Serum urate, metabolic syndrome, and cardiovascular risk factors. A population-based study

We studied the associations between serum urate levels (determined in 503 subjects from a population of 1,344 subjects living in northern Madrid) and both the metabolic syndrome (MS) (defined by the Adult Treatment Panel III criteria) and C-reactive protein (CRP, determined in 382 subjects). MS was diagnosed in 25% (95%CI, 21-28%) and was associated with hyperuricemia (p<0.001). There was a graded increase in serum urate levels with increasing number of MS components. Urate concentrations significantly correlated with waist circumference (r=0,455, p<0.01). Serum urate was not independently associated with CRP levels. This study shows that serum urate levels are associated with the presence of MS and each of its features.     

Metabolic Syndrome in Primary Gout

Background and Objectives. Primary gout has traditionally been associated with obesity, arterial hypertension, and abnormal lipid and glucose homeostasis, but we do not know the prevalence of these vascular risk factors in patients with primary gout from a Mediterranean country. Patients and Method. All patients with primary gout and 2 or more acute arthritis episodes documented by a physician were selected for the study. The diagnosis of MS required ≥3 criteria (ATP III). Patients were classified in two groups: decreased (underexcretors) and normal (normoexcretors) uric acid excretion related to serum urate levels. Results. One hundred and four patients (mean age, 59 years; 100 males) with primary gout were included in the study. MS was diagnosed in 38 subjects (37%). The most frequent triad defining MS was an increased waist circumference, blood pressure, and trygliceride levels. The prevalence of type 2 diabetes mellitus (T2D) was significantly higher in patients with the MS (21/38, 55%) as compared with subjects without the MS (3/66, 5%; p < 0.001). Mean serum urate level in patients with and without MS was identical (8.1 mg/dL), but mean 24-hour uric acid excretion was significantly lower in the former than in the latter (444 ± 110 mg/24-hour/1,73 m² versus 546 ± 221 mg/day/1,73 m²; p = 0.009). Conclusions. The condition of the MS occurs in about one-third of the patients with primary gout. Increased waist circumference, blood pressure, and triglycerides levels is the most frequent MS triad. Diminished urinary uric acid excretion is more severe in gout patients with the MS.     

Increased Serum C-Reactive Protein Level Is Associated with Increased Storage Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Objective

Chronic inflammation is considered as one of the contributing mechanisms of lower urinary tract symptoms (LUTS). Serum C-reactive protein (CRP) level is the widely used biomarker of inflammatory status. This study investigated the association between serum CRP level in men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) before and after medical treatment.

Methods

A total of 853 men with BPH and LUTS were enrolled. All patients completed the International Prostate Symptoms Score (IPSS) questionnaire and urological examinations. The parameters of uroflowmetry (maximum flow rate, Qmax; voided volume, VV), post-void residual (PVR), total prostate volume (TPV) and transition zone index (TZI), serum prostate specific antigen (PSA), and serum CRP levels were obtained. All patients were treated with alpha-blocker or antimuscarinic agent based on the IPSS voiding to storage subscore ratio (IPSS-V/S). Correlation analyses were performed between serum CRP levels with age, IPSS, TPV, TZI, Qmax, PVR, VV, PSA and between baseline and post treatment.

Results

The mean age was 66.9±11.6 years old and the mean serum CRP levels were 0.31±0.43 mg/dL. Univariate analyses revealed serum CRP levels were significantly associated with age (p<0.001), PSA levels (p = 0.005) and VV (p = 0.017), but not significantly associated with TPV (p = 0.854) or PVR (p = 0.068). CRP levels were positively associated with urgency (p<0.001) and nocturia (p<0.001) subscore of IPSS, total IPSS (p = 0.008) and storage IPSS (p<0.001) and negatively associated with IPSS- V/S ratio (p = 0.014). Multivariate analyses revealed that serum CRP levels were significantly associated with age (p = 0.004) and storage IPSS subscore p<0.001). Patients with IPSS-V/S<1 and treated with tolterodine for 3 months had significant decrease of CRP levels after treatment.

Conclusion

Serum CRP levels are associated with storage LUTS and sensory bladder disorders, suggesting chronic inflammation might play a role in the patients with storage predominant LUTS.     

Low serum urate levels are associated to female gender in multiple sclerosis patients

Background

Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain.

Objective

To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables.

Methods

Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC).

Results

Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: −0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis.

Conclusions

Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.     

Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese

Serum uric acid levels are maintained by urate synthesis and excretion. URAT1 (coded by SLC22CA12) was recently proposed to be the major absorptive urate transporter protein in the kidney regulating blood urate levels. Because genetic background is known to affect serum urate levels, we hypothesized that genetic variations in SLC22A12 may predispose humans to hyperuricemia and gout. We investigated rs893006 polymorphism (GG, GT and TT) in SLC22A12 in a total of 326 Japanese subjects. Differences in clinical characteristics among the genotype groups were tested by the analysis of variance (ANOVA). In male subjects, mean serum uric acid levels were significantly different among the three genotypes. Levels in the GG genotype subjects were the highest, followed by those with the GT and TT genotypes. However, no differences between the groups were seen in the distributions of creatinine, Fasting plasma glucose (FPG), HbA(1c), total cholesterol, triglyceride, HDL cholesterol levels or BMI. A single nucleotide polymorphism (SNP) in the urate transporter gene SLC22CA12 was found to be associated with elevated serum uric acid levels among Japanese subjects. This SNP may be an independent genetic marker for predicting hyperuricemia.     

Effect of orlistat on the total ghrelin and leptin levels in obese patients

Obesity, characterized by hyperleptinemia and hypoghrelinemia, has become a major health problem all over the world and is associated with an increased risk of complications including insulin resistance, hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. The use of the pancreatic lipase inhibitor Orlistat can help seriously overweight people to achieve and maintain weight loss. The aim of our study was to compare the serum leptin and ghrelin levels in obese subjects who take orlistat with those receiving only dietary treatment. Twenty-one obese patients and 10 control subjects participated. The obese patients were divided into two groups; one group (n=11) took orlistat (120 mg, 3 times daily) and received dietary treatment and the other (n=10) only received the dietary treatment. The study lasted twelve weeks. The concentrations of serum ghrelin, leptin, insulin and C-peptide, and routine biochemical parameters, were measured in both groups. The serum ghrelin level was higher in control (183±62 fmol/ml) than obese (59±30 fmol/ml) subjects while the plasma leptin level was lower in control (8.7±12 μg/L) than obese (36.7±19 μg/L) subjects (all p<0.001). BMI and the total blood cholesterol, LDL and triglyceride levels fell significantly after both orlistat and dietary treatment in the obese subjects (all p<0.01), and the plasma ghrelin level rose (p<0.01). The leptin level demonstrated the opposite trend in both groups but only the patients taking orlistat showed a significant change (p<0.05).Taken together, these results show that orlistat has no effect on body weight in obese subjects additional to that conferred by a non-pharmacological life-style intervention. We therefore conclude that weight lost rather than type of treatment might be more valuable in obesity.     

Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance

BACKGROUND/AIMS: Insulin resistance is associated with serum C-reactive protein (CRP) levels. We aimed to evaluate the effect of bicalutamide on insulin resistance and serum CRP levels in non-obese polycystic ovarian syndrome (PCOS) patients. METHODS: 40 non-obese patients (BMI < or =25 kg/m2) with PCOS and, 40 age- and BMI-matched healthy women were studied. Patients received bicalutamide orally at the dose of 25 mg/day. Serum CRP levels were measured with immunometric assay. Homeostasis model assessment (HOMA-IR) index was used for insulin resistance. RESULTS: Mean Ferriman-Gallwey score (FGS) (p = 0.001), insulin (p = 0.001), serum glucose (p = 0.001), prolactin (p < 0.003), total (p < 0.04) and free testosterone (p = 0.001) and free androgen index (FAI) levels (p = 0.001) of PCOS subjects were higher than in the control group. Mean HOMA-IR of PCOS patients was higher than in control subjects (2.43 +/- 1.2 and 0.94 +/- 0.37, p = 0.001). CRP levels in subjects with PCOS was also higher than in control subjects (4.27 +/- 1.33 and 0.98 +/- 0.19, p = 0.001). After bicalutamide treatment, FGS, free and total testosterone and FAI decreased (p = 0.001). HOMA-IR, prolactin and CRP levels did not show any statistical difference with bicalutamide treatment. CONCLUSIONS: PCOS patients had insulin resistance and a high CRP level. Bicalutamide treatment did not influence insulin resistance and CRP level in PCOS, and this ineffectiveness of bicalutamide on CRP levels may be the result of insulin resistance and/or high prolactin levels at this time.     

