Biodispoñibilidade oral de hidrocarburos aromáticos policíclicos en materia particulada atmosférica

[Abstract] The transport of deposited particles in lung during breathing to the gastrointestinal tract is one of the clearance mechanism that may occur into the respiratory system. In the context of human health-risk assessment, oral bioavailability refers to the pollutant fraction that diffuses across the gastrointestinal tract and reach the systemic circulation (blood). The main aim of this research is the development of a novel in-vitro testing to assess the oral bioavailability of polycyclic aromatic hydrocarbons (PAHs) in PM10 samples at urban site of A Coruña, and the accurately toxicity prediction of PAHs in PM10 using bioavailable concentrations. In-vitro oral bioavailability test involves the use of pepsin solution for simulated gastric digestion (37 ºC, 150 rpm, 120 min) and pancreatin/bile salts solution for simulated intestinal digestion (37 ºC, 150 rpm, 120 min). During simulated intestinal digestion, a dialysis membrane of 10 kDa MWCO filled PIPES (1,4-Piperazinediethanesulfonic acid sodium salt) solution (pH 7.5) was used to simulate cell walls of the intestine. Total PAHs concentrations of the samples were necessary to determine in order to obtain bioavailable percentages, by using an already developed new green analytical method. Low oral bioavailability ratios (< 1 %) were found for several PAHs such fluoranthene, pyrene, benzo(a)anthracene, chrysene, benzo(e)pyrene and benzo(k)fluoranthene.[Resumen] El transporte de las partículas depositadas en los pulmones durante la respiración al tracto intestinal es uno de los mecanismos de despeje que tienen lugar en el sistema respiratorio. En el contexto humano de la evaluación del riesgo de la salud, la biodisponibilidad oral hace referencia a la fracción de contaminante que se difunde a través del tracto gastrointestinal y llega al sistema circulatorio. El principal objetivo de esta investigación es el desarrollo de un nuevo método in-vitro para evaluar la biodisponibilidad oral de hidrocarburos aromáticos policíclicos (HAPs) en muestras de PM10 procedentes de una zona urbana de la ciudad de A Coruña, y de la predicción apropiada de la toxicidad de los HAPs en PM10 utilizando las concentraciones biodisponibles. El estudio de biodisponibilidad oral in-vitro implica el uso de pepsina para realizar la simulación gástrica (37 °C, 150 rpm, 120 min) y de pancreatina y sales biliares para la simulación de la digestión intestinal (37 °C, 150 rpm, 120 min). Durante la simulación de la digestión intestinal, una membrana de diálisis de 10kDa MWCO que contiene una disolución de PIPES (1,4-Piperazinediethanesulfonic acid sodium salt) a pH 7,53 se emplea para simular las paredes celulares del intestino. Las concentraciones totales de HAPs de las muestras se determinaron para obtener los porcentajes de biodisponibilidad utilizando un método de análisis verde ya desarrollado. Se obtuvieron bajos porcentajes de biodisponibilidad (< 1 %) para algunos HAPs, como para el fluoranteno, pireno, benzo(a)antraceno, criseno, benzo(e)pireno y benzo(k)fluoranteno.[Resumo] O transporte das partículas depositadas nos pulmóns durante a respiración ó tracto intestinal é uno dos mecanismos de despexe que teñen lugar no sistema respiratorio. No contexto humano da evaluación do risco da saúde, a biodispoñibilidad oral fai referencia á fracción de contaminante que se difunde a través do tracto gastrointestinal e chega ó sistema circulatorio. O principal obxectivo desta investigación é o desarrollo dun novo método in-vitro para a avaliación da biodispoñibilidade oral de hidrocarburos aromáticos policíclicos (HAPs) en mostras de PM10 procedentes dunha zona urbana da ciudad de A Coruña, e da predicción apropiada da toxicidad dos HAPs en PM10 utilizando as concentracións biodispoñibles. O estudio de biodispoñibilidade oral in-vitro implica o uso de pepsina para realizar a simulación gástrica (37 °C, 150 rpm, 120 min) e de pancreatina e sales biliares para a simulación da dixestión intestinal (37 °C, 150 rpm, 120 min). Durante a simulación da dixestión intestinal, unha membrana de diálise de 10kDa MWCO que contén unha disolución de PIPES (1,4-Piperazinediethanesulfonic acid sodium salt) a pH 7,53 empléase para simular as paredes celulares do intestino. As concentracións totales de HAPs das mostras foron determinadas para obter as porcentaxes de biodispoñibilidade utilizando un método de análise verde xa desarrollado. Baixas porcentaxes de biodispoñibilidade (< 1 %) foron obtidas para alguns HAPs, como para o fluoranteno, pireno, benzo(a)antraceno, criseno, benzo(e)pireno e benzo(k)fluoranteno.Traballo fin de grao (UDC.CIE). Química. Curso 2018/201

Oral Bioavailability Reveals an Overestimation of the Toxicity of Polycyclic Aromatic Hydrocarbons in Atmospheric Particulate Matter

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Polycyclic aromatic hydrocarbons (PAHs) in atmospheric particulate matter have adverse effects on human health, yet total PAH concentrations should overestimate the toxicity compared to the bioavailable amount of PAHs. To explore this hypothesis, we measured PAHs oral bioavailability in vitro in particulate matter with aerodynamic diameter lower than 10 µm (PM₁₀) using a test that mimics the human digestive system. This assay combines the use of simulated gastrointestinal fluids and a dialysis membrane to simulate intestinal absorption. Results show that oral PAH bioavailability was below 5%, with fluorene, anthracene, acenaphthene and phenanthrene as the most bioavailable PAHs. Data suggest no carcinogenic risk of oral bioavailable PM₁₀-bound PAHs following a health risk assessment via inhalation-ingestion by using benzo(a)pyrene-equivalent carcinogenic concentration and hazard indexes. To our best knowledge, this is the first research study of in vitro oral bioavailability estimation of PM₁₀-associated PAHs.This work was supported by Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (Programa Estatal de I+D+i Orientada a los Retos de la Sociedad, ref: RTI 2018-101116-B-I00) and Xunta de Galicia (Programa de Consolidación y Estructuración de Unidades de Investigación Competitivas ref: ED431C 2017/28-2017-2020). Joel Sánchez-Piñero acknowledges the Xunta de Galicia and the European Union (European Social Fund—ESF) for a predoctoral grant (ED481A-2018/164). The council of A Coruña is acknowledged for its assistance (collaboration agreement between the City of A Coruña and the University Institute of Environment (IUMA) of the University of A Coruña (UDC) for the measurement of PM10 particle levels in the area of Os Castros, A Coruña). The authors would like to thank EXPRELA group (UDC) for their support. Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED431C 2017/28-2017-2020Xunta de Galicia; ED481A-2018/16

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U

II Premio UDC sustentabilidade a traballos fin de grao e mestrado 2019

Recóllense nesta obra os oito traballos premiados no que foi a segunda edición do Premio UDC Sustentabilidade a Traballos de Fin de Grao e Mestrado, correspondente ao ano 2019. A convocatoria destes premios xurdiu dunha proposta recibida desde a Facultade de Ciencias da Educación, no marco do programa internacional Green Campus, e que finalmente a Oficina de Medio Ambiente da Universidade da Coruña materializou