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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus 2019 (COVID-19), which was declared a pandemic in March 2020 by the World Health Organization due the rapid spread representing a global health crisis. The disease is characterized by a wide clinical spectrum ranging from asymptomatic forms until severe viral pneumonia, which can to evolve to severe acute respiratory syndrome, especially in elderly patients and/or with comorbidities. An efficient assembly of the immunological response of the patients becomes fundamental against SARS-CoV-2 infection and it has been demonstrating a significant relationship between the severity of the disease and expression profile of the immune cells and the levels of pro-inflammatory cytokines. This review aims to presents the main immunological mechanisms developed during the infection by SARS-CoV-2 in the evolution of the severe cases of COVID-19. The immune dysregulation of the Th1 cellular response standard, the instability in the production of neutralizing antibodies by plasma B cells, the difference in tropism of CD8+ T cells against virus proteins in early infection, late infection and reinfections, dynamic of alveolar macrophages and pulmonary innate lymphoid cells (TCR γδ) of the natural imune response and the high level of pro-inflammatory cytokines can determine the main cause of breath tissues damages and, consequently, a greater severity of the disease. Therefore, a complete understanding of the main immunological changes involved in SARS-CoV-2 infection can identify possible biomarkers in the evaluation of early prognosis of the severe cases of COVID-19, making possible better therapeutic success to the patients.
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COVID-19 , Pneumonia Viral , Idoso , Humanos , Imunidade Inata , Linfócitos , SARS-CoV-2RESUMO
Corynebacterium pseudotuberculosis is a bacillus that causes caseous lymphadenitis in small ruminants, leading to great losses to rural producers; thus, an efficient diagnosis is necessary for using disease control measures. This study aimed to evaluate the antigenic potential of four C. pseudotuberculosis recombinant proteins (rSodC, rPknG, rNanH, and rSpaC) against sera of goat and sheep experimentally infected with one of three different C. pseudotuberculosis strains. Goats were infected with CAP76 or CAP21 strain (n = 10), sheep with VD57 strain (n = 6), and a group of not-infected animals (goats and sheep) were kept as a healthy control (healthy n = 12). Sera were collected at 0, 14, 60, 90, 180, or 190 days after inoculation for antigenicity testing using Western blotting and enzyme-linked immunosorbent assay (ELISA) techniques. Cross-reactivity tests with recombinant proteins were performed in goat serum experimentally vaccinated with Nocardia sp. or Rhodococcus equi bacterin. The rSodC protein showed discriminatory antigenic reactivity with a statistically significant difference against three different C. pseudotuberculosis strains evaluated in goats and sheep samples, while rPknG showed statistical significance only against two C. pseudotuberculosis strains evaluated in goats. rSodC was proved to be a strong candidate as a tool for diagnosis of C. pseudotuberculosis infection, once it was able to recognize antibodies against all strains evaluated in goats and sheep.
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Infecções por Corynebacterium , Doenças das Cabras , Linfadenite , Doenças dos Ovinos , Animais , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/microbiologia , Infecções por Corynebacterium/veterinária , Doenças das Cabras/diagnóstico , Doenças das Cabras/microbiologia , Doenças das Cabras/prevenção & controle , Cabras , Linfadenite/diagnóstico , Linfadenite/microbiologia , Linfadenite/veterinária , Proteínas Recombinantes/genética , Ovinos , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/microbiologiaRESUMO
Hepatitis C virus (HCV) and human T-lymphotropic virus type 1 (HTLV-1) coinfection occurs in many regions. However, few studies have focused on the natural history of HCV-induced liver disease in coinfected patients. To describe the clinical, epidemiological, and histopathological aspects of HTLV-1/HCV coinfection in Brazil. A cross-sectional study with 23 patients coinfected with HCV/HTLV. The control groups consisted of 21 patients monoinfected with HCV and 20 patients monoinfected with HTLV-1. The cytokine profiles (Th1 and Th2 cell responses), clinical, laboratory features, and histopathological aspects were examined. The control group for cytokine analysis validation consisted of patients monoinfected with HTLV, and a fourth group consisted of healthy blood donors. No anthropometric differences present between the three infected groups. We observed higher serum concentrations of IFN-γ in patients coinfected with HCV/HTLV-1 than those in HCV monoinfected patients. The HCV/HTLV-1 coinfected group also exhibited a higher degree of liver steatosis than the HCV monoinfected patients. Results suggest that HCV/HTLV-1 coinfection may result in a different pattern of HCV infection due to the immunologic disorders likely associated with HTLV-1, but there is no clear evidence of the HTLV role in the natural history of HCV infection. J. Med. Virol. 88:1967-1972, 2016. © 2016 Wiley Periodicals, Inc.
