Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization

Intestinal epithelial cells respond to Salmonella typhimurium by internalizing this pathogen and secreting, in a polarized manner, an array of chemokines which direct polymorphonuclear leukocyte (PMN) movement. Notably, interleukin-8 (IL-8) is secreted basolaterally and directs PMN through the lamina propria, whereas pathogen-elicited epithelial chemoattractant (PEEC) is secreted apically and directs PMN migration across the epithelial monolayer to the intestinal lumen. While most studies of S. typhimurium pathogenicity have focused on the mechanism by which this bacterium invades its host, the enteritis characteristically associated with salmonellosis appears to be more directly attributable to the PMN movement that occurs in response to this pathogen. Therefore, we sought to better understand the relationship between S. typhimurium invasion and epithelial promotion of PMN movement. First, we investigated whether S. typhimurium becoming intracellular was necessary or sufficient to induce epithelial promotion of PMN movement. Blocking S. typhimurium invasion by preventing, with cytochalasin D, the epithelial cytoskeletal rearrangements which mediate internalization did not reduce the epithelial promotion of PMN movement. Conversely, bacterial attainment of an intracellular position was not sufficient to induce model epithelia to direct PMN transmigration, since neither basolateral invasion by S. typhimurium nor apical internalization of an invasion-deficient mutant (achieved by inducing membrane ruffling with epidermal growth factor) induced this epithelial cell response. These results indicate that specific interactions between the apical surface of epithelial cells and S. typhimurium, rather than simply bacterial invasion, mediate the epithelial direction of PMN transmigration. To further investigate the means by which S. typhimurium induces epithelia to direct PMN movement, we investigated whether the same signaling pathways regulate secretion of IL-8 and PEEC. IL-8 secretion, but not PEEC secretion, was activated by phorbol myristate acetate and blocked by an inhibitor (mg-132) of the proteosome which mediates NF-kappabeta activation. Further, secretion of IL-8, but not PEEC, was activated by an entry-deficient (HilDelta) S. typhimurium mutant or by basolateral invasion of a wild-type strain. Together, these results indicate that distinct signaling pathways mediate S. typhimurium invasion, induction of IL-8 secretion, and induction of PEEC secretion in model intestinal epithelia.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

It is time to move from the nursing process to critical thinking

As we reflect on the concept of critical thinking in perioperative nursing practice, we should ask ourselves whether we think critically. If not, we must learn the principles of critical thinking and apply them in our clinical practice settings. Our perioperative nurse managers and directors must demonstrate critical thinking in leading other nurses in the delivery of quality, cost-effective, service-oriented patient care. They also must identify peers who use critical thinking skills to support and sustain them in their quest.     

马尔克海的眼睛

West 8是一个国际性的城市设计和景观设计事务所,由Adriaan Geuze于1987年成立。在过去20年West 8已经成长为一个由景观建筑师和工程师组成的国际领先的实践性公司。     

Unusual case of tracheal agenesis

We describe the clinical presentation and pathological features of an unusual case of tracheal agenesis. The axial derivatives of the primitive foregut between the larynx and stomach were represented by a single structure featuring sequential segmentation into regions showing exclusively tracheal or esophageal differentiation in a pattern that is not easily classified by existing nosologic systems nor explained by the conventional hypothesis of dysontogenesis.     

A Semi-Theoretical Approach to a Correlation for the Thermal Conductivity of a Beryllium Pebble Bed

In the framework of the European Fusion Technology Programme, Lithium ceramics and Beryllium packed pebble beds are foreseen to be used as Tritium breeders and neutron multipliers, respectively, for the Helium Cooled Pebble Bed breeding blanket of a fusion power reactor operating with a D-T plasma. The present work is focused on the semi-theoretical investigation of the thermal conductivity of single size Beryllium pebble beds, starting from the main hypothesis that this conductivity depends linearly on pebble bed local temperature and mechanical volumetric strain and introducing a method to determine the coefficients of such dependence on the basis of the results obtained by the SUPER-PEHTRA experiments. It has been mainly assumed that the SUPER-PEHTRA Beryllium pebble bed can be considered as a homogeneous, isotropic, and linear elastic medium, and the analytical solution of the direct static problem of the thermo-elasticity for such a system has been used to fit the experimental thermal distributions, uncovering the best values for the thermal conductivity function coefficients. This thermal conductivity has been used together with a constitutive model, realistically taking into account the pebble bed mechanical behavior to reproduce the experimental tests. The results of the analyses agree quite well with the experimental ones, thus encouraging the use of the derived thermal conductivity correlation for Beryllium pebble beds undergoing low plastic volumetric strain.