Some current challenges in research on air pollution and health / Desafíos actuales de la investigación sobre contaminación del aire y salud

This commentary addresses some of the diverse questions of current interest with regard to the health effects of air pollution, including exposure-response relationships, toxicity of inhaled particles and risks to health, multipollutant mixtures, traffic-related pollution, accountability research, and issues with susceptibility and vulnerability. It considers the challenges posed to researchers as they attempt to provide useful evidence for policy-makers relevant to these issues. This commentary accompanies papers giving the results from the ESCALA project, a multi-city study in Latin America that has an overall goal of providing policy-relevant results. While progress has been made in improving air quality, driven by epidemiological evidence that air pollution is adversely affecting public health, the research questions have become more subtle and challenging as levels of air pollution dropped. More research is still needed, but also novel methods and approaches to address these new questions.

Este comentario aborda algunos de los temas de interés actual en relación con los efectos de la contaminación del aire sobre la salud, tales como las relaciones exposición-respuesta, la toxicidad y riesgos para la salud de las partículas inhaladas, las mezclas de contaminantes múltiples, la contaminación relacionada con el tráfico, la investigación sobre responsabilidad, y los problemas de susceptibilidad y vulnerabilidad. Considera los retos que se presentan a los investigadores que intentan proporcionar evidencia para los responsables políticos en estas cuestiones. Este texto acompaña otros trabajos con resultados del proyecto ESCALA, un estudio en varias ciudades de América Latina que tiene como objetivo general proporcionar resultados relevantes para la política pública. Aunque ha habido avances para mejorar la calidad del aire, gracias a la evidencia epidemiológica de que la contaminación aérea está afectando negativamente a la salud pública, las preguntas de investigación se han vuelto más sutiles y difíciles a medida que los niveles de contaminación se reducen. Se necesita más investigación, pero también nuevos métodos y enfoques capaces de enfrentar estas preguntas.

Neuromuscular blocking effects of an alkaloidal extract from Inula royleana: contractile and electrical studies on amphibian skeletal muscle in vitro.

The neuromuscular blocking properties of an alkaloidal extract from the root of Inula royleana have been investigated in vitro using a combination of mechanical and electrophysiological approaches. Neurogenic twitches of the frog sartorius were profoundly inhibited by concentrations of the extract > or = 20 micrograms/ml, being reduced to 50% of control amplitude in approximately 90 s at a concentration of > or = 20 micrograms/ml. They were partially reversed by neostigmine (6 micrograms/ml), and by prolonged washout of the extract. Muscle surface action potentials, recorded with extracellular electrodes, also declined rapidly in amplitude in the presence of the extract. Direct muscle stimulation during inhibition by the extract elicited contractions and action potentials whose magnitudes were similar to control responses. Resting membrane potentials, and the intracellular input impedance of the skeletal muscle cells, were not significantly changed by the alkaloids. These results indicate that the extract has significant neuromuscular blocking activity of a partially or slowly reversible nature. The block appears to be exerted at the postjunctional end-plate nicotine receptors, thus offering promise for the identification of novel cholinergic receptor antagonist(s).

The internal horizontal cell of the frog: spatial summation

En la Rana pipiens se estudiaron las propiedades del campo receptivo de las células horizontales internas (CHI). Se determinó la constante de espacio de cada célula usando puntos luminosos de diferentes tamaños o moviendo una abertura luminosa rectangular a lo largo de la retina. Con el primer método, la constante varió entre 100 - 500 um y con el segundo, entre 100 - 720 um. Se describió un rango de valores similar en el Xenopus, aunque sus SHI son más grandes que las de la Rana. Aparentemente, el acoplamiento entre las CHI es más eficiente en la retina de la Rana que en aquellá del Xenopus. El amplio rango de los valores sugiere que entre las células de la misma retina hay una variación importante en la eficiencia del acoplamiento

Structure-activity relationship of reversible cholinesterase inhibitors: activation, channel blockade and stereospeceficity of the nicotinic acetylcholine receptor-ion channel complex

We have shown that alt cholinesterase (ChE) inhibitors, in addition to their well-known anti-ChE activity, have multiple effects on the nicotinic acetylcholine receptor-ion channel (AChR) macromolecule resulting from interactions with the agonist recognition site and with sites located at the ion channel component. Activation, competitive antagonism and different types of noncompetitive blockade occurring at similar concentration ranges and contributing in different proportions result in complex and somewhat unpredictable alterations inn AChR function. The question is now raised as to how each effect of these compounds contributes to their antidotal property against organophosphorus (OP) poisoning, and what set of actions makes one reversible ChE inhibitor a better antidote. Many lines of evidence support the importance of direct interactions with various sites on the AChR: 1) morphological and toxicological studies with (+) physostigmine showed that anti-ChE activity is not essential to protect animals against toxicity by irreversible ChE inhibitors; 2) (-) physostigmine is far more effective against OP poisoning; 3) open channel blockers such as mecamylamine with no significant anti-ChE activity enhance the protective action of (-) physostigmine; 4) neostigmine, pyridostigmine, (-) physostigmine and (+) physostigmine showed qualitatively and quantitatively distinct toxicity and damage to endplate morphology and function. In prophylaxis and during the very early phase of OP poisoning, carbamates, especially (-) physostigmine combined with mecamylamine and atropine, could protect almost 100% of the animals exposed to multiple lethal doses of OPs...

The effect of centrophenoxine at the skeletal neuromuscular junction.

Centrophenoxine exhibited some interesting actions at the neuromuscular junction. The drug was ineffective in rat or chick preparations, but blocked neuromuscular transmission in frog preparations. The blockade was reversed by adrenaline, potassium, choline and physostigmine. The drug had no effect on muscle contractility or endplate cholinoceptor. Hemicholinium 3 induced a neuromuscular blockade in rat (in vivo) which was reversed by choline but not by centrophenoxine. Neither of these two drugs could reverse the blocking effect of hemicholinium in frog preparations. It is concluded that centrophenoxine acts only in frog and the blockade involves a presynaptic mechanism. The work further suggests that choline uptake systems in the rat and the frog may not be identical, since choline competed with hemicholinium for the uptake system in rat and with centrophenoxine (but not with hemicholinium) in the frog.