A5041656388- Atrial Fibrillation Management and Outcomes
- Venous Thromboembolism Diagnosis and Management
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Acute Myocardial Infarction Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Pancreatic function and diabetes
- Muscle Physiology and Disorders
- Diabetes Treatment and Management
- Cardiac Arrhythmias and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Exercise and Physiological Responses
- Antiplatelet Therapy and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Biosimilars and Bioanalytical Methods
- Regulation of Appetite and Obesity
- Cardiac electrophysiology and arrhythmias
- Biochemical Analysis and Sensing Techniques
- Metabolomics and Mass Spectrometry Studies
- Chemotherapy-related skin toxicity
- Venomous Animal Envenomation and Studies
- Gastrointestinal Bleeding Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- Advanced Drug Delivery Systems
Boehringer Ingelheim (Germany)
2012-2023
Boehringer Ingelheim (Canada)
2017
Thomas Jefferson University
2016
Boehringer Ingelheim (United States)
2015
Boehringer Ingelheim (India)
2015
Karolinska Institutet
2005-2011
Karolinska University Hospital
2007
Apple (Israel)
2006
University of Buckingham
2003
Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. We performed multicenter, prospective, open-label study determine whether 5 g intravenous idarucizumab would be able dabigatran in patients who had uncontrolled bleeding (group A) or were about undergo an urgent procedure B). The primary end point maximum percentage reversal within 4 hours after administration idarucizumab, on basis diluted thrombin time ecarin clotting time....
Idarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18-45 years received between 20 mg 8 g idarucizumab 1-hour intravenous infusion 10 sequential dose groups, or 1, 2 4 5-minute infusion. Subjects within each group were randomised 3:1 to placebo. A...
AMP-activated protein kinase (AMPK) is a heterotrimeric that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 β-d-ribonucleoside (AICAR). AS160, Rab GTPase-activating protein, provides mechanism linking AMPK signaling to uptake. We show AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation insulin-independent mechanisms in isolated skeletal muscle. Recombinant complexes (α1β1γ1 α2β2γ1) phosphorylate...
Abstract We identified signaling pathways by which IL-6 regulates skeletal muscle differentiation and metabolism. Primary human cells were exposed to (25 ng/ml either acutely or for several days), small interfering RNA gene silencing was applied measure glucose fat Chronic exposure increased myotube fusion formation the mRNA expression of transporter 4, peroxisome proliferator activated receptor (PPAR)α, PPARδ, PPARγ, PPARγ coactivator 1, glycogen synthase, myocyte enhancer factor 2D,...
Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. Elevated plasma levels of IL-6 are observed in insulin-resistant states. Interestingly, also increase during exercise, with skeletal muscle being the predominant source. Thus, has been suggested promote insulin-mediated glucose utilization. In this study, we determined direct effects on transport and signal transduction human muscle. Skeletal strips were prepared from vastus lateralis biopsies obtained 22...
Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking. Idarucizumab, an antibody fragment, was developed to reverse the anticoagulant effects of dabigatran.
Summary Idarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect dabigatran in animals healthy volunteers. The Study REVERS al E ffects Idarucizumab Patients on A ctive D abigatran (RE-VERSE AD™) is global phase 3 prospective cohort study aimed at investigating idarucizumab dabigatran-treated patients who present with uncontrollable or life-threatening bleeding, those requiring urgent surgery intervention. We describe...
Idarucizumab is an antibody fragment that specifically reverses dabigatran-mediated anticoagulation. Safety, pharmacokinetics and pharmacodynamics of idarucizumab were investigated in dabigatran-treated, middle-aged, elderly renally impaired volunteers with characteristics similar to patients receiving anticoagulant therapy.In this randomized, double-blind, crossover study, 46 subjects (12 45-64 years; 16 elderly, 65-80 18 mild or moderate renal impairment) received dabigatran etexilate (DE;...
The metabolic property of skeletal muscle adapts in response to an increased physiological demand by altering substrate utilization and gene expression. calcium-regulated serine/threonine protein phosphatase calcineurin has been implicated the transduction motor neuron signals alter expression programs muscle. We utilized transgenic mice that overexpress activated form (MCK-CnA*) investigate impact activation on properties Activation glucose incorporation into glycogen lipid oxidation...
We investigated the direct effect of a nitric oxide donor (spermine NONOate) on glucose transport in isolated human skeletal muscle and L6 cells. hypothesised that pharmacological treatment with N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine would increase intracellular cyclic GMP (cGMP) levels promote transport. Skeletal strips were prepared from vastus lateralis biopsies obtained seven healthy men. Muscle incubated absence or presence 5 mmol/l spermine NONOate 120...
Background: Although dabigatran has a favorable risk-benefit profile compared with vitamin K antagonist therapy for venous thromboembolism and nonvalvular atrial fibrillation, major bleeding events, including gastrointestinal (GI) bleeding, may occur. Therefore, our aim was to provide insights into the efficacy safety of idarucizumab urgent reversal in patients GI bleeding. Methods: Patients uncontrollable requiring were enrolled from June 2014 through July 2016 RE-VERSE AD study (Reversal...
5'-AMP-activated protein kinase (AMPK) activity is increased during exercise in an intensity- and glycogen-dependent manner. We previously reported that a mutation the AMPK3 subunit (Prkag3225Q) increases AMPK skeletal muscle glycogen content. Transfection experiments revealed R225Q associated with high basal diminished AMP dependence. Thus, can be considered loss-of-function abolished allosteric regulation by AMP/ATP, causing activity. used transgenic (Tg-Prkag3225Q) knockout (Prkag3-/-)...
Idarucizumab, a humanised monoclonal antibody fragment, binds dabigatran with high affinity and immediately, completely sustainably reverses dabigatran-induced changes on blood coagulation. The present analysis focuses the evaluation of potential procoagulant properties idarucizumab when administered in absence dabigatran. As part two Phase I studies conducted healthy Caucasian Japanese male volunteers, effect (8 g as 1-hour [h] infusion 4 5-minute [min] infusion) placebo calibrated...
Neuregulin, a growth factor involved in myogenesis, has rapid effects on muscle metabolism. In manner analogous to insulin and exercise, neuregulins stimulate glucose transport through recruitment of transporters surface membranes skeletal muscle. Like contraction, have additive with uptake. Therefore, we examined whether are the mechanism by which contraction regulates transport. We show that caffeine-induced increases cytosolic Ca2+ mediate metalloproteinase-dependent release neuregulins,...
Objective: To further examine anticoagulation reversal and clinical outcomes in dabigatran treated patients requiring urgent surgery or procedural interventions. Background: Idarucizumab, a humanized monoclonal antibody fragment, reverses anticoagulation. Methods: Data from surgical RE-VERSE AD, multicenter, open-label, single-arm, prospective cohort of were evaluated. A total 202 this group received 5 g idarucizumab before procedures. Results: The interventions included 49 abdominal, 45...