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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#1
Ancy D Nalli, Sayak Bhattacharya, Hongxia Wang, Derek M Kendig, John R Grider, Karnam S Murthy
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cGMP. The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse and human, L-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser(1756) (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor, s-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705806/roles-of-autophagy-and-metabolism-in-pancreatic-cancer-cell-adaptation-to-environmental-challenges
#2
Sandrina Maertin, Jason M Elperin, Ethan Lotshaw, Matthias Sendler, Steven D Speakman, Kazuki Takakura, Benjamin M Reicher, Olga A Mareninova, Paul J Grippo, Julia Mayerle, Markus M Lerch, Anna S Gukovskaya
Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mTOR...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705805/validation-and-characterization-of-a-novel-method-for-selective-vagal-deafferentation-of-the-gut
#3
Charlene Diepenbroek, Danielle Quinn, Ricky Stephens, Benjamin Zollinger, Seth Anderson, Annabelle Pan, Guillaume de Lartigue
There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the GI hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a sub-population of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine, but not the colon, while leaving vagal efferent neurons intact...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705804/loss-of-nitric-oxide-mediated-inhibition-of-purine-neurotransmitter-release-in-the-colon-in-the-absence-of-interstitial-cells-of-cajal
#4
Leonie Durnin, Andrea Lees, Sheerien Manzoor, Kent C Sasse, Kenton M Sanders, Violeta N Mutafova-Yambolieva
Regulation of colonic motility depends upon the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor α-positive (PDGFRα(+)) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit(W)/Kit(W-v) (W/W(v) ) mice that display lesions in ICC-IM along the gastrointestinal tract...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28684460/abdominal-surgery-induced-gastric-ileus-and-activation-of-m1-like-macrophages-in-the-gastric-myenteric-plexus-prevention-by-central-vagal-activation-in-rats
#5
Pu-Qing Yuan, Yvette Taché
Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. The stable thyrotropin-releasing hormone agonist, RX77368 injected intracisternally (ic) activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by ic RX-77368 in rats. RX77368 (50 ng/rat) or saline was injected ic followed, 1 h later, by laparotomy and small intestinal/cecal manipulation...
July 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28684459/dclk1-expressing-tuft-cells-critical-modulators-of-the-intestinal-niche
#6
Moritz Middelhoff, C Benedikt Westphalen, Yoku Hayakawa, Kelley S Yan, Michael D Gershon, Timothy C Wang, Michael Quante
Dclk1-expressing tuft cells constitute a unique intestinal epithelial lineage that is distinct from enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. Tuft cells express taste-related receptors and distinct transcription factors, and interact closely with the enteric nervous system, suggesting a chemosensory cell lineage. In addition, recent work has shown that tuft cells interact closely with cells of the immune system, with a critical role in the cellular regulatory network governing responses to luminal parasites...
July 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28663304/determinants-of-post-prandial-plasma-bile-acid-kinetics-in-human-volunteers
#7
Jarlei Fiamoncini, Andrianos M Yiorkas, Kurt Gedrich, Milena Rundle, Sanne I Alsters, Guus Roeselers, Tim J van den Broek, Thomas Clavel, Ilias Lagkouvardos, Suzan Wopereis, Gary S Frost, Ben van Ommen, Alexandra I F Blakemore, Hannelore Daniel
Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified amongst the most responsive plasma metabolites in the post-prandial state. We here describe this response to different dietary challenges and report on key determinants linked to its inter-individual variability. Healthy men and women (N=72, 62 ± 8 years) were enrolled into a 12-week weight loss intervention. All subjects underwent an oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) before and after the intervention...
June 29, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28642299/dysfunctional-neutrophil-effector-organelle-mobilisation-and-microbicidal-protein-release-in-alcohol-related-cirrhosis
#8
Thomas Henry Tranah, Godhev K Manakkat Vijay, Jennifer M Ryan, Robin Daniel Abeles, Paul Kevin Middleton, Debbie Lindsay Shawcross
BACKGROUND AND AIMS: Patients with alcohol-related cirrhosis (ALD) are prone to infection. Circulating neutrophils in ALD are dysfunctional and predict development of sepsis, organ dysfunction and survival. Neutrophil granules are important effector organelles containing a toxic array of microbicidal proteins, whose controlled release is required to kill micro-organisms whilst minimising inflammation and damage to host tissue. We investigated the role of these granular responses in contributing to immune disarray in ALD...
