RESUMO

Introduction Cancer is a multifactorial disease dependent on the influence of genetic and environmental factors. About 10% of cancers are associated with germline mutations, which predispose to a higher risk of developing cancer. Currently, the use of panels that identify susceptibility and/or association genes cancer has been increasingly used, both in clinical practice and in scientific research. Objective To investigate genetic mutations in patients with a profile for hereditary cancer in individuals from a region of northeast Brazil, where there is a high frequency of endogenous and consanguineous marriages. Methods A set of 17 genes ( BRCA1 , BRCA2 , APC , TP53 , PTEN , RET , VHL , RB1 , CDKN2 , CDH1 , CHEK2 , MLH1 , MSH2 , MSH6 , MUTYH , XPA , and XPC ) associated with cancer and hereditary syndromes were analyzed. Fifteen patients with a hereditary cancer profile were evaluated. Results The pathogenic variant found was c.1187G > A (p.Gly396Asp), rs36053993 in the MUTYH gene in a male patient diagnosed with melanoma at the age of 43 years and a family history for this tumor. This gene encodes an important enzyme related to DNA repair and has been associated with other types of cancer, this is the first report of an association with melanoma, the biological plausibility of this association is given once the MUTYH protein is expressed in the skin tissue and is responsible for repairing damage caused, for example, by sun exposure. Conclusion The results of this study suggest that this mutation may be important for the hereditary predisposition to melanoma, but a broader investigation of this mutation is needed.

RESUMO

The intracellular protozoan Toxoplasma gondii may cause congenital toxoplasmosis and serious brain damage in fetus. However, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains unclear. For this study, neural progenitor cells (NPCs) were obtained from embryo telencephalons (embryonic day 13) and induced to proliferation in the presence of growth factors (GFs). For gathering insights into the biological effects of resveratrol (RSV) on neurogenesis, this study aimed to investigate effects of RSV concentrations (0.1 to 100 µM) on proliferation, migration and differentiation of NPCs infected by T. gondii. T. gondii infection increased the presence of cells in Sub G1 phase, reducing the global frequency of undifferentiated cells in S and G2/M phases of cell cycle and reduced cell viability/mithochondrial activity of infected NPCs. Moreover T. gondii stimulated neural migration and gliogenesis during neutral differentation. However, the treatment with RSV stimulated cell proliferation, restored cellular viability of infected NPCs and exerted an inhibitory effect on gliogenesis of infected NPCs favorecing neuronal maturation during toxoplasmosis infection. Thus, we have successfully to demonstrated that RSV is promising as therapeutic for congenital toxoplasmosis.

Assuntos

Células-Tronco Neurais/parasitologia , Neurogênese/efeitos dos fármacos , Neuroglia/patologia , Resveratrol/farmacologia , Toxoplasma/fisiologia , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/parasitologia , Encéfalo/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Transmissão Vertical de Doenças Infecciosas , Camundongos , Células-Tronco Neurais/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo

RESUMO

Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRKSm of S. mutans regulates the synthesis of and interaction with sucrose-derived exopolysaccharides (EPS), processes associated with oral and systemic virulence. In this study, we investigated the mechanisms by which VicRKSm affects S. mutans susceptibility to blood-mediated immunity. Compared with parent strain UA159, the vicKSm isogenic mutant (UAvic) showed reduced susceptibility to deposition of C3b of complement, low binding to serum immunoglobulin G (IgG), and low frequency of C3b/IgG-mediated opsonophagocytosis by polymorphonuclear cells in a sucrose-independent way (P<.05). Reverse transcriptase quantitative polymerase chain reaction analysis comparing gene expression in UA159 and UAvic revealed that genes encoding putative peptidases of the complement (pepO and smu.399) were upregulated in UAvic in the presence of serum, although genes encoding murein hydrolases (SmaA and Smu.2146c) or metabolic/surface proteins involved in bacterial interactions with host components (enolase, GAPDH) were mostly affected in a serum-independent way. Among vicKSm -downstream genes (smaA, smu.2146c, lysM, atlA, pepO, smu.399), only pepO and smu.399 were associated with UAvic phenotypes; deletion of both genes in UA159 significantly enhanced levels of C3b deposition and opsonophagocytosis (P<.05). Moreover, consistent with the fibronectin-binding function of PepO orthologues, UAvic showed increased binding to fibronectin. Reduced susceptibility to opsonophagocytosis was insufficient to enhance ex vivo persistence of UAvic in blood, which was associated with growth defects of this mutant under limited nutrient conditions. Our findings revealed that S. mutans employs mechanisms of complement evasion through peptidases, which are controlled by VicRKSm.

Assuntos

Proteínas de Bactérias/metabolismo , Complemento C3b/imunologia , Regulação Bacteriana da Expressão Gênica , Evasão da Resposta Imune , Streptococcus mutans/imunologia , Streptococcus mutans/fisiologia , Bacteriemia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Cárie Dentária/microbiologia , Expressão Gênica , Humanos , Imunoglobulina G/imunologia , Proteínas de Membrana/genética , Mutação , Ligação Proteica , Streptococcus mutans/genética , Sacarose/metabolismo , Virulência

RESUMO

Emerging antibiotic resistance in the oropharyngeal microbiota, of which Streptococcus salivarius is a prominent species, represents a challenge for treating paediatric populations. In this study, we investigated the role of Streptococcussalivarius as a reservoir for antibiotic resistance genes (ARG) in the oral microbiota by analysing 95 Streptococcussalivarius isolates from 22 healthy infants (2-16 months of age). MICs of penicillin G, amoxicillin, erythromycin, tetracycline, doxycycline and streptomycin were determined. ARG profiles were assessed in a subset of 21 strains by next-generation sequencing of genomes, followed by searches of assembled reads against the Comprehensive Antibiotic Resistance Database. Strains resistant to erythromycin, penicillins and tetracyclines were isolated from 83.3, 33.3 and 16.6 %, respectively, of infants aged 2 to 8 months with no prior antibiotic treatment. These percentages were100.0, 66.6 and 50.0 %, by 13 to 16 months of age. ARG or polymorphisms associated with antibiotic resistance were the most prevalent and involved genes for macrolide efflux (mel, mefA/E and macB), ribosomal protection [erm(B), tet(M) and tet(O)] and ß-lactamase-like proteins. Phylogenetically related strains showing multidrug-resistant phenotypes harboured multidrug efflux ARG. Polymorphic genes associated with antibiotic resistance to drugs affecting DNA replication, folate synthesis, RNA/protein synthesis and regulators of antibiotic stress responses were detected. These data imply that Streptococcussalivarius strains established during maturation of the oral microbiota harbour a diverse array of functional ARG, even in the absence of antibiotic selective pressures, highlighting a potential role for this species in shaping antibiotic susceptibility profiles of oropharyngeal communities.

Assuntos

Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Boca/microbiologia , Streptococcus salivarius/efeitos dos fármacos , Streptococcus salivarius/genética , Antibacterianos/classificação , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Genes Bacterianos , Genes MDR , Genoma Bacteriano , Genótipo , Voluntários Saudáveis , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Testes de Sensibilidade Microbiana , Fenótipo , Análise de Sequência de DNA , Streptococcus salivarius/classificação , Streptococcus salivarius/fisiologia

RESUMO

OBJECTIVE: The aim of the study was to establish a correlation between Overactive Bladder (OAB) symptoms and Body Mass Index (BMI) in women aged 20-45. METHODS: We interviewed 1.050 women aged 20-45 in the area of Campinas, Brazil, to investigate the prevalence of overactive bladder symptoms. In this study, we used the ICIQ-OAB questionnaire (ICS standard), in its validated portuguese version and a specific questionnaire for the demographics, which includes information about BMI. RESULTS: Overall, women with BMI ≥30 presented a significantly higher score than women with a lower BMI (18.5 - 24.9) (p=0.0066). In the analysis of individual symptoms, no significant differences were found regarding urinary frequency (p=0.5469). Women with BMI ≥30 presented more nocturia than women with BMI ranging between 18.5 and 24.9 (p=0.0154). Women in the group of BMI 25 - 29.9 presented more urgency than women with BMI 18.5 - 24.9 (p=0.0278). Significant difference was also found regarding urge-incontinence; women with BMI 25 - 29.9 presented a higher score than women in the group 18.5 - 24.9 (p= 0.0017). Analysis was also performed on the visual analogue scale regarding how much each symptom bothers the women (quality of life). There were no significant differences regarding frequency, nocturia or urgency but urgency incontinence bother was significant. Women with BMI 25 - 29.9 were more bothered by incontinence than women with BMI 18.5 - 24.9 (p=0.002). CONCLUSION: In conclusion, this study reinforces the correlation between BMI and OAB symptoms. Obese women present more OAB symptoms than non-obese women.

Assuntos

Índice de Massa Corporal , Pré-Menopausa/fisiologia , Bexiga Urinária Hiperativa/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Noctúria/epidemiologia , Obesidade/epidemiologia , Prevalência , Qualidade de Vida , Inquéritos e Questionários , Incontinência Urinária de Urgência/epidemiologia , Adulto Jovem

RESUMO

OBJECTIVE: To verify whether the combination of transcutaneous electrical neural stimulation (TENS) with oxybutynin in the treatment of women with overactive bladder (OAB) would be more effective than isolated treatments. METHODS: We randomized 75 women with OAB, in three groups: GI--30 min TENS, twice a week; GII--daily slow release 10 mg oxybutynin; and GIII--TENS + oxybutynin (multimodal); all for 12 weeks. Patients were evaluated with validated questionnaires International Consultation on Incontinence-Short Form (ICIQ-SF), International Consultation on Incontinence-OAB (ICIQ-OAB), Symptom bother, and 3-day Voiding diary at weeks 0, 12, and 24. RESULTS: The groups were similar before treatment. After treatment, all groups significantly improved in OAB symptoms and quality of life (QoL). At week 12, ICIQ-OAB scores were 5.9, 4.6, and 2.9, in groups I, II, and III, respectively, p = 0.01. At week 24, GI and GIII kept the scores of the end of treatment (week 12), while GII increased ICIQ-OAB from 4.6 to 9.2, p = 0.0001, ICIQ-SF from 9.8 to 13.3, p = 0.0006, and Symptom bother score from 3.4 to 7.0, p = 0.0001. CONCLUSIONS: The multimodal treatment was more effective and TENS alone or in association presented longer lasting results for improvement of clinical symptoms of OAB and QoL.

Assuntos

Terapia por Estimulação Elétrica/métodos , Ácidos Mandélicos/uso terapêutico , Nervo Tibial/fisiologia , Bexiga Urinária Hiperativa/terapia , Agentes Urológicos/uso terapêutico , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Bexiga Urinária Hiperativa/fisiopatologia

RESUMO

AIM: The aim of the study was to verify the presence of overactive bladder syndrome (OAB) symptoms in premenopausal women and relate them with child-bearing data. MATERIAL AND METHODS: We interviewed 1050 women aged 20-45 years in the area of Campinas, Brazil, to investigate the prevalence of OAB symptoms. In this study we used the International Consultation on Incontinence Questionnaire - Overactive Bladder (ICIQ-OAB) questionnaire (International Continence Society standard), in its validated Portuguese version and a specific questionnaire for the demographics. RESULTS: Overall, multiparous and primiparous women showed significantly higher scores in the ICIQ-OAB questionnaire than nulliparous women. Multiparous women also presented more frequency than nulliparous women (P < 0.0001). Nulliparous women presented less nocturia than primiparous or multiparous women (P < 0.0001). No significant differences were found in urgency (P = 0.0682), and multiparous women presented more urgency incontinence than nulliparous ones (P = 0.0313). CONCLUSIONS: Nulliparous women presented fewer OAB symptoms than primiparous women. Multiparous women presented more symptoms than the other two groups. There were no significant differences between cesarean and vaginal delivery, but the scores of women who had vaginal delivery were higher than those who had cesareans. Both types of delivery were related to higher ICIQ-OAB scores (more severe symptoms) than those of nulliparous women.

Assuntos

Bexiga Urinária Hiperativa/epidemiologia , Adulto , Brasil/epidemiologia , Feminino , Humanos , Noctúria/etiologia , Paridade , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Bexiga Urinária Hiperativa/fisiopatologia , Adulto Jovem

RESUMO

INTRODUCTION: The clitoral blood flow increase is dependent of nitric oxide (NO) and it occurs due to sexual arousal. Female sexual disorder mechanisms are poorly understood and NO therapeutic role in this scenario is to be determined. AIM: To assess topic NO donor S-nitrosoglutationa (GSNO) gel-100 µM effect on clitoral blood flow in healthy women. METHODS: Forty healthy women were double-blinded randomized for Group 1, GSNO gel, n=20 and Group 2, placebo gel, n=20. All patients underwent Doppler ultrasound test in the clitoral artery. Hemodynamic analysis consisted of: systolic peak speed, diastolic speed, and vase resistance rate. Ten random patients were analyzed regarding sexual function after two double-blinded placebo and NO donor gel periods of 30 days. MAIN OUTCOME MEASURES: To consider female sexual dysfunction treatment through local NO-dependent pathway. RESULTS: Mean age was 31 years (20-39) and mean female sexual function index score 31.5 (26-34). Group 1: The mean and standard deviation baseline and 15 minutes after the application of the GSNO gel systolic (11.7±2.1 cm/second to 15.9±2.4 cm/second) and diastolic speeds (2.7±0.3 cm/second to 4.2±0.4 cm/second) and resistance (0.71±0.04 to 1.38±0.06) were significantly increased (P=0.002) (P=0.043), and (P=0.005), respectively. No local or systemic adverse effect was observed in women or in their sexual partners and the sexual function presented a slightly insignificant improvement (P=0.065), although eight of 10 women could subjectively identify the GSNO gel as the preferred and most pleasant between both tried. Group 2 presented no significant differences at baseline and 15 minutes after the application of the placebo gel, P>0.05. CONCLUSION: The topic GSNO gel increased significantly the clitoral blood flow and could be considered therapeutically in selected cases of female sexual dysfunction warranting further investigation.

