Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms.

AIM: We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro. MATERIALS AND METHODS: Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co-localization of myeloperoxidase (MPO)-citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls. RESULTS: The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO-H3Cit-positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters. CONCLUSIONS: The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

Associations between Anxiety, Depression, Chronic Pain and Oral Health-Related Quality of Life, Happiness, and Polymorphisms in Adolescents' Genes.

Adolescence is marked by changes and vulnerability to the emergence of psychological problems. This study aimed to investigate associations between anxiety/depression/chronic pain and oral health-related quality of life (OHRQoL)/happiness/polymorphisms in the COMT, HTR2A and FKBP5 genes in Brazilian adolescents. A cross-sectional study was conducted with ninety adolescents 13 to 18 years. Anxiety, depression and chronic pain were evaluated using the RDC/TMD. The Oral Health Impact Profile was used to assess oral OHRQoL. The Subjective Happiness Scale was used to assess happiness. Single-nucleotide polymorphisms in COMT (rs165656, rs174675), HTR2A (rs6313, rs4941573) and FKBP5 (rs1360780, rs3800373) were genotyped using the Taqman® method. Bivariate and multivariate logistic regression analyses were performed (p < 0.05). Chronic pain and depression were associated with feelings of happiness (p < 0.05). A significant inverse association was found between anxiety and OHRQoL (p = 0.004). The presence of minor allele C of COMT rs174675 was significantly associated with depression (p = 0.040). Brazilian adolescents with depression and chronic pain considers themselves to be less happy than others and those with anxiety are more likely to have a negative impact on OHRQoL. Moreover, the rs174675 variant allele in the COMT gene was associated with depressive symptoms in Brazilian adolescents.

Polymorphisms of Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 genes in trigeminal neuralgia.

SUBJECTS: Trigeminal neuralgia is a neuropathic pain characterized by episodes of severe shock-like pain within the distribution of one or more divisions of the trigeminal nerve. Pain can be influenced by ethnicity, environment, gender, psychological traits, and genetics. Molecules Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 have been involved in mechanisms that underlie pain and neurological conditions. OBJECTIVE: The aim of this case-control study was to investigate the occurrence of genetic polymorphisms in Nav1.6 sodium channel (SCN8A/rs303810), Brain-derived Neurotrophic Factor (BDNF/rs6265/Val66Met), Catechol-O-methyltransferase (COMT/rs4680/Val158Met), and Guanosine Triphosphate Cyclohydrolase 1 (GCH1/rs8007267) genes in trigeminal neuralgia patients. METHODS: Ninety-six subjects were divided into two groups: 48 with trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated by visual analog scale and genomic DNA was obtained from oral swabs and analyzed by real-time polymerase chain reaction. RESULTS: No association was observed among SCN8A, BDNF, COMT or GCH1 polymorphisms and the presence of trigeminal neuralgia. Genotype distribution and allele frequencies did not correlate to pain severity. CONCLUSIONS: Although no association of evaluated polymorphisms and trigeminal neuralgia or pain was observed, our data contributes to the knowledge of genetic susceptibility to trigeminal neuralgia, which is very scarce. Further studies may focus on other polymorphisms and mutations, as well as on epigenetics and transcriptional regulation of these genes, in order to clarify or definitively exclude the role of Nav1.6, BDNF, COMT or GCH1 in trigeminal neuralgia susceptibility and pathophysiology.

Genetic and epigenetic control of ACE2 expression and its possible role in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a pandemic that is claiming hundreds of thousands of lives around the world. Angiotensin-converting enzyme-2 (ACE2) is a key player in COVID-19 due to its pivotal role in the SARS-CoV-2 infection. This enzyme is expressed throughout the body and the studies conducted so far have shown that its expression varies according to several factors, including cell type, sex, age, disease states and probably SARS-CoV-2 infection. Single-nucleotide polymorphisms (SNPs) and epigenetic mechanisms, including DNA methylation, histone post-translational modifications and microRNAs, impact ACE2 expression and may explain structural variation. The understanding of how genetic variants and epigenetic markers act to control ACE2 expression in health and disease states may contribute to comprehend several aspects of COVID-19 that are puzzling researchers and clinicians. This review collects and appraises the literature regarding some aspects in the ACE2 biology, the expression patterns of this molecule, SNPs of the ACE2 gene and epigenetic mechanisms that may impact ACE2 expression in the context of COVID-19.

