Triosephosphate isomerase as a therapeutic target against trichomoniasis.

Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3'-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures. With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.

Developing a new drug against trichomoniasis, new inhibitory compounds of the protein triosephosphate isomerase.

Trichomonas vaginalis is the protozoan parasite responsible for the most prevalent, non-viral, sexually transmitted disease, which affects millions of people around the world. The main treatment against this disease is metronidazole and some other nitroimidazole derivatives. However, between five and 20% of clinical cases of trichomoniasis are caused by parasites resistant to these drugs. Here we present three compounds that were selected using an innovative strategy, to propose them as possible drugs to combat trichomoniasis, using the glycolytic enzyme triose phosphate isomerase (TvTIM) as the drug target. In the genome of Trichomonas vaginalis there are two genes that encode for two isoforms of TvTIM, known as TvTIM1 and TvTIM2, varying by four out of 254 aminoacid residues. In this study, we used high-throughput virtual screening to search molecules that bind specifically to TvTIM isoforms, in which 34 compounds were selected from a library of nearly 450,000 compounds. The effects of the 34 compounds on the conformation and enzymatic activity of both TvTIM isoforms and their human homolog (HsTIM) were evaluated. We found three compounds that bind specifically, modify the conformation and inhibit TvTIM2 only; although the sequence of both isoforms of TvTIM is almost identical. The selectivity of these compounds towards TvTIM2 is explained by the lower conformational stability of this isoform and that these interactions can inhibit the activity of this enzyme and have an effect against this parasite. These compounds represent promising alternatives for the development of new therapeutic strategies against trichomoniasis.

Las Infecciones de Transmisión Sexual: una revisión dirigida a la atención primaria de salud / Sexually Transmitted Infections: A Targeted Review of Primary Health Care

Introducción: las infecciones de transmisión sexual constituyen un grupo heterogéneo de infecciones transmisibles que han adquirido una extrema importancia para la salud pública en todo el mundo, dada su magnitud, trascendencia y repercusión para el paciente, la familia y la sociedad. Afectan todos los niveles sociales y económicos, a casi todos los grupos de edades, con mayor frecuencia a los adultos jóvenes.Objetivos: revisión y actualización de las infecciones de transmisión sexual más frecuentes en la Atención Primaria de Salud –tema que en este nivel de atención ha sido poco abordadoy con ello, elevar el nivel de conocimientos sobre estas infecciones para lograr un manejo adecuado de su prevención y tratamiento. Método: búsqueda automatizada de los últimos cinco años de artículos electrónicos en bases de datos y textos impresos, libros y folletos; y se efectuó intercambio con especialistas que trabajan estas enfermedades. Se excluyeron los artículos no pertinentes completamente al tema. Resultados: las infecciones de transmisión sexual clásicas curables incluyen: Sífilis, Blenorragia, Chancro blando, Linfogranuloma venéreo, Granuloma inguinal, Uretritis no gonocócica y Trichomoniasis. Existen otras curables, no consideradas como clásicas. Ellas son, la Escabiosis, la Pediculosis pubis, la Candidiasis, el Parasitismo intestinal, la Dermatomitosis, el Molusco contagioso y la Vaginosis bacteriana. Dentro de las incurables se encuentran: VIH/sida, Herpes simple genital, Verrugas genitales (Condilomas Acuminados), la Hepatitis B. Conclusiones: es de suma importancia el conocimiento de estas infecciones y de todos los elementos relacionados con ellas, en aras de prevenirlas(AU)

Introduction: sexually transmitted infections are a heterogeneous group of transmissible infections, which have become extremely important for public health worldwide, given its size, significance and impact for the patient, the family and society. They affect all social and economic levels, to almost all age groups, most often young adults. Objectives and Methods: The researchers set a review and update of the subject, realized by the method of automated search electronic of items in databases and printed texts, books and brochures of the last five years; and exchange took place with specialists working in the area. Not relevant completely to the subject articles were excluded. Results: classic curable sexually transmitted infections include: Syphilis, Gonorrhea, Chancroid, lymphogranuloma venereum, granuloma inguinale, non-gonococcal urethritis and trichomoniasis. There are other curable and not considered classics. They are the Scabies, Pediculosis pubis, Candidiasis, the intestinal parasitism, the Dermatomitosis, the Molluscum Contagiosum and bacterial vaginosis. Incurable STDs include: HIV/AIDS, genital Herpes simplex, genital warts (condylomata acuminata), Hepatitis B. Conclusions: It is of utmost importance to understand these infections and all items related to them, in order to prevent them(AU)

Factores relacionados con el contagio de las infecciones de transmisión sexual en la adolescencia / Factors associated with contagion relating to Sexual Transmitted Disease in adolescent

