辛伐他汀致药物性肝损害1例

药物性肝损害(drug induced liver injury,DILI)是严重的药源性疾病之一,约占药物不良反应病例的10%～15%[1]。本文病例为冠心病患者服用调脂药辛伐他汀致药物性肝损害,提示临床药师及医师对使用调脂药的患者要加强肝功能的监测,保障患者临床用药的安全性。     

药物性肝损害55例临床分析

目的:分析引起药物性肝损害的药物种类、临床表现及预后,帮助临床医师早期诊断及治疗。方法:回顾性分析5 5例药物性肝损害患者的病因、临床表现及预后。结果:致肝损害的主要药物以抗结核药物最常见,占2 3.6 %(13/ 5 5 ) ,中药类占18.2 % (10 / 5 5 ) ,抗菌药物占14 .5 % (8/ 5 5 )。本组病例中出现黄疸者占4 1.8% (2 3/ 5 5 ) ,全部病例均有丙氨酸氨基转移酶(ALT)与天门冬氨酸氨基转移酶(AST)的升高,而无严重的消化道症状,多在复查时发现肝功能异常。除1例死于原发病并发症外,其余病例经停止使用或调整用药与使用保肝药物治疗后均获痊愈。结论:药物性肝损害可由各种药物引起,起病隐匿,肝功能检查是早期诊断的主要方法,早期及时停用肝损害药物是治疗的关键     

72例老年药物性肝损害的临床特征及病理分析

目的:分析老年药物性肝损害(DILI)的常见引发药物种类、临床特征、病理特点和预后,以提高对该病的诊治水平。方法:回顾性分析2009年2月～2012年2月72例老年DILI患者资料,对其用药史、临床表现、肝功能、凝血功能、病原学标志、病理表现以及治疗转归进行综合分析。结果:引起老年DILI前5位的药物分别是中药43例(59.8%)、降血糖药8例(11.1%)、心血管药7例(9.7%)、抗菌药6例(8.3%)、抗结核药5例(6.9%)。DILI临床分类:药物性肝衰竭15例(20.8%)、急性药物性肝损害36例(50%)、慢性药物性肝损害17例(23.6%)、药物性肝硬化4例(5.6%)。主要病理改变为肝细胞坏死、肝细胞水样变性、汇管区扩大、肝细胞脂肪变性、纤维组织增生、嗜酸性粒细胞浸润、汇管区或肝窦内混合炎细胞浸润等。72例患者中治愈26例(36.1%),好转31例(43.1%),无效11例(15.3%),死亡4例(5.6%)。结论:老年DILI患者有其不同的引发药物谱,其临床表现和实验室检查缺乏特异性,但死亡率较高。因此,对于老年患者用药应严格把握适应证,密切监测肝功能,早期治疗。     

抗甲状腺药物与甲状腺功能亢进症所致肝功能异常的临床分析

目的比较抗甲状腺药物(ATD)与甲状腺功能亢进症所致肝功能异常的临床特点。方法回顾性分析43例甲状腺功能亢进症合并肝功能异常患者,将其分为对照组(甲状腺功能亢进症性肝损害)24例和试验组(ATD致肝损害)19例。比较2组患者的肝损害临床表现、肝功能、甲状腺激素水平、治疗及转归等指标。结果试验组和对照组出现肝损害临床表现分别为10.53%(2例/19例)和16.67%(4例/24例),差异无统计学意义(P>0.05)。试验组和对照组的谷丙转氨酶(ALT)升高比例分别为94.74%和100.00%,谷草转氨酶(AST)升高比例分别为94.74%和91.67%。试验组和对照组的血清ALT分别为121.00和89.00 U·L^-1,AST分别为78.00和60.50 U·L^-1,差异均有统计学意义(均P<0.05)。结论甲状腺功能亢进症致肝损害和ATD致肝损害患者多数无明显症状,诊断依赖于肝功能监测,ALT和AST是敏感指标,甲状腺功能亢进症致肝损害比ATD致肝损害生化异常更轻。     

我院109例单一怀疑药品所致药物性肝损害不良反应分析

目的:了解我院近10年药物性肝损害(DILI)相关不良反应(ADR)的发生情况及规律,为临床合理用药提供参考。方法:对我院2003-2012年DILI相关ADR报告筛选后,从患者性别、年龄、过敏史、药品品种、给药途径、ADR发生的时间、ADR性质、临床表现及严重ADR等多个方面进行分析。结果:我院药物性肝损害ADR在≥50岁的中老年人中发生居多(占75.23%);引发DILI的药品种类以抗微生物药和循环系统药为主,92.66%为潜伏性,丙氨酸转氨酶(ALT)升高倍数<5倍正常上限值(ULN)例数占77.06%;17.43%有临床表现,症状多较轻微;23.85%痊愈,74.31%好转。结论:DILI发生特点多为潜伏性,临床表现多不明显或轻微,预后较好。医药工作者应积极开展DILI预防和控制工作,以更好地保障患者用药安全。     

