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34Th International Winter Workshop Clinical, Chemical and Biochemical DOI 10.1515/pterid-2015-0007 Pteridines 2015; 26(3): 113–133 Abstracts*) 34th International Winter Workshop Clinical, Chemical and Biochemical Aspects of Pteridines and Related Topics Society for Exploitation of Education and Research in Immunology and Infectious Diseases, Innsbruck, Austria in collaboration with The International Society of Pteridinology and The Austrian Society of Laboratory Medicine and Clinical Chemistry Held in Innsbruck, Tyrol, Austria, February 24th–27th, 2015 Scientific committee: Dietmar Fuchs (Innsbruck), Andrea Griesmacher (Innsbruck), Bohuslav Melichar (Olomouc), Gilbert Reibnegger (Graz), Barbara Strasser (Hall), Guenter Weiss (Innsbruck) and Ernst R. Werner (Innsbruck) Organization: Dietmar Fuchs, Sektion für Biologische Chemie, Biozentrum, Medizinische Universität Innsbruck, Innrain 80, 6020 Innsbruck, Austria, e-mail: [email protected] *)These abstracts have been reproduced directly from the material supplied by the authors, without editorial alteration by the staff of this Journal. Insufficiencies of preparation, grammar, spelling, style, syntax, and usage are the authors’ responsibility. 114 34th International Winter Workshop Circulating neopterin and citrulline concentrations Influence of carbon nanotubes, ZnO and in patients with germ-cell tumors during gold-doped TiO2 nanoparticles on human PBMC chemotherapy in vitro Bartoušková M, Študentová H, Pejpková I, Zezulová M, Adam T, Becker K, Herlin N, Bouhadoun S, Gostner JM, Ueberall F, Schennach Melichar B H, Fuchs D Palacký University Medical School and Teaching Hospital, Olomouc, Divisions of Biological Chemistry and of Medical Biochemistry, Czech Republic Biocenter, Medical University, and Central Institute of Blood ([email protected]) Transfusion and Immunology, University Hospital, Innsbruck, Austria; Au Service des Photons, Atomes et Molécules - Laboratoire Francis Germ-cell tumors are relatively rare neoplasms that affect mostly Perrin, Gif-sur Yvette, France young adults. The poor prognosis of these tumors has significantly ([email protected]) improved after the advent of platinum compound, and most patients with metastatic germ cell tumors can be currently cured with com- Nanomaterials are increasingly produced and used throughout bined modality treatment that comprises surgery, chemotherapy or recent years. Consequently the probability of exposure of humans radiotherapy. With the improved long-term prognosis, acute and to nanoparticles has drastically risen. Because of their small chronic side effects of treatment represent an important issue. In the 1-100 nm size, the physicochemical properties of nanomaterials present study, we evaluated serum neopterin and plasma citrulline, may differ from standard bulk materials and may pose a threat to a biomarker of gut damage in germ-cell tumor patients before and human health. Only little is known about the effects of nanopar- during 3 to 4 cycles of standard platinum-based chemotherapy. We ticles on the human immune system [1]. In this study, we inves- report here the pilot results in the first 15 patients. Baseline serum tigated the effects of carbon nanotubes (CNT), zinc oxide (ZnO) neopterin concentrations were increased in a substantial proportion and gold-doped TiO2 nanoparticles employing the in vitro model of of patients, while plasma citrulline was mostly within the normal human peripheral blood mononuclear cells (PBMC) [2], cytokine- range. A significant negative correlation was observed between base- induced neopterin formation and tryptophan breakdown were line serum neopterin and hemoglobin concentrations while positive monitored (n = 4). PBMC were stimulated with mitogen phyto- concentration was noted between peripheral blood leukocyte count haemagglutinin (PHA). Activated T-cells release pro-inflammatory and neopterin. Changes in the investigated parameters were noted cytokines, leading to an enhanced formation of neopterin and during the course of therapy. The study is ongoing. tryptophan breakdown. Furthermore myelomonocytic THP-1-blue cells, a reporter-cell line, can detect the activation of the redox- sensitive transcription factor nuclear factor-κB (NF-κB) [3]. Stimu- lation of THP-1-blue cells with lipopolysaccharide (LPS) resulted Growing impact of psychoimmunological in the activation of NF-κB, which could be measured by assessing findings to understand pathogenesis of severe the SEAP activity in a colorimetric assay (n = 4). Treatment with mental illness CNT resulted in differential outcome in unstimulated and stimu- lated cells. Neopterin levels were significantly increased after CNT Bechter K, Maxeiner H, Kühne L, Reiber H, Fuchs D, Schneider M exposure (18.75-150 μg/ml) in unstimulated