Gateway Pharmacology Laboratories

Trans Aortic Contriction (TAC)

The  trans-aortic contriction (TAC) surgical model of cardiac hypertrophy. Progressive heart hypertrophy and function can be measured over time non-invasively using echocardiography (Vevo 3100 Ultrasound system) along with terminal measurement of heart weight and histopathology.

_Species:_ Rat, Mouse and Guinea Pig _Disease Models:_ Myocardial Infarction, Trans-Aortic Contriction (TAC), Ischemia/Reperfusion, ZSF1, SHHF, Dahl Salt Sensitive (DSS) (additional models available) - Echocardiography: Systolic and diastolic function and geometry (M-Mode, B-Mode & Doppler) - Radio-Telemetry: Blood pressure, ECG, temperature and activity - Left Ventricular Hemodynamics: +/-dP/dt, Tau, LVEDP and LVESP - Ex Vivo Left Ventricular Pressure/Volume Compliance

_Disease Models:_ 5/6 Nephrectomy, Uninephrectomized, Dahl Salt Sensitive (DSS), Streptozotocin (STZ), ZSF1, Unilateral Urethral Obstruction (UUO), ischemia/reperfusion (IR), Puromycin Aminonucleoside (PAN) (additional models available)

_Endpoints:_ Proteinuria, albuminuria, Glomerular Filtration Rate (GFR), Creatinine Clearance, histological evaluation - Plasma/Urine Biomarkers of damage - Chronic blood pressure monitoring using radio telemetry

• Radio-Telemetry – Continuous measurement of blood pressure, heart rate, ECG, respiration, activity and temperature in conscious, unrestrained animals for up to 6 months

• Tethered Model – Continuous measurement of blood pressure with simultaneous infusion of test compound along with blood, urine and/or fecal collection for up to 10 days

Disease Models: SHR, Dahl Salt Sensitive (DSS), ZSF1, ANGII-induced (additional models available)

Rodent Echocardiography, ultrasound

• Blood Pressure
• ECG
• Activity
• Temperature

Capacity of up to 136 radio-telemeterized rodents

Rat, Mouse and Guinea Pig models available

_Models:_ Unilateral Ureteral Obstruction (UUO), Renal Ischemia/Reperfusion (IR), 5/6 Nephrectomy

_Endpoints:_ Glomerular Filtration Rate (GFR), Collagen/Hydroxyproline Content, Creatinine, BUN, Histological Evaluation

Left Ventricular Function, Cardiac remodeling and Histological evaluation

Methods: Echocardiography (M-Mode, B-Mode & Doppler), Pressure/Volume, Invastive LV Hemodynamics (+/-dP/dT, Tau, LVEDP and LVESP)

Disease Models: Myocardial Infarction (MI), Ischemia/reperfusion (IR), ZSF1, SHHF, Dahl Salt Sensitive (DSS) (additional models available)

_Models:_ Bile Duct Ligation (BDL), Carbon Tetrachloride (CCl4)

_Endpoints:_ Collagen/Hydroxyproline Content - Liver enzymes and Bilirubin - Histological Evaluation

Model: Monocrotaline Rat

• Right Ventricular Systolic Pressure/Pulmonary Arterial Pressure
• Heart and Lung Weight
• Myocardial, Pulmonary Artery and Lung Histology

Infusion Pharmacology Platform in unrestrained rodents

• Continuous infusion of test article for up to 14 days
• Simultaneous blood pressure & heart rate analysis
• Clinical chemistry and hematology
• Clinical observations
• Histopathology

Cardiovascular Safety

• Cardiovascular Telemetry Platform – Continuous measurement of blood pressure, heart rate, ECG, respiration, temperature & activity in conscious, unrestrained animals for up to 6 months. Blood, urine, fecal and tissue sampling available.
• Infusion Pharmacology Platform – Continuous infusion of test compound and simultaneous blood pressure & heart rate analysis for up to 14 days. Clinical observations, blood, urine, fecal and tissue sampling
• Cardiac, Lipid and Metabolic Biomarkers – Markers of tissue and biochemical damage (e.g. CK, CRP, chol, trigs, glucose, HbA1c, etc.)
• Echocardiography – Left Ventricular Function & Dimensions
• Left Ventricular Function – +/-dP/dt, Tau, LVEDP and LVESP

Renal Safety

• Renal Function – Creatinine Clearance, GFR, proteinuria and electrolytes
• Kidney Histology – Glomerulosclerosis, tubular damage, fibrosis, etc.
• Renal Biomarker Panel – Analysis of FDA/EMA approved urinary biomarkers that are predictive of drug-induced renal toxicity and translatable to human nephrotoxicity

