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COVID-19/prevención & control , ChAdOx1 nCoV-19/efectos adversos , Necrosis/diagnóstico , Enfermedades de la Piel/patología , Trombosis/diagnóstico , Administración Tópica , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Biopsia , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Clobetasol/administración & dosificación , Clobetasol/uso terapéutico , Terapia Combinada , Vendajes de Compresión , Diagnóstico Diferencial , Humanos , Masculino , Necrosis/tratamiento farmacológico , Necrosis/terapia , Neomicina/administración & dosificación , Neomicina/uso terapéutico , Nistatina/administración & dosificación , Nistatina/uso terapéutico , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Piel/patología , Enfermedades de la Piel/inducido químicamente , Trombosis/tratamiento farmacológico , Trombosis/terapia , Resultado del TratamientoRESUMEN
Developing rational targeted cancer drugs requires the implementation of pharmacodynamic (PD), preferably non-invasive, biomarkers to aid response assessment and patient follow-up. Magnetic resonance spectroscopy (MRS) allows the non-invasive study of tumour metabolism. We describe the MRS-detectable PD biomarkers resulting from the action of targeted therapeutics, and discuss their biological significance and future translation into clinical use.
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Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Monitoreo de Drogas/métodos , Espectroscopía de Resonancia Magnética/métodos , Neoplasias/metabolismo , Transducción de Señal/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Biomarcadores , Colina/metabolismo , Metabolismo Energético/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Histona Desacetilasas/metabolismo , Humanos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Fosfolípidos/metabolismo , Proteínas Quinasas/metabolismo , Investigación Biomédica Traslacional , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: The objectives of this study were to evaluate the perceptions, expectations and experience of physicians with hospital-based pharmacists in Kuwait. MATERIALS AND METHODS: A piloted self-administered questionnaire was hand delivered to 200 physicians practicing in four government hospitals in Kuwait. Main sections of the questionnaire comprised a series of statements pertaining to physicians' perceptions, expectations and experiences with pharmacists. RESULTS: One hundred and twenty (60%) questionnaires were returned. At least 57% of physicians in Kuwait appear comfortable with pharmacists carrying out patient-directed roles. In addition, they appeared to have high expectations of pharmacists, with 79% of them regarding pharmacists as knowledgeable drug therapy experts. Less than 60% considered pharmacists as applying their drug knowledge in practice and only 29% agreed that pharmacists routinely counselled their patients. There was no correlation between physician variables such as number of years since graduation from medical school, age, area of practice and their perceptions of pharmacists. CONCLUSION: Physicians in Kuwait appear comfortable with pharmacists providing a broad range of services but appear somewhat less comfortable with pharmacists' provision of direct patient care. Physicians considered pharmacists knowledgeable drug therapy experts, but regarded them as not routinely providing a broad range of higher-level pharmacy services.
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Actitud del Personal de Salud , Hospitales Públicos , Farmacéuticos/psicología , Médicos/psicología , Rol Profesional , Adulto , Femenino , Humanos , Relaciones Interprofesionales , Kuwait , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Magnetic resonance spectroscopy is increasingly used as a non-invasive method to investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. (1)H magnetic resonance spectra of live cells showed an increase in methylene signal as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h following induction of apoptosis. To explain this observation, (1)H magnetic resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/-7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of triacylglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal microscopy images of cells stained with the lipophilic dye Nile Red demonstrated the presence of lipid droplets in the cell cytoplasm. Quantification of the stained lipids by flow cytometry showed a good correlation with the magnetic resonance results (P > or =0.05 at 3, 5 and 7 h). (31)P magnetic resonance spectra showed a drop in phosphatidylcholine content of apoptosing cells, indicating that alteration in phosphatidylcholine metabolism could be the source of triacylglycerol accumulation during apoptosis. In summary, apoptosis is associated with an early accumulation of mobile triacylglycerols mostly in the form of cytoplasmic lipid droplets. This is reflected in an increase in the methylene/methyl ratio which could be detected by magnetic resonance spectroscopy.
