thromboxane-b2 and Enterocolitis--Pseudomembranous

Topics: Animals; Biological Assay; Disease Models, Animal; Enterocolitis, Pseudomembranous; In Vitro Techniques; Indomethacin; Intestinal Mucosa; Leukotriene B4; Male; N-Formylmethionine Leucyl-Phenylalanine; Perfusion; Prostaglandins; Rabbits; SRS-A; Thromboxane B2; Vascular Resistance

To compare the local release of arachidonic acid metabolites in inflammatory diarrheal disease, in vivo equilibrium dialysis of the rectum was done in consecutive untreated patients with ulcerative colitis (n = 20), Crohn's colitis (n = 10), and Clostridium difficile colitis (n = 7). All patients had endoscopically proven rectal inflammation. Eicosanoid profiles were determined in rectal dialysates by radioimmunoassay after preliminary purification. Concentrations of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2, but not 6-keto-prostaglandin F1 alpha, were raised in all groups and compared with healthy controls. The highest levels within each group were obtained in patients with widespread epithelial damage, as judged by endoscopy. In patients with ulcerative colitis, an extreme rise in prostaglandin E2 and thromboxane B2 were observed. Similarly, concentrations of leukotriene B4 were substantially increased in ulcerative colitis, but in Crohn's colitis and Clostridium difficile colitis only those patients with rectal ulcerations showed elevations. These findings probably reflect more severe tissue damages in ulcerative colitis, but differences between disease groups in cell-to-cell interaction may also contribute. The data suggest, therefore, that therapeutic inhibition of lipoxygenase pathways may prove more effective in ulcerative colitis than in Crohn's disease.

Topics: Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Colitis; Colitis, Ulcerative; Crohn Disease; Dialysis; Dinoprost; Dinoprostone; Eicosanoic Acids; Enterocolitis, Pseudomembranous; Female; Humans; Leukotriene B4; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Rectum; Thromboxane B2

Necrotizing enterocolitis (NEC) was produced in anesthetized rabbits by transmural injection of intestinal loops with an acidified solution of casein and calcium gluconate, mimicking the luminal milieu of afflicted neonates. Intravenous infusion of superoxide dismutase (SOD) 15 min after NEC induction prevented intestinal damage. In ex vivo perfused intestinal loops, we determined the sites of eicosanoid release and their contribution to the vascular effects of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) in damaged and SOD-salvaged intestine. The vascular effluent was the primary site of stimulated eicosanoid release. The vascular responses to fMLP (vasoconstriction) and PAF (vasodilation) were not altered by SOD, although vascular resistance was higher in the SOD group. SOD treatment attenuated 1) transmural fluid shifts in ex vivo perfused intestinal preparations, an index of vascular permeability, 2) fMLP-induced prostaglandin E2, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) release, and 3) PAF-induced release of 6-keto-PGF1 alpha and LTB4. Stimulated thromboxane B2 release was not altered by SOD. Thus NEC can be established by a luminal insult that causes local generation of free radicals and exaggerated release of prostaglandins and leukotrienes.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Depression, Chemical; Dinoprostone; Disease Models, Animal; Enterocolitis, Pseudomembranous; Leukotriene B4; Leukotrienes; Male; N-Formylmethionine Leucyl-Phenylalanine; Platelet Activating Factor; Prostaglandins; Rabbits; Superoxide Dismutase; Thromboxane B2

Urinary thromboxane B2 levels increased threefold to 20-fold in infants with neonatal necrotizing enterocolitis compared with healthy infants and infants with benign causes of heme-positive stools. Increased urinary thromboxane B2 levels were detected coincidently with the initial signs of necrotizing enterocolitis, and values paralleled the course of the illness. Infants with serious illnesses other than necrotizing enterocolitis had increased urinary thromboxane B2 levels but with lower values than those of infants with necrotizing enterocolitis. Indomethacin therapy appeared to reduce urinary thromboxane B2 levels and reduce their usefulness as a marker of illness. Another product of platelet activation, beta-thromboglobulin, was increased in the urine of infants with necrotizing enterocolitis. Decreased platelet counts in infants with necrotizing enterocolitis correlated inversely with urinary thromboxane. Results of beta-thromboglobulin and platelet studies are consistent with the concept that platelet consumption due to ischemic thrombosis was the source of enhanced thromboxane excretion.

Topics: beta-Thromboglobulin; Enterocolitis, Pseudomembranous; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Occult Blood; Platelet Count; Prospective Studies; Risk; Thrombosis; Thromboxane B2