酒精性肝炎的诊断、预后分析及治疗的探讨

酒精性肝病已经成为世界范围内导致慢性肝病的主要原因,在我国亦成为一个不可忽视的问题。酒精性肝炎是酒精性肝病发展过程中一个重要阶段。重症酒精性肝炎的预后差,治疗难度大,病死率高。本文主要针对酒精性肝炎的诊断、预后分析及治疗情况进行探讨。     

Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.     

Declines in violence and police arrest among female sex workers in Karnataka state,south India,following a comprehensive HIV prevention programme

Introduction

Female sex workers (FSWs) frequently experience violence, harassment and arrest by the police or their clients, but there is little evidence as to the impact that such factors may have on HIV risk or whether community interventions could mitigate this impact.

Methods

As part of the evaluation of the Avahan programme in Karnataka, serial integrated behavioural and biological assessment (IBBA) surveys (four districts) (2005 to 2011) and anonymous polling booth surveys (PBS) (16 districts) (2007 to 2011) were conducted with random samples of FSWs. Logistic regression analysis was used to assess 1) changes in reported violence and arrests over time and 2) associations between violence by non-partners and police arrest and HIV/STI risk and prevalence. Mediation analysis was used to identify mediating factors.

Results

5,792 FSWs participated in the IBBAs and 15,813 participated in the PBS. Over time, there were significant reductions in the percentages of FSWs reporting being raped in the past year (PBS) (30.0% in 2007, 10.0% in 2011, p<0.001), being arrested in the past year [adjusted odds ratio (AOR) 0.57 (0.35, 0.93), p=0.025] and being beaten in the past six months by a non-partner (clients, police, pimps, strangers, rowdies) [AOR 0.69 (0.49, 0.95), p=0.024)] (IBBA). The proportion drinking alcohol (during the past week) also fell significantly (32.5% in 2005, 24.9% in 2008, 16.8% in 2011; p<0.001). Violence by non-partners (being raped in the past year and/or beaten in the past six months) and being arrested in the past year were both strongly associated with HIV infection [AOR 1.59 (1.18, 2.15), p=0.002; AOR 1.91 (1.17, 3.12), p=0.01, respectively]. They were also associated with drinking alcohol (during the past week) [AOR 1.98 (1.54, 2.53), p<0.001; AOR 2.79 (1.93, 4.04), p<0.001, respectively], reduced condom self-efficacy with clients [AOR 0.36 (0.27, 0.47), p<0.001; AOR 0.62 (0.39, 0.98), p=0.039, respectively], symptomatic STI (during the past year) [AOR 2.62 (2.07, 3.30), p<0.001; AOR 2.17 (1.51, 3.13), p<0.001, respectively], gonorrhoea infection [AOR 2.79 (1.51, 5.15), p=0.001; AOR 2.69 (0.96, 7.56), p=0.060, respectively] and syphilis infection [AOR 1.86 (1.04, 3.31), p=0.036; AOR 3.35 (1.78, 6.28), p<0.001, respectively], but not with exposure to peer education, community mobilization or HIV testing uptake. Mediation analysis suggests that alcohol use and STIs may partially mediate the association between violence or arrests and HIV prevalence.

Discussion

Violence by non-partners and arrest are both strongly associated with HIV infection among FSWs. Large-scale, comprehensive HIV prevention programming can reduce violence, arrests and HIV/STI infection among FSWs.     

From the Cover: Hominids adapted to metabolize ethanol long before human-directed fermentation

Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate–ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.One trend in modern medicine attributes diseases in humans to an incomplete adaptation of the human genome to new challenges presented by our changing cultural and demographic environment (1). This attribution is especially convincing for some “lifestyle” diseases. For example, the recent increase in sugar consumption (including sucrose and fructose) is associated with the emergence of obesity, diabetes, and hypertension (2). Under an evolutionary paradigm, an organism fully adapted to a sugar-rich diet would not be expected to become diseased by consuming sugars, suggesting that humankind has not had enough time to adapt to a modern diet rich in such sugars.It is unclear whether the human genome has had more time to adapt to dietary ethanol (“alcohol” in the vernacular), which also produces a disease spectrum (“alcoholism”) common today in many societies (3). In one historical model, ethanol was not a significant part of the hominin “Paleolithic diet” (4) and was also absent from the diets of earlier ancestors. Rather, the model holds that ethanol entered our diets in significant amounts only after humans began to store surplus food (possibly because of the advent of agriculture) and subsequently developed the ability to intentionally direct the fermentation of food (∼9,000 y ago (5), perhaps as a means of preservation (6). In this model, alcoholism as a disease reflects insufficient time since humans first encountered ethanol for their genome to have adapted completely to ethanol. As such, the allelic variants of enzymes in the ethanol metabolic pathway that disfavor ethanol consumption (e.g., ADH1B*47His and ALDH2*487Lys, both of which lead to an accumulation of acetaldehyde—a toxic intermediate that causes headache, nausea, and general discomfort) represent an early stage of adaptation, possibly in association with pathogenic infections (7–10).In an alternative model, primates may have ingested ethanol via frugivory as early as 80 million y ago (Ma), a time corresponding to the origin and diversification of primates (11) and when angiosperm plants first produced fleshy fruits that can become infected by yeast capable of the accumulating ethanol via fermentation (12). In one version of this model, small amounts of ethanol present in slightly fermenting fruit attached to trees attracted arboreal primates foraging in the trees. In this version, our contemporary attraction to ethanol is an “evolutionary hangover” that ceased to be beneficial once that attraction became redirected to beverages with high concentrations of ethanol (13), made possible only after humans developed the tools allowing them to intentionally direct fermentation (and enhanced with the advent of technology to distill ethanol to higher concentrations). Another version of the “ethanol early” model for ethanol exposure recognizes that ethanol itself, as well as the food naturally containing it, can be a significant source of nutrition. This model posits that any organism with metabolic adaptations that permit the exploitation of ethanolic food would have access to a specialized niche or important fallback foods unavailable to organisms without this metabolic capacity.Paleogenetics is an emerging field designed to address such natural historical hypotheses and, in particular, to distinguish between competing historical models (14). Here, to gain a genetic perspective on the natural history of the interaction between our human ancestors and ethanol, we examined the evolution of Class IV alcohol dehydrogenases (ADH4) (see SI Text for a discussion of the various synonyms used within the ADH family). These digestive enzymes are abundant in the stomach, esophagus, and tongue of primates and are active against a wide range of alcohols. Thus, ADH4 is the first alcohol-metabolizing enzyme to encounter ethanol that is imbibed (15), and several studies indicate that ADH4 contributes significantly to the first-pass metabolism of ethanol in humans (16).ADH4 is also active against retinol (in vitro), and ADH4’s high catalytic efficiency for retinol (as defined by its k_cat/K_M ratio) suggests it may play a role in retinoic acid biosynthesis (17). Mice with inactivated ADH4 genes, however, display few complications associated with retinoid metabolism except under extreme conditions of dietary retinol excess or dietary retinoid deficiency (18, 19). Further, dietary retinoids occur in the form of retinyl esters (from animal foods) or carotenoids (from plant foods); these forms of provitamin A are not substrates for ADH4 present in the upper gastrointestinal track and are converted into retinol only after entering the small intestines. Geraniol, however, is a monoterpenoid that is structurally similar to retinol and is commonly found in plants as an antifeedant, making it a physiologically relevant substrate for ADH4 in herbivorous primates.We therefore tested alternative models for the history of primate exposure to ethanol by comparing the enzymatic efficiencies of modern and ancestral ADH4 enzymes toward geraniol and ethanol. These comparisons identified a dramatic evolutionary transition from an ethanol-inactive ADH4 to an ethanol-active ADH4 in our hominin ancestors ∼10 million y ago.This study focuses on the evolution of one component of ethanol metabolism, ADH4. Ethanol metabolism is complex and involves other ethanol-metabolizing enzymes [e.g., ADH1, ADH2, and the microsomal ethanol oxidizing system (MEOS)], enzymes involved in the downstream metabolism of by-products from ethanol metabolism (e.g., ALDH2, which oxidizes acetaldehyde created from ethanol), and enzymes indirectly affected by the by-products of ethanol metabolism (e.g., ALDH1). A more nuanced understanding of primate adaptation to ethanol will develop as future work examines these related enzymes.     

炒九香虫的炮制工艺优化及其质量标准的建立

目的:优选炒九香虫的炮制工艺,并建立其质量标准。方法:采用滚筒式炒药机,以炮制温度、炮制时间、炒药机转速为炮制因素,以镇痛率、多巴胺二聚体含量和醇溶性浸出物得率为考察指标,在单因素试验基础上,通过正交试验优选九香虫的炒制工艺,利用最佳工艺对10个不同批次的九香虫进行炒制,并测定其总灰分和醇溶性浸出物的含量。结果:炒九香虫的最佳工艺为炒制温度170℃,炒制时间5 min,炒药机转速50 r·min~(-1)。建议炒九香虫的总灰分定为不超过5.2%,醇溶性浸出物不得少于16.8%。结论:优选的炮制工艺合理可靠、稳定性好、方法简便,为规范炒九香虫饮片的炮制工艺和质量标准提供科学依据。     

