Delayed decompression for cauda equina syndrome secondary to lumbar disc herniation: long-term follow-up results / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the impact of delayed decompression on long-term neurological and bladder function recovery in patients with cauda equina syndrome (CES) secondary to lumbar disc herniation (LDH).</p><p><b>METHODS</b>The clinical data of 35 patients receiving delayed decompression surgery for CES secondary to LDH were reviewed. The bladder empty function, bowel control, sexual ability and neurological functions of the lower limbs were evaluated after the operation, and the urodynamic changes were assessed in 6 patients with urodynamic data before and after the operation.</p><p><b>RESULTS</b>Surgical decompression was performed at 4.1∓3.9 weeks in 12 patients with complete CES and at 5.5∓7.6 weeks in 23 patients with incomplete CES after the onset of symptoms. The patients were followed up for a mean of 43.0∓28.9 months (3-110 months). In the 23 patients with incomplete CES, 19 obtained full recovery, 4 had slight sensory alterations in the saddle area or the lower limbs. In the 12 patients with complete CES, 2 had full recovery, 4 reported slight sensory alterations in the saddle area or the lower limbs (including 2 with occasional constipation); 6 still had sense deficit in the saddle area and difficulties in bladder or bowl emptying, but they all reported significant improvements compared to the condition before operation. Urodynamic analysis in the 6 patients with pre- and postoperative urodynamic data showed increased abdominal pressure when voiding with significantly reduced residual urine in all the 6 patients; 4 patients with abnormal first desire volume before operation reported recovery after the operation.</p><p><b>CONCLUSION</b>Patients with LDH-induced CES who missed the chance of early decompression can still expect favorable functional recovery in the long term. The improvement of bladder function following decompression is probably a result of recovery of bladder sensation and the compensation by increased intra-abdominal pressure. The key strategy to promote bladder function recovery in these patients is to promote the detrusor recovery.</p>

Teriparatide for conservative treatment of osteoporotic vertebral fracture: analysis of 12 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy of conservative treatment with teriparatide for promoting bone fracture healing in patients with osteoporotic vertebral fracture.</p><p><b>METHODS</b>Twelve postmenopausal patients (aged 73±4.8 years) with osteoporotic spinal fracture confirmed by MRI or CT scanning received conservative treatment with teriparatidesc injection supplemented with calcium and analgesics for 6 months. At the beginning and at the end of the therapy, VAS score, Oswestry Disability Index (ODI), bone mass densitometry, and X-ray of the thoracic and lumbar spine, and serum P1NP and beta-CTX levels were measured. Six of the patients received a second MRI scan after the therapy to evaluate the bone healing.</p><p><b>RESULTS</b>All the 12 patients completed the treatment, during which no new fractures or adverse events occurred. At the end of the first month of treatment, analgesic was withdrawn for all the patients. The average VAS score decreased from 8±2 to 1±2 at 1 month during the therapy, and ODI was reduced from (76±12)% to (20±5)% at 1 month and further to (5±4)% at 6 month. After the 6-month therapy, the height of the fractured vertebrae (presented as the anterior to posterior wall height ratio) was insignificantly decreased from (75±20)% to (61±20)%, the BMD was increased by (20±5)%, P1NP increased significantly from 20.9±11.4 ng/mL to 80.0±41.2 ng/mL, and beta-CTX increased from 0.30±0.17 ng/mL to 0.51±0.3 ng/mL. The 6 patients re-examined with MRI demonstrated complete bone healing after the therapy.</p><p><b>CONCLUSION</b>Teriparatide is effective for conservative treatment of osteoporotic spinal fracture and can promote bone fracture healing, improve the quality of life, and prevents vertebral collapse, and can be therefore an alternative treatment to PVP or BV.</p>

