METHODS AND RESULTS: The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.
CONCLUSIONS: Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.
METHODS: A total of 741 health-care professionals participated in the study by answering 10 simple questions about the role of the pharmacist in the nuclear medicine department and the availability of pharmacist in the nuclear medicine department. An online questionnaire system was used to conduct the study, and participants were invited to participate through personal communications and by promoting the study through social websites including Facebook, LinkedIn and Google (including Gmail and Google+). The study was conducted between April 2013 and March 2014 using the http://www.freeonlinesurveys.com/Webserver. Finally, the data provided by 621 participants was analyzed. Group frequency analysis was performed using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS Inc. USA).
RESULTS: The participants were from Malaysia, India, Pakistan, Sri Lanka, Bangladesh, UAE and Nepal. In total, 312 (50.2%) female health-care professionals and 309 (49.8%) male health-care professionals participated in the study. Of the 621 participants, 390 were working in hospitals, and 231 were not working in hospitals. Of the participants who were working in hospitals, 57.6% were pharmacists. The proportion of study participants who were aware of nuclear pharmacists was 55.39%. Awareness about the role of the pharmacist in nuclear medicine was poor.
CONCLUSION: The role of the pharmacist in a nuclear medicine unit needs to be highlighted and promoted among health-care professionals and hence that the nuclear medicine team can provide better pharmaceutical care.