Publications by authors named "Norma Lucena-Silva"

53 Publications

Polymorphisms at the IL17A and IL17RA genes are associated with prognosis of papillary thyroid carcinoma.

Arch Med Res 2021 Aug 9. Epub 2021 Aug 9.

Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-SP, Brazil; Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo. Ribeirão Preto-SP, Brazil.

Background: Interleukin (IL)-17A has a dual role in tumor immunity, promotes anti-tumor responses and facilitates angiogenesis by interacting with IL-17 receptor A (IL-17RA). Although IL-17A has been associated with the pathogenesis of papillary thyroid carcinoma (PTC), the nucleotide variability at the IL17A and IL17RA genes is still poorly characterized.

Aim: To assess the contribution of the IL17A (-197 G >A, rs2275913) and IL17RA (-947 A >G, rs4819554) single nucleotide polymorphisms (SNP) on the development and progression of PTC and on IL-17 plasma levels.

Methods: We studied 188 PTC patients and 170 healthy controls. SNPs were identified using PCR-amplified DNA and restriction fragment length polymorphism (RFLP) techniques. Plasma levels of IL-17A was evaluated in 83 PTC patients using ELISA. Statistical analyses were performed to evaluate the associations between SNPs and clinicohistopathological features of PTC and IL-17A levels.

Results: No significant difference was observed regarding the allele and genotype distributions of both SNPs between PTC patients and controls. The IL17A GA was associated with poor biochemical and structural incomplete response to therapy, whereas no influence over the IL-17A expression was observed. The IL17RA AG was significantly associated with small-sized tumors, initial tumor stage at diagnosis and better response to therapy.

Conclusions: The IL17A SNP may predict an aggressive manifestation of PTC, whereas the IL17RA SNP was associated with a more favorable clinical outcome.
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http://dx.doi.org/10.1016/j.arcmed.2021.07.004DOI Listing
August 2021

Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 () rs36084323 A Allele in a Dominant Model.

Front Cell Infect Microbiol 2021 1;11:587932. Epub 2021 Jul 1.

Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and expression were evaluated by immunohistochemistry and qPCR, respectively, and the polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased ( = 0.0649), whereas in CIN III was associated with decreased ( = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant -606A allele at single or double doses exhibited increased protein and gene expression when compared to the -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.
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http://dx.doi.org/10.3389/fcimb.2021.587932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288189PMC
July 2021

Peripheral spectrum neurological disorder after arbovirus infection is associated with HLA-F variants among Northeastern Brazilians.

Infect Genet Evol 2021 08 8;92:104855. Epub 2021 Apr 8.

Ribeirão Preto Medical School, University of São Paulo, AV Bandeirantes, 3900, HC, Vila Monte Alegre, 14049900 Ribeirão Preto, SP, Brazil. Electronic address:

Introduction: Non-classical class I human leukocyte antigens (HLA) molecules are known to modulate the function of cytotoxic cells (NK and T CD8+) during viral infection by interacting with inhibitory/activating receptors. However, little is known about the HLA-E/-F genetic variability on arbovirus infections.

Methods: We evaluated by massive parallel sequencing the full HLA-E/-F genetic diversity among patients infected during the arbovirus (ZIKV, DENV, and CHIKV) outbreak leading to a broad range of neurological complications in the Brazilian State of Pernambuco. In parallel, healthy blood donors from the same area were also studied. Plink and R software were used for genetic association study. To limit the false-positive results and enhance the reliability of the results, we adopted P-values <0.01 as significant levels.

Results: Compared to controls, the HLA-F alleles: -1610 C (rs17875375), +1383 G (rs17178385), and +3537 A (rs17875384), all in complete linkage disequilibrium with each other (r = 1), were overrepresented in patients presenting peripheral spectrum disorders (PSD). The HLA-F*Distal-D haplotype that harbored the -1610 C allele exhibited a trend increase in PSD group. No associations were found for HLA-E.

Conclusions: Our findings showed that the HLA-F genetic background seems to be more important than HLA-E on the susceptibility to PSD complications.
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http://dx.doi.org/10.1016/j.meegid.2021.104855DOI Listing
August 2021

Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications.

Front Immunol 2021 12;12:582935. Epub 2021 Mar 12.

Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1β, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (<0.0001), MCP-1 (<0.0001), HGF (= 0.0001), and VEGF (<0.0001) in the acute phase. Fourteen molecules (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.
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http://dx.doi.org/10.3389/fimmu.2021.582935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994272PMC
June 2021

Flexible sensor based on conducting polymer and gold nanoparticles for electrochemical screening of HPV families in cervical specimens.

