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1.
Antioxidants (Basel) ; 13(1)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38275649

RESUMO

OBJECTIVES: This study investigates the role of retinol binding protein 4 (RBP4) in an articular context. RBP4, a vitamin A transporter, is linked to various metabolic diseases. METHODS: Synovial fluid RBP4 levels were assessed in crystalline arthritis (CA) patients using ELISA. RBP4's impact on articular cell types was analysed in vitro through RT-PCR and flow cytometry. Proteomic analysis was conducted on primary human osteoarthritis chondrocytes (hOACs). RESULTS: Synovial fluid RBP4 concentrations in CA patients correlated positively with glucose levels and negatively with synovial leukocyte count and were elevated in hypertensive patients. In vitro, these RBP4 concentrations activated neutrophils, induced the expression of inflammatory factors in hOACs as well as synoviocytes, and triggered proteomic changes consistent with inflammation. Moreover, they increased catabolism and decreased anabolism, mitochondrial dysfunction, and glycolysis promotion. Both in silico and in vitro experiments suggested that RBP4 acts through TLR4. CONCLUSIONS: This study identifies relevant RBP4 concentrations in CA patients' synovial fluids, linking them to hypertensive patients with a metabolic disruption. Evidence is provided that RBP4 acts as a DAMP at these concentrations, inducing robust inflammatory, catabolic, chemotactic, and metabolic responses in chondrocytes, synoviocytes, and neutrophils. These effects may explain RBP4-related metabolic diseases' contribution to joint destruction in various rheumatic conditions like CA.

2.
Nutrients ; 15(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447284

RESUMO

Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1ß for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.


Assuntos
Cerveja , Condrócitos , Polifenóis , Polifenóis/farmacologia , Condrócitos/efeitos dos fármacos , Células Cultivadas , Inflamação , Animais , Camundongos , Sobrevivência Celular , Diferenciação Celular , Simulação de Acoplamento Molecular , Receptores de Estrogênio
3.
Int J Mol Sci ; 24(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36835608

RESUMO

It is well known that patients with attention deficit hyperactivity disorder treated with stimulants, such as methylphenidate hydrochloride (MPH), have reduced height and weight. Even though MPH has an anorexigenic effect, an additional impact of this drug on the growth plate cannot be discarded. In this study, we aimed to determine the cellular effect of MPH on an in vitro growth plate model. We tested the effects of MPH on the viability and proliferation of a prechondrogenic cell line via an MTT assay. In vitro differentiation of this cell line was performed, and cell differentiation was evaluated through the expression of cartilage- and bone-related genes as measured via RT-PCR. MPH did not alter the viability or proliferation of prechondrogenic cells. However, it reduced the expression of cartilage extracellular matrix-related genes (type II collagen and aggrecan) and increased the expression of genes involved in growth plate calcification (Runx2, type I collagen, and osteocalcin) at different phases of their differentiation process. Our results evidence that MPH upregulates genes associated with growth plate hypertrophic differentiation. This may induce premature closure of the growth plate, which would contribute to the growth retardation that has been described to be induced by this drug.


Assuntos
Estimulantes do Sistema Nervoso Central , Lâmina de Crescimento , Metilfenidato , Osteogênese , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Lâmina de Crescimento/efeitos dos fármacos , Metilfenidato/efeitos adversos , Osteogênese/efeitos dos fármacos , Células Cultivadas
4.
Antioxidants (Basel) ; 12(2)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36829930

RESUMO

Osteoarthritis (OA) is hallmarked as a silent progressive rheumatic disease of the whole joint. The accumulation of inflammatory and catabolic factors such as IL6, TNFα, and COX2 drives the OA pathophysiology into cartilage degradation, synovia inflammation, and bone destruction. There is no clinical available OA treatment. Although traditional ayurvedic medicine has been using Boswellia serrata extracts (BSE) as an antirheumatic treatment for a millennium, none of the BSE components have been clinically approved. Recently, ß boswellic acid (BBA) has been shown to reduce in vivo OA-cartilage loss through an unknown mechanism. We used computational pharmacology, proteomics, transcriptomics, and metabolomics to present solid evidence of BBA therapeutic properties in mouse and primary human OA joint cells. Specifically, BBA binds to the innate immune receptor Toll-like Receptor 4 (TLR4) complex and inhibits both TLR4 and Interleukin 1 Receptor (IL1R) signaling in OA chondrocytes, osteoblasts, and synoviocytes. Moreover, BBA inhibition of TLR4/IL1R downregulated reactive oxygen species (ROS) synthesis and MAPK p38/NFκB, NLRP3, IFNαß, TNF, and ECM-related pathways. Altogether, we present a solid bulk of evidence that BBA blocks OA innate immune responses and could be transferred into the clinic as an alimentary supplement or as a therapeutic tool after clinical trial evaluations.

