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Multidrug resistance tuberculosis (MDR-TB) associated with the development of resistance to fluoroquinolones (FQs) especially ofloxacin is a matter of concern, as they had been earlier recommended drugs for usage in the MDR-TB treatment regimens, and moxifloxacin and other quinolones are still on the list. Mycobacterium tuberculosis acquires resistance to FQs mainly through mutations in the quinolone resistance determining regions (QRDRs) of the gyrA gene and less frequently in the gyrB gene. A literature search on the geographical distribution of ofloxacin resistance in TB shows that there is a mild surge in reporting of the resistance to ofloxacin in tuberculosis patients. Molecular tests demonstrating mutations in gyrA and gyrB genes is widely used to detect ofloxacin resistance and the broadly available commercial assay for the rapid detection of second-line-drug resistance, including FQ resistance, the GenoType MTBDRsl assay (Hain Life science, Nehren, Germany), detects the most common mutations found in the QRDR of gyrA while its new version 2.0 detects mutations in the gyrB as well. It has been shown that on reviewing the frequency and geographic distribution of gyrA and gyr B mutations associated with FQ resistance, there do exist geographic differences in the frequencies within and across countries. Cross-resistance to FQs is an area of concern, although some studies show that concordance in resistance among the FQ agents, lower level of cross-resistance has also been reported. The presence of ofloxacin resistance is an alarm signal while Moxifloxacin and other FQs are still the recommended drugs for the resistant TB cases. The WHO recommendation that ofloxacin be phased out from MDR-TB regimens is well justified. It is important that rationale usage of ofloxacin is needed for preventing ofloxacin resistance, to aid in the management of tuberculosis. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) has been identified in skeletons over 6000 years old and still remains as the most prevalent infectious disease in the world; thus, there is a need for development of new drugs or tuning of old drugs. Nanotechnology, an advanced technology, plays a vital role in research for the diagnosis and treatment of TB, thus preventing adverse effects and drug resistance. The objective of this study was to enhance the antimycobacterial activity of isoniazid- (INH) and rifampicin (RIF)-incorporated norbornene (NOR) nanoparticles in comparison with plain INH and RIF without nanoparticles. Methods: Norbornene-polyethylene glycol - Isoniazid copolymer (NOR-PEGINH) and norbornene polyethylene rifampicin Co polymer (NOR-PEG-RIF) were used for this study. The percentage of INH and RIF in NOR nanoparticles was 35% and 74%, respectively. Mycobacterium growth indicator tube containing Middlebrook 7H9 broth, the liquid medium, was used to analyze in vitro activity of the NOR-based drug and the plain drug. Minimum inhibitory concentration (MIC) of the drugs was determined from H37Rv control strain of mycobacterium TB (MTB). Results: The dosage of INH and RIF is minimal in the combination form with the NOR nanoparticles compared to the plain INH and RIF. The results indicate that the minimum concentration of NOR-PEG-INH and NOR-PEG-RIF required inhibiting H37Rv strain of MTB was 0.05 μg/ml and 0.5 μg/ml, respectively. The results were similar to plain INH and RIF MIC. Conclusion: Low dosage of INH and RIF along with NOR nanocarrier has similar activity to that of INH and RIF; thus this is expected to reduce adverse effects and NOR did not alter the functional activity of INH and RIF, thus becoming eligible for the newer drug carrier in TB treatment. [ABSTRACT FROM AUTHOR]

Specific mycobacterial antigens are an important prerequisite in the serodiagnosis of tuberculosis. Many studies have reported the use of both native and recombinant proteins. Even though recombinant proteins can form standardized reagents with unlimited supply, their diagnostic test characteristics were not satisfactory in some cases. In this study we have purified the 38-, 30- (antigen 85B), and 16-kDa native antigens of Mycobacterium tuberculosis by procedures with limited number of steps. Starting with the secreted antigens of M. tuberculosis H37Rv, the 38-kDa form was purified by preparative isoelectric focusing, followed by preparative electrophoresis. Separation of antigen 85 components was achieved by anion-exchange chromatography, followed by hydrophobic interaction chromatography. Gel-permeation chromatography was employed for the isolation of the 16-kDa form, from the cytosol fraction of M. tuberculosis H37Rv. By using a minimal number of steps, considerable yields of these proteins were obtained without loss of immunological activity. The native proteins purified were characterized by analytical two-dimensional electrophoresis, HPLC, and circular dichroism studies. Conformation of the native 38-kDa form purified in our laboratory was different from that of the recombinant 38-kDa form from the WHO Bank. The identities of these native antigens were established by immunoblotting with known monoclonal antibodies from the WHO Bank., (Copyright 2002 Elsevier Science (USA).)