Effects of hyperbilirubinemia on markers of genotoxicity and total oxidant and antioxidant status in newborns.

Hyperbilirubinemia is one of the most common diseases in neonates. Slight elevations in bilirubin levels exert antioxidant effects but high levels may cause oxidative damage in newborns. We assessed the effects of hyperbilirubinemia on DNA damage and total oxidant and antioxidant status in newborns receiving phototherapy. A total of 68 term newborn infants exhibiting idiopathic unconjugated hyperbilirubinemia (UCH) requiring phototherapy and 27 age-matched healthy controls were enrolled in the study. Plasma 8-hydroxy-2 deoxy-guanosine (8-OH-dG) levels, total oxidant status (TOS), and total antioxidant status (TAS) were compared between newborns with UCH requiring phototherapy and age-matched healthy controls. The extent of DNA damage, the TOS, and the TAS were significantly higher in the study group than the control group (p < 0.01). The extent of DNA damage and the TOS increased at lower bilirubin levels; this became significant at bilirubin levels >16 mg/dL. A significant increase in TAS was observed even at low bilirubin levels, and the TAS was positively correlated with the bilirubin level to 30 mg/dL. At slightly elevated levels bilirubin serves as a physiological antioxidant. However, the high bilirubin levels evident in the present study increased DNA damage and oxidative stress.

Endocan: a novel predictor of endothelial dysfunction in obstructive sleep apnea syndrome.

BACKGROUND AND AIMS: Obstructive sleep apnea syndrome (OSA) is an independent risk factor for endothelial dysfunction and cardiometabolic diseases. Plasma endocan levels are elevated in a large number of diseases, and is a novel surrogate endothelial cell dysfunction marker. We aimed to assess the role of serum endocan level as a potential mechanism of endothelial dysfunction in OSA patients. MATERIALS AND METHODS: This was a cohort study in which patients who had undergone a sleep study for diagnosis of OSA were recruited. Included patients were grouped according to apnea-hypopnea index (AHI) as mild, moderate and severe OSA. Patients with AHI < 5 served as control group. Endothelial function was evaluated with flow-mediated dilatation (FMD). Plasma endocan level was measured for all patients. RESULTS: One hundred twenty eight OSA patients included (15 controls, 22 with mild, 22 with moderate and 69 with severe OSA). The mean age was 51.6 ± 11.9 years and 43.8% (56/128) of the study population was female. As expected, the prevalence of hypertension, diabetes and cardiovascular disease increased as the severity of OSA increased. Endocan levels were significantly higher and FMD measurements were lower in patients with OSA compared to healthy controls. There was a positive correlation between AHI and serum endocan levels (rho = 0.826, P < 0.0001) and there was a negative correlation between AHI and FMD (rho = -0.686, P < 0.0001) In addition, we observed a strong negative correlation between serum endocan level and FMD (rho = -0.613, P < 0.0001). In linear regression analysis AHI was independently related both with endocan (P < 0.0001) and FMD (P = 0.011). CONCLUSION: Serum endocan level is strongly associated with the severity of OSA and endothelial dysfunction. Endocan might be a useful early novel marker for premature vascular endothelial system damage in OSA patients.

Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia.

BACKGROUND: Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. METHODS: Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. RESULTS: Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. CONCLUSIONS: Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.

Urotensin II levels in patients with chronic kidney disease and kidney transplants.

OBJECTIVE: Urotensin II is a potent vasoactive peptide that has been implicated in the pathophysiology of many diseases. There is no study reporting the role and level of this peptide in recipients of kidney transplant. So we aimed to study the plasma levels of urotensin II in this group of patients. METHODS: Plasma urotensin II levels were analyzed in 110 subjects, who were divided into three groups: group 1 (35 kidney transplant recipients), group 2 (36 patients with chronic kidney disease), and group 3 (39 healthy controls). RESULTS: Analysis of logarithmic transformation of urotensin II, i.e. log (urotensin II × 1000) levels, with a one-way analysis of variance yielded a P value of 0.001. Post-hoc analysis showed significantly higher log (urotensin II × 1000) levels in group 1 than groups 2 and 3 (P = 0.001 and 0.017, respectively). One of the important features of the subjects of this group was that they were taking immunosuppressive drugs because of renal transplantation. CONCLUSIONS: High urotensin II levels in recipients of kidney transplants could be drug-related (immunosuppressive drugs) and may be of practical importance that may be used to improve the long-term outcome of the patients.