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Coinfecção/epidemiologia , Coinfecção/fisiopatologia , Fígado Gorduroso/virologia , Infecções por HTLV-I/complicações , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Adulto , Brasil/epidemiologia , Coinfecção/complicações , Coinfecção/virologia , Estudos Transversais , Citocinas/imunologia , Fígado Gorduroso/etiologia , Feminino , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Hepacivirus/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Hepatite C/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologiaRESUMO
UNLABELLED: The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαß and TCRγδ+) and NK cells from blood donors in Salvador-Bahia, Brazil. RESULTS: The proportion of included male subjects was 73.7% and the median ages of males (34) and females (35) were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186) cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62) and 24% (9-28), respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03) in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.
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Linfócitos B/citologia , Doadores de Sangue , Células Matadoras Naturais/citologia , Subpopulações de Linfócitos/citologia , Adolescente , Adulto , Brasil , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
The pathogenesis of acute myeloid leukemia (AML) involves mutations in genes such as FLT3 and NPM1, which are also associated with the prognosis of the disease. The immune system influences disease progression, but the mechanisms underlying the interaction between the immune system and AML are not clear. In this study, the profiles of lymphocytes and cytokines were described in individuals with AML stratified by molecular changes associated with prognosis. The participants included in this study were newly diagnosed AML patients (nâ =â 43) who were about to undergo chemotherapy. Subtypes of lymphocytes in peripheral blood, including B cells, T cells, and natural killer cells, and serum concentrations of cytokines, including Th1, Th2, and Th17, were studied by flow cytometry assays (BD FACSCanto II). The correlations between lymphocyte subsets, cytokines, and genetic/prognostic risk stratification (based on the FLT3 and NPM1 genes) were analyzed. The differences in B lymphocytes (%), T lymphocytes (%), plasmablasts (%), leukocytes (cells/µl), and tumor necrosis factor (pg/ml) were determined between groups with FLT3-ITD+ and FLT3-ITD- mutations. The presence of mutations in NPM1 and FLT3-ITD and age suggested changes in the lymphocyte and cytokine profile in individuals with AML.
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Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals' expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies.
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Mieloma Múltiplo , Humanos , Medula Óssea/patologia , Brasil , Hematologia/métodos , Aprendizado de Máquina , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Redes Neurais de Computação , Plasmócitos/patologiaRESUMO
BACKGROUND AND AIMS: Hepatitis Delta virus (HDV) genotype 3 is responsible for outbreaks of fulminant hepatitis in Northeastern South America. This study investigates if systemic inflammatory molecules are differentially expressed in patients with advanced fibrosis chronically infected with Hepatitis Delta virusgenotype 3(HDV-3). METHODS: Sixty-one patients from the north of Brazil coinfected with hepatitis B virus (HBV)/HDV-3 were analyzed. HDV quantification and genotyping were performed by semi-nested real-time polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) methodologies. Ninety-two systemic inflammatory molecules (SIMs) were measured by Proximity Extension Assay (PEA) technology. The Shapiro-Wilk, Student's t-test, Mann-Whitney tests, and logistic regression analysis were used when appropriate. RESULTS: The median age was 41 years, and all patients were HBeAg negative. Advanced fibrosis or cirrhosis was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Established non-invasive fibrosis scores (APRI, FIB-4, and AST/ALT ratio) revealed low sensitivities and positive predictive values (PPVs) with an AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP.4, CCL19, EN.RAGE, SCF, and IL18 showed a positive correlation with fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an odds ratio of 2.202 for advanced fibrosis. CONCLUSIONS: Standard non-invasive fibrosis scores showed poor performance in HDV-3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV-3 infection.
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Morais et al. conducted a pioneering study with Brazilian indigenous populations to determine reference values for immunologic cells from healthy adult individuals. The main findings included a higher relative median for T lymphocyte subsets in females than males, and T CD3+, T CD4+, and T CD8+ relative values were statistically different when compared with Brazilian populations from other Brazilian regions. The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Demographic and ethnic diversity of the Brazilian population can be associated with quantitative modifications in the immunologic cells of healthy individuals. OBJECTIVE: The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. METHODS: Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. RESULTS: The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. CONCLUSION: To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.
