Butox® 7.5 pour on: a deltamethrin treatment of sheep and cattle: pilot study of killing effects on Culicoides species (Ceratopogonidae)

Topical treatment (at the neck and along the vertebral column) with deltamethrin (Butox 7.5 pour on) of cattle (30 ml/400-kg body weight) and sheep (10 ml/60-kg body weight) was done to find out, whether the insecticide may reach in a sufficient dosage the legs, which are known to be the main biting site of Culicoides specimens that are the vectors of the recently introduced Bluetongue virus in central Europe. At days 7, 14, 21, 28, and 35 after treatment, some hair was cut off from the legs--close to the claws. Freshly (the night before) caught Culicoides obsoletus specimens were then exposed for 15, 30, 60, or 120 s to such hair and afterwards transferred to a filter paper within plastic Petri dishes to observe their fate. It turned out that even a short contact of 15 s of the Culicoides specimens with deltamethrin-treated hair of cattle or sheep was sufficient to paralyze and kill Culicoides specimens within a reasonable short time even when the hair were cut off at day 28 after treatment. While the results obtained in cattle and sheep were rather similar for days 7 and 14 after treatment, the speed of the killing effect of treated hair of cattle on Culicoides considerably slowed down beginning from day 21 after treatment. However, all the experiments clearly showed that the insecticide deltamethrin may reach the feet of cattle and may kill Culicoides specimens when the product is poured along the vertebral column. Such a treatment may considerably reduce the risk of transmission of the agents of disease. However, in the case of the thick fleece of sheep, the insecticide must be poured directly into the skin to reach full activity.     

Effects of PerClot® on the healing of full-thickness skin wounds in rats

PerClot^® is a hemostatic material made of polysaccharide from modified starch and has been shown to assist in topical hemostasis. The principal goal in treating surgical and non-surgical wounds is the need for rapid closure of the lesion. This study investigated whether topical application of PerClot^® could improve impaired wound healing in Sprague-Dawley (SD) rats. Full-thickness skin wounds were created on the back of the rats. Immediately, PerClot^® was introduced into the wound bed, while wounds receiving starch or nothing served as controls. Wound closure was monitored using well-recognized wound-healing parameters: histological examination for inflammatory cells and fibroblast infiltration, newly formed capillaries, and collagen deposition. Meanwhile, transforming growth factor (TGF-β1) was measured by immunochemistry. Wound closure was significantly accelerated by local application of PerClot^®. Furthermore, PerClot^®-treated wounds showed significantly increased fibroblast numbers at 5 days post-wounding, and newly formed capillaries at 7 days post-wounding, and collagen regeneration at 7 and 14 days post-wounding. The number of infiltrating fibroblasts expressing TGF-β1 was significantly higher than that in the controls at 7 and 14 days post-wounding. PerClot^® can improve the wound healing and this effect might involve an increase in the activity of fibroblasts and increased release of TGF-β1.     

Bone healing response to a synthetic calcium sulfate/β-tricalcium phosphate graft material in a sheep vertebral body defect model

The introduction of a material able to promote osteogenesis and remodelling activity in a clinically relevant time frame in vertebroplasty and kyphoplasty procedures may have patient benefit. We report the in-vivo performance of a biphasic synthetic bone graft material (Genex Paste, Biocomposites, UK) [test material], composed of calcium sulfate and β-tricalcium phosphate, implanted into a sheep vertebral defect model. Cavities drilled into 4 adjacent vertebrae (L2 to L5) of 24 skeletally mature sheep were; (1) filled with the test material; (2) filled with commercially available polymethylmethacrylate [PMMA] cement; (3) remained empty [sham]. Analysis was performed immediately after implantation and at 8, 16, and 36 weeks post implantation. Sites were evaluated for bone growth with microCT analysis, histological examination, and mechanical testing under compression. The test material exhibited an improved tissue response over the PMMA, indicating a superior biological tolerance. MicroCT and histology indicated marked osteoregenerative capacity of the test material when compared with sham and the PMMA. The percentage of new bone formation was higher for the test material than sham at 16 and 36 weeks post implantation, with bone regeneration almost complete at 36 weeks in this group. Resorption of test material and the integration into new bone tissue were demonstrated. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.     

