血必净注射液对急性百草枯中毒大鼠IL-1、IL-6、TNF-α的影响

目的观察血必净注射液对急性百草枯中毒大鼠IL-1、IL-6、TNF-α的影响,探讨血必净注射液对百草枯中毒炎症反应是否有抑制作用。方法将30只雄性Wistar大鼠随机分为Ⅰ组(空白对照组)、Ⅱ组(百草枯染毒组)、Ⅲ组(血必净治疗组),每组10只。对照组大鼠给予生理盐水10 mL/kg灌胃,其余两组分别给予百草枯20 mg/kg灌胃染毒,染毒后30 min开始,Ⅰ、Ⅱ组大鼠给予生理盐水10 mL/kg,1次/d腹腔注射,直至处死;Ⅲ组大鼠给予血必净10 mL/kg,1次/d腹腔注射,直至处死。每日观察大鼠的生命状态,是否有死亡。分别于3、7、14 d采集大鼠内眦静脉血1.5 mL,高速离心,取上层血清,用酶联免疫吸附法检测细胞白介素1(IL-1),细胞白介素6(IL-6),肿瘤坏死因子-α(TNF-α)的表达水平,分析三组实验数据,探讨三组数值之间的相关性。结果①染毒组、血必净治疗组IL-1、IL-6、TNF-α表达水平较空白组明显升高,差异有统计学意义(P<0.001);②血必净治疗组IL-1、IL-6、TNF-α表达水平较染毒组明显降低,差异有统计学意义(P<0.001)。结论在急性百草枯中毒时,引起体内炎性因子增加,导致多脏器功能受损,而血必净注射液有效降低了内毒素及过量炎性介质的损伤,抑制IL-1、IL-6、TNF-α的升高,疗效较明显,为临床治疗提供了有力的证据。     

血必净对急性百草枯中毒大鼠炎性因子影响的实验研究

目的 观察血必净对百草枯急性中毒大鼠炎性因子的抑制作用.方法 72只SD大鼠随机分为对照组、中毒组和血必净组,分别在给药后6h、2h、72h三个时间点,每个时间点每组8只大鼠,中毒组和血必净组一次性以120mg/kg百草枯灌胃,2h后血必净组腹腔注射血必净10ml/kg,对照组和中毒组腹腔注射等体积0.9%氯化钠注射液,1次/d.于给药后6h、24h、72h取大鼠眼眶血,用酶联免疫(ELISA)检测血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和IL-2.结果 给药后6h中毒组血清TNF-α、IL-1β和IL-2较其他组明显升高(P<0.05),而血必净组较中毒组明显降低(P<0.05);给药后24h中毒组血清TNF-α、和IL-1β较其他组明显升高(P<0.05),而血必净组TNF-α、IL-1β较中毒组明显降低(P<0.05);给药后72h中毒组血清TNF-α仍较其他组明显升高(P<0.05),血必净组TNF-α较中毒组明显降低(P<0.05),而且IL-1β和IL-2已降至对照组水平(P0.05).结论 血必净可以明显抑制急性百草枯中毒大鼠血清TNF-α、IL-1β和IL-2的释放,对急性百草枯中毒大鼠炎性反应具有一定的抑制作用.     

血必净联合盐酸氨溴索在急性百草枯中毒所致肺损伤大鼠中的应用

目的观察血必净与盐酸氨溴索联合使用在急性百草枯重度所导致的肺损伤大鼠中的应用。方法纳入50只健康成年的雄性SD大鼠,并随机平均分成五组,每组10只:空白组(A组)、单纯PQ中毒组(B组)、PQ中毒+血必净治疗组(C组)、PQ中毒+盐酸氨溴索治疗组(D组),PQ中毒+血必净联合盐酸氨溴索治疗组(E组);比较五组大鼠肺组织湿重/干重比(W/D)值、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)水平变化,各组大鼠肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平。结果五组大鼠中,C组、E组IL-6、TNF-α水平均低于D组,差异有统计学意义(P<0.05);C组IL-6、TNF-α水平高于E组,差异有统计学意义(P<0.05);E组W/D值低于C组、D组,SOD水平高于C组、D组,差异有统计学意义(P<0.05);D组SOD水平显著低于C组,差异有统计学意义(P<0.05);C组、D组、E组MDA水平、GSH水平两两比较,差异无统计学意义(P>0.05)。结论血必净与盐酸氨溴索均能够有效降低PQ中毒所致急性肺损伤大鼠的氧化应激反应与炎症反应,但二者联合使用时,对中毒大鼠应激反应及炎性反应的改善作用更显著,临床参考价值高。     

