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Biomedical subjects

A Contreras

Publications and source records attributed to A Contreras.

At least 91 records · Page 5Linked to original sources
PubMed1986

An unusual pattern of Na+ and K+ movements across the horse erythrocyte membrane.

Marked differences in the activities of three monovalent cation transport systems in horse versus human erythrocytes are reported. Whereas horse erythrocytes exhibit a 6-fold higher sodium-lithium countertransport, the unidirectional flux of potassium through the sodium pump is 3-4 times slower and the sodium-potassium cotransport system cannot be detected. In spite of this, horse and human cells are able to maintain similar Na+ and K+ gradients.

Animals↗
PubMed1984

Effects of increased biliary resistance on bile secretion in the rat.

The effects of increased biliary resistance on bile secretion and biliary permeability properties were studied in rats. High biliary resistance produced significant reductions in bile flow and the secretion rate of cholesterol, but did not modify bile salt and phospholipid secretory rates. Decreased bile flow appeared to be secondary to a marked reduction in bile salt-independent fractions of bile flow, and bile salt-dependent flow was simultaneously increased. 14C-erythritol and 3H-inulin clearance studies suggest that decreased net canalicular secretion of water rather than increased water reabsorption at the biliary ducts is the mechanism involved in decreased bile flow. In addition, a marked increase in canalicular permeability to inulin was evident when rats were secreting against increased biliary resistance as well as during recovery.

Animals↗
PubMed1982

[Synthesis, cytostatic activity and mechanism of action of N-glycosylhalomethylazoles. A new class of alkylating agents].

A model to produce a new type of alkylating agents having anti-cancer activity is described. They consist of a halomethyl-azol group of the benzyl type as alkylating center, and a sugar moiety as a carrier fragment. Alkylating nucleosides were produced as halomethyl-pyrazole, -imidazole, 1.2.3-triazole, and 1.2.4-triazole derivatives following the model, and tested upon Ehrlich ascites cancer and P-388 lymphocytic leukemia.

Alkylating Agents↗
PubMed1981

The effect of complete biliary obstruction on bile secretion. Studies on the mechanisms of postcholestatic choleresis in the rat.

It has been previously shown that rats subjected to obstructive cholestasis demonstrate in the postcholestatic period, after release of common duct obstruction, a marked increase in canalicular bile flow relative to bile acid excretion. To characterize this phenomenon further, we investigated whether changes in canalicular permeability and in the activity of (Na+-K+)-ATPase in isolated liver surface membranes are associated with postcholestatic choleresis. With this purpose, the clearances of 14C-erythritol and 3H-insulin were simultaneously measured in rats subjected to a 3-day obstructive cholestasis and in controls, during spontaneous choleresis as well as during the intravenous infusion of sodium taurocholate at both submaximal and saturating rates. In additional groups of bile duct-ligated rats and controls, liver surface membrane fractions were isolated, and the activity of appropriate marker enzymes and (Na+-K+)-ATPase was determined. In both groups 14C-erythritol clearance closely approximated total bile flow, suggesting that bile flow was of canalicular origin. However, cholestatic rats showed a sixfold increase in 3H-inulin clearance compared to controls. These results suggest that canalicular permeability to inulin is markedly increased in cholestatic rats. On the other hand, (Na+-K+)-ATPase activity was significantly higher in cholestatic rats than in controls in both homogenate (1.27 +/- 0.07 and 0.89 +/- 0.07 U/mg of protein, respectively, p less than 0.001) and liver surface membranes (22.6 +/- 1.2 and 17.5 +/- 1.2 U/mg of protein, respectively, p less than 0.001). Thus enhanced choleretic response to bile acids in the postcholestatic period is associated with an increased permeability of canalicular structure to inulin and with a significant increase in both homogenate and surface membrane (Na+-K+)-ATPase activity. In addition, this study points out some important differences between bile secretory function of rats subjected to obstructive cholestasis and that described in models of bile secretory failure induced by drugs or monohydroxy-bile acids.

Animals↗
PubMed1980

Alkylating nucleosides. 4. Synthesis and cytostatic activity of chloro- and iodomethylpyrazole nucleosides.

The synthesis and cytostatic activity of several chloromethyl- and iodomethylpyrazole nucleosides are described. Glycosylation of ethyl 3(5)-(chloromethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(chloromethyl)pyrazole-5(3)-carboxamide (4) with poly(O-acetylated) sugars via an acid-catalyzed fusion method gave the corresponding 3-(chloromethyl)-5-carboxylate and 3-(chloromethyl)-5-carboxamide substituted nucleosides 7 and 9, respectively. From the reaction of 4 with tetra-O-acetyl-beta-D-ribofuranose, the 5-(chloromethyl)-3-carboxamide-substituted derivative 11 was also obtained. Reaction of 7, 9, and 11 with sodium iodide in acetone provided the related iodomethylpyrazole nucleosides 8, 10, and 12. In general, chloromethyl-substituted nucleotides showed moderate activities against HeLa cells, while all the corresponding iodomethyl derivatives exhibited high activities. Some of these latter compounds increased the life span of mice bearing ECA tumor.

