摘要:

Maternal blood alcohol levels, weight gain during pregnancy, parturition time, perinatal mortality, and postnatal growth of offspring were compared in groups of pregnant rats fed one of three ethanol‐containing liquid diets (Kahn's formula = BSA diet, Revised Wiener's = RA6 diet, and Lieber‐DeCarli's high protein 82C diet = LDA diet). The three ethanol diets all contained the same amount of ethanol‐derived energy (36% of total energy), but differed in the amount of energy contributed by protein (17, 30, and 25%), fat (36, 24, and 13%), and carbohydrate (12,10, and 27%), respectively. The experimental design also included dams that were pair‐fed isocaloric ethanol‐free versions of the three ethanol diets (designated BSP, RP6, and LDA, respectively) and a group of dams fed a pelleted casein‐based solid diet (PC diet). All experimental diets were fed ad libitum from gestational day 7 to delivery. The effect of ethanol exposure in utero was most severe in mothers and offspring fed the BSA diet. The feed efficiency ratio (maternal weight gain/total dietary energy consumed) of this low‐protein ethanol diet was less than that of RA6 or LDA diets. The feed efficiency ratio calculated for RA6 and LDA diets was not different from that of PC diet. Compared with rats fed RA6 and LDA diets, the rats that were fed BSA diet exhibited deficient maternal weight gain, greater parturition delay, impaired fetal growth, and increased perinatal mortality among the offspring. BSA dams had the highest blood ethanol levels of all groups fed ethanol diets, and exhibited the least difference in blood ethanol concentrations between the day (2 PM) and night (9 PM) periods of the diurnal cycle. These differences in the peak and the day/night pattern occurred despite the observation that all dams ingested equivalent doses of ethanol (∼11 g/kg/day) over the period of the study. It is therefore postulated that the nutritional status of the pregnant animal plays a role in the absorption and/or metabolism of ethanol and thus modulates the exposure of the developing fetus to high blood

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00530.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The hydrolysis of membrane phosphoinositides is widely recognized as an important signal transduction pathway in brain. One of the products of phosphoinositide hydrolysis, Ins (1,4,5)P3, is thought to participate in signal transduction by mobilizing intracellular calcium and it is now clear that Ins(1,4,5)P3metabolism is a complicated process that may be highly regulated. In addition to being dephos‐phorylated by the action of a 5‐phosphatase, Ins(1,4,5)P3can be phosphorylated by a 3‐kinase to Ins(1,3,4,5)P4. Although the physiological significance of the higher inositol polyphosphates is not clear, recent evidence suggests that Ins(1,3,4,5)P4may also have important second messenger function. Since ethanol is known to have potent effects on synaptic transmission, we investigated the in vitro effects of ethanol on [3H]Ins(1,3,4,5)P4metabolism by rat whole brain homogenates. Ins(1,3,4,5)P4was rapidly hydrolyzed to Ins(1,3,4)P3, inositol bisphosphates [Ins(3,4)P2and Ins(1,3)P2], inositol monophosphates [Ins(l)P/Ins(B)P and Ins(4)P], and to inositol by sequential dephosphorylation. No [3H]Ins(1,4,5)P3was detected. Ethanol (500 mM), significantly accelerated the dephosphorylation of Ins(1,4,5)P3, resulting in a more rapid formation of inositol bisphosphates, monophosphates and inositol. However, intoxicating and sedative‐hypnotic concentrations of ethanol (30‐100 mM) had no effect upon Ins(1,3,4)P3dephosphorylation, suggesting that pharmacologically relevant concentrations of ethanol do not directly effect the enzymes involved in the dephosphorylation of Ins(1,3,4,5)P4to free inositol

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00531.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

In order to clarify the relationships between acetaldehyde (Ac‐CHO) metabolism and low Km(mitochondrial) aldehyde dehydrogenase (ALDHP) genotypes, hepatic ALDHS activity was determined and serial changes of blood Ac‐CHO levels after ethanol administration were analyzed in the individuals homorygous for the normal ALDH2 genes, heterozygous for the normal and mutant ALDH2 genes, and homozygous for the mutant ALDH2 genes. Genomic DNA was extracted from white blood cells and genotyping of ALDH2 was performed using the polymerase chain reaction technique and slot blot hybridization with synthesized oligonucleotide probes specific to the normal and mutant ALDH2 genes.ALDH2 activity was not detectable in the liver in two cases of the mutant homozygote. In four out of eight cases of the heterozygote, hepatic ALDH2 activity was measurable, although the activity was lower compared with that in the normal homozygote. Blood ethanol levels after alcohol administration were not different among the three different ALDH2 genotypes. Blood Ac‐CHO levels after drinking of alcohol were significantly higher in the heterorygotes and the mutant homozygotes than in the normal homozygotes. The levels after a moderate amount of ethanol (0.8 g/kg of body weight) in a case of the mutant homozygote were not different from those of the heterozygotes. However, the levels after a small amount of ethanol (0.1 g/ kg of body weight) were significantly higher in the mutant homorygotes than in the heterozygotes.These results indicate that hepatic ALDH2 activity is lacking completely, and metabolism of Ac‐CHO in the liver is severely impaired in the homozygotes of the mutant ALDH2 genes. On the other hand, the lack of hepatic ALDH2 activity is partial, and impairment of hepatic Ac‐CHO metabolism is mild, in the heterozygotes of the ALDH2 genes. Clear differences of blood Ac‐CHO levels after a small amount of ethanol suggest that blood Ac‐CHO levels after a small amount of ethanol are good markers for the evaluation of AL

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00532.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

A rat renin allele (the S‐allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele—the salt‐sensitive hypertensive rats—have low renin activity compared with the salt‐resistant hypertensive rat that does not have this S‐allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol‐preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S‐allele. After an initial acclimation period, these two groups were first given daily 1‐hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34‐day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S‐allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the e

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00533.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00534.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY