There is an age-associated reduction in the bone healing activity of bone morphogenetic protein -2 (BMP-2) that is currently addressed by administering higher doses of BMP-2 in elderly patients. The unwanted medical complications from high dose BMP-2 motivated this investigation to determine whether the addition of a low dose of fibroblast growth factor 2 (FGF-2) could enhance the ability of a lower dose of BMP-2 to heal calvarial bone defects in old mice (18-20 months old). FGF-2 (5 ng) and BMP-2 (2 μg) were administered by a controlled release two-phase biomaterial scaffold placed into the bone defect. FGF-2 released more rapidly and completely in vitro than BMP-2 (40% vs 2%). In vivo, both BMP-2 and FGF-2+BMP-2 groups formed more new bone in calvarial defects than scaffold alone (p <0.001) or FGF-2 only groups (p < 0.01). The overall total volume of new bone was not statistically increased by the addition of FGF-2 to BMP-2 as measured by microCT, but the pattern of bone deposition was different. In old mice, but not young, there was enhanced bony fill in the central bone defect area when the BMP-2 was supplemented with FGF-2. Histological analysis of the center of the defect revealed an increased bone volume (%BV/TV (p = 0.004)) from the addition of FGF-2. These studies suggest that combining a low dose of FGF-2 with a low dose of BMP-2 has the potential to increase bone healing in old mice relative to BMP-2 alone.

BackgroundBlood lactate concentration is a marker of tissue perfusion and helps guide therapeutic interventions in critically ill horses. In both humans and dogs, administration of corticosteroids can increase blood lactate concentration, leading to type B hyperlactatemia. This effect could be a consequence of the impact of corticosteroids on glucose metabolism.ObjectivesTo investigate the effects of daily IM dexamethasone administration on blood lactate and glucose concentrations in horses.AnimalsNine healthy adult horses.MethodsA randomized, blinded, controlled, cross‐over study design was used. Horses were randomly assigned to 1 of 2 groups, either receiving 0.05 mg/kg of dexamethasone IM or an equivalent volume of saline, daily for 7 days. Blood was collected to determine lactate and glucose concentrations at baseline, 2 hours after the daily injections and 24 hours after the last injection.ResultsDexamethasone treatment had a statistically significant effect on lactate (P = .006) and glucose (P = .033) concentrations. The least squares mean lactate concentration was 0.93 mmol/L (95% CI: 0.87–0.99) in the dexamethasone group compared to 0.71 mmol/L (95% CI: 0.70–0.73) for the saline group. A positive relationship between blood lactate and glucose concentrations was identified, with a 0.07 mmol/L (95% CI: 0.05–0.09) increase in lactate concentration per unit increase in glucose (P < .0001) concentration.Conclusions and Clinical ImportanceDexamethasone induces statistically significant increases in blood lactate and glucose concentrations in healthy horses. Awareness of the potential for corticosteroids to induce type B hyperlactatemia might be important in the management of critically ill horses receiving dexamethasone.

Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/low human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaPCMHACDDP. nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43 mV zeta potential. nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaPCMHA-AF488 was taken up by CD44+/CD24− BT-474EMT breast cancer cells within 18 hours. nCaPCMHACDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaPCMHACDDP. This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.

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