ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

Suplementação com vitamina A: impacto na morbidade e efeitos adversos Vitamin A supplementation: impact on morbidity and adverse effects

Este artigo apresenta uma síntese de dois estudos previamente publicados e que avaliaram diferentes aspectos dos efeitos da suplementação com mega-doses (100.000 ou 200.000 UI) de vitamina A em crianças pré-escolares. O primeiro é um ensaio comunitário, aleatório, duplo cego e placebo controlado, que demonstrou o efeito positivo da suplementação na redução da severidade dos episódios de diarréia. O segundo investigou os potenciais efeitos adversos da suplementação com mega-doses de vitamina A, oferecida conjuntamente com a vacinação em massa, utilizando um desenho de intervenção controlado e não randomizado. Seus resultados indicaram que a suplementação associada com as vacinas rotineiramente utilizadas na infância não elevou as taxas de efeitos adversos (diarréia, febre e vômito). São ainda discutidas as implicações dos resultados destes estudos, que contribuíram não somente para o avanço do conhecimento científico do campo em questão, como também têm fornecido evidências para justificar a implementação de políticas e ações específicas no campo da saúde e da nutrição, que por sua vez têm contribuído para gerar condições mais auspiciosas de sobrevivência na infância. Discute-se também a pertinência e a utilidade de desenhos de estudo com diferentes níveis de rigor metodológico na avaliação de intervenção em saúde.<br>This paper is a synthesis of two previously published studies, which evaluated different aspects of the effects of massive doses of vitamin A (100,000 or 200,000 IU) in pre-school children. The first consisted of a randomized, double blind, placebo-controlled community trial, which demonstrated the effect of supplementation on the reduction of the severity of episodes of diarrhea. The second investigated the potential adverse effects of supplementation with massive doses of vitamin A when given during mass vaccination, using a controlled but not randomized intervention design. The results of this study showed that supplementation did not increase the rates of adverse effects (diarrhea, fever and vomiting) associated with the vaccines routinely used in infancy. In conclusion, we discuss the implications of the results of these studies, which contributed not only towards the advance of scientific knowledge in the field in question but also provided evidence to justify the implementation of policies and specific actions in the field of health and nutrition which have contributed towards creating better conditions for infant survival. We also discuss the pertinence and usefulness of study designs with different levels of methodological robustness in evaluations in health

The Future Perspectives of Dark Fermentation: Moving from Only Biohydrogen to Biochemicals

Dark fermentation, also known as acidogenesis, involves the transformation of a wide range of organic substrates into a mixture of products, e.g., acetic acid, butyric acid, and hydrogen. This bioprocess occurs in the absence of oxygen and light. The ability to synthesize hydrogen, by dark fermentation, has raised its scientific attention. Hydrogen is a nonpolluting energy carrier molecule. However, for energy generation, there are a variety of other sustainable, and less expensive, alternatives to biohydrogen energy, e.g., solar, wind, tide, hydroelectric, biomass incineration, or nuclear fission. Nevertheless, dark fermentation appears as an important sustainable process in another area: the synthesis of valuable chemicals, i.e., an alternative to petrochemical refinery. Currently, acetic acid, butyric acid, and hydrogen are mostly produced by petrochemical reforming, and they serve as precursors of ubiquitous petrochemical-derived products. Hence, the future of dark fermentation relies as a core bioprocess in the biorefinery concept. The present article aims to present and discuss the current and future status of dark fermentation in the biorefinery concept. The first half of the article presents the metabolic pathways, product yields and its technological importance, microorganisms responsible for mixed dark fermentation, and operational parameters, e.g., substrates, pH, temperature, and headspace composition, which affect dark fermentation. The minimal selling price of dark fermentation products is also presented in this section. The second half discusses the perspectives and future of dark fermentation as a core bioprocess. The relationship of dark fermentation with other (bio)processes, e.g., liquid fuels and fine chemicals, algae cultivation, biomethane-biohythane-biosyngas production, and syngas fermentation, is then explored.</p