Assuntos

Clitóris/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , S-Nitrosoglutationa/farmacologia , Administração Intravaginal , Adulto , Clitóris/irrigação sanguínea , Clitóris/diagnóstico por imagem , Método Duplo-Cego , Feminino , Géis/farmacologia , Humanos , Doadores de Óxido Nítrico/administração & dosagem , Poloxâmero/farmacologia , S-Nitrosoglutationa/administração & dosagem , Ultrassonografia , Adulto Jovem

RESUMO

Objective: The aim of this study was to develop an experimental model of inducing interstitial cystitis through intravesical instillation of a polymeric solution containing the NO donor S-nitrousglutathione (GSNO) and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride. Methods: A total of 40 female Wistar rats were used and divided into four groups: 1 - ten rats treated with saline solution + GSNO; 2 - ten rats treated with saline solution + polymeric solution (without GNSO); 3 - ten rats treated with protamine sulphate + KCl; 4 - ten rats treated with protamine sulphate + GSNO. The rats received one application (five animals in each group) or three applications (five animals in each group) of the corresponding substance through intravesical instillation, and after six days (five animals in each group) or nine days (five animals in each group) they were euthanized and their bladders were removed for macroscopic evaluation and histological study. Results: In the macroscopic evaluation edema and hyperemia of the mucosa were observed in 2 (22%) animals in Group 1, in no (0%) animal in Group 2, in 10 (100%) animals in Group 3, and in 5 (50%) animals in Group 4. In the protamine + KCl group and in saline + GSNO, similar effects were observed in the bladder wall. The animals in Group 2 (saline + polymeric solution) showed significantly less vascular congestion compared to the other groups after 9 days of the instillation (p = 0.0035). Significant fibrosis was observed in Groups 3 and 4, 6 days (p = 0.3781) and 9 days (p = 0.0459) after instillations, when compared to controls (Group 2). All groups presented neutrophilic infiltrate of variable intensity, 6 days after instillations (p = 0.7277). After 9 days, there was a regression of the infiltrate, with no evidence of accentuated neutrophilic reaction in all the groups (p = 0.2301). Conclusions: The inflammatory response to bladder instillation with an aqueous solution of S-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl. Instillation of an aqueous solution of S-nitrousglutathione can be considered a new model for experimental induction of interstitial cystitis.

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Objetivo: O objetivo deste estudo foi o desenvolvimento de um modelo experimental para a indução de cistite intersticial, por meio da instilação vesical de uma solução polimérica de gel doador de óxido nítrico S-nitrosoglutationa (GSNO), e compará-lo ao modelo experimental para a indução da cistite intersticial por instilação vesical de protamina e cloreto de potássio. Métodos: Foram utilizadas 40 ratas Wistar, divididas em quatro grupos: 1 - dez ratas tratadas com solução salina + GSNO; 2 - dez ratas tratadas com solução salina + solução de polímeros (sem GNSO); 3 - dez ratas tratadas com sulfato de protamina + KCl; 4 - dez ratas tratadas com sulfato de protamina + GSNO. As ratas receberam uma aplicação (cinco animais em cada grupo) ou três aplicações (cinco animais em cada grupo) da substância correspondente através de instilação vesical, e após seis dias (cinco animais em cada grupo) ou nove dias (cinco animais em cada grupo) foram sacrificadas, e a bexiga foi removida para exame macroscópico e estudo histológico. Resultados: Na avaliação macroscópica observou-se edema e hiperemia da mucosa em 2 animais (22%) do Grupo 1, em nenhum animal (0%) do Grupo 2, em 10 animais (100%) do Grupo 3, e em 5 animais (50%) do Grupo 4. No grupo protamina + KCl e no grupo solução salina + GSNO, observamos efeitos semelhantes sobre a parede da bexiga. Os animais do Grupo 2 (salina + polímeros) apresentaram significantemente menos congestão vascular que os dos outros grupos após 9 dias de instilação (p = 0,0035). Observou-se fibrose significante nos Grupos 3 e 4, 6 dias (p = 0,3781) e 9 dias (p = 0,0459) após as instilações, quando comparados com o grupo controle (Grupo 2). Todos os grupos apresentaram infiltrados neutrofílicos de intensidade variável, 6 dias após as instilações (p = 0,7277). Após 9 dias, observou-se regressão do infiltrado, sem evidência de acentuada reação neutrofílica em todos os grupos (p = 0,2301). Conclusão: A resposta inflamatória à instilação da bexiga com uma solução aquosa de S-nitroglutationa foi muito semelhante àquela induzida pela instilação de protamina e KCl. A instilação de uma solução aquosa de S-nitroglutationa pode ser considerada um novo modelo experimental para a indução da cistite intersticial.

RESUMO

OBJECTIVE: The aim of this study was to evaluate the impact of Global Postural Re-education (GPR) on stress urinary incontinence symptoms and to compare it to Pelvic Floor Muscle Training (PFMT). STUDY DESIGN: Fifty-two women with stress urinary incontinence were distributed into two groups: Group 1 (G1) was submitted to weekly sessions of GPR for three months and Group 2 (G2) performed Pelvic Floor Muscle Training four times a week for three months. Patients were evaluated through the King's Health Questionnaire, a three-day voiding diary including daily pad use and a Functional Evaluation of the Pelvic Floor (FEPF), before treatment (T0), at the end of treatment (T1) and six months after treatment (T2). RESULTS: The number of leaking episodes dropped significantly in both groups at the end of treatment and at six months follow-up, with a significantly greater decrease in G1. Daily pad use dropped significantly in both groups. At the end of treatment, 72% of the patients in G1 and 41% of the patients in G2 needed no pads and at six-month follow-up, 84% and 50%, respectively. FEPF improved significantly in both groups, with no significant difference between the groups (P=0.628). The King's Health Questionnaire demonstrated significant improvement in both groups and in all domains. The GPR group presented higher adherence to treatment, with no dropouts. CONCLUSIONS: GPR could represent an alternative method to treat stress urinary incontinence in women, should the results be long lasting.

Assuntos

Músculos Abdominais/fisiologia , Postura/fisiologia , Incontinência Urinária por Estresse/reabilitação , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Diafragma da Pelve/fisiologia , Modalidades de Fisioterapia , Incontinência Urinária por Estresse/terapia

RESUMO

OBJECTIVE: The aim of this study was to develop an experimental model of inducing interstitial cystitis through intravesical instillation of a polymeric solution containing the NO donor S-nitrousglutathione (GSNO) and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride. METHODS: A total of 40 female Wistar rats were used and divided into four groups: 1 - ten rats treated with saline solution + GSNO; 2 - ten rats treated with saline solution + polymeric solution (without GNSO); 3 - ten rats treated with protamine sulphate + KCl; 4 - ten rats treated with protamine sulphate + GSNO. The rats received one application (five animals in each group) or three applications (five animals in each group) of the corresponding substance through intravesical instillation, and after six days (five animals in each group) or nine days (five animals in each group) they were euthanized and their bladders were removed for macroscopic evaluation and histological study. RESULTS: In the macroscopic evaluation edema and hyperemia of the mucosa were observed in 2 (22%) animals in Group 1, in no (0%) animal in Group 2, in 10 (100%) animals in Group 3, and in 5 (50%) animals in Group 4. In the protamine + KCl group and in saline + GSNO, similar effects were observed in the bladder wall. The animals in Group 2 (saline + polymeric solution) showed significantly less vascular congestion compared to the other groups after 9 days of the instillation (p = 0.0035). Significant fibrosis was observed in Groups 3 and 4, 6 days (p = 0.3781) and 9 days (p = 0.0459) after instillations, when compared to controls (Group 2). All groups presented neutrophilic infiltrate of variable intensity, 6 days after instillations (p = 0.7277). After 9 days, there was a regression of the infiltrate, with no evidence of accentuated neutrophilic reaction in all the groups (p = 0.2301). CONCLUSIONS: The inflammatory response to bladder instillation with an aqueous solution of S-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl. Instillation of an aqueous solution of S-nitrousglutathione can be considered a new model for experimental induction of interstitial cystitis.