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1.
Eur Cell Mater ; 39: 65-76, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31939630

RESUMO

Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if LN could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1ß (IL-1ß) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1ß-induced biological effects. LN also supressed IL-1ß-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1ß and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could provide therapeutic potential in OA.


Assuntos
Cartilagem Articular/patologia , Interleucina-1beta/farmacologia , Osteoartrite/patologia , Peptídeos/farmacologia , Idoso , Animais , Comportamento Animal/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosaminoglicanos/metabolismo , Humanos , Hidroxiprolina/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Dor/patologia , Transdução de Sinais/efeitos dos fármacos
2.
J Frailty Aging ; 7(1): 34-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29412440

RESUMO

BACKGROUND: Hip fractures precipitate several acute adverse outcomes in elderly people, thus leading to chronic adverse outcomes. OBJECTIVES: The objective of our study was to examine the clinical characteristics associated with incident delirium in community dwelling elderly individuals who have a hip fracture. DESIGN: Retrospective observational cohort study. SETTING: Data was collected from an academic tertiary hospital affiliated with McGill University. PARTICIPANTS: 114 elderly individuals who were above 65 years of age, who underwent surgery for a fractured hip. MEASUREMENTS: The main outcome variable was incident delirium, which was assessed by chart reviews of notes and observations recorded by nurses and physicians when patients were admitted post operatively to the surgical unit. Covariates included age, sex, length of stay, delay to surgery, number of medical comorbidities, number of medications and hip fracture location, and were extracted from medical records. Baseline mobility and functional status, preoperative cognitive impairment, postoperative complications, regular psychotropic medications, psychotropic medications in hospital, and location of discharge were also assessed through chart review. RESULTS: The results demonstrated that 17.5% of participants with a diagnosis of delirium had a longer length of hospitalization (p = 0.01), a lower baseline functional status (p = 0.03) and pre-operative cognitive impairment (p = 0.01). Patients receiving new psychotropic medications in hospital were more likely to have delirium (OR = 4.6, p = 0.01) which was independent of pre-operative cognitive impairment. CONCLUSION: We have shown that an association exists between psychotropic medication prescription and incident delirium in patients with hip fractures, even when adjusting for cognitive impairment. Hence, the prescription of psychotropic drugs should be judicious in these patients so as minimize the risk of adverse outcomes.


Assuntos
Delírio/epidemiologia , Fraturas do Quadril/cirurgia , Pacientes Internados , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de Risco
3.
Comput Aided Surg ; 15(1-3): 56-62, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20521862

RESUMO

Several studies have shown that computer-navigated TKA reduces the rate of outliers. Thirty-one consecutive patients were operated on by the same surgeon using a computer assisted navigation system. Data collected by the system included the final mechanical axis of the extremity (HKA angle) and the coronal angle of the tibial and femoral implants. These same values were measured using CAD software on full weight-bearing long X-rays taken 6 weeks post-surgery. Deviations were observed when X-ray measurements were compared to intra-operative data collected from the navigation system. A statistically significant difference was found in the tibial cut (1.29 degrees +/- 1.35 degrees; p < 0.0001) and in the HKA (1.59 degrees +/- 2.36 degrees; p = 0.0007). Outliers of more than 3 degrees were observed in the coronal plane of the tibial implant in 9.6% of patients, in the coronal plane of the femoral implant in 6.4% of patients, and in the HKA angle of 29% of patients. Our results indicate that the use of navigation alone is insufficient to prevent outliers beyond an acceptable range of 3 degrees .


Assuntos
Artroplastia do Joelho/métodos , Monitorização Intraoperatória/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Cirurgia Assistida por Computador/métodos , Suporte de Carga/fisiologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
4.
Open Orthop J ; 2: 1-9, 2008 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-19461923

