Alcohol and porphyrin metabolism

Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem synthesis both in humans and laboratory animals. Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase. Therefore, teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias.     

Alcohol exposure and undernutrition: effects on lipid metabolism and alcohol partitioning in rat brain regions in vitro

The effects of maternal alcohol consumption and undernutrition on lipid metabolism and alcohol partitioning in brain cortical and stem slices of pups were studied under in vitro conditions. Alcohol administration along with a normal diet during gestation and lactation resulted in an increase in the synthesis of cholesterol in cortical and stem slices associated with decreased entry of alcohol. Phospholipid metabolism was not affected in the cortex, whereas the incorporation of [32P] was found to be altered in the brain stem, indicating regional differences with respect to alcohol effects. Undernutrition induced by feeding the mothers a low protein diet, on the other hand, decreased the incorporation of labelled precursors into lipids in cortex and stem. The changes in lipid metabolism observed in the high protein alcohol pups were not evident in the brain regions of undernourished pups exposed to alcohol and the partitioning of alcohol was not altered.     

Alcohol intake and bone metabolism in elderly women

BACKGROUND: Published reports on the effect of alcohol consumption on bone mineral density (BMD) are inconsistent. OBJECTIVE: The objective of this study was to examine the relation between alcohol intake and BMD, calcitropic hormones, calcium absorption, and other biochemical indexes of bone and mineral metabolism in elderly women. DESIGN: The results presented are derived from baseline observations of 489 elderly women (aged 65-77 y) recruited for an osteoporosis study. The nondrinking group comprised 297 women and the drinking group comprised 148 women. Furthermore, the effect of different alcohol intakes (28.6 to 57.2 to 142.9 g/wk) was studied. RESULTS: Women who consumed alcohol had significantly higher spine (10%), total body (4.5%), and midradius (6%) BMD than did nondrinkers. An alcohol intake >28.6 g/wk was associated with higher BMD; maximum effect was seen with an intake of >28.6 to 相似文献   

Alcohol use in pregnancy, craniofacial features, and fetal growth.

STUDY OBJECTIVE--The aim was to study the relationship between the level of alcohol consumption in pregnancy and craniofacial characteristics of the neonate. DESIGN--This was a prospective survey of a sample of pregnant women, stratified on prepregnancy level of alcohol consumption. SETTING--The study was carried out at the public antenatal clinic of Roubaix maternity hospital. PARTICIPANTS--During an eight month period, 684 women (89% of those eligible) were interviewed in a standardised way at their first antenatal clinic visit. Of these, all who were suspected of being alcoholic or heavy drinkers (at least 21 drinks per week) were selected for follow up, as was a subsample of light (0-6 drinks per week) and moderate (7-20 drinks per week) drinkers. Of 347 women selected in this way, 202 had their infants assessed by a standardised morphological examination. MEASUREMENTS AND AND MAIN RESULTS--Suggestive craniofacial characteristics of the infants, present either in isolation or in association with growth retardation ("fetal alcohol effects"), were compared in relation to maternal alcohol consumption (alcoholic 12%; heavy drinking 24%; moderate drinking 28%; light drinking 36%). No differences were found between light and moderate drinkers. Infants born to alcoholics had a greater number of craniofacial characteristics and the proportion with features compatible with fetal alcohol effects was higher. There was a similar trend for infants of heavy drinkers. Infants of heavy drinkers who had decreased their alcohol consumption during pregnancy had fewer craniofacial features. Infants of heavy smokers were also found to have increased numbers of craniofacial characteristics. CONCLUSIONS--Craniofacial morphology could be a sensitive indicator of alcohol exposure in utero. Altered morphology is usually considered specific for alcohol exposure, but the relation observed with smoking needs further exploration.     

Influence of dietary potassium on lysine metabolism in the chick

High levels of dietary cations have been reported to spare the arginine requirement of chicks fed a diet containing excess lysine. The present studies were conducted to determine the nature of this effect, using potassium as the variable cation. The inclusion of 1.8% potassium in a high lysine diet improved growth but did not affect consistently the efficiency of feed utilization, nor did it have a significant effect on arginine metabolism as measured by renal arginase activity, urea excretion or arginine excretion. Lysine catabolism was markedly increased, however. Chicks fed the potassium supplemented diet converted approximately 23% of an oral loading dose of 14C lysine to respiratory 14CO2 over a 6-hour period, in contrast to approximately 9% of the dose in chicks fed the unsupplemented diet containing 0.4% potassium. The activity of hepatic lysine-alpha-ketoglutarate reductase, an initial enzyme in the catabolism of lysine, was increased in response to potassium or arginine supplementation. It is proposed that high levels of potassium or other cations may improve the growth of chicks fed diets containing excess lysine by increasing lysine catabolism. The effect on growth may be mediated primarily by increasing food intake and to a lesser extent by alleviation of the other metabolic manifestation of the lysine-arginine antagonism.     

