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1.
J Clin Med ; 13(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38929945

RESUMO

Objectives: Cervical disc herniation (CDH) leads to pain, numbness, and potential disability. Percutaneous endoscopic cervical discectomy (PECD) offers an anterior or posterior approach. This study aims to compare postoperative disc height and angle changes one year after PECD, considering both approaches. Methods: We retrospectively reviewed the data from patients with CDH who underwent PECD from October 2017 to July 2022. Cervical disc height was measured using the preoperative and one-year postoperative magnetic resonance imaging (MRI) examinations. Lordotic angle (LA), global alignment angle (GAA), segmental alignment angle (SAA), and slippage distance (SD) at the surgical level were measured on radiographs in the neutral, flexion, and extension positions. Results: Thirty-eight patients who underwent posterior PECD (PPECD) and five patients who underwent anterior PECD (APECD) were included in the evaluation. The mean age of the patients was 47.4 years (range: 29-69 years). There was a significant difference in the preoperative and one-year postoperative GAA and SAA in extension in the PPECD group (p = 0.003 and 0.031, respectively). The mean decreased disc height one-year postoperative was 1.30 mm in the APECD group and 0.3 mm in the PPECD group by MRI. A significant disc height decrease was observed in the APECD group (p < 0.001). Conclusions: Treating CDH with PPECD or APECD is feasible, as it can relieve symptoms and reduce disability. Stability remained unaffected during the first year after surgery, even though there was an increase in angulation during extension. Despite a significant decrease in disc space following APECD, patients reported significant symptom improvement and no new symptoms.

2.
Bioeng Transl Med ; 9(2): e10633, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435819

RESUMO

A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%-13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications.

3.
J Neurosurg Spine ; 40(6): 773-781, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38518295

RESUMO

OBJECTIVE: This retrospective study was designed to evaluate the incidence and predisposing factors of heterotopic ossification (HO) after cervical disc arthroplasty (CDA) with a specific implant at 1 and 2 levels, and to investigate the biomechanical effects related to HO. The study goal was to identify ways to reduce the likelihood of HO formation after surgery. METHODS: The study included patients who underwent only 1- or 2-level CDA with the Baguera C disc between November 2014 and December 2021 at a single medical center. All patients were operated on by the same neurosurgeon. The surgical indication included 1-level or 2-level disc herniation between C3 and C7 with radiculopathy, myelopathy, or both, with minimal spondylosis. The various factors were assessed by evaluating plain radiographs and cervical CT scans. The presence of HO was evaluated at different intervals postsurgery, and HO severity was graded using the McAfee classification. RESULTS: Of 107 patients who underwent CDA, 47 (43.9%) had HO at 63 of 171 levels (36.8%). Most cases with HO were grade 1, and no grade 4 was observed. Statistically significant risk factors for HO were the length of endplate coverage ratio and inferior anterior residual exposed endplate (AREE); sex, age, implant height and width, shell angle, and pre- and postoperative functional spinal unit (FSU) angle were not significant. More AREE and greater kyphotic postoperative FSU angle in the flexion position were significant factors differentiating HO grades 0 and 1 from grades 2 and 3. Furthermore, the non-HO group showed a trend of higher range of motion at any postoperative time compared to the HO group, especially at 1 month after surgery. CONCLUSIONS: The HO incidence after CDA was correlated with the residual length of endplate coverage and inferior AREE. Additionally, the AREE and kyphotic postoperative FSU angle in the flexion position were associated with HO grade progression. Patients with HO also showed a trend of lower range of motion at 1 month after surgery. Using an adequately sized implant and encouraging neck motion may help prevent HO development and progression.


Assuntos
Vértebras Cervicais , Ossificação Heterotópica , Humanos , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/epidemiologia , Ossificação Heterotópica/diagnóstico por imagem , Feminino , Masculino , Fatores de Risco , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Deslocamento do Disco Intervertebral/cirurgia , Substituição Total de Disco/efeitos adversos , Substituição Total de Disco/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Disco Intervertebral/cirurgia , Disco Intervertebral/diagnóstico por imagem , Idoso , Artroplastia/efeitos adversos , Artroplastia/métodos , Radiculopatia/cirurgia , Radiculopatia/etiologia , Radiculopatia/epidemiologia
5.
Int J Rheum Dis ; 26(10): 1996-2006, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37565304

RESUMO

AIM: An estimated 88% of rheumatoid arthritis (RA) patients experience various degrees of cervical spine involvement. The excessive movement of the atlantoaxial joint, which connects the occiput to the upper cervical spine, results in atlantoaxial instability (AAI). AAI stabilization is usually achieved by C1 lateral mass-to-C2 pedicle screw-rod fixation (LC1-PC2 fixation), which is technically challenging in RA patients who often show destructive changes in anatomical structures. This study aimed to analyze the clinical results and operative experiences of C1-C2 surgery, with emphasis on the advancement of image-guided surgery and augmented reality (AR) assisted navigation. METHODS: We presented our two decades of experience in the surgical management of AAI from April 2004 to November 2022. RESULTS: We have performed surgery on 67 patients with AAI, including 21 traumatic odontoid fractures, 20 degenerative osteoarthritis, 11 inflammatory diseases of RA, 5 congenital anomalies of the os odontoideum, 2 unknown etiologies, 2 movement disorders, 2 previous implant failures, 2 osteomyelitis, 1 ankylosing spondylitis, and 1 tumor. Beginning in 2007, we performed LC1-PC2 fixation under C-arm fluoroscopy. As part of the progress in spinal surgery, since 2011 we used surgical navigation from presurgical planning to intraoperative navigation, using the preoperative computed tomography (CT) -based image-guided BrainLab navigation system. In 2021, we began using intraoperative CT scan and microscope-based AR navigation. CONCLUSION: The technical complexities of C1-C2 surgery can be mitigated by CT-based image-guided surgery and microscope-based AR navigation, to improve accuracy in screw placement and overall clinical outcomes, particularly in RA patients with AAI.

6.
Biomed Res Int ; 2023: 8010223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36794256

RESUMO

Objectives: The objectives of this study were to identify the risk factors and incidence of anterior bone loss (ABL) after Baguera C cervical disc arthroplasty (CDA) and identify whether design differences in artificial discs affect ABL. Methods: In this retrospective radiological review of patients who underwent single-level Baguera C CDA in a medical center, the extent of ABL and the following radiological parameters were recorded: global and segmental alignment angle, lordotic angle (or functional spinal unit angle), shell angle, global range of motion (ROM), and ROM of the index level. ABL at the index level was grade 0-2. Grade 0 was defined as no remodeling, grade 1 as spur disappearance or mild change in body contour, and grade 2 as obvious bone regression with Baguera C Disc exposure. Results: Combining grade 1 and grade 2, ABL was found in 56 upper adjacent vertebrae and 52 lower adjacent vertebrae of the 77 patients. Only 18 patients (23.4%) had no ABL. Shell angle differed significantly between ABL grades of both the upper and lower adjacent level: 0.0° in grade 0 and 1 ABL vs. 2.0° in grade 2 ABL of the upper adjacent level (p < 0.05); and 0.0° in grade 0 and 1 ABL vs. 3.5° in grade 2 ABL of the lower adjacent level (p < 0.05). A female predominance of ABL was found. Hybrid surgery and artificial disc size were also related to ABL. Conclusions: ABL is more common in Baguera C Disc arthroplasty than Bryan Disc arthroplasty. Larger shell angle was related to ABL after CDA with Baguera C Discs, which may indicate that shell angle is pivotal in determining the incidence of ABL after CDA. Females had more ABL with Baguera C Disc arthroplasty; this might be related to shorter endplate lengths as well as a smaller endplate-implant mismatch.


Assuntos
Doenças Ósseas Metabólicas , Degeneração do Disco Intervertebral , Disco Intervertebral , Substituição Total de Disco , Humanos , Feminino , Masculino , Estudos Retrospectivos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Artroplastia/efeitos adversos , Pescoço/cirurgia , Próteses e Implantes , Resultado do Tratamento , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Substituição Total de Disco/efeitos adversos
7.
Medicine (Baltimore) ; 102(5): e32832, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36749265

RESUMO

The effect of spinal anatomical anomalies on the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for disc herniation repair is unclear. This retrospective review aims to assess the safety and effectiveness of PELD for treating L5-S1 disc herniation with a range of characteristics and to determine the prevalence of lumbosacral transitional vertebrae (LSTV) anatomical anomalies to facilitate pre-surgical planning. From July 2005 to June 2019, 345 patients with L5-S1 disc herniations were treated with PELD. The primary outcome was 1-year postoperative visual analogue scale scores for low back and lower limb pain. The secondary outcomes included the surgical approach used, lumbosacral bony anomalies, presence of a ruptured disc or severely calcified disc, pediatric lumbar disc herniation, recurrent disc herniation management, and the long-term outcome. visual analogue scale scores for most patients were significantly improved after surgery. The prevalence of LSTVs was 4.05% (14/345 patients) in lumbar sacralization and 7.53% (26/345 patients) in sacral lumbarization. The prevalence of ruptured and severely calcified discs was 18.55% (64/345) and 5.79% (20/345), respectively. The prevalence of pediatric lumbar disc herniation was 2.02% (7/345). The recurrence rate was 4.34% (15/345). Two durotomy cases without sequelae and 8 cases of lower limb dysesthesia lasting longer than 3 months postoperatively were reported. PELD is safe and effective for treating L5-S1 disc herniation, including cases complicated by calcified lumbar disc herniation, disc rupture with migration, and the presence of LSTV. Appropriate imaging is essential to identify case-specific factors, including the prevalent LSTV anatomical anomalies, before surgery.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Criança , Deslocamento do Disco Intervertebral/cirurgia , Discotomia Percutânea/métodos , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Endoscopia/métodos , Região Lombossacral/cirurgia , Resultado do Tratamento
8.
Biomed Pharmacother ; 153: 113389, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076477

RESUMO

Alzheimer's disease (AD) is a brain disease that causes problems in memory, thinking, and behavior. Allantoin has been shown to have antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we aimed to investigate the effect and mechanism of action of allantoin on AD-related memory impairment. We investigated the effect of allantoin on an amyloid ß1-42 peptide (Aß1-42)-induced AD model in rats and evaluated its memory-enhancing effect using the Morris water maze test. Pathological changes in the hippocampus and cortex were examined by hematoxylin-eosin staining. The expression of the phosphorylated Tau protein and PI3K/Akt/GSK-3ß signaling pathway was analyzed by western blotting. The results of the water maze test showed that after treatment with allantoin, the rats could reduce their swimming time and travel distances to find the platform. Allantoin treatment also increased the time spent in the quadrant in which the platform was located. Histological assessment showed that Aß1-42 could cause morphological alterations in nerve cells in the hippocampal CA1 region, and that allantoin could repair the damage to these cells. Western blotting revealed that allantoin treatment increased the expression of p-PI3K, p-Akt, and p-GSK-3ß and decreased p-Tau in the hippocampus and cortex of rats. These effects were inhibited by LY294002. These findings showed that allantoin could improve cognitive impairment in Aß1-42-induced rats by activating the PI3K/Akt/GSK-3ß signaling pathway to reduce abnormal hyperphosphorylation of Tau. Thus, allantoin may be a potential therapeutic agent for neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Alantoína/metabolismo , Alantoína/farmacologia , Alantoína/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Proteínas tau/metabolismo
9.
Biomed Pharmacother ; 129: 110328, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32535384

RESUMO

The aim of the present study was to investigate the analgesic effects and mechanism of action of Trametes versicolor (Tv) mycelium powder. Wistar rats were randomly divided into the following three or four groups: i) Saline group, fed saline; ii) Tv 500 group, fed 500 mg/kg Tv; iii) ASA 50 group, fed 50 mg/kg acetylsalicylic acid (ASA); and iv) ASA 100 group, fed 100 mg/kg ASA. Chemical formalin tests and thermal hot plate tests were used to investigate the analgesic effects of each group. ELISAs were performed to detect cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) plasma levels, and high-performance liquid chromatography (HPLC) was used for quality control the active component, oleanolic acid (OA) in Tv that had the analgesic effect. The OA content in aqueous Tv extract was found to be 11.92 % by HPLC assays. The licking frequencies in the early phase and late phase of the formalin test were significantly lower in the Tv 500 and ASA 100 groups than the saline group. The licking time in the late phase were also significantly lower in the Tv 500 and ASA 100 groups than the saline group. The plasma levels of COX-2 and PGE2 were decreased significantly in the Tv 500 and ASA 100 groups compared with that of the saline group at 60 min in the formalin test. In addition, oral feeding with 500 mg/kg Tv may effectively reduce physical pain triggered by hot plates in Wistar rats. Taken together, the acetylsalicylic acid-like analgesic effects of Tv in Wistar rats may be associated with the reduction of the plasma COX-2 and PGE2 levels.


Assuntos
Analgésicos/farmacologia , Aspirina/farmacologia , Ácido Oleanólico/farmacologia , Limiar da Dor/efeitos dos fármacos , Dor/prevenção & controle , Polyporaceae , Analgésicos/isolamento & purificação , Animais , Ciclo-Oxigenase 2/sangue , Dinoprostona/sangue , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Ácido Oleanólico/isolamento & purificação , Dor/sangue , Dor/etiologia , Dor/fisiopatologia , Polyporaceae/química , Ratos Wistar
10.
Spine J ; 20(8): 1211-1218, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32360762

RESUMO

BACKGROUND CONTEXT: Cervical disc arthroplasty (CDA) is an innovative procedure launched in the early 2000s. Compared with anterior cervical discectomy and fusion, many studies show that CDA offers equivalent clinical outcomes while reducing secondary procedures and total cost. PURPOSE: We sought to determine the incidence of anterior bone loss after CDA and the related biomechanical effects. STUDY DESIGN/ SETTING: Retrospective chart review. PATIENT SAMPLE: Patients who underwent CDA with one level Bryan Disc (Medtronic SofamorDanek, Memphis, TN, USA) at one institution. OUTCOME MEASURES: Radiological measurements, including the extent of anterior bone loss, global alignment angle, shell angle, lordotic angle, mean degree of angle of the endplate with the horizontal line, global range of motion (ROM) and ROM of the index level were recorded. The grading of anterior bone loss of the index level was defined as Grade 0, no remodeling; Grade 1, spur disappearance or mild change in body contour; Grade 2, obvious bone regression with Bryan Disc exposure. METHODS: Anatomical measures and ROM were compared by grade of bone loss. RESULTS: Of the 121 patients included in the study, anterior bone loss was found in 53 (43.8%) on the upper adjacent level and 54 (44.6%) on the lower adjacent level. Twenty-nine patients (23.9%) had anterior bone loss in both levels. The majority of cases had Grade 1 anterior bone loss. Grade 2 bone loss was noted in the upper adjacent vertebra in only 5 patients and in 4 patients in the lower adjacent vertebra. Age, sex, operative level, and hybrid surgery had no effect on anterior bone loss. Most radiological assessments, including global alignment angle, lordotic angle, mean degree of angle of the endplate with the horizontal line, global ROM, and ROM of the index level, showed no correlation to anterior bone loss. Shell angle was found to be different in groups with or without remodeling in the upper adjacent level: 5.0 degreesin the Grade 0 group and 7.0 degrees in the Grade 1-2 group, p<.05. CONCLUSIONS: Many more patients than predicted had anterior bone loss. Increasing the shell angle of the artificial disc may increase the incidence of anterior bone loss after CDA. Further study of the biomechanics following CDA should help clarify the mechanisms at work.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Substituição Total de Disco , Artroplastia , Fenômenos Biomecânicos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Substituição Total de Disco/efeitos adversos , Resultado do Tratamento
11.
World J Clin Cases ; 7(19): 3047-3054, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31624753

RESUMO

BACKGROUND: Cervical disc arthroplasty (CDA) is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility. However, the CDA postoperative period is impacted by osteolysis, subsidence, metallosis, or heterotopic ossification (HO). We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty. CASE SUMMARY: A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc (HIVD). After four years, cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels. The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression. Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist. A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome. CONCLUSION: Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.

12.
Eur Spine J ; 27(Suppl 3): 415-420, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29164328

RESUMO

PURPOSE: Cervical disc arthroplasty has been a popular alternative to traditional arthrodesis treatment for maintaining postoperative cervical spine mobility. However, certain adverse reactions to cervical disc arthroplasty have emerged during the last few decades. METHODS: Metallosis or metalloma is a rarely reported complication after spinal fusion or spinal arthroplasty surgery. We report on the first metallosis case occurring in a patient who received Bryan Disc implantation approximately 8 years earlier. She was involved in a traffic accident and sustained a whiplash injury to the cervical spine one and a half years ago. The traumatic Bryan Disc loosening developed after the traffic accident, causing metallosis. RESULTS: To the best of our knowledge, this is the first reported case of spinal metallosis caused by the Bryan Disc. A series of metallosis cases reported in the literature are also reviewed. CONCLUSIONS: Although uncommon, intraspinal metallosis or metalloma should be considered as an infrequent cause of delayed neurological symptoms after spinal surgery involving metallic instrumentation, especially after disc arthroplasty. Once metallosis is suspected, immediate metallic implant removal is mandatory for definite diagnosis and treatment.


Assuntos
Artroplastia/efeitos adversos , Vértebras Cervicais/cirurgia , Próteses e Implantes/efeitos adversos , Falha de Prótese/efeitos adversos , Fusão Vertebral/métodos , Artroplastia/instrumentação , Vértebras Cervicais/lesões , Discotomia/instrumentação , Discotomia/métodos , Feminino , Humanos , Disco Intervertebral/lesões , Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Imageamento por Ressonância Magnética , Metais/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Falha de Prótese/etiologia , Fusão Vertebral/instrumentação , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Traumatismos em Chicotada/cirurgia
13.
J Immunol ; 183(4): 2785-92, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19635908

RESUMO

Peptidoglycan (PGN), the major component of the cell wall of Gram-positive bacteria, activates the innate immune system of the host and induces the release of cytokines and chemokines. We investigated the signaling pathway involved in IL-6 production stimulated by PGN in rheumatoid arthritis synovial fibroblasts. PGN caused concentration- and time-dependent increases in IL-6 production. PGN-mediated IL-6 production was attenuated by TLR2 small interfering RNA and nucleotide-binding oligomerization domain 2 small interfering RNA. Pretreatment with PI3K inhibitor (Ly294002 and wortmannin), Akt inhibitor, and AP-1 inhibitor (tanshinone IIA) also inhibited the potentiating action of PGN. PGN increased the focal adhesion kinase (FAK), PI3K, and Akt phosphorylation. Stimulation of rheumatoid arthritis synovial fibroblast cells with PGN increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the IL-6 promoter. PGN mediated an increase in the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to AP-1 element was inhibited by Ly294002, Akt inhibitor, and FAK mutant. Our results suggest that PGN increased IL-6 production in human synovial fibroblasts via the TLR2 receptor/FAK/PI3K/Akt and AP-1 signaling pathway.


Assuntos
Quinase 1 de Adesão Focal/fisiologia , Interleucina-6/biossíntese , Peptidoglicano/farmacologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/imunologia , Membrana Sinovial/metabolismo , Receptor 2 Toll-Like/fisiologia , Fator de Transcrição AP-1/fisiologia , Adjuvantes Imunológicos/metabolismo , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/fisiologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Células Cultivadas , Fibroblastos/imunologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação da Expressão Gênica/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/fisiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/fisiologia , Membrana Sinovial/enzimologia , Membrana Sinovial/patologia
14.
Mol Immunol ; 45(14): 3693-702, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18621420

RESUMO

Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. It has been shown to induce interleukin-6 (IL-6) expression in inflammatory responses in rheumatoid arthritis. We investigated the signaling pathway involved in IL-6 production caused by BK in synovial fibroblasts. BK caused concentration- and time-dependent increases in IL-6 production. By using pharmacological inhibitors or genetic inhibition of the BK receptor, siRNA revealed that B2 but not B1 BK receptors are involved in BK-mediated up-regulation of IL-6. BK-mediated IL-6 production was attenuated by phospholipase C inhibitor (U73122), protein kinase Cdelta inhibitor (rottlerin), NF-kappaB inhibitor (PDTC), IkappaB protease inhibitor (TPCK) and NF-kappaB inhibitor peptide. Stimulation of synovial fibroblasts with BK activated IkappaB kinase alpha/beta (IKK alpha/beta), IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation at Ser(276), p65 and p50 translocation from the cytosol to the nucleus and kappaB-luciferase activity. BK mediated an increase of IKK alpha/beta and IkappaBalpha phosphorylation, kappaB-luciferase activity and p65 and p50 binding to the NF-kappaB element was inhibited by B2 BK receptor antagonist (HOE140), U73122 and rottlerin. Our results suggest that BK increased IL-6 production in synovial fibroblasts via the B2 BK receptor/PI-PLC/PKCdelta/and NF-kappaB signaling pathway.


Assuntos
Bradicinina/farmacologia , Fibroblastos/metabolismo , Interleucina-6/biossíntese , Antagonistas de Receptor B2 da Bradicinina , Células Cultivadas , Genes Reporter , Humanos , Quinase I-kappa B/fisiologia , Luciferases/metabolismo , Modelos Biológicos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fosforilação , Proteína Quinase C-delta/antagonistas & inibidores , Proteína Quinase C-delta/metabolismo , RNA Mensageiro/análise , Receptor B2 da Bradicinina/metabolismo , Transdução de Sinais , Membrana Sinovial/citologia , Fator de Transcrição RelA/metabolismo , Transfecção , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismo , Regulação para Cima
15.
Cell Signal ; 20(8): 1478-88, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18501560

RESUMO

Leptin, the adipocyte-secreted hormone that centrally regulates weight control, is known to function as an immunomodulatory regulator. We investigated the signaling pathway involved in IL-8 production caused by leptin in both rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). RASF and OASF expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. Leptin caused concentration- and time-dependent increases in IL-8 production. Leptin-mediated IL-8 production was attenuated by OBRl receptor antisense oligonucleotide, JAK2 inhibitor or STAT3 small interference RNA (siRNA). Transfection with insulin receptor substrate (IRS)-1 siRNA or dominant-negative mutant of p85 and Akt or pretreatment with phosphatidylinositol 3-kinase inhibitor (Ly294002 and wortmannin), Akt inhibitor, NF-kappaB inhibitor (PDTC) and NF-kappaB inhibitor peptide also inhibited the potentiating action of leptin. Stimulation of RASF with leptin activated IkappaB kinase alpha/beta (IKK alpha/beta), p65 phosphorylation at Ser(276), p65 translocation from the cytosol to the nucleus, and kappaB-luciferase activity. Moreover, pretreatment with p300 inhibitor (curcumin) also blocked IL-8 expression. The binding of p65 to the NF-kappaB elements, as well as the recruitment of p300 and the enhancement of histone H3 acetylation on the IL-8 promoter was enhanced by leptin, which was inhibited by wortmannin, Akt inhibitor or IRS-1 siRNA. These results suggest that leptin increased IL-8 production in synovial fibroblast via the OBRl/JAK2/STAT3 pathway, as well as the activation of IRS1/PI3K/Akt/NF-kappaB-dependent pathway and the subsequent recruitment of p300.


Assuntos
Artrite Reumatoide/imunologia , Fibroblastos/imunologia , Interleucina-8/biossíntese , Leptina/farmacologia , Osteoartrite/imunologia , Transdução de Sinais , Membrana Sinovial/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Artrite Reumatoide/enzimologia , Sítios de Ligação , Células Cultivadas , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Histonas/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina , Interleucina-8/genética , Janus Quinase 2/metabolismo , NF-kappa B/metabolismo , Osteoartrite/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo , Membrana Sinovial/citologia , Fatores de Transcrição de p300-CBP/metabolismo
18.
Hand Surg ; 10(2-3): 293-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16568531

RESUMO

The superficial radial nerve might be compressed or injured at various anatomical sites along its course in the forearm. Most of the superficial radial nerve neuropathy are caused by pathological lesions such as trauma, a mass or tight band at the distal third of the forearm. Wartenberg's syndrome is the most common cause of sensory radial entrapment at the distal forearm. Compression of superficial radial nerve occurring at the proximal third of forearm is unusual. We present a rare case of superficial radial nerve compression due to a parosteal lipoma of proximal radius. Results of complete physical and radiological examinations are also presented. Surgical intervention of the tumour mass was performed for nerve decompression. The patient reported total relief of the neurological symptom post-operatively. This rare case demonstrates the unique characteristics of parosteal lipoma with unusual superficial radial nerve neuropathy at the proximal radius. This report reminds us that there is the possibility of superficial nerve compression caused by tumour mass over the proximal third of forearm.


Assuntos
Neoplasias Ósseas/complicações , Lipoma/complicações , Síndromes de Compressão Nervosa/etiologia , Nervo Radial , Rádio (Anatomia) , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Humanos , Lipoma/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
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