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Biomedical subjects

G M Laekeman

Publications and source records attributed to G M Laekeman.

At least 19 recordsLinked to original sources
PubMed1991

Prostacyclin/thromboxane ratio in human breast cancer.

In this prospective follow-up study the prognostic value of the tumor prostacyclin/thromboxane ratio in human breast carcinoma was investigated. The stable degradation products of prostacyclin and thromboxane (6-keto-PGF1 alpha and TXB2, respectively), were measured by radio-immunoassay in homogenized primary tumours from 29 patients with primary non-metastatic breast cancer. The median follow-up was 43 months (range 24-58 months). Patients with recurrent disease or patients who died of breast cancer had a significantly higher 6-keto-PGF1 alpha/TXB2 ratio than the disease-free survivors (p = 0.018 and p = 0.047, respectively). There was no significant difference in the 6-keto-PGF1 alpha and TXB2 levels. These data indicate that the prostacyclin/thromboxane balance in the tumour might be a prognostic factor in breast cancer. Prostanoid may contribute to metastasis in breast cancer, but the problem is complex because the different prostaglandins have numerous actions that may produce both undesirable and desirable effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Nutmeg oil: identification and quantitation of its most active constituents as inhibitors of platelet aggregation.

Three distilled or commercially available nutmeg oils were analysed and their chemical composition compared with their capacity to inhibit platelet aggregation in vitro. It could be clearly shown that eugenol and isoeugenol play the major role in the detected activity of nutmeg. Medicinally, it appears that nutmeg oil and nutmeg powder can be replaced by eugenol and/or isoeugenol.

Animals↗
PubMed1989

Prognostic value of prostaglandin F2 alpha concentrations in breast carcinoma.

Prostaglandin F2 alpha (PGF2 alpha) concentrations were measured by radioimmunoassay in homogenised primary tumours from 57 patients with breast cancer. These patients were followed up from 60 to 78 months (median 63 months) after surgery and PGF2 alpha concentrations were related prospectively to metastatic spread and survival. The amounts of PGF2 alpha varied greatly in the different tumours (range 0-90 ng/mg protein), but no significant association was found between PGF2 alpha concentrations and disease free survival, time of relapse, site of recurrence, or overall survival. It therefore seems unlikely that measurement of PGF2 alpha in breast carcinoma is important in the prognosis of the disease.

Adult↗
PubMed1986

Inhibition of rabbit platelet activation by lipoxygenase products of arachidonic and linoleic acid.

The hydroperoxy fatty acids, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 13-hydroperoxy and 9-hydroperoxyoctadecadienoic acid (13- and 9-HPODE) and the corresponding hydroxy compounds (15-HETE and 13-HODE) were synthesized and purified. Washed rabbit platelets were incubated with these fatty acid derivatives before aggregation was induced. Arachidonic acid-induced aggregation, as well as the secretion of ATP and the formation of thromboxane B2 (TXB2) were dose-dependently inhibited by these compounds. Low thrombin-, collagen- and ADP-induced aggregations were also suppressed by 15-HPETE. Platelet activation induced by the calcium ionophore A23187 and by high thrombin concentrations were not affected by 15-HPETE. In addition, doses of 15-HPETE which were inactive by themselves, potentiated the anti-aggregating activity of prostacyclin (PGI2). It is suggested that the hydroperoxy and hydroxy compounds suppress platelet activation by interference with the rise in cytoplasmic calcium in addition to the inhibition of cyclo-oxygenase.

Adenosine Triphosphate↗
PubMed1986

Prostacyclin and thromboxane in benign and malignant breast tumours.

