他克莫司在肾移植术后肝功能异常中的应用

目的 :观察他克莫司 (tacrolimus)在肾移植术后肝功能异常病人中应用的有效性及安全性。方法 :将 47例病人分成环孢素组 ,给予环孢素 1 .5～3 .5mg·kg-1,po,bid ,作对照 ;他克莫司治疗组 ,给予他克莫司 0 .0 5～ 0 .1 5mg·kg-1,po,bid。 2组均同时给予霉酚酸酯、泼尼松及保肝药物治疗 ,观察 3mo。结果 :治疗后 90d,他克莫司组的ALT ,SCr,BUN指标分别下降 (1 0 0±s 45 )IU·L-1,(5 8± 3 9)μmol·L-1和 (7± 4)mmol·L-1,(P <0 .0 1 ) ;环孢素组的ALT下降 (4 6± 2 5 )IU·L-1,(P <0 .0 1 ) ,SCr及BUN分别升高 (4 3± 69) μmol·L-1(P <0 .0 1 )和(3± 6)mmol·L-1(P <0 .0 5 )。 2组间比较P <0 .0 5或P <0 .0 1。不良反应环孢素组出现 1 3例 ,他克莫司组出现 1例。结论 :他克莫司在肾移植术后肝功能异常病人中应用有利于肝功能的恢复 ,是安全有效的免疫抑制药     

促性腺素释放素类似物治疗特发性中枢性性早熟18例

目的 :观察促性腺素释放素类似物 (GnRH A)治疗特发性中枢性性早熟 (ICPP)的临床疗效。方法 :用GnRH A缓释剂治疗 18例 (男性 1例 ,女性 17例 )ICPP病人 ,疗程为 6～ 12mo ,观察第二性征变化 ,男性睾丸 ,女性乳房、子宫、卵巢容积 ,骨龄 ,生长速率 ,促黄体素释放素 (LHRH)激发试验。结果 :经治疗男性睾丸、女性卵巢、子宫容积及乳房均缩小 ,子宫容积和乳房分期治疗 6mo与治疗前比较分别为 [(2 .4±s 0 .3)cm3vs (5 .9± 0 .9)cm3,P <0 .0 1]和 [(1.8± 0 .7)vs (2 .80± 0 .10 ) ],P <0 .0 1]。骨龄延缓 ,BA /CA值随疗程而缩小。治疗后身高、骨龄及实际年龄三者间的差距逐步改善 ,治疗 12mo预测成人终身高 (PAH)从 (15 4.7± 1.7)cm提高到 (15 8± 3)cm。结论 :GnRH A缓释剂治疗ICPP可有效抑制性征发育 ,延缓骨龄成熟 ,并随疗程延长而改善成人终身高     

血清乙肝病毒定量与肝损伤及干扰素疗效的关系

目的 :探讨血清乙肝病毒定量与肝脏损伤及干扰素治疗效果的关系。方法 :对 3 4例乙肝e抗原 (HBeAg)及乙肝表面抗原 (HBsAg)阳性的乙肝患者进行干扰素治疗 ,对患者血清进行乙肝病毒定量测定及白蛋白 (ALB)、白蛋白 /球蛋白比值 (A/G)、谷 -丙转氨酶 (ALT)、谷 -丙转氨酶 (AST)、总胆红素 (TBIL)、直接胆红素 (DBIL)测定 ,将血清病毒含量≥ 10 7、10 6 .9～10 5.1、≤ 10 5 分别定为高、中、低含量组。并于治疗前行肝脏组织病理检查。结果 :3 4例患者血清HBV -DNA含量范围在 10 4～ 10 9拷贝·mL- 1,其中 13例高病毒含量患者 ,ALT值 ( 156 .0± 2 1.3 )IU·L- 1,AST值 ( 14 5.0± 11.0 )IU·L- 1,S值为 ( 2 .0 7±0 .2 1) ,G值为 ( 2 .1± 0 .7) ;14例中病毒含量患者 ,ALT值 ( 2 85.0± 18.0 )IU·L- 1,AST值 ( 12 5.0± 55.8)IU·L- 1,S值为 ( 2 .0±0 .4) ,G值为 ( 2 .4± 0 .4) ;7例低病毒含量患者ALT值 ( 167.0± 2 1.3 )IU·L- 1,AST值 ( 12 8.0± 2 7.7)IU·L- 1,S值为 ( 3 .0 1±0 .11) ,G值为 ( 3 .0 6± 0 .0 9)。 3组数值之间无明显相关性 (P >0 .0 5) ,予干扰素治疗 2 4周后 ,高、中、低病毒含量组患者有 1例( 7.69% ) ,3例 ( 2 1.43 % ) ,3例 ( 4 7.86 % )血清HBVDNA阴转 ,3者之间差异有显著     

