Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 629
Filtrar
1.
Nefrología (Madrid) ; 40(5): 506-513, sept.-oct. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-199031

RESUMO

INTRODUCTION: Sclerostin is an anti-anabolic protein synthesized by osteocytes that may cause osteoporosis by inhibiting bone formation. The aim of our study was to investigate the correlation between sclerostin and bone mineral density (BMD) reduction in renal transplant recipients (RTRs) with more than 1 year after transplantation. MATERIAL AND METHODS: This cross-sectional study was conducted on 80 patients (38 (47.5%) male/42 (52.5%) female) RTRs with a mean age of 44.68±10.39 years. Patients were compared with an age and sex-matched control group of 40 healthy individuals. BMD was measured by dual-energy X-ray absorptiometry. The levels of sclerostin were determined using enzyme-linked immunosorbent assay. RESULTS: The mean sclerostin was 3.77±0.3pg/mL in patients and 3.81±0.21pg/mL in healthy individuals. The mean T score of femoral trochanter (FT) (FT-T), femoral neck (FN) (FN-T), lumbar vertebrae (L1-4) (L1-4-T) were −0.81±0.86, −1.08±1.09 and −0.8±1.2, respectively. The mean Z score of FT (FT-Z), FN (FN-Z), L1-4 (L1-4-Z) were −0.6±0.73, −0.32±0.9 and −0.54±1.13, respectively. FT-Z and L1-4-Z were lower in patients than healthy subjects (p = 0.009, p = 0.021 respectively). Serum creatinine (p < 0.001), intact parathyroid hormone (p < 0.001) were higher and phosphate (p < 0.001), was lower in patients than healthy subjects. Patients with a log10 sclerostin of >3.84pg/mL had higher FT-T (p = 0.040), FT-Z, FN-T (p = 0.018), FN-Z (p = 0.006) than those with a log10 sclerostin of ≤3.84pg/mL. There was a significant correlation between log10 sclerostin and FN-T (r=−0.296, p = 0.009) and FN-Z (r=−0.269, p = 0.019). In linear regression analysis, high sclerostin was found to be correlated with male gender, lower FN-T and lower FN-Z independently of other risk factors. CONCLUSION: The levels of sclerostin can predict reduction of proximal femur BMD and development of mineral and bone disorder in RTRs. There was no difference in sclerostin levels between RTRs and healthy individuals


INTRODUCCIÓN: La esclerostina es una proteína con efecto antianabólico sintetizada por los osteocitos que puede causar osteoporosis al inhibir la formación de hueso. El objetivo de nuestro estudio fue investigar la correlación entre la esclerostina y la reducción de la densidad mineral ósea (DMO) en receptores de trasplante renal (RTR) más de un año después del trasplante. MATERIALES Y MÉTODOS: Este estudio transversal se realizó en 80 pacientes (38 [47,5%] varones/42 [52,5%] mujeres) RTR con una edad media de 44,68±10,39 años. Se comparó a los pacientes con un grupo de comparación emparejado por edad y sexo de 40 individuos sanos. La DMO se midió mediante absorciometría de rayos X de doble energía. Los niveles de esclerostina se determinaron utilizando un enzimoinmunoanálisis de adsorción. RESULTADOS: El nivel medio de esclerostina fue de 3,77±0,3pg/ml en pacientes y 3,81±0,21pg/ml en individuos sanos. La puntuación T media del trocánter femoral (TF) (T-TF), del cuello femoral (CF) (T-CF), las vértebras lumbares (L1-4) (T-L1-4) fue de −0,81±0,86, −1,08±1,09 y −0,8±1,2, respectivamente. La puntuación Z media del TF (Z-TF), CF (Z-CF), L1-4 (Z-L1-4) fue de -0,6±0,73, −0,32±0,9 y −0,54±1,13, respectivamente. Las puntuaciones Z-TF y Z-L1-4 fueron inferiores en los pacientes que en los sujetos sanos (p = 0,009 y p = 0,021, respectivamente). Los niveles de creatinina sérica (p < 0,001) y hormona paratiroidea intacta (p < 0,001) fueron superiores en los pacientes que en los sujetos sanos, y los niveles de fosfato (p < 0,001) fueron inferiores. Los pacientes con un log10 esclerostina >3,84pg/ml tuvieron puntuaciones T-TF (p = 0,040), Z-TF, T-CF (p = 0,018), Z-CF (p = 0,006) superiores a las de los pacientes con un log10 esclerostina ≤3,84pg/ml. Se observó una correlación significativa entre log10 esclerostina y T-CF (r=−0,296, p = 0,009) y Z-CF (r=−0,269, p = 0,019). En el análisis de regresión lineal, se observó que los niveles elevados de esclerostina estaban correlacionados con el sexo masculino, una puntuación T-CF inferior y una puntuación Z-CF inferior independientemente de otros factores de riesgo. CONCLUSIÓN: Los niveles de esclerostina pueden predecir la reducción de la DMO del fémur proximal y el desarrollo de un trastorno mineral y óseo en RTR. No se observaron diferencias en los niveles de esclerostina entre los RTR y los individuos sanos


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Densidade Óssea , Transplante de Rim , Peptídeos e Proteínas de Sinalização Intercelular , Insuficiência Renal Crônica , Osso e Ossos/metabolismo , Proteínas Morfogenéticas Ósseas/efeitos adversos , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Biomarcadores/sangue , Estudos Transversais , Modelos Lineares , Absorciometria de Fóton , Imunossupressores/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Morfogenéticas Ósseas/administração & dosagem
2.
PLoS One ; 15(4): e0231112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310975

RESUMO

Tissue engineering represents a promising alternative for reconstructive surgical procedures especially for the repair of bone defects that do not regenerate spontaneously. The present study aimed to evaluate the effects of the elastin matrix (E24/50 and E96/37) incorporated with hydroxyapatite (HA) or morphogenetic protein (BMP) on the bone repair process in the distal metaphysis of rat femur. The groups were: control group (CG), hydrolyzed elastin matrix at 50°C/24h (E24/50), E24/50 + HA (E24/50/HA), E24/50 + BMP (E24/50/BMP), hydrolyzed elastin matrix at 37°C/96h (E96/37), E96/37 + HA (E96/37/HA), E96/37 + BMP (E96/37/BMP). Macroscopic and radiographic analyses showed longitudinal integrity of the femur in all groups without fractures or bone deformities. Microtomographically, all groups demonstrated partial closure by mineralized tissue except for the E96/37/HA group with hyperdense thin bridge formation interconnecting the edges of the ruptured cortical. Histologically, there was no complete cortical recovery in any group, but partial closure with trabecular bone. In defects filled with biomaterials, no chronic inflammatory response or foreign body type was observed. The mean volume of new bone formed was statistically significant higher in the E96/37/HA and E24/50 groups (71.28 ± 4.26 and 66.40 ± 3.69, respectively) than all the others. In the confocal analysis, it was observed that all groups presented new bone markings formed during the experimental period, being less evident in the CG group. Von Kossa staining revealed intense calcium deposits distributed in all groups. Qualitative analysis of collagen fibers under polarized light showed a predominance of red-orange birefringence in the newly regenerated bone with no difference between groups. It was concluded that the E24/50 and E96/37/HA groups promoted, with greater speed, the bone repair process in the distal metaphysis of rat femur.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fêmur/lesões , Osteogênese/efeitos dos fármacos , Engenharia Tecidual , Tecidos Suporte/química , Animais , Proteínas Morfogenéticas Ósseas/administração & dosagem , Modelos Animais de Doenças , Durapatita/administração & dosagem , Elastina/administração & dosagem , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Humanos , Masculino , Ratos , Fatores de Tempo , Microtomografia por Raio-X
3.
Chin J Traumatol ; 22(1): 51-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30745112

RESUMO

PURPOSE: To compare the efficacy and safety of recombinant human bone morphogenetic protein (rhBMP) and iliac crest autograft in the fusion treatment of lumbar spondylolisthesis. METHODS: The studies using randomized controlled trials to compare the rhBMP with iliac crest autograft in the treatment of lumbar spondylolisthesis were retrieved from Embase, Pubmed, ProQuest dissertations & theses (PQDT), China national knowledge infrastructure (CNKI), Chinese Biomedical Database, Wanfang Data, Cochrane Library (from March 1998 to March 2018). Postoperative fusion rate, clinical success rate, postoperative intervertebral height, complications, operation time, blood loss and duration of hospitalization were chosen as the outcome indicators. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software Revman 5.3 was used for data-analysis. RESULTS: Eleven articles were included in the meta-analysis. The results showed that, comparing the efficacy of rhBMP with iliac crest autograft, statistical significance was found in the 24-month fusion rate post operation [95% CI (1.38, 24.70), p = 0.02] and operation time [95% CI (-14.22, -2.08), p = 0.008]. There is not sufficient evidence for statistical differences in the remaining indicators. CONCLUSION: The current literature shows rhBMP is a safe and effective grafting material in the treatment of lumbar spondylolisthesis. Further evidence is dependent on the emergence of more randomized controlled trials with higher quality and larger sample sizes in the future.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Espondilolistese/cirurgia , Autoenxertos , Bases de Dados Bibliográficas , Humanos , Ílio/transplante , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
4.
Arch Oral Biol ; 99: 43-50, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30605820

RESUMO

OBJECTIVE: It was aimed to investigate the in vivo effects of local injection of sclerostin protein on orthodontic tooth movement. DESIGN: A total of 48 rats underwent orthodontic mesialization of the maxillary first molars on both sides. Local injection was given at the compression side in the alveolar bone on both maxillary sides, with sclerostin protein carried by hydrogel on one side, and the same volume of normal saline carried by hydrogel on the other side serving as the control. After two weeks, the tooth movement amount and effects on the periodontium were assessed through micro-computed tomography (µCT) analysis, tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemistry (IHC) analysis. RESULTS: After two weeks of intervention, tooth movement was significantly greater in the 4 µg/kg and 20 µg/kg sclerostin injection groups, compared to the control. Analysis of the furcation area of the maxillary first molar showed that the 20 µg/kg group had significantly decreased BV/TV. At the compression side, the number of TRAP-positive osteoclasts was significantly increased in 20 µg/kg group compared to the control. The expression of RANKL was statistically higher in all the sclerostin groups, while the expression of OPG was statistically lower in the 4 µg/kg and 20 µg/kg groups, compared to the control. At the tension side, the expression of RUNX2 and COL-1 was statistically higher in the 20 µg/kg group compared to the control. CONCLUSIONS: Local injection of sclerostin protein in the alveolar bone at the compression side accelerates OTM in rats by promoting osteoclastogenesis.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Proteínas Morfogenéticas Ósseas/farmacologia , Osteogênese/efeitos dos fármacos , Técnicas de Movimentação Dentária/métodos , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/metabolismo , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Marcadores Genéticos , Imuno-Histoquímica , Masculino , Maxila/diagnóstico por imagem , Maxila/metabolismo , Maxila/patologia , Dente Molar/metabolismo , Ortodontia , Osteoclastos/efeitos dos fármacos , Periodonto/diagnóstico por imagem , Periodonto/efeitos dos fármacos , Periodonto/metabolismo , Periodonto/patologia , Ligante RANK/metabolismo , Ratos , Ratos Wistar , Fosfatase Ácida Resistente a Tartarato/metabolismo
5.
Adv Healthc Mater ; 8(2): e1801044, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30556328

RESUMO

Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.


Assuntos
Regeneração Óssea , Engenharia Tecidual/métodos , Animais , Proteínas Morfogenéticas Ósseas/administração & dosagem , Proteínas Morfogenéticas Ósseas/metabolismo , Fosfatos de Cálcio , Humanos , Medicina Regenerativa/métodos , Análise Espaço-Temporal , Tecidos Suporte
6.
Curr Drug Deliv ; 16(2): 94-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30360738

RESUMO

BACKGROUND: Owing to their great promise in the spinal surgeries, bone graft substitutes have been widely investigated for their safety and clinical potential. By the current advances in the spinal surgery, an understanding of the precise biological mechanism of each bone graft substitute is mandatory for upholding the induction of solid spinal fusion. OBJECTIVE: The aim of the present review is to critically discuss various surgical implications and level of evidence of most commonly employed bone graft substitutes for spinal fusion. METHOD: Data was collected via electronic search using "PubMed", "SciFinder", "ScienceDirect", "Google Scholar", "Web of Science" and a library search for articles published in peer-reviewed journals, conferences, and e-books. RESULTS: Despite having exceptional inherent osteogenic, osteoinductive, and osteoconductive features, clinical acceptability of autografts (patient's own bone) is limited due to several perioperative and postoperative complications i.e., donor-site morbidities and limited graft supply. Alternatively, allografts (bone harvested from cadaver) have shown great promise in achieving acceptable bone fusion rate while alleviating the donor-site morbidities associated with implantation of autografts. As an adjuvant to allograft, demineralized bone matrix (DBM) has shown remarkable efficacy of bone fusion, when employed as graft extender or graft enhancer. Recent advances in recombinant technologies have made it possible to implant growth and differentiation factors (bone morphogenetic proteins) for spinal fusion. CONCLUSION: Selection of a particular bone grafting biotherapy can be rationalized based on the level of spine fusion, clinical experience and preference of orthopaedic surgeon, and prevalence of donor-site morbidities.


