FK506 sensitizes mammalian cells to high osmolarity by modulating p38 MAP kinase activation

The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004     

Reversal of the inhibitory effect of (2-chloroethyl)trimethyl-ammonium Chloride on the Flowering ofChenopodium rubrum L. by Kinetin

Zusammenfassung Chlorcholinchlorid (CCC) (2 × 10^–3 M) hemmt die Blühinduktion bei der KurztagspflanzeChenopodium rubrum L. Es wird gezeigt, dass diese Hemmung nicht nur durch Gibberellinsäure, sondern auch durch Kinetin (1 mg/l) aufgehoben werden kann. Eine Behandlung mit Kinetin derselben Konzentration allein (ohne vorherige Applikation von CCC) blockiert die Blühinduktion beiC. rubrum fast vollständig. Der Mechanismus der CCC-Wirkung auf die Blühinduktion wird diskutiert.     

Stimulation of pyruvate carboxylation by gastric secretagogues

Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455.     

Evidence that superoxide radicals are involved in the hemolytic mechanism of phenylhydrazine

Summary Phenylhydrazine produces in the red blood cell the same effect as the enzymic system xanthine oxidase-xanthine, a superoxide radical generator system. Both effects are inhibited by the enzyme superoxide dismutase.This work was supported in part by grants Nos. 1045 and 3243 of Oficina Técnica de Desarrollo Científico y Creación Artística de la Universidad de Chile.     

Estrogen action in the male.

Estrogen administration induces a migration of eosinophil leukocytes to ductus deferens.     

The protective effect of small amounts of selenite in sublimate intoxication

Résumé L'injection de très petites quantités de sélénite de sodium, administrées simultanément ou 1 h après l'intoxication par le sublimé corrosif, en abaisse considérablement la toxicité: les rats blancs intoxiqués par une dose létale de sublime corrosif survivent sous l'effet du sélénite dans un % important et les lésions typiques des reins et d'autres organes n'apparaissent pas.     

Occurrence of a characteristic nucleolar structure in pachytene cells

Resumen Se describe el hallazgo de una estructura nucleolar característica en células paquiténicas de anteras deAllium cepa, fijadas en formol y teñidas con fuchsina. Esta estructura se presenta como una pequeña formación semejante a un botón o anillo en el nucleolo de todos los meiocitos observados en ese estadío.

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The work reported in this paper was undertaken during thetenure of a Research Training Fellowship awarded by the International Agency for Research on Cancer.     

Modification of clonazepam anticonvulsive activity by its association with other anti-epileptic drugs

Summary The modification of the anti-epileptic activity of clonazepam by other anticonvulsivants is studied. The results vary according to the drug and technique used. The usefulness of the 2 techniques employed is discussed.