202 research outputs found

    The good and evil of flare: flares in hepatitis B virus chronic hepatitis

    No full text
    Treatment of HBeAg-positive chronic hepatitis B with pegylated interferon achieves HBeAg seroconversion in about 30% of patients and retreatment of nonresponders is followed by a low rate of sustained response. Alanine aminotransferase flares occurring after the introduction of interferon are considered a positive predictor of response. Here we described a young patient with active chronic hepatitis B who underwent four different treatment courses developing lamivudine resistance and showing three elevated flares of different origin and with diverse outcome. We discuss the meaning of each flare and their role in treatment response or virus reactivation

    Altered expression of the tetraspanin CD81 on B and T lymphocytes during HIV-1 infection

    No full text
    CD81 is a member of the tetraspan superfamily and plays a role in immune responses and in hepatitis C virus (HCV) pathogenesis. We analysed CD81 cell surface and mRNA expression in different lymphocytic subpopulations in human immunodeficiency virus (HIV)-1, HCV and dually infected subjects. CD81 cell surface expression was evaluated with fluorescence activated cell sorter (FACS) analysis; mRNA quantification was performed with semiquantitative polymerase chain reaction (PCR). CD81 cell surface expression on CD4(+) T lymphocytes was significantly different by analysis of variance (anova) test (P < 0.001), with reduced expression in HIV-1(+) patients. In B lymphocytes, higher cell surface expression was present in HIV-1, in HCV and in dually infected subjects compared to healthy controls. CD81 expression on B lymphocytes showed a positive correlation with plasma HIV-RNA. CD81 mRNA levels in B lymphocytes were significantly higher in HIV-1(+) patients compared to healthy controls. The potential consequence of the down-regulation of CD81 in CD4(+) cells during HIV-1 infection in conjunction with diverted CD28, CD4 and CD3 expression is the disruption of T cell function. Increased CD81 expression on B lymphocytes might explain the higher prevalence of lymphoproliferative disorders in HIV-1 and HCV infection. Up-regulation of CD81 mRNA on CD4(+) T cells indicates that down-regulation of CD81 occurs at the post-transcriptional/translational level

    Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

    No full text
    OBJECTIVE-High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS-We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses' Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS-We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 x 10(-8)). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS-Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis. Diabetes 60:2197-2201, 201

    Lipid profile improvement in virologically suppressed HIV-1-infected patients switched to dolutegravir/abacavir/lamivudine: data from the SCOLTA project

    No full text
    Paola Bagella,1 Nicola Squillace,2 Elena Ricci,3 Roberto Gulminetti,4 Giuseppe Vittorio De Socio,5 Lucia Taramasso,6 Giovanni Pellican&ograve;,7 Barbara Menzaghi,8 Benedetto Maurizio Celesia,9 Chiara Dentone,10 Giancarlo Orofino,11 Paolo Bonfanti,12 Giordano Madeddu13On behalf of the C.I.S.A.I. Study Group, Italy1Unit of Post-acute Long Term Care, ATS Sardegna, Sassari, Italy; 2Infectious Diseases Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 3Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 4Unit of Infectious Diseases, IRCCS San Matteo Hospital, Pavia, Italy; 5Infectious Diseases Unit Department of Medicine, Azienda Ospedaliero-Universitaria di Perugia, Santa Maria Hospital, Perugia, Italy; 6Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca&lsquo; Granda Ospedale Maggiore Policlinico, Milan, Italy; 7Department of Human Pathology of the Adult and the Developmental Age &lsquo;G. Barresi&lsquo;, Unit of Infectious Diseases, University of Messina, Messina, Italy; 8Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 9Unit of Infectious Diseases, Garibaldi Hospital, Catania, Italy; 10Unit of Infectious Diseases, Sanremo Hospital, Sanremo, Italy; 11Unit of Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy; 12Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy; 13Unit of Infectious Diseases, Department of Clinical, Surgical and Experimental Medicine, University of Sassari, Sassari, ItalyIntroduction: Metabolic disorders are common amongst HIV-infected patients. Data from real-life setting on the impact of DTG/ABC/3TC in virologically suppressed HIV-infected patients are scarce.Methods: We investigated the modification of metabolic profile including fasting glucose, lipid profile and markers of insulin resistance (IR) in experienced patients switching from a boosted protease inhibitors (bPI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to DTG/ABC/3TC in a prospective, observational, multicenter study.Results: We enrolled 131 HIV-infected patients, of whom 91 (69.5%) males, mean age was 50.5&plusmn;10.6 years. CDC stage was A in 66 (50.4%) patients, of whom 91 (69.5%) had acquired HIV through sexual contacts. The previous regimen was bPI-based in 79 patients (60.3%) and NNRTI-based in 52 (39.7%). Patients switching from NNRTI showed a significant reduction at week 24 in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL). Triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio, HDL, median TG and TG/HDL ratio did not show significant modification during follow-up times. Among patients switching from a bPI, we observed a significant reduction in TC and LDL at both follow-up times and a slight increase in HDL. Triglycerides/HDL ratio, median TG and TG/HDL ratio showed a decrease over time that became significant at weeks 24 and 48. Blood glucose levels did not significantly vary during the observation period in patients switching from both bPI and NNRTI-based regimens.Conclusion: Our data suggest an improvement in lipid profile and TG/HDL ratio in pretreated HIV-1-infected patients who switched to DTG/ABC/3TC over 48 weeks, especially in those previously receiving a bPI-based regimen.Keywords: HIV-1 infection, dolutegravir/abacavir/lamivudine, lipid profil

    Role of insulin resistance in kidney dysfunction: Insights into the mechanism and epidemiological evidence

    No full text
    Several lines of evidence suggest a pathogenic role of insulin resistance on kidney dysfunction. Potential mechanisms are mostly due to the effect of single abnormalities related to insulin resistance and clustering into the metabolic syndrome. Hyperinsulinemia, which is inevitably associated to insulin resistance in non diabetic states, also appears to play a role on kidney function by inducing glomerular hyperfiltration and increased vascular permeability. More recently, adipocytokine which are linked to insulin resistance, low grade inflammation, endothelial dysfunction and vascular damage have been proposed as additional molecules able to modulate kidney function. In addition, recent evidences point also to a role of insulin resistance at the level of the podocyte, an important player in early phases of diabetic kidney damage, thus suggesting a new mechanism through which a reduction of insulin action can affect kidney function. In fact, mouse models not expressing the podocyte insulin receptor develop podocytes apoptosis, effacement of its foot processes along with thickening of the glomerular basement membrane, increased glomerulosclerosis and albuminuria.A great number of epidemiological studies have repeatedly reported the association between insulin resistance and kidney dysfunction in both non diabetic and diabetic subjects. Among these, studies addressing the impact of insulin resistance genes on kidney dysfunction have played the important role to help establish a cause-effect relationship between these two traits.Finally, numerous independent intervention studies have shown that a favourable modulation of insulin resistance has a positive effect also on urinary albumin and total protein excretion.In conclusion, several data of different nature consistently support the role of insulin resistance and related abnormalities on kidney dysfunction. Intervention trials designed to investigate whether treating insulin resistance ameliorates also hard renal end-points are both timely and needed. © 2013 The Author

    Weight Gain : A Possible Side Effect of All Antiretrovirals

    No full text
    Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C
    corecore