Purpose
To analyze if live high–train low (LHTL) effectiveness is improved when daily training is guided by heart rate variability (HRV).
Methods
Twenty-four elite Nordic skiers took part in a 15-day ...LHTL study and were randomized into a HRV-guided training hypoxic group (H-HRV,
n
= 9, sleeping in normobaric hypoxia, FiO
2
= 15.0%) and two predefined training groups sleeping either in hypoxia (H,
n
= 9, FiO
2
= 15.0%) or normoxia (N,
n
= 6). HRV and training loads (TL) were recorded daily. Prior (Pre), one (Post-1), and 21 days (Post-21) following LHTL, athletes performed a 10-km roller-ski test, and a treadmill test for determination of
V
˙
O
2max
was performed at Pre and Post-1.
Results
Some HRV parameters measured in supine position were different between H-HRV and H: low and high (HF) frequency power in absolute (ms
2
) (16.0 ± 35.1 vs. 137.0 ± 54.9%,
p
= 0.05) and normalized units (− 3.8 ± 10.1 vs. 53.0 ± 19.5%,
p
= 0.02), HF(nu) (6.3 ± 6.8 vs. − 13.7 ± 8.0%,
p
= 0.03) as well as heart rate (3.7 ± 6.3 vs. 12.3 ± 4.1%,
p
= 0.008). At Post-1,
V
˙
O
2max
was improved in H-HRV and H (3.8 ± 3.1%;
p
= 0.02 vs. 3.0 ± 4.4%;
p
= 0.08) but not in N (0.9 ± 5.1%;
p
= 0.7). Only H-HRV improved the roller-ski performance at Post-21 (− 2.7 ± 3.6%,
p
= 0.05).
Conclusion
The daily individualization of TL reduced the decrease in autonomic nervous system parasympathetic activity commonly associated with LHTL. The improved performance and oxygen consumption in the two LHTL groups confirm the effectiveness of LHTL even in elite endurance athletes.
Chronic exposure to inorganic arsenic, a widely distributed environmental contaminant, can lead to toxic effects, including immunosuppression. Owing to the established roles of human macrophages in ...immune defense, we determined, in the present study, whether inorganic arsenic can affect these major immune cells. Our results demonstrate that noncytotoxic concentrations of arsenic trioxide (As2O3), an inorganic trivalent form, markedly impair differentiated features of human blood monocyte-derived macrophages. First, treatment of macrophages with 1 microM As2O3 induced a rapid cell rounding and a subsequent loss of adhesion. These morphologic alterations were associated with a marked reorganization of actin cytoskeleton, which includes retraction of peripheral actin extensions and formation of a cortical actin ring. In addition, As2O3 reduced expression of various macrophagic surface markers, enhanced that of the monocytic marker CD14, and altered both endocytosis and phagocytosis; unexpectedly, exposure of macrophages to the metalloid also strongly potentiated expression of TNFalpha and IL-8 induced by LPS. Finally, like monocytes, As2O3-treated macrophages can be differentiated into dendritic-like cells. Impairment of macrophage function by As2O3 mainly resulted from activation of a RhoA/Rho-associated kinase pathway; indeed, pretreatment of macrophages with the Rho-associated kinase inhibitor Y-27632 prevented metalloid effects on cytoskeleton and phagocytosis. Moreover, As2O3 was found to increase level of the active GTP-bound form of RhoA and that of phosphorylated-Moesin, a major cytoskeleton adaptor protein involved in RhoA regulation. Taken together, our results demonstrated that human macrophages constitute sensitive targets of inorganic arsenic, which may contribute to immunotoxicity of this environmental contaminant.
Cadmium-induced cellular toxicity has been related to necrosis and/or caspase-dependent apoptosis. In the present study, we show that, on cadmium exposure, the human hepatocarcinoma Hep3B cells ...undergo caspase-independent apoptosis associated with nuclear translocation of endonuclease G and apoptosis-inducing factor, two mitochondrial apoptogenic proteins. Release of these proteins is likely related to calcium-induced alteration of mitochondrial homeostasis. Indeed, it was first preceded by a rapid and sustained increase in cytoplasmic calcium and then by a coincident loss in mitochondrial membrane potential and production of reactive oxygen species. Bapta-AM (acetoxymethyl ester of 5, 5′-dimethyl-bis (
o-aminophenoxy)ethane-
N,
N,
N′,
N′-tetraacetic acid), a calcium chelator, blocked all these events and prevented cadmium-induced apoptosis. Production of reactive oxygen species was inhibited by ruthenium red and rotenone, two mitochondrial inhibitors, and by diphenyleneiodonium, a flavoprotein inhibitor, which also prevented both loss in mitochondrial membrane potential and apoptosis. In addition, Bapta-AM and diphenyleneiodonium were found to almost totally block decreased expression of the mitochondrial anti-apoptotic nuclear factor-κB-regulated bcl-x
L protein in cadmium-treated cells. Taken together, our results show that cadmium induces Hep3B cells apoptosis mainly by calcium- and oxidative stress-related impairment of mitochondria, which probably favors release of apoptosis-inducing factor and endonuclease G.
