Publications (10)57.71 Total impact
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Article: Platelet production and destruction in liver cirrhosis.
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ABSTRACT: Thrombocytopenia is common in liver cirrhosis (LC) but the mechanisms are not fully understood. The purpose of our work was to evaluate platelet kinetics in LC with different etiologies by examining platelet production and destruction. Ninety-one consecutive LC patients (36 HCV, 49 alcoholics, 15 HBV) were enrolled. As controls, 25 subjects with idiopathic thrombocytopenic purpura, 10 subjects with aplastic anemia, and 40 healthy blood donors were studied. Plasma thrombopoietin (TPO) was measured by ELISA. Reticulated platelets (RP) were determined using the Thiazole Orange method. Plasma glycocalicin (GC) was measured using monoclonal antibodies. Platelet associated and serum antiplatelet antibodies were detected by flow cytometry. B-cell monoclonality in PBMC was assessed by immunoglobulin fingerprinting. Serum TPO was significantly lower in LC (29.9±18.1 pg/ml) compared to controls (82.3±47.6 pg/ml). The GC levels were higher in LC (any etiology) than in healthy cases. Conversely, the absolute levels of RP were lower in LC (any etiology) than in healthy controls. The platelet-associated and serum anti-platelet antibodies were higher in HCV+ LC compared to healthy subjects (p<0.0064), alcoholic LC (p<0.018), and HBV+ LC (p<0.0001). B-cell monoclonality was found in 27% of the HCV+LC, while it was not found in HBV+ or alcoholic LC. Patients with LC present decreased plasma TPO, accelerated platelet turnover, and reduced platelet production. This indicates that LC thrombocytopenia is a multifactorial condition involving both increased platelet clearance and impaired thrombopoiesis.Journal of Hepatology 12/2010; 54(5):894-900. · 9.26 Impact Factor -
Article: Whey protein ingestion enhances postprandial anabolism during short-term bed rest in young men.
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ABSTRACT: We tested the relative ability of rapidly digested whey and slowly digested casein to stimulate net whole-body protein synthesis during prolonged physical inactivity. We studied 8 young male volunteers after they consumed isonitrogenous casein or whey mixed meals on d 12 or d 14 of experimental bed rest. Rates of phenylalanine hydroxylation were measured by primed-constant oral administration of L[2-(2)H(2)]tyrosine and L[ring-(2)H(5)]phenylalanine for 3 h in the postabsorptive state and 6 h after an isonitrogenous bolus meal containing sucrose (0.27 g/kg) and casein or whey (0.40 g/kg). Net protein synthesis in the fed state was calculated during the first 6 h postmeal as the difference between phenylalanine hydroxylation and phenylalanine content in the ingested casein or whey. In the fed state, the integrated changes in phenylalanine hydroxylation were lower (P < 0.05) after whey (-2 +/- 8 micromol x kg(-1) x 6 h(-1)) than after casein ingestion (34 +/- 7 micromol x kg(-1) x 6 h(-1)). During bed rest, net postprandial protein synthesis was greater (P < 0.05) after whey (96 +/- 8 micromol phenylalanine x kg(-1) x 6 h(-1)) than after casein ingestion (82 +/- 7 micromol phenylalanine x kg(-1) x 6 h(-1)). The rapidly digested whey protein was more efficient than the slowly digested casein in increasing postprandial net protein synthesis during short-term bed rest.Journal of Nutrition 11/2008; 138(11):2212-6. · 3.92 Impact Factor -
Article: Etiologic treatment of hepatitis C virus-associated mixed cryoglobulinemia.
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ABSTRACT: The treatment of mixed cryoglobulinemia (MC) includes several drugs--steroids, cyclosporins, colchicine, plasmapheresis--but given the documented association between MC and hepatitis C virus (HCV), the treatment of choice seems to be antiviral therapy. Several authors have reported the efficacy of interferon (IFN) alpha in the inhibition of HCV replication and reduction of cryoglobulin levels. The therapy with IFN as monotherapy in MC shows a complete response rate in only 10 -12% of cases. Complete response to therapy using a combination of IFN plus ribavirin varies in different studies from 18% to 64% of cases. There are only two studies on the treatment of MC with peginterferon plus ribavirin. Both studies, given the high number of complete responders, reinforce the idea that peginterferon plus ribavirin is, at present, the best available treatment for cryoglobulinemic syndrome. The results obtained with peginterferon combined therapy are superior to standard interferon plus ribavirin in treatment-naive patients. In fact, a sustained virological response was observed in 44% of patients; the same results were obtained for clinical (purpura and arthralgia disappearance) and biochemical (aminotransaminases normalization) responses. New drug combinations, like peginterferons plus anti-CD20 antibodies, should be considered for treatment of MC in the future.Digestive and Liver Disease 10/2007; 39 Suppl 1:S102-6. · 3.05 Impact Factor -
Article: Activation of naïve B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders.
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ABSTRACT: Infection with hepatitis C virus (HCV), a leading cause of chronic liver diseases, can associate with B lymphocyte proliferative disorders, such as mixed cryoglobulinemia and non-Hodgkin lymphoma. The major envelope protein of HCV (HCV-E2) binds, with high affinity CD81, a tetraspanin expressed on several cell types. Here, we show that engagement of CD81 on human B cells by a combination of HCV-E2 and an anti-CD81 mAb triggers the JNK pathway and leads to the preferential proliferation of the naïve (CD27-) B cell subset. In parallel, we have found that B lymphocytes from the great majority of chronic hepatitis C patients are activated and that naïve cells display a higher level of activation markers than memory (CD27+) B lymphocytes. Moreover, eradication of HCV infection by IFN therapy is associated with normalization of the activation-markers expression. We propose that CD81-mediated activation of B cells in vitro recapitulates the effects of HCV binding to B cell CD81 in vivo and that polyclonal proliferation of naïve B lymphocytes is a key initiating factor for the development of the HCV-associated B lymphocyte disorders.Proceedings of the National Academy of Sciences 01/2006; 102(51):18544-9. · 9.68 Impact Factor -
Article: Muscle glutamine depletion in the intensive care unit.
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ABSTRACT: Glutamine is primarily synthesized in skeletal muscle and enables transfer of nitrogen to splanchnic tissues, kidneys and immune system. Discrepancy between increasing rates of glutamine utilization at whole body level and relative impairment of de novo synthesis in skeletal muscle leads to systemic glutamine deficiency and characterizes critical illness. Glutamine depletion at whole body level may contribute to gut, liver and immune system disfunctions, whereas its intramuscular deficiency may directly contribute to lean body mass loss. Severe intramuscular glutamine depletion also develops because of outward transport system upregulation, which is not counteracted by increased de novo synthesis. The negative impact of systemic glutamine depletion on critically ill patients is suggested both by the association between a lower plasma glutamine concentration and poor outcome and by a clear clinical benefit after glutamine supplementation. Enteral glutamine administration preferentially increases glutamine disposal in splanchnic tissues, whereas parenteral supplementation provides glutamine to the whole organism. Nonetheless, systemic administration was ineffective in preventing muscle depletion, due to a relative inability of skeletal muscle to seize glutamine from the bloodstream. Intramuscular glutamine depletion could be potentially counteracted by promoting de novo glutamine synthesis with pharmacological or nutritional interventions.The International Journal of Biochemistry & Cell Biology 11/2005; 37(10):2169-79. · 4.63 Impact Factor -
Article: Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study.
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ABSTRACT: The aim of this study is to verify the efficacy and safety of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated mixed cryoglobulinemia. Eighteen patients (7 women and 11 men) affected by mixed cryoglobulinemia were included in the study and treated with peg-interferon alfa-2b 1.0 microg/kg once a week plus ribavirin (1000 mg daily) for 48 weeks, regardless of the HCV genotype. At the end of the treatment HCV-RNA became undetectable in 15 patients (83%) and most patients improved clinically. One subject suspended treatment at 13th week due to depression. A large fraction of the patients (8 cases: 44%) relapsed both virologically and clinically a few weeks after the end of therapy. At the end of follow-up, only eight patients (44%) obtained a sustained virological response. Peg-interferon alfa-2b in combination with ribavirin seems safe and useful for patients affected by mixed cryoglobulinemia, but not as effective as in patients with HCV-positive chronic hepatitis without cryoglobulinemia.Journal of Hepatology 06/2005; 42(5):632-8. · 9.26 Impact Factor -
Article: Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors.
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ABSTRACT: Dendritic cells (DCs) play a key role in immune responses through antigen presentation and cytokine secretion. Hepatitis C virus (HCV) is able to escape elimination by the immune system and often establishes a chronic infection. To investigate whether DC dysfunction is involved in this process, we have studied monoycte-derived DCs (Mo-DCs) and plasmacytoid DCs (pDCs), which produce large amounts of IFN-alpha, from chronic HCV patients and healthy donors. We have assessed TNF-alpha and IFN-alpha production by pDCs using intracellular staining after total PBMCs stimulation with unmethylated CG dinucleotides (CpGs). The induction of allogeneic T cell proliferation by immature Mo-DCs was measured using the MLR assay. The up-regulation of maturation markers and the production of TNF-alpha in response to LPS were analyzed using flow cytometry and ELISA, respectively. We have detected comparable frequencies of pDCs producing TNF-alpha and IFN-alpha in both chronic HCV patients and healthy donors and we have found that immature Mo-DCs from both patients and donors similarly induce allogeneic T cell proliferation and mature and secrete TNF-alpha in response to LPS. Our results demonstrate that both pDC and Mo-DCs are not impaired in HCV infected patients.Journal of Hepatology 02/2005; 42(1):61-7. · 9.26 Impact Factor -
Article: Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon.
