来氟米特治疗类风湿关节炎随机双盲平行对照临床试验

目的 研究来氟米特（LEF）治疗类风湿关节炎（RA）的疗效和安全性。方法 用随机双盲双模拟平行对照多中心临床试验，试验组70例患者每日口服来氟米特（LEF）20mg，1天1次；对照组69例患者口服氨甲喋呤（MTX）15mg，1周1次，疗程12周，部分病例积累用药24周。结果 治疗12，24周，试验组与对照组有效率分别为44．28％（70例），79．36％（63例）；49．27％（69例），74．19％（62例），2组比较无显著性差异。2组均能改善RA患者临床症状、体征和关节功能，降低血沉、C-反应蛋白和类风湿因子水平。2组药物不良反应发生率分别为17．14％（12例）和31．88％（22例）（P〈0．05）。结论 来氟米特治疗类风湿性关节炎疗效与耐受性均较氨甲喋呤好。     

来氟米特与甲氨蝶呤治疗类风湿关节炎的开放对照研究

目的：对比来氟米特和甲氨蝶呤治疗类风湿性关节炎患者的临床疗效和安全性。方法：随机选择活动期类风湿性关节炎患者96例,分为LEF组48例,给予来氟米特20mg,口服,每天1次;MIX组48例,给予甲氨蝶呤10mg,口服,每周1次,4—6周后停用。观察两组治疗后症状、体征、不良反应改善情况。结果：两种药物治疗类风湿性关节炎的疗效均在90．0％以上,同时大多数患者耐受性好,不良反应轻,两组相比较,差异无统计学意义。结论：来氟米特与甲氨蝶呤治疗类风湿关节炎疗效都比较好,副作用少,花费较低,是类风湿关节炎的可取治疗方案。     

来氟米特与甲氨喋呤对照治疗类风湿关节炎160例

目的：观察来氟米特（leflunomide,LEF)治疗类风湿关节炎（RA）的疗效和安全性,并用甲氨蝶(methotrexate,MTX)作对照。方法：160例活动性RA患者随机分为23组,每组各80例,用随机双盲方法分别服用LEF20MG.D^-1,或TMX15mg/周,疗程均为24周,比较观察其疗效和不良反应。结果：经治疗24周后,LEF组有效率和显效率分别为81．54％和36．92％,MTX组分别为75．81％和35．48％。不良反应发生率LEF组和TMX组分别为15．39％和26．47％。2组疗效和不良反应发生率均无明显判别,但LEF组的不良反应程度明显较MTX组轻,结论：LEF治疗RA的疗效肯定,且具有料好的耐受性。     

不同组合治疗类风湿关节炎对肝酶的影响

目的研究不同组合治疗类风湿关节炎（RA）对肝酶的影响。方法40例患者,随机分为两组：甲氨喋呤（MTX）＋来氟米特（LEF）组、甲氨喋呤（MTX）＋来氟米特（LEF）＋白芍总苷（TGP）组,每组20例。分别于治疗0、4、8、12周比较肝功。结果治疗第12周疗效比较：MTX＋LEF＋TGP组总有效率95%,明显优于MTX＋LEF组（有效率90%）。MTX＋LEF组的肝损害高于MTX＋LEF＋TGP组。肝损害多见于具有危险因素的患者,多发生于用药4周以后。结论联合应用TGP治疗活动期RA,近期疗效显著优于MTX＋LEF组;联合应用TGP后肝损害减少。     

来氟米特和甲氨蝶呤治疗类风湿关节炎的疗效观察

目的观察来氟米特和甲氨蝶呤治疗类风湿关节炎的临床疗效。方法选取我院自2010年1月至2011年12月收治的类风湿关节炎患者96例随机分为LEF组和MIX组各48例,LEF组给予来氟米特20mg,口服每日一次,MIX组给予甲氨蝶呤10mg口服每周一次,24周为1个观察周期,观察并比较两组用药期间的ACR及药物不良反应,观察两组的治疗效果。结果治疗4、8、12、24周后来氟米特组的ACR20、ACR50有效率明显高于甲氨蝶呤组,两组比较差异有显著性(P<0.05);两组间不良反应发生率差异无显著性(P>0.05)。结论两组治疗类风湿关节炎的疗效都比较好,且副作用少,但来氟米特治疗4、8、12、24周的疗效相比较优于甲氨蝶呤。     

甲氨蝶呤联合来氟米特治疗类风湿关节炎的临床研究

目的观察甲氨蝶呤（MTX）联合来氟米特（LEF）治疗类风湿关节炎（RA）的临床疗效及安全性。方法将82例RA患者随机分为治疗组与对照组,2组同时给予糖皮质激素醋酸泼尼松片10mg／d,关洛昔康7．5mg／d。对照组40例应用甲氨蝶呤（MTX）治疗,10mg,每周1次。治疗组42例在对照组的基础上口服来氟米特（LEF）10mg,1次／d,疗程均为24周,疗程结束后比较2组临床疗效。结果经24周治疗后,治疗组在临床缓解率、总有效率及各项观察指标改善方面均明显优于对照组,表明治疗组疗效显著,组间差异有统计学意义（P＜0．05）。治疗期间2组均出现谷丙转氨酶升高,白细胞减少、恶心、上腹部不适等不良反应。不良反应发生率分别为治疗组21．43％;对照组20．00％,2组相比较,差异无统计学意义（P＞0．05）。结论甲氨蝶呤联合来氟米特治疗RA可明显改善患者的临床症状和实验宦指标．疗效确切．     

