Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation

Anticoagulants are widely used in the prevention of thromboembolic disease (particularly during the postoperative period) and in the curative treatment of deep vein thromboses. Two classes of anticoagulants are currently available: heparins (standard heparin, low molecular weight heparin) and coumarin anticoagulants. The choice of anticoagulant must take into account the clinical context (preventive or curative treatment), as well as the pharmacological and pharmacokinetic properties of the anticoagulant. This treatment requires laboratory monitoring adopted to the anticoagulant selected.     

Complexes of focal adhesion kinase (FAK) and Crk-associated substrate (p130(Cas)) are elevated in cytoskeleton-associated fractions following adhesion and Src transformation. Requirements for Src kinase activity and FAK proline-rich motifs

The focal adhesion kinase (FAK) and Crk-associated substrate, p130(Cas) (Cas), have been implicated in diverse signaling pathways including those mediated by integrins, G-protein-coupled receptors, tyrosine kinase receptors, and the v-src and v-crk oncogenes. The recent identification of a direct interaction between FAK and Cas prompted the examination of potential regulation of FAK.Cas complexes by factors that result in concomitant increase in their phosphotyrosine content, namely cell adhesion and transformation by Src. Both conditions resulted in elevated FAK.Cas complex levels in nonionic detergent-insoluble fractions, indicating increased association with the cytoskeleton. For activated Src, this effect requires an active Src catalytic domain but not its Src homology 2 (SH2) or Src homology 3 (SH3) domains. FAK kinase domain tyrosines 576 and 577 are also required, suggesting that direct phosphorylation of these sites by Src may influence the solubility and/or stability of the complex. FAK-Cas association was only observed in the context of Cas binding to at least one of two distinct proline-rich sites on FAK. These findings firmly establish a direct interaction between FAK and Cas and demonstrate that Src can influence the subcellular localization of the complex by a tyrosine phosphorylation-dependent mechanism.     

Juvenile pilocytic astrocytoma masquerading as amblyopia

PURPOSE: A healthy 13-year-old girl, previously diagnosed with amblyopia in her right eye, was seen in consultation after her vision continued to decrease. METHODS: A complete ophthalmologic examination including visual field testing and optic nerve photography was performed in the neuro-ophthalmologic clinic. Magnetic resonance imaging study was also obtained. RESULTS: Visual sensory deficits and pale optic nerves were noted on clinical examination. Visual field testing showed a chiasmatic junctional defect. Magnetic resonance imaging verified a large chiasmatic mass, histologically proven to be a juvenile pilocytic astrocytoma. CONCLUSION: Early recognition of signs and symptoms of chiasmatic lesions is essential for preventing visual loss.     

Role of lipopolysaccharide in colonization of the mouse intestine by Salmonella typhimurium studied by in situ hybridization

An avirulent, streptomycin-resistant Salmonella typhimurium strain, SL5319, and its lipopolysaccharide (LPS)-deficient mutant strain, SL5325, differ in their ability to colonize the large intestines of streptomycin-treated mice. When fed to mice independently, the strains colonize equally well, but when fed together, the LPS-deficient mutant is outcompeted by the wild-type strain during establishment in the gut (J.J. Nevola, B.A.D. Stocker, D.C. Laux, and P.S. Cohen, Infect. Immun. 50:152-159, 1985). In the present study, the spatial distribution in the intestinal mucosal layer of the two strains was visualized by specific hybridization to bacterial rRNA in histological sections of mouse colon and cecum. The first day after infection, 9.8% of the smooth SL5319 cells observed in mucus were found to be associated with the mouse epithelial cells, but three days after infection, the corresponding fraction of adhering bacteria was reduced to 2.1%. The LPS-deficient S. typhimurium strain was confined to the part of the mucosal layer closest to the colonic lumen and was not observed to adhere to the epithelium either at day 1 or 3 after infection. Quantitative determinations of the distance from the S. typhimurium cells to the epithelial wall confirmed that the average distance for the rough S. typhimurium SL5325 was much larger than for its smooth counterpart, S. typhimurium SL5319. Quantification of the hybridization signal from bacteria isolated from the cecal mucus revealed that the two strains had the same ribosome concentration, indicating that they have the same potential for growth in the intestinal environment. On the basis of these observations, we suggest that the better colonization ability of the strain carrying wild-type LPS is due to the better abilities to penetrate the intestinal mucosal layer and to subsequently bind to the epithelial cells in vivo.     

