@phdthesis{Kochlik2019, author = {Kochlik, Bastian Max}, title = {Relevance of biomarkers for the diagnosis of the frailty syndrome}, doi = {10.25932/publishup-44118}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441186}, school = {Universit{\"a}t Potsdam}, pages = {IV, 99}, year = {2019}, abstract = {Frailty and sarcopenia share some underlying characteristics like loss of muscle mass, low muscle strength, and low physical performance. Imaging parameters and functional examinations mainly assess frailty and sarcopenia criteria; however, these measures can have limitations in clinical settings. Therefore, finding suitable biomarkers that reflect a catabolic muscle state e.g. an elevated muscle protein turnover as suggested in frailty, are becoming more relevant concerning frailty diagnosis and risk assessment. 3-Methylhistidine (3-MH) and its ratios 3-MH-to-creatinine (3-MH/Crea) and 3 MH-to-estimated glomerular filtration rate (3-MH/eGFR) are under discussion as possible biomarkers for muscle protein turnover and might support the diagnosis of frailty. However, there is some skepticism about the reliability of 3-MH measures since confounders such as meat and fish intake might influence 3-MH plasma concentrations. Therefore, the influence of dietary habits and an intervention with white meat on plasma 3-MH was determined in young and healthy individuals. In another study, the cross-sectional associations of plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status (robust, pre-frail and frail) were investigated. Oxidative stress (OS) is a possible contributor to frailty development, and high OS levels as well as low micronutrient levels are associated with the frailty syndrome. However, data on simultaneous measures of OS biomarkers together with micronutrients are lacking in studies including frail, pre-frail and robust individuals. Therefore, cross-sectional associations of protein carbonyls (PrCarb), 3-nitrotyrosine (3-NT) and several micronutrients with the frailty status were determined. A validated UPLC-MS/MS (ultra-performance liquid chromatography tandem mass spectrometry) method for the simultaneous quantification of 3-MH and 1-MH (1 methylhistidine, as marker for meat and fish consumption) was presented and used for further analyses. Omnivores showed higher plasma 3-MH and 1-MH concentrations than vegetarians and a white meat intervention resulted in an increase in plasma 3-MH, 3 MH/Crea, 1-MH and 1-MH/Crea in omnivores. Elevated 3-MH and 3-MH/Crea levels declined significantly within 24 hours after this white meat intervention. Thus, 3-MH and 3-MH/Crea might be used as biomarker for muscle protein turnover when subjects did not consume meat 24 hours prior to blood samplings. Plasma 3-MH, 3-MH/Crea and 3-MH/eGFR were higher in frail individuals than in robust individuals. Additionally, these biomarkers were positively associated with frailty in linear regression models, and higher odds to be frail were found for every increase in 3 MH and 3-MH/eGFR quintile in multivariable logistic regression models adjusted for several confounders. This was the first study using 3-MH/eGFR and it is concluded that plasma 3-MH, 3-MH/Crea and 3-MH/eGFR might be used to identify frail individuals or individuals at higher risk to be frail, and that there might be threshold concentrations or ratios to support these diagnoses. Higher vitamin D3, lutein/zeaxanthin, γ-tocopherol, α-carotene, β-carotene, lycopene and β-cryptoxanthin concentrations and additionally lower PrCarb concentrations were found in robust compared to frail individuals in multivariate linear models. Frail subjects had higher odds to be in the lowest than in the highest tertile for vitamin D3 α-tocopherol, α-carotene, β-carotene, lycopene, lutein/zeaxanthin, and β cryptoxanthin, and had higher odds to be in the highest than in the lowest tertile for PrCarb than robust individuals in multivariate logistic regression models. Thus, a low micronutrient together with a high PrCarb status is associated with pre-frailty and frailty.}, language = {en} } @article{AlkerSchwerdtleSchomburgetal.2019, author = {Alker, Wiebke and Schwerdtle, Tanja and Schomburg, Lutz and Haase, Hajo}, title = {A Zinpyr-1-based Fluorimetric Microassay for Free Zinc in Human Serum}, series = {International journal of molecular sciences}, volume = {20}, journal = {International journal of molecular sciences}, number = {16}, publisher = {MDPI}, address = {Basel}, issn = {1661-6596}, doi = {10.3390/ijms20164006}, pages = {13}, year = {2019}, abstract = {Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual's zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body's zinc status, and its suitability as a future biomarker for an individual's zinc status.}, language = {en} } @misc{AlkerSchwerdtleSchomburgetal.2019, author = {Alker, Wiebke and Schwerdtle, Tanja and Schomburg, Lutz and Haase, Hajo}, title = {A Zinpyr-1-based fluorimetric microassay for free zinc in human serum}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1086}, issn = {1866-8372}, doi = {10.25932/publishup-47283}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472833}, pages = {15}, year = {2019}, abstract = {Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual's zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body's zinc status, and its suitability as a future biomarker for an individual's zinc status.}, language = {en} } @article{AichnerMakhmudovRajabovetal.2019, author = {Aichner, Bernhard and Makhmudov, Zafar and Rajabov, Iljomjon and Zhang, Qiong and Pausata, Francesco Salvatore R. and Werner, Martin and Heinecke, Liv and Kuessner, Marie L. and Feakins, Sarah J. and Sachse, Dirk and Mischke, Steffen}, title = {Hydroclimate in the Pamirs Was Driven by Changes in Precipitation-Evaporation Seasonality Since theLast Glacial Period}, series = {Geophysical research letters}, volume = {46}, journal = {Geophysical research letters}, number = {23}, publisher = {American Geophysical Union}, address = {Washington}, issn = {0094-8276}, doi = {10.1029/2019GL085202}, pages = {13972 -- 13983}, year = {2019}, abstract = {The Central Asian Pamir Mountains (Pamirs) are a high-altitude region sensitive to climatic change, with only few paleoclimatic records available. To examine the glacial-interglacial hydrological changes in the region, we analyzed the geochemical parameters of a 31-kyr record from Lake Karakul and performed a set of experiments with climate models to interpret the results. delta D values of terrestrial biomarkers showed insolation-driven trends reflecting major shifts of water vapor sources. For aquatic biomarkers, positive delta D shifts driven by changes in precipitation seasonality were observed at ca. 31-30, 28-26, and 17-14 kyr BP. Multiproxy paleoecological data and modelling results suggest that increased water availability, induced by decreased summer evaporation, triggered higher lake levels during those episodes, possibly synchronous to northern hemispheric rapid climate events. We conclude that seasonal changes in precipitation-evaporation balance significantly influenced the hydrological state of a large waterbody such as Lake Karakul, while annual precipitation amount and inflows remained fairly constant.}, language = {en} }