Travoprost/Timolol Maleate

Spore-forming bacteria of the Bacillus genus are widely used probiotics known to exert their beneficial effects also through the stimulation of the host immune response. The oral delivery of B. toyonensis spores has been shown to improve the immune response to a parenterally administered viral antigen in mice, suggesting that probiotics may increase the efficiency of systemic vaccines. We used the C fragment of the tetanus toxin (TTFC) as a model antigen to evaluate whether a treatment with B. toyonensis spores affected the immune response to a mucosal antigen.

Purified TTFC was given to mice by the nasal route either as a free protein or adsorbed to B. subtilis spores, a mucosal vaccine delivery system proved effective with several antigens, including TTFC. Spore adsorption was extremely efficient and TTFC was shown to be exposed on the spore surface. Spore-adsorbed TTFC was more efficient than the free antigen in inducing an immune response and the probiotic treatment improved the response, increasing the production of TTFC-specific secretory immunoglobin A (sIgA) and causing a faster production of serum IgG. The analysis of the induced cytokines indicated that also the cellular immune response was increased by the probiotic treatment. A 16S RNA-based analysis of the gut microbial composition did not show dramatic differences due to the probiotic treatment. However, the abundance of members of the Ruminiclostridium 6 genus was found to correlate with the increased immune response of animals immunized with the spore-adsorbed antigen and treated with the probiotic.

Our results indicate that B. toyonensis spores significantly contribute to the humoral and cellular responses elicited by a mucosal immunization with spore-adsorbed TTFC, pointing to the probiotic treatment as an alternative to the use of adjuvants for mucosal vaccinations.

The time to first cigarette (TTFC) of the day has been identified as the best single-item indicator of nicotine dependence. However, TTFC has not been extensively used in clinical settings and is not a criterion for tobacco use disorder, perhaps due to a lack of information about TTFC's predictive value. This review provides a synthesis of the accumulating literature on TTFC's relationships with nicotine dependence, identify gaps, and inform future clinical and epidemiologic research of potential uses of TTFC.

A systematic review of the literature was conducted using PubMed, Google Scholar, and Web of Science ISI databases. We identified 16 articles examining the relation between TTFC and negative outcomes associated with high levels of nicotine addiction and Tobacco Use Disorders (eg, high levels of nicotine and toxicant exposure, progressive use over time, failed cessation, head-and-neck cancers).

Earlier TTFC was consistently associated with greater likelihood of cessation failure and relapse, and higher levels of biomarkers of tobacco exposure. Several of these associations were found among both adult and adolescent smokers, and remained even after accounting for smoking behaviors (eg, cigarettes/day).

Earlier TTFC is a key indicator of greater nicotine dependence. Knowledge of a smoker's TTFC may allow clinicians to accurately inform smokers of health risks and assign greater resources during cessation attempts. Smokers may be able to use TTFC to self-select cessation aids and accurately assess their unique smoking-related health risks. TTFC may be a better item than cigarettes/day for accurately quantifying dependence and risk in epidemiologic studies.