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Apoptosis , Triglicéridos/metabolismo , Citometría de Flujo , Humanos , Células Jurkat , Espectroscopía de Resonancia Magnética , Receptor fas/fisiologíaRESUMEN
OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membranes is implicated in the pathogenesis of osteoarthritis (OA) and inhibitors of NO synthesis may have indications in the treatment or prevention of joint destruction in OA. Because the signaling mechanisms as well as the NOS isoform involved in induction of NO production in human cartilage remain in many parts unclear, the present study was designed to investigate the regulation of inducible NO synthesis in human intact OA cartilage. METHODS: Cartilage specimens were collected from OA patients undergoing knee replacement surgery and studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. J774 macrophages were used for comparison as a well-documented source of iNOS. RESULTS: OA cartilage expressed iNOS and produced NO in the absence of exogenous cytokines. Addition of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS) into the culture medium enhanced NO production in a dose-and time-dependent manner. Various NOS inhibitors suppressed NO production in the following order of potency: 1400W (novel selective iNOS inhibitor)=L-NIO>L-NMMA>L-NAME. Cycloheximide (an inhibitor of protein synthesis), pyrrolidine dithiocarbamate (PDTC; an NF-kappa B inhibitor) and genistein (an inhibitor of tyrosine protein kinases) inhibited cytokine-induced NO production, while dexamethasone, diaminohydroxypyrimidine (DAHP; an inhibitor of tetrahydrobiopterin synthesis) and PD 98059 (p42/44 MAP kinase inhibitor) had no effect. CONCLUSIONS: The results suggest that NO synthesis in human osteoarthritic cartilage derives from the glucocorticoid-insensitive expression of iNOS. Very similar mechanisms appear to regulate inducible NO synthesis in human osteoarthritic cartilage and J774 macrophages with the exception that dexamethasone inhibited NO production in J774 cells but not in osteoarthritic cartilage.
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Cartílago Articular/metabolismo , Glucocorticoides/fisiología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/biosíntesis , Osteoartritis/metabolismo , Análisis de Varianza , Técnicas de Cultivo de Célula , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Humanos , Interleucina-1/fisiología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Técnicas de Cultivo de Órganos , Pirimidinas/farmacología , Estadísticas no Paramétricas , Factores de Tiempo , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
High level of polyamine oxidase activity is detected in sera of depressed as well as in schizophrenic patients. ECT treatment of depressed and schizophrenic patients reduced significantly the level of polyamine oxidase activity in their sera. After ECT treatment, clinically improved depressed and schizophrenic subjects were found to have sera polyamine oxidase activity not significantly differ from that of normal subjects. Possible biochemical mechanisms, which link polyamine oxidase activity, schizophrenia, depression and ECT effect are discussed here.
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Depresión/enzimología , Terapia Electroconvulsiva , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/sangre , Esquizofrenia/enzimología , Depresión/sangre , Depresión/terapia , Humanos , Esquizofrenia/sangre , Esquizofrenia/terapia , Poliamino OxidasaRESUMEN
Patients with long-term orthopedic implants may develop inflammatory reactions due to the accumulation of biomaterial particles both around the implant and in distant organs. The exact impact of these particles on the normal immune cell function still remain relatively unclear. Activation of T-cells following exposure to biomaterial particles is driven by macrophages and requires synergistic signals primed by both antigen presentation and costimulation. The pattern of costimulatory molecule expression (CD80,CD86) was primarily examined using immunohistochemistry on tissue specimens of bone/implant interface membranes taken from sites of bone erosion. Additionally, costimulatory molecule expression was also assessed in the monocytic leukemia cell line U937 following exposure to clinically relevant titanium aluminum vanadium (TiAlV) and stainless steel particles (FeCrNi) cultured in vitro. This study demonstrates the induction and prominent expression of CD86 on almost all macrophage subsets at the bone/implant interface, including fused forms and large multinucleated giant cells (MNGC). In vitro analysis also indicated phagocytosis of metal particles by differentiated U937 caused significant induction of both CD80 and CD86 (p < 0.01), although the expression of CD86 dominated following prolonged exposure. The data presented highlights that CD86 is the predominant costimulatory molecule ligating to the complementary CD28 molecule at the inflammatory lesion of the interface. We propose that the intracellular presence of indigestible implant material, in addition to elevated costimulatory molecule expression, may promote T-cell inflammatory reactions at sites close to and distant from the orthopedic implant.
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Prótesis e Implantes/efectos adversos , Aleaciones/toxicidad , Antígeno B7-1/biosíntesis , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Técnica del Anticuerpo Fluorescente Directa , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Inmunohistoquímica , Inflamación/inmunología , Inflamación/patología , Fagocitosis/efectos de los fármacos , Titanio/toxicidadRESUMEN
Neovascularization is indispensable to both bone remodeling and the development of chronic inflammation. A pro-angiogenic state in the periprosthetic tissue may augment the inflammatory response to wear debris. To investigate if a pro-angiogenic state exists in the bone-implant interface of aseptically loosened joint prosthesis, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR were studied by immunohistochemistry. The VEGF-Flk/KDR pathway has been implicated as a key signaling requirement for pathological angiogenesis. The level of vascularization in periprosthetic tissue was semi-quantitatively compared to osteoarthritic (OA) and rheumatoid arthritic (RA) synovium. The level of vascularization in areas of periprosthetic tissue with heavy or low/moderate wear debris were also compared semi-quantitatively by image analysis. High levels of VEGF expression (16/16 cases) particularly in the implant synovial-like lining layer together with Flk-1/KDR expression by endothelial cells (13/16), suggests that neovascularization is occurring. Morphometric comparison of periprosthetic tissue with RA and OA synovium revealed no significant difference in microvessel density, but did reveal significantly increased microvessel area in RA synovium (P > 0.05). Areas of high wear debris infiltrate also contained a significantly smaller microvessel area (P > 0.01). Suggesting that wear debris may cause behavioral modification of microvessels. Modifying angiogenesis in the periprosthetic tissue could be a potential therapeutic target in reducing inflammation.
RESUMEN
The immunologic response to prosthetic biomaterial particles is characterized by macrophage-rich inflammatory infiltrate, formation of multinucleated giant cells, and aseptic loosening at the site of arthroplasty. We investigated the in vivo expression and tissue distribution of transforming growth factor alpha, macrophage colony-stimulating factor, and the receptor for colony-stimulating factor-1 at the site of bone erosion in patients with clinically failed orthopaedic implants (n = 30). The expression was further compared with that detected in the inflamed synovial membranes from patients with rheumatoid arthritis or osteoarthritis (n = 15) and one patient with osteoclastoma (giant cell tumour of bone). Immunostaining of the tissue demonstrated positivity for transforming growth factor alpha within the inflammatory macrophage and multinucleated giant cell infiltrate in the diseased synovial membrane and the bone-implant interface. A comparative analysis between the synovium and retrieval interface membranes (pseudosynovium) revealed a high level of expression of transforming growth factor alpha, with intense membrane staining on multinucleated giant cells in all failed arthroplasties with pseudosynovium. In addition, the frequency, antigenic phenotype, and pattern of transforming growth factor alpha expression on multinucleated giant cells in the interface were markedly similar to those observed for multinucleated giant cells in osteoclastoma. Multinucleated giant cells within the interface lacked the expression of macrophage colony-stimulating factor and colony-stimulating factor-1 receptor, whereas those at the bone surfaces exhibited strong immunoreactivity. The predominant expression of transforming growth factor alpha by multinucleated giant cells in the bone-implant interface and its similarity to osteoclastoma highlight the importance of assessing transforming growth factor alpha as a possible contributor to the development of bone-resorbing giant cells at the site of failed orthopaedic implants.
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Células Gigantes/metabolismo , Prótesis de Cadera , Prótesis de la Rodilla , Factor Estimulante de Colonias de Macrófagos/biosíntesis , Osteólisis/metabolismo , Receptores del Factor Estimulante de Colonias/biosíntesis , Factor de Crecimiento Transformador alfa/biosíntesis , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Técnica del Anticuerpo Fluorescente Indirecta , Tumor Óseo de Células Gigantes/metabolismo , Tumor Óseo de Células Gigantes/patología , Células Gigantes/patología , Humanos , Osteoartritis/metabolismo , Osteoartritis/patología , Osteólisis/patología , Membrana Sinovial/metabolismo , Membrana Sinovial/patologíaRESUMEN
Osseointegration at the site of orthopedic implants is dependent on the recruitment, attachment, and differentiation of osteogenic cells. Data concerning the effect of a patient's underlying joint disease on the modulation of the cellular activity and the long-term survival of joint prostheses is limited. In this study, immunocytochemistry was used to investigate the osteogenic cell phenotype within the bone-implant interface fibrous membrane in 60 patients with different underlying joint disease. Tissue specimens were removed during revision operations performed at variable times following implantation. The results provided histological evidence of the presence of fibrocartilage tissue and calcified bone within the interface. TGF-beta, metalloproteinases (MMP1 and MMP2) and their inhibitors (TIMP1 and TIMP2) were immunolocalized within fibroblasts, chondrocytes, and osteoblasts throughout the interface, indicating that signals modulating the osteogenic cell phenotype at these sites are highly regulated. Finally, the study identified a significant difference in the histological changes elicited by implant particulate debris in patients of different diagnostic categories. Such observations imply that the activity of the original joint disorder could augment specific cellular activation/immune signals that subsequently affect the degree of the local inflammatory responses to implant wear particles. The negative balance between the rate of bone growth and resorption around the prosthetic joint is central to the pathogenesis of aseptic loosening of implants.
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Artropatías/patología , Artropatías/cirugía , Prótesis Articulares , Oseointegración , Membrana Sinovial/patología , Adulto , Anciano , Colagenasas/análisis , Gelatinasas/análisis , Articulación de la Cadera/patología , Articulación de la Cadera/fisiopatología , Articulación de la Cadera/cirugía , Prótesis de Cadera , Humanos , Inmunohistoquímica , Artropatías/fisiopatología , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla , Masculino , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 2 de la Matriz , Metaloendopeptidasas/análisis , Persona de Mediana Edad , Osteogénesis , Pronóstico , Rango del Movimiento ArticularRESUMEN
Apoptosis was induced by treating L1210 leukaemia cells with mechlorethamine, and SW620 colorectal cells with doxorubicin. The onset and progression of apoptosis were monitored by assessing caspase activation, mitochondrial transmembrane potential, phosphatidylserine externalization, DNA fragmentation and cell morphology. In parallel, 31P magnetic resonance (MR) spectra of cell extracts were recorded. In L1210 cells, caspase activation was detected at 4 h. By 3 h, the MR spectra showed a steady decrease in NTP and NAD, and a significant build-up of fructose 1,6-bisphosphate (F-1,6-P) dihydroxyacetonephosphate and glycerol-3-phosphate, indicating modulation of glycolysis. Treatment with iodoacetate also induced a build-up of F-1,6-P, while preincubation with two poly(ADP-ribose) polymerase inhibitors, 3-aminobenzamide and nicotinamide, prevented the drop in NAD and the build-up of glycolytic intermediates. This suggested that our results were due to inhibition of glyceraldehyde-3-phosphate dehydrogenase, possibly as a consequence of NAD depletion following poly(ADP-ribose) polymerase activation. Doxorubicin treatment of the adherent SW620 cells caused cells committed to apoptosis to detach. F-1,6-P was observed in detached cells, but not in treated cells that remained attached. This indicated that our observations were not cell line- or treatment-specific, but were correlated with the appearance of apoptotic cells following drug treatment. The 31P MR spectrum of tumours responding to chemotherapy could be modulated by similar effects.
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Apoptosis , Neoplasias Colorrectales/patología , Leucemia L1210/patología , Animales , Antineoplásicos/farmacología , Benzamidas/farmacología , Caspasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Dihidroxiacetona Fosfato/metabolismo , Doxorrubicina/farmacología , Fructosadifosfatos/metabolismo , Glicerofosfatos/metabolismo , Humanos , Yodoacetatos/farmacología , Leucemia L1210/tratamiento farmacológico , Leucemia L1210/metabolismo , Espectroscopía de Resonancia Magnética , Mecloretamina/farmacología , NAD/metabolismo , Niacinamida/farmacología , Células Tumorales CultivadasRESUMEN
Joint replacement surgery has a wide clinical application as a successful technique. However, the release of biomaterial in particulate form from various implant components has been implicated as a cause of two major clinical complications: 1) bone lysis with or without aseptic loosening, and 2) dissemination of wear particles to distant sites with adverse local or systemic cellular responses. This review focuses on the analysis of the clinical material obtained at the time of revision operations and its value in identifying the pathological processes taking place within the bone-implant microenvironment. Important issues discussed include the incidence of infection, characterization of wear particles, particle-cell interactions, local histopathological changes that lead to the formation of erosive inflammatory lesions next to the bone, sensitivity reactions, tumor formation, and the induction of inflammatory factors and cytokines that can influence the rate of bone resorption versus bone formation.
