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OBJECTIVE: The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MATERIALS AND METHODS: MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. RESULTS: Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. CONCLUSIONS: This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.
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Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Polpa Dentária/efeitos dos fármacos , Óxidos/farmacologia , Extratos Placentários/farmacologia , Silicatos/farmacologia , Fosfatase Alcalina/efeitos dos fármacos , Compostos de Alumínio/uso terapêutico , Animais , Calcificação Fisiológica/efeitos dos fármacos , Compostos de Cálcio/uso terapêutico , Capilares/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Polpa Dentária/irrigação sanguínea , Polpa Dentária/citologia , Dentina Secundária/efeitos dos fármacos , Combinação de Medicamentos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , MAP Quinase Quinase 4/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Odontoblastos/citologia , Odontoblastos/efeitos dos fármacos , Óxidos/uso terapêutico , Extratos Placentários/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Agentes de Capeamento da Polpa Dentária e Pulpectomia/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Silicatos/uso terapêutico , Serina-Treonina Quinases TOR/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacosRESUMO
BACKGROUND: Locomotion involves an integration of vision, proprioception, and vestibular information. The parieto-insular vestibular cortex is known to affect the supra-spinal rhythm generators, and the vestibular system regulates anti-gravity muscle tone of the lower leg in the same side to maintain an upright posture through the extra-pyramidal track. To demonstrate the relationship between locomotion and vestibular function, we evaluated the differences in gait patterns between vestibular neuritis (VN) patients and normal subjects using a gyroscope sensor and long-way walking protocol. METHODS: Gyroscope sensors were attached to both shanks of healthy controls (n=10) and age-matched VN patients (n = 10). We then asked the participants to walk 88.8 m along a corridor. Through the summation of gait cycle data, we measured gait frequency (Hz), normalized angular velocity (NAV) of each axis for legs, maximum and minimum NAV, up-slope and down-slope of NAV in swing phase, stride-swing-stance time (s), and stance to stride ratio (%). RESULTS: The most dominant walking frequency in the VN group was not different compared to normal control. The NAVs of z-axis (pitch motion) were significantly larger than the others (x-, y-axis) and the values in VN patients tended to decrease in both legs and the difference of NAV between both group was significant in the ipsi-lesion side in the VN group only (p=0.03). Additionally, the gait velocity of these individuals was decreased relatively to controls (1.11 ± 0.120 and 0.84 ± 0.061 m/s in control and VN group respectively, p<0.01), which seems to be related to the significantly increased stance and stride time of the ipsi-lesion side. Moreover, in the VN group, the maximum NAV of the lesion side was less, and the minimum one was higher than control group. Furthermore, the down-slope and up-slope of NAV decreased on the impaired side. CONCLUSION: The walking pattern of VN patients was highly phase-dependent, and NAV of pitch motion was significantly decreased in the ipsi-lesion side. The change of gait rhythm, stance and stride time, and maximum/minimum NAV of the ipsi-lesion side were characteristics of individuals with VN.
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Transtornos Neurológicos da Marcha/fisiopatologia , Marcha/fisiologia , Monitorização Fisiológica/métodos , Neuronite Vestibular/fisiopatologia , Adulto , Feminino , Lateralidade Funcional , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuronite Vestibular/complicações , Caminhada/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs. prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADS-P2A2RC, after percutaneous coronary intervention (PCI). METHODS: This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. RESULTS: Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358-6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868-3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). CONCLUSIONS: The CHADS-P2A2RC risk score is valuable in discriminating high-ischemic-risk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.
