RESUMO
We report an asymptomatic 23-year-old woman with an isolated and persistent increase in serum levels of aspartate aminotransferase (AST). An extensive work up including laboratory and image testing revealed no abnormalities thus suggesting the presence of macro-AST. A polyethylene glycol (PEG) precipitation assay was performed and confirmed the presence of macro-AST.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/enzimologia , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/enzimologia , Adulto JovemRESUMO
We report an asymptomatic 23-year-old woman with an isolated and persistent increase in serum levels of aspartate aminotransferase (AST). An extensive work up including laboratory and image testing revealed no abnormalities thus suggesting the presence of macro-AST. A polyethylene glycol (PEG) precipitation assay was performed and confirmed the presence of macro-AST.
Assuntos
Humanos , Feminino , Adulto Jovem , Aspartato Aminotransferases/sangue , Alanina Transaminase/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/enzimologia , Hepatopatias/diagnóstico , Hepatopatias/enzimologiaRESUMO
BACKGROUND: Male reproductive tract infection and inflammation are important aetiological factors of infertility. Experimental Autoimmune Orchitis (EAO) is a model of chronic inflammation useful to study mechanisms of inflammatory reactions leading to testicular impairment. EAO is characterised by interstitial cell infiltrate of lymphomonocytes, producers of pro-inflammatory cytokines involved in germ cell apoptosis. Nitric oxide (NO), a free radical promoting immune cell activation and apoptosis, is synthesised by conversion of l-arginine to l-citrulline catalysed by NO synthase (NOS). The NOS isoforms are: constitutively endothelial (e) and neuronal (n) NOS and inducible (i) NOS. OBJECTIVES: Although the NO-NOS system was found to be up-regulated by pro-inflammatory mediators in immune and non immune testicular cells, data on its regulation in chronic inflammatory states is lacking. METHODS AND RESULTS: EAO was induced in rats by active immunisation with spermatic antigens and adjuvants; control (C) rats were injected with adjuvants. Untreated normal (N) rats were also studied. We demonstrated that iNOS, eNOS and nNOS was mainly expressed by interstitial cells in N and C rats and that in EAO NOS was up-regulated and also expressed by tubular cells. Constitutive and inducible NOS content (Western blot) as well as NO production and activity increased in the testis of rats with EAO. iNOS content and activity were selectively up-regulated in the testis of rats with orchitis. Flow cytometric analysis of NOS isoforms in testicular macrophages (M) showed that the percentage of ED1(+)ED2(-) and ED1(+)ED2(+) M subsets, expressing constitutive and iNOS isoforms was significantly higher in EAO, but no change in the percentage of ED1(-)ED2(+) resident M was observed compared to C rats. M from EAO rats also released more NO than C and N rats. CONCLUSIONS: In testis of rats with EAO, NO-NOS system was up-regulated and both testicular M and cells from seminiferous tubules contributed to NO increase. NO over production in orchitis was generated mainly by increased iNOS content and activity.
Assuntos
Doenças Autoimunes/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Orquite/metabolismo , Testículo/metabolismo , Adjuvantes Imunológicos , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/enzimologia , Western Blotting , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Macrófagos/enzimologia , Macrófagos/metabolismo , Masculino , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Orquite/induzido quimicamente , Orquite/enzimologia , Ratos , Ratos Sprague-Dawley , Testículo/enzimologia , Testículo/patologia , Regulação para CimaRESUMO
The aim of this work was develop a new combined radioligand-binding assay (RBA-combi) for the rapid and simultaneous determination of two autoimmunity markers, GADA and PAA, known to be differentially distributed in young and in some adult diabetic patients. The methodology was applied to sera from 85 young type 1 and 98 adult-onset diabetic patients with different marker profiles and insulin requirements, and to 53 normal control sera. Among type 1 diabetes sera used as autoimmunity controls, 100% of those with at least one positive marker by single methods and 17.7% of those with double negative markers were positive by RBA-combi (RBA-combi+). Among sera from adult-onset diabetes, 100% of those PAA+ (GADA+ or GADA-), 92.3% of GADA+/PAA-, and 1.3% of GADA-/PAA- were RBA-combi+. In conclusion, the new RBA-combi allowed the simultaneous detection of GADA and PAA markers with acceptable performance. Moreover, 16 out of 18 (88.9%) of adult patients RBA-combi+ evolved to insulin requirement, suggesting that this test is a valuable tool for assessing autoimmune processes associated to future impairment of insulin secretion.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/imunologia , Glutamato Descarboxilase/imunologia , Programas de Rastreamento/métodos , Proinsulina/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/enzimologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Glutamato Descarboxilase/sangue , Glutamato Descarboxilase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proinsulina/sangue , Ensaio RadioliganteRESUMO
This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior. By mean of the production of [U-14C]citrulline from [U-14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in autoimmune atria that was normally absent. The iNOS activity decreased with administration of dexamethasone and in mice treated with monoclonal anti-interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/calmodulin (trifluoperazine) attenuated the iNOS activity. Moreover, autoimmune atria presented contractile alterations (lower values of dF/dt than control). The in vivo treatment with inhibitors of NOS activity or anti-IFN-gamma mAb or dexamethasone improved the contractile activity of autoimmune atria with no change in the contractility of normal atria. The results suggest that the infiltrative cells in myocarditis heart have a potential role in cardiac dysfunction by production of IFN-gamma and subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cytokines induced activation of L-arginine nitric oxide pathway in myocarditis atria leading to contractile dysfunction.