Parathyroid hormone inhibits the apoptosis of osteoblast MC-3T3E1 cells through a non-PLC-dependent protein kinase C pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of the non-PLC-dependent protein kinase C (PKC) pathway of parathyroid hormone (PTH) on the apoptosis and proliferation of osteoblast MC-3T3E1 cells.</p><p><b>METHODS</b>MC-3T3E1 cells were seeded in 96-well plates at the density of 1.5×10(4) cells/mL and incubated for 3 day. The cells were then exposed to 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-28), 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-34), 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-34)+1 µmol/L Go6983, 1 µmol/L Go6983, or deionized water (control) for 1, 24 or 48 h. After the treatments, cell counting kit-8 (CCK-8) and Caspase-Glo® 3/7 Assay (Caspase-3) were used to examine the proliferation and apoptosis of MC3T3-E1 cells.</p><p><b>RESULTS</b>CCK-8 results showed that hPTH(1-34) increased the number of MC3T3-E1 cells compared with hPTH(1-34)+Go6983 at 1 h and 24 h, but this difference was not statistically different. At 48 h, treatment with hPTH(1-34), as compared with hPTH(1-28), significantly increased the number of MC3T3-E1 cells (P<0.05), and this effect was blocked by the PKC inhibitor Go6983 (P<0.05). hPTH(1-34) did not result in significant inhibition of MC3T3-E1 cell apoptosis at 1 h and 24 h as compared with hPTH(1-34)+Go6983, but significantly inhibited the cell apoptosis as compared with hPTH(1-28) (P<0.05); this inhibitory effect was blocked by Go6983 (P<0.05).</p><p><b>CONCLUSION</b>s A relatively long time (for 48 h) of exposure to PTH can inhibit apoptosis and promote the proliferation of MC3T3-E1cells through a non-PLC-dependent PKC pathway.</p>

Activation of phospholipase C-independent protein kinase C signaling pathway of parathyroid hormone enhances CITED1 expression in mouse osteoblasts / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the functions of phospholipase C (PLC)-independent protein kinase C signaling pathway (PTH/nonPLC/PKC) of parathyroid hormone (PTH) and its role in bone metabolism.</p><p><b>METHODS</b>Osteoblasts isolated from the calvaria of 2- or 3-day-old C57BL mice, identified by alkaline phosphatase staining and Alizarin red staining, were treated for 4 h with 100 nmol/L [Gly(1), Arg(19)]hPTH(1-28) plus 10 nmol/L RP-cAMP, 10 nmol/L [Gly(1), Arg(19)]hPTH(1-34) plus 10 nmol/L RP-cAMP , 10 nmol/L PTH(1-34), or and 0.1% trifluoroacetic acid (TFA). The total RNA was then isolated for screening differentially expressed genes related to PTH/nonPLC/PKC pathway using Affymetrix mouse 12x135K gene expression profile microarray, and the identified genes were confirmed by real-time quantitative PCR. MC3T3-E1 cells treated with [Gly(1), Arg(19)]hPTH(1-28)+RP-cAMP, [Gly(1), Arg(19)]hPTH(1-34)+RP-cAMP, [Gly(1), Arg(19)]hPTH(1-34)+ RP-cAMP +100 nmol/L Go6983, or 0.1% TFA were also examined for GR(1-28)- or GR(1-34)-mediated gene expression changes using real-time quantitative PCR.</p><p><b>RESULTS</b>Alizarin red staining visualized red mineralized nodules in the osteoblasts at 28 days of culture. According to the genechip results, we selected 56 target genes related to PTH/nonPLC/PKC pathway, among which CITED1 showed higher expressions in [Gly(1), Arg(19)]hPTH(1-34)+ RP-cAMP group than in both the control group and [Gly(1), Arg(19)]hPTH(1-28)+RP-cAMP group (P<0.05), and its expression was the highest in PTH(1-34) group (P<0.05). RT-PCR of MC3T3-E1 cells yielded consist results with those in the primary osteoblasts, and the cells treated with Go6983 (a PKC inhibitor) did not show GR(1-28)- or GR(1-34)-mediated differential expression of CITED1.</p><p><b>CONCLUSION</b>The activation of PLC-independent protein kinase C signaling pathway of PTH enhances the expression of CITED1 in mouse osteoblasts to mediate the effect of PTH on bone metabolism, and this pathway is not dependent on the activation of PLC or PKA signaling.</p>

