Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral Sclerosis

Objective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS).Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model.Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p < 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = −0.378, p < 0.001), and higher education level (β = 0.424, p < 0.001) could predict higher ECAS score (F = 19.104, R2 = 0.381, p < 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p < 0.001) and the testing set (rs = 0.666, p < 0.001).Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.

Biochemical reference intervals in broiler chickens according to age and strain

The objective of the research was to study the physiological pattern of biochemical variables and to obtain reference intervals for young (less than 1 month) and adult (more than 1 month) broiler chickens of 2 strains. From the jugular vein, blood for analysis was collected, separated, and then immediately analyzed. The influence of age was significant for the majority of the investigated variables in the 2 groups. In Isa15 strain, a significant age-related decrease in plasma uric acid, glucose, cholesterol, triglycerides, phosphorus, potassium and iron was established. Also, a significant age-related increase in plasma calcium and ASAT was obtained in the same broiler strain. In Arbor Acres Plus strain, a significant age-related decrease in plasma glucose, cholesterol, triglycerides and phosphorus was observed. A significant age-related increase in plasma total protein, calcium and ASAT has also been reported in this broiler strain. A significant difference between the two strains was reported for plasma uric acid, glucose, cholesterol, phosphorus, magnesium and iron (p<0.05). For most estimated parameters in the 2 strains, calculation of separate reference intervals for young and adult animals was appropriate. Except for potassium in young Isa15 strain, and phosphorus in young Arbor Acres Plus strain, all variables did not follow a normal distribution. Reference intervals are presented for both ages using non-parametric or robust method. 90% confidence intervals for both groups were calculated non-parametrically, or by the bootstraping method. The established reference intervals will be a useful guide for interpreting plasma biochemical variables in different strains of broiler chickens raised in Algeria, and reared in a mild Mediterranean climate.

Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats

Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.

Genotype-Phenotype Dissociation in Two Taiwanese Children with Molybdenum Cofactor Deficiency Caused by MOCS2 Mutation

Background To describe the genotype-phenotype dissociation in two Taiwanese patients with molybdenum cofactor deficiency (MoCoD) caused by MOCS2 gene mutations. Patient Description Patient 1 exhibited early-onset neurological symptoms soon after birth, followed by subsequent myoclonic seizures and movement disorder. The brain magnetic resonance imaging (MRI) showed diffuse brain injury with cystic encephalomalacia along with bilateral globus pallidi involvement, hypoplasia of corpus callosum, and cerebellar atrophy. Patient 2 had a mild phenotype with prominent movement disorder after intercurrent illness, and the brain MRI showed selective injury of the bilateral globus pallidi and the cerebellum. Both patients had markedly low levels of plasma uric acid and harbored the same MOCS2 homozygous c.16C > T mutation. Patient 1 showed chronic regression of developmental milestones and died of respiratory failure at the age of 8 years, whereas patient 2 demonstrated improvement in motor function. Conclusion Genotype-phenotype dissociation could be noted in patients with MoCoD due to MOCS2 mutation. Patients with neonatal seizures, developmental delay, movement disorder, and motor regression after an illness, as well as focal or bilateral involvement of the globus pallidi on the neuroimages, should undergo biochemical testing of plasma uric acid. A pronounced plasma uric acid level is a good indicator of MoCoD. Early diagnosis can allow early provision of adequate genetic counseling.

RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia

ObjectiveHyperuricemia (HUA) is strongly associated with abnormal glucose metabolism and insulin resistance (IR). However, the precise molecular mechanism of HUA-induced IR is still unclear. Retinol binding protein 4 (RBP4) has been shown to induce IR in type 2 diabetes mellitus. This study was designed to clarify the relationship between RBP4 and HUA-induced IR and its potential mechanisms.MethodsPatients with HUA were collected to detect the levels of plasma RBP4 and clinical biochemical indicators. Rats were fed with 10% high yeast and oteracil potassium (300 mg/kg) via intraperitoneal injection once daily for eight weeks, and gavage with adenine (100 mg/kg) once daily from the fifth week to induce the HUA model. Glucose consumption testing was performed to determine the capacity of glucose intake and consumption in 3T3-L1 adipocytes. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA and protein level of RBP4 and insulin receptor substrate-phosphatidylinositol 3-kinase-active protein kinase (IRS/PI3K/Akt) signaling pathway-related proteins.ResultsThe levels of plasma RBP4 in both HUA patients and HUA rat models were significantly higher than that in the control groups. The level of plasma RBP4 was positively correlated with plasma uric acid, creatinine, fasting insulin, IR index, total cholesterol and triglyceride levels in patients with HUA. In HUA rats, the level of plasma RBP4 was positively correlated with plasma uric acid, IR index, and triglycerides. HUA rats also exhibited IR. After inhibition of RBP4 expression, the phosphorylation levels of the IRS/PI3K/Akt signaling pathway were increased, and IR was significantly improved.ConclusionHUA induced IR both in vitro and in vivo. RBP4 may be involved in HUA-induced IR by inhibiting IRS/PI3K/Akt phosphorylation. Our findings may provide a new insight for the treatment of IR caused by HUA.

Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects

Background Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial. Methods We investigated in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19–73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. Results The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R2 of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes. Conclusions PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.

Caffeine improves biochemical and specific performance after judo training: a double-blind crossover study in a real judo training situation

Background Nutritional ergogenic aids are foods or nutrients that can improve physical performance. Among these foods with ergogenic properties, caffeine has shown that it can increase the fat catabolism, strength, and improve the cognition and time reaction of an athlete, therefore, it is hoped that it can improve the performance of judokas. This study through a double-blind crossover (supplement X placebo) protocol, investigated the effects caffeine supplementation (single capsule containing 5 mg/kg body mass intake 60 min before the session) on biochemical, anthropometrical, physical, subjective and hemodynamic variables measured before, during and after two typical judo trainingcxs sessions (120-min: 40-min of gymnastics; 40-min of specific technics and; 40-min of judo combat). Methods 8 high-level athletes (21.4 ± 2.0 years; 83.6 ± 15.2 kg; 1.8 ± 0.1 m; 17.9 ± 7.0 Fat%) were evaluated before and after each training for body mass, hydration, upper and lower limb power, performance in the special judo fitness test (SJFT), free fatty acids (FFA) in plasma, uric acid, glucose, lactate, heart rate, and pain. In addition, heart rate, FFA in plasma, uric acid, glucose, lactate, rating of perceived exertion and pain were assessed during the training. Results At 120 min, supplementation resulted in a higher concentration of plasma FFA (1.5 ± 0.5 vs. 1.0 ± 0.3 mmol/L; p = 0.047) and lactate (4.9 ± 1.8 vs. 3.0 ± 1.2 mmol/L; p = 0.047), and a lower concentration of uric acid (5.4 ± 0.9 vs. 7.0 ± 1.5 mg/dL; p = 0.04). Supplementation also resulted in performance maintenance (fatigue index) in the SJFT (Δ0.3 ± 2.0 vs Δ1.7 ± 2.5, for caffeine and placebo respectively, p = 0.046). No adverse effects were observed. Conclusion Based on the applied dose, intake time, and sample of this study, we can conclude that caffeine produces an ergogenic biochemical effect, and improves performance in judo athletes.