RESUMO
Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.
Assuntos
Gentamicinas/administração & dosagem , Próteses e Implantes , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Titânio/química , Vancomicina/administração & dosagem , Células 3T3 , Ligas , Animais , Antibacterianos/administração & dosagem , Diferenciação Celular , Proliferação de Células , Portadores de Fármacos , Flúor/farmacologia , Masculino , Camundongos , Nanopartículas/química , Osseointegração , Fósforo/farmacologia , Coelhos , Staphylococcus aureus/efeitos dos fármacosRESUMO
AIM: Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). MATERIAL AND METHODS: Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). RESULTS: There were 4 women and 3 men between 36-91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. CONCLUSIONS: These data suggest different mechanisms of DLBCL development in LPL patients.
Assuntos
Heterogeneidade Genética , Linfoma Difuso de Grandes Células B/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Evolução Clonal , Progressão da Doença , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Fator 88 de Diferenciação Mieloide/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genéticaRESUMO
Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both associated with high morbidity and a substantial cost burden for patients and health systems. The development of a biomaterial capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. Using an in vivo rabbit model, this study evaluates the osseointegration effect of the fluorine (F)- and phosphorus (P)-doped bottle-shaped nanostructured (bNT) Ti-6Al-4V alloy and effectiveness of monitoring urine aluminum concentration to determine the presence of Pseudomonas aeruginosa infection in Ti-6Al-4V implants. Unlike chemically polished (CP) Ti-6Al-4V alloy implants, bNT Ti-6Al-4V alloy implants promoted osseointegration and showed effectiveness as a biomaterial marker. The bNT Ti-6Al-4V alloy implants were associated with a twofold increase in bone thickness and up to 15% greater bone density compared to the CP alloy. Additionally, bNT Ti-6Al-4V alloy implants allowed for discrimination between P. aeruginosa-infected and noninfected animals for 15 days postoperatively, as indicated by the decrease of aluminum concentration in urine, while this difference was only appreciable over the first 7 days when CP Ti-6Al-4V alloy implants were used. Therefore, bNT Ti-6Al-4V alloys could have clinical applications by detecting the infection and by avoiding aseptic loosening.