根据 PK／PD 理论指导哌拉西林他唑巴坦治疗革兰阴性杆菌感染的临床观察

目的：探讨延长哌拉西林他唑巴坦给药时间法治疗革兰阴性杆菌感染的疗效。方法将重症监护病房（ ICU）收治的54例患者随机分为观察组28例和对照组26例。2组均给予哌拉西林他唑巴坦抗感染治疗,观察组静脉输注时间为3h,对照组为30min。观察2组患者的临床疗效、细菌清除率以及不良反应。结果观察组总有效率为82．1％高于对照组的65．4％,差异有统计学意义（P＞0．05）。2组细菌清除率、不良发应发生率差异无统计学意义（P＞0．05）。结论延长哌拉西林他唑巴坦输注时间是治疗革兰阴性杆菌感染治疗更为有效的给药方案,可作为临床的经验治疗方案。     

延长哌拉西林/他唑巴坦输注时间治疗复杂性尿路感染的临床观察

目的:评价延长哌拉西林/他唑巴坦(PIP/TAZ)输注时间治疗复杂性尿路感染的疗效及安全性。方法:将我院于2012年10月-2014年10月收治的84例复杂性尿路感染患者按SPSS 15.0软件随机分组程序分为试验组和对照组各42例。试验组予以PIP/TAZ 4.5 g持续静脉泵入,q8 h,静脉泵入时间为3 h;对照组予以PIP/TAZ 4.5 g静脉滴注,q8 h,静脉滴注时间为30 min。两组均以7 d为1个疗程,观察实验室检查指标、降钙素原与血白细胞计数。结果:两组患者治疗后降钙素原均较治疗前明显下降,差异有统计学意义(P<0.05);且治疗后组间比较差异亦有统计学意义(P<0.05)。两组患者治疗后血白细胞计数均较治疗前明显下降,差异有统计学意义(P<0.05);但组间比较差异无统计学意义(P>0.05)。试验组的临床总有效率为85.4%,对照组的临床总有效率为63.4%,差异有统计学意义(P<0.05)。两组不良反应发生率均为2.4%,差异无统计学意义(P>0.05)。结论:延长PIP/TAZ输注时间治疗复杂性尿路感染疗效确切、安全性高。     

哌拉西林他唑巴坦负荷剂量两步输注治疗ICU病房革兰阴性菌致重症医院获得性肺炎的临床研究

目的 探讨哌拉西林他唑巴坦负荷剂量两步输注与传统延长输注治疗重症监护病房革兰阴性菌（GNB）致重症医院获得性肺炎（HAP）的临床疗效。方法 选择2019年5月—2022年11月入住衡水市人民医院重症监护病房（ICU）的多重耐药革兰阴性菌（GNB）致重症医院获得性肺炎患者150例,按照随机数字表分为对照组和治疗组,每组各75例。对照组静脉泵入注射用哌拉西林钠他唑巴坦钠,4.5 g加入生理盐水100 mL,静脉泵持续输注3 h,1次/8 h。治疗组静脉泵入注射用哌拉西林钠他唑巴坦钠,4.5 g加入生理盐水100 mL,前2.25 g采用静脉泵在30 min内输注,后2.25 g采用静脉泵在150 min内持续输注。两组患者均治疗7～14 d。观察两组患者临床疗效,比较治疗前后两组患者细菌清除率,临床感染症状恢复时间,炎性指标降钙素原（PCT）、C反应蛋白（CRP）和白细胞计数（WBC）水平,及住院时间、机械通气时间和治疗总费用。结果 治疗后,治疗组临床总有效率（85.33%）显著高于对照组（70.67%,P＜0.05）。治疗后,治疗组细菌清除率（73.33%）显著高于对照组（56.00%,P＜0.05）。治疗后,治疗组啰音消失时间、咳嗽咳痰消失时间和退热时间均短于对照组（P＜0.05）;治疗后,两组WBC、PCT和CRP均显著下降（P＜0.05）,且治疗组比对照组下降更显著（P＜0.05）。治疗后,治疗组在住院时间、机械通气时间和治疗总费用方面均明显小于对照组（P＜0.05）。结论 哌拉西林他唑巴坦负荷剂量两步输注能显著提高入住ICU病房GNB致重症HAP的临床疗效和细菌清除率,能明显缩短症状改善时间,从而缩短患者住院时间和降低治疗费用。     

