ABSTRACT
The high prevalence of HIV and syphilis found among female transgender sex workers (FTSWs) in Argentina calls for the study of factors leading to negative health consequences. Given the particular characteristics observed in this population (high marginalization, school dropout, and low adherence to healthcare services), we explored the association of several socio-demographic characteristics with syphilis and HIV infections, and the determinants of condom use. This study revealed that FTSWs from Argentina were exposed to several risk factors decreasing thus their ability to negotiate condom use and leading to increased risk for transmission of HIV and other sexually transmitted infections (STIs). Strategies to reduce HIV and syphilis in this population should consider interventions aimed at decreasing violence and substance use which appear to be the most important determinants. Results of this study will contribute to the global information among FTSWs.
Subject(s)
Condoms/statistics & numerical data , HIV Infections/epidemiology , Sex Workers/statistics & numerical data , Substance-Related Disorders/epidemiology , Syphilis/epidemiology , Transgender Persons/statistics & numerical data , Adult , Argentina/epidemiology , Condylomata Acuminata/epidemiology , Cross-Sectional Studies , Female , Gonorrhea/epidemiology , Health Risk Behaviors , Hepatitis B/epidemiology , Herpes Simplex/epidemiology , Humans , Male , Papillomavirus Infections/epidemiology , Prevalence , Risk Factors , Safe Sex/statistics & numerical data , Sexually Transmitted Diseases/epidemiologyABSTRACT
BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). RESULTS: Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.
Subject(s)
Erythropoietin/administration & dosage , Gene Transfer Techniques , Myocardial Infarction/drug therapy , Myocardial Reperfusion/methods , Vascular Endothelial Growth Factor A/administration & dosage , Vascular Endothelial Growth Factor A/genetics , Animals , Drug Therapy, Combination , Humans , Male , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Sheep, Domestic , Ventricular Function, Left/drug effects , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available. METHODOLOGY/PRINCIPAL FINDINGS: IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho=0.022, p=0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals. CONCLUSIONS/SIGNIFICANCE: Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes.
Subject(s)
Erythrocytes/virology , HIV Antibodies/immunology , HIV Envelope Protein gp120/metabolism , HIV Envelope Protein gp160/metabolism , HIV Infections/immunology , Immunoglobulin G/immunology , Adult , Aged , Case-Control Studies , Cell Line, Tumor , Complement System Proteins , Erythrocytes/cytology , HIV Infections/metabolism , HIV Seropositivity , Humans , Immunoglobulin G/chemistry , Middle Aged , Models, Statistical , Viral LoadABSTRACT
OBJECTIVES: The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities. BACKGROUND: There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated. METHODS: In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes. RESULTS: CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality. CONCLUSIONS: CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.
Subject(s)
Cardiomyopathy, Dilated/pathology , Heart Failure/pathology , Myocytes, Cardiac/pathology , Ventricular Remodeling , Adult , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/mortality , Female , Fibrosis , Heart Failure/complications , Heart Failure/mortality , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Severity of Illness IndexABSTRACT
Studies on cardiac regeneration require large mammalian models of dilated cardiomyopathy (DCM) after acute myocardial infarction (AMI), and pig and sheep models are increasingly used in this field of preclinical research. Given the large interindividual variability in ovine left anterior descending artery (LAD) anatomy, protocols based on the coronary arteries to be ligated often lead to significant variation in infarct sizes and hence to heterogeneous results, ranging from no ventricular remodeling to acute, lethal left ventricular (LV) failure. We designed an ovine model of postinfarction DCM based on estimated infarct size rather than on a predetermined menu of coronary artery ligatures. In seven adult sheep we induced an anterolateral AMI of approximately 25% of the LV mass by ligating the branches of the LAD that, by visual inspection, would lead to such an infarct size. In 10 to 12 weeks, LV end-diastolic volume more than doubled and LV end-systolic volume almost tripled. LV ejection fraction decreased dramatically, as did LV percent fractional shortening and LV percent wall thickening. Infarct size (planimetry) was approximately 25% of the LV endocardial surface. We conclude that in sheep, an anterolateral AMI of approximately 25% of the LV mass--regardless of the coronary branches ligated to attain that infarct size--results in a model of postinfarction DCM that may prove useful in preclinical research on myocardial regeneration.