G. De Gaetano

HÆMOLYTIC-URÆMIC SYNDROME: DEFICIENCY OF PLASMA FACTOR(S) REGULATING PROSTACYCLIN ACTIVITY?

It is suggested that patients with the haemolytic-uraemic syndrome and related disorders (such as thrombotic thrombocytopenic purpura) lack a plasma factor which stimulates prostacyclin (P.G.I2) activity. Normal plasma would supply the missing factor and is a rational treatment for some life-threatening symptoms (thrombocytopenia, haemolytic anaemia, hypertension) of this syndrome.

PROSTACYCLIN-LIKE ACTIVITY AND BLEEDING IN RENAL FAILURE

Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature. The specimens from all three uraemic patients showed more prostacyclin-like activity than those from the controls. After repeated washings, when this activity could hardly be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissue from the three uraemic patients. These findings may be relevant to the pathogenesis of bleeding in renal failure.

PARATHYROID HORMONE INHIBITS HUMAN PLATELET FUNCTION

Abstract Several inhibitors of platelet function have been found in blood from uraemic patients. It has been suggested that parathyroid hormone (PTH) is a major uraemic toxin underlying many manifestations of the uraemic syndrome. Two different preparations of PTH strongly inhibited human platelet aggregation and secretion induced in vitro by different stimuli. The data suggest one possible pathway for the participation of excess PTH in the pathogenesis of the platelet dysfunction and bleeding tendency in uraemia.

Bleeding time in laboratory animals. I. Aspirin does not prolong bleeding time in rats

Abstract A ‘template’, semiauthomatic device, recently developed for measuring bleeding time in man, has been reliably applied to evaluate the bleeding time in rats. This technique allows repeated measurements on the same animal. Following oral or intraperitoneal administration of acetylsalicylic acid (at various dosages), no significant variations of bleeding time were observed, although collagen-and Thrombofax - induced platelet aggregation, measured ex vivo in the aggregometer, was strongly inhibited. These results suggest that platelets might not play a fundamental role in the primary haemostasis of rat, as challenged by the bleeding time technique used in this study.

Growth and metastasis of the Lewis lung carcinoma in mice defibrinated with batroxobin

Abstract Lewis lung carcinoma ( 3 LL) cells were implanted intramuscularly into C 57 B 16 J mice, rendered hypofibrinogenemic by daily intraperitoneal treatment with batroxobin ( 17.5 NIH u/kg body wt, twice per day). When this treatment was continued till spontaneous death of the animals, an increase in both metastasis number and weight was observed, but the primary tumor growth was unchanged. In contrast, both metastasis number and weight tended to decrease when defibrination was started from day 11 after tumor implantation, independently from surgical removal of the primary tumor. These data suggest that fibrinogen and/or its derivatives could play a different role in the various stages of the growth and dissemination of the same experimental tumor.

Characterization of human fibroblasts from cancer patients: loss of fibrin clot retractile activity after 'in vitro' spontaneous transformation,.

Abstract Human fibroblast-like cells cultured from skin and stromal tissue of lung carcinomas, are able to induce fibrin clot retraction similarly to fibroblasts from the skin of normal individuals. Following in vitro spontaneous transformation, these cells loose their retractile property; fibrin clot retraction could be a rather specific parameter to identify fibroblastic cells and to monitor their in vitro oncogenic transformation.

Comparison of radioimmunoassay and high-resolution gas chromatography mass spectrometry for the quantitative determination of serum thromboxane B2 and 6-keto-PGF1α after pharmacological blockade of thromboxane synthetase

Radioimmunoassay (RIA) and high-resolution gas chromatography-mass spectrometry (HRGC-MS) were compared for the determination of serum 6-keto-PGF-1 alpha and TXB2 in a situation of drug-altered arachidonate metabolism. Results were comparable for TXB2 in both conditions. 6-keto-PGF1 alpha RIA determinations (with two different antisera) revealed increased levels in dazoxiben-treated samples, which were not confirmed by HRGC-MS. The assay were repeatedly checked in controlled conditions to investigate these discrepancies. Interference was found with both antisera, due to the drug-induced change in metabolism.

Prostaglandins, Thromboxanes and Platelet Function

During the 1960s it was observed that certain long-chain saturated or unsaturated fatty acids induced aggregation of washed human platelets, but the physiological significance of this phenomenon was questioned [44].

A pharmacokinetic and platelet function study of the combined administration of metoprolol and sulfinpyrazone to healthy volunteers

In a double-blind study on healthy subjects who underwent three 3-week periods of treatment with metoprolol (M) + sulfinpyrazone (S), M + placebo, and S + placebo, pharmacokinetics and plasma levels of M were not affected by concurrent administration of S. Analysis of variance change-over demonstrated a significant difference between treatments only for serum uric acid levels. Analysis of post-treatment and baseline data within each treatment showed: decreased platelet count by M, lowered serum 6-keto PGF1 alpha by all three treatments, decreased serum TXB2 generation and arachidonic acid-induced platelet aggregation by S + M. No negative interaction between S + M was found.

Iloprost and Thrombosis Prevention

It appears from this meeting that Iloprost, originally developed as an antiplatelet agent, mainly acts on mechanisms largely unrelated to platelet function. A so- called, still poorly characterized, cytoprotection seems to be the main mechanism by which Iloprost prevents thromboembolic complications in several diseases.