Airborne environmental injuries and human health.

The concept that the environment in which we live can have detrimental effects on our health has existed for centuries. Obvious examples of substances that can cause human diseases include infectious agents, poisons, chemicals and other noxious agents, drugs, and physical stimuli such as bright lights and loud sounds. Some less obvious agents can include allergens, nontangible agents such as colorless, odorless gases and aerosolized toxins. In recent decades, humans have developed various new materials and compounds. Additionally, we are now producing known compounds, and even naturally occurring substances, in vastly increased amounts. Many of these substances are generally believed to threaten the health of our environment. However, there is also a considerable amount of hype and exaggeration regarding some of these agents (e.g., mold) that is unsubstantiated. This article extensively reviews the data on a large number of airborne-related illnesses and attempted to place scientific reality in the context of clinical medicine

A zinc transporter gene required for development of the nervous system.

The essentiality of zinc for normal brain development is well established. It has been suggested that primary and secondary zinc deficiencies can contribute to the occurrence of numerous human birth defects, including many involving the central nervous system. In a recent study, we searched for zinc transporter genes that were critical for neurodevelopment. We confirmed that ZIP12 is a zinc transporter encoded by the gene slc39a12 that is highly expressed in the central nervous systems of human, mouse, and frog (Xenopus tropicalis).Using loss-of-function methods, we determined that ZIP12 is required for neuronal differentiation and neurite outgrowth and necessary for neurulation and embryonic viability. These results highlight an essential need for zinc regulation during embryogenesis and nervous system development. We suggest that slc39a12 is a candidate gene for inherited neurodevelopmental defects in humans

Chocolate: food as medicine/medicine as food,”

Cocoa and chocolate products have been delicacies for hundreds of years. Only recently have they been recognized as significant sources of phytochemicals with healthful effects. These foods are among the most concentrated sources of the procyanidin flavonoids, catechin and epicatechin. Recent studies have shown that these polyphenols are absorbed from the intestine of animals and humans with epicatechin absorbed much more than catechin. These flavonoids have potent antioxidant and antiplatelet activities following consumption of cocoa or chocolate

Resveratrol given intraperitoneally does not inhibit the growth of high-risk t(4;11) acute lymphoblastic leukemia cells in a NOD/SCID mouse model.

The efficacy of resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL SEM cell line. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with resveratrol (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). Comparisons of the percent of human leukemia cells in blood and survival curves showed resveratrol did not inhibit progression of the disease. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed resveratrol was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, with low to no resveratrol or metabolites observed in sera by 24-48 h. These data indicate that in contrast to findings in in vitro models, parenterally administered resveratrol does not have potential as a preventive agent against high risk t(4;11) ALL

A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain

Zinc (Zn) deficiency during early development can result in multiple brain abnormalities and altered neuronal functions. In rats, a gestational deficit of Zn can affect the fetal brain cytoskeleton, and signaling cascades involved in cellular processes that are central to brain development. In the current paper, we tested the hypothesis that oxidative stress is involved in Zn deficiency-induced altered tubulin dynamics and the associated dysregulation of transcription factor NF-êB.For this purpose, we used two cell culture models (rat cortical neurons, human IMR-32 neuroblastoma cells) and an animal model of Zn deficiency. A low rate of in vitro tubulin polymerization, an increase in tubulin oligomers and a higher protein cysteine oxidation were observed in the Zn deficient neuronal cells, and in gestation day 19 fetal brains obtained from dams fed marginal Zn diets throughout pregnancy. These alterations could be prevented by treating the Zn deficient cells with the reducing agen tris (2-carboxyethyl)phosphine, or the presence of N-acetyl cysteine (NAC) and á-lipoic acid (LA) Consistent with the above, Zn deficiency-induced tubulin-mediated alterations in transcription factor NF-êB nuclear translocation were prevented by treating IMR-32 cells with LA and NAC. Binding of the NF-êB protein p50, dynein and karyopherin alpha (components of the NF-êB transport complex) to â-tubulin as well as the expression of NF-êB dependent genes (bcl-2, cyclin D1 and c-myc) were also restored by the addition of LA and NAC to Zn deficient cells. In conclusion, a deficit in Zn viability could affect early brain development through: 1) an induction of oxidative stress; 2) tubulin oxidation; 3) altered tubulin dynamics, and 4) deregulation of signals (e.q. NF-êB) involved in critical developmental events.Fil: Mackenzie, Gerardo G.. University Of California At Davis; Estados UnidosFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Romero, Carolina. University Of California At Davis; Estados UnidosFil: Keen, Carl L.. University Of California At Davis; Estados UnidosFil: Oteiza, Patricia Isabel. University Of California At Davis; Estados Unido

Fortification and health: challenges and opportunities.

Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness

Flavonoid-membrane Interactions: A Protective Role of Flavonoids at the Membrane Surface?

Flavonoids can exert beneficial health effects through multiple mechanisms. In this paper, we address the important, although not fully understood, capacity of flavonoids to interact with cell membranes. The interactions of polyphenols with bilayers include: (a) the partition of the more non-polar compounds in the hydrophobic interior of the membrane, and (b) the formation of hydrogen bonds between the polar head groups of lipids and the more hydrophilic flavonoids at the membrane interface. The consequences of these interactions are discussed. The induction of changes in membrane physical properties can affect the rates of membrane lipid and protein oxidation. The partition of certain flavonoids in the hydrophobic core can result in a chain breaking antioxidant activity. We suggest that interactions of polyphenols at the surface of bilayers through hydrogen bonding, can act to reduce the access of deleterious molecules (i.e. oxidants), thus protecting the structure and function of membranes

New socio-political environments and the dynamics of European public research systems

The performance of science and technology is being challenged by new socio-political environments. The changes in science policy are influenced by a more systemic view of the understanding on how science and technology evolve. The concept of risk society is mediating the links between science and society. Comparative analyses cast doubts about the possibilities of European institutions to cope with the challenges of the new environment.This paper is based on the work and previous experience of the author and develops some results from the project 'European Comparison of Public Research Systems (EUPSR)', funded by the European Commission TSER programme (contract SOE1-CT96-1036), co-ordinated by J. Senker (SPRU). The author is solely responsible for the work presented in this paper. The support of the EC is gratefully acknowledged as well as that of the Spanish National R&D Plan (SEC97-1382). A preliminary version was presented in the Lisbon Workshop (5-6 June 2000) of the EUROPOLIS project funded by the STRATA Programme

The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives

Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations