Role of the Gut⁻Liver Axis in Driving Parenteral Nutrition-Associated Injury.

For decades, parenteral nutrition (PN) has been a successful method for intravenous delivery of nutrition and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. Although the benefits of PN are evident, its use does not come without a significant risk of complications. For instance, parenteral nutrition-associated liver disease (PNALD)-a well-described cholestatic liver injury-and atrophic changes in the gut have both been described in patients receiving PN. Although several mechanisms for these changes have been postulated, data have revealed that the introduction of enteral nutrition may mitigate this injury. This observation has led to the hypothesis that gut-derived signals, originating in response to the presence of luminal contents, may contribute to a decrease in damage to the liver and gut. This review seeks to present the current knowledge regarding the modulation of what is known as the "gut⁻liver axis" and the gut-derived signals which play a role in PN-associated injury.

Symptoms, impairment and illness intrusiveness--their relationship with depression in women with CFS/ME.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an illness in which physiological and psychological factors are believed to interact to cause and maintain CFS/ME in an individual predisposed to it. The various symptoms and impairments associated with CFS/ME have a large impact on quality of life. The purpose of the present study was to identify the extent to which the core symptoms and impairments associated with CFS/ME relate to depression in women with CFS/ME, and to discover whether these relationships were mediated by illness intrusiveness. CFS/ME was found to be a highly intrusive illness, intruding into more life domains and to a greater degree than other illnesses. The effects of both symptoms and impairment on depression were, in part, mediated by illness intrusiveness. Although symptoms severity and impairment had both direct and indirect effects on depression, illness intrusiveness was the strongest predictor of depression.

Structural polarity and functional bile canaliculi in rat hepatocyte spheroids.

Primary hepatocytes self-assemble into spheroids that possess tight junctions and microvilli-lined channels. We hypothesized that polarity develops gradually and that the channels structurally and functionally resemble bile canaliculi. Immunofluorescence labeling of apical and basolateral proteins demonstrated reorganization of the membrane proteins into a polarized distribution during spheroid culture. By means of fluorescent dextran diffusion and confocal microscopy, an extensive network of channels was revealed in the interior of the spheroids. These channels connected over several planes and opened to pores on the surface. To examine the content of apical proteins in the channel membranes, the bile canalicular enzyme dipeptidyl peptidase IV (DPPIV) was localized using a fluorogenic substrate, Ala-Pro-cresyl violet. The results show that DPPIV activity is heterogeneously distributed in spheroids and localized in part to channels. Bile acid excretion was then investigated to demonstrate functional polarity. A fluorescent bile acid analogue, fluorescein isothiocyanate-labeled glycocholate, was taken up into the spheroids and excreted into bile canalicular channels. Due to the structural polarity of spheroids and their ability to excrete bile into channels, they are a unique three-dimensional model of in vitro liver tissue self-assembly. (Videoanimations of some results are available at http://hugroup.cems.umn.edu/research_movies).