Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma levels and renal uptake of gastrin were determined in ten dogs submitted to complete liver devascularization in order to induce an acute liver failure. Renal function was evaluated by renal plasma flow (RPF) and glomerular filtration rate (GFR) determinations. Liver devascularization was obtained by end-to-side porto-caval shunt (PCS) followed by temporary clamping of the hepatic artery. PCS alone did not affect renal function and renal ability to remove gastrin; after hepatic ischemia, both RPF, GFR and renal extraction of gastrin showed an abrupt decrease. At the end of the period of hepatic ischemia 5 dogs were submitted to glucose infusion, in consideration that: i) glucagon is able both to affect gastrin release and renal hemodynamics, and ii) hypoglycemia that develops after liver failure releases elevated amounts of glucagon. The renal handling of gastrin was not related to glucagon plasma levels, though the higher gastrin levels occurred at the lower glucagon concentrations. These data suggest that in acute liver failure there is a striking decrease of the renal clearance of gastrin associated with the impairment of kidney function. Furthermore, in this pathological condition plasma gastrin levels are affected by blood glucose concentrations through its effect on plasma glucagon levels.
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PMID:Plasma levels and renal removal of gastrin after acute hepatic ischemia in dogs. 647 Apr 35

Melatonin, a pineal hormone, synthesized from L-tryptophan, is known to exist in the gut and to scavenge oxygen free radicals but its role in gastroprotection against acute lesions induced by various strong irritants has been little studied. In this study, we determined the effects of melatonin and L-tryptophan on gastric secretion and the formation of acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), stress, and ischemia-reperfusion (I/R). Area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using a H2-gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentration by specific radioimmunoassay. Intragastric (i.g.) administration of melatonin (2.5-10 mg/kg) or L-tryptophan (25-200 mg/kg) failed to affect gastric lesions by ethanol and ASA but dose-dependently reduced the lesions provoked by stress and I/R; this protective effect was accompanied by a significant rise in plasma melatonin level, GBF, and DNA synthesis and by a marked fall in blood free radicals. L-tryptophan, which significantly elevated the plasma melatonin by about 3-5-fold, also reduced the stress and I/R-induced lesions and blood levels of free radicals, while increasing the GBF, DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE2 by indomethacin abolished the protection and the rise of GBF afforded by melatonin and L-tryptophan, whereas pretreatment with N(G)-nitro-L-arginine (L-NNA), to suppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L-tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hyperemia probably mediated by endogenous prostaglandin but not NO.
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PMID:The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. 939 46

Ischemia followed by reperfusion is known to produce gastric lesions due to oxidative stress, but the role of gastric H(+) secretion in the formation of this mucosal injury remains unknown. We studied alterations in gastric acid secretion and gastric histamine content, as well as the expression of histidine-decarboxylase and interleukin-1beta during the mucosal recovery from ischemia-reperfusion erosions. Gastric secretion was studied in rats (series A) with gastric fistula before, during and after the ischemia induced by clamping of celiac artery for 0.5 h followed by reperfusion in animals pretreated with vehicle (saline), omeprazole, a proton pump inhibitor, or ranitidine, a histamine (H(2)) receptor antagonist. In series B, the animals were submitted to 0.5 h of ischemia followed by 1 h of reperfusion and then anesthetized at 0, 3, 12 and 24 h or 3, 5, 10 or 15 days after the end of ischemia-reperfusion to determine gastric blood flow by H(2)-gas clearance technique, area of gastric lesions, plasma gastrin and interleukin-1beta levels, histamine content by radioimmunoassay (RIA) and expression of histidine-decarboxylase and interleukin-1beta mRNA by reverse transcription polymerase chain reaction. Clamping of celiac artery caused cessation of gastric blood flow and almost complete suppression of basal gastric acid secretion (series A) that returned gradually to the control value at day 3 after ischemia-reperfusion, accompanied by the rise in plasma gastrin levels, pronounced expression of histidine-decarboxylase mRNA and increased mucosal histamine content. Ischemia, followed by 1 h of reperfusion, produced gastric erosions (series B) that reached maximum at 12 h, but then declined at 24 h. These erosions progressed at day 3 into deeper ulcers whose area declined progressively within the next 5-15 days. The gastric blood ceased to flow (series B) during 30 min of clamping and was reduced throughout the period of healing of acute erosions, being accompanied by a gradual rise in mucosal interleukin-1beta mRNA content and in plasma interleukin-1beta levels. Treatment with omeprazole or ranitidine, which completely suppressed gastric acid secretion and significantly raised plasma gastrin level, greatly reduced the formation of erosive lesions preventing the progression of these lesions to chronic gastric ulcers, and this was accompanied by the rise in gastric blood flow and plasma gastrin levels and the significant attenuation of plasma interleukin-1beta levels. The ranitidine and omeprazole-induced suppression of ischemia-reperfusion erosions were abolished by the instillation of exogenous 0.2 N HCl into the stomach of these rats. The histidine-decarboxylase was faintly expressed in the intact gastric mucosa, but strongly upregulated during mucosal recovery from the damage induced by ischemia-reperfusion. We conclude that following ischemia-reperfusion: (1) gastric acid secretion, gastric microcirculation and histamine production markedly decline, while interleukin-1beta release significantly increases, probably playing an important role in the progression of acute lesions into chronic gastric ulcerations; (2) the suppression of gastric acid secretion by omeprazole and ranitidine, that induces hypergastrinemia, prevents the progression of gastric erosions into ulcers; and (3) the addition of exogenous acid restores the progression of the acute lesions into gastric ulcers, indicating that gastric acid plays a key role in ulcerogenesis induced by ischemia-reperfusion.
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PMID:Role of gastric acid secretion in progression of acute gastric erosions induced by ischemia-reperfusion into gastric ulcers. 1085 59

Ischemic preconditioning is considered as the most powerful gastroprotective intervention against mucosal lesions and ulcerations but the mechanism of this phenomenon has been little examined. In this study we tested the effects of inactivation of sensory nerves in new rat model combining acute gastric erosions with subsequent ulcers induced by ischemia-reperfusion (I/R). I/R lesions were produced in rats by clamping the celiac artery for 0.5 h followed by 3 h of reperfusion in rats with intact or inactivated sensory nerves by pretreatment with capsaicin for two weeks before the I/R. The animals were killed at 0 and 3 h and 3 days after I/R and the area of gastric lesions was determined planimetrically, the gastric blood flow (GBF) by H2-gas clearance technique and the plasma levels of gastrin by RIA. Gastric mucosal content of calcitonin gene related peptide (CGRP) was assessed by RIA. Following I/R, gastric erosive lesions occurred after 3 h and these erosive lesions then progressed into gastric ulcers within 3 days in all rats. Sensory-inactivation with capsaicin caused several fold increase in the area of early (at 3 h) acute lesions and later (at 3 d) gastric ulcers induced by I/R. This enhancement of acute and then chronic gastric lesions was accompanied by a significant fall in GBF, an elevation of plasma gastrin and a decrease in mucosal expression of CGRP. Ischemic preconditioning markedly reduced acute lesions and chronic ulcerations induced by I/R and attenuated the changes in plasma gastrin and mucosal CGRP contents but these effects were significantly more pronounced in rats with intact sensory nerves but less in capsaicin-inactivated animals. We conclude that: 1) The I/R resulted in the formation of early acute gastric lesions followed 3 days later by chronic gastric ulcers and this gastric injury was accompanied by an impairment of gastric microcirculation, hypergastrinemia and suppression the gastric mucosal CGRP; 2) Gastric ischemic-preconditioning significantly attenuated both acute mucosal damage and chronic ulcers induced by I/R and this was accompanied by a rise in gastric blood flow; 3) The inactivation of sensory nerves with capsaicin enhanced the formation of I/R-induced acute and chronic gastric lesions and strongly attenuated the gastroprotection afforded by I/R possibly due to the decline in mucosal blood flow and the fall in expression of integrity peptides such as CGRP and 4) The excessive release of gastrin may limit the extent of mucosal lesions observed during progression of gastric erosions into ulcers induced by I/R.
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PMID:Sensory nerves and calcitonin gene related peptide in the effect of ischemic preconditioning on acute and chronic gastric lesions induced by ischemia-reperfusion. 1178 59

Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L-NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGR(8-37) (100 microg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1-20 microg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 microg/kg and 6 microg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 microg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 microg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP(8-37). The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but not those of leptin while capsaicin denervation counteracted leptin-induced protection and rise in the GBF but attenuated significantly those of CCK. We conclude that: 1) central leptin exerts a potent gastroprotective activity against I/R-induced gastric erosions that progress into deeper gastric lesions and this protection depends upon vagal activity and sensory nerves and involves hyperemia probably mediated by NO and 2) leptin mimics the gastroprotective effect of CCK and may be implicated in the protective and hyperemic actions of this peptide against mucosal damage evoked by I/R.
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PMID:Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions. 1178 60

Rat stomach ECL cells release histamine in response to gastrin. Submucosal microinfusion of endothelin or adrenaline, known to cause vasoconstriction and gastric lesions, mobilized striking amounts of histamine. While the histamine response to gastrin is sustainable for hours, that to endothelin and adrenaline was characteristically short-lasting (1-2 h). The aims of this study were to identify the cellular source of histamine mobilized by endothelin and adrenaline, and examine the differences between the histamine-mobilizing effects of gastrin, and of endothelin and adrenaline. Endothelin, adrenaline or gastrin were administered by submucosal microinfusion. Gastric histamine mobilization was monitored by microdialysis. Local pretreatment with the H1-receptor antagonist mepyramine and the H2-receptor antagonist ranitidine did not prevent endothelin- or adrenaline-induced mucosal damage. Submucosal microinfusion of histamine did not cause damage. Acid blockade by ranitidine or omeprazole prevented the damage, suggesting that acid back diffusion contributes. Gastrin raised histidine decarboxylase (HDC) activity close to the probe, without affecting the histamine concentration. Endothelin and adrenaline lowered histamine by 50-70%, without activating HDC. Histamine mobilization declined upon repeated administration. Endothelin reduced the number of histamine-immunoreactive ECL cells locally, and reduced the number of secretory vesicles. Thus, unlike gastrin, endothelin (and adrenaline) is capable of exhausting ECL-cell histamine. Microinfusion of alpha-fluoromethylhistidine (known to deplete ECL cells but not mast cells of histamine) reduced the histamine-mobilizing effect of endothelin by 80%, while 1-week pretreatment with omeprazole enhanced it, supporting the involvement of ECL cells. Somatostatin or the prostanoid misoprostol inhibited gastrin-, but not endothelin-stimulated histamine release, suggesting that endothelin and gastrin mobilize histamine via different mechanisms. While gastrin effectively mobilized histamine from ECL cells in primary culture, endothelin had no effect, and adrenaline, a modest effect. Hence, the striking effects of endothelin and adrenaline on ECL cells in situ are probably indirect, possibly a consequence of ischemia.
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PMID:Submucosal microinfusion of endothelin and adrenaline mobilizes ECL-cell histamine in rat stomach, and causes mucosal damage: a microdialysis study. 1450 42

The role of somatostatin and growth hormone in eye diseases recently became a matter of interest because of its link with proliferative diabetic retinopathy. In diabetic patients the pathologic proliferation of blood vessels as a result of retinal ischemia is a major cause of blindness. The hypoxic portions of the retina release angiogenic factors, stimulating neovascularization. Somatostatin is a natural peptide hormone that affects the release of a number of other hormones, such as growth hormone, glucagon, insulin and gastrin. The somatostatin analog promises to be safe and effective treatment for severe diabetic retinopathy. This compound has been shown to block the local and systemic production of insulin-like growth factor 1 and growth hormone, which promote the angiogenesis and endothelial cell proliferation associated with proliferative retinopathy. Several studies have confirmed that using somatostatin analogs to block insulin-like growth factor 1 production is effective in reducing neovascularization and preventing disease progression to proliferative stage of diabetic retinopathy. Long-acting somatostatin analogs are currently being tested for the treatment of diabetic retinopathy. The development of somatostatin analogs with increased selectivity for receptor subtypes will provide improved outcomes in the management of patients with diabetic retinopathy.
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PMID:Diabetes mellitus and retinopathy. 1507 18

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenase (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hyperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE(2) or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhancement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurrence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE(2) generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.
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PMID:Role of prostaglandins in gastroprotection and gastric adaptation. 1624 88

Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.
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PMID:Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced by noxious agents. 1722 88

This clinical study compares effects between enteral nutrition and parenteral nutrition in the early stage of severe burns. Nineteen cases of severe burn patients were divided randomly into total enteral nutrition group (TEN) and total parenteral nutrition group (TPN). Plasma motilin, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxin, tumor necrosis factor (TNF), serum gastrin, diamine oxidase (DAO), and urine lactulose/mannitol ratio (L/M) was determined on post burn day (PBD) 1, 4, 8, 14, respectively. The results showed that serum gastrin, plasma motilin, and SOD were significantly higher in TEN than in TPN on PBD4, 8 (p<0.05-0.01). Plasma MDA was obviously lower in TEN than in TPN on PBD4, 8 (p<0.01). Plasma endotoxin was significantly lower in TEN than in TPN on PBD4, 8 (p<0.01). Plasma TNF were significantly lower in TEN than in TPN on PBD4, 8, 14 (p<0.01). The level of serum DAO and urine L/M ratio in TEN was obviously lower than in TPN on PBD4 and 8, respectively (p<0.05-0.01). A positive correlation between L/M and DAO, MDA, TNF (r=0.5822-0.7598, p<0.05-0.01), and a negative correlation between L/M and SOD (r=-0.7771, p<0.01), and a positive correlation between plasma endotoxin and TNF, MDA (r=0.9038 and 0.6705, p<0.05-0.01) were found. These results indicate that enteral nutrition was a more effective route to preserve gastrin secretion and motility of gastrointestinal tract, lower intestinal ischemia and reperfusion injury, reduce intestinal permeability, decrease plasma endotoxin and inflammatory mediators, and maintain mucosa barrier function. Whenever gastrointestinal function permits, enteral nutrition was superior to parenteral nutrition early after burn.
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PMID:A comparison study between early enteral nutrition and parenteral nutrition in severe burn patients. 1746 14


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