RESUMEN
The lethality of several individual bleomycin derivatives, i.e., the spermidine derivative (A5), The dimethyl sulfonium aminopropyl derivative (A2), and the agmatine derivative (B2), was compared on mouse fibroblasts. The spermidine derivative, bleomycin A5, was the most toxic, producing more than a 2-log drop in clonability in 50 hr at 20 microng/ml. 6-Azauridine, a relatively nonlethal inhibitor of RNA synthesis and cell multiplication, produced a 60% decrease of adenine incorporation into nucleic acids without inhibiting the lethal action of A5. This result differed from the effects of inhibition of RNA synthesis on the lethality of A5 in Escherichia coli. Hirudonine (1,8-diamidino-spermidine) markedly and specifically inhibited the lethal effects of A5 in L-cells but not in E. coli. However, hirudonine did not affect the toxicity of A2 and B2, separately or together, as it did in the mixture used clinically. Nor did arcaine (diamindinoputrescine) reduce the lethality of the agmatine (monoamidinoputrescine) derivative, B2.
Asunto(s)
Bleomicina/toxicidad , Espermidina/análogos & derivados , Amidinas/farmacología , Azauridina/farmacología , Bleomicina/análogos & derivados , Bleomicina/antagonistas & inhibidores , Supervivencia Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Células L , ARN/biosíntesis , Espermidina/farmacologíaRESUMEN
An innovative teaching strategy focused on problem based approach rather than theorical aiming to facilitate the learning of the research methodology in advanced nursing student has been introduced. Through out a qualitative evaluation of the diary kept by the student nurses involved, advantages and disadvantages of this innovative approach have been evaluated. This paper reports a synthesis of the teaching strategy and its impact on the competences in the research methodology as it has been perceived by the students participants.
Asunto(s)
Investigación en Enfermería Clínica/educación , Educación de Postgrado en Enfermería/métodos , Investigación en Enfermería Clínica/métodos , Conducta Cooperativa , Emociones , Humanos , Entrevistas como Asunto , Italia , Proyectos Piloto , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Registros , Estudiantes de EnfermeríaAsunto(s)
Inhibidores de la Adenosina Desaminasa , Adenosina/farmacología , Desoxiadenosinas/farmacología , Células L/efectos de los fármacos , Nucleósido Desaminasas/antagonistas & inhibidores , Adenina/análogos & derivados , Adenina/farmacología , Animales , Antibacterianos/farmacología , Azepinas/farmacología , Desoxirribonucleósidos/farmacología , Fibroblastos/metabolismo , Células L/enzimología , Ratones , Vidarabina/farmacologíaRESUMEN
The metabolism of polyamines was studied in K(+)-dependent strains of Escherichia coli. When these stringent organisms were in a medium containing Na(+) instead of K(+), protein synthesis was arrested, but synthesis of ribonucleic acid continued as it would in a relaxed organism. The Na(+) medium inhibited synthesis of spermidine and S-adenosylmethionine. However, the synthesis of putrescine was accelerated at least five- to eightfold. Exogenous ornithine doubled even this rate of putrescine synthesis but did not increase the low level of putrescine synthesis in the K(+) medium. In K(+) or Na(+) media, with or without 0.3 mm arginine, putrescine was derived almost entirely from ornithine via ornithine decarboxylase. Addition of spermidine (5 mm) to a Na(+) culture markedly inhibited putrescine synthesis. The ornithine decarboxylase of an extract of a K(-)-dependent strain prepared at low ionic strength was separated from ribosomes, deoxyribonucleic acid, and associated polyamines by centrifugation, and from many ions by ultrafiltration and fractionation on Sephadex G-100. Addition of Na(+) and K(+) salts to 200 mm was markedly inhibitory. The combined reductions both in synthesis of the inhibitor spermidine and in intracellular ionic strength may explain the in vivo activation of this enzyme.
Asunto(s)
Escherichia coli/metabolismo , Potasio/metabolismo , Putrescina/biosíntesis , Espermidina/biosíntesis , Arginina/metabolismo , Proteínas Bacterianas/biosíntesis , Isótopos de Carbono , Carboxiliasas/metabolismo , Sistema Libre de Células , Medios de Cultivo , Escherichia coli/enzimología , Escherichia coli/crecimiento & desarrollo , Metionina/metabolismo , Mutación , Ornitina/metabolismo , ARN Bacteriano/biosíntesis , S-Adenosilmetionina/biosíntesis , Sodio/metabolismo , Espermidina/metabolismo , Urea/biosíntesisRESUMEN
9-beta-D-Arabinofuranosyladenine 5'-monophosphate (araAMP) is more lethal to mouse fibroblasts (L cells) than the identical exogenous concentration of 9-beta-D-arabinofuranosyladenine (araA) (Cancer Res. 32, 1512, 1972). [(3)H,(32)P]AraAMP (0.1 mM) was taken into L cells for 4 hr in the presence of a large excess of (32)P(i). The radioactivity was subsequently found mainly in the adenine nucleotides in the acid-soluble fraction and in the cell DNA. The cellular concentration of 9-beta-D-arabinofuranosyladenine 5'-triphosphate (araATP) exceeded 2 muM. More than 90% of the (3)H was associated with araA in the nucleotides. After degradation of the adenine-containing triphosphates with apyrase, the adenine mononucleotides were separated by thin-layer electrophoresis and chromatography. All of the (32)P and 97% of the (3)H were associated with araAMP. The small amounts of (3)H and (32)P in the acid-insoluble material were similar during a 4 hr incubation. The DNA fraction was degraded enzymatically to 5'-mononucleotides. Both (32)P and (3)H were associated predominantly with 5'-dAMP. Most of the (3)H was in araA, detected after dephosphorylation. Enzymatic degradation of the DNA fraction to 3'-mononucleotides and fractionation revealed (3)H primarily in the 3'-adenine nucleotide and (32)P in each of the deoxynucleoside 3'-monophosphates. After dephosphorylation of the 3'-mononucleotides, 93% of the (3)H was found in araA. These results suggest that small amounts of araAMP penetrated the cell as an intact nucleotide, were further phosphorylated to the triphosphate, and subsequently incorporated in internucleotide linkage into DNA.