Central nervous system

• Evaluation of anti-Parkinsonism disease effects
  - Study in MPTP-induced Parkinsonism model (cynomolgus monkeys)
  The therapeutic effects of a test article are evaluated in Parkinsonism model animals that develop signs of decreased locomotor activity, muscle rigidity and freezing, established by the repeated administration of MPTP.
  Effectes are evaluted based on a scoring system of clinical signs such as tremors, bradykinesia and rigidity of limbs, locomotor activity, the amount of dopamine and its metabolites found in the substantia nigra and corpus striatum, and the number of tyrosine hydroxylase immunostaining-positive neurons in the substantia nigra.

• Evaluation of anti-pain drugs (rats, cynomolgus and rhesus monkeys)
  Details available upon request.

• Evaluation of antipruritic effects
  - Study in Substance P-induced pruritus model (mice)
  To investigate the inhibitory effects of a test article, Substance P is administered intradermally to mice and the number of scratches are automatically counted.

- Study in morphine-induced pruritus model (rhesus monkeys)
The inhibitory effects on morphine-induced skin scratching are observed in non-human primates by video-recording skin-scratching behavior.

• Evaluation of anti-ADHD (Attention Deficit Hyperactivity Disorder) effects (cynomolgus monkeys)
  - Assessment of attentional function (cynomolgus monkeys)
  Effects on attentional function are investigated in animals that are trained to obtain feed by lever-pressing. Reaction latency from lighting a signal lamp to pressing the lever is measured.

Circulatory system

• Evaluation of antihypertension effects
  - Study in hypertensive model (SHR rats)
  Antihypertensive effects of a test article are assessed by non-invasive blood pressure measurements.

Osteology

• Evaluation of anti-osteoporosis drugs
  - Study in ovariectomized osteoporosis model (rats)
  Osteoporosis (OVX) models are induced by carrying out an ovariectomy in mature-aged rats. Prevention and intervention effects are then investigated by osteological analyses, such as measurements of bone density, bone destruction, bone biomarkers and histomorphometry. Periodic measurements of the bone density of the lumbar vertebrae and tibia are conducted in-life.

- Study in osteopenia model (rats)
Prevention and intervention effects on bone loss are evaluated in the osteopenia model by osteological analyses such as measurements of bone density, bone destruction, bone biomarkers and histomorphometry.

- Measurements of bone density using DXA, bone destruction and histomorphometry (mice and rats)
Various measurements are carried out on isolated bones.

Ophthalmology

• Evaluation of ocular hypertension drugs and antiglaucoma drugs
  - Study in ocular hypertension model (cynomolgus monkeys) and glaucoma model (rabbits and cynomolgus monkeys)
  The effects of a test article on intraocular pressure are investigated under conscious conditions in ocular normotensive animals (rabbits and cynomolgus monkeys) or the ocular hypertension model established by argon laser irradiation (cynomolgus monkeys). All animals are fully acclimated to the intraocular pressure measurement procedures.

• Evaluation of effects on corneal endothelium deficiency
  - Assessment of corneal endothelial cells (pigmented rabbits, canines and cynomolgus monkeys)
  The effects of a test article on corneal endothelial cells are pharmacologically evaluated by detecting cell changes using a specular microscope.

• Evaluation of anti-inflammatory drugs
  - Studies on to ocular inflammation
  The effects of a test article on endophthalmitis are evaluated by using a laser flare cell meter to measure protein concentrations in the aqueous humor.

* Intravitreal, anterior chamber and subtenon administrations are also possible.

Blood glucose

• Evaluation of antidiabetic drugs
  - Study in diabetic model (mice and rats)
  Therapeutic effects are evaluated based on blood glucose, insulin, triglyceride, free fatty acid and other measurements in STZ-diabetic mice and ZDF type II diabetic rats. The effects of a test article on insulindependent/independent diabetes mellitus are also evaluated in NOD mice and KK-Ay/Ta mice.

Nephritis, renal failure

The following rat nephritis models are available to determine the effects of a test article on renal damage.

• Nephrosis model
  Nephrosis model established by a single interperitoneal administration of puromycin aminonucleoside (PAN), for screening tests to assess antiproteinuric effects of test articles.

• Renal-failure model
  Acute or chronic renal-failure models induced by partial (3/4) to full nephrectomy are available.

• Glomerulonephritis model
  - Anti-Thy-1 nephritis model
  Mesangioproliferative glomerulonephritis model induced by administration of rabbit anti-rat thymocyte serum, for short-term screening tests to assess the effects of a test article on nephritis.
  
  - Serum sickness nephritis model
  Nephritis is induced by deposition of immune complexes in the glomeruli, resulting from administration of the antigen ovalubumin (OVA).
  
  - Type IV collagen-induced autoimmune glomerulonephritis model
  Anti-glomerular basement membrane (anti-GBM) nephritis model induced by intradermal immunizating with type IV collagen NC1, an antigen purified from bovine glomerul.

Total Parenteral Nutrition (TPN)

• Evaluation of nutritional effects of TPN (canines and cynomolgus monkeys)
  Effects of nutritional parenteral fluid on bodily water, electrolytes, glucose and amino acid metabolism are investigated during or after continuous infusion (24hr IVH) for up to 3 months in canines or non-human primates.
  A canine invasive surgery model is also available.

Other

• Study in arthritis model (rats and mice)
  A collagen or adjuvant-induced arthritis model is used to evaluate the effects on the incidence of arthritis, as well as inflammation and histopathological scores.

• Evaluation of suppressive effects on uterine /vaginal atrophy (rats)
  Effects on reproductive organs (weights, etc.) are evaluated using ovariectomized rats.

• Platelet aggregation test (in vitro, ex vivo)

• Study in xenograft model (mice)

• A variety of spontaneous disease models are also available.

• Collaboration with a technology venture laboratory has expanded our capability of pharmacological study capabilities in monkeys. For details, please contact us.