CD14 genotype and functional dichotomy of CD14+ and CD14- cells are associated with activated immune response and development of Chagas dilated cardiomyopathy.

We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.

An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings.

Childhood obesity is a global burden affecting millions of children worldwide. It is well-known that the adiposity profile in children is critical for future occurrence of diseases. As a multifactorial disease, obesity is associated with genetic and environmental factors. Epigenetic mechanisms link the plethora of environmental clues to a given phenotype. DNA methylation is the most studied epigenetic mark and its importance in several diseases was acknowledged. In childhood obesity, specifically, the studies show a consistent association between adiposity and methylation at the gene and genome-wide scales. The relationship between DNA methylation and childhood obesity has been proved strong for some genes and pathways. However, the studies are heterogeneous in their design, methodologies, and results. The aim of this review is to discuss this heterogeneity and point out some aspects that should be considered in future studies to clarify the role of DNA methylation in childhood obesity.

No Association of Polymorphisms in Nav1.7 or Nerve Growth Factor Receptor Genes with Trigeminal Neuralgia.

OBJECTIVE: Trigeminal neuralgia is defined as a sudden severe shock-like pain within the distribution of the trigeminal nerve. Pain is a subjective experience that is influenced by gender, culture, environment, psychological traits, and genes. Sodium channels and nerve growth factor play important roles in the transmission of nociceptive signals and pain. The aim of this study was to investigate the occurrence of Nav1.7 sodium channel and nerve growth factor receptor TrkA gene polymorphisms (SCN9A/rs6746030 and NTRK1/rs633, respectively) in trigeminal neuralgia patients. METHODS: Ninety-six subjects from pain specialty centers in the southeastern region of Brazil were divided into 2 groups: 48 with classical trigeminal neuralgia diagnosis and 48 controls. Pain was evaluated using the visual analog scale and multidimensional McGill Pain Questionnaire. Genomic DNA was obtained from oral swabs in all individuals and was analyzed by real-time polymerase chain reaction. RESULTS: No association was observed between evaluated polymorphisms and trigeminal neuralgia. For allele analyses, patients and controls had similar frequencies for both genes. Genotype distribution or allele frequencies of polymorphisms analyzed here did not correlate to pain scores. CONCLUSIONS: Although no association of evaluated polymorphisms and trigeminal neuralgia diagnosis or pain severity was observed, our data do not exclude the possibility that other genotypes affecting the expression of Nav1.7 or TrkA are associated with the disease. Further studies should investigate distinct genetic polymorphisms and epigenetic factors that may be important in expression of these molecules.

Ações extensionistas em saúde bucal na rede pública de ensino de Belo Horizonte, MG, Brasil / Extension actions in oral health in the public school system of Belo Horizonte, MG, Brazil

Objetivo:A escola mostra-se como um ambiente favorável para a divulgação e compartilhamento de informações sobre saúde. Este estudo objetivou relatar as ações extensionistas promovidas pelo Projeto "Promoção de Saúde Bucal" em duas escolas públicas de Belo Horizonte/MG. Métodos:Um total de 105 escolares com idade entre 8 e 15 anos participaram do estudo. A equipe do projeto foi constituída por alunos e professores da UFMG. Foram realizadas três intervenções com informações educativas sobre saúde bucal. Os escolares responderam a um questionário para avaliar seus hábitos diários e conhecimentos sobre saúde bucal, antes e após as intervenções. Foram realizadas análises descritivas, testes de McNemar e de Wilcoxon (p < 0,05). Resultados:As intervenções foram capazes de melhorar o conhecimento e atitudes dos escolares sobre saúde bucal. Em relação à primeira avaliação, houve uma redução significativa na quantidade relatada de creme dental colocada na escova dentes (p < 0,001). Além disso, os escolares passaram a utilizar o fio dental com maior frequência, houve redução na frequência da ingestão de doces e menor interesse em utilizar piercings e aparelhos ortodônticos falsos. Conclusão:As atividades extensionistas resultaram em maior conhecimento dos escolares sobre saúde bucal e ressaltam a necessidade de continuidade das ações para que bons hábitos de saúde sejam sedimentados. (AU)

