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Biomedical subjects

C Marco

Publications and source records attributed to C Marco.

At least 55 records · Page 3Linked to original sources

Influence of ethanol on liver and plasma lipid levels during chick embryo development.

Ethanol introduced into the air chamber of the egg during the last week of the chick embryonic period did not induce changes in liver or embryo weights. Alcohol dehydrogenase activity increased during the period studied in both ethanol and control groups, however, ethanol significantly inhibited the enzymatic activity. Alcohol administration did not alter plasma or liver cholesterol levels. On the other hand, three days after the beginning of the treatment, ethanol decreases plasma triglyceride levels increasing simultaneously the content of this lipid in the liver. If the ethanol treatment is continued for ten days the opposite occurs. An increase and decrease in liver and plasma triglycerides were observed respectively. These results suggest that ethanol interferes with processes which maintain plasmatic triglyceride levels.

Alcohol Dehydrogenase↗

Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin.

The usefulness of antibiotic prophylaxis in biliary surgery is well established. When antibiotic prophylaxis is not used, wound infection rates after biliary surgery range from 10% to 25%. With antibiotic prophylaxis, the rates can be reduced to less than 5%. Three questions are still controversial: Do all patients undergoing biliary surgery require antibiotic prophylaxis? What is the ideal antibiotic for use in biliary surgery? What should be the duration of antibiotic prophylaxis? In this study we prospectively evaluated the efficacy of a single dose of antibiotic prophylaxis in biliary surgery, administered to patients at high risk for infection, in a trial comparing cefonicid (a cephalosporin with a long half-life) with mezlocillin (a broad-spectrum ureidopenicillin).

Adult↗

Regulation of mevalonate 5-pyrophosphate decarboxylase in isolated cells from chick intestinal epithelium.

The present studies were undertaken to determine whether mevalonate 5-pyrophosphate decarboxylase (EC 4.1.1.33) is subject to physiological regulation in the intestinal mucosa. Activity was determined in epithelial cells isolated in a villus-to-crypt gradient from chicks fed on different diets in order to vary the sterol flux across the intestinal epithelium. When animals were fed on cholesterol, decarboxylase activity was decreased in all the cell fractions studied, although percentages of inhibition were maximum in crypts of jejunum and ileum. In contrast, decreased sterol flux as a consequence of cholestyramine feeding stimulated decarboxylase activity, especially in villi of the duodenum, where values increased 3-fold with respect to controls. On the other hand, the total cellular sterol content was significantly increased by the cholesterol diet. In duodenum and jejunum, 20-30% of the total cholesterol was in the esterified form under these conditions. However, dietary cholestyramine did not significantly affect amounts of total cellular cholesterol in any of the cell fractions. These results demonstrate that mevalonate 5-pyrophosphate decarboxylase activity changes considerably under different dietary situations and that the existence of secondary sites in the physiological regulation of sterol synthesis in the intestinal mucosa should be considered.

Animals↗

In vivo utilization of [3-14C]acetoacetate for lipid and amino acid synthesis in the 15-day-old chick.

1. The utilization of different concentrations of acetoacetate for the in vivo synthesis of lipids and amino acids has been studied in brain, spinal cord, liver, small intestine and kidney of 15-day-old chicks. Both lipid and amino acid synthesis increased in an almost linear fashion with precursor concentration in the five tissues mentioned. 2. Lipid synthesis was very high in spinal cord, followed in decreasing order by brain, small intestine, liver and kidney. At the highest concentration assayed (48 mM) the main lipids synthesized were triglycerides in liver (75%) and kidney (52%) and cholesterol in brain (47%), spinal cord (47%) and small intestine (42%). 3. Amino acid synthesis from acetoacetate did not vary markedly among the five organs, although brain and spinal cord showed higher rates at the maximal concentrations of precursor. Glutamate was always the main amino acid formed.

Acetoacetates↗

Influence of cholestyramine feeding on mevalonate-activating enzymes.

Phosphorylation and decarboxylation of mevalonic acid have been measured in different tissues of chicks fed a cholestyramine diet from hatching until 18 days of age. Hepatic and intestinal phosphorylation and decarboxylation of mevalonate were slightly although significantly increased from 15 days of treatment. Direct measurements of 5-pyrophosphomevalonate decarboxylase activity using the specific substrate of this enzyme corroborated these data. Brain enzymatic activities remained unaltered with respect to controls. These results suggest that enzymes responsible for the conversion of mevalonate to isopentenyl pyrophosphate from neonatal chick liver and intestine alter their activities in a coordinate fashion and may play an important role in the regulation of cholesterogenesis in these tissues.

Animals↗

Controlled trial of endoscopic sclerosis in bleeding peptic ulcers.

Of 113 patients in whom endoscopy revealed a bleeding gastric or duodenal ulcer 55 were randomly allocated to receive endoscopic sclerosis (ES) (injections of adrenaline/polidocanol) plus cimetidine while 58 received cimetidine alone as controls. 3 patients treated with ES (5.5%) compared with 25 controls (43.1%) had a major recurrent haemorrhage during their hospital stay. ES also led to significant reductions in the need for emergency surgery (3 vs 20 patients), transfusion requirements (mean 0.42 [SD 1.1] vs 2.7 (3.19) U), and the length of hospital stay (11.6 [5.1] vs 16.2 [11.3] days). ES as an adjunct to conventional medical treatment is an effective and safe emergency therapy for gastrointestinal bleeding due to peptic ulcer.

