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INTRODUCTION: Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). METHODOLOGY: The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. RESULTS: We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. CONCLUSIONS: The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.
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Predisposição Genética para Doença , Hanseníase Virchowiana , Polimorfismo de Nucleotídeo Único , Receptores Tipo II do Fator de Necrose Tumoral , Receptores Tipo I de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa , Humanos , México , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hanseníase Virchowiana/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Adulto Jovem , Idoso , Frequência do Gene , Polimorfismo de Fragmento de Restrição , Estudos de Casos e Controles , Genótipo , Adolescente , Reação em Cadeia da PolimeraseRESUMO
Introduction: Helicobacter pylori colonizes the gastric mucosa and induces chronic inflammation. Methods: Using a mouse model of H. pylori-induced gastritis, we evaluated the mRNA and protein expression levels of proinflammatory and proangiogenic factors, as well as the histopathological changes in gastric mucosa in response to infection. Five- to six-week-old female C57BL/6N mice were challenged with H. pylori SS1 strain. Animals were euthanized after 5-, 10-, 20-, 30-, 40- and 50-weeks post infection. mRNA and protein expression of Angpt1, Angpt2, VegfA, Tnf-α, bacterial colonization, inflammatory response and gastric lesions were evaluated. Results: A robust bacterial colonization was observed in 30 to 50 weeks-infected mice, which was accompanied by immune cell infiltration in the gastric mucosa. Compared to non-infected animals, H. pylori-colonized animals showed an upregulation in the expression of Tnf-A, Angpt2 and VegfA at the mRNA and protein levels. In contrast, Angpt1 mRNA and protein expression was downregulated in H. pylori-colonized mice. Conclusion: Our data show that H. pylori infection induces the expression of Angpt2, Tnf-A and Vegf-A in murine gastric epithelium. This may contribute to the pathogenesis of H. pylori-associated gastritis, however the significance of this should be further addressed.
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INTRODUCTION: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. OBJECTIVE: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. METHOD: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). RESULTS: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. CONCLUSION: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases.
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Encefalomielite Autoimune Experimental , Microglia , Acetatos , Animais , Citocinas , Inflamação , Lipopolissacarídeos , Fator de Necrose Tumoral alfaRESUMO
MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with Leishmania amazonensis can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (Nos2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with L. amazonensis. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (Cat1/Slc7a1), Cat2/Slc7a22 and Nos2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of Cat2 and Tnfa and the dysregulation of Nos2, while miR-410 increased Cat1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by L. amazonensis infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism.
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A higher Th17-immune response characterises obesity and obesity-related asthma phenotype. Nevertheless, obesity-related asthma has a more significant Th17-immune response than obesity alone. Retinoid-related orphan receptor C (RORC) is the essential transcription factor for Th17 polarisation. Previous studies have found that adolescents with obesity-related asthma presented upregulation of RORC, IL17A, and TNFA. However, the mechanisms that cause these higher mRNA expression levels in this asthmatic phenotype are poorly understood. Methylation directly regulates gene expression by adding a methyl group to carbon 5 of dinucleotide CpG cytosine. Thus, we evaluated the relationship between RORC, IL17A, and TNFA methylation status and mRNA expression levels to investigate a possible epigenetic regulation. A total of 102 adolescents (11-18 years) were studied in the following four groups: 1) healthy participants (HP), 2) allergic asthmatic participants (AAP), 3) obese participants without asthma (OP), and 4) non-allergic obesity-related asthma participants (OAP). Real-time qPCR assessed the methylation status and gene expression levels in peripheral blood leukocytes. Remarkably, the OAP and AAP groups have lower promoter methylation patterns of RORC, IL17A, and TNFA than the HP group. Notably, the OAP group presents lower RORC promoter methylation status than the OP group. Interestingly, RORC promoter methylation status was moderately negatively associated with gene expression of RORC (r s = -0.39, p < 0.001) and IL17A (r s = -0.37, p < 0.01), respectively. Similarly, the promoter methylation pattern of IL17A was moderately negatively correlated with IL17A gene expression (r s = -0.3, p < 0.01). There is also a moderate inverse relationship between TNFA promoter methylation status and TNFA gene expression (r s = -0.3, p < 0.01). The present study suggests an association between lower RORC, IL17A, and TNFA gene promoter methylation status with obesity-related asthma and allergic asthma. RORC, IL17A, and TNFA gene promoter methylation patterns are moderately inversely correlated with their respective mRNA expression levels. Therefore, DNA methylation may regulate RORC, IL17A, and TNF gene expression in both asthmatic phenotypes.