Introducción: las infecciones de transmisión sexual constituyen un grupo heterogéneo de infecciones, de extrema importancia para la salud pública en todo el mundo, dada su magnitud, trascendencia y repercusión para el paciente, la familia y la sociedad. Afectan con mayor frecuencia a los adolescentes.Objetivo: identificar posibles factores relacionados con el contagio de las infecciones de transmisión sexual en la adolescencia. Material y métodos: se realizó una revisión con el método de búsqueda automatizada de artículos electrónicos publicados de 2009 a 2013 en bases de datos, y de textos impresos, libros y folletos. También se efectuó intercambio con especialistas que investigan este tema. Se excluyeron los artículos no pertinentes completamente al tema. Desarrollo: se determinaron como factores importantes en el binomio infecciones de transmisión sexual/adolescencia a la familia, los sistemas de salud, el nivel y fuentes de información sobre infecciones de transmisión sexual, el inicio precoz de la actividad sexual, el número de parejas y el uso del condón. Conclusiones: las infecciones de transmisión sexual afectan con gran frecuencia a jóvenes entre 15 y 24 años, de ambos sexos, existen factores que influyen en su adquisición. El máximo exponente de la atención y prevención de estas es la atención primaria de salud(AU)

Introduction: Sexual Transmitted Diseases (STD) constitutes a heterogeneous group of infections, of maximum importance for the public health in the World, given his magnitude, transcendence and repercussion for the patient, the family and the society and affect with higher frequency young adult. Objective: identify possible relating factors to contagion of the Sexual Transmitted Diseases in the adolescence. Material and Methods: a review was done using the method of automated search of electronic articles published in Databases and printed texts, books and leaflets during the last five years; and scientific interchange was produced among specialists related to the researched topic. Articles not complete belonging to the research topic were excluded of the search. Development: were determined as important factors in the binomial ITS/adolescent, the family, the Systems of Health, the level and sources of information about STD, the precocious beginning of the sexual activity, the number of couples and the use of the condom. Conclusions: sexual Transmitted Diseases had higher frequency in both sex in adolescent between 15 and 24 years old, and there are factors influencing their contagion The most important exponent in the treatment and prevention of the STD is the Primary Health Care(AU)

Intervención sobre ITS/VIH/sida en adolescentes pertenecientes a dos consultorios del policlínico "Plaza" / Intervention on STI/HIV/AIDS in adolescents who belong to two medical practices of the polyclinic Plaza

Introducción: se observa en el mundo una tendencia ascendente en el padecimiento de las infecciones de transmisión sexual, debido al comienzo de las relaciones sexuales a edades cada vez más tempranas. Objetivo: incrementar el nivel de información acerca de las enfermedades de transmisión sexual. Métodos: se realizó un estudio experimental de intervención, sobre ITS/VIH/sida en un grupo de adolescentes pertenecientes a dos consultorios. De un universo de 125 adolescentes se seleccionó una muestra de 70 de ellos. Se aplicó una encuesta previa al programa de intervención, luego se implementó el curso y después se aplicó nuevamente el cuestionario. Resultados: inicialmente 65 adolescentes (92,8 porciento), respondieron tener información sobre el tema tratado, y después de la intervención se elevó a un 100 porciento. Dentro de las fuentes de obtención de la información, la familia fue la más identificada por 47 encuestados (67,1 porciento) y después de la intervención por 67 (95,7 porciento). Al analizar los grupos de edades a los que afectan las infecciones de transmisión sexual, 62 encuestados (88,5 porciento), identificaron que puede ser a todas las edades y después se elevó a 64 (91,4 porciento). Con respecto a la eficacia en el uso del condón para evitar las infecciones de transmisión sexual, al comienzo respondieron afirmativamente 41 (58,5 porciento) y luego se elevó a un 100 porciento. Conclusiones: en primera instancia los adolescentes conocían muy poco sobre algunos de los aspectos estudiados, y después de impartido el curso, se observó un aumento del conocimiento sobre estas enfermedades en sentido general(AU)

Introduction: There is an upward trend in the world related to sexually transmitted infections, due to the onset of sexual intercourse at increasingly early ages. Objective: to increase the level of information about sexually transmitted diseases. Methods: An experimental study intervention was carried out on STI/HIV/AIDS in a group of teenagers from two medical practices. From a universe of 125 adolescents, we selected a sample of 70 adolescents. These persons had a survey before the intervention program. This survey was implemented one more time after the intervention. Results: initially 65 adolescents (92.8 percent), responded to have information on the topic, and after the intervention this number rose to 100 percent. Among the sources for obtaining the information, the family was the most identified by 47 respondents and after the intervention the number increased to 67 (67.1 percent and 95.7 percent respectively). When analyzing the age groups for those who can be affected by sexually transmitted infections, 62 respondents (88.5 percent) identified at all ages and then the number rose to 64 (91.4 percent). With regard to the efficient use of condoms to prevent sexually transmitted infections at the beginning 41 (58.5 percent) answered affirmatively and 100 percent after the intervention. Conclusions: Firstly, teenagers knew little about some of the aspects studied, and after the course was over, we observed there was an increase of knowledge about these diseases in general(AU)

