Effects of Inhaled Brevetoxins in Allergic Airways: Toxin–Allergen Interactions and Pharmacologic Intervention

During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma). To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (R(L)) after inhalation challenge with lysed cultures of K. brevis (crude brevetoxins). Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 pg/mL; n = 5) increased R (L) 128 ± 6% (mean ± SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the β (2) adrenergic agent albuterol (71%), the anticholinergic agent atropine (58%), and the histamine H(1)-antagonist diphenhydramine (47%). The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and H(1)-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals

Indicators of ocean health and human health: Developing a research and monitoring framework--Commentary

We need to critically assess the present quality of the marine ecosystem, especially the connection between ecosystem change and threats to human health. In this article we review the current state of indicators to link changes in marine organisms with eventual effects to human health, identify research opportunities in the use of indicators of ocean and human health, and discuss how to establish collaborations between national and international governmental and private sector groups. We present a synthesis of the present state of understanding of the connection between ocean health and human health, a discussion of areas where resources are required, and a discussion of critical research needs and a template for future work in this field. To understand fully the interactions between ocean health and human health, programs should be organized around a “models-based” approach focusing on critical themes and attributes of marine environmental and public health risks. Given the extent and complex nature of ocean and human health issues, a program networking across geographic and disciplinary boundaries is essential. The overall goal of this approach would be the early detection of potential marine-based contaminants, the protection of marine ecosystems, the prevention of associated human illness, and by implication, the development of products to enhance human well-being. The tight connection between research and monitoring is essential to develop such an indicator-based effort. Key words: biologic effects, biomarkers, contamination, human health, indicators, ocean health. Environ Health Perspect 110:839–845 (2002). [Online 17 July 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p839-845knap/abstract.htm

Occupational exposure to aerosolized brevetoxins during Florida red tide events: effects on a healthy worker population

Karenia brevis (formerly Gymnodinium breve) is a marine dinoflagellate responsible for red tides that form in the Gulf of Mexico. K. brevis produces brevetoxins, the potent toxins that cause neurotoxic shellfish poisoning. There is also limited information describing human health effects from environmental exposures to brevetoxins. Our objective was to examine the impact of inhaling aerosolized brevetoxins during red tide events on self-reported symptoms and pulmonary function. We recruited a group of 28 healthy lifeguards who are occupationally exposed to red tide toxins during their daily work-related activities. They performed spirometry tests and reported symptoms before and after their 8-hr shifts during a time when there was no red tide (unexposed period) and again when there was a red tide (exposed period). We also examined how mild exercise affected the reported symptoms and spirometry tests during unexposed and exposed periods with a subgroup of the same lifeguards. Environmental sampling (K. brevis cell concentrations in seawater and brevetoxin concentrations in seawater and air) was used to confirm unexposed/exposed status. Compared with unexposed periods, the group of lifeguards reported more upper respiratory symptoms during the exposed periods. We did not observe any impact of exposure to aerosolized brevetoxins, with or without mild exercise, on pulmonary function. Environ Health Perspect 113:644–649 (2005). doi:10.1289/ehp.7502 available via http://dx.doi.org/ [Online 10 February 2005

Overview of aerosolized Florida red tide toxins: Exposures and effects

Florida red tide is caused by Karenia brevis, a dinoflagellate that periodically blooms, releasing its potent neurotoxin, brevetoxin, into the surrounding waters and air along the coast of the Gulf of Mexico. Exposure to Florida red tide toxins has been associated with adverse human health effects and massive fish and marine mammal deaths. The articles in this mini-monograph describe the ongoing interdisciplinary and interagency research program that characterizes the exposures and health effects of aerosolized Florida red tide toxins (brevetoxins). The interdisciplinary research program uses animal models and laboratory studies to develop hypotheses and apply these findings to in situ human exposures. Our ultimate goal is to develop appropriate prevention measures and medical interventions to mitigate or prevent adverse health effects from exposure to complex mixtures of aerosolized red tide toxins. Key words: brevetoxins, harmful algal blooms (HABs), Karenia brevis, red tides, sensitive populations. Environ Health Perspect 113:618–620 (2005). doi:10.1289/ehp.7501 available via http://dx.doi.org/ [Online 10 February 2005]]]> 2009 Marine toxins Red tide--Florida Algal blooms--Florida Neurotoxic agents--Florida English http://libres.uncg.edu/ir/uncw/f/badend2005-3.pdf oai:libres.uncg.edu/536 2014-02-14T06:02:15Z UNCW MARC record services: A comparative study of library practices and perceptions Kemp, Rebecca NC DOCKS at The University of North Carolina Wilmington <![CDATA[ABSTRACT. The number of journal titles available in digital format to libraries through aggregators and publisher packages has increased, but library resources to catalog these titles have not kept pace with the increases. More libraries are therefore turning to MARC record service vendors to provide batches of electronic serials bibliographic records, either full or brief. This study presents the results of a survey asking library personnel about their experiences with and attitudes toward MARC record services. While many survey participants expressed satisfaction with the services, they also responded that they would like a greater number of more accurate full bibliographic records. Also, while a majority of libraries use a separate records approach with the services, a significant minority use a single record approach

Oceans and human health: A new era of environmental opportunities

The National Institute of Environmental Health Sciences (NIEHS) has supported environmental health sciences that overlap with ocean science questions and resources since its inception. The second NIEHS director, David Rall, and NIEHS’s third director, Dr. Kenneth Olden, exhibited active interest in the development and funding of oceans and human health-related research, education, and outreach. The institute has provided fiscal support for regular research grants, center grants, and program project grants; for individual and institutional training grants; and for conference and meeting support. During Dr. Olden’s tenure, the institute has also demonstrated leadership in working with other institutes within the National Institutes of Health to further ocean-based biomedical research and has reached out to other funding agencies and departments of the federal government. The Marine and Freshwater Biomedical Science Center program is the longest lasting, most productive, and high-profile aspect of NIEHS’s funding in the ocean environmental health sciences, and under Dr. Olden’s leadership that program has steadily increased in stature. Developed collaboratively with Rita Colwell, immediate past director of the National Science Foundation, the present Centers for Oceans and Human Health are a joint exercise of the two agencies. The Marine and Freshwater Biomedical Science Center program, the three research foci of the present Centers for Oceans and Human Health program, and increased collaborative oceans and human health research will all contribute to the health of the world’s oceans and, by co-dependence, the health of humans. doi:10.1289/ehp.7964 available via http://dx.doi.org

The effect of brevenal on brevetoxin-induced DNA damage in human lymphocytes

Brevenal is a nontoxic short-chain trans-syn polyether that competes with brevetoxin (PbTx) for the active site on voltage-sensitive sodium channels. The PbTxs are highly potent polyether toxins produced during blooms of several species of marine dinoflagellates, most notably Karenia brevis. Blooms of K. brevis have been associated with massive fish kills, marine mammal poisoning, and are potentially responsible for adverse human health effects such as respiratory irritation and airway constriction in beach-goers. Additionally, the consumption of shellfish contaminated with PbTxs results in neurotoxic shellfish poisoning (NSP). The purpose of the present study was to determine whether PbTx could induce DNA damage in a human cell type, the lymphocyte, and if so, whether the damage could be antagonized or ameliorated by brevenal, a brevetoxin antagonist. The DNA damage may occur through both endogenous and exogenous physiological and pathophysiological processes. Unrepaired or erroneously repaired DNA damage may result in gene mutation, chromosome aberration, and modulation of gene regulation, which have been associated with immunotoxicity and carcinogenesis. A single-cell gel electrophoresis assay, or comet assay, was used to determine and compare DNA damage following various treatments. The data were expressed as tail moments, which is the percentage of DNA in the tail multiplied by the length between the center of the head and center of the tail (in arbitrary units). The negative control tail moment was 29.2 (SE=±0.9), whereas the positive control (hydrogen peroxide) was 72.1 (1.5) and solvent (ethanol) was 24.2 (2.1). The PbTx-2 (from Sigma, St. Louis, MO, USA), 10−8 M was 41.3 (3.6), PbTx-9 (Sigma), 10−8 M was 57.0 (5.3), PbTx-2 (from University of North Carolina at Wilmington, UNCW), 10−8 M was 49.4 (9.9), and PbTx-3 (UNCW), 10−8 M was 64.0 (6.4). 1.0 μg/ml brevenal applied 1 h before the PbTxs protected the lymphocytes from DNA damage; PbTx-2 (Sigma), 31.3 (2.1); PbTx-9 (Sigma), 35.5 (2.9); PbTx-2 (UNCW), 33.9 (1.4); PbTx-3 (UNCW), 34.9 (1.25). The tail moment for 1.0 μg/ml brevenal alone was 30.8 (2.6). The results indicate that extensive genotoxic damage is induced by PbTx-2 and 9 (Sigma), and PbTx-2 and 3 (UNCW) in normal human lymphocytes, which is fully antagonized by brevenal. This suggests that the immune systems of individuals exposed to PbTx during harmful algal bloom (HAB) events may be at risk. Originally published Archives in Toxicology, Vol. 79, No. 11, Nov 200

Characterization of marine aerosol for assessment of human exposure to brevetoxins

Red tides in the Gulf of Mexico are commonly formed by the fish-killing dinoflagellate Karenia brevis, which produces nine potent polyether brevetoxins (PbTxs). Brevetoxins can be transferred from water to air in wind-powered white-capped waves. Inhalation exposure to marine aerosol containing brevetoxins causes respiratory symptoms. We describe detailed characterization of aerosols during an epidemiologic study of occupational exposure to Florida red tide aerosol in terms of its concentration, toxin profile, and particle size distribution. This information is essential in understanding its source, assessing exposure to people, and estimating dose of inhaled aerosols. Environmental sampling confirmed the presence of brevetoxins in water and air during a red tide exposure period (September 2001) and lack of significant toxin levels in the water and air during an unexposed period May 2002). Water samples collected during a red tide bloom in 2001 showed moderate-to-high concentrations of K. brevis cells and PbTxs. The daily mean PbTx concentration in water samples ranged from 8 to 28 µg/L from 7 to 11 September 2001; the daily mean PbTx concentration in air samples ranged from 1.3 to 27 ng/m3. The daily aerosol concentration on the beach can be related to PbTx concentration in water, wind speed, and wind direction. Personal samples confirmed human exposure to red tide aerosols. The particle size distribution showed a mean aerodynamic diameter in the size range of 6–12 µm, with deposits mainly in the upper airways. The deposition pattern correlated with the observed increase of upper airway symptoms in healthy lifeguards during the exposure periods. Published online 2005 February 9. doi: 10.1289/ehp.7496

Initial evaluation of the effects of aerosolized Florida red tide toxins (brevetoxins) in persons with asthma

Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic effects of these toxins among persons with asthma and other chronic respiratory impairment. Environ Health Perspect 113:650-657 (2005). doi:10.1289/ehp.7500 available via http://dx.doi.org/ [Online 10 February 2005

Effects of inhaled brevetoxins in allergic airways: Toxin–allergen interactions and pharmacologic intervention

During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma). To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (R-L) after inhalation challenge with lysed cultures of K brevis (crude brevetoxins). Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 mu g/mL; n = 5) increased R-L 128 +/- 6% (mean +/- SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the beta(2) adrenergic agent albuterol (71%), the anticholinergic agent atropine (58%), and the histamine H-1-antagonist diphenhydramine (47%). The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and HI-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals. Published online 2005 February 10. doi: 10.1289/ehp.7498