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Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1-16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1-16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1-16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1-16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1-16. Thus our study demonstrates that Peptide 1-16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation. [ABSTRACT FROM AUTHOR]

Bacterial porins enhance the thrombin activity upon chromogen substrate chromozym. Should porin-dependent enhancement of thrombin activity take place also upon fibrinogen in vivo, this might greatly increase the fibrin production which, in turn, might lead to blood vessel obstruction. In this study, we demonstrate fibrin hyperproduction in a simplified coagulative system, consisting of fibrinogen and thrombin-pure molecules, in the presence of bacterial porins. In particular, bacterial porins, in the presence of thrombin, significantly increased the fibrin production compared with thrombin alone. Also, fibrin hyperproduction took place even in the presence of the thrombin inhibitors antithrombin III (AT III) or α2 macroglobulin (α2M). However, the thrombin–fibrinogen reaction in the presence of AT III or α2M did not generate fibrin, unless porins were present. In conclusion, porins not only enhance thrombin activity but also inhibit the antithrombin activity exerted by AT III or α2M. We hypothesize that, because of porins activity, fibrin is largely generated due to thrombin hyperactivation. Moreover, further fibrin is produced by thrombin, which is not blocked by two serpins for the presence of porins. These results might be relevant as to the occurrence of disseminated intravascular coagulation in sepsis by gram-negative bacteria, which are known to produce porins. [ABSTRACT FROM AUTHOR]

It is known that low-dose aspirin is effective in coronary artery therapy, although it has not yet been clarified how it exerts its action. Here, we report that treatment of coronary artery patients with 100 mg/day of aspirin does not attenuate thrombin generation, but reduces free thrombin by favouring the formation of thrombin/antithrombin (TAT) complexes. Antithrombin hyperactivation is mediated by inhibition of platelet factor 4 release from α-granules, leading to higher heparin availability. [Copyright &y& Elsevier]

We set constraints on the trilinear Higgs boson self-coupling, λ 3 , by combining the information coming from the W mass and leptonic effective Weinberg angle, electroweak precision observables, with the single Higgs boson analyses targeting the γ γ , Z Z ⁎ , W W ⁎ , τ + τ − and b ¯ b decay channels and the double Higgs boson analyses in the b b ¯ b b ¯ , b b ¯ τ + τ − and b b ¯ γ γ decay channels, performed by the ATLAS collaboration. With the assumption that the new physics affects only the Higgs potential, values outside the interval − 1.8 λ 3 SM < λ 3 < 9.2 λ 3 SM are excluded at 95% confidence level. With respect to similar analyses that do not include the information coming from the electroweak precision observables our analysis shows a stronger constraint on both positive and negative values of λ 3. [ABSTRACT FROM AUTHOR]

Presents a case of proximal deep venous thrombosis occurring following suspension of clopidogrel administration in a patient without inherited and acquired thrombophilia. Association of right lower limb pain with lower limb edema; Assessment of the gene polymorphism of clotting factors II and V; Increase in thrombin generation due to the loss of thrombin inhibition.

SV-IV is a basic, thermostable, secretory protein of low Mr (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen transcriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study of its structure–function relationships and aimed to identify in its polypeptide chain specific peptide fragments possessing the marked anti-inflammatory properties of the protein not associated with other biological activities (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein into peptide derivatives by chemical methods and the organic synthesis on solid phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structural integrity of the whole molecule; (b) the anti-inflammatory activity is located in the N-terminal region of the molecule, the 8–16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivatives do not seem to possess pro-coagulant activity, even though this particular function has been located in the 1–70 segment of the molecule. [ABSTRACT FROM AUTHOR]