Sexual dimorphism in the physiques of World Championship divers

The aim of this study was to evaluate sexual dimorphism in male (n = 43) and female (n = 39) springboard and platform divers at the 1991 World Diving Championships in Perth, Western Australia. In addition to recording the age, height and body mass of each diver, measurements were taken of 8 skinfolds, 13 girths, 8 breadths and depths, and 11 lengths. The derived variables were somatotype, sum of 6 skinfolds (SUM6) and height-adjusted proportional z-scores. The mean (+/- s) values for the males were: age, 22.2 +/- 4.6 years; height, 171 +/- 9 cm; body mass, 66.7 +/- 10.2 kg; somatotype, 2.0-5.3-2.4 +/- 0.5-1.0-0.8; SUM6, 45.9 +/- 11.4 mm. For the females, these values were: age, 20.9 +/- 3.8 years; height, 161 +/- 6 cm; body mass, 53.7 +/- 5.5 kg; somatotype, 2.8-3.8-2.8 +/- 0.7-1.0-0.9; SUM6, 65.6 +/- 17.0 mm. The males were taller, heavier, more mesomorphic, less endomorphic and had a smaller SUM6 than the females (P < 0.01). A series of discriminant function analyses were applied to groups of variables. Wilks' lambda and the overall F-ratio were highly significant (P < 0.001), with correct classification of sex reaching 84-99%. The best combinations of variables were as follows: (1) absolute size, 3 girths + SUM6, or body mass + SUM6 + height (Wilks' lambda = 0.17-0.35); (2) relative size, 2 girths + SUM6 + body mass. Combinations of breadths and lengths, skinfolds, or somatotype components, were less successful, with 84-87% classified correctly (Wilks' lambda = 0.40-0.48). We conclude that, in addition to the expected absolute size differences, sexual dimorphism between male and female divers can be explained by differences in relative size, skinfolds and somatotype, and that these differences may have implications for coaching and selection in diving.     

Differences in the treatment of coronary heart disease between countries as revealed in the Scandinavian Simvastatin Survival Study (4S)

AIM: To assess differences in treatment of ischaemic heart disease in the Scandinavian countries. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study (4S) lasted 5.4 years and showed that death rates in 4444 patients with coronary heart disease were 30% lower in those treated with simvastatin to lower serum cholesterol than in those given placebo. Apart from this main result, the 4S provided detailed information on rates of death and other manifestations of coronary heart disease, as well as on use of non-lipid forms of therapy. There were substantial differences in 4S placebo group rates of mortality, coronary deaths and major coronary events between countries. Surgical and medical therapy varied importantly between countries. CONCLUSIONS: Major inter-country differences in rates of death and myocardial infarction in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking. They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease.     

Grain feeding and the dissemination of acid-resistant Escherichia coli from cattle

The gastric stomach of humans is a barrier to food-borne pathogens, but Escherichia coli can survive at pH 2.0 if it is grown under mildly acidic conditions. Cattle are a natural reservoir for pathogenic E. coli, and cattle fed mostly grain had lower colonic pH and more acid-resistant E. coli than cattle fed only hay. On the basis of numbers and survival after acid shock, cattle that were fed grain had 10(6)-fold more acid-resistant E. coli than cattle fed hay, but a brief period of hay feeding decreased the acid-resistant count substantially.     

Gut-trophic effects of keratinocyte growth factor in rat small intestine and colon during enteral refeeding

BACKGROUND: Keratinocyte growth factor (KGF) induces proliferation of gut epithelium in rat models, but KGF-nutrient interactions have not been studied. An experimental model of fasting-induced gut atrophy followed by different levels of enteral refeeding was used to investigate the influence of nutrient availability on the gut-trophic effects of exogenous KGF. METHODS: After a 3-day fast, rats were enterally refed either ad libitum or at 25% of ad libitum intake for 3 subsequent days. Either intraperitoneal KGF (5 mg/kg/d) or saline was given in each dietary regimen. Wet weight, DNA, and protein content were measured as indices of full-thickness cellularity in duodenum, jejunum, ileum, and colon. Villus height in small bowel segments and crypt depth in all gut tissues were measured as specific indices of mucosal growth. RESULTS: Refeeding at 25% of ad libitum intake significantly decreased full-thickness cellularity and mucosal growth indices in duodenum, jejunum, and ileum. In the colon, only protein content fell significantly and crypt depth was maintained. KGF administration during 25% refeeding did not alter full-thickness indices in any small bowel segment or affect jejunal mucosal growth. In contrast, KGF normalized duodenal villus height (p < .01) and duodenal and ileal crypt depth (p < .05) only in the 25%-refed model. KGF significantly increased ileal villus height in both ad libitum and 25%-refed rats (by 43% and 48%, respectively, p < .05) and markedly increased colonic cellularity and mucosal crypt depth with both levels of refeeding (p < .01). CONCLUSIONS: Rat small bowel growth is more sensitive than colon to the level of enteral refeeding after a 3-day fast. KGF administration does not affect jejunal growth, but specifically prevents atrophy of duodenal and ileal mucosa during hypocaloric, hyponitrogenous refeeding. In ileum and colon, some KGF-mediated growth responses are independent of the level of enteral refeeding. Thus gut-trophic effects of KGF and KGF interactions with the level of nutrient intake are tissue-specific.