Examining motor unit stability of first dorsal interosseous (FDI) and biceps brachii (BB) muscles in healthy and older adults using decomposition-based quantitative electromyography (DQEMG)

Aging of the human neuromuscular system is associated with gradual decline in motor unit (MU) number leading to denervation of muscle fibers and subsequent compensatory reinnervation from surviving MUs. Lower limb muscles exhibit age-related increased MU instability (measured electrophysiologically), however not much is known regarding MU stability of aging upper limb muscles. The purpose of this study was to examine agerelated MU loss in upper limb muscles (first dorsal interosseous [FDI] and biceps brachii [BB]) and the impact on MU stability in younger and older healthy subjects using electrophysiological near fiber analysis from decomposition-based quantitative electromyography (DQEMG). FDI and BB muscles from older (74 ± 5 years) and younger (31 ± 13 years) healthy subjects were examined through surface and intramuscular collection of EMG signals during volitional contractions, which were analyzed with DQEMG. Older subjects showed significantly larger MUs associated with greater instability in the form of near fiber (NF) jiggle and NF jitter in the FDI and BB muscles when compared to younger controls. These results suggest that age-dependent MU remodeling and progressive reduction in FDI and BB MU pools are associated with greater transmission instability at the neuromuscular junction

Tetraoxane antimalarials and their reaction with Fe(II)

Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed