The same mechanism that helps you detect bad-tasting and potentially poisonous foods may also play a role in protecting your airway from harmful substances, according to a study by scientists at the University of Iowa Roy J. and Lucille A. Carver College of Medicine. The findings could help explain why injured lungs are susceptible to further damage.  

The study, published online July 23 in Science Express, shows that receptors for bitter compounds that are found in taste buds on the tongue also are found in hair-like protrusions on airway cells. In addition, the scientists showed that, unlike taste cells on the tongue, these airway cells do not need help from the nervous system to translate detection of bitter taste into an action that expels the harmful substance. 

The hair-like protrusions, called motile cilia, were already known to beat in a wave-like motion to sweep away mucus, bacteria and other foreign particles from the lungs. 

The study is the first to show that motile cilia on airway cells not only have this “clearing” function, but also use the receptors to play a sensory role. The researchers also found that when the receptors detect bitter compounds, the cilia beat faster, suggesting that the sensing and the motion capabilities of these cellular structures are linked. 

“On the tongue, bitter substances trigger taste cells to stimulate neurons, which then evoke a response — the perception of a bitter taste. In contrast, the airway cells appear to use a different mechanism that does not require nerves,” said Alok Shah, a UI graduate student and co-first author of the study. “In the airways, bitter substances both activate the receptors and elicit a response — the increased beating of the cilia — designed to eliminate the offending material.”

Shah and co-first author Yehuda Ben-Shahar, Ph.D., an assistant professor of biology at Washington University who was a postdoctoral fellow at the UI when the study was conducted, worked in the lab of senior study author Michael Welsh, M.D. (photo, upper left), UI professor of internal medicine and molecular physiology and biophysics, who holds the Roy J. Carver Chair of Internal Medicine and Physiology and Biophysics. Welsh also is a Howard Hughes Medical Institute investigator. 

“These findings suggest that we have evolved sophisticated mechanisms to guard ourselves from harmful environmental stimuli,” Ben-Shahar said. “Our work also suggests that losing cilia in the lungs, due to smoking or disease, would result in a reduced general ability to detect harmful inhaled chemicals, increasing the likelihood of further damaging an injured lung.”

In addition to Ben-Shahar, Shah and Welsh, the UI team included Thomas Moninger, assistant director of the UI Central Microscopy Research Facility, and Joel Kline, M.D., UI professor of internal medicine. 

The study was funded by grants from the National Institutes of Health. 

Reference:   University of Iowa, Airway cells use ‘tasting’ mechanism to detect and clear harmful substances, July 24, 2009

International Journal of Occupational and Environmental Health Features Discovery of Asbestos-Related Pain Origin from Scientists at the Karmanos Cancer Institute in Detroit 

Scientists at the Barbara Ann Karmanos Cancer Institute’s National Center for Vermiculite and Asbestos-Related Cancers (NCVAC) have discovered a probable reason for the unrelenting chest pain experienced in certain patients with asbestos-related diseases and cancers. The findings, featured in the July 20, 2009 edition of the International Journal of Occupational and Environmental Health, were published in an academic peer-reviewed manuscript by principal author Michael Harbut, M.D., MPH, co-director of the NCVAC and chief of the Center for Occupational and Environmental Medicine, affiliated with Wayne State University.  

Harbut reported the findings after studying a patient who was exposed to taconite dust as a child.  

Using a new radiography approach developed by Carmen Endress, M.D., FACR, associate professor of Radiology, Wayne State University School of Medicine and radiologist at the NCVAC, there was a documented increase in pleural plaques, causing erosion on the interior wall of the ribs. 

“This action of the pleural plaque against the covering of the bone and the bone itself is a biologically plausible and an anatomically logical explanation of the unrelenting pain which some patients experience,” said Dr. Harbut.

This new imaging approach involves enhancing images obtained on the 64-slice high resolution CT scan using the Vitrea(R) imaging software program by Vital Images. By using this imaging approach, Dr. Harbut was able to demonstrate that: 

Evidence based on the CT findings, the physical examination, pulmonary function studies, epidemiology and history of the patient’s intractable pleural pain meets the criteria for diagnosis of asbestosis. Combined with the known science of taconite dust, a link between the mine where the patient’s father worked and the patient’s disease was established.  

