RESUMO
BACKGROUND AND PURPOSE: The ryanodine receptor 2 (RyR2) is present in both the heart and kidneys, and plays a crucial role in maintaining intracellular Ca2+ homeostasis in cells in these organs. This study aimed to investigate the impact of M201-A on RyR2, as well as studying its effects on cardiac and renal functions in preclinical and clinical studies. EXPERIMENTAL APPROACH: Following the administration of M201-A (1,4-benzothiazepine-1-oxide derivative), we monitored diastolic Ca2+ leak via RyR2 and intracellular Ca2+ concentration in isolated rat cardiomyocytes and in cardiac and renal function in animals. In a clinical study, M201-A was administered intravenously at doses of 0.2 and 0.4 mg·kg-1 once daily for 20 min for four consecutive days in healthy males, with the assessment of haemodynamic responses. KEY RESULTS: In rat heart cells, M201-A effectively inhibited spontaneous diastolic Ca2+ leakage through RyR2 and exhibited positive lusi-inotropic effects on the rat heart. Additionally, it enhanced natriuresis and improved renal function in dogs. In human clinical studies, when administered intravenously, M201-A demonstrated an increase in natriuresis, glomerular filtration rate and creatinine clearance, while maintaining acceptable levels of drug safety and tolerability. CONCLUSIONS AND IMPLICATIONS: The novel drug M201-A inhibited diastolic Ca2+ leak via RyR2, improved cardiac lusi-inotropic effects in rats, and enhanced natriuresis and renal function in humans. These findings suggest that this drug may offer a potential new treatment option for chronic kidney disease and heart failure.
RESUMO
OBJECTIVE: To solve the complicated wires and battery maintenance problems in the application of wearable computing for biomedical monitoring, the electromyography (EMG) measurement system using conductive fabric for power supply and electric shield for noise reduction is proposed. MATERIAL AND METHODS: The basic cable-free network system using conductive fabric, named as "TextileNet" is developed. The conductive fabric has the function of electric shield for noise reduction in EMG measurement, and it enables the precise EMG measurement with wearable system. RESULTS: The specifications of the developed prototype TextileNet system using wear with conductive fabric were communication speed of 9600bit/s and power supply of 3W for each device. The electric shield effect was evaluated for precise EMG measurement, and the shield efficacy of conductive fabric was estimated as high as that of shield room. CONCLUSIONS: TextileNet system solves both the problems of complicated wires and battery maintenance in wearable computing systems. Conductive fabric used in TextileNet system is also effective for precise EMG measurement as electric shield. The combination of TextileNet system and EMG measurement device will implement the cable-free, battery-free wearable EMG measurement system.