Chinese topical herbal medicine gives additive effect on pharmaceutical agent on fracture healing.

OBJECTIVE: To investigate the efficacy on the combination of oral strontium ranelate (SrR) with a topical Chinese herbal paste on facilitation of fracture healing. METHODS: An open fracture was created at the mid-shaft of the right tibia of rat. A herbal paste called CDR containing Honghua (Flos Carthami), Chuanxuduan (Radix Dipsaci Asperoidis) and Dahuang (Radix Et Rhizoma Rhei Palmati) was prepared. The rats were treated with either CDR topically on the fracture site, or SrR orally, or their combinations. Bone turnover biochemical markers in serum were measured. Microarchitecture of the fracture was analyzed using micro-CT after 14 and 28 d, followed by histomorphometrical analysis. RESULTS: Micro-computed tomography analysis revealed that the combined treatment of CDR with 600 mg/g SrR significantly increased the total callus density, mineralized callus volume fraction, mineralized callus mineral content and mineralized callus density of the callus after 28 d of treatment. This result was consistent with the histomorphometrical analysis on the osteoid volume. Analysis of biochemical markers showed that the combined treatments reduced the bone resorption that occurs temporarily after fracture. CONCLUSION: This study demonstrated that the combined treatment of oral SrR and topical CDR is effective to promote fracture healing by their additive effect on promoting bone formation and retarding bone resorption.

Hydrogen peroxide induced tendinopathic changes in a rat model of patellar tendon injury.

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 µM H2 O2 (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 µM but not 500 µM H2 O2 group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 µM H2 O2 group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 µM H2 O2 group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H2 O2 impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H2 O2 -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.

Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in Cultured Rat and Human Tendon Progenitor Cells.

Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs) improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury. An in vitro study demonstrated that supplementation of H2O2 reduced tenogenic marker expression in TDSCs. These findings suggested that the possibility of TDSCs is involved in tendon healing and the cellular activities of TDSCs might be affected by oxidative stress of the local environment. After tendon injury, oxidative stress is increased. Redox modulation might affect healing outcomes via affecting cellular activities in TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities of rat/human TDSCs were measured under different dosages of vitamin C or H2O2 in this study. Lower dose of vitamin C increased cell proliferation, viability and migration; H2O2 affected colony formation and suppressed cell migration, cell viability, apoptosis, and proliferation. Consistent with previous studies, oxidative stresses (H2O2) affect both recruitment and survival of TDSCs, while the antioxidant vitamin C may exert beneficial effects at low doses. In conclusion, redox modulation affected cellular activities of TDSCs and might be a potential strategy for tendon healing treatment.

The Safety of the Thenar Portal: An Anatomical Study of the Thumb Carpometacarpal Arthroscopy.

Purpose To define the localization of the distal course of the motor branches of median nerve (MBMN) and its arborization and its quantitative relationships to the thenar portal of the carpometacarpal (CMC) joint in the hope of evaluating the safety of this portal. Method In 16 embalmed cadaveric upper extremities, the localization of the course of the MBMN and its arborization were defined. In 14 fresh-frozen cadaver upper extremities, the CMC arthroscopic portals, 1-U, 1-R, and a thenar portal, were established, after which the limbs were dissected. Measurements were taken from the portals to the superficial radial nerve, radial artery, and the MBMN. Results The distal course of the MBMN and its terminal branches were all located in the proximal third of the thenar muscles, where the thenar portal was introduced. The mean distances between vital structures and each traditional portal (1-R or 1-U) were consistent with the previously published studies. Both the superficial and the profound branches of MBMN were very close to the thenar portal, and the distance between these two main terminal branches and the thenar portal was 1.2 mm (range: 0-6.2; standard deviation [SD] = 2) and 2.2 mm (range: 0-7; SD = 2.1), respectively. Five (35.7%) of the 14 fresh-frozen specimens indicated the superficial branch lay directly over the portal. One hand (7.1%) had the profound branch crossed over the thenar portal. Four hands (28.5%) indicated both the superficial and profound branches directly overlay the thenar portal. The superficial palmar branch of the radial artery was found in six hands, and in four of them, it crossed over the thenar portal. Conclusion The distal course of the MBMN and its terminal branches were all located in the proximal third of the thenar muscles, where the thenar portal was introduced. Clinical Relevance The thenar portal could improve the view of the CMC joint of the thumb and provide better performance of procedures in this joint. We should bear in mind that the arborization of the MBMN was mostly located in the proximal third of the thenar muscle, and any operation in this area should be performed with great caution.

