双环醇治疗慢性乙型病毒性肝炎43例

目的：探讨双环醇治疗慢性乙型病毒性肝炎(乙肝)的疗效及不良反应。方法：选择慢性乙肝患者85例，随机分成治疗组和对照组，其中治疗组43例，在常规综合治疗基础上，加用双环醇25 mg，po，tid。对照组42例，单纯采用常规综合治疗，两组疗程均为6个月，并随访3个月。观察两组丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)变化及HbeAg、HBV DNA转阴情况和HBeAg/HBeAb血清转换率。结果：疗程结束时，治疗组HBeAg、HBV DNA转阴率和HBeAg/HBeAb血清转换率均明显优于对照组(P＜0.05)，停药3个月随访观察，上述各项指标检测显示，治疗组疗效比对照组更加明显(P＜0.01)，未见明显药物不良反应。结论：双环醇治疗慢性乙肝，疗效显著，可靠，值得临床推广。     

替比夫定联合阿德福韦酯对 HBeAg 阳性慢性乙型肝炎的疗效观察

目的：探讨替比夫定联合阿德福韦酯对HBeAg阳性慢性乙型肝炎患者的疗效。方法将76例慢性乙型肝炎患者分为干扰素组和替比夫定组,干扰素组应用聚乙二醇干扰素α-2a联合阿德福韦酯,替比夫定组给予替比夫定联合阿德福韦酯,治疗48周,观察血清谷氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的含量和正常化率及血清HBsAg、HBeAg和乙肝病毒（HBV） DNA的含量及HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率变化。结果2组治疗后24周和48周ALT和AST的含量及血清HBsAg、 HBeAg和HBV DNA的含量均明显降低（ P ＜0．01）,而替比夫定组治疗后降低量更显著;ALT和AST正常化率,HBeAg阴转率和血清转换率及HBV DNA低于检测下限值率显著增加（ P ＜0．01）,而替比夫定组治疗后的增加量更显著。结论替比夫定联合阿德福韦酯的治疗效果比干扰素联合阿德福韦酯的治疗更加显著。     

373例乙型肝炎患者HBV-DNA定量与乙型肝炎病毒核心抗原及肝脏酶学指标的相关性分析

目的探讨HBV—DNA定量和乙型肝炎病毒核心抗原在诊断乙型肝炎和评价病情中的意义。方法收集373例乙型肝炎患者的HBV—DNA定量、HBeAg与丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转移酶（GGT）等实验室诊断指标,进行相关性分析。结果（1）HBV—DNA定量与HBeAg具有相关性（P〈0．01）。（2）HBV—DNA定量与ALT、AST、GGT结果具有相关性（P〈0．01）。（3）HBeAg与ALT、AST、GGT结果无相关性（P〉0．05）。结论（1）HBeAg一定程度上反映了病毒在体内的复制情况,但HBV—DNA定量是评价体内病毒复制更直接的指标。（2）HBV—DNA定量结果与肝功能受损情况相关,高病毒载量是肝功能受损的危险因素。     

双环醇片联合肌苷片治疗老年脂肪肝疗效及对肝功能和血脂水平的影响

目的:观察双环醇片联合肌苷片治疗老年脂肪肝的临床效果.方法:选取2014年5月～2016年9月于郑州人民医院消化内科治疗脂肪肝的102例老年患者,依照随机数表分为双环组与对照组各51例.双环组予以双环醇片联合肌苷片的药物治疗方案,对照组在药物治疗方面仅予以肌苷片.比较治疗前后两组肝功能[天门冬氨酸氨基转移酶(ALT)、丙氨酸氨基转移酶(AST)]、血脂[血清总胆固醇(TC)、甘油三酯(TG)]水平,并评价疗效.结果:治疗后两组体内ALT、AST水平明显降低,肝功能均有显著改善,且双环组ALT、AST水平远低于同期对照组(P均<0.05);双环组血清内TC、TG水平较治疗前明显降低,且明显低于同期对照组(P均<0.05);双环组治疗有效率明显高于对照组(P<0.05).结论:在药物治疗老年脂肪肝过程中予以双环醇片联合肌苷片可有效改善肝功能、调治血脂,显著提升疗效.     

双环醇的抗病毒与肝细胞保护作用及其作用机制

双环醇是人工合成的一类抗慢性病毒性肝炎新药,具有显著的保肝作用和一定抗肝炎病毒活性。该药50,100,200mg.kg^-1ig对CCl4,D-氨基半乳糖,对乙酰氨基酚引起的小鼠肝损伤以及卡介苗＋脂多糖（LPS）诱导的小鼠免疫性肝炎均有明显降ALT和AST作用,并能减轻肝组织病理损伤。双环醇体外药对2．2．15细胞株分泌HBeAg和HBsAg有抑制作用,该药0．4和0．6g.kg^-1ig对鸭病毒性肝炎血清和肝脏的DHBV－DNA有显著抑制作用,对该药作用的机制进行多方面的研究的结果表明,双环醇不是转氨酶抑制剂,而是有清除自由基作用以保护细胞膜,并且能保护肝细胞核DNA免受损伤和减少细胞凋亡的发生。     

