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Biomedical subjects

B M Peskar

Publications and source records attributed to B M Peskar.

At least 91 records · Page 5Linked to original sources
PubMed1984

Molecular mechanisms of the gastric toxicity of antirheumatic drugs.

Gastric toxicity of non-steroidal antiinflammatory drugs has been suggested to be due to inhibition of prostaglandin synthesis. Proquazone, which is less ulcerogenic than indomethacin, however, is a more potent inhibitor of gastric mucosal prostaglandin synthesis than indomethacin in vitro and equally effective in vivo. These results indicate that additional factors such as pharmacokinetic properties contribute to the gastric toxicity of non-steroidal antiinflammatory drugs. Furthermore, lipoxygenase products of arachidonic acid metabolism might modulate the effects of inhibition of prostaglandin synthesis by non-steroidal antiinflammatory drugs. Using a radioimmunoassay for leukotriene C4 the capacity of ovalbumin-sensitized guinea pig gastric mucosa to release leukotriene C4-like immunoreactivity after antigenic challenge has been demonstrated.

Adult↗
PubMed1984

Plasma levels of 15-keto-13,14-dihydro-prostaglandin E2 in patients with bronchogenic carcinoma.

Plasma levels of the circulating metabolite of prostaglandin (PG) E2, 15-keto-13,14-dihydro-PGE2 (KH2PGE2), were determined radioimmunologically after conversion to the stable degradation product 11-deoxy-15-keto-13,14-dihydro-11,16-cyclo-PGE2 (DKH2-cyclo-PGE2). In healthy volunteers a plasma level of 25 +/- 2 pg/ml (mean +/- S.E.M., n = 24) was found. The plasma level of KH2PGE2 was significantly decreased after administration of acetylsalicylic acid (4 x 1 g/24 hours). A significant elevation of the plasma levels of the circulating metabolite of PGE2 was observed in patients with bronchogenic carcinoma as compared to healthy controls, while no elevation was found in patients with chronic myeloid leukemia, lymphatic leukemia and non-Hodgkin lymphoma. The increased plasma levels of KH2PGE2 in the patients with bronchogenic carcinoma were independent of the clinical condition, histological type of tumor, tumor spread and therapeutic regimen. The results indicate that the elevated plasma level of the circulating PGE2 metabolite in patients with bronchogenic carcinoma is not an expression of malignant disease in general. On the other hand, the results do not suggest that the increase in the plasma level of KH2 PGE2 is a biochemical tumor marker closely related to a particular clinical feature of patients with bronchogenic carcinoma.

Adult↗
PubMed1983

Release of slow-reacting substance of anaphylaxis and leukotriene C4-like immunoreactivity from guinea pig colonic tissue.

Colonic mucosa, muscularis propria and subserosa from ovalbumin-sensitized guinea pigs were incubated and challenged with antigen in vitro. Slow-reacting substance of anaphylaxis (SRS-A) was determined biologically as well as radioimmunologically in terms of leukotriene (LT) C4-like immunoreactivity. Before antigenic challenge release of immunoreactive LTC4 by all tissues was below or close to the detection limit of the radioimmunoassay. After addition of antigen colonic mucosa released considerable amounts of LTC4-like immunoreactivity, while muscularis propria and subserosa were less active. The biological activity of the SRS-A formed after challenge was antagonized by FPL 55712. Contrary to LTC4-like immunoreactivity release of 6-keto-prostaglandin (PG) F1 alpha was predominant in the subserosa and smaller amounts were released from the smooth muscular and mucosal layers. Synthesis of SRS-A and LTC4-like immunoreactivity, respectively, as well as synthesis of 6-keto-PGF1 alpha was inhibited by the dual inhibitor of lipoxygenase and cyclooxygenase BW755c. The results suggest a role for LTs as local mediators of inflammatory reactions in colonic disease states, particularly those with possible involvement of immunological processes.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1983

Release of slow-reacting substance of anaphylaxis from layers of guinea pig aorta.

Release of slow-reacting substance of anaphylaxis (SRS-A) from layers of ovalbumin-sensitized guinea pig aorta after antigenic challenge in vitro was investigated. SRS-A was determined by bioassay and in terms of leukotriene C4-like immunoreactivity using radioimmunoassay. While no SRS-A could be detected before challenge, the adventitia released considerable amounts of SRS-A after addition of antigen to the incubation medium. On the other hand, an inner layer of the aortic wall consisting of smooth muscle tissue with some adherent endothelium released only small amounts of SRS-A after challenge.