Whole extracts of Radix Achyranthis Bidentatae and Radix Cyathulae promote angiogenesis in human umbilical vein endothelial cells in vitro and in zebrafish in vivo.

Although Radix Achyranthis Bidentatae (RAB) and Radix Cyathulae (RC) are from two different medicinal plants, they are both used as 'Niu-Xi', a widely used traditional Chinese medicine that is believed to stimulate menstruation and affect bone injury. Angiogenesis is actively involved in treating these illnesses. The aim of the present study was to investigate whether the whole extracts of RAB and RC possess pro-angiogenic effects. In order to examine this idea whole extracts of RAB and RC were extracted with boiling water followed by ethanol, respectively. Results from the MTT, wound healing and tube formation assays in human umbilical vein endothelial cells (HUVECs) in vitro revealed that the whole extracts of RAB and RC did not increase cell proliferation or tube formation, but enhanced cell migration. Their angiogenic effects were also confirmed in zebrafish in vivo via increasing the sprout numbers in the sub-intestinal vessel. As determined by quantitative polymerase chain reaction, the whole extracts of RAB and RC both regulated the expression of cell migration-related genes in zebrafish. It is concluded that the whole extracts of RAB and RC induced angiogenesis in HUVECs in vitro and in zebrafish in vivo via increasing cell migration.

Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury.

BACKGROUND: Hand flexor tendon injuries are compromised with tendon adhesion. Tendon adhesion forms between flexor tendon and tendon sheath, reduces the range of motion of fingers, and affects their function. Oxidative stress is increased in flexor tendon after injury and might play a role in tendon adhesion formation. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble analog of vitamin E, is antioxidative. Trolox reduced oxidative stress and the expression of fibrotic cytokines in the bile gut ligation animal model. Vitamin C and Trolox are strong antioxidants, but they might also have prooxidant properties. The prooxidant properties of vitamin C and Trolox are different. In this study, our aim was to determine the effect of Trolox in reducing tendon adhesion formation. METHODS: Flexor digitorum profundus tendon injury was induced in 54 Kai-Mei Chicken according to a well-established protocol. After wound closure, an injection of 50 µL saline, 10mM Trolox, or 100mM Trolox was administered into the wound area. At 2 weeks or 6 weeks after the surgery, chicken feet were harvested for gliding test, high-resolution ultrasound measurement on a fibrotic area, and histology. RESULTS: At Week 2 after the surgery, Trolox has no effect on the flexion angle and gliding resistance, whereas a significant improvement was observed in the flexion angle and gliding resistance in the Trolox-treated groups at Week 6. However, no dose response was observed. In the ultrasound measurement, there was no significant difference in the fibrotic mass in the Trolox-treated group as compared to the saline group at Week 2. At Week 6, fibrotic mass was significantly reduced in both Trolox-treated groups. From the histological examination, the Trolox-treated groups presented a higher cellularity at Week 2 as compared to the saline group, and reduced fibrosis and adhesion at Week 6. CONCLUSION: Our results suggest that local administration of Trolox can reduce tendon adhesion, and a higher dose of Trolox did not have negative effects. CLINICAL SIGNIFICANCE: Trolox solution might be feasible to reduce tendon adhesion via intraoperative injection at the wound area during tendon repair.

Integrative Approach to Facilitate Fracture Healing: Topical Chinese Herbal Paste with Oral Strontium Ranelate.

Strontium ranelate (SrR) is one of the pharmaceutical agents reported to be effective on the promotion of fracture healing. This study aimed to evaluate the integrative effect of the oral SrR with a topical Chinese herbal paste, namely, CDR, on facilitation of bone healing. The in vivo efficacy was evaluated using rats with tibial fracture. They were treated with either CDR topically, or SrR orally, or their combined treatments. The in vivo results illustrated a significant additive effect of CDR on SrR in increasing the yield load of the fractured tibia. The in vitro results showed that neither SrR nor CDR exhibited a cytotoxic effect on UMR106 and bone-marrow stem cell (BMSC), but both of them increased the proliferation of BMSC at low concentrations. The combination of CDR at 200 µg/mL with SrR at 200 or 400 µg/ml also showed an additive effect on increasing the ALP activity of BMSC. Both SrR and CDR alone reduced osteoclast formation, and the effective concentration of SrR to inhibit osteoclastogenesis was reduced in the presence of CDR. This integrative approach by combining oral SrR and topical CDR is effective in promoting fracture healing properly due to their additive effects on proosteogenic and antiosteoclastogenic properties.

Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis.

BACKGROUND/OBJECTIVE: Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. METHODS: Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 µL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. RESULTS: Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p = 0.047, Mann-Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20-26) and 20 (range, 9-26), respectively (p = 0.382, Mann-Whitney U test). CONCLUSION: Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

The Course of the Terminal Posterior Interosseous Nerve and Its Relationship with Wrist Arthroscopy Portals.

Purpose The terminal branches of the posterior interosseous nerve (PIN) are the main articular branch on the dorsal aspect of the wrist. Its relationship to dorsal wrist arthroscopic portals has not yet been elucidated. The purpose of this study was to quantitatively describe the anatomical relationships between the dorsal wrist arthroscopic portals and the PIN. Methods Dorsal wrist arthroscopic portals were established in 28 cadaver extremities, after which the limbs were dissected. Measurements were taken from the portals to the PIN. Results The PIN passed ulnar to the 3/4 portal with a mean distance of 4.8 mm (range: 1.2-12.0, standard deviation [SD] = 2.6). The PIN passed radial to the 4/5 portal with a mean interval of 9.0 mm (range: 3.8-12.7, SD = 2.3). The main trunk of PIN or its closest terminal branch was a mean of 7.2 mm (range: 0.0-13.2 mm, SD = 3.1) radial to the midcarpal radial (MCR) portal. In 2 of the 28 specimens, one terminal branch of PIN lay directly over this portal. The distance between the midcarpal ulnar (MCU) portal and the PIN or its closest terminal branch was only a mean of 1.6 mm (range: 0-6.4 mm, SD = 2.0). In 15 of the 28 specimens, the PIN lay directly over the MCU portal, or the portal was located between the terminal branches of PIN. Conclusion The MCU portal was the most precarious, due to the close proximity of PIN and its terminal branches. The 3/4 and MCR portals were also at risk, while the 4/5 portal was relatively safe for the PIN.

Evaluation of a topical herbal agent for the promotion of bone healing.

A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.

Preclinical evaluations on the efficacy of a topical Chinese herbal formula for swelling control and pain relief.