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En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.
In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children Ìs age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.
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Humanos , Criança , Adulto , Tuberculose/diagnóstico , Tuberculose/induzido quimicamente , Terapia Biológica/efeitos adversos , Tuberculose/complicações , Teste Tuberculínico , Tuberculose Latente/diagnóstico , Testes de Liberação de Interferon-gama , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Agentes de Imunomodulação/efeitos adversosRESUMO
Abstract Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. HIGHLIGHTS Acetate was able to exacerbate the production of TNF-α in microglia. Acetate administered as pre-treatment to LPS acts as an anti-inflammatory. Histone deacetylase decreased TNF-α production in Acetate- and LPS-treated cells. Depending on the time of administration, Acetate modulates microglia's activation. Acetate may threaten neurodegenerative and neuropsychiatric diseases.
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SUMMARY: Adriamycin (ADR) is an anthracycline antibiotic used for treatment of many types of cancer. However, its applications may damage to healthy tissues. Chloroquine (CLQ) is an anti-inflammatory agent used in treatment of many inflammation associated diseases such as malaria and rheumatoid arthritis. Moreover, it is used in the treatment of pneumonia caused by COVID-19. The aim of this study is to determine possible therapeutic effects of Chloroquine on Adriamycin-induced testicular toxicity in rats. We investigated the effect of CLQ on testicular injury caused by ADR. Rats were divided into four groups: Control, ADR, CLQ, ADR+CLQ. After administrations, animals were sacrificed, and testis tissues were extracted from the animals for the further examinations. Histopathological changes in testis tissues were evaluated and TNF-α and IL-6 immunostaining were performed to determine the expression levels of these cytokines. TUNEL method were used for evaluation of apoptotic index. Moreover, serum testosterone levels were measured by ELISA assay. We observed that ADR group showed histopathological deterioration when compared to the Control group and CLQ treatment ameliorated this damage induced by Adriamycin.An increase in TNF-α and IL-6 immunoreactivities and in the number of apoptotic cells and a decrease in serum testosterone levels were determined in the ADR group compared to the Control and CLQ group. Furthermore, our examinations showed an improvement in testicular tissue in ADR+CLQ group in terms of these parameters when compared to the ADR group. We suggest that CLQ can be used as a protective agent to reduce the toxic effects of Adriamycin as a result of its anti-inflammatory and anti-apoptotic properties.
RESUMEN: La adriamicina (ADR) es un antibiótico de antraciclina que se usa para el tratamiento de muchos tipos de cáncer. Sin embargo, sus aplicaciones pueden dañar los tejidos sanos. La cloroquina (CLQ) es un agente antiinflamatorio que se utiliza en el tratamiento de enfermedades asociadas a la inflamación, tal como la malaria y la artritis reumatoide. También se utiliza en el tratamiento de la neumonía causada por COVID-19. El objetivo de este estudio fue determinar los posibles efectos terapéuticos de la cloroquina sobre la toxicidad testicular inducida por adriamicina en ratas. Investigamos el efecto de CLQ sobre la lesión testicular causada por ADR. Las ratas se dividieron en cuatro grupos: Control, ADR, CLQ, ADR + CLQ. Después de las administraciones, se sacrificaron los animales y se extrajeron los testículos de los animales para los exámenes adicionales. Se evaluaron los cambios histopatológicos en los tejidos testiculares y se realizó la inmunotinción de TNF-α e IL-6 para determinar los niveles de expresión de estas citocinas. Se utilizó el método TUNEL para la evaluación del índice apoptótico. Además, los niveles de testosterona en suero se midieron mediante un ensayo ELISA. El grupo ADR mostró un deterioro histopatológico en comparación con el grupo Control y observamos que el tratamiento con CLQ mejoró el daño inducido por Adriamicina. Un aumento en las inmunorreactividades de TNF-α e IL-6 y en el número de células apoptóticas además de una disminución en los niveles séricos de testosterona se determinaron en el grupo de ADR en comparación con el grupo de control y CLQ. Además, nuestros exámenes mostraron una mejora en el tejido testicular en el grupo ADR + CLQ en términos de estos parámetros en comparación con el grupo ADR. Sugerimos que CLQ se puede utilizar como agente protector para reducir los efectos tóxicos de la Adriamicina, gracias a sus propiedades antiinflamatorias y antiapoptóticas.
