ROLE OF GABAA RECEPTORS IN THE ACTIONS OF ALCOHOL AND IN ALCOHOLISM: RECENT ADVANCES

Brain GABAergic mechanisms are interesting with regard to theirrole in the actions of ethanol. The present review summarizessome of the more recent studies, most of them biochemical, electrophysiologicaland pharmacogenetic. While there is still a number of controversies,e.g. regarding the molecular mechanisms of ethanol enhancementof GABA_A receptor-mediated anion flux and the effects of chronicalcohol administration on the receptors in experimental animalsand man, there is a substantial body of evidence supportingthe involvement of these mechanisms in many behavioural actionsof ethanoL Two recent findings warrant further molecular biologicalstudies on the interaction between ethanol and the GABA_A receptor,and the extension of the studies to human alcoholics: first,the effects of ethanol on the GABAA receptor are dependent ona specific     

FAILURE OF HYPOGLYCEMIC CONTROL OF FEEDING IN RATS FOLLOWING LESIONS IN THE LATERAL HYPOTHALAMUS

Rats regulating their food intake following temporary aphagia and anorexia as a result of lateral hypothalamic lesions, (as opposed to normal and hypothalamic hyperphagic rats) do not eat more during hypoglycemia induced by insulin.     

ROLE OF THE SALIVARY GLANDS IN PROTECTING THE STOMACH AGAINST ETHANOL

The submandibular gland complex was removed from young adultWistar rats. Sham operations were performed on control animals.Three weeks later, the animals were starved for 24 hr and afterpyloric ligation the stomachs were instilled with 30% ethanol.Two hours later, the animals were killed and the surface areasof the ulcerated mucosae were measured and the values used asulcer index scores. In male, but not female, rats prior sialoadenectomysignificantly exacerbated ethanol-induced gastric ulcerationof the glandular stomach mucosa. This increase in ulcerationwas accompanied by an increase In the backflux of acid Intothe injured tissue. Sialoadenectomy had no statistically significanteffect on histamine-stimulated gastric acid and pepsin secretionwhen these were measured 3 weeks later. Epidermal growth factor (EGF) was administered subcutaneouslyto intact animals in which the stomachs had been filled with30% ethanol. When administered at a dose of 10 µg/kg perhr EGF significantly reduced the ethanol-induced ulceration High molecular weight nerve growth factor (7s NGF) was administeredintragastrically prior to instilling ethanol in the stomachsof intact rats. The NGF had no effect on the seventy of ethanol-inducedulcers. These data suggest that saliva protects the gastric mucosa fromethanol-induced ulceration and that salivary EGF is a possiblecandidate for this protection.     

AGE-RELATED DIFFERENCES IN THE EFFECTS OF ETHANOL ON PERFORMANCE AND BEHAVIOUR IN HEALTHY MEN

Four age groups of healthy men; 20–29, 30–39, 40–49,and 50–59 years (N = 12 per group), drank 0.68 g of ethanol/kgbody weight as neat whisky in the morning after an overnight(10 hr) fast. The concentration of ethanol in fingertip blood,various signs and symptoms of intoxication, body-sway (openand closed eyes), hand-tremor, positional alcohol nystagmus(PAN) and roving ocular movements (ROM) were measured at 30–60min intervals after drinking. Body-sway and hand-tremor increasedwith advancing age in tests made before the ingestion of alcohol(P < 0.05). After drinking alcohol, body-sway and hand-tremorincreased in the four age groups (P < 0.05), being most pronouncedat or near the time of reaching the peak blood alcohol concentration(BAC). The initial impairment subsided when the post-absorptivephase of ethanol kinetics commenced. At 60 min post-drinking,body-sway was most pronounced in men aged 40–49 yearswhen their eyes were closed (P < 0.05). Otheiwise, age-relateddifferences in alcohol impairment in the other age groups werenot statistically significant. Positional alcohol nystagmus(PAN) developed mainly during the acute phase of intoxication,decreasing in intensity as the time after drinking progressed.Roving ocular movements (ROM) were most apparent during thepost-absorptive phase (120–420 min). We conclude thatthe acute effects of a moderate dose of ethanol on sensory andmotor functions are not much different in men aged between 20and 59 years.     

THE ROLE OF GLUCOSE AND INSULIN IN THE EFFECT OF ETHANOL ON PROTEIN SYNTHESIS IN ISOLATED RAT HEPATOCYTES

The incorporation of ¹⁴C-valine into liver protein was studiedin isolated rat liver parenchymal cells. Various glucose levelsin the incubation media did not affect the rate of ¹⁴C-valineincorporation into proteins. The insulin stimulated incorporationof ¹⁴C-valine into proteins was also unaffected by the variousglucose levels. Ethanol decreased the incorporation of ¹⁴C-valineinto liver proteins, affecting stationary and export proteinsto the same extent. This inhibitory action of ethanol on valineincorporation was reversed by increasing exogenous glucose concentrations.The combination of insulin and high glucose level totally preventedthe ethanol inhibition.     

