14 results on '"Nadja Zöller"'
Search Results
2. Assessment of Melanogenesis in a Pigmented Human Tissue-Cultured Skin Equivalent
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August Bernd, Igor Hrgovic, Stefan Kippenberger, Manuel Butting, Jürgen Bereiter-Hahn, Eva Maria Valesky, Roland Kaufmann, Nadja Zöller, and Matthias Hofmann
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Melasma ,Human skin ,Dermatology ,Vitiligo ,Melanin ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Dermatology ,Skin equivalent ,Medicine ,pigmentation ,integumentary system ,kojic acid ,business.industry ,lcsh:RL1-803 ,medicine.disease ,Molecular biology ,Transplantation ,melanocytes ,Basic Research ,chemistry ,tissue engineering ,medicine.symptom ,business ,Kojic acid ,Forskolin ,Postinflammatory hyperpigmentation - Abstract
Background: Organotypic tissue-cultured skin equivalents are used for a broad range of applications either as possible substitute for animal tests or for transplantation in patient-centered care. Aims: In this study, we implemented melanocytes in a tissue-cultured full-thickness skin equivalent, consisting of epidermis and dermis. The versatility of this skin-like model with respect to pigmentation and morphological criteria was tested. Materials and Methods: Pigmented skin equivalents were morphologically characterized, and melanogenesis was evaluated after treatment with kojic acid – a tyrosinase inhibitor and forskolin – a well-known activator of the cyclic adenosine 3,5-monophosphate pathway. Pigmentation was measured either by determination of the extinction at 400 nm after melanin extraction with KOH correlated to a melanin standard curve or by reflectance colorimetric analysis, monitoring reflectance of 660 nm and 880 nm emitting diodes. Results: The morphological analysis revealed characteristic epidermal stratification with melanocytes located at the basal layer. Stimulation with forskolin increased the pigmentation, whereas treatment with kojic acid caused bleaching. Conclusion: The present study demonstrates that the herein-introduced organotypic tissue-cultured skin equivalent is comparable to the normal human skin and its versatility in tests regarding skin pigmentation. Therefore, this model might help understand diseases with dysfunctional pigmentation such as melasma, vitiligo, and postinflammatory hyperpigmentation.
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- 2019
3. Single-center analysis of patients with frontal fibrosing alopecia: evidence for hypothyroidism and a good quality of life
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Nadja Zöller, Markus Meissner, Roland Kaufmann, Manuela Denise Maier, and Eva Maria Valesky
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medicine.medical_specialty ,Medicine (General) ,Clinical Research Reports ,Frontal fibrosing alopecia (FFA) ,Scarring alopecia ,030204 cardiovascular system & hematology ,Single Center ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,hairline ,Quality of life ,Hypothyroidism ,Germany ,Epidemiology ,Medicine ,Humans ,thyroid disease ,atopic predisposition ,Aged ,postmenopausal ,business.industry ,Frontal fibrosing alopecia ,Thyroid disease ,Incidence ,Biochemistry (medical) ,Alopecia ,Cell Biology ,General Medicine ,medicine.disease ,Prognosis ,Dermatology ,Fibrosis ,body regions ,quality of life ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,business ,Follow-Up Studies - Abstract
Objective Frontal fibrosing alopecia (FFA) is an underestimated scarring alopecia. This study aimed to examine epidemiological information, as well as predilection sites, associated diseases, and responses to therapy of patients with FFA. We also aimed to determine whether the extent or duration of disease correlated with the quality of life (QoL). Methods Twelve outpatients with FFA for > 2 years were analyzed. The Erlanger atopic score and the Functional Assessment of Non-life-threatening Conditions (FANLTC) for QoL-assessment were used as scoring systems. Results All patients were women with a mean age of 70.3 years. Most patients did not have any symptoms during their disease progression and no therapy that was used showed any significant effects. FFA was associated with hypothyroidism. There were no correlations between hairline regression, duration of disease, atopic disposition, and QoL. The overall QoL was good. Conclusions The present study shows that there is no correlation between the extent of FFA and QoL or atopic predisposition. There is a strong correlation between the incidence of thyroid disease and FFA.
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- 2018
4. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) - a retrospective study
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Nadja Zöller, Franziska Meier, Markus Meissner, Flavia Angeletti, Eva Maria Valesky, and Roland Kaufmann
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medicine.medical_specialty ,business.industry ,Provocation test ,Anti-Inflammatory Agents, Non-Steroidal ,Retrospective cohort study ,Dermatology ,Inpatient setting ,University hospital ,Acetaminophen ,Drug Hypersensitivity ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Etoricoxib ,0302 clinical medicine ,Non steroidal anti inflammatory ,Pharmaceutical Preparations ,Internal medicine ,Medicine ,Humans ,Medical history ,ddc:610 ,business ,medicine.drug ,Retrospective Studies - Abstract
Background The aim of this study was to verify the validity of clinical history and oral provocation challenges of patients with NSAID hypersensitivity and to identify safe alternatives. The COX-2 inhibitor etoricoxib, in particular, was studied. Patients and methods In all, 104 patients with confirmed diagnoses of NSAID hypersensitivity treated at the Department of Dermatology, Frankfurt University Hospital, Germany between 2004 and 2012 were retrospectively studied. Results The medical history and hypersensitivity symptoms during oral provocation testing (OPT) largely coincided and were mostly mild to moderate. Acetylsalicylic acid (ASA) was the most frequent trigger both anamnestically (27.9 %) and during OPT (47.8 %). Etoricoxib caused the fewest reactions during OPT (4.2 %). Acetaminophen led to reactions in only 6.7 % of the cases studied although it was named more often in clinical histories (14 %). Conclusions OPT should be the aim whenever possible as most symptoms are mild to moderate. To distinguish between selective and cross-hypersensitivity reactions, ASA should be part of the test protocol. Furthermore, the findings of this study indicate that etoricoxib and acetaminophen are safe treatment alternatives in case of NSAID hypersensitivity. However, these drugs should not be administered without prior OPT in an inpatient setting, as severe symptoms can occur.
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- 2020
5. Water-filtered Infrared A and visible light (wIRA/VIS) treatment reduces Chlamydia caviae-induced ocular inflammation and infectious load in a Guinea pig model of inclusion conjunctivitis
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Elisabeth Stein, Nadja Zöller, Jasmin Kuratli, Talin Barisani-Asenbauer, Ana Filipovic, Antonia Frohns, Aleksandra Inic-Kanada, Nicole Borel, Marijana Stojanovic, Radmila Miljkovic, University of Zurich, and Inic-Kanada, Aleksandra
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wIRA/VIS ,Light ,medicine.drug_class ,Infrared Rays ,Ocular Pathology ,030303 biophysics ,Antibiotics ,Guinea Pigs ,Biophysics ,Colony Count, Microbial ,10184 Institute of Veterinary Pathology ,02 engineering and technology ,medicine.disease_cause ,Guinea pig ,03 medical and health sciences ,In vivo ,medicine ,2741 Radiology, Nuclear Medicine and Imaging ,Animals ,Animal model ,Radiology, Nuclear Medicine and imaging ,Chlamydia ,3614 Radiological and Ultrasound Technology ,Trachoma ,Infectivity ,0303 health sciences ,Radiation ,Radiological and Ultrasound Technology ,business.industry ,Conjunctivitis, Inclusion ,021001 nanoscience & nanotechnology ,medicine.disease ,3108 Radiation ,Disease Models, Animal ,Radiology Nuclear Medicine and imaging ,Immunology ,570 Life sciences ,biology ,0210 nano-technology ,business ,Chlamydia trachomatis ,Ex vivo ,1304 Biophysics ,GPIC - Abstract
Trachoma is a devastating neglected tropical disease caused by Chlamydia trachomatis and the leading global cause of infectious blindness. Although antibiotic treatment against trachoma is efficient (SAFE strategy), additional affordable therapeutic strategies are of high interest. Water-filtered infrared A and visible light (wIRA/VIS) irradiation has proven to reduce chlamydial infectivity in vitro and ex vivo. The aim of this study was to evaluate whether wIRA/VIS can reduce chlamydial infection load and/or ocular pathology in vivo, in a guinea pig model of inclusion conjunctivitis. Guinea pigs were infected with 1 × 106 inclusion-forming units/eye of Chlamydia caviae via the ocular conjunctiva on day 0. In infected animals, wIRA/VIS irradiation (2100 W/m2) was applied on day 2 (single treatment) and on days 2 and 4 (double treatment) post-infection (pi). wIRA/VIS reduced the clinical pathology score on days 7 and 14 pi and the conjunctival chlamydial load on days 2, 4, 7, and 14 pi in comparison with C. caviae-infected, not irradiated, controls. Furthermore, numbers of chlamydial inclusions were decreased in wIRA/VIS treated C. caviae-infected guinea pigs on day 21 pi compared to C. caviae-infected, non-irradiated, controls. Double treatment with wIRA/VIS (days 2 and 4 pi) was more efficient than a single treatment on day 2 pi. wIRA/VIS treatment did neither induce macroscopic nor histologic changes in ocular tissues. Our results indicate that wIRA/VIS shows promising efficacy to reduce chlamydial infectivity in vivo without causing irradiation related pathologies in the follow-up period. wIRA/VIS irradiation is a promising approach to reduce trachoma transmission and pathology of ocular chlamydial infection.
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- 2019
6. Water-filtered Infrared a and Visible Light (wIRA/VIS) Treatment Reduces Chlamydial Load and Pathology Score in a Guinea Pig Model of Inclusion Conjunctivitis
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A. Filipovic, Nadja Zöller, R. Miljkovic, Antonia Frohns, Nicole Borel, E. Stein, Marijana Stojanovic, Jasmin Kuratli, T. Barisani-Asenbauer, and Aleksandra Inic-Kanada
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Guinea pig ,Pathology ,medicine.medical_specialty ,General Veterinary ,Infrared ,business.industry ,Medicine ,business ,Inclusion conjunctivitis ,Pathology and Forensic Medicine ,Visible spectrum - Published
- 2020
7. Directing adipose-derived stem cells into keratinocyte-like cells: impact of medium composition and culture condition
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Markus Meissner, S. Wellenbrock, Stefan Kippenberger, L. Petry, Johannes Kleemann, Gabi Reichenbach, U.M. Rieger, Nadja Zöller, Roland Kaufmann, and Eva Maria Valesky
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0301 basic medicine ,Keratinocytes ,Dermatology ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,Extracellular matrix ,03 medical and health sciences ,Type IV collagen ,0302 clinical medicine ,medicine ,Adipocytes ,Humans ,Cells, Cultured ,biology ,business.industry ,Stem Cells ,Transdifferentiation ,Ascorbic acid ,Flow Cytometry ,Immunohistochemistry ,Cell biology ,Fibronectin ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Culture Media, Conditioned ,Cell Transdifferentiation ,biology.protein ,Stem cell ,Wound healing ,Keratinocyte ,business - Abstract
Background Adipose-derived stem cells (ASC) are known to transdifferentiate into a wide range of different cell species in vitro including along the epidermal lineage. This property makes them a promising tool for regenerative medicine to restore the epidermal barrier. Objective This study is dedicated to identify in vitro conditions enabling transdifferentiation to a keratinocyte-like phenotype. In particular, the impact of different culture conditions (media compositions, 2D, 3D cultures) and extracellular matrix (ECM) molecules was evaluated. Methods Adipose-derived stem cells derived from subcutaneous abdominal fat were characterized by stemness-associated markers and subjected to different media. Epithelial differentiation in 2D cultures was monitored by pan-cytokeratin expression using flow cytometry and immunocytochemistry. To evaluate the impact of different ECM molecules on epidermal stratification, 3D cultures were produced, lifted to the air-liquid interface (ALI) and examined by histological analysis and quantitative real-time RT-PCR. Results We identified a medium composition containing retinoic acid, hydrocortisone, ascorbic acid and BMP-4 enabling maximum pan-cytokeratin expression in 2D cultures. Moreover, adhesion to type IV collagen further promotes the pan-cytokeratin expression. When cultures were lifted to the ALI, significant stratification was observed, particularly in supports coated with type IV collagen or fibronectin. Moreover, epidermal differentiation markers (involucrin, cytokeratin 1 and 14) become induced. Conclusion Conditions with hampered wound healing such as non-healing ulcers demand new treatment regimes. The here introduced optimized protocols for transdifferentiation of ASC into keratinocyte-like cells may help to establish more effective treatment procedures.
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- 2018
8. Non-thermal near-infrared exposure photobiomodulates cellular responses to ionizing radiation in human full thickness skin models
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Nadja Zöller, Anja Heselich, Paul G. Layer, Anke König, Stefan Kippenberger, Roland Kaufmann, and August Bernd
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0301 basic medicine ,DNA Repair ,DNA repair ,Infrared Rays ,Biophysics ,Apoptosis ,Ionizing radiation ,03 medical and health sciences ,Optics ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,DNA Breaks, Double-Stranded ,Irradiation ,Cell Proliferation ,Skin ,Radiation ,Radiological and Ultrasound Technology ,business.industry ,Cell growth ,Chemistry ,X-Rays ,Cancer ,Infant ,Dose-Response Relationship, Radiation ,Fibroblasts ,medicine.disease ,030104 developmental biology ,Ki-67 Antigen ,Cell culture ,Cancer research ,Wound healing ,business - Abstract
Ionizing and near-infrared radiation are both part of the therapeutic spectrum in cancer treatment. During cancer therapy ionizing radiation is typically used for non-invasive reduction of malignant tissue, while near-infrared photobiomodulation is utilized in palliative medical approaches, e.g. for pain reduction or impairment of wound healing. Furthermore, near-infrared is part of the solar wavelength spectrum. A combined exposure of these two irradiation qualities - either intentionally during medical treatment or unintentionally due to solar exposure - is therefore presumable for cancer patients. Several studies in different model organisms and cell cultures show a strong impact of near-infrared pretreatment on ionizing radiation-induced stress response. To investigate the risks of non-thermal near-infrared (NIR) pretreatment in patients, a human in vitro full thickness skin models (FTSM) was evaluated for radiation research. FTSM were pretreated with therapy-relevant doses of NIR followed by X-radiation, and then examined for DNA-double-strand break (DSB) repair, cell proliferation and apoptosis. Double-treated FTSM revealed a clear influence of NIR on X-radiation-induced stress responses in cells in their typical tissue environment. Furthermore, over a 24h time period, double-treated FTSM presented a significant persistence of DSBs, as compared to samples exclusively irradiated by X-rays. In addition, NIR pretreatment inhibited apoptosis induction of integrated fibroblasts, and counteracted the radiation-induced proliferation inhibition of basal keratinocytes. Our work suggests that cancer patients treated with X-rays should be prevented from uncontrolled NIR irradiation. On the other hand, controlled double-treatment could provide an alternative therapy approach, exposing the patient to less radiation.
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- 2017
9. ILDS Newsletter No. 32
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Bruna A. Pereira, Xin Li, Stefan Kippenberger, Chuen Seng Tan, Simone Cazzaniga, Enzo Berardesca, Riccardo Sirna, Jun Young Lee, Dario Fai, Marco Ardigò, José Antonio Sanches, Yoonhee Lee, Wei Li, Marianne Chopinaud, Chantal Andre, Shu Jun Wang, Charlotte Gourio, Wen Jie Zhang, Won-Soo Lee, Laurence Verneuil, Natalie Garcia Bartels, Emilie Sbidian, Yang Lu, Enrico Pezzarossa, Yun Pei Koh, Saskia Ingen-Housz-Oro, Maria Letizia Musumeci, Ulrich Mrowietz, Maria Donata Digiuseppe, Manuel Butting, Claudia Grande, Anne Dompmartin, Werner Druck Medien Ag, Pierre Wolkenstein, N. Bellon, Sascha Gerdes, Philippe