RESUMO
Intervertebral disc degeneration is a major cause of low back pain. Despite its long history and large socio-economical impact in western societies, the initiation and progress of disc degeneration is not well understood and a generic disease model is lacking. In literature, mechanics and biology have both been implicated as the predominant inductive cause; here we argue that they are interconnected and amplify each other. This view is supported by the growing awareness that cellular physiology is strongly affected by mechanical loading. We propose a vicious circle of mechanical overloading, catabolic cell response, and degeneration of the water-binding extracellular matrix. Rather than simplifying the disease, the model illustrates the complexity of disc degeneration, because all factors are interrelated. It may however solve some of the controversy in the field, because the vicious circle can be entered at any point, eventually leading to the same pathology. The proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level.
Assuntos
Degeneração do Disco Intervertebral/fisiopatologia , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Humanos , Disco Intervertebral/anatomia & histologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Mecanotransdução Celular/fisiologia , Estresse MecânicoRESUMO
The objective of this study was to investigate the release mechanism and kinetics of the antimicrobial peptide, Dhvar-5, both alone and in combination with gentamicin, from a standard commercial polymethyl methacrylate (PMMA) bone cement. Different amounts of Dhvar-5 were mixed with the bone cement powders of Osteopal and the gentamicin-containing Osteopal G bone cement and their release kinetics from the polymerized cement were investigated. Additionally, the internal structure of the bone cements were analysed by scanning electron microscopy (SEM) of the fracture surfaces. Secondly, porosity was investigated with the mercury intrusion method and related to the observed release profiles. In order to obtain an insight into the mechanical characteristics of the bone cement mixtures, the compressive strength of Osteopal and Osteopal G with Dhvar-5 was also investigated. The total Dhvar-5 release reached 96% in the 100 mg Dhvar-5/g Osteopal cement, whereas total gentamicin release from Osteopal G reached only 18%. Total gentamicin release increased significantly to 67% with the addition of 50mg Dhvar-5/g, but the Dhvar-5 release was not influenced. SEM showed an increase of dissolved gentamicin crystals with the addition of Dhvar-5. The mercury intrusion results suggested an increase of small pores (< 0.1 microm) with the addition of Dhvar-5. Compressive strength of Osteopal was reduced by the addition of Dhvar-5 and gentamicin, but still remained above the limit prescribed by the ISO standard for clinical bone cements. We therefore conclude that the antimicrobial peptide, Dhvar-5, was released in high amounts from PMMA bone cement. When used together with gentamicin sulphate, Dhvar-5 made the gentamicin crystals accessible for the release medium presumably through increased micro-porosity (< 0.1 microm) resulting in a fourfold increase of gentamicin release.
Assuntos
Cimentos Ósseos/química , Preparações de Ação Retardada/química , Gentamicinas/química , Polimetil Metacrilato/química , Proteínas e Peptídeos Salivares/química , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/análise , Peptídeos Catiônicos Antimicrobianos/química , Cimentos Ósseos/análise , Materiais Revestidos Biocompatíveis , Força Compressiva , Preparações de Ação Retardada/análise , Difusão , Gentamicinas/administração & dosagem , Histatinas , Teste de Materiais , Polimetil Metacrilato/administração & dosagem , Proteínas e Peptídeos Salivares/administração & dosagem , Proteínas e Peptídeos Salivares/análiseRESUMO
In two patients, men aged 39 and 66 years, a sternal mass in combination with pain developed. One patient was diagnosed with a non-Hodgkin lymphoma located in the sternum and the other one with a primary chondrosarcoma of the sternum. They both recovered after treatment. The differential diagnosis of disorders of the chest wall is troublesome and includes haematologic, rheumatologic and infectious processes. Tietze's syndrome is a rare cause of pain and non-suppurative swelling of the costosternal joints. However, tumours of the anterior chest wall can also cause these symptoms and these must therefore be excluded if the complaints persist or the swelling progresses. The most common malignant tumours of the chest wall are non-Hodgkin lymphoma, primary chondrosarcoma and metastases. Diagnostics should consist of blood tests and X-rays. CT and MRI scans are more helpful in establishing the diagnosis. A definitive diagnosis can only be determined by biopsy.
Assuntos
Neoplasias Ósseas/diagnóstico , Condrossarcoma/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Idoso , Biópsia , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico por imagem , Dor no Peito/diagnóstico por imagem , Dor no Peito/etiologia , Condrossarcoma/sangue , Condrossarcoma/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , RadiografiaRESUMO
New regenerative treatment strategies are being developed for intervertebral disc degeneration of which the implantation of various cell types is promising. All cell types used so far require in vitro expansion prior to clinical use, as these cells are only limited available. Adipose-tissue is an abundant, expendable and easily accessible source of mesenchymal stem cells. The use of these cells therefore eliminates the need for in vitro expansion and subsequently one-step regenerative treatment strategies can be developed. Our group envisioned, described and evaluated such a one-step procedure for spinal fusion in the goat model. In this review, we summarize the current status of cell-based treatments for intervertebral disc degeneration and identify the additional research needed before adipose-derived mesenchymal stem cells can be evaluated in a one-step procedure for regenerative treatment of the intervertebral disc. We address the selection of stem cells from the stromal vascular fraction, the specific triggers needed for cell differentiation and potential suitable scaffolds. Although many factors need to be studied in more detail, potential application of a one-step procedure for intervertebral disc regeneration seems realistic.