RESUMO
The association between structural changes and pain sensation in osteoarthritis (OA) remains unclear. Joint deterioration in OA leads to the release of protein fragments that can either systemically (serum) or locally (synovial fluid; SF) be targeted as biomarkers and describe structural changes and potentially pain. Biomarkers of collagen type I (C1M), type II (C2M), type III (C3M), type X (C10C), and aggrecan (ARGS) degradation were measured in the serum and SF of knee OA patients. Spearman's rank correlation was used to assess the correlation of the biomarkers' levels between serum and SF. Linear regression adjusted for confounders was used to evaluate the associations between the biomarkers' levels and clinical outcomes. The serum C1M levels were negatively associated with subchondral bone density. The serum C2M levels were negatively associated with KL grade and positively associated with minimum joint space width (minJSW). The C10C levels in SF were negatively associated with minJSW and positively associated with KL grade and osteophyte area. Lastly, the serum C2M and C3M levels were negatively associated with pain outcomes. Most of the biomarkers seemed to mainly be associated with structural outcomes. The overall biomarkers of extracellular matrix (ECM) remodeling in serum and SF may provide different information and reflect different pathogenic processes.
Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/metabolismo , Líquido Sinovial/metabolismo , Biomarcadores/metabolismo , Colágeno Tipo I/metabolismo , Dor/metabolismoRESUMO
INTRODUCTION: Oculodentodigital syndrome (ODDS) is a rare genetic disorder caused by mutations in the gap junction GJA1 gene encoding connexin-43 (chromosome 6q22). A typical ODDS case is presented. MATERIAL AND METHODS: A 40-year-old male patient was examined neurologically and genetically. He had a history of recent parieto-occipital leukodystrophy, some episodes of temporary hearing loss, and characteristic facial features of ODDS. Sequencing of the GJA1 gene was performed in patient's total genomic DNA sample isolated from peripheral blood cells. RESULTS: A novel heterozygous missense mutation (443G>A) was identified in the GJA1 gene, resulting in coding for a different amino acid (Arg148Gln). CONCLUSION: The molecular genetic analysis confirmed the diagnosis of ODDS. The novel mutation, located within a calmodulin binding region of connexin-43, probably affects proper channel function.
Assuntos
Anormalidades Craniofaciais , Deformidades Congênitas do Pé , Sindactilia , Anormalidades Dentárias , Adulto , Anormalidades Craniofaciais/genética , Anormalidades do Olho , Deformidades Congênitas do Pé/genética , Humanos , Masculino , Mutação , Fenótipo , Sindactilia/genética , Anormalidades Dentárias/genéticaRESUMO
Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.
Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/terapia , Receptor PAR-2/sangue , Receptores de Interleucina-6/antagonistas & inibidores , Adulto , Idoso , Anticorpos/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/imunologia , Biomarcadores/metabolismo , Cartilagem/metabolismo , Epitopos/química , Feminino , Humanos , Imunoensaio , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Reprodutibilidade dos Testes , Serina Endopeptidases , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo , Adulto JovemRESUMO
Animal models are valuable tools for studying human cancer as well as for preclinical trials. The hamster model of chemically induced sequential oral carcinogenesis was developed by our group a decade ago in order to study the multistep process of alterations in gene expression during carcinogenesis. The purpose of this review was to discuss the utility of the hamster model of sequential oral carcinogenesis regarding the deciphering of the main pathways altered. An extended search for articles that cited that specific animal models was performed. Many studies have used the hamster model of sequential oral carcinogenesis either for evaluation of the expression of biomarkers alone, or for applying chemopreventive compounds and other therapeutic methods, or combining the use of biomarkers with the anticancer effect of some compounds. It seems that this animal model is indeed a useful tool that enables the study of cell biology, pathology and therapeutics of oral cancer.