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PubMed Central (PMC3 - NLM DTD) (2,823,404 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 121 - 140 de 863

121. Heme oxygenase-1 deficiency promotes the development of necrotizing enterocolitis-like intestinal injury in a newborn mouse model - Schulz, Stephanie; Wong, Ronald J.; Jang, Kyu Yun; Kalish, Flora; Chisholm, Karen M.; Zhao, Hui; Vreman, Hendrik J.; Sylvester, Karl G.; Stevenson, David K.
Necrotizing enterocolitis (NEC) is typified by mucosal destruction, which subsequently can lead to intestinal necrosis. Prematurity, enteral feeding, and bacterial colonization are the main risk factors and, combined with other stressors, can cause increased intestinal permeability, injury, and an exaggerated inflammatory response. Heme oxygenase-1 (HO-1) mediates intestinal protection due to anti-inflammatory, antioxidative, and antiapoptotic effects of its products carbon monoxide, biliverdin, and bilirubin. This study investigates a possible role of HO-1 in the pathogenesis of NEC using a newborn mouse model. We induced NEC-like intestinal injury in 7-day-old HO-1 heterozygous (HO-1 Het, Hmox1+/-) and wild-type (Wt, Hmox1+/+) mice by gavage...

122. Emerging neuropeptide targets in inflammation: NPY and VIP - Chandrasekharan, Bindu; Nezami, Behtash Ghazi; Srinivasan, Shanthi
The enteric nervous system (ENS), referred to as the “second brain,” comprises a vast number of neurons that form an elegant network throughout the gastrointestinal tract. Neuropeptides produced by the ENS play a crucial role in the regulation of inflammatory processes via cross talk with the enteric immune system. In addition, neuropeptides have paracrine effects on epithelial secretion, thus regulating epithelial barrier functions and thereby susceptibility to inflammation. Ultimately the inflammatory response damages the enteric neurons themselves, resulting in deregulations in circuitry and gut motility. In this review, we have emphasized the concept of neurogenic inflammation and the interaction between...

123. Digestive and respiratory tract motor responses associated with eructation - Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza
We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges. We found eructation in three distinct functional phases that were composed of different sets of motor responses: gas escape, barrier elimination, and gas transport. The gas escape phase, activated by gastric distension, consists of relaxation of the lower esophageal sphincter and diaphragmatic hiatus and contraction of the longitudinal muscle of the thoracic esophagus and rectus abdominis. All...

124. Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis - Ziogas, Dimitrios C.; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M.; Najarian, Robert M.; Nagel, Jutta M.; Flier, Sarah N.; Popov, Yury; Tseng, Yu-Hua; Kokkotou, Efi
Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well...

125. Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury - Ge, Xiaodong; Lu, Yongke; Leung, Tung-Ming; Sørensen, Esben S.; Nieto, Natalia
Alcohol consumption is a leading cause of liver disease worldwide; thus, there is an urgent need to develop novel therapeutic interventions. Key events for the onset and progression of alcoholic liver disease result in part from the gut-to-liver interaction. Osteopontin is a cytokine present at high concentration in human milk, umbilical cord, and infants' plasma with beneficial potential. We hypothesized that dietary administration of milk osteopontin could prevent alcohol-induced liver injury perhaps by maintaining gut integrity and averting hepatic inflammation and steatosis. Wild-type mice were fed either the control or the ethanol Lieber-DeCarli diets alone or in combination with milk...

126. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine - Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J.; Mikami, Dean J.; Wood, Jackie D.
Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric...

127. Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids - Zhang, Justine H.; Nolan, Jonathan D.; Kennie, Sarah L.; Johnston, Ian M.; Dew, Tracy; Dixon, Peter H.; Williamson, Catherine; Walters, Julian R. F.
Fibroblast growth factor 19 (FGF19) is proposed to be a negative feedback regulator of hepatic bile acid (BA) synthesis. We aimed to clarify the distribution of FGF19 expression in human intestine and to investigate induction in a novel explant system. Ileal and colonic mucosal biopsies were obtained at endoscopy and analyzed for FGF19 transcript expression. Primary explants were incubated with physiological concentrations of various BA for up to 6 h, and expression of FGF19 and other genes was determined. FGF19 transcripts were detected in ileum but were unquantifiable in colon. No loss of FGF19 mRNA occurred as a consequence of...

