不同剂量辛伐他汀降脂疗效的比较

目的：比较不同剂量辛伐他汀（舒降之）的降脂疗效。方法：79例患者随机分为A、B两组,A组10mg.d^-1,B组20mg.d^-1,疗程均为8周。结果：治疗前比较,A组血清总胆固醇（TC）、甘油三酯（TG）、低脂蛋白胆固醇（LDL－C）分别下降23．4％,20．0％、30．7％（P均＜0．01）,高密度脂蛋白胆固醇（HDL－C升高）17．5％;B组TC、TG和LDL－C分别下降32．75,22．8％,42．8％（P＜0．01）,HDL－C升高13．7％,A组中TC、TG和LDL－C达标率分别为12．85,28．2％,15．4％,B组分别为65．05,57．5％,65．0％,疗程中患者均能很好耐受,未见明显不良反应。结论：口服辛伐他汀20mg.d^-1,降脂疗效显著,达标率高。     

阿托伐他汀治疗异常脂蛋白血症的临床效果

目的：观察阿托伐他汀对异常脂蛋白血症病人的调脂效果。方法：39例异常脂蛋白血症病人随机分为2组：阿托他汀组（21例，10mg/d,po）与普伐他汀组（18例，10mg/d,po)，服药前与服药6周后测定血脂水平。结果：服药6周后，阿托他汀组与普伐他汀组的血清总胆固醇（TC）比用药前降低，降幅分别为26．7％与19．4％（P＜0．01）；血清低密度脂蛋白胆固醇（LDL－C）也比用药前显降低，降幅依次为39．2％与24．2％，（P＜0．01）。阿托他他汀组血清三酰甘油（TG）比用药前明显降低，降幅达25．3％（P＜0．01），而普伐他汀组血清TG仅降低4．1％（P＞0．05）；两组血清高密度脂蛋白胆固醇（HDL－C）比用药前有不同程度升高，阿托伐他汀组显升高达6．4％（P＜0．05），普伐他汀升高4．8％（P＞0．05）。结论：阿托伐汀能够显降低异常脂蛋白血症病人的血清TC、LDL－C与TG水平，可有效地用于异常脂蛋白血症病人的调脂治疗。     

辛伐他汀联用多烯康与两药单独应用治疗混合性血脂异常临床观察(附103例分析)

目的 评价辛伐他汀联用多烯康及两药单用治疗混合性血脂异常患者的疗效与安全性。方法 103例混合性血脂异常患者随机分为三组。辛伐他汀＋多烯康组33例，给予辛伐他汀20mg／d，多烯康4．05g／d；辛伐他汀组42例，给予辛伐他汀20mg／d；多烯康组28例，给予多烯康4．05g／d；治疗12周，观察降脂疗效和不良反应。结果 辛伐他汀＋多烯康组，总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）均显著降低（P〈0．01），高密度脂蛋白胆固醇（HDL-C）升高（P〈0．01）；辛伐他汀组TC、LDL—C显著降低（P〈0．01），HDL—C升高（P〈0．05）；多烯康组TG下降明显（P〈0．01），TC及LDL—C下降、HDL-C升高不明显（P〉0．05）。结论 辛伐他汀＋多烯康组降低TC、TG、LDL—C明显，升高HDL—C明显；辛伐他汀组降低TC、LDL—C及升高HDL-C明显；多烯康组降低TG明显。辛伐他汀＋多烯康组与单用辛伐他汀组不良反应轻微，多烯康组无明显不良反应。提示对混合性血脂异常患者两药联用疗效好而副作用轻微。     

血脂康辛伐他汀治疗2型糖尿病并血脂异常

目的 比较血脂康与辛伐他汀治疗2型糖尿病（DM）并血脂异常的临床疗效。方法 2型DM并血脂异常患者89例，分A组（血脂康组）及B组（辛伐他汀组）分别测定两组患者服药前及服药后3个月的空腹血糖（FG）、餐后2h血糖（2hPG）、空腹胰岛素（Fins）、血胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL—c）、高密度脂蛋白胆固醇（HDL—C）水平，并进行比较。结果 两组患者的血TC、TG、LDL—C都较服药前降低，HDL—C水平较服药前升高，差异有显著意义。A组空腹血糖、餐后血糖明显较服药前降低，差异有显著意义，B组空腹血糖、餐后血糖较服药前降低，但差异无显著意义。两组的胰岛素敏感指数（IAI）都较服药前提高，但A组较明显（P〈0．05），B组不明显（P〉0．05）。结论 血脂康与辛伐他汀都有明显的调节血脂作用，血脂康还有协助降糖及提高胰岛素敏感性作用。     

辛伐他汀治疗合并高血压血脂异常的2型糖尿病患者的疗效观察

目的观察有无合并高血压的血脂异常的2型糖尿病患者服用辛伐他汀的降脂疗效,以期指导辛伐他汀的个体化用药。方法伴血脂异常的2型糖尿病患者80例使用辛伐他汀进行降脂治疗,分为A、B组各40例。分别对患者服药后4周、8周、36周的胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）进行测定。结果服用辛伐他汀4周后A组的TG、LDL值水平较B组组更低,8周后A组TC、TG、LDL值较B组更低,而36周后A组TC、LDL值较B组更低,差异有统计学意义。2组HDL水平差异无统计学意义（P〉0.05）。结论高血压伴血脂异常的2型糖尿病患者服用辛伐他汀的降脂疗效显著。     

辛伐他汀对急性冠脉综合征患者降脂分析

目的：探讨中国人群不同剂量的辛伐他汀(舒降之)治疗急性冠脉综合征(ACS)患者血脂异常24周的疗效及安全性。方法：回顾性分析697例ACS病人资料，共分为3组，A组182例未服用辛伐他汀，B组247例口服辛伐他汀10mg，每晚1次，C组268例口服辛伐他汀20mg，每晚1次。均没有服用其它降脂药物，随访24周，观察血脂(TC、LDL—C、HDL—C、TG)的变化及不良反应。结果：降脂作用方面与A组比较B、C两组有显著性差异(P＜0．01)，C组优于B组(P＜0．01)。不良反应3组间元差异(P＞0．05)。结论：辛伐他汀明显降低ACS患者中TC、LDL—C，并能明显升高HDL—C，且有剂量依赖性，不良反应少，安全性高。     

缺血性脑卒中患者血清 PTX－3水平变化及阿托伐他汀的干预效果

目的：探讨缺血性卒中患者血清PTX－3水平变化及阿托伐他汀的干预影响。方法选择神经内科收入院的缺血性脑卒中患者120例,随机分为对照组和他汀,每组60例。对照组给予常规综合治疗方法,他汀组在常规治疗基础上给予阿托伐他汀40 mg,1次／d,疗程3个月。另选健康体检者30例作为正常组。采用酶联免疫吸附分析（ELISA）检测血清PTX－3水平,全自动生化分析仪检测血清LDL－C、HDL－C、TG及TC水平,并评价对照组和他汀组患者的治疗效果。结果缺血性脑卒中患者血清HDL－C水平较正常组明显下降,血清PTX－3、LDL－C、TC及TG均较正常对照组明显升高,差异有统计学意义（ P ＜0±．05）。对照组和他汀组患者血清PTX－3、HDL－C、LDL－C、TC及TG水平均无统计学差异（ P ＞0．05）。对照组和他汀组治疗后血清PTX－3、LDL、TG、TC水平均较治疗前明显下降,HDL－C较治疗前升高,差异有统计学意义（ P ＜0．05）;2组治疗后相比,他汀组血清PTX－3、LDL、TG、TC水平均较对照组明显下降,HDL－C较对照组明显升高,差异有统计学意义（ P ＜0．05）。他汀组有效率83．33％,对照组有效率66．67％,差异有统计学意义（ P ＜0．05）。结论血清PTX－3水平变化参与了缺血性脑卒中的发生发展,阿托伐他汀可以降低血清PTX－3水平,抑制炎性反应,改善缺血性脑卒中患者的预后。     

冠通I号与血脂平治疗高脂血症的疗效对比

目的：比较冠通I号与血脂平对高脂血症的疗效。方法：将150例原发性高脂血症患者随机分为两组，每组75人：第一组口服冠通I号胶囊，15g/次，3次／日；第二组口服血脂平，0．6g／次，3次／日。1两组治疗前后，分别查血脂（TC，TG，LDL－C，HDL－C Apo A Apo B100），并计算动脉粥样硬化指数（AI）。结果：两组治疗前后自身比较TC，TG，LDL－C，AI及Apo B100均明显下降，HDL－C明显上升，差异有非常显著性意义（P＜0．01）。两组组间比较差异无显著性意义（P＞0．05）。结论：冠通I号能有效地降低原发性高血脂患者的血脂，其疗效及安全性与血脂平相近。而且冠通I号属纯中药制剂，不良反应轻，价格低廉，具有较好的临床应用前景。     

不同剂量辛伐他汀治疗冠心病高脂血症的疗效观察

目的 观察不同剂量辛伐他汀对冠心病高脂血症患者的临床疗效及安全性。方法 将67例冠心病伴高脂血症的患者随机分为A、B两组,其中A组33例,口服辛伐他汀5mg/d,B组34例,口服辛伐他汀20mg/d,比较服药前及服药后8周血脂的变化,将A组没有达标的患者,增加剂量至20mg/d,继续口服8周。结果 两组对降低胆固醇(TC)及低密度脂蛋白(LDL)有显著疗效(P<0.05),B组对降低甘油三脂(TG)有效,两组有效率比较,具有显著性差异,两组治疗前后血糖、肌酐、谷丙转氨酶(ALT)及肌酸激酶(CK)均无统计学差异。结论 对血脂增高的冠心病,口服辛伐他汀5mg/d及20mg/d均有效,但后者比前者疗效显著,随着剂量增加不会导致副作用的增加。     

不同剂量辛伐他汀治疗冠心病高脂血症的疗效观察

目的观察不同剂量辛伐他汀对冠心病高脂血症患者的临床疗效及安全性.方法将67例冠心病伴高脂血症的患者随机分为A、B两组,其中A组33例,口服辛伐他汀5mg/d,B组34例,口服辛伐他汀20mg/d,比较服药前及服药后8周血脂的变化,将A组没有达标的患者,增加剂量至20mg/d,继续口服8周.结果两组对降低胆固醇(TC)及低密度脂蛋白(LDL)有显著疗效(P＜0.05),B组对降低甘油三脂(TG)有效,两组有效率比较,具有显著性差异,两组治疗前后血糖、肌酐、谷丙转氨酶(ALT)及肌酸激酶(CK)均无统计学差异.结论对血脂增高的冠心病,口服辛伐他汀5mg/d及20mg/d均有效,但后者比前者疗效显著,随着剂量增加不会导致副作用的增加.     

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.