分步醇沉对玛咖多糖单糖组成及抗氧化活性的影响

目的:分析分步醇沉所得玛咖多糖的单糖组成,并对各部分玛咖多糖的抗氧化能力进行研究。方法:采用水提醇沉法得到玛咖粗多糖,通过分步醇沉对玛咖粗多糖进行分离、纯化;采用气相色谱分析法对各玛咖多糖的单糖组成进行分析;最后采用三氯乙酸法和清除DPPH自由基的方法考察各部分玛咖多糖的抗氧化能力。结果:分步醇沉随乙醇浓度增加依次得到0~40%乙醇多糖部分,40%~50%乙醇多糖部分,50%~60%乙醇多糖部分,60%~70%乙醇多糖部分及70%~80%乙醇多糖部分,依次命名为MP1,MP2,MP3,MP4和MP5;其中收率最大的为MP1,纯度最高的为MP4,分别为0.856%和68.5%;经气相色谱技术分析发现不同体积分数乙醇所得玛咖多糖的单糖组成种类及比例不同;抗氧化能力试验结果表明各部分玛咖多糖的抗氧化能力存在显著性差异,其中抗氧化能力最强的为MP5,MP4抗氧化能力次之,抗氧化能力最弱的为MP1。结论:分步醇沉所得各部分玛咖多糖的抗氧化能力有较大差异,玛咖多糖的抗氧化活性与其单糖组成的种类、比例及其空间构象密切相关,分步醇沉对分离纯化玛咖多糖具有重要意义,为玛咖多糖进一步分离纯化、结构组成和药理研究提供可靠的参考依据。     

Effects of smoking and drinking habits on the incidence of periodontal disease and tooth loss among Japanese males: a 4-yr longitudinal study

OBJECTIVE: We investigated the risk of periodontal disease and tooth loss, associated with habits of smoking and alcohol consumption, in a longitudinal study. SUBJECTS AND METHODS: The subjects were 1332 Japanese males, 30-59 yr of age, who were free from periodontal disease at the baseline check-up, and who underwent a second check-up 4 yr later. Periodontal disease was diagnosed using the community periodontal index score, based on the clinical probing of pocket depth (> or = 4 mm). Smoking and alcohol consumption patterns were evaluated using a self-administered questionnaire. RESULTS: A dose-response relationship was observed between the amount of smoking and the incidence of periodontal disease in each age group. The overall odds ratios (95% confidence intervals), adjusted for age and alcohol, were 1.51 (0.95-2.22), 1.58 (1.13-2.22) and 2.81 (1.96-4.03), among smokers consuming 1-19, 20 or 21 or more cigarettes per day, respectively, with a significant linear trend (p < 0.0001). A similar association was found between smoking and tooth loss, except for the 50-59-yr-old age group. The adjusted odds ratios were 1.26 (0.60-2.64), 2.01 (1.21-2.32) and 2.06 (1.23-3.48), respectively. A significant linear trend between smoking and tooth loss was also observed (p = 0.01). Ex-smokers showed no significant difference compared with nonsmokers. We also found a significant linear trend between alcohol consumption and tooth loss among 30-39-yr-old subjects, while no relationship was observed between alcohol consumption and periodontal disease. CONCLUSION: Cigarette smoking was found to be an independent risk factor for periodontal disease and tooth loss. Alcohol consumption was a limited risk factor for tooth loss in the younger age group, but was unrelated to periodontal disease. To prevent periodontal disease and tooth loss, health practitioners need to encourage people to stop smoking or not to start.     

Tobacco and alcohol related to the anatomical site of oral squamous cell carcinoma

The aim of the present study was to evaluate the possible relationship between tobacco smoking and alcohol drinking and the anatomical sites of squamous cell carcinoma (SCC) of the lip and oral cavity. For this purpose, a case-case study has been performed in 690 patients. The study was focused on the relative risk (RR) or developing SCC at various (sub)sites, for smokers and drinkers of alcohol (divided into moderate and heavy users) relative to non-smokers and non-drinkers. Estimates of ratios of these relative risks were obtained. The relative risk associated with tobacco smoking, adjusted for the use of alcohol, appeared to be highest for SCC in the retromolar area, followed by the floor of mouth, whereas the lowest RR was found in the cheek mucosa. For alcohol drinking, adjusted for tobacco smoking, RR of SCC of the floor of mouth was significantly higher than for the tongue, whereas the RR of SCC of the cheek appeared to be lowest. Furthermore, this study suggests that the contrasts between relative risks, observed by anatomical site of oral SCC, are more pronounced for tobacco smoking than for the use of alcohol. The possible local and systemic factors responsible for these variations of susceptibility for tobacco and alcohol within the oral cavity are discussed.