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Impact of Betaine on Hepatic Fibrosis and Homocysteine in Nonalcoholic Steatohepatitis - A Prospective, Cohort Study 甜菜碱对非酒精性脂肪性肝炎患者肝纤维化和同型半胱氨酸的影响——一项前瞻性队列研究
Pub Date : 2011-04-29 DOI: 10.2174/1876399501103010001
S. Mukherjee, T. Bernard, K. Kharbanda, A. J. Barak, M. Sorrell, D. Tuma
Introduction: Nonalcoholic steatohepatitis (NASH) is an important cause of cirrhosis and over the past decade has accounted for an increasing proportion of liver transplants in the United States. Unfortunately there is no treatment for NASH except for risk factor modification. The aims of our study were to assess the impact of betaine on liver function tests, homocysteine levels and hepatic fibrosis in a prospective cohort of NASH patients Materials and Methodology: Between July 2003 and June 2006, consecutive patients with NASH were screened to deter- mine treatment eligibility. Eligibility criteria included elevated aminotransferases and a liver biopsy within twelve months of study entry satisfying the Brunt criteria for NASH. Patients were treated with betaine anhydrous 10 grams twice a day for one year. Liver function tests, homocysteine levels and liver biopsy were performed prior to and at the end of treat- ment. Outcomes were calculated using intention to treat analysis. Results: 35 patients were eligible. 23 patients completed treatment, seven were intolerant and five dropped out and were lost to follow up. Improvement or normalization in aminotransferases occurred in 62.9% of patients (p 0.05). Resolution or improvement in steatosis occurred in 57.1% (p<0.05), improvement or sta- bilization of inflammation in 60% (p<0.05) and fibrosis in 62.9% (p<0.05). Conclusion: Betaine appears to improve hepatic function tests, homocysteine levels and histology in this cohort of NASH patients. Large randomized studies with long-term follow up are required to assess the effect of betaine for this growing epidemic.
简介:非酒精性脂肪性肝炎(NASH)是肝硬化的一个重要原因,在过去的十年中,在美国肝移植中占越来越大的比例。不幸的是,除了改变危险因素外,NASH没有治疗方法。本研究的目的是评估甜菜碱对NASH前瞻性队列患者肝功能测试、同型半胱氨酸水平和肝纤维化的影响。材料和方法:在2003年7月至2006年6月期间,连续筛选NASH患者以确定治疗资格。入选标准包括转氨酶升高和入组12个月内肝活检符合布伦特NASH标准。患者服用无水甜菜碱10克,每天两次,持续一年。在治疗前和治疗结束时进行肝功能检查、同型半胱氨酸水平和肝活检。使用意向治疗分析计算结果。结果:35例患者入选。23例患者完成治疗,7例不耐受,5例退出随访。62.9%的患者转氨酶改善或恢复正常(p < 0.05)。脂肪变性的缓解或改善占57.1% (p<0.05),炎症的改善或固化占60% (p<0.05),纤维化的改善占62.9% (p<0.05)。结论:甜菜碱可以改善NASH患者的肝功能测试、同型半胱氨酸水平和组织学。需要长期随访的大型随机研究来评估甜菜碱对这种日益流行的流行病的影响。
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引用次数: 16
Postprandial Lipid Metabolism: The Missing Link Between Life-Style Habits and the Increasing Incidence of Metabolic Diseases in Western Countries? 餐后脂质代谢:生活方式习惯与西方国家代谢性疾病发病率增加之间的缺失环节?
Pub Date : 2010-03-30 DOI: 10.2174/1876399501002010001
E. Bravo, M. Napolitano, K. Botham
Postprandial lipemia is the transient increase in blood lipids which occurs after a meal containing fat and is caused by raised levels of triglyceride-rich lipoproteins (TRLs) in the blood. Delayed clearance of TRLs leads to post- prandial hyperlipidemia, and there is now a great deal of evidence to support the idea that this condition is an important risk factor for cardiovascular disease (CVD). Western lifestyle habits including: diets low in fresh fruit and vegetables and high in fat and processed food, alcohol consumption, smoking, and lack of exercise tend to promote postprandial hyperlip- idemia, and it is a characteristic feature of increasingly common metabolic diseases such as obesity, insulin resistance and type 2 diabetes which are also linked to modern lifestyle behaviour and which carry an increased risk of CVD develop- ment. Modification of lifestyle factors such as changing to a healthier diet, weight loss, reducing alcohol consumption and increasing exercise can cause significant reductions in postprandial hyperlipidemia and thus help to reduce this risk. De- spite the growing recognition that the extent of postprandial lipemia is a good predictor of CVD, no standardized method- ology for its measurement is currently available. Determination of blood TG levels after consumption of a standard test meal is likely to be the most convenient approach for a routine clinical test, and we propose a standard test meal which is easily adaptable for the variations in dietary habits in different countries. Greater use of postprandial lipid determination will aid in the translation of our extensive knowledge on the role of nutrition in health into national and international pol- icy.
餐后脂血症是指在进食含脂肪的食物后血脂短暂升高,由血液中富含甘油三酯的脂蛋白(trl)水平升高引起。trl的清除延迟导致餐后高脂血症,现在有大量证据支持这种情况是心血管疾病(CVD)的重要危险因素的观点。西方的生活习惯包括:少吃新鲜水果和蔬菜,多吃脂肪和加工食品、饮酒、吸烟和缺乏锻炼,往往会促进餐后高脂血症,这是越来越常见的代谢性疾病的一个特征,如肥胖、胰岛素抵抗和2型糖尿病,这些疾病也与现代生活方式行为有关,并增加了心血管疾病发展的风险。改变生活方式因素,如改变健康饮食、减肥、减少饮酒和增加运动,可以显著减少餐后高脂血症,从而有助于降低这种风险。尽管人们越来越认识到餐后脂血症的程度是心血管疾病的一个很好的预测指标,但目前尚无标准化的测量方法。在食用标准试验餐后测定血TG水平可能是常规临床试验中最方便的方法,我们提出了一种标准试验餐,可以很容易地适应不同国家饮食习惯的变化。更多地使用餐后脂质测定将有助于将我们关于营养在健康中的作用的广泛知识转化为国家和国际政策。
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引用次数: 31
Differential Effects of Recombinant Human EGF on Proliferation and Radiation Survival of Normal Fibroblast and Cancer Cell Lines 重组人EGF对正常成纤维细胞和癌细胞增殖和辐射存活的差异影响
Pub Date : 2009-11-05 DOI: 10.2174/1876399500901010009
E. Kwon, Seunghee Lee, Kyubo Kim, Hong-Gyun Wu, Sang‐wook Lee
Objective: To evaluate the effects of recombinant human epidermal growth factor (rhEGF) on proliferation and radiation survival of normal fibroblast and cancer cell lines both in vitro and in vivo. Methods: Using normal fibroblast and cancer cell lines, we evaluated the expression of EGFR, and determined their pro- liferation and survival with rhEGF alone or in combination with radiation. For the combination treatments, we applied 10 nM rhEGF and delivered single radiation doses of 0, 2, 5, and 10 Gy. In the animal study, we introduced EMT-6 cells into BALB/c mice to assay for tumor growth delay. We applied single radiation dose of 10 or 20 Gy, with or without 1.0 mg/Kg of rhEGF, three times a day, for 7 days. Results: In a dose-dependent manner, rhEGF stimulated proliferation of the normal fibroblast, but not the cancer cell lines with low or intermediate expression of EGFR. rhEGF inhibited proliferation of the cancer cell line with the highest EGFR expression. Administration of rhEGF in combination with radiation attenuated the cell killing effect of radiation in normal fibroblast, but it had no effect or even augmented the radiation effect in cancer cell lines. In the animal study, we observed no difference in tumor growth rates when rhEGF was combined with radiation compared to radiation alone. Conclusions: Our results suggested that rhEGF might be useful in preventing and/or treating radiation-induced injury without stimulating tumor growth. Mini-Abstract: rhEGF effectively stimulated proliferation and radiation recovery in normal fibroblasts without promoting the growth of tumor cells. Therefore, it might be useful in preventing and/or treating radiation-induced tissue injury.
