双环醇片联合胸腺肽α1治疗慢性乙型肝炎临床研究

目的观察双环醇片联合胸腺肽α1治疗慢性乙型肝炎患者的疗效。方法选择慢性乙型肝炎76例为治疗组,予以服用双环醇片tid,每次25mg,同时使用胸腺肽α1,1．6mg下注射,每周1次。对照组单用双环醇片tid,每次25mg,疗程6个月。结果治疗组在血清HBV—DNA,HBeAg阴转方面与对照组相比差异有显著性,治疗组及对照组治疗前后ALT、AST复常率差异均有显著性,但两组间差异无显著性。结论两者联合应用可提高抗病毒疗效,并且I有降低转氨酶、改善临床症状的作用。l     

双环醇与拉米夫定治疗慢性乙型肝炎的疗效比较

目的　比较双环醇与拉米夫定对慢性乙型病毒性肝炎抗病毒、保肝降酶的临床疗效。方法　将6 0例慢性乙型肝炎患者随机分成治疗组和对照组,2组在常规治疗的基础上分别予双环醇或拉米夫定。治疗组与对照组疗程分别为2 4和4 8wk。于治疗的不同时间检测肝功能和病毒学指标。结果　治疗组在治疗4、8、12wk时,其ALT复常率高于对照组(P <0 0 5 ) ,从2 4～4 8wk ,2组的ALT复常率的比较P >0 0 5 ;对照组在治疗2 4wk前患者的HBV DNA阴转率均高于治疗组(P <0 0 5 ) ,但在4 8wk时2组的HBV DNA阴转率、HBeAg阴转率和HBeAg血清转换率的比较P >0 0 5。结论　在本组治疗早期,治疗组的降酶作用优于对照组,HBV DNA阴转率逊于对照组,而疗程结束时,2组的临床疗效基本相似     

双环醇治疗慢性乙型肝炎双盲、随机、对照的临床研究

目的 :评估双环醇治疗慢性乙型肝炎的疗效和安全性。方法 :慢性乙型肝炎病人随机分成双环醇组 (2 69例 )和联苯双酯组 (1 3 8例) ,分别服用双环醇或联苯双酯 2 5mg,tid,共 2 4wk。结果 :经双环醇治疗后 ,临床症状有较大程度的改善。ALT和AST的复常率分别为 5 3 .5 %和 48.7% ,停药 1 2wk后分别为 40 .2 %和 48.7%。与联苯双酯组(61 .6%和 44.2 % ;45 .7%和 5 0 .0 % )比较 ,P >0 .0 5。治疗结束和停药 1 2wk后 ,双环醇组血清HBeAg阴转率分别为 2 0 .8%和 2 9.0 % ,HBeAg/抗HBe血清转换率分别为 1 5 .6%和 2 0 .8% ,HBV DNA阴转率分别为 3 9.0 %和 45 .7% ,上述指标均高于联苯双酯组。双环醇组治疗前ALT水平≥ 2 0 0U·L-1者 ,在停药 1 2wk时HBeAg阴转率和血清转换率分别为 48%和 3 8% ,显著高于联苯双酯组 (2 2 %和 1 2 % ) ,(P <0 .0 5 )。病人在治疗期间未出现明显不良反应。结论 :双环醇对改善乙肝病人临床症状和降低转氨酶有很好的疗效 ,不良反应少 ,病人耐受性好     

阿德福韦酯治疗YMDD变异慢性乙型肝炎82例

目的:研究阿德福韦酯治疗YMDD突变后慢性乙型肝炎患者的疗效和安全性。方法:82例YMDD突变的慢性乙型肝炎患者分为对照组和试验组,对照组服用拉米夫定100mg·d-1,48周,试验组服用阿德福韦酯10mg·d-1,48周。服药后第24,48周检测谷丙转氨酶(ALT)、HBV DNA定量、HBeAg及观察不良反应。结果:试验组24及48周HBV DNA下降水平均明显高于对照组(均P<0·01),HBV DNA应答率和ALT复常率也均高于对照组(均P<0·01),HBeAg阴转率两组无显著性统计学差异。两组均未发现明显不良反应。结论:阿德福韦酯治疗YMDD突变的慢性乙型肝炎安全有效。     

免疫调节药联合应用对慢性乙型肝炎病毒标志物阴转率的影响

目的 :观察干扰素α 1b(IFNα 1b)、胸腺因子D(TMD)。乙肝免疫球蛋白 (HBIG)等 3种免疫调节药联合应用与单用干扰素及常规护肝治疗对慢性乙型肝炎病毒 (HBV)标志物HBeAg及HBV DNA的阴转率。方法 :选择 10 8例HBV标志物HBeAg(+) ,HBV DNA(+)患者 ,随机分为 3组 :联合治疗组、单用干扰素组及护肝组 ,各 36例 ,疗程 6mo ,随访 6mo。结果 :6mo疗程结束时 ,联合治疗组和单用干扰素组对HBeAg及HBV DNA阴转率均无显著差异 (P >0 0 5 ) ,与护肝组比较差异均极显著 (P <0 0 1) ;疗程结束后 ,随访 6mo ,联合治疗组HBeAg及HBV DNA阴转率又有提高 ,而单用干扰素组则阴转率下降 ,2组比较 ,差异显著 (P <0 0 1) ,而护肝组无变化。结论 :经 6mo治疗结束时 ,联合治疗组对乙肝病毒标志物HBeAg及HBV DNA阴转率与单用干扰素组相似 ;但治疗结束后 6mo,优于单用干扰素组。     

