FERNANDA DE TOLEDO GONCALVES
Projetos de Pesquisa
Unidades Organizacionais
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from Sao Paulo, Brazil: The role of IFN-lambda 4 polymorphisms(2021) PRATES, Gabriela da Silva; MALTA, Fernanda M.; GONCALVES, Fernanda de Toledo; MONTEIRO, Mariana A.; FONSECA, Luiz Augusto M.; VEIGA, Ana Paula R.; MAGRI, Marcello M. C.; DUARTE, Alberto J. S.; CASSEB, Jorge; ASSONE, TatianeFew studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-lambda 4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-lambda 4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm(3)or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-lambda 4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-lambda 4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-lambda 4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-lambda 4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.
- Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder(2021) CASTALDELLI-MAIA, Joao M.; MALBERGIER, Andre; OLIVEIRA, Adriana B. P. de; AMARAL, Ricardo A.; NEGRAO, Andre B.; GONCALVES, Priscila D.; VENTRIGLIO, Antonio; BERARDIS, Domenico de; ANTONIO, Juliana de; FIRIGATO, Isabela; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoBackground: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.
- Prognosis Markers for Monitoring HTLV-1 Neurologic Disease(2021) PRATES, Gabriela; ASSONE, Tatiane; CORRAL, Marcelo; BALDASSIN, Maira P. M.; MITIKO, Tatiane; SALES, Flavia C. Silva; HAZIOT, Michel E.; SMID, Jerusa; FONSECA, Luiz A. M.; GONCALVES, Fernanda de Toledo; OLIVEIRA, Augusto C. Penalva de; CASSEB, JorgeBackground Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated not only with some severe manifestations, such as HTLV-1-associated myelopathy (HAM) and ATLL, but also with other, less severe conditions. Some studies have reported neurologic manifestations that did not meet all the criteria for the diagnosis of HAM in individuals infected with HTLV-1; these conditions may later progress to HAM or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. This study evaluated the prognostic value and looked for a possible association of those parameters with the intermediate syndrome (IS) status and HAM status. Methods Proviral load (PVL), spontaneous lymphoproliferation, interferon (IFN)-gamma spontaneous production was quantified in samples of asymptomatic and HAM patients, as well as patients with IS. Results The critical age range was 50-60 years for IS outcome and more of 60 years for HAM outcome, with an increased risk of 2.5-fold for IS and 6.8-fold for HAM. IFN-gamma was increased in patients with IS compared with asymptomatic carriers (ACs) (p = 0.007) and in patients with HAM compared with ACs (p = 0.03). Lymphoproliferation was increased in patients with HAM vs ACs (p = 0.0001) and patients with IS (p = 0.0001). PVL was similar between groups. Conclusion IFN-gamma has high specificity of prediction of subject remain asymptomatic compared with PVL and lymphoproliferation assay tests. IFN-gamma has been shown to be a biomarker of progression to intermediate stage and to HAM. The association of other markers with manifestations associated with HTLV-1 infection that does not meet the HAM criteria should be verified.