The effect of cigarette smoke versus vaporized nicotine on healing of a rat femur.

INTRODUCTION: Little data exists regarding the effects of vaporized nicotine on healing. Our goal was to compare vaporized nicotine, combusted nicotine and control with respect to bone healing in a rat femur fracture model. MATERIALS AND METHODS: Forty-five male Sprague Dawley rats were divided into three equal cohorts. Rats were exposed to two cigarettes daily, an equivalent dose of vaporized nicotine, or control, six days a week. Exposures occurred for 4 weeks prior to iatrogenic femur fracture and intramedullary repair. Four additional weeks of exposure occurred prior to sacrifice. Radiographic, biomechanical and histologic analysis was conducted. RESULTS: No significant difference between the three groups was identified for total mineralized bone volume (p = 0.14), total volume of mature bone (p = 0.12) or immature bone (p = 0.15). Importantly, less total mineralized bone volume and immature bone volume was seen in the vaporized nicotine group compared to combusted tobacco, but results were not significant. Biomechanical testing revealed no significant difference in group torsional stiffness (p = 0.92) or maximum torque (p = 0.31) between the three groups. On histologic analysis, chi-square testing showed no significant difference in any category. CONCLUSIONS: This exploratory study compared combusted nicotine, vaporized nicotine and a control on rat femur fractures. While no statistically significant differences were identified, there were trends showing less total mineralized bone volume and immature bone volume in the vaporized nicotine group compared to the other groups. Additional study is warranted based on our findings.

Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation.

Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells' frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA.

Glenoid cement mantle characterization using micro-computed tomography of three cement application techniques.

BACKGROUND: Numerous studies have documented the concern for progressive radiolucent lines, signifying debonding and subsequent aseptic loosening of the glenoid component. In this study, we compared 3 cementation methods to secure a central peg in 15 cadaveric glenoids. METHODS: Cement application techniques consisted of (1) compression of multiple applications of cement using manual pressure over gauze with an Adson clamp, (2) compression of multiple applications of cement using a pressurizer device, and (3) no compression of a single application of cement. Each glenoid was then imaged with high-resolution micro-computed tomography and further processed by creating 3-dimensional computerized models of implant, bone, and cement geometry. Cement morphology characteristics were then analyzed in each of the models. RESULTS: There were no significant differences detected between the 2 types of compression techniques; however, there was a significant difference between compression methods and use of no compression at all. All morphologic characteristics of a larger cement mantle were significantly correlated with greater cortical contact. CONCLUSIONS: We demonstrate that compression techniques create a larger cement mantle. Increased size of the cement mantle is associated with increased contact with cortical bone at the glenoid vault. This method for characterizing the cement mantle by micro-computed tomography scanning techniques and 3-dimensional analysis may also be useful in future finite element analysis studies.