Assuntos
Materiais Biocompatíveis , Transplante Ósseo , Fusão Vertebral , Proteínas Morfogenéticas Ósseas/administração & dosagem , Humanos , Proteínas Recombinantes/administração & dosagem
7.
Sci Rep ; 8(1): 17293, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470794

RESUMO

Aging is the biggest risk factor for several neurodegenerative diseases. Parabiosis experiments have established that old mouse brains are improved by exposure to young mouse blood. Previously, our lab showed that delivery of Growth Differentiation Factor 11 (GDF11) to the bloodstream increases the number of neural stem cells and positively affects vasculature in the subventricular zone of old mice. Our new study demonstrates that GDF11 enhances hippocampal neurogenesis, improves vasculature and increases markers of neuronal activity and plasticity in the hippocampus and cortex of old mice. Our experiments also demonstrate that systemically delivered GDF11, rather than crossing the blood brain barrier, exerts at least some of its effects by acting on brain endothelial cells. Thus, by targeting the cerebral vasculature, GDF11 has a very different mechanism from that of previously studied circulating factors acting to improve central nervous system (CNS) function without entering the CNS.


Assuntos
Envelhecimento , Proteínas Morfogenéticas Ósseas/administração & dosagem , Encéfalo/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Fatores de Diferenciação de Crescimento/administração & dosagem , Hipocampo/efeitos dos fármacos , Neurogênese , Neurônios/efeitos dos fármacos , Animais , Encéfalo/irrigação sanguínea , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Células Endoteliais/citologia , Feminino , Hipocampo/irrigação sanguínea , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Neurônios/citologia , Regeneração
8.
Osteoarthritis Cartilage ; 26(9): 1153-1161, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29580979

RESUMO

Degeneration of articular cartilage (AC) tissue is the most common cause of osteoarthritis (OA) and rheumatoid arthritis. Bone morphogenetic proteins (BMPs) play important roles in bone and cartilage formation. This article reviews the experimental and clinical applications of BMPs in cartilage regeneration. Experimental evidence indicates that BMPs play an important role in protection against cartilage damage caused by inflammation or trauma, by binding to different receptor combinations and, consequently, activating different intracellular signaling pathways. Loss of function of BMP-related receptors contributes to the decreased intrinsic repair capacity of damaged cartilage and, thus, the multifunctional effects of BMPs make them attractive tools for the treatment of cartilage damage in patients with degenerative diseases. However, the development of BMP therapy as a treatment modality for cartilage regeneration has been hampered by certain factors, such as the eligibility of participants in clinical trials, financial support, drug delivery carrier safety, availabilities of effective scaffolds, appropriate selection of optimal dose and timing of administration, and side effects. Further research is needed to overcome these issues for future routine clinical applications. Research and development leading to the successful application of BMPs can initiate a new era in the treatment of cartilage degenerative diseases like OA.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Cartilagem Articular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Regeneração/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Cartilagem Articular/patologia , Feminino , Humanos , Masculino , Osteoartrite/diagnóstico por imagem , Prognóstico , Medição de Risco
9.
Int J Oral Maxillofac Implants ; 33(1): e1-e18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29340346

RESUMO

PURPOSE: One of the suggested methods for enhancing osseointegration is the local application of drug agents around implant surfaces. The aim of this review was to evaluate the methods most commonly used for local drug and chemical compound delivery to implant sites and assess their influence on osseointegration. MATERIALS AND METHODS: An electronic search was undertaken in three databases (PubMed, Scopus, Embase). The search was limited to animal experiments using endosseous implants combined with local drug delivery systems. Meta-analyses were performed for the outcome bone-to-implant contact (BIC). RESULTS: Sixty-one studies met the inclusion criteria. Calcium phosphate (CaP), bisphosphonates (BPs), and bone morphogenetic proteins (BMPs) were the most commonly used chemical compounds. There were two main methods for local drug delivery at the bone-implant interface: (1) directly from an implant surface by coating or immobilizing techniques, and (2) the local application of drugs to the implant site, using carriers. There was a statistically significant increase in BIC for both local drug delivery methods (P = .02 and P < .0001, respectively) compared with the control methods. There was a statistically significant increase in BIC when CaP (P = .0001) and BMPs (P = .02) were either coating implants or were delivered to the implant site, in comparison to when drugs were not used. The difference was not significant for the use of BPs (P = .15). CONCLUSION: It is suggested that the use of local chemical compound delivery systems around implants could significantly improve implant osseointegration in animal models. It is a matter of debate whether these in vivo results might have some significant effect in the human clinical setting in the long term.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/administração & dosagem , Implantes Dentários , Difosfonatos/administração & dosagem , Sistemas de Liberação de Medicamentos , Modelos Animais , Animais , Interface Osso-Implante , Materiais Revestidos Biocompatíveis , Implantação Dentária Endo-Óssea/métodos , Humanos , Osseointegração/efeitos dos fármacos , Propriedades de Superfície , Titânio/química
10.
Orthopade ; 47(1): 10-23, 2018 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29242964