Rochaix, Varvara Kanti, Eva M. Valesky, R.M. Penín, Nadja Zöller, Diana Pérez, Yoke Chin Giam, Vito Ingordo, Amelie Clementine Seghers, Nicolas Meyer, Vito Di Lernia, Daniel Labbé, Jürgen Bereiter-Hahn, Christine Coutanceau, Yen Loo Lim, Carlo Donadio, Catia De Felice, Ji Hoon Chun, Michael B Halstead, Ji Hye Baek, Melisa Barrantes-González, Joyce Siong See Lee, Anne-Dominique Pham, Jean-François Stalder, Wen-Juan Wu, Hervé Bénateau, Ya-Ping Zhang, Andrea Stroux, Hee Chul Eun, Vincenzo Claudio Battarra, Catherine Gentil, Matelda Medri, Carle Paul, August Bernd, Olivier Chosidow, Michele Pellegrino, Satz Mengensatzproduktion, Beatrice Raone, Mercè Espona-Quer, Kirsten Steinz, Seung Hwan Paik, Oh Sang Kwon, Joaquim Marcoval, Li Hu, Mark B Y Tang, Hye Chan Jeon, Jian-Kang Yang, Li He, Josep Ramon Ferreres, Raphael Lopez, Fabricio C. Furlan, Marina Agozzino, Ulrike Blume-Peytavi, Claudia Cavallotti, Ivana Romano, Nicolas Ortonne, Francesca Peccerillo, Jin Yong Kim, Ignacio Garrido, Roland Kaufmann, Luigi Naldi, Ana Giménez-Arnau, Madeline S.L. Ho, Christine Chevreau, Annalisa Patrizi, Coline Munsch, Isabella Sperduti, Esther Salas, Silja Domm, Christoph Bührer, Matthias Hofmann, Chiara Franceschini, Laurence Lamant, John D. Rogers, Mirian Nacagami Sotto, Joan Maria Viñals, Ye-Jin Jung, and Valérie Lauwers-Cances
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medicine.medical_specialty ,business.industry ,Medicine ,Dermatology ,business - Published
- 2014
10. Clinical Application of a Tissue-Cultured Skin Autograft: An Alternative for the Treatment of Non-Healing or Slowly Healing Wounds?
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Matthias Hofmann, Stefan Kippenberger, Eva Maria Valesky, August Bernd, Roland Kaufmann, Nadja Zöller, Jürgen Bereiter-Hahn, and Manuel Butting
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Keratinocytes ,medicine.medical_specialty ,Treatment outcome ,Dermatology ,Risk Assessment ,Severity of Illness Index ,Artificial skin ,Tissue Culture Techniques ,Tissue scaffolds ,Skin Ulcer ,medicine ,Humans ,Autografts ,Healing wounds ,Aged ,Wound Healing ,Cultured skin ,Tissue Engineering ,Tissue Scaffolds ,Treatment regimen ,business.industry ,Biopsy, Needle ,Graft Survival ,Follow up studies ,Skin Transplantation ,Fibroblasts ,Immunohistochemistry ,Surgery ,Treatment Outcome ,Face ,Female ,Graft survival ,business ,Follow-Up Studies - Abstract
Background: The treatment regime of non-healing or slowly healing wounds is constantly improving. One aspect is surgical defect coverage whereby mesh grafts and keratinocyte suspension are applied. Objective: Tissue-cultured skin autografts may be an alternative for the treatment of full-thickness wounds and wounds that cover large areas of the body surface. Methods: Autologous epidermal and dermal cells were isolated, expanded in vitro and seeded on collagen-elastin scaffolds. The developed autograft was immunohistochemically characterized and subsequently transplanted onto a facial chronic ulceration of a 71-year-old patient with vulnerable atrophic skin. Results: Characterization of the skin equivalent revealed comparability to healthy human skin due to the epidermal strata, differentiation and proliferation markers. Within 138 days, the skin structure at the transplantation site closely correlated with the adjacent undisturbed skin. Conclusion: The present study demonstrates the comparability of the developed organotypic skin equivalent to healthy human skin and the versatility for clinical applications.
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- 2014
11. Influence of Biodentine® - A Dentine Substitute - On Collagen Type I Synthesis in Pulp Fibroblasts In Vitro
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Roland Kaufmann, Stefan Kippenberger, Anke König, Eva Maria Valesky, August Bernd, Frangis Nikfarjam, Nadja Zöller, Kim Beyer, Manuel Butting, Detlef Heidemann, Matthias Hofmann, and Karamichos, Dimitrios
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0301 basic medicine ,Teeth ,Physiology ,lcsh:Medicine ,Dentistry ,Cell morphology ,Biochemistry ,0302 clinical medicine ,Animal Cells ,Dentin ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,lcsh:Science ,Cells, Cultured ,Connective Tissue Cells ,Staining ,Multidisciplinary ,Chemistry ,Cell Staining ,medicine.anatomical_structure ,Connective Tissue ,Cell Processes ,Cellular Types ,Anatomy ,Research Article ,Mineral trioxide aggregate ,Adult ,Cell Survival ,Research and Analysis Methods ,Collagen Type I ,Andrology ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Young Adult ,stomatognathic system ,medicine ,Humans ,Secretion ,Viability assay ,ddc:610 ,Immunoassays ,Dental Pulp ,Cell Proliferation ,business.industry ,Cell growth ,Silicates ,lcsh:R ,Biology and Life Sciences ,Proteins ,030206 dentistry ,Cell Biology ,Fibroblasts ,Calcium Compounds ,In vitro ,stomatognathic diseases ,030104 developmental biology ,Biological Tissue ,Jaw ,Specimen Preparation and Treatment ,Immunologic Techniques ,Pulp (tooth) ,lcsh:Q ,business ,Physiological Processes ,Collagens ,Digestive System ,Head ,Pulp Capping and Pulpectomy Agents - Abstract
Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.
- Published
- 2016
12. Vascular Endothelial Growth Factor C-Induced Lymphangiogenesis Decreases Tumor Interstitial Fluid Pressure and Tumor
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Nadja Zöller, August Bernd, Ralph Pflanzer, Jürgen Bereiter-Hahn, Stefan Kippenberger, Diamant Thaçi, Roland Kaufmann, Matthias Hofmann, and Satoshi Hirohata
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Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Interstitial fluid pressure ,Lymphangiogenesis ,Lymphatic system ,Oncology ,Vascular endothelial growth factor C ,In vivo ,medicine ,Tumor growth ,Lymph ,business ,Tumor xenograft - Abstract
Characteristically, most solid tumors exhibit an increased tumor interstitial fluid pressure (TIFP) that directly contributes to the lowered uptake of macromolecular therapeutics into the tumor interstitium. Abnormalities in the tumor-associated lymph vessels are a central brick in the development and prolonged sustaining of an increased TIFP. In the current study, vascular endothelial growth factor C (VEGF-C) was used to enhance tumor-associated lymphangiogenesis as a new mechanism to actively reduce the TIFP by increased lymphatic drainage of the tumor tissue. Human A431 epidermoid vulva carcinoma cells were inoculated in NMRI nu/nu mice to generate a xenograft mouse model. Seven days after tumor cell injection, VEGF-C was peritumorally injected to induce lymphangiogenesis. Tumor growth and TIFP was lowered significantly over time in VEGF-C-treated tumors in comparison to control or VEGF-A-treated animals. These data demonstrate for the first time that actively induced lymphangiogenesis can lower the TIFP in a xenograft tumor model and apparently reduce tumor growth. This model represents a novel approach to modulate biomechanical properties of the tumor interstitium enabling a lowering of TIFP in vivo.
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- 2013
13. Dimethylfumarate protects against TNF-α-induced secretion of inflammatory cytokines in human endothelial cells
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Igor Hrgovic, Veronika König, Roland Kaufmann, Tsige Hailemariam-Jahn, Monika Doll, Markus Meissner, Stefan Kippenberger, Nadja Zöller, and Simon Gerhardt
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Chemokine ,biology ,p65 ,Angiogenesis ,business.industry ,p38 mitogen-activated protein kinases ,Clinical Biochemistry ,Short Report ,Inflammation ,Cell Biology ,ΙκΒα ,Proinflammatory cytokine ,Cell biology ,IκBα ,TNF-α ,Immunology ,medicine ,biology.protein ,Phosphorylation ,ddc:610 ,medicine.symptom ,Signal transduction ,business ,Dimethylfumarate ,MCP-1 - Abstract
Background Inflammation, angiogenesis and oxidative stress have been implicated in the pathogenesis of various vascular diseases. Recent evidence suggests that dimethylfumarate (DMF), an antiposriatic and anti-multiple sclerosis agent, possesses anti-inflammatory, anti-oxidative and anti-angiogenic properties. Here, we analyze the influence of DMF on TNF-α-induced expression of the important pro-inflammatory and pro-atherogenic chemokine MCP-1 and investigate the underlying mechanisms of this expression. Findings We analyzed constitutive and TNF-α-induced expression of MCP-1 in human umbilical vascular endothelial cells (HUVEC) +/− DMF treatment via enzyme-linkes immunosorbent assay (ELISA). DMF significantly inhibited the protein expression levels in a time- and concentration-dependent manner. Furthermore, MCP-1 mRNA expression was also reduced in response to DMF, as demonstrated by RT-PCR. Thus, the regulation occurs at the transcriptional level. Interestingly, DMF prolonged the TNF-α-induced p38 and JNK phosphorylation in HUVEC, as demonstrated by Western blot analysis; however, the p38 and JNK inhibitor SB203580 did not affect the DMF-conveyed suppression of TNF-α-induced MCP-1 expression. DMF suppressed the TNF-α-induced nuclear translocation and phosphorylation (Serine 536) of p65 in these cells. These results were additionally approved by p65 luciferase promoter assays. Furthermore, we found that DMF slightly inhibited the early degradation of IκBα. In addition, we verified our results using other important inflammatory cytokines such as CCL-5, PDGF-BB, GM-CSF and IL-6. Conclusion DMF suppresses various TNF-α-induced pro-inflammatory and pro-atherogenic cytokines/chemokines in human endothelial cells. This action is regulated by reduced p65 activity and nuclear translocation, which can be explained in part by the reduced early degradation of IκBα and more important the reduced phosphorylation of p65 at Serine 536. These effects were independent of the p38, PI3K and p42/44 signaling pathways. As a result, DMF might be suitable for treating patients with vascular diseases. Electronic supplementary material The online version of this article (doi:10.1186/s12950-015-0094-z) contains supplementary material, which is available to authorized users.
- Published
- 2015
14. Impact of Different Spa Waters on Inflammation Parameters in Human Keratinocyte HaCaT Cells
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Matthias Hofmann, Jürgen Bereiter-Hahn, Markus Meissner, Nadja Zöller, Eva Maria Valesky, Roland Kaufmann, Stefan Kippenberger, and August Bernd
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Keratinocytes ,musculoskeletal diseases ,Human keratinocyte ,Inflammation ,Dermatology ,Bioinformatics ,medicine ,ddc:610 ,Interleukin 6 ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Interleukin-6 ,business.industry ,Spa water ,stomatognathic diseases ,HaCaT ,chemistry ,Immunology ,biology.protein ,Original Article ,Thermal spring water ,medicine.symptom ,business - Abstract
Background: The treatment of different skin conditions with spa waters is a long tradition dating back to at least late Hellenism. Interestingly, independent scientific examinations studying the effect of spa waters are scarce. Objective: In the present in vitro study, we compared the effect of culture media supplemented with (a) thermal spa waters (La Roche-Posay, Avène) and (b) two natural mineral drinking waters (Heppinger, Adelholzener) on physiological parameters in HaCaT keratinocytes. Methods: The different medium preparations were investigated with regard to cell proliferation and cell damage. Moreover, the impact on inflammation parameters with and without ultraviolet B (UVB) irradiation was examined. Results: Two popular thermal spring waters were found to suppress cell proliferation and cell damage. Moreover, these waters reversed the induction of interleukin-6, as measured using enzyme-linked immunosorbent assay and promoter transactivation, and the formation of reactive oxygen species after UVB stimulation. Of note, the two natural mineral waters, which are distributed as drinking waters, had some effect on the above-mentioned parameters but to a lesser extent. Conclusion: In summary, our results show that spa waters, and particularly those derived from thermal springs, reduce parameters associated with inflammation. It seems likely that trace elements such as selenium and zinc are critical for the observed effects.
- Published
- 2015
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