RESUMO

Knowledge of factors regulating the turnover, repair, and degeneration of the intervertebral disc (IVD) is lacking. Although type II collagen (CII) fragments accumulate in the degenerative IVD, little is known of how they affect the degenerative process. A better understanding of the cellular interactions with fragments of matrix molecules are a key factor in promoting therapies for degenerative disc diseases. In the present study, we have investigated the effect of the CII (245-270) peptide on the expression of matrix molecules, proteinases, and interleukin genes in cells of the IVD. Cells isolated from the nucleus pulposus (NP) and annulus fibrosus (AF) of adult bovine tails were cultured up to 8 days in the absence (control) or presence of the CII (245-270) peptide. RT-PCR was used to analyze the expression of the different genes. Exposure of these cells to the CII (245-270) peptide led to a transient up-regulation of the aggrecan gene in AF cells while this up-regulation was maintained for a longer time in NP cells. The fragment also enhanced a transient up-regulation of the type II collagen gene in AF cells but had no effect in NP cells. The peptide enhanced transiently the expression of matrix metalloproteinase (MMP)-1 and cathepsin K genes in both AF and NP cells whereas it increased MMP-13 expression only in NP cells. The peptide up-regulated tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, and TIMP-3 gene expression on day 1 in AF cells but had very little effect on their expression in NP cells. Finally, the CII (245-270) peptide had no effect on IL-6 expression while IL-1alpha was not expressed in these cells. In conclusion, our results showed that the CII (245-270) peptide differentially alter the expression of genes in bovine AF and NP cells and suggest that degradation products of collagen may be involved in the regulation of IVD homeostasis.

5.
J Sci Med Sport ; 9(1-2): 81-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16564222

RESUMO

Osteoarthritis (OA) is the most frequent joint disorder in seniors. Systematic reviews suggest that conservative treatment is effective and preferred in mild-moderate cases. The objective of this study was to examine the proportion of patients receiving physiotherapy, exercise or walking aids, and to explore factors associated with their prescription. We conducted a retrospective survey of patients about to undergo total hip arthroplasty for hip osteoarthritis. Patients were asked about past prescriptions for cane use, physiotherapy and exercise. Of 161 patients (36.6% male, mean age 68.7+/-10.1 years), 76% were prescribed a cane (adherence=86.2%). The main reason for not using a cane was vanity. Of the 28.0% patients prescribed physiotherapy, 73.3% received exercises compared to only 2.6% of non-physiotherapy patients. Patients who were older or worked in manual labour were more likely to be prescribed a cane and less likely to be prescribed physiotherapy or exercises. Men were less likely than women to be prescribed all three, but only cane use was statistically significant across genders. In conclusion, physiotherapy and exercise are not commonly prescribed in patients with hip OA.


Assuntos
Bengala/estatística & dados numéricos , Osteoartrite do Quadril/terapia , Modalidades de Fisioterapia/estatística & dados numéricos , Idoso , Terapia por Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prescrições , Estudos Retrospectivos
6.
Technol Health Care ; 11(4): 245-52, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14600335

RESUMO

The short- and long-term success of tibial cementless implants depend on the initial fixation stability often provided by posts and screws. Excessive relative interface motions are known to inhibit bone ingrowth and, hence, biologic fixation. In the present study, the stability of two cementless tibial implants under static and cyclic loading was studied. An apparatus was developed to perform compression tests on tibial components fixed by screws or posts onto resurfaced tibiae. Motion transducers were placed to record liftoff and subsidence displacements. A load of 1000 N was eccentrically applied on the medial plateau via the femoral component. The response was measured under static and repetitive loading up to 4000 cycles at 1 Hz. Experimental results showed that the screw fixation yielded the stiffer response and, hence, provided greater initial stability. The tibial component fixed with posts demonstrated larger lift off displacements. Comparison of measured results of static tests before and after fatigue indicated that the load-displacement behavior was not significantly affected by the cyclic fatigue loading under 1000 N up to 4000 cycles at 1 Hz. Nevertheless, much larger permanent displacements were recorded for the post fixation systems. In contrast to screw fixation, posts fixation systems demonstrated marked deterioration under larger compression loads of approximately 2000 N.


Assuntos
Fixadores Internos , Prótese do Joelho , Tíbia , Idoso , Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Placas Ósseas , Parafusos Ósseos , Força Compressiva , Fricção , Humanos , Teste de Materiais , Desenho de Prótese , Estresse Mecânico , Tíbia/fisiologia
7.
J Biomech Eng ; 123(5): 391-5, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11601722

