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Biomedical subjects

M Udvardy

Publications and source records attributed to M Udvardy.

At least 55 records · Page 3Linked to original sources

[Anti-adhesive and anti-thrombotic effects of integrin-inhibiting tripeptides (Arg-Gly-Asp)].

The RGD (Arg-Gly-Asp) motif has a widespread distribution in the cellular adhesive structures on platelets, lymphocytes, some viruses and matrix proteins. RGD sequence seems to confer adhesive properties to macromolecular proteins like fibronectin, vitronectin, von Willebrand factor, fibrinogen and many others. So RGD tripeptide and its analogues really deserve to be regarded as general disintegrin sequence. A concise review is given to analyze the most important achievements by using RGD peptides as antiplatelet agents along with an overview of the potential clinical application of the disintegrin peptides in other fields of medicine.

Cell Adhesion Molecules↗

Altered lysis resistance of platelet-rich clots in patients with insulin-dependent diabetes mellitus.

The fibrinolytic resistance of platelet-rich arterial thrombi received much attention. Clot lysis method was used to assess the in vitro fibrinolytic properties in diabetes mellitus. Platelet rich (PRP) clots were formed by addition of thrombin, and lysis was induced by tissue-plasminogen-activator. The coagulation and lysis was followed by the light scattering properties. A special pattern of good initial lysis followed by a second clotting phase was observed in more than half of insulin dependent diabetic patients, while a similar pattern of clot-lysis was only occasionally found in non-insulin dependent diabetes mellitus or in the healthy control group. Following the thrombin activation of washed, gel-filtered platelets, the supernatants possessed an inhibitory action on in vitro lysis of PPP-clots. This suppression was remarkably stronger in IDDM, along with the highest PAI-1 activity concentration ratio of the platelet lysates, compared to plasmatic levels. The relation of this special type of PRP clot-lysis resistance to diabetic vascular complications needs further clarifying and investigations.

Adult↗

Hybrid peptide containing RGDF (Arg-Gly-Asp-Phe) coupled with the carboxy terminal part of alpha 2-antiplasmin capable of inhibiting platelet aggregation and promoting fibrinolysis.

The aim of this study was to synthesize and investigate hybrid peptides which contain the RGD (Arg-Gly-Asp) sequence coupled with lysine residues in special arrangements (antiplasmin carboxyterminal peptide) in an effort to simultaneously inhibit platelet aggregation and promote fibrinolysis. The in vitro haemostatic modifying properties of the synthesized peptides were tested by ADP-induced platelet aggregation, plasmin-generation tests and fibrin-clot lysis assays. The hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxyterminal part of antiplasmin (AP26) inhibited platelet activation and increased plasmin generation and in vitro fibrin-clot lysis.

Amino Acid Sequence↗

RGDFAP: platelet aggregation inhibitory and profibrinolytic hybrid peptide (RGDF coupled with the carboxy terminal part of alpha 2-antiplasmin) enhances plasminogen binding to platelets.

As published in a recent issue of Blood Coagulation and Fibrinolysis, the hybrid peptide RGDFAP, composed of RGDF (Arg-Gly-Asp-Phe) coupled to a synthetic peptide residue of the carboxy terminal part of antiplasmin (AP26) inhibited platelet activation and augmented plasmin generation and in vitro fibrin clot lysis. This peptide contains an RGD motif which provides linkage to platelet GP IIb-IIIa. The antiplasmin part of the molecule may attach free plasminogen, which in turn increases the amount of platelet surface bound plasminogen, probably yielding enhanced lytic action at the site of thrombus formation. This hypothesis was investigated and confirmed by the results of platelet-plasminogen binding assays, using FITC-labelled antiplasmin antibodies and radioligand binding analysis. Increased platelet-linked plasminogen was detected by a chromogenic method, along with the acceleration of in vitro lysis of platelet-rich clots in the presence of RGDFAP peptide.

Amino Acid Sequence↗

[Fibrinolysis in chronic liver diseases studied by in vitro blood coagulation tests].

A simple and easily reproducible in vitro clot lysis test less frequently indicated increased rate of fibrinolysis in chronic hepatic disease than expected. In hepatic cirrhosis clot lysis slows down as the condition deteriorates or as the plasma concentration of von Willebrand factor increases, thus the test may have certain prognostic value. The present observations suggest that the occasional acceleration of fibrinolysis in cirrhosis may be related to either increased production or decreased clearance of tPA, and is not due to impaired fibrinolysis inhibitor system.

Adult↗

[Diabetes mellitus and fibrinolysis (experience with an in vitro clot lysis test)].

