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Mei Z.,Tianjin Haihe Hospital | Mei Z.,Tianjin Respiratory Disease Research Institute | Sun Z.,Capital Medical University | Sun Z.,Beijing Tuberculosis and Thoratic Tumor Research Institute | And 14 more authors.
BioMed Research International | Year: 2015

To find the potential reasons for the discrepancies in the drug susceptibility test (DST) of M. tuberculosis isolates, twenty paired isolates with disputed drug susceptibilities to isoniazid (INH) were selected according to the MGIT960 testing and Löwenstein-Jensen (L-J) proportion methods. Their MICs were confirmed again by broth microdilution method and by L-J proportion method. The spoligotyping results showed that, of all the 20 paired strains, 11 paired isolates belonged to the Beijing genotype and 6 paired isolates belonged to SIT1634, and that each of the remaining 3 paired isolates had two genotypes, namely, SIT1 and SIT1634. Those 3 paired isolates with different intrapair spoligotypes were further confirmed as mixed infection by the results that those three pairs of isolates with different 12 locus MIRU intrapair types and one pair carried different base pair at codon 315 (AGC versus AAC). Totally mutations in the katG gene were identified in 13 paired isolates. No mutations were found in the regulatory sequences and open reading frames (ORF) of the inhA and ahpC genes in any of the tested isolates. Those results showed that the different test systems and the mixed infection with particular genotypes of M. tuberculosis strains contributed to the drug susceptibility discrepancies. Copyright © 2015 Zaoxian Mei et al. Source

Bao Y.-C.,Tianjin Respiratory Disease Research Institute | Zhang W.-L.,Tianjin Respiratory Disease Research Institute | Wang Y.,Tianjin Respiratory Disease Research Institute | Zhang J.,Tianjin Respiratory Disease Research Institute | Wang Y.-M.,Tianjin Respiratory Disease Research Institute
Chinese Journal of Tissue Engineering Research | Year: 2013

Background: During conventional treatment for bone tuberculosis, there is a low effective concentration of anti-tuberculosis drugs, and the therapeutic effect is poor. Objective: To develop a new biomaterial as a slow-release artificial carrier that can be directly implanted into the surrounding tissue of bone tuberculosis, maintain a certain anti-tuberculosis drug concentration for a long time, thereby playing an effective therapeutic action. Methods: Rifampicin/polylactic acid/glycolic acid microspheres and isoniazid/polylactic acid/glycolic acid microspheres were prepared using the emulsion-solvent evaporation method. Using α-cyanoacrylate, a biological adhesive, two kinds of microspheres were processed into a long-term slow-release bicomponent drug carrier. Then, in vitro release characteristics of the dual-drug sustained-release carrier were observed. After that, the dual-drug sustained-release carrier was implanted into rabbit intertrochanteric femur bone defects for observing drug release concentrations, histocompatibility and bone defect healing at different time points after drug delivery carrier implantation. Results and conclusion: For rifampicin/polylactic acid/glycolic acid microspheres, the mean particle size was (240±13) μm, and the drug loading load rate was (26±1.5)%. For isoniazid/polylactic acid/glycolic acid microspheres, the mean particle size was (250±10) μm, and drug loading rate was (28±1.8)%. The in vitro cumulative release rate could reach 80% for rifampicin and 90% for isoniazid at day 90. The in vivo released concentration of rifampicin and isoniazid within 90 days was (0.5±0.4) and (0.6±0.3) μg/g, respectively. There were a small amount of infiltrated neutrophils between the fascia and muscle fibers after the drug delivery carrier was implanted, and the amount of neutrophils in the muscle were reduced significantly at day 59. X-ray plain film showed that bone defects decreased obviously in size. These findings indicate that this dual-drug sustained-release carrier can maintain a certain anti-tuberculosis drug concentration in the surrounding tissues of bone tuberculosis, which is expected to provide a new type of dual-drug delivery carrier in the surgical treatment of bone tuberculosis. Source

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