128. Nrf2 is not required for epithelial prohibitin-dependent attenuation of experimental colitis - Kathiria, Arwa S.; Butcher, Mackenzie A.; Hansen, Jason M.; Theiss, Arianne L.
Inflammatory bowel disease is associated with increased reactive oxygen species (ROS) and decreased antioxidant response in the intestinal mucosa. Expression of the mitochondrial protein prohibitin (PHB) is also decreased during intestinal inflammation. Our previous study showed that genetic restoration of colonic epithelial PHB expression [villin-PHB transgenic (PHB Tg) mice] attenuated dextran sodium sulfate (DSS)-induced colitis/oxidative stress and sustained expression of colonic nuclear factor erythroid 2-related factor 2 (Nrf2), a cytoprotective transcription factor. This study investigated the role of Nrf2 in mediating PHB-induced protection against colitis and expression of the antioxidant response element (ARE)-regulated antioxidant genes heme oxygenase-1 (HO-1) and NAD(P)H...

129. Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents - Zhang, Shizhong; Grabauskas, Gintautas; Wu, Xiaoyin; Joo, Moon Kyung; Heldsinger, Andrea; Song, Il; Owyang, Chung; Yu, Shaoyong
Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials...

130. BMP2 inhibits TGF-β-induced pancreatic stellate cell activation and extracellular matrix formation - Gao, Xuxia; Cao, Yanna; Yang, Wenli; Duan, Chaojun; Aronson, Judith F.; Rastellini, Cristiana; Chao, Celia; Hellmich, Mark R.; Ko, Tien C.
Activation of pancreatic stellate cells (PSCs) by transforming growth factor (TGF)-β is the key step in the development of pancreatic fibrosis, a common pathological feature of chronic pancreatitis (CP). Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have anti-fibrogenic functions, in contrast to TGF-β, in the kidney, lung, and liver. However, it is not known whether BMPs have an anti-fibrogenic role in the pancreas. The current study was designed to investigate the potential anti-fibrogenic role of BMPs in the pancreas using an in vivo CP model and an in vitro PSC model. CP was induced by repetitive intraperitoneal injections...

131. The role of plasminogen activator inhibitor-1 in gastric mucosal protection - Kenny, Susan; Steele, Islay; Lyons, Suzanne; Moore, Andrew R.; Murugesan, Senthil V.; Tiszlavicz, Laszlo; Dimaline, Rod; Pritchard, D. Mark; Varro, Andrea; Dockray, Graham J.
Gastric mucosal health is maintained in response to potentially damaging luminal factors. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt protective mechanisms leading to bleeding and ulceration. The plasminogen activator system has been implicated in fibrinolysis following gastric ulceration, and an inhibitor of this system, plasminogen activator inhibitor (PAI)-1, is expressed in gastric epithelial cells. In Helicobacter pylori-negative patients with normal gastric histology taking aspirin or NSAIDs, we found elevated gastric PAI-1 mRNA abundance compared with controls; the increase in patients on aspirin was independent of whether they were also taking proton pump inhibitors. In the same patients, aspirin tended to...

132. A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon - Kurahashi, Masaaki; Nakano, Yasuko; Peri, Lauren E.; Townsend, Jared B.; Ward, Sean M.; Sanders, Kenton M.
Recently platelet-derived growth factor-α-positive cells (PDGFRα+ cells), previously called “fibroblast-like” cells, have been described in the muscle layers of the gastrointestinal tract. These cells form networks and are involved in purinergic motor neurotransduction. Examination of colon from mice with enhanced green fluorescent protein (eGFP) driven from the endogenous Pdgfra (PDGFRα-eGFP mice) revealed a unique population of PDGFRα+ cells in the mucosal layer of colon. We investigated the phenotype and potential role of these cells, which have not been characterized previously. Expression of PDGFRα and several additional proteins was surveyed in human and murine colonic mucosae by immunolabeling; PDGFRα+ cells in...

133. 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...

134. 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...

135. 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...

136. 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...

137. 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...

138. 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...

139. 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...

140. 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...

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