血必净对急性胰腺炎大鼠血清一氧化氮的影响

目的探讨急性胰腺炎(Acute pancreatitis,AP)大鼠血清一氧化氮(Nitric oxide,NO)的变化及血必净注射液对其的影响。方法将90只SD大鼠随机分为假手术组、急性胰腺炎组、血必净组,各组再分为3、6、12 h亚组,假手术组开腹后仅行简单的胰腺翻动,急性胰腺炎组开腹后经十二指肠乳头逆行胆胰管注射5%牛黄胆酸钠建立AP模型,血必净组在AP组基础上予血必净注射液治疗,分别在各时间点采血观察血清中淀粉酶(AMY)、一氧化氮(NO)的变化,并进行胰腺组织病理学检查。结果与假手术组相比,AP组中AMY、NO浓度明显增高,差异有统计学意义(P<0.05);与AP组相比,血必净组中AMY、NO浓度明显降低,差异有统计学意义(P<0.05),光镜下AP组胰腺组织损伤明显,而血必净组损伤明显改善。结论 NO参与急性胰腺炎的发生发展过程,血必净注射液能显著降低血清NO,减轻胰腺组织的损伤。     

血必净对水下爆炸实验兔心肺损伤的治疗作用

目的 研究血必净对水下爆炸实验兔心肺损伤的治疗作用. 方法 实验对象新西兰大白兔随机分为3组,正常对照组、爆炸损伤组和血必净治疗组,每组10只.采用中国科技大学研制的可控爆炸装置对后2组实验兔心肺部位实施爆炸,血必净治疗组于爆炸后立即以50mL/kg血必净进行滴注治疗,正常对照组及爆炸损伤组则以50mL/kg等渗盐水滴注,24h后采集各组标本分别检测动脉血气、心肺组织病理学改变、湿/干重比和MMP-9mRNA的表达情况. 结果 爆炸损伤组动脉血pH为(7.02±1.15),低于正常对照组(7.38±1.04)和血必净治疗组(7.21±1.09),差异有统计学意义(P<0.05);血氧分压为(76.91±5.86)mmHg,低于正常对照组(97.92±15.11)mmHg和血必净治疗组(86.65±8.73)mmHg,差异有统计学意义(P<0.05);二氧化碳分压为(44.81±5.99)mmHg,高于正常对照组(32.20±3.38)mmHg和血必净治疗组(37.54±3.75)mmHg,差异有统计学意义(P<0.05).心组织MMP-9mRNA表达相对含量为(29.24±1.87),高于正常对照组(1.00±0.15)和血必净治疗组(12.53±0.49),差异有统计学意义(P<0.05);肺组织MMP-9mRNA表达相对含量为(13.14±0.77),高于正常对照组(1.14±0.17)和血必净治疗组(6.24±0.51),差异有统计学意义(P<0.05).肺病理损伤明显,可见明显水肿和出血,血必净治疗组病理损伤有所改善;肺组织湿/干重比为(6.16±2.34),高于正常对照组(4.38±0.75)和血必净治疗组(4.62±1.13),差异有统计学意义(P<0.05). 结论 水下爆炸冲击波可对实验兔心肺造成严重损伤,血必净可改善其损伤程度.     

血必净联合大剂量甲泼尼龙琥珀酸钠治疗急性百草枯中毒的疗效评估

目的探讨血必净联合大剂量甲泼尼龙琥珀酸钠治疗急性百草枯中毒患者的临床疗效及安全性。方法 52例口服百草枯中毒患者随机分为治疗组及对照组,各26例,对照组患者仅给予常规治疗及血液灌流治疗。治疗组患者在常规治疗基础上联合应用血必净注射液和静脉注射甲泼尼龙琥珀酸钠,比较两组的治疗效果。结果治疗组患者治疗7 d后,动脉血氧分压、血清生化指标、C-反应蛋白均明显优于对照组,两组比较差异有统计学意义（P〈0.05）。治疗组患者病死率明显小于对照组,两组比较差异有统计学意义（P〈0.05）。结论血必净联合大剂量甲泼尼龙琥珀酸钠早期应用可减小百草枯对重要脏器功能的损害,降低急性百草枯中毒的病死率,可在临床上推广使用。     

