Different impacts of neck circumference and visceral obesity on the severity of obstructive sleep apnea syndrome

Uric acid has both antioxidant and pro-oxidant properties in vitro by scavenging and production of reactive oxygen species (ROS). This cross-sectional study examined whether uric acid possesses effects on oxidative stress under physiological conditions independent of xanthine oxidoreductase (XOR), which is involved in uric acid and ROS production. Serum uric acid level was measured, while plasma XOR activity was determined using our high-sensitive assay in 192 participants (91 males, 101 females) who underwent health examinations and were not taking an antihyperuricemic agent. For antioxidant potential and oxidative stress level, biological antioxidant potential (BAP) and derivative of reactive oxygen metabolites (d-ROMs) in serum, respectively, were measured. Median uric acid level and plasma XOR activity were 5.6 mg/dL and 26.1 pmol/h/mL, respectively, and BAP and d-ROMs levels were 2112.8 μmol/L and 305.5 Carr U, respectively. Multivariable regression analyses revealed no significant association of serum uric acid level with BAP level, whereas serum uric acid level showed a significant association with d-ROMs level independent of plasma XOR activity (p = 0.045), which was prominent in females (p = 0.036; p for interaction = 0.148). Uric acid might contribute to increased oxidative stress independent of XOR activity by increasing ROS production, without affecting ROS scavenging, especially in females.

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Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry.

Xanthine oxidoreductase (XOR) inhibitor administration reduces uric acid and reactive oxygen species (ROS) production, and also lowers blood pressure (BP). However, the associations of plasma XOR activity, uric acid level, and oxidative stress levels with BP remain unclear. This cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. Plasma XOR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. BP was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-ROMs) levels were simultaneously measured. Median plasma XOR activity, serum uric acid, d-ROMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XOR activity (β = 0.211, p = 0.019), but not serum uric acid (β = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-ROMs level, an independent association of plasma XOR activity with MAP was observed (β = 0.428, p = 0.001 and β = 0.019, p = 0.891, respectively; p for interaction = 0.046). XOR may contribute to the pathophysiology of higher BP through ROS but not uric acid production, especially in patients with lower oxidative stress.

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Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry.

Romosozumab reportedly increases bone mineral density (BMD) potently but might adversely affect cardiovascular disease (CVD). We evaluated the efficacy of romosozumab in osteoporotic HD patients with a high risk of fracture. This was a single-center 1-year study in Japanese HD patients. Among 96 HD romosozumab-treated HD patients with high risk of fracture, 76 HD patients completed 1 year of subcutaneous administration of romosozumab (210 mg/4 weeks) for 1 year. Romosozumab-untreated HD patients (n = 55) were also included. Changes in BMD and serum markers, together with fracture occurrence, and CVD events, were monitored. During romosozumab treatment of 76 HD patients, BMD time-dependently increased significantly by 15.3% ± 12.9% at the lumbar spine (L1–4), and 7.2% ± 8.3% at the femoral neck at 1 year. Serum BAP and total P1NP increased significantly and serum TRACP-5b decreased at 4 weeks. Fragility fractures occurred in three (3.8%) patients. Hypocalcemia occurred at 4–48 weeks despite the increased dosing of active vitamin-D derivatives, but without any symptom. New CVD events occurred in 5.2% of romosozumab-treated HD patients and10.9% in romosozumab-untreated HD patients. BMD was increased significantly during romosozumab treatment at the lumbar spine, and the femoral neck, respectively, at 1 year in HD patients. Hypocalcemia occurred but without any intolerable event. There was no apparent increase in CVD events during 1 year of study, suggesting romosozumab as a promising agent for HD patients with severe osteoporosis.

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study

Xanthine oxidoreductase (XOR) is an enzyme regulating uric acid synthesis and generation of reactive oxygen species. Several studies suggested relationship between XOR and atherosclerotic diseases; however, few previous studies have directly examined the relationship between XOR and vascular endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between XOR activity and vascular endothelial function in patients with T1DM. Seventy-one patients with T1DM participated in the study and underwent assessments, including plasma XOR activity and flow-mediated dilation (FMD), to measure vascular endothelial function. The natural logarithm value of XOR activity (ln-XOR) was 3.03 ± 0.99 pmol/h/mL, and FMD was 5.5% ± 2.4%. FMD was inversely and significantly correlated with ln-XOR (correlation coefficient: r = − 0.396, P < 0.001), UA (r = − 0.252, P = 0.034), and asymmetric dimethylarginine (ADMA) (r = − 0.414, P < 0.001). ln-XOR showed positive correlation with HbA1c (r = 0.292, P = 0.013), ALT (r = 0.658, P < 0.001), and ADMA (r = 0.363, P = 0.002). Stepwise multiple regression analysis showed that ln-XOR (standard partial regression coefficient: β = − 0.254, P = 0.018) was an independent explanatory variable of FMD. The results of this study showed for the first time that XOR activity is associated with glycemic control in patients with T1DM and that XOR activity is associated with vascular endothelial dysfunction.

Xanthine oxidoreductase activity correlates with vascular endothelial dysfunction in patients with type 1 diabetes.

Xanthine oxidoreductase activity (XOR-a) plays an important role as a pivotal source of reactive oxygen species. In the present study, we investigated factors associated with plasma XOR-a in 163 hemodialysis patients (age 67.3 ± 10.9 years; 89 males and 74 females), using a newly established, highly-sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Plasma glucose and serum uric acid levels correlated significantly and positively with plasma XOR-a. In multiple regression analyses, the presence of type 2 diabetes mellitus (T2DM) and plasma glucose were associated significantly, independently, and positively with plasma XOR-a. While serum uric acid correlated significantly and positively with plasma XOR-a in hemodialysis patients without T2DM, plasma glucose and serum glycated albumin, a new marker of glycemic control in diabetic hemodialysis patients, correlated significantly and positively with plasma XOR-a in those with T2DM. Multivariate analyses in those with T2DM revealed that plasma glucose and serum glycated albumin were associated significantly and independently with plasma XOR-a, and that serum uric acid was associated significantly and independently with XOR-a in those without T2DM. Our results suggested that glycemic control in hemodialysis patients may be important in regard to a decrease in ROS induced by XOR.

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Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients.

Background: The high prevalence of sleep apnea is reported in hemodialysis patients despite the low prevalence of obesity. The present study compared the occurren

Mari Sakura

Papers

Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients.

High Coronary Heart Disease Risk in Hemodialysis Patients with Central Sleep Apnea: A Pilot Study