目的:研究重组人表皮生长因子(rhEGF)对正常成纤维细胞和癌细胞体外和体内增殖及辐射存活的影响。方法:以正常成纤维细胞和肿瘤细胞株为研究对象,分别检测EGFR的表达,并分别用rhEGF单独或联合放疗检测其增殖和存活情况。对于联合治疗,我们使用10 nM rhEGF,并给予0、2、5和10 Gy的单次辐射剂量。在动物实验中,我们将EMT-6细胞导入BALB/c小鼠体内,检测肿瘤生长延迟。我们使用10或20 Gy的单次辐射剂量,加或不加1.0 mg/Kg的rhEGF,每天三次,连续7天。结果:rhEGF以剂量依赖性的方式刺激正常成纤维细胞的增殖,但对EGFR低或中表达的癌细胞系没有刺激作用。rhEGF抑制EGFR表达最高的癌细胞的增殖。rhEGF联合放疗在正常成纤维细胞中减弱了辐射的杀伤作用,但在癌细胞系中没有作用,甚至增强了辐射作用。在动物实验中,我们观察到rhEGF联合放疗与单独放疗相比,肿瘤生长速率没有差异。结论:我们的研究结果表明,rhEGF可能在不刺激肿瘤生长的情况下预防和/或治疗辐射引起的损伤。摘要:rhEGF在不促进肿瘤细胞生长的情况下,能有效刺激正常成纤维细胞的增殖和辐射恢复。因此,它可能有助于预防和/或治疗辐射引起的组织损伤。
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引用次数: 3
Molecular Genetics of Human Personality Traits for Psychiatric, Behavioral, and Substance-Related Disorders 精神、行为和物质相关障碍的人类人格特征的分子遗传学
Pub Date : 2009-03-06 DOI: 10.2174/1876399500901010001
E. Lin, P. Chen
The investigation of personality genetics had received much attention since the three seminal reports showing an association between genes and personality traits in the general population. Accumulating evidences suggested that per- sonality traits have significant genetic components. Although currently available data are not enough for proof, more and more genetic variants associated with personality traits are being discovered. In this paper, we review related studies of gene polymorphisms and human personality traits for psychiatric, behavioral, and substance-related disorders. First, we briefly describe the commonly-used self-reported temperament measures that define personality dimensions. Then, we summarize the characteristics of the candidate genes for personality traits, and investigate gene variants which have been suggested to be linked with personality traits for individuals with psychiatric, behavioral, and substance-related disorders.
自从三个开创性的报告显示了基因与一般人群的人格特征之间的联系以来,人格遗传学的研究受到了广泛的关注。越来越多的证据表明,个体人格特征具有显著的遗传成分。虽然目前可用的数据不足以证明,但越来越多与人格特征相关的基因变异正在被发现。本文就精神、行为和物质相关障碍的基因多态性与人格特征的相关研究进行综述。首先,我们简要描述了定义人格维度的常用自我报告气质测量。然后,我们总结了人格特质候选基因的特征,并研究了与精神、行为和物质相关障碍个体的人格特质相关的基因变异。
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引用次数: 1
Improved Statistical Methods are Needed to Advance Personalized Medicine. 需要改进的统计方法来推进个性化医疗。
Pub Date : 2009-01-01 DOI: 10.2174/1876399500901010016
Farrokh Alemi, Harold Erdman, Igor Griva, Charles H Evans

Common methods of statistical analysis, e.g. Analysis of Variance and Discriminant Analysis, are not necessarily optimal in selecting therapy for an individual patient. These methods rely on group differences to identify markers for disease or successful interventions and ignore sub-group differences when the number of sub-groups is large. In these circumstances, they provide the same advice to an individual as the average patient. Personalized medicine needs new statistical methods that allow treatment efficacy to be tailored to a specific patient, based on a large number of patient characteristics. One such approach is the sequential k-nearest neighbor analysis (patients-like-me algorithm). In this approach, the k most similar patients are examined sequentially until a statistically significant conclusion about the efficacy of treatment for the patient-at-hand can be arrived at. For some patients, the algorithm stops before the entire set of data is examined and provides beneficial advice that may contradict recommendations made to the average patient. Many problems remain in creating statistical tools that can help individual patients but this is an important area in which progress in statistical thinking is helpful.

常用的统计分析方法,如方差分析和判别分析,在为个体患者选择治疗方法时不一定是最佳的。这些方法依赖于群体差异来识别疾病或成功干预的标记,当亚组数量很大时忽略了亚组差异。在这种情况下,他们给病人提供的建议和一般病人一样。个性化医疗需要新的统计方法,以便根据大量患者特征,为特定患者量身定制治疗效果。其中一种方法是顺序k近邻分析(patient -like-me算法)。在这种方法中,对k个最相似的患者进行顺序检查,直到可以得出关于治疗对患者疗效的统计上显着的结论。对于一些病人来说,算法在检查完整的数据集之前就停止了,并提供了可能与普通病人的建议相矛盾的有益建议。在创建能够帮助个体患者的统计工具方面仍然存在许多问题,但这是统计思维进步的一个重要领域。
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引用次数: 33
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The open translational medicine journal
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