Ex vivo and biochemistry
Equipment
- Animal husbandry
- Certified site and laboratory
- HPLC Dionex with microplate autosampler
- Diode array detector for HPLC (Dionex)
- Fluorescence detector for HPLC (Dionex)
- 5 high-precision scales (Denver, Mettler Toledo)
- Evaporation to dry
- Metabolic cages
- Extractor hood (XPX 15.203) for toxic compounds (Midilabor)
- pH meter (Inolab ph730)
- 3 stereo zoom dissecting microscopes (Wild Heerburg)
- 3 dissecting microscopes (Nikon)
- pH meter (Inolab ph730)
- Oxygenation system
- 3 nitrogen canisters (Taylor Wharton)
- Refrigerated and standard centrifuges (Sigma, Eppendorf)
- Ultracentrifuge (Beckman Coulter Optima TLX)
- Beta radioactivity counting (14C, 3H) or 3H/14C Liquid Scintillation Counter (Perkin Elmer)
- Fluoroskan Ascent microplate fluorometer (Labsystems)
- Microplate spectrophotometer Powerwave HT (Bioteck)
- Software for management/statistical analysis of raw data (Prism)
- Software for kinetic, biochemical and Elisa analyses (Gen5)
- Software for lipoprotein kinetic analysis (SAAMII)
Experiments performed in the laboratory
- Test substance administration (PO, SC, IV, IP, infusion, sublingual, intranasal, etc.)
- Collection of biological samples (sampling and sacrifice)
- Organ and tissue collection
- Determination of test substance and metabolite concentrations in biological matrices
- Determination of radioactivity in biological matrices
- Removal of tissues for ex-vivo tests: preparation of muscles, adipocytes, etc.
- Injection or infusion of radiolabelled tracers (14C, 3H) into tissues
- Tissue/media biochemical measurements
- Measurement of metabolites (tissue, plasma, urine)
- Measurement of hormones (tissue, plasma, urine)
- Measurement of enzymes (tissue, plasma, urine)
- Measurement of inflammatory biomarkers (tissue, plasma, urine)
- Measurement of cytokines (tissue, plasma, urine)
- Measurement of classical plasma biomarkers
Place of these experiments in drug development
- Optimization of treatment schedules, routes and doses
- Urinary and fecal studies
- Drug activity based on plasma and tissue biomarkers of type 2 diabetes, obesity, dyslipidemia and cardiac complications
- Ex vivo drug compound efficacy on glucose/lipid metabolism
- Drug activity in tissues of animal models of type 2 diabetes, obesity, dyslipidemia and cardiac complications
- Large-scale screening of compounds designed to treat obesity, type 2 diabetes and cardiovascular diseases
- Evaluation of adverse effects and/or additional benefits, tissue by tissue
- Studies of drug combinations
- Development and characterization of custom-made experimental models
- Development and validation of custom-made methods
- Histological studies