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Linfócitos B , Monócitos , Adulto , Masculino , Humanos , Feminino , Valores de Referência , Brasil , Citometria de Fluxo , Contagem de LinfócitosRESUMO
UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Hepatitis B (HB) is one of the most prevalent occupational infections in health attendance environments. According to the Brazil Ministry of Health, health professionals must be vaccinated against the hepatitis B virus (HBV) and provide laboratory proof of immunization. AIMS: To evaluate the seroprevalence of HBV infection and to analyze the response to vaccine by measuring serum antibodies against HBV surface antigen (anti-HBs) levels in a sample of students and health professionals at the Federal University of Bahia. RESULTS: As part of this cross-sectional study, a campaign against occupational HB was launched in 2007 and vaccination and blood samples were collected for analysis of the following serological markers: HBV surface antigen (HBsAg) and anti-HBs (measured by enzyme-linked immunoassay) and total antibodies against HBV core antigen (anti-HBc). The study sample comprised 766 people. Global seropositivity for HBV was 1.7%: 0.5% in the students and 8.8% in the professionals. In a group of volunteers, a serological profile compatible with postvaccine immunity was shown by 95% of volunteers with proof of vaccination and by 81.8% of volunteers without proof of vaccination. CONCLUSIONS: In conclusion, this study shows that it is important to promote vaccination campaigns and improve knowledge and awareness about HB among health care workers and higher education students.
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Pessoal de Saúde , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Estudantes , Universidades , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Estudos Transversais , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Estudos Soroepidemiológicos , Resultado do Tratamento , Adulto JovemRESUMO
In this study, we investigated the capacity of the recombinant proteins SpaC, NanH, SodC, and PLD of C. pseudotuberculosis to trigger protective humoral and cellular immune responses against experimentally induced C. pseudotuberculosis infection in sheep. The antigens were produced in a heterologous system and were purified by affinity chromatography. Nine sheep were randomly divided into three groups, which were immunized as follows: Group 1 (control)-a mix of adjuvants composed of the inactivated T1 strain of C. pseudotuberculosis and commercial Montanide™ISA 61 VG (T1M); Group 2-rSpaC, rSodC, rPLD, and T1M; Group 3-rNanH, rSodC, rPLD, and T1M. All groups were immunized twice (on days 0 and 30) and challenged on day 90 of the experiment. Humoral and cellular immune responses were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) to quantify the IgG antibodies and interferon-gamma (IFN-y). Both vaccine formulations with recombinant proteins (groups 2 and 3) could induce a significant humoral IgG immune response in sheep. The proteins rSodC, rPLD, and rNanH were more immunogenic, inducing significant levels of IgG antibodies after the first dose of the vaccine or after the challenge, maintaining constant levels until the end of the experiment. However, it was not possible to differentiate between the cellular responses induced by the vaccines. This lack of effectiveness points toward the need for further studies to improve the efficacy of this subunit-based vaccine approach.
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VEGF and TGF-ß1 are cytokines that stimulate tissue invasion and angiogenesis. These factors are considered as molecular targets for the therapy of glioblastoma. Bevacizumab, a recombinant humanized monoclonal antibody developed against VEGF, inhibits endothelial cell proliferation and vessel formation. Flavonoids obtained from Dimorphandra mollis and Croton betulaster have been described as proliferation inhibitors of a human glioblastoma derived cell line. VEGF and TGF-ß1 levels were dosed by ELISA in a GL-15 cell line treated with bevacizumab and also with the flavonoids rutin, 5-hydroxy-7,4'-dimethoxyflavone, casticin, apigenin and penduletin. Rutin reduced the VEGF and TGF-ß1 levels after 24 h but not after 72 h. The other flavonoids significantly reduced TGF-ß1 production. Bevacizumab reduced only the VEGF levels in the supernatant from GL-15 cultures. These results suggest that the flavonoids studied, and commonly used in popular medicine, present an interesting subject of study due to their potential effect as angiogenic factor inhibitors.
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Inibidores da Angiogênese/farmacologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Flavonoides/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Extratos Vegetais/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Bevacizumab , Croton/química , Fabaceae/química , Glioblastoma/irrigação sanguínea , Humanos , Neovascularização Patológica/metabolismo , FitoterapiaRESUMO
BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.
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Antivirais/uso terapêutico , Antígenos HLA-C/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Polimorfismo Genético , Receptores KIR2DL5/genética , Adulto , Idoso , Estudos de Coortes , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Frequência do Gene , Antígenos HLA-C/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Probabilidade , Prognóstico , Receptores KIR2DL5/efeitos dos fármacos , Receptores de Células Matadoras Naturais/efeitos dos fármacos , Receptores de Células Matadoras Naturais/genética , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Ribavirina/uso terapêutico , Estatísticas não Paramétricas , Falha de Tratamento , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
The potential use of bone marrow mesenchymal stromal cells (BM-MSCs) for the treatment of osteonecrosis in sickle cell disease (SCD) patients is increasing. However, convenient BM-MSC quantification and functional property assays are critical factors for cell-based therapies yet to be optimized. This study was designed to quantify the MSC population in bone marrow (BM) samples from SCD patients with osteonecrosis (SCD group) and patients with osteoarticular complications not related to SCD (NS group), using flow cytometry for CD271+CD45-/low cell phenotype and CFU-F assay. We also compared expanded BM-MSC osteogenic differentiation, migration, and cytokine secretion potential between these groups. The mean total cell number, CFU-F count, and CD271+CD45-/low cells in BM mononuclear concentrate were significantly higher in SCD than in NS patients. A significant correlation between CD271+CD45-/low cell number and CFU-F counts was found in SCD (r = 0.7483; p = 0.0070) and NS (r = 0.7167; p = 0.0370) BM concentrates. An age-related quantitative reduction of CFU-F counts and CD271+CD45-/low cell number was noted. Furthermore, no significant differences in the morphology, replicative capacity, expression of surface markers, multidifferentiation potential, and secretion of cytokines were found in expanded BM-MSCs from SCD and NS groups after in vitro culturing. Collectively, this work provides important data for the suitable measurement and expansion of BM-MSC in support to advanced cell-based therapies for SCD patients with osteonecrosis.
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The effects of arborinine, an alkaloid extracted from Erthela bahiensis and of rutin, a flavonoid obtained from Dimorphandra mollis (Benth.), Brazilian medicinal plants, on the viability and function of a murine B-cell hybridoma as a tumor model were investigated. The flavonoid rutin at 50 microM induced an increase in the number of apoptotic cells of one- to fivefold and reductions in cellular proliferation and monoclonal antibody production. Less but still significant necrosis was also induced by rutin under the same experimental conditions. On the other hand, the alkaloid arborinine exerted no significant effects on the studied parameters.
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Acridinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Fabaceae/química , Extratos Vegetais/farmacologia , Rutaceae/química , Rutina/farmacologia , Acridinas/isolamento & purificação , Animais , Anticorpos Monoclonais/biossíntese , Linfócitos B , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Hibridomas/efeitos dos fármacos , Hibridomas/patologia , Camundongos , Necrose/induzido quimicamente , Rutina/isolamento & purificação , SementesRESUMO
INTRODUCTION: Toxoplasmosis is an asymptomatic disease that can lead to systemic disease in the fetus of pregnant women with primary infection. This study aimed to determine the prevalence of toxoplasmosis, associated factors, and correlation between the serology of pregnant women and their pets, in the municipality of Ilhéus, Bahia, Brazil. METHODS: This cross-sectional study was conducted in 196 pregnant women and their cats or dogs (n=89). Semi-structured interviews were conducted and serum samples from the pregnant women were tested to detect IgM and IgG antibodies against Toxoplasma gondii, and avidity tests were performed for IgM-positive samples. The serum collected from pets were tested for IgG antibodies, and IgM antibodies in cats. A non-conditional logistic regression analysis was performed to identify infection-associated factors. RESULTS: IgG and IgM antibodies were detected in 67.9% (133/196) and 1.5% (3/196) samples, respectively, for women with an avidity of over 60%. Age ≥ 25 and the presence of cats in the vicinity were found to be associated with infection, while the level of education and previous orientation toward prevention of toxoplasmosis were protective factors in pregnant women. IgG antibodies were detected in 46.1% (41/89) of the animals, and cats were found to be negative for IgM. For the animals, age ≥ 1 year was a factor associated with infection. There was no correlation between serology of the pregnant women and the animals (p=0.15). CONCLUSIONS: An elevated prevalence of toxoplasmosis was detected in the region. Therefore, the adoption of preventive measures by public healthcare bodies is recommended.
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Anticorpos Antiprotozoários/sangue , Complicações Parasitárias na Gravidez/epidemiologia , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Adulto , Animais , Brasil/epidemiologia , Gatos , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/etiologia , Prevalência , Fatores de Risco , Toxoplasmose/diagnóstico , Toxoplasmose/etiologiaRESUMO
UNLABELLED: Periodontitis is an inflammatory oral disease caused by multifactorial intrinsic and extrinsic agents, including Gram-negative bacteria such as Porphyromonas gingivalis. OBJECTIVE: To evaluate if there is difference in the serum levels of IgA, IgG and IgG subclasses reactive to Porphyromonas gingivalis in subjects with different periodontal conditions. METHODS: The study included 89 patients divided into four groups: 29 subjects with moderate or severe chronic periodontitis (CP), 12 with aggressive periodontitis (AP), 22 with gingivitis or mild periodontitis (GP), and 26 healthy controls (HC). Humoral response was assayed by enzyme-linked immunosorbent assay (ELISA) to verify serum levels of IgG, IgG1, IgG2, IgG3, IgG4 and IgA serum levels reacting to crude P. gingivalis ATCC 33277 sonicate extract and fraction IV, an enrichment of the immunoreactive bands of the crude extract obtained by chromatography. RESULTS: IgA, IgG (p < 0.01), IgG2, IgG3 and IgG4 serum level reactions to fraction IV were higher in the CP group compared with the healthy control. The CP group had higher levels of IgG and IgG4 to both antigens than the GP group, and higher levels of IgG and IgG4 to sonicate extract than the AP group. There were statistically significant differences in serum levels of IgG to both antigens (p < 0.01), IgG2 to fraction IV (p < 0.01), IgG3 to fraction IV (p < 0.05) and IgG4 to both antigens (p < 0.05) between AP and HC groups. IgG1 titers to sonicate extract were significantly higher (p < 0.05) in the GP group in comparison to the AP group. CONCLUSIONS: The findings of this study suggest that there are differences in the serum levels of IgA, IgG and IgG subclasses in patients with different periodontal conditions.
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Anticorpos Antibacterianos/sangue , Infecções por Bacteroidaceae/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/imunologia , Adulto , Anticorpos Antibacterianos/análise , Antígenos de Bactérias/imunologia , Western Blotting , Cromatografia , Doença Crônica , Eletroforese em Gel de Poliacrilamida , Feminino , Hemorragia Gengival/imunologia , Hemorragia Gengival/microbiologia , Gengivite/imunologia , Gengivite/microbiologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Masculino , Perda da Inserção Periodontal/imunologia , Perda da Inserção Periodontal/microbiologia , Bolsa Periodontal/imunologia , Bolsa Periodontal/microbiologia , Periodontite/imunologia , Frações Subcelulares/imunologiaRESUMO
OBJECTIVE: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. METHODS: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. RESULTS: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. CONCLUSIONS: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.
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Testes Diagnósticos de Rotina/métodos , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose/diagnóstico , Adulto , Antibióticos Antituberculose/uso terapêutico , Brasil , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Centros de Atenção Terciária , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
INTRODUCTION: Latent tuberculosis infection diagnosis based on the release of interferon-gamma in cultures of peripheral blood cells stimulated with Mycobacterium tuberculosis antigens has replaced the tuberculin skin test in many countries with low tuberculosis prevalence. The IFN-γ production can be influenced by genetic polymorphisms, of which the IFNG+874 (rs62559044) locus is the most studied. We investigated the possible influence of the IFNG+874 A/T polymorphism on interferon-gamma test performance. METHODS: Patients diagnosed with pulmonary tuberculosis (75), volunteers with positive tuberculin skin test (70) and healthy volunteers with negative tuberculin skin test and no history of contact with tuberculosis (57) were evaluated regarding the IFNG+874 genotype and the IFN-γ levels in whole blood cultures performed using an interferon-gamma commercial kit (QuantiFERON-TB® Gold In-Tube). RESULTS: IFN-γ production was not influenced by the IFNG+874 genotype, regardless of antigen or mitogen-based stimulation, which suggests that other genes may influence IFN-γ production in response to mycobacteria. The IFNG+874 polymorphism was found to exert no influence over QFT-IT test sensitivity in our study. CONCLUSIONS: The IFNG+874 polymorphism was not shown to influence QuantiFERON-TB® Gold In-Tube test performance in an admixed population from northeastern Brazil.
