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)

This controlled study shows that the rabbit is more vulnerable to erosive gastritis after stress of operation, weight loss, and hypersecretion or acute ischemia than is the cat. Rabbit gastric juice also produces more erosions in the Shay rat preparation after four hours than does cat gastric juice (P less than .05). In vitro, rabbit pepsin has 1.5 times greater specific activity and possesses other kinetic differences. The deleterious effect of these qualitative differences on gastric mucosa may also be augmented by quantitative differences. Hypersecretion of pepsin has been reported once the mucosa is damaged. We conclude that demonstration of species-related differences in pepsin activity helps to explain an apparent discrepancy noted by others--namely, why the rabbit is so much more susceptible to stress-produced erosions than the cat or other experimental animals.
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PMID:Role of pepsin in species differences in erosive gastritis. 31 75

Concerning the pathogenesis of acute gastric mucosal lesions, gastric microcirculatory change has drawn attention as an important factor. In view of this fact, gastric mucosal blood flow and microvascular structure were investigated in normal and in burn stressed rats. Moreover, alterations in acid and pepsin activities in by morphological and biochemical procedures in order to evaluate the relationship between defensive and aggressive factors of the gastric mucosa. Gastric mucosal blood flow decreased significantly in early period after induction of stress (p less than 0.01). The incidence of ulceration showed a correlative relation with the decrease of mucosal blood flow. Reduction of blood flow in burn was due to opening of arteriovenular shunt and it appeared that this was responsible for mucosal ischemia and congestion. Following the decrease of blood flow, acid output was lower in stress than that in control. Finally, the results of these studies demonstrated the importance of defensive factors. The reduction of mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesion.
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PMID:Gastric microcirculatory change and development of acute gastric mucosal lesions (stress ulcer). 251 62

True stress ulcers are primarily superficial gastric fundic lesions that occur in the clinical setting of severe shock, trauma, burns, and sepsis, especially peritonitis. They are to be clearly differentiated from Cushing's ulcers, exacerbation of pre-existent chronic ulcers, and drug-induced gastritis, all of which have completely different pathogenetic mechanisms. The etiology of true stress ulcers is most importantly related to ischemia and tissue acidosis, although luminal acid and pepsin are requisite for ulceration to occur. The sole clinical manifestation of stress ulcers is hemorrhage. Prophylaxis with antacids alone, or with a combination of antacids and H2 receptor antagonists is highly efficacious if luminal pH is carefully monitored. The treatment of exsanguinating hemorrhage, once established, carries with it an extremely high morbidity and mortality.
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PMID:The clinical problem of stress ulcers. 288 24

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.
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PMID:The pathophysiology of peptic ulcer disease. 405 22

Myofibrillar proteins (MPs) were extracted from isolated and perfused rat hearts subjected to different periods of ischemia to investigate the occurrence of protein degradation and/or the association of cytosolic proteins with the myofibrillar pellet. A 23-kD band was detected by SDS-PAGE of MPs after 5 minutes of ischemia, with its density gradually increasing to a plateau after 20 minutes. Longer periods of ischemia were associated with the appearance of a 39-kD band. Irrespective of the duration of ischemia, both these bands persisted during reperfusion. A partial proteolytic degradation of troponin T (TnT) and troponin I (TnI) has been claimed to be responsible for the generation of these peptides. However, the N-terminal sequence of the 39-kD band was identical to that of GAPDH, whereas Edman sequencing after pepsin digestion showed that the 23 kD is alpha B-crystallin. The binding of the two cytosolic proteins to myofibrils was confirmed by immunofluorescence analysis on cryosections of ischemic hearts. In vitro studies showed that acidosis was sufficient to induce the binding of alpha B-crystallin, whereas the inhibition of ATP depletion prevented the binding of GAPDH. Thiol oxidation is unlikely to promote GAPDH binding, since perfusion with iodoacetate under aerobic conditions or treatment of homogenates with N-ethylmaleimide or diamide failed to induce GAPDH association with the myofibrils. These changes of the myofibrillar proteins could be considered as intracellular markers of the evolution of the ischemic damage. In addition, the binding of the 23-kD peptide might be involved in alterations of contractility.
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PMID:Binding of cytosolic proteins to myofibrils in ischemic rat hearts. 862 Jun 2

Systemic administration of melatonin (5 to 20 mg/kg) has been reported to inhibit the induction of acute gastric mucosal lesions by stress or ischemia-reperfusion in rats. We recently demonstrated that intracisternal (i.c.) melatonin at low doses (1 to 100 ng) dose-dependently decreased acid and pepsin outputs in rats. The aim of the present study was to further investigate the peripheral and central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay, we measured melatonin concentrations in the plasma and cerebrospinal fluid (CSF) of the cisterna magna in rats subjected to water immersion restraint stress and given intraperitoneal (i.p.) or i.c. injection of melatonin. Water immersion restraint stress was followed by a significant duration-related increase in peripheral plasma melatonin levels; the stress similarly produced a time-dependent increase in the extent of gastric mucosal lesions. Administration of melatonin (1 or 10 mg/kg, i.p., or 100 ng/10 microl, i.c.) significantly reduced the extent of stress-induced gastric damage, by 46%, 67%, and 54%, respectively. The effective i.c. dose of melatonin was at least 10,000-fold smaller than the effective i.p. dose. Melatonin levels in plasma and CSF after the i.p. injection of melatonin at 10 mg/kg were dramatically higher than those after the i.c. injection of vehicle or 100 ng of melatonin. Our results suggest that the peripheral gastroprotective action of melatonin should be investigated with due regard to these central effects.
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PMID:Melatonin's gastroprotective and antistress roles involve both central and peripheral effects. 1122 76

The effects of electrical and chemical stimulation and electrolytic lesion of lateral hypothalamic area (LHA) on gastric ischemia-reperfusion injury (GI-RI) were investigated in rats whose celiac arteries were clamped for 30 min and reperfused for 60 min by removal of the clamp. The results are as follows. (1) Electrical stimulation of LHA could aggravate GI-RI in an intensity-dependent manner by using 0.2, 0.4 or 0.6 mA current respectively. Microinjection of L-glutamic acid into LHA resulted in a similar effect to that of electrical stimulation of LHA on GI-RI. After electrolytic lesion of bilateral LHA, the area of gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) was smaller than that by electrical stimulation of LHA plus GI-R. (2) Dorsal vagal complex (DVC) lesion or vagotomy could eliminate the effect of electrical stimulation of LHA on GI-RI. (3) Electrical stimulation of LHA increased the content of malondialdehyde (MDA) but decreased the activity of superoxide dismutase (SOD) of ischemia-reperfusion (I-R) gastric mucosa. (4) Electrical stimulation of LHA plus gastric I-R increased gastric juice volume and total acid output, but there were no significant changes in acidity, pepsin activity and gastric barrier mucus. These results indicate that the LHA is an area in the CNS exerting aggravate effects on GI-RI. The DVC and vagus may be involved in the regulative effects of LHA on GI-RI. These effects are associated with increases in gastric mucosal MDA content, gastric juice volume, and total acid output, and a decrease in SOD activity.Acidity, pepsin activity and gastric barrier mucus do not seem to play an important role.
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PMID:[Effects of electrical stimulation of lateral hypothalamic area on gastric ischemia-reperfusion injury in rats]. 1239 27

The effect of taurine on gastric hemorrhage and mucosal erosion in the brain ischemia (BI) is unknown. The aim of the research was to study the involvement of gastric oxidative stress in hemorrhagic erosion produced in BI rats. The protective effect of taurine on this erosion model was evaluated. Male Wistar rats were deprived of food for 24 h. Under chloral hydrate -anesthesia, bilateral carotid artery ligation (BCAL) was performed 12, 18 and 21 h after removal of food to obtain 12, 6 and 3 h of BI duration. The pylorus and carotid esophagus of rats also were ligated. The stomachs were then irrigated for 3 h with normal saline or simulated gastric juice containing 100 mM HCl plus 17.4 mM pepsin and 54 mM NaCl. The stomach was dissected. Gastric samples were harvested. The rat brain was dissected for examination of ischemia by using triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal GSH level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples were measured. The results indicated that BCAL could produce severe BI in rats. Moreover, a BI- duration-dependent exacerbation of various ulcerogenic parameters also was observed in these rats. Intraperitoneal taurine (0-300 mg/kg) dose-dependently ameliorated gastric oxidative stress and hemorrhagic erosion in BI rats. Taken together, BI could produce gastric oxidative stress and hemorrhagic erosions that was ameliorated by taurine through stimulation of GSH biosynthesis and inhibition of oxidative stress.
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PMID:Effect of taurine on gastric oxidative stress and hemorrhagic erosion in brain ischemic rats. 1697 Feb 47

