MYD88, IRAK3 and Rheumatoid Arthritis pathogenesis: Analysis of differential gene expression in CD14 + monocytes and the inflammatory cytokine levels.

Rheumatoid arthritis (RA) is a well-known chronic inflammatory disorder. Two molecular players act in the inflammation balance of the disease: MyD88 (Myeloid differentiation primary response 88) is related to TLR (Toll-like receptors) response and promotes the formation of myddosome complex resulting in increased inflammation; IRAK3 (Interleukin-1 receptor associated kinase 3) acts suppressing the myddosome complex thus decreasing inflammation. In this scenario, MYD88 and IRAK3 gene expression profile in RA patients and its correlation with clinical features is still partially known. So, we evaluated the MYD88 and IRAK3 gene expressions in CD14 + monocytes from RA patients and healthy controls and its relation with patients' clinical features and cytokine plasma levels. CD14 + monocytes were isolated using positive selection by magnetic cell separation. The MYD88 and IRAK3 gene expressions were measured through real time relative quantitative PCR with specific primers; relative quantification was normalized to ACTB, GAPDH, 18S and RPLP0 reference genes. Cytokine levels were analyzed by CBA (cytokine beads assays). CD14 + monocytes from RA patients showed lower IRAK3 expression level compared to controls although with a borderline statistical significance (Fold change (FC) = -1.63; p = 0.054). Furthermore, RA patients with high disease activity had lower levels of IRAK3 when compared to patients with low/moderate activity measured by the CDAI index (FC = -1.78; p = 0.030). No significant differences were observed for MYD88 gene expression (FC = 1.20; p = 0.294) between patients and controls analyzed. Additionally, we did not we did not observe correlation between IRAK3 and MYD88 gene expression and TNF-α, IL-6, IL-2 and IL-10 levels. We suggested that IRAK3 gene expression in CD14 + monocytes appears to be relevant to the RA etiology and clinical activity, whereas, in this study, MYD88 does not play a role in RA onset and development.

Pharmacogenetic profile and the development of the dyskinesia induced by levodopa-therapy in Parkinson's disease patients: a population-based cohort study.

Levodopa-induced dyskinesia (LID) is an adverse effect that negatively impacts the quality of life of patients with Parkinson's disease (PD). Studies report that genetic variations in the genes of the pharmacogenetic pathway of the levodopa (L-DOPA) might be associated with LID development. The goal of the present study was to investigate a possible influence of functional genetic variants in the DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) genes with LID development. A total of 220 patients with idiopathic PD were enrolled. The genotyping for DRD1 (rs4532), DRD2 (rs1800497), DAT1 (rs28363170), and COMT (rs4680) polymorphisms were performed using Restriction Fragment Length Polymorphism (PCR-RFLP). Univariate and multivariate analyses were performed to assess the association of these polymorphisms and risk factors with LID development. Multivariate Cox regression analysis showed increased risk to LID development for both Levodopa Dose Equivalency (LED) (Hazard ratios (HR) = 1.001; 95% CI 1.00-1.01; p = 0.009) and individuals carrying the COMT L/L genotype (HR = 2.974; 95% CI 1.12-7.83; p = 0.010). Furthermore, when performed a Cox regression analysis adjusted for a total LED, we observed that the genotype COMT L/L had a 3.84-fold increased risk for LID development (HR = 3.841; 95% CI 1.29-11.37; p = 0.012). Our results suggest that before treating LID in PD patients, it is important to take into consideration genetic variant in the COMT gene, since COMT LL genotype may increase the risk for LID development.

What Differentiates Probiotic from Pathogenic Bacteria? The Genetic Mobility of Enterococcus faecium Offers New Molecular Insights.

