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Biomedical subjects

L Gil

Publications and source records attributed to L Gil.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Financing research in Chile in biotechnology and other areas related to the productive sector].

This study describes the financial support for research in Chile in different areas related to the productive sector including biotechnology. Four different sources which help research in the country through competitive research grants were analysed. These include: FONDECYT (National Fund for Research and Technology), Fondo de Desarrollo Productivo de CORFO (Fund for Productive Development), Fondo de Investigaciones Agropecuarias (Fund for Research in Agriculture and Livestock) and the IV Program for Technical Cooperation between the Chilean Government and UNDP. Biotechnology appears as one of the areas related to the productive sector having an important number of projects approved with a substantial financial support. Based in a survey, recommendations are made to improve the relationship between the productive and academic sector in biotechnology and other areas.

Biotechnology↗
PubMed1989

Nutritionally triggered alterations in the regiospecificity of arachidonic acid oxygenation by rat liver microsomal cytochrome P450.

Cytochrome P450-dependent oxidation of arachidonic acid was studied in liver microsomes from normal fed, protein-energy malnourished, and refed rats. The overall rate of arachidonic acid oxidation was very similar in microsomes from the three groups, but microsomes from malnourished rats showed a higher turnover rate than microsomes from normal fed and refed rats. The regiospecificity of cytochrome P450 oxidation of arachidonic acid was drastically altered by the animal nutritional status. Thus, protein-energy malnutrition results in a clear stimulation of total omega and omega-1 hydroxylation, concomitant with a marked decrease in olefin epoxidation and allyllic oxidations. These changes, as well as the documented biological activity of some of the cytochrome P450 arachidonate metabolites, suggest that protein-energy deficiency might help to select P450 isozymes which are probably involved in key monooxygenation reactions of physiological substrates.

Animals↗
PubMed1989

[Spontaneous bacterial peritonitis: clinical, microbiological and clinical course study of 89 episodes].

We have retrospectively studied 89 episodes of spontaneous bacterial peritonitis (SBP) attended at our service with the purpose of analyzing clinical features, microbiologic data and possible etiopathogenic factors, treatment and course. The most frequent symptoms were ascites, abdominal pain and fever. Only 3.3% of episodes were asymptomatic. Twenty-four episodes (26.96%) resulted in death of the patient and only the presence of septic shock and prothrombin time lower than 35% statistically correlated with a higher mortality (100% and 53.8%, respectively, p less than 0.01) of the possible factors analyzed. The culture of ascitic fluid (AF) was positive in 52.8% of the episodes and there were no clinical or time course differences between these cases and those who presented negative culture. The isolated microorganisms were the usual ones in this condition, outstanding 37.5% of gram-positive cocci in monomicrobial SBP. Treatment was initiated within the first 12 hours from admittance in 76.4% of cases, between 12 and 72 hours in 12.3% and after 72 hours in 11.2%. Cefotaxime was given to 47.1% of episodes and 52.9% of patients received ampicillin or cefoxitin plus aminoglycoside; the mortality was lower with the first schedule (11.9% versus 40.4%, p less than 0.01).

Adult↗
PubMed1988

Purification and characterization of liver cytochrome P-446 isolated from protein energy malnourished rats.

A liver cytochrome P-450 isozyme has been purified to homogeneity from protein-energy malnourished rats induced with beta-naphthoflavone (beta-NF). The purification steps included chromatography on DEAE-Sephadex-A-25, DEAE-cellulose (DE-53), hydroxylapatite (HA) and carboxymethyl-sephadex (CM) columns. The reduced carbon monoxide difference and absolute spectra showed a Soret peak at 446.5 nm. The wavelength maxima for the oxidized and reduced spectra were at 416 and 408 nm, respectively. Cytochrome P-446 appears to have a predominantly low spin ferric iron, migrates as a single band of molecular weight 56,000 in sodium dodecyl sulfate polyacrylamide gels and has a specific content of 14 nmol/mg of protein. P-446 oxidized various substrates at different rates in a reconstituted system with NADPH-cytochrome P-450 reductase and dilauroyl-phosphatidylcholine. In this system turnover rates for benzo[alpha]pyrene, testosterone and benzphetamine oxidation were: 81.10; 1.85 and 1.42 nmoles product/min/nmol P-446 respectively. While NH2 terminal amino acid sequence analysis of 18 of the first 20 residues suggests that the cytochrome P-446 isolated from malnourished rats is identical with form c, the catalytic activities suggest that this isozyme may be a more effective or efficient catalyst for some substrates.

Animals↗
PubMed1988

Inhibitors of cytochrome P-450-dependent arachidonic acid metabolism.