RESUMO

The short- and long-term successes of tibial cementless implants depend on the initial fixation stability often provided by posts and screws. In this work, a metallic plate was fixed to a polyurethane block with either two bone screws, two smooth-surfaced posts, or two novel smooth-surfaced posts with adjustable inclinations. For this last case, inclinations of 0, 1.5, and 3 deg were considered following insertion. A load of 1031 N was eccentrically applied on the plate at an angle of approximately 14 deg, which resulted in a 1000 N axial compressive force and a 250 N shear force. The response was measured under static and repetitive loading up to 4000 cycles at 1 Hz. The measured results demonstrate subsidence under load, lift-off on the unloaded side, and horizontal translation of the plate specially at the loaded side. Fatigue loading increased the displacements, primarily during the first 100 cycles. Comparison of various fixation systems indicated that the plate with screw fixation was the stiffest with the least subsidence and liftoff. The increase in post inclination from 0 to 3 deg stiffened the plate by diminishing the liftoff. All fixation systems demonstrated deterioration under repetitive loads. In general, the finite element predictions of the experimental fixation systems were in agreement with measurements. The finite element analyses showed that porous coated posts (modeled with nonlinear interface friction with and without coupling) generated slightly less resistance to liftoff than smooth-surfaced posts. In the presence of porous coated posts, Coulomb friction greatly overestimated the rigidity by reducing the liftoff and subsidence to levels even smaller than those predicted for the design with screw fixation. The sequence of combined load application also influenced the predicted response. Finally, the finite element model incorporating measured interface friction and pull-out responses can be used for the analysis of cementless total joint replacement systems during the post-operation period.


Assuntos
Prótese Articular , Desenho de Prótese , Fenômenos Biomecânicos , Engenharia Biomédica , Parafusos Ósseos , Humanos , Técnicas In Vitro , Articulação do Joelho/fisiologia , Prótese do Joelho , Estresse Mecânico
8.
J Biomed Mater Res ; 55(3): 320-9, 2001 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-11255185

RESUMO

Isolation of metal wear particles from hip simulator lubricants or tissues surrounding implants is a challenging problem because of small particle size, their tendency to agglomerate, and their potential for chemical degradation by digestion reagents. To provide realistic measurements of size, shape, and composition of metal wear particles, it is important to optimize particle isolation and minimize particle changes due to the effects of the reagents. In this study (Part I of II), transmission electron microscopy (TEM) was used to examine and compare the effects of different isolation protocols, using enzymes or alkaline solutions, on the size and shape of three different types of cobalt-based alloy particles produced from metal-metal bearings. The effect on particle composition was examined in a subsequent study (Part II). Large particles (<1200 nm) were generated by dry abrasion of CoCrMo alloy against itself and small particles (<300 nm) were generated by hip simulator testing of a metal-metal implant pair in the presence of either distilled-deionized water or a 95% bovine serum solution. The reagents changed particle size and to a lesser extent particle shape. For both large particles and small particles generated in water, the changes in size were more extensive after alkaline than after enzymatic protocols and increased with alkaline concentration and time in solution, up to twofold at 2 h and threefold at 48 h. However, when isolating particles from 95% serum, an initial protective effect of serum proteins and/or lipids was observed. Because of this protective effect, there was no significant difference in particle size and shape for both oval and needle-shaped particles after 2 h in 2N KOH and after enzymatic treatments. However, round particles were significantly smaller after 2 h in 2N KOH than after enzymatic treatments. Particle composition may also have been affected by the 2N KOH treatment, as suggested by a difference in particle contrast under TEM, an issue examined in detail in Part II.


Assuntos
Materiais Biocompatíveis , Metais , Falha de Prótese , Animais , Fenômenos Biomecânicos , Sangue , Bovinos , Prótese de Quadril , Humanos , Técnicas In Vitro , Teste de Materiais , Tamanho da Partícula , Água
9.
J Biomed Mater Res ; 55(3): 330-7, 2001 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-11255186

RESUMO

The isolation of metal wear particles from hip simulator lubricants is important for understanding wear mechanisms and the tissue response to particulate material. Part I of this study demonstrated that isolation protocols involving digestion reagents can chemically attack metal-metal wear particles, reducing their size and changing their shape. In part II of this study, Co and Cr ion concentrations in solution after each digestion protocol were measured by flame atomic absorption spectrometry, and wear particle composition was determined by X-ray analysis spectra. The exposure of wear particles in water to alkaline solutions caused an increasing release of Cr ions in solution with alkaline concentration and time, and a corresponding decrease in particle Cr peak intensity on X-ray spectra. As a result, particles exposed to 12N KOH for 48 h displayed Co peaks and no Cr. In contrast, enzymatic protocols caused a release of Co ions in solution and a corresponding decrease in particle Co peak intensity on X-ray spectra, especially with sodium phosphate as a buffer. However, when isolating particles from 95% serum, there was an initial protective effect of serum proteins, presumably because of their binding to Co and Cr. As a result, the extent of Cr ion release from metal wear particles in 95% serum after alkaline treatments was diminished, although still present, whereas both enzymatic protocols resulted in a negligible release of Co and Cr ions into solution. Particle composition analysis after enzymatic treatments revealed the presence of chromium oxide particles and CoCrMo particles with variable Co/Cr ratios. After alkaline treatments, the chromium oxide particles increasingly disappeared with time and alkaline concentration, demonstrating a change in particle composition after these treatments. This study demonstrated that digestion reagents can induce chemical changes that affect particle composition. Of all the protocols tested, the enzymatic protocols were the least damaging to the particles and appeared to be the best compromise for isolation and characterization of metal particles, especially in 95% serum. Special care on the choice of buffers should be taken when isolating particles from a lower concentration of serum.


