脑心通胶囊治疗颈动脉粥样硬化的疗效及其作用机制

目的观察脑心通胶囊治疗颈动脉粥样硬化的疗效并从血脂及炎症介质方面探讨其疗效机制。方法 90例颈动脉粥样硬化患者随机分为两组,对照组为常规治疗,治疗组在常规治疗基础上加服脑心通胶囊。分别观察治疗前后颈动脉内-中膜厚度值(IMT)、最大厚度(Tmax)、横切面最大面积(Smax)、斑块数量、斑块体积;并测血清TC、TG、LDL-C、HDL-c、APOA1、APOB、hs-CRP、TNF-a、IL-6水平。结果 3个月后,治疗组组血清TC、TG、LDL-C、APOB、hs-CRP、TNF-a、IL-6均有降低(P<0.01);血清HDL-c、APOA1水平升高(P<0.01);IMT、Tmax较前变薄,Smax较前缩小,斑块体积较前较小(P<0.01),斑块数量较前无明显变化。对照组均无明显变化(P>0.05)。结论脑心通胶囊能减轻、逆转动脉粥样硬化、调节脂质代谢、抑制炎症反应。     

普伐他汀对脑梗死伴颈动脉粥样硬化患者血清超敏C反应蛋白和D-二聚体的影响

目的探讨普伐他汀对脑梗死伴颈动脉粥样硬化患者血浆超敏C反应蛋白(hs-CRP)和D-二聚体(D-dimer)的影响。方法选择60例住院脑梗死伴颈动脉粥样硬化患者,随机分为对照组和治疗组。治疗组在对照组常规治疗的基础上加服普伐他汀10mgqd,连用6个月。观察两组治疗前后患者血浆hs-CRP和D-二聚体的变化,并通过彩超观察治疗前后颈动脉粥样硬化斑块的变化。结果治疗组治疗6个月后,血浆hs-CRP和D-二聚体水平均较治疗前明显下降(P<0.01);治疗组斑块大小﹑厚度和中层内膜厚度(IMT)均较治疗前明显减小(P<0.05),两组患者治疗后比较治疗组斑块大小﹑厚度和IMT明显小于对照组(P<0.05)。结论普伐他汀对脑梗死伴颈动脉粥样硬化具有抗炎和抗血栓作用,可降低颈动脉内膜厚度,减少颈动脉斑块大小和厚度,可阻断和逆转颈动脉粥样硬化斑块的作用。     

利拉鲁肽对2型糖尿病患者颈动脉硬化指标及hs-CRP、IL-6、TNF-α水平的影响分析

目的探讨利拉鲁肽对2型糖尿病患者颈动脉硬化指标及hs-CRP、IL-6、TNF-α水平的影响。方法随机选取在2018年6月~2019年12月收治的2型糖尿病患者共60例作为研究对象,按照双盲信封法将其分为对照组和观察组各30例,对照组给予常规治疗,观察组在对照组基础上给予利拉鲁肽治疗,研究观察两组患者的颈动脉内膜中层厚度(IMT)、颈动脉粥样硬化斑块面积大小以及hs-CRP、IL-6、TNF-α水平。结果治疗后观察组患者IMT、颈动脉粥样硬化斑块面积较对照组患者均显著缩小(P<0.05);治疗后两组患者hs-CRP、IL-6、TNF-α水平均下降,且观察组hs-CRP、IL-6、TNF-α水平显著低于对照组,差异具有统计学意义(P<0.05)。结论利拉鲁肽可显著改善2型糖尿病患者的颈动脉硬化指标及hs-CRP、IL-6、TNF-α水平,显著降低各种炎症反应。     