RESUMO

BACKGROUND: Autologous bone grafts (autografts) are used in surgery for defect filling and impaction grafting during hip socket and femur reconstruction. Because of their superior osteoinductive capacity, autografts are considered the "gold standard" for these treatments. However, because of a better cost-benefit ratio, allografts are also often used. In the case of limited donor availability for autologous or allogenic bone grafts, bone substitute materials (BSMs) are a reasonable alternative or supplement. BSM are based on or combine different substances. Growth factors of the bone morphogenetic protein family BMP are recombinant proteins that specifically induce the growth of bone and cartilage tissue. CHARACTERISTICS: One advantage of BSM is the option to combine them with several anti-infective agents. The choice of the anti-infective substance should not only be based on the antimicrobial efficacy, but should also take into account possible dose-dependent cellular and pharmacological side effects at the implantation site. Thus, microbiologists, pharmacists and surgeons should decide together which combination is the most appropriate. COMBINATION PRODUCTS: BSM with active agent additives are considered combination products that are characterized by a main effect (bone replacement function) and a secondary effect (prophylaxis of bacterial recolonization of BSM). Both functions must be thoroughly (clinically) evidenced in the course of the registration process as a class III medical device. Drug authorities evaluate the active agents, their function and corresponding indication. Currently, only a few combination products are available on the market. As a consequence of the only limited availability of such commercial combination products, surgeons in clinical practice often manually add the active agent to BSM in the theatre prior to implantation. However, such a customized addition of antibiotics places the surgeon in a situation of a manufacturer where he assumes liability for the product.


Assuntos
Substitutos Ósseos , Transplante Ósseo/métodos , Portadores de Fármacos , Aloenxertos , Antibacterianos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Proteínas Morfogenéticas Ósseas/administração & dosagem , Humanos , Procedimentos Ortopédicos/métodos , Proteínas Recombinantes/administração & dosagem , Procedimentos Cirúrgicos Reconstrutivos/métodos
11.
Orthopade ; 47(1): 30-38, 2018 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29230489

RESUMO

BACKGROUND: The rising number of primary joint replacements worldwide is causing an increase of endoprosthetic revision surgery due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome, and the use of antibiotic-impregnated bone grafts might control the infection and provide a good support for the implant. In this study, we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. METHODS: Heat-treated, lyophilized and fresh frozen cryopreserved bone chips were impregnated with gentamicin sulphate, gentamicin palmitate and vancomycin, and calcium carbonate/calcium sulphate treated with antibiotics. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B. subtilis, S. aureus and methicillin-resistant Staphylococcus aureus. RESULTS: The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during the entire experiment. This might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high on the first and second days, then decreased and stayed at a low rate until the end of the second week. CONCLUSION: Depending on the surgical strategy, either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within 2 weeks after surgery. In the case of uncemented revision of joint replacements, allogeneic bone can deliver therapeutic doses of gentamicin and peak levels immediately and a fortnight after implantation.


Assuntos
Antibacterianos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Transplante Ósseo/métodos , Portadores de Fármacos , Procedimentos Ortopédicos/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Aloenxertos , Proteínas Morfogenéticas Ósseas/administração & dosagem , Quimioterapia Combinada , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Resultado do Tratamento
12.
Altern Ther Health Med ; 23(6): 42-47, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29055288

RESUMO

Aims • A case study was conducted on a subject with a history of documented bone loss and the observed outcome of bone mineral density (BMD) changes when utilizing supplementation with Cyplexinol, a natural bone morphogenetic protein complex. Method and Results • A case of osteoporosis was reviewed with pertinent medical history and dual energy X-ray absorptiometry history described both pre- and postsupplementation. Results demonstrated a significant change in bone density parameter for the individual when the bone support supplement, Cyplexinol, was used. Given this promising initial result, 3 additional cases were reviewed for potential replication and generalizability. Results showed a range of positive bone density changes of 18.5% to 63.63% during a supplementation period of 2 to 5 y. Conclusions • Cyplexinol may effectively manage BMD loss experienced during osteoporosis, though more studies are warranted with larger samples to replicate these findings. Given that administration of Cyplexinol was found to improve density scores in both mild and severe cases, despite the extent of the patient's history of documented bone loss, Cyplexinol has a more diverse range of applicability than prescription medications, suggesting the first, natural alternative to bisphosphonates, hormone replacement therapies and antireceptor activator of nuclear factor kappa-B ligand (anti-RANKL) agents. Furthermore, due to Cyplexinol's safety profile of no known side effects, it may be the ideal long-term strategy for individuals with bone loss and a possible preventative agent for individuals with known risk factors (eg, cigarette use, alcohol and carbonated drink usage, calcium deficiency, and family history) for osteoporosis. Although a larger pool of subjects is necessary to further support Cyplexinol's role in managing osteoporosis, these data are consistent with other studies examining the benefits of Cyplexinol's protein complex on BMD loss as a potential new, orally bioavailable therapeutic for the effective treatment of osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Proteínas Morfogenéticas Ósseas/administração & dosagem , Suplementos Nutricionais , Osteoporose/tratamento farmacológico , Absorciometria de Fóton , Idoso , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Osteoporose/diagnóstico por imagem
13.
Med Hypotheses ; 105: 63-68, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28735655

