环孢素A滴眼液在角膜移植免疫排斥中应用观察

目的探讨环孢素A（CsA）滴眼液应用于角膜移植手术后防治角膜移植排斥反应的疗效。方法对在我院施行穿透性角膜移植术的33例（33眼）病例,术后7d33眼均应用1％CsA滴眼液和妥布霉素地塞米松滴眼液至6个月。结果角膜移植术后出现角膜排斥反应有6例（6眼）,经治疗有5例（5眼）植片排斥反应得到控制,植片恢复透明,有效率83．3％。结论证明在角膜移植求后应用1％CsA滴眼液防治角膜移植排斥反应确实有效。     

他克莫司滴眼液抑制家兔全角膜移植免疫排斥反应

目的通过家兔全角膜移植动物实验,考察他克莫司滴眼液抑制家兔角膜移植免疫排斥反应的量效关系,为他克莫司滴眼液的临床应用提供实验依据。方法建立家兔全角膜移植排斥反应模型,随机分成A组、B组、C组、D组、E组和F组。其中A组为溶剂对照组,B组、C组、D组、E组质量分数分别为0.01%、0.025%、0.05%、0.1%的他克莫司滴眼液,F组为环孢霉A滴眼液。用裂隙灯记录比较各组排斥反应指数(rejection index,RI)和植片存活时间,连续给药28 d后摘取角膜进行组织学检查。结果术后B组、C组、D组、E组和F组各组与A组比较,角膜植片RI和植片存活时间均有显著差异(P<0.05或P<0.01),呈剂量-效应关系,淋巴细胞浸润及新生血管生成均明显减少。结论质量分数0.05%的他克莫司滴眼液可抑制家兔全角膜移植免疫排斥反应。     

光学性角膜移植术及其排斥反应防治的临床研究

报告角膜移植术255例（256眼）。植片透明率达96．09％，混浊者占3．91％。患者术前视力均≤0．1，术后视力提高率为90．83％，眼局部滴用1％CyclosporinA（CsA，环孢霉素A）有明显防治排斥反应的作用。     

他克莫司滴眼液与环孢素A滴眼液在全角膜移植术后免疫排斥反应的疗效观察

目的观察0.05%他克莫司(FK506)滴眼液与1%环孢素A(CsA)滴眼液在全角膜移植术后免疫排斥反应的临床疗效.方法选择62例(62只眼)全角膜移植术后的患者,按随机原则将其分试验组(FK506组)及对照组(CsA组)各31例31只眼,平均年龄37.8岁.观察应用两种滴眼液后不同时期角膜移植术后角膜免疫排斥的情况.结果在全角膜移植术后第6个月FK506组排斥率为68.4%,CsA组排斥率为92.1%,在统计学有显著差异(P<0.01).结论 FK506滴眼液用于角膜移植术后抗排斥反应疗效明显优于CsA滴眼液.经动物试验及临床应用,未见有不良反应.     

他克莫司滴眼液与环孢素A滴眼液在全角膜移植术后免疫排斥反应的疗效观察

目的　观察 0 .0 5 %他克莫司 (FK5 0 6 )滴眼液与 1%环孢素A(CsA)滴眼液在全角膜移植术后免疫排斥反应的临床疗效。方法　选择 6 2例 (6 2只眼 )全角膜移植术后的患者 ,按随机原则将其分试验组 (FK5 0 6组 )及对照组 (CsA组 )各 31例 31只眼 ,平均年龄 37.8岁。观察应用两种滴眼液后不同时期角膜移植术后角膜免疫排斥的情况。结果　在全角膜移植术后第 6个月FK5 0 6组排斥率为 6 8.4 % ,CsA组排斥率为 92 .1% ,在统计学有显著差异 (P <0 .0 1)。结论　FK5 0 6滴眼液用于角膜移植术后抗排斥反应疗效明显优于CsA滴眼液。经动物试验及临床应用 ,未见有不良反应。     

雷帕霉素微乳滴眼剂的制备及其在大鼠角膜移植排斥反应的应用

目的 制备雷帕霉素微乳滴眼剂,评价其抑制大鼠角膜移植排斥反应的疗效.方法 采用微乳制备方法,研制雷帕霉素微乳滴眼剂;通过大鼠双眼滴加药液进行粘膜刺激性试验和对大鼠角膜移植排斥反应的作用,评价雷帕霉素微乳滴眼液治疗大鼠角膜移植的效果.结果 雷帕霉素微乳滴眼剂为透明或半透明的淡蓝色均一溶液,其平均粒径129.5nm,对粘膜刺激性小;有效减少角膜移植排斥反应的发生,显著延长角膜植片的存活时间.结论 雷帕霉素微乳滴眼剂能够用于治疗大鼠角膜移植手术后的排斥反应.     