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ABSTRACT: Only a small fraction of patients with hepatitis C virus (HCV) positive mixed cryoglobulinemia achieve longterm recovery after interferon (IFN) therapy; we evaluated the effectiveness and safety of combination therapy (interferon plus ribavirin) in nonresponders or those who relapsed after one or more courses of IFN. Twenty-seven patients with HCV positive mixed cryoglobulinemia were studied. All were treated with IFN-a2b (3 MU 3 times weekly) for one year, plus daily oral ribavirin 1000 or 1200 mg. Five patients (18.5%) obtained complete recovery from viral infection and from all signs and symptoms of disease. During treatment, most patients (85%) improved clinically. All 5 responders were "relapsers" to the first treatment(s). Combination therapy of IFN plus ribavirin could be useful for patients with mixed cryoglobulinemia resistant to IFN as monotherapy.The Journal of Rheumatology 09/2003; 30(8):1775-81. · 3.69 Impact Factor -
Article: GBV‐C/HGV and HCV infection in mixed cryoglobulinaemia
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ABSTRACT: Recently, a new, suspected hepatotropic virus has been identified. Named GBV-C/HGV, this virus shares with the hepatitis C virus (HCV) routes of transmission and molecular organization. Indeed, a proportion of HCV-infected patients (10–25%) are also carriers of GBV-C/HGV. Since mixed cryoglobulinaemia (MC) is closely associated with HCV infection, the aim of this study was to determine the prevalence of GBV-C/HGV infection in MC patients, and to investigate whether the double infection influenced the clinical and/or laboratory aspects of the disease.52 patients affected by MC were studied. 100 patients affected by HCV-positive chronic liver disease (CLD) without MC were used as control group. To determine the prevalence of GBV-C/HGV infection in general population, 150 blood donors were studied, as well as 80 patients affected by non-A–E CLD.Among the MC patients, only five (9.6%) were positive for both HCV and GBV-C/HGV infection. No difference was found between patients with and without double infection as regards main clinical and laboratory aspects. Among HCV-positive CLD cases, 27 were positive for double infection. Among blood donors, the prevalence of GBV-C/HGV infection was 8.0%, whereas in cases with cryptogenetic CLD the prevalence was 5.0%.In conclusion, these data show that GBV-C/HGV infection does not play any role in the pathogenesis of MC.British Journal of Haematology 04/2002; 106(2):510 - 514. · 4.94 Impact Factor -
Article: Whey Protein Ingestion Enhances Postprandial Anabolism during Short-Term Bed Rest in
[show abstract] [hide abstract]
ABSTRACT: We tested the relative ability of rapidly digested whey and slowly digested casein to stimulate net whole-body protein synthesis during prolonged physical inactivity. We studied 8 young male volunteers after they consumed isonitrogenous casein or whey mixed meals on d 12 or d 14 of experimental bed rest. Rates of phenylalanine hydroxylation were measured by primed-constant oral administration of L(2-2H2)tyrosine and L(ring- 2 H5)phenylalanine for 3 h in the postabsorptive state and 6 h after an isonitrogenous bolus meal containing sucrose (0.27 g/kg) and casein or whey (0.40 g/kg). Net protein synthesis in the fed state was calculated during the first 6 h postmeal as the difference between phenylalanine hydroxylation and phenylalanine content in the ingested casein or whey. In the fed state, the integrated changes in phenylalanine hydroxylation were lower (P , 0.05) after whey (22 6 8 mmolkg21� 6h 21) than after casein ingestion (34 6 7 mmolkg21� 6h 21). During bed rest, net postprandial protein synthesis was greater (P , 0.05) after whey (96 6 8 mmol phenylalaninekg21� 6h 21) than after casein ingestion (82 6 7 mmol phenylalaninekg21� 6h 21). The rapidly digested whey protein was more efficient than the slowly digested casein in increasing postprandial net protein synthesis
Top Journals
Institutions
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2010
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Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
Trieste, Friuli Venezia Giulia, Italy
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2002–2006
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Università degli Studi di Trieste
Trieste, Friuli Venezia Giulia, Italy
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2003
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Azienda Ospedaliera Santa Maria Degli Angeli
Pordenone, Friuli Venezia Giulia, Italy
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