进口和国产氯吡格雷对PCI术后的血小板功能及预后的影响

目的比较进口和国产氯吡格雷对经皮冠状动脉介入治疗术（PCI）术后的血小板功能的影响以及预防支架内血栓形成的疗效。方法将83例PCI的患者随机分为国产氯吡格雷组（40例）和进品氯吡格雷组（43例）。2组患者均于术前3d开始服用氯吡格雷（泰嘉）75mg每天1次和进口氯吡格雷（波立维）75mg每天1次。随访6个月,比较2组间PCI术后的血小板功能的变化以及支架内血栓形成结果。结果进口和国产氯吡格雷对PCI术后的血小板功能的抑制无显著差异;PCI术后6个月内,2组均无支架内血栓形成。结论进口和国产氯吡格雷均有良好的抗血小板作用,能有效的预防术后急性和亚急性的支架内血栓的形成,表明两者药效相似。     

PCI术后患者联合使用质子泵抑制剂对氯吡格雷疗效的影响

目的:观察经皮冠状动脉介入治疗(PCI)术的患者术后使用质子泵抑制剂(PPIs)对氯吡格雷疗效的影响。方法:回顾性分析2007年7月～2008年6月我院接受PCI术并术后6～12个月内持续服用氯吡格雷+阿司匹林的106名患者,根据患者在使用氯吡格雷+阿司匹林的同时有无联合使用PPIs的情况分成2组,比较2组的死亡率和再入院率。结果:联合使用PPIs组的患者,因不良心血管事件再入院的有18例,比例达到34%,较没有联合使用PPIs组的11例(20%)要高,但差异无统计学意义(P>0.05)。联合使用PPIs组的患者发生不良心血管事件再次入院的危险性是不联合组的2倍(OR为2.07,95%置信区间为1.87～2.20)。结论:本研究结果与国外研究相似,PPIs会影响氯吡格雷抗血小板作用,使不良心血管事件发生而再次入院的危险性增加。提示临床医师在应用时应谨慎。     

双倍剂量氯吡格雷治疗PCI术后氯吡格雷抵抗患者的疗效观察

目的探讨双倍剂量氯吡格雷治疗冠状动脉介入(PCI)术后氯吡格雷抵抗患者的临床疗效。方法选取2014年1月至2016年1月在我院行PCI治疗的氯吡格雷抵抗患者120例,按所使用氯吡格雷剂量分为对照组和试验组,对照组仅给予常规剂量氯吡格雷,试验组给予双倍剂量。比较两组不同时点血小板聚集率(PAR)、术后1个月不良心血管事件发生率和出血事件发生率。结果随访结果显示,术后1、3、6个月试验组PAR均低于对照组,差异有统计学意义(P<0.05)。术后1个月,试验组、对照组的不良心血管事件发生率为11.7%、28.3%,两组比较差异有统计学意义(P<0.05)。两组均未见明显出血事件,试验组、对照组患者分别有4例、3例出现牙龈出血,两组比较差异无统计学意义(P>0.05)。结论双倍剂量氯吡格雷可有效抑制血小板聚集,减少血栓形成及临床缺血事件发生,且不会明显增加出血风险。     

经皮冠状动脉介入术后患者长期服用国产和进口氯吡格雷效果及成本分析

目的评价国产氯吡格雷(泰嘉)和进口氯吡格雷(波立维)对经皮冠状动脉介入治疗(PCI)术后抗血小板治疗的长期疗效及成本。方法将接受冠状动脉支架植入术的118例冠心病患者随机分为泰嘉组(n=60)和波立维组(n=58)。2组均于支架植入术后口服氯吡格雷每日75mg,共服用12个月(药物涂层支架DES)。评价术后12个月主要心血管不良事件及主要不良反应。结果 12个月随访期内,2组患者主要心血管不良事件、主要不良反应差异无统计学意义(P>0.05)。泰嘉组成本4380元,波立维组成本7555.5元。结论国产与进口氯吡格雷临床疗效及安全性相当,国产氯吡格雷经济便宜,值得临床推广。     

国产氯吡格雷对PCI术后患者的长期疗效及安全性观察

目的观察国产氯吡格雷对PCI术后患者的长期疗效及安全性。方法将257例行PCI术患者随机分为2组,其中国产氯吡格雷组129例,进口氯吡格雷组128例。两治疗组PCI术前服用氯吡格雷75mg／d。并于术前至少6h顿服氯吡格雷300mg,两组PCI术后继续服用氯吡格雷75mg／d,观察术后12个月内MACE及主要不良反应。结果国产氯吡格雷对PCI术后12个月内MACE及主要不良反应无统计学意义。结论国产氯吡格雷对PCI术后患者的长期疗效是安全、有效的,经济便宜,值得临床推广。     

国产和进口氯吡格雷对经皮冠状动脉介入治疗术近中期预后的影响

目的观察国产氯吡格雷和进口氯吡格雷对冠心病患者经皮冠状动脉介入术预后的影响。方法将接受冠状动脉支架植入术的426例冠心病患者随机分为两组,其中国产氯吡格雷治疗组224例,进口氯吡格雷治疗组202例,评价PCI术后12个月的主要心血管不良事件发生率以及各种出血并发症。结果两组患者的主要不良心脏事件(MACE)、各种出血并发症无显著差异。结论国产和进口两种氯吡格雷的临床疗效基本相同,安全可靠。     