利培酮对精神分裂症病人内分泌和体液免疫功能的影响

目的 :了解利培酮对精神分裂症病人内分泌和体液免疫功能的影响。方法 :未经治疗的精神分裂症病人 2 0例入院后用利培酮治疗 ,治疗前和治疗 4wk后分别进行PRL ,FSH ,LH ,E2 ,P ,T ,T3,T4 ,FT3,FT4 ,TSH ,rT3,TrAb ,IgG ,IgA ,IgM ,C3 和C4 的测定。结果 :治疗后性激素的改变与性别有关 ,女性的PRL和T分别升高 ( 30± 4 4 ) μg·L- 1和( 5± 7)nmol·L- 1,男性的FSH从 ( 15± 6)IU·L- 1减少为 ( 9± 8)mIU·L- 1;2 0例病人的T4 ,FT3 和rT3分别降低 ( 13± 2 2 )nmol·L- 1,( 0 .5± 0 .6)pmol·L- 1和 ( 0 .13± 0 .2 )nmol·L- 1;体液免疫的指标变化不明显 ;疗效与PRL的变化量有关。结论 :利培酮对精神分裂症病人内分泌功能的影响较大 ,对体液免疫功能的影响不明显。     

长期应用西拉普利对血液透析病人心血管的保护作用

目的 :观察西拉普利对血液透析 (血透 )病人的心血管保护作用。方法 :70例血透病人分为治疗组 (n =36 ) ,用西拉普利 2 .5～ 5mg·d- 1和对照组(n =34) ,给予对心脏重构无影响的降压药。 6mo和 12mo时彩超测心脏指标 ,并测血透前后、血透次日血压。结果 :2组均有降压作用 ,治疗组等容舒张时间 (IRT)和左室重量指数 (LVMI)用药前及用药6 ,12mo分别为 (81±s 10 )ms ,(76± 10 )ms ,(6 9±10 )ms ,(2 18± 32 ) g·m- 2 ,(172± 30 ) g·m- 2 ,(15 3±32 ) g·m- 2 ;治疗后下降 (P <0 .0 5 )。左室射血分数(LVEF) ,心排量 (CO)和舒张早晚期速度比 (EV /AV)治疗前和用药 6 ,12mo分别为 (5 6 .2± 2 .1) % ,(6 0 .2± 1.8) % ,(74 .2± 1.6 ) % ;(5 .6± 1.2 )L·min- 1,(6 .3± 1.3)L·min- 1,(7.5± 1.5 )L·min- 1和 0 .91± 0 .0 4 ,1.0 1± 0 .0 4 ,1.2 1± 0 .0 3;治疗后升高 (P <0 .0 5 ) ,对照组无显著改变。结论 :长期应用西拉普利可有效降压、逆转血透病人的左室肥厚、改善左室舒缩功能     

