Publications by authors named "Sieglinde Zelzer"

57 Publications

Association of vitamin D metabolites with cognitive function and brain atrophy in elderly individuals - the Austrian stroke prevention study.

Aging (Albany NY) 2021 Apr 7;13. Epub 2021 Apr 7.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.

Background: Vitamin D is a well-established regulator of calcium and phosphate metabolism that has neurotrophic and neuroprotective properties. Deficiency of vitamin D has been proposed to promote cognitive dysfunction and brain atrophy. However, existing studies provide inconsistent results. Here we aimed to investigate the association between vitamin D metabolites, cognitive function and brain atrophy in a cohort of well-characterized community-dwelling elderly individuals with normal neurological status and without history of stroke and dementia.

Methods: 25(OH)D, 25(OH)D and 24,25(OH)D were measured by liquid-chromatography tandem mass-spectrometry in serum samples from 390 community-dwelling elderly individuals. All participants underwent thorough neuropsychiatric tests capturing memory, executive function and visuopractical skills. In 139 of these individuals, MRI of the brain was performed in order to capture neurodegenerative and vascular changes.

Results: Total 25(OH)D (ß=0.003, 0.037), 24,25(OH)D (ß=0.0456, p=0.010) and vitamin D metabolite ratio (VMR) (ß=0.0467, p=0.012) were significantly related to memory function. Adjustment for multiple testing weakened these relationships, but trends (p≤0.10) remained. 24,25(OH)D and VMR showed similar trends also for visuopractical skills and global cognitive function. No significant relationships existed between vitamin D metabolites and MRI derived indices of neurodegeneration and vascular changes. Sub-group analyses of individuals with low concentrations of 25(OH)D and 24,25(OH)D showed significantly worse memory function compared to individuals with normal or high concentrations.

Conclusions: Vitamin D deficient individuals appear to have a modest reduction of memory function without structural brain atrophy. Future studies should explore if vitamin D supplementation can improve cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202930DOI Listing
April 2021

Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

Biomedicines 2021 Feb 27;9(3). Epub 2021 Feb 27.

Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight ( = 26), overweight ( = 22), and obese ( = 20) women.

Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women.

Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines9030242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997277PMC
February 2021

Branched-chain amino acids are linked with iron metabolism.

Ann Transl Med 2020 Dec;8(23):1569

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Background: The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are reported to influence erythropoiesis and the human iron status. Large study cohorts encompassing biomarkers of iron metabolism and BCAAs are still lacking.

Methods: We investigated potential interactions between blood concentrations of all three BCAAs valine, leucine and isoleucine and biomarkers of iron metabolism [i.e., hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), iron, transferrin, ferritin, transferrin saturation, soluble transferrin receptor (sTfR)] in 430 outpatients referred for a medical health check-up. Linear regression models were performed to assess possible associations between variables.

Results: All three BCAAs were positively correlated with Hb, ferritin and the sTfR (r-values: 0.145-0.382; P values: <0.001-0.003). The strongest correlation was observed between valine and Hb (r=0.382; P value <0.001). Linear regression models showed a statistically significant influence of all three BCAAs on Hb and ferritin (β-coefficients: 0.173-0.351; all P values: <0.001). Seventeen patients with anemia (4%) were found with significantly lower serum BCAA concentrations compared to 413 non-anemic individuals (P<0.05).

Conclusions: These data indicate a pathophysiological link between the three BCAAs valine, leucine and isoleucine and the human iron indicators Hb and ferritin. Further studies are needed to clarify the exact causal mechanisms of these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-624aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791222PMC
December 2020

The Relationship Between Food Craving, Appetite-Related Hormones and Clinical Parameters in Bipolar Disorder.

Nutrients 2020 Dec 29;13(1). Epub 2020 Dec 29.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, 8036 Graz, Austria.

Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13010076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824587PMC
December 2020

Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

EXCLI J 2020 28;19:1414-1422. Epub 2020 Oct 28.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values < 0.05, ρ = 0.176 and 0.136). Ninety-five individuals with a BDI score > 13 showed significantly higher IL-6 serum levels (1.7 [1.0 - 2.8] vs. 1.1 [0.8 - 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2020-2940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726491PMC
October 2020

Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier: Results from 290 lumbar punctures.

EXCLI J 2020 9;19:1275-1281. Epub 2020 Sep 9.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (Q) and TMAO (Q) quotient and evaluating Q values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with Q and Q determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The Q was significantly associated with the Q (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 - Q3) Q values (4.7 (2.8 - 7.5) vs. 3.8 (2.5 - 5.7) x 10, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. Q showed a relevant influence on Q. Present results indicate that TMAO may cross the blood-CSF barrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2020-2763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590830PMC
September 2020

Simultaneous determination of 24,25- and 25,26-dihydroxyvitamin D3 in serum samples with liquid-chromatography mass spectrometry - A useful tool for the assessment of vitamin D metabolism.

J Chromatogr B Analyt Technol Biomed Life Sci 2020 Nov 6;1158:122394. Epub 2020 Oct 6.

Institute of Chemistry, University of Graz, Graz, Austria.

Vitamin D status is typically assessed by the measurement of 25-hydroxyvitamin D (25(OH)D). However, in selected patient groups the sole determination of 25(OH)D has been proven insufficient for this purpose. The simultaneous measurement of additional vitamin D metabolites may provide useful information for a better evaluation of the vitamin D status. Therefore, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 25(OH)D, 25(OH)D, 24,25(OH)D and additionally 25,26(OH)D, which was identified with a synthesized pure substance. Pure and deuterated substances were used to prepare calibrators and internal standards for all target metabolites. Pre-analytical sample preparation comprised protein precipitation followed by liquid-liquid-extraction and derivatization with 4-Phenyl-1,2,4-triazole-3,5-dione (PTAD) using 50 µL sample volume. Samples were analyzed on an Agilent HPLC 1260 system equipped with a silica-based Kinetex® 5 µm F5 100 Å core-shell column (150 × 4.6 mm) coupled to a Sciex 4500 mass spectrometer. For all four metabolites, limit of detection (LoD) and limit of quantification (LoQ) ranged from 0.3 to 1.5 nmol/L and 1.0 to 3.1 nmol/L, respectively. Recovery varied between 76.1 % and 84.3 %. Intra- and inter-assay imprecision were <8.6 % and <11.5 %, respectively. The analysis of external and internal quality control samples showed good accuracy for 25(OH)D, 25(OH)D, 24(R),25(OH)D and 25,26(OH)D. Method comparison studies with human samples that were also analyzed with two other LC-MS/MS methods showed close agreement. Finally, the present method has been shown capable of identifying patients with 24-hydroxylase deficiency, which proves its clinical utility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2020.122394DOI Listing
November 2020

Periodontal treatment and vascular inflammation in patients with advanced peripheral arterial disease: A randomized controlled trial.

Atherosclerosis 2020 11 23;313:60-69. Epub 2020 Sep 23.

Division of Operative Dentistry, Periodontology and Prosthodontics, Department of Dental Medicine and Oral Health, Medical University of Graz, Austria.

Background And Aims: Observational studies support an association between periodontitis and cardiovascular diseases. The study objective was to assess vascular inflammation after periodontal treatment in patients with peripheral arterial disease.

Methods: Ninety patients with peripheral arterial disease (PAD) and severe periodontitis were enrolled in a randomized, controlled trial. Thirty patients underwent non-surgical periodontal therapy and received additional systemic antibiotics (PT1 group), while 30 patients received the same therapy without antibiotics (PT2 group). The remaining thirty patients did not receive periodontal therapy (CG, control group). The primary outcome of this treatment was a reduction in vascular inflammation three months after periodontal treatment as determined by F-FDG PET/CT values. Secondary outcomes were changes in the inflamed periodontal surface area (PISA) and other periodontal parameters, changes in vascular biomarkers, and adverse cardiovascular events.

Results: After three months of treatment, a significant improvement in periodontal health was observed in the treatment groups. However, no difference in the primary outcome in the aorta was observed in the three study groups (median target to background ratio follow-up/baseline, PT1 1.00; 95% CI 0.97-1.10, PT2 1.00; 95% CI 0.98-1.1, CG 1.1; 95% CI 0.99-1.1, p = 0.75). No significant differences were detected in most diseased segments and active segments. In addition, no differences were observed in F-FDG uptake in the carotid, iliac, femoral, and popliteal arteries. No differences with regard to relative changes in vascular biomarkers were noted, and no serious cardiovascular adverse events occurred.

Conclusions: Periodontal treatment was effective and safe but did not reduce vascular inflammation in patients with PAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.019DOI Listing
November 2020

Determination of Trimethylamine-N-oxide by a Simple Isocratic High-Throughput Liquid-Chromatography Tandem Mass-Spectrometry Method.

Clin Lab 2020 Sep;66(9)

Background: As trimethylamine-N-oxide (TMAO) is considered to be associated with various diseases, rapid determination of serum TMAO concentration is of clinical interest. This study is aimed at evaluating the analytical performance of a simple isocratic liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for TMAO quantification.

Methods: TMAO measurements were performed on a tandem mass spectrometer, SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA), coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies, Santa Clara, CA, USA). The separation was performed on a Hypercarb Porus Grahitic Carbon (PGC) column (ThermoFisher Scientific, Waltham, MA, USA) by isocratic elution mode. Linearity, precision, recovery, and pre-analytical requirements of the TMAO LC-MS/MS method were evaluated. The imprecision acceptance criteria were defined 15%. We investigated sample stability at room temperature (RT) and assessed the serum TMAO concentrations of 188 healthy adults.

Results: The TMAO LC-MS/MS method was linear over the concentration range of 0.5 - 80 μmol/L. Intra- and inter-day precision ranged between 2.24 - 3.37% and 6.95 - 9.97%, recovery between 106 - 114%, respectively. At RT, serum samples were stable for 8 days. The median serum TMAO concentration of 188 healthy adults was 2.27 μmol/L (2.5th and 97.5th percentile: 0.75 - 10.46 μmol/L), respectively.

Conclusions: The isocratic TMAO LC-MS/MS shows a broad analytical range and meets the imprecision acceptance criteria of 15%. This method is a robust and reliable diagnostic tool for the assessment of the human TMAO status. Serum samples are stable at RT for at least 8 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.200122DOI Listing
September 2020

Telomere shortening associates with elevated insulin and nuchal fat accumulation.