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Animais , Masculino , Ratos , Doenças Testiculares/induzido quimicamente , Doenças Testiculares/tratamento farmacológico , Doxorrubicina/efeitos adversos , Cloroquina/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Interleucina-6 , Fator de Necrose Tumoral alfa , Ratos Wistar , Apoptose/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Inflamação , Antibióticos Antineoplásicos/efeitos adversosRESUMO
BACKGROUND: Functional variants -173 G > C (rs755622) and -794CATT5-8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico. MATERIALS AND METHODS: A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes -173 G > C and -794 CATT5-8 MIF polymorphisms was performed by PCR-RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively. RESULTS: The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants -173G > C and -794 CATT5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found. CONCLUSION: The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles -173*C and -794CATT7 are associated with the increase of MIF circulating in women with BC.
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Neoplasias da Mama/genética , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/genética , Fator de Necrose Tumoral alfa/sangue , Adulto , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , México , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Solubilidade , Fator de Necrose Tumoral alfa/genéticaRESUMO
Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality, characterized by chronic inflammation and fibrosis, which are processes associated with higher serum tumor necrosis factor-α (sTNF-α) levels. TNFA -308G>A and -238G>A polymorphisms have been associated with higher sTNF-α levels. In this study, we genotyped the TNFA -308G>A and -238G>A polymorphisms in 53 SSc patients and 115 unrelated control subjects (CS) from southern Mexico. The TNFA mRNA expression and sTNF-α levels were also quantified by qPCR and enzyme-linked immunosorbent assays, respectively. TNFA -308GA genotype was associated with disease susceptibility according to a codominant genetic model (OR = 3.2, 95% CI 1.05-9.75, p = 0.03), and with higher anti-fibrillarin antibodies (p = 0.01), and higher skin thickening (p = 0.006). TNFA -238GA was not associated with SSc risk. TNFA mRNA expression and sTNF-α levels were similar between SSc patients and CS and were not statistically associated with the TNFA polymorphisms; however, a correlation (rho = 0.362, p = 0.009) between sTNF-α levels with anti-RNA polymerase III antibodies was observed in the SSc patients. In conclusion, the -308G>A polymorphism is a genetic marker of SSc susceptibility in population from southern Mexico, and it is associated with skin thickening and anti-fibrillarin antibodies. In addition, sTNF-α levels correlate positively with the anti-RNA pol III antibodies levels.
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Autoanticorpos/metabolismo , Escleroderma Sistêmico/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto , Estudos de Casos e Controles , Proteínas Cromossômicas não Histona/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , RNA Polimerase III/imunologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologiaRESUMO
Abstract Bone development and growth is a non-going, life-long process, varying greatly among individuals and much of this variation could be modulated by genetic factors. The purpose of this study was to evaluate the association between the polymorphisms in the TNF-a gene and skeletal class II malocclusion. Single nucleotide polymorphisms in TNF-a (rs1799724; rs1800629) gene were studied in 79 skeletal class II malocclusion and 102 skeletal class I malocclusion subjects from Straight Wire Group of Studies on Orthodontics and Functional Orthopedics for Maxillary from Rio de Janeiro, Brazil. The Genotyping of these selected polymorphisms was carried out by TaqMan real-time PCR using genomic DNA extracted from buccal cells. All allele and genotype frequencies were compared between the groups using the PLINK® software in a free, in a dominant and in a recessive model using a chi-square test (p≤0.05). There was no significant association of TNF-a (rs1799724; rs1800629) genotype and allele distribution with skeletal class II malocclusion. Regardless of the dominant or recessive genetic model, the preferential genotype associations for rs1799724 and rs1800629 was insignificant. In conclusion, no evidence of association is apparent between genetic polymorphisms involving TNF-a and skeletal class II malocclusion or the position of the maxilla and mandible in the postero-anterior direction.
Resumo O desenvolvimento e crescimento ósseo é um processo contínuo, que dura toda a vida, variando muito entre os indivíduos e grande parte dessa variação pode ser modulada por fatores genéticos. O objetivo deste estudo foi avaliar a associação entre os polimorfismos no gene TNF-a e a má oclusão da classe II esquelética. Polimorfismos no gene TNF-a (rs1799724; rs1800629) foram estudados em 79 indivíduos com má oclusão esquelética de classe II e 102 indivíduos com má oclusão esquelética classe I do Grupo de Estudos em Ortodontia e Ortopedia Funcional dos Maxilares do Rio de Janeiro, Brasil. A genotipagem destes polimorfismos foi realizada por PCR em tempo real, através de DNA genômico extraído de células bucais. Todas as frequências alélicas e genotípicas foram comparadas entre os grupos utilizando o software PLINK® em um modelo livre, dominante e recessivo. Foi aplicado o teste do qui-quadrado (p≤0,05). Não houve associação significativa na distribuição genotipica e alélica do gene TNF-a (rs1799724; rs1800629) com a má oclusão de classe II esquelética. Independentemente do modelo genético dominante ou recessivo, as associações genotípicas preferenciais para rs1799724 e rs1800629 foram insignificantes. Pode-se concluir que, não existe evidência de associação entre polimorfismos genéticos envolvendo TNF-a e má oclusão esquelética de classe II ou a posição da maxila e mandíbula na direção póstero-anterior.
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Humanos , Má Oclusão , Má Oclusão Classe II de Angle , Brasil , Cefalometria , Mandíbula , Maxila , Mucosa BucalRESUMO
BACKGROUND: This study shows the relationship between host factors and environmental factors in the influence of susceptibility to loss of dental implants. PURPOSE: The aim of this study was to investigate the association of clinical aspects and tag SNPs of the genes LTA, TNFA, and LTB with dental implant loss. MATERIALS AND METHODS: The subjects consisted of 244 patients, divided into two groups: control group (C)-163 individuals who did not lose any implants, being in function for at least 6 months; and study group (S)-81 individuals who had lost at least one implant. DNA was collected from saliva, and the genotypes were determined by real time PCR. Univariate and multivariate analysis were employed p < .05. RESULTS: After multivariate analysis, dental implant loss remained associated with the presence of teeth (p = .011), a larger amount of placed implants (p = .001), and allelle C of rs2009658 of the LTA gene (p = .006). For the other tag SNPs of these studied genes, there was no association between the groups C and S with dental implants loss. CONCLUSION: Presence of teeth, number of placed implants and allele C of rs2009658 of LTA gene were associated with implant loss.
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Implantes Dentários , Falha de Restauração Dentária , Linfotoxina-alfa/genética , Linfotoxina-beta/genética , Osseointegração/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Estudos de Casos e Controles , Implantação Dentária Endóssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCCIÓN: La presencia de un estado de inflamación de bajo grado en niños obesos, se debería, entre otros factores, a que el tejido adiposo de los obesos produce moléculas proinflamatorias que contribuyen al desarrollo de aterosclerosis. OBJETIVO: Determinar en una población de niños obesos los niveles séricos de ligando CD-40 soluble (sCD40L), proteína quimioatractante de monocitos 1 (MCP-1), interleuquina 6 (IL-6), Factor de Necrosis tumoral a (TNF-a) y Proteína C Reactiva ultrasensible (PCR-us), comparados con un grupo control y analizar la correlación de estas moléculas con las variables antropométricas y metabólicas. PACIENTES Y MÉTODO: Estudio transversal de 37 niños obesos de 8 a 12 años y 20 niños con peso normal. A todos los pacientes se les realizó una historia clínica consignando edad, peso, talla, IMC, circunferencia de cintura, estadios de Tanner y antecedentes familiares. Se determinaron los niveles séricos de sCD40L, MCP-1, IL-6, TNF-a y PCR-us mediante ELISA, PCR-us por quimioluminiscencia, glucemia, insulina plasmática, perfil lipídico y se calculó el índice HOMA. Los datos se expresaron como la mediana y rango intercuartil y se utilizó el coeficiente de Spearman para investigar las correlaciones entre variables. RESULTADOS: Los niños obesos presentaron valores significativamente mayores de sCD40L, MCP-1, IL-6, TNF-a, PCR-us que los niños controles. El índice de masa corporal y la circunferencia de cintura se correlacionaron positivamente con sCD40L y MCP-1. CONCLUSIÓN: Los niveles elevados de las moléculas estudiadas sugieren la presencia de inflamación de bajo grado asociada a obesidad en esta población.