Inorganic arsenic is an immunotoxic environmental contaminant to which millions of humans are chronically exposed. We recently demonstrated that human primary macrophages constituted a critical ...target for arsenic trioxide (As(2)O(3)), an inorganic trivalent form. To specify the effects of arsenic on macrophage phenotype, we investigated in the present study whether As(2)O(3) could regulate the activity of NADPH oxidase, a major superoxide-generating enzymatic system in human phagocytes. Our results show that superoxide levels were significantly increased in a time-dependent manner in blood monocyte-derived macrophages treated with 1 muM As(2)O(3) for 72 h. Concomitantly, As(2)O(3) induced phosphorylation and membrane translocation of the NADPH oxidase subunit p47(phox) and it also increased translocation of Rac1 and p67(phox). Apocynin, a selective inhibitor of NADPH oxidases, prevented both p47(phox) translocation and superoxide production. NADPH oxidase activation was preceded by phosphorylation of p38-kinase in As(2)O(3)-treated macrophages. The p38-kinase inhibitor SB-203580 prevented phosphorylation and translocation of p47(phox) and subsequent superoxide production. Pretreatment of macrophages with the Rho-kinase inhibitor Y-27632 was found to mimic inhibitory effects of SB-203580 and to prevent As(2)O(3)-induced phosphorylation of p38 kinase. Treatment with As(2)O(3) also resulted in an increased secretion of the proinflammatory chemokine CCL18 that was fully inhibited by both apocynin and SB-203580. Taken together, our results demonstrate that As(2)O(3) induced a marked activation of NADPH oxidase in human macrophages, likely through stimulation of a Rho-kinase/p38-kinase pathway, and which may contribute to some of the deleterious effects of inorganic arsenic on macrophage phenotype.
Arsenic trioxide (As(2)O(3)) is known to be toxic toward leukemia cells. In this study, we determined its effects on survival of human monocytic cells during macrophagic differentiation, an important ...biological process involved in the immune response. As(2)O(3) used at clinically relevant pharmacological concentrations induced marked apoptosis of human blood monocytes during differentiation with either granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor. Apoptosis of monocytes was associated with increased caspase activities and decreased DNA binding of p65 nuclear factor-kappaB (NF-kappaB); like As(2)O(3), the selective NF-kappaB inhibitor (E)-3-(4-methylphenyl)-sulfonyl-2-propenenitrile (Bay 11-7082) strongly reduced survival of differentiating monocytes. The role of NF-kappaB in arsenic toxicity was also studied in promonocytic U937 cells during phorbol 12-myristate 13-acetate-induced macrophagic differentiation. In these cells, As(2)O(3) first reduced DNA binding of p65 NF-kappaB and subsequently induced apoptosis. In addition, overexpression of the p65 NF-kappaB subunit, following stable infection with a p65 retroviral expressing vector, increased survival of As(2)O(3)-treated U937 cells. As(2)O(3) specifically decreased protein levels of X-linked inhibitor of apoptosis protein and FLICE-inhibitory protein, two NF-kappaB-regulated genes in both U937 cells and blood monocytes during their differentiations. Finally, As(2)O(3) was found to inhibit macrophagic differentiation of monocytic cells when used at cytotoxic concentrations; however, overexpression of the p65 NF-kappaB subunit in U937 cells reduced its effects toward differentiation. In contrast to monocytes, well differentiated macrophages were resistant to low concentrations of As(2)O(3). Altogether, our study demonstrates that clinically relevant concentrations of As(2)O(3) induced marked apoptosis of monocytic cells during in vitro macrophagic differentiation likely through inhibition of NF-kappaB-related survival pathways.
The pasta protein network limits starch hydrolysis rate in vivo leading to low post-prandial glycemia. To better understand the mechanisms involved, various pasta products were processed to obtain ...protein network structures differing from that in reference pasta extruded at 40 °C and dried 17 h at 55 °C. After cooking, pasta strands were submitted to in vitro alpha -amylolysis. Compared to reference pasta, higher extrusion temperature (70 °C), high-temperature drying treatment (2 h at 90 °C) or autoclaving (115 °C for 15 or 40 min) had no marked effect on the rate of dextrin release from pasta particles. Protein enrichment at a 20%-level and flour fractionation-reconstruction with removal of insoluble fibre before pasta extrusion significantly (p<0·05) delayed (≥1 h) the rate of dextrin release (−14% at 8 h). Confocal laser scanning microscopy allowed the three-dimensional structure of the protein network from protein-enriched pasta to be observed, and suggested that increased starch encapsulation may explain the reduced accessibility of starch to alpha -amylases. A stronger cohesiveness between starch and protein, due to insoluble fibre removal, was probably responsible for the decrease of starch accessibility to alpha -amylase in fractionated-reconstructed flour pasta. Modified geometrical characteristics (e.gtortuosity) of the protein network were not correlated with starch degradation rates.
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