Enterococcus faecium is a lactic acid bacterium with applications in food engineering and nutrigenomics, including as starter cultures in fermented foods. To differentiate the E. faecium probiotic from pathogenic bacteria, physiological analyses are often used but they do not guarantee that a bacterial strain is not pathogenic. We report here new findings and an approach based on comparison of the genetic mobility of (1) probiotic, (2) pathogenic, and (3) nonpathogenic and non-probiotic strains, so as to differentiate probiotics, and inform their safe use. The region of the 16S ribosomal DNA (rDNA) genes of different E. faecium strains native to Pernambuco-Brazil was used with the GenBank query sequence. Complete genomes were selected and divided into three groups as noted above to identify the mobile genetic elements (MGEs) (transposase, integrase, conjugative transposon protein and phage) and antibiotic resistance genes (ARGs), and to undertake pan-genome analysis and multiple genome alignment. Differences in the number of MGEs were found in ARGs, in the presence and absence of the genes that differentiate E. faecium probiotics and pathogenic bacteria genetically. Our data suggest that genetic mobility appears to be informative in differentiating between probiotic and pathogenic strains. While the present findings are not necessarily applicable to all probiotics, they offer novel molecular insights to guide future research in nutrigenomics, clinical medicine, and food engineering on new ways to differentiate pathogenic from probiotic bacteria.

IL1ß, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study.

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1ß, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1ß (rs1143634), -137 G/C IL18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1ß (rs1143634), -137 G/C IL-18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.

Persistência do HPV em mulheres tratadas para o adenocarcinoma cervical / Persistence of HPV in women treated for cervical adenocarcinoma

Objetivo: determinar a frequência da persistência do HPV em mulheres tratadas para o adenocarcinoma cervical. Método: trata-se de um estudo quantitativo, descritivo, retrospectivo, do tipo coorte, com 77 mulheres genotipadas para o HPV antes do tratamento e com adenocarcinoma cervical. Coletou-se novo material de secreção cervical após o tratamento para a realização da detecção do DNA do HPV por reação de cadeia da polimerase. Utilizou-se o programa estatístico Epi Info 7.1.4. para a análise dos dados. Resultados: observou-se que, das 77 pacientes, foi possível determinar a genotipagem do HPV após o tratamento em 30 mulheres e, destas, 7 (23,3%) apresentaram o HPV detectável. Encontraram-se os tipos de HPV dos quais quatro pacientes (57,1%) estavam com o HPV 31, sendo que, em uma paciente, estava associado ao HPV 18; o 33 em duas mulheres (28,6%), sendo que em uma estava associado ao HPV 16 e uma apresentou os HPV 11 e 56 associados (14,2%). Conclusão: detectou-se o HPV na secreção cervical em 23,3% das mulheres após o tratamento para o adenocarcinoma de colo uterino, sendo o HPV 31 o tipo mais frequente.(AU)

Objective: to determine the frequency of persistence of HPV in women treated for cervical adenocarcinoma. Method: this is a quantitative, descriptive, retrospective, cohort study, with 77 women genotyped for HPV before treatment and with cervical adenocarcinoma. New cervical secretion material was collected after treatment to detect HPV DNA by polymerase chain reaction. The Epi Info 7.1.4 statistical program was used for data analysis. Results: it was observed that, out of 77 patients, it was possible to determine HPV genotyping after treatment in 30 women, and of these, seven (23.3%) had detectable HPV. HPV types were found, of which four patients (57.1%) had HPV 31, and in one patient it was associated with HPV 18; o 33 in two women (28.6%), one of whom was associated with HPV 16 and one had HPV 11 and 56 associated (14.2%). Conclusion: HPV was detected in cervical secretion in 23.3% of women after treatment for cervical adenocarcinoma, with HPV 31 being the most frequent type.(AU)

Objetivo: determinar la frecuencia de persistencia del VPH en mujeres tratadas por adenocarcinoma cervical. Método: estudio de cohorte cuantitativo, descriptivo, retrospectivo, con 77 mujeres genotipadas para el VPH antes del tratamiento y con adenocarcinoma cervical. Se recogió nuevo material de secreción cervical después del tratamiento para detectar el ADN del VPH por reacción en cadena de la polimerasa. Se utilizó el programa estadístico Epi Info 7.1.4. para el análisis de datos. Resultados: se observó que, de las 77 pacientes, fue posible determinar el genotipo del VPH después del tratamiento en 30 mujeres, y de estos, 7 (23.3%) tenían VPH detectable. Se encontraron tipos de VPH, de los cuales cuatro pacientes (57.1%) tenían VPH 31, y en una paciente se asoció con VPH 18; o 33 en dos mujeres (28,6%), una de las cuales estaba asociada con el VPH 16 y una tenía VPH 11 y 56 (14,2%). Conclusión: el VPH se detectó en la secreción cervical en el 23,3% de las mujeres después del tratamiento para el adenocarcinoma de cuello uterino, siendo el VPH 31 el tipo más frecuente.(AU)

Human papillomavirus and risk factors for cervical adenocarcinoma in the state of Pernambuco, Brazil / Papilomavírus humano e fatores de risco para adenocarcinoma cervical no estado de Pernambuco, Brasil

Abstract Objectives: to determine the incidence of the main high oncogenic risk types of the human papillomavirus (HPV) ( 16, 18, 31 and 33) and the risk factors for cervical adenocarcinoma. Methods: a case-control study was carried out with 324 women (69 with adenocarcinoma and 260 healthy controls) between 2001 and 2014. Information on risk factors associated with adenocarcinomawere collected and the detection performed on HPVby using Polymerase Chain Reaction (PCR) method. Results: adenocarcinoma was associated with age ≥40 years old (OR=2.95; 95%CI=1.13-7.71), ≤3 years of schooling (OR=2.34; 95%CI=1.02-5.37), presence of HPV (OR=6.75; 95%CI=2.41-18.91),women in menopausal status (OR=4.76; 95%CI:1.70-13.31) black race (OR=6.71; 95%CI= 2.11-21.32) and never had undergone cervical cancer screening (OR=9.92; 95%CI:2.41-40.81). Andamong the HPV types detected, HPV 18 was observed to be strongly associated with adenocarcinoma of the cervix (OR=99.1; 95%CI=12.96-757.78). Conclusions: the factors associated with cervical adenocarcinoma were ≥40 years old, ≤3 years of schooling, black race, menopausal status, never had undergone cervical cancer screening and the presence of HPV.

Resumo Objetivos: determinar a incidência dos principais Papilomavirus Humano (HPV) de alto risco oncogênico (16, 18, 31 e 33) e os fatores associados ao adenocarcinoma do colo uterino. Métodos: realizado estudo de caso-controle com 324 mulheres (69 com adenocarcinoma e 260 controles saudáveis), de 2001 a 2014. Foram colhidas informações sobre fatores de risco associados ao adenocarcinoma e realizada a detecção do HPV pelo método da Reação em Cadeia da Polimerase (PCR). Resultados: o adenocarcinoma foi associado à idade >40 anos (OR=2,95; IC95%=1,13 - 7,71), escolaridade <3 anos (OR=2,34; IC95%=1,02 - 5,37), presença do HPV (OR=6,75; IC95%=2,41 - 18,91), mulher no estado menopausal (OR=4,76; IC 95%=1,70 - 13,31), raça negra (OR=6,71; IC95%=2,11 - 21,32) e nunca ter feito o exame de prevenção de Papanicolau (OR=9,92; IC95%=2,41 - 40,81). Entre os tipos de HPV encontrados observou-se que HPV 18 teve forte associação (OR=99,1; IC95%=12,96 - 757,78) com o adenocarcinoma de colo uterino. Conclusões: os fatores associados ao adenocarcinoma de colo uterino foram idade >40 anos, escolaridade <3 anos, raça negra, estado menopausal, nunca ter realizado o Papanicolau e presença do HPV.

Influence of DRD1 and DRD3 Polymorphisms in the Occurrence of Motor Effects in Patients with Sporadic Parkinson's Disease.

Parkinson's disease (PD) is a multisystem disorder that affects 2-3% of the population ≥ 65 years of age. The main pharmacologic agent use in the treatment of clinical symptoms of PD is levodopa (L-DOPA). However, the chronic use of L-DOPA might result in the emergence of motor complications such as motor fluctuation and dyskinesia. Previous studies have shown that the inter-individual variability and pharmacogenetic profile of PD patients seem to influence the occurrence of motor complications. For these reasons, the purpose of this study was to evaluate a possible relationship between DRD1 A48G and DRD3 Ser9Gly genetic variants with the occurrence of motor complications in PD patients in a Brazilian population. A total of 228 patients with idiopathic PD were enrolled. Patients were genotyped for DRD1 A48G and DRD3 Ser9Gly polymorphisms using PCR-RFLP. The univariate and multivariate analyses were performed to assess the association of these polymorphisms with the occurrence of motor fluctuation and dyskinesia in PD patients. Multiple Poisson regression analyses showed a protector effect to the occurrence of dyskinesia for individuals carrying of the DRD1 G/G genotype (PR 0.294; CI 0.09-0.87; p ≤ 0.020) after the threshold Bonferroni's. Besides, we verified risk increased to the occurrence of motor complications with daily L-DOPA dosage, disease duration, and users of rasagiline, selegiline, or entacapone (p < 0.05 for all). Our results suggest that the DRD1 A48G polymorphism and the presence of extrinsic and intrinsic factors may role an effect in the occurrence of dyskinesia in PD patients.

Absence of influence of polymorphisms of the MBL2 gene in oral infections by HSV-1 in individuals with HIV.

Polymorphisms in the structural gene MBL-2 (mannose-binding lectin-2) may result in low MBL serum concentration, associated with greater susceptibility to infection. The study evaluated the effects of MBL-2 polymorphisms with the oral manifestations of the HSV in human immunodeficiency virus (HIV)-infected patients. An observational case-control study was carried out, with the sample comprising 64 HIV+ and 65 healthy individuals. The signs and symptoms of HSV oral infection were evaluated, and oral mucosa buccal smears were collected. Polymorphisms of the MBL-2 gene and HSV-1 DNA were amplified through real-time PCR. The data revealed that of 64 HIV+, 29.6% presented signs and symptoms of HSV oral infection. Of these, the HSV-1 DNA was detected through real-time PCR in 21% of cases, and in 13.3% of asymptomatic individuals. There was no statistically significant difference between the symptomatic (p = 1) and the asymptomatic (p = 0.52) individuals, HIV+ and HIV-. Different genotypes (AA, A0, or 00) did not contribute to the oral manifestation of HSV in the HIV+ patients (p = 0.81) or HIV- (p = 0.45). There was no statistically significant difference in either group (p = 0.52). No significant association was identified between the MBL-2 gene polymorphisms in the oral manifestation of HSV infection. However, further studies are recommended with larger population groups before discarding this interrelationship.

Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease.

Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile of Parkinson's disease patients seem to influence the occurrence of visual hallucinations. In our study, we investigated a possible relationship of sequence variants in DRD1, DRD2, DRD3, DAT1, and COMT genes with the presence of visual hallucinations in Parkinson's disease patients. A total of 224 Brazilian patients from the Pro-Parkinson service at the Clinical Hospital of the University of Pernambuco, diagnosed with sporadic Parkinson's disease, were enrolled. Parkinson's disease patients were divided into 2 groups based on the presence or absence of visual hallucinations. The sequence variants for DRD1, DRD2, DRD3, DAT1, and COMT were determined through the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple Poisson regression analyses showed that individuals carrying the DRD3 Ser/Ser and Ser/Gly genotypes presented increased prevalence ratios of visual hallucinations (9.7-fold and 4.4-fold, respectively; P < .001). Regarding DAT1 rs28363170, there was a 9.82-fold increase in the prevalence ratio in patients with the 10/11 genotype, 8.78-fold for the 10/8 genotype, and 2.44-fold for the 9/8 genotypes (P < .001, for all). In addition, visual hallucinations were also associated with use of transdermal patches with rotigotine (PR, 3.7; 95%CI, 1.2-10.9; P = .017) and rasagiline (PR, 2.8; 95%CI, 1.3-6.0; P = .006). Our results suggest that the genetic variants DRD3 and DAT1, along with other therapeutic confounders, may influence the prevalence ratio of visual hallucinations.

MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson's Disease.