Intervención sobre ITS/VIH/sida en adolescentes pertenecientes a dos consultorios del policlínico "Plaza" / Intervention on STI/HIV/AIDS in adolescents who belong to two medical practices of the polyclinic Plaza

Introducción: se observa en el mundo una tendencia ascendente en el padecimiento de las infecciones de transmisión sexual, debido al comienzo de las relaciones sexuales a edades cada vez más tempranas. Objetivo: incrementar el nivel de información acerca de las enfermedades de transmisión sexual. Métodos: se realizó un estudio experimental de intervención, sobre ITS/VIH/sida en un grupo de adolescentes pertenecientes a dos consultorios. De un universo de 125 adolescentes se seleccionó una muestra de 70 de ellos. Se aplicó una encuesta previa al programa de intervención, luego se implementó el curso y después se aplicó nuevamente el cuestionario. Resultados: inicialmente 65 adolescentes (92,8 porciento), respondieron tener información sobre el tema tratado, y después de la intervención se elevó a un 100 porciento. Dentro de las fuentes de obtención de la información, la familia fue la más identificada por 47 encuestados (67,1 porciento) y después de la intervención por 67 (95,7 porciento). Al analizar los grupos de edades a los que afectan las infecciones de transmisión sexual, 62 encuestados (88,5 porciento), identificaron que puede ser a todas las edades y después se elevó a 64 (91,4 porciento). Con respecto a la eficacia en el uso del condón para evitar las infecciones de transmisión sexual, al comienzo respondieron afirmativamente 41 (58,5 porciento) y luego se elevó a un 100 porciento. Conclusiones: en primera instancia los adolescentes conocían muy poco sobre algunos de los aspectos estudiados, y después de impartido el curso, se observó un aumento del conocimiento sobre estas enfermedades en sentido general

Introduction: There is an upward trend in the world related to sexually transmitted infections, due to the onset of sexual intercourse at increasingly early ages. Objective: to increase the level of information about sexually transmitted diseases. Methods: An experimental study intervention was carried out on STI/HIV/AIDS in a group of teenagers from two medical practices. From a universe of 125 adolescents, we selected a sample of 70 adolescents. These persons had a survey before the intervention program. This survey was implemented one more time after the intervention. Results: initially 65 adolescents (92.8 percent), responded to have information on the topic, and after the intervention this number rose to 100 percent. Among the sources for obtaining the information, the family was the most identified by 47 respondents and after the intervention the number increased to 67 (67.1 percent and 95.7 percent respectively). When analyzing the age groups for those who can be affected by sexually transmitted infections, 62 respondents (88.5 percent) identified at all ages and then the number rose to 64 (91.4 percent). With regard to the efficient use of condoms to prevent sexually transmitted infections at the beginning 41 (58.5 percent) answered affirmatively and 100 percent after the intervention. Conclusions: Firstly, teenagers knew little about some of the aspects studied, and after the course was over, we observed there was an increase of knowledge about these diseases in general

Aspectos ginecológicos e frequência de infecções do trato genital inferior em pacientes adolescentes e adultas: existem diferenças? / Gynecological aspects and frequency of lower genital tract infections in teenagers and adult patients: are there any differences?

Introdução: As adolescentes merecem atenção especial em saúde pública, pois ao iniciar atividade sexual se expõem aos riscos das DSTs, da gravidez indesejada, do câncer cervical e de outras doenças inflamatórias pélvicas. Objetivos: Avaliar os aspectos ginecológicos e a frequência de infecções do trato genital inferior em adolescentes. Métodos: Trata-se de um estudo de caso-controle, onde foram estudadas pacientes adolescentes (n=68) e adultas (n=112) atendidas em uma clínica privada, que presta atendimento em ginecologia e obstetrícia. Excluíram-se aquelas que apresentavam qualquer tipo problema que impossibilitasse a realização dos exames necessários (sangramento genital, uso de cremes ou gel vaginal ou relação sexual em intervalo inferior a 72 horas da consulta médica) e as que não assinaram o Termo de Consentimento Livre e Esclarecido (TCLE). As pacientes foram submetidas à anamnese e exame físico, com coleta de material para a realização de citologia, exame a fresco e pesquisa do DNA do Papilomavírus humano (HPV), pela técnica de captura híbrida II. Quando necessário realizou-se a biópsia de colo uterino, guiada pela colposcopia. No teste de significância estatística das diferenças observadas na análise, utilizou-se o teste do qui-quadrado e/ou o teste T de Student, dependendo da natureza dos dados comparados. O nível de significância adotado na análise foi de 5%. Resultados: A frequência de infecção pelo HPV diagnosticada pela captura híbrida foi de 47,3% para as pacientes adultas e de 35,3% para as adolescentes (p=0,42). A frequência de neoplasia intraepitelial de alto grau foi mais frequente em pacientes adultas, mas as adolescentes apresentaram 19% de neoplasia intraepitelial cervical diagnosticada pela histopatologia. Conclusão: Identificou-se percentual elevado de neoplasia intraepitelial cervical em adolescentes, o que pode estar associado ao comportamento de risco deste grupo, com trocas frequentes de parceiros e prática do sexo sem proteção.