异维A酸治疗尖锐湿疣对白细胞介素-2、可溶性白细胞介素-2受体影响

目的 :观察异维A酸治疗尖锐湿疣对血清白细胞介素 2 (IL 2 ) ,可溶性白细胞介素 2受体(sIL 2R)的变化 ,以探讨异维A酸治疗尖锐湿疣的作用机制。方法 :3 2例尖锐湿疣病人 ,初发 1 3例 ,复发 1 9例 ,给异维A酸胶丸 1 0mg,po,tid或bid ,随访 3mo ,治疗前及治疗后mo 4查血清sIL 2R ,IL 2。结果 :痊愈 2 4例 (75 % ) ,显效 3例 ,有效 2例 ,无效 3例 (9% ) ;血清sIL 2R初发病人治疗前为(2 0 1±s 1 2 1 ) pmol·L-1,治疗后mo 4为 (1 93±1 3 2 ) pmol·L-1,P <0 .0 5 ;血清sIL 2R复发病人治疗前为 (693± 1 2 1 )pmol·L-1,治疗后mo 4为 (5 1 9± 1 0 3 ) pmol·L-1,P <0 .0 1 ;血清IL 2初发病人治疗前 (7.0± 1 .2 ) μg·L-1,治疗mo 4为 (7.2± 1 .2 )μg·L-1,P <0 .0 1 ;血清IL 2复发病人治疗前 (6±3 ) μg·L-1,治疗后mo 4为 (8.5± 2 .7) μg·L-1,P<0 .0 1。结论 :异维A酸通过调节免疫及其他多种机制达到治疗尖锐湿疣的作用     

3,6-(二甲氨基)-二苯并碘杂六环葡萄糖酸盐对大鼠缺血再灌注心肌的保护作用

3 ,6 (二甲氨基 ) 二苯并碘杂六环葡萄糖酸盐 (3,6 dimethamidodibenzopyriodoniumgluconate ,IHC 93)是迄今本类药物中水溶性最好的药物。大鼠冠状动脉闭塞 4 0min ,再灌注 12 0min ,造成心肌缺血再灌注损伤(n =10 )。测定大鼠心肌梗死范围 (41± 4 ) % ,肿胀度 (81± 4 ) % ,血清肌酸激酶〔CK ,(5 .6± 0 .9)mmol·min- 1·L- 1〕和肌酸激酶同工酶〔CK MB ,(0 .88± 0 .0 9)mmol·min- 1·L- 1〕活性明显升高 ,血清内皮素 1〔ET 1,(0 .34± 0 .0 4 ) μg·L- 1〕水平明显升高。于冠脉结扎前和再灌注前 1min分别ivIHC 930 .12 5 ,0 .2 5和 0 .5mg·kg- 1(n =10～ 11) ,与缺血再灌组比 ,大鼠心肌梗死范围不同程度缩小 ,分别为 (38± 5 ) % ,(35± 4 ) %和(33± 3) % (中、大剂量组P <0 .0 1) ;心肌肿胀度有所减轻〔(78± 4 ) % ,(76± 3) %和 (77± 2 ) % ,中、大剂量组P <0 .0 1〕 ;CK活性降低〔(5 .1± 0 .8) ,(4.7± 1.0 )和 (4.4± 1.3)mmol·min- 1·L- 1,中、大剂量组P <0 .0 5〕 ;CK MB活性降低〔(0 .12± 0 .0 4 ) ,(0 .11± 0 .0 3)和 (0 .0 9± 0 .0 4 )mmol·min- 1·L- 1,均P <0 .0 1〕 ;ET 1水平降低〔(0 .2 6± 0 .0 3) ,(0 .2 6± 0 .0 3)和 (0 .2 7± 0 .0 3) μg·L- 1,均P <0 .0     

