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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of our experiment was to examine whether the cyclooxygenase inhibitor indomethacin ameliorates neuronal injury in the gerbil hippocampal CA1 sector following 5 minutes of forebrain ischemia. Thirty minutes before bilateral carotid artery occlusion, Mongolian gerbils were injected intraperitoneally with 1 (n = 10), 2 (n = 10), 5 (n = 12), or 10 (n = 7) mg/kg of indomethacin. Seven days after occlusion, the gerbils were perfusion-fixed and neuronal density in the hippocampal CA1 sector was assessed. The mean +/- SEM neuronal density in nine unoperated normal gerbils was 307 +/- 9/mm, in 10 untreated ischemic gerbils 55 +/- 21/mm, and in seven vehicle-treated ischemic gerbils 15 +/- 9/mm. The mean +/- SEM neuronal density in ischemic gerbils treated with 1, 2, 5, or 10 mg/kg indomethacin was 132 +/- 28/mm, 154 +/- 29/mm, 176 +/- 30/mm, and 136 +/- 39/mm, respectively. Indomethacin at any dose significantly ameliorated ischemic neuronal damage in the gerbil hippocampal CA1 sector.
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PMID:Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector. 318 24

Streptozotocin induced diabetic rat hearts were perfused under constant flow conditions with or without 1 x 10(5) U.litre-1 each of superoxide dismutase and catalase (SOD + CAT). Total global ischaemia was produced for 20 min followed by 30 min of reperfusion at pre-ischaemic flow rates. After 5 min of reperfusion, isovolumic LV developed pressure was reduced in diabetic hearts, at 22 (SEM 11)% of baseline v 67(12)% in controls, with increased frequency of ventricular fibrillation (VF) (3/10 v 10/11 hearts). SOD + CAT improved isovolumic LV developed pressure to 67(8)% of baseline during early reperfusion of diabetic hearts but did not affect non-diabetic hearts. SOD + CAT also increased the adenylate energy charge potential in post-ischaemic diabetic hearts to 0.826(0.011) v 0.781(0.012) in diabetic controls, and reduced the incidence and duration of reperfusion induced VF in diabetic hearts. SOD + CAT augmented the production of prostacyclin in coronary effluents during early reperfusion of diabetic hearts, from (baseline) 11.5(1.7) to 18.1(3.0) ng.min-1.g-1 at 2 min, compared with 11.1(1.6) to 12.5(1.9) ng.min-1.g-1 at same interval in diabetic controls. Indomethacin prevented the protective effect of the free radical scavengers on function and VF. In contrast, perfusion with the prostacyclin analogue, iloprost (3 x 10(-8) M), alone completely prevented early post-ischaemic dysfunction and reduced VF from 559(172) to 16(8) s. Oxygen derived free radicals may mediate reperfusion induced contractile dysfunction and VF in acutely diabetic hearts following brief episodes of myocardial ischaemia. The beneficial effects of SOD + CAT appear to be mediated mainly by an increase in prostacyclin production during early reperfusion.
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PMID:Superoxide dismutase plus catalase improves post-ischaemic recovery in the diabetic heart. 325 31

Experiments to explore human platelet protein phosphorylation changes and 5-hydroxytryptamine (5-HT) secretion after challenge with cotton bract tannin were performed. Quantitative changes in sodium phosphate phosphorus 32 incorporation in two platelet proteins of 19 kilodaltons (kd) and 47 kd were assessed by measuring protein band densities on autoradiographs of dried polyacrylamide gels. Secretion of 5-HT was assessed by 14C-5-HT release. Results show that tannin causes increases in phosphorylation of discrete platelet proteins that begin in less than 2 seconds. These increases are maximal in 1 minute for the 47 kd protein and in 3 minutes for the 19 kd protein. Fifty percent of maximum response required less than 2 seconds for both of these proteins, and 50% of maximum 5-HT secretion required 48 seconds. Dose-response studies comparing 0 to 50 micrograms/ml tannin with 0 to 1 U/ml human alpha-thrombin showed that tannin caused 5-HT secretion and protein phosphorylation changes that were very similar to those induced by human alpha-thrombin. Fifty micrograms per milliliter of tannin caused increases in 19 kd protein phosphorylation and 47 kd protein phosphorylation to 312% +/- 34% (SEM) and 204% +/- 13% of control, respectively (n = 14). One unit per milliliter of thrombin induced changes of 350% +/- 40% and 221% +/- 17% of control in the 19 kd and 47 kd proteins, respectively. Release of 5-HT by tannin and thrombin was 61% +/- 3% and 69% +/- 3% of total cellular 5-HT, respectively. Indomethacin had little inhibitory effect on activation by these two different agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein phosphorylation during tannin-mediated activation of human platelets. 334 45