Assuntos
Testes de Liberação de Interferon-gama/métodos , Interferon gama/genética , Mycobacterium tuberculosis/genética , Polimorfismo Genético/genética , Tuberculose Pulmonar/diagnóstico , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Técnicas de Genotipagem , Humanos , Interferon gama/metabolismo , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Teste TuberculínicoRESUMO
Caseous lymphadenitis (LC) is a chronic contagious disease caused by Corynebacterium pseudotuberculosis, which mainly affects goats and sheep. Vaccination is an effective but not yet well-established method, partly due to a lack of knowledge surrounding the most effective immunoprotective components. The present study aimed to quantify and compare the in vivo expression of genes pld (phospholipase D), cpp (CP40), nanH (neuraminidase H), sodC (superoxide dismutase C) and spaC (adhesin) using qRT-PCR, with the respective expression in vitro. Caseous material of abscesses removed from five animals was cultured, with colonies suggestive of C. pseudotuberculosis identified. RNA extraction was performed on these samples, as well as on the respective pellets derived from liquid cultures brain heart infusion. After evaluating RNA integrity, complementary DNA was synthesized, followed by the relative quantification each of the genes of interest. Mean mRNA expression of the five genes found in abscesses and in cultures differed significantly, with respective values of: nanH 811.50 ± 198.27 and 359.35 ± 75.45 (p = 0.009); cpp 856.31 ± 385.11 and 154.54 ± 94.34 (p = 0.0039); plD 922.70 ± 450.73 and 212.41 ± 153.10 (p = 0.016); sodC 1,293.53 ± 564.75 and 223.63 ± 145.58 (p = 0.016); spaC 1,157.10 ± 525.13 and 214.26 ± 125.70 (p = 0,016). Expression was observed to be 6-8 times higher in abscesses than in cultures, Indicative that is a genetic expression of the in vitro bacterium exists, yet in vivo has a greater magnitude corroborating to one of these virulence factors in the pathogenesis of LC.
RESUMO
BACKGROUND: A glioblastoma is a primary CNS tumor that is more aggressive and lethal than other brain tumors. Its location, rapid proliferation, invasive growth, angiogenesis and immunosuppression are the main factors that limit its treatment, making it a major challenge to neuro-oncology. OBJECTIVE: This study investigated the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell death and ß-catenin, NFκB, STAT3/pSTAT3 and interleukins roles. METHOD: In vitro experimental models of human (U251 and GL-15) and murine (C6) glioblastoma cells were cultured in the presence of DHC at increasing concentrations for MTT assay and exclusion trypan blue dye to determine EC50. Afterward, C6 and U251 cells were treated with 100 µM DHC or DMSO 0.1% for cell cycle, annexin and expression of ß-catenin/NFκB/STAT3/pSTAT3 by flow cytometry or immunofluorescence. Interleukin quantification was made by Cytometric Bead Array. RESULTS: A significant decrease was observed in C6 and U251 cell viability in a time and dose-dependent manner. GL-15 cell viability decreased only when treated with 200 µM DHC. This maximum concentration affected neither astrocytes nor microglia viability. A cytostatic effect of DHC was observed in C6 and U251 cells after 48 h of 100 µM DHC treatment. After 72 h of DHC treatment, C6 presented 80% of annexin-V+ cells compared to 10% of annexin-V+ U251 cells. C6 cells demonstrated significant high levels of NFκ B and ß-catenin cytoplasmic fraction. Additionally, DHC treatment resulted in higher significant levels of IL-6 than did other interleukins and STAT3 up-regulation in U251 cells. CONCLUSION: These results demonstrate that DHC acts as a chemosensitizing agent selective for glioma cells not affecting non-tumor cells. Considering tumor heterogeneity, DHC demonstrated an anti-cancer potential to activate different cell death pathways. DHC demonstrated could be used for chemotherapy and immunotherapy applications in glioblastomas in the future.