Antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones.

Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Interesting antiviral EC50 values are obtained against herpes simplex virus-1 and vaccinia virus. The biological activity of acylhydrazones is often attributed to their metal coordinating abilities, so potentiometric and microcalorimetric studies are here discussed to unravel the behavior of the three 2-hydroxy-3-methoxyphenyl compounds in solution. It is worth of note that the acylhydrazone with the higher affinity for Cu(II) ions shows the best antiviral activity against herpes simplex and vaccinia virus (EC50 ~ 1.5 µM, minimal cytotoxic concentration = 60 µM, selectivity index = 40).

Pruebas biológicas complementarias en las muertes por sumersión / Complementary biological tests in death by drowning

En el presente trabajo realizamos una revisión de las pruebas biológicas complementarias para el estudio de sumersión, se exponen pruebas clásicas como son la detección de diatomeas, los criterios analíticos aplicables para su estudio y la interpretación de los resultados.En el campo de los marcadores bioquímicos-químicos de sumersión, se resalta la importancia del estudio del estroncio, especialmente en agua de mar, donde es posible no solo identificar una asfixia por sumersión, sino también diferenciar muertes con pequeñas aspiraciones de agua durante el período vital frente a muertes sin aspiración de agua.Otros marcadores son objeto de consideración, y de manera particular, el estudio de la expresión del canal de agua intrapulmonar aquaporin-5, o la detección de microplacton, mediante la utilización de técnicas moleculares, con proyección cada vez más destacada en el diagnóstico de sumersión.Se recogen las recientes aportaciones diagnósticas del análisis bacteriológico de la sangre, o el estudio del surfactante pulmonar como marcadores complementarios(AU)

The complementary biological tests for drowning death studies are reviewed in present work. The report reviews the scientific research described in literature over the last four decades, where the classic analyses, such as diatoms are described as well as the analytical criteria and their interpretation.As regards the biochemical markers of drowning, it highlights the importance of strontium, especially in salt water drowning cases. It is possible identify a drowning-suffocation death, and even to differentiate those deaths into the water associated with small amounts of water inhalation from deaths without water inhalation.Other markers are also considered, specifically the study of aquaporin-5, or the detection of micro-plankton using biomolecular techniques.Finally, the work looks at the latest diagnostic contributions of bacteriological blood analysis or the study of lung surfactant as complementary markers(AU)

What to do when an endotracheal tube cuff leaks.

The authors describe an approach and a novel technique to solve a leaky endotracheal tube cuff problem in ventilator-dependent patients without immediately resorting to the potentially hazardous task of changing an endotracheal tube.

Biochemical mechanisms of cephaloridine nephrotoxicity.

Large doses of the cephalosporin antibiotic, cephaloridine, produce acute proximal tubular necrosis in humans and in laboratory animals. Cephaloridine is actively transported into the proximal tubular cell by an organic anion transport system while transport across the lumenal membrane into tubular fluid appears restricted. High intracellular concentrations of cephaloridine are attained in the proximal tubular cell which are critical to the development of nephrotoxicity. There is substantial evidence indicating that oxidative stress plays a major role in cephaloridine nephrotoxicity. Cephaloridine depletes reduced glutathione, increases oxidized glutathione and induces lipid peroxidation in renal cortical tissue. The molecular mechanisms mediating cephaloridine-induced oxidative stress are not well understood. Inhibition in gluconeogenesis is a relatively early biochemical effect of cephaloridine and is independent of lipid peroxidation. Furthermore, cephaloridine inhibits gluconeogenesis in both target (kidney) and non-target (liver) organs of cephaloridine toxicity. Since glucose is not a major fuel of proximal tubular cells, it is unlikely that cephaloridine-induced tubular necrosis is mediated by the effects of this drug on glucose synthesis.

Mechanisms mediating cephaloridine inhibition of renal gluconeogenesis.

Incubation of renal cortical slices with cephaloridine (CPH) markedly inhibits pyruvate-supported gluconeogenesis, an effect which is independent of CPH-induced lipid peroxidation. CPH was found to inhibit pyruvate-supported gluconeogenesis in a time-and concentration-dependent manner. Pyruvate-supported gluconeogenesis was inhibited as early as 10 min following incubation of renal cortical slices with 5 mM CPH. Similarly, endogenous gluconeogenesis was impaired following CPH treatment. CPH depressed the renal cortical slice content of ATP by 50%, but only following 90 and 120 min of drug exposure, suggesting that mitochondrial dysfunction does not mediate the inhibition of gluconeogenesis by CPH. To identify the intracellular site(s) of CPH inhibition of gluconeogenesis, the effects of CPH on glucose production were evaluated using substrates catalyzed by rate-limiting reactions. CPH inhibited renal cortical slice gluconeogenesis when the following substrates were used: pyruvate (mitochondrial), oxaloacetate and fructose-1,6-diphosphate (FDP) (postmitochondrial), and glucose-6-phosphate (G6P, endoplasmic reticulum). Inhibition of G6P-supported gluconeogenesis occurred within 5 min of incubation with 5 mM CPH. Direct addition of CPH to microsomal suspensions inhibited G6Pase activity in a concentration-dependent fashion. By contrast, addition of CPH to cytosolic fractions did not affect FDPase activity. CPH increased the Km and decreased the Vmax of G6Pase, indicating mixed competitive and noncompetitive inhibition. These data indicate that the profound inhibition of renal cortical slice gluconeogenesis by CPH is mediated by inhibition of microsomal G6Pase activity.