美罗培南与亚胺培南/西司他丁治疗医院获得性下呼吸道感染

目的比较国产美罗培南与亚胺培南／西司他丁治疗医院获得性下呼吸道感染的有效性和安全性。方法采用随机对照平行试验设计进行研究，治疗组31例，给予美罗培南0．5g，q8h，静脉滴注；对照组32例，给予亚胺培南／西司他丁1．0g，q8h，静脉滴注。两药疗程均为7～10d。结果美罗培南组和亚胺培南／西司他丁组的临床痊愈率分别为45．2％和43．8％；临床有效率分别为74．2％和78．1％；细菌清除率分别为82．6％和78．3％；不良反应发生率分别为6．5％和6．3％。以上指标差异均无显著性（P〉0．05）。结论国产美罗培南治疗医院获得性下呼吸道感染是有效和安全的，与亚胺培南／西司他丁相比无显著性差异。     

亚胺培南／西司他丁钠治疗老年人肺部感染的临床分析

目的探讨亚胺培南／西司他丁钠治疗老年人肺部感染的疗效。方法对亚胺培南／西司他丁钠治疗30例老年人肺部细菌感染进行临床疗效及细菌学评价，并测定其对65株常见呼吸道病原菌的敏感性。结果应用亚胺培南／西司他丁钠治疗后，临床痊愈率为56．7％，临床有效率为86，7％，细菌清除率为85，7％。结论亚胺培南／西司他丁钠治疗老年人肺部感染疗效确切，副作用小，其抗菌谱极广、抗菌活性很高。     

厄他培南治疗呼吸机相关性肺炎的临床疗效

目的比较厄他培南与亚胺培南／西司他丁治疗呼吸机相关性肺炎的有效性和安全性。方法采用随机对照设计,观察厄他培南与亚胺培南／西司他丁治疗60例呼吸机相关性肺炎的临床疗效和不良反应。结果厄他培南组30例,治疗有效率为90．O％,细菌清除率为83．3％;亚胺培南／西司他丁组30例,治疗有效率为86．7％,细菌清除率为82．1％;两组间差异无显著性;两组不良反应发生率均为6．7％。结论厄他培南治疗呼吸机相关性肺炎与亚胺培南／西司他丁相当,安全高效。     

亚胺培南／西司他丁与头孢他啶治疗中,重度细菌感染疗效费用分析…

对我院４５例确诊为中、重度细菌感染住院患者进行了亚胺培南／西司他丁与头孢他啶疗效费用分析比较研究。结果表明：２组病例有效率、死亡率无显著性差异；头孢他啶组较亚胺培南／西司他丁组疗程明显延长。亚胺培南／西司他丁每日所需费用明显高于头孢他啶；治疗结束时，前者全部费用并未超过后者；全部住院费用无明显差异。作者认为：决定２种药物全部费用的因素，除与药物单价和每日费用有关，还与药物疗程密切相关。选用药物抗菌     

亚胺培南/西司他丁不良反应57例文献分析

目的 分析亚胺培南／西司他丁所致药物不良反应。方法 对1994—2004年2月间国内外公开发行的60种医药期刊的相关文献报道进行分析。结果 亚胺培南／西司他丁常见不良反应为精神异常、癫痫、胃肠道反应、过敏性药疹、听力障碍，男性多于女性，老年人更易发生。结论 亚胺培南／西司他丁引起中枢神经系统不良反应最多，应用时应高度重视。     

国产亚胺培南／西司他丁的体内抗菌活性研究

皮下注射国产亚胺培南／西司他丁对金葡球菌、大肠杆菌、铜绿假单胞菌各２株感染小鼠的ＥＤ５０分别为０．０７７和０．０６９ｍｇ／ｋｇ、０．６３３和１．１６９ｍｇ／ｋｇ、０．７３４和０．６４４ｍｇ／ｋｇ，与进口亚胺培南／西司他丁的ＥＤ５０（０．０６９和０．０７３ｍｇ／ｋｇ、０．６７０和１．２９８ｍｇ／ｋｇ、０．６２８和０．６５５ｍｇ／ｋｇ）相近，国产与进口亚胺培南／西司他丁的ＥＤ５０经统计学处理无显著性差异（Ｐ＞０．０５）。     

亚胺培南/西司他丁治疗肾移植后重症肺部感染的临床分析

目的：探讨亚胺培南／西司他丁治疗肾移植术后重症肺炎的疗效。方法：回顾分析亚胺培南／西司他丁治疗22例肾移植术后重症肺部感染患者的临床资料及疗效。结果：22例中治愈10例，显效8例，总有效率81．8％；共分离出致病菌34株，用药后27株细菌被清除，细菌清除率79．4％。结论：亚胺培南／西司他丁对肾移植术后重症肺炎有良好的疗效。可作为临床的经验治疗药物。     

亚胺培南/西司他丁与头孢他啶治疗中、重度细菌感染疗效费用分析比较研究

对我院４５例确诊为中、重度细菌感染住院患者进行了亚胺培南／西司他丁与头孢他啶疗效费用分析比较研究。结果表明：２组病例有效率、死亡率无显著性差异；头孢他啶组较亚胺培南／西司他丁组疗程明显延长。亚胺培南／西司他丁每日所需费用明显高于头孢他啶；治疗结束时，前者全部费用并未超过后者；全部住院费用无明显差异。作者认为：决定２种药物全部费用的因素，除与药物单价和每日费用有关，还与药物疗程密切相关。选用药物抗菌作用越强，用药时间即相应缩短，住院时间必然缩短；最终患者住院费用降低     

国产美洛培南的体外抗菌活性

采用琼脂二倍稀释法测定国产美洛增南和其它５种药物对１３６株临床分离菌的体外抗菌活性,结果表明国产美洛增南与进口美洛增南的体外抗菌活性相近,优于头孢哌酮／舒巴坦、他唑西林和头孢他啶。国产美洛增南对金葡萄菌、铜绿假单孢菌、大肠埃希氏菌和肺炎克雷伯氏菌的抗菌活性优于亚胺培南／西司他丁,对表葡球菌和β－溶血性链球菌的抗菌活性比后者稍差。国产美洛培南的抗菌活性稍受接种菌量、培养基ｐＨ和血清浓度影响。     

哌拉西林／他唑巴坦与亚胺培南／西司他丁随机对照治疗细菌性感染

目的：通过多中心非盲法随机对照试验方法,以亚胺培南／西司他丁作对照药物,并设立开放试验,评价哌拉西林钠／他唑巴坦钠治疗中、重型细菌性感染的有效性与安全性。方法：派拉西林钠／他唑巴坦钠4．5g静脉滴注,每8－12h一次,或亚胺培南／西司他丁0．5g静脉滴注,每12h一次,治疗下呼吸道、泌尿生殖道、皮肤软组织等感染,疗程7－14d。结果：共治疗病人145例,其中试验组与对照组各54例,开放组37例。哌拉西林钠／他唑巴坦钠试验组治疗下呼吸道、泌尿生殖道、皮肤软组织、腹腔内及其它感染有效率92．59％,治愈率81．48％,细菌清除率90．38％;两组各率比较无显著性差异（P＞0．05）。哌拉西林钠／他唑巴坦钠开放治疗组临床有效率86．49％,治愈率75．68％,细菌清除率84．83％。哌拉西林钠／他唑巴坦钠与亚胺培南／西司他丁副作用发生率分别为4．40％与5．56％,1例试验组病人发生过敏性皮疹。体外抗菌活性测定表明,哌拉西林钠／他唑巴坦钠活性明显优于哌拉西林,稍较亚胺培南为差,对革兰阳性菌与阿莫西林／克拉维酸相似,对革兰阴性菌与头孢他定相似。结论：哌拉西林钠／他唑巴坦钠是一高效、安全广谱抗菌药物,对各种中、重型细菌性感染的疗效与亚胺培南／西司他丁相似,两者副作用发生率相近。     

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.

---

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.     

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.     

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.