Hyperuricemia and the Risk of Heart Failure: Pathophysiology and Therapeutic Implications

The association between hyperuricemia and cardiovascular disease (CVD) has been reported and studied in the past two decades. Xanthine oxidase (XO) induced uric acid (UA) serves as a risk factor and has the independent prognostic and functional impact of heart failure (HF), but whether it plays a positive role in the pathogenesis of HF has remained unclear. Growing evidence suggest the up-regulated XO avtivity and increased production of free oxygen radical (ROS) correspondingly are the core pathogenesis of HF with hyperuricemia, which results in a whole cluster of pathophysiologic cardiovascular effects such as oxidative stress, endothelial dysfunction, vascular inflammation, left ventricular (LV) dysfunction as well as insulin resistance (IR). The use of XO inhibition represents a promising therapeutic choice in patients with HF due to its dual effect of lowering serum UA levels as well as reducing ROS production. This review will discuss the pathophysiologic mechanisms of hyperuricemia with HF, the targeted therapeutic interventions of UA lowering therapies (ULT) with XO inhibition and mechanism underlying beneficial effects of ULT. In addition, the review also summarizes current evidence on the role of ULT in HF and compares CV risk between allopurinol and febuxostat for practical and clinical purposes. Guidelines and implementation of CV risk management in daily practice will be discussed as well.

Báo Cáo Một Trường Hợp Ngộ Độc Asen Cấp Tính Được Trị Thành Công Tại Bệnh Viện Nhi Trung Ương

Arsenic is a poisoning metallic element, in which trivalent inorganic arsenic compounds are considered unique. Children can be exposed from arsenic containing water, food and folk remedies with unclear ingredients [1]. The main toxic mechanism of As3+ is inhibition of the pyruvate dehydrogenase (PDH) complex, which leads to decrease in acetyl-CoA production, decrease in cellular respiration and free oxygen radical (0-) and hydrogen peroxide (H202) are born, which make cytotoxic. Arsenic poisoning causes damage to multiple organs: keratosis of the skin, nail and squamous cell cancer, neuropathy, repolarization of the myocardium, liver damage and subsequent sequelaes [1], [2]. Arsenic poisoning has no specific symptoms, so it is easy to overlook, especially in children [2]. The epidemiological exploitation and history of poisoning drugs are very important to avoid missing arsenic poisoning. We report a case of successfully treated arsenic poisoning at the Vietnam National Children’s Hospital.

Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p < 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (rs = 0.622, p < 0.001), in OC-users (rs = 0.442, p < 0.001), and in non-OC-users (rs = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.

The Association Between Alterations in Redox Homeostasis, Cortisol, and Commonly Used Objective and Subjective Markers of Fatigue in American Collegiate Football

Purpose: To assess associations between a free oxygen radical test (FORT), free oxygen radical defense test (FORD), oxidative stress index, urinary cortisol, countermovement jump (CMJ), and subjective wellness in American college football. Methods: Twenty-three male student athlete American college football players were assessed over 10 weeks: off-season conditioning (3 wk), preseason camp (4 wk), and in season (3 wk). Assessments included a once-weekly FORT and FORD blood sample, urinary cortisol sample, CMJ assessment including flight time, reactive strength index modified and concentric impulse, and a daily subjective wellness questionnaire. Linear mixed models analyzed the effect of a 2 within-subject SD change in the predictor variable on the dependent variable. The effects were interpreted using magnitude-based inference and are presented as standardized effect size (ES) ± 90% confidence intervals. Results: Small negative associations were observed between FORT–flight time, FORT–fatigue, FORT–soreness (ES range = −0.30 to −0.48), FORD–sleep (ES = 0.42 ± 0.29), and oxidative stress index soreness (ES = 0.56 ± 0.29). Small positive associations were observed between FORT–cortisol (ES = 0.36 ± 0.35), FORD–flight time, FORD reactive strength index modified and FORD–soreness (0.37–0.41), oxidative stress index concentric impulse (ES = 0.37 ± 0.28), and with soreness–concentric impulse, soreness–flight time, and soreness reactive strength index modified (0.33–0.59). Moderate positive associations were observed between cortisol–concentric impulse and cortisol–sleep (0.57–0.60). Conclusion: FORT/FORD was associated with CMJ variables and subjective wellness. Greater amounts of subjective soreness were associated with decreased CMJ performance, increased FORT and cortisol, and decreased FORD.

The Evaluation of Oxidative Stress Levels in Obesity

The association between elevated values of reactive oxygen species and a decreased antioxidant capacity defines oxidative stress. Oxidative stress involvement is blamed in many diseases, including obesity. We evaluated oxidative stress levels by FORT (Free Oxygen Radical Testing � reactive oxygen species levels) and FORD (Free Oxygen Radical Defence � antioxidant capacity value) assays in obese subjects vs. controls. FORT values were high and FORD values were low in obese patients vs. controls, notably in obese subjects with comorbidities (diabetes, hypertension, dyslipidaemia, coronary heart disease, anaemia, hepatic steatosis). We found positive correlations between FORT values and total cholesterol, uric acid, triglycerides, LDL, body mass index, HDL/total cholesterol ratio, and negative correlations between FORT and age, HDL. FORD levels correlated oppositely to FORT. Our results suggest that obesity and oxidative stress are linked.

A sulfur-free peptide mimic of surfactant protein B (B-YL) exhibits high in vitro and in vivo surface activities

Background: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B covalently joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B. Here, we studied ‘B-YL’, a 41-residue SMB variant that has its four cysteine and two methionine residues replaced by tyrosine and leucine, respectively, to test whether these hydrophobic substitutions produce a surface-active, α-helix hairpin. Methods: Structure and function of B-YL and SMB in surfactant lipids were compared with CD and FTIR spectroscopy, and surface activity with captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits. Results: CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to SMB in lipids. B-YL in surfactant lipids demonstrated excellent in vitro surface activity and good oxygenation and dynamic compliance in lavaged, surfactant-deficient adult rabbits, suggesting that the four tyrosine substitutions are an effective replacement for the disulfide-reinforced helix-turn of SMB. Here, the B-YL fold may be stabilized by a core of clustered tyrosines linking the N- and C-helices through non-covalent interactions involving aromatic rings. Conclusions: ‘Sulfur-free’ B-YL forms an amphipathic helix-hairpin in surfactant liposomes with high surface activity and is functionally similar to SMB and native SP-B. The removal of the cysteines makes B-YL more feasible to scale up production for clinical application. B-YL’s possible resistance against free oxygen radical damage to methionines by substitutions with leucine provides an extra edge over SMB in the treatment of respiratory failure in preterm infants with RDS.