Aim: To evaluate (i) the in vitro activity of eugenol (EUG) and three derivatives against Mycobacterium tuberculosis (Mtb), nontuberculous mycobacteria (NTM) and other bacteria, (ii) the EUG and antituberculosis drugs combinatory effect and (iii) the EUG and its derivatives cytotoxicity. Materials & methods: Minimum inhibitory concentration of the compounds were determined by resazurin microtiter or broth microdilution assay and the drug interaction between EUG and antituberculosis drugs by resazurin drug combination microtiter. The cytotoxicity was carried out in macrophages, HeLa and VERO cells. Results: EUG and derivatives displayed activity and synergic effect of EUG combined with rifampicin, isoniazid, ethambutol, and pyrazinamide in Mtb including multidrug-resistant isolates, with more selectivity to bacillus than macrophages, HeLa and VERO cells (selective index from 0.65 to 31.4). EUG derivatives (4-allyl-2-methoxyphenyl acetate, 4-allyl-2-methoxyphenyl benzoate, and 4-allyl-2-methoxyphenyl 4-nitrobenzoate) were more active against nontuberculous mycobacteria than EUG. EUG and derivatives exhibited low activity in other Gram-positive and -negative bacteria. Conclusion: EUG and its derivatives show activity against Mycobacterium spp. and synergic effect of EUG combined with antituberculosis drugs against Mtb.

No abstract

Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown promising activity as efflux pump (EP) inhibitor and as adjunct in treatment of tuberculosis (TB). The present systematic review investigated scientific studies of the activity of piperine against mycobacteria, with a focus on its mechanism of action, drug interactions, and antimycobacterial activity. A broad and rigorous literature search of three electronic databases (PubMed, Web of Knowledge, and LILACS) was performed according to the PRISMA statement. We considered studies that were published up to December 1, 2017. Google Scholar was also searched to increase the number of publications. We searched for articles using the search terms "piperine" and "Mycobacterium spp." The search yielded a total of 225 articles. After removing duplicate publications, 208 publications remained. Of these, we evaluated the full text of 13 articles. After applying the inclusion criteria, eight studies were included in the present systematic review. The results of the systematic review showed that piperine has promising anti-TB activity, mainly when combined with antimicrobials, and plays an important role as an EP inhibitor.

Carvacrol shows good anti-M. tuberculosis activity and synergism with rifampicin.

The activity of rifampin (RIF) and piperine was evaluated at the relative transcript levels of 12 efflux pumps (EPs), and an additional mechanism was proposed to be behind the synergic interactions of piperine plus RIF in Mycobacterium tuberculosis. AutoDock v4.2.3 and Molegro v6 programs were used to evaluate PIP binding in M. tuberculosis RNA polymerase (RNAP). A hypothesis has been raised that piperine interferes in M. tuberculosis growth through RNAP inhibition, differently from what was previously endorsed for EP inhibition only.

Aim: To evaluate the modulatory effect of piperine (PIP) on streptomycin (SM) activity in Mycobacterium tuberculosis ( Mtb). Materials & methods: SM and PIP minimum inhibitory concentration (MIC) and combinatory activity were determined in Mtb H37Rv and in susceptible and resistant clinical isolates. Ethidium bromide accumulation assay and relative quantification of efflux pumps genes ( rv1258c, rv1218c and rv2942), after SM and SM+PIP combination exposure, were also performed. Results: PIP concentration of 25 μg/ml (1/4× MIC) was able to inhibit efflux pumps activity, to modulate SM activity in Mtb, and conducted changes in the relative quantification of efflux pumps genes. Conclusion: SM+PIP combination was able to rescue the SM susceptible MIC values in SM resistant Mtb.

RESUMOObjetivo: verificar a prevalência da deficiência auditiva em um programa de triagem auditiva neonatal e investigar mutações do gene GJB2 naqueles com suspeita de deficiência auditiva. Método: foi realizado estudo longitudinal com 908 RN a termo, pós-termo e pré-termo que foram submetidos à realização da triagem auditiva por meio do teste de Emissão Otoacústica Evocada por Estímulo Transiente (EOA-T) e reflexo cócleo-palpebral (RCP). Para os recém-nascidos, em que houve falha na triagem auditiva em uma ou ambas as orelhas, eram encaminhados para uma segunda avaliação. No reteste, quando o teste de EOA-T resultasse em não passa em uma ou ambas as orelhas, a criança era encaminhada para avaliação e conduta otorrinolaringológica. Após realização do Potencial Evocado Auditivo de Tronco Encefálico (PEATE) a equipe de avaliadores decidia se deveria encaminhar a criança para investigação da mutação. Quando havia suspeita de deficiência auditiva era colhido 3 mL de sangue venoso periférico para a pesquisa de mutação do gene da conexina 26. Resultados: foi constatado a presença de deficiência auditiva condutiva em 2 recém-nascidos (0,22%) e neurossensorial em 1 (0,11%). Na criança com deficiência auditiva neurossensorial foi detectada a presença da mutação 35delG. Conclusão: a avaliação audiológica em conjunto com exames moleculares das principais mutações do gene GJB2 em recém-nascidos com suspeita da deficiência auditiva contribuiu para a rapidez do diagnóstico audiológico, visando uma intervenção precoce, aconselhamento genético e prognóstico educacional da criança. Conflito de interesses: inexistente intelectual e da linguagem. Este artigo permite contribuir para a epidemiologia da DA, estudando a prevalência em um programa de triagem auditiva neonatal. Alguns estudos citados ao longo deste artigo que contribuíram para a epidemiologia da DA, ora tratam da incidência, ora tratam da prevalência, entretanto possuem significados diferentes. A prevalência DESCRITORES: INTRODUÇÃOA deficiência auditiva (DA) acarreta sérios problemas no desenvolvimento cognitivo, social,