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1.
Orthopade ; 48(11): 949-956, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31515589

RESUMO

Calcification in hyaline and fibrocartilage is caused by the deposition of calcium pyrophosphate dehydrate, commonly referred to as chondrocalcinosis. Clinically, this can lead to arthritis symptoms similar to a gout attack -"pseudogout". Nonetheless, also chronic or asymptomatic disease courses are possible. The prevalence of chondrocalcinosis increases with age. The diagnostic workup of degenerative joint disease, therefore, often reveals calcifications of articular cartilage as harmless incidental findings. However, particularly in patients younger than 60 years of age, chondrocalcinosis can be the symptom of an underlying metabolic disease. This review article highlights these rare diseases and presents unusual manifestations of chondrocalcinosis.


Assuntos
Pirofosfato de Cálcio/metabolismo , Condrocalcinose/diagnóstico , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Humanos , Articulações/patologia , Pessoa de Meia-Idade , Osteoartrite/patologia , Doenças Raras
2.
Toxicol Lett ; 314: 18-26, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299270

RESUMO

Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFß) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFß signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFß signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention.


Assuntos
Articulações/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Osteoartrite/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fatores Etários , Agrecanas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Feminino , Idade Gestacional , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulações/metabolismo , Articulações/patologia , Masculino , Exposição Materna , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Gravidez , Ratos Wistar , Fatores de Risco , Fatores Sexuais
3.
Acta Vet Scand ; 61(1): 29, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221224

RESUMO

BACKGROUND: Owner questionnaires may be used to assess osteoarthritis (OA) in dogs. The validated American College of Veterinary Surgeons' (ACVS) Canine Orthopaedic Index Questionnaire quantifies quality of life in dogs with orthopaedic disease. This index was modified and translated into Swedish and evaluated for validity, reliability and sensitivity. One group with confirmed moderate elbow dysplasia (n = 117) and one healthy control group (n = 146) without radiographic elbow disease and without lameness were included. Telephone interviews with the dog owners were conducted throughout the study using owner-completed questionnaires. RESULTS: A 16-item questionnaire developed from an initial data set including 22 items, were able to differentiate between the affected group and the control group with good readability. Validity was measured through factor analysis which yielded a three-factor model accounting for 66.3% of the variance. Cronbach's α was 0.89 for the total instrument, > 0.7 for stiffness, lameness and function, but < 0.7 for quality of life. Based on the process the modified questionnaire can be used in Swedish, as the ACVS COI, to make intra-patient comparisons and evaluation of disease progression. CONCLUSIONS: A sound owner-completed questionnaire translated into Swedish and modified, able to differ healthy dogs from dogs suffering from chronic osteoarthritis is presented. Performed statistical analysis show the items of the instrument to be reasonable and have high construct validity. The questionnaire may be used in the clinical setting and for research.


Assuntos
Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Membro Anterior/patologia , Articulações/patologia , Osteoartrite/veterinária , Medicina Veterinária/métodos , Animais , Cães , Osteoartrite/diagnóstico , Medição da Dor/veterinária , Índice de Gravidade de Doença , Inquéritos e Questionários
4.
Georgian Med News ; (289): 73-77, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31215883

RESUMO

The aim of the study is to establish the features of the clinical course of psoriatic arthritis in children. 83 patients with psoriatic arthritis (PSA) were examined. The terms of formation of articular and skin syndromes in PSA in children, as well as options for the onset and height of the disease and features of the course in childhood were revealed. Based on the results of the study, it should be concluded that, in contrast to the literature data, the majority of patients with PSA disease debut falls on the age of 6.5 years, the disease begins with skin lesions and in the debut of the joint syndrome. 6-7 years later from the onset of the disease in patients have asymmetric oligoarthritis, spondylitis in combination with the lesion of peripheral joints, also revealed mutilatng arthritis, however, were the leaders of the symmetric rheumatoid option. It should be noted that all observed patients expressed periarticular osteoporosis, which is not typical for this pathology.


Assuntos
Artrite Psoriásica , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/patologia , Criança , Humanos , Articulações/patologia , Pele/patologia
5.
Int J Nanomedicine ; 14: 4145-4155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239673

RESUMO

Background: There is emerging evidence which suggests that cellular ROS including nitric oxide (NO) are important mediators for inflammation and osteoarthritis (OA). Water-soluble polyhydroxylated fullerene C60 (fullerol) nanoparticle has been demonstrated to have an outstanding ability to scavenge ROS. Purpose: The objective of this study is to assess the effects of fullerol on inflammation and OA by in vitro and in vivo studies. Methods: For in vitro experiments, primary mouse peritoneal macrophages and a macrophage cell line RAW264.7 were stimulated to inflammatory phenotypes by lipopolysaccharide (LPS) in the presence of fullerol. For the animal study, OA model was created by intra-articular injection of monoiodoacetate into the knee joints of rats and fullerol was intravenously injected immediately after OA induction. Results: NO production and pro-inflammatory gene expression induced by LPS was significantly diminished by fullerol in both macrophage cell types. Meanwhile, fullerol could remarkably reduce phosphorylation of p38 mitogen-activated protein kinase, and protein level of transcription factors nuclear factor-kappaB and forkhead box transcription factor 1 within the nucleus. The animal study delineated that systematic administration of fullerol prevented OA, inhibiting inflammation of synovial membranes and the damage toward the cartilage chondrocytes in the OA joints. Conclusion: Antioxidative fullerol may have a potential therapeutic application for OA.


Assuntos
Antioxidantes/farmacologia , Fulerenos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Nanopartículas/química , Osteoartrite/patologia , Animais , Células Cultivadas , Feminino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Articulações/efeitos dos fármacos , Articulações/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Modelos Biológicos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Osteoartrite/tratamento farmacológico , Células RAW 264.7 , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
6.
Pharm Res ; 36(7): 97, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31076925

RESUMO

PURPOSE: The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA). METHODS: A sialic acid - cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes. RESULTS: Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression. CONCLUSIONS: SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Dexametasona/farmacocinética , Lipossomos/química , Ácido N-Acetilneuramínico/química , Neutrófilos/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/toxicidade , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Colesterol/química , Dexametasona/administração & dosagem , Dexametasona/toxicidade , Liberação Controlada de Fármacos , Articulações/efeitos dos fármacos , Articulações/patologia , Selectina L/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Neutrófilos/patologia , Palmitatos/química , Ratos Wistar , Distribuição Tecidual
7.
Comput Methods Biomech Biomed Engin ; 22(10): 942-952, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31064209

RESUMO

Quantifying joint deformity in people with rheumatoid (RA) and psoriatic arthritis (PsA) remains challenging. Here, we demonstrate a new method to measure bone erosions and abnormal periosteal growths, based on the difference between a predicted healthy and actual diseased joint surface. We optimized the method by creating and measuring artificial bone erosions and growths. Then we measured 46 healthy and diseased patient surfaces. We found average sensitivity errors of ≤0.27 mm when measuring artificial erosions and growths. Patients had significantly more bone erosion than healthy subjects. Surface based outcomes are a novel way to interpret and quantify bone changes in PsA and RA.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/patologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Processamento de Imagem Assistida por Computador , Articulações/diagnóstico por imagem , Articulações/patologia , Algoritmos , Estudos de Coortes , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Periósteo/diagnóstico por imagem , Periósteo/crescimento & desenvolvimento , Periósteo/patologia , Projetos Piloto
8.
Scand J Immunol ; 90(2): e12792, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31141193

RESUMO

Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21-/low B cells). In this study, we sought to determine whether there was any correlation between CD21-/low B cells and clinical outcome in patients with established RA, either ACPA+ /RF+ (n = 27) or ACPA- /RF- (n = 10). Healthy donors (n = 17) were included as controls. The proportion of the CD21-/low CD27- IgD- memory B cell subset in peripheral blood (PB) was significantly increased in ACPA+ /RF+ RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r = 0.57, P < 0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21-/low cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21-/low , approximately 40% of that population was CD27- IgD- , and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor κB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27- IgD- subset of CD21-/low B cells may mediate joint destruction in patients with ACPA+ /RF+ RA.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Subpopulações de Linfócitos B/imunologia , Imunoglobulina D/metabolismo , Receptores de Complemento 3d/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto , Quimiocina CXCL10/sangue , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/sangue , Quimiocina CXCL9/metabolismo , Feminino , Humanos , Articulações/imunologia , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Ligante RANK/biossíntese , Receptores CXCR3/biossíntese , Líquido Sinovial/metabolismo
9.
Blood Coagul Fibrinolysis ; 30(3): 111-119, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30958454

