RESUMO
OBJECTIVE: To evaluate if fulfilment of the definition of osteoarthritis (OA) based on the American College of Rheumatology (ACR) clinical criteria corresponds to pathological knee findings evaluated by magnetic resonance imaging (MRI). To evaluate if any such criteria is associated with a specific MRI pattern. METHODS: Forty-six consecutive patients aged 50 years or more referred by their general practitioners (GPs) to a radiology department because of non-traumatic knee pain underwent MRI using a dedicated low field (0.2 T) machine. RESULTS: MRI results were compared against the ACR criteria for knee OA. Patients with knee pain fulfilling the ACR criteria showed more severe synovial fluid effusion (OR 6.2, 95% CI 2.02 to 19.1), cartilage lesions in the medial area (OR 2.4, 95% CI 1.2 to 5) and higher mean number of osteophytes (OR 2.3, 95% CI 1.1 to 4.5). The association between single criteria and MRI features was more difficult to establish. Nonetheless, crepitus at joint movement was associated with synovial fluid effusion (p=0.02); bone enlargement was more frequent in patients with lesions of the posterior cruciate ligament (p=0.0001); no palpable warmth was associated with cartilage lesions (p=0.02), and morning stiffness shorter than 30 minutes was associated with the surface of bone edema (p=0.02). CONCLUSIONS: The ACR clinical criteria identify patients showing the most important features of OA. The association between individual clinical ACR criteria and OA pathology depicted by MRI may be difficult to explain on the basis of anatomical changes and needs further evaluation.
Assuntos
Osteoartrite do Joelho , Humanos , Estados Unidos , Osteoartrite do Joelho/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Dor , Imageamento por Ressonância Magnética/métodos , Líquido Sinovial/diagnóstico por imagemRESUMO
PURPOSE OF INVESTIGATION: To propose a multidisciplinary protocol for postmortem disclosure of complex fetal malformations, comparing ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and autopsy in a case of conjoined ischiopagus twins. MATERIALS AND METHODS: A screening second-trimester ultrasound diagnosed ischiopagus twins at 20 gestational weeks in a 31-year-old woman without any previous ultrasound examination. The couple decided for pregnancy termination. The formalin-fixed fetuses underwent full-body CT, MRI, and autopsy. RESULTS: ultrasound accurately diagnosed ischiopagus twins. CT was very accurate in the description of bone components. MRI allowed better visualization of the visceral organs than CT. Only autopsy could disclose the aspect of the two gastrointestinal tracts and the external genitalia. CONCLUSIONS: Prenatal ultrasound represents the standard diagnostic exam for conjoined twins. CT-MRI virtual autopsy (virtopsy) may be an option if the couple refuses to authorize necropsy or may be useful to plan a minimally invasive autopsy preserving the external phenotype.
Assuntos
Gêmeos Unidos/patologia , Adulto , Autopsia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Redução de Gravidez Multifetal/métodos , Segundo Trimestre da Gravidez , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Pré-Natal/métodosRESUMO
Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles. We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.
Assuntos
Inibidores Enzimáticos/farmacologia , Músculos/enzimologia , Músculos/patologia , Distrofia Muscular Animal/tratamento farmacológico , Animais , Distrofina/genética , Fibrose/patologia , Folistatina/metabolismo , Ácidos Hidroxâmicos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculos/efeitos dos fármacos , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/patologia , Fenilbutiratos/farmacologia , Sarcoglicanas/metabolismo , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/enzimologia , Ácido Valproico/farmacologiaAssuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tenossinovite/diagnóstico por imagem , Tenossinovite/etiologia , Ultrassonografia , Articulação do Punho/diagnóstico por imagem , Humanos , Hipestesia/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Nódulo Reumatoide/complicações , Nódulo Reumatoide/diagnóstico por imagem , Sensibilidade e Especificidade , Tendões/patologia , Tenossinovite/patologia , Articulação do Punho/patologiaRESUMO
OBJECTIVES: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. METHODS: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55" and as relative enhancement (RE) at t seconds. RESULTS: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosoppressive treatment at the end of follow-up was predicted by both low RE and high REE. CONCLUSIONS: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist.
Assuntos
Artrite/diagnóstico , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética/métodos , Articulação do Punho , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
Magnetite nanoparticles coated with silica, obtained by a sol-gel process in the reverse micelle microemulsion, were characterized and homogeneously suspended in water in order to assay their biocompatibility toward blood cells, in view of a potential medical use of this material. Their hemolytic, pro-thrombotic and pro-inflammatory properties were observed.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Compostos Férricos/química , Compostos Férricos/farmacologia , Nanopartículas de Magnetita , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Humanos , MicelasRESUMO
Conversion of erythrocyte membrane protein 4.1b to 4.1a occurs through a non-enzymatic deamidation reaction in most mammalian erythrocytes, with an in vivo half-life of approximately 41 days, making the 4.1a/4.1b ratio a useful index of red cell age [Inaba and Maede, Biochim. Biophys. Acta 944 (1988) 256-264]. Normal human erythrocytes distribute into subpopulations of increasing cell density and cell age when centrifuged in polyarabinogalactan density gradients. We have observed that, when erythrocytes were stored at 4 degrees C under standard blood bank conditions, the deamidation was virtually undetectable, as cells maintained the 4.1a/4.1b ratio they displayed at the onset of storage. By measuring the 4.1a/4.1b values in subpopulations of cells of different density at various time points during storage, a modification of the normal 'cell age/cell density' relationship was observed, as erythrocytes were affected by changes in cell volume in an age-dependent manner. This may stem from a different impact of storage on the imbalance of monovalent cations, Na(+) and K(+), in young and old erythrocytes, related to their different complement of cation transporters.
Assuntos
Cátions Monovalentes/análise , Envelhecimento Eritrocítico , Eritrócitos/química , Bancos de Sangue , Separação Celular , Tamanho Celular , Membrana Eritrocítica/química , Eritrócitos/classificação , Humanos , Lactatos/análise , Proteínas de Membrana/análise , Fatores de Tempo , Preservação de TecidoRESUMO
In this study the oxidation state of glutathione and membrane proteins was analyzed in red cells of different age in basal conditions. Red cells of different age were prepared by centrifugation and separated according to their density by two procedures: on self-forming gradients of autologous plasma (Murphy's procedure) and on discontinuous Stractan gradients. The efficiency of the two procedures in the isolation of senescent cells was compared. The results indicate that, despite the evidence that total cell GSH decreases with aging, its concentration, evaluated in the cell preparations of different ages, remains constant throughout the red cell life, when correlated with cell water content. Glutathione disulfide concentration increases with aging. The oxidation state of membrane proteins does not seem to change during the red cell life span.
Assuntos
Membrana Eritrocítica/fisiologia , Eritrócitos/fisiologia , Glutationa/metabolismo , Proteínas de Membrana/metabolismo , Adulto , Contagem de Células , Senescência Celular/fisiologia , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Humanos , Masculino , OxirreduçãoRESUMO
Oxidative lesions to membrane proteins were studied in human erythrocytes of different age and were evaluated on ghost membrane preparations by assaying thiol and methionine sulphoxide groups, and in situ on intact cells, after treating erythrocytes with the fluorochrome N-(7-dimethyl-amino-4-methyl-coumarinyl) maleimide (DACM). DACM reacts with thiol groups and the amount of this reagent bound by membrane proteins was quantified after SDS-PAGE separation. Results obtained show that during aging of normal cells the oxidative state of membrane proteins increases: this was better shown by the assay of methionine sulphoxide residues rather than by the thiol titration, when studies were carried out on ghost membranes. After separation of individual membrane proteins by SDS-PAGE, decreased accessibility of DACM to thiol groups of band 3 and of the main proteins of the membrane skeleton was evident in senescent erythrocytes. These results show that during aging, band 3 and membrane skeleton proteins undergo conformational changes and/or oxidation. Similar results were obtained when thiol distribution was studied in membrane proteins separated by SDS-PAGE in both reducing and non-reducing conditions.
Assuntos
Envelhecimento Eritrocítico/fisiologia , Eritrócitos/metabolismo , Proteínas de Membrana/sangue , Eletroforese em Gel de Poliacrilamida , Humanos , Maleimidas , Metionina/análogos & derivados , Metionina/sangue , Oxirredução , Compostos de Sulfidrila/sangue , Reagentes de SulfidrilaRESUMO
A new synthetic substrate for protein methionine sulfoxide reductase is proposed. We show that extracts from human polymorphonuclear leukocytes can reduce 4-dimethylaminoazobenzene-4'-sulfonyl-L-methionine-dl-sulfoxide [DABS-L-Met-dl-(O)] to the corresponding methionine derivative, in the presence of dithiothreitol or dithioerythritol. The product of the reaction (DABS-Met) was separated by reversed-phase HPLC and detected by reading the absorbance at 436 nm. Due to the chirality of the sulfur atom in the sulfoxide, two diastereomers of Met(O) exist, namely Met-l-sulfoxide and Met-d-sulfoxide. After separation of the two forms and preparation of the DABS-derivatives, we observed a preferential reduction of the l-sulfoxide by polymorphonuclear leukocytes extracts. We discuss the possibility that the observed stereospecificity might have physiological relevance in the field of the oxidative modifications of proteins.
Assuntos
Compostos Azo/metabolismo , Metionina/análogos & derivados , Neutrófilos/enzimologia , Oxirredutases/metabolismo , Sulfóxidos/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Cinética , Metionina/metabolismo , Metionina Sulfóxido Redutases , Oxirredução , Estereoisomerismo , Especificidade por SubstratoRESUMO
The state of oxidation of membrane proteins was analyzed in red cell subpopulations of different age by quantifying the oxidation of methionine to its sulfoxide and by determining the amount of thiol groups in ghost membrane preparations and the reactivity of thiols of individual membrane proteins in intact cells. The results obtained show that oxidation of methionine occurs early during red cell life in the circulation, and can be detected in middle-aged and senescent cells. Thiol content of ghost membranes is kept constant in all the red cell subpopulations analyzed, but reactivity of thiol groups to the thiol reagent N-(7-dimethyl-amino-4-methyl-coumarinyl) maleimide (DACM) in intact cells decreased 30% in alpha-spectrin, band 3 (B3), 4.1 and 4.2 proteins, probably as a consequence of conformational changes of these molecules. Since the role played by band 3 in the exposure of senescence antigen has been described by many authors, the functional activity of the anion transporter has been analyzed by measuring the 4-4'-diisothiocyano-stilbene-2-2-'-disulfonate (DIDS) binding capacity in different red cell subpopulations. The results obtained are in agreement with the possibility that during senescence band 3 undergoes conformational changes involving the anion channel subsite being more exposed to the extracellular space and responsible for binding of DIDS.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Polimialgia Reumática/diagnóstico por imagem , Tendões/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Polimialgia Reumática/patologia , Nódulo Reumatoide/diagnóstico por imagem , Nódulo Reumatoide/patologia , Tendões/patologiaAssuntos
Envelhecimento Eritrocítico , Membrana Eritrocítica/metabolismo , Proteínas de Membrana/metabolismo , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Diamida/farmacologia , Deformação Eritrocítica , Eritrócitos/efeitos dos fármacos , Humanos , Metionina/análogos & derivados , Metionina/sangue , Oxirredução , Compostos de Sulfidrila/sangueRESUMO
Human erythrocytes are equipped with a diversity of receptors and effectors that mediate well-characterized signal transduction pathways in nonerythroid cells. Some of these erythrocyte components may be vestiges of signaling pathways critical to the functions of the erythrocyte's precursors but no longer needed in the mature erythrocyte. Other signaling elements, however, are likely involved in enabling the erythrocyte to detect and respond to the needs of other hematopoietic and endothelial cells with which it comes in contact.
Assuntos
Eritrócitos/fisiologia , Transdução de Sinais , Animais , Humanos , Receptores de Superfície Celular/fisiologiaRESUMO
Human erythrocytes were induced to release membrane vesicles by treatment with Ca2+ and ionophore A23187. In addition to the biochemical changes already known to accompany loading of human erythrocytes with Ca2+, the present study reveals that tyrosine phosphorylation of the anion exchanger band 3 protein also occurs. The relationship between tyrosine phosphorylation of band 3 and membrane vesiculation was analysed using quinine (a non-specific inhibitor of the Ca(2+)-activated K+ channel, and the only known inhibitor of Ca(2+)-induced vesiculation) and charybdotoxin, a specific inhibitor of the apamin-insensitive K(+)-channel. Both inhibitors suppressed tyrosine phosphorylation of band 3. In the presence of quinine, membrane vesiculation was also suppressed. In contrast, at the concentration of charybdotoxin required to suppress tyrosine phosphorylation of band 3, membrane vesiculation was only mildly inhibited (16-23% inhibition), suggesting that tyrosine phosphorylation of band 3 is not necessary for membrane vesiculation. Phosphorylation of band 3 was in fact observed when erythrocytes were induced to shrink in a Ca(2+)-independent manner, e.g. by treatment with the K+ ionophore valinomycin or with hypertonic solutions. These observations suggest that band 3 tyrosine phosphorylation occurs when cell volume regulation is required.
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Calcimicina/farmacologia , Cálcio/farmacologia , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Fosfoproteínas/sangue , Fosfotirosina , Proteína 1 de Troca de Ânion do Eritrócito/efeitos dos fármacos , Apamina/farmacologia , Charibdotoxina/farmacologia , Eletroforese em Gel de Poliacrilamida , Membrana Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Humanos , Cinética , Fosfoproteínas/isolamento & purificação , Fosforilação , Bloqueadores dos Canais de Potássio , Canais de Potássio/fisiologia , Quinina/farmacologiaRESUMO
Human erythrocyte band 3 becomes rapidly phosphorylated on tyrosine residues after exposure of erythrocytes to hypertonic conditions. The driving force for this phosphorylation reaction seems to be a decrease in cell volume, because (1) changes in band 3 phosphotyrosine content accurately track repeated changes in erythrocyte volume through several cycles of swelling and shrinking; (2) the level of band 3 phosphorylation is independent of the osmolyte employed but strongly sensitive to the magnitude of cell shrinkage; and (3) exposure of erythrocytes to hypertonic buffers under conditions in which intracellular osmolarity increases but volume does not change (nystatin-treated cells) does not promote an increase in tyrosine phosphorylation. We hypothesize that shrinkage-induced tyrosine phosphorylation results either from an excluded-volume effect, stemming from an increase in intracellular crowding, or from changes in membrane curvature that accompany the decrease in cell volume. Although the net phosphorylation state of band 3 is shown to be due to a delicate balance between a constitutively active tyrosine phosphatase and constitutively active tyrosine kinase, the increase in phosphorylation during cell shrinkage was demonstrated to derive specifically from an activation of the latter. Further, a peculiar inhibition pattern of the volume-sensitive erythrocyte tyrosine kinase that matched that of p72syk, a tyrosine kinase already known to associate with band 3 in vivo, suggested the involvement of this kinase in the volume-dependent response.