Assuntos
Materiais Biocompatíveis , Metais , Falha de Prótese , Animais , Materiais Biocompatíveis/química , Sangue , Bovinos , Prótese de Quadril , Humanos , Técnicas In Vitro , Íons , Teste de Materiais , Metais/química , Tamanho da Partícula , Espectrometria por Raios X , Água
10.
J Mater Sci Mater Med ; 12(7): 653-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15348259

RESUMO

The terminal events leading to periprosthetic osteolysis are multifactorial in nature and modulation of this process after the stage of osteolytic mediator release has been futile. Recently, the demonstration of the ability of bisphosphonates to inhibit bone resorption that is mediated by particle-stimulated macrophages and their induction of osteoclast apoptosis suggests a potent area for modulation of osteolysis at the prosthesis-bone interface. The purpose of this study was to determine the mode of cell death that occurs at the osteolytic interface of failed total hip arthroplasty (THA). TUNEL staining, DNA laddering, and immunodetection of poly(ADP-ribose)polymerase (PARP) protein were used to identify the presence of apoptosis in interface membranes from 25 patients aged 28-88 years old (mean, 58 years) harvested at the time of hip revision surgery. Our results demonstrated positive TUNEL stain in 100% of specimens with an average 37% of cells (range 12-60%) positively stained for TUNEL whereas less than 8% of control tissue cells showed positive staining. DNA laddering, a characteristic feature of apoptotic cells, was observed in 82% (28/34) of specimens studied at both the acetabular and femoral side of aseptically loose THAs. No laddering was observed in control tissues. Finally, using Western blot analysis, we observed the appearance of the 89 kDa PARP fragment associated with apoptosis in 92% of specimens (30/33). Our results demonstrate the presence of apoptotic cell death in interface membranes of THAs suggesting that apoptosis-related events are indeed associated with periprosthetic osteolysis and could serve as a specific target point for therapeutic modulation.

11.
J Mater Sci Mater Med ; 12(10-12): 949-53, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-15348346

RESUMO

The aim of this study was to evaluate the cytotoxic and apoptotic effects of cobalt and chromium ions on macrophages in vitro, and analyze the implication of caspase-3 in the apoptotic pathway. J774 mouse macrophages (5 x 10(5) cells/ml) were exposed for up to 24 h to 0-10 ppm Co2+ and 0-500 ppm Cr3+. The cytotoxic effect of ions was measured by Trypan blue exclusion. DNA analysis on agarose gel was used as a specific test for detection of DNA fragmentation into oligonucleosomes that occurs in apoptotic cells. The proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), closely associated with the induction of apoptosis, was also analyzed along with the appearance of the active fragment of caspase-3, implicated in several apoptosis pathways. Results demonstrated that both Co2+ and Cr3+ ions induce macrophage mortality in a dose-dependent manner. However, Co2+ is more toxic inducing a cell mortality up to 28% with only 10 ppm vs. 37% with 500 ppm of Cr3+. DNA analysis demonstrated that both Co2+ and Cr3+ ions induce DNA fragmentation, between 6-10 ppm Co2+ and 250-500 ppm Cr3+ after 24 h incubation. PARP cleavage and the appearance of caspase-3 active fragment were observed after 6 h with both Co+ and Cr3+ ions, with a stronger signal after 24 h and 10 ppm of Co2+ or 500 ppm of Cr3+. In conclusion, this study demonstrates that after 24 h incubation, both Co2+ and Cr3+ ions can induce macrophage mortality, and more specifically apoptosis. The results also suggest that apoptosis occurs via a caspase-3 pathway. However, the relative importance of necrosis and apoptosis and the effects of longer exposure times on the induction of macrophage death by these metal ions remain to be investigated.

12.
Arthritis Rheum ; 43(3): 673-82, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10728762

RESUMO

OBJECTIVE: To examine whether type II collagen cleavage by collagenase and loss of proteoglycan are excessive in human osteoarthritic (OA) articular cartilage compared with nonarthritic articular cartilage, and whether this can be inhibited by a selective synthetic inhibitor that spares collagenase 1 (matrix metalloproteinase 1 [MMP-1]). METHODS: Articular cartilage samples were obtained during surgery from 11 patients with OA and at autopsy from 5 adults without arthritis. The articular cartilage samples were cultured in serum-free medium. A collagenase-generated neoepitope, which reflects cleavage of type II collagen, and proteoglycan glycosaminoglycan (GAG), which predominantly reflects aggrecan release, were assayed in culture media. In addition, cultures were performed using either of 2 synthetic MMP inhibitors, both of which inhibited collagenase 2 (MMP-8) and collagenase 3 (MMP-13), but one of which spared collagenase 1. Cultures were also biolabeled with 3H-proline in the presence and absence of these inhibitors to measure collagen synthesis (as tritiated hydroxyproline) and incorporation in articular cartilage. RESULTS: As a group, cleavage of type II collagen by collagenase was significantly increased in OA cartilage samples. In contrast, proteoglycan (GAG) release was not increased. This release of a collagenase-generated epitope was inhibited by both MMP inhibitors in 2 of 5 nonarthritic samples and in 9 of 11 OA cartilage samples. The inhibitor that spared collagenase 1 was generally more effective and inhibited release from 4 of 5 nonarthritic cartilage samples and the same OA cartilage samples. Group analyses revealed that the inhibition of collagenase neoepitope release by both inhibitors was significant in the OA patient cartilage, but not in the nonarthritic cartilage. Proteoglycan loss was unaffected by either inhibitor. Newly synthesized collagen (predominantly, type II) exhibited increased incorporation in OA cartilage, but only in the presence of the inhibitor that arrested collagenase 1 activity. CONCLUSION: These results further indicate that the digestion of type II collagen by collagenase is selectively increased in OA cartilage, and that this can be inhibited in the majority of cases by a synthetic inhibitor that can inhibit collagenases 2 and 3, but not collagenase 1. The results also suggest that in OA, newly synthesized collagen is digested, but in a different manner than that of resident molecules. Proteoglycan release was not increased in OA cartilage and was unaffected by these inhibitors. Inhibitors of this kind may be of value in preventing damage to type II collagen in human arthritic articular cartilage.


Assuntos
Cartilagem Articular/metabolismo , Colágeno/metabolismo , Colagenases/farmacologia , Inibidores Enzimáticos/farmacologia , Proteínas da Matriz Extracelular , Inibidores de Metaloproteinases de Matriz , Osteoartrite/metabolismo , Adulto , Agrecanas , Técnicas de Cultura , Feminino , Humanos , Lectinas Tipo C , Masculino , Metaloproteinase 13 da Matriz , Pessoa de Meia-Idade , Desnaturação Proteica , Proteoglicanas/efeitos dos fármacos , Proteoglicanas/metabolismo
13.
J Orthop Res ; 18(1): 64-7, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10716280

RESUMO

The purpose of this study was to determine whether a marker of bone resorption could be used noninvasively to diagnose and assess treatment of periprosthetic osteolysis. The crosslinked N-telopeptide marker of osteoclast-mediated bone resorption potentially has the sensitivity to detect periprosthetic osteolysis. Second-morning urine specimens were obtained from (a) seven age-matched controls, (b) eight patients who had a hip arthroplasty, hybrid implants at least 1 year after surgery, and no osteolysis, (c) 11 patients who had a hip arthroplasty and osteolysis, and (d) 10 patients who had a hip arthroplasty and with osteolysis before and after 6 weeks of oral Fosamax (alendronate) treatment. The Fosamax treatment consisted of one 10-mg dose per day for 6 weeks. Men and young women (less than 40 years old) were chosen for this study to avoid bone resorption enhanced after menopause as a possible confounder. An enzyme-linked immunosorbent assay technique for quantifying crosslinked N-telopeptides of type-I collagen was performed on all specimens. The patients with osteolysis had significantly elevated levels of N-telopeptide compared with the implant control group. In addition, levels of N-telopeptide were significantly lowered after Fosamax treatment. These findings indicate that a systemic bone-resorption marker (N-telopeptide) can be used to evaluate local particulate-induced osteolysis and its treatment. The study also provides clinical evidence that osteolysis is associated with increased osteoclast-mediated bone resorption and that this locally induced bone resorption can be suppressed by certain bisphosphonates (Fosamax). These insights have potential value in the understanding and clinical management of aseptic loosening.


