Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 µM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 µL/min while passive diffusion clearance was 0.31 µL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level.

Impact of smoking on the effectiveness of TNF-alpha inhibitors in patients with rheumatoid arthritis or Crohn's disease

Cigarette smoking may be associated with the augmentation of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-alpha), which may affect the outcomes of pharmacological agents such as TNF-alpha inhibitors. The purpose of this study was to investigate the impact of smoking on the effectiveness of TNF-alpha inhibitors in patients with rheumatoid arthritis (RA) or Crohn's disease (CD). We used systematic literature review methods. A total of 1,147 articles were selected after exclusion of duplicates through a database search. Among them, 28 articles were finally selected through a review of titles and abstracts and a subsequent review of full articles. The effectiveness of TNF-alpha inhibitors in patients with RA or CD among the selected articles was summarized by their smoking status. Meta-analysis was performed with random effect model. When current smokers were compared with non-smokers for response after adjustments through meta-analysis among patients with RA, current smokers had 59% less response than non-smokers with statistical significance (Pooled adjusted OR=0.41, 95% CI=0.17-0.95). In patients with CD, current smokers tended to have lower clinical response than non-smokers, but statistical significance was not shown. In subgroup analyses for luminar CD or fistulizing CD, current smokers tended to have a lower response in luminar CD (Pooled OR=0.62, 95% CI=0.34-1.14), but smoking status was not associated with drug response in fistulizing CD. This study raises awareness of the adverse effects of smoking in terms of clinical response in patients treated with TNF-alpha inhibitors.

The Analysis of the School Foodservice Employees' Knowledge and Performance Degree of HACCP System in Jeju

The purposes of this study were to (a) analyze school foodservice employees' knowledge and performance degree of HACCP system and (b) provide the basic data for planning the strategies which can be performed for systematic HACCP system in school foodservice. For these purposes, the subjects included 91 dieticians (a response rate 98.9%) and 270 foodservice employees (a response rate 98.2%) at school in Jeju city and they were surveyed from October 21 to November 4, 2006. The data were analyzed by descriptive analysis, reliability analysis, t-test, ANOVA (Duncan multiple range test) and Pearson's correlation coefficients using the SPSS Win Program (version 12.0). In terms of the number of training practice, the result of sanitary training indicated that the dieticians who trained the employees more than once per a week (48.6%) or everyday (36.3%) were 84.7%. And the dieticians who were higher age, full-time job, and working at middle school implemented significantly more training the employees. In the training methods, 40.7% of dieticians used the oral presentation and 37.4 % utilized the printed matters. Also, most of employees (98.1%) have experienced for the training, 39.6% of them did not have regular training experience and 40.7% of them responded that they were understanding the HACCP system well. The result of employees' knowledge level of HACCP system reported that the items of the personal hygiene scored the highest (92.3 points) whereas the items of CCP3 scored the lowest (58.3 points) as the average being 84.2 points (out of 100 scale). In terms of the performance degree of HACCP system, the average was 4.40 (out of 5 scale), the items of the personal hygiene scored the highest as 4.51 whereas the items of CCP2 scored the lowest as 4.31 points. The dieticians' perception degree of employees' performance degree in HACCP system showed that the average was 4.13 (out of 5 scale), so it was significantly lower than actual performance degree as average 4.40 (out of 5 scale). Additionally the employees' knowledge level was positively correlated to performance degree and employees' knowledge level of CCP3, CCP4, and the personal hygiene significantly influenced to the HACCP performance degree. Finally, the dieticians have to recognize correctly the employees' performance degree and on the basis of it must plan the sanitary training which has a proper contents and methods to enhance the employees' knowledge level and achieve more systematic HACCP system in school foodservice.