artículos originales breves0Diagnostic utility of oxidative damage markers for early rheumatoid arthritis in non-smokers and negative anti-ccP patients Utilidad diagnóstica de los marcadores de estrés oxidativo en artritis reumatoide precoz en pacientes no fumadores y anti-CCP negativos resuMen Fundamento. A pesar del desarrollo de nuevos marcadores y criterios diagnósticos para la artritis reumatoide (AR), todavía muchos pacientes son diagnosticados tras varios años de síntomas. Los marcadores de estrés oxidativo se incrementan ya en una fase temprana de la enfermedad. El objetivo del presente estudio fue evaluar el valor diagnóstico adicional de estos marcadores. Método. Se realizó un estudio de casos y controles. Los pacientes reclutados para el estudio cumplían los criterios para AR de la ACR 1987, todos ellos tenían menos de 2 años de síntomas y sin tratamiento previo con fármacos modificadores de la enfermedad antirreumática (DMARD), esteroides o vitamina E. Los controles fueron seleccionados de los familiares del paciente y pareados (1:1) por sexo, edad, hábito tabáquico actual. Los marcadores de daño oxidativo que se midieron fueron malonildialdehído (MDA), hidroperóxidos lipídicos (LOOH) y proteínas carboniladas (CP). El Análisis estadístico se realizó de acuerdo con la STARD. resultados. Se incluyeron sesenta y cinco pacientes con AR sin tratamiento y 65 controles sanos. LOOH, CP, los anticuerpos con péctidos citrulinados (anti-CCP) y el factor reumatoide (FR) fueron significativamente mayores en los pacientes, y MDA fue mayor en los controles. Los mismos resultados se obtuvieron en los subgrupos de pacientes que fuman o no, y en anti-CCP positivos o negativos. El valor diagnóstico de los marcadores tradicionales mostró una buena especificidad pero una baja sensibilidad. La construcción de los modelos logísti-cos con la adicción de LOOH y CP aumenta la sensibilidad y el área bajo la curva ROC, especialmente en los no fumadores (66%) y los pacientes negativos ante-CCP (51%). conclusiones. Al incorporar LOOH o CP a los marcadores de la enfermedad tradicionales en AR, bien por separado o ambos conjuntamente, mejoró el diagnóstico de AR, especialmente en los pacientes no fumadores o aquellos con anticuerpos anti-CCP negativos. Palabras clave. Sensibilidad. Hidroperóxido lipídico. Proteína carbonilada. Tabaco. Artritis reumatoide. abstract background. Besides the development of new markers and diagnostic criteria for rheumatoid arthritis (RA), many patients are still diagnosed after several years of symptoms. Oxidative stress markers are already increased at an early stage of RA. Our aim was to evaluate the additional diagnostic value of these markers. Methods. A case-control study was performed. Patients met the 1987 RA ACR criteria, less than 2 years of symptoms and no previous treatment with disease-modifying anti-rheumatic drugs (DMARD), steroids or vitamin E. Controls were selected from patient's relatives and matched (1:1) by gender, age, and current smoking habit. Oxidative damage markers were malony...

Background Empagliflozin is a potent, highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor used as an effective and well-tolerated antihyperglycaemic agent. Beyond lowering glucose, empagliflozin exerts a favorable effect on a number of nonglycaemic outcomes, including modest reductions in bodyweight and blood pressure, and it has cardioprotective and renoprotective properties in patients with T2D and established cardiovascular disease (EMPA-REG OUTCOME). Purpose Since liver fat content represents a risk factor for cardiovascular diseases, and empagliflozin has been recently suggested to be able to contribute to the early treatment of nonalcoholic fatty liver disease in T2D, we aimed to study the effect of the empagliflozin treatment in the liver metabolome of type 2 diabetic rats. Methods Male ZDF-Leprfa/fa rats were treated with 30 mg/kg/d of empagliflozin p.o for six weeks. Metabolic profiling of the hepatic tissue was analyzed using UHPLC-MS based platforms. We performed a hematoxylin/eosin staining to determine the tissue integrity and liver fat accumulation, and a Masson's trichrome staining to analyze liver fibrosis. All animals were maintained and euthanized following protocols approved by the Animal Care Committee of the University of Santiago de Compostela in accordance with European Union Directive 2010/63. Results Empaglifozin treatment reduced blood glucose levels to normal (128.2±6.51 mg/dL), while untreated control rats showed high glucose levels (404.3±17.49 mg/dL). Hepatic histological analysis did not show differences regarding neither fat accumulation nor fibrosis between empagliflozin treated and control rats. Circulating levels of cholesterol, HDL, LDL, GTP, GGT triglycerides remained unaltered after empaglifozin treatment vs. control. 384 metabolites were analyzed in the liver tissue samples, observing significantly increased levels of 10 types of glycerolipids, 24 phosphatidylcholines, 8 amino acids, 1 polyunsaturated fatty acid, 4 lysophosphatidylethanolamines, 7 lysophosphatidylinositols, 1 carboxylic acid and 1 nucleoside in the empagliflozin treated rats with respect to the control group. In addition, treatment with empagliflozin produced a significant decrease of 1 glycerolipid, 1 phosphatidylcholine, 1 bile acid, 1 nucleoside and the NAD oxidoreduction coenzyme. Conclusions We demonstrated that empagliflozin significantly modify the liver content of the different lipid species, with the most relevant altered metabolic classes belonging to glycerophospholipids, especially monoacyl-species, and aromatic amino acids. Considering the suggested potential beneficial effect of the treatment with empagliflozin in the prevention of liver fibrosis, our metabolomics data can help to evaluate the impact and the mechanism of action of SGLT2 inhibitors at hepatic level. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim

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