吲哚布芬联合氯吡格雷在经皮冠状动脉介入治疗术后非瓣膜性心房颤动中的应用效果

目的探讨吲哚布芬联合氯吡格雷在经皮冠状动脉介入治疗(PCI)术后非瓣膜性心房颤动(NVAF)中的应用效果。方法选取2017年7月—2018年10月于聊城市第二人民医院心内科行PCI术后出现NVAF的患者28例,随机分为对照组15例,观察组13例。两组均给予常规治疗,对照组术后服用阿司匹林联合氯吡格雷,试验组术后服用吲哚布芬联合氯吡格雷,并根据INR调整华法林用量。两组均进行6个月的观察。比较两组术后1、6个月后缺血性脑卒中发生率、心肌缺血未改善率、不良事件发生率、血栓弹力图AA途径抑制率。结果术后1个月,两组缺血性脑卒中发生率、心肌缺血未改善率、血栓弹力图AA途径抑制率比较,差异无统计学意义(P>0.05)。试验组不良事件发生率低于对照组(P<0.05)。术后6个月,两组缺血性脑卒中发生率比较,差异无统计学意义(P>0.05);试验组血栓弹力图AA途径抑制率与术后1个月相比,差异无统计学意义(P>0.05);试验组心肌缺血未改善率和不良事件发生率低于对照组(P<0.05)。结论吲哚布芬联合氯吡格雷在PCI术后NVAF中的应用效果良好,能达到抗血小板和抗凝的双重目的,且安全性较高。     

国产与进口氯吡格雷在冠状动脉介入治疗中的疗效对比分析

目的:对比观察国产氯吡格雷(泰嘉)和进口氯吡格雷(波立维)对经皮冠状动脉介入治疗(PCI)术后的疗效及安全性。方法:将1 258例冠心病患者分为两组,其中国产氯吡格雷组563例,进口氯吡格雷组695例。两组患者术前1 d分别服用泰嘉或波立维300 mg,阿司匹林300 mg作为负荷量,以后泰嘉或波立维75 mg.d-1及阿司匹林100 mg.d-1两联抗血小板治疗,比较泰嘉和波立维对冠心病患者PCI术后9个月的MACE事件、血小板聚集率的影响,以及两药在PCI术后抗血小板作用的安全性。结果:国产和进口氯吡格雷组的血小板聚集率及冠心病患者PCI术后MACE事件差异无统计学意义。结论:国产和进口氯吡格雷均有良好的抗血小板作用,临床疗效相似,不良反应轻微。     

急性冠脉综合征患者置入多支架术后应用国产氯吡格雷的疗效观察

目的观察急性冠脉综合征（ACS）患者于多个支架置入术后应用国产氯吡格雷的临床疗效和安全性。方法入选166例本院自2006年10年至2008年3至诊断为ACS行PCI治疗的患者,每个患者置人支架数均I〉2个,所有患者均接受ACS常规治疗,分为两组,分别于术前给予300mg负荷量、术后长期给予每日75mg维持剂量的国产氯吡格雷（泰嘉）和进口氯吡格雷（波立维）,随访术后6个月内,观察主要临床心血管事件和出血事件的发生情况。结果两组患者基线特征、冠脉造影及PCI特征均无明显统计学差异（P〉0．05）;术后随访6个月内两组患者均未出现心源性死亡、恶性心律失常及颅内出血、消化道大出血等严重出血事件,两组患者临床心血管事件比较未见统计学意义。结论ACS患者多支架植入术后应用国产氯吡格雷（泰嘉）进行抗血小板治疗,与同类进口药物波立维相比,在临床有效性及安全性方面的效果肯定,具有较高的效价比。     

药物洗脱支架术后长期联用氯吡格雷和阿司匹林的临床研究

目的 研究药物洗脱支架(DES)术后长期联用氯吡格雷和阿司匹林的临床疗效.方法 将经皮冠状动脉介入治疗(PCI)植入DES的患者114例,随机分为观察组64例和对照组50例.观察组在PCI术后1个月至1年间发生了胸痛、心力衰竭、恶性心律失常等主要心血管不良事件,随机分为15个月联合用药组(A组,n =32)和12个月联合用药组(B组,n=32)两个亚组.对照组(C组)在PCI术后1个月至1年之间未发生主要心血管不良事件,观察三组远期主要心血管事件及抗血小板药物副作用的发生率.结果 发生主要心血管事件A、B、C组各为11例(34.4％)、21例(65.7％)、3例(6％);再发心绞痛A、B、C组各为7例(21.8％)、15例(46.9％)、2例(4％),A组、B组与对照组(C组)比较,主要心血管事件及心绞痛再发生率增加(P＜0.05);A组与B比较,A组主要心血管事件及心绞痛再发生率均低于B组(P＜0.05);三组间出现抗血小板并发症A、B、C组各为6例(18.8％)、4例(12.5％)、4例(8.0％),发生率差异无统计学意义(P＞0.05).结论 DES支架内高风险患者PCI术后15个月联合使用氯吡格雷和阿司匹林可减少心血管事件的发生率,出血并发症无明显增加.     

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.     

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.

     

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.     

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.