Educational technology to promote father involvement in childbirth and birth.

OBJECTIVES: to build and validate an educational booklet to promote the involvement of parents in labor and birth. METHODS: methodological study developed in five stages: situational diagnosis; bibliographic survey; construction of illustrations, layout, design and texts; content and appearance validation by judges (25 experts) and calculation of the Flesch Readability Index; and validation with the target audience (12 parents). A minimum Content Validity Index of 0.80 was considered. RESULTS: the booklet was entitled "Father Presence" and was developed in 11 topics. In Content and Appearance Validation, the Validity Index obtained an overall score of 0.97. Cronbach's alpha was 0.92, indicating excellent reliability of its content. A global score of 74% for readability was obtained, considered easy to understand. CONCLUSIONS: the material was successful in the validation process, and it can be recommended for parents to use it during the prenatal period, promoting the inclusion of the partner and preparing them for labor and birth.

Educational technology to promote father involvement in childbirth and birth / Tecnología educacional para promoción del involucramiento de padres en el parto y nacimiento / Tecnologia educacional para promoção do envolvimento de pais no parto e nascimento

ABSTRACT Objectives: to build and validate an educational booklet to promote the involvement of parents in labor and birth. Methods: methodological study developed in five stages: situational diagnosis; bibliographic survey; construction of illustrations, layout, design and texts; content and appearance validation by judges (25 experts) and calculation of the Flesch Readability Index; and validation with the target audience (12 parents). A minimum Content Validity Index of 0.80 was considered. Results: the booklet was entitled "Father Presence" and was developed in 11 topics. In Content and Appearance Validation, the Validity Index obtained an overall score of 0.97. Cronbach's alpha was 0.92, indicating excellent reliability of its content. A global score of 74% for readability was obtained, considered easy to understand. Conclusions: the material was successful in the validation process, and it can be recommended for parents to use it during the prenatal period, promoting the inclusion of the partner and preparing them for labor and birth.

RESUMEN Objetivos: construir y validar cartilla educativa para promoción del involucramiento de padres en el parto y nacimiento. Métodos: estudio metodológico desarrollado en cinco etapas: diagnóstico situacional; levantamiento bibliográfico; construcción de ilustraciones, esbozo, diseño y textos; validez de contenido y apariencia por jueces (25 especialistas) y cálculo del índice de Legibilidad de Flesch; y validación con el público objeto (12 padres). Considerado Índice de Validez de Contenido mínimo de 0,80. Resultados: la cartilla intitulada "Presencia de padre" y fue desarrollada en 11 tópicos. En la validez de contenido y apariencia, el Índice de Validez obtuvo escore global de 0,97. El alfa de Cronbach fue 0,92, indicando excelente confiabilidad de su contenido. Puntuación global para legibilidad fue 74%, denotando fácil comprensión. Conclusiones: el material tuvo éxito en el proceso de validación, pudiendo ser recomendado a padres utilizarlo durante el período prenatal, promoviendo la inclusión del compañero y preparándolos al parto y nacimiento.

RESUMO Objetivos: construir e validar uma cartilha educativa para promoção do envolvimento de pais no parto e nascimento. Métodos: estudo metodológico desenvolvido em cinco etapas: diagnóstico situacional; levantamento bibliográfico; construção das ilustrações, layout, design e textos; validação de conteúdo e aparência por juízes (25 especialistas) e cálculo do índice de Legibilidade de Flesch; e validação com o público-alvo (12 pais). Considerou-se Índice de Validade de Conteúdo mínimo de 0,80. Resultados: a cartilha intitulou-se "Presença de pai" e foi desenvolvida em 11 tópicos. Na validação de conteúdo e aparência, o Índice de Validade obteve escore global de 0,97. O alfa de Cronbach foi 0,92, indicando excelente confiabilidade de seu conteúdo. Pontuação global para legibilidade foi 74%, denotando fácil compreensão. Conclusões: o material teve êxito no processo de validação, podendo ser recomendado para os pais utilizarem-no durante o período pré-natal, promovendo a inclusão do parceiro e preparando-os para o parto e nascimento.

Thoracoscopy Approach in Prone Position for Esophagoplasty in Children.

Congenital esophageal stenosis (CES) is a very rare clinical condition found in 1 per 25,000 to 50,000 live births. There are three histological types of CES described: tracheobronchial remnants, fibromuscular stenosis (FMS), and membranous stenosis. The first-line treatment in most cases is the conservative treatment (dilatation with a Savary bougie or balloon), but in some CES types, dilatation may be ineffective or result in esophageal perforation with serious complications or lethal outcome. Resection of the stenotic segment and end-to-end esophageal anastomosis was formerly presented as the most common surgical treatment option for CES. However, esophagoplasty is a safe and feasible alternative for surgical treatment of esophageal stenosis in children. Our aim is to report two cases of FMS submitted to thoracoscopic esophagoplasty. Both cases started with dysphagia and refusal after transition to solid diet, at 6 months old, and the radiological examination showed stricture of the distal esophagus. Esophagoplasty was performed with the patients in prone position. The stenotic esophageal wall was incised longitudinally and transverse synthesis was performed. After surgery, the patients had prompt recovery, without recurrent stenosis, remaining asymptomatic, with good diet acceptance.

Desfechos neonatais associados às intervenções obstétricas realizadas no trabalho de parto em nulíparas / Neonatal outcomes associated with obstetric interventions performed during labor in nulliparous women

RESUMO Objetivo analisar os desfechos neonatais associados às intervenções obstétricas realizadas no trabalho de parto em nulíparas de baixo risco. Métodos estudo observacional de corte transversal, realizado com 534 nulíparas de baixo risco. Resultados a interrupção do contato pele a pele após o parto se mostrou associado às intervenções obstétricas como cardiotocografia na admissão, ocitocina no trabalho de parto, amniotomia e episiotomia. A necessidade de ventilação por pressão positiva e oxigenoterapia tiveram associação ao incentivo à manobra de Valsalva; a realização desta manobra está associada, também às intervenções amniotomia, episiotomia e puxo dirigido. Conclusão o estudo evidenciou que a utilização das intervenções obstétricas durante o trabalho de parto de mulheres de baixo risco está associada aos desfechos neonatais desfavoráveis que acarretam a necessidade de mais intervenções após o parto.

ABSTRACT Objective to analyze neonatal outcomes associated with obstetric interventions performed during labor in low-risk nulliparous women. Methods a cross-sectional observational study of 534 low-risk nulliparous women. Results interruption of skin-to-skin contact after delivery was shown to be associated with obstetric interventions such as cardiotocography at admission, oxytocin in labor, amniotomy, and episiotomy. The need for positive pressure ventilation and oxygen therapy was associated with the encouragement of the Valsalva maneuver; the performance of this maneuver was also associated with interventions such as amniotomy, episiotomy and directed pulling. Conclusion the study showed that the use of obstetric interventions during labor in low-risk women is associated with unfavorable neonatal outcomes that lead to the need for further interventions after delivery.

Factors related to perineal outcome after vaginal delivery in primiparas: a cross-sectional study.

OBJECTIVE: Identify the associations between perineal outcome in primiparas and interventions during labor and delivery, newborn weight and APGAR score. METHOD: Document-based, correlational, retrospective, quantitative study conducted in a tertiary maternity hospital in the state of Ceará, between July 2017 and January 2018. The independent variables were labor induction, amniotomy, non-pharmaceutical methods for relieving pain, forceps, episiotomy, Kristeller maneuver, position in the expulsion stage, shoulder dystocia, and newborn weight and APGAR score, and the dependent variable was perineal outcome. Pearson's chi-square test and Fisher's exact test were used. RESULTS: A total of 226 normal-risk primiparas who had a vaginal delivery. An association was found between horizontal position in the expulsion stage and episiotomy, and between not performing an episiotomy and perineal tearing. The other variables (labor, delivery and neonatal) did not have any effect on perineal tearing. CONCLUSION: Interventions, with the exception of episiotomies, did not have an influence on the occurrence of perineal trauma, but they do need to be carefully assessed. Deliveries in a horizontal position were associated with a higher likelihood of performing an episiotomy.

Factors related to perineal outcome after vaginal delivery in primiparas: a cross-sectional study / Factores relacionados con el resultado perineal tras parto vaginal en primíparas: estudio transversal / Fatores relacionados ao desfecho perineal após parto vaginal em primíparas: estudo transversal

Abstract Objective: Identify the associations between perineal outcome in primiparas and interventions during labor and delivery, newborn weight and APGAR score. Method: Document-based, correlational, retrospective, quantitative study conducted in a tertiary maternity hospital in the state of Ceará, between July 2017 and January 2018. The independent variables were labor induction, amniotomy, non-pharmaceutical methods for relieving pain, forceps, episiotomy, Kristeller maneuver, position in the expulsion stage, shoulder dystocia, and newborn weight and APGAR score, and the dependent variable was perineal outcome. Pearson's chi-square test and Fisher's exact test were used. Results: A total of 226 normal-risk primiparas who had a vaginal delivery. An association was found between horizontal position in the expulsion stage and episiotomy, and between not performing an episiotomy and perineal tearing. The other variables (labor, delivery and neonatal) did not have any effect on perineal tearing. Conclusion: Interventions, with the exception of episiotomies, did not have an influence on the occurrence of perineal trauma, but they do need to be carefully assessed. Deliveries in a horizontal position were associated with a higher likelihood of performing an episiotomy.

Resumen Objetivo: Identificar las asociaciones entre el resultado perineal en primíparas y las intervenciones ocurridas durante el trabajo de parto, parto, peso y APGAR del recién nacido. Método: Estudio documental, correlacional, retrospectivo, cuantitativo, llevado a cabo en una maternidad terciaria en el estado de Ceará, entre julio de 2017 y enero de 2018. Las variables independientes fueron inducción del parto, amniotomía, métodos no farmacológicos de alivio del dolor, fórceps, episiotomía, maniobra de Kristeller, posición en el período expulsivo, distocia de hombro, peso y APGAR del recién nacido, y la variable dependiente fue el resultado perineal. Se emplearon las pruebas de Chi cuadrado de Pearson y la exacta de Fisher. Resultados: Participaron 226 primíparas de riesgo habitual que parieron por vía vaginal. Se verificó asociación entre la posición horizontal en el período expulsivo del parto y episiotomía, y entre la no realización de episiotomía y laceración perineal. La otras variables de trabajo de parto, parto y neonatal no interfirieron en la ocurrencia de laceración perineal. Conclusión: Acciones intervencionistas, salvo la episiotomía, no influenciaron la ocurrencia de trauma perineal, sin embargo requieren evaluación juiciosa. El parto en la posición horizontal se relacionó con la mayor posibilidad de realización de episiotomía.

Resumo Objetivo: Identificar as associações entre o desfecho perineal em primíparas e as intervenções ocorridas durante o trabalho de parto, parto, peso e APGAR do recém-nascido. Método: Estudo documental, correlacional, retrospectivo, quantitativo, realizado em uma maternidade terciária no estado do Ceará, entre julho de 2017 e janeiro de 2018. As variáveis independentes foram indução do parto, amniotomia, métodos não farmacológicos de alívio da dor, fórceps, episiotomia, manobra de Kristeller, posição no período expulsivo, distocia de ombro, peso e APGAR do recém-nascido, e a variável dependente foi o desfecho perineal. Foram utilizados o teste de Qui-quadrado de Pearson e o teste exato de Fisher. Resultados: Participaram 226 primíparas de risco habitual que pariram por via vaginal. Verificou-se associação entre posição horizontal no período expulsivo do parto e episiotomia, e entre a não realização de episiotomia e laceração perineal. As outras variáveis de trabalho de parto, parto e neonatal não interferiram na ocorrência de laceração perineal. Conclusão: Ações intervencionistas, com exceção da episiotomia, não influenciaram a ocorrência de trauma perineal, porém requerem avaliação criteriosa. O parto na posição horizontal relacionou-se a maior probabilidade de realização de episiotomia.

