10 results on '"Brönnimann D"'
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2. Zebrafish caudal fin regeneration -- a novel quantitative angiogenic assay in vivo.
- Author
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Brönnimann, D.
- Subjects
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ZEBRA danio , *NEOVASCULARIZATION - Abstract
Background: Teleostfish, including zebrafish, are able to regenerate heart, retina, spinal cord, and fins after a lesion. The tie2-eGFP zebrafish is a suitable model to study the whole vascular tree down to the capillary level. Therefore, we introduced a novel assay to quantify angiogenesis after partial amputation of the zebrafish caudal fin. Methods: At first, the zebrafish caudal fin was partially amputated. Complete regeneration of the vasculature and the fin itself occurred within five weeks at 30°C. Remarkably, initial size and shape of the fin as well as the vascular parameters and patterns were completely restored. Most importantly, the concept of a reference situation was therefore introduced. Alterations in the neo-angiogenesis induced by external manipulations (pharmaceutical compounds, growth factors, flow disturbance etc.) can be precisely observed and quantified using stereomicroscopic imaging. Because blood vessels run straight and planar at the site of interest, the zebrafish caudal fin is introduced as a 2D-model. Three main quantitative parameters were introduced in this angiogenic assay. First, the total area (TA) represents the area of the fin that regenerated after partial amputation. Second, the vascular projection area (VPA) represents the regenerated vascular area visualized by a stereomicroscope. Third, the contour length (CL) represents the length of the blood vessel wall visualized by a stereomicroscope. During the first seven days of regeneration, extensive angiogenic growth was observed. Therefore, we introduced the short angiogenic assay. It allows evaluation of pro- and anti-angiogenic compounds within a week using unbiased stereological methods. In addition, this novel angiogenic assay includes a multitude of investigations in parallel. By the use of confocal imaging and transmission electron microscopy, morphology is linked to observed alterations in vivo. Hemodynamic conditions and their role in the process of neo-angiogenesis are evaluated. Moreover, the interplay between the two most important modes of angiogenesis (sprouting and intussusceptive angiogenesis) is evaluated. Conclusions: The zebrafish caudal fin regeneration assay is a promising and highly reproducible model for time-efficient quantitative evaluation of angiogenesis. It is useful to assess neo-angiogenic mechanisms and the effects of different pro-and anti-angiogenic treatments. The model has potential implications on future treatment strategies of angiogenesis related diseases such as carcinogenesis, retinopathy, macular degeneration, and wound healing, among others. [ABSTRACT FROM AUTHOR]
- Published
- 2013
3. Treatment reality of patients with BRAF-mutant advanced/metastatic melanoma in Switzerland in the era of choice.
- Author
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Mangana J, Zihler D, Bossart S, Brönnimann D, Zachariah R, and Gérard CL
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- Disease Progression, Female, Humans, Male, Programmed Cell Death 1 Receptor, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Switzerland, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Melanoma genetics, Neoplasms, Second Primary chemically induced, Skin Neoplasms chemically induced, Skin Neoplasms drug therapy, Skin Neoplasms genetics
- Abstract
Cutaneous melanoma represents a major cause of cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15-20% in distant metastatic disease. Evaluating the status quo of treatment standards in advanced melanoma and rationale for therapy decisions in Switzerland between January 2016 and September 2018. In this retrospective, anonymized registry, data of male and female patients with unresectable advanced/metastatic BRAF-positive cutaneous melanoma treated in first-, second- and third-line with registered substances were analyzed using descriptive statistics. Forty-one patients (56.1% male) were included providing a total of 70 treatment lines (first-line: n = 41; second-line: n = 18; and third-line: n = 11). Within the patients presenting with stage III or IV melanoma, immunotherapy with checkpoint inhibitors was more frequently administered as first-line treatment than targeted therapy (TT) (70.7% vs. 29.3%). Across all lines, patients received TT in 47.1% (predominantly combined BRAF-MEK-inhibition) and immunotherapy in 52.9% of the cases (anti-PD-1 monotherapy in 62.2% and anti-PD-1/anti-CTLA-4 combinations in 37.8%). Most commonly, the treatment type was switched from TT to immunotherapy or vice versa upon disease progression. The most frequent rationales for prescribing either TT or immunotherapy were physician's preference (40.0%) or remission pressure (28.6%), respectively. Disease progression led to treatment discontinuation more frequently than undesired events. Patients in Switzerland with unresectable advanced or metastatic BRAF-mutant melanoma predominantly receive guideline-recommended treatments. IO was used as predominant front-line therapy, with TT/immunotherapy switch being the predominant treatment principle. Sequencing studies are underway to identify the optimal treatment regimen for those patients. 32: 366-372 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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4. One man's trash is another man's treasure. Interdisciplinary examination of taphonomic aspects of ceramic sherds, animal bones and sediments from the La Tène period settlement at Basel-Gasfabrik.
