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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28814387/effects-of-nk1-receptors-on-gastric-motor-functions-and-satiation-in-healthy-humans-results-from-a-controlled-trial-with-the-nk1-antagonist-aprepitant
#1
Deepti Jacob, Irene A Busciglio, Duane D Burton, Houssam Halawi, Ibironke Oduyebo, Deborah Rhoten, Michael Ryks, W Scott Harmsen, Michael Camilleri
Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. Effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), effects of aprepitant vs...
August 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28798084/a-small-population-of-liver-endothelial-cells-undergoes-endothelial-to-mesenchymal-transition-in-response-to-chronic-liver-injury
#2
Jordi Ribera, Montse Pauta, Pedro Melgar-Lesmes, Bernat Cordoba, Anna Bosch, Maria Calvo, Daniel Rodrigo-Torres, Pau Sancho-Bru, Aurea Mira, Wladimiro Jimenez, Manuel Morales-Ruiz
BACKGROUND AND AIMS: Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. METHODS: Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28798083/hamp1-mrna-and-plasma-hepcidin-levels-are-influenced-by-sex-and-strain-but-don-t-predict-tissue-iron-levels-in-inbred-mice
#3
Stela McLachlan, Kathryn E Page, Seung-Min Lee, Alex Loguinov, Erika Valore, Simon T Hui, Grace Jung, Jie Zhou, Aldons J Lusis, Brie Fuqua, Tomas Ganz, Elizabeta Nemeth, Chris D Vulpe
Iron homeostasis is tightly regulated and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex and strain dependent differences in mRNA and serum levels of hepcidin. Similarly, conflicting data on the relationship between hepcidin (Hamp1) mRNA levels and iron status as assessed by transferrin saturation and tissue iron concentrations were reported. Our aim was to clarify the relationships between strain, sex and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774871/enteric-serotonin-and-oxytocin-endogenous-regulation-of-severity-in-a-murine-model-of-necrotizing-enterocolitis
#4
Kara Gross Margolis, Jennifer Vittorio, Maria Talavera, Karen Gluck, Zhishan Li, Alina Iuga, Korey Stevanovic, Virginia Saurman, Narek Israelyan, Martha G Welch, Michael D Gershon
Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology, causes a great deal of morbidity and mortality in premature infants. The liver as well as the gut may be affected in NEC. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of experimental NEC in mice. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would increase the severity of NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose NEC...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774870/relationship-of-gastric-emptying-or-accommodation-with-satiation-satiety-and-postprandial-symptoms-in-health
#5
Houssam Halawi, Michael Camilleri, Andres Acosta, Maria I Vazquez-Roque, Ibironke Oduyebo, Duane D Burton, Irene A Busciglio, Alan R Zinsmeister
The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n=285, 73% females, mean BMI 33.5kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) using Ensure® nutrient drink test (30mL/min), and symptoms 30 minutes after MTV...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774869/overactivation-of-intestinal-sterol-response-element-binding-protein-2-promotes-diet-induced-non-alcoholic-steatohepatitis
#6
Pooja Malhotra, Costica Aloman, Aparna Ankireddy, Hani Khadra, Kohtaro Ooka, Ravinder K Gill, Seema Saksena, Pradeep K Dudeja, Waddah A Alrefai
Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver that may progress to hepatic fibrosis and nonalcoholic steatohepatitis (NASH). Mechanisms underlying NAFLD and NASH are not yet fully understood. Dietary cholesterol was recently shown to be a risk factor for the development of NASH suggesting a role for intestinal handling of cholesterol. One important regulator of cholesterol homeostasis is the Sterol Response Element Binding Protein SREBP2 transcription factor. We tested the hypothesis that the overactivation of intestinal SREBP2 increases the susceptibility to diet-induced NASH...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774868/role-of-g-protein-coupled-receptors-microrna-interactions-in-gastrointestinal-pathophysiology
#7
Ivy Ka Man Law, David Miguel Padua, Dimitrios Ilopoulos, Charalabos Pothoulakis
G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal (GI) cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferase in the cytoplasm, and thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiologic responses in different organs and cell types in humans and animals...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28751426/parp2-deficiency-affects-invariant-nkt-cell-maturation-and-protects-mice-from-concanavalin-a-induced-liver-injury
