Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response.

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Background Clinical studies have reported inconsistent outcomes of glucosamine therapy in osteoarthritis patients. One possible reason could be the use of glucosamine products of varying quality. Hence, this study aimed to assess the quality of glucosamine products marketed in Australia and India. This is the first study to investigate both the content and dissolution profiles of glucosamine products. Methods The content and dissolution analysis of Australian (n=25 brands) and Indian (n=21 brands) glucosamine products was performed according to the criteria specified in the United States Pharmacopoeia (USP). Results The quality analysis revealed that 16 and 18% of Australian brands, as well as 24 and 19% of Indian brands, did not fulfil the USP content and dissolution criteria, respectively. In approximately half of these cases, the glucosamine content was only slightly below (<3%) that specified by the USP and dissolution was achieved within 15 min after the duration specified by the USP. Conclusions The majority of the brands did meet both the content and dissolution analysis criteria of the USP. The extent of deviation from the specified criteria for the other brands was probably insufficient to account for the significant variability in clinical effects. Hence, the study proposed that inter-patient pharmacokinetic variations in glucosamine could be another potential reason for inconsistent therapeutic effects.