Cell death at the intestinal epithelial front line.

The intestinal epithelium represents the largest epithelial surface in our body. This single-cell-layer epithelium mediates important functions in the absorption of nutrients and in the maintenance of barrier function, preventing luminal microorganisms from invading the body. Due to its constant regeneration the intestinal epithelium is a tissue not only with very high proliferation rates but also with very prominent physiological and pathophysiological cell death induction. The normal physiological differentiation and maturation of intestinal epithelial cells leads to their shedding and apoptotic cell death within a few days, without disturbing the epithelial barrier integrity. In contrast excessive intestinal epithelial cell death induced by irradiation, drugs and inflammation severely impairs the vital functions of this tissue. In this review we discuss cell death processes in the intestinal epithelium in health and disease, with special emphasis on cell death triggered by the tumour necrosis factor receptor family.

Ventricular repolarization during uni and biventricular pacing in normal subjects.

BACKGROUND: The cardiac depolarization-repolarization process (D-REPP) may differ among various modes of cardiac pacing depending on the paced chamber(s) and lead position. We intended to assess the effect of different modes of cardiac pacing (left, right and biventricular) on the D-REPP as expressed in QRS, QT, peak-to-end of the T wave (PETW) and PETW/QT intervals and their dispersion. These intervals were compared during pacing and sinus rhythm. METHODS: We studied 31 patients without structural heart disease and with normal ventricular function who underwent right, left and biventricular pacing. Simultaneous 12-leads were recorded and electronic calipers were used for measurement of the QRS, QT, corrected QT (cQT), PETW, and PETW/QT ratio. RESULTS: cQT duration, PETW, standard deviation of the PETW, PETW/QT, and QRS duration were shorter during sinus rhythm. Isolated stimulation of the right or the left ventricle produced a similar increase in all the intervals and did not display significant differences in terms of cQT duration, PETW, PETW/QT, or QRS duration. Biventricular pacing produced a significant increase in cQT, QRS, PETW and PETW/QT, but these values were shorter than those obtained during isolated right or left ventricular stimulation. CONCLUSION: In subjects without structural heart disease, cardiac pacing produces a significant increase of the D-REPP. No differences were found when comparing right or left univentricular pacing. Biventricular stimulation induces less perturbation of the D-REPP.

Dimerization of Smac is crucial for its mitochondrial retention by XIAP subsequent to mitochondrial outer membrane permeabilization.

Following the apoptotic permeabilization of the outer mitochondrial membrane, the inter-membrane space protein second mitochondria-derived activator of caspases (Smac) is released into the cytosol. Smac efficiently promotes apoptosis by antagonizing x-linked inhibitor of apoptosis protein (XIAP), an inhibitor of caspases-9, -3, and -7, via a short NH(2)-terminal inhibitor of apoptosis protein (IAP) binding motif (AVPI). Native Smac dimerizes to form a highly stable and inflexible elongated arch, however, a functional role for this outstretched structure so far remained unknown. Using time-lapse single-cell imaging of DLD-1 and HCT-116 colon cancer cells, we here demonstrate that upon mitochondrial outer membrane permeabilization physiological expression levels of XIAP are sufficient to selectively prolong the release of dimeric but not monomeric Smac. Elevating the expression of XIAP further extended the release duration of dimeric Smac and resulted in the mitochondrial retention of a significant proportion of the Smac pool. In contrast, monomeric Smac was always fully released and the release kinetics were not affected by altered XIAP expression. Our findings therefore indicate that the dimerization of Smac is critical for the XIAP-mediated retention of Smac at or inside the mitochondria. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Dietary polyphenols protect against N-nitrosamines and benzo(a)pyrene-induced DNA damage (strand breaks and oxidized purines/pyrimidines) in HepG2 human hepatoma cells.