Análise dos resultados maternos e neonatais associados às intervenções realizadas durante o trabalho de parto de nulíparas de baixo custo / Analysis of maternal and neonatal results associad with interventions performed during labor of low-cost nulliparas

OBJETIVO: Analisar os resultados maternos e neonatais associados às intervenções realizadas durante o trabalho de parto e parto de nulíparas de baixo risco. MÉTODO: estudo observacional, transversal, descritivo e prospectivo, em uma maternidade terciária do estado do Ceará, com 534 parturientes de baixo risco. Foram incluídas: parturientes que nunca pariram e ausência de comorbidades maternas ou fetais. Foram excluídas: as parturientes que se tornaram alto risco durante o trabalho de parto. A coleta de dados foi realizada no período de fevereiro a agosto de 2018, em duas etapas: preenchimento de um questionário a partir da observação da assistência ao trabalho de parto e parto, prestada pela equipe multiprofissional, respondidas pelo observador e, a busca de dados nos prontuários. Foram contempladas as variáveis sociodemográficas, antecedentes obstétricos, intervenções no trabalho de parto e parto, desfecho materno e neonatal. A pesquisa seguiu os preceitos éticos e legais da Resolução 466/12 e foi aprovada pelo CAAE 82266317.0.0000.5050. Foram realizados testes de Qui-quadrado de Pearson e Exato de Fisher, IC 95% e erro de 5%, p<0,05. RESULTADOS: A amostra foi composta por mulheres entre 13 e 39 anos, 69,8% entre 20 e 35 anos, maioria possuía companheiro 51,5%, autodeclaradas pardas 63,5% e procedentes da capital e região metropolitana de Fortaleza 91,9%, entre 6 e 10 anos de estudo 57,5%, maioria sem atividade remunerada 68,3%. Antecedentes obstétricos: 89,9% das mulheres eram primigestas, com idade gestacional entre 37s e 41s4d, média de 7 consultas de pré-natal. Presença de acompanhante 96,4%; ingesta de líquidos livre demanda 78,3%; Partograma 73%; Métodos não Farmacológicos para alívio da dor 65,7% e movimentação durante o trabalho de parto 75%. Intervenções no trabalho de parto: admissão precoce 40,8%; Cardiotocografia na admissão 90,3%; venóclise 64,8%; amniotomia 38%; No parto: prevalência da posição supina/semi-sentada 74%, incentivo a Manobra de Valsalva 72,1%; mais de 4 profissionais/estudantes no parto 76,8%; analgesia farmacológica 8,6%. Percentual de cesariana de 39,5%. Apenas 31% das mulheres não receberam nenhum tipo de intervenção durante o trabalho de parto, 41,2% das mulheres receberam pelo menos uma intervenção. Para desfechos maternos observou-se associação entre as intervenções Manobra de Kristeller com Hemorragia pós-parto (p=0,036) e laceração perineal de grau II (p=0,006); manobra de Valsalva e laceração perineal (p=0,006); posição não vertical e laceração perineal (p<0,001). Para desfechos neonatais observou-se que a realização das intervenções durante o trabalho de parto e parto mostraram-se como fator "protetor", a realização de amniotomia esteve associada a menor necessidade de oxigênio (O2) após o parto (p=0,001) e neonatos encaminhados ao alojamento conjunto (p=0,006). A utilização de ocitocina esteve associada a menor necessidade de O2 (0,043), escore de Apgar ≥ 7 no quinto minuto de vida (p=0,046) e neonatos encaminhados ao alojamento conjunto (p=0,027). A realização de episiotomia esteve associada a menor necessidade de O2 (p=0,017) e recém-nascidos encaminhados ao alojamento conjunto (p=0,017). A Manobra de Valsalva associou-se com menor necessidade de realização de ventilação por pressão positiva (p=0,038), menor necessidade de O2 (p<0,000), escore de Apgar ≥ 7 no quinto minuto (p=0,047) e recém-nascidos em alojamento conjunto (p=0,016). O tempo de período expulsivo prevalente foi de até 2 horas. Houve associação do incentivo a manobra de Valsalva com expulsivo mais curto e analgesia de parto com expulsivos mais longos. Verificou-se que os recém-nascidos eram retirados do contato pele a pele com a mãe sem que houvesse justificativa como: necessidade de ventilação por pressão positiva, uso de O2 e/ou Apgar < 7 no 5º minuto. CONCLUSÃO: A implementação das Boas Práticas é uma rotina do serviço. Com exceção da analgesia de parto, todas as demais intervenções tiveram frequências elevadas. Elevado percentual de cesarianas. As intervenções no trabalho de parto e parto podem reduzir o tempo de período expulsivo, porém apresentam risco aumentado para hemorragia pós-parto. Para os desfechos neonatais a realização das intervenções mostrou-se como fator "protetor" para desfechos dos recém-nascidos. O tempo de período expulsivo prevalente foi de até 2 horas. Houve associação entre o incentivo a Manobra de Valsalva e tempo de expulsivo mais curto e associação da analgesia de parto com expulsivos mais longos. Recém-nascidos hígidos, foram retirados do contato pele a pele mesmo sem a necessidade de ventilação por pressão positiva, uso de O2 ou Apgar < 7 no 5º minuto. (AU)