妥布霉素玻璃酸钠滴眼液与妥布霉素地塞米松滴眼液在超声乳化白内障吸除术后的应用对比研究

目的:评价妥布霉素玻璃酸钠滴眼液与妥布霉素地塞米松滴眼液在超声乳化白内障吸除术后应用的临床有效性和安全性.方法:随机、单盲筛选出白内障病人121例(121眼)施行超声乳化白内障吸除联合人工晶体植入术,分成试验组和对照组两组,试验组术后滴用妥布霉素玻璃酸钠眼液,对照组术后滴用妥布霉素地塞米松眼液,分别于术后第1天以及用药后第3天、第7天和第14天观察眼部症状和体征,并进行统计学分析.结果:两组术后泪膜破裂时间、结膜充血、睫状充血、房水闪辉差异显著,而角膜内皮细胞计数、视力、眼压等差异无显著性.结论:对部分手术创伤小、炎症反应轻的超声乳化白内障吸除术后的患者可以使用妥布霉素玻璃酸钠滴眼液.     

妥布霉素滴眼液的安全性研究

目的考察妥布霉素滴眼液的安全性。方法对比观察妥布霉素滴眼剂、5%辣椒酊、生理盐水局部应用、单次给药和连续给药1周对家兔眼的刺激性。结果妥布霉素滴眼液单次及多次给药对兔眼均无明显影响,双眼角膜透明,无混浊,虹膜纹理清晰,结膜无充血、水肿、分泌物。结论妥布霉素滴眼液临床应用是安全的。     

受体血清保存植片角膜移植术后排斥反应的实验研究

目的和方法：通过建立兔穿透性角膜移植（PKP）模型，对在受体血清和Hanks液分别进行了24h和72h保存后的兔角膜植片PKP术后的排斥反应指数（RI）进行比较，对受体血清保存的植片能否减轻排斥反应作出 初步的评价。结果：72h保存组的RI明显低于其余3组，而血清和Hanks液两之间保存时间相同的情况下，差异无显著性。结论：支持植片保存液24h公上保存比24h以内者排斥反应发生率低的假说；不支持受体血清保存植片能较其它保存方法减少PKP术后排斥反应率的论断。     

妥布霉素-地塞米松滴眼液致角膜溃疡2例

2例患者使用妥布霉素-地塞米松滴眼液后出现角膜溃疡.例1男,54岁,因右眼新生血管性青光眼、右眼中央静脉阻塞行青光眼阀植入术.术后给予妥布霉素-地塞米松滴眼液滴眼,1滴/h.第7天,患者右眼颞侧角膜缘出现一椭圆形浅溃疡,深达1/3角膜厚度,溃疡边缘呈灰色水肿.角膜刮片检查及细菌、真菌培养均呈阴性.考虑角膜溃疡与妥布霉素-地塞米松滴眼液有关.停用该滴眼液,给予重组牛碱性成纤维细胞生长因子滴眼液和羧甲基纤维素钠滴眼液,并口服维生素C和维生素B2.停药第2天,角膜溃疡完全愈合.例2女,28岁,因左眼外伤性白内障、左眼晶状体半脱位行左眼白内障摘除和人工晶体植入术.术后给予妥布霉素-地塞米松滴眼液滴眼治疗,1滴/h.第3天患者左眼颞侧角膜缘出现一条带状溃疡,深达2/3角膜厚度,溃疡边缘呈灰色水肿.角膜刮片检查及细菌、真菌培养均为阴性.考虑角膜溃疡与托布霉素-地塞米松滴眼液有关.停用该滴眼液,给予重组牛碱性成纤维细胞生长因子滴眼液和羧甲基纤维素钠滴眼液,并口服维生素C和维生素B2.停药第3天,角膜溃疡完全愈合.     

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.     

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.