- Author
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Brönnimann D, Wimmer J, Müller-Kissing M, Stopp B, Rissanen H, and Spichtig N
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- Animals, Archaeology, Factor Analysis, Statistical, Geography, Switzerland, Bone and Bones anatomy & histology, Ceramics, Geologic Sediments analysis, Interdisciplinary Studies
- Abstract
As part of an interdisciplinary research project on the Late La Tène period settlement at Basel-Gasfabrik, ceramic sherds, animal bones and archaeological sediments from different archaeological structures (one large pit, two ditches and four archaeological layers) were examined in respect of 21 taphonomic features (proxies). These proxies, in turn, were linked to different processes that can leave traces on objects or sediments: primary use, mechanical stress, heat impact, water, redeposition, exposure, covering and postdepositional processes. The different proxies were compared using a statistical procedure. Our results show significant differences between the different features with regard to taphonomic alteration. For example, ceramic sherds and animal bones from archaeological layers show severe alteration due to exposure, whilst a good and uniform preservation within the pit points to its rapid filling. Furthermore, there is evidence of middens which probably served as material depots. Our results suggest that waste was not simply seen as rubbish, but was stored as a resource. Therefore, materials could take different "paths", each of which resulted in specific taphonomic processes (alterations). The interdisciplinary approach taken in this project has provided new insight into the complex but probably clearly defined handling of various materials at Basel-Gasfabrik, thus allowing us to visualise part of the cultural biography of things., Competing Interests: The authors have declared that no competing interests exist.
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- 2020
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5. Limbic encephalitis as a relapse of Whipple's disease with digestive involvement and spondylodiscitis.
- Author
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Brönnimann D, Vareil MO, Sibon I, Lagier JC, Lepidi H, Puges M, Haneche F, Raoult D, Desclaux A, Neau D, and Cazanave C
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- Biopsy, Cerebrum pathology, Humans, Immunohistochemistry, Limbic Encephalitis microbiology, Limbic Encephalitis pathology, Male, Middle Aged, Polymerase Chain Reaction, Recurrence, Whipple Disease complications, Whipple Disease pathology, Limbic Encephalitis diagnosis, Tropheryma isolation & purification, Whipple Disease diagnosis
- Abstract
Introduction: Many clinical manifestations can be related to Tropheryma whipplei infection., Case Report: We report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple's disease., Discussion: This case is to the best of our knowledge the first proof of the effective brain-blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.
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- 2019
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6. Splitting of circulating red blood cells as an in vivo mechanism of erythrocyte maturation in developing zebrafish, chick and mouse embryos.
- Author
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Brönnimann D, Annese T, Gorr TA, and Djonov V
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- Animals, Cell Division physiology, Erythrocytes ultrastructure, Microscopy, Confocal, Microscopy, Electron, Chick Embryo embryology, Erythrocytes cytology, Erythropoiesis physiology, Mice, Inbred C57BL embryology, Zebrafish embryology
- Abstract
Nucleated circulating red blood cells (RBCs) of developing zebrafish, chick and mouse embryos can actively proliferate. While marrow- or organ-mediated erythropoiesis has been widely studied, transforming in vivo processes of circulating RBCs are under little scrutiny. We employed confocal, stereo- and electron microscopy to document the maturation of intravascular RBCs . In zebrafish embryos (32-72 h post-fertilization), RBC splitting in the caudal vein plexus follows a four-step program: (i) nuclear division with continued cytoplasmic connection between somata; (ii) dumbbell-shaped RBCs tangle at transluminal vascular pillars; (iii) elongation; and (iv) disruption of soma-to-soma connection. Dividing RBCs of chick embryos, however, retain the nucleus in one of their somata. Here, RBC splitting acts to pinch off portions of cytoplasm, organelles and ribosomes. Dumbbell-shaped primitive RBCs re-appeared as circulation constituents in mouse embryos. The splitting of circulating RBCs thus represents a biologically relevant mechanism of RBC division and maturation during early vertebrate ontogeny., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)
- Published
- 2018
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7. Gamma delta T cell expansion in Whipple's disease with muscular granulomatous vasculitis.
- Author
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Brönnimann D, Vandenhende MA, and Viallard JF
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- Anti-Bacterial Agents therapeutic use, Biomarkers, Humans, Male, Middle Aged, Symptom Assessment, Treatment Outcome, Whipple Disease diagnosis, Whipple Disease drug therapy, Granulomatosis with Polyangiitis complications, Lymphocyte Count, Receptors, Antigen, T-Cell, gamma-delta metabolism, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Whipple Disease complications, Whipple Disease immunology
- Abstract
Whipple's disease usually presents as chronic joint pain followed by digestive manifestations. However, many different presentations have been described in the literature. We report here the first proven case of muscular vasculitis related to Whipple's disease, associated with an expansion of circulating activated γδ T lymphocytes.
