Objective To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. Background Critically ill patients are at increased risk for systemic sepsis and, in some cases, multi-organ failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. Methods WT and IAP- KO mice were used to examine gut barrier function and tight junction protein levels during 48 h starvation and fed states. Human ileal fluid samples were collected from 20 patients post ileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 h +/− IAP supplementation in the drinking water. Results The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrates that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. Conclusions IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically-ill patients.

5-Hydroxytryptamine (5-HT) has the most diverse set of receptors in comparison with any other neurotransmitter or hormone in the body. To date, seven families of 5-HT receptors have been characterized. A great number of studies have been published regarding the role of 5-HT and its receptors in seizures. However, with a few exceptions, the net effect of activating or inhibiting each 5-HT receptor subtype on the development or severity of seizures remains controversial. Additionally, the results of studies, which have used knockout animals to investigate the role of 5-HT receptors in seizures, have sometimes been contradictory to those which have used pharmacological tools. The present study aims to review the available data regarding the influence of each receptor subtype on seizure development and, when possible, reconcile between the apparently different results obtained in these studies.