Talanta 2021 May 21;226:122118. Epub 2021 Jan 21.

Programa de Pós-Graduação Em Inovação Terapêutica, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil; Laboratório de Biodispositivos Nanoestruturados, Departamento de Bioquímica, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil. Electronic address:

Considering the low sensitivity of cytological exams and high costs of the molecular methods, the development of diagnostic tests for effective diagnosis of HPV infections is a priority. In this work, biosensor composed of polypyrrole (PPy) films and gold nanoparticles (AuNPs) was obtained for specific detection of HPV genotypes. The biosensor was developed by using flexible electrodes based on polyethylene terephthalate (PET) strips coated with indium tin oxide (ITO). Polymeric films and AuNPs were obtained by electrosynthesis. Oligonucleotides sequences modified with functional amino groups were designed to recognize HPV gene families strictly. The modified oligonucleotides were chemically immobilized on the nanostructured platform. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used for the analysis of the electrode modification and monitoring of molecular hybridization. Electrochemical changes were observed after exposure of the biosensors to plasmid samples and cervical specimens. The biosensor based on the BSH16 probe showed a linear concentration range for target HPV16 gene detection of 100 pg μL to 1 fg μL. A limit of detection (LOD) of 0.89 pg μL and limit of quantification (LOQ) of 2.70 pg μL were obtained, with a regression coefficient of 0.98. Screening tests on cervical specimens were performed to evaluate the sensibility and specificity for HPV and its viral family. The expression of a biomarker for tumorigenesis (p53 gene) was also monitored. In this work, a flexible system has been successfully developed for label-free detection of HPV families and p53 gene monitoring with high specificity, selectivity, and sensitivity.
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http://dx.doi.org/10.1016/j.talanta.2021.122118DOI Listing
May 2021

Differential Frequencies of HLA-DRB1, DQA1, and DQB1 Alleles and Haplotypes Are Observed in the Arbovirus-Related Neurological Syndromes.

J Infect Dis 2021 Aug;224(3):517-525

Immunology Department, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil.

Background: We took advantage of the 2015-2016 Brazilian arbovirus outbreak (Zika [ZIKV]/dengue/chikungunya viruses) associated with neurological complications to type HLA-DRB1/DQA1/DQB1 variants in patients exhibiting neurological complications and in bone marrow donors from the same endemic geographical region.

Methods: DRB1/DQA1/DQB1 loci were typed using sequence-specific oligonucleotides. In silico studies were performed using X-ray resolved dimer constructions.

Results: The DQA1*01, DQA1*05, DQB1*02, or DQB1*06 genotypes/haplotypes and DQA1/DQB1 haplotypes that encode the putative DQA1/DQB1 dimers were overrepresented in the whole group of patients and in patients exhibiting peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD). The DRB1*04, DRB1*13, and DQA1*03 allele groups protected against arbovirus neurological manifestation, being underrepresented in whole group of patients and ESD and PSD groups. Genetic and in silico studies revealed that DQA1/DQB1 dimers (1) were primarily associated with susceptibility to arbovirus infections; (2) can bind to a broad range of ZIKV peptides (235 of 1878 peptides, primarily prM and NS2A); and (3) exhibited hydrophilic and highly positively charged grooves when compared to the DRA1/DRB1 cleft. The protective dimer (DRA1/DRB1*04) bound a limited number of ZIKV peptides (40 of 1878 peptides, primarily prM).

Conclusion: Protective haplotypes may recognize arbovirus peptides more specifically than susceptible haplotypes.
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http://dx.doi.org/10.1093/infdis/jiaa764DOI Listing
August 2021

Metal-polymer hybrid nanomaterial for impedimetric detection of human papillomavirus in cervical specimens.

J Pharm Biomed Anal 2020 Jun 9;185:113249. Epub 2020 Mar 9.

Programa de Pós-Graduação em Inovação Terapêutica, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil; Laboratório de Biodispositivos Nanoestruturados, Departamento de Bioquímica, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil. Electronic address:

The human papillomavirus (HPV) is one of the main sexually transmitted pathogens that infect the anogenital epithelium and mucous membranes. HPV genotypes can be classified as high and low oncogenic risk, with infection by the former resulting in cervical cancer in approximately 100 % of the cases. In this work, we developed an ultrasensitive electrochemical biosensor for the detection and identification of different HPV genotypes. A nanostructured platform based on a matrix of polyaniline (PANI) containing gold nanoparticles (AuNps) was designed for the chemical immobilization of a DNA probe capable of recognizing different HPV types. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM) were used to characterize the genosensor. The impedimetric responses indicate that the proposed sensor was able to detect HPV (types 6, 11, 16, 31, 33, 45, and 58) in cervical specimens (cDNA samples). We obtained different profiles of electrochemical responses for the high and low-risk HPV genotypes. By adopting a three-dimensional quantitative analysis of impedance response variables, it was possible to identify the existence of a pattern of association for samples of high oncogenic risk, which may lead to the differential diagnosis of HPV. The biosensor demonstrated an excellent analytical performance for the detection of HPV genotypes with high sensibility and selectivity. The genosensor exhibited a linear range of response in the 1 pg μL to 100 pg μL range. Besides, a limit of detection (LOD) of 2.74 pg μL and 7.43 pg μL was obtained for HPV11 and HPV16, respectively, with regression coefficients of 99.88 % and 99.47 %. Thus, the proposed sensor may serve as a good prognostic indicator for patients infected with papillomavirus.
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http://dx.doi.org/10.1016/j.jpba.2020.113249DOI Listing
June 2020

Reduced-dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study.

Blood 2020 04;135(17):1458-1466

Department of Global Pediatric Medicine.

Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and < 10 years), white blood cell count of <50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of <0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.
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http://dx.doi.org/10.1182/blood.2019004215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180080PMC
April 2020

Human leukocyte antigen-G 3' untranslated region polymorphism +3142G/C (rs1063320) and haplotypes are associated with manifestations of the American Tegumentary Leishmaniasis in a Northeastern Brazilian population.

Hum Immunol 2019 Nov 13;80(11):908-916. Epub 2019 Aug 13.

Immunogenetic Laboratory, Immunology Department, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Av. Moraes rego, s/n, Campus da UFPE, Cidade Universitária, Recife, PE CEP:50670-465, Brazil. Electronic address:

While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.
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http://dx.doi.org/10.1016/j.humimm.2019.08.001DOI Listing
November 2019

MicroRNA expression profiling provides novel insights into immune-related pathways involved in gastric cancer.

Med Oncol 2019 Aug 9;36(9):81. Epub 2019 Aug 9.

Anatomic Pathology Department, A.C. Camargo Cancer Center, São Paulo, Brazil.

Gastric cancer is one of the most common cancers, and an increasing number of studies have found that microRNAs (miRNAs) play essential roles in gastric cancer progression; however, the roles of specific miRNAs involved in the immune response to this disease remain unclear. We compared the miRNA expression in tissues from primary gastric cancer patients and healthy controls to find miRNAs dysregulated in gastric cancer and used bioinformatics tools to determine potential roles of these miRNAs in the immune system. We evaluated 25 primary gastric cancer tissues and five healthy gastric tissues. Quantitative real-time polymerase chain reaction was performed for a set of miRNAs, followed by the prediction of their target genes and functional enrichment analysis of these targets. Analysis of a microarray dataset showed that the miRNA miR-196a-5p was significantly upregulated, while miR-374a-5p and miR-375 were downregulated in gastric cancer patients. In addition, miR-374-5p was significantly downregulated in patients with metastasis compared with its expression levels in non-metastatic patients (p = 0.03). Bioinformatics analysis suggested that the pathways regulated by these differentially expressed miRNAs were related to the immune response, cell adhesion, and cell migration. Most importantly, this study provides a new insight into the potential use of multiple miRNAs to find distinct pathways of immune regulation in gastric cancer.
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http://dx.doi.org/10.1007/s12032-019-1305-xDOI Listing
August 2019

High prevalence of occult hepatitis C infection in predialysis patients.

World J Hepatol 2019 Jan;11(1):109-118

Laboratory of Immunogenetics of the Aggeu Magalhães Institute - Fiocruz Pernambuco, Pernambuco 50670-420, Brazil.

Background: Occult hepatitis C virus (HCV) infection (OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease (CKD) who are on hemodialysis (HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome. However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy (RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.

Aim: To research the status in predialysis patients when HD patients have high prevalence of OCI.

Methods: A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m (predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies, and patients showing positivity for serological markers of hepatitis B virus (HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serum-negative, in peripheral blood mononuclear cells.

Results: Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age ( = 0.002), patients with CKD of mixed etiology ( = 0.019), and patients with markers of previous HBV infection (., combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody) ( = 0.001).

Conclusion: Among predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.
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http://dx.doi.org/10.4254/wjh.v11.i1.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354127PMC
January 2019

MicroRNA expression profiles discriminate childhood T- from B-acute lymphoblastic leukemia.

Hematol Oncol 2019 Feb 27;37(1):103-112. Epub 2018 Nov 27.

Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Recife, Brazil.

MicroRNAs (miRNAs) play a critical role on biological and cellular processes; the search for functional markers may be of importance for differential diagnosis, prognosis, and development of new therapeutic regimens. In this context, we evaluated the bone marrow miRNA profile of Brazilian children exhibiting T- or B-cell acute lymphoblastic leukemia (T-ALL or B-ALL), using massive parallel sequencing, using the HiSeq 2500 platform (Illumina). The differential expression analysis was conducted considering a leave-one-out approach and FDR ≤ 0.05. Machine learning algorithms were applied to search for the disease subset biomarkers. Target prediction, functional enrichment, and classification of biological categories were also performed. Sixteen miRNAs were differentially expressed between T- and B-ALL, of which 10 (miR-708-5p, miR-497-5p, miR-151a-5p, miR-151b, miR-371b-5p, miR-455-5p, miR-195-5p, miR-1266-5p, miR-574-5p, and miR-425-5p) were downregulated and six (miR-450b-5p, miR-450a-5p, miR-542-5p, miR-424-5p, miR-629-5p, and miR-29c-5p) were upregulated in childhood T-ALL. These miRNAs may be used for distinguishing childhood lymphoblastic leukemia subtypes, since it provided the clear separation of patients in these two distinct groups. Six relevant biological pathways were identified according to their role in leukemia, namely, viral carcinogenesis, cell cycle, and B-cell receptor signaling pathways for induced miRNAs and TGF-beta signaling, apoptosis, and NF-kappa B signaling for the repressed miRNAs, of which several miRNA gene targets participate in cell differentiation and hematopoiesis processes. Machine learning analysis pointed out miR-29c-5p expression as the best discriminator between childhood T- and B-ALL, which is involved in calcium signaling, critical for B-cell lymphocyte fate. Further studies are needed to assure the role of the 16 miRNAs and miR-29c-5p on acute lymphoblastic leukemia subtypes and on disease prognosis.
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http://dx.doi.org/10.1002/hon.2567DOI Listing
February 2019

Variation sites at the HLA-G 3' untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell.

PLoS One 2018 2;13(10):e0204679. Epub 2018 Oct 2.

Department of Immunology, Laboratory of Immunogenetics, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.

Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204679PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168131PMC
March 2019

Impedimetric gene assay for BCR/ABL transcripts in plasmids of patients with chronic myeloid leukemia.

Mikrochim Acta 2018 08 16;185(9):415. Epub 2018 Aug 16.

Programa de Pós-Graduação em Bioquímica e Fisiologia, Universidade Federal de Pernambuco, Recife, PE, 50670-901, Brazil.

A label-free impedimetric biosensor was developed for determination of BCR/ABL transcripts. Specific DNA primers were covalently immobilized on a gold electrode modified with carboxylated multiwalled carbon nanotubes (cMWCNTs) and zinc oxide nanoparticles (ZnO-NPs). Aggregation of the ZnO-NPs is prevented by the introduction of an amino-modified silica coating, which also allows a subsequent covalent linkage to cMWCNTs. The impedimetric biosensor was typically operated at a working voltage of +10 mV vs. Ag/AgCl, in a frequency range from 100 mHz to 100 kHz. Studies on the surface morphology and electrochemical properties of the electrode demonstrated improved bioactivity. Amperometric currents and impedimetric parameters, such as charge transfer resistance, varied significantly throughout the construction of the biosensor. The hybridization process was also evidenced by changes in the topography of the surface after exposure to samples containing BCR/ABL. The gene sensor has a linear concentration range for the target gene of 6.94 aM to 694 fM with a limit of detection as low as 0.039 aM. Also, the biosensor is selective and reproducible with a standard deviation of 4.1%. Three replicates for each experimental condition were used. Hence, it is perceived to be a viable tool for early-stage diagnosis of the BCR/ABL fusion gene and monitoring of major molecular remission in clinical samples. Graphical abstract Schematic of a highly sensitive hybridization assay for the BCR/ABL fusion gene. It is based on ZnO nanoparticle functionalized with 3-(aminopropyl)triethoxysilane.
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http://dx.doi.org/10.1007/s00604-018-2958-4DOI Listing
August 2018

HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's disease patients and HLA-G5 expression is differentially correlated with TNF and IL-10 cytokine expression.

Hum Immunol 2018 Jun 26;79(6):477-484. Epub 2018 Mar 26.

Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil. Electronic address:

HLA-G is an immunomodulatory molecule that can be produced by epithelial cells. Considering that TNF and IL-10 participate in bowel inflammatory disorders and that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA expression by qPCR and HLA-G protein levels by immunohistochemistry in two intestinal samples exhibiting different degree of inflammation within a patient suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were higher in intestinal areas exhibiting intense inflammation compared to areas of low inflammation, and HLA-G protein levels were not associated with degree of mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10, irrespective of the inflammation grade, with little variation of the TNF:IL-10 ratio in the various inflamed areas. TNF and IL-10 expression was correlated with HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene and protein expression of HLA-G; and the HLA-G5 expression is differentially correlated with TNF and IL-10 levels depending on the type of the underlying inflammatory bowel disorder.
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http://dx.doi.org/10.1016/j.humimm.2018.03.006DOI Listing
June 2018

Childhood and Adolescent Cancer in the State of Pernambuco, Brazil: Incidence, Geographical Distribution, and Association With Environmental Health Indicators.

J Pediatr Hematol Oncol 2018 01;40(1):7-14

Immunology Department of the Aggeu Magalhães Research Cente, Oswaldo Cruz Foundation.

Cases of childhood and adolescent cancer diagnosed from 2009 to 2012 in the state of Pernambuco, Brazil, were analyzed considering the patients' sex and age, the type of cancer and the municipality of living to determine the incidence, geographical distribution, and association with environmental health indicators. The spatial distribution pattern of the cancer incidence was estimated using the Global Moran's index. The association between environmental health indicators and cancer incidence was evaluated by multiple regression. From 2009 to 2012, 1261 new cases of cancer were diagnosed in patients younger than 20 years old in the state of Pernambuco. Leukemia/lymphoma were the most common type of cancer contemplating 45.28% of the cases. The average age-adjusted incidence rate was 113 cases per million with no spatial distribution pattern. The municipalities were clustered according to their degree of inequality (P=0.017), human development index (P=0.001), population growth rate (P=0.008), urbanization level (P=0.001), number of agricultural crops per capita (P=0.001), and number of industries per capita (P=0.030). However, only urbanization level was positive correlated with incidence of pediatric cancer (P=0.009) likely because in more developed cities, people are more exposed to potential oncogenic factors, such as air and water pollution and processed and ultraprocessed food. The better access to specialized health services, which increases the chances of early diagnosis, may also contributes for a higher number of cases in more developed cities.
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http://dx.doi.org/10.1097/MPH.0000000000001017DOI Listing
January 2018

Cytokines and soluble HLA-G levels in bone marrow stroma and their association with the survival rate of patients exhibiting childhood T-cell acute lymphoblastic leukemia.

Cytokine 2018 02 10;102:94-101. Epub 2017 Aug 10.

Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, Recife, PE, Brazil; Pediatric Oncology Service, IMIP Hospital, Recife, PE, Brazil. Electronic address:

Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase. Data were analyzed using non-parametric tests, and survival rates were evaluated by Kaplan-Meier method (log-rank test). TNF, IL-10 and IL-6 levels were increased at diagnosis compared to D19 and D49. IL-10 levels<4.57pg/mL at diagnosis were associated with increased survival rate, in presence of positive correlation between IL-2 and IL-17 levels. Increased survival rate was also associated with IFN-γ levels<1.17pg/mL at D49, with a positive correlation observed between IL-4 and IL-2 as well IL-4 and IL-17 levels. In contrast, worse survival rate was associated with IL-2, IL-4 and IL-10 levels imbalance. In addition, increased sHLA-G levels at diagnosis were associated with increased leukocyte count, a well-known factor for poor prognosis. In conclusion, cytokines and sHLA-G play an essential role in marrow T-ALL microenvironment during chemotherapy, especially the immunosuppressive cytokine IL-10 which can be used as biomarker of disease outcome, being also a potential target for novel T-ALL treatments.
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http://dx.doi.org/10.1016/j.cyto.2017.07.014DOI Listing
February 2018

Encephalitis associated with inappropriate antidiuretic hormone secretion due to chikungunya infection in Recife, State of Pernambuco, Brazil.

Rev Soc Bras Med Trop 2017 May-Jun;50(3):417-422

Departamento de Medicina Interna, Universidade Federal de Pernambuco, Recife, PE, Brasil.

The symptoms of chikungunya virus (CHIKV) infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.
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http://dx.doi.org/10.1590/0037-8682-0434-2016DOI Listing
July 2017

The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia.

BMC Pulm Med 2016 12 1;16(1):170. Epub 2016 Dec 1.

