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Giuseppe Agosta

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BC: Articoli scritti da M. Franzini

Marcatori di rimodellamento e fibrosi cardiaca
Markers of cardiac remodeling and fibrosis
<p>Cardiac remodeling is considered the determinant of the clinical progression of heart failure. It is defined as a genome expression resulting in molecular, cellular and interstitial changes, clinically manifested as changes in size, shape and function of the heart. Ventricular remodeling occurs progressively in untreated patients after large myocardial infarction and in those with longstanding cardiomyopathy. Myocyte hypertrophy, cellular apoptosis and increased interstitial collagen deposition are the anatomopathological alterations leading to increased myocardial fibrosis. Myocardial hypertrophy and fibrosis increase left ventricular volume and induce perturbation in the left ventricular chamber geometry, leading to cardiac dysfunction. As a result, the assessment of cardiac fibrosis holds important clinical value in patients with heart failure. Accordingly, there is an increasing interest in the development of new markers for cardiac fibrosis and a number of laboratory tests have been recently proposed. The aim of the present article is to discuss analytical performances and clinical relevance of these markers.</p>
Biochimica Clinica ; 41(1) 023-038
Rassegne - Reviews
 
Disfibrinogenemia indotta da una catena leggera libera kappa delle immunoglobuline
Ig-free light chains induced dysfibrinogenemia
<p>Despite several pathological conditions are associated with free&nbsp;light chains (FLC) deposition in human tissues, only few cases of human diseases caused by the specific binding&nbsp;activity of monoclonal FLC are described. A 65-year old male patient, with highly abnormal functional coagulation&nbsp;tests and undetectable functional fibrinogen was admitted to the Hematological Clinic of the University Hospital of&nbsp;Pisa. The same tests were within the reference intervals one year before. After excluding a number of causes for&nbsp;abnormal coagulation tests, we focused on potential causes of acquired dysfibrinogenemia. Due to the presence of&nbsp;abnormal values of FLC, we performed an immunofixation: while serum did not show any detectable monoclonal&nbsp;band, the immunofixation of a plasma sample revealed the presence of monoclonal FLC of kappa type co-migrating&nbsp;with fibrinogen. The serum kappa FLC concentrations were much lower than plasma levels, suggesting that the&nbsp;majority of these FLC were bound to fibrinogen, remaining associated to fibrin after clotting. Bone marrow biopsy&nbsp;showed 4% monoclonal plasma cells producing kappa light chains. The patient was diagnosed as affected by a FLC&nbsp;MGUS. After two courses of dexamethasone, the plasma concentration of kappa FLC decreased substantially and&nbsp;most of the coagulation tests normalized. The nature of the interaction between fibrinogen and kappa FLC is currently&nbsp;under investigation to elucidate the mechanism able to inhibit fibrinogen polymerization.</p>
Biochimica Clinica ; 39(5) e16-e18
Casi clinici - Case report
 
Stato dell’arte dell’immunodosaggio dei peptidi natriuretici di tipo B
State of the art of B-type natriuretic peptide (BNP) immunoassays
<p>Recent studies have demonstrated that the&nbsp;precursor of BNP (proBNP) constitutes the major part of BNP-related peptides detectable in plasma of patients with&nbsp;heart failure by the commercially available immunoassays considered specific for the BNP hormone. Since proBNP&nbsp;significantly cross-reacts with commercial immunoassays for BNP, manufacturers should test and clearly declare the&nbsp;cross-reaction with proBNP in their BNP methods. Owing to the differences in cross-reaction with proBNP as well as&nbsp;in specificity, respectively, for the NH2- or COOH-terminal part of the peptide hormone chain, BNP immunoassays show&nbsp;significant between-method differences. Immunoassays for NT-proBNP, which all use standard materials and&nbsp;antibodies provided by the same company, show lower differences (generally minore del 20%). Clinicians should take into&nbsp;account these differences among methods when they compare results obtained from different laboratories, which use&nbsp;different BNP immunoassays. Accordingly, the use of a common decisional limit for all BNP immunoassay methods,&nbsp;as suggested by the most recent international guidelines, may be unreliable.</p>
Biochimica Clinica ; 39(5) 312-325
Rassegne - Reviews
 
Rilevanza clinica e interpretazione dei marcatori biochimici nello scompenso cardiaco
Clinical relevance and interpretation of biochemical markers in heart failure
<p>Heart failure (HF) is a global&nbsp;problem with an estimated prevalence of 38 million patients worldwide. Both prevalence and incidence of HF increase&nbsp;progressively with population ageing (prevalence &ge;10% in people &gt;75 years), especially in the high-income countries.&nbsp;HF is considered as the fatal event of all cardiovascular disorders. Despite some progress in diagnosis and treatment,&nbsp;its prognosis is worse than that of most cancers. The disease is heterogeneous in its clinical presentation and the&nbsp;diagnosis is not based on a single test, but on a combination of the history, physical examination and appropriate&nbsp;investigations, including some laboratory tests. As a consequence, the accuracy of diagnosis by clinical signs alone&nbsp;is often inadequate, especially in the early asymptomatic stage of HF. For these reasons, there is an increasing&nbsp;interest in the development of new biomarkers useful for the diagnosis, prognosis and follow-up of patients with HF.&nbsp;The aim of this paper is to provide an overview of biomarkers recommended by international guidelines for HF,&nbsp;discussing their clinical impact and the interpretation of results. Furthermore, a possible strategy for the development&nbsp;and evaluation of novel prognostic biomarkers for HF will be suggested.</p>
Biochimica Clinica ; 39(4) 241-255
Rassegne - Reviews
 
Forme molecolari della y-glutammiltransferasi: caratteristiche e biogenesi
y-Glutamyltransferase (GGT) fractions: characteristics and biogenesis.
<p>Four GGT fractions (b-, m-, s- and f- GGT) have been described in plasma. The aim of this study was to characterize their molecular nature in human plasma and bile. Plasma was obtained from healthy volunteers and primary bile was collected from patients undergoing liver transplant. For each GGT fraction we determined MW, density, sedimentation conditions in centrifugation assays, and the sensitivity to detergent [deoxycholic acid (DOC)] and protease (papain). A partial purification of b-GGT for immunogold analysis was obtained by ultracentrifugation. Plasma b-GGT showed a MW of 2000 kDa and a density between 1.063-1.210 g/mL. Treatment with 1% DOC converted b-GGT into s-GGT fraction, while b-GGT was not sensible to papain treatment. Plasma m-GGT and s-GGT showed a MW of 1000 and 200 kDa, and their densities were between 1.006-1.063 g/mL and 1.063-1.210 g/mL, respectively. Both fractions were unaffected by DOC treatment, while GGT activity was completely recovered in f-GGT peak after their incubation with papain. Plasma f-GGT showed a MW of 70 kDa and a density &gt;1.21 g/mL. In human hepatic bile we identified two peaks showing the same characteristics of plasma b- and f-GGT fractions. Collected data showed that b-GGT is constituted by membrane microvesicles both in bile and plasma, as confirmed by immunogold; m-GGT and s-GGT might be constituted by bile-acid micelles, while f-GGT represents the free-soluble form of the enzyme. The&#160; understanding of the nature and properties of plasma GGT fractions may allow a better clinical utilization of GGT as a clinical biomarker.&#65279;</p>
Biochimica Clinica ; 36(2) 112-120
Contributi Scientifici - Scientific Papers