抗结核药物对肺结核伴乙肝病毒感染患者肝损害的临床分析及对策

目的:分析抗结核药物对肺结核伴乙肝病毒感染者肝损害的临床影响及其对策。方法:选取2014年6月1日—2016年5月31日期间收治的90例肺结核患者,按照乙肝病毒标记物检查结果将其分为阳性组和阴性组,每组45例;两组患者均给予2HREZ/4HR抗结核治疗方案和保肝药物治疗,观察两组患者用药后致肝损害发生情况和肝功能各指标的变化,以及致肝损害出现时间和复常时间。结果:阳性组患者用药后致肝损害的发生率为53.33%;治疗后TBIL、AST、ALT测得值分别为(50.59±6.47)μmol/L,(181.18±29.84)U/L和(239.15±33.84)U/L,均高于阴性组(P<0.05);致肝损害出现时间为(33.57±4.16)d早于阴性组,复常时间为(22.23±3.64)d晚于阴性组,上述指标经组间比较其差别有统计学意义(P<0.05)。结论:采用抗结核药物治疗肺结核伴乙肝病毒感染患者,易导致其肝功能损害,临床应合理使用抗结核药物,采取对应措施,保护患者肝脏功能。     

63例院内药物性肝损害的临床分析与经济学评价

目的:为探索主动预防、及早发现和合理处置院内药物性肝损害(DILI)提供参考。方法:随机抽取2008～2009年某三级甲等综合医院内4975份住院病历,对住院后DILI发生率、因DILI而造成的医疗费用、延长的住院时间及DILI的预防进行回顾分析与经济学评价。结果:DILI发生63例,发生率为1.27%;其中可预防的DILI10例,占总DILI的15.87%。例均DILI增加医疗费用3220.26元,延长住院时间4.38d;例均可预防的DILI增加医疗费用6239.85元,延长住院时间8.30d。引起肝损害的药物前3名依次为抗感染药(含抗结核药)占41.27%、抗肿瘤药占28.57%、降压降脂药占7.94%。DILI的分型:肝细胞损伤型65.08%,胆汁淤积型25.40%,混合型9.52%。结论:DILI在住院患者中发病率较高,且处理的医疗成本较高,但其中一部分是可预防的,DILI的早期识别和及时停药、合理处置具有临床和经济学的双重价值。     

药物性肝损害50例临床分析

目的探索药物性肝损害的病因、临床特点,预防药物性肝损害的发生。方法根据Maria评分标准≥12分,诊断为药性肝损害,回顾我院从2006年至2008年药性肝损害50例。结果男性患者33例(66%),女性患者17例(34%)。年龄主要分布在25-60岁。致肝损害药物类别分布:中药首位(34%),结核抗杆菌化疗药居第二(28%);混合药物居三位(16%)。临床特点除了肝炎的乏力、纳差等一般特点外,部分患者有畏寒、皮疹、关节酸痛、皮肤瘙痒、发热等症状。肝功能除了丙氨酸转氨酶(ALT)升高外,天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(γ-GGT)、硷性磷酸酶(ALP)也升高。部分患者白细胞降低,嗜酸性粒细胞升高。临床分型:肝细胞损伤型28例(56%),胆汁瘀积型12例(24%),混合型10例(20%)。临床分类:急性30(60%),亚急性16例(32%),慢性4例(8%)。按病情轻重分:重型肝炎4例,其中口服结核杆菌化疗药2例(50%),口服中药消核片1例(25%),1例口服降糖药(格列比嗪)1例(25%),轻型药物性肝损害46例,治愈。结论药物性肝损害较常见,其中以中药、结核化疗药、混合药最常见,致重型药物性肝损坏的药物以结核化疗药为首。对治疗疾病所必须用药,应该在用药前监测肝功能,用药期间定期监测肝功能。     

164例住院患者药物性肝损害临床分析

目的 分析药物性肝损害（DILI）的致病药物和临床特点,为临床合理用药提供参考。方法 收集本院2013-01~12住院患者中发生药物性肝损害的病例,对患者的基础疾病、用药史、肝损害分型及预后进行回顾性分析。结果 共筛选到符合DILI诊断标准的患者164例,导致药物性肝损害的前五类药物分别是化疗药（51.98%）、中药（8.42%）、抗结核药（8.42%）、抗菌药（7.43%）和心血管系统用药（5.45%）;肝损害类型以肝细胞型为主,占71.34%,其次为胆汁淤积型（15.24%）和混合型（13.41%）;经过保肝治疗,19.51%的患者治愈,64.63%的患者好转,9.15%的患者无效,1.22%的患者死亡。结论 本院导致肝损害的药物以化疗药为主,多数为肝细胞型,经治疗后预后较好。     

我院104例药物性肝损害临床分析

目的:探讨药物性肝损害(DILI)的临床特点及其发生规律,为临床合理用药提供参考。方法:对我院2005-2014年发生的104例药物性肝损害患者的性别、年龄、发病时间、药品品种、临床表现等临床资料进行回顾性分析。结果:DILI住院病例逐年增多,其中男性47例,女性57例,平均年龄(48.71±13.90)岁;开始用药后至开始出现临床症状时间绝大多数在12周以内;临床症状包括纳差、乏力、身目黄染、上腹不适等,均无特异性;10.57%患者为无症状,临床分型以肝细胞损伤型最多(80.77%),胆汁淤积型次之(12.50%),混合型最少(6.73%)。最常见的引起肝损害药物依次为中药、抗微生物药、抗肿瘤药和神经系统药。结论:DILI患者中女性稍多于男性,好发于40岁以上;临床表现多样且不明显,引起肝损害的药品较多,临床医师在工作中应提高对该病的重视,根据DILI的特征,早期识别,及时停药和合理处置是其诊治的关键。     

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.