#8
Aveline Filliol, Claire Piquet-Pellorce, Sarah Dion, Valentine Genet, Catherine Lucas-Clerc, Françoise Dantzer, Michel Samson
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during Concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells which promote inflammation and induce hepatocyte death, mediated by the activated invariant NKT-(iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs such as spleen, thymus, and bone marrow in Parp2 deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28751425/melatonin-inhibits-hypothalamic-gonandotropin-releasing-hormone-release-and-reduces-biliary-hyperplasia-and-fibrosis-in-cholestatic-rats
#9
Matthew McMillin, Sharon DeMorrow, Shannon Glaser, Julie Venter, Konstantina Kyritsi, Tianhao Zhou, Stephanie Grant, Thao Giang, John F Greene, Nan Wu, Brandi Jefferson, Fanyin Meng, Gianfranco Alpini
Melatonin is a hormone produced by the pineal gland with increased circulating levels shown to inhibit biliary hyperplasia and fibrosis during cholestasis. Melatonin also has the capability to suppress the release of hypothalamic gonadotropin releasing hormone (GnRH), a hormone that promotes cholangiocyte proliferation when serum levels are elevated. However, the interplay and contribution of neural melatonin and GnRH to cholangiocyte proliferation and fibrosis in bile duct-ligated (BDL) rats has not been investigated...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28751424/a-simple-cost-effective-method-for-generating-murine-colonic-3d-enteroids-and-2d-monolayers-for-studies-of-primary-epithelial-cell-function
#10
Elizabeth H Fernando, Michael Dicay, Martin Stahl, Marilyn H Gordon, Andrew Vegso, Cristiane Baggio, Laurie Alston, Fernando Lopes, Kristi Baker, Simon Andrew Hirota, Derek M McKay, Bruce A Vallance, Wallace K MacNaughton
Cancer cell lines have been the mainstay of intestinal epithelial experimentation for decades, due primarily to their immortality and ease of culture. However, because of the inherent biological abnormalities of cancer cell lines, many cellular biologists are currently transitioning away from these models, and toward more representative primary cells. This has been particularly challenging, but recent advances in the generation of intestinal organoids have brought the routine use of primary cells within reach of most epithelial biologists...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729247/adaptive-regulation-of-pancreatic-acinar-mitochondrial-thiamin-pyrophosphate-uptake-process-possible-involvement-of-epigenetic-mechanism-s
#11
Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, Hamid M Said
The essentiality of thiamin stems from its roles as a co-factor (mainly in the form of thiamin pyrophosphate, TPP) in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive-regulation...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729246/vagally-mediated-effects-of-brainstem-dopamine-on-gastric-tone-and-phasic-contractions-of-the-rat
#12
Laura Anselmi, Luca Toti, Cecilia Bove, R Alberto Travagli
Dopamine (DA) containing fibers and neurons are embedded within the brainstem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally-dependent modulation of gastric tone and phasic contractions, i.e. motility, by DA, however, has not been characterized. Using microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were: i) assess the gastric effects of brainstem DA application, ii) identify the DA receptor subtype, and, iii) identify the postganglionic pathway(s) activated...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729245/a-novel-mouse-model-of-radiation-induced-cancer-survivorship-diseases-of-the-gut
#13
Cecilia Magdalena Bull, Dilip Malipatlolla, Marie Kalm, Fei Sjöberg, Eleftheria Alevronta, Rita Grandér, Pedram Sultanian, Linda Persson, Martina Boström, Yohanna Eriksson, John Swanpalmer, Agnes E Wold, Klas Blomgren, Thomas Björk-Eriksson, Gunnar Steineck
A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative in order to prevent, alleviate or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses, while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1,5 cm of the colorectum using a linear accelerator...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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