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Metformin (Met), an anti-diabetes drug, has also shown therapeutic effects for ovariectomy-induced (OVX) osteoporosis. However, similar effects against bone loss induced by a ketogenic diet (KD) have not been tested. This study was aimed to evaluate the microarchitectures and biomechanics of KD-induced osteoporosis with and without administration of Met, and compare the effect of Met on bone loss induced by KD with OVX. Forty female C57BL/6J mice were randomly divided into Sham, OVX, OVX + Met (100 mg/kg/day), KD (3:1 ratio of fat to carbohydrate and protein), and KD + Met (100 mg/kg/day) groups. After 12 weeks, the bone mass and biomechanics were measured in distal cancellous bone and in mid-shaft cortical bone of the femur. The activities of serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), together with immunohistochemistry staining of osteocalcin (OCN) and TRAP, were evaluated. Both OVX and KD induced significant bone loss and compromised biomechanical properties in the cancellous bone, but no effect was found in cortical bone. The administration of Met increased the cancellous bone volume fraction (BV/TV) from 3.78 to 5.23% following the OVX and from 4.04 to 6.33% following the KD, it also enhanced the compressive stiffness from 47 to 160 N/mm following the OVX and from 35 to 340 N/mm with the KD. Met effectively increased serum ALP in the KD group while decreased serum TRAP in the OVX group, but up-regulated expression of OCN and down-regulated expression of TRAP in both OVX and KD groups. The present study demonstrated that Met effectively attenuated the cancellous bone loss induced by KD and maintained the biomechanical properties of long bones, providing evidence for Met as a treatment of by KD-induced osteoporosis in teenage skeleton.
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Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Metformina/farmacología , Osteoporosis/tratamiento farmacológico , Animales , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Hueso Esponjoso/efectos de los fármacos , Hueso Cortical , Dieta Cetogénica/métodos , Femenino , Ratones Endogámicos C57BL , Osteocalcina/farmacologíaRESUMEN
Purpose: To describe the operative technique and clinical effects of three-column enhanced percutaneous vertebroplasty used to treat Kummell's disease. Methods: From April 2017 to April 2020, 39 patients with Kummell's disease were treated via three-column enhanced percutaneous vertebroplasty. There were 12 males and 27 females of average age 70.23 ± 7.41 years. The operative time, volume of bone cement injected, and intraoperative cement leakage were recorded. The patients were re-examined postoperatively. The VAS was used to evaluate low back pain and the ODI score to evaluate improvement in the quality-of-life. Results: All patients were successfully operated upon; the average operation time was 35.1±4.7 min and average volume of bone cement injected 4.5±0.92 mL. Five cases exhibited bone cement leakage during operation, two into the intervertebral disc and three into the anterior upper margin of the vertebral body. No leakage into the vertebral canal occurred. The average hospital stay was 2.50±0.86 days. The VAS score before operation was 7.47±0.24, but low back pain symptoms were significantly relieved after operation (P < 0.05). The VAS scores at 1 day and 1, 3, 6, and 12 months after operation were 2.91±0.09, 2.04±0.07, 1.59±0.05, 1.28±0.15, and 0.8±0.18, respectively. The preoperative ODI score was 72.97±1.45 and significantly decreased postoperatively (P < 0.05), being 30.08±1.79 at 1 day, and 25.35±0.94, 23.19±1.76, 20.49±0.65, and 20.05±0.58 at 1, 3, 6, and 12 months after operation respectively. Conclusion: Three-column enhanced percutaneous vertebroplasty effectively treats Kummell's disease. The surgical trauma is low, recovery rapid, and bone cement fixation firm, especially in patients with stage I and II disease.
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OBJECTIVE: The feasibility of anterior transarticular crossing screw (ATCS) fixation for atlantoaxial instability was confirmed in adults. However, atlantoaxial instability is more common in children. Therefore this study was aimed to ascertain the pediatric morphometric characteristics of ATCS in C1-2. METHODS: Morphometric analysis was conducted on computed tomography scan in 87 pediatric patients who were divided into groups based on ages (1-6 years, 7-10 years, and 11-16 years). Measurements were taken in sagittal and axial planes of computed tomography imaging to determine the range of screw lateral angles, incline angles, and screw lengths. RESULTS: The overall screw lengths were relatively longer in males than females. For those aged 1-6 years, the screw lengths were 25.5-32.8 mm in males and 24.2-31.3 mm in females, respectively. The screw lengths showed no difference in the 7- to 10-year group between sexes, while the incline angle was larger in females than males. And the screw lengths were 33.5-43.2 mm in males and 31.2-40.4 mm in females in the 11- to 16-year group. The screw lengths were increased with age, yet the lateral angles were decreased. We also found that the epiphyseal closure of odontoid reached 93.6% when the age was older than 7 years old. Therefore ATCS was recommended for children older than 7 years. CONCLUSIONS: The overall screw lengths and lateral angles of ATCS were larger in male children than those in females, but the incline angles were larger in females. ATCS is feasible in children, particularly those aged 7 years or older.
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Enfermedades de la Columna Vertebral , Adulto , Tornillos Óseos , Niño , Femenino , Técnicas Histológicas , Humanos , Masculino , Osteogénesis , Tomografía Computarizada por Rayos XRESUMEN
Objective: To investigate the neuroprotective effects of trihydroxyethyl rutin in rats with cervical spinal cord hemi-contusion. Methods: Adult male Sprague-Dawley rats were subjected to hemi-contusion at a stroke depth of 1.2 mm, and then intraperitoneally injected with 50 or 100 mg/kg trihydroxyethyl rutin per day for 12 weeks (T50 and T100 groups, respectively). Changes in somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and behavior were continuously monitored. At 12 weeks post-injury, immunohistochemical staining was performed to assess changes in cervical spinal cord microvascular morphology. Magnetic resonance imaging (MRI) scans were performed to examine end-stage injury in the cervical spinal cord, and Eriochrome cyanine-stained slices of spinal cord tissue were evaluated for injury. Results: There were no significant differences in biomechanical parameters among the spinal cord injury, T50 and T100 rat groups. At 3 days-post-injury, there was a significant decrease in grip strength. At 12 weeks post-injury, grip strength recovery was significantly better in the T50 and T100 groups than in the injury group. Compared with the injury group, the total limb placement frequency was significantly higher in the T50 group at 2, 4, 6, 10, and 12 weeks post-injury and in the T100 group at 2, 6, 8, and 10 weeks post-injury. Ipsilateral SEPs and MEPs were dynamic, increasing in latency and decreasing in amplitude in the injury compared with sham group. MRI scanning demonstrated that the coronal, sagittal, and transversal lesion areas were smaller in the T50 and T100 groups than in the injury group. Microvascular density showed a greater reduction in the injury group compared with the T50 and T100 groups. Eriochrome cyanine staining showed that the ipsilateral side, residual parenchyma, and gray matter areas were larger in the T50 and T100 groups than in the injury group. Conclusion: Trihydroxyethyl rutin exhibits robust neuroprotective effects, improving limb motor function and nerve electrophysiological parameters after spinal cord injury, maintaining microvascular density, and reducing the area of injury and degree of demyelination.
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OBJECTIVE: The feasibility of anterior transarticular crossing screws (ATCS) was confirmed in cadaveric specimens and it has been used in clinic. However, no study has documented the morphometric characteristics of ATCS. This study seeks to determine the morphometric characteristics of ATCS in C1-C2 fixation. METHODS: A total of 100 patients without abnormality of C1-2 were enrolled. The range of screw lateral angles (LAs) and the screw lengths of ATCS on coronal images were measured on multiplanar computed tomography images, as well as the screw incline angles (IAs) in the sagittal plane. The ideal trajectory was designed as toward to the posterosuperior points of the opposite C1 lateral mass, which had the longest screw. RESULTS: The LAs were relatively small in men (31.4°-45.3°) compared with women (32.6°-46.0°). In the sagittal plane, the IAs were ranged from 41.0° to 68.4° in men and from 44.4° to 68.1° in women. The overall screw lengths were longer in men (34.7-44.8 mm) than in women (32.2-39.6 mm). In the ideal path, the LA and IA were 38.4° and 41.0° in men and 39.6° and 44.4° in women, and the screw lengths were 44.8 mm in men and 39.6 mm in women. CONCLUSIONS: This study provides the range of screw angles and lengths of ATCS, which will help surgeons to perform ATCS safely and accurately.
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Articulación Atlantoaxoidea/cirugía , Tornillos Óseos , Vértebras Cervicales/cirugía , Inestabilidad de la Articulación/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fusión Vertebral/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effects of ketogenic metabolism on macrophage polarization, inflammation inhibition, and function recovery after acute spinal cord injury (SCI) in rats. METHODS: Sixty-four adult male Sprague-Dawley rats were randomly and equally divided into sham, standard diet (SD), ketone diet (KD), and 1, 3-butanediol (BD) groups. All animals underwent C5 unilateral laminectomy, whereas the SD, KD, and BD groups underwent C5 spinal cord hemi-contusion. The impact rod with a diameter of 1.5 mm was aligned 22.5° to the left and 1.4 mm to the midline, and then triggered to deliver a set displacement of 1.5 mm at a speed of 100 mm/s. The gene expression of inflammatory factors as well as the protein expression of inducible nitric oxide synthase, arginase-1, and inflammatory factors were measured at 1 week post-injury. Serum ketone and behavior were evaluated every second week for 12 weeks. Then, histological analyses of the gray and white matter at the epicenter were conducted at 12 weeks post-injury. RESULTS: The serum ketone levels of the KD and BD groups were significantly increased when compared with the SD group. The gene and protein expression of TNF-α and IL-1ß tended to increase after the SCI, but were inhibited in the KD and BD groups. The protein expression of inducible nitric oxide synthase, marker of M1 macrophage, was inhibited in the KD and BD groups; on the other hand, the expression of arginase-1, marker of M2 macrophage, was boosted in the KD and BD groups. The usage of the ipsilateral forelimb was higher in the KD group than in the SD group. The hemi-contusive injury resulted in an obvious ipsilateral lesion area at the epicenter, and there was no significant difference between groups regarding the lesion size. However, the spared gray matter area was significantly greater in the KD group than in the SD and BD groups. CONCLUSION: The present study suggests that ketogenic metabolism promotes macrophage polarization to M2, inhibits an inflammatory response, and alleviates the loss of gray matter after SCI. A higher ketone level, such as that induced by the ketogenic diet, seems to benefit function recovery after SCI.
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BACKGROUND: The vertebral endplate (VEP) was damaged after spinal instability induced by cervical muscle section (CMS). Whether CMS induces bone formation and mechanical loading change in the vertebra is still obscure. This study was aimed to explore mechanical loading change and endplate damage after CMS. METHODS: Forty-eight rats were randomly divided into the CMS group and the sham group. The C6/7 segments were harvested at 4, 8, and 12 weeks after surgery. The microarchitectures of the C6 vertebra âand the vertebral endplate lesions and intervertebral disc height of C6/7 were measured by micro-computed tomography. Micro-finite element analysis was used to evaluate biomechanical properties of the C6 vertebra. Bone remodelling of the C6 vertebra âand the endplate âsclerosis and intervertebral disc degeneration of C6/7 were evaluated by histological and immunohistochemical analyses. RESULTS: CMS significantly induced bone formation of the C6 ventral vertebra âand increased the biomechanical properties of mainly the ventral side at 4 weeks, which was gradually rebalanced throughout the rest of the study. CMS also significantly increased protein expression of transforming growth factor-ß1 (TGF-ß1) and phosphorylated small mothers against decapentaplegic (pSmad)2/3 âat 4 weeks. Moreover, tartrate-resistant acid phosphatase staining showed that osteoclast-positive cells were slightly in number decreased at 4 weeks, but were obviously increased at 8 weeks. The VEP of the ventral side was abraded earlier followed by calcification in situ later after CMS, consistent with the biomechanical enhancements observed. The degree of endplate degeneration was aggravated with time. Finally, CMS decreased intervertebral disc height and increased disc degeneration scores with time. CONCLUSIONS: Spinal instability induced by CMS increases bone mass and biomechanical loading of the ventral side of vertebra in the early stage, which might initiate VEP damage and cause intervertebral disc degeneration. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study indicates that vertebral trabecular changes may involve in intervertebral disc degeneration induced by spinal instability. This may help to elucidate the mechanisms by which disc degeneration occur.
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Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. Twelve adult NHPs were divided into an SCI group (n = 8, 24 and 48 weeks) and a control group (n = 4). An impactor (Φ = 4 mm) was driven to compress the left C5 cord at 800 mm/sec. The contusion displacement and peak force was 4.08 ± 0.17 mm and 19.8 ± 4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68 ± 0.47 mm and 5.99 ± 0.24 mm2 at 24 weeks post-injury (wpi), and 5.29 ± 0.17 mm and 5.95 ± 0.24 mm2 at 48 wpi. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced, while the staining intensity increased at 24 wpi and 48 wpi, compared with the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared with pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the dorsal root ganglia (DRG) was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.
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Médula Cervical/diagnóstico por imagen , Médula Cervical/lesiones , Contusiones/diagnóstico por imagen , Traumatismos de la Médula Espinal/diagnóstico por imagen , Animales , Médula Cervical/fisiopatología , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/lesiones , Contusiones/fisiopatología , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Macaca fascicularis , Masculino , Traumatismos de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: The angioarchitecture of the spinal cord and microvascular changes after acute and subacute spinal cord injury (SCI) have been reported in rodents. Microvascular changes after chronic SCI have not been explored. We characterized three-dimensional microvascular changes during the chronic phase of cervical hemicontusion SCI in rats. METHODS: At 12 weeks after 1.2-mm hemicontusion injury, microvascular parameters, including vascular volume, ratio of vascular volume to tissue volume, vascular number, and vascular separation, were measured at the epicenter and each cord segment, and the percentage and volume of spinal vessels with different diameters were measured by micro computed tomography at the injury segment. RESULTS: The 1.2-mm hemicontusion injury applied a compressive force of 1.050 ± 0.103 N to the cord, resulting in a cavity and a significant decrease in microvasculature at the epicenter. The vascular volume, ratio of vascular volume to tissue volume, and vascular number of the C5 cord decreased by 40%, 38%, and 36% at 12 weeks after SCI, whereas vascular separation increased by 54% compared with the control group. In the chronic phase after SCI, the percentage and volume of spinal microvessels at the contusion segment decreased significantly (especially vessels with diameters <40 µm). CONCLUSIONS: Blood supply to the cervical spinal cord is insufficient during the chronic phase of cervical hemicontusion SCI, especially in microvessels with diameters <40 µm. These results may provide a basis to explore microvascular changes of SCI during the chronic phase.
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Médula Cervical/irrigación sanguínea , Médula Cervical/patología , Microvasos/patología , Traumatismos de la Médula Espinal/patología , Animales , Imagenología Tridimensional/métodos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
A ketogenic diet (KD) is composed of low-carbohydrate, high-fat and adequate levels of protein. It has been used for decades as a method to treat pediatric refractory epilepsy. However, recently, its side effects on the bones have received increasing attention. In order to comprehensively evaluate the effect of KD on the microstructures and mechanical properties of the skeleton, 14 male Sprague-Dawley rats were equally divided into two groups and fed with a KD (ratio of fat to carbohydrate and protein, 3:1) or a standard diet for 12 weeks. Body weight, as well as blood ketone and glucose levels, were monitored during the experiment. Bone morphometric analyses via micro-computerized tomography were performed on cortical and trabecular bone at the middle L4 vertebral body, the proximal humerus and tibia. The compressive stiffness and strength of scanned skeletal areas were calculated using micro-finite element analysis. The KD led to higher ketone levels and lower glucose levels, with reduced body weight and total bone mineral density (TBMD). After 12 weeks, the diet reduced the bone volume fraction, the trabecular number of cancellous bone, cortical thickness, total cross-sectional area inside the periosteal envelope and the bone area of cortical bone in the tibia and humerus, while increasing trabecular separation. However, KD may not affect the L4 vertebral body. The serum calcium or phosphate concentrations in the blood remained unchanged. In addition, bone stiffness and strength were clearly decreased by the KD, and significantly correlated with the BMD and bone area at all scanned sites. In conclusion, KD led to significant bone loss and reduced biomechanical function in appendicular bones, with a lesser impact on axial bones.
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Purpose: Barium sulfate and lead oxide are commonly used for angiographic studies, but there is no report on the comparison of two contrast agents in angiography of cervical spinal cord. This study was aimed to compare the microvascular architecture of cervical spinal cord in rats after angiography with the barium sulfate agent to the lead oxide agent. Methods: Twelve adult Sprague-Dawley rats were randomly divided into the barium sulfate group (n=6) and the lead oxide group (n=6). Each rat was perfused under the same protocol using either two contrast agents. The angiography was evaluated with the vascular number at different ranks. The cervical spinal cord samples were scanned using micro-CT with low resolution and high resolution. The microvascular parameters, including ratio of vascular volume to tissue volume (VV/TV), vascular number (V.N), diameter (V.Dm), separation (V.Sp), connectivity density (Conn.D), structure model index (SMI), percentage, and volume of vessels at different diameters were measured. Results: The perfusion was better in the barium sulfate group, with more blood vessel trees of rank II and III visible compared to the lead oxide group. Low-resolution micro-CT analysis showed no difference in microvascular parameters except SMI between the two groups. High-resolution micro-CT analysis results showed that V.N and Conn.D of barium sulfate group were 60% and 290% more than those of the lead oxide group; however, V.Sp was 41% less than the lead oxide group. The percentage of vessels with diameter of 10 µm and 20 µm, and the volume of vessels with diameter of less than 100 µm was higher in the barium sulfate group than in the lead oxide group. The SMI index in the barium sulfate group was higher than that in the lead oxide group at both low resolution and high resolution. Conclusions: Compared with lead oxide, barium sulfate is more suitable for perfusion of cervical spinal cord microvessels, and cheap and nontoxic with high resolution.
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Sulfato de Bario/farmacología , Médula Cervical/diagnóstico por imagen , Medios de Contraste/farmacología , Plomo/farmacología , Óxidos/farmacología , Animales , Sulfato de Bario/química , Médula Cervical/patología , Angiografía por Tomografía Computarizada/métodos , Medios de Contraste/química , Humanos , Imagenología Tridimensional/métodos , Plomo/química , Óxidos/química , Ratas , Ratas Sprague-Dawley , Médula Espinal/diagnóstico por imagen , Microtomografía por Rayos X/métodosRESUMEN
Standard harvest and preparation of human saphenous vein (HSV) for autologous coronary and peripheral arterial bypass procedures is associated with injury and increased oxidative stress that negatively affect graft performance. In this study we investigated the global metabolomic profiles of HSV before (unprepared; UP) and after standard vein graft preparation (AP). AP-HSV showed impaired vasomotor function that was associated with increased oxidative stress, phospholipid hydrolysis and energy depletion that are characteristic of mechanical and chemical injury. A porcine model (PSV) was utilized to validate these metabolomic changes in HSV and to determine the efficacy of an improved preparation technique (OP) using pressure-regulated distension, a non-toxic vein marker, and graft storage in buffered PlasmaLyte solution in limiting metabolic decompensation due to graft preparation. Deficits in vasomotor function and metabolic signature observed in AP-PSV could be largely mitigated with the OP procedure. These findings suggest that simple strategies aimed at reducing injury during graft harvest and preparation represents a straightforward and viable strategy to preserve conduit function and possibly improve graft patency.
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Puente de Arteria Coronaria , Metabolómica , Vena Safena/cirugía , Injerto Vascular/efectos adversos , Animales , Metabolismo Energético , Homeostasis , Humanos , Hidrólisis , Oxidación-Reducción , Estrés Oxidativo , Fosfolípidos/metabolismo , Presión , PorcinosRESUMEN
Helicobacter pylori (H. pylori), one of the most common infections, is associated with various clinical outcomes. In addition to inducing inflammation, immunological clearance of the pathogen is often incomplete. Regulatory T cells (Treg cells) have been recently demonstrated to play an important role in H. pylori infection and the final clinical outcome. The aim of this study was to investigate the number and localization of CD4(+) Foxp3(+) Treg cells in stomachs and spleens of H. pylori-infected mice. The expression levels of Foxp3 as well as anti- and pro-inflammatory cytokines before and after H. pylori triple eradication therapy were examined. We found that the percentages of CD4(+) Foxp3(+) Treg cells out of the lamina propria lymphocytes (LPLs) and spleen lymphocytes in the infection group were higher than the PBS negative control group and the treatment group. H. pylori antigen stimulation was associated with an increased number of Treg cells in vitro. Furthermore, compared with the PBS and treatment groups, a higher mRNA expression level of Foxp3 in the gastric tissue was detected in the infection group. IL-10 and TGF-ß1 contents were increased significantly in the culture supernatant of spleen lymphocyte stimulated with H. pylori antigen. A marked elevation in serum IFN-γ level was observed in H. pylori-infected mice. In addition, gastric tissues of the infection group contained more Foxp3(+) cells. These results indicate that the percentage of CD4(+) Foxp3(+) Treg cells are increased in H. pylori-infected mice, suggesting a role of Treg cells in H. pylori-induced pathologies, even at the early stages of chronic gastritis and gastric tumorigenesis.