Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC₅₀ of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD₅₀, and 9% and 17% decreases in APD₉₀, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.     

Trends of Stroke Incidence and 28-Day All-Cause Mortality after a Stroke in Malaysia: A Linkage of National Data Sources

Background:Data on nationwide trends for stroke metrics are crucial to understand the extent of the disease burden to a country’s health system. Yet, this information remains scarce in low- and middle-income countries.Objectives:This study investigated trends of stroke incidence and 28-day all-cause mortality after a stroke from 2008 to 2016 in Malaysia, through linkage across national data sources.Methods:Hospital admissions with a principal diagnosis of stroke or transient ischemic attack were included. Cases with first stroke were identified through linkage of hospital admission registers where age and sex-standardized trends of stroke incidence and its subtypes were calculated. By linking hospital registers to the National Death Register, the 28-day all-cause mortality rates after a stroke were estimated. Mann-Kendall’s test was used for trend evaluation.Results:From 243,765 records, the trend of stroke incidence showed an increase of 4.9% in men and a drop of 3.8% among women. Incidences were higher in men, at 99.1 per 100,000 population in 2008 and 103.9 per 100,000 in 2016 than women (80.3 per 100,000 in 2008 and 77.2 per 100,000 in 2016). There was a substantial increase in stroke incidence among those below 65 years old, with the largest increase of 53.3% in men aged between 35–39 years and 50.4% in women of similar age group. The trend for 28-day all-cause mortality showed a decline for men at –13.1% and women, –10.6%. Women had higher mortality from stroke (22.0% in 2008 and 19.7% in 2016) than men (19.4% in 2008 to 17.2% in 2016).Conclusion:This first empirical study on stroke trends in Malaysia revealed a worrying increase in stroke incidence among the younger population. Despite a declining trend, mortality rates remained moderately high especially in women. Comprehensive strategies to strengthen the prevention and management of stroke care are warranted.     

Regulatory effect of sense line diet on cholesterol and body weight in mice fed a high-fat diet

BACKGROUND/AIMS: Sense line diet (SLD) is a newly developed dietary functional food that is composed of a lot of herbs. The function of SLD is to help control weight. Although it is reported that each herb has effects on lipid metabolism and obesity, these effects are not the same as SLD. The aim of this study was therefore to investigate whether SLD combined with high fat (HF) diet can influence body weight and fat accumulation. METHODS: An experiment was conducted with 40 C57BL/6J mice with an initial body weight of about 16 g. Body weight was recorded every week, plasma levels of triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed at the end of the study. RESULTS: Weight increases in the 10 or 20% SLD group were significantly less than in the HF diet group (p < 0.05). Plasma triglyceride and LDL cholesterol levels were decreased by 52.1 and 34.2% in the 10% SLD group and 15.4 and 15.4% in the 20% SLD group, respectively, compared to the high-fat diet group. HDL cholesterol level was increased by 7.8% in the 10% SLD and by 54.9% in the 20% SLD group. CONCLUSIONS: Our findings indicate that SLD may be beneficial in the regulation of high-fat-diet-induced blood circulatory disorders as well as overweight.