Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model.

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells.

Temporal Transcript Profiling Identifies a Role for Unfolded Protein Stress in Human Gut Ischemia-Reperfusion Injury.

Background & Aims: Intestinal ischemia-reperfusion injury is a serious and life-threatening condition. A better understanding of molecular mechanisms related to intestinal ischemia-reperfusion injury in human beings is imperative to find therapeutic targets and improve patient outcome.

Methods: First, the in vivo dynamic modulation of mucosal gene expression of the ischemia-reperfusion-injured human small intestine was studied.

Chorioamnionitis induces hepatic inflammation and time-dependent changes of the enterohepatic circulation in the ovine fetus.

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure.

Prevention of intra-abdominal adhesions by a hyaluronic acid gel; an experimental study in rats.

Background: In 80% to 90% of the patients intra-abdominal adhesions occur after abdominal surgery, which can cause small-bowel obstruction, chronic abdominal pain, female infertility and difficulty during reoperation. A novel crosslinked hyaluronic acid gel is evaluated regarding its anti-adhesive capacities in an ischemic button model in rats.

Method: 51 adult, male Wistar rats from a registered breeder, received eight ischemic buttons each and were treated with hyaluronic acid gel (HA, HyaRegen), hyaluronic acid carboxymethylcellulose (HA-CMC, Seprafilm) or no anti-adhesive barrier.

Prophylactic Intra-Uterine β-Cyclodextrin Administration during Intra-Uterine Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep.

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver.

SM22 a Plasma Biomarker for Human Transmural Intestinal Ischemia.

Objective: To evaluate the diagnostic potential of smooth muscle protein of 22 kDa (SM22) as plasma biomarker for the detection of transmural intestinal ischemia.

Background: Acute mesenteric ischemia is an abdominal emergency requiring rapid diagnosis and treatment. Especially, detection of transmural damage is imperative because it mandates emergency surgery.

Prevention of hemolysis-induced organ damage by nutritional activation of the vagal anti-inflammatory reflex*.

Objectives: Acute hemolysis is associated with organ damage, inflammation, and impaired vascular function. Stimulation of the cholecystokinin-1 receptor-dependent vagal anti-inflammatory reflex with lipid-rich enteral nutrition was demonstrated to prevent tissue damage and attenuate inflammation. This study investigates the effects of nutritional activation of the vagal anti-inflammatory reflex on organ integrity, systemic inflammation, and microcirculation during hemolysis.

Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex.

Nutritional stimulation of the cholecystokinin-1 receptor (CCK-1R) and nicotinic acetylcholine receptor (nAChR)-mediated vagal reflex was shown to reduce inflammation and preserve intestinal integrity. Mast cells are important early effectors of the innate immune response; therefore modulation of mucosal mast cells is a potential therapeutic target to control the acute inflammatory response in the intestine. The present study investigates intestinal mast cell responsiveness upon nutritional activation of the vagal anti-inflammatory reflex during acute inflammation.

Starvation compromises Paneth cells.

Lack of enteral feeding, with or without parenteral nutritional support, is associated with increased intestinal permeability and translocation of bacteria. Such translocation is thought to be important in the high morbidity and mortality rates of patients who receive nothing by mouth. Recently, Paneth cells, important constituents of innate intestinal immunity, were found to be crucial in host protection against invasion of both commensal and pathogenic bacteria.

Chylomicron formation and glucagon-like peptide 1 receptor are involved in activation of the nutritional anti-inflammatory pathway.

Enteral administration of lipid-enriched nutrition effectively attenuates inflammation via a cholecystokinin (CCK)-mediated vagovagal anti-inflammatory reflex. Cholecystokinin release and subsequent activation of the vagus are dependent on chylomicron formation and associated with release of additional gut peptides. The current study investigates the intestinal processes underlying activation of the CCK-mediated vagal anti-inflammatory pathway by lipid-enriched nutrition.

Apolipoprotein CI knock-out mice display impaired memory functions.

The ε4 allele of apolipoprotein E (APOE4), which is a well established genetic risk factor for development of Alzheimer's disease (AD), is in genetic disequilibrium with the H2 allele of apolipoprotein C1 (APOC1), giving rise to increased expression of apoC-I. This raises the possibility that the H2 allele of APOC1, either alone or in combination with APOE4, provides a major risk factor for AD. In line herewith, we previously showed that mice overexpressing human APOC1 display impaired learning and memory functions.

Lipid-enriched enteral nutrition controls the inflammatory response in murine Gram-negative sepsis.

Objectives: Controlling the inflammatory cascade during sepsis remains a major clinical challenge. Recently, it has become evident that the autonomic nervous system reduces inflammation through the vagus nerve. The current study investigates whether nutritional stimulation of the autonomic nervous system effectively attenuates the inflammatory response in murine Gram-negative sepsis.

Cholecystokinin/Cholecystokinin-1 receptor-mediated peripheral activation of the afferent vagus by enteral nutrients attenuates inflammation in rats.

