礞寒合剂的制备及辅助氯氮平抗精神病应用研究

目的：观察礞寒合剂辅助氯氮平治疗精神分裂症的临床疗效和不良反应。方法：接处方制备礞寒合剂。将64例精神分裂症患者随机分为试验组（礞寒合剂加氯氮平）36例和对照组（氯氮平）28例，于治疗前及治疗后第1，2，4，8周末采用BPRS量表总分和BPRS量表因子分评定疗效并观察不良反应。结果：试验组有效率94．44％，高于对照组85．71％，但差异无统计学意义。第2周起，两组间BPRS量表总分及因子分比较差异显著（P〈0．05，P〈0．01）。结论：礞寒合剂可提高氯氮平治疗精神分裂症的疗效，减少不良反应，作为氯氮平的辅助药物有临床应用价值。     

利培酮合并小剂量氯氮平治疗精神分裂症32例

目的：评估利培酮合并小剂量氯氮平治疗精神分裂症的临床疗效及不良反应。方法：将96例患者随机平均分为三组,分别给予利培酮和小剂量氯氮平（A组）、利培酮（B）组或氯氮平（C组）治疗,疗程均为12周,采用BPRS和TESS量表评定疗效。结果：A组显效率62．5％,明显优于C组的37．5％（P＜0．05）,B、C两组疗效相当。不良反应发生率A组明显低于B、C组（P＜0．05）。结论：利培酮合并小剂量氯氮平治疗精神分裂症疗效较为理想。     

利培酮对氯氮平血药浓度的影响

目的：观察利培酮对氯氮平血药浓度的影响及两药联用的疗效及安全性。方法：对28例原服用氯氮平的难治性精神分裂症患者合并利培酮治疗4周，分别于联合用药前及联合用药2周未、4周末时测定氯氮平血药浓度，同时进行简明精神病评定量表（BPRS）和不良反应症状量表（TESS）评定。结果：合用利培酮后，氯氮平血药浓度无明显升高，BPRS评分明显降低（P〈0．01），起效快，TESS评分无明显变化（P〉0．05）。不良反应主要为静坐不能、视力模糊。结论：利培酮对氯氮平血药浓度无明显影响，两药联用能增加疗效．安全性高。     

同等剂量氯氮平血药浓度与临床疗效的关系

目的 :探讨同等剂量氯氮平血药浓度与临床疗效的关系。方法 :以固定剂量氯氮平 ( 3 0 0mg·d-1)治疗 61例精神分裂症患者。疗效用简明精神病评定量表 (BPRS)进行评定 ,并测定治疗wk 2及wk 3的血药浓度。结果 :氯氮平及去甲氯氮平血药浓度与临床疗效有明显关系 ,尤以去甲氯氮平血药浓度与临床疗效关系更为密切。结论 :氯氮平及去甲氯氮平血药浓度的监测有助于指导临床个体化合理用药     

氯氮平联合文拉法辛治疗以阴性症状为主的精神分裂症30例

目的探讨氯氮平联合文拉法辛治疗以阴性症状为主的精神分裂症的临床疗效及其安全性。方法将60例以阴性症状为主的精神分裂症患者随机分为治疗组和对照组各30例。治疗组及对照组氯氮平的剂量于3周内加到治疗剂量，治疗组氯氮平剂量150～450 mg·d^-1，对照组氯氮平剂量200～450 mg·d^-1，治疗组另外给予文拉法辛，1周内加至100 mg·d^-1，疗程均为12周。分别于治疗开始第4，8，12周末采用简明精神症状量表(BPRS)及阴性症状量表(SANS)评定疗效，不良反应量表(TESS)评定不良反应。结果治疗开始4周后，两组BPRS、SANS总分及因子分比治疗前明显下降(P＜0.05或P＜0.01)，治疗组部分因子评分下降更早、更快。治疗第4，12周末，治疗组情感平淡与意志缺乏因子分明显低于同期对照组。治疗后第4，8，12周末，治疗组TESS评分均明显低于对照组，且治疗后低于治疗前(P＜0.05或P＜0.01)。治疗组体重增加发生率明显低于对照组(P＜0.01)。结论氯氮平联合文拉法辛治疗以阴性症状为主的精神分裂症更安全可靠，并且可以抑制氯氮平所致的药源性肥胖。     

氯氮平与氯丙嗪治疗精神分裂症的疗效分析

目的：比较氯氮平与氯丙嗪治疗精神分裂症疗效。方法：36例精神分裂症随机分成氯氮平组(18例)和氯丙嗪组(18例)，采用简明精神症状量表(BPRS)及临床疗效评定量表(CGI)，于治疗前、治疗后2、4、6周分别进行评定。结果：氯氮平组和氯丙嗪组在治疗前后BPRS评分差异无显著性(P＞0．05)，但疗效总评(GI)评分中第四周氯氮平组高于氯丙嗪组，但总体疗效相似(P＞0．05)。结论：氯氮平与氯丙嗪对治疗精神分裂症疗效相似。     

奎硫平与氯氮平治疗精神分裂症的对照研究

目的：探讨奎硫平(思瑞康)治疗精神分裂症的疗效和安全性，以氯氮平为对照进行研究。方法：对80例精神分裂症患者分为两组进行8周观察，奎硫平研究组和氯氮平对照组各40例，于治疗前和治疗后每周进行BPRS和TESS评定。结果：奎硫平组和氯氮平组之间疗效无显著性差异，但奎硫平组不良反应明显少于氯氮平组，主要有轻度头昏、低血压、食欲减退等。结论：奎硫平是一种安全有效的抗精神病药。     

奋乃静联合尼莫地平治疗老年期首发精神分裂症30例

目的： 观察奋乃静联合尼莫地平治疗老年期首发精神分裂症的疗效。方法：老年期首发精神分裂症患者60例，随机分为治疗组和对照组各30例。两组均给予奋乃静片，6 mg·d 1开始，每天增加2 mg，到症状缓解停止加量，最大剂量20 mg·d 1，po；治疗组同时加用尼莫地平片20 mg，tid，po。分别在治疗前、治疗后第1，2，4，8周进行简明精神病评定量表(BPRS)评定。结果：在治疗第1，2，4，8周时，治疗组BPRS总分均较对照组明显下降(P＜0.05或＜0.01)，疗效均较对照组明显提高(P＜0.05或＜0.01)。结论： 奋乃静合用尼莫地平治疗老年期首发精神分裂症较单用奋乃静的疗效好，且起效快。     

三种非典型抗精神病药对精神分裂症患者BDNF及认知功能的影响

目的：探讨齐拉西酮、利培酮、氯氮平这3种非典型抗精神病药物对精神分裂症血清脑源性神经营养因子浓度（ BDNF）及认知功能的影响。方法257例确诊为精神分裂症的住院患者随机分为3组,分别给予齐拉西酮、利培酮、氯氮平治疗12周。于治疗前及治疗后4、8、12周监测血清BDNF浓度,疗效评定采用简明精神病量表（ BPRS）,不良反应评定采用副反应量表（ TESS）及实验室检查,认知功能评价采用韦氏记忆量表（WAIS）。结果3组总有效率分别为83.8％、85.1％、88.6％,疗效比较无统计学意义（P＞0.05）。 BDNF浓度比较：疗后8、12周,3组均较治疗前升高,但齐拉西酮组升高更明显（P＜0.05）。认知功能比较：治疗12周后,3组认知功能均较治疗前改善（P＞0.05）,但齐拉西酮组、利培酮组在言语智商及总智商评分上与氯氮平组改善明显（P＜0.05）。结论3种非典型抗精神病药物均能提高精神分裂症患者BDNF浓度及认知功能,以齐拉西酮疗效更加明显,安全有效。     

奎硫平对精神分裂症认知功能的影响

目的比较奎硫平及氯氮平对精神分裂症患者认知功能的影响。方法对60例精神分裂症患者随机分成两组，分别给予奎硫平、氯氮平治疗8周，治疗前和治疗8周末分别进行简明精神病评定量表（BPRS）、韦氏成人记忆量表修订本（WMS—RC）威斯康星卡片分类测验（WCST）和数字划销测验（CT）评定，分别评定其认知功能和临床疗效。结果两组治疗8周后，各项检查项目均有显著好转。结论奎硫平和氯氮平均能明显改善精神分裂症患者的认知功能，相比较而言奎硫平更优。     

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.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.