Pentose phosphate metabolism in Leishmania mexicana.

The metabolism of pentose phosphates was studied in Leishmania mexicana promastigotes. Each of the enzymes of the classical pentose phosphate pathway (PPP) has been identified and specific activities measured. Functioning of the PPP was demonstrated in non-growing cells by measuring the evolution of 14CO2 from [1-14C]D-glucose and [6-14C]D-glucose under normal conditions and also under selective stimulation of the PPP by exposure to methylene blue. The proportion of glucose which passes through the PPP increases in the latter condition, thus suggesting a protective role against oxidant stress. The incorporation into nucleic acids of ribose 5-phosphate provided via either glucose or free ribose was also determined. Results indicate that the PPP enables glucose to serve as a source of ribose 5-phosphate in nucleotide biosynthesis. Moreover, free ribose is incorporated efficiently, implying the presence of a ribose uptake system and also of ribokinase. Ribose was shown to be accumulated by a carrier mediated process in L. mexicana promastigotes and ribokinase activity was also measured in these cells.

Evolution of protein synthesis in a lattice model of replicators.

The traditional chemical-kinetics approach to the study of prebiotic evolution cannot explain the evolution of protein synthesis in a homogeneous population of self-replicating molecules, because the invasion of a resident population of simpler, template-directed replicators by mutant protein-assisted replicators is deemed impossible. Approaching this problem in a spatial cellular automaton framework, we argue here that in such a setting evolution of protein synthesis is a likely event. In addition, we show that the onset of invasion may be viewed as a nonequilibrium phase transition, that can be characterized quantitatively by a set of critical exponents.

Antimycobacterial activity of 4'-bromo-[1,1'-biphenyl]-4-yl 4-x-phenylmethanone derivatives, and their acute toxicity and cytotoxicity.

The antimycobacterial activity of nine biphenyl methanone (BPM) derivatives against standard strains of Mycobacterium kansasii, M. avium and M. malmoense was determined by colorimetric assay in microplates with the dye Alamar Blue. Acute toxicity of these compounds was also analyzed by determination of CO2 concentration in a respirometric assay using Escherichia coli. The compounds showed weak antimycobacterial activity with a minimal inhibitory concentration (MIC) over 0.038 mmol l-1 and no toxicity was found in E. coli up to 400 mmol l-1. No cytotoxicity was observed on V79 cells up to 0.35 mmol l-1 with 7 of the BPM derivatives, with two exceptions (X = SO2CH3, NO2) that showed some toxicity. The greatest antimycobacterial activity was observed with the SO2CH3 derivative and the application of Principal Component Analysis (PCA) showed a relationship between structure and antimycobacterial activity of the compounds. Two descriptors, nucleophilic superdelocalizability of carbon atom and pi-hydrophobic constant, were necessary to describe this relationship.

Uso del ácido fólico en la prevención primaria de malformaciones congénitas / Use of folic acid in the primary prevention of abnormalities

Cuando los países mejoran sus condiciones de salud y alcanzan tasas de mortalidad infantil de alrededor de un dígito, las malformaciones congénitas pasan a ocupar el primer lugar entre sus causas. El énfasis en el tratamiento de las malformaciones congénitas debe estar en diseñar estrategias de prevención primaria. Al respecto, durante los últimos años el uso del ácido fólico ha adquirido un rol preponderante. El uso periconcepcional de ácido fólico ha mostrado un claro efecto protector en relación con los defectos de cierre del tubo neural. Considerando la importancia de la prevención primaria en la morbimortalidad a cualquier edad, se ha estimado fundamental planificar estrategias de prevención aplicables en el ámbito individual y poblacional. Se presentan las bases embrionarias, anatómicas, bioquímicas y moleculares de los defectos de cierre del tubo neural y la importancia de iniciar programas a nivel poblacional que aseguren una ingesta suficiente de ácido fólico en las poblaciones objetivo

Antiproliferative effects of N1,N4-dibenzylputrescine in human and rodent tumor cells.