RESUMO

Among various infections, chronic osteomyelitis is one of the most challenging in terms of treatment. This infection is more common among patients with open fractures and those who have undergone elective orthopedic procedures. The treatment of osteomyelitis requires high antibiotic doses and an aggressive and multifaceted surgical approach. The use of parenteral antibiotics alone, without debridement, is not sufficiently effective, due to the formation of sequestra and the low vascularity of the affected area. The surgical options available for patients with chronic osteomyelitis include sequestrectomy, curettage, and intramedullary reaming, although these procedures usually result in bone defects that require further surgical intervention. Polymethyl methacrylate or calcium phosphate beads, impregnated with antibiotics, are commonly placed in such cases; however, this option has several disadvantages, including the need for future removal of cement, uncontrollable local release of antibiotics, and the need for broad-spectrum agents. The resulting bone defects also require additional treatments involving vascularized fibula grafting, intramedullary nails, use of techniques like Masquelet and Ilizarov, and even soft tissue transfers. All of these methods have certain limitations, such as the eventual requirement of more than one surgical event. Certain growth factors aid in the development and vascularization of new bone, such as bone morphogenetic proteins (BMPs) and insulin-like growth factor I (IGF-1). We propose that nanoparticles of BMPs, IGL-1, and microorganism-specific antibiotics can be placed on the surface of intramedullary nails. These nanoparticles can be attached to various different polymeric materials such as poly(d,l-lactide), which is a biocompatible and biodegradable polymer, and can be positioned in several layers, to ensure controlled and systematic release. The placement of nanoparticles at the infection site alone will also ensure local delivery of the drugs only to the required areas. Moreover, these intramedullary nails will be useful for both infected non-unions and mal-unions. Over time, the nanoparticles will eradicate the infection and stimulate new healthy bone formation, whereas the intramedullary nail itself will provide constant stability and immobilization. This model provides new and revolutionary ideas for the development of individualized technologies in medicine.


Assuntos
Antibacterianos/administração & dosagem , Proteínas Morfogenéticas Ósseas/administração & dosagem , Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fator de Crescimento Insulin-Like I/administração & dosagem , Osteomielite/cirurgia , Doença Crônica , Materiais Revestidos Biocompatíveis , Desbridamento , Sistemas de Liberação de Medicamentos , Desenho de Equipamento , Humanos , Modelos Anatômicos , Nanopartículas , Osteomielite/tratamento farmacológico
14.
J Bone Joint Surg Am ; 99(10): 855-864, 2017 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-28509826

RESUMO

BACKGROUND: Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. METHODS: Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model. Scl-Ab was administered subcutaneously at the time of rotator cuff repair and every 2 weeks until the animals were sacrificed. The effect of Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone morphometric analysis, biomechanical evaluation, histological analysis, and gene expression outcomes. RESULTS: Injury and repair led to a reduction in bone mineral density after 2 and 4 weeks of healing in the control and Scl-Ab treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment had 30% greater bone mineral density than the controls. A decrease in biomechanical properties was observed in both groups after 4 weeks of healing compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl-Ab-treated animals had improved strength (38%) and stiffness (43%) compared with control animals. Histological assessment showed that Scl-Ab promoted better integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant effects on gene expression in bone, indicative of enhanced bone formation, and no effect on the expression of genes in tendon. CONCLUSIONS: This study provides evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator cuff by increasing attachment-site bone mineral density, leading to improved biomechanical properties. CLINICAL RELEVANCE: Scl-Ab treatment may improve outcomes after rotator cuff repair.


