Alcohol stress on cardiac tissue – Ameliorative effects of Thespesia populnea leaf extract

BackgroundCells are naturally equipped with antioxidant defenses to counterbalance free radical production. Overproduction of free radicals is one of the reasons for a variety of diseases. The current investigation was planned to evaluate chronic alcohol- (for 30 days) induced oxidative stress in the cardiac tissue of rat and to explore the effectiveness of Thespesia populnea (TP)-induced cardio-protection in rat heart by utilizing an in vivo model of cardiac injury by alcohol.MethodsTen groups of rats were maintained and were divided into different groups. Alcohol 20% was administered and Thespesia leaf extracts (TPE) were administered at a dose of 250 mg/kg to chronic alcoholic rats for 30 days. The heart tissue was isolated and processed for further analysis, and also blood for estimation of blood alcohol level and serum creatine phosphokinase (CPK). The activities/levels of antioxidant enzymes, malondialdehyde (MDA), and protein carbonyls (PC) were estimated using established protocols. Histopathology was performed as evidence for the work and to establish the results.ResultsActivities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione content (GSH) showed a decrease, while glutathione-S-transferase (GST) activity, MDA, and PC recorded an elevation due to alcohol treatment in the cardiac tissue compared to the control rats. Alcohol-induced myocardial injury was observed, indicated by a significant increase in serum CPK, a well-known biomarker of myocardial injury, and histopathological evidence supported these observations by revealing predominantly extensive edema with vacuolization and severe necrosis.ConclusionTreatment with TPE confers protection on the heart tissue during alcohol-induced oxidative stress, and thereby minimizes oxidative damage to the cardiac tissue as clearly marked in histopathology.     

A Inibição do Metabolismo da Glicose por miR-34a e miR-125b Protege contra a Morte Celular de Cardiomiócitos Causada por Hiperglicemia

Background:It is well-known that insulin resistance and hyperglycemia are important pathological causes for the development of diabetic cardiomyopathy (DCM). However, its precise molecular mechanisms in the pathogenesis of DCM remain unclear.Objectives:Recent studies reveal that microRNAs (miRNA) play essential roles in the pathogenesis of DCM. This project aimed to determine the roles of miR-34a and miR-125b in hyperglycemia-induced cardiomyocyte cell death.Methods:Rat primary cardiomyocytes were isolated and exposed to normal and high concentrations of glucose. Cell viability was measured using MTT assay. Expressions of miR-34a and miR-125b were detected by qRT-PCR. Potential targets of miR-34a and miR-125b were predicted from www.Targetscan.org and validated from human heart tissues. A statistical significance of p<0.05 was considered.Results:The present study shows that miR-34a and miR-125b are downregulated in a human diabetic heart. Moreover, in vitro data from rat primary cardiomyocytes showed that short-term high glucose treatment stimulates miR-34a and miR-125b expressions. Under high glucose, it was found that rat cardiomyocytes displayed increased intracellular glucose metabolism, and glucose uptake and lactate production were significantly increased. It was also found that the key glucose metabolic enzymes, Hexokinase 2 (HK2) and Lactate dehydrogenase-A (LDHA), were direct targets of miR-125b and miR-34a, respectively. Overexpression of miR-125b and miR-34a could prevent hyperglycemia-induced cardiomyocyte cell death. Finally, the restoration of HK2 and LDHA in miR-125b and miR-34a overexpressed cardiomyocytes recovered the cardiomyocytes’ sensitivity to hyperglycemia.Conclusion:Our results proposed a molecular mechanism for the microRNA-mediated diabetic cardiovascular protection and will contribute to developing treatment strategies for diabetes-associated cardiovascular dysfunction.     

糜蛋白酶mRNA水平及其酶活性与糖尿病仓鼠心肌病变的关系

目的 对糖尿病仓鼠模型心肌中糜蛋白酶(chymase) mRNA水平及其酶活性进行检测,观察chymase mRNA水平、酶活性与心肌局部血管紧张素Ⅱ(Ang Ⅱ)水平的关系.方法 腹腔注射链脲菌素诱导糖尿病仓鼠模型,电镜观察心肌超微结构,链霉素-亲和素-生物素-过氧化物酶复合物法(SABC)检测心肌Ⅰ、Ⅲ型胶原水平,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测心肌细胞凋亡,反转录-聚合酶链反应(RT-PCR)检测chymase mRNA水平变化,放射免疫分析法测定心肌chymase和血管紧张素转换酶(ACE)活性、Ang Ⅱ含量.结果 (1)糖尿病组仓鼠心肌细胞线粒体肿胀明显,局部破裂,肌丝广泛溶解,核肿胀,Ⅰ、Ⅲ型胶原沉积、心肌细胞凋亡明显;(2)糖尿病组与对照组比较,心肌chyamse活性明显升高,分别为(0.88±0.07) U/mg组织和(0.54±0.04)U/mg组织(P＜0.01),而ACE活性差异无统计学意义;Ang Ⅱ含量明显升高,分别为(95.8±16.0)pg/mg组织和(51.1±20.8)pg/mg组织(P＜0.01);(3)糖尿病组心肌chyamse mRNA表达水平为0.810±0.026,较对照组0.490±0.087显著升高(P＜0.01).结论 糖尿病仓鼠病变心肌的chymase mRNA表达水平和酶活性明显升高,并伴随心肌局部Ang Ⅱ含量的升高.     

Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: series of six patients and review of literature

BACKGROUND:

Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation.

METHODS AND RESULTS:

The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2 g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7±7.5% at baseline to 50.3±8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53±6% (P not significant versus LVEF at discharge).

CONCLUSIONS:

Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population.     

Sphk1在1型糖尿病心肌病大鼠中的自噬作用的研究

目的:观察鞘氨醇激酶1(Sphk1)在糖尿病性心肌病(DCM)大鼠中的自噬作用,为DCM的防治寻求新的靶点。方法:雄性Wistar大鼠20只被随机分为正常对照组(n=10)、DCM组(n=10)。腹腔注射链脲佐菌素(STZ)70mg/kg建立DCM大鼠模型。每2周观察大鼠体重、空腹血糖,8周后,检测两组左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)、左室射血分数(LVEF)等;取心脏组织,行HE染色观察心脏形态。应用蛋白质印迹法检测Sphk1、自噬相关蛋白LC3II/LC3I、自噬相关蛋白Beclin 1表达水平。结果:造模8周后,与正常对照组比较,DCM组体重[(351±27)g比(198±11)g]显著降低,血糖[(6.84±0.93)mmol/L比(32.45±4.27)mmol/L]显著升高(P均=0.001);LVEDd[(7.12±0.36)mm比(6.46±0.28)mm]显著减小、LVESd[(3.39±0.14)mm比(3.72±0.25)mm]显著增加,LVEF值[(82.69±3.37)%比(62.50±3.08)%]显著降低(P<0.05或<0.01);Sphk1[(0.30±0.02)比(1.12±0.20)]、LC3II/LC3I[(0.44±0.05)比(1.03±0.14)]、Beclin 1[(0.35±0.08)比(0.73±0.12)]蛋白表达显著升高(P<0.05或<0.01)。HE染色可见心肌细胞增生肥大、排列紊乱。结论:Sphk1通过自噬促使大鼠的糖尿病性心肌病的发生发展。     

Biomarkers in Cardiology – Part 1 – In Heart Failure and Specific Cardiomyopathies

Cardiovascular diseases are the leading causes of mortality and morbidity in Brazil. The primary and secondary preventions of those diseases are a priority for the health system and require multiple approaches to increase their effectiveness. Biomarkers are tools used to more accurately identify high-risk individuals, to speed the diagnosis, and to aid in treatment and prognosis determination. This review aims to highlight the importance of biomarkers in clinical cardiology practice, and to raise relevant points of their use and the promises for the coming years. This document was divided into two parts, and this first one discusses the use of biomarkers in specific cardiomyopathies and heart failure.     

高通量血液透析联合左卡尼汀对尿毒症心肌病的临床研究

目的 高通量血液透析联合左卡尼汀对尿毒症心肌病的影响.方法 选取81例于本院门诊和住院部透析的患者,随机分成两组:实验组41例,对照组40例,所有患者均每周3次血液透析,每次4h,实验组自2012年10月开始接受高通量血液透析联合左卡尼汀治疗,对照组进行单纯的高通量血液透析治疗,两组患者都观察8个月.治疗前后检测血红蛋白、血细胞比容,做常规超声心动图,观察左心室舒张期末内径(LVIDd)、左心室收缩末期内径(LVIDs)、室间隔舒张期末期厚度(IVSd)、左室心肌质量(LVM)、左室心肌质量指数(LVMI)、左室后壁厚度(PWTH)、射血分数(EF)、左心室的舒张功能(EPSS)等.结果 治疗8个月后,实验组患者的血红蛋白、血细胞比容与对照组比较明显升高(P＜0.05),超声心动图EF值明显升高,LVIDd、LVIDs、IVSd、PWTH、LVM、LVMI明显降低,差异均有统计学意义(P＜0.05).结论 高通量血液透析联合左卡尼汀在改善尿毒症心肌病患者心肌重构及心功能方面有较好的疗效.