Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 104
Filtrar
1.
Virology ; 577: 99-104, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335770

RESUMO

Capsids of the cowpea chlorotic mottle virus (CCMV) are great candidates for the development into in vivo catalytic or therapeutic nanocarriers. However, due to their limited intrinsic stability at physiological pH, thus far no methods exist for incorporating cargo into these nanoparticles in cellulo. Here, we employ a stabilized VW1-VW8 ELP-CCMV variant for the development of a co-expression-based cargo-loading approach. Co-expression of the non-functionalized VW1-VW8 ELP-CCMV coat protein with fusion proteins with enhanced green fluorescent protein (mEGFP) and pyrrolysine synthase D (PylD) in E. coli enabled the purification of cargo-loaded capsids from the bacteria directly either via affinity chromatography or PEG-precipitation and subsequent size exclusion chromatography. Microscopy results indicated that the co-expression does not harm the E. coli cells and that proper folding of the mEGFP domain is not hampered by the co-assembly. Our co-expression strategy is thus a suitable approach to produce cargo-loaded CCMV nanoparticles.

2.
Osteoarthritis Cartilage ; 29(5): 728-738, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33609695

RESUMO

OBJECTIVE: While the prevalence of radiographic and symptomatic osteoarthritis (OA) is higher in women, male mice are more frequently used in animal experiments to explore its pathogenesis or drug efficacy. In this study, we examined whether sexual dimorphism affects pain and joint degeneration in destabilization of the medial meniscus (DMM) mouse model. METHODS: DMM or sham surgery was performed on the knee of male and female C57BL/6 mice. Joint damage was assessed by safranin O staining and scored using the Osteoarthritis Research Society International (OARSI) scoring system. Von Frey hair, incapacitance, and rotarod tests were conducted to measure joint pain. The analgesic effect of capsazepine (CPZ), a TRPV1 antagonist, was compared between male and female mice. RESULTS: Histology and OARSI scoring analysis showed that cartilage degeneration developed, and progressed in both male and female DMM groups, however, damage was less severe in females at the late stage of OA. Pain behavior, as measured by mechanical allodynia, was displayed for longer in male DMM mice compared to females. Incapacitance data showed that CPZ significantly reduced DMM-induced pain in male mice but not in female mice. Immunofluorescence microscopy analysis demonstrated that DMM surgery increased the expression of TRPV1 in both female and male dorsal root ganglion (DRG). Injection of CPZ significantly suppressed TRPV1 expression in the DRG of male mice only. CONCLUSION: Joint damage develops comparably in both female and male mice after DMM although it progresses less in females. There was a subtle sex difference in pain behaviors and analgesic efficacy of a TRPV1 antagonist, which was accompanied by a differential regulation of TPRV1.


Assuntos
Comportamento Animal , Cartilagem Articular/patologia , Osteoartrite/patologia , Dor/etiologia , Fatores Sexuais , Animais , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Modelos Animais de Doenças , Feminino , Gânglios Espinais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Osteoartrite/tratamento farmacológico , Fármacos do Sistema Sensorial/farmacologia , Joelho de Quadrúpedes/patologia , Canais de Cátion TRPV/metabolismo
3.
Allergy ; 73(2): 361-368, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28857181

RESUMO

BACKGROUND: In mast cells, induction of HSP70 expression during antigen stimulation has not been reported. METHODS: Mouse bone marrow-derived mast cells (BMMC) were stimulated with IgE/Ag or HSP70. Induction of HSP70 expression and signaling protein phosphorylation were evaluated by immunoblotting. RESULTS: HSP70 expression is induced in BMMC at an early stage of IgE/Ag-dependent stimulation, some of which is released from the cells in a granule-associated form. Induction of HSP70 expression was also observed with an IgE/Ag-stimulated human basophilic cell line, indicating that the phenomenon is not restricted to mouse BMMC. The induction of HSP70 expression, and its release, followed a similar time course to that of degranulation. Released HSP70 seems to be responsible for degranulation and production of eicosanoids, at least in part, because a neutralizing anti-HSP70 antibody mitigated these activities and because exogenous HSP70 not only induced immediate degranulation followed by autocrine HSP70 expression but also enhanced degranulation in IgE/Ag-stimulated BMMC. Extracellular HSP70 was found to induce phosphorylation of linker for activation of T cells (LAT) and a series of downstream signaling molecules in BMMC. We further found that Fyn, Lyn, and spleen tyrosine kinase (Syk), which are known to concern LAT phosphorylation in IgE/Ag-stimulated BMMC, were not phosphorylated in HSP70-stimulated BMMC, whereas lymphocyte-specific protein tyrosine kinase (Lck) was phosphorylated. CONCLUSION: FcεRI stimulation in BMMC and basophils induces HSP70 expression and its release. Extracellular HSP70 induces degranulation and mediator release via phosphorylation of LAT.


Assuntos
Degranulação Celular/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Imunoglobulina E/metabolismo , Mastócitos/fisiologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/fisiologia , Degranulação Celular/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Immunoblotting , Imunoglobulina E/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Prata
4.
J Dent Res ; 96(1): 100-106, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27694153

RESUMO

It is not known to what extent residual infection may interfere with the success of pulp regeneration procedures. The aim of this study was to determine, radiographically and histologically, the effect of residual bacteria on the outcome of pulp regeneration mediated by a tissue-engineered construct as compared with traditional revascularization. Periapical lesions were induced in 24 canine teeth of 6 ferrets. After disinfection with 1.25% NaOCl and triple antibiotic paste, ferret dental pulp stem cells, encapsulated in a hydrogel scaffold, were injected into half the experimental teeth. The other half were treated with the traditional revascularization protocol with a blood clot scaffold. After 3 mo, block sections of the canine teeth were imaged radiographically and processed for histologic and histobacteriologic analyses. Associations between variables of interest were evaluated through mixed effects regression models. There were no significant differences between the 2 experimental groups in radiographic root development ( P > 0.05). There was a significant association between the presence of persistent periapical radiolucency and root wall thickness ( P = 0.02). There was also no significant difference in histologic findings between the 2 experimental groups ( P > 0.05). The presence of residual bacteria was significantly associated with lack of radiographic growth ( P < 0.001). The amount of dentin-associated mineralized tissue formed in teeth with residual bacteria was significantly less than in teeth with no residual bacteria ( P < 0.001). Residual bacteria have a critical negative effect on the outcome of regenerative endodontic procedures.


Assuntos
Regeneração Óssea/fisiologia , Polpa Dentária/crescimento & desenvolvimento , Animais , Bactérias , Polpa Dentária/diagnóstico por imagem , Polpa Dentária/microbiologia , Cavidade Pulpar/diagnóstico por imagem , Cavidade Pulpar/crescimento & desenvolvimento , Cavidade Pulpar/microbiologia , Furões , Masculino , Radiografia Dentária , Tratamento do Canal Radicular/métodos , Transplante de Células-Tronco/métodos , Tecidos Suporte/microbiologia , Resultado do Tratamento
5.
Int J Obes (Lond) ; 40(2): 338-45, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26268884

RESUMO

BACKGROUND: It is well known that high-fat diet (HFD) can cause immune system-related pathological alterations after a significant body weight gain. The mechanisms of the delayed pathological alterations during the development of diet-induced obesity (DIO) are not fully understood. METHODS: To elucidate the mechanisms underlying DIO development, we analyzed time-course microarray data obtained from a previous study. First, differentially expressed genes (DEGs) were identified at each time point by comparing the hepatic transcriptome of mice fed HFD with that of mice fed normal diet. Next, we clustered the union of DEGs and identified annotations related to each cluster. Finally, we constructed an 'integrated obesity-associated gene regulatory network (GRN) in murine liver'. We analyzed the epididymal white adipose tissue (eWAT) transcriptome usig the same procedure. RESULTS: Based on time-course microarray data, we found that the genes associated with immune responses were upregulated with an oscillating expression pattern between weeks 2 and 8, relatively downregulated between weeks 12 and 16, and eventually upregulated after week 20 in the liver of the mice fed HFD. The genes associated with immune responses were also upregulated at late stage, in the eWAT of the mice fed HFD. These results suggested that a critical transition occurred in the immune system-related transcriptomes of the liver and eWAT around week 16 of the DIO development, and this may be associated with the delayed pathological alterations. The GRN analysis suggested that Maff may be a key transcription factor for the immune system-related critical transition thatoccurred at week 16. We found that transcription factors associated with immune responses were centrally located in the integrated obesity-associated GRN in the liver. CONCLUSIONS: In this study, systems analysis identified regulatory network modules underlying the delayed immune system-related pathological changes during the development of DIO and could suggest possible therapeutic targets.


