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Limbach-Oberfrohna, Germany

Hocher B.,University of Potsdam | Armbruster F.P.,Immundiagnostik AG | Stoeva S.,Immundiagnostik AG | Reichetzeder C.,University of Potsdam | And 2 more authors.
PLoS ONE | Year: 2012

Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1-84) sample shows TIC-peaks at 18-20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1-84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis. © 2012 Hocher et al.

Jungert A.,Justus Liebig University | Roth H.J.,Limbach Laboratory | Neuhauser-Berthold M.,Justus Liebig University
Nutrition and Metabolism | Year: 2012

Background: Although several studies indicate a link between vitamin D status and blood pressure (BP), the results are inconsistent. The purpose of this study is to investigate whether in predominantly non-obese elderly people without vitamin D deficiency or very high intact parathyroid hormone (iPTH) levels serum 25-hydroxyvitamin D 3[25(OH)D 3] and iPTH are independently associated with BP. Methods. Cross-sectional data of 132 non-institutionalised subjects (90 women and 42 men, aged 66- 96 years) from Giessen, Germany, were analysed. Serum 25(OH)D 3and iPTH were measured by an electrochemiluminescence immunoassay and BP was determined with a sphygmomanometer. We performed univariate and multiple regression analyses to examine the influence of 25(OH)D 3and iPTH on BP with adjustments for age, body composition and lifestyle factors. Results: While iPTH had no impact on BP, 25(OH)D 3was negatively associated with systolic BP in men, but not in women. After splitting the cohort into antihypertensive medication users and non-users, 25(OH)D 3was a significant predictor for systolic and diastolic BP only in men not receiving antihypertensive medicine, even after multiple adjustment. Adjustment for 25(OH)D 3resulted in an inverse association of iPTH with diastolic BP also only in men without intake of antihypertensive medicine. Conclusions: In elderly men without vitamin D deficiency and not taking antihypertensive medicine, 25(OH)D 3may be a negative determinant of BP, independent of iPTH, body composition and lifestyle factors. Furthermore, iPTH may be an independent negative determinant of diastolic BP in men not taking antihypertensive medicine. © 2012 Jungert et al; licensee BioMed Central Ltd.

Jungert A.,Justus Liebig University | Roth H.J.,Limbach Laboratory | Neuhauser-Berthold M.,Justus Liebig University
Nutrition and Metabolism | Year: 2012

Background: Emerging evidence indicates that there is an association between vitamin D and obesity. The aim of this study was to investigate whether the level of serum 25-hydroxyvitamin D 3 [25(OH)D 3] in the elderly is influenced by parameters of anthropometry and body composition independent of potential confounding lifestyle factors and the level of serum intact parathyroid hormone (iPTH). Methods. Cross-sectional data of 131 independently living participants (90 women, 41 men; aged 66-96years) of the longitudinal study on nutrition and health status in senior citizens of Giessen, Germany were analysed. Concentrations of 25(OH)D 3 and iPTH were ascertained by an electrochemiluminescence immunoassay. Body composition was measured by a bioelectrical impedance analysis. We performed univariate and multiple regression analyses to examine the influence of body composition on 25(OH)D 3 with adjustments for age, iPTH and lifestyle factors. Results: In univariate regression analyses, 25(OH)D 3 was associated with body mass index (BMI), hip circumference and total body fat (TBF) in women, but not in men. Using multiple regression analyses, TBF was shown to be a negative predictor of 25(OH)D 3 levels in women even after controlling for age, lifestyle and iPTH (=0.247; P=0.016), whereas the associations between BMI, hip circumference and 25(OH)D 3 lost statistical significance after adjusting for iPTH. In men, 25(OH)D 3 was not affected by anthropometric or body composition variables. Conclusions: The results indicate that 25(OH)D 3 levels are affected by TBF, especially in elderly women, independent of lifestyle factors and iPTH. © 2012 Jungert et al.; licensee BioMed Central Ltd.

Pfeifer Y.,Robert Koch Institute | Schlatterer K.,University of Greifswald | Engelmann E.,Central Laboratory | Schiller R.A.,Institute of Microbiology and Hygiene | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012

Nine carbapenem-resistant Enterobacteriaceae isolates collected from eight patients in five German hospitals were investigated. Six isolates produced the OXA-48 carbapenemase, and three isolates produced OXA-162, which is a point mutant form of OXA-48. Both carbapenemase genes were located on IncL/M-type conjugative plasmids. Insertion sequence IS1999 (truncated or not by IS1R) was located upstream of the bla OXA-48 and bla OXA-162 genes in all of the isolates. Pulsed-field gel electrophoresis typing indicated the clonal transmission of an OXA-48-producing Klebsiella pneumoniae strain in two hospitals. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Tepel M.,University of Southern Denmark | Armbruster F.P.,Immundiagnostik AG | Gron H.J.,Immundiagnostik AG | Scholze A.,Institute of Molecular Medicine | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity. Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system. Results: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P=.002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (X 2, 14.3; P = .0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels. Conclusions: The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality. © 2013 by The Endocrine Society.

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