DSpace Repository :: Browsing by Author "Silva, Nayara Nascimento Toledo"

Browsing by Author "Silva, Nayara Nascimento Toledo"

Now showing 1 - 10 of 10

3'UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions.
(2020) Silva, Nayara Nascimento Toledo; Santos, Ana Carolina da Silva; Nogueira, Verlândia Mendes; Carneiro, Cláudia Martins; Lima, Angélica Alves
Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Methods: Our sample consisted of 106 women, divided into two groups – Remission (n = 60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after 6 months of follow-up (T2), and Persistence (n = 46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5′-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide 1494 in TS 3′-untranslated region (TS3’UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19–8.69), p = 0.021], or the polymorphic genotype – del/del [OR (IC95%): 6.50 (1.71–24.70), p = 0.006] of TS3’UTR. Conclusions: The presence of the TS3’UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.
Association of serum folate and vitamin B12 with pre-neoplastic cervical lesions.
(2020) Silva, Nayara Nascimento Toledo; Santos, Ana Carolina da Silva; Carneiro, Cláudia Martins; Lima, Angélica Alves
Background & aims: Diet and lifestyle play an important role in etiology of various tumors. Serum concentration of folate and vitamin B12may be associated with carcinogenesis since they are involved in DNA methylation and nucleotide synthesis. However, the role of these micronutrients on development of cervical cancer is still controversial. Thus, the aim of this study was to analyze the association of lower status of folate and vitamin B12 with the risk of pre-neoplastic cervical lesions. Methods: Our sample group was divided in Control group (n ¼ 120) - women with normal cytology, and Case groups (n ¼ 57) e women presenting Atypical Squamous Cells of Undetermined Significance (ASCUS, n ¼ 21), Low Grade Squamous Intraepithelial Lesion (LSIL; n ¼ 16), and High-Grade lesions (n ¼ 20). We obtained cervical samples for cytology analysis and HPV detection, and blood samples for evaluation of serum concentration of folate and vitamin B12. Results: No difference of serum folate was observed among Cases and Control groups. On the other hand, women with High-Grade lesions presented significant lower median concentration of vitamin B12 if compared to another groups. Then, we observed increased risk of High-Grade lesions among participants with low vitamin B12 levels was observed in relation to women that presented high levels of the micronutrient and from Control group [OR (95% CI): 2.09 (0.65e6.76), p ¼ 0.216], ASC-US [OR (95% CI): 3.15 (0.82e12.08), p ¼ 0.095], and LSIL [OR (95% CI): 3.10 (0.76e12.70), p ¼ 0.116]. Conclusions: Low concentration of vitamin B12 was associated with an increased risk of High-Grade cervical lesions. Besides, we did not observe any difference of serum folate among women with normal cytology and women with pre-neoplastic cervical lesions.
Bacterial vaginosis : prevalence, risk profile and association with sexually transmitted infections.
(2020) Teixeira, Pedro Moregola; Vital, Wendel Coura; Lima, Angélica Alves; Silva, Nayara Nascimento Toledo; Carneiro, Cláudia Martins; Teixeira, Luiz Fernando de Medeiros; Silva, Glenda Nicioli da
Background and Objectives: Bacterial vaginosis (BV) is the most common cause of vaginal discharge in the world. The study aimed to estimate the prevalence and to identify risk factors associated with bacterial vaginosis. Methods: A cross-sectional study was conducted in Ouro Preto, Brazil, between February and December 2017. Three hundred and forty-one women aged 18 years or older, users of the Brazilian Unified Health System, participated in this study. Women who used oral or topical antibiotics in the four weeks prior to the sample collection and women who had undergone a total hysterectomy were excluded from the study. After signing the Informed Consent Form and filling out a questionnaire containing sociodemographic, behavioral and sexual data, the participants were directed to the collection room, where the nurse collected the samples for the preventive examination of the cervix and also two vaginal swabs. Vaginal swabs and cervical samples were analyzed for cytological abnormalities and BV using Gram staining and cytology. Pathogens causing sexually transmitted infections (STIs) were identified by Polymerase Chain Reaction (PCR). For the analysis of the data, statistical package STATA version 10.0 was used. This study was approved by the Research Ethics Committee of the Federal University of Ouro Preto (UFOP). Results: During the study, 341 women were evaluated. The prevalence of BV using Gram staining (32.5% [CI95% 27.737.7%]) and cytology (27.7% [CI95% 23.032.8%]) was similar, however, the sensitivity of cytology was lower (77.8%). Risk factors associated with BV were smoking (IRR 1.5 [CI95%: 1.1 2.1]), use of an intrauterine device (IRR 2.8 [CI95%: 1.2 6.5]), and past medical history of BV (IRR 1.5 [CI95%: 1.1 2.1]). Correlation between the presence of BV and Trichomonas vaginalis (TV) infection (r=0.24) was observed. Conclusion: The prevalence of BV was affected by life habits and was prevalent in women with TV. Thus, behavioral and social prevention approaches to women with diverse risk profiles may help mitigate TV/BV prevalence and recurrence of BV.
Cofatores genéticos e nutricionais associados às lesões pré-neoplásicas na cérvice uterina.
(2019) Silva, Nayara Nascimento Toledo; Lima, Angélica Alves; Zeferino, Luiz Carlos; Xavier, Marcelo Antônio Pascoal; Vieira, Paula Melo de Abreu; Silva, Glenda Nicioli da; Lima, Angélica Alves
Objetivo: Avaliar a associação de lesões pré-neoplásicas da cérvice uterina com polimorfismos das enzimas Metilenotetrahidrofolato Redutase (MTHFR C677T), Metionina sintase (MS A2756G), Metionina Sintase Redutase (MTRR A66G), Timidilato Sintase (TSER e TS3’UTR), e com os micronutrientes folato e vitamina B12. Métodos: Para avaliação da associação dos cofatores genéticos e nutricionais com as lesões préneoplásicas na cérvice uterina, foram selecionadas 214 mulheres divididas em: (a) Controle (n=120) – mulheres com citologia normal, e (b) Casos (n=94) – mulheres apresentando lesões cervicais préneoplásicas em células escamosas (ASC-US: n=37; LSIL: n=33; HSIL/ASC-H: n=24). Por outro lado, para análise do risco de persistência de alterações citopatológicas de acordo com os polimorfismos genéticos, foram avaliadas 106 participantes: (a) Grupos Remissão (n=66) – mulheres apresentando alteração citopatológica no início do estudo (T1) e citologia normal após seis meses (T2), e (b) Persistência (n=40) – mulheres apresentando lesão cervical pré-neoplásica em T1 e T2. Amostras sanguíneas foram coletadas para dosagem sérica de folato e de vitamina B12, realizada por quimioluminescência. Amostras cervicais foram obtidas para análise citopatológica pelo método de Papanicolaou; detecção e genotipagem do HPV pelas técnicas PCR-RFLP e LAMP; avaliação dos polimorfismos genéticos por PCR-RFLP; e dosagem de folato intracelular cervical por quimioluminescência. O Escore de Risco Genético (GRS) foi calculado para análise de todos os polimorfismos simultaneamente. Resultados: As concentrações medianas de folato intracelular cervical e sérico foram 2,5 ng/mg e 11,9 ng/mL, respectivamente, e menores concentrações deste micronutriente foram observadas em mulheres apresentando lesões cervicais pré-neoplásicas de alto grau (HSIL/ASC-H), embora as diferenças não tenham sido significativas. A concentração sérica mediana de vitamina B12 das participantes desse estudo foi de 274 pg/mL. Observou-se risco elevado de lesões de alto grau em mulheres com baixo nível desse micronutriente se comparado àquelas com níveis altos de vitamina B12 e dos grupos Controle [OR (IC95%): 2,13 (0,67-6,80)], ASC-US [OR (IC95%): 3,53 (0,94- 13,24)] ou LSIL [OR (IC95%): 3,18 (0,78-12,93)]. Em relação aos polimorfismos genéticos, não houve diferença significativa da distribuição dos genótipos e alelos de MTHFR C677T, MS A2756G e TS3’UTR entre os grupos apresentando ou não alteração citopatológica. No entanto, a presença do polimorfismo TS3’UTR foi considerada fator de risco para persistência das lesões cervicais, sendo que os genótipos ins/del e del/del aumentaram o risco de persistência pelos menos três vezes [OR (IC95%): 3,13 (1,21-8,12), p=0,019; OR (IC95%): 5,96 (1,67-21,25), p=0,006 - respectivamente]. A avaliação do risco de lesões pré-neoplásicas na cérvice uterina de acordo com o GRS e os níveis de folato e de vitamina B12, mostrou maior risco de HSIL/ASC-H em mulheres com altos níveis de folato intracelular cervical e com GRS≥3 [OR (IC 95%): 1,85 (0,42-8,11)]. Por outro lado, observou-se risco maior de alterações citológicas de alto grau em mulheres com baixos níveis de vitamina B12 e GRS≥3 [OR (IC 95%): 2,91 (0,46-18,62)]. Conclusão: A presença do polimorfismo TS3’UTR elevou o risco de persistência das lesões cervicais, enquanto os polimorfismos MTHFR C677T e MS A2756G não foram associados a alterações citopatológicas ou ao curso das lesões na cérvice uterina. Altos níveis intracelulares cervicais de folato ou baixos níveis séricos de vitamina B12, associados ao alto número de alterações genéticas, elevaram o risco de lesões cervicais pré-neoplásicas de alto grau. Além disso, a concentração sérica de vitamina B12 também foi associada a aumento do risco de HSIL/ASC-H quando analisada isoladamente.
Comparison of capillary electrophoresis, AGE, and PAGE for MTHFR polymorphism analysis in FFPE cervical samples.
(2018) Silva, Nayara Nascimento Toledo; Reis, Levi Eduardo Soares; Lima, Angélica Alves
Background. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism analysis could help in diagnosis, treatment, and prognosis of some pathologies, since it has been associated with the development of cardiovascular diseases, defects in neural tube formation, psychiatric disorders, and cancer. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) is the most commonly used technique to analyze this polymorphism. Usually, RFLP products are evaluated by agarose gel electrophoresis (AGE) or polyacrylamide gel electrophoresis (PAGE). However, capillary electrophoresis (CE) may represent an alternative for MTHFR C677T polymorphism analysis by PCR-RFLP. Thus, the aim of this study was to compare CE, AGE, and PAGE to MTHFR C677T polymorphism analysis of Formalin-Fixed and Paraffin-Embedded (FFPE) cervical samples. Methods. 150 biopsy blocks of cervical samples were analyzed. MTHFR polymorphism was evaluated by PCR-RFLP, and the products generated were analyzed by CE, AGE, and PAGE. Concordance between the methods was evaluated by rate agreement, Kappa coefficient, and McNemars’s Test. Results. Eight samples (5.4%) showed discordant results according to CE and PAGE or AGE. Differences of CC and CT frequencies were observed between CE and AGE (p=0.016): CC genotype varied from 68.0% to 72.7%, and CT varied from 23.3% to 27.3%. Besides, Kappa coefficient between CE and AGE, or PAGE was very high (κ>0.81). Conclusion. Capillary electrophoresis presented high agreement with PAGE and AGE, and may be an accurate, safe, and quick alternative method for MTHFR polymorphism analysis.
Knowledge about cervical cancer and HPV immunization dropout rate among Brazilian adolescent girls and their guardians.
(2020) Santos, Ana Carolina da Silva; Silva, Nayara Nascimento Toledo; Carneiro, Cláudia Martins; Vital, Wendel Coura; Lima, Angélica Alves
Background: Infections with Human Papillomavirus (HPV) are the main cause of cervical cancer. Since 2014, the HPV vaccine was introduced in the Brazilian National Vaccination Calendar. The purpose of this study was to assess the knowledge of adolescent girls and their mothers/guardians about HPV and HPV vaccine, identify the factors associated with this knowledge, and evaluate immunization dropout rate. Methods: This was a cross-sectional study involving adolescent girls and their mothers/guardians. Participants underwent an interview that addressed sociodemographic data, sexual and gynecological history, and knowledge about HPV, HPV vaccine and cervical cancer. The third quartile of the total score was established as a cutoff for assessing knowledge. Adolescents who correctly answered more than four questions and mothers/guardians who obtained more than five correct responses were categorized into high knowledge. Poisson regression analysis was performed to identify variables associated with low knowledge. Vaccination records were used to assess immunization dropout rates. Any adolescent who did not complete the two-dose vaccination schedule was considered dropout. Results: A total of 666 adolescent girls and 623 mothers/guardians were interviewed. Low knowledge was observed in 76.7% of adolescents and 79.8% of mothers/guardians. Most were unaware of the causal relationship between HPV and cervical cancer, signs and symptoms of HPV infection, and had limited knowledge about the HPV vaccine. Factors associated with low knowledge of adolescents were aged 12 years [IRR 1.2 (95% CI 1. 1-1.3)] or less [IRR 1.3 (95% CI (1. 2-1.4)]; household income lower than US$750 [IRR 1.7 (95% CI 1. 1-2.6)] and household income between US$751 and US$1500 [IRR 1.6 (95% CI 1.0–2.6)]. Among mothers/guardians, low knowledge was related to having completed elementary school or less [IRR 1.5 (95% CI 1. 2-2.0)]; and household income lower than US$750 [IRR 1.2 (95% CI 1.0–1.4)]. Knowledge of adolescents and mothers/guardians was not associated with vaccine uptake. HPV immunization dropout rate was considered high (32.3%). Conclusion: Knowledge about HPV and cervical cancer as well as vaccine uptake was low. Results highlight the need for educational interventions about HPV and cervical cancer. These actions may contribute to improve adherence to HPV vaccination.
Lack of association between methylenetetrahydrofolate reductase C677T polymorphism, HPV infection and cervical intraepithelial neoplasia in Brazilian women.
(2019) Silva, Nayara Nascimento Toledo; Sabino, Adriano de Paula; Tafuri, Alexandre; Lima, Angélica Alves
Background: Cervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. However, many environmental, genetical, and epigenetical cofactors can modulate viral infection and cervical carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. Nevertheless, studies with cervical cancer presented controversial results, and varied according to ethnicity. Thus, the aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer. Methods: A case-control study was performed with 150 histological cervical samples. Case group were divided in Cervical Intraepithelial Neoplasia (CIN) grade I (n = 30), CIN II (n = 30), CIN III (n = 30), and Squamous Cervical Carcinoma (SCC) (n = 30). Control group was composed by 30 samples without lesion, presenting cervicitis. HPV detection was performed by conventional Polymerase Chain Reaction (PCR) with SPF primers set, and by real-time PCR specific for HPV 16 and hr-HPV. MTHFR C677T polymorphism was analyzed by PCR followed by Restriction Fragment Length Polymorphism (RFLP). Results: Frequency of MTHFR CC genotype was 72.7% (n = 109), CT 23.3% (n = 35) and TT 4.0% (n = 6). Polymorphic T allele frequency was 15.7%. No statistically significant association was observed between MTHFR C677T polymorphism and presence of pre-neoplastic or neoplastic cervical lesions. Similar frequencies of T allele was observed in control (23.3%) and cases (13.3%) groups (p = 0.174). In addition, there was no statistically significant association between MTHFR C677T polymorphism and viral infection, even considering hr-HPV or HPV 16 positivity. Conclusion: MTHFR C677T polymorphism was not associated with cervical cancer and HPV infection.
Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples.