Adult↗

Quantitative role of different embryonic tissues in mevalonate metabolism by sterol and nonsterol pathways. Relationship with enzyme activities of cholesterogenesis.

3-Hydroxy-3-methylglutaryl-CoA reductase, mevalonate kinase, mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase activities have been determined in brain, liver, intestine and kidneys from 19-day-old chick embryo. Levels of brain reductase and decarboxylase were clearly higher than those found in the other tissues assayed. However, only small differences were observed in the activity of both kinases among the different tissues. Mevalonate metabolism by sterol and nonsterol pathways has been investigated in chick embryo at the same developmental stage. Mevalonate incorporation into total nonsaponifiable lipids was maximal in liver, followed by intestine, brain and kidneys. The shunt pathway of mevalonate not leading to sterols was negligible in both brain and liver, while a clear CO2 production was observed in intestine and kidneys. Sterols running in TLC as lanosterol and cholesterol were the major sterols formed from mevalonate by brain and kidney slices, while squalene and squalene oxide(s) were found to be mainly synthesized by liver slices. Minor differences in the percentage of different sterols were observed in chick embryo intestine. The importance of free and esterified cholesterol accumulation in the different tissues on the inhibition of cholesterogenic activity is discussed.

Animals↗

Acyl coenzyme A:cholesterol acyltransferase in neonatal chick brain.

An acyl coenzyme A:cholesterol acyltransferase activity which directly incorporates palmitoyl coenzyme A into cholesterol esters using endogenous cholesterol as substrate was demonstrated in microsomal preparations from neonatal chick brain. The enzyme showed, at pH 7.4, about 2-fold greater activity than that observed at pH 5.6. Nearly 10-times higher esterifying activity was found in brain microsomes using palmitoyl coenzyme A than that with palmitic acid. The acyltransferase activity was clearly different from the other cholesterol-esterifying enzymes previously found in brain, which incorporated free fatty acids into cholesterol esters and did not require ATP or coenzyme A as cofactors. Chick brain microsomes also incorporated palmitoyl coenzyme A into phospholipids and triacylglycerols. However, most of the radioactivity from this substrate was found in the fatty acid fraction, due to the presence of an acyl coenzyme A hydrolase activity in the enzyme preparations. Therefore, the formation of palmitate was tested during all the experiments. The brain acyltransferase assay conditions were optimized with respect to protein concentration, incubation time and palmitoyl coenzyme A concentration. Microsomal activity was independent of the presence of dithiothreitol in the incubation medium and microsomes can be stored at -40 degrees C for several weeks without losing activity. Addition of fatty acid-free bovine serum albumin to brain microsomal preparations produced a considerable increase in the acyltransferase activity, while acyl coenzyme A hydrolase was clearly inhibited. Results obtained show the existence in neonatal chick brain of an acyl coenzyme A:cholesterol acyltransferase activity similar to that found in a variety of tissues from different species but not previously reported in brain.

Animals↗

Effects of different nutritional conditions on chick liver mevalonate-activating enzymes.

The response of mevalonate kinase, mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase of chick liver to different dietary situations has been investigated. Fasting inhibited mevalonate kinase and mevalonate-5-pyrophosphate decarboxylase activities, while mevalonate-5-phosphate kinase remained practically unaltered. Refeeding after 72 h of starvation restored mevalonate kinase activity to normal levels after 120 h of refeeding. Likewise, decarboxylase activity reached normal levels at 72 h of refeeding the standard diet and slightly supranormal levels after 120 h. In addition, the sequential response of the three enzymes to a high cholesterol diet was followed throughout a 120 h period. Feeding a 5% cholesterol diet to 13-day-old chicks previously fed with a standard diet from hatching reduced considerably the activity of mevalonate-5-pyrophosphate decarboxylase, while the kinases were less affected. The present results support the idea of a coordinate regulation of the enzymes implied in cholesterol biosynthesis and suggest that mevalonate-5-pyrophosphate decarboxylase may play a significant role in this regulation.

Animals↗

Differential response of chick liver and brain membranes to short ethanol treatment.

The effect of 60 hr ethanol ingestion on lipid composition of liver and brain membranes from 2-day-old chicks was investigated. Analysis of hepatic membrane cholesterol shows that ethanol induced a slight increase in microsomes exclusively due to free cholesterol while mitochondria was not affected. In brain, both fractions showed a clear increase in their cholesterol content, while a high decrease was observed in myelin. Free cholesterol was also the main responsible for the changes found in brain. The ethanol-treated animals showed an alteration in their phospholipid composition exclusively in brain microsomes and myelin. Despite all these changes, the values of cholesterol/phospholipid molar ratio in both liver and brain membranes remained unaltered after short ethanol treatment. Our results indicate that neonatal chick brain membranes appears to be especially sensitive to the presence of ethanol.