PBMC, while in PHA- Clinic for Psychiatry and Psychotherapy II, Ulm University, Germany; stimulated cells additional CNT (37.5 – 150 μg/ml) resulted in a Division of Biological Chemistry, Biocenter, Medical University, decrease of neopterin levels. The same observations were found Innsbruck, Austria for kynurenine to tryptophan ratios (Kyn/Trp) representing trypto- ([email protected]) phan breakdown rates. In THP-1-blue cells CNT were able to raise NF-kB activation significantly in LPS-stimulated cells. TiO2 and Etiology and pathogenesis of severe mental illness, core is the affec- gold doped TiO2 (9.37 – 150 μg/ml) were able to increase neopterin tive and schizophrenic spectrum, remains widely unknown, though production in both stimulated and unstimulated PBMC. However, many researchers assume some biological basis. CSF analysis is a Kyn/Trp levels were only influenced in stimulated cells, where key bodily fluid to assess rather directly the pathogenetic processes inhibition of tryptophan breakdown could be observed. Also ZnO involved in brain diseases. We demonstrated in several research pro- treatment resulted in distinct effects. Lower concentrations (2.34- jects, focused on therapy resistant cases of severe mental illness, 18.75 μg/ml) acted predominantly anti-inflammatory by inhibiting in about 40 % of patients some CSF abnormalities by conventional neopterin production in both stimulated and unstimulated PBMC. sophisticated CSF analysis, in addition increased CSF neopterin in Higher concentrations already influenced cell viability signifi- about 30 %, together indicating immune pathological responses cantly and were able to induce NF-κB activation significantly. Fur- within the intrathecal space in more than 50 % of cases. Also blood thermore results obtained with ZnO (50nm and 100nm and bulk CSF barrier dysfunction was found summing up to 70 % of cases with material) were not size dependent. CSF pathology. However in 100 % of these cases we demonstrated Our results show that not all types of nanoparticles had similar CSF cytokine abnormalities, often paralleled by corresponding effects on PBMC and THP-1-blue cells in vitro. Every type showed par- though not identical cytokine abnormalities in blood. Together our ticular results and have to be explored in more detail on other cell results reveal immune pathology in a large subgroup of patients of types. Additionally exposure to nanoparticle during inflammatory the affective and schizophrenic spectrum, focused within the intrath- conditions may induce different effects as compared with a “healthy” ecal spaces. and unstimulated milieu. 34th International Winter Workshop 115 Support by the Austrian Research Funds (Project 25150-B13) is Interferon-γ-mediated immune activation in patients gratefully acknowledged. with severe symptomatic aortic stenosis and implica- tions of baseline inflammatory markers for risk strati- [1] Becker K, et al. Food Chem Toxicol 2014;65:63-9. [2] Jenny M, et al. Inflamm Res 2011;60:127-35. fication in patients undergoing transcatheter aortic [3] Schroecksnadel S, et al. J Biomed Nanotechnol 2011;7:209-10. valve implantation Csordas A, Fuchs D, Reibnegger G, Nietlispach F, Maier W, Stähli BE, Binder RK, Cahenzli M, Lüscher TF IDO and related pathways as targets for HIV Department of Cardiology, University Heart Center Zürich, Zürich, immunotherapy Switzerland; Division of Biological Chemistry, Biocenter, Medical University, Innsbruck, Austria; and Institute of Physiological Chemistry, Center of Physiological Chemistry, Medical University, Graz, Austria Boasso A ([email protected]) Centre for Immunology and Vaccinology, Chelsea & Westminster Hosp., Imperial College London, UK Transcatheter aortic valve implantation (TAVI) has emerged as a ([email protected]) viable treatment option for patients with severe symptomatic aortic stenosis and a high or prohibitive surgical risk. Neopterin, a pteridine Increased Tryptophan (Trp) catabolism via the Kynurenine (Kyn) mainly synthesized by activated macrophages, is considered a stable pathway is observed in several chronic inflammatory and infec- integral of TH1 immune activation, and elevated neopterin levels have tious diseases, and is caused by increased indoleamine 2,3-dioxy- a solid track record as risk estimates for mortality in atherosclerosis- genase (IDO) activity. In the particular case of HIV-1 infection, IDO related diseases. We prospectively included 128 patients undergoing dysregulation is considered to contribute to different aspects of TAVI. Neopterin, kynurenine, tryptophane, tyrosine and phenylala- immunopathogenesis, including immune deficiency, neurological nine levels were measured at baseline as well as at postoperative day impairment and tissue fibrosis. Increased IDO activity may
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