Ethanol- and acetaldehyde-metabolizing system of rat liver during development of tolerance to ethanol

Institute of Biochemistry, Academy of Sciences of the Belorussian SSR, Grodno. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 2, pp. 161–162, February, 1990.     

Alcohol hangover and Liv.52

Summary Ethanol and acetaldehyde levels in blood and urine have been evaluated in 9 volunteers following administration of Liv.52 and placebo on the evening of the study and on the following morning. On the following morning the volunteers scored their symptoms and completed visual analogue scales. Single dose and multiple dose studies were done.Liv.52 produced a considerable reduction in blood and urine levels of ethanol and acetaldehyde after 12 h. It is possible that Liv.52 prevents the binding of acetaldehyde, bringing about higher initial blood levels followed by rapid elimination. It reduced the hangover symptoms.     

Aldehyde dehydrogenase 2 polymorphism as a protective factor for intracranial vascular stenosis in ischemic stroke in Han Chinese

Aim: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that metabolizes acetaldehyde to acetic acid. ALDH2 gene polymorphism modifies its activity and the mutation of ALDH2 gene has been reported to be associated with the protection against ischemic stroke. However, the potential association of allelic variation of ALDH2 with intracranial vascular stenosis and the clinical characteristics of ischemic stroke without coronary artery disease remains unclear. Methods: In this study, ischemic stroke patients were recruited, National Institutes of Health Stroke Scale scores were analyzed, intracranial arterial stenosis were evaluated by magnetic resonance angiography and gene typing of ALDH2 was determined by polymerase chain reaction and sequencing. Results: We found that the rate of heavy drinking was significantly lower in the ALDH2 mutation group (^*1/^*2 and ^*2/^*2) than in wild-type group (^*1/^*1) (18.6% vs. 38.0%, p = 0.01). Plasma homocysteine (Hcy) levels were significantly different in the two groups (15.45 ± 6.39 vs. 13.14 ± 4.45, p = 0.015). The ALDH2 mutation genotype was negatively correlated with severe intracranial vascular stenosis (OR, 0.34; p = 0.002), even after adjustment for high-density lipoprotein cholesterol, Hcy, and heavy drinking (adjusted OR, 0.44; p = 0.03). Conclusion: ALDH2^*2 could be a protective factor and negative predictor for severe intracranial vascular stenosis in ischemic stroke in Han Chinese.     

HPLC法同时测定乳安凝胶膏剂中4种化学成分的含量

目的 建立乳安凝胶膏剂中淫羊藿苷、延胡索乙素等4种化学成分的HPLC测定方法.方法 Hedera C18柱;以乙腈(A)-0.1％磷酸水溶液(B)为流动相进行梯度洗脱,流速:1mL·min-1,柱温:30℃,检测波长:280nm.结果 4种成分均能达到基线分离,各成分在其线性范围内呈良好的线性关系,加样回收率在95％～105％.结论 上述方法可用于乳安凝胶膏剂的含量测定.     

醇醛脱氢酶基因多态及饮酒习惯与胃癌易感性

[目的]探讨乙醇脱氢酶2（ADH2）和乙醛脱氢酶2（ALDH2）基因多态及饮酒习惯与胃癌易感性的关系。[方法]选取江苏省泰兴市和常熟市382例男性胃癌新发病例作为病例组,同时按同居住地、同性别及年龄±2岁1：1个体匹配抽取对照。收集所有研究对象的饮酒习惯等因素。采用聚合酶链反应（PCR）和变性高效液相色谱法（DHPLC）检测研究对象ADH2和ALDH2基因型。[结果]①病例组与对照组相比,ADH2和ALDH2各基因型分布频度差异均未达统计学意义。（9携带ALDH2G／A或A／A且酒精消耗总量≥2．5kg·年者,患胃癌的OR值分别是携带ALDH2G／G且酒精消耗总量〈2．5kg·年及≥2．5kg·年者的2．53（95％CI：0．86—7．49）和2．46（95％CI：0．90～6．72）倍,亦是携带ALDH2G／A或A／A且酒精消耗总量〈2．5kg·年者的2．72（95％CI：0．89～8-31）倍,但差异均未达到统计学意义（P〉0．05）。②与同时携带ADH2A／A和AI。DH2G／G者相比．同时携带ADH2G／A或G／G和ALDH2G／A或A,A者无论是否饮酒,患胃癌风险均无明显增加,即使当饮酒者的酒精消耗总量≥2．5kg·年亦如此（OR=3．13,95％CI：0．78,12．64）。[结论]本研究未发现ADH2和ALDH2基因多态及饮酒与胃癌易感性有关。     

Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remain incompletely defined and are likely multifactorial. One mechanism seems to be a diminished bioconversion of nitroglycerin, another seems to be the induction of vascular oxidative stress, and a third may include neurohumoral adaptations. Recent studies have revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role in the development of nitrate and crosstolerance. The present review focus first on the role of oxidative stress and second on the role of ALDH-2 in organic nitrate bioactivation leading to the development of tolerance and cross-tolerance (endothelial dysfunction) in response to nitroglycerin treatment. Recently, the role of mitochondrial oxidative stress in the development of nitrate tolerance was demonstrated in a mouse model with a heterozygous deletion of manganese superoxide dismutase (MnSOD^+/?), which is the mitochondrial isoform of this enzyme. Studies from our own laboratory have provided evidence for cross-talk between mitochondrial and cytosolic (Nox-dependent) sources of ROS. We close this review by focusing on the protective properties of the organic nitrate pentaerithrityl tetranitrate, which upregulates enzymes that have strong antioxidative activity, such as heme oxygenase-1 and ferritin, thereby preventing the development of tolerance and endothelial dysfunction.     

Synthesis and purification of mono-PEGylated insulin

Monomethoxypoly(ethylene glycol) 5000 (mPEG5K) and 2000 (mPEG2K) were activated to produce mPEG-aldehyde with content over 80%. Effects of reaction time, pH and initial molar ratio of mPEG-aldehyde to insulin on synthesis of PEGylated insulin were studied, taking mPEG5K-aldehyde as a model. On the optimized condition, approximately 90% of product was mono-PEGylated insulin. Mono-PEGylated insulin was purified by ion-exchange chromatography. The purity of each component was analysed by RP-HPLC and the results showed an efficient purification. Matrix assistant laser desorption ionization time-of-flight mass spectra demonstrated that the modification site of mono-PEGylated insulin was PheB1. The biological activity of all PEGylated insulin was also evaluated.