RESUMO
This study investigated the effects of the protein-free galactomannan obtained from Delonix regia seeds (GM-DR) in an experimental osteoarthritis (OA) model. GM-DR was obtained from water-homogenized endosperms by collection of the supernatant and precipitation with ethanol. The remaining proteins in the galactomannan were removed by alkaline hydrolysis. Weight average molar mass (Mw) of the galactomannan was estimated in 5.8 × 105 g mol-1, presenting mannose:galactose ratio of 2.39:1. Rats received sodium monoiodoacetate (OA groups, 1 mg/25 µL) or saline (sham group) in the right tibio-tarsal joint. GM-DR (30-300 µg) was administered by intra-articular route at days 14 and 21 after OA induction. Hypernociception was evaluated daily by the measurement of the mechanical threshold required to cause joint flexion and paw withdrawal reflex. The 56-day animal groups were euthanized for joint histopahological analysis using the OARSI score system. Lower doses of GM-DR (30 and 100 µg) promoted antinociception from day 15 until the endpoint at day 56. Joint damage was reduced by GM-DR administration (100 µg) in OA-subjected animals, compared to the vehicle-treated OA group (5.9 ± 1.8 vs 19.0 ± 1.8, respectively, p < 0.05). Conclusion: Both antinociception and damage reduction suggest that Delonix regia galactomannan is a promising approach for osteoarthritis therapy.
Assuntos
Analgésicos/uso terapêutico , Mananas/uso terapêutico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Modelos Animais de Doenças , Fabaceae , Articulações do Pé/efeitos dos fármacos , Articulações do Pé/patologia , Galactose/análogos & derivados , Ácido Iodoacético , Masculino , Nociceptividade/efeitos dos fármacos , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Dor/induzido quimicamente , Dor/patologia , Ratos Wistar , SementesRESUMO
AIM: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats. METHODS: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections. RESULTS: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels. CONCLUSION: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.
Assuntos
Anisóis/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Derivados de Alilbenzenos , Animais , Artrite Experimental/sangue , Artrite Experimental/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Citocinas/sangue , Articulações do Pé/efeitos dos fármacos , Articulações do Pé/patologia , Contagem de Leucócitos , Masculino , Nitritos/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Resveratrol and curcumin are two natural polyphenols extensively used due to their remarkable anti-inflammatory activity. The present work presents an inedited study of the in vivo antioedematogenic activity of these polyphenols co-encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)-induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial deposition of preformed polymer. Animals received a single subplantar injection of CFA in the right paw. Fourteen days after arthritis induction, they were treated with resveratrol, curcumin, or both in solution or loaded in lipid-core nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the polyphenols in solution were not able to decrease paw oedema. However, nanoencapsulation improved the antioedematogenic activity of polyphenols at the same doses. In addition, the treatment with co-encapsulated polyphenols showed the most pronounced effects, where an inhibition of 37-55% was observed between day 16 and 22 after arthritis induction. This treatment minimized most of the histological changes observed, like fibrosis in synovial tissue, cartilage and bone loss. In addition, unlike conventionally arthritis treatment, resveratrol and curcumin co-encapsulated in lipid-core nanocapsules did not alter important hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects. This is a promising strategy for the development of new schemes for treatment of chronic inflammation diseases, like arthritis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Experimental/tratamento farmacológico , Curcumina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanocápsulas/administração & dosagem , Estilbenos/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/patologia , Curcumina/química , Curcumina/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Articulações do Pé/patologia , Extrato de Sementes de Uva/química , Hexoses/química , Injeções Intraperitoneais , Masculino , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Poliésteres/química , Polissorbatos/química , Ratos Wistar , Resveratrol , Estilbenos/química , Estilbenos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Immunosuppressive regimen is associated with several metabolic adverse effects. Bone loss and fractures are frequent after transplantation and involve multifactorial mechanisms. METHODS: A retrospective analysis of 130 patients submitted to simultaneous pancreas-kidney transplantation (SPKT) and an identification of risk factors involved in de novo Charcot neuroarthropathy by multivariate analysis were used; P<0.05 was considered significant. RESULTS: Charcot neuroarthropathy was diagnosed in 4.6% of SPKT recipients during the first year. Cumulative glucocorticoid doses (daily dose plus methylprednisolone pulse) during the first 6 months both adjusted to body weight (>78 mg/kg) and not adjusted to body weight were associated with Charcot neuroarthropathy (P=0.001 and P<0.0001, respectively). Age, gender, race, time on dialysis, time of diabetes history, and posttransplantation hyperparathyroidism were not related to Charcot neuroarthropathy after SPKT. CONCLUSIONS: Glucocorticoids are the main risk factors for de novo Charcot neuroarthropathy after SPKT. Protocols including glucocorticoid avoidance or minimization should be considered.
Assuntos
Artropatia Neurogênica/etiologia , Diabetes Mellitus Tipo 1/cirurgia , Glucocorticoides/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Artropatia Neurogênica/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Articulações do Pé/diagnóstico por imagem , Articulações do Pé/patologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Twenty-eight diabetics presenting with acute Charcot foot were immobilized and the temperature difference between limbs measured at each month. All patients had monthly follow-up visits for a year and the relapse rate was zero. We found that skin temperature is a good parameter to ensure safe immobilization withdrawal.
Assuntos
Artropatia Neurogênica/patologia , Articulações do Pé/patologia , Artropatia Neurogênica/fisiopatologia , Feminino , Articulações do Pé/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Temperatura Cutânea/fisiologiaRESUMO
Ipomoea carnea Jacq. ssp. fistulosa (Mart. Ex Choisy; Convolvulaceae; I. carnea) possesses a toxic component: an indolizidine alkaloid swainsonine (SW) that has immunomodulatory effects due to its inhibition of glycoprotein metabolism. It is also known that SW is excreted into both the amniotic fluid and milk of female rats exposed to I. carnea. Thus, the aim of this study was to determine whether SW exposure, either in utero or from the milk of dams treated with I. carnea, modulates offspring immune function into adulthood. In addition, adult (70 days old) and juvenile rats (21 days old) were exposed to I. carnea in order to evaluate several other immune parameters: lymphoid organs relative weight and cellularity, humoral and cellular immune responses. Offspring exposed to I. carnea during lactation developed rheumatoid arthritis (RA) in adulthood after an immunogenic challenge. In addition, both adult and juvenile rats exposed to I. carnea showed discrepancies in several immune parameters, but did not exhibit any decrease in humoral immune response, which was enhanced at both ages. These findings indicate that SW modulates immune function in adult rats exposed to SW during lactation and in juvenile and adult rats exposed to SW as juveniles and adults, respectively.
Assuntos
Fatores Imunológicos/toxicidade , Ipomoea/química , Lactação/imunologia , Swainsonina/toxicidade , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Feminino , Articulações do Pé/patologia , Granuloma/induzido quimicamente , Granuloma/patologia , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/imunologia , Imunidade Humoral/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Extratos Vegetais/toxicidade , Folhas de Planta/química , Gravidez , Ratos , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia , Timo/efeitos dos fármacos , Timo/crescimento & desenvolvimentoRESUMO
BACKGROUND: Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity. METHODS: This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs). RESULTS: Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28-30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity. CONCLUSION: Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice.
Assuntos
Atividades Cotidianas , Artrite Reumatoide/epidemiologia , Avaliação da Deficiência , Deformidades Adquiridas do Pé/epidemiologia , Limitação da Mobilidade , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Colômbia/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Pé/patologia , Pé/fisiopatologia , Deformidades Adquiridas do Pé/diagnóstico , Deformidades Adquiridas do Pé/fisiopatologia , Articulações do Pé/patologia , Articulações do Pé/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Prevalência , Inquéritos e Questionários , Adulto JovemRESUMO
Rheumatoid arthritis (RA) progresses more rapidly in some patients than in others and diverse factors influence radiographic progression in a specific population. Thus, we searched for variables that are associated with an early appearance of substantial joint damage in patients with RA by using radiographic assessments. A cohort of 157 consecutively enrolled Colombian RA patients was followed for an average of 3.2+/-3.1 years. Information on patient demographics and cumulative clinical and laboratory manifestations over the course of the disease was registered, including family history of RA in first-degree relatives, extra-articular manifestations, rheumatoid factor, anti-CCP3 antibodies, TNF single nucleotide polymorphism at -308 position, and HLA-DRB1 status. Radiographs were scored according to the Sharp-van der Heijde method. Survival analyses of the time at appearance of substantial joint damage were performed by using Weibull models. A review of literature about the influence of familial RA on the progression of disease was done. Our results show that family history of RA is consistently associated with joint damage (i.e. erosive and joint narrowing disease). This effect was not found in all the populations reviewed. In addition, we confirm the effect of HLA-DRB1 shared epitope and anti-CCP seropositivity on erosive disease. Family history of RA is a key risk factor for joint damage and depends on the investigated population because variations in both additive and non-additive genetic factors and the environmental variance are specific to the population. Our results emphasize the usefulness of assessing familial disease, testing anti-CCP antibodies and genotyping HLA-DRB1 gene in patients with RA because these factors may be used to predict clinical outcomes and guide therapeutic interventions.
Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Autoanticorpos/sangue , Antígenos HLA-DR/imunologia , Articulações/patologia , Peptídeos Cíclicos/imunologia , Adulto , Idade de Início , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Autoanticorpos/imunologia , Colômbia , Feminino , Seguimentos , Articulações do Pé/patologia , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Articulação da Mão/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Sexuais , Esteroides/uso terapêutico , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Articulação do Punho/patologiaRESUMO
Tumores benignos são responsáveis pela maioria das lesões tumorais nos pés. Neuroma de Morton, fasciite plantar e nódulos reumatóides respondem por 60% a 70% de todas estas doenças. Usualmente, mono-artrite na face plantar dos pés de caráter mecânico induz em mulheres jovens aos diagnósticos referidos. O cisto epidermóide, apesar de ser uma lesão benigna, não é lembrado no diagnóstico diferencial de nódulos dolorosos nos pés. O conhecimento dos achados patológicos destas lesões extra-articulares nos pés ajuda na interpretação da ressonância magnética (RM)