Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.
Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were determined.
Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.
Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.     

烟酰胺腺嘌呤二核苷酸磷酸氧化酶对血管疾病病理过程的影响

氧化应激是一种活性氧(ROS)代谢引起的分子失调,以一氧化氮生物利用度下降为特征。使用抗氧化维生素E和维生素C对心血管疾病无明显疗效,这使得对氧化应激的分子本质的理解产生了变化。氧化应激不再被认为是产生和消除ROS之间的不平衡,而是酶功能的异常,特别是烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶功能的异常。因此,NADPH氧化酶已成为重要的治疗靶点。为了设计正确的抗氧化治疗方案,必须考虑NADPH氧化酶的分子调节作用,以及新型该家族人类同源物Nox1、Nox2、Nox3、Nox4和Nox5。通过发展和评估可靠的局部和系统抗氧化应激技术抑制NADPH氧化酶,可能比使用抗氧化剂非选择性消除所有ROS更加有效。     

舒血宁联合脑苷肌肽治疗血管性痴呆的疗效研究

目的 观察舒血宁联合脑苷肌肽治疗血管性痴呆患者的疗效及对精神行为症状的改善情况.方法 将58例血管性痴呆患者随机分为舒血宁联合脑苷肌肤治疗的观察组和单纯脑苷肌肤治疗的对照组,治疗结束后观察两组患者的临床疗效、简易智能量表(MMSE)、日常生活活动能力量表(ADL)评分以及安全性评价.结果 治疗后,观察组有效率为89.66％,优于对照组的72.41％,组间差异有统计学意义(P＜0.05).治疗后两组患者的MMSE、ADL评分均较治疗前明显增加,差异均有统计学意义(P＜0.05);而组间比较,观察组的MMSE、ADL评分均较对照组明显增加,差异亦有统计学意义(P＜0.05),且均未出现不良反应.结论 舒血宁联合脑苷肌肽治疗血管性痴呆患者,不仅疗效较佳,安全性高,而且可有效改善患者的精神行为症状.     

改良动静脉内瘘成形术120例临床疗效分析

目的：报道应用改良连续缝合加褥式缝合血管进行血液透析内瘘术的临床效果。方法：选取120例需行血液透析患者男55例,女65例,年龄24岁～75岁,行前臂标准位桡动脉头静脉侧端改良连续缝合加褥式缝合内瘘术,通过临床及超声随访验证。结果：手术成功率达99％,内瘘长期有效率达98．2％。结论：应用改良连续缝合加褥式缝合血管行内瘘术能够收到良好的临床效果。     

甲状腺肿瘤组织中VEGF、p73蛋白表达情况及相互关系研究

目的 探析甲状腺肿瘤组织中血管内皮生长因子(VEGF)、肿瘤抑制因子(p73)的表达及其相关性.方法 选取某院2013年1月至2014年1月收治的60例甲状腺癌和60例甲状腺腺瘤患者作为观察对象,并将同期60例健康人群作为对照,采用免疫组化(SP)法检测组织中VEGF和p73的表达,并采用Pearson相关分析研究组织中VEGF和p73的相关性.结果 甲状腺癌组组织中VEGF阳性表达率86.7％(52/60)显著高于甲状腺腺瘤组71.7％(43/60),高于正常对照组0％,差异均有统计学意义(P＜0.05);甲状腺癌组组织中p73阳性表达率93.3％(56/60)显著高于甲状腺腺瘤组80.0％(48/60),高于正常对照组0％,差异均有统计学意义(P＜0.05).甲状腺组织中VEGF和p73呈正相关,在甲状腺癌组织中相关系数r=0.723,P＜0.05,在甲状腺腺瘤组织中相关系数r=0.542,P＜0.05.结论 甲状腺肿瘤患者组织中VEGF和p73蛋白表达均显著升高,且二者呈正相关.     

术后镇痛对断指再植成活的影响

目的 探讨断指再植术后镇痛效果对于患者断指再植成功率的影响。方法 按照患者意愿分为术后患者自控静脉镇痛组和常规对照组。比较两组在镇痛效果、血管危象发生情况、断指再植成活率以及患者血管内皮生长因子(VEGF)表达情况。结果 术后患者自控静脉镇痛组术后0~12 h、12~24 h以及24~72 h疼痛视觉模拟评分分别为(4.3±2.3)、(3.6±1.9)、(2.4±1.7)分,镇痛效果优于常规对照组(P<0.05)。患者自控静脉镇痛组血管危象发生率低于常规对照组(P<0.05)。患者自控静脉镇痛组在术后18~24 h、66~72 h、114~120 h VEGF分别为(56.43±19.64)、(98.40±25.46)、(68.67±18.94)pg/mL,各时间点均高于常规对照组。患者自控静脉镇痛组断指再植成活率94%高于常规对照组76%,差异有统计学意义。结论 断指再植术后镇痛效果影响断指再植成功率。     

