Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity

Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.Fil: Bulacio, Romina Paula. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Anzai, Naohiko. Dokkyo Medical University; JapónFil: Ouchi, Motoshi. Dokkyo Medical University; JapónFil: Torres, Adriana Monica. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A Peer-reviewed Newspaper About_ Machine Feeling

On the ability of technologies to capture and structure feelings and experiences that are active, in flux, and situated in the present. Publication resulting from research workshop at CRASSH, University of Cambridge, organised in collaboration with CRASSH, University of Cambridge and transmediale festival for art and digital culture, Berlin

Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases

Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirme

Na+-D-glucose Cotransporter SGLT1 is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion

To clarify the physiological role of Na(+)-d-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(−/−) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(−/−) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(−/−) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose–free diet. In wild-type mice, passage of d-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(−/−) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2