The most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible relation among selected single-nucleotide polymorphisms (SNPs) in the MAO-B (rs1799836) and COMT (rs4680) genes and the therapeutic response to levodopa (l-dopa). A total of 162 Brazilian patients from the Pro-Parkinson service of Clinics Hospital of Pernambuco diagnosed with sporadic PD and treated with levodopa were enrolled. PD patients were stratified into 2 groups according to the daily levodopa dose. MAO-B and COMT SNP genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism. After multivariate analysis, we observed a significant difference between PD groups for the following variables: sex (P = .02), longer duration of disease (P = .02), longer levodopa therapy duration (P = .01), younger onset of PD (P = .01), and use of COMT inhibitor (P = .02). We observed that patients carrying MAO-B (rs1799836) A and AA genotypes and COMT (rs4680) LL genotype suffered more frequently from levodopa-induced-dyskinesia. In addition, we found an increased risk of 2.84-fold for male individuals carrying the MAO-B G allele to be treated with higher doses of levodopa (P = .04). We concluded that before beginning PD pharmacological treatment, it is important to consider the genetic variants of the MAO-B and COMT genes and the sex, reinforcing the evidence that sexual dimorphism in the genes related to dopamine metabolism might affect PD treatment.

Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive, autoimmune disease for which the previous studies have shown that some functional polymorphisms can influence its etiology. Knowing this, the aim of this study was to investigate the association of +2199 A/C IL-23R (rs10889677), -197 G/A IL-17A (rs2275913), and +7488 A/G IL-17F (rs763780) gene polymorphisms with RA susceptibility and clinical features in a Brazilian population. A total of 127 RA patients and 134 healthy controls were recruited for the analyses of polymorphic variants. Genotyping was performed using RFLP-PCR. Logistic regression was used to analyze the genotype distribution of the polymorphisms. Individuals carrying the homozygous CC genotype for the IL-23R polymorphism seem to be at lower risk for RA development (OR 0.22; p = 0.004), as well as those carrying the variant C allele (OR 0.56; p = 0.002). For the -197 G/A IL-17A polymorphism, the wild-type genotype (GG) was significantly associated with a 3.18-fold (OR 3.18; p = 0.033) increased risk for RA. In relation to the +7488 A/G IL-17F polymorphism, no significant difference was found between RA cases and control subjects (p > 0.05). Moreover, when investigating the relationship between polymorphisms and clinical features, no evidence of an association was found. Our findings suggest that the variants +2199 A/C IL-23R and -197 G/A IL-17A could contribute to RA development in the studied population. However, larger studies are needed to fully understand this genetic predisposition.

Polymorphisms of Il-10 (-1082) and RANKL (-438) Genes and the Failure of Dental Implants.

Background. Genetic polymorphisms in certain cytokines and chemokines have been investigated to understand why some individuals display implant flaws despite having few risk factors at the time of implant. Purpose. To investigate the association of genetic polymorphisms in interleukin- (IL-) 10 [-1082 region (A/G)] and RANKL [-438 region (A/G)] with the failure of dental implants. Materials and Methods. This study included 90 partially edentulous male and female patients who were rehabilitated with a total of 245 Straumann dental implants. An implant was considered a failure if any of the following occurred: mobility, persistent subjective complaint, recurrent peri-implant infection with suppuration, continuous radiolucency around the implant, probing depth ≥ 5 mm, and bleeding on probing. Buccal mucosal cells were collected for analysis of RANKL438 and IL-10. Results. The implant success rate in this population was 34.4%. The mutant allele (G) in RANKL had an incidence of 52.3% and mutant allele (A) in IL-10 was observed in 37.8%. No statistically significant difference was detected between the failure of the implant and the genotypes and allelic frequencies. Conclusion. No association was detected between the genetic polymorphisms of RANKL (-438) and IL-10 (-1082) and the failure of dental implants in the population studied.

Dentifrice Containing Extract of Rosmarinus officinalis Linn.: An Antimicrobial Evaluation.