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Enfermedades Óseas/patología , Huesos/patología , Prótesis Articulares , Materiales Biocompatibles/efectos adversos , Enfermedades Óseas/etiología , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/patología , Prótesis Articulares/efectos adversos , Tamaño de la Partícula , Falla de Prótesis , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/patología , Propiedades de SuperficieRESUMEN
The response to wear particles from orthopaedic implants can lead to inflammation, osteolytic lesions, and aseptic loosening. To gain an insight into the development of this pathogenetic process, immunohistochemical techniques were used to identify the expression and tissue distribution of the potent cell mitogen epidermal growth factor (EGF), and the epidermal growth factor receptor (EGF-R) at the site of bone erosion in 30 patients with clinically failed orthopaedic implants. The results showed a large proportion of the macrophage subsets (Mphi) which expressed EGF and EGF-R, also contained wear particles, indicating their expression is a consequence of Mphi phagocytosis of implant material. The surface membrane expression of EGF-R on fusing Mphi suggests its presence is fundamental to the formation of bone-resorbing multi-nucleated giant cells, and the development of osteolysis. Additionally, there is increasing evidence of the long-term systemic spread of wear particles and their accumulation at distal sites including lymph nodes, liver, and spleen. Elevated expression of mitogenic factors in response to wear particles may result in deviation from normal cell growth and regulation, resulting in changes to immune cell function. Such potential transformations at distal sites are clinically significant, as alterations to the patient's immune system may result in acute divergence from normal immune cell responses.
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IL-4 is a mast cell and T cell produced immune cytokine that is important in the regulation of macrophage function. IL-4 has also been implicated in the induction of foreign body giant cell formation. In patients with long-term joint prostheses, a localized granulomatous inflammation develops in periarticular tissues and other organs where phagocytosis of particulate material from various prosthetic components takes place. In this study we used the inflammatory lesions of the bone-implant interface as a model to investigate the possible production, the frequency and the cellular source of IL-4. 40 samples of the interface membrane obtained from 25 patients undergoing revision of clinically failed implants were analyzed by immunohistochemistry. Cryostat sections were labeled with specific monoclonal antibodies to mast cell products: IL-4, tryptase and the receptor c-kit (CD117). The study has identified a significant level of production of IL-4 by mast cells in all the cases analyzed. There was an apparent difference in the number of mast cells in relation to the histological variants of the interface. The increase in the number of mast cells and IL-4 production was more pronounced in cases with heavy macrophage infiltrate than those exhibiting a predominance of giant cells. The findings imply that the recruitment of mast cell and IL-4 expression precede the granulomatous reaction and may have a role in the induction of a number of immunopathological changes related to mast cell activation by biomaterial particles.
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Our aim was to analyse the influence of the size, shape and number of particles on the pathogenesis of osteolysis. We obtained peri-implant tissues from 18 patients having revision surgery for aseptically loosened Freeman total knee replacements (10), Charnley total hip replacements (3) and Imperial College/London Hospital double-cup surface hip replacements (5). The size and shape of the polyethylene particles were characterised using SEM and their concentration was calculated. The results were analysed with reference to the presence of radiological osteolysis. The concentration of polyethylene particles in 6 areas with osteolysis was significantly higher than that in 12 areas without osteolysis. There were no significant differences between the size and shape of the particles in these two groups. We conclude that the most critical factor in the pathogenesis of osteolysis is the concentration of polyethylene particles accumulated in the tissue.
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Prótesis de Cadera/efectos adversos , Prótesis de la Rodilla/efectos adversos , Osteólisis/etiología , Polietilenos/análisis , Falla de Prótesis , Cromatografía Líquida de Alta Presión , Humanos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Diseño de Prótesis , ReoperaciónRESUMEN
The aim of this study was to evaluate the relative contribution of polyethylene, metal, and polymethylmethacrylate (cement) particles to the overall bone loss in aseptic loosening. Twenty-four interface tissues with adjacent bone were obtained during 17 revision total joint arthroplasties (11 hips and six knees). Osteoclasts and macrophages were identified immunohistochemically on the bone surface. The length of the bone surface in contact with these cell types was measured and analyzed with reference to the particulate species present within the fibrous interface. The presence of abundant polyethylene particles significantly increased the proportion of the bone surface in contact with macrophages but did not have a significant influence on that of osteoclasts. Osteoclastic bone resorption was significantly more extensive in the presence of metal particles. In contrast, the presence of cement particles did not have a significant influence on macrophage or osteoclast coverage of the bone surface. These results highlight the significance of polyethylene particles in macrophage recruitment and subsequent osteolysis and suggest a different mechanism of bone loss related to metal, namely mediation through osteoclastic activities. The relative contribution of cement particles was negligible and needs reevaluation in light of evidence provided by others.
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Prótesis de Cadera , Prótesis de la Rodilla , Osteólisis , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/cirugía , Femenino , Necrosis de la Cabeza Femoral/cirugía , Humanos , Macrófagos/patología , Masculino , Persona de Mediana Edad , Osteoartritis/cirugía , Osteoclastos/patología , Polietilenos , Falla de Prótesis , Reoperación , Espondilitis Anquilosante/cirugíaRESUMEN
Although nitric oxide (NO) is a well documented effector molecule in rodent macrophages, its significance in human mononuclear phagocytic cells has been controversial. The foreign body inflammatory reaction around loosened joint replacement implants leads to formation of an osteolytic granulomatous pseudo-synovial membrane rich in activated macrophages. We studied 13 specimens of interface membrane tissue collected from revision surgery of aseptically loosened hip and knee prostheses for the presence of inducible NO synthase (iNOS). The presence of iNOS was demonstrated immunohistochemically in 10 of these specimens. Within the tissue this enzyme was confined to macrophages and vascular endothelial cells. iNOS activity was demonstrated biochemically by measuring the calcium-independent generation of citrulline from L-arginine, and the presence of iNOS mRNA was demonstrated using reverse transcriptase polymerase chain reaction. NO synthesis in the interface tissue may be an important factor in the maintenance of the inflammatory and osteolytic processes.
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Reacción a Cuerpo Extraño/metabolismo , Macrófagos/enzimología , Óxido Nítrico Sintasa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/análisis , Secuencia de Bases , Reacción a Cuerpo Extraño/patología , Humanos , Inmunohistoquímica , Prótesis Articulares , Activación de Macrófagos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Falla de Prótesis , ARN/aislamiento & purificación , Reoperación , Membrana Sinovial/química , Membrana Sinovial/patologíaRESUMEN
Bone loss induced by the inflammatory response to wear particles is a major cause of long-term failure of total joint replacement. This review describes the cellular reaction occurring in response to these particles and what is currently known about the inflammatory mechanisms contributing to bone resorption.
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Reacción a Cuerpo Extraño , Prótesis Articulares , Falla de Prótesis , Cementos para Huesos , Resorción Ósea , Huesos/citología , Citocinas/análisis , Reacción a Cuerpo Extraño/etiología , Reacción a Cuerpo Extraño/patología , Humanos , Inmunohistoquímica , Inflamación , Osteoclastos/citología , InvestigaciónRESUMEN
An attempt was made to assess the local chronic inflammatory response in patients with failed orthopaedic implant that is clinically associated with osteolysis, bone and bone marrow necrosis. The main objective was to analyse the heterogeneity of the macrophage functional subsets in the bone-implant interface membrane and to evaluate their possible role in the development of an erosive inflammatory lesion within the bone. Immunohistology was performed on 21 specimens of the bone-implant interface obtained from 17 patients during revision arthroplasty, and synovial membranes from rheumatoid (RA, n=4), and osteoarthritis (OA, n=4) patients. Three well-characterized monoclonal antibodies (MAb) recognizing antigenic determinants on specific functional subsets of macrophages (Mphi) were used. RFD1 (interdigitating reticulum cells/antigen presenting cells, (APC), RFD7 (mature phagocytic macrophages), and RFD9 epithelioid cells and foreign body giant cells (FBGC). RFD1 was expressed on a variable number of perivascular and synovial lining Mphi in both RA and OA synovia, at a frequency of 25%-40%. In cases with total joint replacements, the interface showed a marked increase in the expression of RFD1 (20%-90%). A considerably greater percentage of RFD1 positive Mphi and FBGC was noted in the interfaces from cases with a high level of detectable metal particulate wear debris (mean 80%, range 60%-90%) than in cases with polyethylene wear debris (mean 30%, range 0%-50%), p 0.0001. RFD7 labelled most tissue Mphi in each group. Immunoreactivity for RFD9 was restricted to FBGC in all cases analysed. The finding of elevated expression of RFD1 on metal-containing Mphi and FBGC in the bone-implant interface suggests an increase in antigen-presenting phenotype and indicates that metal particles have more impact in the induction of immune-mediated responses. Such responses are characterized by sustained cellular hyperreactivity and phenotypic changes in Mphi subsets.