Due to the clarity and definition of this new imaging approach, it is more likely to detect asbestos-related diseases and cancer at an earlier stage.  

Earlier detection will allow the possibility for additional treatment options to manage the pain caused by pleural plaque beyond the narcotics often prescribed for patients with advanced stages of asbestos disease. This includes exploring other forms of traditional and nontraditional methods to control pain.  

The patient, studied since 2004 and currently 55 years of age, was exposed as a child to taconite dust unknowingly by her father, a taconite miner from 1962 – 1969, who carried the taconite dust on his work clothes. Taconite is used in the production of steel and road-patching material. It has been mined in Michigan and Minnesota. 

The patient has experienced increasing pain on her right side for the past 31 years, a persistent cough and wheezing. As the pain increased so did her medication. Using the new imaging approach, Dr. Harbut was able to show the progression of the patient’s pleural plaque over a three year period, from 2005 – 2008. The patient’s pleuritic pain, as well as the findings of her pulmonary function, physical exam and symptomology are consistent with those diagnosed with asbestosis and pleural plaques, as established by the American Thoracic Society.  

These findings also support earlier human and animal reports that dusts produced by taconite mining can evoke the same biological responses as do other fibers already defined as asbestos or asbestiform materials. 

Harbut added, “Patients often require a lifetime of narcotics to allow functioning, but we are hopeful that with this new imaging technology, more selective pain management approaches with fewer side effects can be instituted resulting in a better quality of life.”

Finally, the report supports the identification of taconite, which has not yet been categorized as asbestos but causes a disease consistent with asbestosis, and recommends a reevaluation of the definition of asbestos. This is especially important within the context of legislative efforts to prohibit the use of asbestos. 

Karmanos scientists are continuing their series of patient studies and will submit similar findings for peer review later this summer.  

In addition to Dr. Harbut, co-authors of the report include Carmen Endress, M.D., FACR; John J. Graff, Ph.D., MS, assistant professor, Wayne State University School of Medicine, and chief, Cancer Surveillance Research at the Barbara Ann Karmanos Cancer Institute; Christopher Weis, Ph.D., National Enforcement Investigations Center, United States Environmental Protection Agency; and Harvey Pass, M.D., director, New York University’s Division of Thoracic Surgery.  

About the National Center for Vermiculite and Asbestos-Related Cancers (NCVAC at Karmanos)  

In response to the United States Environmental Protection Agency’s (EPA) identification of major sources of public asbestos exposure in Michigan, and to address the need for early diagnosis and aggressive treatment of asbestos-related diseases, the Barbara Ann Karmanos Cancer Institute and the Center for Occupational and Environmental Medicine (COEM) affiliated with Wayne State University established Karmanos’ National Center for Vermiculite and Asbestos-Related Cancers. The NCVAC is co-directed by Michael Harbut, M.D., MPH, Karmanos Cancer Institute and Chief of the Center for Occupational and Environmental Medicine; and John J. Graff, Ph.D. MS, chief of Cancer Surveillance Research, Karmanos Cancer Institute and assistant professor, Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine. 

Reference: Barbara Ann Karmanos Cancer Institute, International Journal of Occupational and Environmental Health Features Discovery of Asbestos-Related Pain Origin from Scientists at the Karmanos Cancer Institute in Detroit , US Newswire, DETROIT, July 20, 2009.

CO Exposure could make them more vulnerable to disease

A UCLA study has discovered that chronic exposure during pregnancy to miniscule levels of carbon monoxide damages the cells of the fetal brain, resulting in permanent impairment. The journal BMC (BioMed Central ) Neuroscience published the findings June 22 in its online edition.

“We expected the placenta to protect fetuses from the mother’s exposure to tiny amounts of carbon monoxide,” said John Edmond, professor emeritus of biological chemistry at the David Geffen School of Medicine at UCLA. “But we found that not to be the case.”

The researchers exposed pregnant rats to 25 parts per million carbon monoxide in the air, an exposure level established as safe by Cal/OSHA, California’s division of occupational health and safety.

Dr. Ivan Lopez, UCLA associate professor of head and neck surgery, tested the rats litters 20 days after birth. Rats born to animals who had inhaled the gas suffered chronic oxidative stress, a harmful condition caused by an excess of harmful free radicals or insufficient antioxidants.