A new generation of heteroatom analogs of arachidonic acid are documented as powerful and selective inhibitors of the cytochrome P-450-dependent arachidonic acid oxygenase reaction (IC50, 5-10 microM) with little effect on either cyclooxygenase or soybean lipoxidase at 100 microM. The imidazole derivatives, ketoconazole and clotrimazole, are potent and selective inhibitors of the arachidonic acid epoxygenase and lipoxidase-like activities of phenobarbital-induced rat liver microsomal fractions (IC50, 2.0 and 0.3 microM, respectively). In contrast, the w/w-1 oxygenase activity of ciprofibrate-induced microsomal fractions was relatively resistant to inhibition by these compounds (IC50, 50 and 25 microM for ketoconazole and clotrimazole, respectively). Nordihydroguaiaretic acid (NDGA), eicosatetraynoic acid (ETYA), and indomethacin, extensively utilized inhibitors of the cyclooxygenase and lipoxygenase branches of the arachidonate cascade, also inhibit cytochrome P-450-dependent arachidonic acid metabolism. In decreasing order of potency, they were NDGA, ETYA, and indomethacin (IC50, 15, 40, and 70 microM, respectively).

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1988

Nutrition-related alterations in liver microsomal testosterone hydroxylases.

The oxidation products of testosterone formed by liver microsomes from normal-fed and protein-energy malnourished male rats have been analysed by HPLC. Microsomes from normal-fed rats oxidized testosterone at a rate of 4.52 nmol/min/mg protein. The major products formed were: 6 beta-, 7 alpha- and 16-alpha-hydroxytestosterone; these three metabolites represented 65% of the total testosterone metabolism. Microsomes from protein-energy malnourished rats oxidized testosterone at a reduced rate of 2.03 nmol/min/mg protein. The major product formed was 7 alpha-hydroxytestosterone, which accounted for 43% of total testosterone oxidation. Microsomes from protein-energy malnourished rats showed a CO-reduced cytochrome P-450 spectra with a maxima at 452 nm, and a 38% decrease in the total content of cytochrome P-450. Some testosterone hydroxylases were drastically affected by protein-energy malnutrition but others, such as 7 alpha-hydroxylase, remained unchanged. The present results suggest that nutritional status can modify the relative amounts of individual cytochrome P-450 isozymes, thus explaining the observed changes in several testosterone hydroxylases. Protein-energy malnutrition seems to be an excellent tool with which to obtain a microsomal fraction containing predominantly P-450 isozymes, which are probably involved in key mono-oxygenations of physiological substrates.

Animal Nutritional Physiological Phenomena↗
PubMed1988

Breast milk anti-Escherichia coli heat-labile toxin IgA antibodies protect against toxin-induced infantile diarrhea.

A prospective study to assess whether milk IgA antibodies against Escherichia coli heat labile-toxin protect breast-fed children against labile toxin-induced gastroenteritis was carried out among infants of a marginal urban area in Guatemala. One hundred and thirty children were kept under surveillance for diarrhea by periodic home visits. Stool specimens were collected from each child routinely every 2-3 weeks and during diarrheal episodes, to study the excretion of labile toxin-producing Escherichia coli. Milk samples from the children's mothers were obtained concomitantly with the fecal specimens of the infants to be analyzed for anti-labile toxin antibodies. Twenty infections by heat-labile toxin-producing Escherichia coli as a sole agent were documented among breast-fed infants. Nine of these infections resulted in gastroenteritis, while the remaining 11 were asymptomatic. At the time of infection children who became sick were ingesting breast milk with significantly (p = 0.028) lower titers of antilabile toxin IgA than those who remained healthy. Only one of the 8 infected children receiving breast milk with high titers (greater than or equal to 256) of anti labile toxin IgA developed diarrhea, compared to 8 of the 12 subjects being fed milk with low titers (less than or equal to 64) (p = 0.025). This is the first report documenting protection by IgA antibodies in milk against labile toxin-induced gastroenteritis in infected breast-fed infants.

Bacterial Toxins↗
PubMed1988

Effects of antisecretory drugs on mucosal erosions induced by intragastric distension in rats: a comparative study.

The antiulcer effects of two classical antisecretory agents, cimetidine and pirenzepine, were compared with those of prostaglandin E2 and carbenoxolone sodium. The acid inhibitory action of drugs was not important in our study since the ulcer model employed consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/l). Cimetidine and pirenzepine failed to inhibit gastric erosions, whereas prostaglandin E2 and carbenoxolone greatly reduced the severity of the mucosal lesions. Long-term treatment with cimetidine did not prevent gastric damage. These findings indicate that pure antisecretory agents do not directly increase the capacity of the mucosa to resist damage.