The effects of attention and handedness on coordination dynamics in a bimanual Fitts’ law task

Two experiments were conducted to investigate the effects of attention and handedness on bimanual coordination in the context of a dynamical model of coordinated movements. Participants performed a bimanual, rhythmic Fitts law task in which the relative amount of attention directed to each task was manipulated by the relative difficulty associated with the pair of targets that each hand tapped. In both experiments, participants tended to lead with their preferred hand. The effects of attention, though, were mixed, which suggested that there was a combined effect of an attentional asymmetry and an asymmetry in the hands uncoupled frequency, both of which are captured in the dynamical model.     

The effect of Palamed® G bone cement on early migration of tibial components in total knee arthroplasty

Objective:Migration of the tibial component in total knee arthroplasty (TKA) is subject of many studies using roentgen stereophotogrammetric analysis (RSA). In previous studies of cemented and uncemented tibial components, high migration values were found. Improvements in cementing technique, prosthetic design and pre-coating techniques reduced these values as shown in more recent studies. Material and subjects:A total of 35 patients were initially included in the study and operated on between 12/1999 and 10/2000. All patients received a NexGen® TKA cemented into the proximal tibia using Palamed® G bone cement. The implants and the tibial metaphysis were marked with standard tantalum markers. Radiostereometric analysis was performed post-operatively and after 3, 6 and 12 months using a standard digital radiostereometric analysis. Functional parameters were assessed using the Knee Society Score (KSS) clinical rating system. Results:There were no complications and failures within the first year. After 1 year radiostereometric measurements of the translational parameters along and the rotational parameters around the x-, y- and z-axis revealed: X-Trans –0.19 mm, Y-Trans +0.02 mm, Z-Trans +0.08 mm, X-Rot +0.26°, Y-Rot –0.35°, Z-Rot +0.09°. The maximum total point motion was +0.96 mm and the mean maximum subsidence was –0.23 mm. Except for anterior-posterior, medio-lateral stability and extension leg all endpoints of the KSS clinical rating system showed a significant improvement. Conclusions:After 12 months, the use of Palamed® G bone cement in total knee arthroplasty was demonstrated to be safe. Both the clinical and radiostereometric results were good and comparable to the results reported in other RSA studies in cemented total knee arthroplasty.     

The effects of flumethrin (Bayticol? pour-on) on European ticks exposed to treated hairs of cattle and sheep

Tick infestations in cattle and sheep pose serious health problems when agents of diseases are transmitted. In addition, blood feeding of ticks induces enormous economic losses due to reduced weight gain of infested animals. The present study was designed to investigate the effects of exposure to hairs clipped from cattle and sheep treated with flumethrin (Bayticol?) on European ticks. The dose used was 10 ml/100 kg body weight for both animal species. At intervals of 7 days (days 7, 14, 21, 28 and 35), hairs were cut off from treated and untreated animals along the backline and from the feet just above the claws. These hairs were mingled with stages of the tick species Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus. It was found that in the cases of I. ricinus and D. reticulatus, all specimens died within 5-12 h when coming into contact with cattle hair from the feet or back of animals treated 3 weeks ago and within 6 to 9 h after contact to sheep hair from back or feet. After 4 weeks, the specimens of both tick species that had contact with hair of treated sheep and cattle, independent from the origin backline or feet, were dead after 8 h except for one tick that had contact to hair from feet of cattle. It remained fully motile after a 12-h contact even for the observation time on another 5 days. When having contact to hair of animals treated 5 weeks before, several specimens of Ixodes and Dermacentor survived an exposition of 12 h. There were more survivors in the case of ticks tested on hair of the feet than in the case of contacts with hair of the backline. The exposure of R. sanguineus to hair obtained from animals treated 2 weeks earlier resulted in death in 2-4 h. However, most R. sanguineus ticks when coming in contact with treated hairs (collected from animals treated 3, 4 or 5 weeks earlier) from back or feet survived for atleast 5 days even after exposure for 12 h. These experiments confirmed the positive protection results obtained in former studies with typical cattle ticks in the tropics and/or subtropics. In addition to the killing effects described above, it was noted that flumethrin had a significant repellent effect. If ticks were mingled with treated hair, they tried to flee away and did not seek shelter inside the hair as the controls did in untreated hair.     