This study aimed to evaluate the antimicrobial activity of a dentifrice containing an alcoholic extract of rosemary on oral bacteria, compared to a commercially available herbal dentifrice. Standard strains of Streptococcus mutans (ATCC 25175), Streptococcus oralis (ATCC 9811) and Lactobacillus rhamnosus (ATCC 7469) were used, as well as different toothpastes based on rosemary (TR), on propolis (TH), triclosan (positive control) (TPC) and non-fluoridated dentifrice (negative control) (TNC). Bacteria were seeded in Petri dishes and paper discs soaked with dilutions of dentifrice placed on the plates. The inhibition halos were analyzed. It was observed that TR did not show statistical difference in relation to the TH to inhibit S. mutans and S. oralis, while TH was more active against L. rhamnosus. The toothpaste containing rosemary extract had the ability to inhibit the growth of S. mutans, S. oralis and L. rhamnosus, revealing an antimicrobial activity similar to commercially available toothpastes for inhibition of S. mutans and S. oralis.

Influence of IL-6, IL-8, and TGF-β 1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

Influence of IL-6, IL-8, and TGF-ß1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil.

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-ß1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

Dentifrice Containing Extract of Rosmarinus officinalis Linn: An Antimicrobial Evaluation

Abstract This study aimed to evaluate the antimicrobial activity of a dentifrice containing an alcoholic extract of rosemary on oral bacteria, compared to a commercially available herbal dentifrice. Standard strains of Streptococcus mutans (ATCC 25175), Streptococcus oralis (ATCC 9811) and Lactobacillus rhamnosus (ATCC 7469) were used, as well as different toothpastes based on rosemary (TR), on propolis (TH), triclosan (positive control) (TPC) and non-fluoridated dentifrice (negative control) (TNC). Bacteria were seeded in Petri dishes and paper discs soaked with dilutions of dentifrice placed on the plates. The inhibition halos were analyzed. It was observed that TR did not show statistical difference in relation to the TH to inhibit S. mutans and S. oralis, while TH was more active against L. rhamnosus. The toothpaste containing rosemary extract had the ability to inhibit the growth of S. mutans, S. oralis and L. rhamnosus, revealing an antimicrobial activity similar to commercially available toothpastes for inhibition of S. mutans and S. oralis.

Resumo O estudo teve como objetivo avaliar a atividade antimicrobiana de um dentifrício extrato alcoólico de alecrim sobre bactérias orais, comparando-o a um dentifrício herbal disponível no mercado. Cepas padrão de Streptococcus mutans (ATCC 25175), Streptococcus oralis (ATCC 9811) e Lactobacillus rhamnosus (ATCC 7469) foram utilizadas, bem como diferentes dentifrícios à base de alecrim (TR), própolis (TH), triclosan (controle positivo) (TPC) e sem flúor (controle negativo) (TNC). Placas de Petri foram inoculadas com as bactérias e discos de papel embebidos com diluições de cada dentifrício foram colocados nas placas. Em seguida, foram analisados os halos de inibição. Observou-se que o TR não mostrou diferença estatística em relação ao TH para inibição dos S. mutans e S. oralis, enquanto TH foi mais ativo contra L. rhamnosus. O dentifrício contendo extrato de alecrim foi capaz de inibir o crescimento de S. mutans, S. oralis e L. rhamnosus, revelando uma atividade antimicrobiana semelhante ao dentifrício disponível comercialmente na inibição de S. mutans e S. oralis.

CCR2 and CCR5 genes polymorphisms in women with cervical lesions from Pernambuco, Northeast Region of Brazil: a case-control study.

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

CCR2 and CCR5 genes polymorphisms in women with cervical lesions from Pernambuco, Northeast Region of Brazil: a case-control study

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.

Comparação de critérios de diagnóstico clínico de periodontite em diabéticos / Comparison of clinical diagnostic criteria of periodontitis in diabetics