Background: Adolescents deserve special attention in public health, because when they start sexual activity these are individuals exposed to the risks of STDs, unwanted pregnancies, cervical cancer and other pelvic inflammatory diseases. Aim: To evaluate the frequency of gynecological and lower genital tract infections in adolescents. Methods: This is a case-control study where patients were studied, both adolescents (n = 68) and adults (n=112) attended a private clinic. We excluded those who had any problems that hinder the achievement of the necessary examinations (vaginal bleeding, use of creams or gels or vaginal intercourse at an interval less than 72 hours of medical consultation) and that did not sign the informed consent. The patients underwent history and physical examination, with collection of material for the Pap smear and research DNAHPV, the technique of hybrid capture II. When appropriate a cervix biopsy was done guided by colposcopy. Statistical analysis were performed considering p<0.05. Results: The frequency of HPV infection diagnosed by hybrid capture was 47.3% for adult patients and 35.3% for girls (p=0.42). The frequency of intraepithelial neoplasia of high degree was more frequent in adult patients, but 19% of adolescents had cervical intraepithelial neoplasia diagnosed by histopathology. Conclusion: We identified a high percentage of cervical intraepithelial neoplasia in adolescents, which may be associated with a risky behavior in this group, with frequent partners changes and practice of unprotected sex.

Planejamento familiar: escolhas contraceptivas e comportamento sexual entre alunas de uma universidade no sul do Brasil / Family planning: contraceptive choices and sexual behavior among studentsattending a university in southern Brazil

Introdução: O Planejamento Familiar decorre da necessidade de limitar a prole em número compatível com a capacidade de proporcionar condições dignas de vida. O objetivo do estudo foi verificar as práticas adotadas para controle da fecundidade e demais características sexuais entre universitárias. Métodos: Estudo transversal com mulheres matriculadas em universidade do sul do Brasil no ano de 2009. O questionário autoaplicável e anônimo continha questões sobre características sociodemográficas, sexuais, reprodutivas, gravidez e aborto. A análise estatística dos dados foi feita com auxílio do SPSS versão 16.0. Resultados: Foram estudadas 409 universitárias com média de idade de 22,4 anos e 84,6% eram sexualmente ativas. A maioria (93,4%) tinha relações sexuais com parceiro fixo e sem utilização de preservativo (71,3%). Os métodos contraceptivos mais utilizados foram pílula oral (69,7%) e preservativo (35,5%) e a contracepção de emergência foi reportada por 53%. Entre as universitárias que já engravidaram (16,7%), 7,2% sofreram abortamento espontâneo e 1,8% provocado. Questionadas sobre uma gravidez indesejada, 10,8% afirmaram que abortariam, tendo como principais motivos o fato de atrapalhar os estudos (19,3%). Conclusão: A amostra apresentou perfil similar à maioria da população brasileira, ainda que se trate de uma população altamente escolarizada. A baixa adesão ao uso de preservativo, o uso de drogas e de anticoncepção de emergência mostraram comportamento de risco para DST, gravidez indesejada e aborto.

Introduction: Family planning is the need to limit the offspring in a number compatible with the capacity to provide decent living conditions. The aim of this study was to assess practices related to fertility control and other sexual characteristics in female university students. Methods: A cross-sectional study with women enrolled in a University of Southern Brazil in 2009. The self-administered anonymous questionnaire contained questions about sociodemographic, sexual, and reproductive characteristics, as well as pregnancy and abortion. The statistical analysis was performed with the aid of SPSS, version 16.0. Results: We studied 409 college students with a mean age of 22.4 years and 84.6% were sexually active. The majority (93.4%) had sex with a steady partner without using condoms (71.3%). The contraceptive methods used were oral pill (69.7%) and condoms (35.5%). Emergency contraception was reported by 53%. Among the students that have gotten pregnant (16.7%), 7.2% had miscarriages and 1.8% had abortions. When asked about an unwanted pregnancy, 10.8% said they would have an abortion, the main reason being the fact that it would disrupt the studies (19.3%). Conclusion: The sample showed a similar profile to the majority of the Brazilian population, even though it is a highly educated population. The low frequency of condom use, drug use and emergency contraception evidence risk for STDs, unwanted pregnancy and abortion.