慢性肾脏病患者血清可溶性细胞间粘附分子1与颈动脉粥样硬化的关系

目的研究慢性肾脏病(chronic kidney disease,CKD)患者血清可溶性细胞间粘附分子1(sICAM-1)的水平与颈动脉粥样硬化之间的关系,同时观察sICAM-1与各生化指标之间的关系。方法 64例CKD患者为CKD组,20例健康体检者为对照组。根据高频B超检测将CKD组分为A组(伴发颈动脉粥样硬化)、B组(不伴发颈动脉粥样硬化)2个亚组,记录颈动脉中层内膜厚度(ITM);并记录患者的其他生化及免疫指标;采用SPSS17.0软件进行所有数据的统计分析。结果 CKD组患者sICAM-1水平明显高于对照组,分别为(432.48±175.42)ng/ml、(286.47±90.11)ng/ml,P<0.01。颈动脉IMT值明显升高,同时血肌酐(Scr)、尿素氮(BUN)、甲状旁腺素(PTH)、甘油三酯(TG)也明显增高,红细胞压积(Hct)、钙(Ca)、白蛋白(Alb)、肾小球滤过率(GFR)明显降低。与不伴发颈动脉粥样硬化组相比,伴发颈动脉粥样硬化组sICAM-1、颈动脉IMT、尿酸(UA)、血磷(P)、总胆固醇(CH)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、超敏C反应蛋白(hs-CRP)、空腹血糖(FPG)差异有统计学意义(P<0.05)。单因素相关分析结果示,CKD患者sICAM-1与颈动脉IMT(r=0.728,P<0.01)、hs-CRP(r=0.689,P<0.01)显著正相关。结论 CKD患者血清sICAM-1明显升高,血清sICAM-1与颈动脉IMT和hs-CRP正相关,并可能与CKD患者是否伴发动脉粥样硬化有关。     

苯磺酸氨氯地平联合赖诺普利氢氯噻嗪与阿托伐他汀治疗重度原发性高血压合并颈动脉粥样硬化的临床观察

目的:观察苯磺酸氨氯地平联合赖诺普利氢氯噻嗪与阿托伐他汀治疗重度原发性高血压合并颈动脉粥样硬化的临床疗效和安全性。方法:90例重度原发性高血压合并颈动脉粥样硬化患者以抽签法分为对照组(45例)和观察组(45例)。两组患者入院后均给予阿托伐他汀钙片20 mg/次,口服,每日1次;同时,对照组患者给予苯磺酸氨氯地平片5 mg/次,口服,每日1次;观察组患者在对照组治疗基础上加服赖诺普利氢氯噻嗪片10 mg/次,口服,每日1次。两组疗程均为8周。比较两组患者临床疗效,治疗前后血压水平、颈动脉内膜中层厚度(IMT)、颈动脉峰值流速(PV)、血清超敏C反应蛋白(hs-CRP)、血浆肿瘤坏死因子α(TNF-α)水平,记录治疗期间不良反应发生情况。结果:观察组患者总有效率显著高于对照组,差异有统计学意义(P<0.05);治疗前,两组患者收缩压(SBP)、舒张压(DBP)、IMT、PV、hs-CRP、TNF-α水平比较差异均无统计学意义(P>0.05)。治疗后,两组患者SBP、DBP、IMT、PV、hs-CRP、TNF-α水平显著低于同组治疗前,且观察组显著低于对照组,差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:苯磺酸氨氯地平联合赖诺普利氢氯噻嗪与阿托伐他汀治疗重度原发性高血压合并颈动脉粥样硬化可有效控制患者血压水平,延缓动脉粥样硬化病情进展,降低机体炎症反应程度,且未增加不良反应的发生,安全性较好。     

阿托伐他汀钙联用拉西地平对高血压颈动脉粥样硬化影响分析

目的:分析阿托伐他汀钙联用拉西地平对高血压颈动脉粥样硬化的影响.方法:按照随机原则将70例高血压伴颈动脉粥样硬化患者分成对照组和实验组各35例,对照组给予单纯拉西地平治疗,实验组给予阿托伐他汀钙联合拉西地平治疗.结果:治疗后实验组血压下降显著优于对照组(P<0.05);实验组颈动脉IMT显著小于对照组(P<0.05).结论:阿托伐他汀钙联合拉西地平治疗高血压伴颈动脉粥样硬化具有比较显著的临床疗效,能对患者的血压水平进行有效控制,让患者颈动脉粥样硬化病变显著减轻,值得临床推广.     

阿托伐他汀钙治疗颈动脉粥样硬化的疗效观察

目的观察阿托伐他汀钙治疗颈动脉粥样硬化的疗效。方法选取我院2010年1月—2011年12月颈动脉粥样硬化患者90例。随机分为对照组和治疗组,对照组采取常规治疗,治疗组在对照组的基础上采用阿托伐他汀钙治疗。结果治疗组与对照组经过8周治疗后颈动脉IMT及斑块面积均较治疗前差异有统计学意义(P<0.05);且治疗组治疗后的颈动脉及斑块面积与对照组相比差异有统计学意义(P<0.05);治疗前后治疗组TC、TG、hs-CRP水平比较差异有统计学意义(P<0.05),治疗后两组间TG、hs-CRP水平比较差异有统计学意义(P<0.05)。结论阿托伐他汀钙在颈动脉粥样硬化的治疗中可以明显改善血清胆固醇及三酰甘油水平,使得治疗效果显著提高,值得推广。     

应用C反应蛋白来预测脑梗死进展可能性的研究

目的研究C反应蛋白(C-reactive protein,CRP)与进展性脑梗死、颈动脉粥样硬化之间的关系。方法选择急性进展性脑梗死患者60例为实验组,同时期非进展性脑梗死患者60例作为对照组。均通过颈动脉彩色多普勒超声检测颈部血管动脉内膜中层厚度(IMT)及动脉粥样硬化斑块情况,同时测定血清CRP水平。结果进展组患者CRP值显著高于对照组,而且该组患者颈动脉IMT值明显高于对照组,实验组颈部血管斑块检出率及不稳定斑块发生率均高于对照组,实验组中不稳定斑块的患者血CRP值明显高于稳定斑块者,上述差异均具有统计学意义(P<0.05)。CRP水平与颈动脉IMT和病情严重程度呈正相关。结论血CRP水平与进展性脑梗死相关,并且与颈动脉粥样斑块形成紧密相关。     

高剂量瑞舒伐他汀对急性脑梗死患者血脂及血清hs-CRP的影响

目的 研究高剂量瑞舒伐他汀对急性脑梗死患者患者血脂及血清超敏C-反应蛋白(hs-CRP)的影响.方法 90例急性脑梗死患者随机数字表均分为对照组和观察组,每组45例.对照组患者以瑞舒伐他汀10 mg/d治疗,观察组患者以瑞舒伐他汀20 mg/d治疗,观察2组患者临床症状,测定2组患者治疗前后颈动脉内膜中层厚度(IMT),血脂总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C),血清hs-CRP水平变化情况.同时测定白介素-6 (IL-6)、肿瘤坏死因子-α(TNF-α)水平.结果 2组患者经治疗后的斑块面积和颈动脉IMT均较治疗前显著降低,差异有统计学意义(P＜0.05),且观察组治疗后斑块面积和颈动脉IMT低于对照组,差异有统计学意义(P＜0.05);2组患者血脂TC、TG、LDL-C水平均较治疗前明显下降,而HDL-C水平则相对升高,差异均有统计学意义(P＜0.05),观察组血脂水平改善情况明显好于对照组(P＜0.05).经治疗2组患者hs-CRP、IL-6和TNF-α水平均显著降低;且观察组hs-CRP、IL-6和TNF-α水平均明显低于对照组,差异均有统计学意义(P＜0.05).结论 高剂量瑞舒伐他汀可更好地稳定颈动脉粥样硬化斑块,并降低急性脑梗死患者患者血脂及血清hs-CRP的水平,能够更有效的抵抗炎性反应.     

脑梗死患者25-羟维生素D水平与颈动脉粥样斑块的相关性研究

目的分析血清25羟维生素D[25-(OH)D]与脑梗死患者颈动脉粥样硬化斑块的相关性。方法选取2013年11月至2015年9月在我院就诊的脑梗死患者194例,同期体检中心健康体检者121名作为对照组。所有受试者均行颈动脉超声检查,并检测血25-(OH)D及常规生化指标。根据脑梗死患者血清25-(OH)D水平分为缺乏组(A组)、不足组(B组)和充足组(C组),并对不同组之间临床指标及颈动脉超声结果进行比较,并对颈动脉硬化斑块的影响因素进行Logistic回归分析。结果 (1)脑梗死患者吸烟比例、超敏C反应蛋白(hsCRP)、血钙、25-(OH)D、颈动脉内膜-中层厚度(IMT)、体质量指数、收缩压、舒张压、同型半胱氨酸水平与健康人群组相比,差异具有统计学意义(P<0.05或P<0.01);(2)A组和B组颈动脉IMT、同型半胱氨酸、hs-CRP、收缩压、舒张压水平明显高于C组(均P<0.01);(3)A组和B组超声造影剂到达时间差(DAT)、超声造影剂到达各峰值的时间差(DTTP)、斑块增强强度(EI)、斑块增强密度(DE)水平,与C组之间比较差异均有统计学意义(均P<0.01);(4)Logistic回归风险显示吸烟、同型半胱氨酸、高血压、颈动脉IMT、hs-CRP以及低水平25-(OH)D是颈动脉粥样硬化斑块的独立危险因素。结论在脑梗死患者中,低水平25-(OH)D水平是颈动脉粥样硬化斑块的独立危险因素。     

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.