RESUMO

: Arthrocentesis of an acute hemarthrosis in hemophilia remains a controversial issue. The purpose of this study is to define the role that joint aspiration can play in the recovery from acute hemarthrosis in patients with hemophilia. The study sample included 33 hemophilic patients (55 joints) with acute elbow, knee, and ankle hemarthrosis as confirmed by ultrasonography. Patients were distributed into a treatment group and a control group. Patients in the first group were subjected to joint aspiration, whereas patients in the second were not. Arthrocentesis was carried out immediately after diagnosis of acute hemarthrosis in liquid phase. Patients were infused with the deficient coagulation factor and were instructed to observe relative rest until resolution of hemarthrosis. The following parameters were analyzed: time to full resolution of hemarthrosis (determined by ultrasonography), duration of treatment with the deficient coagulation factor, time to pain relief, time to recovery of prebleed range of motion, and time to resumption of school/work (all of these measured in days). The joints treated with joint aspiration exhibited a significantly faster resolution of bleeding (fewer days). In addition, this group required fewer days of pharmacological treatment, with faster achievement of functional recovery and resumption of school/work activities. No complications were observed. This study shows that joint aspiration under hemostatic cover and in strictly aseptic conditions is a well-tolerated technique that makes the recovery of acute hemarthrosis of hemophilic patients faster.


Assuntos
Artrocentese/métodos , Hemartrose/terapia , Hemofilia A/complicações , Articulações/patologia , Doença Aguda , Adulto , Articulação do Tornozelo , Articulação do Cotovelo , Feminino , Hemartrose/cirurgia , Humanos , Articulação do Joelho , Masculino , Fatores de Tempo , Resultado do Tratamento
10.
Nutrients ; 11(4)2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959746

RESUMO

Lactobacillus strains have shown efficacy in attenuating inflammation. This study evaluated the potential of Lactobacillus fermentum PC1 for the treatment of rheumatoid arthritis (RA) using a murine model of collagen-induced arthritis. On Day 1, healthy DBA/1 mice (six to eight weeks of age) were immunized, with 100 µg of Chicken Type 11 collagen emulsified in complete Freund's adjuvant (CFA) by intradermal injection, at the base of the tail. On Day 21, the mice were immunized intraperitoneally with 100 µg of Bovine Type11 collagen in phosphate buffered saline (PBS). On Day 28, the mice were immunized intraperitoneally with 50 µg of lipopolysaccharide (LPS). Viable L. fermentum PC1 (1 × 108 colony forming units) was given daily from Day two until the end of the experiment. From Day 21 onwards, the mice were monitored daily for clinical signs of arthritis. On Day 44, the experiment was terminated. Paws were obtained for histology and serum for cytokine assays. L. fermentum PC1-fed mice had significantly reduced paw inflammation as well as decreased synovial infiltration and less cartilage damage. Circulating serum cytokine profiles revealed decreased IL-12 and increased anti-inflammatory cytokines, namely IL-4 and IL-10. Thus, early administration of L. fermentum PC1 could prove to be a valuable therapeutic agent in the management of RA.


Assuntos
Artrite Experimental/induzido quimicamente , Colágeno Tipo II/toxicidade , Inflamação/tratamento farmacológico , Lactobacillus fermentum/fisiologia , Probióticos/farmacologia , Animais , Artrite Experimental/terapia , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA
11.
Lancet Haematol ; 6(6): e295-e305, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31003963

RESUMO

BACKGROUND: Emicizumab, a subcutaneously administered, humanised, bispecific, monoclonal antibody, is approved to treat people with haemophilia A of all ages with and without coagulation factor VIII (FVIII) inhibitors. HAVEN 4 assessed emicizumab prophylaxis administered as one dose every 4 weeks in adults and adolescents with haemophilia A, regardless of FVIII inhibitor status. METHODS: In this phase 3, multicentre, open-label, two-stage study, patients aged 12 years and older with severe congenital haemophilia A (<1% of normal FVIII activity in blood) or haemophilia A with FVIII inhibitors, undergoing treatment with either FVIII concentrates or bypassing agents were recruited from three sites in Japan and Spain for a run-in cohort, and from 17 sites in Australia, Belgium, Japan, Poland, Spain, and the USA for a subsequent expansion cohort. Participants in the run-in and expansion cohorts were given emicizumab subcutaneously 6 mg/kg every 4 weeks for 24 weeks or more; for patients in the expansion cohort this regimen was preceded by four loading doses of 3 mg/kg once weekly. In the run-in cohort, we assessed pharmacokinetics after single and multiple (every 4 weeks) subcutaneous administration of 6 mg/kg emicizumab and safety. In the expansion cohort, the efficacy endpoint was efficacy of prophylactic emicizumab in maintaining adequate bleed prevention, assessed in all patients who received at least one dose of emicizumab and reported as annualised bleed rates for treated bleeds, all bleeds (treated and untreated), treated spontaneous bleeds, treated joint bleeds, and treated target joint bleeds. Safety was assessed in all participants given emicizumab. This study is registered with ClinicalTrials.gov, number NCT03020160, and is ongoing. FINDINGS: Between Jan 30, 2017, and Feb 27, 2017, seven patients were enrolled into the initial run-in cohort, which confirmed the expected pharmacokinetic profile and safety of the regimen based on model-based simulations, providing sufficient evidence for opening of the expansion cohort (n=41), which was recruited and enrolled between May 24, 2017, and June 30, 2017. The annualised rate of treated bleeds was 2·4 (95% CI 1·4-4·3). 23 (56·1%; 95% CI 39·7-71·5) of 41 reported no treated bleeds and 37 (90%; 76·9-97·3) reported zero to three treated bleeds. The annualised bleed rate was 4·5 (95% CI 3·1-6·6) for all bleeds, 0·6 (0·3-1·5), for treated spontaneous bleeds, 1·7 (0·8-3·7) for treated joint bleeds, and 1·0 (0·3-3·3) for treated target joint bleeds. The most frequent treatment-related adverse event was injection-site reaction (nine [22%] of 41 patients). We observed no thrombotic events or development of de-novo antidrug antibodies with neutralising potential or FVIII inhibitors. INTERPRETATION: Emicizumab given once every 4 weeks showed clinically meaningful bleed control while being well tolerated. This regimen could improve patient care by decreasing treatment burden and increasing adherence to effective prophylaxis, potentially decreasing the development of secondary complications for people with haemophilia A. FUNDING: F Hoffmann-La Roche and Chugai Pharmaceutical.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemofilia A/tratamento farmacológico , Adolescente , Adulto , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/farmacocinética , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Esquema de Medicação , Meia-Vida , Hemofilia A/patologia , Hemorragia/epidemiologia , Humanos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Nasofaringite/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
Lupus ; 28(5): 583-590, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30841789

RESUMO

Musculoskeletal manifestations are extremely common in patients with systemic lupus erythematosus. Transient and migratory arthralgia is frequently reported even without clinical signs of joint or tendon inflammation. In less than 15% of patients, joints may be more severely affected by deforming (Jaccoud's arthropathy) and/or erosive arthropathy (Rhupus syndrome). In recent years, ultrasound has emerged as a promising imaging technique for the assessment of musculoskeletal involvement in systemic lupus erythematosus, having demonstrated the ability to detect inflammation and structural damage both at articular and periarticular level. Recent ultrasound studies have also revealed new insights into musculoskeletal involvement in patients with systemic lupus erythematosus, some of them questioning the traditional concepts of systemic lupus erythematosus arthropathy, with potential clinical, prognostic and therapeutic implications. In daily clinical practice, the use of ultrasound in the assessment of joint and tendon involvement in patients with systemic lupus erythematosus is still limited. Several methodological issues encountered in ultrasound studies evaluating musculoskeletal involvement in systemic lupus erythematosus patients need to be addressed in order to improve both the reliability and clinical usefulness of ultrasound findings. This paper reviews ultrasound studies assessing musculoskeletal involvement in patients with systemic lupus erythematosus, highlighting certainty, limits, potential applications and future perspectives of ultrasound use in systemic lupus erythematosus patients.


Assuntos
Artropatias/patologia , Articulações/patologia , Lúpus Eritematoso Sistêmico/patologia , Sistema Musculoesquelético/fisiopatologia , Tendões/patologia , Humanos , Artropatias/diagnóstico por imagem , Articulações/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Reprodutibilidade dos Testes , Tendões/diagnóstico por imagem , Ultrassonografia
13.
ACS Appl Mater Interfaces ; 11(12): 11587-11601, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30844228

RESUMO

Intra-articular injection has unique advantages in the treatment of osteoarthritis (OA), although it risks rapid clearance of the therapeutic drugs in the joint cavity. Combining therapeutic agents with functionalized nanocarriers may provide an effective solution. Controlling the therapeutic concentration of the drug in the joint cavity through the drug-loading nanosystem can synergistically treat OA. Here, we proposed an intra-articular drug delivery nanosystem MoS2@CS@Dex (MCD), using the chitosan (CS)-modified molybdenum disulfide (MoS2) nanosheets as near-infrared (NIR) photo-responsive carriers, loaded with the anti-inflammatory drug dexamethasone (Dex). MCD responded to NIR light both in vitro and in vivo and triggered Dex release through photothermal conversion. This enabled the remote-controlled Dex release in the joint cavity by adjusting the radiation behavior of the NIR light. MCD prolonged the residence time of Dex in the joint cavity. The intra-articular injection of MCD in combination with NIR radiation ensured a significant increase in the therapeutic effect of Dex at low systemic doses, which attenuated the cartilage erosion in the OA caused by the secretion of inflammatory factors including TNF-α and IL-1ß. The toxicity and side effects on other internal organs during metabolism were reduced in the body. In addition, the photoacoustic imaging capability of MoS2 nanosheets was used to detect the metabolism of MCD in the joint cavity. Our research indicated that MCD has great potential to treat OA.


Assuntos
Dexametasona/química , Dissulfetos/química , Portadores de Fármacos/química , Raios Infravermelhos , Molibdênio/química , Nanoestruturas/química , Animais , Dexametasona/metabolismo , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Liberação Controlada de Fármacos , Interleucina-1beta/metabolismo , Articulações/efeitos dos fármacos , Articulações/patologia , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Osteoartrite/patologia , Osteoartrite/terapia , Fototerapia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
14.
Arch Dermatol Res ; 311(4): 265-275, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826961

RESUMO

Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. The latest EDS classification recognized 13 subtypes in which the clinical and genetic phenotypes are often overlapping, making the diagnosis rather difficult and strengthening the importance of the molecular diagnostic confirmation. New genetic techniques such as next-generation sequencing (NGS) gave the opportunity to identify the genetic bases of unresolved EDS types and support clinical counseling. To date, the molecular defects have been identified in 19 genes, mainly in those encoding collagen, its modifying enzymes or other constituents of the extracellular matrix (ECM). In this review we summarize the contribution of NGS technologies to the current knowledge of the genetic background in different EDS subtypes.


Assuntos
Colágeno/genética , Tecido Conjuntivo/fisiologia , Síndrome de Ehlers-Danlos/genética , Articulações/patologia , Pele/patologia , Colagenases/genética , Síndrome de Ehlers-Danlos/diagnóstico , Proteínas da Matriz Extracelular/genética , Aconselhamento Genético , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Instabilidade Articular , Mutação/genética , Patologia Molecular , Fenótipo
15.
Nanoscale ; 11(14): 6693-6709, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30900717

RESUMO

Although nitric oxide (NO) can be used to treat osteoarthritis (OA) by inhibiting inflammation, a method for the accurately controlled release of NO in inflammatory cells is still elusive. Herein, photothermal-triggered NO nanogenerators NO-Hb@siRNA@PLGA-PEG (NHsPP) were constructed by assembling photothermal-agents and NO molecules within nanoparticles. In the NHsPP nanoparticles the hemoglobin (Hb) nanoparticles can act as a NO carrier which can absorb near-infrared light at 650 nm (0.5 W cm-2) and convert it into heat to trigger the release of NO. Moreover, after loading Notch1-siRNA, precise treatment can be achieved. Furthermore, using the synergistic effect of photothermal therapy, the NHsPP nanoparticles achieved simultaneous treatment with NO, siRNA and PTT. Through this combination therapy, the therapeutic effect of the NHsPP nanoparticles was significantly enhanced compared to the treatment groups using only NO, siRNA or PTT. This combination therapy inhibits the inflammatory response effectively by reducing the level of pro-inflammatory cytokines and the macrophage response. Subsequently, guided by dual-modal imaging, the NHsPP nanoparticles can not only accumulate effectively in OA mice, but can also reduce the inflammatory response and efficiently prevent cartilage erosion, without causing toxic side effects in the major organs. Therefore, this novel photothermal nanoparticle-based NO-releasing system is expected to be a potential alternative for clinical inflammatory disease therapy and may provide image guidance when combined with other nanotherapy systems.


Assuntos
Nanopartículas/química , Óxido Nítrico/química , Osteoartrite/terapia , RNA Interferente Pequeno/química , Animais , Cartilagem/patologia , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Citocinas/metabolismo , Feminino , Hemoglobina A Glicada/química , Humanos , Raios Infravermelhos , Articulações/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico/farmacologia , Óxido Nítrico/uso terapêutico , Osteoartrite/patologia , Fototerapia , Polietilenoglicóis/química , Poliglactina 910/química , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Receptor Notch1/antagonistas & inibidores , Receptor Notch1/genética , Receptor Notch1/metabolismo
16.
EBioMedicine ; 41: 538-555, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30824383

RESUMO

BACKGROUND: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. METHODS: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. RESULTS: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. CONCLUSIONS: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.


Assuntos
Artrite Experimental/patologia , Artrite Reumatoide/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Articulações/metabolismo , Animais , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Proteínas Ativadoras de GTPase/metabolismo , Haplorrinos , Humanos , Inflamação/patologia , Inflamação/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Articulações/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo
17.
Arch Immunol Ther Exp (Warsz) ; 67(3): 153-160, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30874838

RESUMO

Rheumatoid arthritis (RA) is a common autoimmune disease which impacts a large number of patients worldwide, and new drugs are required for lower the disease burden. Theaflavin-3, 3'-digallate (TFDG) is polyphenol exhibiting inhibition on inflammatory factors. This study aimed to explore the attenuation of TFDG on RA. The collagen-induced arthritis (CIA) mouse model was established and administered with TFDG. The arthritis score and incidence was recorded to assess the amelioration of TFDG on arthritis. Histopathological change of the mouse joint tissues was evaluated by haemotoxylin and eosin staining. The expression of pro-inflammatory mediators including interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 was quantified by ELISA. The activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways in the synovium were determined by Western blotting. In comparison with the control, administration of TFDG significantly reduced arthritis score and incidence in the CIA mouse model. TFDG significantly suppressed the expression of IL-1ß, TNF-α, and IL-6, as well as the levels of MMP-1, MMP-2, and MMP-3 in the synovium. TFDG also showed remarkable inhibition on the activation of NF-κB and the phosphorylation of P38, JNK2, and ERK. This study puts up evidence that TFDG exerts protection on RA via inhibiting the activation of NF-κB- and MAPK-signaling pathways.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Biflavonoides/farmacologia , Catequina/farmacologia , Ácido Gálico/análogos & derivados , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Biflavonoides/uso terapêutico , Catequina/uso terapêutico , Colágeno/administração & dosagem , Colágeno/imunologia , Avaliação Pré-Clínica de Medicamentos , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Humanos , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Articulações/efeitos dos fármacos , Articulações/imunologia , Articulações/patologia , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/imunologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
18.
JAMA ; 321(5): 461-472, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721294

RESUMO

Importance: Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown. Objective: To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission. Design, Setting, and Participants: Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017. Interventions: Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission. Main Outcomes and Measures: Co-primary outcomes were proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life. Results: Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8% [1-sided 95% CI, -13.6% to + ∞; 1-sided P = .19]) and 49 (66%) vs 58 (62%), respectively, reached the primary radiographic end point (risk difference, 4.7% [1-sided 95% CI, -7.0% to + ∞; 1-sided P = .25). Of 10 key secondary end points, 8 were null and 2 showed statistically significant benefit for the MRI treat-to-target group. Seventeen patients (17%) in the MRI-guided treat-to-target group and 6 patients (6%) in the conventional treat-to-target group experienced serious adverse events. Conclusions and Relevance: Among patients with RA in clinical remission, an MRI-guided treat-to-target strategy compared with a conventional treat-to-target strategy did not result in improved disease activity remission rates or reduce radiographic progression. These findings do not support the use of an MRI-guided strategy for treating patients with RA. Trial Registration: ClinicalTrials.gov Identifier: NCT01656278.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Articulações/diagnóstico por imagem , Imagem por Ressonância Magnética , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Medula Óssea/patologia , Progressão da Doença , Edema/diagnóstico por imagem , Feminino , Humanos , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Osteíte/diagnóstico por imagem , Radiografia , Indução de Remissão
19.
Chiropr Man Therap ; 27: 8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792850

RESUMO

Background: Musculoskeletal pain frequently occurs in more than one body region, with up to 80% of adults reporting more than one joint pain site in the last 12 months. Older people and females are known to be more susceptible to multiple joint pain sites, however the association of multisite joint pain with physical and psychosocial functions in this population are unknown. Methods: Cross-sectional data from 579 women were analyzed. Women were asked "Which of your joints have been troublesome on most days of the past month?" Pain qualities were measured using the McGill Pain Questionnaire (Short Form) and PainDETECT, and health was assessed using the SF-36 and sociodemographic variables. Statistical analysis using generalized ordinal logistic regression included comparison of three joint pain groups: no joint pain, 1-4 sites of joint pain and ≥ 5 sites of joint pain. Results: Two thirds of respondents had multisite pain (>1 site), and one third had ≥5 joint pain sites. Compared to women with fewer joint pain sites, women with >5 joint pain sites (multisite joint pain) had significantly poorer physical and emotional health-related quality of life, more severe pain, a higher probability of neuropathic pain, and a longer duration of pain. More than half of women in the multisite joint pain group were still employed, statistically significantly more than women with no joint pain. In the final model, pain duration, the number of medications, pain intensity (discomforting and distressing) and the physical component of health-related quality of life were significantly associated with increased number of joint pain sites. Conclusions: Over one-third of older women in our sample had >5 painful joints in the last month. These women demonstrated significantly poorer psychosocial health, and increased medication use, than women with no or fewer sites of joint pain. Many women with multisite joint pain were still in the workforce, even when nearing retirement age. This study has important implications for future research into musculoskeletal pain, particularly in regards to womens health and wellbeing, and for clinical practice where there should be increased awareness of the implications of concurrent, multisite joint pain.


Assuntos
Artralgia/epidemiologia , Artralgia/psicologia , Idoso , Idoso de 80 Anos ou mais , Artralgia/patologia , Austrália/epidemiologia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Articulações/patologia , Modelos Logísticos , Saúde Mental , Pessoa de Meia-Idade , Manejo da Dor/psicologia , Medição da Dor , Qualidade de Vida , Inquéritos e Questionários
20.
JAAPA ; 32(3): 25-31, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30741851

RESUMO

Acute monoarthritis affects a single joint and has many potential underlying causes, including crystal deposition diseases, infection, trauma, and osteoarthritis. A comprehensive health history and physical examination can help narrow the list of differential diagnoses; judicious diagnostic testing can help pinpoint the diagnosis. Clinicians also must be able to recognize which patients require emergency referral to prevent long-term adverse consequences.


Assuntos
Artralgia/etiologia , Artrite/diagnóstico , Artrite/etiologia , Doença Aguda , Corticosteroides/efeitos adversos , Anticoagulantes/efeitos adversos , Artralgia/patologia , Artrite/classificação , Artrite/patologia , Artrite Infecciosa/complicações , Artrite Reumatoide/complicações , Vacina BCG/efeitos adversos , Condrocalcinose/complicações , Artropatias por Cristais/complicações , Diagnóstico Diferencial , Difosfonatos/efeitos adversos , Diuréticos/efeitos adversos , Gota/complicações , Humanos , Articulações/patologia , Osteoartrite/complicações , Espondiloartropatias/complicações
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