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1.
J Clin Invest ; 123(11): 4909-17, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24216480

RESUMO

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family­based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.


Assuntos
Degeneração do Disco Intervertebral/enzimologia , Degeneração do Disco Intervertebral/genética , Vértebras Lombares , Polimorfismo de Nucleotídeo Único , Sulfotransferases/genética , Regiões 3' não Traduzidas , Povo Asiático/genética , Sequência de Bases , Sítios de Ligação/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 10/genética , Estudos de Coortes , Feminino , Finlândia , Ligação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Degeneração do Disco Intervertebral/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Carboidrato Sulfotransferases
2.
J Bone Miner Metab ; 28(1): 25-34, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19603246

RESUMO

Strontium (Sr) compounds have become increasingly popular in osteoporosis treatment. As a bone seeking element, 98% of Sr deposits in bone and teeth after oral ingestion. However, the quality of new bone after Sr deposition is yet to be extensively investigated. In this study, eight osteopenic goats were divided into two groups: Ca + 40Sr (five goats) and controls (three goats). Controls were fed with low calcium feeds. Ca phosphate was supplied at 100 mg/(kg day), and Sr phosphate at 40 mg/(kg day) in the Ca + 40Sr group. The newly formed bone at the outer cortical area of the femur with Sr deposition was identified from tetracycline labels, and the morphology and lattice structure of the crystals in these regions were investigated. Results showed that Sr concentrations of bone tissue significantly increased 144.37% for Sr administration without significant change in Ca concentration, and the ingested Sr mainly deposited in new bone. The crystal isolated from new bone exhibited the typical character of biological apatite as determined by Fourier transform infrared spectroscopy and selected-area electron diffraction. Transmission electron microscopy examination showed that a crystal with width of 8-10 nm grew along with the (002) lattice and aligned with the same direction in both groups. The elemental analysis of crystals showed that the ingested Sr deposited mainly in the bone matrix or was absorbed on the bone crystal surface, while only a limited amount of Sr replaced Ca in apatite crystals. Our findings showed that Sr administration at current dosages for prevention and treatment of osteoporosis might not change the bone crystal morphology and structure.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Osso e Ossos/ultraestrutura , Osteogênese/efeitos dos fármacos , Fosfatos/farmacologia , Estrôncio/farmacologia , Métodos Analíticos de Preparação de Amostras , Animais , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Osso e Ossos/química , Cálcio/análise , Cálcio/uso terapêutico , Quimioterapia Combinada , Feminino , Fêmur/química , Fêmur/ultraestrutura , Colágenos Fibrilares/ultraestrutura , Corantes Fluorescentes , Cabras , Especificidade de Órgãos , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Fosfatos/uso terapêutico , Distribuição Aleatória , Espectrometria por Raios X , Espectrofotometria Atômica , Espectroscopia de Infravermelho com Transformada de Fourier , Estrôncio/análise , Estrôncio/uso terapêutico
4.
J Neural Eng ; 6(6): 066007, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19918110

RESUMO

The gait outcome measures used in clinical trials of paraplegic locomotor training determine the effectiveness of improved walking function assisted by the functional electrical stimulation (FES) system. Focused on kinematic, kinetic or physiological changes of paraplegic patients, traditional methods cannot quantify the walking stability or identify the unstable factors of gait in real time. Up until now, the published studies on dynamic gait stability for the effective use of FES have been limited. In this paper, the walker tipping index (WTI) was used to analyze and process gait stability in FES-assisted paraplegic walking. The main instrument was a specialized walker dynamometer system based on a multi-channel strain-gauge bridge network fixed on the frame of the walker. This system collected force information for the handle reaction vector between the patient's upper extremities and the walker during the walking process; the information was then converted into walker tipping index data, which is an evaluation indicator of the patient's walking stability. To demonstrate the potential usefulness of WTI in gait analysis, a preliminary clinical trial was conducted with seven paraplegic patients who were undergoing FES-assisted walking training and seven normal control subjects. The gait stability levels were quantified for these patients under different stimulation patterns and controls under normal walking with knee-immobilization through WTI analysis. The results showed that the walking stability in the FES-assisted paraplegic group was worse than that in the control subject group, with the primary concern being in the anterior-posterior plane. This new technique is practical for distinguishing useful gait information from the viewpoint of stability, and may be further applied in FES-assisted paraplegic walking rehabilitation.


Assuntos
Terapia por Estimulação Elétrica/métodos , Paraplegia/fisiopatologia , Paraplegia/terapia , Equilíbrio Postural , Andadores , Caminhada/fisiologia , Adulto , Algoritmos , Braço/fisiologia , Fenômenos Biomecânicos , Avaliação da Deficiência , Feminino , Humanos , Masculino , Modelos Teóricos , Projetos Piloto
5.
Med Sci Monit ; 15(8): MT105-12, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19644428

RESUMO

BACKGROUND: Gait analysis techniques guide the use and design of functional electrical stimulation (FES) systems for paraplegic walking. However, published studies on dynamic gait stability for the effective use of FES are limited. This paper introduces a new risk-tendency graph (RTG) technique to analyze and process gait stability in FES-assisted paraplegic walking. MATERIAL/METHODS: The main instrument was a specialized walker dynamometer system based on a multi-channel strain-gauge bridge network affixed to the frame of the walker. This system collects force information for the handle reaction vector (HRV) between the patient's upper extremities and the walker during walking. The information is then converted into a walker tipping index (WTI), which is an indicator of the patient's walking stability. Dynamic gait stability is then combined with spatio-temporal locating methods for WTI and visually described as morphological curves in the temporal and spatial domains, namely RTGs. RESULTS: To demonstrate the potential usefulness of RTG in gait analysis, a preliminary clinical trial was conducted with one male paraplegic patient who was undergoing FES walking training. The gait stability levels for the patient under different stimulation patterns were quantified using the results of temporal and 3-D spatial RTG. Relevant instable phases in the gait cycle and dangerous inclinations of the patient's body while walking were also clearly identified. CONCLUSIONS: The new RTG technique is a practical method for distinguishing useful gait information from the viewpoint of stability and may be further applied in FES-assisted paraplegic walking rehabilitation.


Assuntos
Terapia por Estimulação Elétrica/métodos , Marcha/fisiologia , Paraplegia/fisiopatologia , Caminhada/fisiologia , Adulto , Fenômenos Biomecânicos , Gravitação , Humanos , Projetos Piloto , Fatores de Tempo
6.
Spine (Phila Pa 1976) ; 34(9): 934-40, 2009 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-19532001

RESUMO

STUDY DESIGN: A cross-sectional population study of magnetic resonance imaging (MRI) changes. OBJECTIVE.: To examine the pattern and prevalence of lumbar spine MRI changes within a southern Chinese population and their relationship with back pain. SUMMARY OF BACKGROUND DATA: Previous studies on MRI changes and back pain have used populations of asymptomatic individuals or patients presenting with back pain and sciatica. Thus, the prevalence and pattern of intervertebral disc degeneration within the population is not known. METHODS: Lumbar spine MRIs were obtained in 1043 volunteers between 18 to 55 years of age. MRI changes including disc degeneration, herniation, anular tears (HIZ), and Schmorl's nodes were noted by 2 independent observers. Differences were settled by consensus. Disc degeneration was graded using Schneiderman's classification, and a total score (DDD score) was calculated by the summation of the Schneiderman's score for each lumbar level. A K-mean clustering program was used to group individuals into different patterns of degeneration. RESULTS: Forty percent of individuals under 30 years of age had lumbar intervertebral disc degeneration (LDD), the prevalence of LDD increasing progressively to over 90% by 50 to 55 years of age. There was a positive correlation between the DDD score and low back pain. L5-S1 and L4-L5 were the most commonly affected levels. Apart from the usual patterns of degeneration, some uncommon patterns of degeneration were identified, comprising of subjects with skip level lesions (intervening normal levels) and isolated upper or mid lumbar degeneration. CONCLUSION: LDD is common, and its incidence increases with age. In a population setting, there is a significant association of LDD on MRI with back pain.


Assuntos
Deslocamento do Disco Intervertebral/diagnóstico , Disco Intervertebral/patologia , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Fatores Etários , Dor nas Costas/diagnóstico , Dor nas Costas/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Incidência , Deslocamento do Disco Intervertebral/epidemiologia , Pessoa de Meia-Idade , Prevalência , Ciática/diagnóstico , Ciática/epidemiologia , Adulto Jovem
7.
J Orthop Res ; 27(6): 758-62, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19025756

RESUMO

Strontium (Sr) has become increasingly attractive for use in the prevention and treatment of osteoporosis by concomitantly inhibiting bone resorption and enhancing bone formation. Strontium shares similar chemical, physical, and biological characteristics with calcium (Ca), which has been widely used as a dietary supplement in osteoporosis. However, the effects of Sr-Ca coadministration on bone growth and remodeling are yet to be extensively reported. In this study, 18 ovariectomized goats were divided into four groups: three groups of five goats each treated with 100 mg/kg/day Ca, Ca plus 24 mg/kg/day Sr (Ca + 24Sr), or Ca plus 40 mg/kg/day Sr (Ca + 40Sr), and three untreated goats fed low calcium feed. Serum Sr levels increased 6- and 10-fold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr-Ca coadministration considerably increased bone mineral apposition rate (MAR). The expression of insulin-like growth factor (IGF)-1 and runt-related transcription factor 2 (Runx2) was significantly upregulated within the Ca + 40Sr treatment group; tumor necrosis factor (TNF)-agr; expression was significantly downregulated in the Ca and Ca + 40Sr groups. The results indicate that Sr-Ca coadministration increases osteogenic gene expression and stimulates new bone formation.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Cálcio/farmacologia , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Estrôncio/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Cálcio/sangue , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Expressão Gênica/efeitos dos fármacos , Cabras , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like II/genética , Osteoporose/prevenção & controle , Ovariectomia , Estrôncio/sangue , Fator de Necrose Tumoral alfa/genética
8.
J Rehabil Med ; 40(2): 126-31, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18509577

RESUMO

OBJECTIVE: To assess the health-related quality of life of patients with traumatic spinal cord injury living in Hong Kong. DESIGN: A cross-sectional retrospective study. SUBJECTS: Subjects with paraplegia following traumatic spinal cord injury were recruited from our department, which is one of the 3 main regional spinal cord injury rehabilitation centres in Hong Kong. A total of 120 potential participants were invited to join the study. The final study group comprised 58 patients (25 (43%) men and 33 (57%) women, 30 (50%) of whom were under 40 years of age). METHODS: Health-related quality of life was assessed using the Hong Kong Chinese version of the World Health Organization Quality of Life Measure Abbreviated version (WHO-QOL-BREF(HK)). Results were summarized and compared with previous results from healthy and other disease populations in Hong Kong. RESULTS: There was no significant difference in quality of life between men and women, or between different durations of spinal cord injury, different educational levels or different marital status (p > 0.05). However, a significant difference in quality of life was found in different age groups and between people with incomplete and complete paraplegia (p < 0.05). Compared with healthy and other disease populations, people with paraplegia had the lowest quality of life in Hong Kong (p < 0.001). CONCLUSION: People with paraplegia in Hong Kong have a lower quality of life than the general Hong Kong population. More community support is required to meet the needs of these patients in the areas of transportation, medical care and social life, in particular.


Assuntos
Qualidade de Vida , Traumatismos da Medula Espinal/psicologia , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/psicologia , Paraplegia/reabilitação , Estudos Retrospectivos , Apoio Social , Fatores Socioeconômicos , Traumatismos da Medula Espinal/reabilitação , Inquéritos e Questionários
9.
BMC Med Genet ; 9: 38, 2008 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-18439317

RESUMO

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D), the -1607 promoter polymorphism, of the MMP1 gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD. METHODS: Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test. RESULTS: Our results showed substantial evidence of association between -1607 promoter polymorphism of MMP1 and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04-1.90) while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01-2.24). Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033-2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029-2.029). Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele. CONCLUSION: We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of MMP1 are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.


Assuntos
Vértebras Lombares , Metaloproteinase 1 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Doenças da Coluna Vertebral/genética , China , Deleção de Genes , Predisposição Genética para Doença , Humanos
10.
Am J Hum Genet ; 82(3): 744-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18304494

RESUMO

Lumbar-disc degeneration (LDD) is a polygenic disease. Susceptibility genes reported so far are mainly extracellular matrix proteins. D14 allele of asporin (ASPN) is associated with osteoarthritis (OA). Candidate-gene association studies showed that the D14 allele is also significantly associated with LDD in Chinese and Japanese individuals. Meta-analysis showed that individuals harboring a D14 allele had higher risk with a summary odds ratio of 1.70 (p = 0.000013). ASPN expression in vertebral discs increased with age and degeneration. Our results indicate ASPN is a LDD gene in Asians, and common risk factors may be considered for OA and LDD.


Assuntos
Povo Asiático/genética , Proteínas da Matriz Extracelular/genética , Predisposição Genética para Doença , Disco Intervertebral , Vértebras Lombares , Osteocondrite/genética , Adolescente , Adulto , Alelos , Ácido Aspártico/química , Ácido Aspártico/genética , Proteínas da Matriz Extracelular/química , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/genética , Polimorfismo Genético , Sequências Repetitivas de Aminoácidos/genética
11.
Spine (Phila Pa 1976) ; 31(18): 2043-7, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16915086

RESUMO

STUDY DESIGN: The 2[125I]iodomelatonin binding assay was used to investigate the involvement of melatonin receptors in the development of scoliosis in pinealectomized chickens. OBJECTIVE: To compare the binding properties of melatonin receptors in the thoracic spinal cord between pinealectomized chickens that had scoliosis develop and those that did not. SUMMARY OF BACKGROUND DATA: Surgical pinealectomy in young chickens induced scoliosis with a reported incidence of 50% to 100%. The factors regulating the development of scoliosis in this animal model are unclear. Melatonin receptors have been shown in the spinal cord of chickens, but their functions are still unknown. This study addresses the question as to whether spinal cord melatonin receptors are related to the pathogenesis of scoliosis in pinealectomized chickens. METHOD: Control and pinealectomized chickens were kept under controlled lighting conditions and monitored for scoliosis development. At 9-11 weeks after pinealectomy, thoracic spinal cords were removed for 2[125I]iodomelatonin binding assay, and blood was collected for serum melatonin assay at either the middle of the light period or middle of the dark period. RESULTS: Pinealectomy in young chickens produced: (1) loss of diurnal variations in serum melatonin levels, (2) 50% incidence of scoliosis, and (3) attenuation in the diurnal variations in the receptor affinity to melatonin. No differences were detected in the serum melatonin levels or binding of spinal cord melatonin receptors between the pinealectomized chickens that had scoliosis develop and those that did not. CONCLUSION: Changes are detected in melatonin receptor binding after pinealectomy. However, these changes cannot account for the reason why scoliosis develops in some chickens after pinealectomy, while it does not in others. Neither low melatonin serum level nor changes in spinal cord melatonin binding can be a sole etiologic factor in the pathogenesis of scoliosis in pinealectomized chickens.


Assuntos
Glândula Pineal/cirurgia , Receptores de Melatonina/sangue , Escoliose/patologia , Medula Espinal/patologia , Animais , Fracionamento Celular , Membrana Celular/metabolismo , Galinhas , Ritmo Circadiano , Modelos Animais de Doenças , Radioisótopos do Iodo , Melatonina/análogos & derivados , Melatonina/farmacocinética , Escoliose/sangue , Escoliose/metabolismo , Medula Espinal/metabolismo , Vértebras Torácicas
12.
Spine (Phila Pa 1976) ; 31(10): 1143-8, 2006 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-16648751

RESUMO

STUDY DESIGN: Large scale, case-control study. OBJECTIVE: To assess the effect of the Taq I alleles in vitamin D receptor on the risk of developing degenerative disc disease in a Southern Chinese population. SUMMARY OF BACKGROUND DATA: Previous studies in Finns and Japanese suggest that the Taq I polymorphism of vitamin D receptor is associated with the development of degenerative disc disease in the lumbar spine. However, sample sizes were small, and the results need to be confirmed in other populations. METHOD: Lumbar degenerative disc disease was defined by magnetic resonance imaging (MRI) on 804 Southern Chinese volunteers between 18 and 55 years of age. Restriction enzyme digestion of polymerase chain reaction products was used to analyze the Taq I alleles. The resulting genotypes were correlated with the presence of lumbar disc degeneration and bulge on MRI. RESULTS: Using logistic regression analysis and adjusting for age and sex, the t allele of Taq I in vitamin D receptor gene was significantly associated with degenerative disc disease, with an odds ratio (OR) of 2.61 (95% confidence interval [CI] 1.15-5.90, P = 0.041). Further subgroup analysis showed that in individuals younger than 40 years, the OR was even higher, at 5.97 (95% CI 1.69-21.15, P = 0.002). Similarly, disc bulge was significantly associated with t allele (OR = 7.17, 95% CI 1.43-36.01, P = 0.001) in individuals younger than 40 years. Anular tears and the Schmorl nodes were not associated with the t allele of Taq I polymorphism. CONCLUSION: To our knowledge, this is the largest scale genetics study to date using MRI to define precisely degenerative disc disease in the Southern Chinese population. We showed that the t allele of vitamin D receptor Taq I is associated with a high risk of degenerative disc disease and disc bulge developing, especially in individuals younger than 40 years.


Assuntos
Predisposição Genética para Doença , Deslocamento do Disco Intervertebral/epidemiologia , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/genética , Taq Polimerase/genética , Adolescente , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Deslocamento do Disco Intervertebral/genética , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia
13.
Spine (Phila Pa 1976) ; 31(7): 736-41, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16582846

RESUMO

STUDY DESIGN: In vitro investigation of vertebral endplate chondrocyte apoptosis. OBJECTIVES: To determine whether Fas antibody caused apoptosis in endplate chondrocytes, and whether insulin-like growth factor-1 (IGF-1) inhibited this effect. Integrin-alpha1 and focal adhesion kinase (FAK) expression in conjunction with apoptosis was also investigated. SUMMARY OF BACKGROUND DATA: Binding of Fas antibody to Fas mimics Fas-FasL ligation, which causes apoptosis. IGF-1 has been shown to have anti-apoptotic effects. MATERIALS AND METHODS: Rat cervical endplate chondrocytes were cultured and treated with Fas antibody, with or without IGF-1. Cellular morphology was examined by microscopy. Apoptotic changes were evaluated by transmission electron microscopy, TUNEL staining, and immunostaining. Apoptosis-induced changes in the expression of integrin-alpha1 chain and FAK were also investigated. RESULTS: Endplate chondrocytes were able to be cultured; a chondrocytic phenotype was maintained. Fas antibody induced apoptosis in endplate chondrocytes; this was confirmed by TUNEL staining. Bcl-2 expression was decreased by Fas antibody, while Bax expression increased. Integrin-alpha1 and FAK expression was decreased by Fas antibody. IGF-1 treatment inhibited these Fas antibody-induced changes. CONCLUSIONS: Fas antibody induces apoptosis and decreases Integrin-alpha1 and FAK expression in cultured endplate chondrocytes; IGF-1 is protective against these changes.