Assuntos
Colágeno/urina , Osteólise/diagnóstico , Peptídeos/urina , Adulto , Idoso , Alendronato/uso terapêutico , Biomarcadores , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/tratamento farmacológico
14.
Biomaterials ; 20(7): 625-30, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10208404

RESUMO

The purpose of this study was to investigate in vitro the presence of apoptotic cell death after macrophage stimulation with different ceramic (Al2O3 and ZrO2) and high density polyethylene (HDP) particles. We also analyzed the effects of particle size, concentration, and composition. The J774 mouse macrophage cell line was exposed to commercial particles of different sizes (up to 4.5 microm) and concentrations (up to 500 particles per macrophage). Fluorescence microscopy and DNA laddering were used to investigate the presence of apoptosis in cell cultures after 24 h of incubation. Fluorescence microscopy of propidium iodide stained cells showed two characteristic morphological features that occur in apoptotic cells, namely nuclear condensation and heterogeneity of stain uptake. The effect of ceramic particles on apoptotic nuclear morphology was size- and concentration-dependent and reached a plateau above 150 particles per macrophage at 1.3 microm. With regards to composition, we did not find any difference in cell morphology between Al2O3 and ZrO2. Ceramic and HDP particles induced DNA fragmentation into oligonucleosomes as evidenced by DNA laddering, another characteristic of apoptosis. The induction of DNA laddering was size- and concentration-dependent whereas particle composition (Al2O3 vs. ZrO2 and Al2O3 vs. HDP) had no effect. In conclusion, our results demonstrated that ceramic and HDP particles induce macrophage apoptotic cell death in vitro and open doors for possible modulation of debris-induced periprosthetic osteolysis.


Assuntos
Óxido de Alumínio , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis , Cerâmica , Macrófagos/efeitos dos fármacos , Polietilenos , Zircônio , Animais , Apoptose/fisiologia , Artroplastia de Quadril , Linhagem Celular , DNA/metabolismo , Dano ao DNA , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Microscopia de Fluorescência , Osteólise , Tamanho da Partícula
15.
J Bone Joint Surg Br ; 81(3): 516-21, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10872377

RESUMO

Although the response of macrophages to polyethylene debris has been widely studied, it has never been compared with the cellular response to ceramic debris. Our aim was to investigate the cytotoxicity of ceramic particles (Al2O3 and ZrO2) and to analyse their ability to stimulate the release of inflammatory mediators compared with that of high-density polyethylene particles (HDP). We analysed the effects of particle size, concentration and composition using an in vitro model. The J774 mouse macrophage cell line was exposed to commercial particles in the phagocytosable range (up to 4.5 microns). Al2O3 was compared with ZrO2 at 0.6 micron and with HDP at 4.5 microns. Cytotoxicity tests were performed using flow cytometry and macrophage cytokine release was measured by ELISA. Cell mortality increased with the size and concentration of Al2O3 particles. When comparing Al2O3 and ZrO2 at 0.6 micron, we did not detect any significant difference at the concentrations analysed (up to 2500 particles per macrophage), and mortality remained very low (less than 10%). Release of TNF-alpha also increased with the size and concentration of Al2O3 particles, reaching 195% of control (165 pg/ml v 84 pg/ml) at 2.4 microns and 350 particles per cell (p < 0.05). Release of TNF-alpha was higher with HDP than with Al2O3 particles at 4.5 microns. However, we did not detect any significant difference in the release of TNF-alpha between Al2O3 and ZrO2 at 0.6 micron (p > 0.05). We saw no evidence of release of interleukin-1 alpha or interleukin-1 beta after exposure to ceramic or HDP particles.


Assuntos
Óxido de Alumínio/toxicidade , Cerâmica , Citocinas/metabolismo , Prótese de Quadril , Macrófagos/efeitos dos fármacos , Polietileno/toxicidade , Falha de Prótese , Zircônio/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Mediadores da Inflamação/metabolismo , Camundongos , Tamanho da Partícula , Fagocitose/efeitos dos fármacos
16.
J Biomed Mater Res ; 41(4): 600-7, 1998 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-9697033

RESUMO

Using the J774 macrophage cell line, we designed an in vitro model to analyze by flow cytometry the effects of size, concentration, and composition of ceramic (Al2O3 and ZrO2) and high density polyethylene (HDP) particles on phagocytosis and cell mortality. Inflammatory mediator (TNF-alpha) also was measured by ELISA. Kinetic studies revealed that phagocytosis of the particles begins very early after cell exposure, increasing with time and particle concentration and reaching a plateau after 15 h. This implies that the optimum period to evaluate cellular response to particulate debris is between 15 and 24 h of incubation. Results also showed that phagocytosis increases with concentration for particles up to 2 microns. For larger particles (up to 4.5 microns), phagocytosis seems to reach a plateau independent of size and concentration, which suggests a saturation of phagocytosis that is most likely dependent on overall particle volume ingested. We did not detect any significant difference in phagocytosis between Al2O3 and ZrO2 at 0.6 microns. Al2O3 seems to be more easily phagocytosed than HDP at the same size (4.5 microns) and concentrations. Cytotoxicity studies revealed that macrophage mortality increases with particle size and concentration for sizes greater than 2 microns. Smaller particles (0.6 microns) cause cell mortality only at higher concentrations (from 1,250 particles per cell), but the mortality is still very low (10%). No significant difference in cell mortality and TNF-alpha release was found between Al2O3 and ZrO2. Effects of Al2O3 and HDP at 4.5 microns were compared by measuring TNF-alpha release. Results showed that TNF-alpha release increases with particle concentrations and is higher with HDP than with Al2O3.


Assuntos
Cerâmica , Macrófagos/citologia , Polietilenos , Óxido de Alumínio , Linhagem Celular , Sobrevivência Celular , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Zircônio
17.
Clin Biomech (Bristol, Avon) ; 13(8): 625-633, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11415842

RESUMO

OBJECTIVE: To investigate the detailed biomechanics of the passive tibiofemoral knee joints in full extension under anterior/posterior drawer forces of up to 400 N. DESIGN: A nonlinear three-dimensional finite element model of the entire human tibiofemoral joint consisting of bony structures, their articular cartilage layers, menisci, and four principal ligaments was utilized. BACKGROUND: The mechanics of the knee joint, specially under drawer forces, have extensively been investigated. Despite all these works, the detailed joint biomechanics, specially the role of boundary conditions, load transmission through menisci/articular cartilage layers, and coupling between menisci and cruciate ligaments are not yet quantified. METHODS: Nonlinear elastostatic analyses were carried out considering the tibiofemoral joint at full extension under anterior and posterior loads of up to 400 N applied either to the tibial or the femoral shaft. Cases with various boundary conditions, cruciate ligament deficiency (anterior or posterior), and total unilateral meniscectomy (medial or lateral) were analysed. RESULTS: In addition to the total primary anterior-posterior motion of about 9 mm at +/-400 N, significant coupled external tibial rotations of about 9 degrees and 10 degrees were computed under 400 N femoral posterior and anterior forces, respectively. The response was influenced by the manner of loading and boundary conditions. The anterior cruciate ligament and posterior cruciate ligament were the primary restraints to femoral posterior and anterior drawer forces, respectively. Section of either of these ligaments drastically increased the joint anterior-posterior motion. In the absence of cruciates, the collaterals became the primary restraints in both anterior-posterior forces. In this case, the tibial plateaus, specially the medial one in the anterior cruciate ligament-deficient joint, experienced much larger compressive forces. In addition to causing an increase in joint primary anterior-posterior laxity and anterior cruciate ligament forces, medial meniscectomy substantially increased coupled tibial external rotation, forces on the lateral plateau, and stresses in the articular cartilage of the lateral plateau. RELEVANCE: Our results suggest an increased role for the medial meniscus in the anterior cruciate ligament-deficient joint. Lateral meniscectomy had much smaller effects on results than the medial one. The success of any anterior cruciate ligament replacement or meniscal transplantation in the restoration of the joint stability and the protection of the articular cartilage against excessive stresses depends on the coupling between the anterior cruciate ligament and medial meniscus. Absence of any of these components would drastically influence the joint response.

18.
Clin Biomech (Bristol, Avon) ; 12(3): 139-148, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11415685

RESUMO

OBJECTIVE: The overall response, load transmission, role of ligaments, and state of stress in various components under varus-valgus moments in the intact and collateral-deficient tibiofemoral joint are investigated. DESIGN: A non-linear finite element model consisting of bony structures (tibia and femur), their articular cartilage layers, medial and lateral menisci and four primary ligaments (cruciates and collaterals) is utilized. BACKGROUND: Valgus and varus stresses are among the primary mechanisms of injury to knee ligaments. Several in vitro studies have investigated the role of ligaments in resisting such loads and on the way deficiency in either collateral may affect the response. METHODS: Cartilage layers are isotropic while menisci are non-homogeneous composite. The articulation of cartilage layers with each other and with the intervening menisci and the wrapping of the medial collateral ligament around the tibial edge are treated as large displacement frictionless contact problems. The non-linear elastostatic response of the joint at full extension is computed under varus-valgus moments applied to the femur with the tibia fixed. Cases simulating deficiency in collaterals and constraint on femoral axial rotation are also studied. RESULTS: The response is non-linear with large coupled axial rotations, internal in varus and external in valgus. In intact and collateral-deficient states, the joint shows varus or valgus openings so that the articulation occurs at one plateau only, medial in varus and lateral in valgus. Large tensile forces in cruciates in collateral-cut models generate higher compression penalty on the loaded plateau. CONCLUSIONS: Collaterals are the primary load-bearing structures; their absence would substantially increase primary laxities, coupled axial rotations, forces in cruciates, and articular contact forces. Good agreement with measurements is found. RELEVANCE: Detailed knowledge of joint biomechanics is essential in the diagnosis, prevention and treatment of observed disorders. Absence of collateral ligaments increases the loads in cruciates and contact stresses transmitted through cartilage layers and menisci, and thus places the affected components at more risk, especially when varus-valgus is accompanied by other modes of loading as well.

19.
J Biomech ; 30(2): 121-9, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9001932

RESUMO

Measured interface nonlinear friction properties are used to develop models to study the short-term fixation response of smooth- and porous-surfaced posts, bone screws, and plates fixed with and without posts/screws. Experimental studies are carried out to validate the model predictions and identify the relative role of posts and screws in fixation of a plate on a polyurethane block under symmetric/eccentric axial compression loads. The idealized Coulomb's friction is also used for the sake of comparison. The incorporation of measured nonlinear, rather than the idealized Coulomb, friction is essential to compute realistic results. For plate fixation, the experimental and finite element results show that the screw fixation yields the stiffest response followed by the smooth- and then porous-coated post fixation. For example, under 1000 N eccentric axial compression, the edge of the plate opposite the loaded edge is measured to lift by 1147 +/- 72, 244 +/- 38, or 112 +/- 28 microns, respectively, for the cases with no fixation, with smooth-surfaced posts, or with screws. The corresponding models predict, respectively, values of 1538, 347, or 259 microns and also 556 microns for the plate fixed with porous coated posts. The satisfactory agreement between numerical and experimental results confirms the importance of proper interface modelling for the analysis of posts, screws, and complex fixation systems. This becomes further evident when considering cementless implants in which the bone-implant interface exhibits relatively large displacements as the maximum resistance force is reached. The developed models can be used to investigate the post-operative short-term stability of various cementless implant designs.


Assuntos
Próteses e Implantes , Cimentos Ósseos , Pinos Ortopédicos , Placas Ósseas , Parafusos Ósseos , Osso e Ossos/cirurgia , Simulação por Computador , Elasticidade , Desenho de Equipamento , Previsões , Fricção , Humanos , Teste de Materiais , Modelos Biológicos , Maleabilidade , Poliuretanos , Porosidade , Pressão , Reprodutibilidade dos Testes , Estresse Mecânico , Propriedades de Superfície
20.
Can J Surg ; 38(5): 421-6, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7553465

RESUMO

OBJECTIVE: To determine whether the knowledge gained through total hip replacement (THR) influences the time to recovery after a second THR. DESIGN: A retrospective study of data gathered prospectively on the recovery course of patients from their preoperative visit to 1 year after surgery. SETTING: A university teaching hospital. PATIENTS: Sixty-nine patients underwent bilateral hip replacements at the Royal Victoria Hospital, Montreal, between May 1985 and May 1992. The inclusion criteria were: (a) similar diagnoses and prostheses bilaterally, (b) time between the two THRs of less than 3 years, (c) both replacements carried out by the same surgeon and (d) attendance at the arthroplasty clinic. Forty-one patients did not fulfil the criteria for inclusion, leaving 28 patients having 56 THRs for the study. An additional 28 patients who had unilateral hip arthroplasty were randomly chosen on the basis of sex and age to act as the control group. INTERVENTION: Bilateral cementless THR. MAIN OUTCOME MEASURES: Harris hip score at one preoperative visit and postoperatively at 6 weeks, 3 months, 6 months and 1 year. RESULTS: There were no significant differences in measures of recovery between the initial and the subsequent hip replacement at any of the time intervals. Significant differences were found only between the various time periods. CONCLUSIONS: Time and not familiarity dictated progress toward recovery for patients who underwent bilateral THR with cementless prostheses. Randomized clinical trials, assessing whether time to recovery, ultimate outcome and cost-effectiveness are affected by preoperative teaching programs, are necessary to further elucidate this important issue.


Assuntos
Prótese de Quadril , Feminino , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Dor , Complicações Pós-Operatórias , Estudos Prospectivos , Amplitude de Movimento Articular , Reoperação , Estudos Retrospectivos
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