Assuntos
Anticorpos/administração & dosagem , Proteínas Morfogenéticas Ósseas/administração & dosagem , Reabsorção Óssea/terapia , Lesões do Manguito Rotador/terapia , Cicatrização/imunologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Fenômenos Biomecânicos , Densidade Óssea , Osso e Ossos , Modelos Animais de Doenças , Marcadores Genéticos , Cabeça do Úmero/patologia , Cabeça do Úmero/fisiologia , Injeções Subcutâneas , Osteogênese/fisiologia , Tendões , Resultado do Tratamento
15.
Biomed Mater Eng ; 28(3): 293-304, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28527192

RESUMO

Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro. I-BCP demonstrated excellent adsorption/retention potential of rhBMP9 with a slow and steady release over a 10 day period by ELISA. Cell attachment at 8 hours and cell proliferation at 1, 3 and 5 days was decreased on I-BCP with/without rhBMP9 when compared to control tissue-culture plastic. While I-BCP had little influence on osteoblast differentiation, its combination with rhBMP9 significantly increased ALP activity at 7 days and mRNA levels of osteoblast differentiation markers including ALP and osteocalcin at 14 days. I-BCP served as an excellent carrier for rhBMP9 clearly demonstrating its osteoinductive potential. We therefore confirm the great potential of rhBMP9 to serve as a future regenerative growth factor for bone applications.


Assuntos
Proteínas Morfogenéticas Ósseas/química , Hidroxiapatitas/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/administração & dosagem , Diferenciação Celular , Linhagem Celular , Fator 2 de Diferenciação de Crescimento/administração & dosagem , Fator 2 de Diferenciação de Crescimento/química , Humanos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química
16.
Clin Orthop Relat Res ; 475(9): 2318-2331, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28462460

RESUMO

BACKGROUND: Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair. QUESTIONS/PURPOSES: (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) and recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered to an intrasynovial flexor tendon repair without adverse effects? (2) Do autologous ASCs modulate the inflammatory response after intrasynovial tendon injury and repair? (3) Does the combined application of autologous ASCs and rBMP-12 modulate the proliferative and remodeling responses after intrasynovial tendon injury and repair? METHODS: Sixteen 1- to 2-year-old female canines were used in this study. Autologous ASC sheets, with and without rBMP-12, were applied to the surface of sutured flexor tendons. Fourteen days after repair, the effects of treatment were determined using quantitative PCR (six per group) for the expression of genes related to macrophage phenotype or inflammation (IL-4, CD163, VEGF, NOS2, IL-1B, and IFNG), cell proliferation (CCND1), and tendon formation (SCX, TNMD, COL1A1 and COL3A1). Proteomics analysis (four per group) was performed to examine changes in tendon protein abundances. CD146 immunostaining and hematoxylin and eosin staining (four per group) were used to detect tendon stem or progenitor cells and to semiquantitatively evaluate cellularity at the tendon repair; analyses were done blinded to group. RESULTS: Gross inspection and cell tracing showed that autologous ASCs and rBMP-12 were delivered to the flexor tendon repair site without the deleterious effects of adhesion and repair-site gap formation. Quantitative assessment of gene and protein expression showed effects of treatment: ASC-sheet treatment modulated the postrepair inflammatory response and facilitated healing by increasing regenerative M2 macrophages (M2 marker CD204, twofold of normal, p = 0.030), inflammatory inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold of normal, p = 0.026), and proteins involved in tendon formation (periostin [POSTN], 1.9-fold of normal, p = 0.035). Consistently, semiquantitative and qualitative evaluations of repaired tissue showed that ASC-sheet treatment reduced mononuclear cell infiltration (12% less than nontreated tendons, p = 0.021) and introduced CD146+ stem or progenitor cells to the repair site. The combined administration of ASCs and rBMP-12 further stimulated M2 macrophages by increasing IL-4 (116-fold of normal, p = 0.002) and led to the increase of M2 effector matrix metalloproteinase-12 involved in matrix remodeling (twofold of normal, p = 0.016) and reduction of a negative regulator of angiogenesis and cell migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% of normal, p = 0.000), thus facilitating the proliferative stage of tendon repair. CONCLUSIONS: ASCs and BMP-12 accelerated the progression of healing in the proliferative stage of tendon repair. The effects of ASCs and BMP-12 on tendon functional recovery should be evaluated in future studies. CLINICAL RELEVANCE: The cell sheet approach is an effective, biocompatible, and surgeon-friendly approach for cell and growth factor delivery during tendon repair. Combined application of ASCs and BMP-12 may accelerate intrasynovial tendon healing while suppressing the adverse inflammatory response.