5.
Biomed Pharmacother ; 155: 113671, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36108390

RESUMO

Osteoarthritis (OA) affects more than 300 million people worldwide and it is about to become the first disabling disease. OA is characterized by the progressive degradation of the articular cartilage but is a disease of the whole joint. Articular innate immune responses (IIR) associated with tissue degradation contribute to its progression. However, no treatment is available to block these IIRs. Through data text mining and computational pharmacology, we identified two clinical available drugs, naloxone, and thalidomide, with potential inhibitory properties on toll-like receptor 4 (TLR4), a major activator of these IIR. Proteome analysis confirmed that activation of this receptor or the IL1 receptor generated OA-like and gout-like proteomic changes in human primary chondrocytes. Both compounds were found to block TLR4 complex and inhibit TLR4 and IL1R-mediated IIR in OA chondrocytes, osteoblasts, and synoviocytes. Furthermore, naloxone and thalidomide inhibitory effects involved the downregulation of the NLRP3 inflammasome pathway, which is downstream of TLR4/IL1R signaling. We demonstrated that these compounds, within a therapeutic range of concentrations, exhibited anti-inflammatory and anti-catabolic properties in joint primary OA cells without any toxic effect. This data underpins naloxone & thalidomide repurpose to treat OA-associated inflammatory responses.


Assuntos
Osteoartrite , Receptor 4 Toll-Like , Humanos , Condrócitos/metabolismo , Reposicionamento de Medicamentos , Imunidade Inata , Inflamassomos/metabolismo , Naloxona/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoartrite/metabolismo , Proteoma/metabolismo , Proteômica , Receptores de Interleucina-1/metabolismo , Talidomida/farmacologia , Receptor 4 Toll-Like/metabolismo , Interleucina-1/metabolismo
6.
Spine J ; 22(6): 1016-1027, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34906741

RESUMO

BACKGROUND CONTEXT: Modernization of 3D printing has allowed for the production of porous titanium interbody cages (3D-pTi) which purportedly optimize implant characteristics and increase osseointegration; however, this remains largely unstudied in vivo. PURPOSE: To compare osseointegration of three-dimensional (3D) titanium cages without bone graft and Polyether-ether-ketone (PEEK) interbody cages with autologous iliac crest bone graft (AICBG). STUDY DESIGN: Animal study utilizing an ovine in vivo model of lumbar fusion. METHODS: Interbody cages of PEEK or 3D-pTi supplied by Spineart SA (Geneva, Switzerland) were implanted in seven living sheep at L2-L3 and L4-L5, leaving the intervening disc space untreated. Both implant materials were used in each sheep and randomized to the aforementioned disc spaces. Computed tomography (CT) was obtained at 4 weeks and 8 weeks. MicroCT and histological sections were obtained to evaluate osseointegration. RESULTS: MicroCT demonstrated osseous in-growth of native cancellous bone in the trabecular architecture of the 3D-pTi interbody cages and no interaction between the PEEK cages with the surrounding native bone. Qualitative histology revealed robust osseointegration in 3D-pTi implants and negligible osseointegration with localized fibrosis in PEEK implants. Evidence of intramembranous and endochondral ossification was apparent with the 3D-pTi cages. Quantitative histometric bone implant contact demonstrated significantly more contact in the 3D-pTi implants versus PEEK (p<.001); region of interest calculations also demonstrated significantly greater osseous and cartilaginous interdigitation at the implant-native bone interface with the 3D-pTi cages (p=.008 and p=.015, respectively). CONCLUSIONS: 3D-pTi interbody cages without bone graft outperform PEEK interbody cages with AICBG in terms of osseointegration at 4 and 8 weeks postoperatively in an ovine lumbar fusion model. CLINICAL SIGNIFICANCE: 3D-pTi interbody cages demonstrated early and robust osseointegration without any bone graft or additive osteoinductive agents. This may yield early stability in anterior lumbar arthrodesis and potentially bolster the rate of successful fusion. This could be of particular advantage in patients with spinal neoplasms needing post-ablative arthrodesis, where local autograft use would be ill advised.


Assuntos
Fusão Vertebral , Titânio , Animais , Autoenxertos , Benzofenonas , Cetonas , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Modelos Animais , Polietilenoglicóis/farmacologia , Polímeros , Impressão Tridimensional , Ovinos , Fusão Vertebral/métodos
7.
Br J Pharmacol ; 179(2): 270-286, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34643941

RESUMO

BACKGROUND AND PURPOSE: Osteoarthritis, a major cause of disability in developed countries does not have effective treatment. Activation of TLR4 and innate immune response factors contribute to osteoarthritis progressive cartilage degradation. There are no clinically available TLR4 inhibitors. Interestingly, the antidepressant amitriptyline could block this receptor. Thus, we evaluated amitriptyline anti-TLR4 effects on human osteoarthritis chondrocytes in order to repurpose it as an inhibitor of innate immune response in joint inflammatory pathologies. EXPERIMENTAL APPROACH: Using in silico docking analysis, RT-PCR, siRNA, elisa, proteomics and clinical data mining of drug consumption, we explored the clinical relevance of amitriptyline blockade of TLR4-mediated innate immune responses in human osteoarthritis chondrocytes. KEY RESULTS: Amitriptyline bound TLR4 but not IL-1 receptor. Interestingly, amitriptyline binding to TLR4 inhibited TLR4- and IL-1 receptor-mediated innate immune responses in human osteoarthritis chondrocytes, synoviocytes and osteoblasts cells. Amitriptyline reduced basal innate immune responses and promoted anabolic effects in human osteoarthritis chondrocytes. Supporting its anti-innate immune response effects, amitriptyline down-regulated basal and induced expression of NLRP3, an inflammasome member from IL-1 receptor signalling linked to osteoarthritis and gout pathologies. Accordingly, mining of dissociated and aggregated drug consumption data from 107,172 elderly patients (>65 years) revealed that amitriptyline consumption was significantly associated with lower colchicine consumption associated with inflammatory gout flare treatment. CONCLUSION AND IMPLICATIONS: Amitriptyline blocks TLR4-, IL-1 receptor and NLRP3-dependent innate immune responses. This together with clinical data amitriptyline could be repurposed for systemic or local innate immune response management in diverse joint inflammatory pathologies.


Assuntos
Gota , Osteoartrite , Idoso , Amitriptilina/efeitos adversos , Condrócitos/metabolismo , Gota/metabolismo , Gota/patologia , Humanos , Imunidade Inata , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoartrite/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/uso terapêutico , Exacerbação dos Sintomas , Receptor 4 Toll-Like/metabolismo
8.
Biomedicines ; 11(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36672539

RESUMO

Adipogenesis-osteoblastogenesis balance-rupture is relevant in multiple diseases. Current human mesenchymal stem cells (hMSCs) in vitro differentiation models are expensive, and are hardly reproducible. Their scarcity and variability make an affordable and reliable method to study adipocyte-osteoblast-equilibrium difficult. Moreover, media composition has been inconstant throughout the literature. Our aims were to compare improved differentiation lab-made media with consensus/commercial media, and to identify a cell-line to simultaneously evaluate both MSCs differentiations. Lab-made media were compared with consensus and commercial media in C3H10T1/2 and hMSC, respectively. Lab-made media were tested on aged women primary pre-osteoblast-like cells. To determine the optimum cell line, C3H10T1/2 and hMSC-TERT cells were differentiated to both cell fates. Differentiation processes were evaluated by adipocytic and osteoblastic gene-markers expression and staining. Lab-made media significantly increased consensus medium induction and overcame commercial media in hMSCs differentiation to adipocytes and osteoblasts. Pre-osteoblast-like cells only properly differentiate to adipocyte. Lab-made media promoted adipocyte gene-markers expression in C3H10T1/2 and hMSC-TERT, and osteoblast gene-markers in C3H10T1/2. Oil Red O and Alizarin Red staining supported these findings. Optimized lab-made media were better at differentiating MSCs compared to consensus/commercial media, and evidenced the adipogenic commitment of pre-osteoblast-like cells from aged-women. C3H10T1/2 is an optimum MSC line by which to study adipocyte-osteoblast differentiation balance.

9.
J Clin Med ; 9(4)2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32325753

RESUMO

Osteoarthritis (OA), the most common chronic rheumatic disease, is mainly characterized by a progressive degradation of the hyaline articular cartilage, which is essential for correct joint function, lubrication, and resistance. Articular cartilage disturbances lead to joint failure, pain, and disability. Hyaline cartilage is also present in the growth plate and plays a key role in longitudinal bone growth. Alterations of this cartilage by diverse pathologies have been related to longitudinal bone growth inhibition (LBGI), which leads to growth retardation. Diet can play a crucial role in processes involved in the OA and LBGI's onset and evolution. Specifically, there is ample evidence pointing to the negative impacts of caffeine consumption on hyaline cartilage. However, its effects on these tissues have not been reviewed. Accordingly, in this review, we summarize all current knowledge in the PubMed database about caffeine catabolic effects on articular and growth plate cartilage. Specifically, we focus on the correlation between OA and LBGI with caffeine prenatal or direct exposure. Overall, there is ample evidence indicating that caffeine intake negatively affects the physiology of both articular and growth plate cartilage, increasing consumers predisposition to suffer OA and LBGI. As a result, caffeine consumption should be avoided for these pathologies.

10.
J Bone Jt Infect ; 4(4): 155-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555500

RESUMO

Introduction: Fracture-related infections (FRIs) are a devastating complication. FRIs are challenging and should be addressed with a multidisciplinary approach. An FRI should be addressed surgically by non-viable bone debridement, local antibiotic deposition, minimization of dead space and fracture stabilization. Antibiotic-laden PMMA-covered nails are a viable option to face these complications. To demonstrate the safety and utility of commercially available antibiotic-laden PMMA-covered nails, we performed a review of the cases operated in our institution and a cost analysis to compare the cost of a commercial nail to other available alternatives. Material and methods: We designed a retrospective study of consecutive cases to demonstrate the safety and efficacy of antibiotic-laden PMMA-covered commercial nails and designed a cost analysis of commercial coated nails compared to other custom-made alternatives. Results: We treated seven tibias and three femurs. Nine patients fully fit the criteria for FRI. There was one case of reintervention because of persistent drainage. All fractures healed, and in the first year post-intervention, there were no signs or symptoms of infection. There were no complications related to the commercially available nail that was used. There is a small increase in the direct quantifiable cost in commercially available nails, but non-quantifiable cost should be assessed individually. Conclusions: Commercially available antibiotic-laden PMMA-covered nails are a safe and useful treatment option for complicated cases of lower limb long bone reconstruction. The low complication rate and the straightforward technique compensate for the direct cost increase in most situations.

11.
J Clin Med ; 8(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394795

RESUMO

Musculoskeletal pathologies (MSPs) such as osteoarthritis (OA) and osteoporosis (OP), are a set of disorders that cause severe pain, motion difficulties, and even permanent disability. In developed countries, the current incidence of MSPs reaches about one in four adults and keeps escalating as a consequence of aging and sedentarism. Interestingly, OA and OP have been closely related to similar risk factors, including aging, metabolic alterations, and inflammation. Visfatin, an adipokine with an inflammatory and catabolic profile, has been associated with several OA and OP metabolic risk factors, such as obesity, insulin resistance, and type II diabetes. Furthermore, visfatin has been associated with the innate immune receptor toll-like receptor 4 (TLR4), which plays a key role in cartilage and bone inflammatory and catabolic responses. Moreover, visfatin has been related to several OA and OP pathologic features. The aim of this work is to bring together basic and clinical data regarding the common role of visfatin in these pathologies and their major shared risk factors. Finally, we discuss the pitfalls of visfatin as a potential biomarker and therapeutic target in both pathologies.