“Oxidative stress damaged the baby rats brain cells, leading to a drop in proteins essential for proper function,” said Lopez. “Oxidative stress is a risk factor linked to many disorders, including autism, cancer, Alzheimer’s, Parkinson’s, Lou Gehrig’s disease, multiple sclerosis and cardiovascular disease. We know that it exacerbates disease.”

“We believe that the minute levels of carbon monoxide in the mother rats environment made their offspring more vulnerable to illness,” added Edmond. “Our findings highlight the need for policy makers to tighten their regulation of carbon monoxide.”

Tobacco smoke, gas heaters, stoves and ovens all emit carbon monoxide, which can rise to high concentrations in well-insulated homes. Infants and children are particularly vulnerable to carbon monoxide exposure because they spend a great deal of time in the home.

No policies exist to regulate the gas in the home. Most commercial home monitors sound an alarm only hours after concentrations reaches 70 parts per million – nearly three times the 25 parts per million limit set by Cal/OSHA.

A grant from the University of California’s Tobacco-related Disease Research Program supported the research.

Reference: Elaine Schmidt, UCLA study reveals how tiny levels of carbon monoxide damage fetal brains, UCLA, 6/25/2009

Bitumen fumes consist essentially of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, some of which are known to be carcinogenic or cocarcinogenic in humans. The aim of this study was to investigate exposure to asphalt fumes among Turkish asphalt workers and determine whether any effects could be detected with genotoxic tests.  

The study included 26 asphalt workers and 24 control subjects. Sister chromatid exchange (SCE) and micronucleus (MN) were determined in peripheral lymphocytes. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAHs.  

The asphalt workers had a significant increase in SCEs and MN (for each, p < 0.001). A positive correlation existed between the duration of exposure and rates of SCE or MN frequencies (r = 0.49, p < 0.05; r = 0.53, p < 0.05, respectively). The concentration of 1-OHP in urine was higher for the asphalt workers than for the controls (p < 0.001). However, we found that there was no statistically significant correlation between the urinary 1-OHP concentration and SCEs or MN frequencies (r = 0.25, p > 0.5; r = 0.17, p > 0.5, respectively).  

This study shows that Turkish asphalt workers have an increased exposure to PAHs from bitumen fumes, and genotoxic effects could be detected by SCEs and MN tests. 

Reference: Karaman A, Pirim I., Exposure to bitumen fumes and genotoxic effects on Turkish asphalt workers, Department of Medical Genetics, State Hospital, Erzurum, Turkey, Clin Toxicol (Phila). 2009 Apr;47(4):321-6.

Many parents worry about their child’s exposure to phthalates, the chemical compounds used as plasticizers in a wide variety of personal care products, children’s toys, and medical devices. Phthalate exposure can begin in the womb and has been associated with negative changes in endocrine function. A new study soon to be published in the Journal of Pediatrics examines the possibility that in utero phthalate exposure contributes to low birth weight in infants. Low birth weight is the leading cause of death in children under 5 years of age and increases the risk of cardiovascular and metabolic disease in adulthood.  

To investigate the associations between in utero phthalate exposure and low birth weight, Dr. Renshan Ge of the Population Council and colleagues from Fudan University and Second Military Medical University in Shanghai studied 201 pairs of newborns and their mothers between 2005 and 2006. Of the 201 infants studied, 88 were born with low birth weight. The researchers analyzed samples of the infants’ meconium, the first bowel movement that occurs after birth, and cord blood to determine phthalate levels.  

They found quantifiable levels of phthalate and phthalate metabolites in more than 70% of the samples. Infants with low birth weight had consistently higher levels of phthalates. According to Dr. Ge, “The results showed that phthalate exposure was ubiquitous in these newborns, and that prenatal phthalate exposure might be an environmental risk factor for low birth weight in infants.” Although these associations are not conclusive, this study supports the accelerating efforts to minimize phthalate exposure. 

Reference: The study, reported in “Phthalate Levels and Low Birth Weight: A Nested Case-Control Study of Chinese Newborns” by Zhang Y, PhD, Lin L, MD, Cao Y, PhD, Chen B, MD, Zheng L, MSC, Ge R, MD, appears in the Journal of Pediatrics, DOI 10.1016/j.jpeds.2009.04.007, published by Elsevier. EurekAlert, June 25, 2009.