Angiocrine Regulation of Epithelial Barrier Integrity in Inflammatory Bowel Disease

Inflammatory bowel disease describes chronic inflammatory disorders. The incidence of the disease is rising. A major step in disease development is the breakdown of the epithelial cell barrier. Numerous blood vessels are directly located underneath this barrier. Diseased tissues are heavily vascularized and blood vessels significantly contribute to disease progression. The gut-vascular barrier (GVB) is an additional barrier controlling the entry of substances into the portal circulation and to the liver after passing the first epithelial barrier. The presence of the GVB rises the question, whether the vascular and endothelial barriers may communicate bi-directionally in the regulation of selective barrier permeability. Communication from epithelial to endothelial cells is well-accepted. In contrast, little is known on the respective backwards communication. Only recently, perfusion-independent angiocrine functions of endothelial cells were recognized in a way that endothelial cells release specific soluble factors that may directly act on the epithelial barrier. This review discusses the putative involvement of angiocrine inter-barrier communication in the pathogenesis of IBD.

Visualization of flow dynamics in the portal circulation using 320-detector-row computed tomography: a feasibility study

Multidetector row computed tomography (CT) scanners perform dynamic scanning and have a wide scan range. Time-resolved three-dimensional CT (i.e., 4D CT) has recently enabled visualization of flow in neurovascular vessels. We hypothesized that 4D CT technology would be a useful and non-invasive method for visualizing the flow dynamics of the portal circulation. The aim of this study was to evaluate the technical feasibility of 4D CT for visualizing flow dynamics in the portal circulation using 320-detector-row CT. 4D CT images of 18 consecutive patients with portal circulation including gastrorenal shunt were retrospectively evaluated for their ability to generate flow dynamics of the portal circulation. Flow dynamics could be visualized by 4D CT in 68 of the 72 vessels in the portal vein, splenic vein, superior mesenteric vein, and gastrorenal shunt. Flow direction could not be identified in four vessels, all of them being superior mesenteric veins. Flow direction was recognized on 4D CT in the 68 vessels of the portal circulation. A preliminary validation study revealed that flow direction of all 19 vessels in the portal circulation had concordance between 4D CT and color Doppler ultrasound. 4D CT could visualize flow dynamics of the portal circulation.

To the microanatomy of the spleen

From a physiological point of view, the spleen has recently attracted special attention as a reserve reservoir of blood. In view of the ability to independently actively change to a very large extent its volume and blood circulation, the spleen is of no small importance as a factor that can significantly affect the overall blood circulation in the vascular system, as well as on the portal circulation.

Endoscopy in Management of Portal Hypertension

Portal hypertension (PH) is a serious consequence of several disease states affecting prehepatic, intrahepatic, or posthepatic portal circulation. Backpressure caused by PH transmits through the collaterals to form varices at various sites. PH also leads to hyperdynamic congestion and altered gastrointestinal mucosal immune response, resulting in portal hypertensive gastropathy (PHG), portal hypertensive enteropathy (PHE), and portal colopathy (PC). These PH associated phenomena may lead to torrential life-threatening bleed or chronic blood loss leading to debilitating chronic anemia. Endoscopy plays a pivotal role in the management of these patients both for diagnostic and therapeutic purpose. The choice of therapeutic strategy depends on many factors: severity of the disease, patient’s clinical performance, and whether it is done as an emergency or as a prophylactic approach. In this chapter, we evaluate the endoscopic management of patients with the gastrointestinal complications of PH.

313 New insights on liver abscess syndrome in cattle using metagenomic investigations

Liver abscess syndrome (LAS) is a well-recognized and important problem for beef production in all types of cattle. LAS has been shown to be associated with decreased growth efficiency and lower carcass quality, in addition to losses associated with carcass trimming and condemnation of materials at slaughter. The etiopathogenesis of LAS has traditionally attributed a few bacterial species as being the principal causes (Fusobacterium necrophorum, and Trueperella pyogenes), based on the theory that these bacteria are translocated from the rumen into portal circulation, allowing them to seed the liver. Research regarding the pathogenesis and prevention of LAS has long been limited to data derived from culture-based investigations. Advances in genomic sequencing provide tremendous opportunities for re-evaluation of traditional perspectives on LAS. Recent metagenomic investigations of liver abscesses conducted by our research team have found that liver abscesses are far more polymicrobial than previously believed, suggesting that the etiology is more complex than previously believed. This presentation will present data from culture-based investigations and those using metagenomic sequencing as we re-evaluate traditional dogma regarding LAS.

Endoscopic ultrasound-guided sampling and profiling of portal circulation in human patients for metabolic research studies and biomarker assessment

The technical aspects, feasibility, and safety of endoscopic ultrasound (EUS)-guided needle access for portal venous blood collection are presented in this technical report. Despite the very small diameter of the endoscopic needle, portal blood samples have the same quality as those collected from systemic circulation. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison with a group without cirrhosis.

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.