ATP-binding cassette (ABC) transporters in normal and pathological lung

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases

Urinary Mutagenicity in Chemical Laboratory Workers Exposed to Solvents

Solvents represent an important group of environmental pollutants to which people are exposed daily in the workplace. The physico chemical properties of solvents may result in disturbances to cellular structures, including damage to DNA. However, the effects of mixtures of solvents are not well known. Mutations caused by environmental agents are related to cancer development and other degenerative diseases. The work in a research laboratory that uses several types of solvents is equally predisposed to these hazards. In this study, we evaluated the mutagenicity of urine from 29 subjects exposed occupationally to solvents in a chemistry research laboratory and 29 subjects without occupational exposure (controls). Urine samples were collected in polyethylene containers at the end of the work shift. For the concentration and extraction of urine samples the XAD-2 resin was used with acetone as an eluting agent. Several strains of Salmonella typhimurium (TA100, TA98, TA97a, TA1535, YG1024) should be used to assess mutagenic susceptibilities among workers exposed to organic solvents. Different doses of extract (1.5; 3.0; 6.0 and 12.0 m/ equivalents of urine per plate) were tested on S. typhimurium strains TA100 and YG 1024, with and without metabolic activation. The mutagenic activity, measured in Salmonella typhimurium YGI1024 with S9 mix, was significantly greater in urine from workers than from controls (p <= 0.05). These results indicate the relevance of using biomarkers to assess the risk of occupational exposure to organic solvents

Una ruta metodológica para determinar escenarios de interacción entre procesos fluviales y el entorno construido residencial en Patagonia Occidental

It is a complex task to identify plausible scenarios of interaction between fluvial processes and the residential built environment. It entails of determining and quantifying the propagation of flows in the river channels and flood plains, and the way in which these flows could affect the different elements of the built environment leading to economic damage. This paper proposes a methodological roadmap to identify and structure scenarios of interaction between fluvial processes and the built environment with emphasis on fluvial systems disturbed by volcanic eruptions in Chilean Patagonia. Aware that the elaboration of these scenarios always involves a high degree of uncertainty and that the dynamics of fluvial processes in basins affected by natural hazards may have more than one surprise in store, we argue that the structuring of these scenarios by linking process, impact and response models allows to quickly correct the initial hypotheses and conjectures that are not supported by the evidence and to integrate the new knowledge acquired. This represents an essential condition for decision-making in terms of risk mitigation and for increasing the resilience of structures exposed to the impacts of fluvial processes.Vislumbrar cuales podrían ser escenarios plausibles de interacción entre procesos fluviales y el entorno construido residencial es una tarea compleja. Esta consiste en determinar y cuantificar la propagación de los flujos en los cauces y en las planicies de inundación, además, hay que precisar el modo en que estos flujos podrían afectar a los distintos elementos del entorno construido conllevando daños económicos. En este trabajo se propone una ruta metodológica para identificar y estructurar escenarios de interacción entre procesos fluviales y el entorno construido con énfasis en los sistemas fluviales perturbados por erupciones volcánicas en la Patagonia Chilena. Conscientes de que la elaboración de estos escenarios siempre conlleva un alto grado de incertidumbre y que la dinámica de los procesos fluviales en cuencas afectadas por peligros naturales puede reservar más de una sorpresa, argumentamos que la estructuración de estos escenarios concadenando modelos de proceso, impacto y respuesta, permite corregir ágilmente las hipótesis y conjeturas iniciales que no resultasen avaladas por las evidencias e integrar los nuevos conocimientos adquiridos. Esto representa una condición imprescindible para la toma de decisiones en materia de mitigación de riesgos y para aumentar la resiliencia de las estructuras expuestas a los impactos de los procesos fluviales