Objective: The current study investigates activation of the nutritional anti-inflammatory pathway by lipid-rich nutrition.

Background: Enteral nutrition activates humoral and neural pathways to regulate food intake and sustain energy balance. Recently, we demonstrated that enteral nutrition and in particular lipid-rich nutrition modulates inflammation and prevents organ damage.

Protection against early intestinal compromise by lipid-rich enteral nutrition through cholecystokinin receptors.

Objective: Early gut wall integrity loss and local intestinal inflammation are associated with the development of inflammatory complications in surgical and trauma patients. Prevention of these intestinal events is a potential target for therapies aimed to control systemic inflammation. Previously, we demonstrated in a rodent shock model that lipid-rich enteral nutrition attenuated systemic inflammation and prevented organ damage through a cholecystokinin receptor-dependent vagal pathway.

N-acetyl resonances in in vivo and in vitro NMR spectroscopy of cystic ovarian tumors.

An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients.

Lipid-rich enteral nutrition reduces postoperative ileus in rats via activation of cholecystokinin-receptors.

Objective: This study investigates the effect of lipid-rich nutrition on the local inflammatory response and gastrointestinal hypomotility in a rat model of postoperative ileus.

Background: Postoperative ileus is a major clinical problem, in which inflammation of the intestinal muscularis plays a key pathogenic event. Previously, administration of lipid-rich nutrition has been shown to reduce inflammation by activation of the autonomic nervous system via cholecystokinin-receptors.

High-fat nutrition reduces hepatic damage following exposure to bacterial DNA and hemorrhagic shock.

Background/aims: Bacterial infection combined with hypotension results in exacerbation of the inflammatory response with release of interferon (IFN) gamma. This excessive inflammation may lead to development of hepatic damage and liver failure. This study investigates the effect of dietary lipids on release of IFN-gamma and development of hepatic damage following exposure to synthetic bacterial DNA (CpG-ODN) and hemorrhagic shock.

Postshock intervention with high-lipid enteral nutrition reduces inflammation and tissue damage.

Objective: To investigate the effects of high-lipid enteral nutrition in a setting of developing inflammation and tissue damage.

Background: An excessive inflammatory response following severe trauma is associated with poor clinical outcome. Currently, therapies directed at attenuation of an ongoing inflammatory cascade are lacking.

Intestinal cytoskeleton degradation precedes tight junction loss following hemorrhagic shock.

Hemorrhagic shock (HS) leads to intestinal barrier loss, causing systemic inflammation, which in turn can ultimately lead to multiorgan dysfunction syndrome. Barrier function is based on tight junctions (TJs) between intact epithelial cells. These TJs are anchored in the cell via the filamentous actin (F-actin) cytoskeleton.

Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic inflammation and gut barrier loss via an IFN-gamma-dependent route.

Objective: To investigate the role of bacterial DNA in development of an excessive inflammatory response and loss of gut barrier loss following systemic hypotension.

Summary Background Data: Bacterial infection may contribute to development of inflammatory complications following major surgery; however, the pathogenesis is not clear. A common denominator of bacterial infection is bacterial DNA characterized by unmethylated CpG motifs.

Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve.

The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autonomic nervous system plays an important role in sensing luminal contents in the gut by way of hard-wired connections and chemical messengers, such as cholecystokinin (CCK).

Strain-specific effects of probiotics on gut barrier integrity following hemorrhagic shock.

Probiotic therapy modulates the composition of the intestinal flora and inhibits the inflammatory response. These properties may be of benefit in the preservation of gut barrier integrity after injury or stress. In this study, we examined the effect of two Lactobacillus strains selected for their pathogen exclusion properties on intestinal barrier integrity following hemorrhagic shock.

High-fat enteral nutrition reduces endotoxin, tumor necrosis factor-alpha and gut permeability in bile duct-ligated rats subjected to hemorrhagic shock.

Background/aims: Cholestatic patients are prone to septic complications after major surgery due to an increased susceptibility to endotoxin and hypotension. High-fat enteral nutrition reduces endotoxin after hemorrhagic shock. However, it is unknown whether this nutritional intervention is protective in biliary obstruction.

Enteral administration of high-fat nutrition before and directly after hemorrhagic shock reduces endotoxemia and bacterial translocation.

Objective: To determine whether potential enhancement of endotoxin neutralization via high-fat enteral nutrition affects endotoxemia and bacterial translocation after hemorrhage.

Summary Background Data: Endotoxin and bacterial translocation due to gut barrier failure are important initiating events in the pathogenesis of sepsis after hemorrhage. Systemic inhibition of endotoxin activity attenuates bacterial translocation and distant organ damage.

Pretreatment with high-fat enteral nutrition reduces endotoxin and tumor necrosis factor-alpha and preserves gut barrier function early after hemorrhagic shock.

Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins and gut barrier function loss. Recently, we found that high-fat enteral nutrition protects against late bacterial translocation in a model of hemorrhagic shock in rats. However, the basis for this protection is unknown.