BACKGROUND: Dietary polyphenols have been reported to have a variety of biological actions, including anticarcinogenic and antioxidant activities. AIM OF THE STUDY: In the present study we investigated the protective effect of dietary polyphenols against N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR) and benzo(a)pyrene (BaP)-induced DNA damage (strand breaks and oxidized purines/pyrimidines) in HepG2 cells. METHODS: Human hepatocellular carcinoma (HepG2) cells, which retain many specialized liver functions and drug metabolizing enzyme activities, were used as in vitro model for human hepatocytes. NDMA, NPYR and BaP were employed to induce DNA damage. DNA damage (strand breaks, oxidized pyrimidines and oxidized purines) was evaluated by the alkaline single cell gel electrophoresis or comet assay. RESULTS: None of the polyphenols concentrations tested in presence or absence of Fpg (formamidopyrimidine-DNA glycosylase), or Endo III (Endonuclease III) caused DNA damage per se. Increasing concentrations of BaP (25-100 microM) induced a significant increase of DNA strand breaks, Fpg and Endo III sensitive sites in a dose dependent manner. Myricetin and quercetin decreased DNA strand breaks and oxidized pyrimidines induced by NDMA, but not oxidized purines. However, both flavonoids reduced oxidized pyrimidines and purines induced by NPYR. DNA strand breaks induced by NPYR were prevented by quercetin, but not by myricetin. BaP-induced DNA strand breaks and oxidized pyrimidines were strongly reduced by myricetin and quercetin, respectively. While oxidized purines induced by BaP were reduced by quercetin, myricetin had no protective effect. (+)-Catechin and (-)-epicatechin reduced DNA strand breaks, oxidized pyrimidines and oxidized purines induced by NDMA. DNA strand breaks, and oxidized purines induced by NPYR were also prevented by (+)-catechin and (-)-epicatechin, while the maximum reduction of oxidized pyrimidines was found by (+)-catechin and (-)-epicatechin at 10 microM. (+)-Catechin and (-)-epicatechin decreased also DNA strand breaks and oxidized pyrimidines but not oxidized purines induced by BaP. CONCLUSIONS: Our results clearly indicate that polyphenols protect human derived cells against DNA strand breaks and oxidative DNA damage effects of NDMA, NPYR or BaP, three carcinogenic compounds which occur in the environment.

Efecto de la administración de BCG sobre la hiperreactividad bronquial y valores de IgE en niños con asma / Effect of the administration of BCG on the bronchial hyperreactivity and values of IgE in children with asthma

El objetivo de este estudio fue determinar el efecto de la administración intradérmica de BCG sobre la hiperreactividad bronquial (HRB) y valores séricos de IgE total en niños con asma bronquial. Se realizó un estudio experimental autocontrolado en 15 niños con asma bronquial persistente, a los cuales se les realizaron determinaciones basales de flujo espiratorio máximo (PEF, por sus siglas en inglés) determinando su HRB mediante prueba de provocación bronquial con el ejercicio (PBE) en bicicleta ergométrica, y simultáneamente se dosificaron sus niveles de IgE sérica total por método de electroquimioluminisencia. Al inicio del estudio se procedió a la administración de 0,1 cc de BCG intradérmica, repitiendo la PBE y la determinación de IgE a las 6 semanas. Se analizó la información mediante prueba de t de Student para grupos pareados, con un nivel e significancia de p<0,05. Los resultados demuestran una mejoría estadísticamente significativa en la tolerancia al ejercicio, siendo la caída del PEF postejercicio mucho menor -6,88 por ciento vs. -18,05 por ciento (t=4,44; p=0,01) luego de las 6 semanas, sin existir un tiempo preciso en que se logre una mejor disminución porcentual (p=0,53). Los valores promedio de IgE, si bien fueron similares antes y después de la administración de BCG: 320 Ul/ml (p=0,53), muestran una disminución significativa luego del tratamiento en la mayoría de los casos estudiados (73,33 por ciento; p=0,01). Finalmente existe una asociación significativa (r=0,69; p=0,004) entre ésta disminución y la mejoría del PEF con la administración de BCG. Se concluye, que la administración intradérmica de BCG produce mejoría clínica significativa de la HRB y disminución de los niveles de IgE en una proporción significativa de pacientes. Se requieren más estudios clínicos en grupos estratificados y controlados antes de recomendar el uso de la BCG como inmunoterapia para el asma.

Análisis de recetas antihipertensivas despachadas en el hospital "Jaime Mendoza" servicio de farmacia / Analisys of antihypertensive prescriptions delivered in \"Jaime Mendoza\" hospital

El presente estudio comprende un universo de 22.786 recetas despachadas en la farmacia del Hospital "Jaime Mendoza" de la C.N.S. en los meses de mayo a julio de 1997. Demostrándose que solo el 3.6 por ciento eran de medicación antihipertensica; se demostró asimismo que el 62 por ciento pertenecen al sexo femenino y que prescribían con mayor frecuencia en los servicios de Medicina Interna y Endocrinología. Se observó también que el medicamento con más demanda fue el Enalapril en un porcentaje del 36 por ciento