Nitric oxide-mediated beta 2-adrenoceptor relaxation is impaired in mesenteric veins from portal-hypertensive rats

BACKGROUND & AIMS: beta-Adrenergic relaxation seems to be mediated by nitric oxide. The aim of this study was to evaluate changes induced by portal hypertension in beta 2-adrenergic vasorelaxation. METHODS: Isolated rat mesenteric veins were relaxed by salbutamol, and nerve-mediated vasocontractions were induced by electrical field stimulation. Responses were evaluated in the presence of NG-nitro-L-arginine methyl ester (L-NAME) or tetrodotoxin. Immunocytochemical techniques were used for localization of neuronal NO synthase. RESULTS: Salbutamol-induced relaxations were decreased in rings from portal-hypertensive animals. L-NAME reduced these relaxations, but its effects were more pronounced in sham-operated rats. Tetrodotoxin decreased the effect of salbutamol only in rings from sham-operated animals. Combination of L-NAME and tetrodotoxin did not exert a greater effect than either of these agents alone. Veins from portal-hypertensive animals were more sensitive to S-nitroso-N-acetyl penicillamine. L-NAME increased vasocontractions by electrical stimulation only in rings from sham-operated rats. Veins from portal-hypertensive animals exhibited a specific degeneration of NO-containing nerve endings. CONCLUSIONS: beta 2-Adrenergic relaxation is impaired in mesenteric veins from portal-hypertensive rats, possibly as a result of a defective neuronal release of NO.     

Toxicological and kinetic study of musk xylene in rainbow trout, Oncorhynchus mykiss

In a prospective study of 6301 surgical patients in a university hospital, we examined the strength of association between ASA physical status classification and perioperative risk factors, and postoperative outcome, using both univariate analysis and calculation of the odds ratio of the risk of developing a postoperative complication by means of a logistic regression model. Univariate analysis showed a significant correlation (P < 0.05) between ASA class and perioperative variables (intraoperative blood loss, duration of postoperative ventilation and duration of intensive care stay), postoperative complications and mortality rate. Univariate analysis of individual preoperative risk factors demonstrated their importance in the development of postoperative complications in the related organ systems. Estimating the increased risk odds ratio for single variables, we found that the risk of complication was influenced mainly by ASA class IV (risk odds ratio = 4.2) and ASA class III (risk odds ratio = 2.2). We conclude that ASA physical status classification was a predictor of postoperative outcome.     

Fungal biotransformation of 6-nitrochrysene

The fungus Cunninghamella elegans was used to biotransform 6-nitrochrysene, a mutagen that is a widespread environmental contaminant. After 6 days, 74% of the 3H-labeled 6-nitrochrysene added had been metabolized to two isomeric sulfate conjugates. These conjugates were separated by high-performance liquid chromatography and identified by UV-visible, 1H nuclear magnetic resonance, and mass spectral techniques as 6-nitrochrysene 1-sulfate and 6-nitrochrysene 2-sulfate.     

Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion

The ab initio folding problem can be divided into two sequential tasks of approximately equal computational complexity: the generation of native-like backbone folds and the positioning of side chains upon these backbones. The prediction of side-chain conformation in this context is challenging, because at best only the near-native global fold of the protein is known. To test the effect of displacements in the protein backbones on side-chain prediction for folds generated ab initio, sets of near-native backbones (< or = 4 A C alpha RMS error) for four small proteins were generated by two methods. The steric environment surrounding each residue was probed by placing the side chains in the native conformation on each of these decoys, followed by torsion-space optimization to remove steric clashes on a rigid backbone. We observe that on average 40% of the chi1 angles were displaced by 40 degrees or more, effectively setting the limits in accuracy for side-chain modeling under these conditions. Three different algorithms were subsequently used for prediction of side-chain conformation. The average prediction accuracy for the three methods was remarkably similar: 49% to 51% of the chi1 angles were predicted correctly overall (33% to 36% of the chi1+2 angles). Interestingly, when the inter-side-chain interactions were disregarded, the mean accuracy increased. A consensus approach is described, in which side-chain conformations are defined based on the most frequently predicted chi angles for a given method upon each set of near-native backbones. We find that consensus modeling, which de facto includes backbone flexibility, improves side-chain prediction: chi1 accuracy improved to 51-54% (36-42% of chi1+2). Implications of a consensus method for ab initio protein structure prediction are discussed.     

Jejunogastric intussusception: a rare complication of gastric surgery

Jejunogastric intussusception is a rare complication of gastric surgery. We report a case in a 41-year-old woman subjected to gastrojejunostomy with truncal vagotomy 3 years before for pyloric stenosis. The jejunogastric intussusception was diagnosed by upper gastrointestinal series, ultrasonography, and computed tomography. Surgical management consisted of reduction and fixation. Treatment should be as early as possible to prevent gangrene of the invaginated segment.     

The use of cultured hepatocytes to investigate the mechanisms of drug hepatotoxicity

In the course of biotransformation reactions catalyzed both by cytochrome P450 and by conjugating enzymes, drug-derived reactive metabolites and active oxygen species can appear that may escape the detoxification process, initiating radical chain reactions (e.g., lipid peroxidation), covalently binding to macromolecules (proteins, DNA), or impairing the energetic balance of cells. This is usually followed by alterations of ion homeostasis that precede irreversible biochemical changes and cell death. There are, however, cellular mechanisms of defense that prevent, or repair, the damage caused by these reactive intermediates. Ultimately it is the balance between bioactivation, detoxification, and defense mechanisms that determines whether a compound will or will not elicit a toxic effect. Cultures of hepatocytes, including those of human origin, can be used to elucidate the mechanisms of drug toxicity. This is illustrated in the study of the mechanism of hepatotoxicity by diclofenac. Much less cytotoxicity is observed in nonmetabolizing hepatomas than in hepatocytes. The observed cell dysfunction parallels the biotransformation of the drug, and particularly the formation of the minor metabolite N,5-dihydroxydiclofenac by hepatocytes. This compound is able to inhibit mitochondrial ATP synthesis in hepatocytes.