胎儿脑组织中12种元素的含量和分布

分析了１１８例１６～３８周流产胎儿脑组织１２种无机元素（锌、铜、铁、钙、镁、铝、钠、钾、磷、锰、镉、铬）的含量和变化。结果表明：在脑中八个部位（颞叶、额叶、顶叶、枕叶、小脑、脑干、延髓、海马）中，锌、铁、钙在小脑中含量较高；钠、钾、磷在大脑皮层的含量较高；在脑发育期间，小脑中的锌含量，颞叶、顶叶中的铁含量及除脑干外的脑中七个部位铜的含量持续升高。并给出了正常胎体脑组织１２种元素的含量和分布。     

Alcohol inhibition of NMDA-stimulated catecholamine efflux in aging brain.

The influence of aging on the ability of ethanol to inhibit N-methyl-D-aspartate-stimulated catecholamine overflow in rat brain was examined. Alcohol effects on N-methyl-D-aspartate stimulated [3H]norepinephrine or [3H]dopamine overflow from the cortex, hippocampus, and striatum of aged (24-28 months) middle aged (12-14 months), and young (3-5 months) rats were examined. N-methyl-D-aspartate (500 microM) stimulated catecholamine overflow in all brain regions, with aged rats showing declines in overflow of 33% in the hippocampus and 41% in the striatum. Alcohol (30-200 mM) produced a concentration-dependent inhibition of overflow at all ages and brain regions tested. The IC50 for alcohol inhibition of NMDA-stimulated catecholamine release was not significantly different in aged brain or across brain regions. These results indicate that alcohol's ability to inhibit NMDA-stimulated catecholamine release is not significantly altered with aging.     

超声筛查在胎儿颅脑畸形的应用及研究

目的探讨分析超声筛查在胎儿颅脑畸形的应用价值,研究超声筛查的作用。方法选取该院2011年1月1日—2012年12月31日间进行超声筛查胎儿颅脑畸形的孕妇5430例,采用多切面序贯扫查法对胎儿颅脑进行筛查,对于超声诊断颅脑严重畸形的胎儿,进行中止妊娠。结果超声筛查检出19例胎儿颅脑畸形,经产后证实检出率为100%(6/6)。在进行超声筛查胎儿颅脑畸形的过程中,检出心脏畸形18例,唇腭裂12例,羊膜束带综合征1例,先天性膈疝3例,先天性肺囊腺瘤2例,四肢短小3例。结论超声筛查在胎儿颅脑畸形的应用价值巨大,对胎儿颅脑畸形的检出率高,同时可以检出胎儿自身患有的畸形,为临床提供有价值的信息。     

Enzyme markers of maternal malnutrition in fetal rat brain

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.     

胎儿生长受限对物质代谢影响的动物模型研究

胎儿生长受限(FGR)在人类中的发病率约为8％,其为导致围产期婴儿发病和新生儿死亡的重要原因之一,且与成年期多种疾病相关.多种动物模型已运用于FGR机制的研究.在FGR动物模型中观察到胃肠道结构和功能的改变,消化液分泌下降,肠道有效吸收率降低.这种变化与胃肠道细胞的基因表达改变有关;同时还可观察到多种代谢关键酶的活性改变.这些结构和功能的改变最终影响FGR动物的消化吸收和物质代谢,并与多种疾病相关.该文主要针对不同种动物FGR的模型研究进行了分析.     

Alcohol intake during prenatal life affects neuroimmune mediators and brain neurogenesis

Several lines of evidence suggest that alcohol exposure during prenatal gestation, or during early postnatal life may be a risk factor for the manifestation of neurological and for immune-related disorders in later life. The cellular, biochemical and molecular mechanisms of ethanol toxicity, however, have not been yet clearly established. Recent studies indicated that neurotrophin signaling pathways may be involved in ethanol mediated cell death. The present investigation addressed the question of whether nerve growth factor (NGF), which is the first and best characterized member of the neurotrophin family, and NGF-target cells are affected by prenatal exposure to alcohol. The result of our study indicates that NGF synthesis and the functional activity of NGF-target cells localized in the brain are markedly influenced by ethanol intake. The possible link between such changes and the hypothesis that these alterations may contribute to certain of the neuropathology observed following alcohol exposure would be discussed.