血必净注射液在急性重度百草枯中毒中的应用

目的:评价血必净注射液治疗急性百草枯中毒的临床疗效。方法:选择我院重症监护室2002年1月～2008年4月收治的急性重度百草枯中毒患者35例为研究对象,分为血必净治疗组(n=20)与对照组(n=15),血必净治疗组在对照组的基础上应用血必净注射液100mL,每日2次,7～10d为1个疗程。结果:2组治疗后肝酶和血肌酐均明显下降,血必净治疗组显著低于对照组(P<0.05);1周后血必净治疗组的氧分压明显高于对照组(P<0.05);血必净治疗组的死亡率明显低于对照组(P<0.05)。结论:早期应用血必净可减轻百草枯对重要脏器的损害,降低百草枯中毒的病死率。     

血必净对严重感染患者血清IL-6水平时效和量效的影响

目的:探讨血必净对严重感染患者重要炎症因子血清白细胞介素(IL)-6水平的时效和量效影响,了解血必净治疗严重感染性疾病的最佳有效剂量。方法:随机抽取48例严重感染患者,并随机分为治疗组(35例)和对照组(13例);对照组仅给予抗感染等常规治疗,死亡3例;治疗组同时给予血必净治疗,死亡5例,并依据血必净应用剂量100、300和500mL/d平均分为剂量1～3组。所有患者在入院和治疗第1周内每天留取静脉血,应用ELISA法检测血清IL-6水平。结果:对照组和各剂量组在不同测定时间的差异有统计学意义(P<0.01)。随着时间增加严重感染患者血清IL-6先显著增加,在3d内感染得到控制,IL-6达到峰值,然后均出现显著降低;但随着治疗组血必净剂量增加,严重感染得到控制的时间缩短,IL-6峰值降低。对照组和不同剂量组间IL-6差异有统计学意义(P<0.01)。对照组分别与剂量1～3组之间,剂量1组与剂量2组、剂量3组之间血清IL-6的差异均有统计学意义(P<0.05),但剂量2组和剂量3组之间的差异无统计学意义。结论:血必净可使严重感染患者得到控制的时间缩短,血清IL-6峰值降低,其最佳应用剂量为300mL/d。     

大鼠急性百草枯中毒血清中细胞因子的动态变化

目的观察细胞因子TGF-β1、PDGFI、GF-1在急性百草枯中毒动物模型中的变化规律,探讨百草枯中毒致肺损伤的作用机制。方法72只Wister大鼠随机分为1个对照组和3个染毒组,分82、4、72 h 3个观察时段,观察不同剂量组在染毒后不同时间大鼠静脉血细胞因子TGF-β1、PDGFI、GF-1的动态变化,同时作病理检查。结果染毒大鼠于染毒后出现的中毒表现,8、247、2 h各剂量组所监测细胞因子的水平增加,24与72 h组与对照组比较,差异均有统计学意义(P<0.05;P<0.01)。72 h高剂量组各指标与同时间点低剂量组比较,差异有统计学意义(P<0.05)。72 h高、中、低3个剂量组与8 h时间点比较,差异有统计学意义(P<0.05)。病理检查示染毒后8 h出现肺泡毛细血管扩张、充血、中性白细胞浸润,24 h肺泡毛细血管扩张及炎性粒细胞浸润更加明显,有大量渗出液;72 h出现广泛弥漫的间质纤维化的表现。结论在百草枯中毒急性肺损伤机制中细胞因子TGF-β1、PDGFI、GF-1可能起到了重要作用。     

血必净注射液治疗急性百草枯中毒的疗效观察

目的探讨血必净注射液治疗百草枯中毒的疗效。方法选择2006年1月-2009年12月百草枯中毒患者35例为研究对象,随机分为血必净治疗组（A组18例）和对照组（B组17例）,A组在B组的基础上应用血必净注射液50m1静脉点滴,每日2次,连用1周。结果A组死亡率50．O％;B组死亡率70．6％,且A组脏器损害数、损害程度均轻于B组,两组对比差异有统计学意义。结论血必净注射液治疗急性百草枯中毒可有效降低死亡率,减轻脏器损害。     

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.