We investigated the role of pepsin in the development of ischemia/reperfusion (I/R)-induced gastric lesions in rats. Under urethane anesthesia, the pylorus was ligated, the celiac artery was clamped, and 1 ml of HCl (50-150 mM) was instilled in the stomach. Then, reperfusion was established 15 min later by removing the clamp, and 2 h later the stomach was assessed for gross mucosal damage. Pepstatin (a specific pepsin inhibitor) or pepsin was given i.g. after the pylorus was ligated while cimetidine, omeprazole, or atropine was given s.c. 30 min before the ligation. I/R produced hemorrhagic gastric injury, with a concomitant increase in the amount of pepsin secreted, and the degree of both these responses was dependent on the concentration of HCl. The formation of lesions by IR in the presence of 100 mM HCl was significantly prevented by atropine or bilateral vagotomy, but neither omeprazole nor cimetidine had any effect. Intragastric administration of pepstatin dose-dependently reduced the severity of the I/R-induced gastric lesions, the effect being significant even at 0.1 mg/kg, while that of pepsin markedly aggravated these lesions. The increased pepsin output during I/R was associated with luminal acid loss and significantly inhibited by bilateral vagotomy or pretreatment with atropine but not cimetidine or omeprazole, while pepstatin significantly inhibited the pepsin activity. In conclusion, we suggest that pepsin plays a pivotal role in the pathogenesis of I/R-induced gastric lesions, and pepsin secretion is increased during I/R, the process being associated with acid back-diffusion and mediated through a vagal-cholinergic pathway.
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PMID:Pathogenic importance of pepsin in ischemia/reperfusion-induced gastric injury. 1739 12

The gastric mucosa maintains structural integrity and function despite continuous exposure to noxious factors, including 0.1 mol/L HCl and pepsin, that are capable of digesting tissue. Under normal conditions, mucosal integrity is maintained by defense mechanisms, which include preepithelial factors (mucus-bicarbonate-phospholipid "barrier"), an epithelial "barrier" (surface epithelial cells connected by tight junctions and generating bicarbonate, mucus, phospholipids, trefoil peptides, prostaglandins (PGs), and heat shock proteins), continuous cell renewal accomplished by proliferation of progenitor cells (regulated by growth factors, PGE(2) and survivin), continuous blood flow through mucosal microvessels, an endothelial "barrier," sensory innervation, and generation of PGs and nitric oxide. Mucosal injury may occur when noxious factors "overwhelm" an intact mucosal defense or when the mucosal defense is impaired. We review basic components of gastric mucosal defense and discuss conditions in which mucosal injury is directly related to impairment in mucosal defense, focusing on disorders with important clinical sequelae: nonsteroidal anti-inflammatory drug (NSAID)-associated injury, which is primarily related to inhibition of cyclooxygenase (COX)-mediated PG synthesis, and stress-related mucosal disease (SRMD), which occurs with local ischemia. The annual incidence of NSAID-associated upper gastrointestinal (GI) complications such as bleeding is approximately 1%-1.5%; and reductions in these complications have been demonstrated with misoprostol, proton pump inhibitors (PPIs) (only documented in high-risk patients), and COX-2 selective inhibitors. Clinically significant bleeding from SRMD is relatively uncommon with modern intensive care. Pharmacologic therapy with antisecretory drugs may be used in high-risk patients (eg, mechanical ventilation >or=48 hours), although the absolute risk reduction is small, and a decrease in mortality is not documented.
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PMID:Gastric mucosal defense and cytoprotection: bench to bedside. 1854 14


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