Alkylating Agents↗
PubMed1979

Selective inhibition of protein synthesis in virus-infected mammalian cells.

A number of translation inhibitors were tested for their effects on both control and encephalomyocarditis virus-infected mouse 3T6 cells. The virus-infected cells were specifically inhibited by gougerotin, edeine, and blasticidin S, whereas these drugs failed to penetrate into uninfected cells. Inhibition of infected cells by gougerotin became apparent when the synthesis of viral proteins commenced, suggesting that the latter process is accompanied by a permeability change in the cells that allows uptake of the drug. This permeability change was not observed in cells treated with cycloheximide soon after viral infection, although treatment with actinomycin D did not prevent inhibition of gougerotin. It is possible, therefore, that a specific viral protein is involved in the permeability change of the plasma membrane. Moreover, gougerotin was unable to inhibit protein synthesis in the presence of zinc ions, thus preventing gougerotin from entering into the infected cell. Membrane leakiness was not restricted to the encephalomyocarditis virus-3T6 system; it was also observed in mengovirus-infected 3T6 cells, Semliki Forest virus-infected BHK cells, and simian virus 40-infected CVI1 cells at the time in which the synthesis of late proteins is maximal.

Anti-Bacterial Agents↗
PubMed1979

The effect of complete biliary obstruction on bile flow and bile acid excretion: postcholestatic choleresis in the rat.

Bile secretory function was studied in rats subjected to a 7-day obstructive cholestasis induced by complete common duct obstruction. Bile flow and bile acid excretion were examined during bile depletion, following the release of the biliary obstruction, and during the infusion of sodium taurocholate at submaximal and saturating rates. A highly significant increase, greater than 100%, in bile flow was evident in cholestatic rats at any bile acid excretory rate, when compared to control sham-operated rats. 14C-erythritol clearance measurements performed during bile depletion and during the infusion of taurocholate suggest that bile flow was mainly of canalicular origin in cholestatic rats. Estimated taurocholate transport maximum (mumol/min per rat) was not statistically different between cholestatic and control rats. However, significantly greater taurocholate plasma levels at Tm in cholestatic rats suggest a decreased efficiency of the bile acid transport process. In addition, the relationship between bile flow and bile acid excretion was found to be nonlinear at low bile acid excretory rates in cholestatic rats. Thus important changes in bile formation occurred in rats subjected to temporary obstructive cholestatis, which differ from those observed in other models of cholestasis that are associated to a reduction in bile flow and bile acid transport capacity.

Animals↗
PubMed1978

Cytostatic quinones. 3. Synthesis of benzotriazolequinones by a new oxidation with m-chloroperbenzoic acid. Biochemical studies.

Oxidation of N-1 and N-2 alkylbenzotriazoles with m-chloroperbenzoic acid afforded 1-alkylbenzotriazole 3-oxides and 2-alkylbenzotriazole-4,4-diones, respectively. The quinonic compounds inhibited the "in vitro" growth of both HeLa and KB cells, the synthesis of macromolecules (DNA, RNA, and proteins), and the uptake of glucose by Ehrlich carcinoma ascites cells. A possible mode of action is suggested.

Animals↗
PubMed1978

Inhibition, by selected antibiotics, of protein synthesis in cells growing in tissue cultures.

A large number of compounds including actinobolin, adrenochrome, amicetin, anisomycin, aurintricarboxylic acid, blasticidin S, chartreusin, chlortetracycline, cycloheximide, doxycycline, edeine A1, edeine complex, emetine, fusidic acid, gougerotin, GppCH2p, oxytetracycline, pactamycin, polydextran sulphate, puromycin, pyrocatechol violet, sparsomycin and tubulosine have been tested for inhibitory effects on protein synthesis in cultured cells from both mouse fibroblasts (3T6 cells) and chick embryo fibroblasts (CEF). Essentially, similar results were obtained with both cell types with the most effective inhibitors being pactamycin, emetine, tubulosine, anisomycin and cycloheximide and with no significant inhibitory activity being detected with edeine complex, edeine A1, GppCH2p, polydextran sulphate, aurintricarboxylic acid, pyrocatechol violet and adrenochrome. The concentration of pactamycin required to produce 50% inhibition of protein synthesis approximated 5 X 10(-9) M, but for most of the inhibitors it ranged from 5 X 10(-6) M to 5 X 10(4) M. The molecular basis underlying these differences may be related, in addition to their intrinsic inhibitory power, to differences in permeability of the cells towards the various drugs tested. Alternatively, active accumulation of the drugs by the cells may be the variable parameter.

Animals↗
PubMed1978

Effect of aging on biliary lipid composition and bile acid metabolism in normal Chilean women.