观察注射用他唑巴坦钠/哌拉西林钠治疗新生儿感染的疗效

目的:探讨注射用他唑巴坦钠/哌拉西林钠治疗新生儿感染的临床疗效.方法:选取2014年12月~2015年12月于我院就诊的新生儿感染患者共106例,随机分为观察组和对照组,每组53例,给对照组利用青霉素G钠进行治疗;给观察组采用他唑巴坦钠/哌拉西林钠注射治疗,比较两组治疗效果、细菌清除情况、不良反应发生率.结果:观察组治疗总有效率为98.11%;对照组治疗的总有效率为77.36%.观察组治疗总有效率显著优于对照组,P<0.05;观察组和对照组细菌清除率分别为98.28%和77.97%,观察组的细菌清除效果优于对照组,P<0.05;另外观察组出现的不良反应情况和对照组出现的不良反应情况,无显著差异.结论:临床上在治疗新生儿感染时,可以采用注射用他唑巴坦钠/哌拉西林钠,能提高治疗效率,清除患者体内的细菌,不良反应发生率低,能够促进患者症状的改善.     

喜炎平注射液联合哌拉西林他唑巴坦治疗老年性肺炎的疗效分析

目的:分析喜炎平注射液联合哌拉西林他唑巴坦治疗老年性肺炎的临床疗效。方法:选择本院2017年6月—2019年6月收治的82例老年性肺炎患者作为研究对象,随机平均分为对照组和治疗组,各41例。对照组采纳哌拉西林他唑巴坦治疗,治疗组采纳喜炎平注射液+哌拉西林他唑巴坦治疗,对比两组临床疗效、实验室指标、不良反应发生情况。结果:治疗组临床总有效率95.12%(39/41)明显高于对照组70.73%(29/41),治疗组治疗1周后CRP、PCT、WBC指标均明显低于对照组,差异均具有统计学意义(P<0.05)。治疗组不良反应发生率7.32%(3/41)与对照组4.88%(2/41)比较,差异无统计学意义(P>0.05)。结论:喜炎平+哌拉西林他唑巴坦可有效减轻老年性肺炎患者临床症状及炎症反应,且不良反应较少,值得借鉴。     

哌拉西林钠-他唑巴坦钠优选给药方案的评估及应用的研究现状

目的为哌拉西林钠-他唑巴坦钠的临床合理用药提供参考。方法对哌拉西林钠-他唑巴坦钠的优选给药方案的药动/药效学研究、临床试验及具体实施情况进行综述。结果哌拉西林钠-他唑巴坦钠的优选给药方案（延长输注或持续输注）可最大化地达到药效学目标,改善临床有效性。结论需积极完善优化方案用于临床实践的策略。     

哌拉西林-他唑巴坦钠与阿莫西林克拉维酸钾对肺部感染患者的临床疗效与安全性比较

目的:比较哌拉西林-他唑巴坦钠与阿莫西林克拉维酸钾对肺部感染患者的临床疗效与安全性。方法:选取2018年1月—2019年1月间收治的肺部感染患者62例资料,按治疗用药的不同将其分为对照组和观察组,每组31例;对照组患者给予阿莫西林-克拉维酸钾治疗,观察组患者则给予哌拉西林-他唑巴坦钠治疗,比较两组肺部感染患者用药后的总有效率、细菌清除率、用药期间不良反应发生率及临床症状(咳嗽、肺部鸣啰音、体温、白细胞计数)复常时间的差异。结果:观察组患者用药后临床症状(咳嗽、肺部鸣啰音、体温、白细胞计数)复常时间均早于对照组(P<0.05),治疗后的总有效率、细菌清除率均高于对照组(P<0.05),用药期间不良反应发生率低于照组(P<0.05)。结论:采用哌拉西林-他唑巴坦钠治疗肺部感染患者的疗效优于阿莫西林-克拉维酸钾,有效提高了细菌的清除率,加快了症状的复常,且安全性高。     

