Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.465
Filtrar
4.
Chem Biol Interact ; 313: 108824, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542397

RESUMO

Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Inflamação/complicações , Insetos/química , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Produtos Biológicos/farmacologia , Colite/tratamento farmacológico , Colite/etiologia , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/etiologia
5.
J Appl Oral Sci ; 27: e20180602, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508794

RESUMO

OBJECTIVE: This study aimed to evaluate the effect of avocado/soybean unsaponifiables (ASU) on periodontal repair in rats with induced periodontitis and arthritis. METHODOLOGY: Forty-five rats were submitted to periodontitis induction by insertion of ligatures into the upper second molars, maintained for 15 days. These animals were randomly allocated to 3 groups according to the presence of induced arthritis (ART) and the application of the ASU: Control (CTR) group-healthy animals, where saline solution was administered; ART-animals with induced arthritis, where saline solution was administered; ART/ASU-animals with induced arthritis, where ASU (0.6 mg/ kg) was administered. The drugs were administered daily by gavage and the animals were euthanized after 7, 15 and 30 days of the ligature removal. Bone resorption, inflammatory infiltrate composition and marker proteins expression of the differentiation and formation of osteoclasts (RANKL and TRAP) were assessed. RESULTS: The ART/ASU group presented higher bone volume than the ART group at 7 and 30 days after the ligature removal. Furthermore, the ART group presented higher quantity of inflammatory cells and expression of TRAP and RANKL than the other groups. CONCLUSION: ASU administration improves the repair of periodontal tissues in an experimental periodontitis model in rats with induced arthritis.


Assuntos
Artrite/tratamento farmacológico , Periodontite/tratamento farmacológico , Persea/química , Extratos Vegetais/farmacologia , Soja/química , Animais , Artrite/patologia , Imuno-Histoquímica , Masculino , Periodontite/patologia , Ligante RANK/análise , Distribuição Aleatória , Ratos , Reprodutibilidade dos Testes , Fosfatase Ácida Resistente a Tartarato/análise , Fatores de Tempo , Resultado do Tratamento , Microtomografia por Raio-X
6.
J Enzyme Inhib Med Chem ; 34(1): 1678-1689, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31530032

RESUMO

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artrite/tratamento farmacológico , Cromonas/farmacologia , Interleucina-6/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Artrite/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cromonas/síntese química , Cromonas/química , Relação Dose-Resposta a Droga , Adjuvante de Freund , Interleucina-6/biossíntese , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/biossíntese
7.
Schweiz Arch Tierheilkd ; 161(9): 559-568, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488397

RESUMO

INTRODUCTION: The clinical, ultrasonographic, radiographic, cytologic and bacteriologic findings, diagnosis and surgical treatment of two heifers with septic metacarpal physitis (type-1 osteomyelitis) and concurrent serofibrinous arthritis of the metacarpophalangeal (MCP) joint are described. Osteomyelitis likely occurred by haematogenous spread following bronchopneumonia in one heifer and developed post-traumatically in the other. In both patients, ultrasonographic examination using the 7.5 MHz linear probe showed moderate effusion of the palmar and dorsal MCP joint pouches and highly irre-gular bone contours with depression and periosteal new bone formation at the metacarpal growth plate. Radiographs showed an extensive radiolucent area with poorly defined margins at the level of the metacarpal growth plate. Surgical treatment was carried out under sedation and regional intravenous anesthesia and involved meticulous debridement of the osteomyelitic lesion of the meta-carpal growth plate combined with arthrotomy of the MCP joint and repeated lavage of the bone cavity and joint. Successful outcomes were achieved by combined use of systemic and locoregional antibiotics, NSAIDs, temporary external coaptation and adequate housing.


Assuntos
Artrite/veterinária , Doenças dos Bovinos/cirurgia , Osteomielite/veterinária , Animais , Artrite/diagnóstico por imagem , Artrite/tratamento farmacológico , Artrite/cirurgia , Bovinos , Doenças dos Bovinos/diagnóstico por imagem , Doenças dos Bovinos/tratamento farmacológico , Feminino , Osteomielite/diagnóstico por imagem , Osteomielite/tratamento farmacológico , Osteomielite/cirurgia , Resultado do Tratamento
8.
Drug Deliv ; 26(1): 820-830, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31389248

RESUMO

Arthritis treatment has been challenging because of low drug exposure to the articular cavity. This study was intended to develop hyaluronic acid (HA)-functionalized bilosomes for targeted delivery of tripterine (Tri), an antiphlogistic phytomedicine, to the inflamed joint via ligand-receptor interaction. Tri-loaded bilosomes (Tri-BLs) with cationic lipid (DOTAP) were prepared by a thin film hydration method followed by HA coating to form HA@Tri-BLs. HA@Tri-BLs were then characterized by particle size (PS), entrapment efficiency (EE), and structural morphology. The in vitro drug release, hemocompatibility test and cellular uptake were performed to examine the formulation performances of HA@Tri-BLs. The in vivo pharmacokinetics and antiarthritic efficacy were evaluated in arthritic models, respectively. The obtained HA@Tri-BLs possessed a PS of 118.5 nm around with an EE of 99.56%. HA@Tri-BLs exhibited excellent cellular uptake and targeted delivery efficiency for Tri, which resulted in elongation of circulatory residence time and enhancement of intra-arthritic bioavailability (799.9% relative to Tri solution). The in vivo antiarthritic efficacy of HA@Tri-BLs was also significantly superior to uncoated Tri-BLs that gave rise to obvious inflammation resolution. Our findings suggest that HA-functionalized bilosomes are a promising vehicle for articular delivery of antiphlogistic drugs to potentiate their efficacy.


Assuntos
Artrite/tratamento farmacológico , Ácido Hialurônico/química , Inflamação/tratamento farmacológico , Lipossomos/química , Triterpenos/administração & dosagem , Triterpenos/química , Animais , Disponibilidade Biológica , Cátions/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ácido Hialurônico/administração & dosagem , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos DBA , Tamanho da Partícula , Células RAW 264.7 , Ratos Sprague-Dawley
10.
Int J Antimicrob Agents ; 54(4): 456-462, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319190

RESUMO

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11-13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.


Assuntos
Antibacterianos/administração & dosagem , Artrite/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Colistina/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Infecções Relacionadas à Prótese/tratamento farmacológico , Animais , Artrite/microbiologia , Artrite/cirurgia , Desbridamento , Modelos Animais de Doenças , Feminino , Injeções Intra-Articulares , Injeções Intramusculares , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/cirurgia , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Coelhos , Resultado do Tratamento
11.
BMC Infect Dis ; 19(1): 631, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315565

RESUMO

BACKGROUND: Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment. Here we reported a rare case of recurrent arthritis caused by Candida parapsilosis. CASE PRESENTATION: A 56-year-old Chinese male suffered from recurrent pain and swelling in his right knee after several times of "small needle-knife" acupuncture and corticosteroid injection of the joint. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer (ITS) gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified. The patient underwent thorough arthroscopic debridement and then set on fluconazole 400 mg daily for 12 months. His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. parapsilosis arthritis episodes from past to now were studied. CONCLUSION: With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C. parapsilosis arthritis - its clinical settings, laboratory features, radiological characteristics, arthroscopic findings and experience of management.


Assuntos
Artrite/microbiologia , Candida parapsilosis/patogenicidade , Candidíase/tratamento farmacológico , Antifúngicos/uso terapêutico , Artrite/tratamento farmacológico , Artrite/cirurgia , Candida parapsilosis/isolamento & purificação , Desbridamento , Fluconazol/uso terapêutico , Humanos , Joelho/microbiologia , Joelho/patologia , Masculino , Pessoa de Meia-Idade , Líquido Sinovial/microbiologia
12.
Laeknabladid ; 105(6): 267-275, 2019 06.
Artigo em Islandês | MEDLINE | ID: mdl-31192789

RESUMO

ntroduction: To collect nationwide data in Iceland on pregnancy and its outcomes among female patients with active inflammatory arthritides we linked two registers, the ICEBIO register and the Icelandic Medical Birth Register. METHODS: We used multivariate analysis to evaluate the risk of preterm birth, Caesarean section, low Apgar score at 5-minutes and low birth weight among females with inflammatory arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) in comparison with healthy controls matched on age and parity. We also investigated pregnancies before and after the diagnosis of respective rheumatic disease and especially in respect to treatment with TNFα inhibitors (TNFi). RESULTS: In the end of 2016, 723 female patients were registered in ICEBIO as they had received treatment with TNFi due to inflammatory arthritis. Of those, 412 women had given birth to 801 children, whereof 597 were delivered before confirmed diagnosis of the mother and 53 were delivered after the start of the TNFi treatment. Relative risk of Caesarean section among these female with various arthritis conditions were 1.47 (95% CI: 1.19-1.82; p < 0,001) compared to controls and was highest in the group with PsA or 2.06 (1.41-3.02; p<0,001). We did not find increased risk of preterm delivery or low Apgar score. Patients with inflammatory arthritis had lower risk of children with low birth weight or 0.37 compared to healthy controls (95% CI: 0.36-0.37; p < 0.05). Due to low numbers of deliveries after the initiation of TNFi therapy (n=53) we were not able to perform any analysis for that group. CONCLUSION: Icelandic female patients with inflammatory arthritis are at an increased risk of Caesarean section in comparison to healthy controls. However, their newborns are in good condition and healthy at birth. Analysis of the impact of treatment with TNFi on pregnancy is not yet possible due to limited data.


Assuntos
Artrite/tratamento farmacológico , Cesárea , /uso terapêutico , Índice de Apgar , Artrite/diagnóstico , Artrite/epidemiologia , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Islândia/epidemiologia , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Resultado da Gravidez , Sistema de Registros , Medição de Risco , Fatores de Risco , /efeitos adversos
13.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243159

RESUMO

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NBS) are 2 overlapping syndromes caused by mutations in genes of the barrier-to-autointegration factor chromatin-remodeling complex, presenting with multiple malformations and intellectual disability. Musculoskeletal changes such as noninflammatory prominence of interphalangeal joints in hands, feet, and, to a lesser extent, knee joints are common in NBS (up to 85%) and also reported in CSS. We present the case of a 7-year-old boy with polyarthritis of several years' duration (without uveitis), developmental delay, microcephaly, and dysmorphic features reminiscent of NBS. Sanger sequencing of the SMARCA2 gene revealed no mutations. Laboratory test results were normal. With synovial biopsy, we confirmed a chronic inflammatory synovitis. Brain MRI revealed dysgenesis of the corpus callosum. Treatment with methotrexate and, subsequently, etanercept led to significant clinical improvement. Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the ARID1B gene, resulting in a premature stop codon (c.C5404T; p.R1802×), a genotype consistent with CSS. The absence of significantly raised inflammatory markers and a clinical diagnosis of a genetic syndrome associated with noninflammatory joint changes may have contributed to this patient's polyarthritis being missed for several years. We propose that some patients with CSS may have inflammatory arthritis (with or without coexisting skeletal dysplasia), which may be helped by treatment as described herein. Early recognition and treatment of inflammatory arthritis in CSS would have a significant impact on reducing disease burden and improving quality of life for patients with this rare genetic syndrome.


Assuntos
Anormalidades Múltiplas/diagnóstico , Artrite/diagnóstico , Face/anormalidades , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Micrognatismo/diagnóstico , Pescoço/anormalidades , Anormalidades Múltiplas/genética , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/tratamento farmacológico , Criança , Códon sem Sentido , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Etanercepte/uso terapêutico , Facies , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas da Mão/genética , Humanos , Hipotricose/diagnóstico , Deficiência Intelectual/genética , Masculino , Metotrexato/uso terapêutico , Micrognatismo/genética , Fatores de Transcrição/genética
14.
BMC Musculoskelet Disord ; 20(1): 286, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31200688

RESUMO

BACKGROUND: McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. METHODS: Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. RESULTS: Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups. CONCLUSIONS: Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.


Assuntos
Anticorpos/administração & dosagem , Artrite/tratamento farmacológico , Entesopatia/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Artrite/imunologia , Artrite/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Entesopatia/imunologia , Entesopatia/patologia , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Receptores de Interleucina-6/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
15.
Curr Med Chem ; 26(33): 6149-6173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218947

RESUMO

Catalpol, a famous molecule of iridoids, possesses extensive pharmacological activities. Our studies found that compounds with low-polarity substituents at the 6-O position of catalpol exhibited higher NF-κB inhibitory potency than catalpol. However, catalpol derivatives are not much focused. Here this review provides extensive coverage of naturally occurring catalpol derivatives discovered from 1888 until 2018. It covers their distribution, chemotaxonomic significance, chemical structures, and bioactivities from more than 200 peer-reviewed articles, and highlights the structure-activity relationship of catalpol derivatives.


Assuntos
Glucosídeos Iridoides/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Artrite/tratamento farmacológico , Humanos , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/uso terapêutico , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Plantas/química , Plantas/metabolismo
16.
PLoS Comput Biol ; 15(5): e1006933, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31071076

RESUMO

Anti-TNF agents have been in the first line of treatment of various inflammatory diseases such as Rheumatoid Arthritis and Crohn's Disease, with a number of different biologics being currently in use. A detailed analysis of their effect at transcriptome level has nevertheless been lacking. We herein present a concise analysis of an extended transcriptomics profiling of four different anti-TNF biologics upon treatment of the established hTNFTg (Tg197) mouse model of spontaneous inflammatory polyarthritis. We implement a series of computational analyses that include clustering of differentially expressed genes, functional analysis and random forest classification. Taking advantage of our detailed sample structure, we devise metrics of treatment efficiency that take into account changes in gene expression compared to both the healthy and the diseased state. Our results suggest considerable variability in the capacity of different biologics to modulate gene expression that can be attributed to treatment-specific functional pathways and differential preferences to restore over- or under-expressed genes. Early intervention appears to manage inflammation in a more efficient way but is accompanied by increased effects on a number of genes that are seemingly unrelated to the disease. Administration at an early stage is also lacking in capacity to restore healthy expression levels of under-expressed genes. We record quantifiable differences among anti-TNF biologics in their efficiency to modulate over-expressed genes related to immune and inflammatory pathways. More importantly, we find a subset of the tested substances to have quantitative advantages in addressing deregulation of under-expressed genes involved in pathways related to known RA comorbidities. Our study shows the potential of transcriptomic analyses to identify comprehensive and distinct treatment-specific gene signatures combining disease-related and unrelated genes and proposes a generalized framework for the assessment of drug efficacy, the search of biosimilars and the evaluation of the efficacy of TNF small molecule inhibitors.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite/genética , Perfilação da Expressão Gênica/métodos , Adalimumab/farmacologia , Animais , Artrite/tratamento farmacológico , Medicamentos Biossimilares , Certolizumab Pegol/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/imunologia , Infliximab/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transcriptoma/genética , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
17.
BMC Infect Dis ; 19(1): 455, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117984

RESUMO

BACKGROUND: Leprosy typically manifests with skin and peripheral nerve involvement. Musculoskeletal complaints are the third most common, and can be the sole presenting manifestation. They range from arthralgia/arthritis in reactional states to full mimics of systemic rheumatic diseases. Remitting Seronegative Symmetrical Synovitis with Pitting Oedema syndrome has only been described once in a patient with already diagnosed Leprosy. CASE REPORT: A 68-year-old male, from an endemic region of familial amyloid polyneuropathy, presented with an inaugural Remitting Seronegative Symmetrical Synovitis with Pitting Oedema like syndrome, more that 20 years after travelling to Leprosy endemic areas. Arthritis would resurface whenever oral prednisone was tapered, so methotrexate was started, controlling the complaints. Only one year later, after the appearance of peripheral neuropathy and skin lesions, it was possible to diagnose Leprosy, through the identification of Mycobacterium leprae bacilli in a peripheral nerve biopsy. CONCLUSION: This report is an example of the heterogeneity of manifestations of Leprosy, namely rheumatic, and the challenge of diagnosing it when typical complaints are absent. It is also a reminder that this disease should be considered whenever a patient with a combination of skin/neurologic/rheumatic complaints has travelled to endemic countries in the past.


Assuntos
Edema/diagnóstico , Hanseníase/etiologia , Mycobacterium leprae/isolamento & purificação , Sinovite/diagnóstico , Idoso , Antibacterianos , Artrite/tratamento farmacológico , Artrite/etiologia , Edema/etiologia , Humanos , Hanseníase/tratamento farmacológico , Hanseníase/microbiologia , Masculino , Mycobacterium leprae/patogenicidade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Pele/microbiologia , Pele/patologia , Síndrome , Sinovite/etiologia
19.
Int Immunopharmacol ; 72: 504-510, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055232

RESUMO

Neuroendocrine changes are essential factors contributing to the progression and development of rheumatoid arthritis. However, the role of estrogen in the innate immunity during arthritis development is still controversial. Here, we evaluated the effect of estrous cycle, ovariectomy, estradiol replacement therapy and treatment with estrogen receptor (ER)α and ERß specific agonists on joint edema formation, neutrophil recruitment, and articular levels of cytokines/chemokines in murine zymosan-induced arthritis. Our results showed that articular inflammation of proestus/estrus was similar to metaestus/diestrus animals indicating that the inflammatory response in acute arthritis is not affected by the estrous cycle. However, ovariectomy increased joint swelling, neutrophil migration, and TNF-α level. Treatment for six consecutive days with estradiol cypionate re-established the acute inflammation in ovariectomized arthritic mice to responses similar to those in SHAM-proestrus/estrus or naive mice. Moreover, treatment with propylpyrazoletriol and diarylpropionitrile, two ERα and ERß selective agonists, respectively, inhibited both edema and neutrophil recruitment. Finally, the non-genomic properties of estradiol were analyzed with an acute treatment with ß-estradiol-water soluble, which reduced the edema only. In the present study, estradiol replacement therapy improves the innate immune responses in ovariectomized arthritic mice by activating nuclear estrogen receptors. These results suggest that estradiol can induce a protective anti-inflammatory effect in arthritis during ovaries failure, as observed in the menopause.


Assuntos
Artrite/tratamento farmacológico , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Terapia de Reposição Hormonal , Animais , Artrite/imunologia , Feminino , Imunidade Inata/efeitos dos fármacos , Camundongos , Neutrófilos/efeitos dos fármacos , Ovariectomia
20.
PLoS One ; 14(5): e0216702, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31075142

RESUMO

Hyaluronic acid injections have been a mainstay of arthritis treatment for decades. However, much controversy remains about their clinical efficacy and their potential mechanism of action. This approach to arthritis therapy is often called viscosupplementation, a term which is rooted in the elevated viscosity of the injected solutions. This terminology also suggests a mechanical pathway of action and further implies that their efficacy is dependent on viscosity. Notably, previous studies of the relationship between viscous properties of hyaluronic acid solutions and their clinical efficacy have not been definitive. Recently we developed an experimental and analytical framework for studying cartilage lubrication that captures the Stribeck-like behavior of cartilage in an elastoviscous transition curve. Here we apply this framework to study the lubricating behavior of six hyaluronan products currently used for injectable arthritis therapy in the US. Despite the fact that the source and chemical modifications endow these products with a range of lubricating properties, we show that the lubricating effect of all of these materials can be described by this Stribeck-like elastoviscous transition. Fitting this data to the elastoviscous transition model enables the calculation of effective lubricating viscosities for each material, which differ substantially from the viscosities measured using standard rheometry. Further we show that while data from standard rheometry are poor predictors of clinical performance of these materials, measurements of friction coefficient and effective lubricating viscosity correlate well (R2 = 0.77; p < 0.005) with assessments of improved clinical function reported previously. This approach offers both a novel method that can be used to evaluate potential clinical efficacy of hyaluronic acid formulations and provide new insight on their mode of action.


Assuntos
Elasticidade , Fricção , Ácido Hialurônico/química , Reologia , Artrite/tratamento farmacológico , Composição de Medicamentos , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Injeções , Resultado do Tratamento , Viscosidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA