Lipopolysaccharide transport during long-chain fatty acid exposure is mediated by caveolin-1 dependent endocytosis in murine jejunum.

The entry of bacterial-derived lipopolysaccharides (LPS) from the intestinal lumen to the circulation induces low-grade systemic inflammation. We have found that LPS is transcellularly transported to the portal vein during luminal long-chain fatty acid (LCFA) exposure via CD36- and lipid raft-mediated pathways in rat jejunum, consistent with the involvement of caveolae-mediated endocytosis. We thus examined LPS transport in wild-type (WT) and caveolin-1 (Cav1) knockout (KO) murine jejunum.

Alteration of the microbiota with vancomycin and high-fiber diet affects short-chain fatty acid/free fatty acid receptor signaling in rat caecum.

Microbial short-chain fatty acids (SCFA) regulate intestinal functions via free-fatty acid (FFA) receptors type 2 and 3. Though the caecum is the most important fermentation chamber in many species, it is unknown whether this signaling system is modulated in dependence on the rate of fermentation within the lumen of this part of the large intestine. Thus, we asked the question whether alteration of the microbiota composition by antibiotic treatment or high-fiber diet affects the SCFA/FFA signaling using rat caecum as model system.

Restraint stress exacerbates indomethacin-induced gastric antral ulcers by gastroparesis via activation of corticotropin-releasing factor 2 receptors in refed mice.

We examined the effects of stress on the indomethacin (IND)-induced gastric antral ulcer formation in refed mice. Male mice underwent refeeding of diet for 2 hours after a fast for 22 hours, followed by IND injection; the lesion index was measured 24 hours later. Mice also underwent a defined diet for 2 hours following a fast for 22 hours, and the stomachs were collected 1.

Sometimes Small Is Beautiful: Discovery of the Janus Kinases (JAK) and Signal Transducer and Activator of Transcription (STAT) Pathways and the Initial Development of JAK Inhibitors for IBD Treatment.

The Janus kinase/signal transducer and activator of transfection (JAK/STAT) system is comprised of multiple cell surface receptors, receptor tyrosine kinases, and signal transducers that are key components of numerous systems involved in malignancy, inflammation, immune surveillance and development, cellular proliferation, metabolism, differentiation, apoptosis, and hematologic disorders, all of which when disrupted can produce severe disease. Nevertheless, small molecule inhibitors of the four known JAKs, termed JAKinibs, have found therapeutic indications for a broad category of diseases. In this perspective, I will summarize the development of JAK inhibitors, whose origins were in antiquity, with particular attention to their use in treating patients with inflammatory bowel disease (IBD).

Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

Background/aims: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice.

Methods: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT and Dopamine D Receptors in Mice.

Background/aims: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice.

Methods: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.

Iodine contrast exposure and incident COVID-19 infection.

Background: Iodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited and data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection.

Excess iodine exposure acutely increases salivary iodide and antimicrobial hypoiodous acid concentrations in humans.

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN) into hypoiodous acid (HOI) and hypothiocyanite (OSCN), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN, HOI and OSCN were measured using standard methodology.

It's Not What You Take Up, It's What You Keep: How Discoveries from Diverse Disciplines Directed the Development of the FDG PET/CT Scan.

Although imaging glucose metabolism with positron emission tomography combined with X-ray CT (FDG-PET/CT) has become a standard diagnostic modality for the discovery and surveillance of malignant tumors and inflammatory processes, its origins extend back to more than a century of notable discoveries in the fields of inorganic and organic chemistry, nuclear physics, mathematics, biochemistry, solute transport physiology, metabolism, and imaging, accomplished by pioneering and driven investigators, of whom at least ten were recipients of the Nobel Prize. These tangled and diverse roots eventually coalesced into the FDG-PET/CT method, that through its many favorable characteristics inherent in the isotope used (F), the accurate imaging derived from coincidence detection of positron annihilation radiation combined with computed tomography, and the metabolic trapping of 2-deoxy-2-[F]fluoro-D-glucose (FDG) in tissues, provides safety, sensitivity, and specificity for tumor and inflammation detection. The authors hope that this article will increase the appreciation among its readers of the insight, creativity, persistence, and drive of the many investigators who made this technique possible.

Duodenal cholinergic tuft cell number is increased in functional dyspepsia.

Background: Low-grade duodenal inflammation has recently been identified in patients with functional dyspepsia (FD). Chemosensory tuft cells were reported to be associated with gastrointestinal diseases. We therefore assessed duodenal tuft cell density and microinflammation in patients with FD to determine whether these measures could serve as useful biomarkers, and also correlated tuft cell density and microinflammation in FD patients.

Short-chain fatty acid receptors involved in epithelial acetylcholine release in rat caecum.

Short-chain fatty acids (SCFAs) produced by the microbial fermentation of carbohydrates are important energy substrates for mammals. Intestinal epithelia respond to these metabolites by stimulation of anion secretion via the release of epithelial acetylcholine. The present experiments were performed to discover which of the known receptors for SCFAs are expressed in rat caecum, the most important site of fermentation within the intestine of non-ruminant mammals.

Duodenal chemosensory system: enterocytes, enteroendocrine cells, and tuft cells.

Purpose Of Review: The gut barrier serves as the primary interface between the environment and host in terms of surface area and complexity. Luminal chemosensing is a term used to describe how small molecules in the gut lumen interact with the host through surface receptors or via transport into the subepithelial space. In this review, we have summarized recent advances in the understanding of the luminal chemosensory system in the gastroduodenal epithelium consisting of enterocytes, enteroendocrine, and tuft cells, with particular emphasis on how chemosensing affects mucosal protective responses and the metabolic syndrome.

Lipopolysaccharides transport during fat absorption in rodent small intestine.

Lipopolysaccharides (LPS) are potent pro-inflammatory molecules that enter the systemic circulation from the intestinal lumen by uncertain mechanisms. We investigated these mechanisms and the effect of exogenous glucagon-like peptide-2 (GLP-2) on LPS transport in the rodent small intestine. Transmucosal LPS transport was measured in Ussing-chambered rat jejunal mucosa.

PowerPoint to the People: The Four Secrets to Delivering a Great Medical Talk.

Medical talks are a staple of post-medical school education, but the effectiveness of these lectures can be quite variable. One significant reason for this is that while physicians and trainees are well trained at presenting information to one another, they have little to no formal training on giving hour-long medical didactics. Focusing on four specific categories including creating a strong first impression, effective use of PowerPoint, impactful delivery of information, and thorough preparation a physician at any stage in training can become a strong presenter.