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)

Aggressive treatment with H(2) receptor blocking agents and/or antacids has been advocated as effective prophylaxis against and treatment for "stress ulcer," based on the logical but infrequently tested assumption that the severity of the disease is critically determined by the concentration of intraluminal acid. The present study investigated this assumption in a model which employed topical acid, topical bile acid and mucosal ischemia to induce ulcerogenesis. With vascularized, chambered ex vivo wedges of canine proximal gastric wall, groups of animals were studied during three sequential periods using topical test solutions (TS) containing either 0 mM, 100 mM or 160 mM HCI. During period 1, mucosae were exposed to TS alone; during period 2, either to TS containing 1 mM sodium taurocholate (TC) or to TS and concomitant vasopressin infusion (VP); and during period 3, to TS + TC + VP. Parameters evaluated included net H(+) flux ( big up tri, openH(+)), aminopyrine clearance (AC), a measure of mucosal blood flow, net TC flux ( big up tri, openTC) and the lesion index, graded 0-5. The data indicate that in nonischemic mucosa exposed to constant [TC], AC was significantly increased, big up tri, openH(+) ("back-diffusion") increased as a linear function of [H(+)] and no lesions were observed. Under the same circumstances in ischemic mucosa, big up tri, openH(+) increased as linear function of [H(+)]. As a consequence, lesion severity was also a linear function of [H(+)]. big up tri, openTC was enhanced at low pH but bore no relation to the degree of mucosal damage induced. Assuming applicability of the model, these studies provide support for the use of H(2) receptor blocking agents and/or antacids to prevent or ameliorate "stress ulcer" disease.
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PMID:Influence of hydrogen ion concentration on bile acid induced acute gastric mucosal ulcerogenesis. 3 49

6-[6-(4-Hydroxypiperidinyl)hexyloxy]-3-methylflavone HCI, (NPC 16377), a potent and highly selective sigma-site ligand, was evaluated in tests predictive of antipsychotic and neuroprotective potential and for toxicity. Like haloperidol, clozapine and remoxipride, and the sigma-ligands BMY 14802, ifenprodil and rimcazole, NPC 16377 reversed amphetamine-induced hyperactivity and apomorphine-induced climbing in mice. Additional evidence for antipsychotic activity was obtained in rats with NPC 16377, clozapine, BMY 14802, ifenprodil, haloperidol and rimcazole, all of which reduced conditioned avoidance responses at doses that did not reduce escape behavior. NPC 16377 did not induce catalepsy in mice, suggesting a decreased liability for producing extrapyramidal side effects. NPC 16377 extended survival time for mice exposed to a hypoxic environment. In a model of global ischemia using conscious gerbils, NPC 16377 prevented damage to hippocampal CA1 neurons after either intraperitoneal or oral administration. NPC 16377 did not disrupt prepulse inhibition or block the disruption of prepulse inhibition induced by the phencyclidine site-selective ligand (+)MK-801. In rats trained to discriminate phencyclidine from saline, NPC 16377 did not substitute for the psychotomimetic. These data are consistent with the notion that selective sigma-agents may possess antipsychotic and neuroprotective activities. Moreover, the results from prepulse inhibition and drug discrimination experiments suggest that NPC 16377 is devoid of phencyclidine-like effects.
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PMID:NPC 16377, a potent and selective sigma-ligand. II. Behavioral and neuroprotective profile. 809 65

The three-compartment model of brain acid-base regulation postulates that under circumstances of changing function or disease, hydrogen ion concentrations may differ considerably in the interstitial space (ISS), the neurons and the glial cells. During hyperglycemia plus profound ischemia, for example, direct measurements by microelectrodes followed by intracellular HRP staining show that intraglial pH can fall transiently as low as 3.9, although more often the nadir drops to the 4.5-5.5 range. Concurrently, ISS-pH and, by calculation, neuronal pH fails to and remains constant (but not necessarily the same) at pH 6.2. By contrast, during spreading depression, ISS and intraglial pH at first move rapidly and transiently in opposite directions, ISS [H+] rising, intraglial falling. These two then gradually stabilize, whereas neuronal pH remains substantially more steady and near normal, shifting only minimally from resting baseline levels over several minutes' time. Similar but less pronounced effects follow direct electrical stimulation. The net change represents complex biophysical transmembrane and buffering mechanisms that appear to guard neuronal homeostasis. Studies carried out on embryonic rat forebrain neurons and glia show that these cells have considerably different vulnerabilities to extracellular acidity depending on the anionic nature of the acid in the bathing medium. In cultures to which HCI was added to the medium, neurons and neuronal processes almost all survived ten minute exposures to pH 3.8, whereas glial cells succumbed after ten minute exposures at pH not lower than 4.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo and in vitro control of acid-base regulation of brain cells during ischemic and selective acidic exposure. 842 56

Recently increased production of endothelin-1 has been implicated in the pathogenesis of gastric ischemia-reperfusion injury. We have investigated the effects of endothelin converting enzyme inhibition on local gastric ischemia-reperfusion injury in rats by using two metalloprotease inhibitors, phosphoramidon and thiorphan. In presence of exogenous 0.15M HCI intragastrically, local ischemia was induced by the clamping of left gastric artery for 15 min and reperfusion was done for 30 min. In separate group of rats, phosphoramidon (10-60 mg/kg) or thiorphan (60 mg/kg) were given as i.v. bolus injection immediately before the induction of ischemia. Phosphoramidon dose dependently attenuated the macroscopic and microscopic mucosal injuries while thiorphan did not. These results indicate that phosphoramidon-sensitive endothelin converting enzyme activity is highly present in stomach and phosphoramidon, by inhibiting the conversion of big endothelin-1 to endothelin-1 attenuated the gastric mucosal damage in this model.
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PMID:Phosphoramidon, an endothelin converting enzyme inhibitor attenuates local gastric ischemia-reperfusion injury in rats. 929 43

The neuroprotective activity of the non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist GYKI-52466 (1-[4-aminophenyl]-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodia zep ine HCI; EGIS-8159) was studied in the gerbil bilateral carotid occlusion (BCO) model of global ischemia. Drug effect on hippocampal CA1 neuronal loss, hypermotility, and cognitive deficit (decrease in spontaneous alternation (SA) behaviour in the Y-maze) induced by 5-min or 3-min BCO were measured. GYKI-52466 was administered at 4 x 15 mg/kg intraperitoneal (i.p.) doses 30, 45, 60, and 75 min following surgery. The competitive AMPA antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline) applied at 3 x 30 mg/kg i.p. doses 60, 70, and 85 min after reperfusion was also tested for comparison. Both compounds showed weak and non-significant effects on 5-min BCO-induced changes in all the three variables. However, following 3-min ischemia GYKI-52466 and NBQX produced significant inhibition (49% and 48%, respectively) on CA1 cell loss. Moreover, GYKI-52466, but not NBQX, significantly inhibited the 3-min ischemia induced hypermotility and decrease in SA. At their neuroprotective doses, both compounds caused long-lasting (min. 8 h) hypothermia in gerbils. GYKI-52466 induced much higher decrease in body temperature (6 degrees C at peak level) than NBQX did (2 degrees C at peak level). Administration of 4 x 10 mg/kg i.p. chlorpromazine to gerbils 15 min before and 0, 15, and 30 min after 3-min BCO resulted in considerable hypothermia (5.5 degrees C peak effect, 8 h duration), but no protective action of the compound on CA1 cell loss and hypermotility was observed. However, chlorpromazine inhibited the ischemia-induced cognitive impairment. The results suggest that drug-induced hypothermia may differentially influence the histological and the behavioural outcomes of ischemic intervention.
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PMID:The neuroprotective and hypothermic effect of GYKI-52466, a non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-antagonist on histological and behavioural variables in the gerbil global ischemia model. 1056 79

We examined the influence of diabetes on ischemia/reperfusion-induced gastric damage in rats, in relation to the antioxidative system. Animals were injected with streptozotocin (STZ: 70 mg/kg, i.p.) and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Gastric mucosal blood flow (GMBF) was measured before, during and after 20 min of ischemia (1.5 ml bleeding per 100 g body weight from the carotid artery) followed by a 15-min reperfusion in the presence of acid (100 mM HCI). At the end of each experiment, gastric damage was observed macroscopically. GMBF was reduced by ischemia in all groups of rats, followed by a gradual return after reperfusion. Ischemia/reperfusion produced hemorrhagic lesions in normal rat stomachs in the presence of 100 mM HCl. These lesions were significantly aggravated when the animals were pretreated with diethyldithiocarbamate, an inhibitor of superoxide dismutase (SOD). Ischemia/reperfusion-induced damage was also markedly exacerbated in STZ-diabetic rats, but this aggravation was significantly suppressed by pretreatment with exogenous SOD or glutathione (GSH). Diabetic rat stomachs showed significantly less SOD activity as well as GSH content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to ischemia/reperfusion was significantly mitigated by decreasing the blood glucose levels by daily insulin treatment. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to ischemia/reperfusion-induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced SOD activity and GSH content.
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PMID:Aggravation of ischemia/reperfusion-induced gastric lesions in streptozotocin-diabetic rats. 1102 55

We examined the effect of ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, on gastric lesions induced by ammonia plus ischemia or ischemia/reperfusion in rats, in relation to the antioxidative system. Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, and the following two experiments were performed; 1) a stomach was made ischemic (1.5 ml/100 g body weight) for 20 min, followed by reperfusion for 15 min in the presence of 100 mM HCl; 2) a stomach was made ischemic by bleeding from the carotid artery (1 ml/100 g body weight), followed by intragastric application of ammonia (NH4OH: 120 mM). EA (0.1-10 mg/ml) was applied in the chamber 30 min before the onset of ischemia. Gastric potential difference (PD) and mucosal blood flow (GMBF) were measured before, during and after 20 min of ischemia. Ischemia/reperfusion caused a profound drop in GMBF followed by a return, and resulted in hemorrhagic lesions in the stomach in the presence of 100 mM HCI. These lesions were dose-dependently prevented by EA with suppression of lipid peroxidation but no effect on GMBF, and the effect at 6 mg/ml was almost equivalent to that of superoxide dismutase (SOD: 15000 unit/kg/hr) infused i.v. during a test-period. On the other hand, application of NH4OH to the ischemic stomach produced a marked reduction in PD, resulting in severe hemorrhagic lesions. These changes were prevented with both EA and SOD. In addition, EA had a potent scavenging action against monochloramine in vitro. These results suggest that EA exhibits gastric protective action against gastric lesions induced by NH4OH or reperfusion in the ischemic stomach, probably due to its anti-oxidative activity. This property of EA partly explains the less damaging effect of whisky in the stomach and may be useful as the prophylactic for Helicobacter pylori-associated gastritis.
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PMID:Effect of ellagic acid on gastric damage induced in ischemic rat stomachs following ammonia or reperfusion. 1184 98

Recent studies have shown that selenium afforded protection against ethanol and stress-induced gastric lesions in rats. The present study was undertaken to investigate the effect of selenium on ischemia-reperfusion-induced gastric injuries in which rats were subjected to 30 minutes of ischemia in the presence of 100 mM HCI and a reperfusion for 60 minutes duration. Intraluminal bleeding was assessed macroscopically and gastric lesions were graded microscopically under an inverted microscope. Nonprotein sulphydryl levels were measured spectrophotometrically. The severity of gastric lesions, intraluminal bleeding as well as the depletion of nonprotein sulphydryls during the reperfusion periods was significantly different from that of control. Pretreatment with selenium (0.125-2.0 mg/kg, intraperitoneally) 30 minutes before the ischemia-reperfusion, dose-dependently attenuated the gastric lesions, reduced the severity of intraluminal bleeding and prevented the depletion of nonprotein sulphydryls in the stomach. These results suggest that the gastric protection effect of selenium may be due to its antioxidant properties. Furthermore, endogenous nonprotein sulphydryls may play a significant role in the protective mechanisms of selenium.
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PMID:Selenium protects against ischemia-reperfusion-induced gastric lesions in rats. 1986 89