中、低热量饮食,中等量运动和二甲双胍治疗青少年肥胖病人初探

目的 :探讨中、低热量饮食 ,中等量运动和二甲双胍治疗青少年肥胖的疗效。方法 :2 4例单纯性肥胖青少年志愿者 ,随机分为A ,B 2组。A组 1～ 8wk和B组 17～ 2 4wk服用二甲双胍 0 .2 5 g ,tid ;B组 1～ 8wk和A组 17～ 2 4wk服用安慰剂 1片 ,tid。结果 :A ,B 2组病人治疗前后的BMI分别为 (35±s 9vs 2 6± 6;35± 9vs 2 5± 6)kg·m- 2 ,WHR (1.0 2± 0 .10vs 0 .84± 0 .0 6;1.0 1± 0 .0 8vs0 .84± 0 .0 6) ,Fins[(80± 2 1) ,(5 9± 14) ;(80± 2 3) ,(5 4± 13)mU·L- 1],TG[(3.8± 1.6) ,(1.8± 1.0 ) ;(3.9± 1.5 ) ,(1.6± 0 .9)mmol·L- 1],TC[(6.8±2 .1) ,(5 .0± 1.1) ;(6.9± 2 .1) ,(5 .0± 1.7)mmol·L- 1],BUA[(4 93± 132 ) ,(35 6± 79) ;(4 91± 15 3) ,(378± 10 6) μmol·L- 1]和γ GT [(5 2± 13) ,(32±10 ) ;(5 1± 12 ) ,(32± 10 )U·L- 1]均明显降低 (均P<0 .0 5 ) ;A组 1～ 8wk服用二甲双胍时BMI ,WHR ,FIns ,TG ,γ GT的降低较B组更明显 ,而B组 17～ 2 4wk加用二甲双胍后与A组的差异消失。结论 :中、低热量饮食 ,中等量运动和二甲双胍对青少年肥胖病人有一定治疗作用     

4种非甾体抗炎药治疗类风湿关节炎的成本-效果分析

目的 :探讨 4种口服非甾体抗炎药治疗类风湿性关节炎 6mo的成本和效果。方法 :4 6 1例病人随机分成 4组 ,双氯芬酸组 131例 ,服用双氯芬酸 75～ 10 0mg·d- 1,萘丁美酮组 131例 ,服用萘丁美酮 10 0 0mg·d- 1,美洛昔康组 14 4例 ,服用美洛昔康 15mg·d- 1,塞来昔布组 5 5例 ,服用塞来昔布 2 0 0mg·d- 1,疗程均为 6mo。运用成本 -效果分析对 4组病人进行分析评价。结果 :双氯芬酸、萘丁美酮、美洛昔康、塞来昔布 4组完成疗程病例数分别为12 5 ,12 7,139和 5 5例。在疗程结束时 ,4组间疗效无显著差异 (P >0 .0 5 ) ,塞来昔布组不良反应率明显低于其他 3组 (P <0 .0 1)。 4组总成本分别为(14 0 0±s 32 6 ) ,(15 31± 36 ) ,(2 0 18± 5 2 7) ,(32 2 5±76 7)元 ;成本 -效果比为 (2 0 4 1± 6 12 ) ,(2 5 6 0±6 81) ,(2 985± 70 6 ) ,(4 6 6 7± 1389)元·例 - 1;经敏感度分析后的成本 -效果比为 (1896± 4 5 5 ) ,(2 36 6±6 38) ,(2 6 6 9± 5 89) ,(3978± 96 3)元·例 - 1。结论 :双氯芬酸为治疗类风湿性关节炎的较佳方案 ,在经济许可的情况下 ,偏重考虑药物安全性 ,塞来昔布也是一个较佳选择。     

氯沙坦对心力衰竭病人肿瘤坏死因子的影响

目的 :研究氯沙坦对心力衰竭 (CHF)病人血肿瘤坏死因子 (TNF α)、内皮素 (ET 1)、醛固酮(Ald)水平的影响。方法 :采用放免法测定CHF病人 (5 4例 )及健康志愿者 (2 8例 )血TNF α ,Ald及ET 1水平。 5 4例CHF病人分为 2组 ,非氯沙坦组给予常规抗心力衰竭治疗 ;氯沙坦组在非氯沙坦组药物治疗基础上加氯沙坦 2 5～ 5 0mg·d- 1,共 1mo。结果 :CHF病人TNF α ,Ald及ET 1水平分别为(2 .7±s 0 .8) μg·L- 1,(195± 33)ng·L- 1,(90±16)ng·L- 1,显著高于健康对照组 [(1.2± 0 .2 ) μg·L- 1,(117± 38)ng·L- 1,(5 9± 11)ng·L- 1,P <0 .0 1];氯沙坦组经治疗后TNF ,Ald及ET 1水平显著降低 ;非氯沙坦组治疗后血Ald水平明显降低(P <0 .0 1)。结论 :氯沙坦可明显降低心力衰竭病人血TNF α及ET 1水平     

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.