There is increasing evidence for the involvement of inflammatory cells in the development of intimal hyperplasia. This study examines the effect of human neutrophils on the incorporation of [3H]-thymidine into acid precipitable materials (DNA) in cultured rabbit vascular smooth muscle cells. Co-culture of intact neutrophils and vascular smooth muscle cells caused [3H]-thymidine incorporation by these cells to increase 209 +/- 22% (mean +/- SEM) of control. Sonication of the neutrophils abolished this effect (117 +/- 10%). Neutrophil conditioned medium prepared in the presence or absence of fetal calf serum had a similar effect on [3H]-thymidine incorporation by vascular smooth muscle cells (204 +/- 20% and 172 +/- 17% respectively). Stimulation of neutrophils with either Concanavalin A or serum-activated zymosan failed to increase production of the factor(s). The neutrophil derived factor(s) prepared in minimal essential medium was partially stable at 56 degrees C, but inactivated by boiling. Dialysis (pore size 12,000-14,000) did not remove the factor(s). Cyclooxygenase inhibition with indomethacin did not inhibit production of the factor(s) by neutrophils, but indomethacin caused an increase in [3H]-thymidine incorporation by vascular smooth muscle cells (181 +/- 11%). Indomethacin together with intact neutrophils had an additive effect on [3H]-thymidine incorporation (273 +/- 42%) into cellular DNA. These data show that neutrophils produce a factor(s) that stimulates [3H]-thymidine incorporation into DNA by vascular smooth muscle cells and suggests that vascular smooth muscle proliferation and intimal hyperplasia may be initiated by neutrophils adherent to sites of endothelial injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A neutrophil derived factor(s) stimulates [3H]thymidine incorporation by vascular smooth muscle cells in vitro. 336 83

Indomethacin is a potent agent in the treatment of premature labor, but its use has been limited because of concern about its constrictive effects on the fetal ductus arteriosus. To study these effects we used serial fetal echocardiography in 13 pregnant women in premature labor who received indomethacin according to three different dose schedules, ranging from 100 to 175 mg per day, for a maximum of 72 hours. The gestational ages of the fetuses ranged from 26.5 to 31.0 weeks. The detection of ductal constriction in 7 of the 14 fetuses by echocardiography led to the discontinuation of indomethacin. Three fetuses also had tricuspid regurgitation. There was no statistically significant difference between the mean (+/- SEM) gestational age of the fetuses with ductal constriction and that of those without constriction (29.3 +/- 0.59 and 28.4 +/- 0.52, respectively). There was no relation between serum indomethacin levels in the mothers and ductal constriction. In all seven fetuses affected, ductal constriction had resolved by the time they were restudied 24 hours after the discontinuation of indomethacin. Persistent fetal circulation was not detected in any of the 11 neonates studied after delivery. Indomethacin used to treat premature labor appears to cause transient constriction of the ductus arteriosus in some fetuses, even after short-term use.
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PMID:Indomethacin in the treatment of premature labor. Effects on the fetal ductus arteriosus. 339 94

We investigated whether the trophic actions of prostaglandins, omeprazole, and indomethacin on gastric mucosa lead to accelerated healing of gastric ulcers in the rat. Cryoulcers were produced in the corpus area and treated with 16,16-dimethyl prostaglandin E2 (5 or 100 micrograms/kg b.i.d., intragastrically), omeprazole (40 mumol/kg once daily, subcutaneously), indomethacin (2 mg/kg b.i.d., subcutaneously), or placebo. At the end of the treatment, plasma gastrin, cell labeling index (autoradiography with [3H]thymidine), and the size and depth of mucosal defects were measured. Compared with placebo, omeprazole accelerated ulcer healing as indicated by a smaller ulcer area [1.1 +/- 0.2 vs. 4.8 +/- 1.2 mm2 (mean +/- SEM)] and smaller ulcer depth (383 +/- 31 vs. 488 +/- 41 microns) after 10 days of treatment. Prostaglandins did not affect ulcer healing despite thickening of gastric corpus mucosa. Indomethacin delayed ulcer healing and reduced the labeling index. Omeprazole induced a marked hypergastrinemia (208 +/- 12 vs. 66 +/- 12 pmol/L on day 5, and 469 +/- 23 vs. 58 +/- 16 pmol/L on day 10). The results indicate that abolishment of acid secretion by omeprazole accelerates healing. Trophic actions and "cytoprotective" effects by prostaglandins are not relevant for ulcer healing in this model.
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PMID:Influence of prostaglandins, omeprazole, and indomethacin on healing of experimental gastric ulcers in the rat. 291 61

Multiple potentially injurious agents are present in smoke but the importance of each of these agents in producing lung injury as well as the mechanisms by which the lung injury is produced are unknown. In order to study smoke inhalation injury, we developed a synthetic smoke composed of a carrier of hot carbon particles of known size to which a single known common toxic agent in smoke, in this case HCI, could be added. We then exposed rats to the smoke, assayed their blood for the metabolites of thromboxane and prostacyclin, and intervened shortly after smoke with the cyclooxygenase inhibitors indomethacin or ibuprofen to see if the resulting lung injury could be prevented. Smoke exposure produced mild pulmonary edema after 6 h with a wet-to-dry weight ratio of 5.6 +/- 0.2 SEM (n = 11) compared with the non-smoke-exposed control animals with a wet-to-dry weight ratio of 4.3 +/- 0.2 (n = 12), p less than 0.001. Thromboxane B, and 6-keto-prostaglandin F1 alpha rose to 1,660 +/- 250 pg/ml (p less than 0.01) and to 600 +/- 100 pg/ml (p greater than 0.1), respectively, in the smoke-injured animals compared with 770 +/- 150 pg/ml and 400 +/- 100 pg/ml in the non-smoke-exposed control animals. Indomethacin (n = 11) blocked the increase in both thromboxane and prostacyclin metabolites but failed to prevent lung edema.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ibuprofen prevents synthetic smoke-induced pulmonary edema. 353 56

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.
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PMID:Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids. 354 78

Macrophages have been identified in the developing corpus luteum in several species, including man, and also constitute approximately 90% of cells in the peritoneal cavity. We studied the effect of peritoneal macrophages or blood monocytes on progesterone (P) synthesis by human granulosa cells from preovulatory follicles obtained at laparoscopy of 14 women undergoing in vitro fertilization. Pooled granulosa cells from follicles with mature ova were isolated by Ficoll-Hypaque gradient centrifugation. Washed granulosa cells (0.75 X 10(5)/ml) were incubated in Dulbecco's Minimum Essential Medium containing 20% calf serum with varying concentrations of pelvic macrophages (0.8-29 X 10(5)/ml) or fresh and mature blood monocytes (0.25-2.5 X 10(5)/ml). P production was determined by RIA of medium at 24-h intervals for 24-48 h. In situ concentrations of pelvic macrophages from 8 patients with tubal infertility increased cumulative P production to 140 +/- 17.8% (mean +/- SEM) of the control values. A similar increase (182 +/- 62.7%) was found with macrophages from 6 patients with endometriosis or unexplained infertility. Both fresh and mature monocytes stimulated P production to 225% and 261% of control values, respectively. Indomethacin (10(-4) M) or monoclonal antibody to somatomedin-C did not prevent stimulation of P production. These results suggest that peritoneal macrophages may exert luteotropic effects on cumulus cells while the ovulated oocyte resides in the tube, and incoming monocytes may be important in stimulating luteal cells in the developing corpus luteum.
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PMID:Peritoneal macrophages modulate human granulosa-luteal cell progesterone production. 404 79

Indomethacin, a cyclo-oxygenase inhibitor, stimulates virtually continuous breathing movements in the fetal sheep. We measured blood flow (radioactive microsphere distribution) to major brain regions and analyzed arterial and sagittal vein blood samples for oxygen and carbon dioxide tensions, pH and for oxygen contents and glucose concentrations in 13 fetal lambs between 122-132 days of gestation. The measurements were done before and again after 4 to 5 h of an indomethacin infusion. We found that indomethacin caused a mild arterial acidosis and hypoxemia and a 23 +/- 6% (SEM, P less than 0.01) decrease in blood flow to the cerebral hemispheres. Similar decreases were also observed in all other brain regions except for the cerebellum. Arteriovenous concentration differences for both oxygen and glucose widened such that there was no significant change in cerebral metabolism. Sagittal vein hydrogen ion concentration was 44.3 +/- 0.06 nmoles 1(-1) during control and rose by 4.5 +/- 1.4 nmol.1(-1) (P less than 0.01) with the indomethacin. These results are consistent with the hypothesis that one mechanism by which indomethacin augments the incidence of fetal respiratory efforts is by stimulating central chemoreceptors.
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PMID:The effect of indomethacin on breathing movements and cerebral blood flow and metabolism in the fetal sheep. 404 29


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