Scanning electron microscopic observation of apical sites of open-type paraneurons in the stomach, intestine and urethra.
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The apical region of open-type paraneurons in tubular organs functions as a receptor site for chemical information in the lumen. Electron microscopic studies have demonstrated a tuft of microvilli on the luminal surface of cells, but failed to visualize it three-dimensionally. The present scanning electron microscope (SEM) observation succeeded in viewing, from the luminal side, open-type paraneurons distributed in epithelia of the stomach, intestine, and urethra. The pyloric antrum of avian species and the duodenum of human fetuses, the latter forming an endocrine cell colony at every villus tip, were chosen for SEM observation in order to eliminate visual obstruction by adjacent epithelial cells with developed microvilli. The luminal surface of gut endocrine cells was consistently covered with a tuft of 80-200 microvilli. Pyloric paraneurons possessed thick and stiff microvilli as compared with those of exocrine cells. The microvilli on intestinal paraneurons were more irregular in length and more loosely grouped than those composing the striated border of enterocytes. Urethral paraneurons containing serotonin were surrounded by three or four polygonal epithelial cells. Their narrow apical surface was provided with 30-100 microvilli which varied in length from cell to cell, and which were conspicuously projected above the luminal surface of the urethra. The microvillous crown of the gut and urethral paraneurons was so prominent and constant a structure on the apical surface as to allow easy identification of open-type paraneurons under the SEM. (+info)
Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity.
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AIMS: To investigate the "gut origin of sepsis" hypothesis. METHODS: Prospective controlled study of 279 surgical patients in which cultures of nasogastric aspirates were compared with those obtained from mesenteric lymph nodes taken at laparotomy and the organisms cultured from subsequent septic complications. Bacterial translocation was confirmed if positive cultures were obtained from mesenteric lymph nodes. Postoperative sepsis was defined as any positive culture in the postoperative period. Bacterial species obtained in gastric microflora, mesenteric lymph nodes, and postoperative septic complications were compared. RESULTS: Only 85/279 patients (31%) had a sterile nasogastric aspirate; the most frequently identified organism was Candida spp. (54%) and the most common enteric organism cultured was E coli (20%). Multiple organisms were isolated in 39% and occurred more frequently in patients aged over 70 years, those undergoing non-elective surgery, and in those requiring proximal gastrointestinal surgery. Postoperative sepsis was more common in these patients. Bacterial translocation occurred in 21% and was significantly more frequent in those with multiple organisms in their nasogastric aspirates. E coli was the commonest organism isolated from the lymph node specimens (48%) and septic foci (53%). Fungal translocation did not occur. An identical genus was identified in the nasogastric aspirate and the septic focus in 30% of patients, in the nasogastric aspirate and the lymph node in 31%, and in the lymph node and a postoperative septic focus in 45%. CONCLUSIONS: Proximal gut colonisation is associated with both increased bacterial translocation and septic morbidity. The commonality of organisms identified supports the gut origin of sepsis hypothesis. (+info)
Gastric emptying rate assessment based on the proportion of intra-abdominal radioactivity in the stomach.
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Using scintigraphic techniques, the rate of gastric emptying is calculated by quantifying the absolute radioactivity within a gastric region of interest (intragastric method) with the time of meal completion considered 100% retention. However, this technique has significant limitations arising from subject movement and radionuclide gamma-ray attenuation, which may render curve fitting difficult, particularly in patients with gastroparesis. In an attempt to minimize these limitations, we have expressed the intragastric content as a percentage of the total abdominal radioactivity (abdominal method) and compared these two methods. METHODS: Forty-five subjects in a sitting position consumed a meal consisting of two fried eggs labeled with 99mTc, two slices of toast and 300 mL 5% glucose water (412 kcal). Data were acquired at a rate of one frame every 5 min from the left anterior oblique view. Using the two methods, the intragastric retention ratios at 30, 60, 90, 120 and 240 min and the 50% emptying time (T50) were obtained from both observation and calculation by power exponential fit. R2, representing goodness of fit of the nonlinear curve fitting, was calculated. RESULTS: There were no differences in the calculated values of T50 between the two methods. Quantitative estimates of T50 by extrapolation of a power exponential fit were feasible in 42 of the 45 subjects when the abdominal method was used, compared with only 29 of the 45 subjects when the intragastric method was used. In the 23 subjects with delayed emptying, quantitative estimates of T50 were feasible in 20 subjects when the abdominal method was used, compared with 7 subjects when the intragastric method was used. Using the abdominal method as opposed to the intragastric method also significantly improved R2. The difference between observed values and estimated values of T50 and intragastric retention ratios at 30, 90 and 120 min was smaller using the abdominal method. CONCLUSION: Scintigraphic measurement of gastric emptying calculated using the proportion of the abdominal radioactivity in the stomach offers substantial advantages over conventional methods, particularly in patients with gastroparesis. (+info)
Hepatic denervation does not affect plasma vasopressin response to intragastric hypertonic saline in conscious rats.