Spatio-temporal expression profile of matrix metalloproteinase (Mmp) modulators Reck and Sparc during the rat ovarian dynamics.

BACKGROUND: Matrix metalloproteinases (Mmps) and their tissue inhibitors (Timps) are widely recognized as crucial factors for extracellular matrix remodeling in the ovary and are involved in follicular growth, ovulation, luteinization, and luteolysis during the estrous cycle. Recently, several genes have been associated to the modulation of Mmps activity, including Basigin (Bsg), which induces the expression of Mmps in rat ovaries; Sparc, a TGF-ß modulator that is related to increased expression of Mmps in cancer; and Reck, which is associated with Mmps inhibition. However, the expression pattern of Mmp modulators in ovary dynamics is still largely uncharacterized. METHODS: To characterize the expression pattern of Mmps network members in ovary dynamics, we analyzed the spatio-temporal expression pattern of Reck and Sparc, as well as of Mmp2, Mmp9 and Mmp14 proteins, by immunohistochemistry (IHC), in pre-pubertal rat ovaries obtained from an artificial cycle induced by eCG/hCG, in the different phases of the hormone-induced estrous cycle. We also determined the gene expression profiles of Mmps (2, 9, 13 14), Timps (1, 2, 3), Sparc, Bsg, and Reck to complement this panel. RESULTS: IHC analysis revealed that Mmp protein expression peaks at the early stages of folliculogenesis and ovulation, decreases during ovulation-luteogenesis transition and luteogenesis, increasing again during corpus luteum maintenance and luteolysis. The protein expression patterns of these metalloproteinases and Sparc were inverse relative to the pattern displayed by Reck. We observed that the gene expression peaks of Mmps inhibitors Reck and Timp2 were closely paraleled by Mmp2 and Mmp9 suppression. The opposite was also true: increased Mmp2 and Mmp9 expression was concomitant to reduced Reck and Timp2 levels. CONCLUSION: Therefore, our results generate a spatio-temporal expression profile panel of Mmps and their regulators, suggesting that Reck and Sparc seem to play a role during ovarian dynamics: Reck as a possible inhibitor and Sparc as an inducer of Mmps.

Resultados obstétricos e neonatais de partos assistidos / Obstetric and neonatal results of assisted childbirths

Objetivo: avaliar resultados obstétricos e neonatais de partos assistidos. Metodo: estudo quantitativo, descritivo, retrospectivo, com parturientes assistidas pelas enfermeiras residentes. Os dados foram coletados a partir das informações referentes aos partos, anotadas no livro de registro, analisados no SPSS, versão 20.0, agrupados em tabelas e submetidos à análise descritiva e numérica inferencial. Resultados: as enfermeiras residentes assistiram 147 partos de parturientes com faixa etária entre 20 e 24 anos e 44,9% eram nulíparas. Destas, 43 tiveram períneo íntegro após o parto; 61 apresentaram laceração de primeiro grau; 38, de segundo grau e cinco, de terceiro grau. O índice de episiotomia foi de 4,8%. Os métodos não farmacológicos de alívio da dor mais utilizados durante o trabalho de parto foram a respiração, o banho de aspersão e a massagem. Todos os recém-nascidos tiveram Apgar no quinto minuto igual ou maior que sete e 93,2% deles foram colocados em contato pele a pele com a mãe. Conclusão: os resultados maternos e neonatais foram favoráveis demonstrando que o programa de residência em Enfermagem Obstétrica se norteia nas evidências científicas e resulta em menos intervenções no processo de parturição.(AU)

Indicadores de parto e nascimento de mulheres soropositivas para vírus da imunodeficiência humana / Indicadores de parto e nascimento de mulheres soropositivas para vírus da imunodeficiência humana

Objetivo: avaliar os indicadores de parto e nascimento das parturientes soropositivas para vírus da imunodeficiência humana. Métodos: estudo documental realizado com 92 prontuários e fichas de investigação de mulheres soropositivas para vírus da imunodeficiência humana, com análise das variáveis sociodemográficas, obstétricas e neonatais. Utilizou-se o teste qui-quadrado para verificar associação entre as variáveis preditoras e desfecho. Resultados: as parturientes receberam profilaxias perinatais (77,2%) e no parto (91,3%); 52,2% realizaram sete consultas pré-natais. Quanto aos recém-nascidos, 8,7% nasceram prematuros, 18,5% com baixo peso e 92,4% receberam profilaxia com antirretroviral nas primeiras 24h do nascimento. Conclusão: a vulnerabilidade e o maior risco de adoecer ocorrem em adultos jovens, com escolaridade e nível socioeconômico baixos. O indicador de cobertura de gestantes necessita melhorar seus índices, uma vez que pouco mais da metade das mulheres realizou sete consultas pré-natais, impactando negativamente na evolução da gravidez com percentual de profilaxias na gestação abaixo do desejado. (AU)

Avaliação de partos assistidos na água por enfermeiras obstetras / Obstetrical nurses evaluation of water births

Objetivo: avaliar os indicadores do parto na água, assistido por enfermeiras obstetras e residentes de enfermagem obstétrica. Método: estudo quantitativo, exploratório e descritivo, retrospectivo, de análise documental, realizado em um Centro de Parto Normal, composto por 18 partos assistidos no primeiro ano da implementação de uma banheira com água morna. Os dados foram coletados de um livro de indicadores para parto na água. Para organização dos dados foi utilizado o programa estatístico Statistical Package for the Social Sciences versão 22.0, sendo estes agrupados em tabelas e submetidos à análise descritiva e numérica inferencial, bem como à luz da literatura. Resultados: de 2400 partos vaginais realizados no CPN, 18 (0,7%)ocorreram na água, em mulheres jovens, com gestação à termo, primíparas (n=12), maioria em fase ativa do trabalho de parto, no momento da internação, sob a assistência de enfermeiras obstétricas e residentes de Enfermagem Obstétrica. Conclusão: são muitas lacunas presentes nas evidências científicas acerca da assistência ao parto na água. Assim, mais estudos são necessários para fortalecer essa assistência por se tratar de um direito da mulher decidir onde e como deseja parir.

Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis.

Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M. tuberculosis. A panel of 17 M. tuberculosis clinical strains were characterized for drug resistance associated mutations and antibiotic profiles in the presence and absence of efflux inhibitors. The correlation between the effect of the efflux inhibitors and the resistance levels was assessed by quantitative drug susceptibility testing. The bacterial growth/survival vs. growth inhibition was analyzed through the comparison between the time of growth in the presence and absence of an inhibitor. For the same mutation conferring antibiotic resistance, different MICs were observed and the different resistance levels found could be reduced by efflux inhibitors. Although susceptibility was not restored, the results demonstrate the existence of a broad-spectrum synergistic interaction between antibiotics and efflux inhibitors. The existence of efflux activity was confirmed by real-time fluorometry. Moreover, the efflux pump genes mmr, mmpL7, Rv1258c, p55, and efpA were shown to be overexpressed in the presence of antibiotics, demonstrating the contribution of these efflux pumps to the overall resistance phenotype of the M. tuberculosis clinical isolates studied, independently of the genotype of the strains. These results showed that the drug resistance levels of multi- and extensively-drug resistant M. tuberculosis clinical strains are a combination between drug efflux and the presence of target-gene mutations, a reality that is often disregarded by the tuberculosis specialists in favor of the almost undisputed importance of antibiotic target-gene mutations for the resistance in M. tuberculosis.

An Experimental Model for the Rapid Screening of Compounds with Potential Use Against Mycobacteria.

Infections caused by Mycobacterium tuberculosis and other mycobacteria are major challenges for global public health. Particularly worrisome are infections caused by multidrug-resistant bacteria, which are increasingly difficult to treat because of the loss of efficacy of the current antibacterial agents, a problem that continues to escalate worldwide. There has been a limited interest and investment on the development of new antibacterial agents in the past decades. This has led to the current situation, in which there is an urgent demand for innovative therapeutic alternatives to fight infections caused by multidrug-resistant pathogens, such as multidrug-resistant tuberculosis. The identification of compounds that can act as adjuvants in antimycobacterial therapeutic regimens is an appealing strategy to restore the efficacy lost by some of the antibiotics currently used and shorten the duration of the therapeutic regimen. In this work, by setting Mycobacterium smegmatis as a model organism, we have developed a methodological strategy to identify, in a fast and simple approach, compounds with antimycobacterial activity or with potential adjuvant properties, by either inhibition of efflux or other unrelated mechanisms. Such an approach may increase the rate of identification of promising molecules, to be further explored in pathogenic models for their potential use either as antimicrobials or as adjuvants, in combination with available therapeutic regimens for the treatment of mycobacterial infections. This method allowed us to identify a new molecule that shows promising activity as an efflux inhibitor in M. smegmatis.

Toxocara canis: Larvicidal activity of fatty acid amides.

Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay.

Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil.

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

Synthesis and antimycobacterial activity of isoniazid derivatives from renewable fatty acids.

This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity.

Medicinal plants from open-air markets in the State of Rio de Janeiro, Brazil as a potential source of new antimycobacterial agents.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants are traditionally traded in open-air markets in Rio de Janeiro State (Brazil) to treat tuberculosis (TB) and related symptoms. AIMS OF THE STUDY: Conduct a survey in the open-air markets of 20 cities of Rio de Janeiro State to find medicinal plants that are popularly used to treat tuberculosis and other related diseases and assess their in vitro antimycobacterial activity. MATERIALS AND METHODS: We used direct observation and semi-structured interviews and asked herbalists to list species (free listing) in order to gather data about the plant species most commonly used for lung problems. We calculated a Salience Index and acquired two species of "erva-de-passarinho" (mistletoe), Struthanthus marginatus and Struthanthus concinnus (Loranthaceae), commonly used to treat tuberculosis for a bioassay-guided isolation of the antimycobacterial active principles. Extracts, fractions and isolated compounds of both species were assayed in vitro against susceptible (H37Rv) and rifampicin-resistant (ATCC 35338) Mycobacterium tuberculosis strains. RESULTS: From the interviews, we generated a list of 36 plant species belonging to 12 families. The mistletoes Struthanthus marginatus and Struthanthus concinnus showed high Salience Index values among plants used to treat tuberculosis. Bioassay-guided fractionation of hexane extracts from both species led to the isolation and/or identification of steroids and terpenoids. The Minimum Inhibitory Concentration (MIC) of the extracts and isolated compounds ranged from 25 to 200 µg/mL. Some of the isolated compounds have been previously assayed against Mycobacterium tuberculosis, others are reported here for the first time (obtusifoliol: MIC H37Rv 50 µg/mL, MIC ATCC 35338 12.5 µg/mL; 3-O-n-acil-lup-20(29)-en-3ß,7ß,15α-triol: MIC H37Rv 200 µg/mL, MIC ATCC 35338 100 µg/mL). CONCLUSIONS: This study demonstrated the importance of ethnobotanical surveys in markets as a source for new drugs and also for scientific validation of folk medicine.

1,3-Azoles from ortho-naphthoquinones: synthesis of aryl substituted imidazoles and oxazoles and their potent activity against Mycobacterium tuberculosis.

Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented MIC values in the range of 0.78 to 6.25 µg/mL against susceptible and resistant strains of M. tuberculosis. Five structures were solved by X-ray crystallographic analysis. These substances are promising antimycobacterial prototypes.

In vitro anti-mycobacterial activity of (E)-N'-(monosubstituted-benzylidene) isonicotinohydrazide derivatives against isoniazid-resistant strains.

A series of twenty-three N-acylhydrazones derived from isoniazid (INH 1-23) have been evaluated for their in vitro antibacterial activity against INH- susceptible strain of M. tuberculosis (RG500) and three INH-resistant clinical isolates (RG102, RG103 and RG113). In general, derivatives 4, 14, 15 and 16 (MIC=1.92, 1.96, 1.96 and 1.86 µM, respectively) showed relevant activities against RG500 strain, while the derivative 13 (MIC=0.98 µM) was more active than INH (MIC=1.14 µM). However, these derivatives were inactive against RGH102, which displays a mutation in the coding region of inhA. These results suggest that the activities of these compounds depend on the inhibition of this enzyme. However, the possibility of other mechanisms of action cannot be excluded, since compounds 2, 4, 6, 7, 12-17, 19, 21 and 23 showed good activities against katG-resistant strain RGH103, being more than 10-fold more active than INH.

The activity of flavones and oleanolic acid from Lippia lacunosa against susceptible and resistant Mycobacterium tuberculosis strains

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is the world's number one killer among infectious diseases. The search for new naturalproducts that can act as drugs against TB has received increased attention duringthe last years. In this work we describe the isolation and identification of the active antimycobacterial principles of the dichloromethane extract from Lippia lacunosa Mart. & Schauer, Verbenaceae. Compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (susceptible and rifampicin resistantstrain) using a redox bioassay. From the dichloromethane extract of L. lacunosa leaves, seven methoxy-flavones named cirsimaritin (1), eupatilin (2), eupatorin (3), salvigenin (4), 3'-O-methyl-eupatorin (5), 3',7-dimethoxy-5,6,4'- trihydroxyflavone (6), and 7'-O-methylapigenin (7), and one triterpene, named oleanolic acid (8), were isolated. All compounds were found to display antimycobacterial activity against susceptible strain, with MIC ranging from 25 to 200 µg/mL. None of them was active against rifampicin resistant strain. This is the first report in the antimycobacterial activity of 6-substituted flavones, as well as the first report of the occurrence of these substances in L. lacunosa.