大豆染料木素抑制小鼠结肠肿瘤发生过程中PPAR-γ的作用和机制

目的研究染料木素(Genistein)抑制小鼠结肠肿瘤发生过程中,过氧化物酶增殖物激活受体(PPAR-γ的作用和机制。方法用DSS/AOM法诱导雌性KM小鼠结肠肿瘤发生,小鼠共30只,分成正常对照组(normal,N)、结肠肿瘤诱导组(DSS/AOM)和日粮+Genistein(450mg/kg)的结肠肿瘤诱导组(DSS/AOM+Gen)三组,每组10只。分析小鼠结肠肿瘤的发生情况和健康状况,用Western-blot测定小鼠结肠组织相关蛋白的表达变化。结果 Genistein的添加明显降低了小鼠结肠肿瘤发生率,改善了结肠组织结构。结肠肿瘤小鼠PPARγ及PAT家族蛋白,包括Perilipin、TIP-47和ADRP等蛋白的表达显著提高,肿瘤抑制因子FOXO3a蛋白的表达显著降低(P0.05),Genistein的添加对上述蛋白的表达起到了显著的逆转作用(P0.05)。结论 PPARγ蛋白在结肠肿瘤中过表达,而Genistein的添加,抑制了其表达,从而进一步抑制了PAT家族蛋白的表达,使LDs积累减少,FOXO3a蛋白的表达活性升高,最终抑制结肠肿瘤的发生发展。[营养学报,2019,41(2):178-182]     

单纯超滤在治疗扩张型心肌病顽固性心衰中的作用

目的探讨单纯超滤结合基础药物在治疗扩张型心肌病顽固性心衰中的作用。方法对扩张型心肌病充血性心力衰竭,全身重度浮肿,并胸、腹腔内积液等体内严重水潴留患者4例,采用单纯超滤结合基础药物治疗及胸、腹腔内穿刺抽液,进行临床观察。结果4例患者均能耐受2小时单纯超滤,单纯超滤后心脏功能明显改善,心悸、气促症状缓解,病情稳定,血氧饱和度明显提高,外围水肿明显减轻。救治成功率100%,未出现单纯超滤急性并发症。结论单纯超滤结合基础药物治疗及胸、腹腔内穿刺抽液,是一种安全、有效的救治措施。近期疗效十分满意,值得临床推广应用。     

绞股蓝总皂甙对氯化镉所致睾丸生殖细胞毒性的影响

目的：观察绞股蓝总皂甙（GPS）对雄性小鼠染镉后对睾丸生殖细胞的保护作用。方法：预先灌服GPS200mg/kg／d，连续16d后，腹腔注入氯化镉（Cd)3mg/kg/d 5d，观察睾丸病理切片和精子畸形率。结果：预服GPS的小鼠染镉后，其精子畸形率 比单纯染镉组下降53．01％（P＜0．01）。睾丸病理切片单纯染镉组出现病理改变，与预服GPS组相比未见明显差别。表明GPS对Cd所致小鼠精子畸形率有较好的抑制作用。结论：GPS可用于防治Cd对生殖系统的损害作用。     

ALCOHOLIC WOMEN: INHIBITION OF PROTEIN SYNTHESIS IN THE PLACENTA

[4,5,³H]L-Leucine incorporation into proteins in placental slicesof alcoholic and normal women was measured in the first andsecond trimesters of pregnancy, and on the day of birth. Inthis study, alcoholic women were defined as women who drinkdaily at least 150 ml, calculated as 100% ethanol. Leucine incorporationinto proteins was significantly decreased in alcoholic womencompared with normal placentas: 72% in the first, 70% in thesecond trimester, and 82% in term placenta. The data indicatethat not only can chronic maternal alcohol consumption inducedefects in protein synthesis, but also that heavy alcohol ingestion,even during the beginning of pregnancy, could be toxic for thehuman placenta and development of the fetus.     

Bcl-2家族蛋白在维生素E琥珀酸酯诱导人胃癌细胞凋亡中的作用

目的:研究Bcl-2家族蛋白在维生素E琥珀酸酯(RRR-α-tocopheryl succinate,α-TOS;vitamin E succinate,VES)诱导人胃癌SGC-7901细胞凋亡线粒体途径中的作用。方法:采用噻唑蓝(MTT)法测定VES对SGC-7901细胞的半数抑制浓度(IC50值);吖啶橙/溴化乙啶(AO/EB)染色观察细胞凋亡;Mito Tracker Red CMXRos染色观察线粒体膜电位(ΔΨm)的改变;Western Blot法检测不同剂量VES对人胃癌SGC-7901细胞Bid、Bax、Bcl-2蛋白表达和细胞色素C(cytochrome C,Cyt C)蛋白表达与定位的影响。结果:VES对SGC-7901细胞的IC50值为101.45μg/ml;VES可引起SGC-7901细胞发生凋亡和线粒体膜电位下降;并引起Cyt C蛋白在细胞内重新定位、Bid蛋白剪切活化、Bax蛋白表达增加和Bcl-2蛋白表达减少。结论:VES可抑制SGC-7901细胞的生长,并通过线粒体途径诱导凋亡,其机制可能是通过剪切活化Bid蛋白、上调Bax/Bcl-2相对水平来实现的。     

DRINK-DRIVING: THE ROLE OF STRUCTURAL MEASURES IN PRIMARY PREVENTION

The contribution alcohol makes to traffic crashes is the focus of considerable public and political concern. Popular responses concentrate on the individual drinker and driver: the preferred solution of the alcohol industry is an exclusive focus on information based education; however, there is public support for enforcement of breath analysis legislation. Such enforcement has had positive effects on fatal accident rates in both Australia and New Zealand. Current emphasis on individual-based strategies excludes broader structural changes, such as taxation changes, which affect ease of access to alcohol for the population as a whole. Controls over access to alcohol have some empirical support as methods to prevent alcohol-related problems, including alcohol-related traffic crashes. The individual focus is open to criticism on the grounds of being both relatively less cost effective and of victim-blaming. Structural changes should be considered as complementary to effective individual focus strategies such as well publicised enforcement of breath analysis.     

PHLOGISTIC ACTION OF ETHANOL: A STUDY OF THE VASCULAR RESPONSE IN THE GASTRIC AND DUODENAL MUCOSAE

Ethanol-induced vascular response in the gastric and duodenalmucosae was investigated by light and electron microscopy usingthe colloidal carbon technique. Investigations were done infed and starved animals, with a time-response study in eachgroup for 24 hr after ethanol administration. The results showcytoprotection of food against the hazardous effects of ethanol.     

HETEROGENEITY IN ACTION: THE ROLE OF PASSIVE PERSONALIZATION IN COMPARATIVE EFFECTIVENESS RESEARCH

Despite the goal of comparative effectiveness research (CER) to inform patient‐centered care, most studies fail to account for the patient‐centeredness of care that already exist in practice, which we denote as passive personalization (PP). Because CER studies describe the average effectiveness of treatments rather than heterogeneity in how individual patients respond to therapies, clinical or coverage policies that respond to CER results may undermine PP in clinical practice and generate worse outcomes. We study this phenomenon empirically in the context of use of antipsychotic drugs in Medicaid patients with schizophrenia using novel instrumental variable methods. We find strong support for PP in clinical practice and demonstrate that the average effects from a CER study cannot be replicated in practice because of the presence of PP. In contrast, providing physicians with evidence to further personalize treatment can produce significant benefits. Copyright © 2013 John Wiley & Sons, Ltd.     

caspase-3和caspase-9在甘氨鹅脱氧胆酸钠诱导肝癌细胞SMMC7721细胞凋亡中的影响

[目的]观察甘氨鹅脱氧胆酸钠(glycochenodeoxycholate,GCDCA)诱导人肝癌细胞SMMC7721凋亡过程中caspase3,9活性变化,探讨GCDCA诱导肝癌细胞凋亡的机制。[方法]体外培养SMMC7721细胞,GCDCA为处理因素,Annexin V—FITC/PI双染色法结合流式细胞技术仪检测细胞凋亡率,比色法测定caspase3,9活性。[结果]200μmol/L的GCDCA处理SMMC7721细胞24h,48h,72h后,其细胞凋亡率明显增加;caspase3,9活性表达水平明显升高,并与GCDCA呈浓度依赖性,与对照组相比差异有统计学意义(P﹤0.05)。[结论]GCDCA可明显诱导肝癌SMMC7721细胞凋亡,caspase3,9参与GCDCA诱导SMMC7721细胞凋亡调控。     

HEALTH CARE REFORM IN THE UNITED STATES: THE CRITICAL ROLE OF MEDICAL EDUCATION

The discussions surrounding health care reform in the United States have involved virtually every aspect of the health care system. Medical education—including its undergraduate and postgraduate components — is very much a part of these deliberations and is an extremely important component of long-term reform in the system as a whole.     

PRIVY SYMPOSIUM. II: ROLE OF THE LATRINE IN CONTROL OF HOOKWORM DISEASE

Passing from construction to disease relations, two maladies are here considered in connection with the privy. Dr. Ferrell discusses hookworm and gives a few rules that can eliminate the link of soil pollution. Dr. Smith presents results in typhoid and asserts that the sanitary privy, properly maintained can be an important factor in its control.     

PRIVY SYMPOSIUM. II: ROLE OF THE LATRINE IN CONTROL OF HOOKWORM DISEASE

Passing from construction to disease relations, two maladies are here considered in connection with the privy. Dr. Ferrell discusses hookworm and gives a few rules that can eliminate the link of soil pollution. Dr. Smith presents results in typhoid and asserts that the sanitary privy, properly maintained can be an important factor in its control.