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1.
Pain Med ; 23(4): 807-814, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-34264315

RESUMO

BACKGROUND: Neurovascular compression (NVC) in patients with trigeminal neuralgia (TN) can be a factor of treatment outcome, especially in microvascular decompression and stereotactic radiosurgery. No such effect has been reported in percutaneous radiofrequency rhizotomy (RF). This study aims to investigate whether NVC affects the efficacy of RF in patients with TN. METHODS: We retrospectively reviewed patients with TN who received RF in our institution. Pretreatment magnetic resonance imaging was performed in every patient, and the presence of NVC was reviewed independently by two physicians. The patients were followed up at least for a year after the treatment. Pain severity was assessed with a numeric rating scale (NRS). RESULTS: Sixty-two patients were included in the study. All of the patients had single-sided lesions, and 35 patients had NVC. There were no significant differences between these two groups of patients in terms of gender distribution, age, and pretreatment pain severity. Comparable pain severity improvement was found at 1-year follow-up between these two groups (NRS 7.93 ± 0.492 without compression vs 7.57 ± 0.451 with compression, P = 0.600). No significant difference in posttreatment pain severity at 1 year was found between these two patient groups (NRS 1.37 ± 0.466 without compression vs 1.66 ± 0.458 with compression, P = 0.667). CONCLUSIONS: For patients with TN treated by RF, the presence or absence of NVC is not likely to affect the 1-year pain control rate.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Humanos , Imageamento por Ressonância Magnética , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Rizotomia , Resultado do Tratamento , Neuralgia do Trigêmeo/cirurgia
2.
Acta Neurochir (Wien) ; 164(6): 1575-1585, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35484311

RESUMO

BACKGROUND: Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors. METHODS: The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures. RESULTS: Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p < 0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern. CONCLUSIONS: This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.


Assuntos
Forame Oval , Neuralgia do Trigêmeo , Eletrocoagulação/métodos , Forame Oval/cirurgia , Humanos , Rizotomia/efeitos adversos , Resultado do Tratamento , Gânglio Trigeminal/diagnóstico por imagem , Gânglio Trigeminal/cirurgia , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/cirurgia
3.
BMC Musculoskelet Disord ; 22(1): 171, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573634

RESUMO

BACKGROUND: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. METHODS: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. RESULTS: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. CONCLUSION: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.


Assuntos
Fusão Vertebral , Titânio , Animais , Benzofenonas , Desenvolvimento Ósseo , Feminino , Cetonas , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Polietilenoglicóis , Polímeros , Porosidade , Suínos , Microtomografia por Raio-X
4.
Int J Mol Sci ; 22(16)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34445447

RESUMO

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured -34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 µg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Quitosana , Embucrilato , Células-Tronco Pluripotentes Induzidas/fisiologia , Nanopartículas/química , Transfecção/métodos , Animais , Diferenciação Celular , Camundongos , Neurônios , Plasmídeos
5.
Neurobiol Dis ; 145: 105071, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890774

RESUMO

Spreading depolarization (SD) represents a neurological process characterized by a massive, self-sustaining wave of brain cell depolarization. Understanding its mechanism is important for treating ischemic or hemorrhagic stroke and migraine with aura. Many believed that ion fluxes through NMDA receptors (NMDARs) are responsible for neuronal transmembrane currents of SD. However, the explicit role of NMDARs remains ambiguous. This is in part due to the limitation of traditional pharmacological approaches in resolving the contribution of NMDARs in different intercellular and intracellular processes of SD. Here, we applied single-cell blockade and genetic deletion methods to remove functional NMDARs from individual hippocampal CA1 neurons in order to examine the role of NMDARs in the depolarization mechanism without affecting the propagation of SD. We analyzed neuronal membrane potential changes to demonstrate that NMDARs are not required for initiating the depolarization. Consistently, neuronal input resistance (RN) revealed a sharp decline at the start of SD, which was unaffected by blocking NMDARs. Instead, the recovery of both membrane potential and RN during the late phase of SD was facilitated by inhibition of NMDARs, indicating that NMDARs are responsible for sustaining the depolarization. Our results strongly indicate that NMDAR activation is not a determinant of the initiation of depolarization but is important for sustaining transmembrane ion fluxes during SD.


Assuntos
Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Região CA1 Hipocampal/metabolismo , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos ICR
6.
BMC Cancer ; 19(1): 756, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370819

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is the most severe type of primary brain tumor with a high mortality rate. Although extensive treatments for GBM, including resection, irradiation, chemotherapy and immunotherapy, have been tried, the prognosis is still poor. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug for the clinical treatment of GBM; however, its effects are very limited because of the chemoresistance. Valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitor activity, has been shown to have synergistic effects with TMZ against GBM. The mechanism of action of VPA on TMZ combination therapy is still unclear. Accumulating evidence has shown that secreted proteins are responsible for the cross talking among cells in the tumor microenvironment, which may play a critical role in the regulation of drug responses. METHODS: To understand the effect of VPA on secreted proteins in GBM cells, we first used the antibody array to analyze the cell culture supernatant from VPA-treated and untreated GBM cells. The results were further confirmed by lentivirus-mediated knockdown and exogenous recombinant administration. RESULTS: Our results showed that amphiregulin (AR) was highly secreted in VPA-treated cells. Knockdown of AR can sensitize GBM cells to TMZ. Furthermore, pretreatment of exogenous recombinant AR significantly increased EGFR activation and conferred resistance to TMZ. To further verify the effect of AR on TMZ resistance, cells pre-treated with AR neutralizing antibody markedly increased sensitivity to TMZ. In addition, we also observed that the expression of AR was positively correlated with the resistance of TMZ in different GBM cell lines. CONCLUSIONS: The present study aimed to identify the secreted proteins that contribute to the modulation of drug response. Understanding the full set of secreted proteins present in glial cells might help reveal potential therapeutic opportunities. The results indicated that AR may potentially serve as biomarker and therapeutic approach for chemotherapy regimens in GBM.


Assuntos
Anfirregulina/metabolismo , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Temozolomida/farmacologia , Ácido Valproico/farmacologia , Anfirregulina/genética , Anticorpos Bloqueadores/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Técnicas de Silenciamento de Genes , Humanos , Lentivirus/genética
7.
Acta Neurochir (Wien) ; 161(7): 1427-1434, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31098700

RESUMO

BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief. METHOD: This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging. RESULT: The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness. CONCLUSION: This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief.


Assuntos
Cateterismo/métodos , Forame Oval/cirurgia , Hipestesia/etiologia , Complicações Pós-Operatórias/etiologia , Rizotomia/métodos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Cateterismo/efeitos adversos , Feminino , Humanos , Hipestesia/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Rizotomia/efeitos adversos , Tomografia Computadorizada por Raios X
8.
Int J Mol Sci ; 20(1)2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30621332

RESUMO

The brain-derived neurotrophic factor (BDNF) is vital in the neural differentiation of neural stem/progenitor cells, and together may have therapeutic potential for neural regeneration. In this study, a multiplexed polybutylcyanoacrylate nanoparticle (PBCA NP) delivery platform was constructed, incorporating either surface-adsorbed or encapsulated BDNF for the induction of neural differentiation in induced pleuripotent stem cells (iPSCs), where tween 80 (T80) and superparamagnetic iron oxide (SPIO) were added for central nervous system (CNS) targeting and magnetic resonance (MR) image tracking, respectively. Both methods by which the BDNF was carried resulted in loading efficiencies greater than 95%. The nanoparticle-mediated delivery of BDNF resulted in neural differentiation of iPSCs detected on immunofluorescence staining as early as 7 days, with enhanced differentiation efficiency by 1.3-fold compared to the control on flow cytometry; the delivery system of surface-adsorbed BDNF gave rise to cells that had the best neural development than the encapsulated formulation. T80-coating disrupted the in vitro blood⁻brain barrier model with a corresponding 1.5- to two-fold increase in permeability. SPIO-loaded PBCA NPs exhibited a concentration-dependent, rapid decay in signal intensity on the phantom MR experiment. This study demonstrates the versatility of the PBCA NP, and the surface-adsorption of BDNF is the preferred method of delivery for the differentiation of iPSCs.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Embucrilato/farmacologia , Células-Tronco Pluripotentes Induzidas/citologia , Nanopartículas/química , Neurônios/citologia , Adsorção , Animais , Barreira Hematoencefálica/metabolismo , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Impedância Elétrica , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Imageamento por Ressonância Magnética , Camundongos , Modelos Biológicos , Nanopartículas/ultraestrutura , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Tamanho da Partícula , Imagens de Fantasmas , Ratos , Eletricidade Estática , Propriedades de Superfície
9.
Acta Neurochir (Wien) ; 160(6): 1283-1289, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29696504

RESUMO

BACKGROUND: The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. METHODS: We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. RESULTS: Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. CONCLUSIONS: PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.


Assuntos
Anestesia por Condução/métodos , Dor nas Costas/cirurgia , Fraturas por Compressão/cirurgia , Gânglios Espinais/cirurgia , Neuronavegação/métodos , Fraturas da Coluna Vertebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Anestesia por Condução/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuronavegação/efeitos adversos , Complicações Pós-Operatórias/epidemiologia
10.
Int J Mol Sci ; 19(9)2018 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-30200660

RESUMO

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Melanoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
11.
Int J Mol Sci ; 18(3)2017 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-28335495

RESUMO

Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of -14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Diferenciação Celular , Embucrilato/química , Células-Tronco Pluripotentes Induzidas/citologia , Nanopartículas/química , Neurônios/citologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipóxia Celular , Linhagem Celular , Embucrilato/efeitos adversos , Vetores Genéticos/administração & dosagem , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Polissorbatos/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA/administração & dosagem , Elementos de Resposta
12.
Int J Mol Sci ; 18(7)2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28703746

RESUMO

Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay. Cellular ROS production was measured using the CellROX assay, while mitochondrial ROS production was evaluated using the MitoSOX assay. It was observed that cudraflavone C inhibited growth in A375.S2 melanoma cells, and promoted apoptosis via the mitochondrial pathway mediated by increased mitochondrial ROS production. In addition, cudraflavone C induced phosphorylation of MAPKs (p38, ERK, and JNK) and up-regulated the expression of apoptotic proteins (Puma, Bax, Bad, Bid, Apaf-1, cytochrome C, caspase-9, and caspase-3/7) in A375.S2 cells. Pretreatment of A375.S2 cells with MitoTEMPOL (a mitochondria-targeted antioxidant) attenuated the phosphorylation of MAPKs, expression of apoptotic proteins, and the overall progression of apoptosis. In summary, cudraflavone C induced apoptosis in A375.S2 melanoma cells by increasing mitochondrial ROS production; thus, activating p38, ERK, and JNK; and increasing the expression of apoptotic proteins. Therefore, cudraflavone C may be regarded as a potential form of treatment for malignant melanoma.


Assuntos
Apoptose/efeitos dos fármacos , Flavonas/farmacologia , Melanoma/enzimologia , Melanoma/patologia , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Flavonas/química , Humanos , Melanoma/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fosforilação/efeitos dos fármacos
13.
J Stroke Cerebrovasc Dis ; 26(9): 1885-1891, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28739345

RESUMO

BACKGROUND: Early neurological deterioration after ischemic stroke (stroke-in-evolution [SIE]) is associated with poorer outcomes. Previous studies have demonstrated a link between hydration status and the development of SIE. In this study, we tested the hypothesis that rehydration therapy, administered on the basis of urine-specific gravity (USG) findings, might reduce the development of SIE. METHODS: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the study group, a USG higher than 1.010 was taken as an indication for rehydration. Control group patients were rehydrated without referring to USG. An increase in National Institutes of Health Stroke Scale (NIHSS) score of 4 or higher within 3 days was defined as having SIE. RESULTS: A total of 445 patients were analyzed, 167 in the study group and 278 in the control group. The proportion of patients who developed SIE was numerically, but not significantly, lower in the study group (5.9%; 10 of 167) compared with the control group (11.5%; 32 of 278). Among patients with a USG higher than 1.010 at admission, the SIE rate was significantly reduced in the study group compared with the control group (6.1% versus 16.0%; P = .021), while the rate of SIE was similar in those with a USG of 1.010 or lower at admission. Multivariate logistic regression analysis confirmed that USG-based hydration was an independent factor associated with reducing SIE. CONCLUSIONS: USG might be a convenient and useful method for guiding fluid therapy in patients with acute ischemic stroke. USG-based hydration reduced the incidence of SIE among patients with a USG higher than 1.010 at admission.


Assuntos
Isquemia Encefálica/terapia , Desidratação/terapia , Hidratação/métodos , Acidente Vascular Cerebral/terapia , Equilíbrio Hidroeletrolítico , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/urina , Estudos de Casos e Controles , Desidratação/diagnóstico , Desidratação/fisiopatologia , Desidratação/urina , Progressão da Doença , Feminino , Estudo Historicamente Controlado , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Gravidade Específica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/urina , Fatores de Tempo , Resultado do Tratamento , Urinálise , Urina/química
14.
Am J Emerg Med ; 34(12): 2414-2418, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27717719

RESUMO

BACKGROUND: Dehydration is associated with acute ischemic stroke. However, the relationship between hydration therapy given during acute ischemic stroke and clinical outcomes remains unclear. AIMS: We determined whether hydration therapy in patients with a blood urea nitrogen/creatinine (BUN/Cr) ratio of at least 15 improved clinical outcome. METHODS: We conducted a nonblinded, phase II, single-arm, prospective study of patients with acute ischemic stroke and BUN/Cr ratio of at least 15 with historical controls. The hydration group received intravenous bolus (300-500 mL) saline followed by maintenance saline infusion (40-80 mL/h for the first 72 hours), whereas the control group received maintenance saline infusion (40-60 mL/h for the first 24 hours and 0-60 mL/h for 24-72 hours after stroke). The study end point was the percentage of patients with a favorable outcome defined as modified Rankin scale score of 2 or lower at 3 months after stroke. RESULTS: A total of 237 patients were enrolled (hydration, n = 134; control, n = 103). The mean volume of saline infused within the first 72 hours was significantly larger (P < .001), and the rate of favorable outcome at 3 months after stroke was significantly higher (P = .016) in the hydration group than in the controls. Further analysis revealed that the difference was significant in the lacunar stroke subtype (P = .020) but not in the nonlacunar subtype. CONCLUSIONS: Blood urea nitrogen/Cr ratio-based saline hydration therapy in patients with acute ischemic stroke significantly increased the rate of favorable clinical outcome with functional independence at 3 months after stroke.


Assuntos
Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Desidratação/tratamento farmacológico , Soluções para Reidratação/administração & dosagem , Cloreto de Sódio/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taiwan , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
15.
J Neurosci Res ; 93(1): 178-88, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25042403

RESUMO

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Hemorragia Cerebral/complicações , Dexametasona/uso terapêutico , Encefalite , Neurônios/efeitos dos fármacos , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Complexo CD3/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Dexametasona/farmacologia , Modelos Animais de Doenças , Encefalite/tratamento farmacológico , Encefalite/etiologia , Encefalite/patologia , Masculino , Proteínas de Neurofilamentos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
16.
J Biopharm Stat ; 25(5): 1005-19, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24918528

RESUMO

Threshold-dependent accuracy measures such as true classification rates in ordered multiple-class (k > 3) receiver operating characteristic (ROC) hyper-surfaces have recently been used to assist with medical decision making. However, based on low power performance in some circumstances, we construct a new method that relies on the kappa coefficient to solve such diagnostic problems. Under the approach proposed in the present article, the statistics depend strongly on the [Formula: see text] cutoff threshold, which can be chosen to maximize the kappa statistics of true disease status and of the new biomarker. The Monte Carlo simulation results confirm the effectiveness of the proposed method in terms of its predictive power. The proposed design is then compared with the volume under the ROC hyper-surface by applying it to intracerebral hemorrhagic patients classified into five stroke classes using the National Institutes of Health Stroke Scale.