Polyamines (putrescine, spermidine and spermine) increase in proliferating tissues and are essential for cellular growth and cell division processes. We had previously shown that alkyl substituted putrescines can inhibit cell proliferation. We now tested the effects of the (N(alpha),N(omega)-dibenzyl derivatives of the simple diamines putrescine, cadaverine and 1,3-diaminopropane on the growth of three human squamous cell carcinoma (SCC) lines and a rat hepatoma (H-4-II-E) cell line. Survival assays were measured by treating exponentially-growing SCC cultures with N1,N4-dibenzylputrescine (DBP) (270 microM) or a rat hepatoma cell culture with DBP (100 microM) for 48 hrs. Inhibition of cell growth was measured either by the colony forming assay or by cell counting. DBP inhibited proliferation of the rat hepatoma (H-4-II-E) cell line and induced cytotoxicity when used at a concentration of 100 microM for >48 hrs. N1,N5-dibenzylcadaverine (DBC) also induced cytotoxicity at a similar concentration, while N1,N3-dibenzyl-1,3-diaminopropane (DBPr) was a much weaker inhibitor of cell growth. Inhibition of cell growth by DBP resulted in marked modifications of cell morphology, such as vacuole formation, decrease in size, pycnosis, change in staining behavior toward trypan blue and lack of adherence. DBP was also growth inhibitory in the three human SCC cell lines tested. The concentration of DBP required to achieve growth inhibition of SCC cells could be dramatically decreased in the presence of N1,N4-bis(buta-2,3-dienyl)butanediamine, a specific inhibitor of polyamine oxidase (PAOI). Moreover, although the presence of PAOI only prevented the oxidation (debenzylation) of approximately 20% of intracellular DBP over a 5-day period, it produced a 5-fold increase in the inhibition of cell proliferation by DBP. DBP (and DBC) inhibited putrescine uptake by rat hepatoma (H-4-II-E) cells in what appears to be a competitive reaction. A tenfold excess of putrescine over DBP did not inhibit the antiproliferative or cytotoxic effects of the latter. DBP administered for 72 hrs. depleted intracellular levels of putrescine, spermidine and spermine in the SCC lines by 50-100% of control values. It was found that DBP inhibited nucleic acid and protein synthesis at an early stage of cell proliferation, hence its growth inhibitory effect may be related to inhibition of the synthesis of macromolecules.

Biología celular y molecular / Cellular and molecular biology

Muestra los adelantos en la biología celular y molecular, sobre todo en lo que se refiere a: membrana celular, retículo endoplásmico, interacciones celulares, citoesqueleto, motilidad celular, endoxomas, perixomas, estructura de los cromosomas, regulación del gen, transcripción del RNA, y diferenciación celular. Las novedades mas importantes son: los oncogenes, célula cancerosa, sistema inmunitario, ingeniería genética y la neurobiología celular y molecular

Biología celular y molecular / Cellular and molecular biology

Muestra los adelantos en la biología celular y molecular, sobre todo en lo que se refiere a: membrana celular, retículo endoplásmico, interacciones celulares, citoesqueleto, motilidad celular, endoxomas, perixomas, estructura de los cromosomas, regulación del gen, transcripción del RNA, y diferenciación celular. Las novedades mas importantes son: los oncogenes, célula cancerosa, sistema inmunitario, ingeniería genética y la neurobiología celular y molecular

Fundamentos de biología celular y molecular / Fundament of cellular and molecular biology

Muestra los adelantos en: membrana celular, retículo endoplásmico, interacciones celulares, citoesqueleto, secreción celular, estructura de cromosomas, diferenciación celular, la regulacion del gen, los endoxomas y los peroxisomas. Las novedades mas salientes son con respecto a los oncogenes, célula cancerosa, sistema inmunitario e ingeniería genética

Fundamentos de biología celular y molecular / Fundament of cellular and molecular biology

Muestra los adelantos en: membrana celular, retículo endoplásmico, interacciones celulares, citoesqueleto, secreción celular, estructura de cromosomas, diferenciación celular, la regulacion del gen, los endoxomas y los peroxisomas. Las novedades mas salientes son con respecto a los oncogenes, célula cancerosa, sistema inmunitario e ingeniería genética

Studies in vivo on the methionine-sparing effect of cysteine in rats.

This investigation was conducted to clarify the role of cysteine on its methionine-sparing effect by studying in vivo the various parameters that are directly related to the metabolism of the methionine carbon, such as conversion to CO2, and incorporation of the methionine carbon into proteins, phospholipids and nucleic acids. At low (0.4%) dietary level of methionine, cysteine had a depressive effect on the oxidation of the methionine carbon to carbon dioxide, and with 0.51% cysteine in the diet the oxidation of the methyl or carboxyl carbon of methionine to CO2 was depressed by 29 and 20%, respectively. The amount of the label in urine samples was unaltered by the level of cysteine in the diet, and the body retention of either the methyl or carboxyl carbon of methionine was greater at low methionine intake when cysteine in the diet was increased. Under these conditions, rat growth was enhanced by feeding increasing amounts of cysteine. The incorporation of methionine methyl carbon into tissue nucleic acids and phospholipids was depressed by high (0.51%) levels of cysteine in the diet, at a low (0.4%) methionine intake. Under these conditions there was an increased incorporation of the methionine methyl or carboxyl carbon into tissue proteins. In addition, it appears that the resynthesis of methionine from homocysteine is enhanced by increasing the amounts of cysteine in the diet. All of these findings suggest that the addition of cysteine increases the avilability of methionine for protein synthesis and, hence, growth.