双环醇治疗肾移植术后肝损伤的应用

目的:研究双环醇治疗肾移植术后环孢素致肝损伤的疗效.方法:12例因环孢素致肝损伤的肾移植术后患者每日口服双环醇75mg,持续给药2周.口服双环醇前后患者自肘静脉采血,在自动生化分析仪上测定肝功能,并以特异性荧光偏振免疫法测定环孢素全血药物浓度.结果:全部12例肾移植术后患者在口服双环醇(75mg)2周后,血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)均显著下降(P＜0.01),ALT水平从(126.8±99.3)U/L显著降至(31.5±12.4)U/L(P＜0.01),AST水平从(67.4±55.5)U/L显著降至(29.6±14.9)U/L;同时环孢素血药浓度明显降低(P＜0.05),从(243.72±67.22)ng/mL减少至(157.71±54.73)ng/mL.12例患者中没有观察到药物不良反应.结论:双环醇能有效且比较安全地应用于肾移植术后环孢素致肝损伤患者,但环孢素血药浓度有改变,应注意临床监测.     

荧光定量检测HBV DNA与ELISA法测两对半相关性分析

目的 探讨荧光定量检测HBV DNA与乙肝两对半之间的关系及临床意义。方法 运用荧光定量PCR(FQ—PCR)与ELISA两种方法同时检测242份血清，对其结果加以对比分析。结果 51例乙肝大三阳患者血清HBV DNA检出率100％(51／51)；60例乙肝小三阳患者血清HBV DNA检出率51．7％(31／60)；9例HBsAg( )、抗—HBs( )、HBeAg( )血清HBV DNA检出率100％(9／9)；5例HBsAg( )、HBeAg( )、抗—HBe( )血清HBV DNA检出率100％(5／5)；11例抗—HBs( )及31例抗—HBs( )、抗—HBe( )、抗—HBc( )血清HBVDNA检出率o；38例抗—HBs( )、抗—HBc( )患者血清HBVDNA检出率7．9％；17例HBsAg( )、抗—HBc( )血清HBV DNA检出率58．8％；20例抗—HBc( )血清HBV DNA检出率10％。结论 荧光定量PCR检测HBV DNA具有准确、灵敏、特异等优点，对于乙肝患者临床诊断、疗效观察及预后判断具有重要的临床意义。     

乙肝疫苗微卡联合潘生丁治疗慢性乙型肝炎DNA定量动态观察

目的：探讨血清乙型肝炎病毒（HBV）DNA水平与标志物HBV—M水平复制、肝功能状态、肝内炎症的关系。方法：对105例除甲、丙、丁和戊型肝炎病毒的混合与重叠感染患者中的HBsAg阳性的慢性乙型肝炎患者进行HBV DNA定量,采用荧光定量PCR分析系统,HBV—M采用EUS法。结果：血清HBV DNA水平与HBV M表现模式有关,HBsAg与HBeAg的存在影响HBV DNA水平变化。在HB8Ag阳性患者中,HBV DNA水平与肝脏B超异常相关。血清谷丙转氨酶（ALT）水平与HBV DNA水平无明显相关。结论：乙肝疫苗、微卡联合潘生丁免疫治疗可促进慢性乙型肝炎HBV DNA完全阴转者,ALT持续正常,联合应用可提高治愈率。     

乙肝病毒载量测定与前S1抗原、谷氨酸氨基转移酶测定之比较及其临床价值

目的研究乙肝患者血清中乙肝病毒的核酸载量与乙肝病毒前S1抗原阳性以及谷氨酸氨基转移酶(ALT)水平之间的相关性与符合率,以及三者检测的临床价值。方法用荧光定量聚合酶链反应的方法检测334份怀疑HBV感染的血清中HBV—DNA的病毒拷贝数．同时检测血清中ALT和乙肝前Sl抗原。结果275份HBV—DNA拷贝数大于10^3copies／ml样本中,前S1阳性率80．0％(220／275)。ALT异常率为69．5％(191／275)：而59份HBV—DNA拷贝数小于10^3copies／ml的血清．其前S1抗原阳性率为25．4％．ALT的异常率为22％．且前S1抗原的阳性率和ALT异常率随着HBV—DNA载量升高而增加。结论HBV—DNA的载量与前S1抗原的阳性、ALT水平三者之间,有符合性和互补性,因此三者联合检测．对全面了解HBV感染者的病情、以及药物治疗的评价和预后判断等均有较高的临床应用价值。     

慢性乙肝患者体内HBeAg、HBV DNA和肝功能指标检测结果分析

目的检测慢性乙肝患者血清HBV DNA、HBeAg及ALT、AST的水平及相关性分析,为临床乙肝的诊断和治疗提供参考依据。方法化学发光法检测530例我院HBsAg阳性患者的HBeAg,荧光定量PCR检测HBV-DNA的水平,速率法检测血清ALT和AST的水平。结果 HBeAg阳性组中患者体内HBV DNA水平、ALT异常率、AST异常率显著高于HBeAg阴性组;两组患者血清ALT、AST水平相比较没有统计学差异;在HBeAg阳性组中,当HBV DNA水平大于103时HBeAg水平与HBV DNA水平呈正相关;HBV DNA水平与ALT及AST水平均没有相关性。结论同时检测HBeAg、HBV DNA和ALT水平,才能准确反映患者HBV感染、复制及肝功能损伤程度,从而为临床诊断及治疗提供有价值的依据。     

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.