙坦与氨氯地平均能显著降压 ,并使左室肥厚逆转     

依那普利-氢氯噻嗪治疗原发性高血压的临床疗效

目的:研究依那普利-氢氯噻嗪治疗中国人原发性高血压的临床疗效、安全性和耐受性。方法:采用随机、双盲、平行对照临床试验。126例轻、中度原发性高血压[95mmHg≤平均坐位舒张压(DBP)<110mmHg,平均坐位收缩压(SBP)<180mmHg(1mmHg=0.133kPa)],口服安慰剂2wk后, DBP仍在95-110mmHg的病人,随机分为3组,A组口服依那普利-氢氯噻嗪(10mg:6.25mg),qd;B组口服依那普利-氢氯噻嗪(10mg:12.5mg),qd;C组口服依那普利10mg,qd,4wk后如DBP≥90mmHg,各组剂量均加倍,疗程为8wk。安慰剂期末和治疗2,4,6,8wk测量坐位、立位血压和心率,记录不良反应。结果:8wk末,A组DBP由(99±4)mmHg降至(83±6)mmHg,降低(15±4)mmHg, SBP降低(18±14)mmHg;B组DBP由(100±5)mmHg降至(83±6)mmHg,降低(16±7)mmHg, SBP降低(17±16)mmHg;C组DBP由(97.0±2.0)mmHg降至(89±8)mmHg,降低(8±8)mmHg, SBP降低(3±14)mmHg。各组内DBP与治疗前相比均有非常显著差异(P<0.01),A,B两组组间差异无显著意义(P>0.05),A,B两组降压幅度优于C组,组间比较差异显著(P<0.05)。A,B,C组降压总有效率分别为86％,83％及60％,A,B两组比较无显著差异,分别与C组比较差异显著,优于C组(P<0.05)。3组主要不良反应为咳嗽、干咳,组间比较发生率无显著差异。结论:依那普利-氢氯噻嗪治疗轻、中度原发性高血压疗效优于单药制剂,6.25mg与12.5mg氢氯噻嗪的复方制剂降压疗效相似,复方制剂和单药一样安全,且耐受性好。     

氯沙坦与依那普利治疗高血压合并高尿酸血症各34例的比较

目的 :观察氯沙坦和依那普利对轻、中度原发性高血压合并高尿酸血症病人血尿酸代谢和降压疗效。方法 :6 8例轻、中度原发性高血压合并高尿酸血症病人分为 2组 ,氯沙坦组 34例 ,用氯沙坦 5 0mg ,po ,qd ,依那普利组 34例 ,用依那普利 10mg ,po ,qd ,均持续 4wk。结果 :wk 4末降压总有效率氯沙坦组 76 % ,依那普利组 79%。 2组疗效比较 ,P >0 .0 5。血尿酸水平在wk 4末氯沙坦组较治疗前下降 (12 5±s 4 0 ) μmol·L- 1,依那普利组下降(34± 38) μmol·L- 1,氯沙坦组和依那普利组降血尿酸总有效率为 74 %和 2 1% ,2组疗效比较 (P <0 .0 1)。结论 :氯沙坦不仅降压而且降低血尿酸水平。     

氯沙坦、吲哒帕胺单药或联合治疗对血压、血钾和尿酸的影响

目的 :观察氯沙坦、吲哒帕胺单药及联合治疗对原发性高血压病人血压、血钾和血尿酸的影响。方法 :60例轻、中度原发性高血压病人 ,男性 3 4例 ,女性 2 6例 ,年龄 (4 6±s9)a,分为 3组 ,每组 2 0例。氯沙坦组服氯沙坦 5 0mg,po,qd ;吲哒帕胺组服吲哒帕胺 2 .5mg ,po,qd;联合治疗组 2药服法同上 ,疗程均为 1 2wk。检测各组治疗前后血压、血钾和尿酸值。结果 :3组治疗后收缩压和舒张压均较治疗前明显降低 (P <0 .0 1 ) ,联合治疗组降压幅度最大 ,1 2wk时收缩压下降(3 .4± 1 .1 )kPa,舒张压下降 (2 .7± 0 .5 )kPa。吲哒帕胺组治疗后血钾值较治疗前降低 ,氯沙坦组血钾上升 ,但均在正常范围之内。吲哒帕胺组血尿酸升高而氯沙坦组则降低 ,与治疗前相比有非常显著意义 (P <0 .0 1 )。联合治疗组治疗前后血钾和血尿酸无明显变化 (P >0 .0 5 )。结论 :氯沙坦有降低血尿酸的作用 ,其与吲哒帕胺联合治疗不仅有协同降压作用 ,而且能抵消吲哒帕胺单用所引起的血钾下降和血尿酸上升的不良反应     

厄贝沙坦单用及合用治疗轻、中度原发性高血压60例

目的 :比较国产厄贝沙坦单用以及与非洛地平或雷米普利合用对轻、中度原发性高血压的降压疗效。方法 :6 0例轻、中度高血压病人 ,经 2wk安慰剂导入期后 ,单服厄贝沙坦 15 0mg ,qd。 4wk后随机分 2组 ,分别联合服用非洛地平 5mg ,qd ,或雷米普利 5mg ,qd ,均为 4wk。治疗前及治疗后 4wk和 8wk行 2 4h动态血压监测 ,并测治疗前后坐位血压。结果 :厄贝沙坦单用 4wk后 ,坐位血压和2 4h动态血压均下降 (P <0 .0 5或P <0 .0 1) ,收缩压和舒张压的谷峰比值为 0 .82和 0 .86。厄贝沙坦与非洛地平或雷米普利合用 4wk后 ,坐位血压总有效率从 4 0 %增加为 89%和 70 % ;动态血压显示联合用药降压作用较明显。结论 :厄贝沙坦单用有长效的降压作用 ,与非洛地平或雷米普利联合用药有叠加降压作用     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.