A5067123710- Cardiac Arrest and Resuscitation
- Sepsis Diagnosis and Treatment
- Trauma Management and Diagnosis
- Trauma and Emergency Care Studies
- Bone fractures and treatments
- Immune Response and Inflammation
- Complement system in diseases
- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mesenchymal stem cell research
- Neuroscience of respiration and sleep
- Hip and Femur Fractures
- Cardiovascular Function and Risk Factors
- Advanced Glycation End Products research
- Orthopedic Surgery and Rehabilitation
- S100 Proteins and Annexins
- Mechanical Circulatory Support Devices
- Extracellular vesicles in disease
- Elbow and Forearm Trauma Treatment
- Immune cells in cancer
- Shoulder Injury and Treatment
- Orthopedic Infections and Treatments
- Inflammasome and immune disorders
- Hemodynamic Monitoring and Therapy
Friedrich-Alexander-Universität Erlangen-Nürnberg
2020-2025
Universitätsklinikum Erlangen
2020-2025
Universität Ulm
2012-2025
University Hospital Ulm
2015-2024
University of Michigan
2014-2024
Qatar Airways (Qatar)
2024
University of California, San Francisco
2020-2022
San Francisco General Hospital
2022
Orthopaedic Trauma Association
2021
Heidelberg University
2021
The inflammasome is a key factor in innate immunity and senses soluble pathogen danger-associated molecular patterns as well biological crystals (urate, cholesterol, etc.), resulting expression of IL-1β IL-18. Using standard model acute lung injury (ALI) mice featuring airway instillation LPS, ALI was dependent on availability NLRP3 caspase-1, which are known features the inflammasome. appearance IL-1β, product activation, detected bronchoalveolar lavage fluids (BALF) macrophage-...
Cardiac dysfunction develops during sepsis in humans and rodents. In the model of polymicrobial induced by cecal ligation puncture (CLP), we investigated role NLRP3 inflammasome heart. Mouse heart homogenates from sham-procedure mice contained high mRNA levels IL-1β. Usingthe inflamm a some protocol, exposure cardiomyocytes (CMs) to LPS followed ATP or nigericin caused release mature Immuno staining left ventricular frozen sections before 8 h after CLP revealed presence IL-1β proteins inCMs....
The purpose of this study was to define the relationship in polymicrobial sepsis (in adult male C57BL/6 mice) between heart dysfunction and appearance plasma extracellular histones. Procedures included induction by cecal ligation puncture measurement function using echocardiogram/Doppler parameters. We assessed ability histones cause disequilibrium redox status intracellular [Ca2+]i levels cardiomyocytes (CMs) (from mice rats). also studied disturb both functional electrical responses hearts...
The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation infection. For migration to the inflamed region, we hypothesized that activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure human neutrophils dose- time-dependently resulted a rapid receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar were observed after...
Abstract Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model investigate physiological, morphologic and inflammatory changes, Male pigs ( sus scrofa ) sustained (including unilateral chest trauma, femur fracture, liver laceration hemorrhagic shock)....
Abstract During sepsis, excessive activation of the complement system with generation anaphylatoxin C5a results in profound disturbances crucial neutrophil functions. Moreover, because activity is highly dependent on intracellular pH (pHi), we propose a direct mechanistic link between and pHi. In this article, demonstrate that vitro exposure human neutrophils to significantly increased pHi by selective sodium/hydrogen exchanger. Upstream signaling C5a-mediated alkalinization was C5aR1,...
Postmenopausal females display a chronic inflammatory phenotype with higher levels of circulating pro-inflammatory cytokines. Furthermore, the response to injury may be altered under estrogen-deficiency, because it was shown previously that estrogen-deficient mice displayed increased cytokines Midkine (Mdk) and Interleukin-6 (IL-6) in early fracture hematoma. Because balanced immune is required for successful bone regeneration, this might contribute delayed healing frequently observed...
