RESUMEN
Neural stem cell (NSCs) transplantation has great potential in the treatment of spinal cord injury (SCI). Previous studies have indicated that the Wnt pathway could regulate the expression of basic helix-loop-helix (bHLH) family factor Hes5 and Mash1 in NSCs, but not through the notch intracellular domain. This suggests that there are other signals involved in this process. The aim of this study was to investigate the role of Wnt-Gli2 pathway in the treatment of SCI by transplanting neural stem cells. NSCs were isolated from the striata of embryonic day 14 mice. Activation of the Wnt pathway was achieved using Wnt3a protein, while Gli2 was inhibited using Gli2-siRNA. Expression levels of Gli2 and bHLH factors were assessed using western blotting. NSCs proliferation was evaluated using CCK-8 assay, and neural differentiation was determined by immunofluorescence staining. Finally, the modified NSCs were transplanted into mice with SCI, and their effects were assessed using behavioral and histological tests. Our results demonstrated that Wnt3a promoted the expression of Mash1 through Gli2. Moreover, the expression of Ngn1 and Hes1 was up-regulated, while Hes5 was down-regulated. Wnt3a also promoted NSCs proliferation and neural differentiation through this signaling pathway. In vivo experiments showed that NSCs transplantation mediated by Wnt3a-Gli2 signaling increased the number of neurons and resulted in improved Basso Mouse Scale scores. In conclusion, our findings suggest that Gli2 plays a role in mediating the regulation of Wnt3a signaling on promoting NSCs proliferation and neural differentiation. This pathway is therefore important in NSCs-mediated SCI recovery.
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Células-Madre Neurales , Traumatismos de la Médula Espinal , Ratones , Animales , Vía de Señalización Wnt , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Traumatismos de la Médula Espinal/cirugía , Traumatismos de la Médula Espinal/metabolismo , Regeneración Nerviosa , Diferenciación Celular/fisiología , Médula Espinal/metabolismoRESUMEN
Introduction: Heart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated. Methods: In this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1-/-) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF. Results: Compared with the WT-ISO group, Sigmar1-/- aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1-/- exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar-/--ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues. Conclusion: Taken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.
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Cerebrospinal fluid leakage can lead to postoperative refractory headaches and meningitis. Dural injury is the main cause of postoperative cerebrospinal fluid leakage. Previously, we performed a comprehensive anatomic study on the dorsal meningovertebral ligaments in the lumbosacral regions and concluded that these ligaments are an anatomic factor leading to dural laceration. However, no clinical study has examined the relationship between dorsal meningovertebral ligaments and the incidence of intraoperative cerebrospinal fluid leakage. The goal of this study was to investigate the effect of prophylactic intraoperative pretreatment of the meningovertebral ligaments on the incidence of cerebrospinal fluid leakage during surgery. [Orthopedics. 2023;46(1):e66-e71.].
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Ligamentos , Procedimientos Ortopédicos , Humanos , Pérdida de Líquido Cefalorraquídeo/epidemiología , Pérdida de Líquido Cefalorraquídeo/prevención & control , Pérdida de Líquido Cefalorraquídeo/cirugía , Duramadre/cirugía , Incidencia , Ligamentos/cirugía , Región Lumbosacra/cirugía , Complicaciones Posoperatorias/prevención & controlRESUMEN
OBJECTIVES: To study the changes of bacterial flora after a series of preoperative oral disinfection and the postoperative recovery of nerve function of patients with craniovertebral junction disorders who were treated with transoral approach operations. METHODS: This research analyzed 20 cases collected from October 2009 to May 2010. All these patients were with CVJ disorders, including 8 males and 12 females, aged 2 to 66 (38.1 on average), and they were all treated with transoral approach operations. The mucosa samples of the posterior pharyngeal wall were sent for bacteria culture. These samples were collected by sterile cotton swabs at four crucial points, including 3 days before operation/before gargling, 3 days after continuous gargling/after anesthesia intubation on the day of operation, after intraoperative cleaning and washing of the mouth, and after intraoperative iodophor immersion. The microflora was stained by means of smear and further counted after an investigation by microscope. The neural function of patients was evaluated by the ASIA classification and the JOA scores. All patients but two with posterior stabilization performed respectively underwent transoral atlantoaxial reduction plate (TARP) fixation consecutively in the same sitting. A regular reexamination of cervical vertebra with lateral and open mouth X-ray, CT and MRI was conducted after operation to evaluate the reduction of atlantoaxial dislocation, internal fixation position, bone graft fusion, inflammatory lesions and tumor recurrence. RESULTS: This bacteriological research showed that the mucosa of the posterior pharyngeal wall of all the patients was in a sterile state after a series of oral preoperative preparations and intraoperative iodophor disinfection, which was considered as type I incision. The bacterial culture results of the mucosa samples of the posterior pharyngeal wall collected at different time points showed significant differences (χ2 = 42.762, P = 0.000). All the patients had improvement in ASIA, and their neural functions were improved to different levels after operation. There was a significant difference in JOA scores before and after operation (t = 8.677, P = 0.000). Postoperative imaging examination showed that the atlantoaxial screw position was good and firm, and the CVJ disorders were treated appropriately. CONCLUSION: It is safe and effective to cut the posterior pharyngeal muscle layer and implant internal fixation by means of transoral approach.
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Fusión Vertebral , Masculino , Femenino , Humanos , Fusión Vertebral/efectos adversos , Fusión Vertebral/métodos , Estudios de Seguimiento , Resultado del Tratamiento , Bacterias , YodóforosRESUMEN
Intervertebral disc (IVD) degeneration is one of the most important causes of lower back pain. Tissue engineering provides a new method for the experimental treatment of degenerative disc diseases. This study aims to develop a natural, acellular, 3D interconnected porous scaffold derived from the extracellular matrix (ECM) of nucleus pulposus. The nucleus pulposus (NP) was decellularized by sequential detergent-nuclease methods, including physical crushing, freeze-drying and cross-linking. These 3D porous scaffolds were fabricated with a high porosity of (81.28 ± 4.10)%, an ideal pore size with appropriate mechanical properties. Rabbit bone marrow mesenchymal stem cells (rBMSCs) were seeded and cultured on the scaffolds. And the mechanical tests showed the compressive elastic modulus of the scaffolds cultured for 4 weeks reached 0.12 MPa, which was better than that of the scaffolds cultured for 2 weeks (0.07 MPa) and that of the control group (0.04 MPa). Scanning electron microscopy (SEM), histological assays, molecular biology assays revealed that the scaffolds could provide an appropriate microstructure and environment for the adhesion, proliferation, migration and secretion of seeded cells in vitro. As assays like histology, immunohistochemistry and the real-time qRT-PCR showed, NP-like tissues were preliminarily formed. In conclusion, the 3D porous scaffold derived from NP ECM is a potential biomaterial for the regeneration of NP tissues. A natural, acellular, 3D interconnected porous scaffold derived from the extracellular matrix (ECM) of nucleus pulposus was developed by sequential detergent-nuclease and freeze-drying method, which can reduce the damage of protein activity to the minimum. It is very similar to the composition and internal environment of the natural nucleus pulposus, because it derived from the natural nucleus pulposus. Scanning electron microscopy (SEM), histological assays, molecular biology assays revealed that the scaffolds could provide an appropriate microstructure and environment for the adhesion, proliferation, migration, and secretion of seeded cells in vitro.
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Biomimética , Núcleo Pulposo/metabolismo , Animales , Materiales Biocompatibles/metabolismo , Células de la Médula Ósea/citología , Técnicas de Cultivo de Célula , Proliferación Celular , Supervivencia Celular , Matriz Extracelular , Células Madre Mesenquimatosas/citología , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Porosidad , Presión , Conejos , Estrés Mecánico , Sales de Tetrazolio/química , Tiazoles/química , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
Bone related-bacterial diseases including wound infections and osteomyelitis (OM) remain a serious problem accompanied with amputation in most severe cases. In this work, we report an exceptional effective antibacterial alginate aerogel, which consists of tigecycline (TGC) and octahedral Cu crystal as an organo-inorganic synergy platform for antibacterial and local infection therapy applications. The alginate aerogel could greatly prolong the release of copper ions and maintain effective antibacterial concentration over 18 days. The result of in-vitro experiments demonstrated that the alginate aerogel has an exceptional effective function on antibacterial activity. Cytotoxicity tests indicated that the alginate aerogel has low biological toxicity (average cell viability >75%). These remarkable results suggested that the alginate aerogel exhibits great potential for the treatment of OM, and has a prosperous future of application in bone tissue engineering.
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Alginatos/química , Antibacterianos/química , Huesos/efectos de los fármacos , Cobre/química , Escherichia coli/efectos de los fármacos , Geles/química , Alginatos/síntesis química , Alginatos/toxicidad , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Huesos/microbiología , Proliferación Celular/efectos de los fármacos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Geles/síntesis química , Geles/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Iones/química , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Tigeciclina/químicaRESUMEN
A meta-analysis was performed to compare cervical arthroplasty with anterior cervical diskectomy and fusion for single-level cervical spondylosis. A comprehensive search was conducted with PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, to April 30, 2015. Random-effects models were used for heterogeneous data. Fixed-effects models were used for pooled nonheterogeneous data. Mean difference or standard mean difference was used for continuous outcomes, and odds ratio, risk ratio, or risk difference was used for dichotomous outcomes. [Orthopedics. 2017; 40(1):e23-e34.].
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Artroplastia/métodos , Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Discectomía/métodos , Degeneración del Disco Intervertebral/cirugía , Disco Intervertebral/cirugía , Fusión Vertebral/métodos , Espondilosis/cirugía , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Osteosarcoma is a malignant bone cancer of which the survival rate is still low. One reason for this low survival rate is drug resistance. In the past, it has been shown that microRNAs may play critical roles in osteosarcoma development and drug resistance. The mechanisms by which osteosarcoma cells acquire this resistance have, however, remained largely unknown. Here, we aimed at assessing the role of microRNA-488 in the acquisition of drug resistance by osteosarcoma cells. METHODS: Quantitative RT-PCR was used to measure the expression of microRNA-488 in primary osteosarcoma samples and in osteosarcoma-derived cells, whereas microRNA-488 mimics and inhibitors were used to modify its expression in these cells. Luciferase reporter, Western blotting, cell viability, apoptosis and ChIP assays were used to assess the various effects of modified microRNA-488 expression in osteosarcoma-derived cells. RESULTS: We found that microRNA-488 is over-expressed in primary osteosarcoma tissues and osteosarcoma-derived cells and that hypoxia can induce microRNA-488 expression via binding to the hypoxia response element (HRE) in its promoter. We also found that exogenous over-expression of microRNA-488 promotes the proliferation, reduces the apoptosis and decreases the sensitivity to chemotherapy (doxorubicin) of osteosarcoma cells via direct targeting of the tumor suppressor Bim, which is a mediator of apoptosis. In contrast, we found that transfection of a microRNA-488 inhibitor resulted in an increase in both apoptosis and drug sensitivity, and a decrease in proliferation. CONCLUSIONS: Our data suggest that miRNA-488 may serve as a predictor of response to chemotherapy and as a therapeutic target in human osteosarcomas.
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Apoptosis/genética , Proteína 11 Similar a Bcl2/metabolismo , Neoplasias Óseas/patología , Resistencia a Antineoplásicos/genética , MicroARNs/genética , Osteosarcoma/patología , Western Blotting , Neoplasias Óseas/genética , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Técnicas de Silenciamiento del Gen , Humanos , Osteosarcoma/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Expandable screws have greater pullout strength than conventional screws. The purpose of this study was to compare the biomechanical stability provided by a new built-in expandable anterior spinal fixation system with that of 2 commonly used anterior fixation systems, the Z-Plate and the Kaneda, in a porcine partial vertebral corpectomy model. METHODS: Eighteen porcine thoracolumbar spine specimens were randomly divided into 3 groups of 6 each. A vertebral wedge osteotomy was performed by removing the anterior 2/3 of the L1 vertebral body and the T15/L1 disc. Vertebrae were fixed with the Z-Plate, Kaneda, or expandable fixation system. The 3-dimensional spinal range of motion (ROM) of specimens in the intact state (prior to osteotomy), injured state (after osteotomy), and after internal fixation were recorded. The pullout strength and maximum torque of common anterior screws, the expandable anterior fixation screw unexpanded, and the expandable anterior fixation screw expanded was tested. RESULTS: After internal fixation, the expandable device and Z-plate system exhibited higher left bending motion than the Kaneda system (5.50° and 5.37° vs. 5.04, p = 0.001 and 0.008, respectively), and the Z-plate and Kaneda groups had significantly higher left axial and right axial rotation ROM as compared to the expandable device group (left axial rotation: 5.23° and 5.02° vs. 4.53°; right axial rotation: 5.23° and 5.08° vs. 4.49°). The maximum insertion torque of the expandable device was significantly greater than of a common screw (5.10 vs. 3.75 Ns). The maximum pullout force of the expandable device expanded was significantly higher than that of the common screw and the expandable device unexpanded (3,035.48 N vs. 1,827.38 N and 2,333.49 N). CONCLUSIONS: The built-in anterior fixation system provides better axial rotational stability as compared to the other 2 systems, and greater maximum torque and pullout strength than a common fixation screw.
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Fenómenos Biomecánicos/fisiología , Fijadores Internos/normas , Vértebras Lumbares/fisiología , Ensayo de Materiales/normas , Rotación , Vértebras Torácicas/fisiología , Animales , Placas Óseas/normas , Tornillos Óseos/normas , Ensayo de Materiales/métodos , Distribución Aleatoria , PorcinosRESUMEN
In this study, the scaffolds based on mineralized silver-loaded coral hydroxyapatites (SLCHAs) were developed for bone regeneration in the radius of rabbit with a 15-mm infective segmental defect model for the first time. The SLCHAs were achieved by surface adsorption and ion-exchange reaction between Ca(2+) of coral hydroxyapatite (CHA) and Ag(+) of silver nitrate with different concentration at room temperature. Release experiment in vitro, X-ray diffraction and scanning electron microscopy equipped with energy-dispersive X-ray spectrometer were applied to exhibit that the scaffold showed some features of natural bone both in main component and hierarchical microstructure. The three-dimensional porous scaffold materials imitate the microstructure of cancellous bone. Mouse embryonic pre-osteoblast cells (MC3T3-E1) were used to investigate the cytocompatibility of SLCHAs, CHA and pure coral. Cell activity were studied with alkaline phosphataseenzyme assay after 2, 4, 6 days of incubation. It was no statistically significant differences in cell activity on the scaffolds of Ag(+)(13.6 µg/mL)/CHA, Ag(+)(1.7 µg/mL)/CHA, CHA and pure coral. The results indicated that the lower silver concentration has little effect on cell activity. In the implantation test, the infective segmental defect repaired with SLCHAs was healed up after 10 weeks after surgery, and the implanted composites were almost substituted by new bone tissue, which were very comparable with the scaffold based on mineralized CHA. It could be concluded that the SLCHAs contained with appropriate silver ionic content could act as biocidal agents and maintain the advantages of mineralized CHA or coral, while avoiding potential bacteria-dangers and toxical heavy-metal reaction. All the above results showed that the SLCHAs with anti-infective would be as a promising scaffold material, which whould be widely applied into the clinical for bone regeneration.
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Antozoos/química , Durapatita/química , Osteogénesis/fisiología , Fracturas del Radio/cirugía , Plata/química , Andamios del Tejido , Animales , Materiales Biocompatibles Revestidos/síntesis química , Diseño de Equipo , Análisis de Falla de Equipo , Ensayo de Materiales , Conejos , Fracturas del Radio/patologíaRESUMEN
OBJECTIVE: To explore the osteogenic potential of the nano-hydroxyapatite/collagen/calcium alginate composite implanted in animals. METHODS: Eighteen 3-month-old New Zealand white rabbits were adopted to prepare 15 mm segmental defect model at the middle part of radius. Rabbit models were randomly divided into experimental group and blank control group. Nano-hydroxyapatite/collagen/calcium alginate was implanted into the defects of experimental group. Four, 8, and 12 weeks after operation, all specimens were examined by X-ray and histological methods. RESULTS: All the 18 rabbit models entered the final analysis. X-ray showed that osteotylus was seen in the whole defect area in the experimental group 12 weeks after operation, during which osteogenesis was more obvious than in weeks 4 and 8 and the bridge grafting of defect area was obviously visible. In the blank control group, osteotylus was only observed at the two ends of the defects, and no osteogenesis was found in the central part of the defect area. Histological examination showed that new osteoid formation was seen in internal porous zone in the experimental group in weeks 4 and 8; in week 12, more woven bone-like tissues were visible and trabecular-like structure was formed. CONCLUSION: The nano-hydroxyapatite/ collagen/calcium alginate has good osteogenic potential.
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Alginatos/química , Colágeno/química , Durapatita/química , Osteogénesis , Radio (Anatomía)/anatomía & histología , Animales , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Conejos , Ingeniería de Tejidos , Cicatrización de HeridasRESUMEN
OBJECTIVE: To investigate the therapeutic effect of the chitosan/polyethylene glycols-succinate/ mitomycin C (CH/PEG-SA/MMC) film on epidural scarring tissues. METHODS: According to a specific proportion of respective materials, the film of CH/PEG-SA/MMC was developed under some condition. Thirty SD rats were selected and randomized into 6 groups with 5 rats in each group. A rat model of lumbar laminectomy was used. The amount of 20 mg of the CH film was implanted into the animals in group I, 20 mg of CH/PEG film in group II, 20 mg of CH/PEG-SA film in group III, 0.05 mg/mL of the MMC soaking for 5 minutes in group IV, 20 mg of CH/PEG-SA/MMC film in group V, and nothing was done in group VI. Specimens were harvested 4 weeks after the above procedures and were then subjected to immunohistochemical and histological examinations to compare their therapeutic effects on epidural cicatricial tissues. RESULTS: All rats were in good conditions after operation, without gait abnormality, restlessness, infection and death. There was no significant difference among the 6 groups in the postoperative Rydell score (P < 0.05). The content of hydroxyproline in groups I, II, III, IV, V and VI was (0.570 8 +/- 0.345 0), (0.728 6 +/- 0.150 6), (0.553 4 +/- 0.122 3), (0.313 3 +/- 0.106 4), (0.261 9 +/- 0.102 1) and (1.020 1 +/- 0.120 6) microg/mg, respectively. There was a significant difference between groups IV, V and groups I, II, III (P < 0.05), and there was significant difference between group VI and the rest 5 groups (P < 0.05). According to the histological observation, group V had less collagenous fiber paralleling the dura mater, with few inflammatory cells infiltration, with few capillary vessels and no reaction of macrophages. CONCLUSION: CH/PEG-SA/MMC films can effectively reduce the amount of Hyp in epidural scarring tissues after lumbar laminectomy and therefore is a good treating method in preventing scarring tissue adhesion.
