A5073494000- Diabetes Treatment and Management
- Traumatic Brain Injury and Neurovascular Disturbances
- Blood Coagulation and Thrombosis Mechanisms
- Traumatic Brain Injury Research
- Cerebrospinal fluid and hydrocephalus
- Metabolism, Diabetes, and Cancer
- Dialysis and Renal Disease Management
- Diabetes Management and Research
- Neuropeptides and Animal Physiology
- Anesthesia and Neurotoxicity Research
- Atrial Fibrillation Management and Outcomes
- Intracranial Aneurysms: Treatment and Complications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Diet and metabolism studies
- Erythropoietin and Anemia Treatment
- Intraoperative Neuromonitoring and Anesthetic Effects
- Receptor Mechanisms and Signaling
- Cerebrovascular and Carotid Artery Diseases
- Anesthesia and Sedative Agents
- Blood properties and coagulation
- Spinal Fractures and Fixation Techniques
- Spine and Intervertebral Disc Pathology
- Vitamin K Research Studies
- Bone Tumor Diagnosis and Treatments
- Fetal and Pediatric Neurological Disorders
Sanofi (Germany)
2005-2019
Medizinische Hochschule Hannover
1991-2012
Sanofi (France)
2007-2010
Saarland University
2010
Charité - Universitätsmedizin Berlin
2008
Medical University of Vienna
2005
Vifor Pharma (Germany)
2004
University of Vienna
2002-2004
Kettering University
2000
Friedrich-Alexander-Universität Erlangen-Nürnberg
1998
To determine the effects of lixisenatide, a new once-daily (QD) glucagon-like peptide-1 receptor agonist, on postprandial glucose (PPG) and gastric emptying, relationship between these in patients with type 2 diabetes mellitus (T2DM).Data were obtained from randomized, double-blind, placebo-controlled, parallel-group study treatment duration 28 days T2DM receiving ≤2 oral antidiabetic drugs. Lixisenatide was injected subcutaneously using an ascending dose range (5-20 μg) increased every...
Dual activation of the glucagon-like peptide 1 (GLP-1) and glucagon receptor has potential to lead a novel therapy principle for treatment diabesity. Here, we report series peptides with dual activity on these receptors that were discovered by rational design. On basis sequence analysis structure-based design, structural elements engineered into selective GLP-1 agonist exendin-4, resulting in hybrid potent GLP-1/glucagon activity. Detailed structure-activity relationship data are shown....
Since 1978, decompressive craniotomy was performed according to a standardized protocol. Exclusion criteria were age ≥ 40 years, deleterious primary brain damage, operable space occupying lesions, larger infarctions in CT scan or irreversible stem incarceration/ischaemic damage as shown by bulbar syndrome, loss BAEP oscillating flow TCD. Indication given progressive intra-cranial hypertension not controllable conservative methods, if ICP decompensation correlated with clinical (GCS,...
Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets enzyme. Interactions were probed by systematic substitution 2-carboxyindole scaffold, in combination privileged and P4 substituents. Combining most favorable substituents at indole nucleus led to discovery remarkably inhibitor displaying K(i) value 0.07 nM....
Novel peptidic dual agonists of the glucagon-like peptide 1 (GLP-1) and glucagon receptor are reported to have enhanced efficacy over pure GLP-1 with regard treatment obesity diabetes. We describe novel exendin-4 based designed an activity ratio favoring versus receptor. As result iterative optimization procedure that included molecular modeling, structural biological studies (X-ray, NMR), design synthesis, experimental activity, solubility profiling, a candidate molecule was identified. SAR...
Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars formed during β-eliminative cleavage heparin. To investigate effect terminal anAS on antithrombin (AT) binding inhibition factor Xa (FXa), two octasaccharides containing AT-binding pentasaccharide sequences were isolated from...
Aim We performed acute and chronic studies in healthy diet‐induced obese animals using mouse‐specific or monkey‐specific dual GLP‐1R/GCGR agonists to investigate their effects on food intake, body weight, blood glucose control insulin secretion. The selective GLP‐1R agonist liraglutide was used as comparator. Methods were tested lean wild type, knockout mice at different doses. A study DIO the effect consumption total energy expenditure (TEE) diabetic monkeys with a focus weight intake....
We assessed the therapeutic contribution of individual components glucagon-like peptide-1 receptor (GLP-1R) and glucagon (GCGR) agonists alone in combination upon energy homeostasis glycemic control diet-induced obese, diabetic nonhuman primates. The pharmacological active dose ranges selective were established through a dose-finding study, followed by 6-week chronic study. Repeated subcutaneous administration GCGR agonist (30 µg/kg once daily) did not affect food intake or body weight,...
Catheterization of narrow ventricles may prove difficult resulting in misplacement or inefficient trials with potential damage to brain tissue.The application a new module for navigated ventricular catheterization using flexible electromagnetic navigation and dynamic reference frame is presented.Navigated catheter placement was successful accurate pilot study. Electromagnetic interferences had be taken into consideration.Flexible useful tool as it reduces the risk repeated trials.
Summary The thrombin-activatable fibrinolysis inhibitor (TAFI) is a key mediator in the regulation of endogenous fibrinolysis, down-regulating clot lysis by degrading C-terminal lysine residues from fibrin, which are important for binding and activating plasminogen. Elevated TAFI antigen levels have been suggested to be associated with promoter variants Ala147Thr polymorphism; increased stability antifibrinolytic potential instead Thr325Ile polymorphism. We investigated influence these two...
During 2007–2008, serious adverse events were reported following iv administration of certain batches commercially available heparin in humans. Anaphylactoid reactions with acute hypotension the hallmark these cases. Subsequently, it was shown that a contaminant, oversulfated chondroitin sulfate (OSCS), responsible for events. The present study undertaken to further elucidate risks related OSCS-contaminated preparations. Using an anesthetized rat hemodynamic model, marked diastolic blood...
Summary We investigated the dynamic accumulation of platelets and fibrin after balloon injury carotid arteries in rabbits vivo. In addition, effects heparin dipyridamole treatment were also tested. Autologous 99mTc-labelled platelet 123I-labelled was measured at one minute intervals for 4 hours following artery. Platelet occurred rapidly, with a ~125% increase occurring within 30 min injury. There no further activity up to hours. This could be inhibited an intravenous infusion PGI2 (500...