Detection of antibodies in cardiac autoimmunity

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Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis

Background/Objectives: The increase of bone disease in adult cystic fibrosis (CF) patients is partly attributed to inadequate serum concentrations of 25-OH cholecalciferol (25 (OH) D) blamed on fat malabsorption. Based on physiological, clinical and biochemical observations this pathogenesis is debatable. The objective was to ascertain the relative importance of different 25 (OH) D sources. Subjects/Methods: Over 4 consecutive years, 474 annual 25 (OH) D serum concentrations from 141 CF patients of all ages were compared with values of healthy peers and weighed against annual ultraviolet B (UVB) exposure. Results: Ranked per month, 25 (OH) D concentrations depicted a curve strikingly parallel to the amount of UVB exposure in the preceding months. A significant difference exists between 25 (OH) D concentrations in the 'Months with high UVB exposure' (May-October) and the 'Months with low UVB exposure' (November-April) but not with healthy controls in the same period. Conclusions: 25 (OH) D concentrations clearly respond to the amount of sunshine in preceding months. They are not clearly influenced by daily oral supplements of 800 IU of cholecalciferol. Sun exposure should be encouraged, and the recommended dosage of oral supplements increased

Evolution of vitamin D binding protein concentration in sera from cardiac surgery patients is determined by triglyceridemia

Background: Multiple human and animal studies have reviewed the (non-)actin scavenger functions of vitamin D binding protein (DBP). Recently, we demonstrated the partially lipid bound character of DBP. The purpose of the present study was to explore the link between actin, lipids and DBP in a cohort of patients undergoing cardiac surgery. Methods: The interplay between DBP, actin and lipids was investigated in a cohort study of 35 Caucasian patients who underwent cardiac surgery. Total and actin-free DBP concentrations were assessed by immunonephelometry and ELISA. Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase (-MB) and C-reactive protein (CRP) were measured using routine methods. Low-density lipoprotein cholesterol was calculated according to the Friedewald formula. The DBP phenotypes and the macromolecular bound DBP fractions were determined by polyacrylamide gel electrophoresis (PAGE) and confirmed by Western blotting. Results: Using PAGE and Western blotting with an antihuman DBP polyclonal antibody, the actin-bound DBP complex was identified in serum. Following cardiac surgery, total serum DBP concentrations were characterized by a two phased course. This was paralleled by a similar pattern in serum total cholesterol, HDL-cholesterol and triglyceride concentrations. Good correlation was found between total and actin free serum DBP concentrations (r=0.69, p<0.0001). The serum actin free DBP/total DBP ratio remained stable throughout the study period. Although no significant correlation between cumulative CK-MB enzyme release and delta serum total DBP concentration was observed (p=NS), the latter value correlated significantly with delta serum triglyceride concentrations (r=0.37, p<0.05). Conclusions: The lipid bound character is an underestimated property of DBP in the extracellular actin-scavenger system. Clin Chem Lab Med 2010;48:1345-50

Vitamin D binding protein and the need for vitamin D in hemodialysis patients

Objective: Vitamin D binding protein (DBP) is a polymorphic serum protein with a predominant role in a spectrum of biological activities. Chronic renal failure is characterized by deficient vitamin D metabolism. The present study investigates the impact of DBP polymorphism on the need for vitamin D in hemodialysis patients. Design: This was a retrospective study. Setting: This study included hemodialysis patients from the Renal Unit of Ghent University Hospital (Ghent, Belgium) and the Algemeen Stedelijk Ziekenhuis Geraardsbergen Hospital (Geraardsbergen, Belgium). Methods: One hundred and ninety-one hemodialysis patients and 211 healthy subjects were recruited from the hemodialysis database. The DBP phenotypes were determined by polyacrylamide gel electrophoresis. Serum DBP, parathyroid hormone, 25-hydroxyvitamin D-3, 1,25-dihydroxyvitamin D-3, calcium, albumin, and phosphate were measured. Information regarding the intake of vitamin D analogues was collected. Results: The phenotypic distributions of DBP were in agreement with Hardy-Weinberg equilibrium. Comparing allele frequencies of the two groups, there was an increased proportion of the DBP 2 allele in hemodialysis patients (P <.05). The median serum DBP concentration was lowest in the DBP 2-2 group. The need for oral vitamin D differed significantly (P <.01) between DBP phenotypes, and was greatest in DBP 2-2. Conclusions: The present study demonstrates an altered DBP allele frequency in hemodialysis patients, compared with the general population. More importantly, vitamin D intake differs depending on the DBP polymorphism, and is greatest for end-stage renal disease patients with a DBP 2-2 phenotype. Therefore, vitamin D treatment deserves more careful monitoring among DBP 2-2 patients with end-stage renal disease

Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

CONTEXT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. METHODS: 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. RESULTS: Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. CONCLUSIONS: Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity

The post-load course of triglyceride alterations during 3 h after an 75 g OGTT in obese females are statistically different (***) according to tertiles of visceral adipose tissue (3rd tertile: females with largest amount of visceral adipose tissue).

<p>See supporting <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045145#pone.0045145.s001" target="_blank">information S1</a>.</p

Results from general linear models with fasting serum triglycerides as dependent variable.

<p>If appropriate, variables were transformed into their natural logarithm.</p