We investigated the effect of nitric oxide (NO) and reactive nitrogen intermediates on the in vitro growth of Penicillium marneffei both in a cell-free system and in a novel macrophage culture system. In the cell-free system, NO that was chemically generated from NaNO 2 in acid media (pH 4 and 5) markedly inhibited the growth of P. marneffei. On the contrary, inhibition of growth did not occur in neutral medium (pH 7.4) in which NO was not produced. P. marneffei conidia were phagocytized by nonstimulated murine J774 macrophages after 2 h of incubation. During the following 24 h, P. marneffei grew as yeast-like cells replicating by fission in the J774 macrophages. The intracellular growth of P. marneffei damaged nonstimulated J774 macrophages, as confirmed by electron microscopy. When J774 cells were stimulated by gamma interferon and lipopolysaccharide, which led to enhanced production of reactive nitrogen intermediates, the percentage of yeast-like cells was significantly reduced and P. marneffei conidia were damaged in the J774 macrophages. The inhibition of NO synthesis by N-monomethyl-L-arginine restored the intracellular growth of P. marneffei. The inverse correlation between intramacrophage growth and the amount of nitrite detected in culture supernatants supports the hypothesis that the L-arginine-dependent NO pathway plays an important role in the murine macrophage immune response against P. marneffei.
Purpose
Muscle–tendon length can influence central and peripheral motor unit (MU) characteristics, but their interplay is unknown. This study aims to explain the effect of muscle length on MU firing and contractile properties by applying deconvolution of high-density surface EMG (HDEMG), and torque signals on the same MUs followed at different lengths during voluntary contractions.
Methods
Fourteen participants performed isometric ankle dorsiflexion at 10% and 20% of the maximal voluntary torque (MVC) at short, optimal, and long muscle lengths (90°, 110°, and 130° ankle angles, respectively). HDEMG signals were recorded from the tibialis anterior, and MUs were tracked by cross-correlation of MU action potentials across ankle angles and torques. Torque twitch profiles were estimated using model-based deconvolution of the torque signal based on composite MU spike trains.
Results
Mean discharge rate of matched motor units was similar across all muscle lengths (P = 0.975). Interestingly, the increase in mean discharge rate of MUs matched from 10 to 20% MVC force levels at the same ankle angle was smaller at 110° compared with the other two ankle positions (P = 0.003), and the phenomenon was explained by a greater increase in twitch torque at 110° compared to the shortened and lengthened positions (P = 0.002). This result was confirmed by the deconvolution of electrically evoked contractions at different stimulation frequencies and muscle–tendon lengths.
Conclusion
Higher variations in MU twitch torque at optimal muscle lengths likely explain the greater force-generation capacity of muscles in this position.
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