INTRODUCTION: Obesity is a chronic disease that affects adults as well as children and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. One of the reasons for the presence of low-grade inflammation in these patients could be that adipose tissue of the obese produces proin flammatory molecules that favor the development of atherosclerosis. OBJECTIVE: To determine serum levels of soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-Α) and high sensitivity CRP (hsCRP), in an obese chil dren population compared to a control group, also to analyze the correlation of these molecules with the anthropometric and metabolic variables. PATIENTS AND METHOD: A cross-sectional, observational study was carried out on 37 obese children, aged 8 to 12 years, and 20 children with normal weight. Serum levels of sCD40L, MCP-1, IL-6, TNF-Α and hsCRP were determined. Data were expressed as the median and interquartil range and Spearman coefficient was used to investigate correlations between variables. RESULTS: Compared to the control group, obese children presented significantly higher values of sCD40L, MCP-1, IL-6, TNF-Α, and hsCRP than control group. Body mass index and waist circumference correlated positively with sCD40L and MCP-1. CONCLUSION: Elevated levels of the studied molecules studied suggest the presence of low-grade inflammation associated with obesity in this population.
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Humanos , Masculino , Feminino , Criança , Obesidade Infantil/fisiopatologia , Inflamação/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Obesidade Infantil/sangue , Inflamação/diagnóstico , Inflamação/sangueRESUMO
Spinal cord injury causes neuron nerve fiber loss. The aim of this study was to investigate the neuroprotective, inflammatory and angiogenetic effects of melatonin on rat spinal cord injury (SCI). For spinal cord injury, a standard weight reduction method was used that caused moderate severity of injury (100 g / cm force) at T10 Melatonin (10 mg/kg intraperitoneally ) was administered for 10 days after trauma. Each group consisted of 10 animals. of these, six were used for biochemical and four were used for the evaluation of histological analysis. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity. Spinal cord injury and melatonin treated group were compared. Melatonin administration in spinal cord injury increased the activity of glial cells in the radial and funicular cells and ependymal cells and increased the activity of glial cells and also showed a positive effect on inflammation and vascular endothelial cells in synaptic connections in the nerve fibers undergoing spinal injury endothelial degeneration It is thought that it can regulate the degenerative effect which is caused by both the inflammatory effect and the angiogenic effect which will have a positive effect on the neural connection.
La lesión de la médula espinal (SCI) provoca daño en la fibra nerviosa, que puede conducir a alteraciones motoras y sensitivas, incluso la muerte. El objetivo de este estudio fue investigar los efectos neuroprotectores, proinflamatorios y proangiogénicos de la melatonina en un modelo de SCI inducida en rata. Para tal efecto se utilizaron dos grupos: Grupo 1 (n:10) se le indujo una SCI, mediante el método de reducción de peso estándar (100 g/cm fuerza), provocando una lesión de severidad moderada. Grupo 2 (n:10) inducción SCI más aplicación de T10 Melatonina (10 mg / kg v.i.) durante 10 días después del trauma. Muestras de seis animales de cada grupo fueron usados para análisis bioquímicos y los otros cuatro para la evaluación histológica. Se tomaron muestras de médula espinal para el examen histológico y para la determinación de niveles de malondialdehído (MDA) y glutatión (GSH), actividad mieloperoxidasa (MPO) y se comparó la lesión de la médula espinal y el grupo tratado con melatonina. La administración de melatonina en la lesión de la médula espinal aumentó la actividad de las células gliales en las células radiales, funiculares y ependimocitos. Ademas mostró un efecto positivo sobre la inflamación y angiogénesis en las conexiones sinápticas en las fibras nerviosas sometidas a lesión espinal. Pudiendo este participar en la regulación del efecto degenerativo causado, principalmente, por acción de angiogénesis e inflamación local.
Assuntos
Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Melatonina/metabolismo , Melatonina/uso terapêutico , Imuno-Histoquímica , Fator de Necrose Tumoral alfa/metabolismo , Endotelina-1/metabolismoRESUMO
OBJECTIVE: To evaluate gene polymorphisms and their association with susceptibility to dengue. METHODS: A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system. RESULTS: We observed a protective association of IL-10 (-819 C/T) C allele (P = 0.028, OR = 0.56, CI = 0.34-0.91) against DHF, while the C/T (P = 0.047, OR = 2.10, CI = 1.01-4.38) and T/T (P = 0.008, OR = 3.82, CI = 1.38-10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA -308 GA + AA (P = 0.043, OR = 0.45, CI = 0.20-1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P = 0.02, OR = 0.46, CI = 0.24-0.89) and DHF (P = 0.034, OR = 0.43, CI = 0.19-0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P = 0.022, OR = 2.95, CI = 1.18-7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P = 0.035, OR = 0.28, CI = 0.08-0.90) with protection against the development of DHF. CONCLUSIONS: This research identifies the association of the IFNG (+874 A/T), TNFA (-308G/A), IL-10 (-819 C/T) genotypes as a factor for protection, susceptibility and severity to dengue.
RESUMO
Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFatherapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Psoriásica/complicações , Artrite Reumatoide/complicações , Tuberculose Latente/epidemiologia , Espondilite Anquilosante/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Brasil/epidemiologia , Estudos de Casos e Controles , Incidência , Estudos Longitudinais , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Fatores SocioeconômicosRESUMO
OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p < 0.05). A statistically significant higher mean level serum neopterin concentration (p < 0.05) was found in JIA patients (20.43 ± 8.73 nmol/L) than in controls (6.88 ± 2.87 nmol/L) (p < 0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-a, IL-6, MCP-1, and JADAS-27 (p < 0.05). No correlation was found between serum neopterin and CRP (p > 0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05).CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.
OBJETIVO: Avaliar as concentrações plasmáticas de neopterina em pacientes com artrite idiopática juvenil (AIJ) ativa e correlacioná-las com a atividade da doença.MÉTODOS: Foram recrutados da clínica de Alergia e Imunologia Infantil da Universidade Ain Shams 60 pacientes diagnosticados com AIJ ativa, bem como 60 crianças aparentemente saudáveis com a mesma idade e o mesmo sexo no grupo de controle. A atividade da doença foi avaliada pelo Escore de Atividade da Doença da Artrite Juvenil em 27 Articulações (JADAS-27). Foram feitas investigações laboratoriais em todos os pacientes, incluindo a determinação da concentração de hemoglobinas, a taxa de sedimentação de eritrócitos e a proteína C-reativa. Foram mensuradas as concentrações séricas do fator de necrose tumoral alfa, interleucina-6 e proteína quimiotática de monócitos-1 e neopterina.RESULTADOS: Foi encontrada uma diferença significativa entre os pacientes com AIJ e os controles quanto às médias de Hb, TSE, FNT-a, IL-6 e MCP-1 (p < 0,05). Foi encontrado um nível estatística e significativamente maior de concentração média de neopterina sérica (p < 0,05) em pacientes com AIJ (valor médio de 20,43 ± 8,73 nmol/L) do que em controles (valor médio de 6,88 ± 2,87 nmol/L) (p < 0,05). Foram detectadas correlações positivas significativas entre a neopterina sérica e TSE, FNT-a, IL-6, MCP-1 e JADAS-27 (p < 0,05). Não foi encontrada correlação entre a neopterina sérica e a PCR (p > 0,05). A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05).CONCLUSÃO: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Artrite Juvenil/sangue , Neopterina/sangue , Artrite Juvenil/imunologia , Sedimentação Sanguínea , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , /análise , /imunologia , Ativação de Macrófagos , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
Apathy is intimately associated with dementia. Unfortunately, its pathophysiology remains poorly understood. The motivational impairment that characterizes this disorder might share the same inflammatory mechanisms, as suggested by the sickness behavior theory. OBJECTIVE: The primary aim of this study was to investigate the association between apathy symptoms and serum levels of tumor necrosis factor alpha (TNF-a) and its soluble receptors. Brain-derived neurotrophic factor (BDNF) levels were also analyzed since these have been associated with depression, a condition which shares abulic features with apathy. METHODS: The sample consisted of 27 subjects with mild Alzheimer's disease or amnestic mild cognitive impairment, who were submitted to specific apathy evaluation using the Apathy Scale (AS) and provided blood samples for biomarker analysis. Participants were categorized into two groups according to median AS scores (17 points). RESULTS: Subjects with higher apathy symptoms (n=13) displayed higher levels of TNF-a soluble receptors (type 1: p=0.03; type 2: p=0.04). No other difference was found between groups. CONCLUSION: These findings point to the involvement of inflammatory mediators in the genesis of apathy symptoms, as suggested by the sickness behavior theory.