Assuntos
Imunidade Adaptativa/genética , Tecido Adiposo Branco/patologia , Fígado/patologia , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Resistência à Insulina , Metabolismo dos Lipídeos/imunologia , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologia , Transcriptoma , Regulação para Cima
6.
Eur Cell Mater ; 29: 281-9, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25978116

RESUMO

Many attempts have been made to reduce complications of bone implant, such as pedicle screw loosening. To address this problem, the authors suggest a new concept of bone-to-bone biologic fixation using recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded cannulated pedicle screws. Recombinant human bone morphogenetic protein-2 is an osteoinductive cytokine. Four types of titanium pedicle screws were tested (uncannulated, cannulated with no loading, beta-tricalcium phosphate (TCP)-loaded, and TCP/BMP2 loaded) using 16 miniature pigs. Radiological evaluation was conducted to assess the fusion and loosening of pedicle screws. Twelve weeks after implantation, peak torsional extraction torque was measured, and the pedicle screw and bone interface was evaluated by micro-computed tomography (µCT) and histologic examination. The mean value of the radiological score was significantly greater in the TCP/BMP2 loaded group at 12 weeks post-operation compared to those in the other groups. CT images showed distinct bone formation surrounding TCP/BMP2 loaded cannulated pedicle screws compared to the other groups. Mean extraction torsional peak torque at 12 weeks postoperative was more than 10-fold higher in the TCP/BMP2 loaded pedicle screw group than in the other groups. Bone surface and bone volume, as quantitated through µCT, were higher in the TCP/BMP2 loaded group. Histologic examination revealed bone-to-bone fixation at the interface of pedicle screws and pre-existing bone. Bone-to-bone biologic fixation through the holes of TCP/BMP2 loaded pedicle screws significantly increased fixation strength and represents a novel method that can be applied to osteoporotic or tumour spine surgeries.


Assuntos
Osso e Ossos/cirurgia , Procedimentos Ortopédicos/instrumentação , Parafusos Pediculares , Titânio , Animais , Proteína Morfogenética Óssea 2/farmacologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Fosfatos de Cálcio/farmacologia , Feminino , Humanos , Procedimentos Ortopédicos/métodos , Osseointegração/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Suínos , Porco Miniatura , Fatores de Tempo , Torque , Fator de Crescimento Transformador beta/farmacologia , Microtomografia por Raio-X
7.
Eye (Lond) ; 28(7): 825-31, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24788012

RESUMO

PURPOSE: To evaluate the effect of image compression of spectral-domain optical coherence tomography (OCT) images in the examination of eyes with exudative age-related macular degeneration (AMD). METHODS: Thirty eyes from 30 patients who were diagnosed with exudative AMD were included in this retrospective observational case series. The horizontal OCT scans centered at the center of the fovea were conducted using spectral-domain OCT. The images were exported to Tag Image File Format (TIFF) and 100, 75, 50, 25 and 10% quality of Joint Photographic Experts Group (JPEG) format. OCT images were taken before and after intravitreal ranibizumab injections, and after relapse. The prevalence of subretinal and intraretinal fluids was determined. Differences in choroidal thickness between the TIFF and JPEG images were compared with the intra-observer variability. RESULTS: The prevalence of subretinal and intraretinal fluids was comparable regardless of the degree of compression. However, the chorio-scleral interface was not clearly identified in many images with a high degree of compression. In images with 25 and 10% quality of JPEG, the difference in choroidal thickness between the TIFF images and the respective JPEG images was significantly greater than the intra-observer variability of the TIFF images (P=0.029 and P=0.024, respectively). CONCLUSIONS: In OCT images of eyes with AMD, 50% of the quality of the JPEG format would be an optimal degree of compression for efficient data storage and transfer without sacrificing image quality.


Assuntos
Compressão de Dados , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Ranibizumab , Estudos Retrospectivos , Líquido Sub-Retiniano , Degeneração Macular Exsudativa/tratamento farmacológico
8.
Drug Res (Stuttg) ; 64(12): 651-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24549963

RESUMO

Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 µg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 µg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · µg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated.


Assuntos
Benzamidas/administração & dosagem , Benzamidas/farmacocinética , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Adulto , Área Sob a Curva , Química Farmacêutica/métodos , Estudos Cross-Over , Humanos , Mesilato de Imatinib , Masculino , República da Coreia , Comprimidos/administração & dosagem , Comprimidos/farmacocinética , Equivalência Terapêutica , Voluntários
9.
J Clin Pharm Ther ; 39(2): 192-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24325365

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A antagonist that inhibits platelet aggregation and vasoconstriction. The aim of this study was to compare the pharmacokinetics of a sarpogrelate controlled-release formulation (CR) with those of the immediate-release formulation (IR). The effect of food on the pharmacokinetics of CR sarpogrelate was also evaluated. METHODS: A randomized, open-label, 3-period, 3-treatment crossover study was conducted in 50 healthy male subjects. Subjects were allocated into one of six sequence groups. In one period, a 100-mg IR formulation was administered three times at 6-h intervals, and in the other two periods, a 300-mg CR formulation was administered once to fasting and once to fed subjects. Each period was separated by a 7-day washout period. Serial blood samples were collected up to 24 h after the first drug administration in each period. The plasma concentrations of sarpogrelate were analysed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental methods. RESULTS AND DISCUSSION: After the administration of the IR formulation, the plasma concentration reached a peak at 0·48 h and the drug was eliminated with a half-life (t1/2 ) of 0·7 h. After administration of the CR formulation, the plasma concentration reached a peak at 0·5 h and the drug was eliminated with a t1/2 of 3·23 h. The geometric mean ratios (CR/IR) for sarpogrelate area under the plasma concentration-time curve (AUC) and the maximum plasma drug concentration (Cmax) were 1·2040 (90% confidence interval (CI): 1·0992-1·3188) and 0·9462 (90% CI: 0·8504-1·0529). When CR was administered to fed subjects, the time to peak concentration was prolonged to 3·97 h and t1/2 was shortened to 1·45 h. The geometric mean ratios (fasting/fed) for sarpogrelate AUC and Cmax were 0·8573 (90% CI: 0·7687-0·9561) and 0·6452 (90% CI: 0·5671-0·7341). WHAT IS NEW AND CONCLUSION: After the administration of CR and IR formulations of the same daily dose of sarpogrelate hydrochloride, the overall systemic exposure was slightly higher for the CR than for the IR formulation, whereas peak concentration was comparable between the two formulations. Food reduced the bioavailability of sarpogrelate CR.


Assuntos
Interações Alimento-Droga , Inibidores da Agregação Plaquetária/farmacocinética , Succinatos/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida , Estudos Cross-Over , Preparações de Ação Retardada , Esquema de Medicação , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Inibidores da Agregação Plaquetária/administração & dosagem , Succinatos/administração & dosagem , Espectrometria de Massas em Tandem , Adulto Jovem
10.
Br J Cancer ; 109(6): 1482-7, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23963141

RESUMO

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is dysregulated in small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor. METHODS: This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg once daily in combination with paclitaxel (175 mg m(-2)) once every 3 weeks in previously treated SCLC patients. The primary end point was to determine the maximum tolerated dose of everolimus. RESULTS: Among 21 enrolled patients, common drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain, hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of three patients receiving everolimus 10 mg. The overall objective response rate was 28%. CONCLUSION: Everolimus showed an acceptable safety profile and preliminary antitumour activity at the dose of 5 mg once daily when combined with 3-weekly paclitaxel 175 mg m(-2) in patients with SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Relação Dose-Resposta a Droga , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados
11.
Water Sci Technol ; 67(11): 2568-75, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23752390

RESUMO

For the successful scale-up of microbial fuel cell (MFC) systems, enrichment strategies are required that not only maximise reactor performance but also allow anodic biofilms to be robust to environmental change. Cluster analysis of Denaturing Gradient Gel Electrophoresis community fingerprints showed that anodic biofilms were enriched according to substrate type and temperature. Acetate produced the highest power density of 7.2 W m(-3) and butyrate the lowest at 0.29 W m(-3), but it was also found that the trophic conditions used to acclimate the electrogenic biofilms also determined the MFC response to different substrate types, with both acetate and butyrate substrates recording power densities of 1.07 and 1.0 W m(-3) respectively in a sucrose enriched reactor. When temperature perturbations were introduced to investigate the stability of the different substrate acclimated electrogenic biofilms, the 20 °C acclimated acetate reactor was unaffected by 10 °C operation but all reactors acclimated at 35 °C were adversely affected. When the operating temperature was raised back to 35 °C both the acetate and butyrate reactors recovered electrogenic activity but the sucrose reactor did not. It is thought that this was due to the more complex syntropic interactions that are required to occur when metabolising more complex substrate types.


