dinoprost and 7-hydroxy-5-11-dioxotetranorprostane-1-16-dioic-acid

Every year, major chest injury is involved in 56% of deaths in trauma victims. Blunt chest trauma apparently plays a crucial role in trauma-induced death of multiply injured patients. Therefore, the aim of this study was to evaluate the impact of different types of injuries, including lung tissue damage, on the release of various prostanoids. In a prospective study, the release of arachidonic acid (AA) metabolites was estimated in patients suffering blunt chest trauma alone, i.e., single thoracic injury, and in multiple injured patients including blunt chest trauma. The results were compared with those of patients suffering from single long bone fractures of the leg without additional injury. The plasma concentrations of the AA metabolites, prostacyclin, thromboxane, prostaglandin F2 alpha, and prostaglandin M were determined immediately after admission and in hourly and daily intervals thereafter. Despite clearly different injury scores, elevated levels of circulating AA metabolites were found in the plasma in all patients. This study reveals that any trauma increases significantly the release of prostanoids into the peripheral blood without regard to the impact of tissue damage. This phenomenon is, however, most pronounced following lung injury. On the basis of these results we suggest that there is a specific impact of those mediators in blunt chest trauma. The prostanoids apparently are suitable to describe and even to monitor the extent of thoracic trauma, thus giving additional information in some respect to the individual outcome.

Topics: Adolescent; Adult; Aged; Dinoprost; Epoprostenol; Female; Humans; Male; Middle Aged; Prospective Studies; Prostaglandins; Thoracic Injuries; Thromboxanes; Vasomotor System; Wounds, Nonpenetrating

Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE(2) promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD(2) may suppress tumors, but a role for biosynthetic enzymes for PGD(2) in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in Apc(Min/+) mice led to approximately 50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, Apc(Min/+) mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11beta-PGF(2alpha) and a lower excretion of a PGE(2) metabolite in transgenic mice, but differences (30-40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE(2) or inhibition of the nuclear factor-kappaB cascade by PGD(2) metabolites.

Topics: Adenomatous Polyposis Coli; Animals; Dinoprost; Female; Hematopoietic System; Intramolecular Oxidoreductases; Lipocalins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Prostaglandin D2; Prostaglandins

Clinical and biochemical effects of indomethacin were monitored in a patient with congenital chloride diarrhea (CCD) before and after 10 days of therapy. During indomethacin treatment, no clinical improvement could be achieved whereas hyperreninemia and hyperaldosteronism improved. Excretion rates of prostaglandin (PG) E2, PGF2 alpha, as well as PGE-M were found to be slightly raised and decreased during therapy with indomethacin. However, loss of electrolytes remained substantially unchanged. Prostaglandins, therefore, seem to play no important role in intestinal loss of electrolytes in CCD, and it is suggested that indomethacin is of no importance in the treatment of patients with CCD.

Topics: 18-Hydroxycorticosterone; Aldosterone; Chlorine; Diarrhea; Dinoprost; Dinoprostone; Humans; Indomethacin; Infant; Male; Potassium Chloride; Prostaglandins; Renin; Sodium Chloride; Water-Electrolyte Balance