阿立哌唑对舒必利所致高催乳素血症的影响

目的 探讨阿立哌唑对舒必利所致高催乳素血症的影响及安全性.方法 对61例服用舒必利6周后的精神分裂症患者,随机分为治疗组31例,对照组30例.治疗组在服用原药的基础上,每天加用阿立哌唑10 mg,对照组维持以前的药物治疗.服用舒必利治疗第6周及第9周末分别测定患者血清催乳素水平,并进行比较.同时用不良反应量表（TESS）评定不良反应.结果 经阿立哌唑治疗后,治疗组患者血清催乳素水平明显下降（P<0.01）,对照组血清催乳素水平无明显变化.两组TESS评分差异无显著性（P>0.05）.结论 阿立哌唑对舒必利所致高催乳素血症有一定的治疗作用,并且相对安全.     

阿立哌唑合并小剂量奥氮平治疗精神分裂症的对照研究

目的研究阿立哌唑合并小剂量奥氮平对精神分裂症患者疗效和安全性。方法 68例精神分裂症患者随机分成治疗组(36例)和对照组(32例),分别给予阿立哌唑合并小剂量奥氮平及阿立哌唑单药治疗。比较两组治疗前、治疗1周、2周、4周后PANSS量表评分。结果治疗组显效率77.8%明显优于对照组63.3%(P<0.05)。PANSS评分减分率治疗组明显优于对照组(P<0.05或P<0.01)。结论阿立哌唑合并小剂量奥氮平治疗精神分裂症的疗效和安全性优于单一用药阿立哌唑。     

小剂量阿立哌唑合并帕罗西汀治疗难治性抑郁症的对照研究

目的探讨小剂量阿立哌唑联合帕罗西汀治疗难治性抑郁症的疗效与安全性。方法将64例难治性抑郁症患者随机分为治疗组(帕罗西汀合并阿立哌唑治疗)和对照组(单用帕罗西汀治疗),每组各32例,观察8周。于治疗前和治疗1周、2周、4周及8周末采用汉密尔顿抑郁量表(HAMD-17)评定疗效,用副反应量表(TESS)评定不良反应。结果治疗组显效率为68.75%,对照组为46.8%。治疗组从第2周末起HAMD分低于对照组,差异有统计学意义。两组间不良反应差异无统计学意义。结论阿立哌唑合并帕罗西汀治疗不伴精神病性症状的难治性抑郁症较单用帕罗西汀的疗效好,不良反应少。     

小剂量阿立哌唑治疗利培酮所致女性精神分裂症患者高催乳素血症的效果分析

目的分析小剂量阿立哌唑治疗利培酮所致女性精神分裂症患者高催乳素血症的效果,探讨有效干预方法。方法 120例利培酮所致高催乳素血症的女性精神分裂症患者,根据临床前瞻性研究原则,按照随机数字表法分为观察组与对照组,每组60例。两组均维持原有利培酮治疗不变,观察组予以小剂量阿立哌唑治疗,对照组不予以干预措施。比较两组治疗前后血催乳素水平、闭经及泌乳情况;治疗前后阳性和阴性症状量表(PANSS)、简明精神病评定量表(BPRS)评分;不良反应发生情况。结果治疗后,观察组患者血催乳素(43.9±15.2)ng/ml低于对照组的(112.7±11.6)ng/ml,闭经、自发泌乳以及闭经+自发泌乳占比分别为25.00%(15/60)、20.00%(12/60)、5.00%(3/60),均明显低于对照组的81.67%(49/60)、70.00%(42/60)、40.00%(24/60),差异均有统计学意义(P<0.05)。治疗前、后,两组PANSS、BPRS评分比较,差异均无统计学意义(P>0.05)。与治疗前比较,两组患者治疗后的PANSS、BPRS评分均降低,差异具有统计学意义(P<0.05)。观察组不良反应发生率为13.33%(8/60),对照组为10.00%(6/60),比较差异无统计学意义(χ^2=0.32, P>0.05)。结论小剂量阿立哌唑治疗利培酮所致女性精神分裂症患者高催乳素血症效果明显,且不影响患者疗效及安全性。     