类风关Ⅰ号联合来氟米特治疗类风湿关节炎临床观察

目的观察类风关Ⅰ号联合来氟米特(LEF)治疗类风湿关节炎(RA)的临床疗效。方法选择60例类风湿关节炎患者,随机分为对照组和治疗组各30例。对照组口服来氟米特50mg/d,3d后改为20mg/d;治疗组在对照组服用来氟米特治疗的基础上,加服类风关Ⅰ号30mL,3次/d,总疗程12周。观察晨僵、关节疼痛(压痛)数、关节肿胀数,平均握力,进行血沉(ESR)、C反应蛋白(CRP),DAS28评分。结果两组治疗12周后,治疗组与对照组相比,差异显著(P<0.05);治疗组达ACR70者明显高于对照组(P<0.05)。结论类风关Ⅰ号联合来氟米特口服治疗类风湿关节炎疗效肯定,优于单用来氟米特治疗,且无明显不良反应,值得推广应用。     

来氟米特治疗类风湿关节炎的临床观察

目的 观察来氟米特（LEF）治疗活动期类风湿关节炎（RA）的疗效及安全性。方法活动期RA患者90例,随机分为治疗组45例,给予LEF20mg／d;对照组45例,给予甲氨蝶呤15mg,每周1次,24周为1个疗程,观察两组的治疗效果及不良反应。结果两组患者的症状、体征及实验室指标改善情况均较治疗前差异有统计学意义（均P〈0．05）;治疗组与对照组总有效率分别为93．3％、91．1％（P〉0．05）;两组不良反应发生率分别为13．3％、15．6％（P〉O．05）。结论LEF治疗RA与甲氨蝶呤同样有效,且不良反应小。     

来氟米特与环磷酰胺治疗狼疮肾炎的对照观察

目的比较来氟米特（LEF）和环磷酰胺（CTX）治疗狼疮肾炎（LN）的疗效、不良反应及安全性。方法43例活动性LN患者在使用激素的基础上随机分为两组,LEF组22例和CTX组21例,LEF组给予LEF20mg／d,半年为一疗程;CTX组间断给予CTX12mg·k^-1·d^-2加入10％葡萄糖注射液250ml中静脉滴注,每2周为一疗程,环磷酰胺总累计量控制在150mg／kg以内,随访6个月,监测血常规、血清白蛋白（Alb）、血肌酐（SCr）、ANA、ds—DNA、血24h尿蛋白定量、尿沉渣红细胞计数和白细胞计数和可能伴随的不良反应。结果治疗总有效率LEF组81．8％,CTX组85．7％,组间差异无统计学意义。不良反应CTX组13例（61．9％）,LEF组3例（13．6％）,组间差异有统计学意义。结论LEF治疗LN疗效与CTX相当,但其不良反应相对较轻,耐受性较好。     

来氟米特和甲氨蝶呤治疗幼年大鼠关节炎

目的：对比观察来氟米特(LEF)和甲氨蝶呤(MTX)治疗幼年大鼠关节炎的疗效及副作用。方法：皮内注射Ⅱ型胶原，复制胶原关节炎大鼠模型。将大鼠模型随机分为3组，每组20只：LEF组，每只给予LEF 0.4 mg·d 1，泼尼松(Pred) 1 mg·d 1，ig，疗程4周；MTX组，每只给予MTX 0.1 mg·d 1，Pred l mg·d 1，ig，疗程4周；对照组，0.9%氯化钠溶液，ig，qd，共4周。观察指标为关节炎指数评分、足掌体积、运动平衡能力、踝关节的X线改变、滑膜及肝脏病理改变、血清IgG、C 反应蛋白。结果：治疗第1周后，LEF组与MTX组比较，大鼠脚掌肿胀减轻、平衡能力增强，两组差异有显著性(P＜0.05)；治疗4周后，LEF与MTX组大鼠脚掌肿胀均完全消失；处死动物，IgG、C 反应蛋白、肾、踝关节组织病理改变，LEF组与MTX组相比，差异无显著性(P＞0.05)；与对照组相比较均差异有显著性(P＜0.05)。肝组织病理检查，MTX组部分大鼠肝脏组织切片苏木精 伊红(HE)染色可见肝细胞玻璃样变性、点状坏死，LEF组与MTX组相比，差异有显著性(P＜0.05)。结论：来氟米特和甲氨蝶呤治疗幼年大鼠关节炎模型均有明显疗效，但LEF起效快，毒性低。     

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.     

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.