12.
Expert Opin Ther Targets ; 23(7): 607-618, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31074669

RESUMO

Introduction: The rising prevalence of musculoskeletal pathologies in developed countries has caused a dramatic impact on social welfare. Amidst these musculoskeletal pathologies is Rheumatoid arthritis (RA), a chronic systemic autoimmune disease that mostly affects the synovium. RA metabolic-associated alterations, including distorted adipokine production, enhance RA inflammatory environment. Among the altered adipokines, visfatin is particularly involved in RA inflammation and catabolism and stands out as an essential enzyme linked to critical cell features. Areas covered: We discuss the potential mechanism supporting the contribution of visfatin to RA and the association between RA and obesity. We discuss the repurposing of cancer-tested drugs to inhibit visfatin in the context of RA. Additionally, we address the possibility of combining these drugs with current RA therapy. Finally, we explore the future of visfatin as an RA biomarker or therapeutic target. Expert opinion: Inhibition of visfatin has become an interesting therapeutic approach for RA pathology. Such a feat has already been attained in oncology using small molecule inhibitors, which suggest that a similar course of action would be worth pursuing in the RA context. Visfatin will become an important biomarker and therapeutic target for RA.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Citocinas/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Animais , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Citocinas/metabolismo , Humanos , Nicotinamida Fosforribosiltransferase/metabolismo
13.
J Shoulder Elbow Surg ; 28(1): 48-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30111502

RESUMO

BACKGROUND: Proximal humeral fractures are common and a major concern in public health resources utilization. There is an increase in the use of reverse total shoulder arthroplasty (RTSA) as an option for complex fractures in the elderly. The complexity of the technique in RTSA is increased because of the fracture. To find an advantage of locking stems in RTSA for the treatment of proximal humeral fractures, we designed a comparative study between fracture-dedicated locking stems vs. cemented stems. MATERIALS AND METHODS: We retrospectively studied 58 patients treated with an RTSA after a fracture. We compared how the implant design and the tuberosity consolidation affects patient outcome through measuring range of motion and the Constant score. RESULTS: The groups were similar in age, sex, time to surgery, and Constant score in the uninjured side. Patients treated with a dedicated locking noncemented stem performed better, with an increased Constant score (P > .05) and reached more mobility with no statistical significance. We found that 13 of the 24 fractures (54%) treated with a cemented stem consolidated, and 26 of 34 tuberosities (76%) healed in the noncemented locked stems. Patients with tuberosity consolidation acquired better range of motion and Constant scores (P < .05). CONCLUSIONS: A dedicated stem improves tuberosity healing and increases outcomes seen in Constant scores. Tuberosity consolidation is a main goal when treating proximal humeral fractures with RTSA.


Assuntos
Artroplastia do Ombro/instrumentação , Fraturas do Ombro/cirurgia , Prótese de Ombro , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
14.
Injury ; 50(2): 415-419, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30503226

RESUMO

PURPOSE: Antegrade intramedullary nailing is an alternative for humeral shaft fracture treatment. This surgical technique can be especially demanding in some fracture patterns, leading to problems like malunion and non-union. The purpose of our study is to demonstrate that the use of a nail with cerclage wires could be a safe procedure that facilitate reduction, specially in fractures with abduction of the proximal fragment. MATERIALS AND METHODS: Fifty-six patients were included, from January 2007 to March 2016. In this cohort forty-two patients were females and eighteen males; mean age was sixty-seven (32-89). The fractures were reduced using a cerclage wire through a small lateral or anterior approach, then, antegrade intramedullary nailing was performed. Fracture healing was established by clinical and radiographic evaluation. Shoulder function was assessed using the Constant Score. RESULTS: Fifty-three patients healed (94.6%) adequately. Two patients developed a non-union (3.5%). One patient developed an infection (1.8%). Transient radial nerve palsy was observed in two patients (3.5%). The mean Constant Score at the end of the study was 70 points (range from 34 to 98 points). CONCLUSIONS: Surgical treatment of humeral shaft fractures with cerclage wire and intramedullary nailing is a safe technique to improve fracture reduction. The use of cerclage wires leads to better bone contact while minimizing malunions. The rate of non-union in our study is lower than the rate reported in the literature for humeral shaft fractures treated by intramedullary nailing alone.


Assuntos
Fios Ortopédicos , Fixação Intramedular de Fraturas , Consolidação da Fratura/fisiologia , Fraturas do Úmero/cirurgia , Fraturas do Ombro/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoroscopia , Fixação de Fratura , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/fisiopatologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/fisiopatologia , Resultado do Tratamento
15.
Front Physiol ; 9: 504, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867550

RESUMO

Inflammation is a process whose main function is to fight against invading pathogens or foreign agents. Nonetheless, it is widely accepted that inflammation takes part in multiple processes in a physiological or pathophysiological context. Among these processes the inflammation has been closely related to bone metabolism. It is well-known that in systemic inflammatory diseases such as rheumatoid arthritis the inflammatory environment contributes to the reduction of the bone mineral density. This has been further evidenced in different animals models of osteoporosis where the deletion of key inflammatory molecules dramatically reduced the bone loss. On the contrary, it is also well-known that certain degree of inflammation is required to allow bone fractures healing. In fact, excessive use of anti-inflammatory drugs inhibits bone fracture consolidation. The innate immune responses (IIRs) contribute to the development and maintenance of the inflammation. These responses have been observed in cells of the musculoskeletal system. Chondrocytes and osteoblasts are equipped with the molecular repertoire necessary to setting up these IIR, including the expression of several toll-like receptors. Specifically, toll-like receptor 4 (TLR4) activation in mesenchymal stem cells, osteoblasts, and osteocytes has been involved in catabolic and anabolic process. Accordingly, in this review we have summarized the current knowledge about the physiology of TLR4, including its signaling, and its endogenous agonists. In addition we have focused on its role on osteoblast metabolism and function.

16.
Eur Spine J ; 27(11): 2738-2744, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29926212

RESUMO

PURPOSE: Lateral mass screws combined with rods are the standard method for posterior cervical spine subaxial fixation. Several techniques have been described, among which the most used are Roy Camille, Magerl, Anderson and An. All of them are based on tridimensional angles. Reliability of freehand angle estimation remains poorly investigated. We propose a new technique based on on-site spatial references and compare it with previously described ones assessing screw length and neurovascular potential complications. METHODS: Four different lateral mass screw insertion techniques (Magerl, Anderson, An and the new described technique) were performed bilaterally, from C3 to C6, in ten human spine specimens. A drill tip guide wire was inserted as originally described for each trajectory, and screw length was measured. Exit point was examined, and potential vertebral artery or nerve root injury was assessed. RESULTS: Mean screw length was 14.05 mm using Magerl's technique, 13.47 mm using Anderson's, 12.8 mm using An's and 17.03 mm using the new technique. Data analysis showed significantly longer lateral mass screw length using the new technique (p value < 0.00001). Nerve potential injury occurred 37 times using Magerl's technique, 28 using Anderson's, 13 using An's and twice using the new technique. Vertebral artery potential injury occurred once using Magerl's technique, 8 times using Anderson's and none using either An's or the new proposed technique. The risk of neurovascular complication was significantly lower using the new technique (p value < 0.01). CONCLUSION: The new proposed technique allows for longer screws, maximizing purchase and stability, while lowering the complication rate.


Assuntos
Parafusos Ósseos , Vértebras Cervicais , Fusão Vertebral , Vértebras Cervicais/anatomia & histologia , Vértebras Cervicais/cirurgia , Humanos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos
17.
Eur J Orthop Surg Traumatol ; 26(1): 27-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26126588

RESUMO

Paget's disease of bone (PDB) is a disease characterized by a disorder in the bone metabolism. The spine is the second region affected after the pelvis. Surgical treatment is reserved for cases refractory to medical treatment. We performed a systematic review of patients with Paget disease of bone affecting the spine, treated surgically in the last 30 years. The main objective of the review is to find out indications for surgery, outcomes of these patients and also the standard perioperative management.


Assuntos
Osteíte Deformante/cirurgia , Doenças da Coluna Vertebral/cirurgia , Cimentos Ósseos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Vértebras Cervicais/cirurgia , Difosfonatos/uso terapêutico , Humanos , Vértebras Lombares/cirurgia , Polimetil Metacrilato/uso terapêutico , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Vértebras Torácicas/cirurgia , Resultado do Tratamento
18.
Eur J Orthop Surg Traumatol ; 25(4): 661-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25249480

RESUMO

Periprosthetic knee fractures following total knee arthroplasty are increasing proportionally to the number of primary procedures done. We performed a retrospective review of Rorabeck type II fractures treated with a retrograde nail, trying to find the relationship between failure and the number of distal locking screws used. Twenty-six patients were included. The number of distal interlocking screws (patients with one or two distal interlocking screws and patients with three screws) correlated with nonunion (p < 0.1), did not correlate with the malunion rate (p > 0.1) and correlated with the reintervention rate (p < 0.1).


Assuntos
Artroplastia do Joelho/instrumentação , Pinos Ortopédicos/efeitos adversos , Parafusos Ósseos/efeitos adversos , Fraturas não Consolidadas/etiologia , Fraturas Periprotéticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Feminino , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Humanos , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Falha de Prótese/etiologia , Infecções Relacionadas à Prótese/etiologia , Reoperação , Estudos Retrospectivos , Fatores de Risco
19.
Eur J Orthop Surg Traumatol ; 23(2): 125-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23412442

RESUMO

Open fractures constitute a major trauma mostly sustained by young adults during high-energy injuries. Management of long bone open fractures is a very complex issue and is often complicated by nonunion and deep infection being among the most devastating and difficult to cure. It is generally recommended that wound debridement and stabilization of open fractures should be performed as early as possible, preferably within 6-8 h on the basis of historical comment and laboratory data. The rationale for this rule is believed to originate from Freidrich's historical study of guinea pigs. The literature lacks strong evidence addressing the primary issue of timing and delay on the incidence of deep infection and nonunion in open fractures. In the light of the actual literature regarding this topic, it seems that time to debridement of open fractures is not a prognostic factor of infection as well as nonunion.


Assuntos
Desbridamento/métodos , Fraturas Expostas/cirurgia , Humanos , Fatores de Tempo , Cicatrização , Infecção dos Ferimentos/prevenção & controle
20.
J Pediatr Orthop B ; 22(2): 148-52, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22561910

RESUMO

Juxta-epiphyseal/Salter-Harris fractures are the most common hand fractures in children and the proximal phalanx is involved in most cases. In the absence of soft-tissue interposition, these growth plate injuries are simple to reduce and are stable. However, in some cases, flexor tendon entrapment could be present. We report on an 11-year-old girl who sustained a fall onto her outstretched hand with subsequent injuries in her long, ring, and small fingers. Plain radiographs showed a severely displaced juxta-epiphyseal proximal phalanx fracture in her ring finger associated with mildly displaced juxta-epiphyseal proximal phalanx fractures of the long and small fingers. Fracture reduction could not be achieved after a closed reduction attempt. An open reduction and stabilization using Kirschner wires was performed in the fourth and fifth fingers, because of entrapment of the flexor digitorum profundus tendon. Excellent functional as well as radiological outcomes were achieved. These types of injuries are very uncommon and a high index of suspicion on the basis of clinical as well as radiological findings is needed to make an early diagnosis and for adequate treatment. Multiple proximal phalangeal fractures could be associated with the simultaneous entrapment of flexor tendons in different fingers as in our case; this is important to keep in mind as it is useful when planning the definitive surgical treatment and doing so will have a positive impact on the final functional as well as radiological outcomes.


Assuntos
Falanges dos Dedos da Mão/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Amplitude de Movimento Articular/fisiologia , Dedo em Gatilho/cirurgia , Acidentes por Quedas , Fios Ortopédicos , Criança , Feminino , Traumatismos dos Dedos/diagnóstico por imagem , Traumatismos dos Dedos/etiologia , Traumatismos dos Dedos/cirurgia , Falanges dos Dedos da Mão/cirurgia , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/diagnóstico por imagem , Força da Mão , Humanos , Radiografia , Recuperação de Função Fisiológica , Medição de Risco , Futebol/lesões , Resultado do Tratamento , Dedo em Gatilho/diagnóstico por imagem
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