Standard treatment of alpha-tocopherol in Alagille patients with severe cholestasis is insufficient

Alpha-tocopherol (alpha-T) is the most effective lipid-soluble antioxidant present in cells. We investigated the efficacy of alpha-T supplements for preventing lipid peroxidation in patients with Alagille syndrome, according to the severity of cholestasis. Patients were assigned to two groups on the basis of plasma bilirubin concentration (group I, bilirubin <100 microM; group II, bilirubin >100 microM). alpha-T concentrations were determined in plasma, in isolated lipoproteins, and in red blood cell membranes. In both groups of patients, alpha-T concentrations in plasma were similar to those in control subjects, but the distribution of alpha-T in lipoproteins was affected by the abnormal lipoprotein pattern in these patients. The efficacy of alpha-T was estimated by determining the amount of hydroperoxide produced from phosphatidylcholine and phosphatidylethanolamine (PE) molecular species owing to oxidative stress induced by lipoxygenase treatment. The concentrations of phosphatidylcholine molecular species and its corresponding hydroperoxides were significantly higher in both groups of patients. In group I, alpha-T and PE molecular species concentrations were similar to those in control subjects, but PE hydroperoxide concentrations were higher than those in the control subjects. In group II, alpha-T concentration was significantly lower and the concentrations of some PE molecular species and all PE hydroperoxides were lower than those in the control subjects. In conclusion, erythrocyte membrane alpha-T concentration was significantly lower only in patients with severe jaundice, despite alpha-T supplementation, raising the question as to whether the usual treatment was appropriate in this group.     

The epidemiology of female genital tract cancers

Endometrial, ovarian and cervical cancer are among the leading causes of death in women. The role of unopposed estrogens in endometrial carcinogenesis is well established. Any factor that increases the exposure of the endometrium to unopposed estrogen, such as menopausal replacement treatment, obesity, or irregular menstrual cycles tends to raise the risk of the disease, while factors that lower exposure to estrogens or increase progesterone levels, such as oral contraceptives (OC) or smoking, decrease the risk. These well-established risk factors can have different effects at different ages, particularly in pre- and postmenopausal women: more generally, the interaction between various factors is still not totally defined. With reference to ovarian cancer, OC and parity, late menopause and lifelong regular menstrual periods increase the risk of the disease. In terms of biologic mechanisms, these factors are thought to act on ovarian cancer risk by affecting lifetime number of ovulations. Along this line, 'incessant ovulation' could be the relevant exposure that defines the incidence of the neoplasm. Among the factors other than reproductive or hormonal, diet is likely to be the most relevant, but it is still. however, poorly quantified. There is now consistent evidence that Human Papillomavirus (HPV) has a causal role in the ethiology of cervical cancer and that sexual habits and reproductive/hormonal factors are associated with the risk of invasive cervical cancer. Less clear is the role of smoking and dietary habits, but recent studies have shown a direct relationship between smoking and the risk of invasive cervical cancer and an inverse one between selected vitamin intake and risk of the disease. In this paper we review and discuss these evidences.     

Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype

Levels of aromatic DNA adducts in foundry workers and controls were followed at four annual samplings. During this time exposure to polycyclic aromatic hydrocarbons (PAH) decreased and the level of DNA adducts decreased accordingly. In the total group exposure was related to the level of adducts. Adduct levels correlated with urinary 1- hydroxypyrene (LOGU1OH), air benzo[a]pyrene, weekly working hours and daily cigarette consumption. In a multivariate model 1-hydroxypyrene had a consistent effect. Neither glutathione transferase M1 (GSTM1) nor cytochrome P450 1A1 (CYP1A1) genotypes had clear effects. Yet the individuals lacking GSTM1 had a stronger effect of LOGU1OH and some effect by other sources of PAH, such as charcoal broiled food, although all these variables were not significant in the multivariate model. The rare individuals with a CYP1A1 polymorphism MspI containing an amino acid change at isoleucine had an increased level of adducts. The results showed that the postlabelling method used was able to detect an increase in aromatic DNA adducts in leukocytes when exposure to benzo[a]pyrene in air was approximately 5 ng/m3. At such low levels smoking and charcoal broiled food may be important contributors to adducts.      

妊娠肝内胆汁淤积症患者脂质过氧化作用的变化与雌激素水平及受体的关系

目的　探讨妊娠肝内胆汁淤积症 (intrahepatic cholestasis of pregnancy,ICP)患者血清丙二醛 (MDA)和超氧化物岐化酶 (SOD)含量的变化与游离雌三醇 (E3 )和胎盘雌激素受体 (ER)水平之间的关系。　方法　取 ICP患者 33例为研究组 ,另选同期入院的正常产妇 30例作为对照组 ,两组均在分娩前 30 min内取肘静脉血 3ml,测定 MDA、SOD、E3 及 β- h CG。随机选择 ICP组和正常对照组2 0例测定胎盘组织中 ER和 HCG水平。　结果　 ICP组中 MDA为 (6 .4± 2 .1) m ol/L、E3 为 (19± 9)ng/m l高于对照组 (5 .2± 1.4) m ol/L,14± 6 ) ng/ml(P<0 .0 1)。 SOD、β- h CG与对照组相比无显著差异 (P>0 .0 5 )。ICP组中胎盘组织 ER的阳性表达百分比 70 %高于对照组 2 5 % (P<0 .0 5 ) ,而 HCG的阳性百分比在两组间无显著差异 (P>0 .0 5 )。 ICP组 E3 与胎盘 ER水平之间有正相关关系 r=0 .6 3。而 β- h CG与胎盘 HCG水平则无显著相关 (P>0 .0 5 )。　结论　妊娠期 ICP患者体内氧化和抗氧化失衡及雌激素水平升高与胎盘 ER表达增强 ,对 ICP的发生可能起重要的作用