阿立哌唑对精神分裂症患者血清催乳素的影响

目的探讨阿立哌唑对精神分裂症患者血清催乳素的影响。方法选取60例精神分裂症患者,随机分为阿立哌唑组和利培酮组,分别给予阿立哌唑和利培酮治疗8周,在治疗前及治疗后2、4、8周末采用阳性与阴性症状量表（PANSS）对两组进行评定,并于治疗前、治疗后4周末、8周末采用放射免疫法测查PRL水平。结果两组PANSS量表评分治疗8周末均比治疗前极显著减少（P〈0.01）,但两组间相比差异无统计学意义（P〉0.05）;治疗前后阿立哌唑组PRL水平比较差异无统计学意义（P〉0.05）,利培酮组治疗8周末PRL水平明显升高（P〈0.05）;出现月经紊乱或泌乳阿立哌唑组较利培酮组明显为少（P〈0.05）。结论阿立哌唑对精神分裂症患者有较好的疗效,对PRL的影响较小,是一种有效而安全的新型抗精神病药物。     

阿立哌唑与利培酮治疗精神分裂症效果及对血清催乳素的影响比较

目的探讨阿立哌唑与利培酮治疗精神分裂症的疗效及对血清催乳素的影响。方法将86例精神分裂症患者随机分为两组,每组43例,分别给予阿立哌唑与利培酮治疗,疗程12周,于治疗前及治疗4、8、12周末分别采用阳性与阴性症状量表(PANSS)、副反应量表评分,检测血清催乳素。结果治疗12周末阿立哌唑组治愈率23.3%,有效率86.1%;利培酮组治愈率25.6%,有效率88.4%;两组治愈率及有效率比较差异无统计学意义。两组均未发生相关的严重不良事件,阿立哌唑对血清催乳素的影响较利培酮小。结论阿立哌唑治疗精神分裂症的疗效与利培酮相当,对血清催乳素无明显影响,是一种安全有效的抗精神病药物。     

阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响

目的：比较阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响。方法：2005年5月至2006年5月在我院治疗的80例精神分裂症患者，随机分为两组：阿立哌唑组（40例）和利培酮组（40例），阿立哌唑组给予阿立哌唑初始剂量10mg／d，2周末增至20～30mg／d，利培酮组给予利培酮初始剂量1mg,／d，2周末增至4—6mg／d。总疗程为8周。采用阳性和阴性症状量表（PANSS）、副反应量表（TESS）评定临床疗效及不良反应；采用化学发光法测定血清催乳素（PRL）水平。结果：经8周治疗，阿立哌唑组显效率72．5％；利培酮组显效率77、5％，两者差异无显著性（P〉0．05）。阿立哌唑组主要不良反应为：嗜睡，头痛，胃肠道反应，也可产生静坐不能，但未发现泌乳或闭经现象；利培酮组主要不良反应为：急性肌张力障碍、震颤、静坐不能、泌乳或闭经、体重增加等。利培酮组治疗8周后，血清PRL水平较治疗前明显升高，差异非常显著（P〈0．01），其中男性PRL升高3．5倍，女性PRL升高8倍；而阿立哌唑组血清PRL水平无变化。结论：阿立哌唑是一种较为安全、有效的抗精神病药物。     