Abstract There is accumulating evidence during sepsis that cardiomyocyte (CM) homeostasis compromised, resulting in cardiac dysfunction. An important role for complement these outcomes now demonstrated. Addition of C5a to electrically paced CMs caused prolonged elevations intracellular Ca2+ concentrations diastole, together with the appearance spontaneous transients. In polymicrobial mice, we found three key homeostasis-regulating proteins were reduced: Na+/K+-ATPase, which vital effective...
Polymicrobial sepsis in mice causes myocardial dysfunction after generation of the complement anaphylatoxin, component 5a (C5a). C5a interacts with its receptors on cardiomyocytes (CMs), resulting redox imbalance and cardiac that can be functionally measured quantitated using Doppler echocardiography. In this report we have evaluated activation MAPKs Akt CMs exposed to vitro cecal ligation puncture (CLP) vivo both cases, caused (phosphorylation) CMs, which required availability receptors....
Introduction Clinical and preclinical data suggest accelerated bone fracture healing in subjects with an additional traumatic brain injury (TBI). Mechanistically, altered metabolism neuro-endocrine regulations have been shown to influence formation after combined TBI, thereby increasing the content callus. However, early inflammatory response towards TBI has not investigated detail so far. This is of great importance, since phase known be essential for initiation downstream regenerative...
Sepsis, both in humans and rodents, is associated with persistent immunosuppression accompanied by defects innate immunity during the acute phase of sepsis. Mice were rendered septic cecal ligation puncture (CLP) followed induction lung injury, employing distal airway deposition IgG immune complexes, order to quantitatively evaluate responses following Suppression occurred as early 12 h after CLP up 21 days thereafter. The mechanism included a reduced leak albumin into lungs together levels...
Osteosarcoma is the leading primary bone cancer in young adults and exhibits high chemoresistance rates. Therefore, characterization of both alternative treatment options underlying mechanisms essential. Simvastatin, a cholesterol-lowering drug, has among its pleiotropic effects anticancer potential. Characterizing this potential osteosarcoma subject present study. Human cells (SaOS-2 U2OS) were treated with simvastatin (4-66 µM) for 48 or 72 h. The downstream substrate mevalonate (MA)...
Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes leads to cardiac dysfunction, thus worsening the outcome polytrauma patients. This study investigates molecular changes in heart tissue 4 h multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model polytrauma. We determined mediators (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a...
ABSTRACT Mast cells are important tissue-resident sensor and effector immune but also play a major role in osteoporosis development. increased numbers the bone marrow of postmenopausal osteoporotic patients, mast cell–deficient mice protected from ovariectomy (OVX)-induced loss. In this study, we showed that Mcpt5-Cre R-DTA were OVX-induced disturbed fracture healing, indicating critical for pathomechanisms impaired repair under estrogen-deficient conditions. We revealed trigger...
Abstract Mental traumatization is associated with long-bone growth retardation, osteoporosis and increased fracture risk. We revealed earlier that mental trauma disturbs cartilage-to-bone transition during bone repair in mice. Trauma tyrosine hydroxylase-expressing neutrophils marrow callus. Here we show hydroxylase expression the hematoma of patients correlates positively acknowledged stress, depression, pain scores as well individual ratings healing-impairment pain-perception...
Abstract Purpose Sepsis is a life-threatening condition with cardiac complications being an independent predictor of poor outcome. Although their mechanisms have been widely investigated, therapeutic options remain limited. One promising tool are mesenchymal stromal cells (MSCs). The aim this study to investigate the immunomodulatory effects human MSCs from two different sources (bone marrow/BMMSC and adipose tissue/ASC) evaluate cardioprotective potential. Methods 60 adult male C57BL/6 mice...
As a crucial element of innate immunity, the complement cascade becomes activated after severe trauma. Regulation and protection against complement-mediated tissue destruction is provided by selection soluble membrane-bound regulatory proteins (CRegs). To date, leukocyte expression profile CRegs in multiple injured patients unknown. In present study, C5a receptor (CD88) was analyzed on neutrophils, monocytes, lymphocytes flow cytometry. Whole blood samples were obtained from healthy...