ETHNOPHARMACOLOGICAL RELEVANCE: Patients suffering from musculoskeletal pain and swellings occupy many hospital beds and demand many rehabilitation facilities. Chinese Medicine is offering many alternatives to ameliorate pain and swelling. However, evidence-based scientific publications supporting their efficacy on pain relief are inadequate. The in vitro and in vivo efficacy of a topical use Chinese herbal bath formula (HB) on anti-inflammation and swelling control was studied. MATERIALS AND METHODS: The therapeutic mechanisms of HB were studied in vitro via anti-inflammatory and pro-angiogenic assays on RAW264.7 and HUVEC cells, respectively. Fibroblast proliferation was also studied with Hs27 cells. The in vivo angiogenic effect of HB was also studied using zebrafish model, while its efficacy of in vivo anti-Inflammation and swelling control were investigated using rat paw edema model. The affected paw was treated by immersing it in the HB or distilled water as control. The sensation of pain, change in paw thickness and inflammation marker in serum were analyzed. RESULTS: In the anti-inflammation assay, HB significantly inhibited nitrite release from RAW264.7 by 47.6% at 800 µg/ml. In the pro-angiogenic assays, it reduced wound area in HUVEC by 8.2% and increased tube formation of HUVEC by 11.5% at 300 µg/ml. HB also stimulated Hs27 proliferation up to 23.5% at 1200 µg/ml. It showed in vivo pro-angiogenic effect by increasing the mean sprout number in the embryos of zebrafish by 2.4 folds. The in vivo therapeutic effects of HB on edema was illustrated by the significant longer thermal withdrawal latency and thinner paw thickness compared with control. After 14 days of treatment, HB also reduced the IL-6 concentration in the serum of rat by 20.9% significantly. CONCLUSIONS: This study showed that HB is effective for swelling control and pain relief from edema due to its anti-inflammatory and pro-angiogenic properties.

Pro-angiogenic effects of Carthami Flos whole extract in human microvascular endothelial cells in vitro and in zebrafish in vivo.

AIM: Carthami Flos (CF) is a Chinese herb traditionally used for cardiovascular disease and bone injury in China with pharmacological effects on improving blood circulation. The aim of this study was to investigate the angiogenic potential of CF whole extract (extracted by boiling with water, followed by ethanol) and the underlying mechanisms in human microvascular endothelial cells (HMEC-1) in vitro and in transgenic TG(fli1:EGFP)(y1)/+(AB) zebrafish with transgenic endothelial cells expressing EGFP (Enhanced Green Fluorescent Protein) in vivo. METHODS: Effects of CF whole extract on cell proliferation, migration and tube formation in HMEC-1 cells in vitro were detected by MTT assay, wound healing assay and tube formation assay. Its angiogenic effect in zebrafish was investigated by monitoring the sprout number in the sub-intestinal vessel (SIV), and the underlying mechanisms were tested by quantitative real-time PCR. RESULTS: CF whole extract increased cell proliferation, migration and tube formation in vitro in HMEC-1 cells. Its angiogenic effect was also confirmed in vivo in zebrafish by increasing the sprout number in the SIV. As determined by quantitative real-time PCR, CF whole extract up-regulated the expression of angiogenesis-related genes in zebrafish, including angiogenic and its associated growth factors and receptors (e.g. IGF1, CTGF, NRP2, and VEGFR3), transcription factor (e.g. HIF1A), matrix degradation and endothelial cell migration-related factors (e.g. MMP2, MMP9, TIMP2, PLG and PLAU), cell adhesion molecules (e.g. ITGAV, ITGB3, beta-catenin and PECAM1), tubule formation factors (e.g. ANGPT1, TIE-2, PDGFR-B, CDH5, S1PR1, FGF2, Shh, and TGFRB1), and blood vessel maturation/formation factor (e.g. Ephrin B2). CONCLUSIONS: CF whole extract increased angiogenesis in HMEC-1 cells in vitro and in zebrafish in vivo with multiple mechanisms.

Effect of anti-osteoporotic agents on the prevention of bone loss in unloaded bone.

Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied. Pharmaceutical studies for the treatment and prevention of osteoporosis depend on the ovariectomized rat model, which is a suitable model for the disease in women. Disuse osteoporosis affects men and women, but there is lack of awareness and relevant pharmaceutical studies for this condition. The objectives of this study were to verify the validity of an unusual tail-suspension rat model in the induction of disuse osteoporosis and subsequent pharmaceutical treatments. This model was created by unloading the hind limbs of the rats in order to create a state of weightlessness in their hindlimb bones. Validation of the model was performed with non-suspended rats. This study included five groups of suspended rats fed with different agents, such as distilled water (control), high-, medium- and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted for 28 days. Comparisons were made between the suspended control and treatment groups. Ovariectomized and sham­operated rats were also included as a reference for bone changes during osteoporosis. Changes in bone mineral density (BMD) at the distal femur and proximal tibia, microarchitecture at the distal femur and biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and deterioration of trabeculae were similar between the suspended control and ovariectomized rats. Loss of BMD induced by tail suspension was reduced most effectively by medium-dose raloxifene. Deterioration of trabecular microarchitecture was also prevented by raloxifene. The tail-suspension rat model is suitable for the study of disuse osteoporosis under the effects of various therapeutic agents. The preventive effects of raloxifene against bone loss under disuse conditions have been demonstrated using this model.

Local vitamin-C injection reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury.

BACKGROUND: Adhesion formation is a complication of hand flexor tendon repair. Normal gliding function of flexor tendons can be impaired by an excessive fibrotic response, which may be caused by intraoperative and postoperative hemorrhage. As tissue damage and hemorrhage can disturb redox regulation, thereby favoring fibrotic responses, the purpose of this study was to investigate if antioxidants can reduce tendon adhesion by antagonizing oxidative stress. METHODS: Flexor digitorum profundus tendon injury was induced in fifty-seven chickens. In twelve chickens, oxidative stress preinjury, immediately after injury, and two and six weeks postinjury (n = 3 at each time period) was estimated by measuring tissue levels of the reduced form of glutathione (GSH) and oxidized glutathione (glutathione disulfide [GSSG]) in the proximal interphalangeal joint. In the remaining chickens, 50 µL of saline solution or vitamin-C solution (5 or 50 mg/mL) was injected into the wound immediately after closure of the tendon sheath. Samples were harvested at two weeks (n = 6 in each group) or six weeks (n = 6 in each group) postinjury for a gliding test, ultrasound imaging, and histological examination. Three chickens from each group were killed at two weeks postinjury for GSH and GSSG measurements to evaluate the treatment effects on postoperative oxidative stress. RESULTS: The GSH level was significantly decreased at two and six weeks postinjury, and the GSSG level was significantly increased at six weeks postinjury. Both 5 and 50-mg/mL vitamin C led to higher tissue levels of GSH at two weeks postinjury, as compared with that in the saline solution group, but no significant change in the GSSG level was detected. Chickens with vitamin-C supplementation showed no significant improvement in gliding resistance and no significant reduction of the fibrotic size at two weeks postinjury, but they did show significant improvement in gliding resistance at six weeks postinjury and the 5-mg/mL vitamin-C group showed a significant reduction of the fibrotic size at six weeks. Histological examination showed less peritendinous adhesion in the vitamin-C groups. CONCLUSIONS: Our results suggest that local injection of vitamin-C solution can reduce the extent of adhesion of healing tendons, probably by redox modulation, in a chicken model.

Arthroscopic reconstruction of triangular fibrocartilage complex (TFCC) with tendon graft for chronic DRUJ instability.

PURPOSE: To report the 10-years' experience of a novel arthroscopic assisted anatomical TFCC reconstruction in treatment of chronic DRUJ instability resulting from irreparable TFCC injuries. MATERIALS AND METHODS: 15 patients (7 males, 8 females) with mean age of 37 (17-49) suffering from irreparable TFCC injuries received arthroscopic assisted reconstruction using palmaris longus graft. Three skin incisions were made with creation of one radial and one ulna tunnel for passage of graft following the path of dorsal and palmar radio-ulnar ligaments under fluoroscopic and arthroscopic guidance. The joint capsule was kept intact. Early mid-range forearm rotation was started since 4th week postoperatively. RESULTS: The mean follow-up was 85.53 months (32-138). Mayo wrist score improved from 62.5 to 88 (p<0.05). Comparing contralateral side, total prono-supination range increased from 76.6% to 92.1% and grip strength increased from 56.1% to 76.9%. Twelve patients resumed previous jobs. No evidence of DRUJ arthritis was noticed. Complications included 2 late graft ruptures and one unexplained dystonia. CONCLUSIONS: Our arthroscopic assisted approach on TFCC reconstruction is safe, produces comparable results as the standard technique and may achieve better range of motion with less soft tissue dissection and earlier mobilization.

The effects of an antiosteoporosis herbal formula containing epimedii herba, ligustri lucidi fructus and psoraleae fructus on density and structure of rat long bones under tail-suspension, and its mechanisms of action.

An innovative anti-osteoporosis herbal formula containing epimedii herba, ligustri lucidi fructus and psoraleae fructus (ELP) has been previously shown its bone protecting effects in ovariectomized osteoporotic rats and also in post-menopausal osteopenic women. This study aimed to investigate the efficacy of ELP against bone loss during physical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model was used for studying the effects of ELP on bone mineral density (BMD) and bone micro-architecture. For in vitro mechanistic studies, rat mesenchymal stem cells (MSCs) and mouse macrophage cells (RAW264.7) were used for studying the effects of ELP on osteogenic/adipogenic differentiations and osteoclastogenesis, respectively. Our data illustrated that ELP had a significant preventive effect against bone loss induced by tail-suspension (TS) at day 28 (p < 0.01) as indicated in the reduction in BMD loss and the preservation of bone micro-architecture. ELP could significantly promote the osteogenesis and suppress the adipogenesis (p < 0.05) in MSCs. Besides, significant inhibition of osteoclast formation (p < 0.01) was found in ELP-treated RAW264.7 cells upon receptor activator of nuclear factor kappa-B ligand induction. Our study presents the first scientific evidence that ELP had a significant preventive effect against bone loss induced by TS through the actions of enhancing osteogenesis, suppressing adipogenesis and osteoclastogenesis.

In Vivo Study on the Pharmacological Interactions between a Chinese Herbal Formula ELP and Antiresorptive Drugs to Counteract Osteoporosis.

Antiresorptive drugs, alendronate and raloxifene, are effective in lowering bone mineral density (BMD) loss in postmenopausal women. However, long-term treatment may be associated with serious side effects. Our research group has recently discovered that a Chinese herbal formula, ELP, could significantly reduce BMD loss in animal and human studies. Therefore, the present study aimed to investigate the potential synergistic bone-protective effects of different herb-drug combinations using ovariectomized rats. To assess the efficacy of different combinations, the total BMD was monitored biweekly in the 8-week course of daily oral treatment. Bone microarchitecture, bone strength, and deoxypyridinoline level were also determined after 8 weeks. From our results, coadministration of ELP and raloxifene increased the total tibial BMD by 5.26% (2.5 mg/kg/day of raloxifene; P = 0.014) and 5.94% (0.25 mg/kg/day of raloxifene; P = 0.026) when compared with the respective dosage groups with raloxifene alone. Similar synergistic effects were also observed in BMD increase at distal femur (0.25 mg/kg/day; P = 0.001) and reduction in urinary deoxypyridinoline crosslink excretion (2.5 and 0.25 mg/kg/day; both P = 0.02). However, such interactions could not be observed in all alendronate-treated groups. Our data provide first evidence that ELP could synergistically enhance the therapeutic effects of raloxifene, so that the clinical dosage of raloxifene could be reduced.

Sushi hand roll dressing for thumb polydactyly.

Surgery for thumb polydactyly is a commonly performed orthopaedic procedure in Asia Pacific region. Despite extensive publications on topical dressing methods and dressing materials in paediatric wounds, there is no single design that affords a secure and yet comfortable post-operative wound dressing for thumb polydactyly. We have devised a new dressing method, which can easily be fabricated for such purpose from readily available materials in operation theatre.