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Peripheral osmoreceptors monitor dietary NaCl and modify central nervous system and renal sympathetic nervous system activity accordingly. Experimental evidence suggests that these responses are dependent on the hepatic nerves. Peripheral osmoreceptors also modify arginine vasopressin (AVP) secretion. However, although hepatic denervation reportedly blunts activation of both supraoptic and paraventricular hypothalamic neurons after intraportal NaCl infusion, the role of the hepatic nerves in the AVP release has not been directly examined. The present study tests the hypothesis that the hepatic nerves modify AVP release in response to intragastric NaCl infusion. Wistar-Kyoto rats (WKY) received either hepatic denervation or a sham operation. Intragastric NaCl infusion significantly elevated plasma AVP in both sham-operated WKY and hepatic-denervated WKY, and the responses were not different between these groups. Second, previous studies suggest that both AVP secretion and baroreflexes are blunted in spontaneously hypertensive rats (SHR), deficits that contribute to the observed hypertension in SHR. We hypothesized that SHR also have a blunted peripheral osmoreceptor reflex and that this contributes to NaCl-sensitive hypertension. In contrast to our prediction, in SHR intragastric NaCl infusion induced an increase in plasma AVP that was similar to that in the WKY groups. Thus, although hepatic osmoreceptors are important for chronic regulation of arterial pressure, renal sympathetic nervous system activity, and the activity of hypothalamic neurons, they do not appear to influence plasma AVP concentration in response to intragastric NaCl. (+info)
Lessons from genetically engineered animal models. I. Physiological studies with gastrin in transgenic mice.
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The role of gastrin in the regulation of gastrointestinal growth and acid secretion has been addressed through recent studies involving transgenic and knockout mice. The role of gastrin as a key modulator of parietal cell function and gastric acid secretion has been confirmed through studies in mice deficient in either gastrin or the gastrin/CCK-B receptor. However, although gastrin-deficient mice show no changes in gastric proliferation, they do show reduced colonic proliferation, and rates of colonic proliferation are increased in transgenic mice overexpressing glycine-extended gastrin or progastrin. This themes article highlights recent progress in our understanding of the biology of gastrin through studies in genetically modified mice. (+info)
Expression of somatostatin receptor subtypes on guinea pig gastric and colonic smooth muscle cells.
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In vivo and in vitro studies have demonstrated that somatostatin can influence motility and smooth muscle contractility of the stomach and colon. Recent studies have proposed that some of these effects may be mediated by somatostatin receptors (sst) directly on the smooth muscle cells. If this is correct, the sst receptor subtypes that are present are unknown. This study aimed to resolve these points. Because nucleotide sequences of guinea pig sst genes are unknown, we used sst subtype-specific primers based on comparisons of human and rat sst subtypes and performed RT-PCR of DNase I-treated total RNA from guinea pig total brain. PCR products were cloned in pCR II and sequenced and showed 87% (sst(1)), 90% (sst(2)), 90% (sst(3)), 99% (sst(4)), and 80% (sst(5)), respectively, nucleotide homology to the same region (transmembrane 4-6) of the human sst genes. Homology to rat sequences were lower. PCR products were obtained from first-strand cDNA derived from DNase I-treated RNA from dispersed guinea pig gastric and colonic smooth muscle cells. In gastric and colonic smooth muscle cells, we detected sst(1)-sst(3) and sst(5), and all were confirmed by sequencing. The presence of sst(4) was shown by Southern blot analysis and hybridization with a guinea pig sst(4)-specific primer. RT-PCR from cultured colonic and gastric smooth muscle cells devoid of any neural elements gave identical results. These results demonstrate that in the guinea pig all five sst subtypes are present directly on gastric and colonic smooth muscle cells. Previous studies have suggested that a predominant sst(3) subtype on gastric and a sst(5) subtype on colonic muscle cells mediated somatostatin's contractile effects, but the finding here that all five sst subtypes exist on both of these cells suggests that other sst subtypes have only a small or no contractile effect, sst subtypes in guinea pig have a different pharmacological profile from rat or human sst, or these other sst subtypes have some yet undescribed physiological function in muscle cells. (+info)
Peripheral injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks peripheral CRF- and abdominal surgery-induced delayed gastric emptying in rats.