June 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28642298/does-acid-base-equilibrium-correlate-with-remnant-liver-volume-during-stepwise-liver-resection
#9
Mohammad Golriz, Sepehr Abbasi, Parham Fathi, Ali Majlesara, Thorsten Brenner, Arianeb Mehrabi
Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 gram remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and post-hepatectomy liver failure has been postulated, but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75%, 50% and 25% respectively)...
June 22, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28619730/consumption-of-a-high-iron-diet-disrupts-homeostatic-regulation-of-intestinal-copper-absorption-in-adolescent-mice
#10
Jung-Heun Ha, Caglar Doguer, James F Collins
High-iron feeding of rodents has been commonly used to model human iron-overload disorders. We recently noted that high-iron consumption impaired growth and caused severe systemic copper deficiency in growing rats, but the mechanism by which this occurred could not be determined due to technical limitations. In the current investigation, we thus utilized mice; first to determine if the same phenomenon occurred in another mammalian species, and secondly since we could assess in vivo copper absorption in mice...
June 15, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28619729/characterization-and-mechanisms-of-the-supragastric-belch-in-the-cat
#11
Ivan M Lang, Bidyut K Medda, Reza Shaker
A response, i.e., the supragastric belch (SGB), in which a belch occurs without gastric involvement has been characterized in humans. The aims of this study were to determine whether animals have an SGB and if so to determine its mechanisms. Studies were conducted in decerebrate cats (N=30) with EMG electrodes on hyoid, pharyngeal, esophageal, and diaphragm muscles. The effects of distending different regions of the esophagus in different manners using a balloon were quantified to determine the most appropriate stimulus for activating the cat SGB...
June 15, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28619728/activated-notch-signaling-cascade-is-correlated-with-stem-cell-differentiation-toward-absorptive-progenitors-after-massive-small-bowel-resection-in-a-rat
#12
Igor Sukhotnik, Arnold G Coran, Yulia Pollak, Eviatar Kuhnreich, Drora Berkowitz, Amulya K Saxena
Notch signaling is thought to act to drive cell versification in the lining of the small intestine. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiationin the late stages of intestinal adaptation after massive small bowel resection in a rat. Male Sprague-Dawley rats were randomly assigned to one of two experimental groups of 8 rats each: Sham rats underwent bowel transection and re-anastomosis, SBS- rats underwent 75% small bowel resection. Rats were sacrificed on day 14...
June 15, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28619727/rna-seq-implicates-deregulation-of-the-immune-system-in-the-pathogenesis-of-diverticulitis
#13
Kathleen M Schieffer, Christine S Choi, Scott Emrich, Leonard Harris, Sue Deiling, Dipti M Karamchandani, Anna Salzberg, Yuka I Kawasawa, Gregory S Yochum, Walter A Koltun
Individuals with diverticula or outpouchings of the colonic mucosa and submucosa through the colonic wall have diverticulosis, which is usually asymptomatic. In 10-25% of individuals, the diverticula become inflamed, resulting in diverticulitis. Very little is known about the pathophysiology or gene regulatory pathways involved in the development of diverticulitis. To identify these pathways, we deep sequenced RNAs isolated from full-thickness sections of sigmoid colon from diverticulitis patients and control individuals...
June 15, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28596277/the-liver-in-regulation-of-iron-homeostasis
#14
Gautam Rishi, V Nathan Subramaniam
The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism...
June 8, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28572086/functional-morphology-of-the-lower-esophageal-sphincter-and-crural-diaphragm-determined-by-3-d-high-resolution-pressure-profile-ct-imaging
#15
Ravinder K Mittal, Ali Zifan, Dushyant Kumar, Melissa Ledgerwood-Lee, Erika Ruppert, Gary Ghahremani
The lower esophageal sphincter (LES) and crural diaphragm (CD) provide the closure mechanism at esophago-gastric junction (EGJ). We used CT imaging in combination with 3D EGJ pressure recordings to determine the functional morphology of the LES and CD and its relationship to the EGJ anatomy. A 3D-HRM catheter recorded the EGJ pressure in 10 healthy subjects. A 0.5 mm diameter metal ball (BB) was taped to the catheter, adjacent to transducer #1. The EGJ pressure was recorded under following conditions; 1) end-expiration (LES pressure) a) before swallow, b) after swallow, and 2) peak inspiration (CD contraction) c) tidal inspiration and d) forced inspiration...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28572085/cdx2-upregulates-slc26a3-gene-expression-in-intestinal-epithelial-cells
#16
Ishita Chatterjee, Anoop Kumar, Rosa Maria Castilla Madrigal, Oscar Pellon-Cardenas, Ravinder K Gill, Waddah A Alrefai, Alip Borthakur, Michael Verzi, Pradeep K Dudeja
SLC26A3 (Down Regulated in Adenoma, DRA) plays a key role in mammalian intestinal NaCl absorption via mediating apical membrane Cl(-)/HCO3(-) exchange. DRA function and expression are significantly decreased in diarrhea associated with inflammatory bowel diseases (IBD). DRA is also considered to be a marker of cellular differentiation, and is predominantly expressed in differentiated epithelial cells. Caudal type homeobox protein-2 (CDX2) is known to regulate genes involved in intestinal epithelial differentiation and proliferation...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28572084/ductular-and-proliferative-response-of-esophageal-submucosal-glands-in-a-porcine-model-of-esophageal-injury-and-repair
#17
Leandi Krüger, Liara M Gonzalez, Tiffany A Pridgen, Shannon J McCall, Richard von Furstenberg, Ivan Harnden, Gwendolyn E Carnighan, Abigail M Cox, Anthony T Blikslager, Katherine Schuver Garman
Esophageal injury is a risk factor for diseases such as Barrett's Esophagus (BE) and Esophageal Adenocarcinoma. In order to improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28572083/oatmeal-particle-size-alters-glycemic-index-but-not-as-a-function-of-gastric-emptying-rate
#18
Alan R Mackie, Balazs Bajka, Neil M Rigby, Peter J Wilde, Fatima Alves-Pereira, Ellen F Mosleth, Anne Rieder, Bente Kirkhus, Louise J Salt
SCOPE: The aim of this study was to determine the extent to which oat particle size in a porridge could alter glucose absorption, gastric emptying, gastrointestinal hormone response and subjective feelings of appetite and satiety. METHOD AND RESULTS: Porridge was prepared from either oat flakes or oat flour with the same protein, fat, carbohydrate and mass. These were fed to eight volunteers on separate days in a crossover study and subjective appetite ratings, gastric contents and plasma glucose, insulin, and gastrointestinal hormones were determined over a period of three hours...
June 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28546285/anti-inflammatory-effects-and-mechanisms-of-vagal-nerve-stimulation-combined-with-electroacupuncture-in-a-rodent-model-of-tnbs-induced-colitis
#19
Haifeng Jin, Jie Guo, Jiemin Liu, Bin Lyu, Robert D Foreman, Jieyun Yin, Zhaohong Shi, Jiande Dz Chen
The purpose of this study was to determine effects and mechanisms of vagal nerve stimulation (VNS) and additive effects of electroacupuncture (EA) on colonic inflammation in a rodent model of IBD. Chronic inflammation in rats was induced by intrarectal TNBS (2,4,6-Trinitrobenzenesulfonic acid). The rats were then treated with sham-ES (electrical stimulation), VNS or VNS+EA for 3 weeks. Inflammatory responses were assessed by disease activity index (DAI), macroscopic scores and histological scores of colonic tissues, and plasma levels of TNF-α, IL-1β and IL-6, myeloperoxidase (MPO) activity of colonic tissues...
May 25, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28546283/high-resolution-mapping-of-gastric-slow-wave-recovery-profiles-biophysical-model-methodology-and-demonstration-of-applications
#20
Niranchan Paskaranandavadivel, Leo K Cheng, Peng Du, Jack M Rogers, Gregory O'Grady
Slow waves play a central role in coordinating gastric motor activity. High-resolution mapping of extracellular potentials from the stomach provides spatiotemporal detail on normal and dysrhythmic slow-wave patterns. All mapping studies to date have focused exclusively on tissue activation; however, the recovery phase contains vital information on repolarization heterogeneity, the excitable gap, and refractory tail interactions, but has not been investigated. Here, we report a method to identify the recovery phase in slow-wave mapping data...
May 25, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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