Single-dose local administration of parathyroid hormone (1-34, PTH) with ß-tricalcium phosphate/collagen (ß-TCP/COL) enhances bone defect healing in ovariectomized rats.

Parathyroid hormone (1-34, PTH) combined ß-tricalcium phosphate (ß-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by ß-TCP/collagen (ß-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, ß-TCP/COL was prepared by mixing sieved granules of ß-TCP and atelocollagen for medical use, then ß-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of ß-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and ß-TCP/COL showed a stronger effect on accelerating the local bone formation than ß-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and ß-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

Prevention of ovariectomy-induced osteoporosis in rats : Comparative study of zoledronic acid, parathyroid hormone (1-34) and strontium ranelate.

Recently, the use of the pharmacological agents strontium ranelate (SR), parathyroid hormone (1-34, PTH) and zoledronic acid (ZA) has come to prominence for the treatment of osteoporosis due to their ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on which one is more effective. There is still no direct comparative study on these three drugs. The aim of the present study was to investigate the effect of SR, PTH, ZA on preventing ovariectomy-induced osteoporosis in rats. After bilateral ovariectomy the rats randomly received vehicle, SR (500 mg/kg body weight/day, orally), PTH (20 µg/kg/day, subcutaneously) or a single injection of ZA (0.1 mg/kg, i.v.) until death at 12 weeks. The distal femurs were harvested for evaluation of bone metabolism. The rats treated with ZA demonstrated the highest levels of new bone formation as assessed by microcomputed tomography (CT), biomechanical strength, histological analysis and bone metabolism. Furthermore, PTH and SR showed a stronger effect on improving trabecular bone mass at 12 weeks. The results from the present study demonstrate that systemic administration of PTH, SR and ZA could prevent bone loss, while a single dose of ZA has a better effect on preventing ovariectomy-induced osteoporosis than either PTH or SR.

Inhibition of inflammatory cytokines after early decompression may mediate recovery of neurological function in rats with spinal cord injury.

A variety of inflammatory cytokines are involved in spinal cord injury and influence the recovery of neuronal function. In the present study, we established a rat model of acute spinal cord injury by cerclage. The cerclage suture was released 8 or 72 hours later, to simulate decompression surgery. Neurological function was evaluated behaviorally for 3 weeks after surgery, and tumor necrosis factor α immunoreactivity and apoptosis were quantified in the region of injury. Rats that underwent decompression surgery had significantly weaker immunoreactivity of tumor necrosis factor α and significantly fewer apoptotic cells, and showed faster improvement of locomotor function than animals in which decompression surgery was not performed. Decompression at 8 hours resulted in significantly faster recovery than that at 72 hours. These data indicate that early decompression may improve neurological function after spinal cord injury by inhibiting the expression of tumor necrosis factor α.

[Posterior short-segment fixation with undermining decompress for upper lumbar burst fractures].

OBJECTIVE: To observe clinical effects of posterior short-segment fixation with undermining decompress by posterior ligament complex for the treatment of upper lumbar burst fractures. METHODS: From October 2010 to March 2013,23 patients with upper lumbar burst fractures (Denis B type) were treated by posterior short-segment fixation with undermining decompress by posterior ligament complex. There were 18 males and 5 females aged from 26 to 64 years old with an average of 45.7 years old. Twelve patients were caused by falling down, 5 cases were caused by traffic accident, 4 cases were the bruise injury caused by heavy object and 2 cases were caused by other injury. Fourteen patients were L1 fracture and 9 patients were L2 fracture. Thirteen patients were combined with nerve injuries (degree D according to ASIA classification). Internal fixation were removed from 12 to 20 months with an average of 14.3 months. JOA scores and imaging changes were recorded and compared at different time points. RESULTS: All patients were followed up from 18 to 24 months with an average of 20.4 months. Thirteen patients with nerve injuries were completely recovered at 3 to 6 months after operation. JOA score at 1 year after operation was 20.63 ± 0.92, and 20.38 ± 1.06 at 3 months after removal of internal fixation,which were improved obviously than 9.90 ± 2.73 at 3 months after operation. (P > 0.05) Anterior height of injured vertebrae, vertebral body angle and local Cobb angle was (95.0 ± 0.53)%, (2.78 ± 1.36) and (2.43 ± 1.52) °respectively, and improved obviously than that of before operation (P < 0.05). There was no statistical significance in JOA scores at 3 months after removal of internal fixation and 1 year after operation (P > 0.05). CONCLUSION: posterior short-segment fixation with undermining decompress by posterior ligament complex for the treatment of upper lumbar burst fractures has advantages of minimally invasive, could effective recover vertebrae height, maintain stability of spine, decrease low back pain. It is a safe and effective operative method.

The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells.

