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1.
BMC Med Imaging ; 10: 3, 2010 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-20089151

RESUMO

BACKGROUND: The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas. METHODS: In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits. RESULTS: Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (rs = 0.68 and rs = 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (rs = 0.64, p < 0.001). CONCLUSION: Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.


Assuntos
Artrografia/métodos , Modelos Animais de Doenças , Fêmur/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Animais , Ligamento Cruzado Anterior/cirurgia , Humanos , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
J Nucl Med ; 50(9): 1533-40, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19690032

RESUMO

UNLABELLED: Assessment of osteosarcoma response to neoadjuvant chemotherapy is performed by histopathologic analysis after surgical resection of the primary tumor. The purpose of this study was to evaluate whether (18)F-FDG PET could be a noninvasive surrogate to histopathologic analysis and allow for earlier response evaluation to neoadjuvant chemotherapy in osteosarcoma. METHODS: Metabolic response to neoadjuvant chemotherapy was assessed in immunocompetent rats with a preestablished orthotopic osteosarcoma using (18)F-FDG PET before and after receiving 2 doses of ifosfamide. Comparison was then made by assessing histologic responses on euthanized animals. RESULTS: Maximum standardized uptake value (SUVmax) measured by (18)F-FDG PET after 2 doses of chemotherapy was correlated to histologic classification (P < 0.01). An SUVmax less than 15 corresponded to good responders, whereas an SUVmax greater than 15 but less than 20 and an SUVmax greater than 20 corresponded to partial responders or nonresponders, respectively. A 40% decrease in SUVmax between the first and second (18)F-FDG PET scans distinguished between partial and good response to chemotherapy. CONCLUSION: Determination of SUVmax using semiquantitative (18)F-FDG PET predicts response to neoadjuvant chemotherapy earlier than does histologic analysis.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Fluordesoxiglucose F18/farmacocinética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Tomografia por Emissão de Pósitrons/métodos , Animais , Neoplasias Ósseas/diagnóstico por imagem , Quimioterapia Adjuvante , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Taxa de Depuração Metabólica , Terapia Neoadjuvante , Osteossarcoma/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Estatística como Assunto , Resultado do Tratamento
3.
Biomed Mater ; 12(1): 015023, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28102826

RESUMO

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium-zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 µg ml-1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium-zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium-zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium-zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.


Assuntos
Materiais Biocompatíveis/toxicidade , Cerâmica/toxicidade , Fibroblastos/efeitos dos fármacos , Nanopartículas/toxicidade , Óxido de Alumínio/química , Óxido de Alumínio/toxicidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cerâmica/química , Cerâmica/farmacocinética , Cério/química , Cério/toxicidade , Fibroblastos/citologia , Fibroblastos/fisiologia , Humanos , Teste de Materiais , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Zircônio/química , Zircônio/toxicidade
4.
Leuk Res ; 47: 1-7, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27235717

RESUMO

New B-cell receptor-targeted therapies such as ibrutinib, a Bruton tyrosine kinase inhibitor, are now proposed for lymphoid pathologies. The putative benefits of its combination with glucocorticoids were evaluated here. We compared the effects of dexamethasone (DXM), ibrutinib and their in vitro combination on proliferation and metabolic stress markers in stimulated normal B-lymphocytes and in malignant lymphocytes from chronic lymphocytic leukemia (CLL) patients. In both cellular models, cell cycle progression was globally inhibited by DXM and/or ibrutinib. This inhibition was significantly amplified by DXM addition to ibrutinib and was related to a significant decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E. Apoptosis increased especially with DXM/ibrutinib combination and was associated with a significant decrease in Mcl-1 expression. Treatment effects on metabolic stress were evaluated by DNA damage recognition after 53BP1 foci labeling. The percentage of cells with more than five 53BP1 foci decreased significantly with ibrutinib in normal and CLL lymphocytes. This decrease was strongly reinforced, in CLL, by DXM addition. Our data indicated that, in vitro, DXM potentiated antiproliferative effects of ibrutinib and decreased DNA damage in lymphoid B-cells. Thus their combination may be proposed for CLL treatment.


Assuntos
Linfócitos B/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dexametasona/farmacologia , Leucemia Linfocítica Crônica de Células B/patologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Adenina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperidinas , Estresse Fisiológico/efeitos dos fármacos , Células Tumorais Cultivadas
5.
Biomaterials ; 31(8): 2043-54, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20053439

RESUMO

In order to improve the reliability and the mechanical properties of orthopaedic hip prosthesis, new ceramic composites starting with nanosized powders of alumina and zirconia have been recently developed. The aim of the present study was to investigate the biological tolerance of one of these sintered ceramics and of its alumina and zirconia constitutive nanosized powders with both in vitro and in vivo approaches. At first, osteoblasts and fibroblasts were cultured either upon sintered ceramic discs with polished or rough surfaces or in the presence of the corresponding alumina or zirconia powders at various concentrations. Thereafter, we chronically injected these powders in the knee articulation of rats. In vitro, the materials showed no deleterious effect on cell proliferation, extra-cellular matrix production (human type I collagen and fibronectin) or on cell morphology. In vivo, the histological examination showed only a very moderate and non-specific granulomatous response of the synovial membrane but no major inflammation as clinically described with metals or polyethylene wear debris. Besides its improved physical properties, this recently developed alumina-zirconia composite showed satisfactory biocompatibility.


Assuntos
Óxido de Alumínio , Artroplastia , Materiais Biocompatíveis , Próteses e Implantes , Zircônio , Óxido de Alumínio/química , Óxido de Alumínio/metabolismo , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Células Cultivadas , Cerâmica/química , Fibroblastos/citologia , Fibroblastos/fisiologia , Humanos , Articulação do Joelho/citologia , Articulação do Joelho/patologia , Masculino , Teste de Materiais , Osteoblastos/citologia , Osteoblastos/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Zircônio/química , Zircônio/metabolismo
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