Animals↗
PubMed1987

Nutritional effects on mitochondrial bioenergetics. Alterations in calcium uptake by rat liver mitochondria.

The uptake of Ca2+ by energized liver mitochondria was compared in normal fed as well as in protein-energy malnourished rats. In the presence of phosphate, mitochondria obtained from both groups were able to accumulate Ca2+ from the suspending medium and eject H+ during oxidation of common substrates which activate different segments of the respiratory chain. The rate of Ca2+ uptake was significantly lower in mitochondria from protein-energy malnourished rats. The rates of oxygen consumption and H+ ejection were decreased by 20-30% during oxidation of substrates at the three coupling sites. Similarly, mitochondria from protein-energy malnourished rats exhibit a 34% decrease in the maximal rate of Ca2+ uptake and a 25% lower capacity for Ca2+ load. The stoichiometric relationship of Ca2+/2e- remained unaffected. In steady state, with succinate as a substrate in the presence of rotenone and N-ethylmaleimide, mitochondria from normal fed and protein-energy malnourished rats showed a similar rate of Ca2+ uptake. Furthermore in both groups the stoichiometry of the H+/O ratio was close to 8.0 (H+/site ratio close to 4.0), and of Ca2+/site was close to 2.0. The diminished rate of Ca2+ uptake observed in mitochondria from protein-energy malnourished rats could be explained on the basis of a depressed rate of electron transport in the respiratory chain rather than by an effect at the level of the Ca2+ or H+ transport mechanism per se.

Animals↗
PubMed1986

The locus of inhibition of NADH oxidation by benzothiadiazoles in beef heart submitochondrial particles.

6-Chloro-1,2,3-benzothiadiazole (6-Cl-BTD) is an effective inhibitor of NADH oxidase (site I) but not of succinate oxidase in beef heart submitochondrial particles. For NADH oxidase activity maximal inhibition (80-85%) was achieved at 0.75mM 6-Cl-BTD. A similar level of inhibition was also observed (half maximal inhibitory concentration 0.5mM) towards NADH-duroquinone reductase; NADH-juglone reductase was slightly inhibited (23%) at 0.5mM 6-Cl-BTD while NADH-ferricyanide reductase was unaffected. The data suggest that 6-Cl-BTD interacts with an electron transport site on the oxygen side of NADH dehydrogenase and inhibitory studies with 6-Cl-BTD and rotenone indicate that it might correspond with one of the two sites affected by rotenone. The substituted 1,2,3-benzothiadiazoles (BTDs) are perhaps best known for their activity as inhibitors of cytochrome P-450-mediated mixed-function oxidation (MFO). In vitro, the BTDs are potent inhibitors of MFO activities in microsomes from mammalian liver and insect tissues and they have been demonstrated to inhibit aminopyrine metabolism in perfused rat liver. In vivo, they reportedly prolong hexobarbital sleeping time in mice, inhibit the irreversible binding of labeled trichloro-ethylene to microsomal protein and effectively enhance the toxicity (synergize) of pyrethrin, organophosphorus-containing and carbamate insecticides to insects.

Animals↗
PubMed1985

Effects of guanethidine on electron transport and proton movements in rat heart, brain and liver mitochondria.

Guanethidine at 5-25 mM concentrations was found to induce up to 79% inhibition of ADP-stimulated (state III) oxygen consumption in isolated rat heart, brain or liver mitochondria, when the added substrate was glutamate or succinate, but the inhibition was considerably lower (24% or less) when respiration was supported by ascorbate plus tetramethylphenylenediamine (TMPD). Comparable results were seen regarding ADP-stimulated proton uptake, where even greater inhibition (up to 94% with glutamate or succinate, but not ascorbate plus TMPD) was found. Similar but somewhat less marked effects were also seen in resting (state IV) respiration and on the acceptor control ratio (state III/state IV respiration). 2,4-Dinitrophenol was unable to relieve guanethidine-induced inhibition of electron transport. These results indicate that guanethidine inhibits primarily mitochondrial electron transport itself, and that the site where such inhibition is more marked is located in the span between ubiquinone and cytochrome c of the respiratory chain. It is, therefore, suggested that active guanethidine uptake by noradrenergic neurons can lead to a high drug concentration in their cytoplasm and hence to mitochondrial alterations that can contribute to the pharmacological effect of this drug. Our results demonstrate the interaction between guanethidine and the electron transport chain of mitochondria derived from different tissues and, therefore, support this hypothesis.

Adenosine Diphosphate↗