脉络通颗粒联合尤瑞克林治疗脑梗死的临床研究

目的探讨脉络通颗粒联合注射用尤瑞克林治疗脑梗死的临床疗效。方法选择2018年12月—2020年1月在郑州大学附属郑州中心医院进行治疗的126例脑梗死患者,根据数字表法随机分为对照组和治疗组,每组各63例。对照组患者静脉滴注注射用尤瑞克林,0.15 PNA溶于100 mL 0.9%氯化钠注射液中,1次/d。治疗组患者在对照组治疗基础上口服脉络通颗粒,6 g/次,3次/d。7 d为1个疗程,两组患者均连续治疗4个疗程。观察两组的临床疗效,比较两组的美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数评定表(MBI)评分、脑血流量、脑血容量、血浆黏稠度、血清炎性因子水平。结果治疗后,治疗组总有效率96.83%,对照组为85.71%,治疗组显著高于对照组(P0.05)。治疗后,两组患者的NIHSS评分显著降低,MBI评分显著升高(P0.05),治疗组的改善程度显著优于对照组(P0.05)。治疗后,两组患者脑血流量、脑血容量均显著提高,血浆黏稠度显著下降(P0.05),治疗组脑血流量、脑血容量显著高于对照组,血浆黏稠度显著低于对照组(P0.05)。治疗后,两组患者血清核转录因子-κB(NF-κB)、肿瘤坏死因子(TNF-α)、超敏C反应蛋白(hs-CRP)水平较治疗前均显著下降(P0.05),治疗组NF-κB、TNF-α、hs-CRP水平下降程度显著大于对照组(P0.05)。结论脉络通颗粒联合注射用尤瑞克林治疗脑梗死患者有较好的疗效,可有效改善患者神经功能、脑血流量、血浆黏稠度及血清中各项相关指标,促进患者日常活动能力恢复,具有一定临床使用价值。     

脑栓通胶囊联合注射用阿替普酶治疗急性脑梗死疗效及对患者血清NT-proBNP、TNF-α水平的影响观察

摘要：目的:探讨脑栓通胶囊联合注射用阿替普酶治疗急性脑梗死的疗效,及对患者血清N-末端脑钠肽前体（NT-proBNP）、肿瘤坏死因子-α（TNF-α）水平的影响。方法:90例急性脑梗死患者随机分为两组各45例。对照组在基础治疗同时给予注射用阿替普酶治疗,观察组在对照组基础上再加用脑栓通胶囊治疗。治疗14 d后,比观察两组临床疗效和药品不良反应发生情况,比较两组治疗前后改良Rankin量表（mRS）和神经功能缺损评分量表（NIHSS）评分,以及血清NT-proBNP与TNF-α水平变化情况。结果:观察组临床有效率为93.33%,明显高于对照组的75.56%（P<0.05）。治疗后,两组患者的NIHSS评分和mRS评分,以及血清NT-proBNP、TNF-α水平均较前明显降低（P<0.05）;且观察组上述指标均明显优于对照组（P<0.05）。两组药品不良反应发生率（8.87%vs. 17.78%）无明显差异（P>0.05）。结论:脑栓通胶囊联合注射用阿替普酶治疗急性脑梗死临床疗效显著,能有效改善患者神经功能,降低血清NT-proBNP、TNF-α水平,且安全性较高,值得临床应用推广。     

