Improvement in glycemic control and outcome corresponding to intensive insulin therapy protocol development.

Background: Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control.

Tight glycaemic control: a prospective observational study of a computerised decision-supported intensive insulin therapy protocol.

Introduction: A single centre has reported that implementation of an intensive insulin protocol, aiming for tight glycaemic control (blood glucose 4.4 to 6.1 mmol/l), resulted in significant reduction in mortality in longer stay medical and surgical critically ill patients.

Role of the PDZ scaffolding protein in tubule cells in maintenance of polarised function.

Polarized tubule epithelial cell functions are dependent on correct delivery of effector proteins to the target apical or basolateral plasma membrane and associated cortical cytoskeleton. PDZ (Postsynaptic density protein 95/Drosophila Disks large/Zona occludens-1) domain-containing proteins have been identified as playing a critical role in membrane trafficking and sorting of ion transporters, receptors and other signalling proteins. These scaffolding proteins coordinate the assembly of functional plasma membrane multiprotein complexes, through PDZ domain binding to a consensus amino acid motif within the carboxyl-terminus of target proteins.

Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output.

Nitric oxide (NO), produced via inducible NO synthase (iNOS), can modulate polarized epithelial processes such as solute transport. Given the high reactivity of NO, we hypothesized that optimal NO regulation of polarized epithelial functions is achieved through compartmentalization of iNOS, allowing local NO delivery to its molecular targets. Here, we show that iNOS localizes to the apical domain of epithelial cells within a submembranous protein complex tightly bound to cortical actin.

Coexpressed nitric oxide synthase and apical beta(1) integrins influence tubule cell adhesion after cytokine-induced injury.

In sepsis-induced acute renal failure, actin cytoskeletal alterations result in shedding of proximal tubule epithelial cells (PTEC) and tubular obstruction. This study examined the hypothesis that inflammatory cytokines, released early in sepsis, cause PTEC cytoskeletal damage and alter integrin-dependent cell-matrix adhesion. The question of whether the intermediate nitric oxide (NO) modulates these cytokine effects was also examined.