Aim:Schools have proven to be favorable environments for the dissemination and sharing of health information. This study aimed to report the extension actions promoted by the Project "Oral Health Promotion" in two public schools in Belo Horizonte/MG. Methods:A total of 105 students, 8 to 15 years of age, participated in the study. The project team consisted of students and professors from UFMG. Three interventions were carried out using educational information on oral health. The students answered a questionnaire to evaluate their daily habits and knowledge about oral health before and after the interventions. Descriptive analyzes, as well as McNemar and Wilcoxon tests, were performed (p < 0.05). Results:Interventions were able to improve students' knowledge and attitudes about oral health. In relation to the first assessment, there was a significant reduction in the reported amount of toothpaste placed on the toothbrush (p < 0.001). In addition, the schoolchildren began to use dental floss more frequently, there was a reduction in the frequency of the intake of candies and less interest in using piercings and false orthodontic appliances. Conclusion:The extension activities resulted in greater knowledge of the students about oral health and highlighted the need for continuous actions so that good health habits are solidified. (AU)

Associação entre metilação do DNA e periodontite crônica: revisão de literatura / Association between DNA methylation and chronic periodontitis: literature review

A periodontite crônica (PC) é uma doença bucal caracterizada pela presença de bactérias que promovem a inflamação dos tecidos de suporte e inserção dos dentes, como resultado de complexas interações entre patógenos periodontais e a resposta imune do hospedeiro. A PC é multifatorial e os fatores envolvidos com a regulação gênica podem interferir na predisposição ao aparecimento dos sinais e sintomas da doença. Neste contexto estão os mecanismos epigenéticos caracterizados por modificação na expressão dos genes sem afetar a sequência do DNA. As principais evidências de alterações epigenéticas na PC se relacionam à análise do perfil de metilação em genes relacionados à resposta imunoinflamatória. A metilação do DNA é um mecanismo epigenético caracterizado pela adição de um grupo metil no carbono 5' do anel de citosina, inibindo efetivamente a transcrição gênica. O objetivo do estudo foi revisar a literatura sobre a metilação do DNA na PC e avaliar sua associação com a patogênese da doença. Foi realizada uma busca na base de dados (Pubmed), sem restrição de ano e/ou idioma, utilizando os seguintes descritores: (Methylation [MeSh] OR Methylation OR DNA methylation [MeSh] OR DNA methylation) and (Chronic periodontitis [Mesh] OR Chronic periodontitis). Apesar dos estudos epigenéticos em doença periodontal ainda serem escassos, com diversos pontos a serem elucidados, os achados sugerem o envolvimento da metilação do DNA em genes da resposta imunoinflamatória na patogênese da PC. (AU)

Chronic periodontitis (CP) is an oral disease characterized by the presence of bacteria that promote inflammation of the supporting tissues of the teeth, as a result of complex interactions between periodontal pathogens and the host immune response. The CP is multifactorial and the factors involved in gene regulation may interfere with the predisposition on the appearance of the signs and symptoms of the disease. In this context it has been observed the epigenetic mechanism characterized by change ingene expression without affecting the sequence of DNA. The main evidence of epigenetic changes in CP are related to the analysis of the methylation profile in genes involved with the immune response. DNA methylation is an epigenetic mechanism characterized by the addition of a methyl group on the 5' carbon of the cytosine ring, effectively inhibiting the gene transcription. The aim of this study was to review the literature on DNA methylation in CP and evaluate its association with the pathogenesis of the disease. The search was performed in the database (Pubmed) without year or language restriction restriction, using the following key words: (Methylation [MeSh] OR Methylation OR DNA methylation [MeSh] OR DNA methylation) and (Chronic periodontitis [Mesh] OR Chronic periodontitis). Despite the epigenetic studies on periodontal disease are still scarce, with several points to be elucidated, the findings suggest the involvement of DNA methylation in immune response genes in the pathogenesis of CP (AU)

Methylation pattern of the CD14 and TLR2 genes in human dental pulp.

INTRODUCTION: Pattern recognition receptors, such as toll-like receptor 2 (TLR-2) and TLR-4, participate in the activation of immune cells by microorganisms in dental pulp. However, the expression levels of pattern recognition receptors can be modulated by epigenetic factors, especially DNA methylation. In this study, the methylation status of the TLR-2 and CD14 (TLR4 co-receptor) genes in healthy and inflamed human dental pulp was examined. METHODS: The Methyl-Profiler DNA Methylation qPCR Assay was used to verify the DNA methylation patterns. RESULTS: No differences in the methylation patterns were observed between the 2 groups. Most DNA was unmethylated in both groups. CONCLUSIONS: The hypomethylation of TLR2 and CD14 genes is a usual feature in human dental pulp.

Hypermethylation and low transcription of TLR2 gene in chronic periodontitis.

Periodontitis is an inflammatory disorder characterized by interactions between periodontal pathogens and host's immune response. Epigenetic may contribute to disease development and outcome by influencing the expression of genes involved in the immune response. It has been shown that Toll-like receptors (TLR) play an important role in the response to periodontopathic bacteria. The aim of study was to evaluate the methylation status and the expression of TLR2 gene in gingival samples from individuals with and without periodontitis. DNA was analyzed using the Methyl Profiler DNA Methylation qPCR assay. DNA methylation and transcript levels were evaluated by real-time polymerase chain reaction. The periodontitis group showed a hypermethylated profile and a low expression of gene. Positive correlation between the TLR2 methylation frequency and probing depth was observed. This study gives the first evidence of methylation frequency in inflamed periodontal tissues and of the possible participation of methylation in the development of periodontitis.

Transcription factor STAT1 gene polymorphism is associated with the development of severe forms of periodontal disease.

INTRODUCTION: Periodontal disease (PD) is one of the most common inflammatory diseases, affecting about 10 % of the world population. The establishment of PD is influenced by polymorphisms in genes involved with the inflammatory response. Signal Transducer and Activator of Transcription (STAT)-1 is a transcription factor that plays a key role in the intracellular signaling triggered by cytokines and, thus, its activation is critical in inflammatory diseases. AIM AND METHODS: We aim to evaluate the occurrence of association between STAT-1 (rs3771300) polymorphism and distinct clinical forms and severity of PD; we genotyped 180 subjects using realtime PCR. RESULTS AND CONCLUSION: We observed that the presence of the G allele for STAT-1 was associated with twice as high of a chance to develop aggressive periodontitis, and the most severe form of the disease.

Expression, polymorphism and methylation pattern of interleukin-6 in periodontal tissues.

Periodontitis is considered an inflammatory disorder of bacterial etiology that results in periodontal tissue destruction, as a result of complex interactions between periodontal pathogens, host and immune response. Genetic and epigenetic mechanisms may modulate the individual response since it is able to influence the gene expression. The aim of this study was to evaluate the impact of -174 G/C polymorphism and the methylation status of the promoter region of IL-6 gene on the expression of IL-6 in gingival samples from individuals with chronic periodontitis. Gingival biopsies were collected from 21 patients with chronic periodontitis and 21 controls. Histologic sections stained by hematoxylin-eosin were used for histopathological evaluation. The IL-6 gene expression was assessed by quantitative real-time PCR. The polymorphism IL-6 -174 C/G was studied by polymerase chain reaction (PCR) amplification and restriction endonuclease digestion (HspII). Methylation-specific polymerase chain reaction was used to verify the DNA methylation pattern. The number of inflammatory cells in tissue fragments from individuals with chronic periodontitis was higher than in the control group and the inflammatory infiltrate was predominantly mononuclear. The expression of IL-6 was higher in the group with periodontitis. In polymorphism assay, no statistical difference in the distribution of genotypes and alleles in both groups were observed. The most of samples were partially methylated. No difference was observed in methylation pattern from two different regions of the IL-6 gene among groups. The high expression of IL-6 is an important factor related to chronic periodontitis, but was not associated with methylation status or the -174 (G/C) genetic polymorphism, suggesting that other mechanisms are involved in this gene transcription regulation.

Evaluation of IL17A expression and of IL17A, IL17F and IL23R gene polymorphisms in Brazilian individuals with periodontitis.

The IL23/Th17 axis plays an important role in the pathogenesis of cell-mediated tissue damage caused either by autoimmunity or immune responses against bacterial infection. Single nucleotide polymorphisms in the IL17A, IL17F and IL23R genes have been associated with several inflammatory diseases. However, these polymorphisms have not yet been studied in periodontitis. The aim of present study was to evaluate the expression of IL17A and occurrence of the IL17A (rs2275913), IL17F (rs763780) and IL23R (rs11209026) gene polymorphisms in different clinical forms or severity of periodontitis in a sample of Brazilian individuals. Peripheral blood was obtained from 30 non-smoker individuals and analyzed by flow cytometry to determine IL-17 expression. Genomic DNA was obtained from oral swabs in 180 individuals and analyzed by Real-time PCR. The study group was composed by individuals without periodontitis (control), with aggressive periodontitis (AP) and with chronic periodontitis (CP). Higher frequency of IL17A+CD4+ T cells was observed in control group. The A+ genotype from IL17A (rs2275913) was associated with lack of disease. No association was found considering the IL17F and IL23R polymorphisms. Our data suggest that IL17A and the presence of IL17A (rs2275913) A allele are associated with the absence of periodontal disease.

Hypomethylation of tumor suppressor genes in odontogenic myxoma.

Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

Methylation pattern of IFN-γ and IL-10 genes in periodontal tissues.

UNLABELLED: DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands. Unmethylated CpGs are related to transcriptionally active structure, whereas methylated CpG recruits methyl-binding proteins that promote chromatin compaction. DNA methylation can influence the expression of cytokines and affect the development of periodontal disease. OBJECTIVES: The purpose of the present study was to evaluate the methylation status of the interferon gamma (IFN-γ) and interleukin-10 (IL-10) genes in periodontal tissues. DESIGN: Methylation-specific polymerase chain reaction (MSP) and DNA sequencing analysis were used to verify the DNA methylation status of the IFN-γ and IL-10 genes, respectively, in samples from subjects without periodontitis and individuals with chronic periodontitis. Histological sections stained by hematoxylin-eosin were used for histopathological evaluation of samples. RESULTS: The methylation status of the IFN-γ and IL-10 genes was similar among the groups. Most of the samples were positive for IFN-γ methylation. Only 11% of the periodontitis group showed unmethylated DNA. Considering the IL-10 gene, no unmethylated sample was observed. The profile of total or partial methylation was detected in CpGs evaluated. CONCLUSIONS: The results showed evidence that methylation of IFN-γ and IL-10 genes is a usual feature on periodontal tissues. Further studies are needed to determine the functional relevance of these alterations.

Hypomethylation of tumor suppressor genes in odontogenic myxoma

Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

O mixoma odontogênico (MO) é um tumor odontogênico benigno de origem mesenquimal caracterizado pela presença de células fusiformes ou estreladas dispostas em abundante matriz extracelular mucóide. A metilação do DNA é caracterizada pela adição de grupos metil em citosinas constituintes de ilhas CpG na região promotora do gene. A metilação pode diminuir a expressão de genes supressores de tumor e contribuir para o desenvolvimento de lesões neoplásicas. O objetivo deste trabalho foi avaliar o padrão de metilação nos genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53), RB1 nos MO e na polpa dental. A metilação foi avaliada pela reação em cadeia da polimerase específica para a metilação. A transcrição dos genes foi estudada em alguns casos pela reação da transcriptase reversa (PCR quantitativa). Uma maior frequência de amostras não metiladas para os genes P27, P53 e RB1 foi observada nos MO quando comparados à polpa dental. Os MO expressaram RNAm de todos os genes avaliados. Considerando todas as amostras juntas, a expressão de Rb foi maior em amostras não metiladas comparadas as amostras parcialmente metiladas. Esta investigação mostrou a hipometilação dos genes P27, P53 e RB1 nos MO. Adicionalmente, a metilação nos genes supressores de tumor é um evento frequente em polpa dental normal.

Imunologia da retinocoroidite toxoplásmica / Immunology of the toxoplasmic retinochoroiditis

A infecção pelo Toxoplasma gondii é uma importante causa de doença ocular, tanto em indivíduos imunocomprometidos como em imunocompetentes. A patogênese da destruição retinocoroidiana associada a essa infecção ainda não está totalmente esclarecida. Nesta revisão, discute-se o papel do sistema imune no controle da infecção pelo Toxoplasma, especialmente, no olho.

Toxoplasma gondii infection is an important cause of ocular disease in both immunocompromised and immunocompetent subjects. The pathogenesis of retinochoroidal lesion associated with this infection is not fully understood. In this review, the role of the immune system in the control of Toxoplasma infection, especially in the eye, is discussed.

Effect of age on the association between p16CDKN2A methylation and DNMT3B polymorphism in head and neck carcinoma and patient survival.

De novo DNA methylation is a relevant epigenetic mechanism, which represses gene transcription and commonly inactivates tumor suppressor genes in carcinogenesis. A single nucleotide polymorphism of DNMT3B, C46359T (-149C-->T) was reported to modulate individual's susceptibility to cancer. We investigated the role of this polymorphic variant regarding the methylation status of the p16CDKN2A gene in young and older patients with head and neck squamous cell carcinoma (HNCC) matched by the TNM staging system, together with its impact on patients survival. The results showed that the presence of the allele T of the polymorphism DNMT3B (-149C-->T) was associated with advanced TNM staging and smoking habit, but no association was found between this polymorphisms and DNMT3B immunostaining. While p16CDKN2A methylation was significantly associated with smoking habit in older patients, this parameter was associated with family history of cancer in young patients. Moreover, in older patients the absence of p16CDKN2A promoter methylation had a negative impact on survival. In conclusion, nucleotide polymorphism of DNMT3B is not associated with methylation of p16CDKN2A gene in HNSCC. The association of p16CDKN2A gene methylation with smoking, family history of cancer and survival is dependent on age.

Gingival overgrowth in cyclosporine, tacrolimus, or sirolimus-based immunosuppressive regimens and the single nucleotide IL-6 (-174 G/C) gene polymorphism.

OBJECTIVE: Interleukin-6 (IL-6) may be involved in drug-induced gingival overgrowth (GO). The present study was conducted to assess the association between IL-6 (-174 G/C) gene polymorphism and GO in renal transplant recipients under cyclosporine (CsA), tacrolimus (Tcr), or sirolimus (Sir)-based regimens. METHODS: Within an eligible population, 45 unrelated subjects were selected for each CsA, Tcr, and Sir group, totaling a sample of 135 subjects. GO was visually assessed and subjects were assigned as controls (non-responders) or cases (responders) in a post hoc definition. IL-6 gene polymorphism was assessed using the polymerase chain reaction amplification and digestion. The distribution of genotypes and allele frequencies in responders and non-responders were compared using the Chi-squared test. RESULTS: The number of responders was 27 (60.0%), 13 (28.9%), and 7 (15.6%) in the CsA, Tcr, and Sir groups, respectively. No differences could be observed at frequencies of -174GG, -174CG, and -174CC genotypes when comparing responders to non-responders in the CsA, Tcr, and Sir groups. Similar to genotypes, allele frequencies showed no differences between responders and non-responders in all groups. CONCLUSIONS: No association between IL-6 (-174 G/C) gene polymorphism and gingival overgrowth was observed in renal transplant recipients under CsA, Tcr, or Sir-based immunosuppressive maintenance regimens.