RESUMO
Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1/miR-4731 and miR-4731/TNXB (Tenascin XB) interactions were predicted and validated by luciferase reporter assay. Colony formation, wound-healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis-related protein (alpha smooth muscle actin (α-SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase-2 (MMP-2) and TNXB) in LF whereas miR-4731-5p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR-4731-5p. Co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects of circPDK1 or TNXB. The circPDK1-miR-4731-TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.
Assuntos
Ligamento Amarelo , MicroRNAs , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Ligamento Amarelo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose , Hipertrofia/metabolismoRESUMO
BACKGROUND: One- and two-level lumbar interbody fusion with unilateral instrumentation is as effective as that with bilateral instrumentation. The height of the interbody cage influences the operated segment stability and the fusion technique success. The purpose of this research was to determine the effect of the fusion cage height (i.e. long and short) on both the stability (based on flexibility measures) and load sharing of the unilateral and bilateral instrumented transforaminal lumbar interbody fusion (TLIF) technique. METHODS: The flexibility and load sharing tests were performed on seven human lumbar spines. Different configurations combining a long or short cage with a unilateral, bilateral, or no posterior fixation were used to stabilize the operated segment. Two sets of modular cages were designed for each type of test to simulate the long and short cages. During the flexibility test, a pure-moment load of 7.5 Nm was applied. The range of motion (ROM) was recorded for flexion-extension, lateral bending, and axial rotation. During the load sharing test, an axial-compression load of 400 N was applied. The load bearing of the cages was recorded using a cage-embedded load cell. RESULTS: When the fusion cage height decreased 2 mm, the segment flexibility with unilateral fixation showed a significant increase in the ROM for flexion-extension, lateral bending, and axial rotation of 74.9, 83.8, and 175.2% (P < 0.01), respectively. In contrast, for bilateral fixation, the height decrease resulted in no significant change in ROM for flexion-extension (P = 0.686), lateral bending (P = 0.698), and axial rotation (P = 0.133). Using a short fusion cage, the load bearing decreased in 17.1, 21.5, and 54.1% (P < 0.05) for the cage alone, unilateral, and bilateral fixation, respectively. CONCLUSIONS: A cage longer than the intervertebral space should be chosen to increase the stability and intervertebral graft load borne when performing TLIF with unilateral instrumentation.
Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/fisiologia , Parafusos Pediculares , Próteses e Implantes , Fusão Vertebral/instrumentação , Idoso , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Radiografia , Amplitude de Movimento Articular , Fusão Vertebral/métodos , Suporte de Carga/fisiologiaRESUMO
Low back pain is associated with intervertebral disc degeneration (IVDD) due to cellular loss through apoptosis. Mechanical factors play an important role in maintaining the survival of the annulus fibrosus (AF) cells and the deposition of extracellular matrix. However, the mechanisms that excessive mechanical forces lead to AF cell apoptosis are not clear. The present study was to look for how AF cells sense mechanical changes. In vivo experiments, the involvement of mechanoreceptors in apoptosis was examined by RT-PCR and/or immunoblotting in the lumbar spine of rats subjected to unbalanced dynamic and static forces. In vitro experiments, we investigated apoptotic signaling pathways in untransfected and transfected AF cells with the lentivirus vector for rat ß1 integrin overexpression after cyclic stretch. Apoptosis in AF cells was assessed using flow cytometry, Hoechst 33258 nuclear staining. Western blotting was used to analyze expression of ß1 integrin and caspase-3 and ERK1/2 MAPK signaling molecules. In the rat IVDD model, unbalanced dynamic and static forces induced apoptosis of disc cells, which corresponded to decreased expression of ß1 integrin. Cyclic stretch-induced apoptosis in rat AF cells correlated with the activation of caspase-3 and with decreased levels of ß1 integrin and the phosphorylation levels of ERK1/2 activation level. However, the overexpression of ß1 integrin in AF cells ameliorated cyclic stretch-induced apoptosis and decreased caspase-3 activation. Furthermore, ERK1/2-specific inhibitor promotes apoptosis in vector ß1-infected AF cells. These results suggest that the disruption of ß1 integrin signaling may underlie disc cell apoptosis induced by mechanical stress. Further work is necessary to fully elucidate the pathophysiological mechanisms that underlie IVDD caused by unbalanced dynamic and static forces.
