RESUMO
OBJECTIVE: Vitamin A derivatives are widely used therapeutic agents for the treatment of dermatological and rheumatological disorders. Long-standing administration of these drugs, in turn, causes skeletal changes including ossification of ligaments, premature fusion of epiphyses and abnormalities of modeling. Recent in vitro experiments have further suggested that retinoid treatment of cultured chondrocytes may cause apoptotic cell death. The present study aims to address detailed cartilage changes associated with in vivo administration of vitamin A derivatives. METHODS: Retinyl acetate was administrated to experimental mice, C3H-Heston, for more than 12 months. Modified morphometry on the articular cartilage and fluorescent labeling of the subchondral bone were carried out to address the changes in the articular cartilage and subchondral bone. In order to address the detailed chondrocytes phenotypes, electron microscopy was carried out. Since findings of these studies suggested that biological properties of the cartilage matrix might be altered, the present study also immunolocalized functional matrix molecules, type I collagen and osteoblast-stimulating factor-1 (OSF-1). RESULTS: Histomorphometry demonstrated that retinoid administration lead to progressive atrophy of the articular cartilage with concomitant proliferation of subchondral bone. Furthermore, detailed light and electron microscopy suggested that the subchondral bone proliferates into the degenerating cartilage. The affected articular cartilage also resembled that of osteoarthritis in terms of ectopic type I collagen production. Furthermore, the affected articular cartilage produced a developmentally regulated matrix molecule, osteoblast-stimulating factor-1 (OSF-1) that is normally expressed in both the fetal cartilage and the epiphyseal growth plate cartilage but not in the articular cartilage. CONCLUSION: The present results indicate that the systemic retinoid administration may alter the biological properties of the articular cartilage.
Assuntos
Adjuvantes Imunológicos/farmacologia , Cartilagem Articular/efeitos dos fármacos , Condrócitos/metabolismo , Vitamina A/análogos & derivados , Vitamina A/farmacologia , Animais , Atrofia/imunologia , Atrofia/fisiopatologia , Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Diferenciação Celular , Condrócitos/efeitos dos fármacos , Condrócitos/fisiologia , Diterpenos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Microscopia Eletrônica , Osteoblastos/imunologia , Osteoblastos/fisiologia , Osteogênese/imunologia , Osteogênese/fisiologia , Fenótipo , Ésteres de RetinilRESUMO
OBJECTIVE: To evaluate the possible role of the antioxidant ebselen in the treatment of cerebral vasospasm, we examined the effects of ebselen on the vasoactive mechanisms induced by endothelin (ET)-1, oxyhemoglobin, and oxygen-derived radicals. METHODS: Isolated rabbit basilar arteries with intact endothelium were fixed in a perfusion system and perfused intraluminally. Contraction of the artery was detected as an increase in perfusion pressure. RESULTS: Ebselen, in a certain concentration range (3 x 10(-6) and 10(-5) mol/L), significantly reduced the contractile response to ET-1 (10(-10) to 10(-8) mol/L) but not the contraction induced by 40 mmol/L potassium. It reduced the contraction induced by 10(-4) mol/L 1,2-dioctanoyl-sn-glycerol, a protein kinase C activator. Addition of 10(-5) mol/L dithiothreitol, a sulfhydryl-reducing agent, partially reversed the inhibitory effects of ebselen on ET-1- and 1,2-dioctanoyl-sn-glycerol-induced contractions. Ebselen (10(-5) mol/L) as well as a combination of catalase (1000 units/mL) and superoxide dismutase (150 units/mL) inhibited the potentiating effects of oxyhemoglobin (10(-5) mol/L) on ET-1-induced contraction. Both ebselen and catalase inhibited the contractile response to hydroxyl radical generated by ferrous ion (10(-3) mol/L) plus hydrogen peroxide (10(-2) mol/L). Ebselen reduced the response to potassium when a high dose (3 x 10(-5) mol/L) was applied and failed to preserve contractility of the preparation after exposure to hydroxyl radical. CONCLUSION: Ebselen suppressed ET-1-induced contraction and synergetic interaction between oxyhemoglobin and ET-1, where free radical formation was involved. These effects may result from modification of the intracellular regulatory system including protein kinase C, as well as from protection against free radicals.
Assuntos
Antioxidantes/farmacologia , Azóis/farmacologia , Artéria Basilar/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Artéria Basilar/fisiologia , Diglicerídeos/farmacologia , Ditiotreitol/farmacologia , Sinergismo Farmacológico , Endotelina-1/farmacologia , Radical Hidroxila/farmacologia , Técnicas In Vitro , Isoindóis , Masculino , Concentração Osmolar , Oxirredutases/farmacologia , Oxiemoglobinas/antagonistas & inibidores , Oxiemoglobinas/farmacologia , Perfusão , Potássio/farmacologia , Coelhos , Reagentes de Sulfidrila/farmacologia , Vasoconstritores/farmacologiaRESUMO
We evaluated the potential application of ion-exchange resins for the enhancement of intranasal immune response to influenza HA vaccine in mice. Female Balb/c mice were intranasally immunized with inactivated influenza HA vaccine with one of four kinds of resin microparticles: sodium polystyrene sulfonate, calcium polystyrene sulfonate, polystyrene benzyltrimetylammonium chloride, or polystyrene divinylbenzene. Haemagglutinin-inhibiting antibodies were measured in the serum and IgA antibodies in the nasal wash after 4 weeks. The results demonstrated that intranasal administration of influenza HA vaccine in combination with the 20-45 microns sized particles of sodium polystyrene sulfonate resin induced the highest levels of mucosal IgA, and enhanced systemic haemagglutinin-inhibiting antibodies. While the Th2-type cytokine IL-4 was detected in the sera after intranasal immunization with HA vaccine and sodium polystyrene sulfonate, neither IFN-gamma nor IL-2 could be detected. Furthermore, mice intranasally immunized with HA vaccine together with sodium polystyrene sulfonate resin showed higher protection against viral challenge than those that received HA vaccine alone. Intranasal administration of influenza HA vaccine with sodium polystyrene sulfonate resin might be both a safe and an effective means of immunization.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Resinas de Troca Iônica/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Citocinas/biossíntese , Feminino , Imunoglobulina A/sangue , Vacinas contra Influenza/imunologia , Camundongos , Cavidade Nasal/imunologia , Tamanho da Partícula , Poliestirenos/administração & dosagemAssuntos
Cromoblastomicose/microbiologia , Cladosporium/isolamento & purificação , Fungos Mitospóricos/isolamento & purificação , Pele/microbiologia , Administração Oral , Idoso , Cromoblastomicose/patologia , Cromoblastomicose/terapia , Feminino , Flucitosina/administração & dosagem , Humanos , Hipertermia Induzida , Pele/patologiaRESUMO
Growth cartilage cells were isolated from the ribs of young rats and cultured at high cell density in Ham's F-12 medium supplemented with 10% fetal calf serum. During 7 days, glycosaminoglycans and proteoglycans were actively synthesized and secreted, forming a metachromatic matrix. When cultured together with growth cartilage cells precultured and biosynthetically prelabeled with 35SO4(2-) in their glycosaminoglycans, bone marrow cells caused release of 35S-labeled material into the culture medium. Glycosaminoglycan was also released by addition of conditioned medium obtained from cultures of bone marrow cells or peritoneal macrophages to the growth cartilage cell cultures. Electron microscopic studies of the extracellular matrix of growth cartilage cells cocultured with bone marrow cells showed that needles of apatite mineral were deposited within and in close apposition to the surfaces of matrix vesicles. These findings suggest that enzymes released from bone marrow cells or macrophages removed glycosaminoglycan or proteoglycans, which may be inhibitors of mineral growth, and consequently mineralization was initiated. From these findings, sequential culture of growth cartilage cells and bone marrow cells is promising as an experimental system for investigating the mechanism of the initial stage of endochondral ossification.