Altered active zones, vesicle pools, nerve terminal conductivity, and morphology during experimental MuSK myasthenia gravis.

Recent studies demonstrate reduced motor-nerve function during autoimmune muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). To further understand the basis of motor-nerve dysfunction during MuSK-MG, we immunized female C57/B6 mice with purified rat MuSK ectodomain. Nerve-muscle preparations were dissected and neuromuscular junctions (NMJs) studied electrophysiologically, morphologically, and biochemically. While all mice produced antibodies to MuSK, only 40% developed respiratory muscle weakness. In vitro study of respiratory nerve-muscle preparations isolated from these affected mice revealed that 78% of NMJs produced endplate currents (EPCs) with significantly reduced quantal content, although potentiation and depression at 50 Hz remained qualitatively normal. EPC and mEPC amplitude variability indicated significantly reduced number of vesicle-release sites (active zones) and reduced probability of vesicle release. The readily releasable vesicle pool size and the frequency of large amplitude mEPCs also declined. The remaining NMJs had intermittent (4%) or complete (18%) failure of neurotransmitter release in response to 50 Hz nerve stimulation, presumably due to blocked action potential entry into the nerve terminal, which may arise from nerve terminal swelling and thinning. Since MuSK-MG-affected muscles do not express the AChR γ subunit, the observed prolongation of EPC decay time was not due to inactivity-induced expression of embryonic acetylcholine receptor, but rather to reduced catalytic activity of acetylcholinesterase. Muscle protein levels of MuSK did not change. These findings provide novel insight into the pathophysiology of autoimmune MuSK-MG.

Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes? Review on E-cigarette vapor versus tobacco smoke.

OBJECTIVES/HYPOTHESIS: Development and utilization of electronic cigarettes (ECs) resulted from the search for healthier alternatives to conventional tobacco cigarettes (TCs) and the search for alternative methods for quitting TCs. This review compares the potential disease burden presented by TC smoke to that of EC vapor. METHODS: Potential disease burden of EC vapor versus TC smoke was assessed by reviewing clinical studies that measured inhaled components. Chemicals and carcinogens produced by vapor versus smoke were compared. RESULTS: Studies show that EC vapors contain far less carcinogenic particles than TC smoke. Whereas ECs have the ability to reach peak serum cotinine/nicotine levels comparable to that of TCs, ECs do not cause an increase in total white blood cell count; thus, ECs have the potential to lower the risk of atherosclerosis and systemic inflammation. Use of ECs has been shown to improve indoor air quality in a home exposed to TC smoke. This reduces secondhand smoke exposure, thus having the potential to decrease respiratory illness/asthma, middle-ear disease, sudden infant death syndrome, and more. However, some studies claim that propylene glycol (PG) vapor can induce respiratory irritation and increase chances for asthma. To minimize risks, EC manufacturers are replacing PG with distilled water and glycerin for vapor production. CONCLUSION: Based on the comparison of the chemical analysis of EC and TC carcinogenic profiles and association with health-indicating parameters, ECs impart a lower potential disease burden than conventional TCs.