Assuntos
Condrócitos/metabolismo , Integrina beta1/genética , Degeneração do Disco Intervertebral/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Osteoblastos/metabolismo , Animais , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Condrócitos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Integrina beta1/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Lentivirus/genética , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Mecanotransdução Celular/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteoblastos/patologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , TransfecçãoRESUMO
BACKGROUND: Endostatin inhibits the pro-angiogenic action of basic fibroblast growth factor and vascular endothelial growth factor in different human cancers. This study assessed the efficacy of endostatin combined with concurrent chemoradiotherapy of non-small cell lung cancer (NSCLC). METHODS: Nineteen patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-l, and adequate organ function were treated with 60-66 Gy thoracic radiation therapy over 30-33 fractions concurrent with weekly 7.5 mg/m(2) endostatin for 14 days, 50 mg/m(2) paclitaxel, and 2 mg/mL/min carboplatin over 30 min. Patients were then treated with 7.5 mg/m(2) endostatin for 14 days, 150 mg/m(2) paclitaxel, and 5 mg/mL/min carboplatin every 3 weeks for 2 cycles as the consolidation treatment. The objective response rate was recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS: Six patients were unable to complete the consolidation treatment (4 pulmonary toxicity, 1 tracheoesophageal fistulae, and 1 progressive disease). Seventeen patients were included for data analysis. Specifically, one (5.9%) patient had a complete response and 12 (70.6%) had a partial response, whereas two patients had stable disease and the other two had disease progression. The overall response rate was 76% (95% confidence interval [CI], 51%-97%). The median progression-free survival was 10 months (95% CI, 7.6-12.3 months), and the median overall survival was 14 months (95% CI, 10.7-17.2 months). Early 10 patients who completed the treatment regimen showed that four patients experienced grade III pulmonary toxicity a few months after chemoradiotherapy, leading to the early closure of the trial according to the study design. CONCLUSIONS: The result of concurrent endostatin treatment with chemoradiotherapy in locally advanced unresectable NSCLC did not meet the goal per study design with unacceptable toxicity. The real impact of endostatin as the first-line treatment combined with chemoradiotherapy on the survival of NSCLC patients remains to be determined. (NCT 01158144).
Assuntos
Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endostatinas/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada , Intervalo Livre de Doença , Endostatinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Indução de RemissãoRESUMO
The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer's disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-ß peptides (A ß) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And A ß 40 and A ß 42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of A ß overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of A ß and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Diabetes Mellitus Experimental/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Animais , Comportamento Animal , Glicemia , Encéfalo/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Ativação Enzimática , Hipocampo/metabolismo , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
PURPOSE: To determine the effectiveness of bilateral decompression via a unilateral approach using unilateral pedicle screw fixation for two-level lumbar stenosis with instability. METHODS: Between October 2006 and October 2010, 98 patients (61 men and 37 women) who had reached the three-year follow-up interval were treated with unilateral pedicle screw fixation at the authors' institution. All patients underwent two-level transforaminal lumbar interbody fusion (TLIF), and the mean age was 59.6 years (range, 40-72). Visual analog scale (VAS) scores and Oswestry Disability Index (ODI) were used to assess the pre-operative and postoperative clinical results. Fusion status, the disc space height, and the whole lumbar lordotic angle were analysed for the radiological evaluation. RESULTS: The ODI scores decreased significantly in both early and late follow-up evaluations and the visual analog scale (VAS) score demonstrated significant improvement in late follow-up (P < 0.01). The disc space height (P < 0.05) and the whole lumbar lordotic angle (P < 0.05) were increased at the final follow-up. Successful fusion was achieved in all patients. CONCLUSION: Bilateral decompression via a unilateral approach using unilateral pedicle screw fixation for two-level lumbar stenosis with instability, which can maintain the lumbar lordosis and the disc space height, is an effective and less invasive method than with bilateral constructs.
Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Adulto , Idoso , Parafusos Ósseos , Descompressão Cirúrgica/instrumentação , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Fusão Vertebral/instrumentação , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/patologia , Resultado do Tratamento , Escala Visual AnalógicaRESUMO
PURPOSE: The aim of this study was to analyse the clinical and radiological outcomes of unilateral versus bilateral instrumented TLIF in two-level degenerative lumbar disorders. METHODS: A prospective randomised clinical study was performed from January 2008 to May 2011. Sixty-eight consecutive patients with severe low back pain and radicular pain were divided randomly into the unilateral (n = 33) or bilateral (n = 35) pedicle screw fixation group based on a random number list. Operative time, blood loss, duration of hospital stay, fusion rate, complication rate and implant costs were recorded and analysed statistically. Visual analog scale (VAS) scores, Oswestry Disability Index (ODI), and SF-36 were used to assess the preoperative and postoperative clinical results in the two groups. RESULTS: No differences were observed between the two groups with respect to demographic data. The patients of the two groups had significant improvement in functional outcome compared to preoperatively. There was no significant difference comparing fusion rate, complication rate and duration of hospital stay between the two groups at postoperative follow-up (P > 0.05). However, compared with the bilateral pedicle screw group, a significant decrease occurred in operative time, blood loss and implant costs in the unilateral group. CONCLUSION: Two-level unilateral instrumented TLIF is an effective and safe method with reduced operative time and blood loss for multiple-level lumbar diseases. But it is imperative that the larger cage should be appropriately positioned to support the contralateral part of the anterior column by crossing the midline of the vertebral body.
Assuntos
Parafusos Ósseos , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Avaliação da Deficiência , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Estudos Prospectivos , Fusão Vertebral/instrumentação , Resultado do TratamentoRESUMO
The accumulation of beta amyloid (Aß) can cause synaptic impairments, but the characteristics and mechanisms of the synaptic impairment induced by the accumulation of Aß in Alzheimer's disease (AD) remain unclear. In identified single neurons in a newly developed Drosophila AD model, in which Aß accumulates intraneuronally, we found an age-dependent reduction in the synaptic vesicle release probability that was associated with a decrease in the density of presynaptic calcium channel clusters and an increase in the presynaptic and postsynaptic contact length. Moreover, these alterations occurred in the absence of presynaptic bouton loss. In addition, we found that Aß expression also produced an age-dependent decrease in the amount of Bruchpilot (Brp), which plays an important role in controlling Ca(2+) channel clustering and synaptic vesicle release in the presynaptic active zone. Our study indicates that the chronic accumulation of intraneuronal Aß can induce functional and structural changes in the presynaptic active zone prior to a loss of presynaptic buttons in the same neuron.
Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/efeitos adversos , Sinapses/ultraestrutura , Envelhecimento/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Drosophila melanogaster , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/ultraestruturaRESUMO
BACKGROUND/AIMS: Activation of astrocytes is a common feature of Alzheimer's disease (AD). Proinflammatory molecules produced by activated astrocytes contribute to neuronal damage in AD. Moreover, dl-3-n-butylphthalide (NBP) has been reported to attenuate astroglial activation and exert neuroprotective effects in AD transgenic mice. However, the mechanism by which NBP inhibits activated astrocytes is poorly understood. METHODS: In this study, the primary astrocytes were obtained from the cerebral cortices of 1-day-old Sprague-Dawley rats. The levels of GFAP, COX-2, NF-κB, and IκBα were examined by Western blotting and the levels of TNF-α and IL-6 were determined by ELISA. RESULTS: NBP inhibited the amyloid-ß (Aß)-induced activation of astrocytes and the up-regulation of proinflammatory molecules. Importantly, NBP markedly suppressed Aß-induced IκBα degradation and nuclear factor-κB (NF-κB) translocation. CONCLUSION: Our results suggest that NBP attenuates Aß-induced activation of astrocytes and neuroinflammation via inhibition of the NF-κB signaling pathway.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Astrócitos/efeitos dos fármacos , Benzofuranos/farmacologia , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Ciclo-Oxigenase 2/metabolismo , Proteínas I-kappa B/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Transgênicos , Inibidor de NF-kappaB alfa , Proteínas do Tecido Nervoso/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: To investigate the potential of T2 mapping for characterizing the process of intervertebral disc degeneration (IDD) in a rabbit model. METHODS: Thirty-five rabbits underwent an annular stab to the L4/5 discs (L5/6 discs served as internal normal controls). Degenerative changes were graded according to the modified Thompson classification and quantified in T2 respectively at pre-operation, 1, 3, 6, 12 and 24 weeks postoperatively. After MRI analysis, expression analysis of aggrecan and type II collagen gene in nucleus pulposus (NP) was performed using real time polymerase chain reaction (real-time PCR). The longitudinal changes in NP T2 and gene expressions were studied by repeated measures and ANOVA, linear regression was performed for their correlations through the process of IDD. The reliability analysis of method of measurement of NP T2 was also performed. RESULTS: There was a strong inverse correlation between NP T2 and Thompson grades (r = -0.85). The decline of L4/5 NP T2 through 24 weeks was nonlinear, the most significant decrease was observed in 3 weeks postoperatively (P<0.05). The tendency was confirmed at gene expression levels. NP T2 correlated strongly with aggrecan (R² = 0.85, P<0.01) and type II collagen (R² = 0.78, P<0.01) gene expressions. The intraclass correlation coefficients for interobserver and intraobserver reliability were 0.963 and 0.977 respectively. CONCLUSIONS: NP T2 correlates well with aggrecan and type II collagen gene expressions. T2 mapping could act as a sensitive, noninvasive tool for quantitatively characterizing the process of IDD in longitudinal study, help better understanding of the pathophysiology of IDD, assist us to detect the degenerative cascade, and develop a T2-based quantification scale for evaluation of IDD and efficacy of therapeutic interventions.
Assuntos
Degeneração do Disco Intervertebral/etiologia , Imageamento por Ressonância Magnética/métodos , Animais , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Feminino , Expressão Gênica , Degeneração do Disco Intervertebral/metabolismo , Estudos Longitudinais , CoelhosRESUMO
In recent studies, the glutamate (Glu) level has been quantified using the modified STEAM sequence on 3T MRI. We enrolled 15 healthy volunteers and a group of 51 patients who experienced stroke for the first time and had a good prognosis. The patients with infarction were divided into three groups according to their scores by using the DSM-IV diagnostic criteria for major depressive disorder and the 17-item Hamilton Depression Rating Scale (HDRS). We studied the association between post-stroke depression and (1)H-MRS measurements in unaffected frontal lobes. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was performed to assess N-acetylaspartate/creatine (NAA)/Cr, (Glu)/Cr, choline (Cho)/Cr, and myoinositol (mI)/Cr ratios in stroke patients. The 11 patients (21.5%) who met the criteria for depression and 9 patients (17.6%) who had a high score for HDRS, (>14) but were not depressed, had a significantly higher Glu/Cr ratio than patients who scored ≤14 on HDRS and control groups (p < 0.001). No differences were found in NAA/Cr, Cho/Cr, or mI/Cr between the groups after stroke. These findings suggest that post-stroke depression is accompanied by changes in glutamate levels in the frontal lobe.
Assuntos
Encéfalo/metabolismo , Depressão/patologia , Ácido Glutâmico/metabolismo , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Mapeamento Encefálico , Creatina/metabolismo , Depressão/etiologia , Feminino , Humanos , Inositol/metabolismo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prótons , Escalas de Graduação Psiquiátrica , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: Lower preoperative Hounsfield Unit (HU) values of vertebral body are associated with pedicle screw (PS) loosening after implantation with traditional trans-pedicular trajectory. However, the relationship between trajectory HU value and PS fixation quality remains unknown. This study aimed to investigate if 3-dimensionally (3D)-printed guider directed accurate implantation of pedicle screw could increase the anti-pulling properties of screws. METHODS: 3D models of cadaveric spines were reconstructed by using computed tomography image and PS trajectories were designed for both sides of vertebra. The designed trajectories were divided into high HU group and low HU group. PS implantation with 3D-printed screw guide can be in complementary shape with target vertebra. Throughout 3D finite element analysis and biomechanical tests, the pull-out strength of screws in high or low trajectory HU groups were compared. RESULTS: The HU value was 132 ± 13 (mean ± standard deviation) in low HU group and 189 ± 17 in high HU group. The distance between planned trajectories and actual trajectories was 1.69 ± 0.4 mm. Biomechanical tests showed that in the high trajectory HU group the pull-out strength of screws was 750.41 ± 80.65 N; compared with 655.83 ± 74.31 N in the low trajectory HU group, the difference was statistically significant. When simulated with the finite element method, the pull-out strength of low HU trajectory pedicle screws was lower than that of high HU trajectory pedicle screws. CONCLUSIONS: Preoperative computer-assisted trajectory design using a 3D-printed screw guide may direct more accurate implantation with optimal implantation trajectory, and may provide a new way to improve pedicle screw fixation.
Assuntos
Parafusos Pediculares , Fusão Vertebral , Fenômenos Biomecânicos , Densidade Óssea , Osso e Ossos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Impressão Tridimensional , Fusão Vertebral/métodosRESUMO
Alzheimer's disease (AD) is attributable to synapse dysfunction and loss, but the nature and progression of the presynaptic structural and functional changes in AD are essentially unknown. We expressed wild-type or arctic form of beta amyloid(1-42) (Abeta) in a small group of neurons in the adult fly and performed extensive time course analysis of the function and structure of both axon and presynaptic terminals at the identified single-neuron level. Abeta accumulated intracellularly and induced a range of age-dependent changes, including depletion of presynaptic mitochondria, slowdown of bi-directional transports of axonal mitochondria, decreased synaptic vesicles, increased large vacuoles, and elevated synaptic fatigue. These structural and functional synaptic changes correlated with age-dependent deficit in motor behavior. All these alterations were accelerated in flies expressing the arctic form of Abeta. The depletion of presynaptic mitochondria was the earliest detected phenotype and was not caused by the change in axonal transport of mitochondria. Moreover, axonal mitochondria exhibited a dramatic reduction in number but a significant increase in size in aged Abeta-expressing flies, indicating a global depletion of mitochondria in the neuron and an impairment of mitochondria fission. These results suggest that Abeta accumulation depletes presynaptic and axonal mitochondria, leading to other presynaptic deficits.
Assuntos
Envelhecimento/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sistema Nervoso Central/metabolismo , Drosophila/metabolismo , Degeneração Neural/metabolismo , Terminações Pré-Sinápticas/metabolismo , Peptídeos beta-Amiloides/genética , Animais , Transporte Axonal/genética , Sistema Nervoso Central/patologia , Sistema Nervoso Central/ultraestrutura , Modelos Animais de Doenças , Regulação para Baixo/genética , Drosophila/ultraestrutura , Metabolismo Energético/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Degeneração Neural/genética , Degeneração Neural/patologia , Terminações Pré-Sinápticas/patologia , Terminações Pré-Sinápticas/ultraestrutura , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/patologia , Vesículas Sinápticas/ultraestrutura , Vacúolos/metabolismo , Vacúolos/patologia , Vacúolos/ultraestrutura , Degeneração Walleriana/genética , Degeneração Walleriana/metabolismo , Degeneração Walleriana/patologiaRESUMO
BACKGROUND: The safety of intravenous (IV) thrombolysis when administered between 4.5 and 6 h after acute ischemic stroke with alteplase has not been established. PURPOSE: The objective of this study was to investigate the safety of IV alteplase thrombolysis within a 6-hour time frame following ischemic stroke. METHODS: Eligible patients were categorized as having treatment within 4.5 h or from 4.5 to 6 h and were evaluated for the following end points: disability at 90 days as measured by the modified Rankin Scale, incidence of mortality, and type 2 parenchymal hemorrhages. RESULTS: 100 patients were enrolled in our study (58 within 4.5 h after stroke and 42 between 4.5 and 6 h). After 90 days, 47.6% of the patients in the 4.5-6 h group reached independence in comparison to 44.8% patients in the 4.5 h group (p = 0.840). The incidence of type 2 parenchymal hemorrhage in the patients treated between 4.5-6 h and those treated within 4.5 h were 7.1 and 8.6%, respectively (p = 1.00). The incidence of mortality was 7.1 and 17.2% for the 4.5-6 and 4.5 h groups, respectively (p = 0.228). CONCLUSIONS: IV thrombolysis in patients who fulfill the NINDS study criteria may still be considered up to 6 h after ischemic stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Distribuição de Qui-Quadrado , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this paper was to evaluate the treatment outcome of multimodal treatment for 196 patients with locoregional recurrent esophageal cancer after curative treatment and to determine the prognostic factors of recurrence. METHODS: One hundred and ninety six patients with locoregional recurrent esophageal cancer curatively treated in our hospital were included in this study. Kaplan-Meier method was used to analyze the survival rate. Log rank test was used to evaluate the difference between the groups. Multivariate survival analysis was conducted using a Cox proportional hazard regression model with a backward stepwise procedure. RESULTS: The overall 1-, 2- and 3-year survival rates were 29.8%, 5.9% and 4.0%, respectively, with a median survival time of 8.0 months. The univariate analysis showed that ECOG PS, the interval between initial treatment and recurrence, the regimens of initial treatment and retreatment were independent prognostic factors. The multivariate analysis showed that the regimens of initial treatment and retreatment were independent prognostic factors. Retreatment methods significantly influenced the survival. The median survival time of chemoradiotherapy, radiation therapy alone, chemotherapy alone, EGFR-TKI and best supportive care were 13.0, 7.0, 6.0, 4.0 and 3.0 months, respectively (P = 0.000). CONCLUSIONS: The prognosis of patients with locoregional recurrent esophageal cancer after curative treatment is poor. The main prognostic factors are the regimens of initial treatment and retreatment. Multimodal treatment including radiotherapy and chemotherapy may improve the long-term survival of the patients.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Terapia Combinada , Esofagectomia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radioterapia de Alta Energia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: To investigate the comparative effectiveness of stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small cell lung cancer (NSCLC) considered to be high-risk lobectomy patients. METHODS: From January 2012 to December 2015, patients who underwent SBRT or SLR for clinical stage I NSCLC were examined retrospectively. Propensity score matching (PSM) was performed to reduce selection bias in SBRT and SLR patients. RESULTS: Data from 86 SBRT and 79 SLR patients was collected. Median follow-up periods of the SBRT and SLR groups were 32 and 37 months, respectively. Patients treated with SBRT exhibited significantly higher age, higher likelihood of being male, larger tumor diameter, lower forced expiratory volume in 1 second (FEV1), and poorer performance status compared with SLR patients. There were no significant differences between SBRT and SLR patients for 3-year overall survival (OS) (80.3% and 82.3%, P=0.405), cause-specific survival (CSS) (81.3% and 83.4%, P=0.383), and local control (LC) (89.7% and 86.0%, P=0.501). Forty-nine patients were identified from each group after performing PSM. After patients were matched for age, gender, performance status, tumor characteristics and pulmonary function, no significant differences were observed in 3-year OS (85.4% and 73.3%, P=0.649), CSS (87.2% and 74.9%, P=0.637) and LC (95.6% and 82.1%, P=0.055). Prevalence of significant adverse events (grade 3 or worse) was 0% and 10.2% in the matched SBRT and SLR groups (P=0.056), respectively. CONCLUSIONS: Disease control and survival in the SBRT patients was equivalent to that seen in SLR patients with stage I NSCLC considered high-risk lobectomy candidates. SBRT could therefore be an alternative option to SLR in treating patients with a high operative risk.
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OBJECTIVE: To evaluate the safety and efficacy of Wuling Capsule combined with Deanxit in treating post-stroke depression (PSD). METHODS: One hundred and fourteen patients with PSD were randomly divided into Wuling Capsule-treated group (n=39), Deanxit-treated group (n=37) and Wuling Capsule plus Deanxit-treated group (n=38). Patients in Wuling Capsule-treated group were administered with three Wuling Capsules three times a day, and patients in Deanxit-treated group were administered with Deanxit 10.5 mg twice daily, while patients in the Wuling Capsule plus Deanxit-treated group were administered with both Wuling Capsule and Deanxit. Patients in the three groups were all treated for six weeks. Treatment efficacy was evaluated with Hamilton Depression Scale (HAMD) and the side effects were evaluated with Treatment Emergent Symptom Scale (TESS) before treatment and after 2-, 4-, and 6-week treatment. The blood and urine routine examinations were performed, and the hepatorenal functions and electrocardiogram were examined as well. RESULTS: There was no statistical difference in the total efficacy rate between Wuling Capsule-treated group and Deanxit-treated group (64.1% vs 64.9%, P>0.05), but the total efficacy rate of Wuling Capsule plus Deanxit-treated group was higher than that of the monotherapy (89.5% vs 64.1%, 89.5% vs 64.9%, P<0.05). There were no significant side effects in Wuling Capsule-treated group, while the incidence of side effects was 9% in both groups administered with Deanxit. CONCLUSION: The efficacy of Wuling Capsule plus Deanxit is better than that of the monotherapy in treating PSD.
Assuntos
Antracenos/uso terapêutico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Flupentixol/uso terapêutico , Fitoterapia , Acidente Vascular Cerebral/complicações , Idoso , Antracenos/efeitos adversos , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Cápsulas , Depressão/etiologia , Combinação de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Flupentixol/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To formulate radiological indexes based on CT for further MRI examination to detect posterior ligamentous complex injury (PLC) or disc injury in thoracolumbar burst fractures without neurological deficit in the emergent setting. MATERIALS AND METHODS: Patients with a single thoracolumbar burst fracture and no neurological deficit were included into this study. Radiological indexes on CT included canal compromise (CC), anterior and posterior vertebral height ratio (PVH and AVH ratio), local kyphosis (LK) and regional kyphosis (RK). PLC and disc injury were assessed on MRI. Statistical analysis was performed to identify the predictive power for radiological indexes for any MRI findings either or both disc and PLC injury. RESULTS: Eighty-four patients were included in this study. According to MRI, patients with no PLC and disc injury were allocated into MRI finding negative group, others were defined as positive group. There was no significant difference in AVH ratio, PVH ratio and RK between these two groups. The CC and LK were significant higher in positive group than that in negative group (pâ¯<â¯0.001).The areas under receiver operating characteristic curve were 0.826 and 0.893 for CC and LK respectively and without significant difference. The best thresholds for CC and LK were 0.19 (sensitivity: 69.4%; specificity: 87.5%) and 14.00° (sensitivity: 83.3%; specificity: 83.3%), respectively. CONCLUSION: The presence of CCâ¯>â¯0.19 and/or LKâ¯>â¯14.00° on CT scan can predict MRI findings including PLC and disc injury. These thresholds may be the guideline for MRI examination in patients with neurologically intact thoracolumbar burst fracture in the emergent condition.
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Disco Intervertebral/diagnóstico por imagem , Ligamentos/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Disco Intervertebral/lesões , Ligamentos/lesões , Vértebras Lombares/lesões , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/patologia , Vértebras Torácicas/lesões , Vértebras Torácicas/patologia , Adulto JovemRESUMO
BACKGROUND: To investigate the outcomes of using percutaneous kyphoplasty in the treatment of the secondary osteoporotic vertebral compression fractures. METHODS: Eighty-one patients had the secondary single segmental osteoporotic vertebral compression fractures after the initial fractures and treated by percutaneous kyphoplasty were reviewed, 74 of them had minimum 2 years follow-up were included in this study. The 74 patients with primary osteoporotic vertebral compression fractures treated by percutaneous kyphoplasty at the same time period were matched as control group in 1:1 ratio. Visual Analogue Scales (VAS) and Oswestry Disability Index (ODI) were used to assess the back pain and functional outcomes. The kyphotic angulation (KA) and compression ratio (CR) of the fractured vertebra was measured too. RESULTS: Both the secondary fracture group and control group had significantly relieved back pain, improved functional outcomes, corrected KA and restored CR after operation, but no difference was found between two groups. CONCLUSIONS: Our findings suggest that percutaneous kyphoplasty is an effective and safe procedure for patients with secondary single segmental osteoporotic vertebral compression fractures; it can achieve similar clinical outcomes to the primary osteoporotic vertebral compression fractures.
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BACKGROUND: The L5 nerve root could be compressed at both L4-5 and L5-S1 regions. If L5 nerve root has confirmed compression at L4-5 level and questionable compression at L5-S1 foramina, performing both surgeries at L4-5 and L5-S1 levels may induce unnecessary extra surgery on L5-S1; however, ignoring foraminal stenosis of L5/S1 may require re-exploration. METHODS: Two hundred seventeen patients with L5 nerve root compressed at L4-5 lateral access were performed with L4-5 decompression and interbody fusion. Lee et al. grade classification was used to assess the foraminal stenosis of L5-S1 preoperatively. Nerve root probe was designed and used to detect if there were foraminal stenosis at L5-S1 level that compressing the exiting L5 nerve root. Visual analog scale (VAS) of low back pain, leg pain and Oswestry Disability Index (ODI) were used to assess clinical outcomes. RESULTS: For all of 217 patients who underwent L4-5 surgery, L5-S1 foramina were preoperatively assessed as: grade 0: 125 cases, grade 1: 58 cases, grade 2: 23 cases, and grade 3: 11 cases. After intra-operative L5 nerve root detection, 11/11 patients with grade 3 radiographic foraminal stenosis, 6/23 (26.1%) with grade 2 and 2/58 (3.4%) who had grade 1 underwent L4-5 and L5-S1 transforaminal lumbar interbody fusion (TLIF), the others received only L4-5 TLIF. Compared to pre-operative baseline data, both L4-5 TLIF and L4-5 and L5-S1 TLIF groups had significant decreased VAS of low back pain and leg pain, and ODI at 3 and 24 months after operation. CONCLUSIONS: We suggested that our novel nerve root probe combined with pre-operative radiographic grade may be helpful to surgeons to identify the single or double compression of L5 nerve root and make a more precise surgical strategy to improve surgical outcome than the method depended on pre-operative radiographic grade alone.