Assuntos
Proteínas Morfogenéticas Ósseas/uso terapêutico , Macrófagos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Traumatismos dos Tendões/genética , Cicatrização/fisiologia , Animais , Proteínas Morfogenéticas Ósseas/administração & dosagem , Proliferação de Células/genética , Modelos Animais de Doenças , Cães , Feminino , Expressão Gênica , Mediadores da Inflamação/análise , Fenótipo , Proteômica , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/administração & dosagem , Traumatismos dos Tendões/etiologia , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/cirurgia , Transplante Autólogo , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
18.
Pharm Res ; 34(6): 1152-1170, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28342056

RESUMO

Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action. A major challenge with these efforts is that the protein stability should be maintained. With this review we attempt to shed light on how the stability of BMPs can be affected in the formulation and delivery processes. We first provide a short overview of the current standing of the complications experienced with BMP products. We then discuss the different delivery parameters studied in association with BMPs, and their influence on the efficacy and safety of BMP treatments. In particular, the literature addressing the stability of BMPs and their possible interactions with components of the delivery system as well as their sensitivity to conditions of the formulation process is reviewed. In summary, recent developments in the fields of bioengineering and biopharmaceuticals suggest that a good understanding of the relationship between the formulation/delivery conditions and the stability of growth factors such as BMPs is a prerequisite for a safe and effective treatment.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Animais , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Polímeros/química , Transdução de Sinais , Engenharia Tecidual , Tecidos Suporte/química
19.
J Pediatr Orthop ; 37(6): e375-e378, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27603194

RESUMO

BACKGROUND: The use of bone morphogenetic protein (BMP) has been associated with a number of complications in adult patients. However, this association is less established in children. The aim of this study was to evaluate the safety of BMP use in children by determining the complication rates after BMP use at multiple institutions. METHODS: In a retrospective study (2000 to 2013), the medical records of all patients who received BMP at any of the 5 institutions were reviewed. Demographic information, preoperative data, and postoperative follow-up data were collected on those patients who were under the age of 18 at the time of surgery. RESULTS: A total of 312 pediatric patients underwent surgery with BMP application during the study period. The surgical procedures consisted of 228 spinal fusions, 39 pars repairs, 33 nonunion repair, and 12 other various procedures. Overall 21% (65/312) of patients who had BMP utilized had a complication. Fifty-five percent (36/65) of patients with a complication required a revision surgery. The average follow-up was 27 months (range, 3 to 96 mo); 80% of patients had a follow-up period of >12 months. The average age at the time of surgery was 13 years (range, 1 to 17 y). Males and females were almost equally represented in the study: 143 males (46%) and 168 females (54%). Of the patients who received BMP, 9% had minor complications and 13% had major complications. Wound dehiscence without infection was the most common minor complication and occurred in 59% (16/27) of patients with minor complications. Infection and implant failures were the most frequent major complications, occurring in 38% (15/39) and 33% (13/39) of patients with major complications, respectively. Five of 312 (2%) patients had neurological injury, 3 of which were only temporary. CONCLUSIONS: This multicenter study demonstrates a relatively high rate of complications after the use of BMP in children. However, further study is needed to attribute the complications directly to the use of BMP. LEVEL OF EVIDENCE: Level IV.


Assuntos
Proteínas Morfogenéticas Ósseas/efeitos adversos , Procedimentos Ortopédicos/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Adolescente , Proteínas Morfogenéticas Ósseas/administração & dosagem , Criança , Feminino , Humanos , Masculino , Uso Off-Label , Período Pós-Operatório , Reoperação/estatística & dados numéricos , Estudos Retrospectivos
20.
AAPS J ; 19(2): 431-437, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27924614

RESUMO

Loss of skeletal muscle mass and function results in loss of mobility for elderly patients. Novel therapies that can protect and/or restore muscle function during aging would have profound effects on the quality of life for this population. Growth differentiation factor 11 (GDF11) has been proposed as a "youthful" circulating factor that can restore cardiac, neural, and skeletal muscle functions in aging animals. However, conflicting data has been recently published that casts doubt on these assertions. We used a complex rat model of skeletal muscle injury that physiologically mimics injuries seen in patients; to investigate the ability of GDF11 and to enhance skeletal muscle regeneration after injury in older rats. Our data showed that GDF11 treatment resulted in a significant increase in tissue fibrosis, accompanied by attenuated functional recovery, as compared to animals treated with vehicle alone. GDF11 impaired the recovery of skeletal muscle function in older rats after injury.


Assuntos
Envelhecimento/fisiologia , Proteínas Morfogenéticas Ósseas/toxicidade , Fatores de Diferenciação de Crescimento/toxicidade , Músculo Esquelético/metabolismo , Regeneração/fisiologia , Animais , Proteínas Morfogenéticas Ósseas/administração & dosagem , Modelos Animais de Doenças , Fibrose , Fatores de Diferenciação de Crescimento/administração & dosagem , Humanos , Masculino , Músculo Esquelético/lesões , Qualidade de Vida , Ratos , Ratos Endogâmicos Lew
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...