analyzed and interrupted the results; Kunming Qi, Gang Wang, Qingyun Wu and Zhenyu Li designed the figures; Jiang Cao and Shiyuan Wang wrote the manuscript. All authors critically reviewed the final draft prior to submission.

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.

Hypoxia-mediated red blood cell (RBC) sickling is central to the pathophysiology of sickle cell disease (SCD). The signalling nucleoside adenosine is thought to play a significant role in this process. This study investigated expression of the erythrocyte type 1 equilibrative nucleoside transporter (ENT1), a key regulator of plasma adenosine, in adult patients with SCD and carriers of sickle cell trait (SCT). Relative quantitative expression analysis of erythrocyte ENT1 was carried out by Western blot and flow cytometry. Patients with SCD with steady state conditions, either with SS or SC genotype, untreated or under hydroxycarbamide (HC) treatment, exhibited a relatively high variability of erythrocyte ENT1, but with levels not significantly different from normal controls. Most strikingly, expression of erythrocyte ENT1 was found to be significantly decreased in patients with SCD undergoing painful vaso-occlusive episode and, unexpectedly, also in healthy SCT carriers. Promoting hypoxia-induced adenosine signalling, the reduced expression of erythrocyte ENT1 might contribute to the pathophysiology of SCD and to the susceptibility of SCT individuals to altitude hypoxia or exercise to exhaustion.

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Background and objective: Warm exposure places high demands on thermoregulation mechanisms, which depend on the effectiveness of the microvascular function. The associations between the microcirculation and metabolism in warm environments have received little attention. The purpose of this study was to explore skin blood flow (SkBF) in response to food intake in a warm environment compared to control. Methods: Thirty-two healthy, acclimated-to-warm-environment and physically active participants were recruited (20 females and 12 males). They participated in two sessions (warm environment: 31 C and control: 20 C, presented in randomized order). SkBF was measured before and after standardized food intake through the acquisition of perfusion signals by laser Doppler flowmetry (Periflux System 5000), following a local heating protocol. Results: SkBF was affected by the environmental temperature, showing an increase in the warm environment compared to control (all p < .001). SkBF was significantly affected by food intake (all p < .007), being reduced after meals. In the men's group, SkBF was reduced in both environmental temperatures after meals. In women, meals affected SkBF at 20 C but not in the warm environment. Conclusion: These results may indicate a competition between thermo-and glyco-regulation in a warm environment to the detriment of glucose homeostasis in women.