Orbitazine fumarate

Mycobacterium kansasii is a bacterium included in non-tuberculous mycobacteria (NTM) that can cause lung disease. It shares a significant number of antigens with Mycobacterium tuberculosis (Mtb), suggesting that it has the potential to be used as a tuberculosis (TB) vaccine. Therefore, we subcutaneously vaccinated mice with reference strain, M. kansasii -ATCC12478 [ M. kansasii -American Type Culture Collection (ATCC)], and clinically isolated strain, M. kansasii -SM-1 to evaluate potential as a TB vaccine by comparing with bacille Calmette-Guerin (BCG) vaccine. Ten weeks after vaccination, we evaluated immunogenicity of M. kansasii -ATCC and M. kansasii -SM-1, and M. kansasii -SM-1 immunization induces potent Mtb antigen-specific IFN-γ-producing CD4 + T cells than M. kansasii -ATCC. Upon Mtb infection, M. kansasii -SM-1 provided better protection than M. kansasii -ATCC, which was comparable to the efficacy of BCG. These results showed that the clinical strain M. kansasii -SM-1, which exhibits an enhanced Mtb antigen-specific Th1 response, shows greater vaccine efficacy compared to M. kansasii -ATCC. In this study, we demonstrated that vaccine efficacy can vary depending on the strain of M. kansasii and that its efficacy can be comparable to BCG. This suggests that M. kansasii has the potential to be a live TB vaccine candidate.

Mycobacterium kansasii , a non-tuberculous mycobacteria (NTM) species causing lung disease, shares key antigens with Mycobacterium tuberculosis (Mtb), indicating its potential for TB vaccine development. Subcutaneous vaccination of mice with M. kansasii strains reference strain M. kansasii -ATCC12478 [( M. kansasii -American Type Culture Collection (ATCC)] and clinically isolated strain M. kansasii -SM-1 revealed differences in immunogenicity. M. kansasii -SM-1 induced a robust Mtb antigen-specific IFN-γ-producing CD4 + T cell response compared to M. kansasii -ATCC. Additionally, M. kansasii -SM-1 conferred better protection against Mtb infection than M. kansasii -ATCC, which is comparable to bacille Calmette-Guerin (BCG). These findings underscore the variable vaccine efficacy among M. kansasii strains, with M. kansasii -SM-1 exhibiting promising potential as a live TB vaccine candidate, suggesting its comparative effectiveness to BCG.

Thomas Dahl, PO Box 404, Guilford, CT 06437 USA. Email: tadahl@outlook.com. The objectives of the study were to demonstrate the efficacy and safety of SM-1 in a circadian challenge model of transient insomnia. Randomized, double-blind, placebo-controlled cross-over study utilizing a 5-h phase advance model of transient insomnia. Subjects were 85 healthy adults reporting a history of transient insomnia, with an average age of 38.9 years. Both SM-1 and placebo were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time determined by polysomnography. Secondary endpoints included wakefulness after sleep onset, latency to persistent sleep, number of awakenings, subjective total sleep time and subjective sleep onset latency, total sleep time by quarters of the night, subjective number of awakenings, and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale, Digit Symbol Substitution Test, and predischarge evaluation (tandem gait and Romberg tests). SM-1 provided an increase of 94.4 min in total sleep time over placebo (p < 0.0001). Wakefulness after sleep onset, subjective total sleep time, subjective sleep onset latency, and total sleep time in the first quarter of the night also showed significant improvement. SM-1 was well-tolerated with both type and frequency of adverse events being comparable to placebo, and no residual sleepiness upon awakening (i.e., after 8 h). SM-1 provided a robust and statistically significant increase in total sleep time compared to placebo in a circadian model of transient insomnia, without evidence of next-day impairment.