培元通脑胶囊联合桂哌齐特治疗老年急性脑梗死的临床研究

目的探讨培元通脑胶囊联合马来酸桂哌齐特治疗老年急性脑梗死的临床疗效。方法选取天津市静海区医院2017年8月—2019年8月收治的老年急性脑梗死患者76例,随机分为对照组(38例)和治疗组(38例)。对照组静脉滴注马来酸桂哌齐特注射液,320 mg加入5%葡萄糖或生理盐水250 mL,1次/d。治疗组在对照组的基础上口服药物培元通脑胶囊,3粒/次,3次/d。两组患者治疗14 d。观察两组患者临床疗效,同时比较治疗前后两组患者白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平及NIHSS评分和不良反应情况。结果治疗后,对照组和治疗组临床有效率分别为65.79%和97.37%,两组比较差异具有统计学意义(P<0.05)。治疗后,两组患者IL-1、IL-6、TNF-α水平均明显降低(P<0.05),且治疗组明显低于对照组(P<0.05)。治疗7、14 d,治疗组患者NIHSS评分均低于对照组患者(P<0.05)。治疗中,对照组不良反应发生率为47.37%,显著高于治疗组的13.16%,两组比较差异具有统计学意义(P<0.05)。结论培元通脑胶囊联合马来酸桂哌齐特注射液治疗老年急性脑梗死效果显著,能有效降低机体血清炎性因子水平,显著改善脑组织细胞缺血、缺氧症状。     

培元通脑胶囊联合依达拉奉治疗急性脑梗死的临床研究

目的研究培元通脑胶囊联合依达拉奉注射液治疗急性脑梗死的临床疗效。方法选取2015年10月—2018年10月海口市人民医院收治的80例急性脑梗死患者为研究对象,将所有患者随机分为对照组和治疗组,每组各40例。对照组患者静脉滴注依达拉奉注射液30 mg/次,加入适量生理盐水中稀释后,30 min内滴完,2次/d;治疗组在对照组基础上口服培元通脑胶囊,3粒/次,3次/d。两组患者均接受治疗14 d。观察两组的临床疗效,比较两组的美国国立卫生研究院卒中量表(NIHSS)评分、Barthel(BI)指数评分、血清炎性因子水平。结果治疗后,对照组和治疗组的总有效率分别为77.50%、92.50%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者NIHSS评分明显降低,BI指数评分显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组NIHSS评分和BI指数评分明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组血清炎性因子水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论培元通脑胶囊联合依达拉奉注射液治疗急性脑梗死具有较好的临床疗效,能改善患者神经功能和日常生活能力,降低血清炎性因子水平,具有一定的临床推广应用价值。     

葛酮通络胶囊联合尤瑞克林治疗急性脑梗死的临床研究

目的探讨葛酮通络胶囊联合尤瑞克林治疗急性脑梗死的临床效果。方法选取2015年3月—2018年3月海南省人民医院收治的122例急性脑梗死患者,随机分为对照组和治疗组,每组各61例。对照组静脉滴注注射用尤瑞克林,0.15 PNA单位加入生理盐水100 m L中均匀混合后给药,1次/d。治疗组在对照组治疗基础上口服葛酮通络胶囊,2粒/次,2次/d。两组均连续治疗2周。观察两组的临床疗效,比较两组治疗前后NIHSS评分、血浆黏度(PV)、血沉(ESR)、平均血小板体积(MPV)、血小板分布宽度(PDW)、舒张末期血流速度(Vd)、收缩期峰值血流速度(Vs)及平均血流速度(Vm)、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、内皮素-1(ET-1)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为78.7%、91.8%,两组比较差异具有统计学意义(P0.05)。治疗后,两组NIHSS评分、PV、ESR、MPV、PDW值较治疗前均显著降低,两组Vd、Vs、Vm值较治疗前均显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组NIHSS评分、PV、ESR、MPV、PDW显著低于对照组,治疗组Vd、Vs、Vm值显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清MDA、ET-1水平均显著降低,但血清SOD、NO水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组血清MDA、ET-1水平显著低于对照组,血清SOD、NO水平显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论葛酮通络胶囊联合尤瑞克林治疗急性脑梗死具有较好的临床疗效,能明显减轻患者神经功能缺损,改善血流变状态,调节血小板功能,提高局部脑血流量,具有一定的临床推广应用价值。     