General Safety and Toxicology

• Chronic Infusion Studies – Continuous infusion of test agent for up to 14 days. Clinical observations, blood, urine, fecal and tissue sampling
• Hematology – 23-parameter complete blood count plus 5-point WBC differential analysis on blood samples from in-life studies
• Clinical Chemistry – 180 analytes available including markers of liver, kidney, cardiac, pancreas and bone damage; as well as lipids, metabolic and inflammation
• Histopathology – Standard or tailored to your target tissue of interest

Gastrointestinal Safety and Function

• Intestinal Motility – Charcoal meal test
• Intestinal Secretion – Closed and Open loop models of fluid and electrolyte secretion as well as compound absorption

Microscopy & Histology

• We offer a wide range of microscopy and histology services to enable detailed quantitative organ/tissue analysis and morphometry
• Fixation and processing of samples into paraffin, OCT and plastic
• Sectioning and staining of tissue blocks for LM histology and EM ultrastructure
• Range of quantitative microscopy techniques including; Epi-fluorescence, Laser scanning & capture, Electron microscopy

Pharmacokinetic and ADME Studies

• Standard PK
• 1st Pass Metabolism
• Enterohepatic Re-circulation
• Biliary/Renal/Fecal Clearance

Cassette dosing and analysis is available and economical!

Routes of Dosing:

• Oral, Intravenous (bolus and continuous), Intraperitoneal, Subcutaneous, Intramuscular, Mini-osmotic pump

Sample Collection:

• Simultaneous blood, bile, urine and fecal sampling in conscious, unrestrained rats
• Repeated, small volume blood sampling and fluid replenishment using the Automated Blood Sampler allows for reduction in animal use and minimizes test compound quantity requirement

Species: Rat, Mouse and Guinea Pig

Pharmacokinetic and ADME Studies

• Standard PK
• 1st Pass Metabolism
• Enterohepatic Re-circulation
• Biliary/Renal/Fecal Clearance

Cassette dosing and analysis is available and economical!

Routes of Dosing:

• Oral, Intravenous (bolus and continuous), Intraperitoneal, Subcutaneous, Intramuscular, Mini-osmotic pump

Sample Collection:

• Simultaneous blood, bile, urine and fecal sampling in conscious, unrestrained rats
• Repeated, small volume blood sampling and fluid replenishment using the Automated Blood Sampler allows for reduction in animal use and minimizes test compound quantity requirement

Species: Rat, Mouse and Guinea Pig

• Infectious Diarrhea – Rotavirus-induced diarrhea
• Intestinal Secretion – Open and closed loop models of secretion induced by cholera toxin or ETEC (LT/ST)
• Stool Output – Castor oil-induced diarrhea model
• Intestinal Motility – Charcoal meal test

With years experience in drug discovery and development and proven track records of advancing projects from lead development to clinical trial and product launch, our professional consultants have multi-disciplinary skills including pharmacology, PK/PD, medicinal chemistry, toxicology, project management and regulatory strategy and submission.

Senior Consultants

• Brian R. Bond, PhD – Pharmacology
  Dr. Bond has 15 years of experience in pharmaceutical drug development advancing numerous compounds from preclinical to clinical development.
• Sandy Curtiss, PhD – Safety/Toxicology
  Dr. Curtiss has 15 years of experience in investigative toxicology advancing numerous compounds through development in the pharmaceutical industry.
• John Walker, PhD – Medicinal Chemistry
  Dr. Walker has 12 years of pharmaceutical research experience with Searle, Pharmacia and Pfizer where he co-invented seven clinical candidates in multiple therapeutic areas.
• Jon Jacobsen, PhD – Medicinal Chemistry
  Dr. Jacobsen had a distinguished, 25 year career with Upjohn, Pharmacia, and Pfizer where he led teams that advanced eight compounds from Lead Development through Phase I/II clinical studies.
• John Long, DVM, DACLAM – Veterinarian
  Dr. Long is chairman of the Comparative Medicine Department at Saint Louis University and also has experience supporting drug development in the pharmaceutical industry.

• We offer a wide range of microscopy and histology services to enable detailed quantitative organ/tissue analysis and morphometry
• Fixation and processing of samples into paraffin, OCT and plastic
• Sectioning and staining of tissue blocks for LM histology and EM ultrastructure
• Range of quantitative microscopy techniques including; Epi-fluorescence, Laser scanning & capture, Electron microscopy

• We offer a wide range of histology services to enable detailed quantitative organ/tissue analysis and morphometry
• Fixation and processing of samples into paraffin, OCT and plastic
• Sectioning and staining of tissue blocks for LM histology and EM ultrastructure
• Range of quantitative microscopy techniques including; Epi-fluorescence, Laser scanning & capture, Electron microscopy

Pharmacology Services