Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease.

While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

NO-1886对高糖高脂饲料喂养新西兰兔糖代谢的影响

合成药NO-1886是脂蛋白脂肪酶(LPL)的激动剂，能降低血浆甘油三酯(TG)并升高高密度脂蛋白胆固醇(HDL-c)水平。我们曾发现NO-1886还具有降低血糖的作用。本研究主要观察NO-1886对糖尿病兔胰岛素抵抗及β-细胞功能方面的影响。用高糖高脂饲料诱导，使新西兰兔血浆葡萄糖升高，发生胰岛素抵抗。在高糖高脂饲料中添加1％NO-1886进行治疗。结果：发现NO-1886可抑制血清葡萄糖升高，经糖耐量和胰岛素敏感性试验检测，NO-1886可保护胰岛素的急性相分泌，增强胰岛素对葡萄糖的清除能力。研究结果提示NO-1886具有改善胰岛素抵抗、降低血糖的作用。     

高果糖诱导IR大鼠模型血清脂质代谢的改变及意义

目的: 评估高果糖膳食对机体胰岛素敏感性及血清脂质代谢的影响及意义.方法:以高果糖膳食(果糖占总热量34.5%)诱导并经钳夹技术证实建立胰岛素抵抗(IR)大鼠模型,生化比色法测定血清游离脂肪酸(FFA),生化酶法测定血清甘油三酯(TG)及总胆固醇(TC).结果:高果糖膳食喂养4周后,实验组大鼠葡萄糖输注率由(11.5±0.6)mg/kg·min-1下降至(6.6±0.4)mg/kg·min-1(P<0.01);血清FFA由(0.45±0.09)mmol/L增至(0.78±0.19)mmol/L(P<0.01);TG由(0.54±0.10)mmol/L增至(0.96±0.22)mmol/L(P<0.01);TC由(1.96±0.32)mmol/L增至(2.42±0.21)mmol/L(P<0.01).结论:高果糖膳食可导致机体严重IR,是建立IR大鼠模型的有效手段;该模型同时伴有血清脂代谢各相关指标的明显异常,血脂的变化既是IR的结果,也是IR向纵深发展的原因和必要条件.     

明党参鲜根与药材饮片中精油成分和氨基酸含量比较

对明党参鲜根和饮片中的精油及氨基酸成分进行了比较分析,鉴定出27种精油成分,并发现炮制前后氨基酸成分含量变化较大。     

The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation

Abstract Short-chain carboxylic acids (SCCA; C≤5: e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacteria] presence; SCCA concentration: and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r≥0.47; all p≤ 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (?0.31 ≤r≤ 0.39; 0.08 ≤p 0.75) for any of the locations. Finally, the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially mediated periodontal attachment loss.     

Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.     

Improved Cellular Delivery of Antisense Oligonucleotides Using Transferrin Receptor Antibody-Oligonucleotide Conjugates

This work is dedicated to the memory of the late Dr Ian Walker.     

The growth and development of vegan children

The results of prospective study on the growth and diets, estimated from 7-day weighed food intake records, of 20 life vegan children (aged 5.8–12.8 years) are presented. The growth and development of the children were normal but they tended to be lighter in weight and exceptionally lean compared with standards. Heights were around the median of the Tanner-Whitehouse standards but were lower than the medians recently proposed by the Department of Health. Energy intakes were similar to those reported in children of the same age in the general population, but dietary fibre intakes were very high which may have influenced the digestible energy. Sugar provided an average 15.6% of the dietary energy and this was supplied mainly by fruit and fruit juice. Mean fat intakes were close to the dietary reference values. Daily intakes of essential nutrients generally met the amounts recommended, with the exceptions of calcium and vitamin B₁₂. Many children received supplementary sources of vitamin B₁₂ and only two children had intakes below the lower recommended nutrient intake. Intakes of saturated fatty acids were low and those of linoleic acid were high. The ratio of linoleic/α-linolenic acid was high. As docosahexaenoic acid is absent from vegan diets, it is suggested that vegans should use oils with a lower ratio of linoleic/α-linolenic acid. Future studies should also consider the influence of a vegan diet on retinal function. None of the children was immunized against whooping cough and 11 had not been immunized against polio: 16 of the children had suffered from whooping cough. Future studies need to take into account factors other than diet when assessing the health of vegans. The results of this study show that children can be successfully reared on a vegan diet providing sufficient care is taken to avoid the known pitfalls of a bulky diet and vitamin B₁₂ deficiency.     

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: Comparison with thallium-201 and fluorine-18 fluorodeoxyglucose

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the²⁰¹Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection²⁰¹T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress²⁰¹T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)²⁰¹T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that²⁰¹T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and²⁰¹T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,²⁰¹T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs²⁰¹T1 reinjection). In all circumstances, MIHA was less specific than²⁰¹T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to²⁰¹T1.