Publications by authors named "Ulrike E Rolle-Kampczyk"

10 Publications

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Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis.

Sci Rep 2021 Feb 25;11(1):4577. Epub 2021 Feb 25.

Department of Nephrology and Hypertension, Friedrich-Alexander-University (FAU) Erlangen-Nuremberg, Erlangen, Germany.

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, "the" actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient's serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.
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http://dx.doi.org/10.1038/s41598-021-83883-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907124PMC
February 2021

Wood emissions and asthma development: Results from an experimental mouse model and a prospective cohort study.

Environ Int 2021 Feb 18;151:106449. Epub 2021 Feb 18.

UFZ - Helmholtz Centre for Environmental Research Leipzig-Halle, Department of Environmental Immunology, Leipzig, Germany; Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, University of Leipzig, Leipzig, Germany. Electronic address:

Background: Increased use of renewable resources like sustainably produced wood in construction or for all sorts of long-lived products is considered to contribute to reducing society's carbon footprint. However, as a natural, biological material, wood and wood products emit specific volatile organic compounds (VOCs). Therefore, the evaluation of possible health effects due to wood emissions is of major interest.

Objectives: We investigated the effects of an exposure to multiple wood-related VOCs on asthma development.

Methods: A murine asthma model was used to evaluate possible allergic and inflammatory effects on the lung after short- or long-term and perinatal exposure to pinewood or oriented strand board (OSB). In addition, wood-related VOCs were measured within the German prospective mother-child cohort LINA and their joint effect on early wheezing or asthma development in children until the age of 10 was estimated by Bayesian kernel machine regression (BKMR) stratifying also for family history of atopy (FHA).

Results: Our experimental data show that neither pinewood nor OSB emissions even at high total VOC levels and a long-lasting exposure period induce significant inflammatory or asthma-promoting effects in sensitized or non-sensitized mice. Moreover, an exposure during the vulnerable time window around birth was also without effect. Consistently, in our mother-child cohort LINA, an exposure to multiple wood-related VOCs during pregnancy or the first year of life was not associated with early wheezing or asthma development in children independent from their FHA.

Conclusion: Our findings indicate that emissions from wood and wood products at levels commonly occurring in the living environment do not exert adverse effects concerning wheezing or asthma development.
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http://dx.doi.org/10.1016/j.envint.2021.106449DOI Listing
February 2021

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH.

Biomedicines 2020 Sep 14;8(9). Epub 2020 Sep 14.

Applied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany.

Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.
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http://dx.doi.org/10.3390/biomedicines8090350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554948PMC
September 2020

The Activation of Mucosal-Associated Invariant T (MAIT) Cells Is Affected by Microbial Diversity and Riboflavin Utilization .

Front Microbiol 2020 22;11:755. Epub 2020 Apr 22.

Department of Environmental Immunology, Helmholtz-Centre for Environmental Research - UFZ Leipzig, Germany.

Recent research has demonstrated that MAIT cells are activated by individual bacterial or yeasts species that possess the riboflavin biosynthesis pathway. However, little is known about the MAIT cell activating potential of microbial communities and the contribution of individual community members. Here, we analyze the MAIT cell activating potential of a human intestinal model community (SIHUMIx) as well as intestinal microbiota after bioreactor cultivation. We determined the contribution of individual SIHUMIx community members to the MAIT cell activating potential and investigated whether microbial stress can influence their MAIT cell activating potential. The MAIT cell activating potential of SIHUMIx was directly related to the relative species abundances in the community. We therefore suggest an additive relationship between the species abundances and their MAIT cell activating potential. In diverse microbial communities, we found that a low MAIT cell activating potential was associated with high microbial diversity and a high level of riboflavin demand and vice versa. We suggest that microbial diversity might affect MAIT cell activation via riboflavin utilization within the community. Microbial acid stress significantly reduced the MAIT cell activating potential of SIHUMIx by impairing riboflavin availability through increasing the riboflavin demand. We show that MAIT cells can perceive microbial stress due to changes in riboflavin utilization and that riboflavin availability might also play a central role for the MAIT cell activating potential of diverse microbiota.
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http://dx.doi.org/10.3389/fmicb.2020.00755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189812PMC
April 2020

Maternal paraben exposure triggers childhood overweight development.

Nat Commun 2020 02 11;11(1):561. Epub 2020 Feb 11.

