No abstract

Caffeine is a widely consumed stimulant with the potential to enhance physical performance through multiple mechanisms. However, recent in vitro findings have suggested that caffeine may block skeletal muscle anabolic signaling through AMP-activated protein kinase (AMPK)-mediated inhibition of mechanistic target of rapamycin (mTOR) signaling pathway. This could negatively affect protein synthesis and the capacity for muscle growth. The primary purpose of this study was to assess the effect of caffeine on in vivo AMPK and mTOR pathway signaling, protein synthesis, and muscle growth. In cultured C2C12 muscle cells, physiological levels of caffeine failed to impact mTOR activation or myoblast proliferation or differentiation. We found that caffeine administration to mice did not significantly enhance the phosphorylation of AMPK or inhibit signaling proteins downstream of mTOR (p70S6k, S6, or 4EBP1) or protein synthesis after a bout of electrically stimulated contractions. Skeletal muscle-specific knockout of LKB1, the primary AMPK activator in skeletal muscle, on the other hand, eliminated AMPK activation by contractions and enhanced S6k, S6, and 4EBP1 activation before and after contractions. In rats, the addition of caffeine did not affect plantaris hypertrophy induced by the tenotomy of the gastrocnemius and soleus muscles. In conclusion, caffeine administration does not impair skeletal muscle load-induced mTOR signaling, protein synthesis, or muscle hypertrophy.

Major histocompatibility complex (MHC) class I molecules and their receptors play fundamental roles in neuronal death during diseases. T-cell receptors (TCR) function as MHCI receptor on T-cells and both MHCI and a key component of TCR, CD3ζ, are expressed by mouse retinal ganglion cells (RGCs) and displaced amacrine cells. Mutation of these molecules compromises the development of RGCs. We investigated whether CD3ζ regulates the development and degeneration of amacrine cells after RGC death. Surprisingly, mutation of CD3ζ not only impairs the proper development of amacrine cells expressing CD3ζ but also those not expressing CD3ζ. In contrast to effects of MHCI and its receptor, PirB, on other neurons, mutation of CD3ζ has no effect on RGC death and starburst amacrine cells degeneration after optic nerve crush. Thus, unlike MHCI and PirB, CD3ζ regulates the development of RGCs and amacrine cells but not their degeneration after optic nerve crush.

PurposeTo study the accuracy and reliability of optical pachymetry using the Alcon WaveLight EX500 during laser-assisted in situ keratomileusis (LASIK).Materials and methodsThis was a retrospective chart review of 90 eyes from 45 patients who had undergone LASIK (mean age 35.2±8.2 years; 19 males, 26 females). The WaveLight FS200 femtosecond laser was programmed to cut LASIK flaps at a desired depth of 120 μm. Optical low-coherence reflectometry (WaveLight EX500) was used to measure central corneal thickness prior to lifting the flap, and the residual stromal bed immediately after excimer ablation. Flap thickness (FT) was calculated using simple subtraction. Optical coherence tomography (OCT) was used to measure central corneal thickness, flap thickness, and residual stromal bed in the postoperative period and the results compared to intraoperative measurements.ResultsMean programmed FS200 FT was 119 μm. Mean FT using EX500 optical pachymetry was 109 μm. The difference between FS200- programmed and EX500-measured FT was 9 μm (P<0.001). There was also a significant difference between the EX500 and OCT FT (109 μm vs 119 μm, respectively; P<0.001).ConclusionFT values calculated using intraoperative EX500 optical pachymetry were significantly lower than programmed FS200 values or OCT measurements.