Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
J Phys Ther Sci ; 31(1): 53-56, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30774205

RESUMO

[Purpose] Sports activity has been shown to improve postural stability and vestibular function in healthy older adults. The hypothesis was that healthy young adults undertaking sports activity will also have better postural stability and vestibular function compared with healthy young adults who do not undertake sports activity. The purpose of this study was to investigate the differences in postural stability and vestibular function between healthy young adults who undertake sports activity and those who do not undertake such activity. [Participants and Methods] Thirty-nine healthy young adults were recruited and divided into sports and non-sports groups on the basis of their response to a questionnaire concerning regular participation in sports activities over the past 12 months. In both groups, postural stability was measured during quiet standing and standing during head rotation, and dynamic visual acuity was assessed during head rotation. [Results] The results showed significant differences in postural stability during head rotation and dynamic visual acuity between the two groups, whereas no significant differences were found in postural stability during quiet standing. [Conclusion] The results suggest that healthy young adults who undertake sports activity have better postural stability during head rotation and better dynamic visual acuity. The causal effect of these differences is not clear and further investigation is warranted.

2.
Int J Hyperthermia ; 35(1): 658-666, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30295115

RESUMO

BACKGROUND: Recurrence after wide excision or residual tumor after an unplanned excision of a malignant soft tissue sarcoma (STS) is a complex problem, due to a higher recurrence rate and poorer survival rate compared with primary resection. Regional hyperthermia was used, with the expectation that it will enhance the anti-tumor effects of chemotherapy and radiotherapy. This study aimed to assess the efficacy of neoadjuvant concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for salvage of recurrent or residual malignant STS. METHODS: We identified 64 patients with recurrent or residual STS treated between 1994 and 2013. After excluding those with low-grade malignancy, with recurrent bone tumor in the soft tissues, with truncal STS, and who declined to participate, 23 patients (7 with recurrence and 16 with residual tumor) underwent RHC. The histologic diagnoses were undifferentiated pleomorphic sarcoma (n = 11), synovial sarcoma (n = 3), leiomyosarcoma and myxoid liposarcoma (n = 2 each), and other histologic types. As primary outcomes, the 5-year overall survival (OS), distant metastasis-free survival (D-MFS), and local control (LC) rates were evaluated by Kaplan-Meier analysis. RESULTS: The median follow-up period was 112.3 months. The 5-year OS, D-MFS, and LC were 86.4%, 77.4%, and 86.7%, respectively. In the univariate analysis, tumor depth was considered as a negative prognostic factor for OS and D-MFS, and a positive margin was also a negative prognostic factor for OS, D-MFS LC with retained on Cox proportional hazards model in OS, and D-MFS. CONCLUSION: RHC is an effective option for salvage treatment of recurrent and residual STS.


Assuntos
Terapia de Salvação/métodos , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Resultado do Tratamento
3.
BMC Musculoskelet Disord ; 19(1): 268, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30053808

RESUMO

BACKGROUND: Although aneurysmal bone cysts (ABCs) are benign tumours, they have the potential to be locally aggressive. Various treatment approaches, such as en bloc resection, open curettage, radiotherapy, sclerotherapy, and embolization have been proposed, but the most appropriate treatment should be selected after considering the risk of tumour recurrence and treatment complications. Endoscopic curettage (ESC) may be a less invasive alternative to open curettage for ABC treatment. We aimed to describe the use of ESC for the treatment of ABCs and to report our clinical outcomes, including the incidence rate of recurrence, radiological appearance at final follow-up, time to solid union, complications, and postoperative function. METHODS: Between 1998 and 2015, 30 patients (18 men and 12 women; mean age, 17.4 years) underwent ESC for the treatment of primary ABCs at our hospital (mean postoperative follow-up, 55 months). ESC was performed under arthroscopic guidance for direct visualization, and curettage extended until normal bone was observed in the medullary cavity. To investigate bone healing after ESC, we evaluated the consolidation of cysts at the final evaluation (based on the modified Neer classification) and time to solid union after surgery, which was defined as sufficient cortical bone thickness to prevent fracture and allow physical activities. RESULTS: Recurrence was identified in 3 cases (10%). Curative outcomes were obtained after repeated ESC or open curettage. A log-rank analysis indicated that age < 10 years (p = 0.004) and contact of the tumour with the physis (p = 0.01) increased the risk of tumour recurrence. Residual tumours were identified in 9 cases (30%); these lesions remained inactive over the extended follow-up period. The average time to solid union after endoscopic curettage was 3.2 months. Transient radial nerve palsy was identified in 1 case. Good postoperative functional recovery occurred in all cases. CONCLUSIONS: ESC is a minimally invasive technique for the treatment of ABCs, and the tumour recurrence rate is comparable to that of other standard procedures. However, the application of this method should be carefully considered, especially for patients < 10 years and when the tumour comes in contact with the physis.


Assuntos
Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Curetagem/métodos , Endoscopia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Adulto Jovem
4.
J Orthop Sci ; 22(5): 874-879, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28559103

RESUMO

BACKGROUND: Recently several authors have reported on the quantitative evaluation of the pivot-shift test using cutaneous fixation of inertial sensors. Before utilizing this sensor for clinical studies, it is necessary to evaluate the accuracy of cutaneous sensor in assessing rotational knee instability. To evaluate the accuracy of inertial sensors, we compared cutaneous and transosseous sensors in the quantitative assessment of rotational knee instability in a cadaveric setting, in order to demonstrate their clinical applicability. METHODS: Eight freshly frozen human cadaveric knees were used in this study. Inertial sensors were fixed on the tibial tuberosity and directly fixed to the distal tibia bone. A single examiner performed the pivot shift test from flexion to extension on the intact knees and ACL deficient knees. The peak overall magnitude of acceleration and the maximum rotational angular velocity in the tibial superoinferior axis was repeatedly measured with the inertial sensor during the pivot shift test. Correlations between cutaneous and transosseous inertial sensors were evaluated, as well as statistical analysis for differences between ACL intact and ACL deficient knees. RESULTS: Acceleration and angular velocity measured with the cutaneous sensor demonstrated a strong positive correlation with the transosseous sensor (r = 0.86 and r = 0.83). Comparison between cutaneous and transosseous sensor indicated significant difference for the peak overall magnitude of acceleration (cutaneous: 10.3 ± 5.2 m/s2, transosseous: 14.3 ± 7.6 m/s2, P < 0.01) and for the maximum internal rotation angular velocity (cutaneous: 189.5 ± 99.6 deg/s, transosseous: 225.1 ± 103.3 deg/s, P < 0.05), but no significant difference for the maximum external rotation angular velocity (cutaneous: 176.1 ± 87.3 deg/s, transosseous: 195.9 ± 106.2 deg/s, N.S). CONCLUSIONS: There is a positive correlation between cutaneous and transosseous inertial sensors. Therefore, this study indicated that the cutaneous inertial sensors could be used clinically for quantifying rotational knee instability, irrespective of the location of utilization.


Assuntos
Ligamento Cruzado Anterior/fisiopatologia , Instabilidade Articular/diagnóstico , Articulação do Joelho , Exame Físico/instrumentação , Exame Físico/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Rotação
5.
Arch Biochem Biophys ; 542: 39-45, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24333336

RESUMO

Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses various beneficial properties for human health. In the present study, we investigated the mechanism underlying the effects of prostaglandin F2α (PGF2α) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG synthesis in osteoblast-like MC3T3-E1 cells. PGF2α stimulated both the release of the OPG protein and the expression of OPG mRNA. Treatment with PD98059, SB203580 and SP600125, specific inhibitors of MEK1/2, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) all suppressed the OPG release induced by PGF2α. Resveratrol also significantly reduced the PGF2α-stimulated OPG release and the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1, also suppressed the PGF2α-stimulated OPG release. Resveratrol and SRT1720 both attenuated the phosphorylation of p44/p42 MAP kinase, MEK1/2, Raf-1, p38 MAP kinase and SAPK/JNK induced by PGF2α. These findings strongly suggest that resveratrol suppresses PGF2α-stimulated OPG synthesis by inhibiting the MAP kinase pathways in osteoblasts, and that the effect is mediated via SIRT1 activation.


Assuntos
Dinoprosta/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoblastos/citologia , Osteoprotegerina/biossíntese , Estilbenos/farmacologia , Células 3T3 , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resveratrol
6.
Int J Mol Sci ; 15(10): 17886-900, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25290095

RESUMO

It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Regulação para Baixo/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Osteoprotegerina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estilbenos/farmacologia , Células 3T3 , Animais , Antracenos/farmacologia , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Flavonoides/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoprotegerina/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Piridinas/farmacologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Resveratrol , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Arch Biochem Biophys ; 535(2): 227-33, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23624146

RESUMO

Stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK)(1) which belongs to the MAP kinase superfamily regulates many cellular events. We previously reported that interleukin 1 (IL-1) stimulates the synthesis of interleukin 6 (IL-6) through activation of ERK and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that AMP-activated protein kinase (AMPK) negatively regulates the IL-1-induced IL-6 synthesis through IκB/NF-κB pathway. In the present study, we investigated the role of SAPK/JNK in the IL-1-stimulated IL-6 synthesis in these cells. IL-1 induced the phosphorylation of SAPK/JNK. SP600125, an inhibitor of SAPK/JNK, increased the release and the mRNA expression levels of IL-6 induced by IL-1. IL-1-stimulated IL-6 release was significantly up-regulated in SAPK/JNK-knocked down cells. SP600125 remarkably suppressed the IL-1-induced phosphorylation of both IκB and NF-κB, whereas SP600125 failed to affect the IL-1-induced phosphorylation of AMPK, STAT3 or Src. Compound C, an AMPK inhibitor, attenuated the IL-1-induced phosphorylation of SAPK/JNK. SP600125 enhanced IL-1-stimulated IL-6 release also in normal human osteoblasts. These results strongly suggest that SAPK/JNK negatively regulates IL-1-stimulated IL-6 synthesis and acts at the point between AMPK and IκB/NF-κB in osteoblasts.


Assuntos
Interleucina-1/farmacologia , Interleucina-6/biossíntese , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Osteoblastos/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antracenos/farmacologia , Linhagem Celular , Técnicas de Silenciamento de Genes , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Camundongos , NF-kappa B/metabolismo , Osteoblastos/efeitos dos fármacos , Fosforilação , Pirazóis/farmacologia , Pirimidinas/farmacologia , RNA Mensageiro/biossíntese , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/metabolismo , Quinases da Família src/metabolismo
8.
Asian Spine J ; 16(1): 1-8, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33940773

RESUMO

STUDY DESIGN: A cadaveric study. PURPOSE: To investigate the anatomical features of segmental arteries and veins in the anterior part of the spinal column to prevent segmental vessel injury. OVERVIEW OF LITERATURE: The lateral transpsoas approach to the lumbar intervertebral discs (IVD) is associated with the risk of segmental vessel injury. Previous studies have described the vascular anatomy on the lateral part of the vertebral body. However, there are no studies that describe the segmental vessels on its anterior aspect. Here, we report the important anatomical features of the segmental arteries and veins that can intersect the anterior part of the IVD. These vessels are considered at risk of vascular injury when placing the anterior retractors during lateral lumbar interbody fusion or cutting the anterior longitudinal ligament during anterior column realignment. METHODS: Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2-L5 range and their course on the anterior part of the spinal column. RESULTS: The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively. CONCLUSIONS: The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.

9.
J Pediatr Orthop ; 31(4): 381-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21572275

RESUMO

BACKGROUND: Residual subluxation of the hip is a major problem in pediatric orthopaedics. Corrective surgery by Salter innominate osteotomy is performed for residual subluxation before school age. Common indications for corrective surgery are determined based on the clinical condition, x-ray images, and arthrographic images. However, the surgical indications vary among institutions. Thus, further information that can predict acetabular growth with certainty is needed for precise decision- making. This study focused on signal intensity changes on magnetic resonance (MR) images within the weight-bearing portion of the acetabulum to determine whether these signal intensity changes could predict acetabular growth. METHODS: Thirty-six patients who showed residual subluxation after reduction of developmental dysplasia of the hip and whose MRIs were taken when they were around 3 years old were studied. Corrective surgery was performed in 14 patients, whereas the remaining 22 patients were followed conservatively. The presence of a high-signal intensity area (HSIA) within the weight-bearing portion of the acetabular cartilage on T2-weighted MR coronal section images was investigated, and the correlation between HSIA presence and acetabular growth was examined. RESULTS: All patients who underwent corrective surgery showed an HSIA within the weight-bearing portion of the acetabular cartilage on T2-weighted MR images before surgery. After surgery, all patients showed HSIA disappearance or decrease. In patients who were followed conservatively, HSIA-positive patients had poor acetabular growth, whereas HSIA-negative patients had favorable acetabular growth. CONCLUSIONS: HSIAs in the acetabular cartilage may be caused by an extraordinary stress load from the femoral head. The presence of HSIA on MRI may prevent acetabular growth. HSIA on MRI appears to be a significant decision-making tool for corrective surgery.


Assuntos
Acetábulo/patologia , Luxação Congênita de Quadril/diagnóstico , Imageamento por Ressonância Magnética/métodos , Acetábulo/crescimento & desenvolvimento , Adolescente , Criança , Tomada de Decisões , Feminino , Cabeça do Fêmur/patologia , Seguimentos , Luxação Congênita de Quadril/patologia , Luxação Congênita de Quadril/cirurgia , Humanos , Masculino , Estudos Retrospectivos
10.
Asian Spine J ; 15(6): 713-720, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33355843

RESUMO

STUDY DESIGN: Human ligamentum flavum-derived cells (HFCs) were obtained from surgical samples for a basic experimental study. PURPOSE: We sought to evaluate the inflammatory response of human ligamentum flavum cells to investigate hypertrophic changes occurring in the ligamentum flavum. OVERVIEW OF LITERATURE: Lumbar spinal stenosis (LSS) is a disease commonly observed in the elderly. The number of patients with LSS has increased over time, yet the pathomechanisms of LSS still have not been fully elucidated. One of the clinical features of LSS is hypertrophy of the ligamentum flavum, which results in narrowing of the lumbar spinal canal. Some reports have suggested that ligamentum flavum hypertrophy is associated with inflammation and fibrosis; meanwhile, the p38 mitogen-activated protein (MAP) kinase is involved in the hypertrophy of human ligamentum flavum cells. METHODS: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. RESULTS: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. CONCLUSIONS: This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

11.
Prostaglandins Other Lipid Mediat ; 90(1-2): 1-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19524699

RESUMO

We have previously shown that prostaglandin E(1) (PGE(1)) stimulates the synthesis of vascular endothelial growth factor (VEGF) through p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of Rho-kinase in the PGE(1)-stimulated VEGF synthesis in these cells. PGE(1) induced within 3min the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase. Y27632 and fasudil, specific inhibitors of Rho-kinase, which attenuated the MYPT-1 phosphorylation, significantly suppressed the PGE(1)-stimulated VEGF synthesis. Y27632 and fasudil markedly reduced the PGE(1)-induced phosphorylation of SAPK/JNK without affecting the phosphorylation levels of p38 MAP kinase or p44/p42 MAP kinase. These results strongly suggest that Rho-kinase functions at a point upstream of SAPK/JNK and regulates PGE(1)-stimulated VEGF synthesis in osteoblasts.


Assuntos
Alprostadil/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Osteoblastos/citologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Células 3T3 , Amidas/farmacologia , Animais , Linhagem Celular , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Int J Mol Med ; 24(1): 77-82, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19513538

RESUMO

We previously reported that sphingosine 1-phosphate induces heat shock protein 27 (HSP 27) via activation of phosphatidylinositol 3-kinase (PI3K)/Akt and p38 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is implicated in sphingosine 1-phosphate-stimulated induction of HSP27 in MC3T3-E1 cells. Sphingosine 1-phosphate time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a Rho-kinase substrate. Y27632, a specific Rho-kinase inhibitor, significantly reduced sphingosine 1-phosphate-stimulated HSP27 induction, as well as MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, also suppressed sphingosine 1-phosphate-stimulated HSP27 induction. Y27632, as well as fasudil, attenuated sphingosine 1-phosphate-induced phosphorylation of p38 MAP kinase. However, Akt phosphorylation induced by sphingosine 1-phosphate was not affected by either Rho-kinase inhibitor. These results strongly suggest that Rho-kinase regulates sphingosine 1-phosphate-stimulated induction of HSP27 at a point upstream of p38 MAP kinase in osteoblasts.


Assuntos
Proteínas de Choque Térmico HSP27/biossíntese , Lisofosfolipídeos/fisiologia , Osteoblastos/metabolismo , Esfingosina/análogos & derivados , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Amidas/farmacologia , Animais , Linhagem Celular , Lisofosfolipídeos/farmacologia , Camundongos , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve , Fosforilação , Piridinas/farmacologia , Esfingosina/farmacologia , Esfingosina/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases Associadas a rho/antagonistas & inibidores
13.
Int J Mol Med ; 23(2): 267-72, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19148552

RESUMO

We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In addition, p70 S6 kinase activated by FGF-2 negatively regulates VEGF release via SAPK/JNK. In the present study, we investigated the effects of tacrolimus (FK506) and cyclosporine A, well-known immunosuppressants, on the FGF-2-induced VEGF release in these cells. Tacrolimus, but not cyclosporine A which alone had no effect on VEGF basal levels, significantly enhanced FGF-2-stimulated VEGF release. Tacrolimus markedly enhanced FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP or p38 MAP kinases. SP600125, a specific inhibitor of SAPK/JNK, reduced the amplification by tacrolimus of the FGF-2-induced VEGF release. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by tacrolimus. These results strongly suggest that tacrolimus enhances FGF-2-stimulated VEGF release via up-regulation of SAPK/JNK through modulating p70 S6 kinase in osteoblasts.


Assuntos
Ciclosporina/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Imunossupressores/farmacologia , Osteoblastos/metabolismo , Tacrolimo/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Regulação para Cima
14.
Int J Mol Med ; 24(2): 197-203, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19578793

RESUMO

We previously reported that sphingosine 1-phosphate stimulates the induction of heat shock protein 27 (HSP27) through p38 mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase/Akt in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), the major polyphenol found in green tea, affects the induction of HSP27 in these cells and its mechanism, since it was previously reported that catechin, including EGCG, suppresses bone resorption. EGCG significantly reduced the induction of HSP27 stimulated by sphingosine 1-phosphate in a dose-dependent manner between 10 and 30 microM. Immunofluorescence microscopy studies revealed that sphingosine 1-phosphate certainly stimulated the induction of HSP27 in the cytosol of these cells, and that EGCG clearly suppressed its induction. However, sphingosine 1-phosphate-stimulated phosphorylation of p38 MAP kinase or MAPKAP-2 was not affected by EGCG. By contrast, EGCG markedly suppressed the phosphorylations of both Akt and glycogen synthase kinase-3beta stimulated by sphingosine 1-phosphate. These results strongly suggest that EGCG suppresses the induction of HSP27 stimulated by sphingosine 1-phosphate via attenuation of, not the p38 MAP kinase pathway, but of the phosphatidylinositol 3-kinase/Akt pathway in osteoblasts.


Assuntos
Catequina/análogos & derivados , Proteínas de Choque Térmico HSP27/metabolismo , Lisofosfolipídeos/farmacologia , Osteoblastos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esfingosina/análogos & derivados , Animais , Animais Recém-Nascidos , Western Blotting , Catequina/farmacologia , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Microscopia de Fluorescência , Modelos Biológicos , Osteoblastos/citologia , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esfingosina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Neurospine ; 16(2): 347-353, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30653910

RESUMO

OBJECTIVE: This study was conducted to clarify the validity of the short posterior arch screw (S-PAS). The S-PAS is inserted only in the pedicle-analogue portion of the posterior arch. The S-PAS screw length is almost half that conventional C1 lateral mass screws inserted via the posterior arch (via-PAS). S-PAS reduces the risk of vertebral artery injury (VAI) because it never reaches the transverse foramen. Although the biomechanical validity of various C1 lateral mass screws (C1LMS) analyzed in young specimens have been published, that of unicortically inserted C1LMS such as the unicortical Harms screw, S-PAS, and via-PAS for elderly patients is concerning because of the high prevalence of osteoporosis in the elderly. METHODS: Nine fresh frozen cadavers (average age at death, 72.1 years) were used for pullout testing. The bone mineral density of each specimen was evaluated using quantitative computed tomography. RESULTS: The pullout strength of via-PAS (1,048.5 N) was significantly greater than that of the unicortical Harms screw (257.9 N) (p<0.05). The pullout strength of S-PAS was 720.3 N, which was also significantly greater than that of the unicortical Harms screw (p<0.05). CONCLUSION: The via-PAS and S-PAS are valid surgical options, even in elderly patients. Along with sufficient biomechanical strength, the S-PAS screw prevents VAI.

16.
Neurosurgery ; 84(4): 898-907, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29718359

RESUMO

BACKGROUND: There have been no reports describing how cervical reconstruction surgery affects global spinal alignment (GSA). OBJECTIVE: To elucidate the effects of cervical reconstruction for GSA through a retrospective multicenter study. METHODS: Seventy-eight patients who underwent cervical reconstruction surgery for cervical kyphosis were divided into a Head-balanced group (n = 42) and a Trunk-balanced group (n = 36) according to the values of the C7 plumb line (PL). We also divided the patients into a cervical sagittal balanced group (CSB group, n = 18) and a cervical sagittal imbalanced group (CSI group, n = 60) based on the C2 PL-C7 PL distance. Various sagittal Cobb angles and the sagittal vertical axes were measured before and after surgery. RESULTS: Cervical alignment was improved to achieve occiput-trunk concordance (the distance between the center of gravity [COG] PL, which is considered the virtual gravity line of the entire body, and C7 PL < 30 mm) despite the location of COG PL and C7PL. A subsequent significant change in thoracolumbar alignment was observed in Head-balanced and CSI groups. However, no such significant change was observed in Trunk-balanced and CSB groups. We observed 1 case of transient and 1 case of residual neurological worsening. CONCLUSION: The primary goal of cervical reconstruction surgery is to achieve occiput-trunk concordance. Once it is achieved, subsequent thoracolumbar alignment changes occur as needed to harmonize GSA. Cervical reconstruction can restore both cervical deformity and GSA. However, surgeons must consider the risks and benefits in such challenging cases.


Assuntos
Vértebras Cervicais/cirurgia , Cifose/cirurgia , Procedimentos Ortopédicos , Procedimentos de Cirurgia Plástica , Vértebras Cervicais/fisiopatologia , Humanos , Estudos Retrospectivos
17.
Auris Nasus Larynx ; 46(1): 70-77, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30691599

RESUMO

OBJECTIVE: Dizziness is one of the most common symptoms in the general population. Patients with dizziness experience balance problems and anxiety, which can lead to decreased physical activity levels and participation in their daily activities. Moreover, recovery of vestibular function from vestibular injury requires physical activity. Although there are reports that decreased physical activity is associated with handicap, anxiety, postural instability and reduced recovery of vestibular function in patients with chronic dizziness, these data were collected by self-report questionnaires. Therefore, the objective data of physical activity and the relationships between physical activity, handicap, anxiety and postural stability in patients with chronic dizziness are not clear. The purpose of this research was to objectively measure the physical activity of patients with chronic dizziness in daily living as well as handicap, anxiety and postural stability compared to healthy adults. Additionally, we aimed to investigate the relationships between physical activity, handicap, anxiety and postural stability in patients with chronic dizziness. METHODS: Twenty-eight patients with chronic dizziness of more than 3 months caused by unilateral vestibular hypofunction (patient group) and twenty-eight age-matched community dwelling healthy adults (healthy group) participated in this study. The amount of physical activity including time of sedentary behavior, light physical activity, moderate to vigorous physical activity and total physical activity using tri-axial accelerometer, self-perceived handicap and anxiety using questionnaires, and postural stability were measured using computerized dynamic posturography. RESULTS: The results showed worse handicap, anxiety and postural stability in the patient group compared to the healthy group. Objective measures of physical activity revealed that the patient group had significantly longer time of sedentary behavior, shorter time of light physical activity, and shorter time of total physical activity compared to the healthy group; however, time of moderate to vigorous physical activity was not significantly different between groups. Moreover, there were correlations between physical activity and postural stability in the patient group, while there were no correlations between physical activity, handicap or anxiety in the patient group. CONCLUSION: These results suggest that objectively measured physical activity of the patients with chronic unilateral vestibular hypofunction is lower compared to the healthy adults, and less active patients showed decreased postural stability. However, the details of physical activity and causal effect between physical activity and postural stability were not clear and further investigation is needed.


Assuntos
Ansiedade/complicações , Exercício Físico , Equilíbrio Postural , Doenças Vestibulares/fisiopatologia , Acelerometria , Idoso , Tamanho Corporal , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença Crônica , Pessoas com Deficiência , Exercício Físico/fisiologia , Exercício Físico/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Autoavaliação (Psicologia) , Inquéritos e Questionários , Doenças Vestibulares/psicologia , Testes de Função Vestibular
18.
Global Spine J ; 9(1): 6-13, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30775202

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Determine the indications, complications, and clinical outcomes in patients requiring fusions from the cervical spine to the pelvis. Several investigators have examined fusions from the thoracic spine to the sacrum, but no similar study has been performed for cervical-to-pelvis fusions. METHODS: Patients from 2003 to 2014 with an upper instrumented vertebrae (UIV) in the cervical spine (any level) and a lower instrumented vertebrae (LIV) in the sacrum or pelvis were included in the study. Those with infectious or acute trauma-related deformities were excluded. Patient demographics, medical history, diagnosis, operative procedure, and health-related quality of life measures were analyzed. Student's t test, Kruskal-Wallis test, and χ2 test were used as appropriate; significance was set at P < .05 for all tests. RESULTS: Fifty-five patients met inclusion criteria for the study. Average follow-up was 2.8 years. Proximal junctional kyphosis was the most common indication for cervical-to-pelvis fusions (36%). The most common UIV was C2 (29%) followed by C7 (24%). There was an average 31° correction in maximum kyphosis and a 3.3 cm improvement in sagittal vertical axis. In adults, the rate of complication was 71.4%, with a major complication rate of 39.3% and reoperation rate of 53.6%. There was significant improvement in the Scoliosis Research Society (SRS-22r) score (3.0 to 3.5; P < .01). CONCLUSION: Proximal junctional kyphosis is the most common indication for patients requiring fusion to the cervical spine. Adult patients incur a significant risk of major complications and reoperations. However, significant improvement in SRS-22r outcomes are noted in these patients.

19.
Mol Cell Endocrinol ; 291(1-2): 27-32, 2008 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-18586382

RESUMO

We have previously reported that prostaglandin F(2alpha) (PGF(2alpha)) stimulates interleukin-6 (IL-6), a potent bone resorptive agent, through p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is implicated in the PGF(2alpha)-stimulated IL-6 synthesis in MC3T3-E1 cells. PGF(2alpha) time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a Rho-kinase substrate. Y27632, a specific Rho-kinase inhibitor, significantly reduced the PGF(2alpha)-stimulated IL-6 synthesis as well as the MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, suppressed the PGF(2alpha)-stimulated IL-6 synthesis. Y27632 and fasudil failed to affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase. SB203580 and BIRB0796, potent inhibitors of p38 MAP kinase, suppressed the IL-6 synthesis induced by PGF(2alpha). While SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), failed to reduce the synthesis. Y27632 as well as fasudil attenuated the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. These results strongly suggest that Rho-kinase regulates PGF(2alpha)-stimulated IL-6 synthesis via p38 MAP kinase activation in osteoblasts.


Assuntos
Dinoprosta/metabolismo , Interleucina-6/biossíntese , Osteoblastos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/metabolismo , Células 3T3 , Animais , Dinoprosta/genética , Inibidores Enzimáticos/metabolismo , Camundongos , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve , Osteoblastos/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-18771907

RESUMO

We have previously reported that prostaglandin D2 (PGD2) stimulates interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is implicated in the PGD2-stimulated IL-6 synthesis in MC3T3-E1 cells. PGD2 time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a Rho-kinase substrate. Y27632, a specific Rho-kinase inhibitor, significantly reduced the PGD2-stimulated IL-6 synthesis as well as the MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, suppressed the PGD2-stimulated IL-6 synthesis. The PGD2-stimulated IL-6 synthesis was reduced by PD98059, a MEK inhibitor, and SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase, but not SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). However, Y27632 and fasudil failed to affect the PGD2-induced phosphorylation of p44/p42 MAP kinase. On the other hand, Y27632 as well as fasudil markedly attenuated the PGD2-induced phosphorylation of p38 MAP kinase. In addition, PGD2 additively induced IL-6 synthesis in combination with endothelin-1 which induces IL-6 synthesis through p38 MAP kinase regulated by Rho-kinase. These results strongly suggest that Rho-kinase regulates PGD2-stimulated IL-6 synthesis via p38 MAP kinase activation in osteoblasts.


Assuntos
Interleucina-6/biossíntese , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Prostaglandina D2/farmacologia , Quinases Associadas a rho/fisiologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Amidas/farmacologia , Animais , Antracenos/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Endotelina-1/farmacologia , Flavonoides/farmacologia , Imidazóis/farmacologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Quinase de Cadeia Leve de Miosina/efeitos dos fármacos , Quinase de Cadeia Leve de Miosina/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA