Recreational exposure during algal bloom in carrasco beach, uruguay: A liver failure case report

In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child’s case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II-III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr-1 tissue) and [D-Leu1]MC-LR (75.4 ng·gr-1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.Fil: Vidal, Flavia. Hospital Italiano; ArgentinaFil: Sedan, Daniela Yazmine. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Centro de Investigaciones del Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: D'Agostino, Daniel. Hospital Italiano; ArgentinaFil: Cavalieri, María Lorena. Hospital Italiano; ArgentinaFil: Mullen, Eduardo. Hospital Italiano; ArgentinaFil: Parot Varela, María Macarena. Hospital Italiano; ArgentinaFil: Flores, Cintia. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Caixach, Josep. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Andrinolo, Dario. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Centro de Investigaciones del Medio Ambiente; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

High resolution mass spectrometric analysis of secoiridoids and metabolites as biomarkers of acute olive oil intake - an approach to study inter-individual variability in humans

SCOPE: Phenolic compounds are minor components of extra virgin olive oil (EVOO). Secoiridoids are the major components contributing to the phenolic content of EVOO. {Silva, 2015 #95}Information is lacking regarding their potential as biomarkers for EVOO intake. METHODS AND RESULTS: Healthy volunteers (n = 9) ingested 50 mL of EVOO in a single dose containing 322 mg/kg total phenolic content (caffeic acid equivalents) and 6 mg/20g hydroxytyrosol and its derivatives. Plasma was collected before (0h) and at 0.5, 1, 2, 4 and 6h after ingestion. Urine samples were collected prior to ingestion (0h) and at 0-4, 4-8, 8-15 and 15-24h. Samples were analysed by UPLC coupled with an Exactive Orbitrap MS. Partial Least Squares Discriminant Analysis with Orthogonal Signal Correction was applied to screen for metabolites that allowed samples discrimination. Plasma biomarkers and urine biomarkers were selected although individual variability was observed among volunteers. Results are in accordance with in vitro experiments performed (in vitro digestion and hepatic microsomal activity assays). CONCLUSIONS: Plasma (elenolic acid + H2 ; p-HPEA-EA + H2 + glucuronide) and urinary (3,4-DHPEA-EA, 3,4-DHPEA-EA + H2 +glucuronide, methyl 3,4-DHPEA-EA + H2 +glucuronide) secoiridoid compounds were selected as biomarkers to monitor EVOO intake showing good predictive ability according to multivariate analysis

TAVI for Pure Native Aortic Regurgitation: Are We There Yet?

Treatment of degenerative aortic stenosis has been transformed by transcatheter aortic valve implantation (TAVI) over the past 10–15 years. The success of various technologies has led operators to attempt to broaden the indications, and many patients with native valve aortic regurgitation have been treated ‘off label’ with similar techniques. However, the alterations in the structure of the valve complex in pure native aortic regurgitation are distinct to those in degenerative aortic stenosis, and there are unique challenges to be overcome by percutaneous valves. Nevertheless some promise has been shown with both non-dedicated and dedicated devices. In this article, the authors explore some of these challenges and review the current evidence base for TAVI for aortic regurgitation

The Role of Serum Biomarkers in Predicting Fibrosis Progression in Pediatric and Adult Hepatitis C Virus Chronic Infection

Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection.Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested. = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598–0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736–0.994), 0.894 (IC95% 0.689–0.984) and 0.835 (IC95% 0.617–0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1.In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients

Serum apoptosis markers related to liver damage in chronic hepatitis C: sFas as a marker of advanced fibrosis in children and adults while M30 of severe steatosis only in children

Background: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. Methods: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. Results: sFas was associated with fibrosis severity in pediatric (significant fibrosis p=0.03, advanced fibrosis p=0.01) and adult patients (advanced fibrosis p=0.02). M30 levels were elevated in pediatric patients with severe steatosis (p=0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p=0.03) and they were associated with hepatitis severity (p=0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). Conclusions: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.Fil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casciato, Paola. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Galoppo, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gadano, Adrián Carlos. Hospital Italiano; ArgentinaFil: Galdame, Omar. Hospital Italiano; ArgentinaFil: Galoppo, María Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Mullen, Eduardo. Hospital Italiano; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Hepatic lymphocytes involved in the pathogenesis of pediatric and adult non-alcoholic fatty liver disease

The immune response is critical in NAFLD pathogenesis, but the liver infiltrate’s composition and the role of each T cell population is still up for debate. To characterize liver pathogenesis in pediatric and adult cases, frequency and localization of immune cell populations [Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Foxp3+) and Th17 (IL-17A+)] were evaluated. In portal/periportal (P/P) tracts, both age groups displayed a similar proportion of CD8+ and CD4+ lymphocytes. However, comparable Foxp3+ and IL-17A+ cell frequencies were observed in pediatric cases, meanwhile, in adults Foxp3+ was higher than IL-17A+ cells. Interestingly, IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area in both age groups. In intralobular areas, both pediatric and adult cases showed CD8+ lymphocytes predominance with lower frequencies of CD4+ lymphocytes followed by Foxp3+. Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes (p = 0.026) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥ 2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ (p = 0.023) and intralobular CD8+ (p = 0.027) and CD4+ cells (p = 0.012). In NAFLD cases, the lymphocyte liver infiltrate composition differs between histological areas. Treg and Th17 balance seems to condition damage progression, denoting their important role in pathogenesis.Fil: Cairoli, Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Rios, Daniela Alejandra. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Galoppo, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Casciato, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina. Ministerio de Defensa. Armada Argentina. Hospital Naval Buenos Aires Cirujano Mayor Dr. Pedro Mallo; ArgentinaFil: Mullen, Eduardo. Ministerio de Defensa. Armada Argentina. Hospital Naval Buenos Aires Cirujano Mayor Dr. Pedro Mallo; Argentina. Hospital Italiano; ArgentinaFil: Giadans, Cecilia Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Bertot, Gustavo. Instituto Universidad de la Fundación "Héctor Barceló"; ArgentinaFil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentin

Chronic hepatitis b and chronic hepatitis C immunopathogenesis: similar but not the same

HBV and HCV are hepatotropic viruses which differ in the way they induce chronic disease. We aimed to compare the hepatic immune response in Chronic Hepatitis B (CHB) and C (CHC) infections and assess their role in liver damage. Immunostaining was done in 68 formalin-fixed and paraffin-embedded liver biopsies from 26 CHB and 42 CHC treatment-naive patients to characterize liver infiltrate: [Th (CD4+), Th1 (Tbet+), Th17 (IL-17A+), Treg (Foxp3+), and CTL (CD8+)]. Quantification: portal (P)= +/total lymphocytes or lobular= + lymphocytes in 10 fields; (400x). Hepatitis severity and fibrosis were assessed by the modified Knodell (HAI) and METAVIR. Comparing CHB and CHC lymphocyte prevalence was alike in P areas (Th>CTL>Treg>Th17>Th1). However, CHC patients showed higher frequencies of Treg, Th17 and Th1 cells (p=0.001, p=0.005 and p=0.003, respectively, U-test). In contrast, cell distribution was different in the lobular area (CHB: CTL> Treg>Th17=Th1>Th vs CHC: CTL>Th1>Treg>Th=Th17) with higher frequencies of Th, Th17 and Th1 cells in CHC (p=0.04, p=0.001 and p=0.001, respectively, U-test) compared with CHB. Regarding liver damage, patients with analogous disease stage showed similar cell frequencies but only in CHC P Th17 were associated with advanced fibrosis (p=0.03, U-test) and just in CHB P Th (p=0.04, U-test) and lobular CTLs and Th17 cells (p=0.02 and p=0.01, respectively; U-test) were increased in severe hepatitis cases.Even when all studied populations were identified in CHB and CHC, common and particular features related to liver damage were detected. Lobular CTLs prevalence in both infections implies their contribution in hepatitis pathogenesis. As for CHB, despite the presence of a regulatory microenvironment, CTLs and Th17 cells promote hepatitis severity, suggesting a Treg failure in limiting liver damage but favouring viral persistence. By contrast, CHC showed a highly inflammatory context with CTL and Th1 majority and Th17 cells enhancing liver fibrosis.Fil: Giadans, Cecilia Graciela. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Rios, Daniela Alejandra. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Cairoli, Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Alonso, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pietrantonio, Adriana M.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Mullen, Eduardo. Hospital Italiano; ArgentinaFil: Heinrich, Fabiana. No especifíca;Fil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Preciado, Maria Victoria. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina Fisiologí

Compound A, a Dissociated Glucocorticoid Receptor Modulator, Inhibits T-bet (Th1) and Induces GATA-3 (Th2) Activity in Immune Cells

Background: Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has antiinflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively. Results: Using Western analysis and reporter gene assays, we show in murine T cells that, similar to GCs, CpdA inhibits T-bet activity via a transrepressive mechanism. Different from GCs, CpdA induces GATA-3 activity by p38 MAPK-induction of GATA-3 phosphorylation and nuclear translocation. CpdA effects are reversed by the GR antagonist RU38486, proving the involvement of GR in these actions. ELISA assays demonstrate that modulation of T-bet and GATA-3 impacts on cytokine production shown by a decrease in IFN-c and an increase in IL-5 production, respectively. Conclusions: Taken together, through their effect favoring Th2 over Th1 responses, particular dissociated GR ligands, fo

Coupled simulation of performance of a crossed compound parabolic concentrator with solar cell

An optimal installation of a compound parabolic concentrator (CCPC) into a scalable solar thermoelectrics and photovoltaics system is desirable by applying analytical tools to improve the optical and thermal performance of a CCPC with a solar cell. In this paper, the optical and thermal performances of an isolated CCPC with solar cell are investigated by employing commercial software ‘ANSYS CFX 15.0’ with a coupled optical grey and multiphysics model. Numerical results are validated against the experimental data at various incidence angles, especially for the optical concentration ratio and optical efficiency. Results confirm that ‘ANSYS CFX’ is an effective numerical tool for determining correctly both the optical and thermal behaviour of CCPC. The very important finding is a highest temperature core in the silicon layer of solar cell which may be responsible for a solar cell to work properly. The limitation of the work is that the electric performance of the solar cell is not involved and the simulations are steady