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

Background

Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods

We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6?months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2?? and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results

Patients with severe OSAS had higher urinary 8-iso-PGF2?? (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2?? (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions

The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.     

Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease

Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson’s correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p < 0.001), NO (p < 0.001), and CRP levels were significantly higher in CLD patients than in control subjects. The antioxidant vitamin C (p < 0.001) and trace element zinc (p < 0.001) were comparatively lower in the CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.     

Uric Acid Metabolism in Patients with Primary Gout and the Metabolic Syndrome

Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73m² in the former and 609 mg/day/1.73m² in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS.     

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Objectives

To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.

Methods

The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls.

Results

Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10⁻⁹), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels.

Conclusions

DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.     

Compromised antioxidant status and persistent oxidative stress in lung transplant recipients

Oxidative stress may be a key feature, and hence important determinant, of tissue injury and allograft rejection in lung transplant recipients. To investigate this, we determined the antioxidant status (urate, ascorbate, thiols and α-tocopherol) and lipid peroxidation status (malondialdehyde) in bronchoalveolar lavage (BAL) fluid and blood serum of 19 consecutive lung transplant recipients 2 weeks and 1, 2, 3, 6, and 12 months post-surgery. BAL fluid and blood samples from 23 control subjects and blood from 8 patients two days before transplantation were obtained for comparison. Before surgery, the antioxidant status of patients was poor as serum ascorbate and total thiol concentrations were significantly (p < 0.05) lower than control subjects. Two weeks post-surgery, ascorbate and total thiol concentrations were still low and urate concentrations had fallen compared to control subjects (p < 0.01). At this time, BAL fluid urate concentration was higher (p < 0.01), ascorbate concentration was lower (p < 0.01) and reduced glutathione concentrations were similar to control subjects. MDA, a product of lipid peroxidation, was higher (p < 0.01) in both BAL fluid and serum obtained from transplant patients compared to control subjects. During the first 12 months post-surgery, little improvement in antioxidant status or extent of lipid peroxidation was seen in transplant recipients. Regression analysis indicated no difference in serum or BAL fluid antioxidant status in patients with acute rejection compared to those without. In conclusion, lung transplant recipients have a compromised antioxidant status before surgery and it remains poor for at least the first year following the operation. In addition, these patients have elevated MDA concentrations in both their lung lining fluid and blood over most of this time. Oxidative stress is not, however, a sufficiently sensitive endpoint to predict tissue rejection in this group.     

Iron Supplementation and Mortality in Incident Dialysis Patients: An Observational Study

Background

Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting.

Methods

In our observational single-center cohort study (INVOR study) we prospectively studied 235 incident dialysis patients. Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality, cardiovascular and sepsis-related mortality. Furthermore, the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein (CRP) levels (<0.5 mg/dL) and elevated CRP levels (≧0.5 mg/dL) was evaluated by using non-linear P-splines to allow flexible modeling of the association.

Results

One hundred and ninety-one (81.3%) patients received intravenous iron, 13 (5.5%) patients oral iron, whereas 31 (13.2%) patients were never supplemented with iron throughout the observation period. Eighty-two (35%) patients died during a median follow-up of 34 months, 38 patients due to cardiovascular events and 21 patients from sepsis. Baseline CRP levels were not different between patients with and without iron supplementation. However, baseline serum ferritin levels were lower in patients receiving iron during follow up (median 93 vs 251 ng/mL, p<0.001). Iron supplementation was associated with a significantly reduced all-cause mortality [HR (95%CI): 0.22 (0.08–0.58); p = 0.002] and a reduced cardiovascular and sepsis-related mortality [HR (95%CI): 0.31 (0.09–1.04); p = 0.06]. Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality, whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality.

Conclusions

Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients. While serum ferritin levels up to 800 ng/mL appear to be safe, higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation.     

Association of leptin receptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects

Objectives

Leptin is a hormone secreted from adipocytes. It regulates metabolism and energy homeostasis through the leptin receptor (LEPR) which is localized centrally in hypothalamus as well as in peripheral tissues. The aim of this study was to investigate the association of leptin receptor gene Q223R polymorphism on obesity in association with body mass index (BMI), lipid parameters, plasma leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR).

Design and methods

The study included 110 obese and 90 non-obese subjects. The LEPR Q223R polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Plasma leptin levels, serum lipid and antropometric parameters were measured.

Results

No association was found between LEPR gene Q223R polymorphism and BMI in both study and control groups. Strikingly study group with non-obese subjects and with the RR genotype (homozygous mutant) had significantly higher serum total cholesterol (p < 0.001) and low density lipoprotein cholesterol (LDL-cholesterol) levels (p < 0.05) than QR (heterozygous) and QQ (wild type) genotypes. In obese group, subjects with the RR genotypes had significantly higher triglycerides (p < 0.05) levels, waist (p < 0.05) and hip circumferences (p < 0.001) than the QQ and QR genotypes.

Conclusions

Our results suggest that the LEPR gene Q223R polymorphism has an association with waist and hip circumferences in obese group but no direct association with obesity although there is a significant influence on lipid profile both in obese and non-obese subjects.     

脑脊液乳酸和血清降钙素原及C反应蛋白 对小儿细菌性脑膜炎的诊断价值

目的探讨脑脊液乳酸、血清降钙素原及C反应蛋白对小儿细菌性脑膜炎的诊断价值。方法选取我院2016年4月至2017年6月收治的50例细菌性脑膜炎患儿以及50例病毒性脑膜炎患儿进行作为研究对象,比较2类患儿脑脊液乳酸(LA)、血清降钙素原(PCT)及C反应蛋白(CRP)的水平,并分析其诊断价值。结果细菌性脑膜炎组患儿脑脊液LA、血清PCT及CRP水平显著高于病毒性脑膜炎患儿(均P0.05)。血清PCT诊断的灵敏度和特异度最高(96.4%、90.9%,P0.05)。3项指标联合检测的灵敏度(100.0%)和特异度(95.5%)明显高于任一单项指标(均P0.05)。经过Pearson相关性分析,脑脊液LA、血清PCT及CRP与小儿细菌性脑膜炎均呈显著正相关关系(均P0.05)。结论脑脊液乳酸、血清PCT及CRP对小儿细菌性脑膜炎的诊断和治疗效果监测有重要应用价值。     

Frecuencia y características del síndrome metabólico y de la resistencia a la insulina en familiares de primer grado de personas con diabetes mellitus tipo 1

AimTo determine the frequency of metabolic syndrome (MS) and insulin resistance (IR) in first-degree relatives of type 1 diabetic patients (FDR1) and to study the relationship between these two disorders and some clinical, biochemical and immunological characteristics.Subjects and methodsWe studied 289 persons, of which 193 were children/adolescents and 96 were adults. Weight, height, waist and hip circumference, blood pressure, blood glucose, insulin, cholesterol, triglycerides, high-density lipoprotein-cholesterol, glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies were determined. IR was assessed through the insulin resistance index (HOMA-IR). The criteria of the World Health Organization for adults and the Cuban consensus for children and adolescents were used to define MS.ResultsThe prevalence of MS in child and adolescent FDR1 was 5.7% (11/193) while IR was found in 24.9% (48/193). For adult FDR1, the frequency of MS was 6.2% (6/96) and that of IR was 14.6% (14/96). Interestingly, an association was found between IR and MS in adults but not in children and adolescents. IR was more frequent in children and adolescents than in adults (p<0.05). The presence of GADA was associated with IR but not with MS (p<0.05).ConclusionsThe frequency of MS in child and adolescent FDR1 was similar to that found in the general population according to studies using similar definitions of MS. In contrast, the frequency of MS in adults was lower than that reported in Cuba for the first-degree relatives of patients with type 2 diabetes. IR was not only associated with MS in first-degree relatives. The association of IR with the presence of GADA may reflect the fact that β cell hyperactivity increases autoantigen expression.     

Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction

To assess whether allantoin levels in serum and urine are influenced by exhaustive and moderate exercise and whether allantoin is a useful indicator of exercise-induced oxidative stress in humans, we made subjects perform exhaustive and moderate (100% and 40% VO₂max) cycling exercise and examined the levels of allantoin, thiobarbituric acid reactive substances (TBARS) and urate in serum and urine. Immediately after exercise at 100% VO₂max, the serum allantoin/urate ratio was significantly elevated compared with the resting levels while the serum urate levels was significantly elevated 30 min after exercise. The serum TBARS levels did not increase significantly compared with the resting levels. Urinary allantoin excretion significantly increased during 60 min of recovery after exercise, however, urinary urate excretion decreased significantly during the same period. The urinary allantoin/urate ratio also rapidly increased during 60 min of recovery after exercise. Urinary TBARS excretion decreased during the first 60 min of the recovery period and thereafter significantly increased during the latter half of the recovery period. On the contrary, after 40% VO₂max of exercise, no significant changes in the levels of urate, allantoin and TBARS in serum or urine were observed. These findings suggest that allantoin levels in serum and urine may reflect the extent of oxidative stress in vivo and that the allantoin which appeared following exercise may have originated not from urate formed as a result of exercise but from urate that previously existed in the body. Furthermore, these findings support the view that allantoin in serum and urine is a more sensitive and reliable indicator of in vivo oxidative stress than lipid peroxidation products measured as TBARS.     

Serum Thyroid-Stimulating Hormone and Anti-Thyroglobulin Antibody Are Independently Associated with Lesions in Spinal Cord in Central Nervous System Demyelinating Diseases

Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR]  = 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.     

Efficacy and Safety of a Urate Lowering Regimen in Primary Gout

Background and Objectives. Pharmacologic urate lowering therapy (ULT), at full maintenance doses, has been associated with acute gout arthritis (in up to 80% of patients). The American College of Rheumatology has recently advocated gradually titrating the maintenance dose upward to chosen serum urate target. Few studies have examined the efficacy and safety of a ULT in primary gout. Patients and Methods. The ULT regimen examined included allopurinol (50 mg/day, with increases of 50 mg/month up to 300 mg/day) and colchicine, as prophylaxis to prevent acute gouty attacks. The efficacy and safety of this regimen was examined in 42 patients in whom allopurinol was withheld for ≥3 months and restarted after this assessment and followed up for 12 months. The efficacy and safety of the ULT regimen was related to the serum urate decrease and to the incidence of acute gout flares, respectively. Results. Fifty-nine patients (mean age 59 years, 56 men) with primary gout received the gradually titrated ULT regimen. Baseline serum urate was (mean ± SD) 8.4 ± 0.8 mg/dL. At 3, 6, 9, and 12 months serum urate fell by a mean of 1.8, 2.5, 2.7, and 2.5 mg/dL, respectively (p < 0.001). A serum urate level <6.0 mg/dL was achieved by 38/59 (64%) patients. During the 12 months following the start of the ULT we documented 10 acute arthritis episodes (17% of patients). Conclusions. A gradually titrated hypouricemic regimen for 6 months in patients with primary gout appears to be effective and safe.     

Relationship Between Metabolic Syndrome,Circadian Treatment Time,and Blood Pressure Non-Dipping Profile in Essential Hypertension

There is a strong association between metabolic syndrome (MS) and increased cardiovascular risk. Moreover, elevated nighttime blood pressure (BP) and non-dipping (subjects with <10% decline in the asleep relative to the awake BP mean) have been also linked to increased cardiovascular morbidity and mortality. We investigated the relation between MS, circadian time of hypertension treatment, and impaired nighttime BP decline in a cross-sectional study on 3352 (1576 men/1776 women) non-diabetic hypertensive subjects, 53.7?±?13.1 (mean?±?SD) yrs of age. Among them, 2056 were ingesting all their prescribed hypertension medication upon awakening, and 1296 were ingesting at least one of their BP medications at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours to substantiate reproducibility of the dipping pattern. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate mean BP when awake and asleep for each subject. MS was present in 52.6% of the subjects. The prevalence of an altered non-dipper BP profile was significantly higher among subjects with MS (52.0% vs. 39.5% in subjects without MS, p < .001). Non-dipping was significantly more prevalent among subjects ingesting all BP-lowering medications upon awakening (56.8%) than among those ingesting at least one of their BP medications at bedtime (29.1%; p < .001). Subjects with MS had significantly higher values of uric acid (6.0 vs. 5.3?mg/dL, p < .001), plasma fibrinogen (331 vs. 315?mg/dL, p < .001), and erythrocyte sedimentation rate (14.8 vs. 12.4?mm, p < .001). Non-dipping was significantly associated with the presence of MS and treatment upon awakening in a multiple logistic regression model adjusted by significant confounding factors, including age, creatinine, erythrocyte sedimentation rate, and cigarette smoking. This cross-sectional study documents a significant increase of a blunted sleep-time BP decline in treated hypertensive subjects with MS. Even in the presence of MS, treatment at bedtime is significantly associated with lower prevalence of a high-risk non-dipper BP profile. (Author correspondence: rhermida@uvigo.es)