Ganciclovir (GCV) affects the molecular mechanism of cell death and DNA damage by the rAAV (recombinant adeno-associated virus)-mediated Tet-On/HSV-tk/GCV suicide gene system in human breast cancer cell line MCF-7. A rAAV/TRE/Tet-On/HSV-tk combining a Tet-On regulating system and a suicide gene HSV-tk was used to transfect human breast cancer cell line MCF-7, and therapeutic effects on this system were studied. Afterwards, we used RT-PCR, western blotting, and a modified comet-assay to explore the potential mechanism of the HSV-tk/GCV suicide gene system in breast cancer treatments. MTT assay has shown that the cell number of GCV+rAAV+Dox group was significantly decreased compared with that of other groups after treatment and flow cytometric analysis detected that there was a substantial increase of S phase cells in this group, which means the HSV-tk/GCV suicide gene system probably works on the cell cycle. RT-PCR detected the expression level of p21 increased and PCNA had an opposite trend. Western blotting detected the protein expression of p21 and p53 increased and PCNA, CDK1, cyclin B decreased in GCV+rAAV+Dox group. The modified comet-assay shown that the very small extra fragments generated by the GCV+rAAV+Dox group treatment are visible as a small cloud extending from the comet in the direction of electrophoresis. The therapeutic mechanism of the HSV-tk/GCV suicide gene system on human breast cancer cell line MCF-7 is probably by upregulating the expression of p21 through a p53-dependent DNA damage signalling pathway, leading the decrease of protein expression of PCNA, cyclin B, CDK1 in MCF-7 cells and promoting the cell cycle arrest at G1/S phase. In summary, the HSV-tk/GCV suicide gene system arouses the death of MCF-7 cells from blocking the cell cycle and DNA damage.

Surgical Outcome in Thoracolumbar Fractures Managed by Short-segment Pedicle Instrumentation.

INTRODUCTION: This study aims to evaluate the efficiency of short-segment instrumentation in treating thoracolumbar fractures in our institute. MATERIALS AND METHODS: Twenty-two patients underwent posterior short-segment instrumentation for thoracolumbar fractures in our institute from 2007 to 2010 were included in this retrospective study. Radiological evaluations were carried out by measuring regional kyphosis angle (RA), anterior vertebral body compression percentage (AVC), and sagittal index (SI) during preoperative, postoperative and final follow-up, with the aim to investigate the rate of correction loss and implantation failure in relation to the Arbeitsgemeinschaft für Osteosythese(AO) classification of fracture system and the Load Sharing score system. CT scans were also used to determine the preoperative to postoperative canal compromise ratio. During the final follow-up, clinical outcomes were analysed based on scores from the Denis' Pain's and Work scales and neurological function was scored according to the Frankel classification. RESULTS: At the final follow-up (average duration of 15 months), 21 patients (95%) who partially or fully recovered from thoracolumbar fractures were able to resume daily activities with no complaints of pain, or only slight pain. No deterioration in neurological function were recorded. Upon evaluation at each point of time, (preoperative, postoperative and final follow-up), the average RA improved from 21º to 3.5º to 5.6º, average AVC improved from 40.8% to 90.2% to 88.2%, and average SI changed from 19.1º to 3.1º to 4.1º, respectively. Average canal compromise ratio decreased from 45% to 6.7% after surgery. No correlation was found between loss of correction and AO classification of fracture system, and loss of correction and Load Sharing system scores. Also, no correlation was found between clinical outcomes and the correction loss limited to 10º. CONCLUSION: Posterior short-segment fixation in thoracolumbar fractures showed a satisfactory outcome in 95% of the patients based on a 15-month follow-up in our institute, even among patients with comminuted fractures injuries.

[Diagnosis and management for the non-traumatic epidural sequestered cervical disc extrusion].

OBJECTIVE: To explore the clinical characteristics and management of non-traumatic epidural sequestered cervical disc extrusion. METHODS: From January 2002 to July 2011, the clinical data of 10 patients with non-traumatic epidural sequestered cervical disc extrusion were treated by anterior cervical mostly vertebraectomy and nucleus pulposus removal after decompression and internal fixation through longitudinal ligament resection. Of them,there were 6 males and 4 females with an average age of 48.2 years old (ranged from 42 to 65), the course of disease ranged from 1 month to 4 years (mean, 15 months). All patients manifested numbness and weakness of four limbs, unstable walking and sphincter of oddi dysfunction. Preoperative MRI showed segmental cervical spinal cord compression. JOA scoring criteria was applied to evaluate preoperative and follow-up neurologic function. RESULTS: Ten patients were followed up, and the duration ranged from 15 to 32 months, with an average of 21 months. No complications related to opreation occurred. Preoperative MRI showed nucelus puplposus sequestered longitudinal ligament were on equal signal on T1-weighted and corresponding pathological,while it showed equal and high signal on T2-weighted. JOA score were increased from 7.20 +/- 1.55 preoperative to 13.60 +/- 1.90 postoperative (t = -11.8, P < 0.001), and excellent in 3 cases, good in 6 cases and moderate in 1 case. CONCLUSION: Anterior cervical mostly vertebraectomy and nucleus pulposus removal after decompression and internal fixation through longitudinal ligament resection after early diagnosis is the key to success of treating non-traumatic epidural sequestered cervical disc extrusion.