NFU1 gene mutation and mitochondrial disorders.

Mitochondrial respiratory chains consist of approximately 100 structural proteins. Thirteen of these structural proteins are encoded by mitochondrial DNA (mtDNA), and the others by nuclear DNA (nDNA). Mutation in any of the mitochondrial structural-protein related genes, regardless of whether they are in the nDNA or mtDNA, might cause mitochondrial disorders. In the recent past, new nuclear genes required for assembly, maintenance, and translation of respiratory chain proteins have been found. Mutation in these genes might also cause mitochondrial disorders (MD). NFU1 gene is one of such genes and has a role in the assembly of iron-sulfur cluster (ISC). ISCs are included in a variety of metalloproteins, such as the ferredoxins, as well as in enzymatic reactions and have been first identified in the oxidation-reduction reactions of mitochondrial electron transport. It is important to be aware of NFU1 gene mutations that may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

BACKGROUND: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). METHODS: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. RESULTS: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. CONCLUSIONS: Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. TRIAL REGISTRATION ID: ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Plasma total homocysteine concentrations in a Turkish population sample.

OBJECTIVES: The purpose of this study is to determine the reference of plasma total homocysteine levels from a Turkish population and to investigate the relationship of plasma total homocysteine levels with sex and age groups. DESIGN AND METHODS: Plasma total homocysteine levels were measured in 2257 Turkish individuals (1381 men and 876 women) aged 1-90 years. Plasma total homocysteine concentrations were determined using high performance liquid chromatography with fluorescence detector. RESULTS: The mean plasma total homocysteine level was significantly higher in men (mean, 10.6 micromol/L) than in women (mean, 8.7 micromol/L), P < 0.001. The mean plasma total homocysteine levels for the 1-10, 11-20, 21-30, and 31-40, 41-50, 51-60, and 61-70, 71-80, 81-90 age groups, were 6.5, 9.6, 10.1, and 10.4, 10.5, 10.9, and 11.3, 12.7, 14.6 miromol/L in men and 7.1, 7.6, 7.5, and 7.8, 8.7, 9.4, and 10.3, 11.2, 13.3 micromol/L in women, respectively. CONCLUSIONS: These data indicate the significance of sex- and age-associated differences of plasma total homocysteine levels in Turkish subjects. Plasma total homocysteine levels were increasing with age and men were found to have higher levels than women, as is found in other populations.

Metformin decreases circulating acylation-stimulating protein levels in polycystic ovary syndrome.

AIM: There are no studies that examine the circulating acylation-stimulating protein (ASP) levels in patients with polycystic ovary syndrome (PCOS). The present study was designed to determine the ASP levels in PCOS and to evaluate the effect of metformin on plasma fasting ASP concentrations. METHODS: Twenty women with PCOS and 20 healthy controls matched for age and body mass index (BMI) were included in the study. We determined ASP and other biochemical parameters before and after treatment. RESULTS: Baseline levels of plasma ASP, complement 3 (C3), waist-to-hip ratio (WHR), homeostasis model assessment-insulin resistance index (HOMA-IR), fasting insulin, triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) were significantly higher in patients than in controls. After 3 months of metformin treatment, BMI, WHR, ASP, C3, fasting glucose, fasting insulin, HOMA-IR, total cholesterol, TG, VLDL-C and free testosterone decreased significantly, whereas apolipoprotein A-I and high-density lipoprotein cholesterol increased significantly. CONCLUSIONS: The major novel information of the present study is that ASP and C3 values are markedly increased in non-obese patients with PCOS, with a decrease evidenced with metformin treatment.