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Biomedical subjects

G Defreyn

Publications and source records attributed to G Defreyn.

At least 37 records · Page 2Linked to original sources
PubMed1982

Abnormal prostacyclin metabolism in the hemolytic uremic syndrome: equivocal effect of prostacyclin infusions.

In a child with the hemolytic uremic syndrome, plasma 6 keto-prostaglandin F1 alpha levels remained undetectable throughout the acute phase of the disease. The patient's plasma failed to stimulate prostacyclin production by "exhausted" rat aorta rings. In vitro study of the patient's vessels indicated that they retained the capacity to synthesize prostacyclin from exogenous arachidonic acid but that their endogenous arachidonic acid stores were either depleted or non-available. The response to repeated infusion of exogenous prostacyclin was equivocal, suggesting that abnormal prostacyclin metabolism in the hemolytic uremic syndrome may not be the only factor in its pathogenesis.

Child, Preschool↗
PubMed1981

Thromboxane synthetase inhibition as antithrombotic strategy.

The imidazole derivative UK-37 248, a thromboxane synthetase inhibitor, reduces the in-vitro formation of thromboxane B2 and hydroxyheptadecatrienoic acid by washed platelets, and this is compensated for by an increased production of prostaglandins E2 and F2 alpha; arachidonic acid challenged platelets pretreated with UK-37 248 also stimulate the production of prostacyclin by aspirin pretreated cultured endothelial cells. In a double-blind placebo controlled study to examine the in vivo properties of UK-37 248, human volunteers ingested 200 mg of the compound. Their serum thromboxane B2 levels dropped and their plasma 6-keto-prostaglandin F1 alpha values rose. Arachidonic acid induced platelet aggregation was completely inhibited whereas that elicited by adenosine-5'-diphosphate was unaffected. By reducing formation of pro-aggregatory tromboxane A2 and increasing production of anti-aggregatory prostacyclin, thromboxane synthetase inhibitors may be better than aspirin as antithrombotic agents.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Arterial thrombosis, intrauterine death and "lupus" antiocoagulant: detection of immunoglobulin interfering with prostacyclin formation.

In a 31-year-old woman with a history of recurrent arterial thrombosis, both of whose pregnancies had resulted in intrauterine death at 23 and 24 weeks, a "lupus" anticoagulant was identified. The patient's IgG fraction, containing the lupus anticoagulant, reduced the release of prostacyclin (PGI2) from rat aorta rings or pregnant human myometrium. This inhibitory effect was abolished in the presence of arachidonic acid. The production of 6-keto-PGF1 alpha by cultured bovine endothelial cells was also decreased in the presence of the patient's IgG fraction. The plasma level of 6-keto-PGF1 alpha was reduced. An antibody in this patient may interfere with the production or release of PGI2 by the vessel wall, possibly by interfering with the availability of arachidonic acid. This mechanism could play a role in this patient's arterial disease and obstetric problems.

Adult↗
PubMed1981

The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF1 alpha levels.

We have infused synthetic prostacyclin (PGI2) continuously for approximately 72 h at the maximum tolerated dose (ranging from 5 to 60 ng/kg/min) into nine patients with advanced arterial disease. Prior to the infusion seven out of nine patients had spontaneous platelet aggregation and five out of six patients tested had an abnormal circulating platelet aggregate ratio. During the infusion only one patient still had spontaneous aggregation and all the abnormal circulating platelet aggregate ratios returned to the normal range. However, none of the patients showed any suppression of ADP induced aggregation. The level of exogenous PGI2 required in vitro prior to the infusion to completely inhibit ADP induced aggregation was 5-10 ng/ml in three of the four patients tested. Ten healthy adults showed complete inhibition with 1 ng/ml of PGI2. It appears that the platelets of some patients with arterial disease are more resistant to the anti-aggregating properties of PGI2. Plasma 6-keto PGF1 alpha levels, measured by radioimmunoassay, were within the normal range (100-381 pg/ml) in all but one of the patients prior to the infusion. During the infusion plasma 6-keto PGF1 alpha levels rose proportionally to the infusion dose. After stopping the infusion 6-keto PGF1 alpha levels declined according to an exponential process with a half life of 18-29 min, prolonged to 47 min in one patient who was anuric. The linear increase in 6-keto PGF1 alpha levels suggests this as a useful indicator of increased circulating PGI2.

