AIM OF THE STUDY: The present study was carried out to examine the potential modulatory effects of three commercially available active components (asiaticoside, asiatic acid and madecassic acid) and four extracts (aqueous, ethanol, dichloromethane and hexane) of CA on three major cDNA-expressed human cytochrome P450 (CYP) isoforms.
MATERIALS AND METHODS: High-performance liquid chromatography (HPLC)-based enzyme assays, namely tolbutamide 4-methyhydroxylase, dextromethorphan O-demethylase and testosterone 6beta-hydroxylase assays were developed to probe activities of CYP2C9, CYP2D6 and CYP3A4, respectively. Probe substrates were incubated with or without each active component and extract for each isoform, followed by examination of the kinetics parameters, IC(50) and K(i), to characterize modulatory effects.
RESULTS: CYP2C9 was more susceptible to inhibitory effects by CA extracts compared to CYP2D6 and CYP3A4. Moderate degree of inhibition was observed in ethanol (K(i)=39.1 microg/ml) and dichloromethane (K(i)=26.6 microg/ml) extracts implying potential risk of interaction when CYP2C9 substrates are consumed with CA products. The two extracts however showed negligible inhibition towards CYP2D6 and CYP3A4 (IC(50)'s of 123.3 microg/ml and above). Similarly CA aqueous and hexane extracts did not significantly inhibit all three isoforms investigated (IC(50)'s of 117.9 microg/ml and above). Among the active constituents investigated, asiatic acid and madecassic acid appeared to selectively inhibit CYP2C9 and CYP2D6 more than CYP3A4. Of particular interest is the potent inhibitory effect of asiatic acid on CYP2C9 (K(i)=9.1 microg/ml). This signifies potential risk of interaction when substrates for this isoform are taken together with CA products with high asiatic acid content. Inhibitions of asiatic acid with the other isoforms and that of madecassic acid with all isoforms were only moderate (K(i)'s ranged from 17.2 to 84.4 microg/ml). On the other hand, the IC(50) values for asiaticoside were high (1070.2 microg/ml or above) for all three isoforms, indicating negligible or low potential of this compound to modulate CYP enzymatic activity.
CONCLUSION: Centella asiatica extracts and active constituents inhibited CYP2C9, CYP2D6 and CYP3A4 activities with varying potency with CYP2C9 being the most susceptible isoform to inhibition. Significant inhibition was observed for asiatic acid and CA ethanol and dichloromethane extracts, implying involvement of semipolar constituents from CA in the effect. This study suggested that CA could cause drug-herb interactions through CYP2C9 inhibition.
METHODS: An online questionnaire was distributed randomly to 1,050 HCWs from the Ministry of Health facilities in the Klang Valley who were involved directly in managing or screening COVID-19 cases from May to August 2020. The questionnaire was divided into five domains, which were concerns, impact on life and work, practice, perceived adequacy of preventive measures, and Revised Impact of Event Scale (IES-R). Logistic regression was used to identify sociodemographic predictors of the five domains.
RESULTS: A total of 907 respondents (86.4%) participated in this survey. Approximately half of the respondents had a low concern (50.5%), most of them had a good practice (85.1%), with 67.5% perceiving there were adequate preventive measures, and they perceived the outbreak had a low impact (92%) on their life and work. From the IES-R domain, 18.6% of respondents potentially suffered from post-traumatic stress disorder (PTSD).
CONCLUSION: During the second wave of the COVID-19 outbreak in Malaysia, HCWs practiced high levels of precautions and preventive measures because they were aware of the risk of infection as an occupational hazard. With the adequate implementation of policy and control measures, the psychological wellbeing of the majority HCWs remained well and adequately supported.
OBJECTIVE: This study aims to translate and validate UDI-6 and IIQ-7 in Malay language.
METHODS: A cross sectional study, which recruited 100 participants from two urogynecology clinics. Both questionnaires were initially translated from English to Bahasa Malaysia followed by back translation and final correction done by the professional translators. The participants were requested to maintain a urinary record of the upcoming week for three days that assisted in quantifying the severity of symptoms. None of the subjects were assigned any treatment during the study period. Validity and reliability of the translated questionnaires were determined by checking the internal consistency and also by doing test-retest.
RESULTS: The internal consistency levels of the UDI-6 and IIQ-7 Bahasa Malaysia questionnaires were 0.73 and 0.90 respectively with good test-retest (0.86 and 0.95). Incontinence episodes were strongly associated with obstructive, irritative, and stress symptoms. The factor of day time voiding had strong correlation with obstructive and irritative symptoms.
CONCLUSION: UDI-6 and IIQ-7 did not measure similar outcomes; however, both questionnaires have their strengths in clinical settings. Analysis has also revealed that the Malaysian versions of both questionnaires had appropriate test-retest validity and reliability. Thus, it can be said that both of the questionnaires had great importance for screening patients with urinary incontinence in Malaysia.