Federal University of Pernambuco, Pediatrics, Recife, Brazil.

Background: To identify markers for earlier diagnosis of severe pneumonia, we assess the correlation between serum cytokine profile of children with different pneumonia severity.

Methods: In 25 hospitalized children, 7 with mild pneumonia and 18 with severe pneumonia, the serum concentration of 11 cytokines in three sampling times were dosed. Statistical analysis included parametric and non-parametric tests, Pearson correlation and ROC curve for cut-off definition of cytokines.

Results: At admission, IL-6 serum levels were high in mild or severe pneumonia, and was associated to vomiting (P = 0.019) in both groups; and also to dyspnea (P = 0.012) and white blood cell count (P = 0.045) in patients with severe pneumonia. IL-10 levels were also high in patients with pneumonia and were associated to lymphocytosis (P = 0.025). The ROC curve of the IL-6:IL-10 serum levels ratio discriminated severe pneumonia cases at admission, and persistence of infection in the third day of antibiotic therapy, with positive predictive values of 93% and 89%, respectively.

Conclusions: The balance between IL-6 and IL-10 serum levels showed to be a more discriminative marker for severity definition and evaluation of recovery in patients with pneumonia.
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http://dx.doi.org/10.1186/s12890-016-0324-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131553PMC
December 2016

Detection of Mycobacterium bovis in artisanal cheese in the state of Pernambuco, Brazil.

Int J Mycobacteriol 2016 09 14;5(3):269-272. Epub 2016 May 14.

Federal Rural University of Pernambuco, Dois Irmãos, Recife, Pernambuco, Brazil. Electronic address:

Objective/background: The present study was aimed at detecting Mycobacterium bovis in artisanal cheese using real-time quantitative polymerase chain reaction.

Methods: One hundred seven cheese samples (250g) were purchased in 107 commercial establishments including neighborhood grocery stores, bakeries, and open-air markets from 19 municipalities of the state of Pernambuco, Brazil. Ten grams of each cheese sample were macerated with sterile saline solution in a sterile bag and DNA was extracted from 20mg of the macerated material using the Wizard SV Genomic DNA Purification System. The quantitative polymerase chain reaction amplified a fragment corresponding to the region of difference 4 of M. bovis.

Results: Of the 107 samples analyzed, three (2.8%) were positive for M. bovis and their identities were confirmed by sequencing. This is perhaps the first report of the presence of M. bovis in artisanal cheese in the state of Pernambuco, Brazil.

Conclusion: The results of the present study highlight the need for improving sanitary measures during the production of artisanal cheese to prevent zoonotic tuberculosis in humans, resulting from the consumption of food contaminated with M. bovis.
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http://dx.doi.org/10.1016/j.ijmyco.2016.04.007DOI Listing
September 2016

Attomolar electrochemical detection of the BCR/ABL fusion gene based on an amplifying self-signal metal nanoparticle-conducting polymer hybrid composite.

Colloids Surf B Biointerfaces 2016 Dec 22;148:576-584. Epub 2016 Sep 22.

Programa de Pós-Graduação em Bioquímica e Fisiologia, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil; Programa de Pós-Graduação em Inovação Terapêutica, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil. Electronic address:

In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The working principle of the biosensor rests on measuring the conductivity resulting from the non-covalent interactions between the hybrid nanocomposite and the DNA probe. The nanostructured platform exhibits a large surface area that enhances the conductivity. Positive cases, which result from the hybridization between DNA probe and targeted gene, induce changes in the amperometric current and in the charge transfer resistance (R) responses. Atomic force microscopy (AFM) images showed changes in the genosensor surface after exposure to cDNA sample of patient with leukemia, evidencing the hybridization process. This new hybrid sensing-platform displayed high specificity and selectivity, and its detection limit is estimated to be as low as 69.4 aM. The biosensor showed excellent analytical performance for the detection of the BCR/ABL oncogene in clinical samples of patients with leukemia. Hence, this electrochemical sensor appears as a simple and attractive tool for the molecular diagnosis of the BCR/ABL oncogene even in early-stage cases of leukemia and for the monitoring of minimum levels of residual disease.
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http://dx.doi.org/10.1016/j.colsurfb.2016.09.029DOI Listing
December 2016

Implementation of a simplified flow cytometric assays for minimal residual disease monitoring in childhood acute lymphoblastic leukemia.

Cytometry B Clin Cytom 2018 01 8;94(1):94-99. Epub 2016 Jul 8.

Pediatric Oncology, CEHOPE/Institute of Integral Medicine Professor Fernando Figueira, Recife, Brazil.

Background: Monitoring minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL) to assess treatment response is crucial for risk assignment. Flow cytometry can be used to monitor MRD in ALL but the implementation of this approach requires extensive expertise. If resources are limited, the costs of full flow cytometric MRD testing might be prohibitive.

Objective: We evaluated the applicability of a previously reported simplified MRD assay, designed to distinguish leukemic from normal lymphoblastic during remission induction therapy.

Methods: Fifty-nine samples from children with ALL, enrolled in the RE-LLA study at a pediatric oncology center in Recife (Brazil), were evaluated for MRD on day 19 and on day 26 of remission induction therapy. We compared results obtained by a trainee in Recife and an expert.

Results: The method was implemented successfully and the concordance between results obtained by the trainee and the expert was practically absolute at the end of the study.

Conclusions: It is possible to implement reliable measurements of MRD during remission induction therapy in childhood ALL despite limited resources. The simplicity of the MRD method used in this study does not require extensive prior training in leukemia immunophenotyping. © 2016 International Clinical Cytometry Society.
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http://dx.doi.org/10.1002/cyto.b.21394DOI Listing
January 2018

Molecular detection of Mycobacterium bovis in cattle herds of the state of Pernambuco, Brazil.

BMC Vet Res 2016 Feb 20;12:31. Epub 2016 Feb 20.

Federal Rural University of Pernambuco (Universidade Federal Rural de Pernambuco - UFRPE), Rua Dom Manuel de Medeiros, s/n, Dois Irmãos, Recife, Pernambuco, CEP 52171-900, Brazil.

Background: The present study aimed to direct detect Mycobacterium bovis in milk (n = 401) and blood (n = 401) samples collected from 401 dairy cows of 20 properties located in the state of Pernambuco, Brazil, by real-time quantitative PCR (qPCR) targeting the region of difference 4 (RD4). Risk factors possibly associated with bovine tuberculosis (BTB) were also evaluated.

Results: Of the 802 samples analyzed, one milk (0.25%) and eight blood (2%) samples were positive for M. bovis in the qPCR and their identities were confirmed by sequencing. Animals positive for M. bovis were found in six (30%) of the 20 properties visited. None of the risk factors evaluated were statistically associated with BTB.

Conclusions: M. bovis DNA was detected in one milk sample what may pose a risk to public health because raw milk is commonly consumed in Brazil.
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http://dx.doi.org/10.1186/s12917-016-0656-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761206PMC
February 2016

Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus.

Hum Immunol 2016 Apr 13;77(4):358-64. Epub 2016 Feb 13.

Faculty of Medicine of Ribeirão Preto, University of São Paulo, Department of Medicine, Ribeirão Preto, SP, Brazil.

Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G.
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http://dx.doi.org/10.1016/j.humimm.2016.02.001DOI Listing
April 2016

Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients.

Mem Inst Oswaldo Cruz 2014 Sep 29;109(6):805-13. Epub 2014 Aug 29.

Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães-Fiocruz, Recife, PE, Brasil.

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238774PMC
http://dx.doi.org/10.1590/0074-0276130542DOI Listing
September 2014

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil.

Mem Inst Oswaldo Cruz 2014 Sep 22;109(6):738-47. Epub 2014 Aug 22.

Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, PE, Brasil.

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4⁺ lymphocyte count < 200/mm³ (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238765PMC
http://dx.doi.org/10.1590/0074-0276140070DOI Listing
September 2014

The efficacy of aerobic training in improving the inflammatory component of asthmatic children. Randomized trial.

Respir Med 2014 Oct 29;108(10):1438-45. Epub 2014 Aug 29.

Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Rua dos Coelhos, 300, Boa Vista, 50070-550 Recife, PE, Brazil.

Few studies have been conducted on the effects of aerobic exercise in children with asthma, particularly on the inflammatory component and functional outcomes. This study evaluated the effect of aerobic exercise on inflammation, functional capacity, respiratory muscle strength, quality of life and symptoms scores in asthmatic children. This was a 6-week randomized trial (NCT0192052) of 33 moderately asthmatic children (6-17 years). Patients were randomized aerobic training (exercise group; n = 14), while another group did not exercise (control; n = 19). Primary endpoint was evaluations serum cytokines (IL-17, IFN, TNF, IL-10, IL-6, IL-4 and IL-2) assessed by flow cytometry. The six-minute walk test, pulmonary function, quality of life and symptoms (asthma-free days) were secondary endpoint. The Mann-Whitney test was used to evaluate the independent variables and the Wilcoxon test for paired variables. The t-test was used for the remaining calculations. Significance was determined at 5%. Aerobic training failed to modify the inflammatory component. In the exercise group, an increase occurred in functional capacity (p < 0.01) and peak expiratory flow (p = 0.002), and maximal inspiratory (p = 0.005) and expiratory pressure (p < 0.01) improved. Furthermore, there was a significant increase in all the domains of the PAQLQ. The children who exercised had more asthma-free days than the controls (p = 0.012) and less sensation of dyspnea at the end of the study (p < 0.01). In conclusion, six weeks of aerobic exercise no changes in plasma cytokine patterns in asthmatic children and adolescents; however, an improvement was found in functional capacity, maximal respiratory pressure, quality of life and asthma-related symptoms. ClinicalTrials.gov Identifier: NCT0192052.
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http://dx.doi.org/10.1016/j.rmed.2014.07.009DOI Listing
October 2014

Prognostic evaluation of DNA index in HIV-HPV co-infected women cervical samples attending in reference centers for HIV-AIDS in Recife.

PLoS One 2014 21;9(8):e104801. Epub 2014 Aug 21.

Departamento de Medicina Tropical, Universidade Federal de Pernambuco (UFPE), Recife, Brasil.

Introduction: Persistence of cervical infection caused by human papillomavirus (HPV) types with high oncogenic risk may lead to cervical intraepithelial neoplasia (CIN). The aim of the present study was to evaluate whether, in HIV-positive women, the presence of aneuploidy in cervical cell samples is associated with presence and evolution of CIN.

Methods: The present study had two stages. In the first stage, comprising a cross-sectional study, the association between the presence of aneuploidy seen via flow cytometry and sociodemographic characteristics, habits and characteristics relating to HPV and HIV infection was analyzed. In the second stage, comprising a cohort study, it was investigated whether aneuploidy was predictive of CIN evolution.

Results: No association was observed between the presence of aneuploidy and HPV infection, or between its presence and alterations seen in oncotic cytological analysis. On the other hand, aneuploidy was associated with the presence of CIN (p = 0.030) in histological analysis and with nonuse of antiretroviral therapy (p = 0.001). Most of the HIV-positive women (234/272) presented normal CD4+ T lymphocyte counts (greater than 350 cells/mm3) and showed a greater aneuploidy regression rate (77.5%) than a progression rate (23.9%) over a follow-up of up to two years.

Conclusion: Although there was an association between the presence of cervical tissue lesions and the DNA index, the latter was not predictive of progression of the cervical lesion. This suggests that progression of the cervical lesion to cancer in HIV-positive women may also be changed through improvement of the immunological state enabled by using antiretroviral therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140713PMC
May 2015

Comparison of six-minute walk test in children with moderate/severe asthma with reference values for healthy children.

J Pediatr (Rio J) 2014 May-Jun;90(3):250-7. Epub 2013 Nov 1.

Instituto de Medicina Integral Prof. Fernando Figueira, Recife, PE, Brazil.

Objective: to compare physical performance and cardiorespiratory responses in the six-minute walk test (6MWT) in asthmatic children with reference values for healthy children in the same age group, and to correlate them with intervening variables.

Methods: this was a cross-sectional, prospective study that evaluated children with moderate/severe asthma, aged between 6 and 16 years, in outpatient follow-up. Demographic and spirometric test data were collected. All patients answered the pediatric asthma quality of life (QoL) questionnaire (PAQLQ) and level of basal physical activity. The 6MWT was performed, following the American Thoracic Society recommendations. Comparison of means was performed using Student's t-test and Pearson's correlation to analyze the 6MWT with study variables. The significance level was set at 5%.

Results: 40 children with moderate or severe asthma were included, 52.5% males, 70% with normal weight and sedentary. Mean age was 11.3±2.1 years, mean height was 1.5±0.1 m, and mean weight was 40.8±12.6 Kg. The mean distance walked in the 6MWT was significantly lower, corresponding to 71.9%±19.7% of predicted values; sedentary children had the worst values. The difference between the distance walked on the test and the predicted values showed positive correlation with age (r=0.373, p=0.018) and negative correlation with cardiac rate at the end of the test (r=-0.518, p<0.001). Regarding QoL assessment, the values in the question about physical activity limitations showed the worst scores, with a negative correlation with walked distance difference (r=-0.311, p=0.051).

Conclusions: asthmatic children's performance in the 6MWT evaluated through distance walked is significantly lower than the predicted values for healthy children of the same age, and is directly influenced by sedentary life style.
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http://dx.doi.org/10.1016/j.jped.2013.08.006DOI Listing
December 2014
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