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PubMed Central (PMC3 - NLM DTD) (2.636.741 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).

American Journal of Physiology - Gastrointestinal and Liver Physiology

Mostrando recursos 1 - 20 de 731

1. Differentiation-dependent regulation of intestinal vitamin B2 uptake: studies utilizing human-derived intestinal epithelial Caco-2 cells and native rat intestine - Subramanian, Veedamali S.; Ghosal, Abhisek; Subramanya, Sandeep B.; Lytle, Christian; Said, Hamid M.
Intestinal epithelial cells undergo differentiation as they move from the crypt to the villi, a process that is associated with up- and downregulation in expression of a variety of genes, including those involved in nutrient absorption. Whether the intestinal uptake process of vitamin B2 [riboflavin (RF)] also undergoes differentiation-dependent regulation and the mechanism through which this occurs are not known. We used human-derived intestinal epithelial Caco-2 cells and native rat intestine as models to address these issues. Caco-2 cells showed a significantly higher carrier-mediated RF uptake in post- than preconfluent cells. This upregulation was associated with a significantly higher level...

2. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release - Ji, Yong; Sakata, Yasuhisa; Li, Xiaoming; Zhang, Chao; Yang, Qing; Xu, Min; Wollin, Armin; Langhans, Wolfgang; Tso, Patrick
Diamine oxidase (DAO) is abundantly expressed in mammalian small intestine catalyzing the oxidative breakdown of polyamines and histamine. The aim of this study was to determine the relationship between stimulation of intestinal diamine oxidase secretion with intestinal fat absorption and histamine release. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated and intraduodenal tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic DAO activity and protein secretion were analyzed by radiometric assay and Western blot, respectively. Lymphatic histamine concentration was measured by ELISA. Infusion of Liposyn II (4.43 kcal/3 ml) resulted...

3. Sex differences in brain response to anticipated and experienced visceral pain in healthy subjects - Kano, Michiko; Farmer, Adam D.; Aziz, Qasim; Giampietro, Vincent P.; Brammer, Michael J.; Williams, Steven C. R.; Fukudo, Shin; Coen, Steven J.
Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain...

4. Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts - Chen, Yishi; Chitapanarux, Taned; Wu, Jianfeng; Soon, Russell K.; Melton, Andrew C.; Yee, Hal F.
Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-l-arginine (l-NNA) or NG-monomethyl-l-arginine (l-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, l-NNA, and l-NMMA also prevented CNP-induced elevations in cGMP concentrations, and l-NNA or l-NMMA...

5. Stromal cells participate in the murine esophageal mucosal injury response - Shaker, Anisa; Binkley, Jana; Darwech, Isra; Swietlicki, Elzbieta; McDonald, Keely; Newberry, Rodney; Rubin, Deborah C.
We identified α-smooth muscle actin (α-SMA)- and vimentin-expressing spindle-shaped esophageal mesenchymal cells in the adult and neonate murine esophageal lamina propria. We hypothesized that these esophageal mesenchymal cells express and secrete signaling and inflammatory mediators in response to injury. We established primary cultures of esophageal mesenchymal cells using mechanical and enzymatic digestion. We demonstrate that these primary cultures are nonhematopoietic, nonendothelial, stromal cells with myofibroblast-like features. These cells increase secretion of IL-6 in response to treatment with acidified media and IL-1β. They also increase bone morphogenetic protein (Bmp)-4 secretion in response to sonic hedgehog. The location of these cells and...

6. NLRP1 and NLRP3 inflammasomes are essential for distinct outcomes of decreased cytokines but enhanced bacterial killing upon chronic Nod2 stimulation - Hedl, Matija; Abraham, Clara
Upon chronic microbial exposure and pattern-recognition receptor (PRR) stimulation, myeloid-derived cells undergo a distinct transcriptional program relative to acute PRR stimulation, with proinflammatory pathways being downregulated. However, other host-response pathways might be differentially regulated, and this concept has been relatively unexplored. Understanding mechanisms regulating chronic microbial exposure outcomes is important for conditions of ongoing infection or at mucosal surfaces, such as the intestine. The intracellular PRR nucleotide oligomerization domain 2 (Nod2) confers the highest genetic risk toward developing Crohn's disease (CD). We previously identified mechanisms mediating downregulation of proinflammatory pathways upon chronic Nod2 stimulation; here we sought to define how...

7. Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate - Moss, Angela K.; Hamarneh, Sulaiman R.; Mohamed, Mussa M. Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N.; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S.; Narisawa, Sonoko; Millán, José Luis; Warren, H. Shaw; Hohmann, Elizabeth; Malo, Madhu S.; Hodin, Richard A.
Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory...

8. Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury - Perepelyuk, Maryna; Terajima, Masahiko; Wang, Andrew Y.; Georges, Penelope C.; Janmey, Paul A.; Yamauchi, Mitsuo; Wells, Rebecca G.
Liver fibrosis is characterized by excessive deposition of extracellular matrix proteins by myofibroblasts derived from hepatic stellate cells and portal fibroblasts. Activation of these precursors to myofibroblasts requires matrix stiffness, which results in part from increased collagen cross-linking mediated by lysyl oxidase (LOX) family proteins. The aims of this study were to characterize the mechanical changes of early fibrosis, to identify the cells responsible for LOX production in early injury, and to determine which cells in normal liver produce collagens and elastins, which serve as substrates for LOXs early after injury. Hepatocytes and liver nonparenchymal cells were isolated from normal...

9. Keratinocyte growth factor-2 stimulates P-glycoprotein expression and function in intestinal epithelial cells - Saksena, Seema; Priyamvada, Shubha; Kumar, Anoop; Akhtar, Maria; Soni, Vikas; Anbazhagan, Arivarasu Natarajan; Alakkam, Anas; Alrefai, Waddah A.; Dudeja, Pradeep K.; Gill, Ravinder K.
Intestinal P-glycoprotein (Pgp/multidrug resistance 1), encoded by the ATP-binding cassette B1 gene, is primarily involved in the transepithelial efflux of toxic metabolites and xenobiotics from the mucosa into the gut lumen. Reduced Pgp function and expression has been shown to be associated with intestinal inflammatory disorders. Keratinocyte growth factor-2 (KGF2) has emerged as a potential target for modulation of intestinal inflammation and maintenance of gut mucosal integrity. Whether KGF2 directly regulates Pgp in the human intestine is not known. Therefore, the present studies were undertaken to determine the modulation of Pgp by KGF2 using Caco-2 cells. Short-term treatment of Caco-2...

10. Physiology of esophageal sensorimotor malfunctions in neonatal neurological illness - Jadcherla, Sudarshan R.; Chan, Chin Yee; Moore, Rebecca; Fernandez, Soledad; Shaker, Reza
We aimed to define the sensorimotor characteristics of aero-digestive reflexes evoked upon midesophageal provocations in neuropathology infants. Provocative esophageal motility testing was performed in 20 neuropathology infants and 10 controls at 42.3 ± 0.6 and 38.9 ± 0.9 wk postmenstrual age. Data from 1,073 infusions were examined for the sensory thresholds, response frequencies, response magnitude of upper esophageal sphincter (UES) contractile reflexes, lower esophageal sphincter (LES) relaxation reflexes, and peristaltic reflexes using mixed statistical models. Threshold volumes for air and liquid in neuropathology and control infants were similar for all reflexes. Graded air- and liquid volume-dependent UES contractile reflex, LES...

11. p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways - Huynh, Nhi; Yim, Mildred; Chernoff, Jonathan; Shulkes, Arthur; Baldwin, Graham S.; He, Hong
Gastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and...

12. Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment - Lalor, Patricia F.; Herbert, John; Bicknell, Roy; Adams, David H.
Platelets have recently been shown to drive liver injury in murine models of viral hepatitis and promote liver regeneration through the release of serotonin. Despite their emerging role in inflammatory liver disease, little is known about the mechanisms by which platelets bind to the hepatic vasculature. Therefore, we referenced public expression data to determine the profile of potential adhesive receptors expressed by hepatic endothelium. We then used a combination of tissue-binding and flow-based endothelial-binding adhesion assays to show that resting platelets bind to human hepatic sinusoidal endothelial cells and that the magnitude of adhesion is greatly enhanced by thrombin-induced platelet...

13. Anatomical and functional characterization of a duodeno-pancreatic neural reflex that can induce acute pancreatitis - Li, Cuiping; Zhu, Yaohui; Shenoy, Mohan; Pai, Reetesh; Liu, Liansheng; Pasricha, Pankaj Jay
Neural cross talk between visceral organs may play a role in mediating inflammation and pain remote from the site of the insult. We hypothesized such a cross talk exists between the duodenum and pancreas, and further it induces pancreatitis in response to intraduodenal toxins. A dichotomous spinal innervation serving both the duodenum and pancreas was examined, and splanchnic nerve responses to mechanical stimulation of these organs were detected. This pathway was then excited on the duodenal side by exposure to ethanol followed by luminal mustard oil to activate transient receptor potential subfamily A, member 1 (TRPA1). Ninety minutes later, pancreatic...