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OBJECTIVES: The purpose of this study was to find proper dentin substitute for standardized dentin barrier test and perform the cytotoxicity test of commercial bonding agents with the proper substitute. MATERIALS AND METHODS: The three-dimensional cells attached to dentin disc or millipore filters as the dentin substitute were tested in a dentin barrier test by perfusion. MTT assay was performed as an evaluation method for the cell survival rate. The cytotoxicity test of serial phenol dilution by bovine dentin disc was done to determine a standard toxic material, and the test of this proper phenol by using various millipore combinations was performed to find the suitable dentin substitute. Also, the cytotoxicity test of bonding agents was performed by this standardized substitute. The cell viability was expressed as percentages of untreated group. RESULTS: Phenol concentration of 0.05 % was selected as the standard toxic material. The different combinations of millipore filters--two sheets of 0.45 µm, two sheets of 0.22 µm, and the combination of 0.65, 0.45, and 0.22 µm--showed similar cytotoxicity to natural dentin discs by 0.05 % phenol (p > 0.05). The millipore combination of 0.65, 0.45, and 0.22 µm that had structural similarity to natural dentin discs was used as the substitute for cytotoxicity test of bonding agents. The toxic level of Adper Prompt L-Pop using the selected substitute was significantly the highest among four kinds of dentin bonding agents (p < 0.05). Also, the dentin barrier test by the substitute showed constant results compared with the one by the natural dentin disc. CONCLUSIONS: The millipore filter combination of 0.65, 0.45, and 0.22 µm could be used as the substitute for the cytotoxicity test of materials applied to dentin. CLINICAL RELEVANCE: Dentin barrier test by standardized substitutes would be helpful for considering the potential toxicity of dentin bonding agents prior to clinical adaptations and reducing the variations of natural bovine dentin that has individually different characteristics.
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Adesivos Dentinários/toxicidade , Dentina/efeitos dos fármacos , Filtros Microporos , Animais , Bovinos , Adesão Celular/fisiologia , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes , Permeabilidade da Dentina/efeitos dos fármacos , Cultura em Câmaras de Difusão , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Teste de Materiais/instrumentação , Teste de Materiais/métodos , Metacrilatos/toxicidade , Camundongos , Nylons/química , Perfusão , Fenol/toxicidade , Cimentos de Resina/toxicidade , Espectrofotometria , Propriedades de Superfície , Sais de Tetrazólio , Tiazóis , Alicerces Teciduais/químicaRESUMO
We sought to investigate the relation between worsening renal function (WRF) at 1-year follow-up and clinical outcomes at 3 years after acute myocardial infarction (AMI). We analyzed data from 13,104 patients enrolled in the national AMI registry from November 2011 to December 2015. Patients with all-cause death, recurrent myocardial infarction (re-MI), and rehospitalization for heart failure at 1-year follow-up after AMI were excluded. A total of 6,235 patients were extracted and divided into WRF and non-WRF groups. WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline to 1-year follow-up. The primary outcome was 3-year major adverse cardiac events, a composite of all-cause death, re-MI, and rehospitalization for heart failure. On average, a -1.5 ml/min/1.73 m2/y rate of decrease in eGFR was exhibited, and 575 patients (9.2%) exhibited WRF at 1-year follow-up. After multiple adjustments, WRF at 1-year follow-up was independently associated with increased risks of major adverse cardiac events (adjusted hazard ratio 1.498, 95% confidence interval 1.113 to 2.016, p = 0.01), all-cause death, and re-MI at 3-year follow-up. Older age, female, diabetes mellitus, hypertension, non-ST-segment elevation AMI, anterior AMI, anemia, left ventricular ejection fraction <35%, and baseline eGFR <30 ml/min/1.73 m2 were identified as independent predictors of WRF after AMI. In conclusion, WRF at 1-year follow-up after AMI intuitively seems like a risk marker indicating multiple co-morbidities. Monitoring serum creatinine in patients at 1-year follow-up after AMI may help to identify those who are at the highest risk and guide effective long-term therapeutics.
