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The absorption process in animals of TAK-491, designed as ester-based prodrug with medoxomil moiety, was evaluated. In the plasma of rats and dogs, TAK-536, the pharmacologically active metabolite, was present as the main component with hardly detectable concentrations of TAK-491 after oral administration of TAK-491. In the rat portal plasma, TAK-536 was(More)
Crystalline 1 (TAK-599) is a novel N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin 2a (T-91825) that has high affinity for penicillin-binding protein (PBP) 2' (IC(50); 0.90 microg/mL) and shows potent in vitro anti-MRSA activity (MIC against MRSA N133; 1.56 microg/mL), comparable to that of vancomycin (1.56(More)
Weight training (WT) is the most common method of maintaining and increasing muscle strength. WT, however, is not always useful as it requires the external resistance and stabilization. We have developed a "hybrid training" (HYB) approach that avoids these problems by using electrically stimulated muscles to provide resistance to the motion of a muscle(More)
The binding of PET radiotracer [(11)C]flumazenil to the GABA(A) receptors is described by the receptor density (B(max)) and binding affinity (K(D)). The estimation of B(max) and K(D) is usually based on Scatchard analysis including at least two PET scans at steady state of various specific activities. Recently, a novel full saturation method to estimate(More)
Background: [C]Flumazenil and positron emission tomography (PET) are used clinically to assess gammaaminobutyric acid (GABA)-ergic function and to localize epileptic foci prior to resective surgery. Enhanced Pglycoprotein (P-gp) activity has been reported in epilepsy and this may confound interpretation of clinical scans if [C]flumazenil is a P-gp(More)
INTRODUCTION A variety of techniques have been used with variable success in an attempt to reverse the loss of muscle strength, bulk, and endurance that occurs during spaceflight. This study was designed to evaluate a new "hybrid" approach that uses the resistance provided by an electrically stimulated antagonist muscle to resist the volitional contraction(More)
OBJECTIVE To assess an exercise program that uses electrically stimulated antagonists to resist agonist muscle contractions. DESIGN In 1 limb, electrically stimulated antagonists resisted elbow flexion and extension. In the other, stimulation occurred without volitional muscle contraction. SETTING A biomechanics laboratory in Japan. PARTICIPANTS(More)
Extreme skeletal muscle atrophy is rampant in astronauts exposed to extended periods of microgravity (muG), and it is one of the main problems in human space exploration. A "Hybrid training" (HYB) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a possible solution. A wearable HYB device and a virtual(More)
The "Hybrid training" (HYBT) method utilizing combined electrical stimulation and voluntary muscle contraction has been developed as a muscle training method. It has already been shown that the method is technically sound and clinically effective in healthy young subjects. The purpose of this study was to investigate the effect of the HYBT method on the(More)
"Hybrid" exercise uses forces generated by an electrically stimulated muscle to resist the motion of a volitionally contracting agonist. This approach is effective in increasing muscle bulk and strength. Its safety, however, has not been studied and the purpose of this study was to address this lack by assessing the impact of a hybrid strengthening regimen(More)