Assuntos
Anticorpos Monoclonais/fisiologia , Apoptose/fisiologia , Condrócitos/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Receptor fas/imunologia , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais Murinos , Afinidade de Anticorpos , Apoptose/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Proteína Ligante Fas , Integrina alfa1/biossíntese , Glicoproteínas de Membrana/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Necrose Tumoral/metabolismo , Receptor fas/metabolismo
14.
Spine (Phila Pa 1976) ; 31(4): 414-9, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16481951

RESUMO

STUDY DESIGN: Continuous dynamic lumbar intervertebral flexion-extension is assessed by a videofluoroscopy with a new auto-tracking system. OBJECTIVES: To develop and validate a new method for the continuous assessment of lumbar kinematics. SUMMARY OF BACKGROUND DATA: Instability of the lumbar spine is thought to be associated with low back pain, but the diagnosis remains difficult. Functional radiographs have been used for diagnosis of spinal instability but error and limitation exist, whereas videofluoroscopy provides a cost-effective way for such analysis. However, common approaches of image analysis of videofluoroscopic video are tedious and time-consuming because of the low quality of the images. Physicians have to extract the vertebrae manually in most cases; thus, continuous motion analysis is hardly achieved. METHODS: A new system that can perform automatic vertebrae segmentation and tracking is developed. In vitro and in vivo validity were evaluated. Intervertebral flexion and extension was assessed in 30 healthy volunteers. RESULTS: In vitro and in vivo validity tests have been conducted with good results. A linear-liked pattern of the intervertebral flexion-extension (IVFE) curves in different levels was found, and the IVFE decreased in descending order from L1-L5 at different points of range of motion in flexion. Conversely, extension is evenly contributed at different levels, and the concavity of lumbar lordosis increases steadily in backward movement. CONCLUSIONS: The newly developed technique in assessing the dynamic lumbar motion is reliable and able to analyze the lumbar intervertebral movement from videofluoroscopic images automatically and accurately. The proposed system requires less human intervention than common approaches. It may have a potential value in the evaluation of spinal "instability" in clinical practice.


Assuntos
Fenômenos Biomecânicos , Técnicas e Procedimentos Diagnósticos , Vértebras Lombares/fisiologia , Movimento/fisiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Feminino , Fluoroscopia/instrumentação , Fluoroscopia/métodos , Humanos , Processamento de Imagem Assistida por Computador , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/fisiologia , Masculino , Modelos Biológicos
15.
Spine (Phila Pa 1976) ; 30(24): 2735-42, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16371896

RESUMO

STUDY DESIGN: Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD. OBJECTIVES: To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. SUMMARY OF BACKGROUND DATA: A Finnish study found an association between LBP and sciatica with two variants of the alpha-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study. METHODS: Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles. RESULTS: The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population. CONCLUSION: This largest-ever population study using MRI to define DDD demonstrates for the first time that the Trp2 allele is a significant risk factor for the development and severity of degeneration. The association is age- dependent as it is more prevalent in some age groups than in others. The contrasting Trp allele frequencies between the Finns and the Chinese are the first indication that the genetic risk factors for DDD varies between ethnic groups.


Assuntos
Alelos , Colágeno Tipo IX/genética , Disco Intervertebral/patologia , Doenças da Coluna Vertebral/genética , Doenças da Coluna Vertebral/patologia , Adolescente , Adulto , Fatores Etários , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Variação Genética/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Doenças da Coluna Vertebral/etiologia
16.
Spine (Phila Pa 1976) ; 30(18): 2009-13, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16166887

RESUMO

STUDY DESIGN: Prospective study on pinealectomy in primates. OBJECTIVE: To evaluate whether pinealectomy in a bipedal nonhuman primate model will result in the development of scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomy in newborn chickens consistently resulted in scoliosis development. Published data suggest that the surgical removal of the pineal, loss of melatonin secretion, and a bipedal posture are important elements in the development of scoliosis in lower animal models. METHOD: There were 18 rhesus monkeys between 8 and 11 months old that underwent pineal excision. All monkeys were kept in a regulated 12-hour light-dark cycle. Monthly radiographs assessed scoliosis development. Completeness of pineal excision was assessed by measurement of a major metabolite of melatonin in the urine, 6-sulfatoxymelatonin, using an enzyme-linked immunosorbent assay assessed. RESULTS: Mean follow-up was 28 months (range 10-41). Seven monkeys died prematurely, and 11 survived to date; the data from those that died could still be used, although follow-up was shortened. At the latest follow-up or death, scoliosis did not develop in any of the monkeys. Urinary 6-sulfatoxymelatonin measurements revealed 3 patterns. Group 1 consisted of 10 monkeys, which showed definite evidence of complete pineal excision. Group 2 consisted of an uncertain group of 2 monkeys in which the nighttime melatonin level is slightly high. Group 3 consisted of 6 monkeys that had incomplete pineal excision or ectopic melatonin production. CONCLUSIONS: To our knowledge, this is the first report of pinealectomy in nonhuman primates. Of the 18 monkeys, 10 had a loss of melatonin secretion, for a mean of 29 months after surgery. Because none of the monkeys had scoliosis develop, this study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings.


Assuntos
Procedimentos Neurocirúrgicos/efeitos adversos , Glândula Pineal/cirurgia , Escoliose/etiologia , Animais , Ritmo Circadiano , Macaca mulatta , Melatonina/metabolismo , Período Pós-Operatório , Radiografia , Coluna Vertebral/diagnóstico por imagem , Fatores de Tempo
17.
Spine (Phila Pa 1976) ; 30(17 Suppl): S84-91, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16138071

RESUMO

STUDY DESIGN: A review of the laboratory and clinical data for a new strontium-containing hydroxyapatite bioactive bone cement. OBJECTIVES: To compare the properties of the strontium-containing bioactive bone cement with those of polymethyl methacrylate (PMMA) and hydroxyapatite (HA) bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty using conventional PMMA bone cements have been effectively used to treat osteoporotic spine fractures with good short- and medium-term results. However, PMMA has some undesirable properties, including its high setting temperature, lack of osseointegration, and large stiffness mismatch with osteoporotic bone. These properties are responsible for some postoperative complications. METHODS: Strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement consists of a filler blend of strontium-containing hydroxyapatite, fumed silica and benzoyl peroxide; and a resin blend of bisphenol A diglycidylether methacrylate, triethylene glycol dimethacrylate, poly(ethylene glycol) methacrylate, and N, N-dimethyl-p-toluidine. Its properties, including mechanical strength, setting temperature, biocompatibility, and osseoinduction, were compared with other cements in vitro and in vivo. Early clinical results are presented. RESULTS: The Sr-HA cement has a setting time of 15 to 18 minutes, a maximum setting temperature of 58 degrees C, a compressive strength of 40.9 MPa, bending strength of 31.3 MPa, and a bending modulus of 1,408 MPa. The bending strength and modulus are closer to human cancellous bone. Sr-HA cement promotes osteoblast attachment and mineralization in vitro and bone growth and osseointegration in vivo. In a pilot study, 23 cases of osteoporotic fractures treated with this cement with a mean follow-up of 18 months suggest that it is as effective as PMMA in relieving pain. DISCUSSIONS: Oral strontium has been shown to induce new bone formation and is effective in reducing fracture risk in osteoporosis. Our data suggest that strontium delivered locally has the same effect; thus, the combination of strontium with HA in a cement with a low setting temperature, adequate stiffness, and low viscosity makes this a good bioactive cement for vertebroplasty and kyphoplasty.


Assuntos
Cimentos Ósseos/uso terapêutico , Durapatita/uso terapêutico , Fraturas Espontâneas/terapia , Fraturas da Coluna Vertebral/terapia , Estrôncio/uso terapêutico , Animais , Materiais Biocompatíveis , Fenômenos Biomecânicos , Cimentos Ósseos/síntese química , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fraturas Espontâneas/etiologia , Humanos , Teste de Materiais , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/ultraestrutura , Osteoporose/complicações , Projetos Piloto , Coelhos
19.
Spine (Phila Pa 1976) ; 30(8): E204-9, 2005 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15834318

RESUMO

STUDY DESIGN: An in vitro biomechanical study on lumbar intervertebral joints. OBJECTIVES: To examine the mechanical properties of lumbar motion segments under pure shear loading and establish whether a simple model for functional differentiation between the anterior column and the posterior elements is applicable. SUMMARY OF BACKGROUND DATA: Anteroposterior shear has been implicated as a major factor in spinal instability. There is a substantial amount of data on shear motion as a coupled part of flexion-extension; data on the pure shear properties of intervertebral joints is limited. METHODS: Eighteen human cadaver lumbar motion segments were subject to nondestructive testing under pure shear loads (anterior shear and posterior shear). An MTS standard testing machine was used to record the load-deformation characteristics of specimens subject to deformation at a constant rate to a maximum shear load of approximately 250 N. Tissue sectioning was then performed with the specimen mounted in the testing machine. Eight specimens were sectioned through the intervertebral disc, including the anterior and posterior longitudinal ligaments, and 8 specimens were sectioned through the pedicles to remove the posterior elements. The same deformation pattern applied to the intact specimen was then reapplied to the sectioned specimen, and the load-deformation characteristics following sectioning were evaluated. RESULTS: The shear stiffness of the intact segments were found to be higher in anterior shear (mean group A = 583.8, B = 607 N/mm) than in posterior shear (mean group A = 469, B = 438.4 N/mm). Section of the anterior column and adjacent longitudinal ligaments resulted in a mean stiffness decreased by 22.8% of the intact value under anterior shear and 23.9% under posterior shear. Much larger change in shear stiffness was seen, and the mean sectioned stiffness dropped by 77.7% in anterior shear and 79% in posterior shear after removal of the posterior elements. After the anterior column was sectioned, 12% and 18% increases in the deformation for anterior and posterior directions were seen, whereas a distinct increase in the deformations was found after posterior elements sectioned. CONCLUSIONS: The posterior elements of the lumbar spine are more efficient in resisting anterior and posterior shear loads. However, the anterior column will exhibit similar load-displacement characteristics if subject to greater deformations. The sum of the normalized mean shear loads of the anterior column and posterior elements sustained at maximum intact deformation is significantly different from the shear load sustained by the intact spine at the same deformation. A simple concept of load sharing between the anterior column and the posterior elements may not be valid.


Assuntos
Dissecação , Vértebras Lombares , Coluna Vertebral/fisiologia , Coluna Vertebral/cirurgia , Suporte de Carga , Adulto , Fenômenos Biomecânicos , Cadáver , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Estresse Mecânico , Resistência à Tração
20.
Spine (Phila Pa 1976) ; 29(15): 1636-41, 2004 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-15284509

RESUMO

STUDY DESIGN: Dynamic lumbar flexion-extension motions were assessed by an electrogoniometer and a videofluoroscopy unit simultaneously. OBJECTIVES: The aims of this study were to assess the motion profile of lumbar spine in different genders and age groups and to assess their differences. SUMMARY OF BACKGROUNDS DATA: The dynamic lumbar flexion-extension motions analysis method has been developed and validated. However, data profile of the spinal motions of healthy volunteers has not been established. METHODS.: A total of 100 healthy volunteers, including 50 men and 50 women, were recruited. They were then divided into four equal groups, following their age ranges of 21 to 30 years, 31 to 40 years, 41 to 50 years, and 51 years and older. Lumbar flexion-extension motion was assessed with an electrogoniometer and videofluoroscopy simultaneously. Radiologic images of the lumbar spine were captured during flexion-extension in 10 degrees intervals. Intervertebral flexion-extension (IVFE) of each vertebral level was calculated. The spinal motion of different genders was compared segment by segment with independent t test. The spinal motion of different age groups was compared with one-way analysis of variance. RESULTS: A linear-liked pattern of the IVFE curves was observed in different genders and age groups. No statistically significant difference in the pattern of motion was found between genders. However, statistically significant difference in the slope of IVFE curves was found at all lumbar levels in subjects whose age was 51 years or older (P < 0.05). CONCLUSIONS: Assessment of motion profile was found to be helpful for the identification of spinal disorders in clinical practice. Because of the normal variation of spinal motion of subjects in different age ranges, interpretation of spinal motion disorders should be careful. Although the sample size in this study was limited, the database generated might be useful to assist the diagnosis of spinal "instability" in the future.


Assuntos
Vértebras Lombares/fisiologia , Adulto , Fatores Etários , Feminino , Fluoroscopia , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Movimento , Fatores Sexuais
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