Sci Rep 2020 04 22;10(1):6863. Epub 2020 Apr 22.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Obesity and relative leucocyte telomere length (RTL) are both linked to accelerated aging and premature mortality. We examined if nuchal subcutaneous adipose tissue (SAT) thickness, a surrogate marker of central trunk-weighted obesity, is an independent predictor of RTL that provides information beyond BMI, metabolic and inflammatory markers. RTL and nuchal SAT thickness were determined in 362 participants of the STYJOBS/EDECTA study (STYrian Juvenile Obesity Study, Early DEteCTion of atherosclerosis), which included overweight individuals and matched eutrophic controls. Fasting plasma samples were used for the measurement of leptin, resistin, adiponectin, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), liver enzymes, creatinine, cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, oxidized LDL, triglycerides, homocysteine and uric acid. Furthermore, all participants underwent carotid artery ultrasound. Obese individuals had markedly higher body mass index (BMI), nuchal SAT thickness, hip and waist circumferences and carotid intima media thickness (IMT) than eutrophic controls. In addition, they showed typical biochemical abnormalities related to energy metabolism, systemic inflammation and liver function. RTL was inversely correlated with nuchal SAT thickness, IMT, hs-CRP, alkaline phosphatase, insulin, resistin, and leptin. Positive correlations were seen with homocysteine and creatinine. Stepwise linear regression analyses identified nuchal SAT thickness and insulin as the only significant predictors of RTL. In conclusion, nuchal SAT thickness is a robust predictor of RTL that provides information beyond traditional obesity-related metabolic and inflammatory biomarkers. This suggests an important role of fat depots at the neck for accelerated telomere shortening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-63916-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176638PMC
April 2020

Age progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.

J Pharmacokinet Pharmacodyn 2020 04 25;47(2):145-161. Epub 2020 Feb 25.

Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria.

Background: Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task.

Methods: Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (C) to gradually reach 3.5 μg mL over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis.

Results: Age was significant covariate for baseline BIS effect (E), inhibitory propofol concentration at 50% BIS decline (IC) and maximum BIS decline (E). First-order rate constant K of 0.47 min in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended C of 3.5 μg mL for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year.

Conclusion: We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol C of 3.5 μg mL might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of C 3.5 μg mL for 20-29 year should be gradually decreased to 2.0 μg mL for 80-89 year.

Clinical Trial Registry Numbers: European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10928-020-09678-0DOI Listing
April 2020

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers.

Dis Markers 2020 6;2020:7897240. Epub 2020 Jan 6.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.

Background: The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA.

Methods: Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T polymorphism genotyping and fructose H/CH breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire.

Results: The median TMAO and zonulin serum concentrations were 2.66 (1.93-4.14) mol/L and 40.83 (34.73-47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms ( = 0.011, = 0.160). The strongest correlations were observed in 87 females ( = 0.010, = 0.274) and 49 males ( = 0.027, = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA ( = 0.062, = -0.269).

Conclusion: This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7897240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969987PMC
September 2020

Vitamin D testing: advantages and limits of the current assays.

Eur J Clin Nutr 2020 02 6;74(2):231-247. Epub 2020 Jan 6.

Department of Medicine, Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA.

Vitamin D deficiency and insufficiency has become a pandemic health problem with a consequent increase of requests for determining circulating levels of 25-hydroxyvitamin D [25(OH)D]. However, the analytical performance of these immunoassays, including radioimmunoassay and ELISA, is highly variable, and even mass spectrometric methods, which nowadays serves as the gold standard for the quantitatively determination of 25(OH)D, do not necessarily produce comparable results, creating limitations for the definition of normal vitamin D status ranges. To solve this problem, great efforts have been made to promote standardization of laboratory assays, which is important to achieve comparable results across different methods and manufacturers. In this review, we performed a systematic analysis evaluating critically the advantages and limits of the current assays available for the measure of vitamin D status, i.e., circulating 25(OH)D and its metabolites, making suggestions that could be used in the clinical practice. Moreover, we also suggest the use of alternatives to blood test, including standardized surveys that may be of value in alerting health-care professionals about the vitamin D status of their patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-019-0553-3DOI Listing
February 2020

A Micromethod for Polyphenol High-Throughput Screening Saves 90 Percent Reagents and Sample Volume.

Antioxidants (Basel) 2019 Dec 21;9(1). Epub 2019 Dec 21.

Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Devision of Physiological Medicine, Medical University of Graz, Graz 8010, Austria.

There is ample evidence that polyphenols are important natural substances with pronounced antioxidative properties. This study aimed to develop a fast and reliable method to determine total polyphenol content (TPC) in foodstuffs and human samples. The microtitration format offers the advantage of low sample volumes in the microlitre range, facilitating high-throughput screening with 40 samples simultaneously. We accordingly adjusted the so-called Folin-Ciocalteu method to a microtitre format (polyphenols microtitre-PPm) with 90% reduction of reagents. The assay was standardized with gallic acid in the range between 0.1 and 3 mM, using a 20 µL sample volume. The intra-assay coefficient of variation (CV) was less than 5%, and inter-assay CV was in the range of 10%. Wavelength was measured at 766 nm after two hours of incubation. This micromethod correlates significantly with both the classical Folin-Ciocalteu method and High-Performance Thin-Layer Chromatography (HPTLC) (r = 0.9829). We further observed a significant correlation between PPm and total antioxidants (r = 0.918). The highest polyphenol concentrations were obtained for red, blue, and black fruits, vegetables, and juices. Extracts of red grapes could be harvested almost sugar free and might serve as a basis for polyphenol supplementation. Beer, flour, and bread contained polyphenol concentrations sufficient to meet the minimal daily requirement. We conclude that PPm is a sensitive and reliable method that detects polyphenols even in samples diluted 10-fold. The literature strongly recommends further investigations on the effects of polyphenol uptake on human and animal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023636PMC
December 2019

Vitamin D assessment in perioperative medicine and critical care : A prospective observational pilot study.

Wien Klin Wochenschr 2021 Feb 4;133(3-4):79-85. Epub 2019 Dec 4.

Div. of Endocrinology and Diabetology, Dept. of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: There is controversy about the impact of acute illness on vitamin D levels. This study was carried out to assess the influence of perioperative fluid loading on 25-hydroxy-vitamin D [25(OH)D] levels. The study evaluated the clinical utility of a commonly available chemiluminescence assay (ECLIA, IDS-iSYS) and liquid chromatography/mass spectrometry (LC-MS/MS) in the diagnosis of vitamin D deficiency in this setting.

Methods: In this prospective observational pilot study in adult patients undergoing cardiovascular surgery on cardiopulmonary bypass (CPB), blood samples drawn at preoperative baseline (t1), after weaning from CPB (t2), on intensive care unit (ICU) admission (t3) and on the first (t4) and second (t5) postoperative days were analyzed.

Results: A total of 26 patients (130 samples) were included in this study. Fluid loading by CPB led to a median reduction of 25(OH)D by -22.6% (range -54.5% to -19.5%) between t1 and t2. Cohen's kappa (κ) for method agreement for vitamin D deficiency (tested cut-off values 20 ng/ml and 12 ng/ml), was κ = 0.291 (p < 0.001) and κ = 0.469 (p < 0.001), respectively. The mean difference between measurements by ECLIA and LC-MS/MS was 4.8 ng/ml (±5.7), Pearson's r for correlation was 0.73 (p < 0.001). The biologically inactive C3-epimer did not contribute to 25(OH)D levels assessed by LC-MS/MS.

Conclusion: The 25(OH)D measurements by chemiluminescence assays can noticeably deviate from those measured by LC-MS/MS, which can be considered the unequivocal gold standard. These assays may still be acceptably reliable in the screening for vitamin D deficiency, especially in the setting of low vitamin D levels. Stricter definitions, e.g. serum 25(OH)D levels lower than 12 ng/ml, may be used to diagnose deficiency with low false positive rate.

Trial Registration: DRKS00009216, German Clinical Trials Registry ( www.drks.de ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-019-01584-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875852PMC
February 2021

Associations between tryptophan and iron metabolism observed in individuals with and without iron deficiency.

Sci Rep 2019 10 10;9(1):14548. Epub 2019 Oct 10.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Current literature proposes associations between tryptophan metabolism and anaemia. However, study cohorts are rather small and final conclusions are still lacking. Here, we evaluated potential associations of tryptophan, kynurenine, and kynurenic acid with indicators of iron metabolism (i.e., mean corpuscular volume, mean corpuscular haemoglobin, ferritin, transferrin saturation, serum iron, transferrin, soluble transferrin receptor, reticulocyte haemoglobin) and haemoglobin in 430 individuals grouped by the presence or absence of iron deficiency or anaemia. Indicators of tryptophan metabolism were positively correlated with haemoglobin and markers of iron metabolism (p-values: <0.001-0.038; r-values: 0.100-0.305). The strongest correlation was observed between tryptophan and haemoglobin (p < 0.001, r = 0.305). The cubic regression model yielded the highest R-square values between haemoglobin and tryptophan markers. Overall, 115 patients with iron deficiency showed lower tryptophan and kynurenic acid concentrations compared to 315 individuals without iron deficiency. Six patients with anaemia of chronic disease were observed with the lowest serum tryptophan levels and the highest kynurenine/tryptophan ratio compared to 11 individuals with iron deficiency anaemia and 413 non-anaemic patients. This study showed little/moderate associations between haemoglobin, biomarkers of iron metabolism and tryptophan markers. Further studies are needed to get better insight in the causality of these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-51215-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787180PMC
October 2019

Weight Gain During Treatment of Bipolar Disorder (BD)-Facts and Therapeutic Options.

Front Nutr 2019 11;6:76. Epub 2019 Jun 11.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

Bipolar disorder (BPD) is a mood disorder, which is characterized by alternating affective states, namely (hypo)mania, depression, and euthymia. Evidence is growing that BPD has indeed a biologic substrate characterized by chronic inflammation, oxidative stress, and disturbed energy metabolism. Apart from this, there is obviously a hereditary component of this disease with multi-genetic factors. Most probably a susceptibility threshold favors the outbreak of clinical disease after a cascade of stress events that remain to be elucidated in more detail. Evidence is also growing that weak points in brain energy metabolism contribute to outbreak and severity of BPD. Conventional psychopharmacologic therapy must be reassessed under the aspects of weight cycling and development of central obesity as a deterioration factor for a worse clinical course leading to early cardiovascular events in BPD subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2019.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579840PMC
June 2019

Iron status determination in individuals with Helicobacter pylori infection: conventional vs. new laboratory biomarkers.

Clin Chem Lab Med 2019 06;57(7):982-989

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Background Helicobacter pylori has been associated with iron deficiency (ID). This study is aimed at investigating ID with conventional (ferritin, transferrin saturation [TSAT]) and new biomarkers (soluble transferrin receptor [sTfR], sTfR/log ferritin, reticulocyte hemoglobin content [CHr], hepcidin-25) in patients sub-grouped by the presence or absence of H. pylori infection. Methods In total, 200 consecutive outpatients, who were referred for the H. pylori 13C-urea breath test (13C-UBT), underwent blood testing for ID. Additionally, Thomas-plot (TP)-analyses (sTfR/log ferritin, CHr) were calculated. Results Fifty-three and 147 individuals were found with and without H. pylori infection, respectively. Patients with H. pylori infection showed a higher sTfR concentration (p<0.02) and a higher sTfR/log ferritin ratio (p<0.05). Based on a ferritin <30 μg/L and/or a TSAT <20%, 25/53 (47.2%) patients with H. pylori infection and 63/147 (42.9%) without H. pylori infection showed ID. Based on TP-analyses, 10/53 (18.9%) patients with and 17/147 (11.6%) without H. pylori infection were identified with ID. Completed eradication therapy tended to be associated with functional ID. Conclusions Helicobacter pylori infection was associated with significantly higher plasma sTfR concentrations and sTfR/log ferritin ratios. Patients with H. pylori eradication therapy were more often detected with functional ID compared to patients without eradication therapy, when using the new biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2018-1182DOI Listing
June 2019

Evaluation of a commercial liquid-chromatography high-resolution mass-spectrometry method for the determination of hepcidin-25.

Biochem Med (Zagreb) 2019 Jun 15;29(2):020701. Epub 2019 Apr 15.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Introduction: Reliable determination of hepcidin-25, a key regulator of iron metabolism, is important. This study aimed at evaluating the performance of the Hepcidin-25 Liquid Chromatography-Tandem Mass-Spectrometry (LC-MS/MS) Kit (Immundiagnostik AG, Bensheim, Germany) for quantification of the hepcidin-25 protein.

Materials And Methods: Precision, accuracy, linearity, and preanalytical requirements of the liquid-chromatography high-resolution mass-spectrometry (LC-HR-MS) method were evaluated. The imprecision and bias acceptance criteria were defined ≤ 15%. We investigated sample stability at room temperature (RT) and after repeated freeze and thaw cycles. Additionally, we assessed serum hepcidin-25 concentrations of 165 healthy adults referred for a medical check-up.

Results: The hepcidin-25 LC-MS/MS assay was linear over the concentration range of 3 - 200 ng/mL. Within- and between-run precision ranged between 1.9 - 8.6% and 5.1 - 12.4%, respectively. The mean bias of the low and high control material was - 2.7% and 2.1%, respectively. At RT, serum samples were stable for 3 h (mean bias + 0.3%). After two and three freeze and thaw cycles, hepcidin-25 concentrations showed a bias of + 8.0 and + 20%, respectively. Of 165 healthy adults, 109 females had a significantly lower median of 8.42 (range: 1.00 - 60.10) ng/mL compared to 56 males with 15.76 (range: 1.50 - 60.50) ng/mL (P = 0.002).

Conclusions: The hepcidin-25 LC-MS/MS kit shows a broad analytical range and meets the imprecision and bias acceptance criteria of ≤ 15%. Serum samples can be stored at RT for 3 h and resist up to two freeze and thaw cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11613/BM.2019.020701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457918PMC
June 2019

Subcutaneous adipose tissue distribution and telomere length.

Clin Chem Lab Med 2019 08;57(9):1358-1363

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Background Overweight and obese individuals have a reduced life expectancy due to cardiovascular disease (CVD), type 2 diabetes, stroke and cancer. Systemic inflammation and premature telomere shortening have been discussed as potential mechanisms linking these conditions. We investigated the relation of subcutaneous adipose tissue (SAT) distribution to leukocyte relative telomere length (RTL). Methods We measured RTL in 375 participants of the observational STYJOBS/EDECTA cohort (ClinicalTrials.gov Identifier NCT00482924) using a qPCR based method. SAT distribution was determined by lipometry yielding a percent body fat value and SAT thicknesses at 15 standardized locations across the entire body. A correlation analysis between RTL, age, sex, lipometry data and conventional body measures (body mass index [BMI], waist-, hip circumference, waist-to-hip ratio, waist-to-height ratio) was calculated. The strongest determinants of RTL were determined by a stepwise multiple regression analysis. Results RTL was not associated with age or sex. RTL was significantly negatively correlated with BMI, percent body fat, waist-, hip circumference and waist-to-height ratio. Furthermore, RTL correlated with SAT at the following locations: neck, triceps, biceps, upper back, front chest, lateral chest, upper abdomen, lower abdomen, lower back, hip, front thigh, lateral thigh, rear thigh and calf. Stepwise regression analysis revealed nuchal and hip SAT as the strongest predictors of RTL. No significant association was seen between RTL and waist-to-hip ratio. Conclusions RTL is negatively associated with parameters describing body fat composure. Nuchal and hip SAT thicknesses are the strongest predictors of RTL. Central obesity appears to correlate with premature genomic aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2018-0801DOI Listing
August 2019

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

Clin Nutr 2019 12 10;38(6):2913-2921. Epub 2019 Jan 10.

Department of Immunology and Pathophysiology, Medical University of Graz, Otto Loewi Research Center, Heinrichstraße, Graz, Austria.

Background & Aims: Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches.

Methods: The SAT of AN patients (n = 18, body mass index (BMI) 15.3 ± 1.3 kg/m) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (D) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined.

Results: The mean MI was 15.7 ± 1.4 kg/m. The D considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low D: 1.3-28.4 mm, and Group 2 showed values up to 58.2 mm (corresponding to approximately 6 kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2 at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level.

Conclusion: Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2018.12.031DOI Listing
December 2019

Adiponectin is decreased in bipolar depression.

World J Biol Psychiatry 2019 12 20;20(10):813-820. Epub 2018 Sep 20.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Graz, Austria.

Bipolar disorder (BD) is often accompanied by medical comorbidities, which affect illness course and prognosis. Adipokines may not only be involved in the aetiopathogenetic mechanisms of these comorbidities; there might be an association between adipokines and the neuropsychiatric core features of BD such as mood disturbances and cognitive deficits. In this investigation, fasting blood samples from 120 individuals with BD (75 euthymic and 45 with mild depressive symptoms) and 68 control subjects were taken and adiponectin and leptin concentrations were analysed. We found that, in female participants, adiponectin levels differed significantly between patients and controls indicating lower levels in individuals with BD, even after controlling for BMI ((1,92) = 4.65,  = 0.034, partial η = 0.05). After stratification by mood status we found a significant difference in adiponectin between controls, euthymic and depressive patients ((2, 180) = 4.90,  = 0.008, partial η = 0.05). This investigation confirms previous findings of an association between low adiponectin levels and depressive state in individuals with BD. Beyond its immediate effect on central nervous system function, adiponectin might interfere with pathophysiological mechanisms of BD and its somatic comorbidities via involvement in metabolic and inflammatory processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15622975.2018.1500033DOI Listing
December 2019

Branched-chain amino acids are associated with metabolic parameters in bipolar disorder.

World J Biol Psychiatry 2019 12 27;20(10):821-826. Epub 2018 Jul 27.

Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.

An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analysed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters. BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton Depression-Scale, and Beck Depression Inventory II, in male individuals Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases or insulin resistance), health state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15622975.2018.1487077DOI Listing
December 2019

Work Intensity, Low-Grade Inflammation, and Oxidative Status: A Comparison between Office and Slaughterhouse Workers.

Oxid Med Cell Longev 2018 18;2018:2737563. Epub 2018 Apr 18.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.

Limited knowledge exists about the impact of physical workload on oxidative stress in different occupational categories. Thus, we aimed to investigate the oxidative and inflammatory status in employees with different physical workloads. We enrolled a total of 79 male subjects, 27 office workers (mean age 38.8 ± 9.1 years) and 52 heavy workers, in a slaughterhouse (mean age 40.8 ± 8.2 years). Fasting blood was drawn from an antecubital vein in the morning of the midweek before an 8-hour or 12-hour work shift. The antioxidative capacity was assessed measuring total antioxidant capacity (TAC), uric acid, total polyphenols (PPm), and endogenous peroxidase activity (EPA). Total peroxides (TOC), malondialdehyde (MDA), and myeloperoxidase (MPO) were analyzed as prooxidative biomarkers, and an oxidative stress index (OSI) was calculated. In addition, hsCRP, interleukin-6 (IL-6), MDA-LDL IgM antibodies, galectin-3, adrenocorticotropic hormone (ACTH), and the brain-derived neurotrophic factor (BDNF) were measured as biomarkers of chronic systemic inflammation and emotional stress. TOC ( = 0.032), TAC ( < 0.001), ACTH ( < 0.001), OSI ( = 0.011), and hsCRP ( = 0.019) were significantly increased in the heavy workers group, while EPA, BDNF ( < 0.001), and polyphenols ( = 0.004) were significantly higher in office workers. Comparison between 8 and 12 h shifts showed a worse psychological condition in heavy workers with increased levels for hsCRP ( = 0.001) and reduced concentration of BDNF ( = 0.012) compared to office workers. Oxidative stress and inflammation are induced in heavy workers and are particularly pronounced during long working hours, that is, 12-hour versus 8-hour shifts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/2737563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932461PMC
October 2018

Prospective cohort studies of beta-trace protein and mortality in haemodialysis patients and patients undergoing coronary angiography.

Nephrol Dial Transplant 2018 11;33(11):1984-1991

Division of Nephrology, Department of Internal Medicine I, Medical University of Bonn, Bonn.

Background: Beta-trace protein (BTP) is a low-molecular-weight glycoprotein, which may serve as an endogenous biomarker of kidney function and cardiovascular risk.

Methods: We examined cardiovascular and all-cause mortality according to BTP concentrations in 2962 individuals referred for coronary angiography from the Ludwigshafen Risk and Cardiovascular Health study and in 907 patients with Type 2 diabetes mellitus undergoing haemodialysis from the German Diabetes and Dialysis (4D) study.

Results: Haemodialysis patients had considerably higher median (interquartile range) BTP concentrations [6.00 (4.49-7.96) mg/L] and experienced a 4-fold increased mortality rate compared with coronary angiography patients [BTP concentration: 0.55 (0.44-0.67) mg/L]. After adjustment for age, sex, cardiovascular risk factors and creatinine, 4D patients in the highest quartile (>7.96 mg/L) had a 1.6-fold increased rate of all-cause mortality [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.19-2.20] compared with the lowest quartile (<4.49 mg/L) (P = 0.002) In patients undergoing coronary angiography, the adjusted HRs (95% CI) for all-cause and cardiovascular mortality were 1.23 (1.0-1.51) and 1.27 (0.99-1.63) in the highest (>0.67 mg/L) compared with the lowest (<0.44 mg/L) quartile (P = 0.043 and 0.062). In both cohorts, the BTP/creatinine ratio was a stronger predictor of all-cause and cardiovascular mortality compared with BTP.

Conclusion: BTP was associated with all-cause mortality independently of renal function in haemodialysis patients. The BTP/creatinine ratio was more predictive for all-cause and cardiovascular mortality in haemodialysis patients and individuals referred for angiography compared with BTP as single marker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfy025DOI Listing
November 2018

The relationship between inflammatory state and quantity of affective episodes in bipolar disorder.

Psychoneuroendocrinology 2018 04 3;90:61-67. Epub 2018 Feb 3.

Medical University of Graz, Department of Psychiatry and Psychotherapeutic Medicine, Graz, Austria.

Objectives: Immunological/inflammatory processes have been proposed to play an important role in the pathophysiology of mood disorders, including bipolar disorder (BD). The present study aimed to examine the influence of immune activation, measured on the basis of inflammatory markers, on the course of illness, proxied by the number of affective episodes, in patients with BD.

Methods: We investigated the relationship between high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6), two inflammatory markers and characteristics of course of illness (e.g. number of affective episodes, depressive and manic symptoms) amongst a group of 190 individuals with BD.

Results: Among females with BD, there was a positive correlation between levels of hsCRP and the number of manic and depressive episodes. Moreover, levels of hsCRP and IL-6 were positively correlated with current manic symptoms, as measured by Young-Mania-Rating-Scale. There were no significant correlations between levels of the foregoing inflammatory markers, and manic and depressive symptoms in male individuals with BD. Furthermore, compared to their untreated counterparts, female patients treated with lithium demonstrated higher levels of hsCRP and male patients treated with atypical antipsychotics lower levels of hsCRP, respectively.

Conclusions: Our results are suggesting that the association between inflammatory state and affective response in patients with BD may be gender-dependent. A future research would be to evaluate whether or not these gender differences can be observed in other inflammatory pathways associated with BD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2018.01.024DOI Listing
April 2018

Assessment of tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.

Psychiatry Res 2018 04 22;262:595-599. Epub 2017 Sep 22.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. Electronic address:

This prospective cross-sectional study aimed to investigate the potential association between primary-adult lactose malabsorption, fructose malabsorption, tryptophan (TRP) metabolism and the presence of depressive signs. Overall 251 patients, who were referred for lactase gene C/T polymorphism genotyping and fructose hydrogen/methane breath testing, were included. All participants filled out the Beck Depression Inventory (BDI II). Serum concentrations of tryptophan (TRP), kynurenine (KYN), kynuric acid (KYNA), and TRP competing amino acids (leucine, isoleucine, valine, phenylalanine, tyrosine) were measured by high-pressure liquid-chromatography. Logistic regression analysis was performed with lactose malabsorption, fructose malabsorption and all potential biomarkers of TRP metabolism to assess the effect on signs of depression, defined as a BDI II score > 13. Primary-adult lactose malabsorption and fructose malabsorption was detected in 65 (25.90%) and 65 (25.90%) patients, respectively. Fructose malabsorption was significantly associated with BDI II score, whereas no such relationship was found for lactose malabsorption. Serum levels of TRP and TRP metabolites were no predictors of depression. The authors suggest to conduct further prospective longitudinal studies in order to get further insight of associations between carbohydrate malabsorption, biomarkers and mood disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2017.09.049DOI Listing
April 2018

Adiponectin Predicts High-Density Lipoprotein Cholesterol Efflux Capacity in Adults Irrespective of Body Mass Index and Fat Distribution.

J Clin Endocrinol Metab 2017 11;102(11):4117-4123

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.

Context: Obesity is associated with hypoadiponectemia, dyslipidemia, and increased risk of cardiovascular disease (CVD). Mechanisms linking these conditions remain to be fully understood. Cholesterol efflux capacity (CEC) is a crucial functional property of high-density lipoprotein (HDL) that strongly predicts CVD incidence.

Objective: We investigated whether age, fat distribution, and other obesity-related factors affect CEC in juvenile and adult overweight/obese participants of the STYJOBS/EDECTA cohort (NCT00482924).

Design: We performed an observational study.

Main Outcome Measures: CEC and its association with body measures and related metabolic parameters was assessed in 683 participants (281 juveniles, of whom 227 were overweight/obese; 402 adults, of whom 197 were overweight/obese).

Results: Pearson correlation analysis showed that, after Bonferroni correction, CEC was significantly inversely correlated with body mass index (BMI), carotid diameter, waist circumference, waist-to-hip, waist-to-height ratio, oxidized low-density lipoprotein, and uric acid and with the liver markers alanine-aminotransferase and choline esterase. CEC was positively correlated with HDL cholesterol, total cholesterol, apolipoprotein A1, and adiponectin in adults, whereas in juveniles only apolipoprotein A1 showed a significant positive correlation with CEC. Age-stratified linear regression analyses with CEC as the outcome variable identified adiponectin as the most significant predictor of CEC in adults. The results did not change when either BMI or waist-to-hip ratio as a factor of fat distribution was included in the models.

Conclusions: Hypoadiponectemia is a robust predictor of reduced cholesterol efflux capacity in adults irrespective of BMI and fat distribution. Further investigations are needed to assess whether adiponectin is a causal determinant of CEC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2017-00933DOI Listing
November 2017

Tryptophan breakdown and cognition in bipolar disorder.

Psychoneuroendocrinology 2017 Jul 27;81:144-150. Epub 2017 Apr 27.

Department of Psychiatry and Psychotherapy, Medical University of Graz, Graz, Austria.

Introduction: It has been demonstrated that bipolar disorder (BD) is often accompanied by cognitive deficits across all subdomains including verbal memory, attention and executive functioning. Cognitive deficits are observed both during episodes of mania or depression, as well as during the euthymic phase. It has been proposed that chronic immune-mediated inflammation in the central nervous system results in alterations in neural structures that subserve cognitive function. Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity. Herein, we sought to determine whether serum levels of kynurenine and/or its metabolites were associated with cognitive function in BD.

Methods: In this investigation 68 euthymic individuals with BD according to DSM-IV completed a cognitive test battery to asses premorbid intelligence (Multiple Choice Word Test; MWT-B), verbal memory (California Verbal Learning Test; CVLT), attention (d2 Test of Attention; d2 test, Trail Making Test-A; TMT-A, Stroop word reading/Stroop color naming) and executive functioning (TMT-B, Stroop interference). In addition, fasting blood samples were taken and serum levels of kynurenine and its metabolites 3-hydroxykynurenine and kynurenic acid were analyzed. Subsequently ratios were formed from individual parameters. Patient data were compared with those of a mentally healthy control group (n=93).

Results: In male participants with BD only we found a significant negative correlation between the 3-hydroxykynurenine to kynurenic acid ratio and performance on the CVLT. Additionally, the kynurenine to 3-hydroxykynurenine ratio was associated with performance on a sub-score of the CVLT. Those associations were neither present in female individuals with BD nor in the control group.

Discussion: Our findings suggest that a shift towards the hydroxykynurenine arm of the kynurenine pathway may be associated with poorer memory performance due to its effects on neuronal functioning and neurogenesis in the hippocampus. Our results implicate a mechanistic role of central inflammatory processes in cognitive functions in adults with bipolar disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2017.04.015DOI Listing
July 2017

Myeloperoxidase, asymmetric dimethyl-arginine and the renin-angiotensin-aldosterone-system in cardiovascular risk patients: Cross-sectional findings from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

Clin Biochem 2017 Sep 18;50(13-14):739-745. Epub 2017 Mar 18.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address:

Objectives: The leukocyte-derived myeloperoxidase (MPO), the nitric oxidase synthase (NOS) inhibitor asymmetrical dimethyl-arginine (ADMA) and the renin-angiotensin-aldosterone-system (RAAS) are associated with cardiovascular diseases (CVD). This study aimed to investigate potential interactions between the RAAS, ADMA and MPO in cardiovascular risk patients.

Design And Methods: All in all, 1446 patients, who were referred to coronary angiography, were included in this prospective study. MPO, ADMA and circulating serum markers of the RAAS system were measured. Additionally, all-cause and CVD mortality, cardiovascular risk factors, inflammatory and endothelial markers, and medication use were investigated.

Results: MPO concentrations were significantly associated with ADMA (P=0.002), renin (P=0.001) and angiotensin II levels (P=0.015), whereas ADMA was in tendency associated with renin (P=0.059) and significantly with angiotensin II (P=0.001). Both, ADMA and MPO were inversely correlated with angiotensinogen, angiotensin I and the angiotensin I/angiotensin II ratio. ADMA and angiotensin II were found stronger independent risk factors for all-cause and CVD mortality compared to MPO.

Conclusions: MPO concentrations were significantly associated with higher ADMA levels and an up-regulated circulating RAAS in patients with CVD. Moreover, serum levels of ADMA and angiotensin II were shown to be more predictive for all-cause and CVD mortality compared to MPO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2017.03.013DOI Listing
September 2017