N-端脑钠肽前体与肿瘤坏死因子-α对慢性阻塞性肺疾病急性加重期及合并全身炎症反应综合征诊断的意义

目的探讨N-端脑钠肽前体(NT-proBNP)及肿瘤坏死因子-α(TNF-α)对于慢性阻塞性肺疾病急性加重期(AECOPD)及合并全身炎症反应综合征(SIRS)患者的诊断意义。方法选取2018年1月1日至2019年12月31日收治北京市垂杨柳医院的患者,依据病历资料选取AECOPD患者(AECOPD组,n=108例),同期同年龄段门诊稳定期COPD患者(稳定期COPD组,n=52)以及健康对照组(n=48),对NT-pro BNP及TNF-α水平进行比较。AECOPD组根据患者是否合并SIRS分为伴SRIS组(78例)及不伴SIRS组(30例)两个亚组,比较两组NT-pro BNP及TNF-α水平,评估伴SIRS组患者NT-pro BNP与TNF-α的相关性。结果比较同期同年龄段健康对照组,AECOPD组及稳定期COPD组患者NT-pro BNP及TNF-α水平均明显升高,差异有统计学意义(P 0.05)。AECOPD组比较稳定期COPD组NT-pro BNP及TNF-α水平升高更为显著,差异有统计学意义(P 0.05)。而伴SIRS组患者NT-pro BNP及TNF-α水平更高于不伴SIRS组,差异有统计学意义(P 0.05),伴SIRS组NT-proBNP与TNF-α水平呈正相关,差异有统计学意义(P 0.05)。结论检测血清中NT-pro BNP与TNF-α水平有助于COPD急性加重及合并SIRS的识别。     

三七通舒胶囊联合神经节苷脂治疗急性脑梗死的临床研究

目的研究三七通舒胶囊联合单唾液酸四己糖神经节苷脂钠注射液治疗急性脑梗死的临床疗效。方法选取2016年8月—2018年8月延安大学咸阳医院收治的85例急性脑梗死患者为研究对象,将所有患者随机分为对照组(42例)和治疗组(43例)。对照组患者静脉滴注单唾液酸四己糖神经节苷脂钠注射液,40 mg加入到0.9%氯化钠注射液250 mL中,1次/d;治疗组在对照组基础上口服三七通舒胶囊,1粒/次,3次/d。两组患者持续治疗4周。观察两组的临床疗效,比较两组的美国国立卫生研究院卒中量表(NHISS)评分,以及丙二醛(MDA)、神经元特异性烯醇化酶(NSE)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、脑源性神经营养因子(BDNF)和谷胱甘肽过氧化物酶(GSH-Px)水平。结果治疗后,对照组和治疗组的总有效率分别为83.33%、95.35%,两组比较差异有统计学意义(P0.05)。治疗后,两组MDA、NSE、TNF-α、IL-6水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组MDA、NSE、TNF-α、IL-6水平明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者NIHSS评分显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者NIHSS评分明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者BDNF和GSH-Px水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者BDNF和GSH-Px水平明显高于对照组,两组比较差异有统计学意义(P0.05)。结论三七通舒胶囊联合单唾液酸四己糖神经节苷脂钠注射液治疗急性脑梗死具有较好的临床疗效,能改善神经功能缺损情况,调节MDA、NSE、TNF-α、IL-6、BDNF和GSH-Px水平,具有一定的临床推广应用价值。     

脑栓通胶囊联合脑苷肌肽治疗急性脑梗死的临床研究

目的探索脑栓通胶囊联合脑苷肌肽治疗急性脑梗死的疗效观察。方法选取2017年5月—2019年6月洛阳市第一中医院收治的急性脑梗死患者144例,随机分成对照组和治疗组,每组各72例。对照组患者静脉滴注脑苷肌肽注射液,20 mL加入生理盐水250 mL,1次/d。治疗组患者在对照组的基础上口服脑栓通胶囊,3粒/次,3次/d。两组患者均治疗14 d。观察两组患者临床疗效,同时比较治疗前后两组患者脑血流动力学、脂蛋白相关磷脂酶A2(Lp-PLA2)和血栓弹力图指标。结果治疗后,对照组和治疗组临床有效率分别为70.83%和87.50%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者平均血流量(Q_m)和平均血流速度(V_m)、水平均明显上升(P0.05),而外周阻力(Rv)和动态阻力(DR)水平显著降低(P0.05),且治疗组明显优于对照组(P0.05)。治疗后,两组患者Lp-PLA2和血栓弹力图指标中血细胞凝集块形成速率(α)和最大血块强度(MA)明显降低(P0.05),两组患者血栓弹力图指标中凝血反应时间(R)和血细胞凝集块形成时间(K)明显提高(P0.05),且治疗组患者明显好于对照组(P0.05)。结论脑栓通胶囊联合脑苷肌肽注射液治疗急性脑梗死,可明显提高临床疗效,改善脑血流动力学指标,降低血清Lp-PLA2水平,优化血栓弹力图指标。     

通心络胶囊联合阿托伐他汀治疗急性心肌梗死PCI术后炎性反应的临床研究

目的探讨通心络胶囊联合阿托伐他汀治疗急性心肌梗死PCI术后炎性反应的临床研究。方法 2011年6月—2014年6月衡水市第二人民医院收治的急性心肌梗死患者80例,随机分为对照组和治疗组,每组40例。对照组在基础治疗上口服阿托伐他汀钙胶囊,2粒/次,1次/d。治疗组在对照组基础上加用通心络胶囊,4粒/次,3次/d。两组均连续用药3个月。比较两组患者治疗前后气虚血瘀症状和SAQ评分,同时比较两组C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、细胞间黏附因子(ICAM-1)和白细胞介素-6(IL-6)、N末端B型利钠肽原(NT-pro BNP)水平。结果治疗后,两组患者气虚血瘀症状评分较同组治疗前显著降低,SAQ评分显著升高,同组治疗前后差异有统计学意义(P0.05);且治疗组气虚血瘀症状和SAQ评分改善程度优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者的炎症因子CRP、TNF-α、IL-6、ICAM-1和NT-pro BNP均较治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗后治疗组各因子水平均低于对照组,两组比较差异有统计学意义(P0.05)。结论通心络胶囊联合阿托伐他汀治疗急性心肌梗死PCI术后炎性反应具有较好的临床疗效,可改善患者临床症状,同时能够降低患者术后炎症因子水平,具有临床推广价值。     

三七通舒胶囊联合鼠神经生长因子治疗急性脑梗死的临床研究

目的探讨三七通舒胶囊联合注射用鼠神经生长因子治疗急性脑梗死的临床疗效。方法选取2015年6月—2018年6月成都市第二人民医院接收的118例脑梗死患者为研究对象,将所有患者采用随机数字表法分为对照组和治疗组,每组各59例。对照组肌肉注射注射用鼠神经生长因子,30μg溶于氯化钠注射液2mL中,1次/d;治疗组患者在对照组基础上口服三七通舒胶囊,1粒/次,3次/d。两组患者接受治疗4周。观察两组的临床疗效,比较两组的美国国立卫生研究院卒中量表(NIHSS)评分、Barthel(BI)指数评分和血液流变学指标血浆黏度(CP)、血细胞比容(HCT)和全血高切黏度(HS)水平。结果治疗后,对照组和治疗组的总有效率分别为84.48%、96.55%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者NIHSS评分显著降低,BI评分显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组NIHSS评分和BI评分明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者CP、HCT和HS水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组CP、HCT和HS水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论三七通舒胶囊联合注射用鼠神经生长因子治疗急性脑梗死具有较好的治疗效果,能够提高患者神经功能和日常生活能力,改善血液流变学,具有一定的临床推广应用价值。     

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.

     

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.     

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.     

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.     

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.     

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.