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The effect of the corticotropin-releasing factor (CRF) receptor antagonists astressin and D-Phe CRF(12-41) injected i.v. on CRF-induced delayed gastric emptying (GE) was investigated in conscious rats. Gastric transit was assessed by the recovery of methyl cellulose/phenol red solution 20 min after its intragastric administration. The 55% inhibition of GE induced by CRF (0.6 microgram i.v.) was antagonized by 87 and 100% by i.v. astressin at 3 and 10 microgram, respectively, and by 68 and 64% by i.v. D-Phe CRF(12-41) at 10 and 20 microgram, respectively. CRF (0.6 microgram)-injected intracisternally (i.c.) induced 68% reduction of GE was not modified by i.v. astressin (10 microgram) whereas i.c. astressin (3 or 10 microgram) blocked by 58 and 100%, respectively, i.v. CRF inhibitory action. Abdominal surgery with cecal manipulation reduced GE to 7.1 +/- 3.1 and 27.5 +/- 3.3% at 30 and 180 min postsurgery, respectively, compared with 40.3 +/- 4.3 and 59.5 +/- 2.9% at similar times after anesthesia alone. Astressin (3 microgram i.v.) completely and D-Phe CRF(12-41) (20 microgram i.v.) partially (60%) blocked surgery-induced gastric stasis observed at 30 or 180 min. The CRF antagonists alone (i.v. or i.c.) had no effect on basal GE. These data indicate that CRF acts in the brain and periphery to inhibit GE through receptor-mediated interaction and that peripheral CRF is involved in acute postoperative gastric ileus; astressin is a potent peripheral antagonist of CRF when injected i.v. whereas i.c. doses >/=3 microgram exert dual central and peripheral blockade of CRF action on gastric transit. (+info)
Depletion and restoration of the putative photosensitive materials store yielding nitric oxide in the isolated mouse gastric fundus.
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We investigated the possibility of there being any photosensitive materials stores yielding nitric oxide (NO), and combined for the first time electrical field stimulation (EFS)- and UV light-induced relaxations in mouse gastric fundus. The tissue responded with relaxation to long wave UV light (366 nm). Repeated exposure to light decreased the fundic photorelaxation in that the initial photorelaxation was 31.5 +/- 6.9% whereas the last (10th) photorelaxation was 2.3 +/- 0.8%. There were no significant differences between EFS (30 V, 0.5 ms, 1 Hz, 15 s)-induced relaxations obtained before (39.7 +/- 7.7%) and after (33.4 +/- 9.1%) UV irradiation, which were completely blocked by 10(-4) M L-N(G)-nitro-arginine methyl ester. Treatment of the tissue with NaNO(2), L-N(G)-nitro-arginine, S-nitrosoglutathione, or sodium nitroprusside for 30 min followed by prolonged washout restored the photorelaxation, whereas glyceryl trinitrate or L-arginine did not produce any improvement. EFS (30 V, 0.5 ms, 3 Hz) applied for 60 min significantly recovered the reduction of the photorelaxation. L-N-(delta)iminoethyl-L-ornithine, which does not contain NO(2) moiety, abolished electrically induced relaxation; however, it did not change photorelaxations. UV irradiation caused relaxation only when the adventitial surface of the preparation was oriented to the source of UV light. These results indicate that there could be a photosensitive relaxant materials store yielding NO in the smooth muscle layer of the gastric fundus from mouse. This putative store can be refilled by NaNO(2), L-N(G)-nitro-arginine, sodium nitroprusside, S-nitrosoglutathione, or long-term EFS but not glyceryl trinitrate or L-arginine. Possible candidates for NO-yielding substances might not be an organic nitrate but an intracellular nitrite, nitrosylated substances, and unknown nitro-containing compounds, which could be all sensitive to UV light. (+info)