Publications by authors named "Patrícia Moura"

72 Publications

Screening of COVID-19 in outpatient children with cancer or solid organ transplantation: preliminary report.

Eur J Pediatr 2021 Mar 26. Epub 2021 Mar 26.

Department of Pediatrics, Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, RJ, Brazil.

Clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric immunosuppressed patients is unknown. Emerging data describe a milder or asymptomatic course in children compared with adults in this scenario. We present the seroprevalence and clinical features of coronavirus disease 2019 in a prospective cohort of 114 immunosuppressed children and adolescents from three groups: kidney transplantation, liver transplantation, and cancer patients. Among the thirty-five (30.7%) patients who had a positive serological test for SARS-CoV-2, 77% did not report previous symptoms and none of them developed any complications of coronavirus disease 2019 (COVID-19) after 30 or more days of follow-up. Among those who were symptomatic, diarrhea, fever, and cough were the most common findings.Conclusion: Seroprevalence of SARS-CoV-2 infection is high among immunosuppressed children and adolescents. COVID-19 has a mild or asymptomatic course in most of these patients. What is Known: • The number of immunosuppressed patients with coronavirus disease 2019 is increasing. • Viral infections have the potential for greater severity in immunocompromised children. What is New: • Seroprevalence for severe acute respiratory syndrome coronavirus 2 in immunocompromised pediatric patients was 31%. • A quarter of the serology-positive patients reported mild symptoms and none of them developed multisystem inflammatory syndrome in children associated with coronavirus disease 2019.
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http://dx.doi.org/10.1007/s00431-021-04044-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994062PMC
March 2021

Intrinsic and Extrinsic Cell Apoptotic Pathways in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Systematic Review.

Viral Immunol 2021 Jan 19. Epub 2021 Jan 19.

Post-graduation Program in Neuropsychiatry and Behavioral Sciences (POSNEURO), Federal University of Pernambuco (UFPE), Recife, Brazil.

We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity.
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http://dx.doi.org/10.1089/vim.2020.0131DOI Listing
January 2021

Acute myeloid leukemia associated with a novel mutation: a case report and the importance to identify haplodeficiency.

Leuk Lymphoma 2020 12 27;61(12):3010-3013. Epub 2020 Jul 27.

Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.

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http://dx.doi.org/10.1080/10428194.2020.1795163DOI Listing
December 2020

Characterization of Antibacterial Proanthocyanidins of Dalbergia monetaria, an Amazonian Medicinal Plant, by UHPLC-HRMS/MS.

Planta Med 2020 Aug 29;86(12):858-866. Epub 2020 May 29.

Natural Products Research Institute (IPPN), Center of Health Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.

is an Amazonian plant whose bark is widely used to treat urinary tract infections. This paper describes a bio-guided study of ethanolic extracts from the bark and leaves of , in a search for metabolites active against human pathogenic bacteria. assays were performed against 10 bacterial strains, highlighting methicillin-sensitive and methicillin-resistant and . Fractioning of the extracts was performed using instrumental and classical techniques, and samples were characterized by UHPLC-HRMS/MS. Ethyl acetate fractions from bark and leaves showed similar antibacterial activities. EAFB is enriched in isoflavone -glucosides and EAFL enriched in proanthocyanidins. Subfractions from EAFL presented higher activity and showed a complex profile of proanthocyanidins constructed by ()-cassiaflavan and ()-catechin units, including dimers, trimers and tetramers. The fragmentation pattern emphasized the neutral loss of cassiaflavan units by quinone-methide fission. Fraction SL7-6, constituted by ()-cassiaflavan-()-cassiaflavan-()-catechin isomers, showed the lowest MIC against the and with values corresponding to 64 and 32 µg/mL, respectively. Cassiaflavan-proanthocyanidins have not been found previously in another botanical genus, except in and the traditional medicinal use of might be related to the antibacterial activity of proanthocyanidins characterized in the species.
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http://dx.doi.org/10.1055/a-1170-8016DOI Listing
August 2020

Association between interferon lambda 3 rs12979860 polymorphism and clinical outcome in dengue virus-infected children.

Int J Immunogenet 2020 Aug 17;47(4):351-358. Epub 2020 Feb 17.

Instituto de Ciências Biológicas, Universidade de Pernambuco, Recife, Brasil.

Single nucleotide polymorphisms (SNPs) in immune-related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue-related symptoms (aged 1-15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV-infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98-3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07-3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08-0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN-λ expression and DENV immunopathogenesis.
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http://dx.doi.org/10.1111/iji.12477DOI Listing
August 2020

Reduced Expression of IL-1β and IL-18 Proinflammatory Interleukins Increases the Risk of Developing Cervical Cancer.

Asian Pac J Cancer Prev 2019 09 1;20(9):2715-2721. Epub 2019 Sep 1.

Laboratory of Molecular Biology of Viruses, Biological Sciences Institute, University of Pernambuco, Brazil.

Background: The objective of this study was to analyze the gene expression profile of the proinflammatory interleukins, (IL-1β and IL-18) in patients with premalignant lesions and cervical cancer. Methods: Total IL-1β and IL-18 mRNA was quantified by qPCR to obtain the expression data in cervical tissues. A total of 74 cervical biopsies were obtained from women undergoing a colposcopy. The samples were divided into: normal (19), low level lesions (LSIL) or NIC I (17), high level lesions (HSIL) or CIN II and CIN III (29) and cancer (9). The normal cervical tissue samples were included as controls. The OR and 95% CI were calculated for the determination of the risk of progression between each type of lesion and cancer using logistic regression. Results: The results showed that an increase in the risk of progression of pre-neoplastic lesions to cancer was between 2.5 and 2.08 times higher in women with lower IL-1β and IL-18 expression, respectively. Conclusions: This study provided evidence that IL-1β and IL-18 are potential biomarkers that can be explored in further studies for monitoring the evolution of pre-neoplastic lesions and avoiding overtreatment or undertreatment of the patients.
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http://dx.doi.org/10.31557/APJCP.2019.20.9.2715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976845PMC
September 2019

Improving the non-sterile food waste bioconversion to hydrogen by microwave pretreatment and bioaugmentation with Clostridium butyricum.

Waste Manag 2019 Apr 27;88:226-235. Epub 2019 Mar 27.

LNEG, Laboratório Nacional de Energia e Geologia, Unidade de Bioenergia, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal. Electronic address:

This work targeted the energy recovery from food waste (FW), aiming at the implementation of a potentially participative process of FW conditioning before the non-sterile biological conversion to hydrogen (H). Food waste conversion was initially performed under sterile conditions, achieving a maximum H productivity of 249.5 ± 24.6 mL H (L h) and a total H production to 4.1 ± 0.2 L L. The non-sterile operation was implemented as a way of process simplification, but the total H production decreased by 59% due to the FW native microorganisms. To counteract this effect, FW was submitted to acid, microwave (MW), and combined acid and MW pretreatment. The application of 4 min MW, 550 W, efficiently controlled the FW microbial counts. The Clostridium butyricum bioaugmented conversion of MW-pretreated FW accelerated the H production to 406.2 ± 8.1 mL (L h) and peaked the total H production and conversion yield to 4.6 ± 0.5 L L and 234.6 ± 55.6 mL (g sugar), respectively. These results exceeded in 63, 12 and 4%, respectively, the H productivity, total production and sugar conversion yield obtained under sterile conditions, and are encouraging for the future implementation of increasingly responsible waste valorisation practices.
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http://dx.doi.org/10.1016/j.wasman.2019.03.021DOI Listing
April 2019

Interactions of mannose binding-lectin with red blood cells by employing cationic quantum dots.

Int J Biol Macromol 2019 Mar 12;125:1168-1174. Epub 2018 Dec 12.

Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. Electronic address:

Mannose-binding lectin (MBL) plays important roles by interacting with specific molecular patterns on cell surfaces, triggering first-line host defense. We investigated the MBL interaction with healthy red blood cell membranes as well as its effects on the membrane rheology. We explored electrostatic interactions between cationic quantum dots (QDs) and negatively charged red blood cell surfaces to quantitatively evaluate membrane electrical charges as well as to investigate the MBL binding to healthy erythrocytes. Results showed that cationic QDs labeled efficiently red blood cells. However, the MBL interaction with erythrocytes prevents the QD labeling. We also observed that red blood cells treated with MBL are more resistant to lysis, suggesting a membrane-stabilizing effect. Moreover, we used a fluorescent anti-MBL antibody and Candida albicans cells to further study the MBL interaction with erythrocytes. Our results of this comparative labeling suggested that either this probe was not effective to detect MBL bound to healthy red blood cells (by its carbohydrate-recognition domain) or the MBL binding to those cells might be occurring via another portion. Thus, our results demonstrated the ability of MBL interacting with healthy red blood cells and pointed out to a new role of this protein as a membrane-stabilizing molecule.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.12.098DOI Listing
March 2019

A portrait of germline mutation in Brazilian at-risk for hereditary breast cancer.

Breast Cancer Res Treat 2018 Dec 29;172(3):637-646. Epub 2018 Aug 29.

Departamento de Biologia Celular e Genética, Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Natal, 59078-970, Brazil.

Purpose: Knowledge about the germline mutational spectrum among Brazilian with hereditary breast and ovarian cancer (HBOC) is limited. Only five studies have performed comprehensive BRCA sequencing, corresponding to 1041 individuals among a Brazilian population of over 207 million people. Herein we aimed to determine the clinical and molecular characteristics of Brazilian patients who underwent oncogenetic counseling and genetic testing of a panel of high-risk and moderate-risk genes from 2009 to 2017.

Methods: Massively parallel sequencing was applied in 157 individuals (132 breast cancer-affected and 25 breast cancer-unaffected individuals) selected according NCCN criteria for hereditary breast cancer. Analysis of mutation segregation in family members was performed by capillary bidirectional sequencing, clinical response after treament and survival analysis was estimated by Kaplan-Meier.

Results: Nineteen germline variants were identified,15 pathogenic and 4 VUS (Variants of Uncertain Significance) in 27 individuals (27/157; 17% P < 0.0001) distributed among 7 genes. Sixty-eight percent of patients (13/19) harbor mutation in BRCA genes and 32% (6/19) in moderate risk genes. This is the first study reporting ATR deleterious germline mutation in association with hereditary breast cancer. Cancer-affected patients with moderate- risk mutation present a more aggressive phenotype, with bilateral cancer (25% vs. 13%, P = 0.0305), high-grade tumors (79.2% vs. 46.3%, P = 0.0001) and triple-negative (50% vs. 22.4%, P < 0.0001). However, no difference in the 5 years overall survival was observed between BRCA and moderate risk groups.

Conclusions: This work highlights the benefits of large-scale sequencing for oncogenetic counseling and extends our understanding about the genetics of hereditary breast cancer in the multi-ethnic Brazilian population.
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http://dx.doi.org/10.1007/s10549-018-4938-0DOI Listing
December 2018

Molecular profile of mannan-binding lectin in hepatitis C patients with MBL gene polymorphisms by a modified mannan-coated nitrocellulose assay.

J Immunol Methods 2018 09 3;460:101-106. Epub 2018 Jul 3.

Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, PE, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.

The aim of this study was to develop an assay to analyze the serum profile of Mannose-binding lectin (MBL) through a simple and "in-house" method (called "dot-N-man"). Furthermore, the study attempted to associate molecular masses of MBL to the profile of MBL gene polymorphisms in patients with hepatitis C. Heterogeneity in molecular masses of MBL is due to the impairment of oligomers formation, which is linked to genetic polymorphisms in the MBL gene. Individuals with AA genotype (wild-type) produce high-molecular-mass proteins, whereas AO and OO individuals produce intermediate and low-molecular-mass proteins, respectively. Sera of thirty patients carrying the hepatitis C virus (HCV) were investigated using MBL binding assay with mannan-coated nitrocellulose (dot-N-man). Purified MBL was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Dot-N-Man assay yielded MBL with molecular masses ranging between 55 and 320 kDa, comparable to low and high molecular mass forms of MBL. Nonreducing SDS-PAGE showed high molecular mass bands in all AA individuals while bands of 270 and 205 kDa were observed in sera for a number of patients with AO and OO genotypes, respectively. Immunoblotting confirmed the MBL samples obtained from the dot-N-man. These results provide new insights to understand the MBL molecular forms profile in patients infected with HCV- which could be useful in future investigations on the influence of the MBL structure/genotype on both the progression of infection and the response to hepatitis C therapy.
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http://dx.doi.org/10.1016/j.jim.2018.06.015DOI Listing
September 2018

Two sides of a coin: GG genotype of C7 provides protection against fibrosis severity while showing a higher risk for hepatocellular carcinoma in patients with hepatitis C.

Hum Immunol 2018 Sep 30;79(9):702-707. Epub 2018 Jun 30.

Institute of Biological Sciences/ICB-UPE, University of Pernambuco, Brazil.

The complement system (CS) is a key element of immunity against pathogens but also seems to influence other events, such as tumorigenesis and tissue repair. Complement component 7 (C7) is a key component of the lytic pathway of CS, leading to the formation of the membrane attack complex (MAC). This study aimed to investigate the existence of the association of a polymorphism in the C7 gene, rs1063499, with hepatic fibrosis and the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C. We analyzed 456 samples from patients with chronic hepatitis C. Real-time PCR was used for allelic discrimination. Patients were classified by their METAVIR score as F1 (n = 100), F2 (n = 83), F3 (n = 101) or F4 (n = 66); 106 patients were diagnosed with HCC. Patients carrying the G/G genotype of C7 had a lower chance of developing severe fibrosis in the recessive model (p = 0.042; OR: 0.65 95% CI 0.41-1.02). However, the G/G genotype frequency was higher in patients with HCC (P = 0.01; OR: 2.07 95% CI 1.20-3.53) and in those with larger tumors (p = 0.04). The G/G C7 genotype seems to be a protective factor against advanced fibrosis; however, it was associated with a higher risk of HCC and the occurrence of larger hepatic nodules, suggesting the involvement of C7 in the physiopathogenesis of HCC and fibrosis in patients with hepatitis C virus (HCV).
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http://dx.doi.org/10.1016/j.humimm.2018.06.009DOI Listing
September 2018

Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy.

Parasitol Int 2018 10 24;67(5):593-596. Epub 2018 May 24.

Aggeu Magalhães Institute, IAM-FIOCRUZ, PE, Brazil. Electronic address:

Chagas disease (CD) is a global problem. Currently, it affects approximately 15 million individuals in Latin America. It is well know that the human immune response is related to different clinical manifestations. Mannose binding lectin (MBL) plays an important role in innate immunity, and it mediates the phagocytosis and complement-mediated destruction of pathogens. The binding capacity is enhanced by the oligomerization of MBL. In this study, we evaluated the serum concentration and the binding capacity of MBL in patients with chronic chagasic cardiomyopathy. A total of 77 patients with chronic CD were included with indeterminate (n = 19), mild cardiac (n = 29) and severe cardiac (n = 29) forms. The serum concentration and the binding capacity were measured using enzyme-linked immunosorbent assays (ELISA). There was no significant difference in the serum MBL levels between the groups of patients. However, we found a relationship between the binding capacity and the groups studied. Our results suggest that binding capacity of MBL could be an indicator of clinical manifestation in Chronic Chagas cardiomyopathy. Furthermore, combined with the Mannose Binding Index results in a useful clinical tool for management of Chronic Chagas Patients.
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http://dx.doi.org/10.1016/j.parint.2018.05.009DOI Listing
October 2018

Enhancement of fermentative hydrogen production from Spirogyra sp. by increased carbohydrate accumulation and selection of the biomass pretreatment under a biorefinery model.

J Biosci Bioeng 2018 Aug 23;126(2):226-234. Epub 2018 Mar 23.

Unidade de Bioenergia, Laboratório Nacional de Energia e Geologia, Estrada do Paço do Lumiar 22, 1649-038 Lisboa, Portugal. Electronic address:

In this work, hydrogen (H) was produced through the fermentation of Spirogyra sp. biomass by Clostridium butyricum DSM 10702. Macronutrient stress was applied to increase the carbohydrate content in Spirogyra, and a 36% (w/w) accumulation of carbohydrates was reached by nitrogen depletion. The use of wet microalga as fermentable substrate was compared with physically and chemically treated biomass for increased carbohydrate solubilisation. The combination of drying, bead beating and mild acid hydrolysis produced a saccharification yield of 90.3% (w/w). The H production from Spirogyra hydrolysate was 3.9 L H L, equivalent to 146.3 mL H g microalga dry weight. The presence of protein (23.2 ± 0.3% w/w) and valuable pigments, such as astaxanthin (38.8% of the total pigment content), makes this microalga suitable to be used simultaneously in both food and feed applications. In a Spirogyra based biorefinery, the potential energy production and food-grade protein and pigments revenue per cubic meter of microalga culture per year was estimated on 7.4 MJ, US $412 and US $15, respectively, thereby contributing to the cost efficiency and sustainability of the whole bioconversion process.
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http://dx.doi.org/10.1016/j.jbiosc.2018.02.017DOI Listing
August 2018

Association of the Polymorphism (Val16Ala) and SOD Activity with Vaso-occlusive Crisis and Acute Splenic Sequestration in Children with Sickle Cell Anemia.

Mediterr J Hematol Infect Dis 2018 21;10(1):e2018012. Epub 2018 Feb 21.

Biological Science Institute, University of Pernambuco Pernambuco, Brazil.

The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively). These results suggest that the SOD2 polymorphism associated with low SOD activity could be a susceptibility factor for the occurrence of VOC and ASS.
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http://dx.doi.org/10.4084/MJHID.2018.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841937PMC
February 2018

Cognitive Dysfunction and Single Nucleotide Polymorphisms in Hepatitis C Virus-Infected Persons: A Systematic Review.

Viral Immunol 2017 12 10;30(10):703-707. Epub 2017 Oct 10.

6 Hospital Universitário Oswaldo Cruz; Medical Sciences College, Universidade de Pernambuco (UPE) , Recife, PE, Brazil .

The aim of this study was to realize a systematic review to identify data reported in the literature involving people infected by hepatitis C virus (HCV) with cognitive dysfunctions and single nucleotide polymorphisms (SNPs). The research was realized in six databases and the selection of studies was performed in two stages. Initially, we searched indexed articles from the following electronic databases: SciELO, MEDLINE, PubMed, HighWire, LILACS, and ScienceDirect. Then the articles were completely read and those that did not meet the eligibility criteria were excluded. Therefore, 5,669 articles were obtained and, of these, 25 were selected. Finally, one article involving people with HCV and cognitive impairment was included in the review. The frequency of the APOE-ɛ4 allele in people with HCV and mild liver disease was significantly lower in those with work memory impairment (p = 0.003) and attention (p = 0.008). This situation differs from other studies that showed an association between ɛ4 allele high frequency and cognitive decline. Thus, studies with larger samples involving people with HCV, cognitive alterations, and SNPs are necessary, in view of the lack of this theme in the literature and the divergences in the findings.
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http://dx.doi.org/10.1089/vim.2017.0084DOI Listing
December 2017

Combined genotypes of the MBL2 gene related to low mannose-binding lectin levels are associated with vaso-occlusive events in children with sickle cell anemia.

Genet Mol Biol 2017 Jul-Sep;40(3):600-603. Epub 2017 Aug 21.

Instituto de Ciências Biológicas/Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, PE, Brazil.

Sickle cell anemia (SCA) presents heterogenous clinical manifestations that cannot be explained solely by alterations to hemoglobin (Hb); other components such as endothelial adhesion, thrombosis and inflammation may be involved. The mannose-binding lectin (MBL) has an important role in innate immunity and inflammatory diseases. In this report, we describe an association between MBL2 polymorphism related to low production of serum MBL and the frequency of vasoocclusive events (FVOE) in children ≤ 5 years old with SCA (p = 0.0229; OR 5.55; CI 1.11-27.66). Further studies are needed to explore the role of low MBL2 in the pathophysiology of vasoocclusive events in SCA.
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http://dx.doi.org/10.1590/1678-4685-GMB-2016-0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596363PMC
August 2017

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects.

Hum Immunol 2017 Oct 29;78(10):649-656. Epub 2017 Jul 29.

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil. Electronic address:

Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.
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http://dx.doi.org/10.1016/j.humimm.2017.07.013DOI Listing
October 2017

Mediators Go Together: High Production of CXCL9, CXCL10, IFN-γ, and TNF-α in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.

AIDS Res Hum Retroviruses 2017 Nov 25;33(11):1134-1139. Epub 2017 Jul 25.

1 Department of Virology and Experimental Therapy (LaViTE), Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz) , Recife, Brazil .

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic demyelinating and disabling syndrome caused by human T lymphotropic virus 1 (HTLV-1). Although the pathogenic mechanisms that lead to HAM/TSP outcome have not been elucidated, genetic and immunological factors may be involved in the myelopathy occurrence. This study aimed to compare cytokines, chemokines, and nitric oxide (NO) levels in asymptomatic and HAM/TSP HTLV-1-infected patients. The study group consisted of 21 HAM/TSP and 48 asymptomatic HTLV-1 patients. Chemokines (CCL5, CCL2, CXCL8, CXCL9, and CXCL10) and cytokines [IL-2, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10] were measured using cytometric bead array, whereas NO production was measured after reaction of supernatants with nitrate reduction solution. CXCL9 and CXCL10 chemokines levels were found to be higher in the HAM/TSP group. CXCL9 was also strongly correlated with CXCL10 and both CXCL9 and CXCL10 were moderately correlated with CCL2 and CCL5 levels, in both HAM/TSP and asymptomatic groups. There was no significant difference related to NO, IL-4, IL-6, and IL-10 levels between the clinical groups but TNF-α and IFN-γ levels were increased in HAM/TSP patients. Thus, factors such as CXCL9, CXCL10, TNF-α, and IFN-γ could be good prognostic biomarker candidates, and further studies may help to clarify their association with HAM/TSP immunopathogenesis.
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http://dx.doi.org/10.1089/AID.2016.0296DOI Listing
November 2017

Bifidobacterial growth stimulation by oligosaccharides generated from olive tree pruning biomass.

Carbohydr Polym 2017 Aug 9;169:149-156. Epub 2017 Apr 9.

Department of Chemical, Environmental and Materials Engineering, Universidad de Jaén, Campus Las Lagunillas, 23071, Jaén, Spain. Electronic address:

This work aims to evaluate the prebiotic potential of oligosaccharides (OS) obtained from autohydrolysis of olive tree pruning biomass (OTPB). Two selected fractions (F1 and F2) were characterized and used in in vitro fermentations by two Bifidobacterium spp. (B. adolescentis and B. longum) and one fecal inoculum. The fraction F1 presented a lower average degree of polymerization (DP) mainly with OS ranging from 3 to 6 DP, whereas the fraction F2 corresponded to a pool of unsubstituted and acetylated oligomers with DP between 4 and 19. In the fermentation by Bifidobacterium, F1 supported a higher biomass formation, OS consumption and organic acids production than F2. With the fecal inoculum, the accumulation of organic acids, as the sum of acetate, propionate and butyrate, was similar for F1 and F2 (107 and 101mM, respectively). The bifidobacteria counts also increased during the incubation time for both OS fractions.
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http://dx.doi.org/10.1016/j.carbpol.2017.04.014DOI Listing
August 2017

IL17A Polymorphism Is Not Associated with Human T-Lymphotropic Virus 1-Associated Myelopathy/Tropical Spastic Paraparesis.

Viral Immunol 2017 05 14;30(4):298-301. Epub 2017 Apr 14.

1 Department of Virology, Centro de Pesquisas Aggeu Magalhães (CPqAM) Research Center , Fundação Oswaldo Cruz (Fiocruz), Recife, Brazil .

The human T-lymphotropic virus 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study investigated the association between the rs2275913 polymorphism in the IL17A gene and the development of HAM/TSP. Peripheral blood samples were collected from 116 patients (29 symptomatic patients with HAM/TSP and 87 asymptomatic) with a positive diagnosis of HTLV-1. The single nucleotide polymorphism genotyping was carried out by real time PCR using TaqMan probes. In addition, serum levels of IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, and IL-17 were measured in 64 infected individuals from the study (47 asymptomatic and 17 HAM/TSP), using cytometric bead array technique. No significant differences were found in genotypic and allelic frequencies between the groups. Analysis of cytokine levels showed highest concentrations of IFN-γ and TNF-α in HAM/TSP patients. The results of the present study, therefore, suggest a lack of association between the rs2275913 polymorphism in the IL17A gene and the presence of HAM/TSP.
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http://dx.doi.org/10.1089/vim.2016.0152DOI Listing
May 2017

Serum cytokine/chemokine profiles in patients with dengue fever (DF) and dengue hemorrhagic fever (FHD) by using protein array.

J Clin Virol 2017 04 17;89:39-45. Epub 2017 Feb 17.

Departamento de Virologia, Centro de Pesquisas Aggeu Magalhães-Fundação Oswaldo Cruz-Fiocruz, Recife, PE, Brazil. Electronic address:

Background: DENV infection can induce different clinical manifestations varying from mild forms to dengue fever (DF) or the severe hemorrhagic fever (DHF). Several factors are involved in the progression from DF to DHF. No marker is available to predict this progression. Such biomarker could allow a suitable medical care at the beginning of the infection, improving patient prognosis.

Objectives: The aim of this study was to compare the serum expression levels of acute phase proteins in a well-established cohort of dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, in order to individuate a prognostic marker of diseases severity.

Study Design: The serum levels of 36 cytokines, chemokines and acute phase proteins were determined in DF and DHF patients and compared to healthy volunteers using a multiplex protein array and near-infrared (NIR) fluorescence detection. Serum levels of IL-1ra, IL-23, MIF, sCD40 ligand, IP-10 and GRO-α were also determined by ELISA.

Results: At the early stages of infection, GRO-α and IP-10 expression levels were different in DF compared to DHF patients. Besides, GRO-α was positively correlated with platelet counts and IP-10 was negatively correlated with total protein levels.

Conclusions: These findings suggest that high levels of GRO-α during acute DENV infection may be associated with a good prognosis, while high levels of IP-10 may be a warning sign of infection severity.
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http://dx.doi.org/10.1016/j.jcv.2017.02.007DOI Listing
April 2017

Role of Interleukin-22 in chronic liver injury.

Cytokine 2017 10 2;98:107-114. Epub 2016 Nov 2.

Instituto de Ciências Biológicas, Universidade de Pernambuco (UPE), Recife, Brazil.

Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and frequently requires liver transplantation. The host immune response has an important role driving fibrosis deposition by activating hepatic stellate cells (HSCs). Interleukin-22 (IL-22) is a cytokine that plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces. Data from literature suggest that IL-22 has a protective role in the liver by reducing fibrosis in some pathological conditions, however the results are contradictory. This review highlights current knowledge of IL-22' role in chronic liver injury, as well as its therapeutic potential for the treatment of chronic liver injury.
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http://dx.doi.org/10.1016/j.cyto.2016.08.023DOI Listing
October 2017

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia.

PLoS One 2016 7;11(9):e0162297. Epub 2016 Sep 7.

Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.

Introduction: Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.

Objective: To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.

Materials And Methods: SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.

Results: GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012).

Conclusion: Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014331PMC
August 2017

The association between vitamin D receptor gene polymorphisms (TaqI and FokI), Type 2 diabetes, and micro-/macrovascular complications in postmenopausal women.

Appl Clin Genet 2016 1;9:131-6. Epub 2016 Aug 1.

Division of Endocrinology and Diabetes, Agamenon Magalhães Hospital.

Introduction: Since there is evidence of the action of vitamin D as a modulator of insulin release and atherosclerosis, it may well be that the vitamin D receptor polymorphisms are associated with diabetes and its chronic complications.

Aims: To examine the associations between vitamin D receptor polymorphisms (FokI and TaqI) and Type 2 diabetes (T2DM) and its associated chronic complications in postmenopausal women.

Methods: This cross-sectional study analyzed 100 postmenopausal women with T2DM (mean age 65.7±7.18 years) and 100 postmenopausal women without diabetes in the control group (mean age 65.1±9.18 years; P=0.1608). We evaluated clinical and metabolic parameters and analyzed TaqI and FokI polymorphisms.

Results: There were no significant differences in genotype and allele frequencies between patients and controls in either of the polymorphisms studied. In the group of patients with diabetes, there were no significant differences in either polymorphism in relation to stroke, retinopathy, nephropathy, or neuropathy. However, in patients with T2DM and coronary artery disease, f genotype (P=0.0361) and the combination of Ff + ff genotypes were observed less frequently (P=0.0462).

Conclusion: This study suggests the potential protective factor of FokI polymorphism for coronary artery disease in postmenopausal women with T2DM in the recessive model.
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http://dx.doi.org/10.2147/TACG.S101410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975152PMC
August 2016

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase.

Mem Inst Oswaldo Cruz 2016 May;111(6):378-84

Fundação Oswaldo Cruz, Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Virologia, Recife PE , Brasil, Fundação Oswaldo Cruz, Centro de Pesquisas Aggeu Magalhães, Departamento de Virologia, Recife, PE, Brasil.

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.
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http://dx.doi.org/10.1590/0074-02760150453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909036PMC
May 2016

Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity.

Hum Immunol 2016 Jul 11;77(7):571-5. Epub 2016 May 11.

Instituto de Ciências Biológicas, Universidade de Pernambuco (UPE), Brazil. Electronic address:

Dengue is the main arbovirosis in the tropical and subtropical areas of the world. The majority of infected individuals present an asymptomatic outcome while others progress to dengue fever (DF) or dengue haemorrhagic fever (DHF). Dengue infection evolution to severe outcomes is in part, related to innate immunity response. The MBL2 gene encodes for a pathogen recognition pattern molecule, the mannose-binding lectin (MBL). Variant alleles at promoter and structural regions of the MBL2 are related to serum MBL levels and function. Due to the important inflammatory modulation role of MBL, MBL2 polymorphisms could influence dengue progression. Therefore, this study investigated associations of MBL2 polymorphisms and serum MBL levels in patients with dengue. Genotyping of promoter and structural regions of MBL2 was performed by real-time PCR using Taqman® probes in 161 patients presenting DF or DHF outcome. For the serum MBL determination a commercial ELISA kit was used. The variant OO genotype and O allele were associated with DHF (p=0.008 and p=0.009 respectively). Haplotypes correlated to MBL low levels were associated with DHF (p=0.04). Our results support the hypothesis that patients carrying genotypes or haplotypes of low production of MBL would be more susceptible to DHF.
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http://dx.doi.org/10.1016/j.humimm.2016.05.006DOI Listing
July 2016

Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome.

Ann Hum Genet 2016 May 18;80(3):145-53. Epub 2016 Mar 18.

Instituto de Ciências Biológicas - ICB, Universidade de Pernambuco - UPE, Brazil.

The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.
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http://dx.doi.org/10.1111/ahg.12152DOI Listing
May 2016

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

J Med Virol 2016 09 21;88(9):1587-95. Epub 2016 Mar 21.

Setor de Virologia do Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Brazil.

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24501DOI Listing
September 2016

A label-free electrochemical immunosensor for hepatitis B based on hyaluronic acid-carbon nanotube hybrid film.

Talanta 2016 28;148:209-15. Epub 2015 Oct 28.

Biomedical Engineering Laboratory, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235-Cidade Universitária, 50670-901 Recife, Pernambuco, Brazil. Electronic address:

An electrochemical immunosensor developed for detection of antibodies to hepatitis B core protein (anti-HBc) is described. Anti-HBc is the earliest serological marker from hepatitis B virus (HBV) infection, remaining all life after contact with virus, being considered the most important marker for uses in screening of blood bank. A nanohybrid surface assembled onto a glassy carbon electrode consisting of amino carbon nanotubes recovered by hyaluronic acid was used as sensing platform to detect the anti-HBc. All the steps of electrode surface modification were characterized by Scanning Electronic Microscopy and extensively evaluated by electrochemical techniques. The electrode response was measured by direct anti-HBc antigen interactions by square wave voltammetry, dispensing uses of label or chemical mediators. Under optimal conditions, the anodic peak current which was proportional to the anti-HBs concentration. The immunosensor response was linear toward anti-HBc in concentrations up to 6 ng mL(-1), with a detection limit of 0.03 ng mL(-1). The linear range achieved was according to clinical level, indicating the immunosensor as promising tool for use as a criterion for blood bag disposal. The enhancement of the hyaluronic acid by carbon nanotube promoted an increase of charge electron transfer, besides a stable platform for HBc.
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http://dx.doi.org/10.1016/j.talanta.2015.10.083DOI Listing
September 2016
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