A5016339618- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Immunodeficiency and Autoimmune Disorders
- Biomedical Research and Pathophysiology
- Diabetes and associated disorders
- Neurogenetic and Muscular Disorders Research
- Blood disorders and treatments
- Lipoproteins and Cardiovascular Health
- Liver Disease and Transplantation
- Diet, Metabolism, and Disease
- Urticaria and Related Conditions
- Parathyroid Disorders and Treatments
- Autoimmune Bullous Skin Diseases
- Erythrocyte Function and Pathophysiology
- Alcohol Consumption and Health Effects
- Bone health and treatments
- Genetic Neurodegenerative Diseases
- Dermatological and Skeletal Disorders
- Glycogen Storage Diseases and Myoclonus
- Inflammatory Myopathies and Dermatomyositis
- Hemoglobinopathies and Related Disorders
- Eosinophilic Disorders and Syndromes
- Adrenal Hormones and Disorders
- Cannabis and Cannabinoid Research
- Genetic Syndromes and Imprinting
Klinikum Konstanz
2018-2019
University of Bonn
2010-2017
Heidelberg University
2003-2016
University Hospital Heidelberg
2003-2016
Columbia University
2005-2016
University Hospital Bonn
2013
Rodin Therapeutics (United States)
2013
University Medical Centre Mannheim
2003-2010
Sichuan University
2010
West China Hospital of Sichuan University
2010
The endogenous cannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces apoptosis in many cell types. Although AEA levels are elevated liver fibrosis, its role fibrogenesis remains unclear. This study investigated effects of primary hepatic stellate cells (HSCs). Anandamide blocked HSC at concentrations 1 to 10 μmol/L but did not affect or activation nanomolar concentrations. At higher (25–100 μmol/L), rapidly dose-dependently induced death culture-activated...
Activation of the renin angiotensin system resulting in stimulation angiotensin-II (AngII) type I receptor (AT1R) is an important factor development liver fibrosis. Here, we investigated role Janus kinase 2 (JAK2) as a newly described intracellular effector AT1R mediating Fibrotic samples from rodents and humans were compared to respective controls. Transcription, protein expression, activation, localization JAK2 downstream effectors analyzed by real-time polymerase chain reaction, western...
Voluntary alcohol intake in rats can be influenced by deprivation phases and stress. We investigated the magnitude of effects both stress (forced swimming cold water foot-shock had been chosen as stressors distinct their physical psychological features) on influence these experiences time course drinking behavior. For procedure, a long-term model self-administration originally developed for heterogeneous Wistar was used compared with different alcohol-preferring rat lines.Adult male Alko...
Background: Onset of alcohol use during adolescence has potentially long‐lasting consequences, e.g., prospective dependence. To obtain new insight into the effects early chronic ethanol consumption, we compared drinking behavior two adult male Wistar rat groups: one that initiated consumption (adolescent group) and other their adulthood (adult in a model long‐term self‐administration. We investigated magnitude deprivation stress on intake influence these events across time. Methods:...
The endocannabinoid system is an important regulator of hepatic fibrogenesis. In this study, we determined the effects 2-arachidonoyl glycerol (2-AG) on stellate cells (HSCs), main fibrogenic cell type in liver. Culture-activated HSCs were highly susceptible to 2-AG-induced death with >50% at 10 microM after 18 h treatment. HSC showed typical features apoptosis such as PARP- and caspase 3-cleavage depended reactive oxygen species (ROS) formation. Confocal microscopy revealed mitochondria...
Background: Alcohol is a common cause of hepatic liver injury with steatosis and fibrosis. Cannabinoid receptors (CB) modulate steatosis, inflammation fibrogenesis. To investigate the differences between CB1 CB2 in response to chronic alcohol intake, we examined CB knockout mice (CB1−/−, CB2−/−). Methods: Eight- 10-week-old CB1−/−, CB2−/− wild-type received 16% ethanol for 35 weeks. Animals receiving water served as controls. We analysed triglyceride hydroxyproline contents homogenates. mRNA...
Abstract: The liver has a role in T cell tolerance induction, which is mainly achieved through the functions of tolerogenic hepatic antigen-presenting cells (APCs) and regulatory cells. Hepatic stellate (HSCs) are known to have various immune functions, range from immunogenic antigen presentation induction apoptosis. Here we report novel for vetoing priming naive CD8 Murine human HSCs stromal (but not hepatocytes) prevented activation by dendritic cells, artificial APCs, phorbol 12-myristate...
Serum amyloid A (SAA) is an evolutionary highly conserved acute phase protein that predominantly secreted by hepatocytes. However, its role in liver injury and fibrogenesis has not been elucidated so far. In this study, we determined the effects of SAA on hepatic stellate cells (HSCs), main fibrogenic cell type liver. potently activated IκB kinase, c-Jun N-terminal kinase (JNK), Erk Akt enhanced NF-κB-dependent luciferase activity primary human rat HSCs. induced transcription MCP-1, RANTES...
Quantitative data defining the relationship between hepatic microcirculation and development of liver pathological changes could provide a basis for better understanding fibrogenic processes, such as cirrhosis. Therefore, we established technique intravital fluorescence microscopy computer-assisted analysis systems in developing cirrhosis rats with aim quantitatively assessing association microvascular morphology its disordered acinar architecture, nonparenchymal cell transformation collagen...
The endocannabinoid anandamide (AEA) induces cell death in many types, but determinants of AEA-induced remain unknown. In this study, we investigated the role AEA-degrading enzyme fatty acid amide hydrolase (FAAH) liver. Primary hepatocytes expressed high levels FAAH and were completely resistant to death, whereas primary hepatic stellate cells (HSCs) low highly sensitive death. Hepatocytes that pretreated or with inhibitor URB597 isolated from FAAH(-/-) mice displayed increased reactive...
In the present study, we describe a new role of neuronal nitric oxide synthase (nNOS) gene in regulation alcohol drinking behavior. Mice deficient nNOS (nNOS -/-) and wild-type control mice were submitted to two-bottle free-choice procedure with either water or increasing concentrations (2-16%) for 6 weeks. -/- did not differ consumption preference low from animals; however, consumed sixfold more highly concentrated solutions than mice. Taste studies sucrose quinine revealed that intake is...
The endocannabinoid system is a crucial regulator of hepatic fibrogenesis. We have previously shown that the anandamide (AEA) lipid mediator blocks proliferation and induces death in stellate cells (HSCs), main fibrogenic cell type liver, but not hepatocytes. However, effects other endocannabinoids such as N-arachidonoyl dopamine (NADA) yet been investigated. NADA-synthesizing enzyme tyrosine hydroxylase was mainly expressed sympathetic neurons portal tracts. Its expression pattern stayed...
ng/L, P = 0.0576) although not reaching the statistical significance.IFN-γ and soluble CD14 levels were increased.In vitro , LPS stimulated significantly dosedependently IL-18 secretion from PBMC.Incubation with ethanol reduced LPS-stimulated by about 50%.The mRNA expression of in PBMC response to was similar CP patients controls.In PBMC, no significant differences protein detected between controls.IL-18 increased tissues compared normal pancreatic tissues.IL-18 expressed acinar cells...
Abstract: Background/Aims: Collagen production by activated hepatic stellate cells (HSCs) is a key event in liver fibrosis, and number of factors have been characterized that trigger HSC activation collagen production. However, it remains unclear if these act locally at the site injury or also affect HSCs distant to injury. Methods: A model partial bile duct ligation (PBDL) which fibrogenesis can be compared between injured ligated lobe non‐ligated lobe. Results: After PBDL, showed an...