No abstract

In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24 h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24 h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS (P < 0.05) or tubercle bacilli (P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1beta, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.

Background No study has reported the relationship between secondhand smoke (SHS) exposure and diabetes mellitus in self-reported never-smokers verified by nicotine metabolite. Purpose The aim of this study is to determine the relationship between SHS exposure and diabetes mellitus in self-reported and cotinine-verified never-smokers. Methods A total of 131,724 self-reported and cotinine-verified never-smokers (42,681 men; age 35.0±7.1 years) enrolled in Kangbuk Samsung Health Study (KSHS) and Kangbuk Samsung Cohort study (KSCS) between 2011 and 2016 were included. Cotinine-verified never-smoker was defined as individuals having urinary cotinine <50 ng/mL. SHS exposure was defined as having experienced passive smoking indoors at home or the workplace. Diabetes mellitus was defined as having a fasting blood glucose level of ≥7.0mmol/L, hemoglobin A1C ≥6.5% or taking anti-diabetic medication(s). Results The frequency of diabetes mellitus in the overall population was 1.6%; the frequency in males was higher than that in females (2.2% versus 1.3%, p<0.001). The overall frequency of SHS exposure was 22.9%, with rates of 27.6% for males and 20.7% for females (p<0.001). The frequency of diabetes mellitus in group with SHS exposure was higher than that in group without SHS exposure only in females (1.8% versus 1.2%, p<0.001 for females; 2.2% versus 2.2%, p=0.956 for males). There was significant gender interaction for the relationships between SHS exposure and diabetes mellitus (p for interaction <0.001). A multivariate regression model was adjusted for the baseline variables including age, waist circumference, body mass index, frequency of alcohol drinking and vigorous exercise, systolic blood pressure, blood urea nitrogen, creatinine, uric acid, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, and hsCRP. Only in females, SHS exposure was significantly associated with diabetes mellitus (odds ratio [95% confidence interval], 1.40 [1.20, 1.65] for females; 1.00 [0.85, 1.19] for males). Higher frequency and longer duration of SHS exposure were also significantly associated with diabetes mellitus (p<0.001) for all trends). In particular, females with SHS exposure of ≥1 hours/day, ≥3 times/week, and ≥10 years increased the risk of diabetes mellitus 51–64% above that for those without SHS exposure (1.64 [1.25, 2.13], 1.51 [1.21, 1.87], and 1.59 [1.30, 1.95], respectively. Conclusions This study showed that the SHS exposure in females was significantly associated with diabetes mellitus in self-reported never-smokers verified by urinary cotinine and this association was proportional to the frequency and duration of SHS exposure. These findings suggest the importance of banning smoking in the home and public to reduce the risk of diabetes mellitus. Acknowledgement/Funding None