El análisis de las tasas de reingreso en la unidad de cuidados intensivos después de la puesta en práctica de un equipo de respuesta rápida en un hospital universitario / The analysis of re-entry rates in the intensive care unit after the implementation of a rapid response team in a university hospital

Objetivos. Comparar las tasas de reingreso en la UCI antes y después de la implementación de un equipo de respuesta rápida (RRT) e identificar los factores de riesgo para la readmisión. Diseño Estudio cuasiexperimental before-after. Lugar Hospital universitario. Pacientes Todos los pacientes que fueron dados de alta de la UCI de enero a diciembre de 2008 (grupo control) y de enero 2010 a diciembre 2012 (grupo intervención). Intervención Implementación de un RRT. Principales variables de interés Los datos incluidos demográfica, los diagnósticos de ingreso, readmisión UCI, APACHE II, SOFA y TISS 28 puntuación y de evaluación de los pacientes dados de alta de la UCI por un TSR. Resultados Durante el período de estudio, 380 pacientes fueron analizados en el período anterior a la implementación de la RRT y 1,361 después de la implementación. Hubo una tendencia a disminuir las tasas de reingreso después de un año de la implementación de un RRT. APACHE II y SOFA de alta de la UCI fueron factores independientes asociados a la readmisión, así como lo tipo de paciente médico. Conclusiones La intervención del RRT resultó en una reducción sostenida de las tasas de reingreso un año después de la implementación de este servicio. El uso de un equipo especializado en instituciones de salud puede ser recomendado para los pacientes supervivientes de la UCI.

Lip squamous cell carcinoma in a Brazilian population: epidemiological study and clinicopathological associations.

OBJECTIVES: It was evaluated epidemiological aspects of primary lip squamous cell carcinoma (LSCC) and its associations with clinicopathological factors. STUDY DESIGN: This retrospective, cross-sectional study analysed a socio-demographic, clinical, and morphological data of HNSCC in a Brazilian population (n=30). Data analysis included descriptive statistics and bivariate analyses using the chi-square and Fisher 's exact tests to compare the variables. RESULTS: The LSCC represented 10.8% of all oral cavity squamous cell carcinoma. Lip malignant disease was more prevalent in elderly men, with male-to-female ratio of 5:1. Lower lip was more affected. It was observed high rates of chronic solar exposure, and tobacco and alcohol drinking habits. Clinically, early TNM staging, small tumour lesions, and non-metastatic disease were predominant findings. It was identified a high frequency of well differentiated tumor samples. Worse Karnofsky performance status was associated with cervical metastasis. CONCLUSIONS: Our findings showed that LSCC patients exhibited similar epidemiological and clinical profiles as noted in other studies. Still, the occurrence of metastatic disease was associated with a worse physical performance status of the LSCC patients during diagnosis.

Connexin36, an essential element in the rod pathway, is highly expressed in the essentially rodless retina of Gallus gallus.

Electrical coupling provided by connexins (Cx) in gap junctions (GJ) plays important roles in both the developing and the mature retina. In mammalian nocturnal species, Cx36 is an essential component in the rod pathway, the retinal circuit specialized for night, scotopic vision. Here, we report the expression of Cx36 in a species (Gallus gallus) that phylogenetic development endows with an essentially rodless retina. Cx36 gene is very highly expressed in comparison with other Cxs previously described in the adult retina, such as Cx43, Cx45, and Cx50. Moreover, real-time PCR, Western blot, and immunofluorescence all revealed that Cx36 expression massively increased over time during development. We thoroughly examined Cx36 in the inner and outer plexiform layers, where this protein was particularly abundant. Cx36 was observed mainly in the off sublamina of the inner plexiform layer rather than in the on sublamina previously described in the mammalian retina. In addition, Cx36 colocalized with specific cell markers, revealing the expression of this protein in distinct amacrine cells. To investigate further the involvement of Cx36 in visual processing, we examined its functional regulation in retinas from dark-adapted animals. Light deprivation markedly up-regulates Cx36 gene expression in the retina, resulting in an increased accumulation of the protein within and between cone synaptic terminals. In summary, the developmental regulation of Cx36 expression results in particular circuitry-related roles in the chick retina. Moreover, this study demonstrated that Cx36 onto- and phylogenesis in the vertebrate retina simultaneously exhibit similarities and particularities.

Mechanisms of the deleterious effects of tamoxifen on mitochondrial respiration rate and phosphorylation efficiency.

Tamoxifen (TAM), the widely prescribed drug in the prevention and therapy of breast cancer, is a well-known modulator of estrogen receptor (ER) that also inhibits the proliferation of different cell types that lack the ER. However, the ER-independent action mechanisms of TAM and its side effects have not been yet clarified. Mitochondria are essential in supporting the energy-dependent regulation of cell functions. Changes in mitochondria result in bioenergetic deficits leading to the loss of vital functions to cell survival. Therefore, this study describes the effects of TAM on mitochondrial bioenergetics, contributing to a better understanding of the biochemical mechanisms underlying the multiple antiproliferative and toxic effects of this drug. TAM at concentrations above 20 nmol/mg protein, preincubated with isolated rat liver mitochondria at 25 degrees C for 3 min, significantly depresses, in a dose-dependent manner, the phosphorylation efficiency of mitochondria as inferred from the decrease in the respiratory control and ADP/O ratios, the perturbations in mitochondrial transmembrane potential (DeltaPsi), the fluctuations associated with mitochondrial energization, and the phosphorylative cycle induced by ADP. Furthermore, TAM at up to 40 nmol/mg protein stimulates the rate of state 4 respiration and at higher concentrations it strongly inhibits state 3 and uncouples the mitochondrial respiration. The stimulation of state 4 respiration parallels the decrease of DeltaPsi as a consequence of proton permeability. The TAM-stimulatory action of ATPase is also observed in intact mitochondria, suggesting that TAM promotes extensive permeability to protons due to destructive effects in the structural integrity of the mitochondrial inner membrane. These multiple effects of TAM on mitochondrial bioenergetic functions, causing changes in the respiration, phosphorylation efficiency, and membrane structure, may explain the cell death induced by this drug in different cell types, its anticancer activity in ER-negative cells, and its side effects.

Mitochondrial permeability transition induced by the anticancer drug etoposide.

Etoposide (VP-16) is widely used for the treatment of several forms of cancer. The cytotoxicity of VP-16 has been assigned to the induction of apoptotic cell death but the signaling pathway for VP-16-induced apoptosis is essentially unknown. There is some evidence that this process depends on events associated with the loss of mitochondrial membrane potential (Delta Psi) and/or release of apoptogenic factors, putatively as a consequence of mitochondrial permeability transition (MPT) induction. This work evaluates the interference of VP-16 with MPT in vitro, which is characterized by the Ca(2+)-dependent depolarization of Delta Psi, the release of matrix Ca(2+) and by extensive swelling of mitochondria. Delta Psi depolarization and Ca(2+) release were measured with ion-selective electrodes, and mitochondrial swelling was monitored spectrophotometrically. Incubation of rat liver mitochondria with VP-16 results in a concentration-dependent induction of MPT, evidenced by an increased sensitivity to Ca(2+)-induced swelling, depolarization of Delta Psi, Ca(2+) release by mitochondria and stimulation of state 4 oxygen consumption. All of these effects are prevented by preincubating the mitochondria with cyclosporine A, a potent and specific inhibitor of the MPT. Therefore, VP-16 increases the sensitivity of isolated mitochondria to the Ca(2+)-dependent induction of the MPT. Together, these data provide a possible mechanistic explanation for the previously reported effects of VP-16 on apoptosis induction.

Modulation of the low affinity Ca2+-binding sites of skeletal muscle and blood platelets Ca2+-ATPase by nordihydroguaiaretic acid.

The antioxidant nordihydroguaiaretic acid (NDGA) inhibited the different sarco/endoplasmic reticulum Ca2+-ATPase isoforms found in skeletal muscle and blood platelets. For the sarcoplasmic reticulum, but not for the blood platelets Ca2+-ATPase, the concentration of NDGA needed for half-maximal inhibition was found to vary depending on the substrate used and its concentration in the assay medium. The phosphorylation of the sarcoplasmic reticulum Ca2+-ATPase by ATP and by Pi were both inhibited by NDGA. In leaky vesicles, measurements of the ATP<-->Pi exchange showed that NDGA increases the affinity for Ca2+ of the E2 conformation of the enzyme, which has low affinity for Ca2+. The effects of NDGA on the Ca2+-ATPase were not reverted by the reducing agent dithiothreitol nor by the lipid-soluble antioxidant butylated hydroxytoluene.

Uncoupling of Ca2+ transport ATPase in muscle and blood platelets by diacylglycerol analogues and cyclosporin A antagonism.

The possibility that diacylglycerol analogues might have a wider spectrum of intracellular targets than the well-known protein kinase C was investigated with vesicles containing the Ca2+-ATPase derived from the dense tubular system in platelets and from the sarcoplasmic reticulum of skeletal muscle. The diacylglycerol analogues PMA and 1-oleoyl-2-acetyl-rac-glycerol (OAG) inhibited Ca2+ accumulation by these vesicles, an effect that was antagonized by cyclosporin A. The inhibitory activity of PMA and OAG resulted from the uncoupling of the Ca2+-ATPase, characterized by a pronounced inhibition of Ca2+ uptake accompanied by a discrete decrease in ATPase activity and by the inhibition of the enzyme's phosphorylation by Pi, leading to both a decrease in ATP synthesis and an enhancement of Ca2+ efflux. The inhibition of Ca2+ uptake by PMA was found to decrease as the Ca2+ concentration in the medium was raised from 0.1 to 10.0 microM. This was observed with muscle, but not with platelet vesicles. In contrast, the ability of cyclosporin A to antagonize the inhibition of Ca2+ uptake by PMA also increased when the Ca2+ concentration in the medium was raised from 0.1 to 10.0 microM, but this was observed with both muscle and platelet vesicles. The fact that phospholipase C activity and products from the inositol metabolism have been described as localized in regions of the sarcoplasmic reticulum where Ca2+-ATPase and Ca2+ channels are found suggests a possible physiological role for these products in the regulation of cytosolic Ca2+ levels.

Modulation by fatty acids of Ca2+ fluxes in sarcoplasmic-reticulum vesicles.

The fatty acids palmitic (C16:0), stearic (C18:0), arachidic (C20:0) and arachidonic (C20:4) acids inhibit Ca2+ uptake and enhance Ca2+ efflux measured in vesicles derived from the sarcoplasmic reticulum of skeletal muscle. These effects of the fatty acids are impaired by the Ca(2+)-ATPase ligands Mg2+, Ca2+ and K+, and by drugs that block the leakage of Ca2+ through the Ca(2+)-ATPase such as Ruthenium Red, spermine [de Meis (1991) J. Biol. Chem. 266, 5736-5742] and thapsigargin [de Meis and Inesi (1992) FEBS Lett. 299, 33-35].

The enhancement of Ca2+ efflux from sarcoplasmic reticulum vesicles by urea.

Urea, in nondenaturing concentrations, inhibited Ca2+ uptake by sarcoplasmic reticulum vesicles with no concomitant effect on ATP hydrolysis. This inhibition was antagonized by 5 mM oxalate and 20 mM orthophosphate. At concentrations of 0.2 to 1.0 M, urea induced an increase in the Ca2+ efflux from preloaded vesicles diluted in a medium at pH 7.0 containing 2 mM ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid, 0.1 mM orthophosphate, and 0.1 mM MgCl2. The urea-induced efflux was arrested by ligands of the (Ca(2+)-Mg2+) ATPase, namely, K+, Mg2+, Ca2+, and ADP, and by ruthenium red and the polyamines spermine, spermidine, and putrescine. In the case of polyamines a dissociation between the effect on the efflux and the net Ca2+ uptake was observed, as only the efflux could be blocked by the drugs. Glycine betaine, trimethylamine-N-oxide, and sucrose antagonized the effects of urea on both the net Ca2+ uptake and the rate of Ca2+ efflux.