Correlación de escalas de riesgo en hemorragia digestiva alta no variceal con mortalidad, resangrado y necesidad de intervención / Correlation of risk scales in non-variceal upper gastrointestinal bleeding with mortality, rebleeding and need for intervention

La hemorragia digestiva alta (HDA) es una urgencia frecuente. La evaluación inicial con escalas pronósticas pre y postendoscópicas es fundamental para conocer los pacientes con mayor riesgo de complicaciones y con ello decidir la realización de una intervención de urgencia. Hipótesis: Las escalas pronósticas pre y postendoscópicas validadas para HDA no variceal predicen mortalidad, resangrado y necesidad de intervención en nuestra población de pacientes. Objetivos. Primarios. Evaluar la correlación de las escalas pronósticas preendoscópicas Blatchford y Rockall y las post endoscópicas Forrest y Rockall con mortalidad, resangrado y necesidad de intervención intra-hospitalaria en HDA no variceal. Evaluar la concordancia entre los resultados de las escalas pre y postendoscópicas. Secundarios. Describir las causas más frecuentes y la mortalidad de HDA no variceal. (AU)

High digestive haemorrhage (HDA) is a frequent emergency. The initial evaluation with pre and postendoscopic prognostic scales is fundamental to know the patients with greater risk of complications and with this, decide to perform an emergency intervention. Hypothesis: The pre and postendoscopic prognostic scales validated for non-variceal HDA predict mortality, rebleeding and need for intervention in our patient population Objective: To evaluate the correlation of Blatchford and Rockall preendoscopic prognostic scales and post-endoscopic Forrest and Rockall with mortality, rebleeding and need for in-hospital intervention in nonvariceal HAD. To evaluate the concordance between the results of the pre and postendoscopic scales. Describe the most frequent causes and non-variceal HDA mortality. (AU)

Granulomatous lung masses in an elderly patient with inactive Crohn's disease.

This is a case report of a 77-year-old female with Crohn's disease manifested by recurrent bowel obstructions, who required surgical resections on two occasions but no further medical treatment. She presented 2 years later with pulmonary infiltrates, hilar adenopathy, and multiple lung masses. Biopsies of the masses demonstrated noncaseating granulomatous inflammation and fibrosis similar to the pathology from her bowel resection. Six months later, these pulmonary lesions partially resolved without therapy. This case illustrates significant pulmonary manifestations of Crohn's disease in the absence of active gastrointestinal disease.

Internal trehalose protects endocytosis from inhibition by ethanol in Saccharomyces cerevisiae.

Endocytosis in Saccharomyces cerevisiae is inhibited by concentrations of ethanol of 2 to 6% (vol/vol), which are lower than concentrations commonly present in its natural habitats. In spite of this inhibition, endocytosis takes place under enological conditions when high concentrations of ethanol are present. Therefore, it seems that yeast has developed some means to circumvent the inhibition. In this work we have investigated this possibility. We identified two stress conditions under which endocytosis was resistant to inhibition by ethanol: fermentation during nitrogen starvation and growth on nonfermentable substrates. Under these conditions, yeast accumulates stress protectors, primarily trehalose and Hsp104, a protein required for yeast to survive ethanol stress. We found the following. (i) The appearance of ethanol resistance was accompanied by trehalose accumulation. (ii) Mutant cells unable to synthesize trehalose also were unable to develop resistance. (iii) Mutant cells that accumulated trehalose during growth on sugars were resistant to ethanol even under this nonstressing condition. (iv) Mutant cells unable to synthesize Hsp104 were able to develop resistance. We conclude that trehalose is the major factor in the protection of endocytosis from ethanol. Our results suggest another important physiological role for trehalose in yeast.

Monoubiquitination is sufficient to signal internalization of the maltose transporter in Saccharomyces cerevisiae.

Monoubiquitination of the 12-transmembrane segment (12-TMS) Saccharomyces cerevisiae maltose transporter promoted the maximal internalization rate of this protein. This modification is similar to that of the 7-TMS alpha-factor receptor but different from that of the 12-TMS uracil and general amino acid permeases. This result shows that binding of ubiquitin-Lys63 chains is not required for maximal internalization of all 12-TMS-containing proteins.

Clathrin and two components of the COPII complex, Sec23p and Sec24p, could be involved in endocytosis of the Saccharomyces cerevisiae maltose transporter.

The Saccharomyces cerevisiae maltose transporter is a 12-transmembrane segment protein that under certain physiological conditions is degraded in the vacuole after internalization by endocytosis. Previous studies showed that endocytosis of this protein is dependent on the actin network, is independent of microtubules, and requires the binding of ubiquitin. In this work, we attempted to determine which coat proteins are involved in this endocytosis. Using mutants defective in the heavy chain of clathrin and in several subunits of the COPI and the COPII complexes, we found that clathrin, as well as two cytosolic subunits of COPII, Sec23p and Sec24p, could be involved in internalization of the yeast maltose transporter. The results also indicate that endocytosis of the maltose transporter and of the alpha-factor receptor could have different requirements.

Catabolite inactivation of the maltose transporter in nitrogen-starved yeast could be due to the stimulation of general protein turnover.

Addition of glucose to Saccharomyces cerevisiae inactivates the maltose transporter. The general consensus is that this inactivation, called catabolite inactivation, is one of the control mechanisms developed by this organism to use glucose preferentially whenever it is available. Using nitrogen-starved cells (resting cells), it has been shown that glucose triggers endocytosis and degradation of the transporter in the vacuole. We now show that maltose itself triggers inactivation and degradation of its own transporter as efficiently as glucose. This fact, and the observation that glucose inactivates a variety of plasma membrane proteins including glucose transporters themselves, suggests that catabolite inactivation of the maltose transporter in nitrogen-starved cells is not a control mechanism specifically directed to ensure a preferential use of glucose. It is proposed that, in this metabolic condition, inactivation of the maltose transporter might be due to the stimulation of the general protein turnover that follows nitrogen starvation.

Moderate concentrations of ethanol inhibit endocytosis of the yeast maltose transporter.

The maltose transporter in Saccharomyces cerevisiae is degraded in the vacuole after internalization by endocytosis upon nitrogen starvation in the presence of a fermentable substrate. This degradation, known as catabolite inactivation, is inhibited by the presence of moderate concentrations (2 to 6%, vol/vol) of ethanol. We have investigated the mechanism of this inactivation and have found that it is due to the inhibition of the internalization of the transporter by endocytosis. The results also indicate that this inhibition is due to alterations produced by ethanol in the organization of the plasma membrane which also affects to endocytosis of other plasma membrane proteins. Apparently, endocytosis is particularly sensitive to these alterations compared with other processes occurring at the plasma membrane.

Catabolite inactivation of the yeast maltose transporter requires ubiquitin-ligase npi1/rsp5 and ubiquitin-hydrolase npi2/doa4.

The maltose transporter in Saccharomyces cerevisiae is degraded in the vacuole after internalization by endocytosis when protein synthesis is impaired and a fermentable substrate is present. The possible implication of the ubiquitin pathway in this inactivation, known as catabolite inactivation, has been investigated. Using mutants deficient in npi1/rsp5 ubiquitin-protein ligase and npi2/doa4 ubiquitin-protein hydrolase, we have shown that these two enzymes are required for normal endocytosis and degradation of the transporter. These facts indicate that the ubiquitin pathway is involved in catabolite inactivation of the maltose transporter. The results also revealed that both enzymes act in the internalization step of endocytosis.

Catabolite inactivation of the yeast maltose transporter is due to proteolysis.

The maltose transport capacity of fermenting Saccharomyces cerevisiae rapidly decreases when protein synthesis is impaired. Using polyclonal antibodies against a recombinant maltose transporter-protein we measured the cellular content of the transporter along this inactivation process. Loss of transport capacity was paralleled by a decrease of cross-reacting material which suggests degradation of the transporter. We also show that in ammonium-starved cells the half-life of the maltose transporter is 1.3 h during catabolism of glucose and > 15 h during catabolism of ethanol.