Department for Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.
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http://dx.doi.org/10.1038/s41467-019-14202-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012887PMC
February 2020

Prospects and challenges of multi-omics data integration in toxicology.

Arch Toxicol 2020 02 8;94(2):371-388. Epub 2020 Feb 8.

Helmholtz Centre for Environmental Research - UFZ, 04318, Leipzig, Germany.

Exposure of cells or organisms to chemicals can trigger a series of effects at the regulatory pathway level, which involve changes of levels, interactions, and feedback loops of biomolecules of different types. A single-omics technique, e.g., transcriptomics, will detect biomolecules of one type and thus can only capture changes in a small subset of the biological cascade. Therefore, although applying single-omics analyses can lead to the identification of biomarkers for certain exposures, they cannot provide a systemic understanding of toxicity pathways or adverse outcome pathways. Integration of multiple omics data sets promises a substantial improvement in detecting this pathway response to a toxicant, by an increase of information as such and especially by a systemic understanding. Here, we report the findings of a thorough evaluation of the prospects and challenges of multi-omics data integration in toxicological research. We review the availability of such data, discuss options for experimental design, evaluate methods for integration and analysis of multi-omics data, discuss best practices, and identify knowledge gaps. Re-analyzing published data, we demonstrate that multi-omics data integration can considerably improve the confidence in detecting a pathway response. Finally, we argue that more data need to be generated from studies with a multi-omics-focused design, to define which omics layers contribute most to the identification of a pathway response to a toxicant.
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http://dx.doi.org/10.1007/s00204-020-02656-yDOI Listing
February 2020

Characterization of a multianalyte GC-MS/MS procedure for detecting and quantifying polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives from air particulate matter for an improved risk assessment.

Environ Pollut 2019 Dec 29;255(Pt 2):112967. Epub 2019 Aug 29.

Helmholtz Centre for Environmental Research GmbH - UFZ, Dep. of Molecular Systems Biology, Permoserstr. 15, 04318 Leipzig, Germany; University of Leipzig, Faculty of Life Sciences, Institute of Biochemistry, Talstr. 33, 04103 Leipzig, Germany.

A correct description of the concentration and distribution of particle bound polycyclic aromatic hydrocarbons is important for risk assessment of atmospheric particulate matter. A new targeted GC-MS/MS method was developed for analyzing 64 PAHs including compounds with a molecular weight >300, as well as nitro-, methyl-, oxy- and hydroxyl derivatives in a single analysis. The instrumental LOD ranged between 0.03 and 0.7 pg/μL for PAHs, 0.2-7.9 pg/μL for hydroxyl and oxy PAHs, 0.1-7.4 pg/μL for nitro PAHs and 0.06-0.3 pg/μL for methyl-PAHs. As an example for the relevance of this method samples of PM were collected at six sampling sites in Medellin, Colombia, extracted and the concentration of 64 compounds was determined. The 16 PAHs from the EPA priority list contributed only from 54% to 69% to the sum of all analyzed compounds, PAH with high molecular weight accounted for 8.8%-18.9%. Benzo(a)pyrene equivalents (BaP) were calculated for the estimation of the life time cancer (LCR). The LCR according to the samples ranged from 2.75 × 10 to 1.4 × 10 by a calculation with toxic equivalent factors (TEF) and 5.7 × 10 to 3.8 × 10 with potency equivalent factor (PEF). By using the new relative potency factors (RPF) recommended by US Environmental Protection Agency (U.S.EPA) the LCR ranged from 1.3 × 10 to 7.2 × 10. Hence, it was around six times higher than the well-known TEF. The novel method enables the reliable quantification of a more comprehensive set of PAHs bound on PM and thus will facilitate and improve the risk assessment of them.
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http://dx.doi.org/10.1016/j.envpol.2019.112967DOI Listing
December 2019

Metabolomics reveals effects of maternal smoking on endogenous metabolites from lipid metabolism in cord blood of newborns.

Metabolomics 2016;12:76. Epub 2016 Mar 8.

Department of Metabolomics, Helmholtz Centre for Environmental Research - UFZ Leipzig, Leipzig, Germany ; Department of Proteomics, Helmholtz Centre for Environmental Research - UFZ Leipzig, Leipzig, Germany ; Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ Leipzig, Leipzig, Germany ; Faculty of Biosciences, Pharmacy and Psychology, Institute of Biochemistry, Universität Leipzig, Leipzig, Germany ; Department of Chemistry and Bioscience, Center for Microbial Communities, Aalborg University, Aalborg, Denmark.

Introduction: A general detrimental effect of smoking during pregnancy on the health of newborn children is well-documented, but the detailed mechanisms remain elusive.

Objectives: Beside the specific influence of environmental tobacco smoke derived toxicants on developmental regulation the impact on the metabolism of newborn children is of particular interest, first as a general marker of foetal development and second due to its potential predictive value for the later occurrence of metabolic diseases.

Methods: Tobacco smoke exposure information from a questionnaire was confirmed by measuring the smoking related metabolites S-Phenyl mercapturic acid, S-Benzyl mercapturic acid and cotinine in maternal urine by LC-MS/MS. The impact of smoking on maternal endogenous serum metabolome and children's cord blood metabolome was assessed in a targeted analysis of 163 metabolites by an LC-MS/MS based assay. The anti-oxidative status of maternal serum samples was analysed by chemoluminiscence based method.

Results: Here we present for the first time results of a metabolomic assessment of the cordblood of 40 children and their mothers. Several analytes from the group of phosphatidylcholines, namely PCaaC28:1, PCaaC32:3, PCaeC30:1, PCaeC32:2, PCaeC40:1, and sphingomyelin SM C26:0, differed significantly in mothers and children's sera depending on smoking status. In serum of smoking mothers the antioxidative capacity of water soluble compounds was not significantly changed while there was a significant decrease in the lipid fraction.

Conclusion: Our data give evidence that smoking during pregnancy alters both the maternal and children's metabolome. Whether the different pattern found in adults compared to newborn children could be related to different disease outcomes should be in the focus of future studies.
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http://dx.doi.org/10.1007/s11306-016-0983-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783445PMC
March 2016

Well water--one source of Helicobacter pylori colonization.

Int J Hyg Environ Health 2004 Sep;207(4):363-8

Centre for Environmental Research Leipzig-Halle, Department of Human Exposure Research and Epidemiology, Leipzig, Germany.

Helicobacter pylori (H. pylori) is one of the world's most widespread microorganisms. Its acquisition in humans remains poorly understood, however, epidemiological studies have identified drinking water as reservoir for the bacterium. The aim of this study was to investigate the prevalence of H. pylori infection among individuals using or drinking previously H. pylori tested well water. Applying household cluster sampling, a total of 91 subjects, all using or drinking well water (13 of either H. pylori positive or negative wells), were screened for their H. pylori status. The group was comprised of 73 adults and 19 children under the age of 18. H. pylori infection was determined using the [13C]urea breath test. A self-administered or parent-completed questionnaire provided information on living conditions and lifestyle habits including the use or drinking of well water. Logistic regression analyses associated the drinking of H. pylori positive well water with a positive colonization status [Odds Ratio (OR) 8.3; 95% confidence interval (95% CI) 2.4-29]. In summary, the use or drinking of H. pylori contaminated well water appears associated with the acquisition of a H. pylori infection. This study is based on a relatively small and inhomogeneous population sample and should be repeated to confirm the results.
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http://dx.doi.org/10.1078/1438-4639-00301DOI Listing
September 2004

Passive smoking, excretion of metabolites, and health effects: results of the Leipzig's Allergy Risk Study (LARS).

Arch Environ Health 2002 Jul-Aug;57(4):326-31

Institute for Environmental Hygiene and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany.

Over a 5-yr period, the Leipzig's Allergy Risk Study (LARS) investigated the influence of typical indoor-contaminant burdens on the development of allergies and upper respiratory tract infections in allergy-prone children. Typical indoor volatile organic compounds (VOCs) and excretion of certain VOC metabolites in urine were measured in children 3 yr of age. Data analyses were based on parent-completed questionnaires, exposure measurements, and medical examinations. Evaluation of passive smoking was of special interest. Generally, residences with a high burden of passive smoking had higher benzene concentrations than residences inhabited by nonsmokers. Obstructive bronchitis was observed more frequently in children exposed to increased concentrations of benzene, as well as toluene, styrene, and m,p-xylene. In addition, atopic symptoms were associated with excretion of certain VOC metabolites. For example, the authors found an association between eczema and exposure to toluene and between eczema and increased excretion of the toluene metabolite S-benzylmercapturic acid. The results suggest that if an association with certain health effects is to be demonstrated, evaluation of external exposures should be supplemented with evaluations of internal exposure.
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http://dx.doi.org/10.1080/00039890209601416DOI Listing
January 2003