重组干扰素α-1b联合苦参素治疗慢性乙型肝炎的临床观察

目的 :探讨重组干扰素α 1b(干扰素 )联合苦参素治疗慢性乙型肝炎的疗效及不良反应。方法 :选择慢性乙型肝炎患者 87例 ,随机分成干扰素 +苦参素组 45例 ,给予干扰素治疗 ,第 1～ 4wk 3 0 μg·d-1,im ,以后改为隔日 3 0 μg,im ,疗程为 3mon,同时加苦参素注射液 60 0mg·d-1,im ,疗程为 3mon。干扰素组 42例 ,单用干扰素治疗 ,剂量、疗程与治疗组相同 ,在疗程结束时 ,观察两组患者肝功能、乙型肝炎病毒血清学 (HBVM)标志的变化。结果 :两组患者血清谷丙转氨酶 (ALT)的复常率分别为 88.9%和60 % ,组间差异有显著性 (P <0 .0 5 ) ;HBeAg阴转率分别为 5 5 .6%和 3 5 .7% ,HBV DNA阴转率分别为5 7.8%和 42 .9% ,治疗组的疗效明显优于对照组 (P<0 .0 5 ) ,未见明显不良反应。结论 :干扰素联合苦参素具有改善肝功能和抑制乙肝病毒复制等功效 ,两者联合应用可作为慢性乙型肝炎的一种治疗方案。     

苷必妥治疗慢性乙型肝炎40例疗效观察

目的:观察苷必妥治疗慢性乙型肝炎的疗效。方法:慢性乙型肝炎HBeAg阳性80例随机分为二组:治疗组、对照组各40例。对照组给一般护肝治疗,治疗组在一般护肝治疗基础上加用苷必妥肌注,每次肌注1mg,第一个月每日一次,第二、三个月隔日一次,3 mo为一个疗程。结果:治疗组,HBeAg转阴率为42.5％(17/40);HBVDNA阴转率为44.4％(16/36);6例虽无阴转,但HBV DNA定量检测时,滴度明显下降。而对照组HBeAg转阴率为10％;HBV DNA阴转率为2.7％,而HBV DNA定量检测无改变。结论:苷必妥可改变人体细胞免疫应答,对慢性乙型肝炎患者的HBeAg和HBV DNA的清除有一定的作用。     

抗乙肝转移因子治疗慢性乙型肝炎

目的 :观察抗乙肝转移因子治疗慢性乙型肝炎疗效。方法 :慢性乙型肝炎病人 72例 ,分成 2组。对照组给予护肝基础治疗 (维生素E 0 .1g ,po ,qd ,水飞蓟素 77mg ,po ,tid ,丹参 3片 ,po ,tid) ;治疗组在基础治疗上加用抗乙肝转移因子 ,mo 1给 2mg ,im ,qd ;mo 2～ 3改为 qod ,3mo为一个疗程。结果 :治疗组HBsAg阴转率 2 0 % ,HBeAg阴转率4 0 % ,HBV DNA阴转率 2 8% ;对照组分别为 0 ,9% ,3%。结论 :抗乙肝转移因子治疗慢性乙型肝炎有较好疗效。     

双环醇治疗慢性乙型肝炎25例

目的:研究双环醇治疗慢性乙型肝炎的疗效。方法:慢性乙型肝炎46例,随机分成两组:治疗组25例,在一般保肝治疗(水飞蓟宾)基础上加用双环醇25mg,tid,疗程6个月;对照组21例,使用一般保肝(水飞蓟宾)治疗,疗程6个月。两组均停药后继续观察3个月。结果:治疗组在HBV-DNA阴转、HBeAg阴转、HBeAg/HBeAb转换率上均较对照组高,差异有显著性(P<0.05)。结论:双环醇具有明显的降酶和一定的抗病毒疗效,其抗病毒作用随时间延长而增高。     

左旋咪唑涂布剂治疗慢性乙型肝炎疗效观察

我们采用左旋咪唑涂布剂治疗慢性乙型肝炎,按观察要求选择慢性乙型肝炎病人,分治疗组和对照组各30例,结果:治疗组3mo后HBeAg、抗HBc-IgM,HBVDNA转阴率分别是26.27％、33.33％和30.00％;6mo后上述转阴率又分别是40.00％、40.00％和43.33％.而对照组3mo后HBeAg,抗HBc-IgM,HBV DNA转阴率分别是13.33％、13.33％和10.00％;6mo后上述转阴率又分别是16.67％、20.00％和16.67％。治疗组治疗6mo后HBeAg、HBV DNA转阴率与对照组比较有显著性差异(P<0.05)。治疗组治疗6mo后肝功能ALT、AST好转率分别是86.1％和88.3％;对照组ALT、AST好转率分别是82.4％和86.7％,两组无显著性差异(P>0.05)。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.