6-keto-PGF1 alpha and thromboxane B2 were determined by radioimmunoassay in 37 extracts of breast carcinomata, 8 fibroadenomata, 12 sclerocystic-disease specimens and 51 normal breast tissues. More prostanoids were extracted from carcinomata than from normal specimens, fibroadenomata or sclerocystic-disease tissues (P less than 0.05). The 6-keto-PGF1 alpha/TXB2 ratio was higher in carcinomata than in normal tissues and fibroadenomata (P less than 0.05) but was not significantly different from the ratio in sclerocystic disease. The prostaglandin levels and the 6-keto-PGF1 alpha/TXB2 ratios from carcinomata did not correlate significantly with age, tumour size, differentiation, lymph node status, nuclear-cytoplasmic ratio, host cell reaction, mast cells, necrosis, elastosis, fibrosis or blood vessel density. Lower nuclear density was associated with lower 6-keto-PGF1 alpha/TXB2 ratios (P = 0.01) whereas the latter value was higher when infiltration was lower (P = 0.03). There was a positive correlation between mitotic index and the 6-keto-PGF1 alpha/TXB2 ratio (P = 0.04). Cumulation of variables revealed lower prostanoid ratios in tumours greater than 2 cm without lymph node metastasis then tumours less than 2 cm with lymph node metastasis (P = 0.04). A first follow-up (14 months) showed a higher 6-keto-PGF1 alpha/TXB2 ratio in patients who developed metastasis (P = 0.04). Our study does not confirm the hypothesis that high prostacyclin levels are a good prognostic index in breast cancer.

Adolescent↗
PubMed1986

6-keto-PGF1 alpha levels and prostacyclin therapy in 2 adult patients with hemolytic-uremic syndrome.

Evidence supports the hypothesis that plasma prostacyclin activity is deficient in hemolytic-uremic syndrome (HUS). We studied 2 adult patients with HUS. Plasma levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Both patients were found to have elevated 6-keto-PGF1 alpha levels. These findings are in contradiction with the prostacyclin deficiency hypothesis and with earlier reports of low or undetectable plasma levels of this metabolite. The patients were treated with IV prostacyclin after a single plasma exchange. The first patient, admitted with advanced renal failure, obtained a rapid remission but renal function did not recover; the second patient, admitted with a less pronounced degree of renal failure, reacted slowly to therapy but renal function partially recovered. We believe that, if any benefit is to be expected from prostacyclin therapy in HUS, it should be started early in the course of the disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Vernolepin: an antiplatelet compound of natural origin.

Vernolepin, a natural compound isolated from Vernonia amygdalina Del., shows platelet anti-aggregating properties. In this paper some of its pharmacological activities towards rabbit platelets are studied. Vernolepin has a "stabilizing" effect during freeze-thawing of platelets, it inhibits arachidonic acid, ADP and collagen-induced platelet aggregation and interferes with ATP-release. Electromicroscopy shows a protection of platelets by the drug against adhesion and a desaggregating effect. All these activities are time dependent; a steep dose response relationship is seen. A concentration of 1 X 10(-5) g/ml seems to be optimal.

Adenosine Diphosphate↗
PubMed1985

Prostaglandin F2 alpha in benign and malignant breast tumours.

Prostaglandin F2 alpha (PGF2 alpha) was determined by radioimmunoassay in 57 breast carcinomata, 16 fibroadenomata, and 33 sclero-cystic-disease (SCD) specimens. In 41 cases of carcinoma and 10 cases of fibroadenoma, histologically non-malignant tissue was also obtained from the same breast. PGF2 alpha levels were significantly elevated in breast cancer when compared with the normal tissues and benign diseases (P less than 0.005 for each group). High PGF2 alpha levels were positively correlated with differentiation, positive oestrogen and progestagen receptor status, and low mitotic index. Tumours with good prognosis (less than 20 mm, negative lymph nodes, some degree of differentiation) showed significantly higher PGF2 alpha levels than tumours with a bad prognosis (greater than 20 mm, positive nodes and undifferentiated). A tendency for elevated PGF2 alpha levels was observed with negative lymphatic permeation, postmenopausal status, low grade of nuclear and cellular polymorphism and high degree of elastosis and fibrosis. No correlation was observed between PGF2 alpha levels and host-cell reaction. Plasma levels of 15-keto-13, 14-dihydro-PGF2 alpha were not elevated in cancer patients when compared with the SCD-group. The present study demonstrates that PGF2 alpha levels are high in tumours with good prognosis. However, since other authors have suggested that a high PGE2 production is a bad prognostic index, it is possible that conversion of PGE2 to PGF2 alpha by 9-keto-reductase explains this relationship. Nevertheless, the presented results question the unrestricted use of prostaglandin-synthesis-inhibitors in the treatment of breast cancer.

Adenofibroma↗
PubMed1985

Formation of prostanoids during intravascular complement activation in the rabbit.

Plasma concentrations of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (TXB2) were measured by radioimmunoassay in arterial blood before and after injections of the complement activator, cobra venom factor (CVF). During the control period, the concentration of 6-oxo-PGF1 alpha, which gives the sum of prostacyclin plus 6-oxo-PGF1 alpha, and TXB2 were, respectively, less than 20 pg ml-1 and 70 +/- 15 pg ml-1. Intravenous injections of CVF induced dose-dependent, reversible elevations in the plasma levels of both prostanoids. The time courses for the increases of 6-oxo-PGF1 alpha and TXB2 paralleled the arterial hypotension and thrombocytopenia, suggesting the existence of a causal relationship between these parameters. The results further support our hypothesis that complement-dependent formation of arachidonic acid metabolites contributes to some of the haemodynamic and haematological changes occurring during endotoxin shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1979

The Schultz-Dale reaction of the guinea-pig ileum: influence by beta-adrenoceptor agonists and theophylline.

One of the organs that can be used to study the Schultz-Dale reaction, is the guinea-pig ileum. The reaction is characterized by a specific pattern: a quick contraction, followed by a quick relaxation and a second, more slow contraction. A description is given of this typical reaction. Selective inhibition of the slow contraction could be obtained using beta-adrenoceptor agonists. Also theophylline inhibited the slow contraction, but this inhibition was only selective within a narrow range of concentration. These findings encourage further investigation about a possible involvement of cyclic nucleotides in the liberation of the mediators involved in the Schultz-Dale reaction of the guinea-pig ileum. Furthermore they provide more information about this preparation which could be used as a screening model for anti-allergic drugs of distinct pharmacological groups.

Adrenergic beta-Agonists↗
PubMed1979

Involvement of SRS-A in the Schultz-Dale response of the guinea-pig small intestine.

1 The anaphylactic reaction of the guinea-pig ileum, the so called Schultz-Dale reaction, shows a biphasic response: a short rapid contraction followed by a partial relaxation and a slow contractile response. 2 Dose-response curves with ovalbumin as an antigen were obtained for the quick and slow contraction of this anaphylactic reaction. 3 Mepyramine (1 microgram/ml) blocked the rapid first contraction, but failed to abolish the slow one in about 50% of the animals studied. 4 The SRS-A antagonist, FPL 55712, significantly depressed the slow sustained contraction during the Schultz-Dale reaction. Disodiumcromoglycate was without effect on both phases when it was added 5 min before addition of the antigen. However, when added simultaneously with the antigen it produced a 30% suppression of the slow phase in the highest concentration used.

Anaphylaxis↗
PubMed1978

Prostaglandins restore the hyoscine-induced inhibition of the guinea-pig ileum.

Prostaglandins E1, E2 and F2alpha as well as arachidonic acid partially increase the hyoscine inhibited twitch and tetanic responses of the guinea-pig ileum to electrical stimulation. They also produce a shift to the left of the dose-effect curve for acetylcholine and histamine previously displaced to the right by the administration of hyoscine or mepyramine. These results indicate a postsynaptic sensitization effect of the prostaglandins rather than a presynaptic facilitatory activity.

Acetylcholine↗