Adult↗
PubMed1981

Familial bleeding tendency with partial platelet thromboxane synthetase deficiency: reorientation of cyclic endoperoxide metabolism.

Three family members from three successive generations presented with a moderate bleeding tendency and a functional platelet defect. They had absent aggregation with arachidonic acid (0.6--3 microM), reversible aggregation with ADP (4 microgram) and cyclic endoperoxide analogues, single wave aggregation only with adrenaline (5.4 microgram) and a prolonged template bleeding time (> min). Malondialdehyde formation was reduced after N-ethylmaleimide stimulation (2--6 nmol/10(9) platelets; control values 8--12 nmol) and serum thromboxane B2 values were reduced (33--101 ng/ml; control values 200--700 ng/ml). When the platelets were incubated with [3H]arachidonic acid the final metabolite of the lipoxygenase pathway (HETE) was produced in normal amounts but the production of thromboxane B2 and HHT was decreased whereas prostaglandin F2a, and E2 and probably D2 were increased. Evidence for enhanced production of prostaglandin D2 was also provided by the rise in the patient's platelet cyclic AMP levels following stimulation with arachidonic acid. The patient's washed platelets stimulated the production of 6-keto PGF 1a by aspirin-pretreated cultured bovine endothelial cells. The plasma levels of 6-keto PGF1a (439--703 pg/ml; normal 181 +/- 46 pg/ml) were raised. The decreased production of thromboxane B2, HHT and malondialdehyde and increased formation of prostaglandin F2a, E2, D2 and of 6-keto PGF1a are compatible with a partial platelet thromboxane synthetase deficiency and reorientation of cyclic endoperoxide metabolism. The markedly prolonged bleeding time would result not only from reduced formation of thromboxane A2 but also from increased production of the aggregation inhibiting prostaglandins PGI2 and PGD2.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1979

The reaction of nitrogen monoxide and of nitrite with deoxyhaemocyanin and methaemocyanin of Helix pomatia.

Deoxyhaemocyanin, treated with NO under strictly anaerobic conditions, yielded methaemocyanin and N2O in a fast reaction. In a further slow reaction this methaemocyanin lost its triplet electron paramagnetic resonance (EPR) signal at g = 4 and yielded a nitrosyl derivative with a characteristic g = 2 Cu(II) EPR signal, indicating the binding of a single NO per copper pair. Thus under strictly anaerobic conditions deoxyhaemocyanin and methaemocyanin, treated with NO, gave the same derivative as shown by circular dichroism and EPR spectra. Methaemocyanin yielded, moreover, reversibly a nitrite derivative, characterized by a triplet signal at g = 4 with 7 hyperfine lines.

Animals↗
PubMed1977

Multiple molecular forms of phosphorylase phosphatase associated with particulate glycogen and extracted from the cytosol of dog liver.

The glycogen pellet of dog liver extracts contains a phosphorylase phosphatase which has characteristics different from those of the phosphatases extracted from the cytosol. The phosphatase associated with glycogen is characterized by a M, of 51,000, a half maximal inhibition at 0.3 mM ATP (Hill coefficient : 2) and a Ki for Mg2+ of 1 mM. Treatment with urea or mercaptoethanol of the phosphatase associated with glycogen does not influence the activity, the Mr or the half maximal inhibition by ATP, but a decrease of the Hill coefficient for ATP is observed. A similar treatment of the phosphatases extracted from the high speed supernatant results in a decrease of the Mr of the spontaneously active form from 215,000 to 43,000, without an effect on the Ki for ATP (7 micronM), but accompanied by an increase in activity. The ATP-Mg dependent form of the phosphatase from the high speed supernatant (Mr : 138,000 ; Ka for ATP in the presence of 0.1 mM Mg2+ : 0.3 micronM), is denatured by urea or mercaptoethanol. The phosphatase associated with particulate glycogen cannot be found in the supernatant, nor the phosphorylase phosphatases present in the supernatant in the glycogen pellet. When all the glycogen is mobilized (starvation, glucagon) the phosphatase specifically associated with glycogen cannot be found as such in the cytosol. No activation of synthase beta can be detected neither with the phosphatases extracted from the cytosol nor with the enzyme released from the glycogen pellet.

Adenosine Triphosphate↗