vapiprost and Acute-Disease

To determine the role of inflammatory products of phospholipid metabolism in acute otitis media (AOM), we infected 128 chinchillas with Streptococcus pneumoniae and randomly assigned them to one of four equal-sized treatment groups receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally), of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d orally). All treatments were begun on day 2 postinoculation and continued for 10 days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed. Effusions were recovered for biochemical assay, and the right middle ears were prepared for histologic study. Differences among groups in the number of ears with effusion or in effusion volume were not statistically significant. In comparison to the control group, mucosal thickness and the number of ears with histopathologic signs of inflammation were significantly less in the GR and WEB treatment groups, but not the MK group. Also, effusion concentrations of free fatty acids, protease, and hydrolytic enzymes were significantly less in those groups. These results show that the addition of a receptor blocker for either platelet activating factor and/or thromboxane to ampicillin in the treatment of AOM reduces mucosal inflammation and decreases the production of other inflammatory chemicals. The failure of a receptor blocker of leukotrienes to moderate disease expression suggests either a less important role for these chemicals in AOM or an insufficient bioavailability of the specific MK 571 inhibitor. These results confirm that platelet activating factor and thromboxane are active mediators of inflammation in AOM.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Azepines; Biphenyl Compounds; Chinchilla; Dinoprostone; Ear, Middle; Fatty Acids, Nonesterified; Heptanoic Acids; Hydrolases; Leukotriene Antagonists; Leukotriene C4; Mucous Membrane; Otitis Media; Phospholipids; Platelet Activating Factor; Platelet Membrane Glycoproteins; Pneumococcal Infections; Propionates; Quinolines; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Thromboxane; Thromboxane B2; Triazoles

ePTFE interposition grafts in the common carotid arteries of 16 adult sheep were used to study the effect of a thromboxane receptor antagonist. Vapiprost (GR 32191, Glaxo research group, London, UK). After insertion of the grafts the sheep were randomised to treatment (n = 8) or control (n = 8). Treatment was given as an intravenous injection with GR 32191 of 1 mg/kg body weight. The flow in one of the two inserted grafts was restricted from normal (190 ml/min) to 25 ml/min. Autologous 111-In labelled platelets and human 125-I labelled fibrinogen were injected intravenously. The radioactivity over each graft was measured for 4 h at two separate points with a gamma scintillation technique. Due to technical complications immediately before the start of the measurements one sheep in each group was excluded from the study. In the treated group three out of seven grafts with restricted flow occluded compared to all seven grafts with a flow reduction in the control group (p less than 0.05). The grafts with unrestricted flow occluded in two of seven in both groups. In the open grafts with unrestricted flow the fibrinogen activity was significantly reduced in the treated group compared to the control group. The platelet activity was not significantly reduced. It is concluded that GR 32191 significantly reduced the fibrinogen uptake as well as graft occlusions of ePTFE grafts in a low flow situation.

Topics: Acute Disease; Animals; Biphenyl Compounds; Blood Vessel Prosthesis; Carotid Arteries; Disease Models, Animal; Female; Graft Occlusion, Vascular; Heptanoic Acids; Male; Polytetrafluoroethylene; Receptors, Prostaglandin; Receptors, Thromboxane; Sheep; Thrombosis