14. Activation of G protein-coupled bile acid receptor, TGR5, induces smooth muscle relaxation via both Epac- and PKA-mediated inhibition of RhoA/Rho kinase pathway - Rajagopal, Senthilkumar; Kumar, Divya P.; Mahavadi, Sunila; Bhattacharya, Sayak; Zhou, Ruizhe; Corvera, Carlos U.; Bunnett, Nigel W.; Grider, John R.; Murthy, Karnam S.
The present study characterized the TGR5 expression and the signaling pathways coupled to this receptor that mediates the relaxation of gastric smooth muscle. TGR5 was detected in gastric muscle cells by RT-PCR and Western blotting. Treatment of cells with the TGR5-selective ligand oleanolic acid (OA) activated Gαs, but not Gαq, Gαi1, Gαi2, or Gαi3, and increased cAMP levels. OA did not elicit contraction, but caused relaxation of carbachol-induced contraction of gastric muscle cells from wild-type mice, but not tgr5−/− mice. OA, but not a selective exchange protein activated by cAMP (Epac) ligand (8-pCPT-2′-O-Me-cAMP), caused phosphorylation of RhoA and the phosphorylation...

15. Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism - Groschwitz, Katherine R.; Wu, David; Osterfeld, Heather; Ahrens, Richard; Hogan, Simon P.
Mast cells regulate intestinal barrier function during disease and homeostasis. Secretion of the mast cell-specific serine protease chymase regulates homeostasis. In the present study, we employ in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction. Chymase stimulation of intestinal epithelial (Caco-2 BBe) cell monolayers induced a significant reduction in transepithelial resistance, indicating decreased intestinal epithelial barrier function. The chymase-induced intestinal epithelial barrier dysfunction was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Consistent with this observation, in vitro analysis revealed chymase-induced PAR-2 activation and increased MAPK activity...

16. Epidermal growth factor receptor expression and signaling are essential in glutamine's cytoprotective mechanism in heat-stressed intestinal epithelial-6 cells - Niederlechner, Stefanie; Baird, Christine; Petrie, Benjamin; Wischmeyer, Erhard; Wischmeyer, Paul E.
Epidermal growth factor receptor (EGFR) expression and signaling can induce cellular protection after intestinal inflammation. l-Glutamine (GLN) is known to prevent apoptosis after intestinal injury by activating MAPK and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. However, the role of EGFR expression and signaling in GLN-mediated cellular protection in intestinal epithelial-6 (IEC-6) cells after heat stress (HS) is unknown. To address the role of EGFR in GLN-mediated protection, IEC-6 cells were treated with GLN in the presence or absence of EGFR small interfering RNA, the EGFR tyrosine kinase inhibitor AG1478, the ERK1/2 inhibitor PD98059, the p38MAPK inhibitor SB203580, or the PI3-K/Akt inhibitor LY294002...

17. Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis - Michael, E. S.; Kuliopulos, A.; Covic, L.; Steer, M. L.; Perides, G.
Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2−/− mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca2+ concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury...

18. Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits - Camilleri, Michael; Kolar, Gururaj J.; Vazquez-Roque, Maria I.; Carlson, Paula; Burton, Duane D.; Zinsmeister, Alan R.
Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by χ2 test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model....

19. Colesevelam suppresses hepatic glycogenolysis by TGR5-mediated induction of GLP-1 action in DIO mice - Potthoff, Matthew J.; Potts, Austin; He, Tianteng; Duarte, João A. G.; Taussig, Ronald; Mangelsdorf, David J.; Kliewer, Steven A.; Burgess, Shawn C.
Bile acid sequestrants are nonabsorbable resins designed to treat hypercholesterolemia by preventing ileal uptake of bile acids, thus increasing catabolism of cholesterol into bile acids. However, sequestrants also improve hyperglycemia and hyperinsulinemia through less characterized metabolic and molecular mechanisms. Here, we demonstrate that the bile acid sequestrant, colesevelam, significantly reduced hepatic glucose production by suppressing hepatic glycogenolysis in diet-induced obese mice and that this was partially mediated by activation of the G protein-coupled bile acid receptor TGR5 and glucagon-like peptide-1 (GLP-1) release. A GLP-1 receptor antagonist blocked suppression of hepatic glycogenolysis and blunted but did not eliminate the effect of...

20. Evidence of functional cross talk between the Notch and NF-κB pathways in nonneoplastic hyperproliferating colonic epithelium - Ahmed, Ishfaq; Roy, Badal; Chandrakesan, Parthasarathy; Venugopal, Anand; Xia, Lijun; Jensen, Roy; Anant, Shrikant; Umar, Shahid
The Notch and NF-κB signaling pathways regulate stem cell function and inflammation in the gut, respectively. We investigate whether a functional cross talk exists between the two pathways during transmissible murine colonic hyperplasia (TMCH) caused by Citrobacter rodentium (CR). During TMCH, NF-κB activity and subunit phosphorylation in colonic crypts of NIH Swiss mice at days 6 and 12 were associated with increases in downstream target CXC chemokine ligand (CXCL)-1/keratinocyte-derived chemokine (KC) expression. Blocking Notch signaling acutely for 5 days with the Notch blocker dibenzazepine (DBZ) failed to inhibit crypt NF-κB activity or CXCL-1/KC expression. Chronic DBZ administration for 10 days,...

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