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Extramural Papers of the Month

By Jerry Phelps
November 2008

Particulate Air Pollution Can Alter the Electrical Functioning in the Heart

New research findings from NIEHS grantees suggest that exposure to the fine particulate air pollution and black carbon particles generated in areas of heavy traffic can adversely effect the heart's ability to conduct electrical signals in people with pre-existing coronary artery disease. The study, conducted with 48 Boston-area heart patients, found changes in the ST-segment of the patient's electrocardiograms, possibly indicating inadequate blood flow to the heart or inflamed heart muscle — even when breathing air is not considered hazardous.

All the patients had undergone in-hospital procedures to examine or open blocked coronary arteries. The ST-segment changes observed in the study were asymptomatic, but the findings expand the evidence that air pollution can affect heart health, either through inflaming the heart muscle or through reducing blood flow to the heart. The heart effects were highest within the first month after hospitalization and for heart attack patients or those with diabetes.

This study provides additional rationale for avoiding or reducing heavy traffic exposure for people with heart conditions because of the potential exposure to elevated levels of air pollution particles. The study authors suggest additional research is necessary to determine whether the pollution-related ST-segment changes are due to increased heart inflammation, reduced blood flow, oxidative stress or increased risk of arrhythmias.

Citation: Chuang KJ, Coull BA, Zanobetti A, Suh H, Schwartz J, Stone PH, Litonjua A, Speizer FE, Gold DR( Exit NIEHS. 2008. Particulate air pollution as a risk factor for ST-segment depression in patients with coronary artery disease. Circulation 118(13):1314-1320.

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Acetaminophen May Increase the Risk of Developing Asthma

A new epidemiologic study, supported by NIEHS and conducted with 345 pregnant women, adds to the growing evidence suggesting a causal link between the use of the non-steroidal anti-inflammatory drug acetaminophen and the rise in the incidence of asthma in children.

Acetaminophen became the drug of choice for pain and fever relief after the FDA ordered manufacturers to place a warning label on bottles about the link between aspirin use and Reyes syndrome in 1986. Afterwards, pediatricians nationwide started noticing a rise in asthma incidence, and some suspected a link to acetaminophen. Unlike aspirin and ibuprofen, acetaminophen decreases the level of the antioxidant glutathione in the lungs and other tissues.

For the study, women responded to a questionnaire related to respiratory outcomes in their newborns during their first year of life. Use of acetaminophen in the second and third trimesters was significantly related to wheezing in the first year, a known symptom of asthma in young children.

The researchers will continue to follow these children until they reach five years of age to determine more precise estimates of asthma incidence. The researchers point out that this is only the second study of its type and that the link needs further research.

Citation: Persky V, Piorkowski J, Hernandez E, Chavez N, Wagner-Cassanova C, Vergara C, Pelzel D, Enriquez R, Gutierrez S, Busso A( Exit NIEHS. 2008. Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life. Ann Allergy Asthma Immunol 101(3):271-278.

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Green Tea Polyphenol Combats Health Effects of High Fat Diet

Green tea, consumed widely in East Asian countries, contains caffeine and polyphenolic compounds known as catechins. The most common catechin compound in green tea is epigallocatechin-3-gallate (EGCG). EGCG has been suggested as the catechin responsible for the potential health benefits experienced with long-term consumption of green tea, a link supported by findings from a new NIEHS-funded study.

In the study, mice were fed a diet containing 60% of energy as fat for 16 weeks, at which point some mice were given EGCG for another 16 weeks. Mice treated with EGCG had lower body weights, decreased insulin resistance and lower plasma cholesterol than the untreated mice. EGCG treatment also decreased liver weight and liver triglycerides. Subsequent histological examination of liver tissue revealed decreased lipid accumulation in the liver cells of the treated mice. In another experiment, obese mice given four weeks of EGCG treatment also showed decreased body fat and blood glucose as compared to the untreated controls.

These results indicate that physiological relevant doses of EGCG treatment can mitigate the development of obesity, symptoms of metabolic syndrome and liver fat accumulation. The researchers conclude that these effects could be mediated by decreased fat absorption, decreased inflammation or other mechanisms.

Citation: Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS( Exit NIEHS. 2008. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. J Nutr 138(9):1677-1683.

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A Fruit Fly Model for Amyotrophic Lateral Sclerosis

A multi-university research team funded by NIEHS has developed a new laboratory model for studying the motor neuron disease amyotrophic lateral sclerosis (ALS). The researchers created a transgenic fruit fly that is able to express human copper, zinc-superoxide dismutase (SOD1), an antioxidant enzyme that has been implicated in the hereditary form of ALS.

ALS is a progressive and fatal neurodegenerative disease of the motor nervous system. It is characterized by the loss of muscle function caused by dysfunction and death of motor neurons throughout the body. About one-fifth of hereditary ALS cases are linked to mutations in the gene encoding for SOD1. Uncovering how mutations in the enzyme lead to the dysfunction and death of motor neurons could illuminate how ALS develops and progresses in patients with both sporadic and hereditary forms of the disease.

In experiments using the new model, the researchers found that expression of the enzyme in the flies induced neurological damage along with accumulation of the enzyme in motor neurons accompanied by a stress response in the surrounding glial cells. This work suggests that SOD1 can cause cell-autonomous damage to motor neurons. It also highlights the usefulness of the fruit fly model for studying ALS.

Citation: Watson MR, Lagow RD, Xu K, Zhang B, Bonini NM ( Exit NIEHS. 2008. A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1. J Biol Chem 283(36):24972-24981.

(Jerry Phelps is a program analyst in the Program Analysis Branch of the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)

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November 2008 Cover Page

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