Objetivo: A diversidade de critérios de diagnóstico clínico para periodontite em trabalhos científicos tem dificultado a determinação adequada da frequência desta doença e diminuído a possibilidade de comparações entre os estudos. O objetivo foi comparar cinco critérios encontrados na literatura que a associam a profundidade de sondagem (PS) e a perda de inserção clínica (PIC) na determinação da doença periodontal. Material e Métodos: 92 pacientes diabéticos foram submetidos à avaliação periodontal, sendo registrado medidas de PS e PIC em seis sítios em cada dente, e sangramento a sondagem. Com os dados registrados foi calculada a frequência da doença periodontal aplicando os diferentes critérios e posteriormente foi avaliado a concordância entre 5 critérios, utilizando o índice de Kappa (K). Resultados: A frequência de casos de periodontite para os critérios I (PIC ≥ 5 mm em 4 ou mais sítios, e pelo menos um deles com PS ≥ 4 mm), II (PS ≥ 4 mm e PIC ≥ 4 mm em pelo menos um sítio), III (4 ou mais dentes com pelo menos 1 sítio com PS ≥ 4 mm e PIC ≥ 3 mm), IV (2 ou mais dentes com pelo menos 1 sítio PS ≥ 4 mm e PIC ≥ 3mm) e V (PIC ≥ 6 mm em 2 ou mais dentes e PS ≥ 5 mm em 1 ou mais sítios) foi de 59,8%, 67,4%, 51,1%, 56,5% e 57,6%, respectivamente. A concordância entre os critérios de diagnósticos clínicos pelo Kappa variou entre 0,47 (47%) e 0,89 (89%). Conclusão: A frequência de distribuição da periodontite em pacientes diabéticos utilizando diversos critérios de diagnóstico não apresentou grande variação, e a concordância foi considerada entre razoável a boa e excelente. (AU)

Objective: The variability of clinical diagnostic criteria for periodontitis in scientific papers has difficulted the proper determination of the frequency of this disease and decreases the possibility of comparisons between studies. The aim of this study was to compare five criteria found in the literature associated with probing depth (PD) and clinical attachment loss (CAL) in the determination of periodontal disease. Methods: 92 diabetic patients underwent periodontal evaluation, and measures of PD and CAL was performed at six sites on each tooth, and bleeding on probing. With the recorded data the frequency of periodontal disease was calculated by applying different criteria and was subsequently evaluated the correlation between 5 criteria, using the Kappa index (K). Results: The frequency of cases of periodontitis for the criteria I (CAL ≥ 5 mm in 4 or more sites, with at least one site PD ≥ 4 mm), II (PD ≥ 4 mm and CAL ≥ 4 mm in at least one site), III (4 or more teeth with at least one site PD ≥ 4 mm and CAL ≥ 3 mm), IV (2 or more teeth with at least one site PD ≥ 4 mm e CAL ≥ 3mm) e V (CAL ≥ 6 mm in 2 or more teeth and PD ≥ 5 mm in one or more sites) was 59.8%, 67.4%, 51.1%, 56.5% and 57.6%, respectively. The agreement between the criteria for clinical diagnosis by Kappa ranged from 0.47 (47%) and 0.89 (89%). Conclusion: The frequency distribution of periodontitis in diabetic patients using various diagnostic criteria did not show great variation, and the agreement was considered reasonable to good and excelente (AU)

[Prevalence of HPV-induced lesions in the anal canal among women with cervical intraepithelial neoplasia 2 and 3: cross-sectional study]. / Prevalência da lesão HPV induzida em canal anal de mulheres com neoplasia intraepitelial cervical 2 e 3: um estudo de corte transversal.

PURPOSE: To determine the prevalence of HPV-induced lesions in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade 2/3. METHODS: A cross-sectional study was carried out from December 2008 to June 2009, in Pernambuco, northeastern Brazil. Only women with grade 2/3 CIN were included, and those who could not undergo anoscopy during their first visit were excluded. A cyttobrush was used for sample collection in order to identify HPV DNA through PCR and anal cytology. An anal biopsy was obtained in cases of abnormal anal cytology or major alterations in high resolution anoscopy (HRA). RESULTS: Thirty-two percent (n=37/115) of HRA were normal and 63.5% (n=73/115) showed acetowhite epithelium. Twenty-two percent (n=26/115) of anal cytologies were abnormal. Among the latter, 12.2% (n=14/26) were low-grade anal intraepithelial lesions and 3.4% (n=4/26) were high-grade anal intraepithelial lesions. Twenty-two anal biopsies were performed, 13.7% of which (n=3/22) were grade 2 anal intraepithelial neoplasia (AIN2) and 9% (n=2/22) were grade 3 AIN. Th HPV DNA was identified in 72.1% of cases (n=83/115). CONCLUSION: Women with CIN grade 2/3 showed a high prevalence of anal HPV infection and HPV-induced lesions.