哌拉西林他唑巴坦治疗医院获得性肺炎的疗效观察

目的观察哌拉西林他唑巴坦治疗医院获得性肺炎的疗效。方法将80例医院获得性肺炎患者随机分成两组,每组各40例。观察组接受哌拉西林他唑巴坦20ml＋5%葡萄糖注射液250ml静脉滴注,每次至少30min,疗程为7～10d。对照组接受头孢噻肟钠2～6g,分2～3次静脉滴注,每次加入5%葡萄糖注射液250ml,1g/12h,疗程为7～10d。疗程结束后比较两组疗效、症状缓解时间、住院时间。结果观察组疗效优于对照组,症状缓解时间、住院时间明显缩短,差异均有统计学意义（P〈0.05）。结论哌拉西林他唑巴坦对医院获得性肺炎有理想疗效,使用时应严格把握适应证,避免药物滥用。     

氯吡格雷配合哌拉西林-他唑巴坦钠与头孢哌酮-舒巴坦钠对老年脑卒中伴肺部感染患者的临床疗效评价

目的:评价氯吡格雷配合哌拉西林-他唑巴坦钠与头孢哌酮-舒巴坦钠对老年脑卒中伴肺部感染患者的疗效与安全性。方法:选取2015年7月—2017年7月期间诊治的老年脑卒中伴肺部感染患者82例资料,按用药不同将其分为对照组和观察组,每组41例;对照组患者给予哌拉西林-他唑巴坦钠和头孢哌酮-舒巴坦钠联用治疗,观察组患者给予哌拉西林-他唑巴坦钠、头孢哌酮-舒巴坦钠和氯吡格雷治疗,比较两组患者治疗后总有效率、不良反应发生率的差异,以及治疗前后T淋巴细胞亚群(CD4、CD8和CD4/CD8)水平的变化情况。结果:观察组患者治疗后的总有效率高于对照组(P<0.05),不良反应发生率低于对照组(P<0.05),患者治疗后CD4、CD4/CD8水平均高于对照组(P<0.05),CD8水平低于对照组(P<0.05)。结论:采用氯吡格雷配合哌拉西林-他唑巴坦钠与头孢哌酮-舒巴坦钠联用治疗老年脑卒中伴肺部感染患者的疗效较显著,有效改善了T淋巴细胞亚群的免疫功能,且安全性较高。     

哌拉西林/他唑巴坦钠联合阿奇霉素治疗支气管扩张合并感染的疗效分析

目的:探讨哌拉西林/他唑巴坦钠联合阿奇霉素治疗支气管扩张合并感染的疗效。方法:收集2016年1月～2017年12月雅安市人民医院呼吸内科56例经住院确诊为支气管扩张合并感染患者临床资料进行回顾性分析,按入院顺次分为对照组和观察组,每组28例,对照组给予哌拉西林/他唑巴坦钠抗感染、止咳、祛痰、止血、体位引流、对症等治疗,观察组在此基础上联合阿奇霉素分散片口服治疗,对比两组患者感染指标控制情况、平均住院日、胸部影像学改变,综合评价疗效。结果:观察组患者临床症状消失时间早于对照组,平均住院日短于对照组,住院总费用少于对照组,经组间成组t检验(p0.05)。两组患者治疗前血WBC、血清hs-CRP比较(p0.05)。治疗后,两组患者血WBC、血清hs-CRP均较治疗前明显下降(p0.05);但观察组下降趋势更显著(p0.05)。两组治疗前支气管扩张范围、扩张程度、管壁厚度评分比较(p0.05);观察组治疗后支气管扩张范围评分无明显改善(p0.05),但支气管扩张程度及管壁厚度评分均显著改善(p0.05);对照组治疗后支气管扩张范围、扩张程度、管壁厚度评分均无明显变化(p0.05)。结论:哌拉西林/他唑巴坦钠联合阿奇霉素治疗支气管扩张合并感染患者总体疗效显著于单一用药,且缩短住院时间,减轻患者经济负担,值得临床广泛运用。     

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.     

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.