Prostaglandins and Leukotrienes in Gastrointestinal Diseases

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Relation to activation of the renin--angiotensin system and hyponatremia. Pharmacological interactions between prostacyclin and thromboxanes. Br Med Bull. Mechanisms of hemostasis and therapy of thrombosis: new concepts based on the metabolism of arachidonic acid by platelets and endothelial cells. Adv Pharmacol Chemother. Hemostasis, thrombosis, and thromboembolic disorders. The role of arachidonic acid metabolites in platelet-vessel wall interactions. Eicosanoids and the blood vessel wall. Effect of cholesterol on production of thromboxane b2 by platelets in vitro.

Increased platelet thromboxane synthesis in diabetes mellitus. J Lab Clin Med. Stimulation of vascular smooth muscle cell prostacyclin and prostaglandin E2 synthesis by plasma high and low density lipoproteins. Circ Res. Cigarette smoking inhibits prostacyclin formation. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. Platelets, carotids, and coronaries.

Critique on antithrombotic role of antiplatelet agents, exercise, and certain diets. Am J Med. Aspirin as an antithrombotic medication. Arachidonate metabolism in vascular disorders. Prostaglandins and prostaglandin inhibitors in ischemic heart disease. Clinical potential of prostacyclin. Adv Prostaglandin Thromboxane Leukot Res.

Platelet protection and heparin sparing with prostacyclin during regular dialysis therapy. Prostacyclin to prevent platelet activation during charcoal haemoperfusion in fulminant hepatic failure. A double blind study of prostacyclin in cardiopulmonary bypass surgery. Br J Haematol. Successful therapy of advanced arteriosclerosis obliterans with prostacyclin. Treatment of ischaemic stroke with prostacyclin.


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Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin PGI2. Br J Dermatol. Epoprostenol prostacyclin and severe arterial disease. A double-blind trial. Intermittent epoprostenol prostacyclin infusion in patients with Raynaud's syndrome. A double-blind controlled trial. A randomized, placebo controlled trial of prostacyclin PGI2 in peripheral arterial disease. Thromb Res. Regulation of the immune response by prostaglandins.

J Clin Immunol. The release of leukotriene B4 during experimental inflammation. Prostaglandins and their regulation in rheumatoid inflammation. Ann N Y Acad Sci. Mononuclear cell modulation of connective tissue function: suppression of fibroblast growth by stimulation of endogenous prostaglandin production. Role of prostaglandin endoperoxide PGG2 in inflammatory processes. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen interleukin A mechanism for the increased degradation of muscle proteins during fever.

Mediators of fever and muscle proteolysis. Leukotriene B4 stimulates polymorphonuclear leukocyte adhesion to cultured vascular endothelial cells. The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis. J Invest Dermatol. Increased concentrations of nonesterified arachidonic acid, 12L-hydroxy-5,8,10,eicosatetraenoic acid, prostaglandin E2, and prostaglandin F2alpha in epidermis of psoriasis.

Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. Increased production of prostaglandin D2 in patients with systemic mastocytosis.

Control of lymphokine secretion by prostaglandins. Immunologic effects of nonsteroidal anti-inflammatory drugs. Prostaglandins in reproductive processes. The measurement of E and hydroxy E prostaglandins in human seminal plasma. The relation between fertility and prostaglandin content of seminal fluid in man. Fertil Steril. Inhibition of ovulation in rabbits by intrafollicular injection of indomethacin and prostaglandin F antiserum.

Life Sci. The effects of an inhibitor of prostaglandin synthesis indomethacin on ovulation, pregnancy, and pseudopregnancy in the rabbit. Aspects concerning the role of prostaglandins for ovarian function. Acta Obstet Gynecol Scand Suppl. Potent bronchoconstrictor activity of keto prostaglandin F2alpha. Uterine luteolytic hormone: a physiological role for prostaglandin F2alpha. Physiol Rev. Prostaglandins and nonsteroidal antiinflammatory drugs in dysmenorrhea. Annu Rev Pharmacol Toxicol. Prostaglandins and the non-pregnant uterus.

The pathophysiology of primary dysmenorrhea. Prostaglandin synthetase inhibitors in the treatment of primary dysmenorrhea. Outcome trials reviewed. Am J Obstet Gynecol. Reduction of menstrual blood-loss by prostaglandin-synthetase inhibitors. Endogenous prostaglandin synthesis and abortion. A mini-review.

Induction of abortion by prostaglandins in the second trimester of pregnancy. A review. Response of pregnant human uterus to prostaglandin-F2-alpha-induction of labour. Br Med J. Labor induction with prostaglandins. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol. Oestrogens, prostaglandins, and cervical ripening. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. Pharmacologic closure of patent ductus arteriosus in the premature infant.

Pharmacologic use of prostaglandin E1 in infant with congenital heart disease. Am Heart J. Studies of pulmonary prostaglandin biosynthetic and catabolic enzymes as factors in ductus arteriosus patency and closure. Evidence for a shift in products with gestational age.

Pediatr Res. Prostaglandins, renal function and vascular regulation.

Arachidonic Acid & Eicosanoids

Prostaglandins and the kidney. Am J Nephrol. Arachidonic acid metabolism, prostaglandins and the kidney. Renal syndromes associated with nonsteroidal antiinflammatory drugs. Renal effects of prostaglandins and clinical adverse effects of nonsteroidal anti-inflammatory agents. Medicine Baltimore May; 63 3 — Bartter's syndrome with hyperplasia of renomedullary cells: successful treatment with indomethacin.

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Metabolic mimicry of Bartter's syndrome by covert vomiting: utility of urinary chloride determinations. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Prostaglandins: modulators of renal function and pressor resistance in chronic liver disease. J Clin Endocrinol Metab. Functional renal alterations in chronic liver diseases. Interrelationship between prostaglandins and renin release. Role of prostaglandins in renin secretion. Role of renal prostaglandins in the control of renin release.

Evidence for a direct stimulatory effect of prostacyclin on renin release in man. The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man. Aspirin triggers previously unrecognized bioactive eicosanoids in human endothelial cell-leukocyte interactions. The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, prostaglandin metabolism in cyclooxygenase knockout mice. Gastroenterology : 94—, The apology of a second-class man. Annu Rev Physiol 47 : 1—15, Why the stomach does not digest itself.

Sci Am : 87—93, Aspirin induces a rapid up-regulation of cyclooxygenase-2 expression in the rat stomach. Aliment Pharmacol Ther 11 : —, Oxygen free radicals interact with indomethacin to cause gastrointestinal injury. Agents Actions 17 : —, A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in the rat. Bacterial colonization and healing of gastric ulcers: the effects of epidermal growth factor.

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Gastric ulcer perforation, associated with the use of injectable ketorolac. Ann Pharmacother 27 : 42—43, Effect of indomethacin on gastric acid and bicarbonate secretion in humans. Gastroenterology 87 : —, Impaired vasodilatory responses in the gastric microcirculation of anesthetized rats with secondary biliary cirrhosis. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs.

The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Cyclooxygenasederived lipoxin A 4 increases gastric resistance to aspirin-induced damage. Gastrointestinal safety of NO-aspirin NCX in healthy human volunteers: a proof of concept endoscopic study. Interaction of COX-2 inhibitor with aspirin and NO-aspirin in the human gastric mucosa: evidence for a protective role of nitric oxide.

Coxibs and cardiovascular disease. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol 4-acetamidophenol.


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    A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 74 : 38—43, Effects of specific inhibition of cyclo-oxygenase-1 and cyclo-oxygenase-2 in the rat stomach with normal mucosa and after acid challenge. Br J Pharmacol : —, Inhibition by prostaglandins of leukotriene B 4 release from activated neutrophils. Cell loss from normal and stressed gastric mucosae of the rat. Gastroenterology 72 : —, Prostaglandin E 2 aggravates gastric mucosal injury induced by histamine in rats through EP1 receptors.

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    Gut 52 : —, Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis. Br J Clin Pharmacol 32 : 77—83, Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 10 : —, Gastric mucosal barrier, hydrophobic lining to the lumen of the stomach.

    Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ : —, Dig Dis Sci 49 : —, Prostaglandins inhibit inflammatory mediator release from rat mast cells. Role of prostaglandins in regulation of gastric mucosal blood flow and acid secretion. Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 91 : —, Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury.

    Afferent nerve-mediated protection against deep mucosal damage in the rat stomach. Enhanced gastric mucosal leukotriene B 4 synthesis in patients taking non-steroidal anti-inflammatory drugs. Gut 34 : —, Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance.

    Dig Dis Sci 50 : —, Acid transport through channels in the mucous layer of rat stomach. Hydrocortisone and indomethacin negatively modulate EGF-R signaling in human fetal intestine. Pediatr Res 62 : —, Effect of 16,dimethyl prostaglandin E 2 on lipidic organelles of rat gastric surface mucous cells.

    Dual action of prostaglandin E 2 on gastric acid secretion through different EP-receptor subtypes in the rat. Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation. Gastroenterology 93 : —, Stimulation by a hypertonic environment in vitro. Prostaglandins 15 : —, Prostaglandin E receptor EP1 subtype but not prostacyclin IP receptor involved in mucosal blood flow response of mouse stomachs following barrier disruption. Digestion 67 : —, Inhibition of nitric oxide synthase delays healing of chronic gastric ulcers. Eur J Pharmacol : —, J Pharmacol Exp Ther : —, Arachidonic acid metabolites regulate interleukin-1 production.

    Biochem Biophys Res Commun : —, Prostaglandins as endogenous mediators of interleukin 1 production. J Immunol : —, Regulation of macrophage tumor necrosis factor production by prostaglandin E 2. Phosphatidylcholine-associated aspirin accelerates healing of gastric ulcers in rats. Dig Dis Sci 43 : —, Rapid epithelial restitution of the rat gastric mucosa after ethanol injury. Lab Invest 51 : —, Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis.

    Approaches to non-steroidal anti-inflammatory drug use in the high-risk patient. Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration.

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    The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract. Gut 47 : —, Endothelium-derived relaxing factor nitric oxide has protective actions in the stomach. Life Sci 45 : —, Selective cyclooxygenase-2 inhibitors aggravate ischaemia-reperfusion injury in the rat stomach. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1 : —, Gastrointestinal inflammation: a central component of mucosal defense and repair. Exp Biol Med : —, Annexin-1 modulates gastric mucosal healing.

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    Ulcers, Helicobacter pylori infection, platelets and gastrointestinal complications of non-steroidal anti-inflammatory drugs: what are the connections? Eur J Surg Suppl : 89—99, Relative roles of acid and mucosal compression in ulcerogenesis in indomethacin-insulin-treated rat. Dig Dis Sci 33 : —, Nitric oxide and mucosal defense: a little goes a long way. Cyclooxygenaseregulated vascular endothelial growth factor release in gastric fibroblasts. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. The roles of ethanol and of acid in the production of gastric mucosal erosions in rats.

    Virchows Arch B Cell Pathol 38 : 23—38, A functional model for extracellular gastric mucus in the rat. Virchows Arch B Cell Pathol 46 : —, Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Involvement of prostaglandin E receptor EP2 subtype and prostacyclin IP receptor in decreased acid response in damaged stomach. J Physiol Pharmacol 58 : —, Ablation of capsaicin sensitive afferent nerves impairs defense but not rapid repair of rat gastric mucosa. Nonsteroidal anti-inflammatory drugs inhibit re-epithelialization of wounded gastric monolayers by interfering with actin, Src, FAK, tensin signaling.

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    Cytoprotection by prostaglandins in rats. Intravenous, oral and intrajejunal administration. Gastroenterology 70 : —, Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature : 54—56, The hydrogen sulphide-releasing derivative of diclofenac protects against ischaemia-reperfusion injury in the isolated rabbit heart. The nitric oxide-releasing naproxen derivative displays cardioprotection in perfused rabbit heart submitted to ischemia-reperfusion. Inhibition of cyclo-oxygenase-2 exacerbates ischaemia-induced acute myocardial dysfunction in the rabbit.

    Membrane prostaglandin E synthase a novel therapeutic target. Pharmacol Rev 59 : —, Nature : 51—54, Gut 35 : —, Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats. Comparison of the COX-inhibiting nitric oxide donator AZD and rofecoxib in treating the signs and symptoms of osteoarthritis of the knee. Arthritis Rheum 53 : —, Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage.

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    Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach. Platelets accelerate gastric ulcer healing through presentation of vascular endothelial growth factor. Hydrogen sulfide enhances ulcer healing. Platelet-activating factor mediates gastric damage induced by hemorrhagic shock. Potential cardioprotective actions of no-releasing aspirin. Nat Rev Drug Discov 1 : —, Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti-inflammatory without gastropathy.

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    Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat. Gastroenterology 80 : 94—98, Gastric ulcer formation and cyclo-oxygenase inhibition in cat antrum follows parenteral administration of aspirin but not salicylate.

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    Molecular determinants of aspirin-induced neutrophil adherence to endothelial cells. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. Annexin-1 mediates the gastroprotective effects of dexamethasone against indomethacin. Previous Back to Top. Figures References Related Information Cited By The polysaccharide-rich tea of Ximenia americana barks prevents indomethacin-induced gastrointestinal damage via neutrophil inhibition.

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    Prostaglandins, Thromboxanes and Leukotrienes in Clinical Medicine

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