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PURPOSE: To investigate the occurrence of altered central pain modulation in patients with degenerative lumbar diseases (DLDs) and to analyze its association with physical activity (PA) 3 years after lumbar decompression and fusion. METHODS: Preoperative assessments of pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) and pain were, respectively, recorded in 304 patients. These patients further underwent International Physical Activity Questionnaire (IPAQ) and both pain-related and psychological assessments 3 years post-operation. RESULTS: Preoperatively, the patients had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy subjects (P < 0.05). Postoperatively, 53.9% (164/304) patients showed PA below healthy-related thresholds (< 600 MET min/w). Low PA group showed a greater postoperative weight gain and bone loss and a higher postoperative prevalence of both moderate anxiety and marginal depression than high PA group (P < 0.05). All covariates with differences between the high and low PA groups were subjected to multivariate logistic regression, and long preoperative disease duration, low preoperative PPT in pain-free area, high preoperative TS, revision surgery, severe postoperative low back pain and significant postoperative pain catastrophizing thought were independently associated with low postoperative PA (P < 0.05). CONCLUSIONS: This study supports the existence of central sensitization (CS) caused by abnormal central pain modulation in DLDs. Pre-existing CS in these patients may be associated with low PA after lumbar surgeries, and this low-activity lifestyle may predispose patients to multiple adverse health outcomes. Preoperative dynamic quantitative sensory testing may provide information for the identification of at-risk patients.
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Neuralgia , Humanos , Estudos Retrospectivos , Procedimentos Neurocirúrgicos , Região Lombossacral , Dor Pós-Operatória , Exercício FísicoRESUMO
PURPOSE: This prospective randomized controlled trial aimed to investigate the impact of early postoperative sequential motor control (starting first day post-operatively) and core stabilization training (starting fifth week post-operatively) compared to conventional exercise (starting fifth weeks post-operatively) on the risk of developing persistent spinal pain syndrome type-2 (PSPS-T2). METHODS: 395 patients with lumbar degenerative diseases (LDDs) undergoing modified transforaminal lumbar interbody fusion and a 12-week postoperative exercise program (sequential vs. conventional exercise: 214 vs. 181) were evaluated for low back pain (LBP) intensity, Oswestry Disability Index (ODI), pressure pain threshold (PPT), temporal summation (TS), fatty infiltration of paraspinal muscles, transversus abdominis (TrA) activation capacity and Fear-Avoidance Beliefs Questionnaire (FABQ) pre-operatively, 3 months post-operatively, and 1 year post-operatively. RESULTS: At 3-month postoperative assessment, LBP in sequential exercise group were lower than those in conventional exercise group (P < 0.05), and sequential-exercise patients had greater local-area PPTs, lower TS, lower TrA activation capacities and less fatty infiltration of erector spinae than did the conventional-exercise patients (P < 0.05). At 1-year postoperative assessment, fewer sequential-exercise patients had PSPS-T2 compared with conventional-exercise patients (11/214 vs. 20/181; P < 0.05). LBP at rest and FABQ were lower in sequential-exercise patients than conventional-exercise patients (P < 0.05). Furthermore, both PPT and TS at 1-year postoperative assessment were associated with these measurements at 3-month postoperative assessment in patients with PSPS-T2 (P < 0.05). CONCLUSIONS: Postoperative sequential exercise has more positive effects to avoid PSPS-T2 than conventional exercise in patients with LDDs possibly because of its advantages in improving central and peripheral sensitization.
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INTRODUCTION/AIMS: Some patients with Hirayama disease (HD) may have generalized joint hypermobility (GJH), which may excessively increase cervical range of motion (ROM) and then worsen the HD. The purpose of this study was to identify the frequency of GJH in HD patients and to analyze the effect of GJH on cervical ROM and the severity of HD. METHODS: The Beighton scoring system (≥4) was used to diagnose GJH in 84 HD patients. All patients underwent assessments of cervical-flexion/extension ROM; motor unit number estimation in bilateral abductor pollicis brevis (APB) muscles; handgrip strength; and the disabilities of the arm, shoulder, and hand assessments. RESULTS: Concomitant GJH was identified in 20 (23.8%) HD patients. The HD patients with GJH exhibited greater cervical-flexion (P < .001) and cervical-extension (P = .033) ROM than those without GJH. Both greater single motor unit potential amplitudes (symptomatic side: P = .005; less-symptomatic side: P = .011) and lower motor unit numbers (symptomatic side: P = .008; less-symptomatic side: P = .013) in bilateral APB, along with lower compound muscle action potential amplitudes on the symptomatic-side APB (P = .039), were observed in patients with GJH than those without GJH. There was a mild negative correlation between motor unit number and cervical-flexion ROM in HD patients (symptomatic side: r = -0.239, P = .028; less-symptomatic side: r = -0.242, P = .027). DISCUSSION: The frequency of GJH in HD patients may be higher than in the general population. Importantly, GJH may exacerbate excessive cervical-flexion ROM, thereby worsening motor unit loss in HD patients. A cautious approach should be taken when treating HD due to possible comorbid GJH.
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OBJECTIVE: To quantify the cervical sagittal alignment in patients with Hirayama disease (HD) and to investigate the effect of loss of cervical sagittal alignment upon the cervical spinal lesions in HD. METHODS: Cervical sagittal alignments were measured in 253 HD patients and 63 healthy subjects by C2-C7 Cobb and a modified method of Toyama et al. Motor unit number estimation (MUNE) was performed in bilateral abductor pollicis brevis (APB) in all HD patients, and 31 patients further underwent cervical diffusion tensor imaging (DTI). RESULTS: Compared with healthy subjects, HD patients showed lower C2-C7 Cobb (P < 0.05), and 83.4% patients showed loss of cervical lordosis (cervical straight or kyphosis), which was greater than healthy subjects (55.6%, P < 0.05). Compared with lordotic/straight group, patients with cervical kyphosis showed lower MUNE values and greater single motor unit potential (SMUP) in bilateral APB, and higher apparent dispersion coefficient (ADC) and lower fractional anisotropy were observed at C4/C5 level in the latter than the former (P < 0.05). C2-C7 Cobb was associated with both C4/C5 ADC and bilateral SMUP (P < 0.05). CONCLUSIONS: Most HD patients showed loss of cervical sagittal alignments, and both MUNE and DTI detections demonstrated a positive correlation between loss of cervical sagittal alignments and cervical spinal lesions in HD. These findings supported that loss of cervical sagittal alignments may worsen motor impairments in HD. Therefore, it is necessary for clinicians to be aware of restoring cervical sagittal alignments during HD treatment.
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Cifose , Lordose , Humanos , Imagem de Tensor de Difusão , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Lordose/diagnóstico por imagem , Lordose/patologia , Cifose/diagnóstico por imagem , Cifose/patologia , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the use of the modified and simplified vertebral bone quality (VBQ) method based on T1-weighted MRI images of S1 vertebrae in assessing bone mineral density (BMD) for patients with lumbar degenerative diseases. METHODS: We reviewed the preoperative data of patients with lumbar degenerative diseases undergoing lumbar spine surgery between January 2019 and June 2022 with available non-contrast T1-weighted magnetic resonance imaging (MRI), computed tomography (CT) images and dual-energy X-ray absorptiometry (DEXA). S1 vertebral bone quality scores (S1 VBQ) and S1 CT Hounsfield units were measured with picture archiving and communication system (PACS). One-way ANOVA was applied to present the discrepancy between the S1 VBQ of patients with normal bone density (T-score ≥ - 1.0), osteopenia (- 2.5 < T-score < - 1.0) and osteoporosis (T-score ≤ - 2.5). The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of S1 VBQ in distinguishing low BMD. Statistical significance was set at p < 0.05. RESULTS: A total of 207 patients were included. The S1 VBQ were significantly different between groups (p < 0.001). Interclass correlation coefficient for inter-rater reliability was 0.86 (95% CI 0.78-0.94) and 0.94(95% CI 0.89-0.98) for intra-rater reliability. According to the linear regression analysis, the S1 VBQ has moderate-to-strong correlations with DEXA T-score (r = - 0.48, p < 0.001). The area under the ROC curve indicated a predictive accuracy of 82%. A sensitivity of 77.25% with a specificity of 70% could be achieved for distinguishing low BMD by setting the S1 VBQ cutoff as 2.93. CONCLUSIONS: The S1 VBQ was a promising tool in distinguishing poor bone quality in patients with lumbar degenerative diseases, especially in cases where the previously reported VBQ method based on L1-L4 was not available. S1 VBQ score could be useful as opportunistic assessment for screening and complementary evaluation to DEXA T-score before surgery.
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Densidade Óssea , Doenças Ósseas Metabólicas , Humanos , Reprodutibilidade dos Testes , Absorciometria de Fóton/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Doenças Ósseas Metabólicas/patologia , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
PURPOSE: To investigate the impact of early versus delayed surgery on sensory abnormalities in acute traumatic central cord syndrome (ATCCS). METHODS: Pressure pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM) and pain assessments were performed in 72 ATCCS patients (early vs. delayed surgical treatment: 32 vs. 40) and 72 healthy subjects in this ambispective cohort study. These examinations, along with mechanical detection threshold (MDT) and disabilities of arm, shoulder and hand (DASH), were assessed at 2 years postoperatively. RESULTS: Preoperatively, more delayed surgical patients had neuropathic pain below level compared with early surgical patients (P < 0.05). Both early and delayed surgical patients showed reduced PPT in common painful areas and increased TS, while reduced CPM only existed in the latter (P < 0.05). Reduced PPT in all tested areas, along with abnormalities in TS and CPM, was observed in patients with durations over 3 months. Both incidences and intensities of pain and pain sensitivities in common painful areas were reduced in both treatment groups postoperatively, but only early surgical treatment improved the CPM and TS. Follow-up analysis demonstrated a higher MDT and lower PPT in hand, greater TS, greater DASH, lower pain intensities and higher incidence of dissatisfaction involving sensory symptoms in delayed surgical patients than in early surgical patients (P < 0.05). CONCLUSIONS: Central hypersensitivity may be involved in the persistence of sensory symptoms in ATCCS, and this augmented central processing may commence in the early stage. Early surgical treatment may reverse dysfunction of endogenous pain modulation, thus reducing the risk of central sensitization and alleviating sensory symptoms.
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Síndrome Medular Central , Neuralgia , Humanos , Estudos de Coortes , Síndrome Medular Central/complicações , Síndrome Medular Central/cirurgia , Limiar da Dor , Medição da DorRESUMO
BACKGROUND: Surgical treatment has been increasingly performed in Hirayama disease (HD) patients to limit excessive neck flexion and restore cervical lordosis. However, postoperative recurrence of cervical lordosis loss may restart the progress of HD. Many studies have demonstrated a relationship between neck muscle strength and cervical lordosis, and it is widely accepted that leisure-time physical activity (LTPA) can increase muscle strength. However, there are few reports about the correlation between LTPA and maintenance of postoperative cervical curvature. OBJECTIVE: To quantify the cervical lordosis and motor function before and after operation in HD patients and to analyze the impact of postoperative LTPA levels on the changes in these measurements. METHODS: C2-7 Cobb were measured in 91 HD patients before, 2-5 days and approximately 2 years after operation. Motor unit number estimation (MUNE) and handgrip strength (HGS) were performed in all patients before and approximately 2 years after operation, and both cross-sectional area and fatty infiltration of posterior cervical muscles were measured in 62 patients. Long-form international Physical Activity Questionnaire and its different domains was administered to all patients at postoperative 2-year assessments. RESULTS: The C2-7 Cobb was larger immediately and approximately 2 years after operation than that at preoperative assessment (P < 0.05). The preoperative to postoperative change in C2-7 Cobb was associated with postoperative changes in the symptomatic-side HGS and bilateral MUNE measurements (P < 0.05). Importantly, the patients performing LTPA had greater improvements in C2-7 Cobb from immediate to approximately 2 years after operation and greater C2-7 Cobb at last follow-up than those without LTPA, and postoperative improvements in both symptomatic-side MUNE measurements and symptomatic-side HGS were also greater in the former than in the latter (P < 0.05). CONCLUSIONS: Postoperative LTPA has a positive effect on recovery/maintenance of cervical lordosis after operation, which may alleviate the motor unit loss of distal upper limbs in HD patients. Therefore, postoperative LTPA may be beneficial for postoperative rehabilitation or early conservative treatment of HD patients.
