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PubMed Central (PMC3 - NLM DTD) (2,707,507 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 788

121. Advances in cholangiocyte immunobiology - Syal, Gaurav; Fausther, Michel; Dranoff, Jonathan A.
Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes,...

122. Mechanism and regulation of vitamin B2 (riboflavin) uptake by mouse and human pancreatic β-cells/islets: physiological and molecular aspects - Ghosal, Abhisek; Said, Hamid M.
Riboflavin (RF) is essential for the normal metabolic activities of pancreatic β-cells and provides protection against oxidative stress. Very little is known about the mechanism of RF uptake by these cells and how the process is regulated. We addressed these issues using mouse-derived pancreatic β-TC-6 cells and freshly isolated primary mouse and human pancreatic islets. Our results showed 3H-RF uptake by β-TC-6 cells is Na+ independent, cis inhibited by RF-related compounds, trans stimulated by unlabeled RF, and saturable as a function of concentration (apparent Km of 0.17 ± 0.02 μM). The latter findings suggest involvement of a carrier-mediated process. Similarly,...

123. Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis - Linden, David R.
Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during “acute” inflammation. Hyperexcitability persisted at 6 days post-TNBS during...

124. Cocaine- and amphetamine-regulated transcript is the neurotransmitter regulating the action of cholecystokinin and leptin on short-term satiety in rats - Heldsinger, Andrea; Lu, Yuanxu; Zhou, Shi-Yi; Wu, Xiaoyin; Grabauskas, Gintautas; Song, Il; Owyang, Chung
Vagal CCK-A receptors (CCKARs) and leptin receptors (LRbs) interact synergistically to mediate short-term satiety. Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed by vagal afferent neurons. We sought to demonstrate that this neurotransmitter regulates CCK and leptin actions on short-term satiety. We also examined the signal transduction pathways responsible for mediating the CART release from the nodose ganglia (NG). ELISA studies coupled with gene silencing of NG neurons by RNA interference elucidated intracellular signaling pathways responsible for CCK/leptin-stimulated CART release. Feeding studies followed by gene silencing of CART in NG established the role of CART in mediating short-term satiety. Immunohistochemistry...

125. Insights from a novel model of slow-transit constipation generated by partial outlet obstruction in the murine large intestine - Heredia, Dante J.; Grainger, Nathan; McCann, Conor J.; Smith, Terence K.
The mechanisms underlying slow-transit constipation (STC) are unclear. In 50% of patients with STC, some form of outlet obstruction has been reported; also an elongated colon has been linked to patients with STC. Our aims were 1) to develop a murine model of STC induced by partial outlet obstruction and 2) to determine whether this leads to colonic elongation and, consequently, activation of the inhibitory “occult reflex,” which may contribute to STC in humans. Using a purse-string suture, we physically reduced the maximal anal sphincter opening in C57BL/6 mice. After 4 days, the mice were euthanized (acutely obstructed), the suture...

126. Autophagy and pancreatitis - Gukovskaya, Anna S.; Gukovsky, Ilya
Acute pancreatitis is an inflammatory disease of the exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. Recent findings from experimental models and genetically altered mice summarized in this review reveal that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis and that one cause of autophagy impairment is defective function of lysosomes. We propose that the lysosomal/autophagic dysfunction is a key initiating event in pancreatitis and a converging point of multiple deranged pathways. There is strong evidence supporting this hypothesis. Investigation of autophagy in pancreatitis has just started, and many questions about the “upstream”...

127. Activated hepatic stellate cells upregulate transcription of ecto-5′-nucleotidase/CD73 via specific SP1 and SMAD promoter elements - Fausther, Michel; Sheung, Nina; Saiman, Yedidya; Bansal, Meena B.; Dranoff, Jonathan A.
Adenosine is a potent modulator of liver fibrosis and inflammation. Adenosine has been shown to regulate such diverse activities as chemotaxis, contraction, and matrix production in hepatic stellate cells (HSC). Ecto-5′-nucleotidase/CD73 [EC 3.1.3.5] is the rate-limiting enzyme in adenosine production. Cd73-deficient mice are resistant to experimental liver fibrosis and have impaired adenosine generation. However, cell-specific expression and regulation of CD73 within the fibrotic liver have not been defined. In particular, prior evidence demonstrating that liver myofibroblasts, the cells believed to be responsible for matrix formation in the liver, express CD73 is lacking. Thus we tested the hypothesis that HSC and...

128. PGC-1α overexpression results in increased hepatic fatty acid oxidation with reduced triacylglycerol accumulation and secretion - Morris, E. Matthew; Meers, Grace M. E.; Booth, Frank W.; Fritsche, Kevin L.; Hardin, Christopher D.; Thyfault, John P.; Ibdah, Jamal A.
Studies have shown that decreased mitochondrial content and function are associated with hepatic steatosis. We examined whether peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) overexpression and a subsequent increase in mitochondrial content and function in rat primary hepatocytes (in vitro) and Sprague-Dawley rats (in vivo) would comprehensively alter mitochondrial lipid metabolism, including complete (CO2) and incomplete (acid-soluble metabolites) fatty acid oxidation (FAO), tricarboxylic acid cycle flux, and triacylglycerol (TAG) storage and export. PGC-1α overexpression in primary hepatocytes produced an increase in markers of mitochondrial content and function (citrate synthase, mitochondrial DNA, and electron transport system complex proteins) and an increase in FAO,...

129. Pancreatic and biliary secretion are both altered in cystic fibrosis pigs - Uc, Aliye; Giriyappa, Radhamma; Meyerholz, David K.; Griffin, Michelle; Ostedgaard, Lynda S.; Tang, Xiao Xiao; Abu-El-Haija, Marwa; Stoltz, David A.; Ludwig, Paula; Pezzulo, Alejandro; Abu-El-Haija, Maisam; Taft, Peter; Welsh, Michael J.
The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR...

130. Active cathepsins B, L, and S in murine and human pancreatitis - Lyo, Victoria; Cattaruzza, Fiore; Kim, Tyson N.; Walker, Austin W.; Paulick, Margot; Cox, Daniel; Cloyd, Jordan; Buxbaum, James; Ostroff, James; Bogyo, Matthew; Grady, Eileen F.; Bunnett, Nigel W.; Kirkwood, Kimberly S.
Cathepsins regulate premature trypsinogen activation within acinar cells, a key initial step in pancreatitis. The identity, origin, and causative roles of activated cathepsins in pancreatic inflammation and pain are not defined. By using a near infrared-labeled activity-based probe (GB123) that covalently modifies active cathepsins, we localized and identified activated cathepsins in mice with cerulein-induced pancreatitis and in pancreatic juice from patients with chronic pancreatitis. We used inhibitors of activated cathepsins to define their causative role in pancreatic inflammation and pain. After GB123 administration to mice with pancreatitis, reflectance and confocal imaging showed significant accumulation of the probe in inflamed pancreas...

131. Cell-specific effects of luminal acid, bicarbonate, cAMP, and carbachol on transporter trafficking in the intestine - Jakab, Robert L.; Collaco, Anne M.; Ameen, Nadia A.
Changes in intestinal luminal pH affect mucosal ion transport. The aim of this study was to compare how luminal pH and specific second messengers modulate the membrane traffic of four major ion transporters (CFTR, NHE3, NKCC1, and NBCe1) in rat small intestine. Ligated duodenal, jejunal, and ileal segments were infused with acidic or alkaline saline, 8-Br-cAMP, or the calcium agonist carbachol in vivo for 20 min. Compared with untreated intestine, lumen pH was reduced after cAMP or carbachol and increased following HCO3−-saline. Following HCl-saline, lumen pH was restored to control pH levels. All four secretory stimuli resulted in brush-border membrane...

