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Biomedical subjects

M B Donati

Publications and source records attributed to M B Donati.

At least 19 recordsLinked to original sources
PubMed1992

Modulation of fibrinolytic response to venous occlusion in humans by a combination of low-dose aspirin and n-3 polyunsaturated fatty acids.

Aspirin at high but not at low doses reduces the fibrinolytic response to venous occlusion. Inhibition of vascular prostacyclin synthesis could be involved in this effect. Fish oil supplementation may redirect prostanoid metabolism toward an overall "antithrombotic" condition but with controversial effects on prostacyclin formation. In this study we investigated the effect of low-dose aspirin together with n-3 polyunsaturated fatty acid (PUFA) supplementation on the fibrinolytic response to venous occlusion. Following a double-blind, randomized, crossover design, six healthy volunteers (three men and three women, 24-37 years old) were given for 29 days 5.3 g eicosapentaenoic and docosahexaenoic acids or a corresponding dose of n-6 PUFAs as control; aspirin (40 mg/day) was then added for an additional 14 days. A 2-month washout period was allowed before the crossover. Blood was collected before and after venous stasis on days 0, 29, and 43 of each test period. A combination of aspirin with n-3 PUFAs reduced the fibrinolytic response to venous occlusion in all subjects, the mean value of fibrinolytic activity after stasis being 240 +/- 40 mm2, a value significantly lower than at baseline (366 +/- 51 mm2, mean +/- SEM, p < 0.05). Similarly, the tissue-type plasminogen activator (t-PA) antigen level was lower in the aspirin + PUFA-treated group. Plasminogen activator inhibitor activity before stasis was enhanced by n-3 PUFA supplementation (from 7.5 +/- 2 to 14.8 +/- 3 IU/ml, p < 0.05), an effect not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Action of brinase on human fibrinogen and plasminogen.

Brinase added to human plasma in vitro caused a decrease in fibrinogen concentration, positive paracoagulation tests and formation of a friable clot in sequence. Agarose gel filtration of these samples revealed the presence of fibrinogen derivatives both larger and smaller than the parent molecule. Infusion of the enzyme in vivo resulted in a decreased fibrinogen level, a prolonged thrombin time and an increase in fibrinogen related antigen (FRA) in serum. The elution pattern of FRA in the plasma samples obtained after infusion of Brinase was similar to that of the in vitro samples. The plasma pool of fibrinogen was partially consumed by infusion of Brinase, but the turnover of plasminogen remained unaffected. Purified plasminogen was partially degraded by addition of the enzyme but this was accompanied by a generation of proteolytic activity. These findings confirm that Brinase induces a proteolytic degradation of fibrinogen in plasma without activation of the plasminogen-plasmin system. Exposure of polymerization site(s) in the fibrinogen molecule is probably responsible for the reported clot promoting effect of the enzyme.

Antigens↗
PubMed1979

Early increase of a new platelet coagulant activity in rats fed a thrombogenic diet.

A recently described platelet coagulant activity (factor X activating activity), whose pathophysiological significance is as yet unknown, was studied in rats fed a fat-rich (thrombogenic) diet for 1, 2 and 7 weeks and compared to rats fed normal laboratory chow. Whatever the duration of the special feeding period, a highly significant shortening of the clotting time, used for measuring this activity, was observed. When the platelet coagulant activity of individual "fat-fed"rats was quantitated by reference to that of individual control animals, we found a mean increase of 350% (n = 9) after one week and 267% (n = 3) after two weeks of dietary treatment. Partial thromboplastin time, thrombin time and soluble fibrin monomer complexes did not differ in control and treated animals. It seems that platelet coagulant activity, as measured in our test system, is one of the first laboratory parameters to be modified by fat-rich diets. These findings may be relevant to an understanding of the role of platelet coagulant activities other than platelet factor 3 in thrombotic phenomena.

Animals↗
PubMed1979

Prostacyclin and human foetal circulation.

Tissues from human umbilical cord arteries and placental veins generated much greater prostacyclin activity than vessels from normal adults. High prostacyclin generation could contribute to maintaining the low peripheral vascular resistance typical of foetal circulation in which blood pressure is low despite very high cardiac output.

Adolescent↗
PubMed1979

Evidence that cells from experimental tumours can activate coagulation factor X.

The procoagulant activity of cells from some experimental tumours isolated in culture or in single-cell suspensions from ascitic fluid was investigated. Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, Factor VIII- and Factor VII-deficient but not of Factor X-deficient human plasma. The same cells generated thrombin when mixed with a source of prothrombin and Factor X, absorbed bovine serum (as a source of Factor V), phospholipid and calcium chloride. Thrombin formation was not influenced by the presence of Factor VII. Cells from Sarcoma 180 ascites were completely inactive in both test systems. It is concluded that cells from some experimental tumours have the capacity to activate Coagulation Factor X directly. These findings suggest the existence of an alternative "cellular" pathway in the initiation of blood clotting distinct from both the intrinsic and extrinsic mechanisms.

Animals↗
PubMed1979

Vascular prostacyclin and plasminogen activator activity in experimental and clinical conditions of disturbed haemostasis or thrombosis.

In several experimental and clinical conditions associated with thrombotic tendency, or complicated by thrombotic episodes, either prostacyclin (which inhibits platelet aggregation) or plasminogen activator (which promotes fibrinolysis), or both, appear to be decreased in the vessel wall. In other conditions, however, either activity may not change or even be increased. Possibly, vascular damage is followed by an early stimulation of both activities (a defence mechanism?) which may be subsequently reduced or exhausted. While the role of vascular plasminogen activator in haemorrhagic conditions is apparently unknown, prostacyclin activity appears to be markedly enhanced both in experimental animals and in patients with uraemia and bleeding complications. There is a suggestive evidence that uraemic plasma powerfully stimulates vascular prostacyclin generation.

Arteriosclerosis↗
PubMed1979

Bleeding in renal failure: a possible role of vascular prostacyclin (PGI2).

Specimens of venous tissues from a group of 25 patients with chronic uremia and 7 patients with acute renal failure generated significantly higher PGI2-like (platelet aggregation inhibiting) activity than venous tissues from 30 normal subjects. After repeated washings, when this activity could barely be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissues from uremic patients. Both prolonged bleeding times and increased PGI2-like activity returned to normal in 4 acute uremic patients on restoration of their renal function. These findings may be relevant to the pathogenesis of bleeding in renal failure.

Acute Kidney Injury↗
PubMed1978

Haemolytic-uraemic 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.

Anemia, Hemolytic↗