After a concise review on fibrinolysis in diabetes mellitus, special attention is given to the observations suggesting impaired fibrinolysis in non-insulin dependent diabetes mellitus and in hyperinsulinaemia. This fibrinolytic defect, based mainly upon indirect data, may contribute to the development of macroangiopathy. The results discussed here, gained by a simple in vitro clot lysis assay revealed decreased fibrinolytic properties in some of the non-insulin dependent diabetic patients, however the mean value did not differ significantly from the control. The potential profibrinolytic effect of different antidiabetic treatment profibrinolytic effect of different antidiabetic treatment modalities also received attention. The clinical significance of the apparent alteration of fibrinolysis in diabetes mellitus should be evaluated appropriately as a part of a complex disturbance of haemostatic balance in diabetes mellitus. Further studies and improved fibrinolytic methods seems to be required to ascertain a causal relationship between altered fibrinolysis and diabetic vascular complications.

Adult↗

[Correlation between thrombocytes and fibrinolysis].

After a concise review of the fibrinolysis modifying effect of platelets, a simple, reliable and reproducible in vitro microplate clot-lysis method is described which is able to demonstrate the lytic resistance of platelet rich clots. The same method proved to be suitable to show the enhanced lysis in platelet rich lytic environment, caused probably by plasminogen attached to platelet surface. The results discussed here suggest that these effects need the presence of intact platelets.

Adult↗

[Correlation between adhesive factors of primary hemostasis and liver fibrogenesis in alcoholic live cirrhosis].

Colchicine administration is able to reduce collagen production and the fibrogenetic process in alcoholic liver diseases in the same time. The decrease of the serum lipid peroxidation capacity along with type III procollagen propeptide level was associated with the simultaneous reduction of plasmatic von Willebrand factor, fibronectin and beta-thromboglobulin levels. This observation suggest a connection between the regulation of primary haemostasis and liver fibrogenesis.

Colchicine↗

Cyclic relapses of thrombotic thrombocytopenic purpura.

A 24-year-old male patient was first observed with full-blown acute thrombotic thrombocytopenic purpura in 1991. Complete remission was achieved with plasma and plasmapheresis therapy, but in spite of continuous corticosteroid and aspirin administration, thrombocytopenic (megakaryocytic) relapses were observed every 26-30 days. Splenectomy and danazol failed to prevent the recurrence of the disease. Surprisingly, cyclosporin A (5 mg/kg/day) administration resulted in a complete transitional remission, but after dose reduction a less regular pattern of repeated milder recurrences was observed. Cryopreserved plasma, obtained from the patient during remission also proved to be effective in treating the last two thrombocytopenic episodes.

Adult↗

Endothelium releases more von Willebrand factor and tissue-type plasminogen activator upon venous occlusion in patients with liver cirrhosis than in normals.

Venous occlusion was used in 8 patients with liver cirrhosis and in 10 normals to investigate the pathomechanism of long-term elevation of plasma von Willebrand factor antigen (vWFAg) in liver cirrhosis. The following parameters were determined at baseline, and immediately, 60 min and 24 h after 10 min venous occlusion: vWFAg, ristocetin cofactor (RiCoF), in vitro platelet retention (Adeplat T), and tissue-type plasminogen activator (t-PA). Every baseline value in the liver cirrhosis group was significantly higher than in the controls. In both groups the 10-min values were significantly higher than their corresponding baseline results. Hence, comparing the two groups, in liver cirrhosis a significantly higher release of vWFAg and t-PA could be observed. These findings suggest on the one hand that the increased release contributes substantially to the sustained elevation of plasma vWF level in liver cirrhosis. On the other hand, the results indicate that not only the vascular surface of the diseased liver but most probably the total endothelium plays an important role in this phenomenon.

Adult↗

[Primary hemostasis studies in Conn syndrome].

The various components of haemostasis seems to be affected by the high cortisol level in Cushing's disease. Increase in coagulation factor levels, decreased fibrinolysis, high von Willebrand factor plasmatic levels along with easy bruising due to vascular damage have been described. In this report a similar but less accentuated elevation of von Willebrand factor levels are documented in aldosterone producing adrenocortical adenoma, and in the same time enhanced platelet activation was also found. The primary haemostatic alterations correlated well with aldosterone levels and subsided significantly after the removal of the ademonas. Further studies seem to be desirable to analyse and elucidate haemostatic functions in Conn's syndrome.

Adult↗

Presence and possible origin of epsilon(gamma-glutamyl)lysine isodipeptide in human plasma.

epsilon(gamma-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 mumol/l. Incubation of in vitro clotted plasma at 37 degrees C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.

Blood Coagulation Disorders↗