The stability of a transfemoral prosthesis when walking on flat ground has been established by recent advances in knee joint mechanisms and their control methods. It is, however, difficult for users of a transfemoral prosthesis to ascend stairs. This difficulty is mainly due to insufficient generation of extension moment around the knee joint of the prosthesis to lift the body to the next step on the staircase and prevent any unexpected flexion of the knee joint in the stance phase. Only a prosthesis with an actuator has facilitated stair ascent using a step-over-step gait (1 foot is placed per step). However, its use has issues associated with the durability, cost, maintenance, and usage environment. Therefore, the purpose of this research is to develop a novel knee joint mechanism for a prosthesis that generates an extension moment around the knee joint in the stance phase during stair ascent, without the use of any actuators. The proposed mechanism is based on the knowledge that the ground reaction force increases during the stance phase when the knee flexion occurs. Stair ascent experiments with the prosthesis showed that the proposed prosthesis can realize stair ascent without any undesirable knee flexion. In addition, the prosthesis is able to generate a positive knee joint moment power in the stance phase even without any power source.
Background/Aims: Validation studies have shown that 18 F-THK5351 PET signal contribute the binding to monoamine oxidase B (MAO-B) and correlates with tau and astrogliosis in neurodegenerative diseases. The aim of study was to develop selective tau and MAO-B PET tracers through compound optimization from 18 F-THK5351 to visualize tau pathology and astroglisis, respectively. Methods: In vitro competitive binding assay against recombinant MAO-B, MAO-A, and tau aggregates in AD brain homogenates was performed to evaluate binding affinity of test compounds. In vitro autoradiography in frozen human brain tissues was performed using 18 F-labeled compounds to evaluate selective binding to each target. Results: In vitro competitive binding assays demonstrated lower binding affinity of several quinoline derivatives against MAO-B (Ki > 100 nM) than THK5351. On the other hand, we identified several quinoline derivatives that possess higher affinity against MAO-B than THK5351, but little binding to MAO-A and tau aggregates. Furthremore, in vitro autoradiography of AD brain sections showed the selective binding ability of these compounds to tau protein deposits or MAO-B. Conclusions: Compound optimization resulted in successful improvement of binding selectivity of quinoline derivatives as tau and MAO-B selective PET tracers, respectively. Selective imaging of tau and MAO-B would be promising markers for monitoring neurodegeneration and neuroinflammatory changes.
Objective: Some histamine H 1 receptor (H 1 R) antagonists have sedative effects, caused by the blockade of histamine neural transmission. Desloratadine is a newly-marked antihistamine, but its sedative properties have not been examined by positron emission tomography (PET). We examined the brain H 1 R binding potential ratio (BPR), H 1 R occupancy (H 1 RO) and the subjective sleepiness after oral administration of desloratadine and loratadine, the prodrug of desloratadine.Methods: Eight healthy male volunteers underwent PET imaging with [ 11 C]doxepin after single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPRs and H 1 ROs in the cerebral cortices were calculated. Subjective sleepiness was quantified by the LARS and the SSS. Results: BPR after loratadine administration was significantly lower than placebo (p<0.05), but BPR after desloratadine was not significant. There was no significant difference, however, between H 1 RO after desloratadine and loratadine administration. The subjective sleepiness was not significantly different among the two antihistamines and placebo. Conclusion: At therapeutic dose, desloratadine did not bind significantly to brain H 1 Rs and did not cause significant sedation.
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