Animals↗

Characterization of acyl-CoA:cholesterol acyltransferase from neonatal chick liver.

Endogenous cholesterol esterification in chick liver microsomes was catalyzed by acyl-CoA:cholesterol acyltransferase using palmitoyl-CoA as substrate. An acyl-CoA hydrolase activity was also found in our microsomal preparations. Acyltransferase activity was stable after microsomes storage at -40 degrees C for 6 weeks and increased linearly with the preincubation time between 0 and 45 min. In our assay conditions, cholesteryl ester formation was linear up to 0.3 mg of microsomal protein in the reaction vial and 10 min of incubation. Maximal activity was found in reactions carried out in the presence of 1-2 mM dithiothreitol and 1.2 mg of bovine serum albumin, while acyl-CoA hydrolase was clearly inhibited by increasing albumin amounts.

Animals↗

The fatty acid composition of mitochondria, microsomes and myelin from neonatal chick brain. Susceptibility to short and chronic treatment with ethanol.

Short-term and long-term effects of ethanol on the fatty acid composition of mitochondrial, microsomal and myelin fractions in brain have been investigated. Microsomal membranes were not modified by treatment for 60 hr, while in mitochondrial membranes there was a significant decrease in arachidonic and docosahexaenoic acids, responsible for the decrease in the double-bond index. A clear decrease in the 18:1/18:0 ratio was found in myelin after short-term treatment, whereas no significant variations were observed in the other subcellular membranes under the same conditions. On the other hand, chronic exposure to ethanol for 18 days induced a significant increase in oleic and docosahexaenoic acids in microsomal membranes. However, no significant changes were detected in the composition of fatty acids of mitochondrial membranes after 18 days of administration of ethanol. Contrary to that found with short-term treatment, a significant increase was observed in the 18:1/18:0 ratio of the myelin fraction after chronic consumption of ethanol. These results suggest that alcohol intoxication of neonatal chicks induces different modifications in composition of fatty acids of different membranes in the brain, those observed in the myelin fraction being specially important.

Animals↗

Embryonic development of mevalonate metabolism by sterol and nonsterol pathways in chick brain and liver.

The embryonic development of the sterol and nonsterol mevalonate metabolism has been investigated in chick brain and liver. The shunt pathway of mevalonate was negligible in both tissues throughout 10-21 days of embryo development. Mevalonate incorporation into nonsaponifiable lipids was higher in liver than in brain. A pronounced peak was found in liver at 12 days of incubation, while only small differences were observed in brain. Lanosterol and cholesterol were the major sterols synthesized in brain, followed by desmosterol and squalene. Their relative percentages did not change significantly during 10-16 days and slightly decreased thereafter. In liver, cholesterol and squalene were the major sterols observed during the first days of incubation with a developmental pattern similar to that found in the mevalonate incorporation into nonsaponifiable lipids, while relative percentage of squalene oxides sharply increased between 12 and 16 days of embryonic development. The importance of cholesterol esters accumulation in the inhibition of cholesterogenic activity is discussed.

Animals↗

Alterations induced by chronic ethanol treatment on lipid composition of microsomes, mitochondria and myelin from neonatal chick liver and brain.

The effect of 18 days ethanol consumption on the lipid composition of microsomes, mitochondria and myelin have been studied in neonatal chick liver and brain. Neither cholesterol nor phospholipid content was modified in both liver microsomes and mitochondria. However, cholesterol content of brain microsomes, mitochondria and myelin was clearly increased, mainly due to an enhancement of free cholesterol. Likewise, ethanol consumption induced a clear increase of phospholipid content in brain mitochondria and myelin. As a consecuence of these changes, the cholesterol/phospholipid molar ratio strongly increased only in the myelin fraction. The myelin phospholipid composition markedly varied by ethanol treatment. Our results indicate that the maximal modifications were induced by ethanol in membranes with a high cholesterol content, suggesting that differences in the chemical composition of membranes could be responsible for differences in the response to the ethanol consumption.

Animals↗

Role of mevalonate-5-pyrophosphate decarboxylase in the regulation of chick intestinal cholesterogenesis.

The response to different dietary conditions of the enzymes responsible for the transformation of mevalonic acid to isopentenyl pyrophosphate has been studied for the first time in the small bowel of the chick to elucidate the role of these enzymes in the regulation of intestinal cholesterogenesis. Feeding a 2% cholesterol diet from hatching resulted in a small but significant inhibition of mevalonate-5-pyrophosphate decarboxylase, while mevalonate kinase and mevalonate-5-phosphate kinase remained unaltered. Similar results were obtained for the three enzymes when 13-day-old chicks fed a standard fat-free diet were switched to a 5% cholesterol diet. Starved chicks exhibited lower intestinal decarboxylase activity than chicks fed a standard diet, while refeeding resulted in levels of activity similar or slightly greater than controls. None of the enzymes effecting the conversion of mevalonate to isopentenyl pyrophosphate in the small intestine presented diurnal variations. Results obtained suggest that mevalonate-5-pyrophosphate decarboxylase may play a significant role in the regulation of cholesterol synthesis in the small intestine.

Animals↗