Animals↗
PubMed1982

Release of leukotriene C4 from human polymorphonuclear leucocytes as determined by radioimmunoassay.

Rabbits were immunized with a conjugate of leukotriene (LT) C4 and bovine serum albumin prepared by coupling the single free amino group of the hapten to the protein using gluteraldehyde. Binding of [3H]LTC4 to the antibodies obtained is inhibited by 50% with 1.5 ng LTC4. The relative cross-reaction of LTD4 is 16% and of LTC4-methyl ester 3.6%. The validity of the radioimmunoassay was demonstrated by comparison with bioassay using the isolated guinea pig ileum. Using the radioimmunoassay it could be shown that endogenous LTC4 is released in a dose-dependent manner by human polymorphonuclear leucocytes stimulated with the divalent cation ionophore A23187.

Animals↗
PubMed1981

Release of prostaglandins by small intestinal tissue of man and rat in vitro and the effect of endotoxin in the rat in vivo.

Rat jejunal tissue in vitro synthesizes large amounts of prostaglandin (PG) D2 and smaller amounts of 6-keto-PGF1 alpha and PGE2, whereas human small intestinal mucosa synthesizes much smaller amounts of the three PG determined with about equal amounts of PGE2 and PGD2. Intraperitoneal administration of bacterial endotoxin to rats induce fluid accumulation in the small intestine and increases significantly the release of PGD2, PGE2 and 6-keto-PGF1 alpha into the small intestinal lumen in vivo. Endotoxin-induced stimulation of PG release is particularly pronounced for PGD2. Fluid accumulation and PG output are inhibited by indomethacin. It seems possible that the different total amounts of PG synthesized by small intestinal tissue of man and rat as well as the different pattern of PG released might contribute to species-specific responses of the gastrointestinal tract to various pathophysiological stimuli.

Animals↗
PubMed1980

Prostaglandins and prostaglandin metabolites in human gastric juice.

Human gastric juice contains higher concentrations of PG metabolites than of unmetabolized PG indicating that local metabolism might play a role in limiting the biological activity of PG in gastric mucosa and has to be considered when investigating endogenous gastric PG. A major fraction of the 15-keto-13,14-dihydro-PGE2 (KH2PGE2) formed in gastric mucosa and released into the gastric lumen seems to be rapidly dehydrated to a compound co-chromatographing with KH2PGA2, while the amounts of the bicyclic degradation product 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-PGE2 (11-deoxy-KH2-cyclo-PGE2), as measured by radioimmunoassay, in freshly extracted gastric juice are negligible. Stimulation of secretion with pentagastrin does not influence significantly the concentrations of PG and PG metabolites in human gastric juice, but total output tends to increase parallel to the increase in secretion volume. Levels of immunoreactive 6-keto-PGF1 alpha in human gastric juice are much lower than those of PGE2. Since human gastric mucosa synthesizes conciderable amounts of PGI2 and 6-keto-PGF1 alpha in vitro, the low levels of 6-keto-PGF1 alpha in gastric juice might indicate that PGI2 formed by gastric mucosa in vivo is, like PGE2 and PGF2 alpha, rapidly metabolized and/or removed preferentially via the blood stream.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Effect of carbenoxolone on prostaglandin synthesizing and metabolizing enzymes and correlation with gastric mucosal carbenoxolone concentrations.

Carbenoxolone in a dose dependent manner inhibits the activity of the prostaglandin (PG) metabolizing enzymes 15-hydroxy-PG-dehydrogenase and delta 13-PG-reductase in vitro, while this drug in the same dose range does not influence gastric mucosal PG synthesis by a microsomal cell fraction. Using a radioimmunoassay for carbenoxolone determination, we could show that during absorption high levels of the drug are reached within the gastric mucosa of human volunteers and gastric ulcer patients. From the tissue levels reached it seems possible that carbenoxolone inhibits PG inactivating enzymes of gastric mucosa in vivo as it does in vitro. Thus, decreased inactivation cytoprotective PG synthesized within the gastric mucosa, might contribute to the ulcer healing effect of carbenoxolone.

15-Oxoprostaglandin 13-Reductase↗