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Materiales Biocompatibles/administración & dosificación , Cicatriz/prevención & control , Sistemas de Liberación de Medicamentos , Laminectomía/efectos adversos , Complicaciones Posoperatorias/prevención & control , Animales , Quitosano/administración & dosificación , Cicatriz/etiología , Modelos Animales de Enfermedad , Espacio Epidural/patología , Masculino , Mitomicina/administración & dosificación , Polietilenos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Succinatos/administración & dosificaciónRESUMEN
OBJECTIVE: To develop a chitosan (CH)/polyethylene glycols succinate acid (PEG-SA)-mediated mitomycin C (MMC) delivery system and investigate its drug release characteristics in vitro and its effect against scar tissue adhesion in vivo. METHODS: Mitomycin C loading in the composite CH/PEG-SA/MMC films was determined using ultraviolet. The freeze-dried films were dispersed in 1 ml PBS (pH7.4) and mitomycin C release in vitro was determined according to the mitomycin C concentration-UV value standard curve. The influence of the film structure on the drug release was evaluated. The drug delivery system was then implanted in SD rats, and 4 weeks later, immunohistochemical and histological examinations were carried out to assess the therapeutic effect on epidural scar tissue. RESULTS: The linear regression equation of the mitomycin C concentration-UV value standard curve was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R(2)=1.000). The film demonstrated good drug delivery capability, and 20 mg of the samples in PBS showed a peak mitomycin C release after 12 days of 14.9616 microg/ml, which was higher than the ID(50) of mitomycin C (10.4713 microg/l) to the fibroblasts. On days 18 and 32, another two drug release peaks occurred (14.4824 microg/ml and 11.4092 microg/ml, respectively), followed by maintenance of slow release. Till day 60, the accumulative mitomycin release reached 0.1793 microg/ml, and the loaded drug was ultimately completely released. Significant differences were noted in the hydroxyproline content in the scar tissues of different groups (F=12.085, P=0.000), and the CH/PEG-SA/MMC DDS reduced the amount of scar tissue and promoted its orderly alignment to control potential scar hyperplasia that may compress the spinal cord and nerve roots. CONCLUSION: The composite film for drug delivery possesses good flexibility and mechanical properties and allows sustained drug release of mitomycin C to prevent epidural scar tissue adhesion following lumbar laminectomy.
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Sistemas de Liberación de Medicamentos , Disco Intervertebral/efectos de los fármacos , Mitomicina/administración & dosificación , Adherencias Tisulares/prevención & control , Animales , Quitosano/química , Disco Intervertebral/fisiopatología , Disco Intervertebral/cirugía , Mitomicina/química , Polietilenglicoles/química , Polietilenos/química , Ratas , Ratas Sprague-Dawley , Succinatos/químicaRESUMEN
OBJECTIVE: To develop the chitosan/polyethylene glycols succinate (CH/PEG-SA) mitomycin C (MMC) film drug delivery system and its release effect in vitro. METHODS: MMC loading in composite films was determined using a UV-visible spectrophotometer. Freeze-dried films (90 mg) were immersed in 1 mL PBS buffer (pH 7.4). The concentrations of MMC releasing in vitro were calculated refer to the standard curve of relationship between the concentrations of MMC and the value of UV-visible spectrophotometer. The curve of the concentrations of MMC releasing from the films in vitro was drawn at different time. The relationship between the films, structure and the drug releasing was revealed. RESULTS: The films showed swelling without brittleness. The equation of Linear Regression was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R2=1.000). The film had a good drug delivery capability. The samples weighing 20 mg were soaked into the liquid of PBS, the releasing concentrations of MMC were 14.9616 microg/mL at 12 days, 14.4824 microg/mL at 18 days and 11.4092 microg/mL at 32 days, which was higher than ID50 of MMC (10.4713 microg/L) to fibroblast. Then MMC was released at a low concentration. The releasing concentrations of MMC was 0.1793 microg/mL at 60 days until being delivered completely. CONCLUSION: The flexibility is enhanced , and the mechanical function is improved, so that there is better nature of membrane. The initial burst is avoided more effectively, and the drug releasing would be maintained for a certain time.
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Quitosano/administración & dosificación , Sistemas de Liberación de Medicamentos , Mitomicina/administración & dosificación , Polietilenglicoles/administración & dosificación , Técnicas In VitroRESUMEN
OBJECTIVE: To evaluate the accuracy of ultrasonographic diagnosis for central slip rupture of the finger extensor tendon mechanism of the proximal interphalangeal joint. METHODS: Sixty-seven consecutive patients with injuries to the proximal interphalangeal joint underwent ultrasonic examination with a linear 5-10 MHz hockey stick-shaped scanner head. Meanwhile three methods of physical examination were applied to assess the injury, and the results of ultrasonic detection and physical examinations were compared with surgical findings. RESULTS: Thirty-nine patients with central slip rupture of the finger extensor mechanism were confirmed. Ultrasonography achieved good consistence with surgical findings in injury detection. For ultrasound and physical examinations, the sensitivity for injury detection was 100% and 89.74% with specificity of 96.43% and 82.14%, respectively, showing significant difference (P<0.01). CONCLUSION: As an accurate noninvasive method, ultrasonographic diagnosis can identify central slip rupture in the extensor mechanism of the finger over the proximal interphalangeal joint in early stages.
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Traumatismos de los Dedos/diagnóstico por imagen , Articulaciones de los Dedos/diagnóstico por imagen , Traumatismos de los Tendones/diagnóstico por imagen , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , UltrasonografíaAsunto(s)
Apoptosis/efectos de los fármacos , Imidazoles/farmacología , Piridinas/farmacología , Traumatismos de la Médula Espinal/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Inhibidores Enzimáticos/farmacología , Ratas , Transducción de Señal , Traumatismos de la Médula Espinal/patologíaRESUMEN
OBJECTIVE: To study the effects of aminoguanidine (AG), the inhibitor of inducible nitric oxide synthase (NOS), on the recovery of rat hindlimb motor function after spinal cord injury and explore the possible mechanism. METHODS: Thirty rat models of spinal cord compression injury were established according to Nystrom's method. AG therapy was administered for 4 times at 1 h before and 8, 24, 36 h after the injury, and 24 h after the completion of the therapy, spectrophotography was performed to measure the content of NO and activity of NOS in the injured spinal cord, followed by flow cytometry for determining the apoptotic rate 48 h later. The evaluation of the hindlimb motor function recovery was conducted by electrophysiological method and by measuring the behavior scores. RESULTS: AG significantly decreased the NO content (from 2.2714+/-0.4239 micromol/g.pro to 0.8466+/-0.0477 micromol/g.pro, P <0.05) and NOS activity (from 0.3408+/-0.0228 U/mg pro to 0.2702+/-0.0148 U/mg pro, P <0.05) in the injured spinal cord. The apoptotic rats were also reduced (from 7.88% +/-0.79% to 3.10% +/-0.66%, P <0.05). Four weeks after the therapy, the behavior score of the rats improved from 7.1+/-4.5 to 17.3+/-4.7 (P <0.01), and the latency and amplitude of the motor evoked potentials improved from 0 ms to 8.89+/-0.91 ms and from 0 mv to 1.99+/-0.48 mv respectively, showing significant therapeutic effect of AG (P <0.05). CONCLUSION: AG can improve motor functions of injured spinal cord in rats, possibly resulting from decreased apoptotic cells of the neurons in the spinal cord in the early stages of the injury.
