American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · Feb 2010
Comparative StudyNoninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model.
Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. ⋯ In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jan 2010
Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice.
The excitatory ion channel transient receptor potential ankyrin-1 (TRPA1) is prominently expressed by primary afferent neurons and is a mediator of inflammatory pain. Inflammatory agents can directly activate [e.g., hydroxynonenal (HNE), prostaglandin metabolites] or indirectly sensitize [e.g., agonists of protease-activated receptor (PAR(2))] TRPA1 to induce somatic pain and hyperalgesia. However, the contribution of TRPA1 to visceral pain is unknown. ⋯ Direct activation of TRPA1 causes visceral hyperalgesia, and TRPA1 mediates PAR(2)-induced hyperalgesia. TRPA1 deletion markedly reduces colitis-induced mechanical hyperalgesia in the colon. Our results suggest that TRPA1 has a major role in visceral nociception and may be a therapeutic target for colonic inflammatory pain.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jan 2010
Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall.
Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. ⋯ The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Dec 2009
Randomized Controlled TrialCharacterizing the application of transcranial direct current stimulation in human pharyngeal motor cortex.
Transcranial direct current stimulation (tDCS) is a novel intervention that can modulate brain excitability in health and disease; however, little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex. Here, we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to designing a therapeutic intervention in dysphagic patients. Healthy subjects (n = 17) underwent seven regimens of tDCS (anodal 10 min 1 mA, cathodal 10 min 1 mA, anodal 10 min 1.5 mA, cathodal 10 min 1.5 mA, anodal 20 min 1 mA, cathodal 20 min 1 mA, Sham) on separate days, in a double blind randomized order. ⋯ There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects. In conclusion, anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner, with little evidence for transcallosal spread. Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Nov 2009
Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI.
This study assessed the effects of meal volume (MV) and calorie load (CL) on gastric function. MRI and a minimally invasive fiber-optic recording system (FORS) provided simultaneous measurement of gastric volume and pressure changes during gastric filling and emptying of a liquid nutrient meal in physiological conditions. The gastric response to 12 iso-osmolar MV-CL combinations of a multinutrient drink (MV: 200, 400, 600, 800 ml; CL: 200, 300, 400 kcal) was tested in 16 healthy subjects according to a factorial design. ⋯ GCV half-emptying time decreased with CL at 18 +/- 6 min for each additional 100-kcal load (P < 0.001). These findings indicate that gastric wall stress (passive strain and active tone) provides the driving force for gastric emptying, but distal resistance to gastric outflow regulates further passage of nutrients. The distinct early phase of gastric emptying with relatively rapid, uncontrolled passage of nutrients into the small bowel, modulated by meal volume but not nutrient composition, ensures that the delivery of nutrients in the later postprandial period is related to the overall calorie load of the meal.