Apatia está intimamente associada à demência. Lamentavelmente, sua fisiopatologia ainda é pouco compreendida. O comprometimento motivacional que caracteriza este transtorno poderia compartilhar mecanismos inflamatórios como sugere a teoria do comportamento associado à doença. OBJETIVO: O principal objetivo deste estudo foi investigar a associação entre apatia e os níveis séricos do fator de necrose tumoral alfa (TNF-a) e de seus receptores solúveis. Os níveis de fator neurotrófico derivado do cérebro também foram analisados já que estes foram associados à depressão, que compartilha aspectos abúlicos com a apatia. MÉTODOS: A amostra consistiu de 27 indivíduos com doença de Alzheimer leve ou com comprometimento cognitivo leve amnéstico, que foram submetidos à avaliação de apatia pela Escala de Apatia (EA), e proveram amostra de sangue para análise de biomarcadores. De acordo com a mediana de escores na EA (17 pontos), a amostra foi divida em dois grupos. RESULTADOS: O grupo com mais sintomas de apatia apresentou maiores níveis séricos de receptores solúveis de TNF-a (tipo 1: p=0,03 ; tipo 2: p=0,04). Nenhuma outra diferença foi encontrada entre os grupos.CONCLUSÃO: Estes achados sugerem o envolvimento de mediadores inflamatórios na gênese de sintomas de apatia, assim como sugere a teoria do comportamento associado à doença.
Assuntos
Humanos , Fator de Necrose Tumoral alfa , Fator Neurotrófico Derivado do Encéfalo , Demência , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Apatia , Doença de Alzheimer , Disfunção CognitivaRESUMO
El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-a), ejerciendo un efecto deletéreo sobre la función vascular. El objetivo de este trabajo fue evaluar niveles de TNF-a en una población infantojuvenil con sobrepeso y su relación con otras variables. Se estudiaron 30 niños con sobrepeso (12 varones) de edades entre 8-13 años, se midió circunferencia de cintura (CC) e índice de masa corporal (IMC) y fueron comparados con 20 controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC = 85 < 95 percentilo para edad y sexo. En ambos grupos se determinó: glucemia en ayunas (método glucosa oxidasa), insulina plasmática (ECLIA), fibrinógeno (Fg, método de Clauss), proteína C reactiva ultrasensible (uPCR, método inmunoturbidimétrico), TNF-a (ELISA), perfil lipídico (métodos enzimáticos), eritrosedimentación y se calculó el índice HOMA. Los datos se expresaron como mediana y rango intercuartil y con el coeficiente de Spearman se investigaron las correlaciones entre variables, considerándose significativo un p < 0.05. Los niveles de TNF-a fueron mayores en los sujetos con sobrepeso [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. También resultaron más elevados los valores de Fg, insulina plasmática, índice HOMA, uPCR y triglicéridos. El TNF-a se correlacionó con la CC (r = 0.654; p = 0.021). Los niveles elevados de TNF-a, uPCR y Fg encontrados confirman un estado proinflamatorio asociado a obesidad abdominal en la población estudiada.(AU)
The child overweight is associated with overweight/obesity at the adult age. The obese adipose tissue produces an increase of proinflammatory cytokines as the tumor necrosis factor alpha (TNF-a), causing a deleterious effect on vascular functions. The aim of this work was to evaluate TNF-a levels in a children’s population with overweight and its relationship with clinical and laboratory variables. Thirty overweight children were studied, with ages between 8-13 years old, and twenty control children. In both groups waist circumference was measured and body mass index (BMI) calculated. The inclusion criterium was a >85th < 95 th BMI percentile for age and sex. In both groups were determined: fasting blood glucose (glucose-oxidase method); plasma insulin (ECLIA); plasma fibrinogen (Fg, Clauss method); high sensitivity C reactive protein (hsCRP, immunoturbidimetric method); plasma myeloperoxidase (ELISA); TNF-a (ELISA); lipid profile (enzymatic methods); erythrosedimentation rate (ESR) and homeostasis model assessment index (HOMA). Data were expressed as the median and interquartile range. Correlations between variables were investigated with the Spearman’s coefficient. A p < 0.05 was considered significant. The TNF-a levels were higher in overweight children [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. Levels of Fg, plasma insulin, HOMA index, uCRP and triglycerides were also statistically significant higher than the control group. The TNF-a was positively correlated with the waist circumference (r = 0.654; p = 0.021). The high TNF-a levels found, with the CRP and Fg levels, confirm a low grade proinflammatory state associated to abdominal obesity in the studied population.(AU)
Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Sobrepeso/sangue , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos de Casos e Controles , Colesterol/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Insulina/sangue , Valores de Referência , Estatísticas não Paramétricas , Circunferência da CinturaRESUMO
El sobrepeso infantil está asociado a sobrepeso/obesidad en la edad adulta. El tejido adiposo en obesos produce una cantidad incrementada de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-a), ejerciendo un efecto deletéreo sobre la función vascular. El objetivo de este trabajo fue evaluar niveles de TNF-a en una población infantojuvenil con sobrepeso y su relación con otras variables. Se estudiaron 30 niños con sobrepeso (12 varones) de edades entre 8-13 años, se midió circunferencia de cintura (CC) e índice de masa corporal (IMC) y fueron comparados con 20 controles de edad y sexo semejantes. Se consideró criterio de inclusión un IMC = 85 < 95 percentilo para edad y sexo. En ambos grupos se determinó: glucemia en ayunas (método glucosa oxidasa), insulina plasmática (ECLIA), fibrinógeno (Fg, método de Clauss), proteína C reactiva ultrasensible (uPCR, método inmunoturbidimétrico), TNF-a (ELISA), perfil lipídico (métodos enzimáticos), eritrosedimentación y se calculó el índice HOMA. Los datos se expresaron como mediana y rango intercuartil y con el coeficiente de Spearman se investigaron las correlaciones entre variables, considerándose significativo un p < 0.05. Los niveles de TNF-a fueron mayores en los sujetos con sobrepeso [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. También resultaron más elevados los valores de Fg, insulina plasmática, índice HOMA, uPCR y triglicéridos. El TNF-a se correlacionó con la CC (r = 0.654; p = 0.021). Los niveles elevados de TNF-a, uPCR y Fg encontrados confirman un estado proinflamatorio asociado a obesidad abdominal en la población estudiada.
The child overweight is associated with overweight/obesity at the adult age. The obese adipose tissue produces an increase of proinflammatory cytokines as the tumor necrosis factor alpha (TNF-a), causing a deleterious effect on vascular functions. The aim of this work was to evaluate TNF-a levels in a children’s population with overweight and its relationship with clinical and laboratory variables. Thirty overweight children were studied, with ages between 8-13 years old, and twenty control children. In both groups waist circumference was measured and body mass index (BMI) calculated. The inclusion criterium was a >85th < 95 th BMI percentile for age and sex. In both groups were determined: fasting blood glucose (glucose-oxidase method); plasma insulin (ECLIA); plasma fibrinogen (Fg, Clauss method); high sensitivity C reactive protein (hsCRP, immunoturbidimetric method); plasma myeloperoxidase (ELISA); TNF-a (ELISA); lipid profile (enzymatic methods); erythrosedimentation rate (ESR) and homeostasis model assessment index (HOMA). Data were expressed as the median and interquartile range. Correlations between variables were investigated with the Spearman’s coefficient. A p < 0.05 was considered significant. The TNF-a levels were higher in overweight children [15.4 (13.2-24.0) vs. 12.7 (11.2-14.8) pg/ml; p = 0.028]. Levels of Fg, plasma insulin, HOMA index, uCRP and triglycerides were also statistically significant higher than the control group. The TNF-a was positively correlated with the waist circumference (r = 0.654; p = 0.021). The high TNF-a levels found, with the CRP and Fg levels, confirm a low grade proinflammatory state associated to abdominal obesity in the studied population.