(2013) Sana, Dandara Emery Morais; Miranda, Priscila Mayrink de; Pitol, Bruna Caroline Vieira; Silva, Nayara Nascimento Toledo; Silva, Ismael Dale Cotrim Guerreiro da; Stocco, Rita de Cássia; Beçak, Willy; Lima, Angélica Alves; Carneiro, Cláudia Martins
Herein, we evaluated cervical samples from normal tissue or HPV-infected tissue, to determine if the relative nuclear/cytoplasmic ratio (NA/CA) and the presence of nonclassical cytological criteria are a novel cytological criterion for the diagnosis of HPV. Significantly, larger NA/CA ratios were found for the HPV−ATYPIA+ and HPV+ATYPIA+ groups compared with HPV−ATYPIA− group, regardless of collection method. For the samples collected with a spatula, only three samples from the HPV−ATIPIA− group showed four or more nonclassical parameters (i.e., were positive), while a larger number of the samples in the HPV−ATYPIA+, HPV+ATYPIA−, and HPV+ATYPIA+ groups were positive (13, 4, and 13 samples, respectively). Among those collected with a brush, no sample showed four or more nonclassical criteria in the HPV−ATYPIA− group, while a number of samples were positive in the HPV−ATYPIA+, HPV+ATYPIA−, and HPV+ATYPIA+ groups (4, 3, and 4 samples, respectively). HPV infection was associated with significant morphometrical changes; no increase in the NA/CA ratio was found in the HPV+ATYPIA- samples, compared with the HPV−ATIPIA− samples collected with either a spatula or a brush. In conclusion, by including nonclassical cytological criteria into the patient diagnosis, we were able to reduce the number of false negative and false positive HPV diagnoses made using conventional cytology alone. Diagn. Cytopathol.
Persistence or clearance of human papillomavirus infections in women in Ouro Preto, Brazil.
(2013) Miranda, Priscila Mayrink de; Silva, Nayara Nascimento Toledo; Pitol, Bruna Caroline Vieira; Silva, Ismael Dale Cotrim Guerreiro da; Lima Filho, José Luiz de; Carvalho, Rodrigo Franco de; Stocco, Rita de Cássia; Beçak, Willy; Lima, Angélica Alves
Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer.We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18–75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 orGP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the followup. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer.
Polimorfismo C677T no gene da enzima metilenotetrahidrofolato redutase e o risco de desenvolvimento do câncer cervical.
(2015) Silva, Nayara Nascimento Toledo; Lima, Angélica Alves
A Metilenotetrahidrofolato Redutase (MTHFR) é uma enzima que atua no metabolismo do folato e polimorfismos em seu gene vêm sendo associados de maneira controversa ao desenvolvimento do câncer cervical. Esta neoplasia, causada principalmente pela infecção persistente pelo Papilomavírus Humano (HPV), possui altas taxas de prevalência e mortalidade na população feminina. Neste trabalho, a pesquisa de HPV nas amostras histológicas foi realizada por Imunohistoquímica e Reação em Cadeia da Polimerase (PCR) com os iniciadores SPF e GP5+/GP6+. O polimorfismo C677T no gene da enzima MTHFR foi analisado por PCR seguida de digestão enzimática (RFLP) utilizando eletroforese em gel de agarose, em gel de poliacrilamida e eletroforese capilar. Após a definição da metodologia mais adequada para a detecção viral e a avaliação desse polimorfismo no material parafinado, as análises foram realizadas em 240 amostras, sendo 120 do grupo controle e 120 casos. A frequência dos genótipos da MTHFR na amostragem foi de 64% CC, 31% CT e 5% TT. Associação estatisticamente significativa foi encontrada entre o polimorfismo C677T da MTHFR e a presença de lesões intraepiteliais cervicais/carcinoma epidermoide invasor, sendo que o alelo T foi observado em 33,1% do grupo controle e em apenas 21,6% dos casos (p=0,023). A avaliação de risco (Odds ratio – OR) sugeriu que a presença do alelo polimórfico pode agir com um fator de proteção para lesões cervicais (OR: 0,557; IC95% 0,355- 0,925; p=0,024). Resultados similares foram encontrados no grupo com faixa etária superior a 30 anos. Por outro lado, não foi observada associação estatisticamente significativa entre a infecção viral e o polimorfismo C677T da MTHFR. Assim, pode-se concluir que mulheres com o polimorfismo C677T no gene da MTHFR possuem um risco menor de apresentarem lesões préneoplásicas e neoplásicas da cérvice uterina.

Browsing by Author "Silva, Nayara Nascimento Toledo"

Results Per Page

Sort Options