Inflammation and oxidative stress play a key role in the pathophysiology of sickle cell disease (SCD). However, the potential influence of different sickle genotypes, or hydroxyurea (HU) treatment, ...on these factors remains poorly documented. The present study compared several plasma markers of inflammation and oxidative stress, as well as microvascular function, between patients with sickle SC disease (HbSC, n = 19) and patients with sickle cell anemia (HbSS) under hydroxyurea (HU) treatment (n = 16), or not (n = 13). Hemorheological parameters and levels of inflammatory (IL‐6, IL‐8, IFN‐γ, MCP‐1, MIP‐1β, TNF‐α) and oxidative stress (AOPP, MDA, MPO) markers were determined. Peripheral microcirculatory cutaneous blood flow and immediate microvascular response to local heat were evaluated using laser Doppler flowmetry. Oxidative stress and inflammation were lower in HbSC patients and HbSS patients under HU therapy compared to HbSS patients not treated with HU. Blood viscosity was higher in HbSC than in HbSS patients treated with or not with HU. Vasodilation response of the cutaneous microcirculation to heat stress was higher in HbSS patients receiving HU treatment. Our results clearly established that both sickle cell genotype and HU treatment modulate inflammation and oxidative stress.
Article Note: Sophie Antoine-Jonville and Philippe Connes equivalent position. Byline: Marc Romana, Karen Reminy, Berenike Moeckesch, Keyne Charlot, Marie-Dominique Hardy-Dessources, Lydia Doumdo, ...Benoit Tressieres, Maryse Etienne-Julan, Nathalie Lemonne, Christopher Denton, Thomas Coates, Marie Petras, Sophie Antoine-Jonville, Philippe Connes
Blood viscosity is an important determinant of local flow characteristics, which exhibits shear thinning behavior: it decreases exponentially with increasing shear rates. Both hematocrit and plasma ...viscosity influence blood viscosity. The shear thinning property of blood is mainly attributed to red blood cell (RBC) rheological properties. RBC aggregation occurs at low shear rates, and increases blood viscosity and depends on both cellular (RBC aggregability) and plasma factors. Blood flow in the microcirculation is highly dependent on the ability of RBC to deform, but RBC deformability also affects blood flow in the macrocirculation since a loss of deformability causes a rise in blood viscosity. Indeed, any changes in one or several of these parameters may affect blood viscosity differently. Poiseuille's Law predicts that any increase in blood viscosity should cause a rise in vascular resistance. However, blood viscosity, through its effects on wall shear stress, is a key modulator of nitric oxide (NO) production by the endothelial NO-synthase. Indeed, any increase in blood viscosity should promote vasodilation. This is the case in healthy individuals when vascular function is intact and able to adapt to blood rheological strains. However, in sickle cell disease (SCD) vascular function is impaired. In this context, any increase in blood viscosity can promote vaso-occlusive like events. We previously showed that sickle cell patients with high blood viscosity usually have more frequent vaso-occlusive crises than those with low blood viscosity. However, while the deformability of RBC decreases during acute vaso-occlusive events in SCD, patients with the highest RBC deformability at steady-state have a higher risk of developing frequent painful vaso-occlusive crises. This paradox seems to be due to the fact that in SCD RBC with the highest deformability are also the most adherent, which would trigger vaso-occlusion. While acute, intense exercise may increase blood viscosity in
Summary
Human red blood cells (RBC) express an active and functional endothelial‐like nitric oxide (NO) synthase (RBC‐NOS). We report studies on RBC‐NOS activity in sickle cell anaemia (SCA), a ...genetic disease characterized by decreased RBC deformability and vascular dysfunction. Total RBC‐NOS content was not significantly different in SCA patients compared to healthy controls; however, using phosphorylated RBC‐NOS‐Ser1177 as a marker, RBC‐NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt‐Ser473). The higher RBC‐NOS activation in SCA led to higher levels of S‐nitrosylated α‐ and β‐spectrins, and greater RBC nitrite and nitrotyrosine levels compared to healthy controls. Plasma nitrite content was not different between the two groups. Laser Doppler flowmetric experiments demonstrated blunted microcirculatory NO‐dependent response under hyperthermia in SCA patients. RBC deformability, measured by ektacytometry, was reduced in SCA in contrast to healthy individuals, and pre‐shearing RBC in vitro did not improve deformability despite an increase of RBC‐NOS activation. RBC‐NOS activation is high in freshly drawn blood from SCA patients, resulting in high amounts of NO produced by RBC. However, this does not result in improved RBC deformability and vascular function: higher RBC‐NO is not sufficient to counterbalance the enhanced oxidative stress in SCA.
Understanding the regulation of human food intake in response to an acute exercise session is of importance for interventions with athletes and soldiers, as well as overweight individuals. However, ...the influence of hot and cold environments on this crucial function for the regulation of body mass and motor performance has not been summarized. The purpose of this review was to exhaustively search the literature on the effect of ambient temperature during an exercise session on the subsequent subjective feeling of appetite, energy intake (EI) and its regulation. In the absence of stress due to environmental temperature, exercise-induced energy expenditure is not compensated by EI during an ad libitum meal following the session, probably due to decreased acylated ghrelin and increased peptide tyrosine tyrosine (PYY), glucagon-like peptide 1 (GLP-1), and pancreatic polypeptide (PP) levels. No systematic analysis has been yet made for major alterations of relative EI in cold and hot environments. However, observed eating behaviors are altered (proportion of solid/liquid food, carbohydrate/fat) and physiological regulation appears also to be altered. Anorexigenic signals, particularly PYY, appear to further increase in hot environments than in those that are thermoneutral. Ghrelin and leptin may be involved in the observed increase in EI after exercise in the cold, in parallel with increased energy expenditure. The potential influence of ambient thermal environment on eating behaviors after an exercise session should not be neglected.
The antenatal period provides an important opportunity for giving advice on healthy lifestyle choices. However, the prevalence of maternal obesity is increasing, and women report that they do not ...receive counseling. We investigated the information given to pregnant women on gestational weight gain, physical activity, and nutrition during pregnancy in relation with their initial weight status, current gestational weight gain and diagnoses of either pre-pregnancy overweight/obesity or excessive gestational weight gain.
Cross-sectional survey using a questionnaire. Pregnant participants (
= 141) were recruited from a midwife center. They completed a structured questionnaire on the information they received during their pregnancy and we assessed its relationship with their weight.
We found that many pregnant women did not receive advice about physical activity, gestational weight gain and nutrition (37.5, 53.2, and 66.2%, respectively). Women with weight problems (pre-pregnancy overweight/obesity and excessive gestational weight gain) were less targeted for counseling, although more than 80% of the women viewed receiving information on these topics as positive. Also, being informed of a weight problem was associated with a greater chance of receiving information about physical activity, gestational weight gain and nutrition (all
< 0.05). However, verbalization of the weight problems was low (14.0% of women with pre-pregnancy overweight were informed of their status).
Health professionals should dispense more information, especially on PA and particularly for women with weight problems. Verbalization of the weight problem seems associated with more frequent transmission of information.
Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis ...in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals
experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.
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