Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio

BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Event-related potential changes due to early-onset Parkinson’s disease in parkin (PARK2) gene mutation carriers and non-carriers

ObjectiveTo investigate cognitive functions in non-demented patients with early-onset Parkinson's disease (PD), and to compare PARK2 gene mutation carriers and non-carriers by means of event-related brain potentials (ERPs).MethodsThe participants comprised patients with early-onset PD (EOPD) and healthy controls (HC). Patients with EOPD were divided into two groups as carriers of known pathogenic variants of PARK2 gene (EOPD-PC) and non-carriers of genes involved in familial PD (EOPD-NC). ERP data were collected during auditory oddball and visual continuous performance test (CPT).ResultsBoth EOPD groups (EOPD-PC and EOPD-NC) displayed reduced and delayed P3 in response to oddball target and CPT NoGo. CPT Go P3 was reduced in EOPD-NC but not in EOPD-PC. Oddball target N1 was reduced and P2 was enhanced in both EOPD-PC and EOPD-NC. In both cognitive tasks, RTs were prolonged and accuracy was lower in EOPD-PC and EOPD-NC.ConclusionsWe found several EOPD-related neurophysiologic changes, implying impairments in cognitive functions. Pairwise comparisons between EOPD-PC and EOPD-NC revealed no significant ERP marker.SignificanceIn this study, the confounding effect of normative aging was somewhat excluded compared with many previous studies. In contrast with the many oddball studies in non-demented PD, we clearly observed reduced and prolonged P3 in early-onset PD. Our NoGo P3 findings also contribute to the limited ERP research concerning response inhibition.     

电针“足三里”穴对脾气虚大鼠小肠黏膜转运体SGLT1及GLUT2表达的影响

目的:观察电针双侧"足三里"穴对脾气虚模型大鼠小肠黏膜上皮组织内的钠依赖葡萄糖转运体(SGLT1),葡萄糖运载蛋白2(GLUT2)的基因及蛋白表达的影响。方法:将40只SD雄性大鼠随机分为正常组、脾气虚组、足三里组、非经非穴组,每组10只。所有大鼠均在SPF级动物实验中心饲养。除正常组外,其余3组均采用劳倦过度和不规则饮食复合法建立脾气虚证的大鼠模型。造模成功之后,对足三里组、非经非穴组大鼠分别进行电针"足三里"穴、非经非穴点干预处理7天。采用HE染色方法观察各组大鼠小肠黏膜组织形态变化;采用荧光定量PCR法检测大鼠小肠黏膜上皮的SGLT1和GLUT2的mRNA表达水平;采用蛋白质免疫印迹法(WB)检测大鼠小肠黏膜上皮组织内的SGLT1和GLUT2的蛋白含量变化。结果:脾气虚组大鼠小肠黏膜组织部分损伤,足三里组的小肠黏膜组织有一定程度的恢复;脾气虚组和非经非穴组大鼠小肠黏膜组织内的SGLT1和GLUT2蛋白和基因表达水平均明显低于正常组(P 0. 05);足三里组大鼠小肠黏膜组织内的SGLT1和GLUT2蛋白和基因表达水平相比于脾气虚组有所升高(P 0. 05),非经非穴组未见显著性差异(P 0. 05)。结论:电针"足三里"穴可以调节脾气虚大鼠小肠黏膜上皮组织内的SGLT1和GLUT2基因及蛋白的异常表达,参与小肠对葡萄糖的吸收作用进而改善脾气虚证。     

Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Volatile molecules for COVID-19: A possible pharmacological strategy?

COVID-19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID-19 should have a balance between its lung exhalation characteristics and both antiviral and anti-inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID-19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8-cineole is provided in view of a possible clinical use and also for asymptomatic COVID-19.     

Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke

AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXs^miR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXs^miR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.     

Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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莫西沙星联合信必可都保对AECOPD疗效及免疫炎症反应的影响

目的探讨维生素D(VitD)联合鱼油对糖尿病前期(PDM)患者糖脂代谢、胰岛β细胞功能的影响。 方法选取PDM患者132例,随机均分为联合组(VitD+鱼油)、VitD组(VitD)和对照组(不干预)。比较各组糖脂代谢、胰岛β细胞功能、炎症反应、血管内皮功能等指标。 结果与干预前比较,干预后联合组甘油三酯降低,白细胞介素-10增高(P＜0.05),联合组和VitD组低密度脂蛋白胆固醇、肿瘤坏死因子-α、胰岛素抵抗指数、前列腺素E2、瘦素、抵抗素降低(P＜0.05),空腹胰岛素、胰岛β细胞功能指数、脂联素增高(P＜0.05),且联合组改善更为明显(P＜0.05)。 结论维生素D联合鱼油治疗PDM患者可改善其脂代谢和胰岛功能相关指标,具有一定临床应用价值。