Establishment of a rabbit model of scoliosis induced by asymmetric load using springs / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish rabbit model of scoliosis induced with stable asymmetric lumbar loads.</p><p><b>METHODS</b>Scoliosis was induced in 10 two-month-old New Zealand rabbits using 316L stainless steel springs placed between the unilateral transverse processes of L2 and L5. Serial radiographs were documented before and at 1, 4, 8, 9 and 12 weeks after the operation. At weeks, the rabbits were randomly divided into SR group (n=5) with the spring removed and SK group (n=5) without spring removal.</p><p><b>RESULTS</b>All the rabbits survived the experiment with Cobb angle all greater than 10 degree at the end of the experiment. Significant changes were found in the Cobb angles and kyphotic angles at 1, 4 and 8 weeks after the operation (P<0.05). At 8 weeks, the Cobb angle, the kyphotic angle and the length of the spring were similar between SR and SK groups (P>0.05), and in the 4 weeks following spring removal in SR group, the Cobb angle and the kyphosis decreased significantly compared with those in SK group (P<0.05). Micro-CT showed that the BV/TV of the concave side was greater than that of the convex side. The length of the spring did not show obvious changes during the experiment (P>0.05).</p><p><b>CONCLUSIONS</b>Asymmetric lumbar loading is a convenient, time-saving, and highly reproducible approach for establishing rabbit models of scoliosis.</p>

Fluorescence resonance energy transfer analysis for detecting protein kinase C activation / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a sensitive and direct method for detecting the activation of protein kinase C (PKC) using fluorescence resonance energy transfer (FRET) technique.</p><p><b>METHODS</b>HEK293 cells were transfected with C kinase activity reporter (CKAR) plasmid or/and parathyroid receptor 1 plasmid , and after incubation for 72 h, the fluorescence resonance energy transfer was measured with or without parathyroid or TPA stimulation.</p><p><b>RESULTS</b>TPA reduced the efficiency of FRET and increased the emission ratio of CFP/YFP (C/Y) in HEK293 cells transfected with CKAR. PTH(1-34) could increase the emission ratio of C/Y in HEK293 cells co-transfected with CKAR and PTHR1 but not in cells transfected with CKAR.</p><p><b>CONCLUSION</b>FRET analysis using CKAR can be utilized to detect the activation of PKC, which provides a useful means for studying the signaling pathways associated with PKC.</p>

Determination of the concentrations of interleukin-18 and other cytokines in the synovial fluid in patients with osteoarthritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine the concentrations of interleukin-18 (IL-18), IL-6, IL-8, and prostaglandin E2 (PGE2) in the synovial fluid in patients with osteoarthritis (OA), and explore the role of IL-18 in the pathogenesis of OA.</p><p><b>METHODS</b>The synovial fluid was collected from 30 patients with knee OA, and the concentrations of IL-18 and the other cytokines were measured using enzyme-linked immunosorbent assay (ELISA). A linear regression was performed between IL-18 and the other cytokines.</p><p><b>RESULTS</b>The average IL-18 and PGE2 concentrations were 220-/+304 pg/ml and 89-/+104 pg/ml in the synovial fluid, respectively, and the two cytokines showed a positive correlation in the synovial fluid (r=0.628, P=0.001). The IL-18 concentration was also correlated to the concentrations of IL-6 (1200-/+1587 pg/ml, n=22; r=0.590, P=0.008) and IL-8 (5190-/+6024 pg/ml, n=9; r=0.776, P=0.014).</p><p><b>CONCLUSION</b>IL-18 can promote PGE2 production, which causes cartilage degradation in OA, thus therapies targeting this cytokine may prove an effective approach to early OA treatment.</p>