Assuntos
Fenômenos Fisiológicos Bacterianos , Fontes de Energia Bioelétrica , Biofilmes , Acetatos/metabolismo , Adaptação Fisiológica , Butiratos/metabolismo , Clima , Eletroforese em Gel de Gradiente Desnaturante , Eletroquímica , Eletrodos , Sacarose/metabolismo , Temperatura
12.
Eye (Lond) ; 27(7): 809-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23598679

RESUMO

PURPOSE: To evaluate the variability in subfoveal choroidal thickness measurements in patients with age-related macular degeneration (AMD) and central serous chorioretinopathy using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: One hundred and sixty eyes of 160 patients who were diagnosed with early AMD (N=40), exudative AMD (N=40), polypoidal choroidal vasculopathy (PCV, N=40), or central serous chorioretinopathy (CSC, N=40) were included in this retrospective observational study. In addition, we included 40 normal eyes of 40 subjects. Subfoveal choroidal thickness was measured manually by two masked observers based on EDI-OCT images. The correlation of choroidal thickness with the absolute value of the difference in the choroidal thickness measurement was estimated for all 200 eyes. Intraobserver and interobserver coefficients of repeatability (CRs) were calculated. RESULTS: There was a significant positive correlation between subfoveal choroidal thickness and both intraobserver (P<0.001) and interobserver (P<0.001) difference in choroidal thickness measurements. The mean intraobserver CRs in nonexudative AMD, exudative AMD, PCV, CSC, and normal eyes were ~15-21, 23-29, 24-35, 32-38, and 19-25 µm, respectively. The mean interobserver CRs were ~24-28, 30-36, 39-45, 46-57, and 26-35 µm, respectively. CONCLUSIONS: Relatively great measurement variability should be considered when investigating eyes with pathologic conditions related to a thick choroid, including PCV or CSC.


Assuntos
Coriorretinopatia Serosa Central/patologia , Corioide/patologia , Fóvea Central/patologia , Degeneração Macular/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
J Laryngol Otol ; 126(7): 729-32, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22613806

RESUMO

OBJECTIVE: We report two extremely rare cases of polyps from unilateral accessory middle turbinates, one of which coexisted with a polyp from an inferomedially projecting, pneumatised, secondary middle turbinate. METHODS: Case report and literature review concerning accessory middle turbinate and secondary middle turbinate. RESULTS: Two patients presented with unilateral nasal obstruction. In both patients, nasal endoscopy revealed polypoid masses originating from the middle meatus. Paranasal sinus computed tomography and histopathological analysis confirmed the presence of polyps originating from an accessory middle turbinate and secondary middle turbinate, which were resected uneventfully via endoscopic sinus surgery. CONCLUSION: To our knowledge, this is the first report in the world literature of polyps originating from a unilateral accessory middle turbinate and secondary middle turbinate. Pre-operative recognition of these rare anatomical variations is of particular importance in avoiding intra-operative complication.


Assuntos
Obstrução Nasal/patologia , Pólipos Nasais/patologia , Conchas Nasais/patologia , Adulto , Endoscopia , Feminino , Humanos , Obstrução Nasal/diagnóstico , Obstrução Nasal/diagnóstico por imagem , Obstrução Nasal/cirurgia , Pólipos Nasais/diagnóstico , Pólipos Nasais/diagnóstico por imagem , Pólipos Nasais/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos , Radiografia , Conchas Nasais/anormalidades , Conchas Nasais/diagnóstico por imagem
14.
Cell Death Differ ; 19(4): 703-12, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22052190

RESUMO

Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified. Knockdown of PATZ1 in young cells accelerated premature EC senescence, which was confirmed by growth arrest, increased p53 protein level and senescence-associated ß-galactosidase (SA-ß-gal) activity, and repression of EC tube formation. In contrast, overexpression of PATZ1 in senescent cells reversed senescent phenotypes. Cellular senescence induced by PATZ1 knockdown in young cells was rescued by knockdown of p53, but not by knockdown of p16(INK4a). PATZ1 knockdown increased ROS levels, and pretreatment with N-acetylcysteine abolished EC senescence induced by PATZ1 knockdown. Notably, PATZ1 immunoreactivity was lower in ECs of atherosclerotic tissues than those of normal arteries in LDLR(-/-) mice, and immunoreactivity also decreased in ECs of old human arteries. These results suggest that PATZ1 may have an important role in the regulation of EC senescence through an ROS-mediated p53-dependent pathway and contribute to vascular diseases associated with aging.


Assuntos
Envelhecimento/metabolismo , Aterosclerose/metabolismo , Senescência Celular , Células Endoteliais/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Animais , Artérias/metabolismo , Artérias/patologia , Aterosclerose/genética , Aterosclerose/patologia , Pontos de Checagem do Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Células Endoteliais/patologia , Técnicas de Silenciamento de Genes , Humanos , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Proteína Supressora de Tumor p53/genética
15.
Cell Death Differ ; 19(1): 121-31, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21637294

RESUMO

Skeletal myogenesis is precisely regulated by multiple transcription factors. Previously, we demonstrated that enhancer of polycomb 1 (Epc1) induces skeletal muscle differentiation by potentiating serum response factor (SRF)-dependent muscle gene activation. Here, we report that an interacting partner of Epc1, ret finger protein (RFP), blocks skeletal muscle differentiation. Our findings show that RFP was highly expressed in skeletal muscles and was downregulated during myoblast differentiation. Forced expression of RFP delayed myoblast differentiation, whereas knockdown enhanced it. Epc1-induced enhancements of SRF-dependent multinucleation, transactivation of the skeletal α-actin promoter, binding of SRF to the serum response element, and muscle-specific gene induction were blocked by RFP. RFP interfered with the physical interaction between Epc1 and SRF. Muscles from rfp knockout mice (Rfp(-/-)) mice were bigger than those from wild-type mice, and the expression of SRF-dependent muscle-specific genes was upregulated. Myotube formation and myoblast differentiation were enhanced in Rfp(-/-) mice. Taken together, our findings highlight RFP as a novel regulator of muscle differentiation that acts by modulating the expression of SRF-dependent skeletal muscle-specific genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Células Musculares/metabolismo , Desenvolvimento Muscular/genética , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Fator de Resposta Sérica/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Sítios de Ligação , Diferenciação Celular , Linhagem Celular , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Knockout , Células Musculares/citologia , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Fator de Resposta Sérica/genética , Fatores de Transcrição , Ativação Transcricional , Ubiquitina-Proteína Ligases
16.
Bioresour Technol ; 102(18): 8534-42, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21621996

RESUMO

Acidogenic fermentation can be used to produce hydrogen from a range of biomass sources. The effluent from this process can be utilised in a number of biological processes enabling further recovery of energy from the biomass. In this review a number of candidate technologies are assessed including conventional methanogenic anaerobic digestion, dark fermentative hydrogen production, photo-fermentation, and bioelectrochemical systems. The principles, benefits and challenges associated with integrating these technologies are discussed, with particular emphasis on integration with fermentative hydrogen production, and the current state of integrative development is presented. The various system configurations for potential integrations presented here may simultaneously permit an increase in the conversion efficiency of biomass to energy, improved adaptability to varying operating conditions, and improved stability. Such integration, while increasing system complexity, may mean that these bioprocesses could be deployed in a wider range of scenarios and be used with a greater range of substrates.


Assuntos
Biocombustíveis/análise , Biotecnologia/métodos , Fermentação/fisiologia , Hidrogênio/metabolismo , Fermentação/efeitos da radiação , Luz
17.
J Bone Joint Surg Br ; 93(4): 537-41, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21464496

RESUMO

The use of allografts for the treatment of bone tumours in children is limited by nonunion and the difficulty of finding a suitable graft. Furthermore, appositional growth can't be expected of an allograft. We used an overlapping allograft in 11 children, with a mean age of ten years (4 to 15), with a mean follow-up of 24.1 months (20 to 33). There were five intercalary and six intra-articular resections, and the tumours were in the femur in six cases and the humerus in five. Rates of union, times to union, remodelling patterns and allograft-associated complications were evaluated. No allograft was removed due to a complication. Of the 16 junctional sites, 15 (94%) showed union at a mean of 3.1 months (2 to 5). Remodelling between host and allograft was seen at 14 junctions at a mean of five months (4 to 7). The mean Musculoskeletal Tumor Society score was 26.5 of 30 (88.3%). One case of nonunion and another with screw protrusion required re-operation. Overlapping allografts have the potential to shorten time to union, decrease rates of nonunion and have positive appositional growth effect.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Procedimentos Ortopédicos/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Fêmur/cirurgia , Seguimentos , Humanos , Úmero/cirurgia , Masculino , Transplante Homólogo/métodos , Resultado do Tratamento
18.
J Bone Joint Surg Br ; 92(10): 1452-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20884987

RESUMO

Excision of a physeal bar and filling the space with interposition material may allow resumption of normal growth. Both the extent and the location of the bar and the amount of growth remaining from physis must be determined. Computer-assisted surgery is being used increasingly in various fields of orthopaedics. We describe the management of a patient with premature physeal arrest of the right distal tibia in which resection of a physeal bar was achieved under real-time three-dimensional intra-operative monitoring by computer-assisted navigation. The advantage of this method over other means of imaging is that intra-operative identification can increase the accuracy of resection of the bar.


Assuntos
Lâmina de Crescimento/cirurgia , Cirurgia Assistida por Computador/métodos , Tíbia/cirurgia , Criança , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fraturas Salter-Harris , Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Tomografia Computadorizada por Raios X
19.
Clin Exp Immunol ; 160(3): 348-58, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20345977

RESUMO

CS1 (CRACC, CD319) and 2B4 (CD244), members of the signalling lymphocyte activation molecule (SLAM) family receptors, regulate various immune functions. Genes encoding SLAM family receptors are located at 1q23, implicated in systemic lupus erythematosus (SLE). In this study, we have investigated the expression and alternative splicing of CS1 and 2B4 in immune cells from SLE patients. The surface expression of CS1 and 2B4 on total peripheral blood mononuclear cells (PBMCs), T, B, natural killer (NK) cells and monocytes in 45 patients with SLE and 30 healthy individuals was analysed by flow cytometry. CS1-positive B cell population was increased significantly in SLE patients. Because CS1 is a self-ligand and homophilic interaction of CS1 induces B cell proliferation and autocrine cytokine secretion, this could account for autoreactive B cell proliferation in SLE. The proportion of NK cells and monocytes expressing 2B4 on their surface was significantly lower in patients with SLE compared to healthy controls. Our study demonstrated altered expression of splice variants of CS1 and 2B4 that mediate differential signalling in PBMC from patients with SLE.


Assuntos
Processamento Alternativo/imunologia , Antígenos CD/imunologia , Leucócitos Mononucleares/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptores Imunológicos/imunologia , Transdução de Sinais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/biossíntese , Comunicação Autócrina/imunologia , Estudos de Casos e Controles , Proliferação de Células , Cromossomos Humanos Par 1/imunologia , Cromossomos Humanos Par 1/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/biossíntese , Família de Moléculas de Sinalização da Ativação Linfocitária
20.
J Oral Rehabil ; 37(4): 262-70, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20113391

RESUMO

The purpose of this study was to compare the short- and long-term changes in condylar position related to the glenoid fossa, and skeletal and occlusal stability after orthognathic surgery. All of the study patients were assessed by cone-beam computed tomography images for condylar rotational changes and anteroposterior position in the pre-surgery, post-surgery and post-retention period. The condylar positions were evaluated on three planes: axial, coronal and sagittal. In the skeletal and occlusal measurements, there was no significant difference between the post-surgery group and the post-retention group. After sagittal split ramus osteotomy (SSRO), the condyle on the axial plane rotated inward (P < 0.05) and maintained during the post-retention period. In the anteroposterior condylar position related to the glenoid fossa, the condyles had changed from the anterior position in the pre-surgery group to a concentric position in the post-surgery group and then returned to the anterior position in the post-retention groups. These results suggested that the changed anteroposterior condylar position in the glenoid fossa after SSRO with rigid fixation had moved from a concentric to anterior position for post-retention period.


Assuntos
Remodelação Óssea/fisiologia , Mandíbula/cirurgia , Côndilo Mandibular/anatomia & histologia , Prognatismo/cirurgia , Articulação Temporomandibular/anatomia & histologia , Adaptação Fisiológica , Adulto , Cefalometria , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Técnicas de Fixação da Arcada Osseodentária , Estudos Longitudinais , Masculino , Mandíbula/anormalidades , Mandíbula/anatomia & histologia , Côndilo Mandibular/fisiologia , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteotomia , Recidiva , Estudos Retrospectivos , Estatísticas não Paramétricas , Articulação Temporomandibular/fisiologia , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...