Simulation of the in vivo resorption rate of β-tricalcium phosphate bone graft substitutes implanted in a sheep model

A few years ago, a model was proposed to predict the effect of the pore architecture of a bone graft substitute on its cell-mediated resorption rate. The aim of the present study was to compare the predictions of the model with the in vivo resorption rate of four β-tricalcium phosphate bone graft substitutes implanted in a sheep model. The simulation algorithm contained two main steps: (1) detection of the pores that could be accessed by blood vessels of 50 μm in diameter, and (2) removal of one solid layer at the surface of these pores. This process was repeated until full resorption occurred. Since the pore architecture was complex, μCT data and fuzzy imaging techniques were combined to reconstruct the precise bone graft substitute geometry and then image processing algorithms were developed to perform the resorption simulation steps. The proposed algorithm was verified by comparing its results with the analytical results of a simple geometry and experimental in-vivo data of β-TCP bone substitutes with more complex geometry. An excellent correlation (r(2)>0.9 for all 4 bone graft substitutes) was found between simulation results and in-vivo data, suggesting that this resorption model could be used to (i) better understand the in vivo behavior of bone graft substitutes resorbed by cell-mediation, and (ii) optimize the pore architecture of a bone graft substitute, for example to maximize its resorption rate.     

Inhibitory effects ofγ-interferon on bradykinin-induced bone resorption and prostaglandin formation in cultured mouse calvarial bones

The effects of mouse recombinant-interferon (-IFN) and indomethacin on bone resorption stimulated by bradykinin, Lys-bradykinin, Met-Lys-bradykinin, des-Arg⁹-bradykinin and prostaglandin E₂ (PGE₂) have been studied using cultures of neonatal calvarial bones and analyzing the release of⁴⁵Ca from prelabelled bones as a paramenter of bone resorption. In addition, the effects of-IFN and indomethacin on formation of PGE₂ in bone cultures stimulated by bradykinin was analyzed. Indomethacin (1 mol/l) totally abolished bradykinin (1 mol/l) induced⁴⁵Ca release. The inhibitory effect of indomethacin could be fully reversed by addition of PGE₂ (1 mol/l).-IFN (1000 U/ml) almost totally inhibited⁴⁵Ca release stimulated by bradykinin (1 mol/l), but the inhibitory effect could only be partially overcome by PGE₂.-IFN and indomethacin also inhibited the stimulatory effects of Lys-bradykinin, Met-Lys-bradykinin and des-Arg⁹-bradykinin (1 mol/l) on⁴⁵Ca release. The stimulatory effects of PGE₂ (1 mol/l) on radioactive calcium mobilization was partially inhibited by-IFN (1000 U/ml), whereas indomethacin (1 mol/l) was without effect. The inhibitory effect of-IFN on⁴⁵Ca release stimulated by bradykinin and PGE₂ was dose-dependent with threshold for action at 3–30 U/ml. Comparative dose-response curves showed that-IFN was most potent as inhibitor of bradykinin induced⁴⁵Ca release. Bradykinin (1 mol/l) significantly stimulated PGE₂ formation by a mechanism that was completely inhibited by indomethacin (1 mol/l).-IFN (1000 U/ml) partially inhibited the stimulatory effect of bradykinin on PGE₂ formation. These data show that i)-IFN is a potent inhibitor of bone resorption induced by bradykinin and bradykinin analogues and ii) that the mechanism of action can be mainly explained by an inhibition of kinin induced prostaglandin biosynthesis. The results, however, also show that-IFN can inhibit bone resorption by mechanisms unrelated to prostaglandin formation.     

Atorvastatin effects on proliferation and apoptosis of rat bone marrow-derived endothelial progenitor cells in vitro北大核心

BACKGROUND: Atorvastatin has a cardiovascular protective effect that significantly improves endothelial function and promotes the mobilization, migration, and differentiation of endothelial progenitor cells. However, the screening of atorvastatin concentration for in vitro cell culture is not well documented. OBJECTIVE: To investigate the effects of different concentrations of atorvastatin on rat bone marrow-derived EPCs growth characteristics. METHODS: Bone marrow mononuclear cells from Sprague-Dawley rats were induced in selective culture fluid to culture EPCs. Immunofluorescence staining was used to identify cell surface markers. Harvested EPCs were divided into control group and atorvastatin groups with four different concentrations (0.01, 0.1, 1, and 10 µmol/L) for culture. The growth and proliferation of EPCs were observed under light microscope and MTT assay. Flow cytometry was used to detect apoptosis in EPCs. Nitric oxide and endothelial nitric oxide synthase levels in the culture fluid were measured by nitrate reductase method. RESULTS AND CONCLUSION: The number of cells tended to increase in the control and atorvastatin groups, and it was highest in the 1 µmol/L atorvastatin group. The cell number in the 10 µmol/L atorvastatin group began to decrease at 7 days of culture. Among the five groups, the apoptotic rate of cells was lowest in the 1 µmol/L atorvastatin group and highest in the 10 µmol/L atorvastatin group. The levels of nitric oxide and endothelial nitric oxide synthase were significantly higher in the 0.01, 0.1 and 1.0 µmol/L atorvastatin groups compared with the control group (P < 0.01), but lower in the 10 µmol/L atorvastatin group compare with the other groups (P < 0.01). Overall, atorvastatin can promote the proliferation of endothelial progenitor cells and reduce apoptosis by increasing the production of endothelial nitric oxide synthase and nitric oxide, and 1 µmol/L atorvastatin is most suitable for the EPCs culture. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

The effect of lubrication on the friction and wear of Biolox®delta

The performance of total hip-joint replacements depends strongly on the state of lubrication in vivo. In order to test candidate prosthetic materials, in vitro wear testing requires a lubricant that behaves in the same manner as synovial fluid. The current study investigated three lubricants and looked in detail at the lubrication conditions and the consequent effect on ball-on-flat reciprocating wear mechanisms of Biolox®delta against alumina. Biolox®delta, the latest commercial material for artificial hip-joint replacements, is an alumina-matrix composite with improved mechanical properties through the addition of zirconia and other mixed oxides. Three commonly used laboratory lubricants, ultra pure water, 25 vol.% new-born calf serum solution and 1 wt.% carboxymethyl cellulose sodium salt (CMC-Na) solution, were used for the investigation. The lubrication regimes were defined by constructing Stribeck curves. Full fluid-film lubrication was observed for the serum solution whereas full fluid-film and mixed lubrications were observed in both water and the CMC-Na solution. The wear rates in the CMC-Na and new-born calf serum were similar, but were an order of magnitude higher in water. The worn surfaces all exhibited pitting, which is consistent with the transition from mild wear to severe or “stripe” wear. The extent of pitting was greatest in the serum solution, but least in the water. On all worn surfaces, the zirconia appeared to have fully transformed from tetragonal to monoclinic symmetry. However, there was no evidence of microcracking associated with the transformed zirconia. Nevertheless, AFM indicated that zirconia was lost preferentially to the alumina grains during sliding. Thus, the current study has shown conclusively that the wear mechanisms for Biolox®delta clearly depend on the lubricant used, even where wear rates were similar.     

The Effects of Matrigel® on the Survival and Differentiation of a Human Neural Progenitor Dissociated Sphere Culture

We have previously developed an in vitro organotypic culture setting in order to investigate the performance of cellular substrates transplanted to the auditory nervous system. We have utilized this system to predict the efficacy of human neural progenitor cells (HNPCs) in transplantation to the auditory nerve to facilitate regeneration of sensory auditory nerve structures in vivo and in vitro. To optimize the growth and differentiation of HNPCs we have introduced an expansion of our in vitro system, exploring the impact of a growth factor-altered microenvironment. Here, we seeded HNPCs as a dissociated sphere culture on a hydrogel matrix coating (Matrigel®). We evaluated the performance of HNPCs by studying their survival, differentiation, and their axon-forming capacity. In identical culture conditions, we found that the overall survival rate of HNPCs on Matrigel coated surfaces was better than that on surfaces that were not coated with Matrigel. Furthermore, cells on Matrigel differentiated into neuronal cells to a far greater extent leading to strong synaptic marker signatures. Overall, our findings show that the present Matrigel matrix setting offers an experimental environment for the HNPCs to grow where these cells show novel and promising phenotypic characteristics suitable for further in vivo transplantation to the auditory nerve. Anat Rec, 303:441–450, 2020. © 2019 American Association for Anatomy     

Is hydroxyapatite cement an alternative for allograft bone chips in bone grafting procedures? A mechanical and histological study in a rabbit cancellous bone defect model

To evaluate in vivo performance of hydroxyapatite cement (HAC) as a porous bone graft substitute, HAC was mixed (1:1 ratio) with either porous calcium-phosphate granules (80% tricalcium phosphate, 20% hydroxyapatite) or defatted morsellized cancellous bone (MCB) allograft and implanted bilaterally in cylindrical drill holes in distal femurs of rabbits. Groups with empty defects and impacted MCB were used for reference. After 8 weeks, one femur from each pair was examined histologically. All contralateral specimens and Time-0 specimens were used for mechanical indentation tests. Histology showed that some empty defects were filled with newly formed osteopenic bone after 8 weeks. The impacted MCB showed remodeling into new vital bone. Incorporation of the HAC/MCB composite was incomplete, whereas minimal new bone ingrowth was found in the HAC/granule composites. Though not different from each other, both composites were significantly stronger than empty defects, incorporated impacted MCB, and intact cancellous bone. At Time 0, the mechanical behavior of impacted MCB was similar to both HAC composites. In conclusion, composites of HAC and porous biomaterials can maintain relatively high strength over 8 weeks in vivo, but their incorporation into a new bony structure is slower than impacted MCB. The HAC/MCB composite showed favorable incorporation behavior.     