Biliary lipid composition was determined in fasting gallbladder bile of 12 young and 12 elderly asymptomatic Chilean women with normal weights and recent, normal cholecystograms. The proportion of biliary cholesterol and the lithogenic index were significantly higher in elderly females. Moreover, supersaturated bile was present in 8.3% of the young and in 41.7% of the older women studied. Obesity enhances the saturation of bile in older females: lithogenic bile was found in 100% of 4 elderly, obese women with radiologically normal gallbladders. The bile acid pool and cholic acid metabolism were studied in 5 young and 4 older normal females. Both groups showed similar values of bile acid pool, cholic acid synthesis, and turnover. These results indicate that aging per se modifies the proportions of biliary lipids in Chilean women, and provide a partial explanation for the frequency of gallstones observed among them. The increment in the lithogenic index of gallbladder bile with age takes place without significant changes in bile acid metabolism, suggesting that the canalicular secretion of cholesterol increases with aging.

Adolescent↗
PubMed1977

Cooperative and antagonistic interactions of peptidyl-tRNA and antibiotics with bacterial ribosomes.

There is a single-site interaction of [methylene-14C]thiamphenicol and [methylene-14C]chloramphenicol with run-off ribosomes with dissociation constants Kd = 6.8 micronM and Kd = 4.6 micronM respectively. Similar affinities for the antibiotics are observed in polysomes totally deprived of nascent peptides, or bearing nascent peptides on the A-site. However, two types of interaction are observed in endogenous polysomes with some ribosomes bearing nascent peptides on the P-site and other in the A-site. The lower-affinity bindings (dissociation constants Kd = 6.4 micronM and Kd = 1.5 micronM for thiamphenicol and chloramphenicol respectively) are due to the ribosomes bearing nascent peptides on the A-site. The higher-affinity bindings (dissociation constants Kd = 2.3 micronM and Kd = 1.5 micronM for thiamphenicol and chloramphenicol, respectively) are due to the ribosomes bearing nascent peptides on the P-site. Therefore binding of nascent peptides to the A-site does not affect the affinities of thiamphenicol and chloramphenicol for the ribosome. On the other hand interaction of the nascent peptides with the P-site of the ribosomes increases the affinities of both antibiotics for the ribosome. Thiamphenicol and chloramphenicol are thus good inhibitors of peptide bond formation in ribosomes and polysomes. Their affinities are increased precisely when the peptidyl-tRNA is placed in the P-site preceeding the peptide bond formation step, which is specifically blocked by the antibiotics. There is a single-site interaction per ribosome for [35S]thiostrepton, which does not appear to be affected by the attachment to the ribosomes of mRNA, tRNA and nascent peptides either to the A or the P-site. [N-methyl-14C]Lincomycin, [N-methyl-14C]erythromycin, [G-3H]streptogramin B and [G-3H]-streptogramin A bind to run-off ribosomes and polysomes totally free from nascent peptides. However, these antibiotics do not interact with ribosomes bearing nascent peptides either in the A or the P-site and therefore are not active on preformed polysomes. Thus lincomycin and streptogramin A only interact with free ribosomes and 50-S subunits and block the early rounds of peptide bond formation prior to polysome formation. Erythromycin and streptogramin B do not inhibit either initiation or the first round of peptide bond formation. However, erythromycin and streptogramin B, prebound to the ribosome, block peptide elongation probably by steric hindrance with the growing oligopeptide chain when this reaches a certain critical length.

Anti-Bacterial Agents↗
PubMed1977

Synergistic interaction of the streptogramins with the ribosome.

Quantitative binding studies of [G-3H]streptogramin A and [G-3H]streptogramin B with high-salt-washed ribosomes were carried out in the presence of a minimum of 10% (v/v) ethanol because of the antibiotic insolubility in water. It was observed that the presence of streptogramin A increases the affinity of [G-3H]streptogramin B for the ribosome. Thus the dissociation constant for [G-3H]-streptogramin B interaction with the ribosome is Kd=13.3 nM in the presence of streptogramin A and Kd=59 nM in its absence. Furthermore the values for the dissociation constants for [G-3H]-streptogramin B interaction in the presence of 50% (v/v) ethanol, were Kd=0.13 micronM in the presence of streptogramin A and Kd=0.70 micronM in its absence. This increased affinity of [G-3H]streptogramin B in the presence of streptogramin A can explain the synergistic effects of mixtures of streptogramins A and B at the ribosome level.

Anti-Bacterial Agents↗
PubMed1975

The mode of action of griseoviridin at the ribosome level.

The antibiotic griseoviridin binds to the larger subunit of Escherichia coli ribosomes blocking the interaction between the 3' terminal end of peptidyl-tRNA and the donor site of the peptidyl transferase centre. Griseoviridin inhibits binding of chloramphenicol, thiamphenicol, lincomycin, erythromycin and streptogramin A to bacterial ribosomes. Moreover griseoviridin protects the ribosomal binding site of gougerotin from the drastic conformational changes taking place in the presence of ethanol. Griseoviridin is also able to interact with eukaryotic ribosomes as shown by its effects on model systems and on anisomycin, trichodermin and gougerotin binding studies. Nevertheless, griseoviridin affinity for the 80-S type ribosomes (yeast or human) is two orders of magnitude smaller than with E. coli ribosomes. The inhibitory spectrum and mode of action of griseoviridin on ribosomes is compared to that of antibiotics of the streptogramin A group and found to be essentially the same.

Anti-Bacterial Agents↗