132. Loss of MLK3 signaling impedes ulcer healing by modulating MAPK signaling in mouse intestinal mucosa - Kovalenko, Pavlo L.; Kunovska, Lyudmyla; Chen, Jian; Gallo, Kathleen A.; Basson, Marc D.
Mixed-lineage kinase 3 (MLK3) activates multiple MAPK pathways and can initiate apoptosis, proliferation, migration, or differentiation in different cell types. However, whether MLK3 signaling regulates intestinal epithelial cell sheet migration in vivo is not known. We sought to investigate whether MLK3 signaling is important in intestinal mucosal healing and epithelial cell motility in vivo and in vitro. In vivo, we compared the healing of jejunal mucosal ulcers induced in MLK3 knockout (KO) mice with healing in wild-type (WT) mice. Ulcer healing was 20.8% less at day 3 (P < 0.05) and 18.9% less at day 5 (P < 0.05) in...

133. Role of lipase-generated free fatty acids in converting mesenteric lymph from a noncytotoxic to a cytotoxic fluid - Qin, Xiaofa; Dong, Wei; Sharpe, Susan M.; Sheth, Sharvil U.; Palange, David C.; Rider, Therese; Jandacek, Ronald; Tso, Patrick; Deitch, Edwin A.
Recent studies have shown that mesenteric lymph plays a very important role in the development of multiple-organ dysfunction syndrome under critical conditions. Great efforts have been made to identify the biologically active molecules in the lymph. We used a trauma-hemorrhagic shock (T/HS) model and the superior mesenteric artery occlusion (SMAO) model, representing a global and a localized intestinal ischemia-reperfusion insult, respectively, to investigate the role of free fatty acids (FFAs) in the cytotoxicity of mesenteric lymph in rats. Lymph was collected before, during, and after (post) shock or SMAO. The post-T/HS and SMAO lymph, but not the sham lymph, manifested...

134. Loss of intracellular lipid binding proteins differentially impacts saturated fatty acid uptake and nuclear targeting in mouse hepatocytes - Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Martin, Gregory G.; Landrock, Kerstin K.; Landrock, Danilo; Payne, H. Ross; Kier, Ann B.; Schroeder, Friedhelm
The liver expresses high levels of two proteins with high affinity for long-chain fatty acids (LCFAs): liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2). Real-time confocal microscopy of cultured primary hepatocytes from gene-ablated (L-FABP, SCP-2/SCP-x, and L-FABP/SCP-2/SCP-x null) mice showed that the loss of L-FABP reduced cellular uptake of 12-N-methyl-(7-nitrobenz-2-oxa-1,3-diazo)-aminostearic acid (a fluorescent-saturated LCFA analog) by ∼50%. Importantly, nuclear targeting of the LCFA was enhanced when L-FABP was upregulated (SCP-2/SCP-x null) but was significantly reduced when L-FABP was ablated (L-FABP null), thus impacting LCFA nuclear targeting. These effects were not associated with a net decrease in expression...

135. Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum - Inoue, Takuya; Wang, Joon-Ho; Higashiyama, Masaaki; Rudenkyy, Sergiy; Higuchi, Kazuhide; Guth, Paul H.; Engel, Eli; Kaunitz, Jonathan D.; Akiba, Yasutada
Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal l-glutamate (l-Glu) and 5′-inosine monophosphate (IMP) synergistically increases duodenal HCO3− secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3− secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3− secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. l-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without...

136. Altered colorectal afferent function associated with TNBS-induced visceral hypersensitivity in mice - Feng, Bin; La, Jun-Ho; Tanaka, Takahiro; Schwartz, Erica S.; McMurray, Timothy P.; Gebhart, G. F.
Inflammation of the distal bowel is often associated with abdominal pain and hypersensitivity, but whether and which colorectal afferents contribute to the hypersensitivity is unknown. Using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, we investigated colorectal hypersensitivity following intracolonic TNBS and associated changes in colorectum and afferent functions. C57BL/6 mice were treated intracolonically with TNBS or saline. Visceromotor responses to colorectal distension (15–60 mmHg) were recorded over 8 wk in TNBS- and saline-treated (control) mice. In other mice treated with TNBS or saline, colorectal inflammation was assessed by myeloperoxidase assay and immunohistological staining. In vitro single-fiber recordings were...

137. CD18 is required for optimal lymphopenia-induced proliferation of mouse T cells - Sarin, Ritu; Abraham, Clara
Lymphocyte numbers are tightly regulated; with acute lymphopenia, T cell numbers are reestablished through lymphopenia-induced proliferation. In contrast to the costimulation requirements of antigen-driven proliferation, a number of costimulatory molecules are not required for lymphopenia-induced proliferation. However, the requirement for major histocompatibility complex (MHC)-T cell receptor (TCR) interactions and the enhanced lymphopenia-induced proliferation in T cells with higher TCR affinity argue for a role for surface molecules that contribute to efficient MHC-TCR interactions, in particular adhesion molecules. CD18 is an integrin that contributes to the activation of peripheral and intestinal T cells through adhesive and costimulatory mechanisms. We found that...

138. Luminal hypertonicity and acidity modulate colorectal afferents and induce persistent visceral hypersensitivity - La, Jun-Ho; Feng, Bin; Schwartz, Erica S.; Brumovsky, Pablo R.; Gebhart, G. F.
Carbohydrate malabsorption such as in lactose intolerance or enteric infection causes symptoms that include abdominal pain. Because this digestive disorder increases intracolonic osmolarity and acidity by accumulation of undigested carbohydrates and fermented products, we tested whether these two factors (hypertonicity and acidity) would modulate colorectal afferents in association with colorectal nociception and hypersensitivity. In mouse colorectum-pelvic nerve preparations in vitro, afferent activities were monitored after application of acidic hypertonic saline (AHS; pH 6.0, 800 mosM). In other experiments, AHS was instilled intracolonically to mice and behavioral responses to colorectal distension (CRD) measured. Application of AHS in vitro excited 80% of...

139. Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats - Dippold, Rachael P.; Vadigepalli, Rajanikanth; Gonye, Gregory E.; Hoek, Jan B.
Liver regeneration is an important repair response to liver injury. Chronic ethanol consumption inhibits and delays liver regeneration in experimental animals. We studied the effects of chronic ethanol treatment on messenger RNA (mRNA) and microRNA (miRNA) expression profiles during the first 24 h after two-thirds partial hepatectomy (PHx) and found an increase in hepatic miR-21 expression in both ethanol-fed and pair-fed control rats after PHx. We demonstrate that the increase of miR-21 expression during liver regeneration is more robust in ethanol-fed rats. Peak miR-21 expression occurs at 24 h after PHx in both ethanol-fed and control rats, corresponding to the...

140. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation - Bajaj, Jasmohan S.; Hylemon, Phillip B.; Ridlon, Jason M.; Heuman, Douglas M.; Daita, Kalyani; White, Melanie B.; Monteith, Pamela; Noble, Nicole A.; Sikaroodi, Masoumeh; Gillevet, Patrick M.
Although hepatic encephalopathy (HE) is linked to the gut microbiota, stool microbiome analysis has not found differences between HE and no-HE patients. This study aimed to compare sigmoid mucosal microbiome of cirrhotic patients to controls, between HE vs. no-HE patients, and to study their linkage with cognition and inflammation. Sixty cirrhotic patients (36 HE and 24 no-HE) underwent cognitive testing, stool collection, cytokine (Th1, Th2, Th17, and innate immunity), and endotoxin analysis. Thirty-six patients (19 HE and 17 no-HE) and 17 age-matched controls underwent sigmoid biopsies. Multitag pyrosequencing (including autochthonous genera, i.e., Blautia, Roseburia, Fecalibacterium, Dorea) was performed on stool...

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