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- 2018
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8. Synchrotron microbeam irradiation induces neutrophil infiltration, thrombocyte attachment and selective vascular damage in vivo.
- Author
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Brönnimann D, Bouchet A, Schneider C, Potez M, Serduc R, Bräuer-Krisch E, Graber W, von Gunten S, Laissue JA, and Djonov V
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- Animal Fins blood supply, Animal Fins radiation effects, Animal Fins ultrastructure, Animals, Connective Tissue pathology, Hemostasis, Inflammation pathology, Perfusion, Zebrafish, Blood Platelets radiation effects, Blood Vessels pathology, Neutrophil Infiltration radiation effects, Platelet Adhesiveness radiation effects, Synchrotrons
- Abstract
Our goal was the visualizing the vascular damage and acute inflammatory response to micro- and minibeam irradiation in vivo. Microbeam (MRT) and minibeam radiation therapies (MBRT) are tumor treatment approaches of potential clinical relevance, both consisting of parallel X-ray beams and allowing the delivery of thousands of Grays within tumors. We compared the effects of microbeams (25-100 μm wide) and minibeams (200-800 μm wide) on vasculature, inflammation and surrounding tissue changes during zebrafish caudal fin regeneration in vivo. Microbeam irradiation triggered an acute inflammatory response restricted to the regenerating tissue. Six hours post irradiation (6 hpi), it was infiltrated by neutrophils and fli1a(+) thrombocytes adhered to the cell wall locally in the beam path. The mature tissue was not affected by microbeam irradiation. In contrast, minibeam irradiation efficiently damaged the immature tissue at 6 hpi and damaged both the mature and immature tissue at 48 hpi. We demonstrate that vascular damage, inflammatory processes and cellular toxicity depend on the beam width and the stage of tissue maturation. Minibeam irradiation did not differentiate between mature and immature tissue. In contrast, all irradiation-induced effects of the microbeams were restricted to the rapidly growing immature tissue, indicating that microbeam irradiation could be a promising tumor treatment tool.
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- 2016
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9. Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.
- Author
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Brönnimann D, Djukic T, Triet R, Dellenbach C, Saveljic I, Rieger M, Rohr S, Filipovic N, and Djonov V
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- Animals, Blood Flow Velocity drug effects, Electrocardiography, Heart physiology, Heart Rate drug effects, Regional Blood Flow, Stress, Physiological drug effects, Veins drug effects, Cardiotonic Agents pharmacology, Heart drug effects, Hemodynamics drug effects, Isoproterenol pharmacology, Nitroprusside pharmacology, Vasodilator Agents pharmacology, Zebrafish physiology
- Abstract
Introduction: Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo., Materials and Methods: Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations., Results: Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03)., Discussion: In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.
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- 2016
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10. Zebrafish Caudal Fin Angiogenesis Assay-Advanced Quantitative Assessment Including 3-Way Correlative Microscopy.
- Author
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Hlushchuk R, Brönnimann D, Correa Shokiche C, Schaad L, Triet R, Jazwinska A, Tschanz SA, and Djonov V
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- Animal Fins drug effects, Animal Fins physiology, Animals, Cost-Benefit Analysis, Microscopy economics, Phthalazines pharmacology, Pyridines pharmacology, Regeneration drug effects, Tail, Time Factors, Animal Fins blood supply, Microscopy methods, Neovascularization, Physiologic drug effects, Zebrafish
- Abstract
Background: Researchers evaluating angiomodulating compounds as a part of scientific projects or pre-clinical studies are often confronted with limitations of applied animal models. The rough and insufficient early-stage compound assessment without reliable quantification of the vascular response counts, at least partially, to the low transition rate to clinics., Objective: To establish an advanced, rapid and cost-effective angiogenesis assay for the precise and sensitive assessment of angiomodulating compounds using zebrafish caudal fin regeneration. It should provide information regarding the angiogenic mechanisms involved and should include qualitative and quantitative data of drug effects in a non-biased and time-efficient way., Approach & Results: Basic vascular parameters (total regenerated area, vascular projection area, contour length, vessel area density) were extracted from in vivo fluorescence microscopy images using a stereological approach. Skeletonization of the vasculature by our custom-made software Skelios provided additional parameters including "graph energy" and "distance to farthest node". The latter gave important insights into the complexity, connectivity and maturation status of the regenerating vascular network. The employment of a reference point (vascular parameters prior amputation) is unique for the model and crucial for a proper assessment. Additionally, the assay provides exceptional possibilities for correlative microscopy by combining in vivo-imaging and morphological investigation of the area of interest. The 3-way correlative microscopy links the dynamic changes in vivo with their structural substrate at the subcellular level., Conclusions: The improved zebrafish fin regeneration model with advanced quantitative analysis and optional 3-way correlative morphology is a promising in vivo angiogenesis assay, well-suitable for basic research and preclinical investigations.
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- 2016
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