Synergistic effects of dimethyloxalylglycine and butyrate incorporated into α-calcium sulfate on bone regeneration

Osteogenesis is closely related to angiogenesis, and the combined delivery of angiogenic and osteogenic factors has been suggested to enhance bone regeneration. Small molecules have been explored as alternatives to growth factors for tissue regeneration applications. In this study, we examined the effects of the combined application of angiogenic and osteogenic small molecules on bone regeneration using a prolyl hydroxylase, dimethyloxalylglycine (DMOG), and a histone deacetylase inhibitor, butyrate. In a critical size bone defect model in rats, DMOG and butyrate, which were incorporated into α calcium sulfate (αCS), resulted in synergistic enhancements in bone and blood vessel formation, eventually leading to bone healing, as confirmed by micro-CT and histological analyses. In MC4 pre-osteoblast cultures, DMOG and butyrate enhanced the pro-angiogenic responses and osteoblast differentiation, respectively, which were evaluated based on the levels of hypoxia inducible factor (HIF)-1α protein and the expression of pro-angiogenic molecules (VEGF, home oxidase-1, glucose transporter-1) and by alkaline phosphatase (ALP) activity and the expression of osteoblast phenotype marker molecules (ALP, α1(I)col, osteocalcin, and bone sialoprotein). DMOG combined with butyrate synergistically improved osteoblast differentiation and pro-angiogenic responses, the levels of which were drastically increased in the cultures on αCS disks. Furthermore, it was demonstrated that αCS increased the level of HIF-1α and as a consequence VEGF expression, and supported osteoblast differentiation through the release of calcium ions from the αCS. Altogether, the results of this study provide evidence that a combination treatment with the small molecules DMOG and butyrate can expedite the process of bone regeneration and that αCS can be an efficient delivery vehicle for the small molecules for bone regeneration.     

TNFα receptor knockout in mice reduces adverse effects of magnesium deficiency on bone

Epidemiologic studies have linked low dietary magnesium (Mg) intake to osteoporosis. Dietary Mg restriction in animal models has demonstrated a decrease in bone mass and an increase in skeletal fragility. The exact mechanism for the decrease in bone mass is not clear but a decrease in osteoblast number and an increase in osteoclast number (Oc.No/B.Pm) suggests an uncoupling of bone formation and bone resorption favoring skeletal loss. Mg depletion results in an increase in inflammatory cytokines, which could explain the increase in bone resorption. We have previously demonstrated an increase in TNFα in bone from Mg deficient rodents. Here we report results of a 3 week study of a low magnesium (LM) diet and normal Mg diet in 35-day-old TNFα receptor knockout mice (TNF-r-KO) versus wild type (WT) control mice. Our results indicated that a LM diet resulted in a greater increase in Oc.No/B.Pm in the WT mice, with a trend toward greater eroded bone perimeter, as compared to TNF-r-KO. These findings suggest that TNFα may play a role in Mg deficiency-induced bone loss.     

The effects of progressive dehydration on strength and power: is there a dose response?

This study examined the effect of exercise- and heat-induced dehydration on strength, jump capacity and neuromuscular function. Twelve recreationally active males completed six resistance exercise bouts (baseline and after each 5 exposure sessions) in an increasing state of hypohydration obtained by repeated heat exposure and exercise sessions (5 periods of 20 min jogging at up to ~80% age predicted heart rate maximum at 48.5 ± 0.48°C, relative humidity 50 ± 4%). Relative to starting values, body mass decreased 1.0 ± 0.5, 1.9 ± 0.7, 2.6 ± 0.8, 3.3 ± 0.9 and 3.9 ± 1.0% after exposure 1, 2, 3, 4 and 5, respectively. However, plasma volume remained constant. No significant differences existed amongst trials in vertical jump height, electromyography data or isokinetic leg extension at a rate of 120° s⁻¹. Isometric leg extensions were significantly reduced (P < 0.05) after the first (1% body mass loss) and subsequent exposures in comparison to baseline. Isokinetic leg extensions at a rate of 30° s⁻¹ were significantly reduced after the third (2.6% body mass loss) and subsequent exposures compared with baseline. No dose response was identified in any of the tested variables yet a threshold was observed in isometric and isokinetic strength at 30° s⁻¹. In conclusion, dehydration caused by jogging in the heat had no effect on vertical jumping or isokinetic leg extensions at a rate of 120° s⁻¹. Alternatively, exercise-induced dehydration was detrimental to isometric and isokinetic leg extensions at a rate of 30° s⁻¹, suggesting the force–velocity relationship in hypohydration merits further research.     

The effects of COX-2 selective and non-selective NSAIDs on the initiation and progression of atherosclerosis in ApoE−/− mice

In this study, we investigated the effects of prolonged administration of the selective COX-2 inhibitors celecoxib and rofecoxib and the non-selective NSAID naproxen on the initiation and progression of atherosclerosis. ApoE(-/-) mice, as well as corresponding wild-type mice, were fed either a normal chow or a high fat Western diet with or without addition of the respective drugs over a period of 16 weeks. Thereafter, aortic lesion size, plasma lipid levels, and COX-2 expression in the plaques were determined. The results showed that neither the COX-2 selective inhibitors nor naproxen had a significant impact on the initiation and progression of atherosclerosis in diet-fed ApoE(-/-) mice, although both celecoxib and rofecoxib showed a tendency to reduce plaque size. This slight effect may be due to selective inhibition of COX-2 activity because the COX-2 expression was not altered in the plaque. Plasma lipid levels were also not significantly influenced by these drugs. Interestingly, in ApoE(-/-) mice that have been fed with normal chow, we found an increased incidence of plaque formation after treatment with celecoxib and rofecoxib, indicating that coxibs may promote the initiation of atherosclerosis. This effect was probably masked in diet-fed mice by the more pronounced effects of the high cholesterol diet. In conclusion, the reduction in diet-induced plaque size in animals fed a high fat diet and the promotion of atherosclerosis in mice on a normal diet indicate a dual role of the coxibs. In advanced stages of atherosclerosis, they may exert antithrombotic properties due to their COX-2 inhibiting activity, whereas in very early stages they may favor the initiation of atherogenesis. However, because these results were only observed in ApoE(-/-) and not in wild-type animals, coxibs may increase the risk of thrombosis in patients with a predisposition for thrombotic complications.     

Inhibitory effects of intrathecal p38β antisense oligonucleotide on bone cancer pain in rats

Objective: To evaluate the effects of intrathecal administration p38β antisense oligonucleotide on the development of bone cancer pain rats. Methods: Forty female SD rats weighing 180~220 g were randomly divided into 4 groups (n = 10 each): Group A (control group): intra-tibial injection of 3 μl Hank’s solution; group B (model group): intra-tibial injection of 3 μl MADB-106 mammary gland carcinoma cells of rats (4.8 × 10³/μl); group C (p38β-SODN 20 μg); group D (p38β-ASODN 20 μg). The model procedures in group C and D were same to those in the group B. From the 14^th day after operation, p38β-SODN 20 μg and p38β-ASODN 20 μg were respectively intrathecally administrated in group C and D once daily for 6 days whereas normal saline was for group A and B. Mechanical withdrawal threshold and radiant heat threshold of rat hind paws were measured before operation and every other day until 22 d of post-operation. The lumbar 4-6 spinal cord was removed on the 22^nd day. The expression of spinal p38β protein was determined by Western blot. Results: No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in control group. During the first 6 days after operation there were obvious differences in radiant heat stimulus between control group between the other groups (P < 0.05); During 14-22 days after operation, mechanical pain threshold and radiant heat threshold between p38β-SODN group and Model group were significantly changed compared with that in control group (P < 0.05). However, the differences were not remarkable between control group and p38β-ASODN group (P > 0.05). The expression of p38β protein in lumbar spinal cord was significantly higher between p38β-SODN group and Model group than that in control group (P < 0.05). There was no significant difference in p38β protein expression between p38β-ASODN group and control group (P > 0.05). Conclusions: Hyperalgesia induced by bone cancer can be inhibited by intrathecal administration of p38β antisense oligonucleotide, which is achieved by reducing expression of p38β protein.     

The stimulation of healing within a rat calvarial defect by mPCL–TCP/collagen scaffolds loaded with rhBMP-2

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly ?-caprolactone/tricalcium phosphate (mPCL–TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL–TCP/collagen scaffolds with 5 μg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing micro-computed tomography (μCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL–TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non-BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by μCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, micro-compression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL–TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL–TCP/collagen < mPCL–TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL–TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects.