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1.
J Thromb Haemost ; 15(9): 1834-1844, 2017 09.
Article in English | MEDLINE | ID: mdl-28632940

ABSTRACT

Essentials Elevated lipoproteinp(a) is an independent and causal risk factor for atherothrombotic diseases. rs3798220 (Ile/Met substitution in apo(a) protease-like domain) is associated with disease risk. Recombinant I4399M apo(a) altered clot structure to accelerate coagulation/delay fibrinolysis. Evidence was found for increased solvent exposure and oxidation of Met residue. SUMMARY: Background Lipoprotein(a) (Lp[a]) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo[a]), the distinguishing component of Lp(a), is homologous with plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence for atherothrombotic diseases. A single-nucleotide polymorphism (SNP) (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile→Met substitution in the protease-like domain (I4399M variant). In population studies, the I4399M variant has been correlated with elevated plasma Lp(a) levels and higher coronary heart disease risk, and carriers of the SNP had increased cardiovascular benefit from aspirin therapy. In vitro studies suggested an antifibrinolytic role for Lp(a) containing this variant. Objectives We performed a series of experiments to assess the effect of the Ile→Met substitution on fibrin clot formation and lysis, and on the architecture of the clots. Results We found that the Met variant decreased coagulation time and increased fibrin clot lysis time as compared with wild-type apo(a). Furthermore, we observed that the presence of the Met variant significantly increased fibrin fiber width in plasma clots formed ex vivo, while having no effect on fiber density. Mass spectrometry analysis of a recombinant apo(a) species containing the Met variant revealed sulfoxide modification of the Met residue. Conclusions Our data suggest that the I4399M variant differs structurally from wild-type apo(a), which may underlie key differences related to its effects on fibrin clot architecture and fibrinolysis.


Subject(s)
Apoprotein(a)/blood , Apoprotein(a)/genetics , Blood Coagulation/genetics , Fibrinolysis/genetics , Lipoprotein(a)/blood , Lipoprotein(a)/genetics , Polymorphism, Single Nucleotide , Thrombosis/blood , Thrombosis/genetics , Adult , Apoprotein(a)/chemistry , Female , Fibrin/chemistry , Fibrin/metabolism , Genetic Predisposition to Disease , HEK293 Cells , Homozygote , Humans , Lipoprotein(a)/chemistry , Male , Methionine , Middle Aged , Molecular Dynamics Simulation , Oxidation-Reduction , Phenotype , Protein Conformation , Recombinant Proteins/blood , Structure-Activity Relationship , Transfection
2.
Transplant Proc ; 46(7): 2203-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25242751

ABSTRACT

BACKGROUND: Fluid effusion (blood, lymph, or urine) in kidney transplantation may give rise to several complications, directly, such as hematoma, seroma, lymphocele, and/or urinoma, or consequently, such as increased infection risk, longer hospital stay, graft compression--with or without functional impairment--and necessity of further hospitalizations. The aim of this study was to evaluate effectiveness of hemostatic biomaterials in prevention of fluid effusions, especially lymphocele in kidney transplant patients. METHODS: We selected 40 patients who underwent kidney transplantation from 2009 to 2012 in which we used hemostatic biomaterials, and compared their results with those of other transplant patients from our center in which we did not used these biomaterials. Evaluated parameters were: fluid effusion, graft function, quality and quantity of drainage, blood count, and operative time. RESULTS: There was no difference in operative time. The incidence of complications on which biomaterials can have a role decreased; particularly, we observed a reduction from 24.21% to 7.5% of fluid effusions (lymphocele). There was no evidence of complications due to biomaterials. CONCLUSIONS: Hemostasis is important in surgery, and in kidney transplantations lymphostasis also has a significant role. In addition to the traditional hemostatic methods, recently some biomaterials, with the purpose of providing atraumatic hemostasis, were added. In our experience they are easy to use, and their use has proved to be effective for both hemostasis and lymphostasis with consequent reduction of fluid effusions.


Subject(s)
Kidney Transplantation , Lymphocele/prevention & control , Postoperative Complications/prevention & control , Adult , Aged , Cyanoacrylates/therapeutic use , Drainage , Drug Combinations , Female , Fibrinogen/therapeutic use , Hemorrhage/prevention & control , Hemostatics , Humans , Male , Middle Aged , Operative Time , Starch/therapeutic use , Thrombin/therapeutic use
3.
Updates Surg ; 62(3-4): 207-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21069587

ABSTRACT

Lipoma is a benign tumour composed of well-differentiated adipocytes and is the most common soft tissue mass. We present a case of an intraluminal lipoma of the iliofemoral axis presenting as lower limb venous obstruction. In our case, definite diagnosis is impossible as there is aspecific symptomatology and radiologic imaging methods are not able to provide diriment data, considering rarity of the disease. Therefore, we could make correct diagnosis only intraoperatively. We preferred a direct reconstruction of the wall of vein. At 12-month follow-up, we have had complete disappearance of symptoms and functional diseases.


Subject(s)
Femoral Vein , Lipoma , Humans , Lipoma/surgery
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