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Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Prognóstico , Volume Sistólico , Prevalência , Função Ventricular Esquerda , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Rim/fisiologiaRESUMO
AIM: To test the hypothesis that the impact of diabetes mellitus on clinical outcomes after acute myocardial infarction (AMI) can vary by age. METHODS: A total of 12,600 AMI patients from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and December 2015 was classified into young (n = 3,590 [29%]) and old (n = 9,010 [72%]). Those less than 55 years of age were considered young. We performed comparisons of baseline characteristics, in-hospital treatments, and 3-year clinical outcomes between patients with and without diabetes after stratification according to age group. RESULTS: The prevalence of diabetes mellitus was 27% in the young AMI group. In the multivariable adjusted model of the entire cohort, diabetes mellitus was associated strongly with 3-year all-cause mortality (13% vs. 6.8%; adjusted hazard ratio [HR], 1.318; 95% confidence interval [CI], 1.138-1.526; P<0.001). When the entire cohort was subdivided into two age groups, young diabetic patients showed a 107% higher mortality rate than those without diabetes (adjusted HR, 2.07 [1.15-3.72];P = 0.015). Meanwhile, old diabetic patients had a 25% higher risk of mortality than non-diabetic patients (adjusted HR, 1.25 [1.08-1.46];P = 0.004). The interaction of diabetes with age was significant (adjusted P for interaction = 0.008). CONCLUSIONS: Diabetes mellitus is not uncommon in younger AMI patients, and the relative risk of 3-year mortality is significantly higher in young patients than in older counterparts. More aggressive treatments are needed to prevent future cardiovascular events in younger patients after AMI.
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Diabetes Mellitus , Infarto do Miocárdio , Idoso , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de RiscoRESUMO
Gender difference studies in mortality after acute myocardial infarction (AMI) have shown inconsistent results. A total of 13,104 patients from the KAMIR-NIH between November 2011 and December 2015 were classified into young (n = 3837 [29.3%]) and elderly (n = 9267 [70.7%]) patients. For the study, women <65 and men <55 years of age were considered "young". In the adjusted model of the entire cohort, there was no significant difference in three-year all-cause mortality between women and men (17.8% vs. 10.3%; adjusted hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.799-1.137). However, when the entire cohort was subdivided into two age groups, young women showed an 84.3% higher mortality rate than young men (adjusted HR, 1.843; 95% CI, 1.098-3.095). Contrariwise, elderly women patients had a 20.4% lower hazard of mortality compared with elderly men (adjusted HR, 0.796; 95% CI, 0.682-0.929). The interaction of gender with age was significant, even after multiple adjustments (adjusted p for interaction = 0.003). The purpose of this study was to assess whether gender differences depend on the patients' age. Based on our analysis, higher mortality of young women remains even in the contemporary era of AMI. A better understanding of the mechanisms underlying these differences is warranted.
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OBJECTIVES: Subjective visual horizontal (SVH) and subjective visual vertical (SVV) used to assess otolith dysfunction and ipsilesional deviation of SVV and SVH in unilateral vestibular dysfunction is well known. The goal of this study was to investigate the clinical use of SVH/SVV and a dizziness scale in the clinical setting of acute unilateral vestibular neuritis. METHODS: Thirty-five patients with unilateral vestibular neuritis were investigated. Every patient was diagnosed by physical examination and electronystagmography. Subjective visual horizontal and SVV were assessed during the acute or subacute period; the Dizziness Handicap Inventory (DHI) and Vestibular Disorder Activities of Daily Living Scale (VADL) were used for a self-dizziness scale at the same time. All patients underwent rehabilitation therapy. Subjective visual horizontal/SVV and DHI/VADL were assessed again approximately 4 weeks later. Postrehabilitation SVH/SVV and DHI/VADL data were compared with initial data. RESULTS: Dizziness Handicap Inventory and VADL were improved after 4 weeks of rehabilitation, and the deviation toward ipsilesional side SVH and SVV was also improved. CONCLUSION: These results demonstrate that SVH and SVV correlated with clinical dizziness symptoms in patients with acute unilateral vestibular neuritis. Therefore, SVH and SVV would be useful tools for the evaluation of clinical manifestations of unilateral vestibular neuritis.
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Tontura/diagnóstico , Neuronite Vestibular/diagnóstico , Adulto , Tontura/fisiopatologia , Tontura/reabilitação , Feminino , Seguimentos , Lateralidade Funcional/fisiologia , Humanos , Masculino , Nistagmo Fisiológico/fisiologia , Membrana dos Otólitos/fisiopatologia , Estimulação Luminosa , Equilíbrio Postural/fisiologia , Neuronite Vestibular/fisiopatologia , Neuronite Vestibular/reabilitaçãoRESUMO
Dental light-cured resins can undergo different degrees of polymerization when applied in vivo. When polymerization is incomplete, toxic monomers may be released into the oral cavity. The present study assessed the cytotoxicity of different materials, using sample preparation methods that mirror clinical conditions. Composite and bonding resins were used and divided into four groups according to sample preparation method: uncured; directly cured samples, which were cured after being placed on solidified agar; post-cured samples were polymerized before being placed on agar; and "removed unreacted layer" samples had their oxygen-inhibition layer removed after polymerization. Cytotoxicity was evaluated using an agar diffusion test, MTT assay, and confocal microscopy. Uncured samples were the most cytotoxic, while removed unreacted layer samples were the least cytotoxic (p < 0.05). In the MTT assay, cell viability increased significantly in every group as the concentration of the extracts decreased (p < 0.05). Extracts from post-cured and removed unreacted layer samples of bonding resin were less toxic than post-cured and removed unreacted layer samples of composite resin. Removal of the oxygen-inhibition layer resulted in the lowest cytotoxicity. Clinicians should remove unreacted monomers on the resin surface immediately after restoring teeth with light-curing resin to improve the restoration biocompatibility.
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OBJECTIVE: The increasing use of primary gamma-knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) has led to a concomitant increase in the number of patients requiring salvage surgery for GKS failure. When patients underwent GKS as the primary treatment, it is known that dissecting tumor from adjacent nerves during salvage surgery is more difficult. In this report, we share our clinical experience with such patients and analyze the clinical findings of patients with tumor regrowth/recurrence. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary center. PATIENTS: Nine patients who underwent salvage surgery for VS regrowth/recurrence after GKS or microsurgery were enrolled. MAIN OUTCOME MEASURES: Symptom progression, radiological changes, intraoperative findings, and surgical outcomes were evaluated and compared. RESULTS: Six patients with previous GKS and three with previous microsurgery underwent salvage microsurgery. The most obvious symptom of tumor regrowth was aggravation of hearing loss. Salvage surgery in all patients was limited to subtotal or near-total resection via a translabyrinthine/transotic approach. Severe adhesion, thickening, and fibrosis were more prominent findings in the GKS than in the previous microsurgery group. Dissection of the tumor from the facial nerve was more difficult in the GKS than in the microsurgery patients. Despite anatomical preservation of the facial nerve in all the six patients, three in the GKS group, but none in the revision microsurgery group, had worsening of facial nerve function. CONCLUSION: Salvage microsurgery of VS after failed GKS is more difficult than revision microsurgery, and the facial nerve outcomes are relatively poor. Therefore, the primary method of VS treatment should be carefully chosen. Additional imaging studies are recommended in patients with a sudden change in hearing loss who underwent GKS.
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Perda Auditiva/cirurgia , Microcirurgia , Neuroma Acústico/cirurgia , Radiocirurgia , Adulto , Nervo Facial/cirurgia , Feminino , Perda Auditiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Estudos Retrospectivos , Terapia de Salvação , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the clinical significance of vibration-induced nystagmus (VIN) in unilateral vestibular asymmetry and vestibular schwannoma. METHODS: Thirteen patients with vestibular schwannoma underwent the VIN test, in which stimulation was applied to the mastoid processes and sternocleidomastoid (SCM) muscles on the ipsilateral and contralateral sides of lesions. Preoperative VIN was measured, and changes in VIN were followed up for 6months after tumor removal. Significance of VIN was determined by evaluation of its sensitivity, correlation with vestibular function tests and tumor volume, and postoperative changes. RESULTS: The overall pre and postoperative sensitivities of VIN were 92.3% and 100%, respectively, considering stimulation at all four sites. Maximum slow-phase velocity (MSPV) of VIN was linearly correlated with caloric weakness and tumor volume, especially when stimulation was applied to the SCM muscle. Postoperative MSPV of VIN exhibited stronger linear correlation with postoperative changes in canal paresis value and inverse correlation with tumor size upon stimulation of the ipsilateral SCM muscle than upon stimulation of other sites. During the 6-month follow-up period, persistence of VIN without changes in MSPV was observed even after vestibular compensation. CONCLUSIONS: Evoking VIN by stimulation of the mastoid processes and SCM muscles is effective for detecting vestibular asymmetry. It could also help determine the degree of vestibular asymmetry and volume of vestibular schwannoma if stimulation is applied to the SCM muscle. SIGNIFICANCE: The results of this study could provide clues for the basic application of VIN in patients with vestibular loss and vestibular schwannoma.
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Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/fisiopatologia , Nistagmo Patológico/diagnóstico por imagem , Nistagmo Patológico/fisiopatologia , Vibração/efeitos adversos , Adulto , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Processo Mastoide/fisiologia , Pessoa de Meia-Idade , Nistagmo Patológico/etiologia , Carga Tumoral/fisiologiaRESUMO
Familial paraganglioma (PGL) is a dominantly inherited disorder characterized by development of PGLs in the head and neck region. Germline mutations in genes coding for succinate dehydrogenase (SDH) subunits D, B, and C (SDHD, SDHB, SDHC) are found in almost all familial PGL patients. A 19-year-old female presented with pulsatile tinnitus and a reddish pulsating mass in the external auditory canal, and her mother complained of similar symptoms. Paraganglioma was found in both patients and was surgically removed. We report a case of germline SDHB mutation. This mutation was a deletion of thymine at nucleotide position 757 in exon 7 of the SDHB gene (c.757delT).
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Mutação em Linhagem Germinativa , Paraganglioma/genética , Succinato Desidrogenase/genética , Povo Asiático/genética , Neoplasias da Orelha/genética , Neoplasias da Orelha/cirurgia , Feminino , Heterozigoto , Humanos , Paraganglioma/cirurgia , Zumbido/genética , Zumbido/patologia , Membrana Timpânica/patologia , Adulto JovemRESUMO
Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone.
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Diferenciação Celular/efeitos dos fármacos , Campos Magnéticos , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Alicerces Teciduais/química , Animais , Feminino , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Integrinas/genética , Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Osteoblastos/citologia , Paxilina/genética , Paxilina/metabolismo , Poliésteres/química , Ribonuclease Pancreático/genética , Ribonuclease Pancreático/metabolismo , Transdução de Sinais , Engenharia Tecidual , Regulação para Cima , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTPRESUMO
Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and ß3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering.
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Polpa Dentária/efeitos dos fármacos , Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Odontogênese/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Dexametasona/farmacologia , Vidro , Humanos , Integrinas/metabolismo , Nanofibras/administração & dosagem , Nanopartículas/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Engenharia Tecidual/métodosRESUMO
OBJECTIVES: Central hemodynamics may better represent the load imposed on the coronary and cerebral arteries and thereby bear a stronger relationship to cardiovascular outcomes. METHODS: Patients who had confirmed hypertension as assessed by daytime 24-hour ambulatory blood pressure monitoring (≥135/85 mmHg) were enrolled. Central blood pressure and radial augmentation index (AIx) corrected for a heart rate of 75 bpm (radial AIx 75) were measured for all patients. We evaluated the association of age, height, and sex with central hemodynamics in patients with never-treated hypertension. RESULTS: A total of 203 patients were enrolled, of whom men numbered 101 (49.7%). The median height of all patients was 162 cm, and mean age was 53.2 years. In the Pearson correlation analysis, regardless of sex difference (R=-0.627 for height, R=0.035 for age, P-value =0.005), a stronger relationship was observed between height and radial AIx 75 than between age and radial AIx 75. In the multiple regression analysis, the sex difference and height were strongly associated with elevated radial AIx 75 in all patients (adjusted R (2)=0.428, ß=6.237, 95% confidence interval [CI] for women 1.480-10.995, P-value =0.011 and ß=-0.632, 95% CI for height -0.929 to -0.335, P-value =0.009, respectively). CONCLUSION: In patients with never-treated hypertension, female sex and shorter height are the important risk factors of elevated radial AIx 75.
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Estatura , Hipertensão/fisiopatologia , Caracteres Sexuais , Adulto , Idoso , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Feminino , Frequência Cardíaca , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , República da Coreia , Fatores de Risco , Rigidez VascularRESUMO
CONCLUSION: The three-point fix tympanoplasty procedure is a stable and effective technique - with a high degree of graft take and satisfactory hearing results - for reconstruction of most tympanic membrane (TM) perforations. OBJECTIVE: It is difficult to repair a TM perforation, including subtotal perforation, involving the anterior part of the annulus. Reperforation can occur when an underlay graft technique is used. An overlay graft technique may result in anterior blunting/lateralization. We introduce a three-point fix tympanoplasty procedure, which can provide additional support to yield a stable graft. METHODS: The study enrolled a total of 234 patients who underwent a three-point fix tympanoplasty procedure from November 2005 to June 2011. Anatomic success was defined as an intact, repaired TM, while functional success was defined as a significant decrease in the air-bone gap at the end of follow-up compared with preoperative hearing (air-bone gap). The complication rate was also analyzed. RESULTS: The anatomic success rate was 93.2% (218/234 patients). The functional success rate after an average of 1 year was 73.5%. The postoperative average pure-tone air-bone gap (15.4 ± 11.4 dB) decreased successfully in comparison with the preoperative average air-bone gap (20.6 ± 12.1 dB). There were few postoperative complications (7.7%).
Assuntos
Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Otoscopia , Retalhos Cirúrgicos/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Pathologic diagnosis of a cardiac mass is vital in determining the proper treatment modality. Open heart surgery or transesophageal echocardiography guided biopsy can be feasible methods to confirm the pathology. However, the former is highly invasive and both methods require general anesthesia. The introduction of intracardiac echocardiography (ICE) can provide good anatomic information of heart and does not require general anesthesia. In this report, we present two cases of cardiac tumors which were confirmed by percutaneous biopsy under the guidance of an ICE. The patients underwent cardiac biopsy without any complications.
RESUMO
OBJECTIVES/HYPOTHESIS: This study was undertaken to investigate the prevalence, inheritance patterns, and clinical characteristics of familial Meniere's disease (MD) in a South Korean population. STUDY DESIGN: Direct interviews, telephone interviews, and reviews of the medical records of definite Meniere's disease patients and their families. METHODS: Direct and telephone interviews were performed for 286 definite MD patients and their family members who were suspected of having MD. The diagnosis of MD in family members was made by obtaining a detailed history, performing basic neurotological examinations and reviewing hearing test results. The clinical characteristics as well as the prevalence and inheritance patterns of familial MD were analyzed. RESULTS: The prevalence of familial Meniere-like syndrome (at least one family member with definite MD and other members with probable MD) and definite familial MD (two or more family members with definite Meniere's disease) were 9.8% and 6.3%, respectively, and the most common inheritance pattern was autosomal dominant with incomplete penetrance. The significant clinical characteristics of familial cases were an early disease onset and a higher prevalence of migraines. CONCLUSIONS: This is the first report describing the genetic aspects of MD in a single large Asian population. The prevalence of definite familial MD was 6.3% with an incomplete autosomal dominant inheritance pattern in most cases. Early-onset age and a high prevalence of migraines were significant clinical features of familial MD in this South Korean population. These data could provide a basis for the analysis of the genetic mechanism of familial MD in Asian populations. LEVEL OF EVIDENCE: 4.
Assuntos
Família , Predisposição Genética para Doença , Doença de Meniere/genética , Adulto , Idade de Início , Feminino , Humanos , Masculino , Doença de Meniere/epidemiologia , Pessoa de Meia-Idade , Linhagem , Prevalência , República da Coreia/epidemiologia , Inquéritos e QuestionáriosRESUMO
Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, ß1 and ß3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering.