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Biomedical subjects

Y Denizot

Publications and source records attributed to Y Denizot.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of the platelet-activating factor receptor antagonist BN 52021 on hematologic variables and blood loss during and after cardiopulmonary bypass.

Cardiopulmonary bypass (CPB)-induced thrombocytopenia and leukopenia is augmented after heparin reversal of protamine. Platelet-activating factor (PAF) might be implicated in these disorders. To evaluate the effects of PAF on the hematologic disorders and blood loss during and after CPB, patients were pretreated with BN 52021, a PAF receptor antagonist, or a placebo. BN 52021 (120 mg) (n = 13) or placebo (n = 15) were infused intravenously before vascular cannulation and before cross-clamp release. Platelet and leukocyte counts were assessed in venous blood before and after the first dose of BN 52021 or placebo, 2 min after the beginning of CPB (at the entry of the oxygenator), at the end of CPB, 1, 15, and 30 min after protamine infusion, and 6 and 24 h after CPB. The decrease in platelet and leukocyte counts were the same between groups during and after CPB and after protamine infusion. Bleeding times were not modified by the pretreatment of patients with BN 52021. During surgery, blood loss reached 1660 +/- 297 mL in the BN 52021 group and 1599 +/- 283 mL in the placebo group (P > 0.05). Forty-eight hours postoperatively, the chest tube outputs were not different between groups (1460 +/- 418 mL vs 1640 +/- 362 mL in the BN 52021 and placebo groups, respectively). This study shows that BN 52021 infusion did not change the hematologic variables studied. Moreover, a PAF antagonist pretreatment did not protect the patients against CPB- or protamine-induced hematologic changes.

Analysis of Variance↗
PubMed1993

[Fecal platelet-activating factor (PAF). A marker of digestive inflammatory disorders].

PAF (platelet-activating factor) is a phospholipid compound with harmful inflammatory effects on the gastrointestinal tract of animals. Recent studies have reported the presence of PAF in the stools of patients with inflammatory gut diseases such as Crohn's disease, ulcerative colitis, pouchitis and bacterial diarrhoea. PAF might be implicated in the occurrence and perpetuation of the digestive tract inflammatory symptoms observed in these diseases. The beneficial use of PAF antagonists in inflammatory diseases of the gastrointestinal tract deserves to be assessed.

Bacterial Infections↗
PubMed1993

Effects of eicosanoid metabolism inhibitors on growth of a human gastric tumour cell line (HGT).

HGT cells are a human gastric cell line derived from a tumour of the stomach. We have investigated the effects of lipoxygenase and cyclooxygenase metabolism inhibitors on HGT cell proliferation, on fatty acid composition of HGT cells and on the incorporation and distribution of arachidonic acid (AA) in HGT lipids. The cyclooxygenase inhibitor aspirin and both cyclooxygenase and the lipoxygenase inhibitor BW 755C suppressed cell proliferation in a concentration-dependent manner. The inhibition of HGT proliferation did not result from a modulation of the fatty acid composition of membrane lipid, which was not affected by treatment with the various inhibitors. Inhibitors of AA metabolism did not alter acylation of exogenous AA into HGT cells nor its subsequent distribution in the lipid and phospholipid species. The role of cyclooxygenase eicosanoids in HGT proliferation is discussed.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1993

Incorporation of arachidonic acid in a human cancer gastric tumor cell line (HGT) at various stages of cell proliferation.

Human cancer gastric cells (HGT) in culture were labeled with [14C]arachidonic acid. The kinetic of acylation of arachidonic acid was similar using cells after 3, 5 and 7 days of culture. However, the duration of the proliferation enhanced the acyltransfer to triglycerides and inhibited the transfer to phospholipids. After 8 h of incubation with [14C]arachidonic acid the radioactivity was predominantly recovered in the phosphatidylcholine and phosphatidylethanolamine species. Prelabeling-chase experiments indicated a preferential incorporation of arachidonic acid into phosphatidylcholine followed by a transfer of arachidonate to phosphatidylethanolamine.

Acylation↗
PubMed1993

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation.

Acetylation↗
PubMed1992

Significance and regulation of gastric secretion of platelet-activating factor (PAF-acether) in man.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the present study, we compared the gastric output of PAF and its precursors with gastric acid output, in patients with various upper gastrointestinal tract diseases and healthy controls. PAF and precursors were also extracted from gastric biopsies from subjects with chronic gastritis and/or gastric colonization by Helicobacter pylori. Under basal conditions, hourly gastric PAF output increased in esophagitis and erosive gastritis, but not in duodenal ulcer or Zollinger-Ellison syndrome. In the gastric juice of duodenal ulcer patients, PAF output rose after secretin, but in patients with Zollinger-Ellison syndrome, PAF was only detected when gastric acid secretion had been reduced by antisecretory drugs and no concurrent changes were observed in serum gastrin levels. After pentagastrin, patients and controls exhibited a significant decrease in PAF output and a negative correlation was found between PAF and acid outputs (r = -0.57, p < 0.01). When PAF was incubated with gastric juice in vitro, it underwent degradation irrespective of the medium pH. We found no relation between the outputs of PAF and precursors and the severity of gastritis or gastric colonization by H. pylori. Overall, these results suggest that PAF might be released in the stomach by gastric epithelial cells and could be responsible for mucosal injury of the upper gastrointestinal tract.

Adult↗
PubMed1992

PAF-acether and acetylhydrolase in stool of patients with Crohn's disease.

PAF-acether (PAF) is a phospholipid mediator with potent biological effects on the digestive tract. We report the presence of PAF in stool of patients with active Crohn's disease (39.1 +/- 13.5 ng/g of stool, mean +/- SEM, N = 19) and its absence in patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. Fecal PAF acetylhydrolase activity was higher (P less than 0.04) in patients with Crohn's disease as compared to patients with irritable bowel syndrome with diarrhea and diarrhea with malabsorption. We also report a solid-phase extraction of fecal PAF using silica minicolumns, which yielded results highly correlated with those obtained with a high-performance liquid chromatography method (r = 0.86, P less than 0.001, N = 16). These findings may allow us to implicate PAF in the onset and perpetuation of digestive tract inflammatory symptoms observed during Crohn's disease. They would warrant to investigate the influence of various therapeutic agents, including PAF antagonists, on fecal PAF levels during inflammatory digestive ailments.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1992

Variations of blood PAF-acether levels during coronary artery surgery.

Extracorporeal circulation (ECC) is associated with thrombocytopenia and transient leukopenia. After ECC and coronary artery bypass graft (CABG) surgery, some patients can develop pulmonary and cardiac dysfunction, which might be related to the release of various mediators such as thromboxane A2, C5a, and C3a anaphylatoxins. The involvement of PAF-acether (PAF), a potent vasoactive thrombocytopenic and leukoneutropenic agent, has not been determined. Therefore, 10 patients were studied during and after CABG. The release of PAF, lipo PAF (PAF bound to blood lipoproteins), and lyso PAF (PAF precursor and metabolite) was measured in blood from the left atrium, radial artery, and pulmonary artery before and after CABG. PAF, lipo PAF, and lyso PAF were also determined during ECC at the entry and exit points of the oxygenator. Hemodynamic parameters, platelet, and leukocyte counts in the pulmonary artery were measured simultaneously. PAF did not increase significantly during ECC; it showed a transitory six-fold increase immediately after CABG in the radial artery (0.18 +/- 0.13 v 1.09 +/- 0.36 ng/mL, P < 0.05), but not in the pulmonary artery (0.10 +/- 0.03 v 0.56 +/- 0.21 ng/mL, P > 0.05). Blood PAF amounts in the radial artery were significantly higher than in the left atrium following ECC (1.09 +/- 0.36 v 0.06 +/- 0.04, P < 0.05), probably indicating PAF production in the heart. No variation of blood lipo PAF and lyso PAF was observed. No correlation was seen between PAF amounts and blood cell count.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Variations in blood platelet-activating-factor levels after protamine reversal of heparin in humans.

The potent inflammatory mediator PAF-acether (PAF = platelet-activating factor) can produce the same hemodynamic and hematological effects as protamine infusion. In 10 patients, blood PAF and precursor levels were measured in the left atrium, the pulmonary and the radial artery before and after protamine reversal of heparin during coronary artery bypass graft. Blood PAF level in the left atrium increased 6-fold (17 +/- 12 pg.ml-1 vs 98 +/- 46 pg.ml-1, P = 0.03) after protamine infusion. By contrast, a 4-fold decrease was observed in the pulmonary artery blood (130 +/- 48 pg.ml-1 vs 31 +/- 23 pg.ml-1, P = 0.03) and a 9-fold decrease was noted in the radial artery blood (285 +/- 104 pg.ml-1 vs 31 +/- 15 pg.ml-1, P = 0.01). No cardiovascular impairment was observed but all patients exhibited thrombocytopenia. After protamine, PAF in the left atrium reached lower levels than those observed in the pulmonary and radial artery before protamine infusion. Moreover, no significant correlation was observed between platelet counts and PAF levels. Thus PAF seems not to mediate the platelet drop induced by heparin-protamine complexes. A positive correlation was obtained between leukocyte counts in the pulmonary artery and PAF levels in the left atrium (r = 0.78, P = 0.02). Protamine infusion may stimulate PAF biosynthesis by leukocytes in the lung, on the one hand, and accelerate the disappearance of PAF in the arterial bed, on the other hand.

Coronary Artery Bypass↗