Article
Journal of Medicinal Chemistry, 2010, Vol. 53, No. 18 6697
was anesthetized with 50 mg/kg (10 mg/mL) ketamine/15 mg/kg
(2 mg/mL) zylazine. A whole body noninvasive density scan was
performed to assess body fat content (PIXImus densitometer,
Lunar Corp.). At 3-4 h after recovering from anesthesia the
animal received the appropriate treatment once a day for a
period of 35 days. Disease progression and severity were
assessed every Monday, Wednesday, and Friday for 5 weeks.
A clinical scoring system was used whereby each limb was
graded as follows: 0, normal; 1, erythema and edema in 1-2
digits; 2, erythema and edema in >2 digits or severe edema and
erythema encompassing the tarsal and metatarsal joints; 3,
edema and erythema encompassing the tarsal and metatarsal
joints along with joint deformity. At termination (day 35), a
serum sample was collected for biomarker analysis. Triglyceride
levels were determined with the Wako L-Type TG-H kit (Wako
Diagnostics, Richmond, VA). Free fatty acids in serum were
measured using the Wako NEFA-C microtiter procedure
(Wako Diagnostics, Richmond, VA, catalog no. 994-75409).
For the serum insulin assay, the Ultra Sensitive Rat Insulin
ELISA kit (Crystal Chem Inc., Chicago, IL, catalog no. 90060)
and mouse insulin standard, 1.28 ng (catalog no. 90090), were
used.
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Acknowledgment. We thank Ronald Magboo, Scott
Leonard, and Scott Pennino for their analytical support
and Paige Mahaney for proofreading the manuscript.
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Supporting Information Available: Spectral data for key
compounds (R)-16 and (R)-37. This material is available free
€
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