Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 g. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling. (J Bone Miner Res 1998;13:942-949)
The distribution of IVDE site in French Bulldogs within the thoracolumbar and lumbar spine was different from Dachshunds. IVDE sites were not located at the sites of vertebral anomaly. French Bulldogs appeared to have T-L IVDE at younger ages, with higher male predisposition and higher risk of developing progressive hemorrhagic myelomalacia from grade 5 compared with Dachshunds.
In monkeys, dogs and swine (six each) we tested the reduction of the isoflurane MAC (minimal alveolar concentration) produced by 2 mg.kg-1 morphine intravenously (i.v.) and the concurrent effect on PCO2 with spontaneous ventilation. MAC fell to a minimum of 55% of control at 53 min in monkeys, 50% at 38 min in dogs and 13% at 33 min in swine. PaCO2 rose at constant MAC with morphine to 55-60 mmHg, but did not fall over the next several hours despite the decline of plasma morphine concentration, and the resulting needed rise in isoflurane concentration to keep the anaesthesia depth at 1 MAC. After isoflurane concentration had returned to pre-morphine control levels, naloxone immediately reduced PaCO2 to or below control level. Morphine pharmacokinetics in the three species studied conformed to a two-compartment model.
Obesity and high body mass index are associated with a higher incidence of osteoarthritis (OA). The aim of this study is to investigate the involvement of the infrapatellar fat pad (IPFP) in the sub-acute effect of a high fat diet (HFD) on the development of knee-OA. C57BL/6J male mice were fed either a HFD or a normal diet beginning at seven weeks of age. Tissue sections were evaluated with immunohistological analysis. The IPFP was excised, and mRNA expression profiles were compared using real-time RT-PCR analysis. Osteoarthritic changes were initiated in the HFD group after eight weeks of the HFD. Increased synovial cell number and angiogenesis at the anterior edge of the tibial plateau were exhibited prior to osteophyte formation. Quantitative histological analysis indicated that osteophyte volume was significantly increased in the HFD group after eight weeks, along with an increase in the IPFP volume, the size of individual adipocytes and the number of vessels in the IPFP. Histomorphometrical analysis revealed osteophyte area was significantly associated with IPFP area, individual adipocyte area and vascular area. Real-time RT-PCR analysis demonstrated elevated mRNA expression of inflammatory cytokines, growth factor, and adipokines in the IPFP after eight weeks of the HFD. These findings are in parallel with increased expression of the CD68 macrophage marker after eight weeks of the HFD. Expression levels of the adipokines were significantly correlated with expression of TNF-α, VEGF and TGF-β. Immunohistological analysis revealed that the Nampt protein was highly expressed in the IPFP especially around the site of osteophyte formation. Apoptosis and proliferation of chondrocytes were both enhanced at the site of osteophyte formation, indicating higher cell turnover at this region. These observations suggest the IPFP plays a pivotal role in the formation of osteophytes and functions as a secretory organ in response to a HFD.
We prepared fragmin/protamine microparticles (F/P MPs) as cell carriers to enhance cell viability. Use of material consisting of a low-molecular-weight heparin (fragmin) mixed with protamine resulted in water-insoluble microparticles (about 0.5-1 microm in diameter). In this study, we investigated the capability of F/P MPs to enhance the viabilities of human microvascular endothelial cells (HMVECs), human dermal fibroblasts (fibroblasts), and adipose tissue-derived stromal cells (ATSCs) in suspension culture. F/P MPs were bound to the surfaces of these cells, and the interaction of these cells with F/P MPs induced cells/F/P MPs-aggregate formations in vitro, and maintained viabilities of those cells for at least 3 days. The ATSCs/F/P MPs-aggregates adhered to and grew on suspension culture plates in a fashion similar to those on type I collagen-coated plates. The cultured ATSCs secreted significant amounts of angiogenic heparin-binding growth factors such as FGF-2. When the ATSCs/F/P MPs-aggregates were subcutaneously injected into the back of nude mice, significant neovascularization and fibrous tissue formation were induced near the site of injection from day 3 to week 2. The ATSCs/F/P MPs-aggregates were thus useful and convenient biomaterials for cell-therapy of angiogenesis.
Propofol was used as an induction agent of general anesthesia in 77 dogs and 64 cats, all client owned, for a variety of surgeries/treatments or diagnostic procedures. The mean intravenous doses of propofol required to achieve endotracheal intubation in dogs and cats were 6.5 +/- 1.4 mg/kg and 10.1 +/- 2.8 mg /kg, respectively. Most of the animals could be induced to anesthesia smoothly by the administration of propofol with a high incidence of apnea. Propofol is a clinically valuable anesthetic induction agent in both dogs and cats, however, care must be taken for apnea.
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