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Lordose , Fusão Vertebral , Humanos , Lordose/diagnóstico por imagem , Lordose/cirurgia , Lordose/etiologia , Estudos Retrospectivos , Força da Mão , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Fusão Vertebral/efeitos adversos , Exercício Físico , Atividades de LazerRESUMO
BACKGROUND: Postoperative axial pain (PAP), characterized by pain and/or stiffness around the posterior neck, periscapular areas and/or shoulder region, is a vexing complication affecting 5-60% of patients undergoing posterior cervical decompression. Given its relatively high frequency and negative impact on patients' physical and mental status, efforts preoperatively to confirm patients at risk of developing PAP to offer more efficient pain management to minimize this complication have a high priority. The aim of this study is to investigate the role of preoperative dynamic quantitative sensory testing (QST) in predicting the PAP after posterior cervical decompression. METHODS: This longitudinal observational study included 122 patients with degenerative cervical myelopathy undergoing laminoplasty or laminectomy. Preoperatively, all patients underwent the assessment of pressure pain thresholds (PPTs) at local and remote pain-free areas and both temporal summation (TS) and conditioned pain modulation (CPM) at remote pain free-areas. These patients underwent further pain-related, psychosocial and clinical function assessments before and/or after operation. RESULTS: In the present study, 21 patients (21/122, 17.2%) developed PAP, and the 6-month postoperative follow-up demonstrated that 8 of these 21 patients developed chronic PAP (CPAP). All preoperative covariates with significant differences between the PAP and non-PAP groups were subjected to multivariate logistic regression, and the presence of preoperative axial pain, surgical plan including C2 decompression, total international physical activity questionnaire score (cutoff value [CV]: 2205.5, sensitivity: 82.4%; specificity: 61.1%) and TS value (CV: 2.5, sensitivity: 42.9%; specificity: 83.2%) were independently associated with PAP (P < 0.05). Logistic regression further revealed that the presence of preoperative axial pain, TS value (CV: 2.5, sensitivity: 62.5%; specificity: 83.2%) and CPM value (CV: 0.65, sensitivity: 87.5%; specificity: 61.4%) were significant predictors of CPAP (P < 0.05). CONCLUSIONS: The findings of this study support the hypothesis that preoperative endogenous pain modulation efficiency may be associated with axial pain after posterior cervical decompression. Clinically, preoperative estimation of both TS and CPM in remote pain-free areas may provide additional useful information for identifying patients who may be at risk of developing both PAP and CPAP, which may be beneficial in enabling stratification in the perioperative period of patients based on individual vulnerabilities to avoid/reduce this complication.
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Laminoplastia , Doenças da Medula Espinal , Vértebras Cervicais/cirurgia , Humanos , Laminectomia/efeitos adversos , Laminoplastia/efeitos adversos , Cervicalgia/complicações , Cervicalgia/etiologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Doenças da Medula Espinal/cirurgiaRESUMO
Val-Val-Tyr-Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride-induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non-alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L-02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine-choline-deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non-esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis-related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24-7 and Bacteroidia in high-fat diet (HFD)-fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)-associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut-liver axis activation. VVYP might be a promising drug candidate for NASH.
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Retroalimentação Fisiológica/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Oligopeptídeos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Substâncias Protetoras/farmacologiaRESUMO
PURPOSE: To investigate the feasibility of both needle electromyography (EMG) and proximal nerve conduction studies (NCS) in predicting C5 palsy after posterior cervical decompression. METHODS: This study included 192 patients with cervical myelopathy undergoing laminoplasty or laminectomy. Preoperatively, all patients accepted bilateral needle EMG detection and proximal NCS that consisted of supramaximally stimulating Erb's point and recording compound muscle action potential (CMAP) from bilateral deltoid. RESULTS: In the present study, 11 (11/192, 5.7%) patients developed unilateral C5 palsy after operation, and more patients with C5 palsy showed abnormal spontaneous activity in C5-innervated muscles compared to those without C5 palsy (8/11 vs. 16/181, p < 0.05). The sensitivity and specificity of spontaneous activity in C5-innervated muscles in predicting postoperative C5 palsy were 72.7% and 91.2%, respectively. Furthermore, there were significant left-to-right differences of deltoid CMAP amplitudes between the patients with and without C5 palsy (p < 0.05), and this measurement was also demonstrated to be useful for distinguishing patients with C5 palsy from cases without C5 palsy by receiver operating characteristic (ROC) curve analysis (cut-off value: 2.1 mV, sensitivity: 63.6%; specificity: 95.0%). In addition, the sensitivity and specificity of a series application of these two measurements were 63.6% and 100.0%, respectively. CONCLUSIONS: The findings of this study support the hypothesis that pre-existing progressive C5 root injury may be a risk factor for C5 palsy after posterior cervical decompression. Clinically, the estimation of NCS and needle EMG in C5-innervated muscles may provide additional useful information for predicting C5 palsy after cervical spinal surgery. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
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Vértebras Cervicais , Descompressão Cirúrgica , Vértebras Cervicais/cirurgia , Estudos Transversais , Humanos , Laminectomia , Músculos , Paralisia/diagnóstico , Paralisia/etiologia , Complicações Pós-Operatórias , Estudos Retrospectivos , Raízes Nervosas Espinhais/cirurgiaRESUMO
BACKGROUND: Postoperative delirium (PD), as an acute brain failure, is widely reported as a very common postoperative complication, and it is closely associated with increased morbidity and mortality. Recently, malnutrition is reported as one of the risk factors for PD. The prognostic nutritional index (PNI) is a simple method for nutritional evaluation. However, few studies have discussed the effectiveness of PNI as a nutritional assessment in predicting PD after primary total joint arthroplasty (TJA). The aim of this study is to investigate potential risk factors including PNI for PD following primary TJA. METHODS: A retrospective analysis of 994 patients was performed to identify risk factors associated with PD after primary TJA by using univariate and multivariate analyses. A receiver operating characteristic curve and the area under the curve were applied to evaluate the significant results of the multivariate analysis and the optimal cutoff value (CV). RESULTS: Postoperatively, sixty-seven patients (67/994, 6.7 %) experienced PD. Univariate analysis demonstrated that operative time, duration of anesthesia, age, hypertension, serum albumin, and PNI differed between the PD and non-PD groups (P < 0.05). Multivariate logistic regression analysis showed that the preoperative PNI (odds ratio [OR]: 0.908; 95 % confidence interval [CI]: 0.840-0.983; CV: 47.05), age of patients (OR: 1.055; 95 % CI: 1.024-1.087; CV: 73.5 years), and hypertension (OR: 1.798; 95 % CI: 1.047-3.086), were independently associated with PD (P < 0.05). CONCLUSIONS: A low preoperative PNI associated with malnutrition was demonstrated to be an independent risk factor for PD following primary TJA. Patients with preoperative low PNI should be cautioned and provided with adequate nutritional intervention to reduce postoperative PD.
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Delírio , Avaliação Nutricional , Idoso , Artroplastia , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: We investigated the feasibility of motor unit number index (MUNIX) in quantitatively assessing motor root lesions and tracking different treatment outcomes in lumbosacral radiculopathy (LR). METHODS: Bilateral MUNIX was recorded from the abductor hallucis, extensor digitorum brevis, and tibialis anterior in 44 normal controls and 108 patients with LR, and this was repeated approximately 12 months after treatment in 60 patients with LR. RESULTS: More abnormalities were observed when side-to-side differences of MUNIX measurements were used to evaluate LR (P < .05). Motor unit number index measurements worsened without progression of muscle weakness after conservative treatment, and MUNIX measurements improved with or without increased muscle strength after surgical treatment (P < .05). DISCUSSION: Motor unit number index may identify a specific L5 or S1 motor root lesion even before muscle weakness occurs, especially when side-to-side differences are used. Changes in MUNIX were larger than those in motor function measures after treatments for LR.
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Vértebras Lombares , Neurônios Motores/fisiologia , Radiculopatia/fisiopatologia , Recrutamento Neurofisiológico/fisiologia , Sacro , Raízes Nervosas Espinhais/fisiopatologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiculopatia/diagnóstico , Resultado do TratamentoRESUMO
Various neuropeptides related to the energy equilibrium affect bone growth in humans and animals. Neuropeptides W (NPW) are identical in the internal ligands of the two G-protein receptors (GPRs) included in subtypes 7 and 8. Neuropeptides W inhibits proliferation in the cultivated rat calvarial osteoblast-like (ROB) cells. This study examines the expression of NPW and GPR7 in murine chondrocyte and their function. An immunohistochemical analysis showed that NPW and GPR7 were expressed in the proliferative chondrocytes of the growth plates in the hind limbs of mice. The NPW mRNA quickly elevated in the early differentiation (7-14 days) of ATDC5 cells, while NPW and GPR7 mRNA were reduced during the late stage (14-21 days) of differentiation. Neuropeptide W-23 (NPW-23) promoted the proliferation of ATDC5 cells, which was attenuated by inhibiting the GPR7, protein kinase A (PKA), protein kinase C (PKC) and ERK1/2 pathways. Neuropeptide W-23 enhanced the early cell differentiation, as evaluated by collagen type II and the aggrecan gene expression, which was unaffected by inhibiting the ERK1/2 pathway, but significantly decreased by inhibiting the PKA, PKC and p38 MAPK pathways. In contrast, NPW-23 was not involved in the terminal differentiation of the chondrocytes, as evaluated by the mineralization of the chondrocytes and the activity of the alkaline phosphatase. Neuropeptides W stimulated the PKA, PKC, p38 MAPK and ERK1/2 activities in a dose- and time-dependent manner in the ATDC5 cells. These results show that NPW promotes the proliferation and early differentiation of murine chondrocyte via GPR7 activation, as well as PKA and PKC-dependent signalling cascades, which may be involved in endochondral bone formation.
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Diferenciação Celular/genética , Proliferação de Células/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Neuropeptídeos/genética , Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Condrogênese/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Neuropeptídeos/metabolismo , Neuropeptídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Incorporation of carbobenzoxy-glycylprolyl (Z-GP) to either α or ß position of the hydrazine moiety in procarbazine (Pcb) has been carried on in 5-steps process. The overall yield was 32.7%. The new entity Z-GP-Pcb was confirmed targeting to fibroblast activation protein-α (FAPα). Z-GP-Pcb may be hydrolyzed by either isolated rhFAPα or tumor homogenate. It was shown far less cytotoxicity against NCI-H460 cell line than Pcb. Z-GP-Pcb was displayed the potency to reduce spermatoxcity in H22-bearing mice. The mechanism may be ascribed to the blockade of dehydrogenation by α-glycerolphosphate dehydrogenase. This candidate was further proved equal antitumor activity to Pcb. However, the introduction of Z-GP scaffold decreased myelosuppression. All the evidences support that Z-GP-Pcb is a better antitumor agent than Pcb.
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Antineoplásicos/uso terapêutico , Células Sanguíneas/efeitos dos fármacos , Dipeptídeos/uso terapêutico , Procarbazina/uso terapêutico , Pró-Fármacos/uso terapêutico , Espermatozoides/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Contagem de Células Sanguíneas , Plaquetas/efeitos dos fármacos , Linhagem Celular Tumoral , Dipeptídeos/síntese química , Dipeptídeos/farmacologia , Dipeptídeos/toxicidade , Desenho de Fármacos , Endopeptidases , Eritrócitos/efeitos dos fármacos , Gelatinases/metabolismo , Humanos , Hidrólise , Leucócitos/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Tamanho do Órgão , Procarbazina/síntese química , Procarbazina/farmacologia , Procarbazina/toxicidade , Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Serina Endopeptidases/metabolismo , Contagem de Espermatozoides , Testículo/efeitos dos fármacosRESUMO
PURPOSE: To investigate F-wave as a method to identify a specific root lesion of L5 or S1 and to quantitatively evaluate the severity and progression of motor root lesions in lumbosacral radiculopathies (LR). METHODS: Both peroneal and tibial F-waves were performed bilaterally in 142 patients with unilateral L5 or S1 radiculopathies and 37 controls along with Medical Research Council (MRC) evaluation, and soleus H-reflexes were tested bilaterally in 78 of these 142 cases. Both F-wave and MRC were re-evaluated approximately 1 year after initial examination in 65 patients. RESULTS: Abnormal peroneal F-waves were found in 34 patients with L5 radiculopathy (34/67, 50.7%) along with normal tibial F-waves and soleus H-reflexes in all tested cases. By contrast, 27 patients with S1 radiculopathy presented abnormal tibial F-waves (27/76, 36.0%) along with normal peroneal F-waves in all 76 cases and abnormal soleus H-reflexes in 38 of 47 (80.9%) cases. There were significant differences in involved side F-duration among different MRC scales in both radiculopathy groups (P < 0.05). Follow-up analysis demonstrated slow progression of both F-wave abnormalities and muscle weakness in patients undergoing conservative treatment (P < 0.05). CONCLUSIONS: Comparisons of F-waves between the same nerve on both sides and between peroneal and tibial nerves in the same leg may clearly increase the validity of F-waves for evaluating a specific motor root lesion of L5 or S1. Furthermore, a quantitative comparison of F-waves may provide additional information on the severity of individual root lesions and their progression even in the early stages of disease. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Eletromiografia/métodos , Nervo Fibular/fisiopatologia , Radiculopatia/diagnóstico , Nervo Tibial/fisiopatologia , Adulto , Tratamento Conservador/métodos , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Plexo Lombossacral/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Debilidade Muscular/terapia , Radiculopatia/terapiaRESUMO
PURPOSE: To identify and compare the features of compound muscle action potential (CMAP) decrements in repetitive nerve stimulation (RNS) in patients with cervical spondylotic amyotrophy (CSA) and in patients with amyotrophic lateral sclerosis (ALS). METHODS: The cohort consisted of 43 CSA (distal-type to proximal-type ratio: 27-16) and 35 ALS patients. Five muscles, including abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), middle deltoid (Del), and upper trapezius (Trap), were tested by 3-Hz RNS. Decrements greater than cutoff values (APB > 5.8%; ADM > 4.8%; BB > 5.2%; Del > 6%; Trap > 5.1%) determined using receiver operating characteristic (ROC) curves were defined as abnormal, and the conventional criterion (≥10%) was also considered. RESULTS: A significant CMAP decrement (>cutoff values) was recorded from at least one tested muscle in 91.4% of ALS patients, and was most common in the proximal muscle, a finding that differed significantly from CSA patients (32.6%, P < 0.05). The application of cutoff values greatly improved the sensitivity of RNS over the conventional criterion (≥10%) for the detection of ALS (P < 0.05). The specificity of this technique remained higher when performing RNS in the proximal muscles, especially in the upper trapezius (AUC = 0.864, sensitivity = 0.643, and specificity = 1.000). The decrement percentages were significantly greater in the proximal muscles of ALS patients than in those of the CSA patients (P < 0.05). In addition, illness duration was not correlated with decrement percentage in either patient group, and no difference in the frequency of decrement among different ALS diagnostic categories was observed (P > 0.05). CONCLUSIONS: The application of RNS, especially in proximal muscles, may provide a simple accurate and noninvasive supplementary test for distinguishing CSA from ALS, even in the early stage of these diseases. A combination of RNS, needle EMG, clinical features and cervical magnetic resonance imaging may yield sufficient diagnostic information to differentiate CSA and ALS.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Músculo Esquelético/fisiopatologia , Atrofia Muscular Espinal/etiologia , Exame Neurológico/métodos , Espondilose/diagnóstico , Potenciais de Ação , Adulto , Idoso , Esclerose Lateral Amiotrófica/fisiopatologia , Diagnóstico Diferencial , Estimulação Elétrica , Eletromiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Espondilose/fisiopatologiaRESUMO
BACKGROUND: An ideal animal model has always been the key to research the pathogenesis and treatment of adolescent idiopathic scoliosis (AIS), while available methods have obvious disadvantages. The deficiency of melatonin has been proved relating to AIS. In this research, we intended to apply Luzindole, the melatonin antagonist, in bipedal rat model, for the block of combination of melatonin and its receptor, to inhibit the melatonin effect, and then to understand whether this method can effectively improve the scoliosis rate of bipedal rat model, and investigate the role of melatonin in scoliosis. To investigate the feasibility of improving the success rate of bipedal rat scoliosis model via intraperitoneal injection of melatonin antagonist (Luzindole). METHODS: A total of 60 3-weeks-old Sprague-Dawley rats were included in this study, and were divided into 3 groups (A, B and C). Each group included 20 rats. Osteotomy of the bilateral proximal humerus and proximal tailbone was performed in group A and group B; intraperitoneal injection of Luzindole (0.2 mg/kg) was performed in group A and group C. X-rays were taken before the surgery, 1 month after the surgery, 3 months after the surgery, and 6 months after the surgery, to calculate the Cobb's angle of the spine (>10° was considered scoliosis). The weight of every rat was also measured at the same time. Rats were euthanized 6 months after surgery to determine the calmodulin level in thrombocytes. RESULTS: The rate of scoliosis in group A (14/20) was significantly higher than those in group B (6/20) and group C (0/20) (P < 0.05). The differences in the weights of the 3 groups were non-significant; as were differences in the calmodulin level in thrombocytes. CONCLUSION: The application of the melatonin antagonist of Luzindole can improve the success rate of the bipedal rat scoliosis model. Meanwhile, this study indicates that a decreased melatonin level is not the primary cause of scoliosis, but that it may increase the likelihood and severity of scoliosis.
Assuntos
Modelos Animais de Doenças , Melatonina/antagonistas & inibidores , Escoliose/etiologia , Triptaminas , Animais , Distribuição Aleatória , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To assess the effect of chronic cervical spinal cord compression upon remote motor unit function in patients with cervical spondylotic myelopathy (CSM). METHODS: Fifty-three CSM patients and 47 healthy subjects were included. Bilateral motor unit number estimations (MUNEs) were recorded from both abductor digiti minimi and abductor pollicis brevis, and bilateral flexor carpi radialis (FCR) H-reflexes were examined in all subjects along with the nine-hole peg test (NHPT). The main outcome measures included the number of motor units, the average single motor unit potential (SMUP) area, the FCR Hmax/Mmax ratios and the NHPT time. RESULTS: Statistically significant results compared to healthy controls included increased average SMUP area, increased FCR Hmax/Mmax ratio and increased NHPT time (p < 0.05). Abnormal SMUP was observed in 10/53 (18.9%) CSM patients along with reduced motor units in 3 of these 10 patients, while the FCR Hmax/Mmax ratios in the CSM patients with abnormal MUNE were higher than those in others (p < 0.05). There was a positive correlation between the NHPT time and the average SMUP area, and a negative correlation was noted between the NHPT time and the number of motor units (p < 0.05). CONCLUSION: In CSM patients, the motor units below the level of compression may exhibit dysfunction, which is likely a result of trans-synaptic degeneration. Both cervical spinal cord compressive injury and this trans-synaptic degeneration contribute to the impairment of fine motor ability in CSM patients. Therefore, treatment and rehabilitation efforts should account for these two dysfunctions.
Assuntos
Medula Cervical/patologia , Neurônios Motores/patologia , Músculo Esquelético/inervação , Degeneração Retrógrada/patologia , Compressão da Medula Espinal/complicações , Espondilose/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recrutamento Neurofisiológico , Degeneração Retrógrada/etiologia , Degeneração Retrógrada/fisiopatologia , Compressão da Medula Espinal/etiologiaRESUMO
PURPOSE: Tarsal tunnel syndrome (TTS) is a painful foot condition. Lumbosacral radiculopathy (LR) may also present with symptoms occurring in TTS. However, no studies have been reported to determine the possible coexistence of these two conditions. The aim of our study was to identify the prevalence of TTS in patients with confirmed LR and to analyze the clinical and electrodiagnostic features of patients with both TTS and LR. METHODS: Medial and lateral plantar nerve mixed studies, peroneal motor studies and deep peroneal sensory studies were performed in 81 normal subjects and 561 patients with LR. The Tinel's test and other provocative tests were performed in the LR patient group, and the clinical symptoms of TTS were also analyzed. The frequency of TTS was investigated in all radiculopathy group patients with different nerve root lesions. RESULTS: Concomitant TTS was found in 27 (4.8%) patients with LR. Abnormal results of sensory/mixed conduction tests were observed in 25/27 (92.6%) patients, and 11/27 (40.7%) patients had abnormal results of motor conduction tests. Positivity for the Tinel's test and special provocative tests was found in 15/27 (55.6%) and 17/27 (63.0%) patients, respectively. Overall, 9/27 (33.3%) patients had typical symptoms, and suspicious clinical symptoms were found in the other 14/27 (51.9%) patients. The frequency of coexisting TTS was not statistically different among the single-level L4, L5 or S1 radiculopathy, or between the single-level and multi-level radiculopathies (P > 0.05). CONCLUSIONS: The findings suggest that the prevalence of TTS is significant in patients with LR. Thus, more caution should be paid when diagnosing and managing patients with LR due to the possible existence of TTS, as their management strategies are quite different.
Assuntos
Radiculopatia/complicações , Síndrome do Túnel do Tarso/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Exame Neurológico , Prevalência , Radiculopatia/diagnóstico , Síndrome do Túnel do Tarso/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: To identify whether there is significant changes between the cervical neutral F-waves and cervical flexion F-waves in the patients with Hirayama disease. METHODS: This study was performed on 25 normal subjects and 22 male patients with identified Hirayama disease (age: 15 to 44 years; height: 165 to 183 cm; duration: 6 to 240 months) between May 2010 and March 2014. Both cervical flexion F-wave (cervical flexion 45 °, 30 minutes) and conventional F-waves to median nerve stimulation and to ulnar nerve stimulation were performed in all subjects bilaterally. RESULTS: were analyzed by t-test or Fisher exact probability. RESULTS: In the normal subjects, all measurements of the bilateral F-waves didn't have any difference between the cervical flexion position and the cervical neutral position. On the cervical neutral position, the persistence (t = 5.209, P = 0.000), average latencies (t = 4.731, P = 0.022) and minimal latencies (t = 23.843, P = 0.006) of ulnar F-wave on the symptomatic heavier side from the patients with identified Hirayama disease were significantly lower or longer than those from the normal subjects, and the repeat F-waves were found in 3 patients (13.6%). On the symptomatic lighter side, the ulnar F-waves only had lower persistence (t = 22.306, P = 0.001) along with 5 repeat F-waves. Only lower persistence were found in the median F-wave on the both side (higher side t = 23.696, P = 0.000; lighter side t = 23.998, P = 0.000), along with 5 (22.7%) repeat F-waves on the symptomatic heavier side and 6 (27.3%) ones on the symptomatic lighter side. After cervical flexion maintaining 30 minutes, the increased maximal amplitudes (t = -2.552, P = 0.019), average amplitudes (t = -3.322, P = 0.003), duration (t = -3.323, P = 0.00), persistence (t = -2.604, P = 0.017) and frequency of repeat F-waves (9/22, 41%) (P = 0.044) were found on the symptomatic heavier side of ulnar F-wave, and 5 of 10 absent ulnar F-wave on the cervical neutral position were also recover. The median F-wave on the symptomatic heavier side mainly had increased maximal amplitude (t = -3.847, P = 0.001), average amplitudes (t = -2.188, P = 0.040) and persistence (t = -2.421, P = 0.025), and 1 of 6 absent median F-wave on the cervical neutral position were also recover after cervical flexion. CONCLUSION: The cervical flexion F-waves have significant regular changes compared to the cervical neutral F-waves in patients with Hirayama diseases, especially maximal and average amplitudes of F-waves.