Growth hormone replacement improved oocyte quality in a patient with hypopituitarism: A study of follicular fluid

BackgroundGrowth hormone (GH) is known to be involved in ovarian folliculogenesis and oocyte maturation. In patients with poor ovarian response without growth hormone deficiency (GHD), adjuvant GH treatment improves in-vitro fertilization (IVF) results. Improvement of oocyte quality in IVF by GH replacement was reported in only a few patients with GHD. We report on a new case with study of follicular fluid.MethodsA 29-year-old patient with hypopituitarism was referred to our infertility center. She was undergoing hormonal replacement for hypogonadotropic hypogonadism and diabetes insipidus, and did not consider at first GH replacement. Four IVF procedures were performed between 2011 and 2014. Growth hormone replacement (somatotropin 1.1 mg/day) was initiated before the fourth IVF procedure and unmasked central hypothyroidism; levothyroxine (75 mg/day) was introduced. It took 10 months to reach the treatment objectives for insulin-like growth factor 1 (IGF1), free triiodothyronine (fT3) and free thyroxine (fT4). GH, IGF1 and thyroid hormones were measured in the blood and follicular fluid before and after GH and thyroid hormone replacement. Oocyte and embryo quality were also compared.ResultsThe first 3 IVF procedures were performed without GH replacement. 62% to 100% of mature oocytes presented one or more morphologic abnormalities: diffuse cytoplasmic granularity, large perivitelline space with fragments, fragmentation of the first polar body, ovoid shape, or difficult denudation. Embryo quality was moderate to poor (grade B to D), and no pregnancy was obtained after embryo transfer. After GH replacement, hormones levels increased in follicular fluid: GH [7.68 vs. 1.39 mIU/L], IGF1 [109 vs. < 25 ng/mL], fT3 [3.7 vs. 2.5 pmol/L] and fT4 [1.45 vs. 0.84 ng/mL]. Concomitantly, there was dramatic improvement in oocyte quality (no abnormal morphologies) and embryo quality (grade A), allowing an embryo transfer with successful pregnancy.ConclusionsThis is the first report illustrating changes in hormonal levels in follicular fluid and the beneficial effect of GH replacement on oocyte and embryo quality during an IVF procedure in a patient with hypopituitarism. These results suggest that GH replacement is beneficial for oocyte quality in patients with GHD.     

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G₀/G₁ to S phase of the cell cycle, as measured by [³H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G₀/G₁ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.     

Zerumbone,Sesquiterpene Photochemical from Ginger,Inhibits Angiogenesis

Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.     

Pacientes Naïve Infectados por HIV Apresentam Disfunção Concomitante com Diminuição de Anticorpos Naturais contra Autoantígenos Derivados da Apolipoproteína B Definidos

Fundamento:Fatores de risco definidos para HIV e tradicionais podem estar associados a um aumento de eventos cardiovasculares. Estudos recentes sugerem que a resposta imune humoral à LDL modificada pode estar associada ao processo de aterosclerose.Objetivos:Avaliar a presença de anti-LDL oxidada e de peptídeos derivados da Apolipoproteína B no sangue, bem como sua associação à função endotelial na infecção por HIV.Métodos:Este estudo incluiu consecutivamente sujeitos com idade, sexo e dados demográficos correspondentes em dois grupos: (1) indivíduos infectados com HIV e naïve para terapia antiviral e (2) indivíduos não infectados. A aterosclerose subclínica foi avaliada pela espessura íntima-média, utilizando-se a ultrassonografia das artérias carótidas. A função endotelial foi determinada pela dilatação mediada por fluxo (DMF) da artéria braquial por ultrassonografia. Os níveis de autoanticorpos (IgM, IgG) de lipoproteínas de baixa densidade antioxidadas (LDL-ox), fragmentos de peptídeos antiapolipoproteína B (peptídeos ApoB-D e 0033G-Cys), e citocina foram avaliados por meio de ELISA.Resultados:Os resultados deste estudo não mostraram diferenças na aterosclerose subclínica entre os grupos. Entretanto, os sujeitos infectados com HIV apresentaram uma DMF mais baixa, em comparação com os sujeitos não infectados. Portanto, os sujeitos infectados com HIV apresentaram níveis mais altos de citocinas inflamatórias, títulos de IgG anti-LDL-ox, e IgG anti-ApoB-D. Em contraste, títulos de IgM anti-ApoB-D foram mais baixos em indivíduos infectados com HIV e associados a funções endoteliais diminuídas.Conclusões:Os resultados deste estudo mostram que a infecção por HIV, em sujeitos naïve, está associada à disfunção endotelial e à diminuição de anticorpos naturais para antígenos Apo-B.