1 Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E8xLDLR8) develop atherosclerosis and endothelial dysfunction. The aim of this study was to characterize the roles of L-arginine and tetrahydrobiopterin (BH 4 ) for endothelium-dependent relaxation and the changes in the vasoconstrictor response to endothelin-1 (ET-1) in thoracic aortic rings of E8xLDLR8 mice. 2 Histological examination revealed severe atherosclerosis of the thoracic aorta of E8xLDLR8 mice. Relaxations induced by acetylcholine (Ach), but not that to sodium nitroprusside, were signi®cantly impaired in E8xLDLR8 mice compared to control mice indicating attenuated endothelium-dependent relaxations. 3 Preincubation with the nitric oxide (NO) substrate L-arginine did not a ect, whereas the cofactor for NO synthase, BH 4 , slightly improved the relaxations induced by Ach. Combined preincubation with L-arginine and BH 4 induced a pronounced enhancement of Ach-induced relaxations in E8xLDLR8 mice. The relaxations induced by Ach in E8xLDLR8 mice in the presence of L-arginine and BH 4 were not di erent from those observed in control mice. 4 Preincubation with superoxide dismutase did not a ect Ach-induced relaxations in aorta from E8xLDLR8 mice. 5 The contractile response to ET-1 was enhanced in E8xLDLR8 mouse aorta. The contractions were abolished by the ET A receptor antagonist LU 135252. The ET B receptor agonist sarafotoxin 6c did not induce contractions or relaxations. 6 It is concluded that endothelial dysfunction of E8xLDLR8 mouse aorta is reversed by combined administration of L-arginine and BH 4 . In addition, the ET A receptor-mediated vasoconstriction by ET-1 is enhanced in E8xLDLR8 mice.
During BIPC adenosine acting on the A1R appears necessary for myocardial protection. MAPK signalling may possibly be involved in organ protection during the delayed phase of remote, delayed adaptation.
Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.
Quarantine inspection at the airports, follow-up observation by local authorities, and overall concomitant efforts may have contributed to secondary infection control in Japan.
Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF) during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.
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