Oxidative stress and autonomic nervous system functions in restless legs syndrome.

BACKGROUND: Oxidative stress has been implicated in over 100 disorders in recent years; however, the situation in restless legs syndrome (RLS) has not been studied yet. METHODS: Fifty patients with RLS not medicated for RLS and 50 sex- and age-matched, healthy controls and controls with no pathology except mild iron deficiency or iron deficiency anaemia were enrolled. Patients with secondary RLS other than iron deficiency were excluded. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), arylesterase (ARE), paraoxonase (PON), stimulated paraoxonase (stim-PON), lipid hydroperoxides (LOOHs), acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE) were measured. Heart rate variability (HRV) analysis was performed. RESULTS: TOS, ARE and AChE were increased (P = 0·018, P < 0·001 and P < 0·001, respectively), whereas LOOHs were decreased (P < 0·001) in RLS group. TAS, OSI, PON and stim-PON were comparable. Erythrocyte sedimentation rate (ESR) and mean platelet volume (MPV) were increased (P = 0·021 and P = 0·037, respectively) in RLS group. HRV triangular index (HRVi) was lower (P = 0·012) in RLS group. Other HRV parameters were similar. CONCLUSIONS: Increased AChE and decreased LOOHs, which were influenced by increased PON1, were considered as indicators of efforts towards the protection of dopaminergic activity in central nervous system in RLS group. Increased ESR, MPV and low HRVi indicate elevated sympathetic activity in RLS group. Elevated sympathetic activity might be beneficial in relieving RLS symptoms, also causing increases in TOS. The evidence we found regarding oxidative stress and autonomic nervous system might be seminal in RLS treatment.

Prevalence of gluten sensitive enteropathy antibodies in restless legs syndrome.

The prevalence of restless legs syndrome (RLS) is increased in gluten sensitive enteropathy (GSE); but prevalence of GSE is not known in RLS. 96 RLS patients and 97 healthy controls, both with or without iron deficiency were enrolled. All secondary RLS patients except iron deficiency were excluded. Subjects underwent a thorough biochemistry and routine blood analyses, and tissue transglutaminase antibodies (TTGA), endomysium antibodies (EMA) and gliadin antibodies (AGA) were also tested. In RLS patients positivity rates of all GSE antibodies were similar to those in controls. The rate of iron deficiency anaemia in RLS patients with at least one positive GSE antibody was significantly higher than that of RLS patients whose GSE antibodies were all negative. The prevalence of GSE antibodies in RLS patients is not increased. GSE might have a role in the aetiology of RLS in association with iron deficiency anaemia. Since the prevalence of GSE antibodies is not increased in RLS, it seems unlikely that GSE is involved in the aetiology of RLS through different mechanisms (e.g. immunological mechanisms) other than iron deficiency as proposed in some published papers.

Commutability limitations influence quality control results with different reagent lots.

BACKGROUND: Good laboratory practice includes verifying that each new lot of reagents is suitable for use before it is put into service. Noncommutability of quality control (QC) samples with clinical patient samples may preclude their use to verify consistency of results for patient samples between different reagent lots. METHODS: Patient sample results and QC data were obtained from reagent lot change verification records for 18 QC materials, 661 reagent lot changes, 1483 reagent lot change-QC events, 82 analytes, and 7 instrument platforms. The significance of between-lot differences in the results for QC samples compared with those for patient samples was assessed by a modified 2-sample t test adjusted for heterogeneity of QC and patient sample measurement variances. RESULTS: Overall, 40.9% of reagent lot change-QC events had a significant difference (P < 0.05) between results for QC samples compared with results for patient samples between 2 reagent lots. For QC results with differences <1.0 SD interval (83.1% of total), 37.7% were significantly different from the changes observed for patient samples. For QC results with differences ≥1.0 SD interval (16.9% of total), 57.0% were significantly different from those for patient samples. CONCLUSIONS: Occurrence of noncommutable results for QC materials was frequent enough that the QC results could not be used to verify consistency of results for patient samples when changing lots of reagents.