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Biomedical subjects

J Vermylen

Publications and source records attributed to J Vermylen.

At least 253 records · Page 14Linked to original sources
PubMed1983

Enkephalins modify granulocyte-endothelial interactions by stimulating prostacyclin production.

Granulocyte (PMN)-endothelial interactions have been implicated in the primary events of vascular injury and atherogenesis. We now present data which show that endogenous opioid peptides, e.g. enkephalins (ENK), dampen immune-triggered, granulocyte-induced endothelial damage by enhancing prostacyclin production. Concurrent exposure of human umbilical vein endothelial cells (HUEC) to Met5-enkephalin increased arachidonic acid (AA, 20 muM) and thrombin (T, 10 U/ml) induced 6-keto-PGF1 alpha-release to respectively 197.2 +/- 28.1% and 204.1 +/- 17.8% (mean +/- SEM) of base line stimulation (p less than 0.025). The increases noted were significant at ENK-concentrations as low as 10(-12)M. Simultaneous addition of naloxone with ENK completely abolished the enhanced 6-keto-PGF1 alpha-release. Addition of a protease resistant enkephalin analogue significantly (p less than 0.01 over several different concentrations) reduced PMN adherence to HUEC; concomitantly 51Cr-leakage from HUEC that had been exposed to PMN plus activated serum complement was decreased. The even further enhanced 51Cr-leakage that occurs when platelet release products (e.g. serotonin) are included is also decreased by added enkephalin. These data suggest that endogenous neurotransmitters may affect endothelial prostaglandin metabolism, and by so doing provide a protective effect during in vitro, and perhaps in vivo, PMN mediated endothelial injury. This link between neurohumoral and inflammatory systems might enhance our understanding of stress-related phenomena in inflammation and vascular diseases.

Cell Adhesion↗
PubMed1983

Prostacyclin production by whole blood from children: impairment in the hemolytic uremic syndrome and excessive formation in chronic renal failure.

The capacity of leukocytes to produce prostacyclin (PGI2) from endogenous and from platelet-derived endoperoxides was tested in whole blood. During the acute phase of the hemolytic uremic syndrome (H.U.S.), the PGI2-production was lower than the controls, whereas the blood from children with chronic renal failure produced higher amounts. Production of PGI2 by blood from children 3/12 to 6 years after the acute phase of H.U.S. was normal, as was the case with blood from their parents. Furthermore, in two H.U.S.-patients studied serially, the decreased PGI2-production capacity normalized 2 1/2 months after the acute phase.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Reorientation of prostaglandin endoperoxide metabolism by a thromboxane synthetase inhibitor: in vitro and clinical observations.

1 Work with dazoxiben in vitro and in vivo suggests that a diminished capacity of platelets to synthesize thromboxane A2 results in a reorientation of the metabolism of cyclic endoperoxides. 2 Platelets of patients with congenital thromboxane synthetase deficiency show the same phenomenon. 3 In the presence of endothelium or leukocytes which have prostacyclin synthetase capacity, significant amounts of prostacyclin can be generated if thromboxane synthesis is blocked. 4 The local generation of aggregation inhibiting prostaglandins in areas of vascular damage may be an interesting therapeutic concept. 5 Pilot clinical studies of thromboxane synthetase inhibitor dazoxiben (UK 37248) in a small number of patients with peripheral arterial disease did not reveal major or consistent haemodynamic changes. 6 Attention is directed towards optimizing pharmacologically the generation and efficacy of the inhibitory prostaglandins produced when thromboxane synthetase is inhibited.

Adult↗
PubMed1983

Prostacyclin production in whole blood throughout normal pregnancy.

In a longitudinal study of twelve normal pregnant women the base-line plasma values of 6-keto prostaglandin (PG)F1 alpha, the stable degradation product of prostacyclin, were determined. At the same time the capacity of their blood to produce prostacyclin was assessed using a stimulation test. When collagen is added to citrated whole blood there is a prompt rise in plasma 6-keto PGF1 alpha, which results from the synthesis of prostacyclin by leukocytes. These cells use cyclic endoperoxides in part coming from activated platelets and in part derived from endogenous substrate to produce prostacyclin. Both the base-line values and the capacity to produce prostacyclin fell significantly after 33 weeks of pregnancy. The decreased capacity to produce prostacyclin in the later stages of pregnancy may help account for the relatively diminished refractoriness to angiotensin II, characterizing the last two months of normal pregnancies.

Blood Platelets↗
PubMed1982

The effect of sulphinpyrazone on whole blood thromboxane and prostacyclin generation in man.

A new method, based on the observation that leukocytes contain PGI2-synthetase activity, was used to measure the effect of pharmacological levels of sulphinpyrazone on the TXA2 and PGI2 production in whole blood. Four human volunteers took 400 mg sulphinpyrazone twice daily for 5 1/2 days. Blood was drawn before the study started, 3-4 h after the initial dosage, 12 h after the 10th dosage on the 5th day, and 3-4 h after the 11th (final) dosage on the 6th day. Collagen was added to the citrated blood samples to stimulate prostaglandin production. Aliquots were removed at regular intervals and TXB2 and 6-keto-PGF1 alpha measured by radioimmunoassay. The production of PGI2 was significantly inhibited in all the samples collected after sulphinpyrazone intake (p less than 0.01). The production of TXA2 was significantly inhibited only in the samples collected 3-4 h after sulphinpyrazone intake on the 6th day (p less than 0.01). These results confirmed the cyclooxygenase inhibitory action of sulphinpyrazone and also showed that in the whole blood system, PGI2 production was more effectively inhibited than TXA2 production.

Adult↗
PubMed1982

A thromboxane synthetase inhibitor reorients endoperoxide metabolism in whole blood towards prostacyclin and prostaglandin E2.

During incubation of citrated blood at 37 degrees C the levels of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and prostaglandin E2 (PGE2) remain constant, but rise markedly within one minute after the addition of collagen, particularly when thromboxane synthetase is blocked. The amount of 6-keto PGF1 alpha formed is dose-dependent for both collagen and the thromboxane synthetase inhibitor (UK-37,248). Moreover, the number of platelets will determine the extent of the 6-keto PGF1 alpha jump, that does not occur when blood is drawn after aspirin ingestion. The production of 6-keto PGF1 alpha in function of time is composed of a fast platelet-related (intercept) and a slower probably leukocyte-dependent contribution (slope). In the absence of UK-37,248 the intercept is 115 +/- 85 pg/ml, the slope is 12.9 +/- 7.7 pg/min/ml whereas in the presence of the thromboxane synthetase inhibitor they are 411 +/- 177 pg/ml and 56.2 +/- 25 pg/min/ml respectively. The present findings indicate that a thromboxane synthetase inhibitor, by not only reducing thromboxane A2 production but also enhancing prostacyclin generation with blood is exposed to thrombogenic stimuli such as collagen, should be superior to aspirin as an antithrombotic agent, although possible interference by enhanced PGE2 production should be taken into account.

Blood Platelets↗
PubMed1982

Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant.

Evidence exists of an association between the presence of a "lupus" anticoagulant in plasma, recurrent fetal loss, and repeated thromboembolic accidents, also in the absence of systemic lupus erythematosus. Presented is an example of this association, with morphologic and biologic studies to elucidate its pathogenesis. In the case reported, the placenta showed massive infarction. In the spiral arteries of the basal plate of the placenta, lesions of intimal thickening, fibrinoid necrosis, acute atherosis, and intraluminal thrombosis were observed. The plasma of the patient contained a lupus anticoagulant and inhibited the formation of prostacyclin by rat aortic rings. Vascular production of prostacyclin is a major natural defense mechanism against thrombosis. Lack of generation of prostacyclin may account for the decidual vasculopathy and consequent placental infarction and for the generalized thrombotic tendency of some patients with lupus anticoagulant.

Abortion, Habitual↗
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↗