Objective—To determine whether sustained release
of transforming growth factor (TGF)-β1 from a gelatin
hydrogel would enhance bone regeneration in critical-sized
long-bone defects and overcome inhibitory
effects of preoperative irradiation.
Animals—24 adult New Zealand White rabbits.
Procedure—Rabbits were allocated to 2 groups.
Twelve rabbits received localized megavoltage radiation
to the right ulna by use of a cobalt 60 teletherapy
unit, and 12 rabbits received no irradiation. Then, a
1.5-cm defect was aseptically created in the right ulna
of each rabbit. Gelatin hydrogel that contained 5 µg of
adsorbed recombinant-human (rh) TGF-β1 was placed
in the defect of 12 rabbits (6 irradiated and 6 nonirradiated),
and the other 12 rabbits received hydrogel
without rhTGF-β1. Rabbits were euthanatized 10
weeks after surgery. New bone formation within the
defect was analyzed by use of nondecalcified histomorphometric
methods. A 1-way ANOVA was used to
compare differences among groups.
Results—New bone formation within the defect was
significantly greater in TGF-β1–treated rabbits than in rabbits
treated with hydrogel carrier alone. Local delivery of
rhTGF-β1 via a hydrogel carrier in irradiated defects
resulted in amounts of bone formation similar to those
for nonirradiated defects treated by use of rhTGF-β1.
Conclusions and Clinical Relevance—Local delivery
of TGF-β1 by use of a hydrogel carrier appears to have
therapeutic potential for enhancing bone formation in
animals after radiation treatments.
Impact for Human Medicine—This technique may
be of value for treating human patients at risk for
delayed bone healing because of prior radiation therapy.
(Am J Vet Res 2005;66:1039–1045)
Objective—To determine whether rosiglitazone, an agonist of the peroxisome proliferator-activated receptor (PPAR) γ, could alleviate intestinal damage induced by Escherichia coli lipopolysaccharide (LPS) in weaned pigs.
Procedures—Pigs were allocated to 3 treatments (6 pigs/treatment). Control pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with sterile saline (0.9% NaCl) solution, LPS-treated pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with LPS (100 μg/kg, IP), and rosiglitazone plus LPS-treated pigs were injected with rosiglitazone (3 mg/kg, IP) and then injected 30 minutes later with LPS (100 μg/kg, IP). Pigs were euthanized 3 hours after challenge exposure, and samples of the small intestines were collected for histologic, biochemical, and immunohistochemical examination.
Results—Rosiglitazone alleviated LPS-induced intestinal damage, which was manifested as a lower crypt depth in the duodenum and a higher villus height-to-crypt depth ratio in the duodenum, jejunum, and ileum. Rosiglitazone also mitigated inhibition of crypt cell proliferation in the jejunum and ileum induced by LPS injection. Pretreatment with rosiglitazone significantly increased the number of cells that stained for PPARγ and significantly decreased the number of cells that stained for inducible nitric oxide synthase.
Conclusions and Clinical Relevance—Rosiglitazone alleviated intestinal damage induced by LPS injection in weaned pigs. The protective effects of rosiglitazone on the intestines may be associated with inhibition of intestinal proinflammatory mediators, such as inducible nitric oxide synthase. (Am J Vet Res 2010;71:1331–1338)