Isocyanates, polyurethane and childhood asthma.

Isocyanates are the most prominent and well-studied cause of occupational asthma. Over the decades, airborne isocyanates have been regulated to extremely low levels in the workplace, some of the lowest for any organic compound. Yet the incidence of isocyanate-induced occupational asthma remains high and the role of dermal exposure in disease etiology is only slowly being recognized. Almost completely overlooked is the potential relationship between isocyanates in consumer products and increasing prevalence of asthma in the general population, especially children. The steady rise in asthma over the past decades points strongly to a potential role of environmental exposures in its development. Imbalances in the immune system favoring respiratory diseases have been linked to biological and chemical stressor exposures early in life. Evidence for the presence of isocyanates in many polyurethane-containing materials, especially polyurethane foams, is presented as a possible contributor to the increase in asthma. Polyurethane foam is ubiquitous in western societies and used in bedding, furniture, automobile seats, footwear, etc., and numerous medical materials. Theoretical, epidemiologic, experimental and clinical evidence of a role for isocyanates and polyurethanes in the genesis of non-occupational allergy and respiratory disease are reviewed. These data all point to the urgent need for additional research on the links between isocyanates, polyurethanes and the role of the skin in non-occupational asthma.

Controlling hyperglycemia as an adjunct to cancer therapy.

Hyperglycemia is commonly manifested in cancer patients. Although high intakes of sugar and refined carbohydrates and elevated blood glucose are strongly associated with the risk of cancer, much less is known about their effects on survival after cancer diagnosis. There is evidence that high carbohydrate intake is associated with poorer survival after diagnosis for early breast cancer. We measured glycated hemoglobin in a group of cancer patients (some with active disease and some in remission) and found a statistically significant lower average blood glucose in those in remission. Glycated hemoglobin provides an indication of average blood glucose over 2 to 3 months. The authors discuss lifestyle changes including diet and physical activity that can reduce average blood glucose. Ascorbic acid (AA) supplementation as an adjunct to cancer therapy is also considered. Furthermore, they present a biologically plausible explanation for how hyperglycemia can impair the actions of AA and damage immune effectiveness and hinder cancer survival. One mechanism is likely a reduction in intracellular AA; high intracellular levels of AA are necessary for optimal activity of the hexose monophosphate shunt. This metabolic pathway is important for maintaining proper cellular antioxidant status in immune cells including lymphocytes involved in cell-mediated immunity.

Ascorbic acid, glycation, glycohemoglobin and aging.

The glycation of proteins alters both their structure and function. These changes have been linked to diabetic disorders and aging. The glycation of hemoglobin is also used as a diagnostic tool; the extent of glycation being a reflection of blood glucose averaged over a two to three month period. Accurate measures of average blood sugar (e.g., glycohemoglobin (GHb)) are important in clinical management of diabetes, pregnancy, cancer, etc. Ascorbic acid (AA) can react with proteins, including hemoglobin, and possibly interfere with GHb measurements. Past reports on the impact of AA on in vivo glycation have been equivocal. We studied GHb in subjects supplementing up to 20 g AA daily and found that for each 30 micromol/L increase in plasma AA, GHb was reduced by approximately 0.1. These results suggest that high AA intake can depress glycation, reduce GHb and lead to a clinically relevant underestimation of average blood sugar. Because AA is the most commonly consumed dietary supplement, awareness of an AA-associated bias in GHb is imperative. Of even broader significance is the possibility of AA-mediated inhibition of glycation in all proteins and the implications for aging. Moreover, AA could contribute through several other mechanisms to slowing of human aging (e.g., antioxidant properties, acceleration of pentose phosphate pathway, replacement of structural proteins).

Diisocyanates and nonoccupational disease: a review.

More than 32 million people in the United States suffer from chronic lung diseases; 12 million experienced at least one asthma attack in 2002. The causes of this "epidemic" are complex and uncertain; however, there is a strong possibility that environmental exposures play a role. The most common and well-studied cause of occupational asthma is diisocyanates, but their use in consumer products as a potential cause of respiratory disease in the general population has been overlooked. These substances are found in or are used to produce an array of polyurethane-containing products, including adhesives, sealants, paints, flexible foams, and rigid foams, among others. The world market for polyurethane products has tripled since 1985 to more than 9.3 billion kg in the year 2000. In this article, the author reviews biologically plausible explanations, as well as the epidemiologic, experimental, and clinical evidence for the role of diisocyanates and polyurethanes in the genesis of nonoccupational allergy and respiratory disease.

Polyurethanes and childhood asthma.

BACKGROUND: Asthma is the most common chronic disease of children. Its prevalence in affluent nations has steadily and dramatically increased in recent decades. Genetic and environmental factors play a role in development of atopy and asthma. Imbalance in the immune system favoring respiratory diseases has been linked to exposure to environmental stressors (e.g, biological and chemical) very early in life. Isocyanates, used in the production of polyurethane, can elicit asthma and produce immune responses (e.g, antibodies, cytokines, etc.) typical of atopy. MATERIAL/METHODS: Numerous medical materials that directly contact human neonates are constructed of polyurethanes. A detailed survey and listing of such materials was undertaken in the neonatal unit of a large urban hospital. Representative samples of polyurethane-containing materials were tested for isocyanate residues using a semi-quantitative colorimetric method. RESULTS: Isocyanate residues were detected in wound dressings, adhesive films, oximetry sensors, etc, that directly contact neonatal skin. CONCLUSIONS: Dermal exposure to polyurethane and, thus, to isocyanates could occur early in life through contact with medical materials. In an animal model, dermal exposure to isocyanates leads to dermal sensitization and asthma. We postulate that dermal contact with polyurethane-containing medical materials may be involved in dysregulation of the neonatal immune system and could predispose infants to the development of childhood asthma.

Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity.

Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon4 groups was found in the patients p<0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam. The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients. Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.

Chemical contaminants in juvenile gray whales (Eschrichtius robustus) from a subsistence harvest in Arctic feeding grounds.

Gray whales are coastal migratory baleen whales that are benthic feeders. Most of their feeding takes place in the northern Pacific Ocean with opportunistic feeding taking place during their migrations and residence on the breeding grounds. The concentrations of organochlorines and trace elements were determined in tissues and stomach contents of juvenile gray whales that were taken on their Arctic feeding grounds in the western Bering Sea during a Russian subsistence harvest. These concentrations were compared to previously published data for contaminants in gray whales that stranded along the west coast of the US during their northbound migration. Feeding in coastal waters during their migrations may present a risk of exposure to toxic chemicals in some regions. The mean concentration (standard error of the mean, SEM) of sigmaPCBs [1400 (130) ng/g, lipid weight] in the blubber of juvenile subsistence whales was significantly lower than the mean level [27,000 (11,000) ng/g, lipid weight] reported previously in juvenile gray whales that stranded in waters off the west coast of the US. Aluminum in stomach contents of the subsistence whales was high compared to other marine mammal species, which is consistent with the ingestion of sediment during feeding. Furthermore, the concentrations of potentially toxic chemicals in tissues were relatively low when compared to the concentrations in tissues of other marine mammals feeding at higher trophic levels. These chemical contaminant data for the subsistence gray whales substantially increase the information available for presumably healthy animals.

Commercial Food Processing Operations and Mutagen Formation.

Thermally-induced bacterial mutagens are formed when foods are processed by some commercial food preservation techniques. The processes which involve longer times and higher temperatures are most likely to produce mutagens (e.g., canning and evaporative concentration). Pasteurization and spray drying processes possess a low potential for creation of mutagens. The types of food products with the greatest tendency to contain mutagens following heat treatments are muscle foods such as canned meats and fish. Canned beef broth, chili, hash, roast beef, pink and red salmon, and mackerel contain substances which induce mutation rates up to 20 times higher than spontaneous revertant colonies in the Ames Salmonella mutagenicity assay. Using canned pink salmon as a representative product, reprocessing increased mutagen content, whereas addition of Maillard-browning reaction inhibitors led to significant decreases in mutagen formation. Even though thermally-induced mutagens can arise during household cooking (e.g., frying and charcoal grilling), the consumer can choose to minimize their production through use of lower temperature methods such as boiling, steaming or microwave heating. This option is not available to the consumer of commercially canned foods. Hence, further research into the reduction of mutagen formation during thermal processing is needed.