Browsing by Author "Llobera, M."

Ethanol is transformed in the mother by the catalytic action of alcohol and acetaldehyde-dehydrogenases, and the products of these reactions (NADH and acetaldehyde) are responsable of most of the negative effects of ethanol. Ethanol crosses the placenta freely, reaching in the feta! circuk.tion the same levels as in the mother. The placenta has the capacity to oxidyze acetaldehyde, thus maternal acetaldehyde does not reach the fetus. Besides this, the fetus does not have etha11ol metabolyzing enzymes. By using the rat as experimental model, we have found that metabolites known to cross the placenta such as glucose and ketone bodies vary in the fetus in a parallel manner as in the mother after alcohol intake. However, compounds known not to cross the placenta such as triglycerides do not change in the fetus whereas they increase in both plasma and liver of the mother after alcohol intake. After birth, retarded development of newborns from mothers receiving alcohol throughout gestation is progressivelly recuperated, but this recuperation depends on the parameter studied and the nutritional and environmental condition. The animal model herein used is valid for studies on the feta! alcohol syndrome, and although extrapolation to humans must be done with caution. present results indicate that most negative effects of maternal alcohol ingestion on the fetus are secondarv to ethanol action on maternal metabolism. and the\' mav be ameliorated by an adequate postnatal nutritional condition.

After receiving an i.p. glucose load, 24 h fasted thyroidectomized rats showed a progressive increase in blood glucose and a slow decrease in blood ketone bodies. Both liver glycogen and plasma insulin levels showed no differences within 60 min of the glucose administration. It is suggested that the glucose intolerance in these animals is partly due to an insulin deficiency. Thyroidectomized rats treated daily with 25 11g of L-thyroxine/100 g body weight for 40 days responded to the glucose test with a supranormal and more persistent elevation o( blood glucose but with a faster and a greater fall in blood ketone bodies, as compared to controls. Sixty min after the glucose loading, liver glucogen levels were lower and plasma insulin were slightly higher than controls. It is suggested that a diminished extraction of glucose during transhepatic passage can be responsible for the impaired glucose tolerance observed in the hyperthyroid animals.

In the offspring of ethanol-treated rats during geHlation (25 %, ethanol in drinking water) decreased lilter size, increased postnatal mort.ality rate, reduced body weight and body size delayed car opening, eyelid opening and teeth cruptrnn, retnrded air r,ghting reflex acquisition, impaired brain growth, reduced cortical thickness and delayed maturation of layer Vth's pyramidal neurons: (a) reduced basilar dendritic arborization and (b) decreased number of i,;pincs in th,i apical dendrite, were observed wlwn compared with agc-matclwd conlr ils fed with a standard di<'t. Minimal effects were found in the offRpring of fihrc-tn•ated rats during gestation (standard dic1 mixed with cellulo:w) in which the body weight wm; similar to that of controls, although both the calorific intake from fnod and the mother's weig-ht gain during ptc~nancy were similar to those of the et.hanol-treat(•d group. All theHe a mormal parameters hecamc norm,il :it the end of the lirst month of pod. rntal life, indicating recovery of these developmenta I ,!Pfccts produced by prenatal ethanol consumption.

I. After a pulse of [3- 14C]pyruvate, 24 hr starved rats were infused through the portal vein with two different doses of glucose (7.8 or 20.8 mg/min) or the medium, and blood was collected from the inferior cava vein at the level of the suprahepatic veins. 2. The highest dose of glucose enhanced the appearance of [14C]glucose in blood from the 2nd to the 20th min after tracer delivery. It also enhanced production of [14C]glycogen and concentration of glycogen in the liver after 5 and 20 min. At 20 min of glucose infusion the appearance of [14C]glyceride glycerol in liver as well as liver lactate concentration and lactate/pyruvate ratio were increased. 3. The low dose of glucose used enhanced liver values of [14C]glycogen, [14C]glycogen specific activity and glycogen concentration. 4. Our results support the hypothesis that in the starved rat glucose is converted into C3 units prior to being deposited as liver glycogen and based on the liver zonation model (Jungermann et al., 1983) it is proposed that glucose stimulated gluconeogenesis by shifting the liver to the cytosolic redox state as a secondary consequence of increased glycolytic activity.

Some aspects of small intestine maturation have been studied in the newborns from chronic ethanol-treated pregnant rats (25 % ethanol in drinking fluid) immediately after birth (before suckling) and after 30 days of life. Litters delivered by mothers fed ad libitum with a standard diet diluted 50% with cellulose were used as a nutritional control. At birth, pups from ethanol-treated mothers showed significant decreases in total intestinal length and thickness, low total lactase activity and low somatostatin intestinal content. The intestinal alterations of these neonatal parameters are not present in newborns from mothers on fiberdiluted diet. From delivery, pups from different experimental groups were nursed by normal lactating dams. At 30 days of age neither of those parameters differed among the groups. We propose that the low levels of total lactase activity in newborns from alcoholic mothers, that are a consequence of a lower intestinal mucosa content, are a direct effect of ethanol in utero on the fetal gastrointestinal system.

To determine to what extent lipoprotein lipase activity in the liver of the newborn rat depends on milk ingestion, its changes were studied during different nutritional conditions. Newborns were placed with nurse rats with or without ligated nipples and they were killed at 0, 8 or 24 h of life. Lipoprotein lipase in newborns liver was characterized by its inhibition in the presence of 1.0 M NaCl, its specific elution at 1.5 M NaCl on heparin-Sepharose 4B column and its requirement for serum in the assay mixture to manifest its activity. In fed animals lipoprotein lipase activity and triacylglycerol content in liver as well as circulating triacylglycerols and ketone bodies increased progressively after birth. When newborns were kept starved the change in enzyme activity was significantly enhanced, whereas the increase found after birth in the other parameters disappeared. Starvation produced reduction in circulating RIA-insulin levels in the newborn rats. Results show that liver lipoprotein lipase activity in the newborn rat is controlled by a mechanism which resembles that of the enzyme in the adult heart and indicate that its presence facilitates the uptake by the liver of fatty acids from circulating triacylglycerols for their oxydation rather than deposit.