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The Preclinical Model Development core provides the investigators with professional services by experienced physiologist in the choice of the appropriate preclinical model including the design and analysis of the experiments. Due to the complexity of the interactions found in physiological responses of preclinical models, the choices made in the design of the experiments can alter the results. Even minor changes in dietary composition can alter the rate of development of metabolic diseases and their associated conditions.
The core provides physiological testing of metabolic, cardiovascular and renal function in preclinical models. Metabolic services include the determination of the basic metabolic status of the preclinical models using the CLAMS unit by Columbus Instruments. This device determines metabolic parameters by indirect calorimetry and is enclosed in an environmentally controlled chamber. Additionally, the units are capable of monitoring activity, food and water consumption as well as optional telemetry.
Additional metabolic testing available are glucose and insulin tolerance testing to determine the energy metabolic status of the preclinical model. The core also provides hyperinsulinemic, euglycemic clamp procedures that are the gold standard of determining insulin resistance. The use of tracer molecules additionally allows us to determine the site of the metabolic disorders.
Metabolic disorders have a basis in the energy imbalance resulting in the deposition of excessive fat. This fat is associated with increases in systemic inflammation and an increase in oxidative stress. The core has an EchoMRI that allows us to determine the lean-to-fat ratios in a variety of samples by NMR, ranging from 10mg to 100g. Additionally, the core has a Luminex 200 machine to assay the various inflammatory molecules in blood samples.
Metabolic pathophysiologies are associated with many other disorders, including cardiovascular and renal complications. The development of vascular complications is the leading cause of mortality and morbidity in patients with diabetes. The core has several methods to assess vascular parameters and their associated cardiac effects in preclinical models. The core has equipment, software and experienced personnel able to utilize the accepted, specialized methods for the assessment of atherosclerosis in preclinical models. The histology of tissues can be determined using a Nikon 90i upright microscope with fluorescence and differential interference contrast attached to a state-of-the-art image analysis system.
Cardiac abnormalities can be assessed using the Vevo 770 High-Resolution in vivo Micro-imaging System. This system can also be used in the assessment of other morphological changes, such as tumor detection, tissue composition or blood flow, and has the capability to produce 3-dimensional images from scans. We also have Micromarker Contrast Agent kits for enhancement of the images or the detection of specific molecules. Additional cardiac function data can be supplied by the use of pressure-volume loop catheters from Scisense. Hypertension and blood pressure can be monitored by the use of the Visitech BP2000 System or telemetrically using the Data Sciences International Physiotel System.
Renal function requires the collection of urine over a 24 hour period due to diurnal variations. The core has the specialized equipment to accurately and reliably collect urine from preclinical models for a 24 hour period. Additionally, the core has expertise in the assessment of the renal function by analysis of the albumin and creatinine in the collected urine. The core can also determine the filtration rate of the kidneys using inulin clearance as an additional assay of renal function.