Assuntos
Biomarcadores/análise , Pesquisa Biomédica/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Área Sob a Curva , Simulação por Computador , Interpretação Estatística de Dados , Humanos , Método de Monte Carlo , Análise Numérica Assistida por Computador , Variações Dependentes do Observador , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Tamanho da Amostra
17.
Acta Neurochir (Wien) ; 157(8): 1443-8; discussion 1448, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26066533

RESUMO

BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) has been an effective treatment modality for medically refractory trigeminal neuralgia. Our group has established a protocol for this procedure that includes intraoperative computed tomography (iCT) navigation. The depth of the puncture needle in our protocol was based on cadaveric studies, and anatomical localization was mainly by electric stimulation test. The limitation of the invisibility of the trigeminal cistern on CT imaging and bias from the patient's subjective expression during neurophysiologic stimulation might affect the accuracy of the needle tip and the treatment effect.This study aimed to evaluate the feasibility and preliminary results of the application of magnetic resonance imaging (MRI) and iCT fusion imaging in RF-TR. METHOD: The study included 13 patients who received RF-TR with iCT navigation and with recurrence within 3 years. Repeated RF-TR was performed with real-time guidance by MRI and iCT fusion imaging. RESULTS: A pain-free or partial satisfactory response was reported with 12 patients (92 %). There was a statistically significant difference in the depth of the needle tip before and after application of MRI and iCT fusion imaging. CONCLUSIONS: This preliminary study demonstrated that the application of MRI and iCT fusion could help with anatomical localization of the trigeminal cistern intraoperatively. The improvement in neuronavigation provides a choice in the treatment of recurrent or persistent trigeminal neuralgia after previous intervention. Long-term follow-up of the result is necessary to evaluate the benefit in terms of durability of therapeutic efficacy.


Assuntos
Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Neuronavegação/métodos , Radiocirurgia/métodos , Rizotomia/métodos , Tomografia Computadorizada por Raios X/métodos , Nervo Trigêmeo/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Formos Med Assoc ; 114(7): 577-82, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24113352

RESUMO

BACKGROUND/PURPOSE: In patients with traumatic brain injury, the degree of brain midline shift is related to prognosis. In this study, we evaluated the impact of the presence of a preoperative brain midline shift on the Glasgow Coma Scale (GCS) scores and muscle power (MP) improvement after cranioplasty. METHODS: In this 6-year retrospective cohort study, we compared cranioplasty patients from Taiwan with and without a preoperative brain midline shift. We assigned the patients to the following two groups: the midline shift group and the nonmidline shift group. The GCS score and MP contralateral to the lesion site were recorded and analyzed both prior to and 1 year after the operation. RESULTS: We enrolled 56 cranioplasty patients (35 patients with a midline shift and 21 without a midline shift) and analyzed their complete clinical characteristics. There were significant improvements in the GCS (p = 0.0078), arm MP (p = 0.0056), and leg MP (p = 0.0006) scores after cranioplasty. There was also a significant improvement in the GCS score in the brain midline shift group (0.4 ± 0.149 in the brain midline shift group vs. 0.05 ± 0.48 in the nonmidline shift group, p = 0.03). CONCLUSION: For patients who underwent craniectomy, an improvement in neurological function 1 year after cranioplasty was observed. The patients with brain midline shift showed more improvement in consciousness after cranioplasty than those without a brain midline shift. The presence of a preoperative brain midline shift may be an isolated determinant for the prediction of the outcome after cranioplasty.


Assuntos
Lesões Encefálicas/cirurgia , Encéfalo/diagnóstico por imagem , Crânio/cirurgia , Adulto , Encéfalo/patologia , Feminino , Escala de Coma de Glasgow , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Prognóstico , Estudos Retrospectivos , Taiwan , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
19.
Br J Neurosurg ; 28(6): 796-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25046145

RESUMO

A 23-year-old male presented with a parasellar lesion which was suspected as disseminated intracranial germ cell tumour. The diagnosis of germinoma was made using immunohistochemistry from percutaneous trans-foramen ovale biopsy. This report describes the role of neuronavigation-guided biopsy through the foramen ovale for lesions in the parasellar region.


Assuntos
Neoplasias Encefálicas/diagnóstico , Forame Oval/cirurgia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neuronavegação/métodos , Adulto , Biópsia , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Radiografia , Sela Túrcica/patologia , Adulto Jovem
20.
J Fungi (Basel) ; 10(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38248971

RESUMO

Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total of 53 patients from a multi-centered database in Taiwan were included in this study. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to one-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic (ROC) curve was used to express the performance of our IFSD scoring model. Results: Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or <0.4 103/µL, hemoglobin < 8 g/dL, and evidence of candidemia. One-year mortality rates for patients with IFSD scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the ROC curve was 0.823. Conclusions: We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of one-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

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