3种干预方法对抗精神病药物致高催乳素血症的影响

目的 探究3种干预方法对抗精神病药物致高催乳素血症的疗效影响。方法 招募2019年1月至2020年12月因服用抗精神病药致高催乳素血症而住院治疗的90例患者为研究对象，采用随机数字表法分为阿立哌唑组、逍遥丸组和维生素B₆组，各30例，疗程8周。治疗前及治疗4、8周后比较血清催乳素水平、阳性和阴性精神症状评定量表(PANSS)、治疗伴发症状量表(TESS)及不良反应发生情况。结果 治疗后3组血清催乳素水平均降低，阿立哌唑组、逍遥丸组低于维生素B₆组，差异有统计学意义(P <0.05);3组PANSS评分均有所降低，但组间差异无统计学意义(P> 0.05)；治疗后TESS评分排序为阿立哌唑组>消遥丸组>维生素B₆组，组间差异均有统计学意义(P <0.05)；不良反应发生率排序为阿立哌唑组>逍遥丸组=维生素B₆组，阿立哌唑组与其他2组之间差异具有统计学意义(P <0.05)。结论 3种干预方法对抗精神病药致高催乳素血症都有显著疗效，阿立哌唑和逍遥丸的疗效优于维生素...     

阿立哌唑治疗舒必利所致高催乳素血症70例

目的 探讨阿立哌唑治疗舒必利所致高催乳素血症的疗效及安全性. 方法 60例男性、80例女性舒必利所致高催乳素血症患者,分别随机分为治疗组、对照组（男性：治疗组、对照组各30例; 女性：治疗组、对照组各40例）. 维持舒必利治疗不变,分别加用阿立哌唑（5 mg）、维生素C治疗,疗程6周. 于治疗前和6周末检测催乳素（PRL）; 评定简明精神病量表（BPRS）、不良反应量表. 结果 6周末,治疗组男、女性PRL分别为（21.5±6.4）和（26.9±7.1） μg&#8226;L^-1,较基线（84.8±15.9）和（136.5±38.2） μg&#8226;L^-1下降,差异有极显著性（均P＜0.01）; 对照组男、女性PRL分别为（79.3±15.5）和（122.8±34.0） μg&#8226;L^-1,与基线（85.1±16.7）和（129.8±37.9） μg&#8226;L^-1比较差异无显著性（均P＞0.05）. 治疗组男、女性PRL的下降率分别为（74.7±5.9）%和（78.3±9.5）%,高于对照组PRL的下降率［分别为（6.5±5.8）%,（4.9±4.3）%］（均P＜0.01）. 治疗组和对照组男、女性BPRS评分与基线的差异均无显著性（均P＞0.05）; 两组总体不良反应发生率相近（P＞0.05）. 结论 阿立哌唑治疗舒必利所致男、女性高催乳血症有效、安全.     

阿立哌唑对利培酮所致催乳素升高的作用研究

目的探讨阿立哌唑对男性抗精神病药所致的高催乳素（PRL）副作用的治疗作用。方法对74例利培酮治疗的男性精神分裂症患者随机分组,均采用利培酮治疗,起始1 mg/d,并根据精神症状调整药量至治疗量4-6 mg/d。研究组于第3周开始加用阿立哌唑5 mg/晚,直至研究结束不再增加阿立哌唑剂量,分别于0、2、4、8、12周末进行催乳素检测,对治疗中出现的其他不良反应进行TESS评定。结果加用阿立哌唑后,研究组PRL在12周末时（164.54±69.26）μIU/mL与基线期（151.97±64.66）μIU/mL比较差异无统计学意义（P=0.435,t=0.785）,而对照组第2周后PRL持续增高（177.28±45.18）μIU/mL,第4周末时明显异常（351.41±61.56）μIU/mL。但第8周（379.59±73.62）μIU/mL和12周（382.50±76.89）μIU/mL相比较变化不大。两组不良反应发生率差异无统计学意义（χ2=3.12,P=0.077）。但不良反应的构成存在一定差异,研究组静坐不能7例（20%）,震颤6例（17.14%）,头痛11例（31.43%）,肌强直3例（8.57%）,对照组静坐不能10例（31.25%）,震颤9例（28.12%）,肝功能异常3例（9.38%）,肌强直9例（28.13%）,便秘6例（18.75%）,体重增加11例（34.38%）。结论阿立哌唑对于利培酮导致的男性催乳素升高有一定的控制及治疗作用。且两药联用并未增加副反应的风险。     

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.