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Guanidinas/uso terapéutico , Miembro Posterior/fisiopatología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Potenciales Evocados Motores/efectos de los fármacos , Masculino , Óxido Nítrico/análisis , Óxido Nítrico Sintasa/metabolismo , Ratas , Ratas Sprague-Dawley , Médula Espinal/química , Médula Espinal/patología , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatologíaRESUMEN
OBJECTIVE: To study the role of antisense oligodeoxynucleotides (ASODN) of inducible nitric oxide synthase (iNOS) on the apoptosis and p-p38 mitogen-activated protein kinase (p-p38 MAPK) signal transduction of the neurons after spinal cord injury (SCI). METHODS: Antisense and non-sense oligodeoxynucleotides of iNOS were designed and synthesized, and injected into the subarachnoid space 12 h before the compressive injury was given to the rat spinal cord. Reverse transcription-PCR and flow-cytometry were used to examine the iNOS mRNA expression and the apoptosis of the neurons within the injured spinal cord. The changes of p-p38 MAPK signal transduction pathway were detected by Western blotting. RESULTS: Obvious increase in iNOS expression and up-regulated p-p38 MAPK were detected after SCI, and neuronal apoptosis was observed in the injured spinal cord. ASODN-iNOS treatment resulted in decreased expression levels of iNOS mRNA and p-p38 MAPK, and the neuronal apoptosis was alleviated. CONCLUSION: ASODN-iNOS inhibits iNOS expression and neuronal apoptosis following SCI which may be related to the p-p38 MAPK signal transduction pathway.
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Apoptosis , Proteínas Quinasas Activadas por Mitógenos/fisiología , Neuronas/patología , Óxido Nítrico Sintasa/fisiología , Oligonucleótidos Antisentido/farmacología , Transducción de Señal/fisiología , Traumatismos de la Médula Espinal/patología , Animales , Western Blotting , Citometría de Flujo , Masculino , Neuronas/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Fosforilación , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Traumatismos de la Médula Espinal/metabolismo , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
OBJECTIVE: To investigate gene expression of three nitric oxide synthase isozymes in injured spinal cord tissue. METHODS: Thirty-six adult SD rats were randomly divided into six groups: a normal group and five injury groups, with six per each group. Animals in the injury groups were sacrificed at 2, 6, 12, 24, 48 h after injury. A compression injury model on the spinal cord was made according to Nystrom B et al and gene expression of the three NOS isozymes were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Gene expression of nNOS and eNOS were detectable in the normal group and were up-regulated quickly after injury, reaching a maximum at 6 h: (0.633 +/- 0.012) and (1.236 +/- 0.207). Gene expression of iNOS was detectable only in the injury groups and it was gradually up-regulated after injury, reaching a maximum at 24 h: (1.043 +/- 0.049). CONCLUSION: Injury to the spinal cord leads to early up-regulation of cNOS and late up-regulation of iNOS. Different NOS isozymes may play different roles in secondary spinal cord injury.
Asunto(s)
Óxido Nítrico Sintasa/genética , Traumatismos de la Médula Espinal/enzimología , Animales , Femenino , Regulación Enzimológica de la Expresión Génica , Masculino , Óxido Nítrico Sintasa de Tipo I , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , ARN/genética , ARN/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Médula Espinal/enzimología , Médula Espinal/patología , Traumatismos de la Médula Espinal/genéticaRESUMEN
OBJECTIVE: To investigate the gene expression of two kinds of constitutive nitric oxide synthase (cNOS): neuronal NOS (nNOS) and endothelial NOS (eNOS) in injured spinal cord tissue. METHODS: Thirty-six adult Sprague-Dawley rats were divided randomly into six groups: the normal group and the injury groups (2, 6, 12, 24, 48 h after injury, respectively). A compression injury model of the spinal cord wa s ma de and gene expression of nNOS and eNOS were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The gene expression of nNOS and eNOS was detected in the normal group and they were up-regulated quickly after injury, reaching the maximum at 6 h. There was no difference between gene expression of nNOS and eNO S in the normal group, but in each injury group the gene expression of eNOS was much higher than that of nNOS. CONCLUSIONS: Expression of constitutive NOS (cNOS) in spinal co rd tissue was up-regulated after injury mainly in the early stage. cNOS as a wh ole offers protection in spinal cord injury, but different cNOS may play different roles.