Indinavir is a viral protease inhibitor used for the treatment of HIV infection. Unconjugated hyperbilirubinemia develops in up to 25% patients receiving indinavir, prompting drug discontinuation and further clinical evaluation some instances. We postulated that this side-effect due indinavir-mediated impairment bilirubin UDP-glucuronosyltransferase (UGT) activity would be most pronounced individuals with reduced hepatic enzyme levels, as occurs ≈10% population manifesting Gilbert's...

Glucagon-like peptide 1 (GLP-1) is a gastrointestinal hormone secreted in response to meal ingestion by enteroendocrine L cells located predominantly the lower small intestine and large intestine. GLP-1 inhibits secretion motility of upper gut has been suggested play role "ileal brake." In this study, we investigated effect recombinant GLP-1-(7-36) amide (rGLP-1) on lipid absorption intestinal lymph duct-cannulated rats. addition, effects rGLP-1 production apolipoprotein (apo) B apo A-IV,...

Sucralose is a calorie-free high-intensity artificial sweetener that widely used in thousands of foods and beverages all over the world. Although it had been initially regarded as safe inert food additive, its adverse effect on gut microbiota health has drawn more attention evidence accumulates. Studies by us others revealed sucralose exacerbated damage inflammation animal models for inflammatory bowel disease (IBD) including both ulcerative colitis Crohn's disease. Our study demonstrated...

Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis apoE knockout animals even the presence a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal development atherosclerosis, antioxidative activity apoAIV was investigated. Fasting intestinal lymph used mimic conditions interstitial fluid, potential site for vivo. ApoAIV (10 μg/ml) significantly inhibited copper-mediated lymph....

Gut injury and loss of normal intestinal barrier function are key elements in the paradigm gut-origin systemic inflammatory response syndrome, acute lung injury, multiple organ dysfunction syndrome (MODS). As hypoxia-inducible factor (HIF-1) is a critical determinant physiological pathophysiological to hypoxia ischemia, we asked whether HIF-1 plays proximal role induction gut subsequent injury. Using partially HIF-1α-deficient mice an isolated superior mesenteric artery occlusion (SMAO)...

In Brief Objective: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in pathogenesis of trauma shock–induced gut lung injury. Background: Gut origin sepsis studies have highlighted importance systemic component (ischemia-reperfusion) injury, whereas intraluminal is less well studied. Methods: rats subjected to hemorrhagic shock (T/HS) or sham shock, role pancreatic enzymes injury was tested by diversion via duct exteriorization...

Lay Summary Building on my long-standing hypothesis that impaired inactivation of digestive proteases by deconjugated bilirubin may be the unifying feature and mechanism inflammatory bowel disease (IBD), this paper explores potential connections among different subtypes IBD through sequential changes in total serum bilirubin.

Loss of the gut barrier has been implicated in pathogenesis multiple organ dysfunction syndrome, and, thus, understanding intestinal is potential clinical importance. An important, but relatively neglected, component unstirred mucus layer, which through its hydrophobic and other properties serves as an important to bacterial factors within lumen. Thus, goal this study was establish a reproducible method measuring mucosal hydrophobicity test hypothesis that conditions decrease are associated...

It is well documented that the gut injury plays a critical role in development of systemic inflammation and distant organ conditions associated with splanchnic ischemia. Consequently, understanding mechanisms leading to important. In this context, recent work suggests protective for intestinal mucus layer an injury-inducing luminal pancreatic proteases. Thus, we explored barrier function by observing how removal affects ischemia-reperfusion-mediated rats as potential proteases pathogenesis...

Unconjugated bilirubin (UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on interaction between intestinal flora and organisms how influences immune responses remain unresolved.To investigate role UCB in barrier function inflammation mice with dextran-sulfate-sodium-induced colitis.Acute colitis was induced by 3% (w/v) dextran sulfate sodium salt drinking water 6 d followed untreated 2 d. Concurrently, were...

Recent studies have shown that mesenteric lymph plays a very important role in the development of multiple-organ dysfunction syndrome under critical conditions. Great efforts been made to identify biologically active molecules lymph. We used trauma-hemorrhagic shock (T/HS) model and superior artery occlusion (SMAO) model, representing global localized intestinal ischemia-reperfusion insult, respectively, investigate free fatty acids (FFAs) cytotoxicity rats. Lymph was collected before,...

Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis ulcerative colitis (UC). Fecal transplantation (FMT) has drawn more and attention become an important therapeutic approach. This study aims to examine facts about effective components look into potential mechanisms FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) drinking water for 7 days. mice were administered oral gavage with fecal suspension, supernatant, bacteria or...

There is substantial evidence that gut barrier failure associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors mechanisms involved in are unknown. Our primary hypothesis loss of intestinal mucus layer will result normal exacerbated by presence luminal pancreatic proteases. secondary produced production biologically active mesenteric lymph consequently (i.e., lung) injury. To test this hypothesis, five groups rats were studied: 1)...

We tested whether exogenous peptide YY (PYY) can stimulate synthesis and lymphatic secretion of intestinal apolipoprotein AIV (apo AIV). Rats with mesenteric lymph fistulas right atrial cannulas were given continuous intravenous infusions control vehicle or PYY at 25, 50, 75, 100, 200 pmol ⋅ kg −1 h . (75–200 ) stimulated apo output from 1.5- to 3.5-fold higher than basal output. In separate experiments, (100 produced a 60% increase in jejunal mucosal but had no effect on mRNA levels doses...

We tested the hypothesis that testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut and subsequent production of biologically active mesenteric lymph.Male, castrated male, flutamide-treated (25 mg/kg subcutaneously after resuscitation) were subjected to a laparotomy (trauma), lymph duct cannulation, 90 minutes shock (35 mm Hg) sham-shock. Mesenteric was collected preshock, during shock, postshock. Gut determined...

Core tip: In my opinion, ulcerative colitis is more like bacterial pneumonia with the involvement of mainly neutrophils, capacious exudates into cavity but limited damage tissue, while Crohn's disease pneumoconiosis, such as silicosis or berylliosis, tuberculosis lung macrophages and manifested granulomatous inflammation in interstices, destruction extensive proliferation fibroblasts formation fibrosis.Qin X.Why to mucosa transmural disease?

Sucralose is one of the most widely used artificial sweeteners, free nutrients and calories. Its approval uses correlate with many worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us others showed that sucralose exacerbated ileitis SAMP1/YitFc mice 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. In this study, we further investigated effect on dextran sulfate sodium (DSS)-induced associated mechanisms. Male C57BL/6 received...

Background: We tested the hypothesis that females are more resistant to trauma-hemorrhagic shock (T/HS)-induced gut injury than males, and this is related better preservation of their intestinal mucus layer, which influenced in turn by estrus cycle stage at time injury. Methods: Male, proestrus diestrus female rats underwent a laparotomy (trauma) 90 minutes (∼35 mm Hg). At 3 hours after reperfusion, terminal ileum was harvested stained with Carnoy's Alcian Blue for assessment, hematoxylin...

I nflammatory bowel disease (IBD) (which includes both ulcerative colitis and Crohn's [CD]) emerged dramatically increased in the past century (1).Early studies revealed that IBD was most prevalent countries such as United Kingdom, States those northern Europe (1).Compared with these countries, prevalence of Canada much lower.This demonstrated early epidemiological conducted Canada.According to a review by Mayberry Rhodes (2), study published 1972 reported incidence CD Sherbrooke, Quebec, at...