Functional pectoralis minor muscle flap transplantation for reconstruction of thumb opposition: an anatomic study and clinical applications.

In this report, we present the results of an anatomic study on the dimensions of the pectoralis minor muscle and its neurovascular supply in 10 adult human cadavers, in attempt to evaluate the feasibility of microsurgical transplantation of a part of the muscle for thumb opposition reconstruction. A series of five patients consequently underwent thenar reconstruction with the pectoralis minor muscle flap from December 2004 to October 2006. The transferred muscle was reinnervated with the third lumbrical branch of the ulnar nerve. Follow-up assessment showed that the patients recovered functional opposition of carpometacarpal joint with 24 degrees of pronation, and a muscle power with M4 to M5. All patients were satisfied with the appearance of reconstructed thenar eminence. We recommend this new technique for thenar and opposition reconstruction in patients who have severe loss of thenar muscles, injury to the median nerve, and wish to improve the appearance of thenar eminence.

Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model.

OBJECTIVE: To establish a drill-hole defect model in osteoporotic mouse femur by comparing temporal cortical bone healing pattern between OVX-induced osteoporotic bone and sham-operated bone. METHODS: 3-month-old female C57BL/6 mice were randomly divided into an ovariectomy group (OVX) and a sham-operated group (Sham). At 6 weeks post-surgery, 7 mice from each group were sacrificed to examine the distal femur and femoral shaft by both micro-CT and mechanical testing for confirming established osteoporosis induced by OVX. In the remaining mice, a cortical bone defect 0.8mm in diameter was created on the mid-diaphysis of the right femur. The local repair process at days 0, 3, 7, 10, 14 and 21 after creation of the drill-hole was in vivo monitored by high-resolution micro-CT scanning. At each time point, each animal was scanned four times and was removed from the scanner between scans to determine reproducibility. Mice were sacrificed at each time point (n=12 at days 0, 3, 7, 10 and 14; n=20 at day 21). Before sacrifice, sera were collected to examine expression of bone formation marker P1NP (procollagen type I N-terminal propeptide) and bone resorption marker CTX (C-terminal telopeptide of type I collagen). After sacrifice, callus samples were collected and subjected to the following analyses: micro-CT-based angiography; histological examination; immunohistochemical staining to determine estrogen receptor expression; quantitative real-time PCR analysis of collagen type I, collagen type II, collagen type X, osteocalcin, tartrate-resistant acid phosphatase, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) gene expression; and three-point mechanical testing. RESULTS: At 6 weeks post-surgery, OVX mice had significantly lower bone mass, impaired bone micro architecture and compromised mechanical properties compared to the Sham mice. In vivo micro-CT analysis revealed that the bone volume fraction in the defect region was significantly lower in the OVX group from day 10 to day 21 post-injury as compared to the Sham group, and was significantly lower in the intra-medulla region in the OVX group from day 7 to day 14 as compared to the Sham group, consistent with the histological data. Analysis of bone biochemical markers indicated that circulating P1NP levels normalized by baseline in the OVX mice were significantly lower than in the Sham mice from day 7 to day 10, and that temporal expression of circulating CTX levels normalized by baseline was also lower in the OVX mice as compared to the Sham mice. These results were consistent with quantitative real-time PCR analysis. ER alpha mRNA expression was significantly lower in the OVX mice, whereas ER beta mRNA expression was significantly higher in the OVX mice as compared to the Sham mice at all time points examined, consistent with immunohistochemical staining. The restoration of femoral mechanical property, determined based on ultimate load and energy-to-failure, was significantly lower in the OVX mice than in the Sham mice. In addition, in vivo micro-CT scanning for quantifying new bone formation in the defect site was highly reproducible in this model. CONCLUSION: The bone healing of the drill-hole defect was impaired in mice with OVX-induced osteoporosis. The present study provides a model to investigate the functional role of specific gene in osteoporotic bone healing and may facilitate development of novel therapeutic strategies for promoting osteoporotic bone healing.