THE ACUTE EFFECTS OF ETHANOL AND ACETALDEHYDE ON THE SYNTHESIS OF MIXED AND CONTRACTILE PROTEINS OF THE JEJUNUM

An investigation was made into the acute effects of ethanoland acetaldehyde with or without enzyme inhibitors of alcoholdehydrogenase (4-methylpyrazole) and aldehyde dehydrogenase(cyanamide) on fractional rates of protein synthesis of mixedand contractile proteins of the jejunum. Ethanol decreased thefractional rates of mixed and contractile protein synthesis(i.e. k_o defined as the percentage of tissue protein renewedeach day) by -25%. Pretreatment with 4-methylpyrazole followedby treatment with ethanol further reduced mixed and contractilek_o by -30%, when compared with saline plus saline and 4-methylpyrazoleplus saline groups. The greatest reductions in k_o of mixed andcontractile proteins occurred with cyanamide pretreatment followedby ethanol treatment: mixed and contractile protein k_o in thecyanamide plus ethanol group decreased by -60% when comparedwith saline plus saline and cyanamide plus saline groups, whereask_o decreased by -45% when compared with the saline plus ethanolinjected group. Acetaldehyde treatment alone caused no significantinhibition of protein synthesis. However, 4-methylpyrazole pretreatmentplus acetaldehyde treatment significantly reduced mixed andcontractile k_o by -20% when compared with the saline group,and by -15% when compared with the 4-methylpyrazole plus salineand saline plus acetaldehyde groups. These data show that ethanolalone and perhaps high levels of acetaldehyde may be responsiblefor the inhibition of intestinal protein synthesis and relatedpathological derangements, e.g. motility disturbances due toloss of contractile proteins.     

THE BINDING OF ACETALDEHYDE TO THE ACTIVE SITE OF RIBONUCLEASE: ALTERATIONS IN CATALYTIC ACTIVITY AND EFFECTS OF PHOSPHATE

Ribonuclease A was reacted with [1-¹³C, 1.2-¹⁴ C] and sodiumcyanoborohydride in the presence or absence of 0.2 M phosphate.After several hours of incubation at 4°C (pH 7.4) stableacetaldehyde-RNase adducts were formed, and the extent of theirformation was similar regardless of the presence of phosphate.Although the total amount of covalent binding was comparablein the absence or presence of phosphate, this active site ligandprevented the inhibition of enzymatic activity seen in its absence.This protective action of phosphate diminished with progressiveethylation of RNase, indicating that the reversible associationof phosphate with the active site lysyl residue was overcomeby the irreversible process of reductive ethylation. ModifiedRNase was analysed using ¹³C proton decoupled NMR spectroscopy.Peaks arising from the covalent binding of enriched acetaldehydeto free amino groups in the absence of phosphate were as follows:NH₂-terminal alpha amino group, 47.3 ppm; bulk ethylation atepsilon amino groups of nonessential lysyl residues, 43.0 ppm;and the epsilon amino group of lysine-41 at the active site,47.4 ppm. In the spectrum of RNase ethylated in the presenceof phosphate, the peak at 47.4 ppm was absent. When RNase wasselectively premethylated in the presence of phosphate, to blockall but the active site lysyl residues and then ethylated inits absence, the signal at 43.0 ppm was greatly diminished,and that arising from the active site lysyl residue at 47.4ppm was enhanced. These results indicate that phosphate specificallyprotected the active site lysine from reaction with acetaldehyde,and that modification of this lysine by acetaldehyde adductformation resulted in inhibition of catalytic activity.     

五种淀粉类食物引起的血糖和C肽反应

将４５例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人随机分成４组，每组６～１８人，被观察当日上午不使用药物，并以１０名健康人作对照。收集上述研究对象空腹及进食实验食物餐后３０、６０’１２０’１８０ｍｉｎ的血液样本，动态观察血浆葡萄糖和血清Ｃ肽的变化。实验食物包括馒头、米饭、莲子、芡实和淮山（均含碳水化物５０ｇ），其中馒头作为参照食物标准，其血糖指数和Ｃ肽指数均定作１００，其余实验食物的血糖指数和Ｃ肽指数分别是米饭８９，９１；莲子６２，７２；其实１０２，１０２；淮山１０３，１０２。实验结果表明，莲子的血糖指数和Ｃ肽指数均明显降低。在五种实验食物中，莲子控制ＮＩＤＤＭ病人血糖和胰岛素水平的作用最好，可作为糖尿病饮食治疗的一种首选食物。     

能量限制对大鼠糖代谢、非酶糖化蛋白产物的影响

方法：雄性大鼠７２只，断奶后喂养在无特殊病原体、恒温、恒湿、定时光照的动物房。于１４周龄时，随机分成能量限制（ＣＲ）与自由进食（ＡＬ）组，ＣＲ鼠接受饲料能量为ＡＬ鼠的６０％。至１８周龄时，分批处死动物并测其体重、血糖、胰岛素、果糖胺、糖化白蛋白、总蛋白、白蛋白、球蛋白等。结果：与ＡＬ鼠比较，ＣＲ鼠的血糖、胰岛素、果糖胺及糖化血清白蛋白浓度显著降低，体重及肝重也显著下降；两组动物的果糖胺与糖化白蛋白存在显著性相关；血清蛋白浓度两组间无显著差异。结论：ＣＲ可显著改变大鼠的糖代谢，并可能通过降低大鼠血糖及胰岛素浓度、减少非酶糖化蛋白形成而发挥延缓机体老化，进而延长寿命的作用     

EFFECTS OF ETHANOL AND ACETALDEHYDE ON THE ENZYMES OF GLYCOGEN METABOLISM

This report concerns a study of the effect of ethanol and acetaldehydeon the regulatory enzymes of glycogen metabolism. It demonstratesan inhibition of glycogen phosphorylase kinase at pH 6.8 ata very low concentration of ethanol. There was no effect ofacetaldehyde on this enzyme. Neither ethanol not acetaldehydehas been shown to have any effect on glycogen synthase, glycogenphosphorylase, protein phosphatase or independent and cAMP-dependentprotein kinases. This inhibition could explain the high concentrationof glycogen in the muscle tissue of chronic alcoholics thatis found when ethanol is present in skeletal muscle.     

MEASURING AND REPORTING THE CONCENTRATION OF ACETALDEHYDE IN HUMAN BREATH

Most of the acetaldehyde generated during the metabolism ofethanol becomes tightly bound to endogenous molecules such ashaemoglobin, amino acids and certain phospholipids. Free acetaldehydepasses the blood-brain bamer and traces of this toxic metaboliteare excreted through the lungs and can be detected in the expiredair. The blood/air partition coefficient of acetaldehyde at34 %C, the average temperature of endexpired air, is about 190:1.Because of various problems associated with measuring acetaldehydein blood samples, several research groups have instead investigatedthe analysis of acetaldehyde in breath which offers an indirectand alternative approach for clinical and research purposes.However, care is needed when interpreting the results of breathacetaldehyde measurements, because of the possibility of localformation from microflora inhabiting the upper airways and mouth.The concentration of acetaldehyde exhaled in breath after drinkingalcohol demonstrates large inter-individual differences dependingon various genetic (racial) and environmental factors. Moreover,acetaldehyde is an endogenous metabolite and even without drinkingany alcohol the concentrations expelled in breath span from0.2 to 0.6 nmol/l, with higher levels observed in smokers andabstinent alcoholics. Breath acetaldehyde concentration reachedbetween 5 and 50 nmol/l in European subjects who drank a moderatedose of ethanol (0.4–0.8 g/kg), with the highest valuesseen in smokers. The concentration of breath acetaldehyde inJapanese subjects after drinking alcohol reached between 200and 500 nmol/l at the peak. These much higher levels followbecause a large proportion of Orientals (40–50%) inheritan inactive form of the low K_m mitochondrial isoenzyme of aldehydedehydrogenase (ALDH₂). The highest concentrations of breathacetaldehyde were seen in healthy Caucasians who drank a smalldose of alcohol (0.25 g/kg) after taking the alcohol-sensitizingdrug calcium carbimide, which blocks the action of ALDH isozymes.During the most intense acetaldehyde-flush reaction, breathacetaldehyde reached between 200 and 1300 nmol/l, but even theseabnormally high concentrations did not interfere with the analysisof ethanol in breath by means of non-specific infrared analyserscurrently used in many countries for testing drinking drivers.     

GLUCOSE INGESTION AND THE CONTROL OF LIPOGENESIS

Studies of lipogenesis in meal-eating mice show that ingestion of glucose plays an important role in controlling the rate of flux from glucose to tissue fatty acids.     

汞和甲基汞对乙醛作业工人的健康危害

对接触组厂房环境污染和接触组与对照组工人健康状况进行检测，结果表明：接触组厂房空气中汞和甲基汞平均浓度分别为０．２４ｍｇ／ｍ３和２．３μｇ８／ｍ３。接触组发生慢性轻度汞中毒５８名（４９．１５％），职业性慢性甲基汞中毒１０名（８．５％）和观察对象１１名（９．３％）。而对照组无汞中毒和甲基汞中毒，两组间差异非常显著（Ｐ＜０，０１）。     

THE IN VITRO BINDING OF ACETALDEHYDE TO COLLAGEN STUDIED BY NEUTRON DIFFRACTION

The location of acetaldehyde binding sites in the axial unitcell of tendon collagen was investigated by neutron diffraction.Acetaldehyde forms spontaneous cross-links with specific residuesin collagen. The use of deuterated acetaldehyde increased theneutron scattering length of these groups. The introductionof deuterated acetaldehyde at specific locations allowed theacetaldehyde-reacted collagen to be treated as multiple isomorphousderivatives for neutron fibre diffraction. The low resolutionaxially projected structure was determined using amplitudesof the first eight meridional reflections (d = 67 nm). Resultsindicate that the process of acetaldehyde labelling takes placeat different rates at different sites within the collagen fibril.The position of acetaldehyde attachment correlates well withthe position of lysine and hydroxylysine residues especiallyin the regions of the molecular termini. This information isrelevant to the process of cirrhosis and fibrosis of the liversince adduction of collagen by acetaldehyde may interfere withnormal Schiff base cross-link formation at the C- and N-termini.This may result in subsequent alterations in the intra- andinter-molecular cross- linking pattern of collagen molecules.     

ETHANOL-INDUCIBLE CYTOCHROME P-450 ACTIVITY AND INCREASE IN ACETALDEHYDE BOUND TO MICROSOMES AFTER CHRONIC ADMINISTRATION OF ACETALDEHYDE OR ETHANOL

Chronic ethanol consumption results in acetaldehyde adduct formationwith proteins such as haemoglobin and liver proteins in vivo.Our purpose was to study the binding of acetaldehyde to livermicrosomal proteins, a site of ethanol oxidation via cytochromeP-450 (especially P-450 II E1), after chronic administrationof ethanol or acetaldehyde for 21 days to rats. The liver microsomaloxidation of 1-butanol by the ethanol-inducible P-450 also wasexamined. Acetaldehyde bound to liver microsomal proteins washigher in ethanol-fed rats compared with acetaldehyde-treatedrats (0.735 vs 0.413 nmol/mg of protein respectively). The biotransformationof n-butanol to butyraldehyde by liver microsomes was increased(by 136%) in ethanol-fed rats vs controls, whereas in acetaldehyde-treatedrats this increase was much lower (only 27%). However, in thislast group, a significant negative relationship between thequantity of acetaldehyde bound to microsomal proteins and themonooxygenase-catalyzed transformation of butanol by liver microsomeswas demonstrated (r = –0.79, P < 0.01). These resultssuggest that proteins of liver microsomes are a target for acetaldehydebinding during ethanol oxidation and such adduct formation couldimpair the oxidative properties of the alcohol-inducible cytochromeP-450.     

低聚葡萄糖的评价和应用

作者研制了一种低聚葡萄糖,主要由麦芽糖至麦芽第七糖组成。25％水溶液的pH为6.5,渗透压275mOsm/kgH_2O,可大量使用而无副作用。食品卫生学、毒理学、营养学的评价说明安全无毒,产生的能量可被机体很好地利用。9人6天以此作碳水化物的来源,提供总能量的62.5％,可保持体重和体力劳动能力,不影响维生素B_2和C的吸收。适用于经肠营养制剂、方便饮食、婴儿、儿童及老年人食物。     

RELATIONSHIP OF BLOOD-BRAIN-BARRIER GLUCOSE TRANSPORT TO CIRCULATING GLUCOSE SUPPLY

Chronic hypoglycemia, produced by experimental hyperinsulinism, selectively increased the transport of glucose across the blood-brain barrier in rats.     

不同量和质的蛋白质对运动大鼠血糖,乳酸及耐力的影响

本文通过蛋白质７、１７、２７％（Ｗ／Ｗ）三种水平及不同质量组成的蛋白质喂养的三批大鼠游泳实验，以血乳酸、肌乳酸、血糖及肌糖原含量变化对大鼠运动耐力进行了观察。结果表明：在能量相等和平衡的情况下，饲料蛋白质含量以１７％水平为宜，其组成优质蛋白质占总蛋白量的４０％较好。     

组蛋白乙酰转移酶和去乙酰化酶的研究

染色质和染色体是细胞核中同种物质的不同形态，由基本组成单位核小体经螺旋、盘绕、压缩而成。核小体的中部是由4种组蛋白（H2A、H2B、H3、H4）各两个分子构成的八聚体，N端尾部为单一的H1，核小体周围绕着两圈长约166bp的DNA，之间的连接DNA约10—80bp，并通过组蛋白H1缩成直径为30nm的纤丝。     

THE ENZYMES AND KINETICS OF HEPATIC RETINOL METABOLISM

Retinoids, retinol turnover, retinoid-metabolizing enzymes, and retinoid-binding proteins have been quantitated in hepatocytes and stellate cells in rats.     

参芪降糖颗粒对糖耐量异常患者血糖、血脂的影响

目的观察参芪降糖颗粒对糖耐量异常(IGT)患者的血糖、总胆固醇、三酰甘油等指标的影响。方法将58例IGT患者随机分为观察组和对照组各29例,对照组采用单纯生活方式干预治疗,治疗组在对照干预治疗的基础上口服参芪降糖颗粒。观察两组血糖、总胆固醇、三酰甘油等指标的变化。结果观察组服用参芪降糖颗粒6个月以后,血糖、总胆固醇、三酰甘油等明显低于对照组。结论参芪降糖颗粒对IGT患者有治疗作用。     

以优质医院建设为契机 推进床旁血糖检测的规范化管理

笔者分析了影响床旁血糖检测结果的因素主要是血糖仪和操作人员专业性不够,结合优质医院创建的要求,提出了床旁血糖检测规范化管理需要多部门参与,各司其职,包括规范仪器管理,制定制度规范,强化人员培训,加强日常监管,提高信息支持,从而提高医疗质量。     

ACETALDEHYDE INVOLVEMENT IN ETHANOL-INDUCED POTENTIATION OF RAT HEPATOCYTE DAMAGE DUE TO THE CARCINOGEN 1,2-DIBROMOETHANE

Previous experiments with hepatocytes isolated from ethanol-treatedrats showed that alcohol potentiates the toxic action of 1,2-dibromoethane(DBE) by inhibiting its metabolism via glutathione-S-transferase.The aim of this study was to investigate whether acetaldehyde,the main product of ethanol metabolism, may be responsible forsuch inactivation By pretreatment with 4-methylpyrazole, aninhibitor of acetaldehyde formation, the ethanol inactivationof glutathione transferase was actually prevented. As a consequenceof this protective action, 4-methylpyrazole also prevented thehigh basal lipid peroxidation and the potentiated DBE toxicityobserved in hepatocytes from ethanol-dosed animals. Finally,the inactivation of glutathione-S-transferase by concentrationsof acetaldehyde likely to occur in the ethanol-intoxicated animalwas confirmed in an in vitro model by direct aldehyde additionto hepatocyte suspensions.