Avaliação da atividade antimicobacteriana da lignana diidrocubebina extraída da Piper cubeba e de seus derivados semissintéticos / Evaluation of antimycobacterial activity of dihydrocubebin lignan extracted from Piper cubeba and its semisynthetic derivatives

RESUMO: A atividade antimicobacteriana de diidrocubebina (1), uma lignana dibenzilbutanodioica obtida a partir de extrato etanólico de sementes da Piper cubeba, e seus derivados foram avaliados in vitro contra três diferentes cepas de Mycobacterium utilizando o método de microdiluição. Dentre as lignanas avaliadas 3 e 4 foram as mais ativas, exibindo valores de CIM de 62,5 µg/mL contra M. avium e M. tuberculosis, respectivamente. Os derivados 2-6 obtidos por síntese parcial possuem diferentes substituintes nos carbonos 9 e 9 ', que alteram polaridade, solubilidade e limitam as rotações livres entre C8-C8' em relação de material (1) de partida. As diferenças estruturais entre estes compostos podem fornecer informações importantes sobre a relação estrutura-atividade antimicobacteriana do esqueleto dibenzilbutanodioico, obtido a partir de fonte natural, como um possível alvo para o desenvolvimento de drogas mais potentes contra a tuberculose

ABSTRACT: Evaluation of antimycobacterial activity of dihydrocubebin lignan extracted from Piper cubeba and its semisynthetic derivatives. The antimycobacterial activity of the dihydrocubebin (1), a dibenzylbutanedioiclignan obtained from ethanolic extract of Piper cubeba seeds, and its derivatives were examined in vitro against three different strains of Mycobacterium using amicrodilution method. Among the lignans evaluated, the 3 and 4 samples were the most active ones, displaying MIC values of 62.5 µg/mL against M. avium and M. tuberculosis, respectively. The derivatives 2-6, obtained for partial synthesis, had different substituents in the carbons 9 and 9', fact thatalters the polarity, solubility and restricts the free rotations between the bonds C8-C8' in relation to the starting material (1). The structural differences among these compounds provide important information about the antimycobacterial structure-activity relationship of the dibenzylbutanodioic skeleton, obtained from natural source, such as a possible target for the development of more powerful drugs against tuberculosis

Comentarios clínicos acerca de las micobacteriosis pulmonares / Pulmonary mycobacterioses: clinical commentaries

Las micobacteriosis pulmonares son afecciones provocadas por micobacterias ambientales, de evolución crónica y clínicamente similares a la tuberculosis. Se analiza una serie de 26 casos asistidos en el Hospital Muñiz de la Ciudad de Buenos Aires, con una edad promedio de 59.2 años, 73.1% de sexo femenino y 80.1% de los casos de nivel socioeconómico mediano a alto. Se hallaron enfermedades predisponentes en el 88.5% de los casos (tuberculosis previa, EPOC, silicosis, reflujo gastroesofágico). Desde el punto de vista radiológico se observaron nódulos, bronquiectasias y cavidades pequeñas en 14 casos y lesiones bilaterales cavitarias extensas en 12. Se destacó la mayor frecuencia de Mycobacterium avium complex como patógeno, la mejor evolución de los pacientes con menor compromiso pulmonar y la de los afectados por M. avium en relación con otras micobacterias. Los fármacos más utilizados en el tratamiento fueron claritromicina y azitromicina, asociados a etambutol. La proporción global de curaciones fue baja (57.7%) pero superior en los casos provocados por M. avium (86.7%).

Mycobacterium avium subspecies paratuberculosis diagnosis and strain typing--present status and future developments.

Mycobacterium avium subspecies paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic gastroenteritis of ruminants and has zoonotic importance. We present here a review of MAP with respect to--(i) present diagnostic techniques and important developments; and (ii) MAP strain-typing tools. A summary of the findings to date is presented, and advantages and disadvantages of each of the methods are compared and discussed.

Genotype analysis of human Mycobacterium avium isolates from India.

BACKGROUND & OBJECTIVE: Mycobacterium avium has emerged as a major opportunistic pathogen, infecting nearly 50 per cent of HIV/AIDS patients in the western world. There is no report from India regarding the typing profile of M. avium, a potential pathogen, the present study was undertaken to assess the genotypic diversity of Indian M. avium isolates of human origin. METHODS: A total of 65 biochemically identified M. avium isolates from sputum samples of patients with chronic pulmonary illness were subjected to IS1245 based restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) typing. RESULTS: IS1245 insertion sequence based RFLP demonstrated polymorphism in 84.6 per cent isolates, while 15.4 per cent isolates did not hybridize on Southern blot and therefore were RFLP negative. Among the 55 RFLP positive isolates, 8 showed 1-3 bands, 19 had bands ranging between 4-9, and 28 isolates had >10 bands each. Although the isolates could be clubbed on the basis of number of bands, the banding profile was highly polymorphic. Among the 55 isolates typeable by RFLP, four clusters and 40 unique types of polymorphism were observed. Application of IS1245 based PCR typing on the same isolates showed that 87.7 per cent isolates were typeable. Interestingly the 10 isolates that were not typeable by IS1245 RFLP were typeable by IS1245 based PCR typing. Among the 57 PCR typed isolates a cluster of 14 isolates with identical 3-banded pattern was observed. Notably, 5 of the ten IS1245 RFLP negative isolates were within this cluster. INTERPRETATION & CONCLUSION: Our results demonstrated that M. avium isolates from India were highly polymorphic with remarkable genetic diversity and heterogeneous RFLP profile. We observed that 47 per cent (n=27) isolates had RFLP profile suggestive of bird and animal origin indicating a strong association with the environment. By applying two typing methods based on IS1245 on the isolates 100 per cent typeability could be achieved.

Mycobacterium avium restriction fragment lenght polymorphism-IS IS1245 and the simple double repetitive element polymerase chain reaction typing method to screen genetic diversity in Brazilian strains

Simple double repetitive element polymerase chain reaction (MaDRE-PCR) and Pvu II-IS1245 restriction fragment length polymorphism (RFLP) typing methods were used to type 41 Mycobacterium avium isolates obtained from 14 Aids inpatients and 10 environment and animals specimens identified among 53 mycobacteria isolated from 237 food, chicken, and pig. All environmental and animals strains showed orphan patterns by both methods. By MaDRE-PCR four patients, with multiple isolates, showed different patterns, suggesting polyclonal infection that was confirmed by RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium strains demonstrated that the method seems to be useful as simple and less expensive typing method for screening genetic diversity in M. avium strains on selected epidemiological studies, although with limitation on analysis identical patterns except for one band.

Comparison of biochemical characterisation of ICRC bacilli with M. leprae: effect of substrate alteration in the medium.

ICRC-bacilli strain C-44 when grown in Dubos medium of its equivalent, express M. avium taxonomic biochemical characters. Assuming that difference in characters of M. leprae and ICRC bacilli, could be due to 'in vivo' and 'in vitro' milieu, we altered the substrates in the medium. The bacilli grow well in the new medium containing selenium, ferric nitrate, magnesium chloride and deleting Tween 80. The ICRC strain C-44 grown in new medium expressed characters: 9/10 similarity with M. leprae. The 10 day tween hydrolysis reaction in weak but positive. It is probable that 'M. leprae culture isolate', may have acquired 'in vitro' growth potential by recombination with M. avium, an ubiquitous mycobacterium. The M. leprae culture isolate thus may express some characters of both M. leprae and M. avium.