Circulating α-Klotho Counteracts Transforming Growth Factor-ß-Induced Sarcopenia.

α-Klotho is a longevity-related protein. Its deficiency shortens lifespan with prominent senescent phenotypes, including muscle atrophy and weakness in mice. α-Klotho has two forms: membrane α-Klotho and circulating α-Klotho (c-α-Klotho). Loss of membrane α-Klotho impairs a phosphaturic effect, thereby accelerating phosphate-induced aging. However, the mechanisms of senescence on c-α-Klotho loss remain largely unknown. Herein, with the aging of wild-type mice, c-α-Klotho declined, whereas Smad2, an intracellular transforming growth factor (TGF)-ß effector, became activated in skeletal muscle. Moreover, c-α-Klotho suppressed muscle-wasting TGF-ß molecules, including myostatin, growth and differentiation factor 11, activin, and TGF-ß1, through binding to ligands as well as type I and type II serine/threonine kinase receptors. Indeed, c-α-Klotho reversed impaired in vitro myogenesis caused by these TGF-ßs. Oral administration of Ki26894, a small-molecule inhibitor of type I receptors for these TGF-ßs, restored muscle atrophy and weakness in α-Klotho (-/-) mice and in elderly wild-type mice by suppression of activated Smad2 and up-regulated Cdkn1a (p21) transcript, a target of phosphorylated Smad2. Ki26894 also induced the slow to fast myofiber switch. These findings show c-α-Klotho's potential as a circulating inhibitor counteracting TGF-ß-induced sarcopenia. These data highlight the potential of a novel therapy involving TGF-ß blockade to prevent sarcopenia.

[Comparison of 3 commercial metallo-beta-lactamase detection kits].

Using 41 metallo-beta-lactamase producing isolates and 8 metallo-beta-lactamase nonproducing and ceftazidime-resistant isolates from Kyushu Island, metallo-beta-lactamase was detected by 3 commercial metallo-beta-lactamase detection kits, which were Metallo-beta-lactamase SMA Eiken (SMA, disk diffusion, Eiken Chemical Co.), dry plate Eiken DPD1 (DPD, two-fold serial broth microdilution, Eiken Chemical Co). and Cica beta test I/ MBL (CIC, coloring reaction, Kanto Chemical Co.). Detection rate by SMA, DPD, and CIC was 97.5, 100, and 100%. Neither method used in this study produced false-positive or false-negative results. The rates of metallo-beta-lactamase nonproducer identification were 37.5%, 62.5%, and 100% for the SMA, DPD, and CIC kits, respectivily. These three methods have the following features, SMA is useful for routine work because SMA utilizes disk diffusion, which is widely used by medical technologists, and it is the least expensive of the three kits. CIC can detect metallo-beta-lactamase after only 15 minutes and can determine the presence of non-metallo-beta-lactamase producers at a high rate. DPD can simultaneously identify the MIC of some agents. Consequently these three metallo-beta-lactamase detection kits were very useful for detecting metallo-beta-lactamase producing isolates.