American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · Aug 2004
Absence of increasing cortical fMRI activity volume in response to increasing visceral stimulation in IBS patients.
Cerebral cortical activity associated with perceived visceral sensation represents registration of afferent transduction and cognitive processes related to perception. Abnormalities of gut sensory function can involve either or both of these processes. Cortical registration of subliminal viscerosensory signals represents cerebral cortical activity induced by stimulation of intestinal sensory neurocircuitry without the influence of perception-related cortical activity, whereas those associated with perception represent both neural circuitry and cognitive processes. ⋯ In control subjects, there was a direct relationship between stimulus intensity and cortical activity volumes, ie., the volume of fMRI cortical activity in response to subliminal (3,226 +/- 335 microl), liminal (5,751 +/- 396 microl), and supraliminal nonpainful stimulation (8,246 +/- 624 microl) were significantly different (P < 0.05). In contrast, in IBS patients this relationship was absent and fMRI activity volumes for subliminal (2,985 +/- 332 microl), liminal (2,457 +/- 342 microl), and supraliminal nonpainful stimulation (2,493 +/- 351 microl) were similar. Additional recruitment of cortical fMRI activity volume in response to increasing stimulation from subliminal to liminal and supraliminal domains is absent in IBS patients, suggesting a difference in the processing of perceived stimulation compared with controls.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Apr 2004
Ischemic preconditioning attenuates ischemia-reperfusion-induced mucosal apoptosis by inhibiting the mitochondria-dependent pathway in rat small intestine.
Ischemic preconditioning provides a way of protecting organs from damage inflicted with prolonged ischemia-reperfusion. In this study, we investigated the mechanism of ischemic preconditioning involved in inhibition of prolonged ischemia-reperfusion-induced mucosal apoptosis in rat small intestine. Ischemic preconditioning was triggered by a transient occlusion of the superior mesenteric artery followed by reperfusion. ⋯ Pretreatment with 20-min ischemia followed by 5-min reperfusion significantly inhibited the prolonged ischemia-reperfusion-induced mucosal apoptosis by 30%. Ischemic preconditioning ameliorated mitochondrial respiratory dysfunction by 50%, reduced reactive oxygen species generation by 38%, and suppressed mitochondrial lipid peroxidation by 36%, resulting in improvement of the mitochondrial membrane potential and prevention of cytochrome c release as well as caspase-6 activation. Results suggest that ischemic preconditioning attenuated ischemia-reperfusion-induced mucosal apoptosis partly by inhibiting the reactive oxygen species-mediated mitochondria-dependent pathway in the rat small intestine.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jan 2004
High-resolution visualization of oxygen distribution in the liver in vivo.
Microcirculatory failure after stress events results in mismatch in oxygen supply and demand. Determination of tissue oxygen distribution in vivo may help elucidate mechanisms of injury, but present methods have limited resolution. Male Sprague-Dawley rats were anesthetized, prepared for intravital microscopy, and received intravenously the oxygen-sensitive fluorescent dye Tris(1,10-phenanthroline)ruthenium(II) chloride hydrate [Ru(phen)3(2+)]. ⋯ Ethanol did not alter Ru(phen)3(2+) fluorescence but increased NADH fluorescence indicating independence of P(O2) and redox state imaging. Intravenous administration of Ru(phen)3(2+) for intravital videomicroscopy represents a new method to visualize the hepatic tissue P(O2). Combined with NADH autofluorescence, it provides additional information regarding the tissue redox state.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Dec 2003
Circumferential, not longitudinal, colonic stretch increases synaptic input to mouse prevertebral ganglion neurons.
The relationship between longitudinal and circular muscle tension in the mouse colon and mechanosensory excitatory synaptic input to neurons in the superior mesenteric ganglion (SMG) was investigated in vitro. Electrical activity was recorded intracellularly from SMG neurons, and muscle tension was simultaneously monitored in the longitudinal, circumferential, or both axes. Colonic intraluminal pressure and volume changes were also monitored simultaneously with muscle tension changes. ⋯ There was no increase in synaptic input when tubular colon segments were stretched in their long axes up to 20% beyond their resting length. The circumferential stretch-sensitive increase in the frequency of synaptic input to SMG neurons persisted when the colonic muscles were relaxed pharmacologically by nifedipine (2 microM) or nicardipine (3 microM). These results suggest that colonic mechanosensory afferent nerves projecting to the SMG function as length or stretch detectors in parallel to the circular muscle layer.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Apr 2003
Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3.
Cytokines may cause an acquired growth hormone (GH) resistance in patients with inflammatory diseases. Anabolic effects of GH are mediated through activation of STAT5 transcription factors. We have reported that TNF-alpha suppresses hepatic GH receptor (GHR) gene expression, whereas the cytokine-inducible SH2-containing protein 1 (Cis)/suppressors of cytokine signaling (Socs) genes are upregulated by TNF-alpha and IL-6 and inhibit GH activation of STAT5. ⋯ Inhibition of STAT5 activation by LPS was temporally associated with phosphorylation of STAT3 and upregulation of Cis and Socs-3 protein in WT and TNFR1 null mice; STAT3, Cis, and Socs-3 were not induced in IL-6 null mice. IL-6 inhibits hepatic GH signaling by upregulating Cis and Socs-3, which may involve activation of STAT3. Therapies that block IL-6 may enhance GH signaling in inflammatory diseases.