report on Toxic Red Tides

[Guest guest]

Forgive me if this is old news to you , but I am just getting around to it.

I esp noted the " cough " from the toxins. There are several symptoms noted in

this report

that are common with mold exposure, ie: toxic mold. I would guess those docs

among us

may have read this, but if not, happy reading.

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http://www.sciencenews.org/articles/20050723/bob8.asp

Science News Report

July 23, 2005

Toxic Tides

Toxic Surfs

Homing in on an alga's threat—and therapeutic promise

Janet Raloff

On a warm, sunny day, you can hear the presence of a " red tide " of toxic algae

on popular

Florida beaches, says Barbara Kirkpatrick. It's not the roar of coastal waves or

the gurgle of

flowing water, she explains, but " one continuous cough, " as thousands of

sunbathers and

swimmers respond to airborne irritants that the algae expel in the surf.

<PHOTO>

RED IN NAME ONLY. Because ia brevis cells (inset) aren't red, substantial

blooms of

the microscopic algae create a " red tide " that's actually a muddy yellow-green

or brown.

Fish and Wildlife Res. Inst., Fla. Fish & Wildlife Conserv. Comm.; (inset) Mote

Marine

Laboratory

Kirkpatrick, manager of environmental health at the Mote Marine Laboratory in

Sarasota,

Fla., heard the sound last February when she visited Siesta Key Beach. Southwest

Florida

was in the throes of a red tide—in this case, a misnomer because the alga

causing it,

ia brevis, turns water yellow-green. Some traditional signs of the bloom

were in

evidence on beaches and in canals. Most obviously, manatees were dying. By the

end of

spring, officials had retrieved more than 4 dozen sea cow carcasses, weighing up

to 1,000

pounds apiece.

As in the past, health officials had warned people not to eat local shellfish.

It's long been

known that their accumulated K. brevis toxins can cause vomiting, diarrhea,

excessive

urination, and a temporary reversal of temperature sensation—ice feels hot and

near-

boiling water feels frigid.

But new concerns are accompanying the latest K. brevis bloom because scientists

have

recently uncovered far wider health effects of the algal toxins.

Five years ago, in response to a rising incidence of red tides, the National

Institute of

Environmental Health Sciences began sponsoring research into how K. brevis

toxins, called

brevetoxins, function. The findings, announced this spring in more than a dozen

papers

and scientific talks, are largely disquieting. They show that the alga's poisons

have several

means of wreaking havoc beyond the neurotoxicity that had been previously

recognized.

On a more positive note, this research has also revealed that along with its

toxins, K.

brevis produces counteracting agents. Scientists are working to harness these

novel

compounds as antidotes to brevetoxins or even as treatments for unrelated lung

diseases,

such as cystic fibrosis.

Quadruple trouble

Each K. brevis cell is a microscopic poison factory churning out 9 to 13

different toxins.

Wave action readily ruptures the cells, turning the water along coastlines or in

a tidal canal

into a poisonous soup that can kill fish, sea turtles, and marine mammals such

as

manatees and dolphins. Birds can die after eating tainted prey. Filter-feeding

shellfish,

such as mussels, accumulate brevetoxins without harm, but their flesh can poison

animals, including people, that eat it.

The recent spate of research has clarified these neurotoxic effects. These

studies trace to

the toxins' effect on sodium channels in nerves, explains G. Baden of the

University

of North Carolina at Wilmington's Center for Marine Science. Normally, the

channels open

momentarily to pass a signal along a nerve cell.

Brevetoxins " act like little doorstops, " Baden says. " Once the sodium channel

opens, they

keep it open, " incapacitating the cell.

In March at the Society of Toxicology meeting in New Orleans, Baden reported

that in the

rodent brain, brevetoxins accumulate in the cerebellum, a region that affects

cognitive

function, breathing, and muscle control. If the same happens in manatees, he

says, it

might explain their disorientation and seeming inability to swim away from a red

tide.

Bad as the neurotoxic effect might be, Baden's team unveiled at the meeting

three new

mechanisms of brevetoxin poisoning—detrimental changes in lung function,

immunity,

and DNA. Aspects of the first two might explain respiratory distress, which is

the most

prevalent symptom that the algae trigger in people.

As mucus clears from an animal's airways, it removes pollutants and debris.

Small doses of

the toxins reduced the clearance rate of mucus by 35 percent in sheep. This

impairment

lasted about 2 hours, notes research-team member M. Abraham, a pulmonary

physiologist at Mt. Sinai Medical Center in Miami Beach, Fla.

The scientists' studies also showed that the poisons attack the sheep immune

system.

White blood cells called neutrophils ordinarily protect the body by entering the

lungs,

gobbling up the poisons and the cells that they have damaged, and then quickly

exiting.

Abraham says that in sheep exposed to brevetoxins, however, neutrophils stick

around,

causing inflammation of the airways.

Another group of immune cells, macrophages, normally removes germs, damaged

cells,

and other debris from the lungs. In brevetoxin-exposed sheep, however,

macrophages'

destruction of trash fell by about 30 percent. This effect persisted for days.

Baden notes that his team's experiments in mice showed that brevetoxins can also

depress

an animal's response to infection by inactivating cathepsins, enzymes that

immune cells

use to break down debris as they attack it.

Finally, he and Abraham reported in March that brevetoxins induced significant

DNA

damage in lab cultures of human lymphocytes, which are white blood cells active

in

immunity.

Ticklish situation

" Most people in Florida have experienced what we call the red tide tickle, " says

Heil of the state's Fish and Wildlife Research Institute in St. sburg.

" It's kind of a back-

of-the-throat, just-beginning-to-get-a-cold feeling. "

People aren't alone in suffering from airborne algae. Heil and other researchers

are

studying the manatees killed by the recent K. brevis tide (see " Marine Mystery, "

below).

D. Bossart, a veterinarian and pathologist at Harbor Branch

Oceanographic

Institution in Fort Pierce, Fla., studied a similar die-off of manatees in a

1996 red tide. By

treating tissues from dead animals with antibodies that stain the toxins, he and

his

colleagues pegged inhalation as a primary route of the poisons.

" We were able to trace [the brevetoxins] from their nasal cavities down to the

lymph nodes

and spleen, " he says. " They were all loaded with toxin, " and there were smaller

amounts in

the animals' brains and livers, says Bossart. In healthy people, Kirkpatrick

notes, upper-

airway symptoms are transitory. Indeed, she monitored some 28 healthy lifeguards

before

and after their work shifts. She examined the young men and women on 5

consecutive

days during which the air was largely free of brevetoxins and on 5 consecutive

days

marked by moderate air concentrations—ranging from 3 to 27 nanograms of

brevetoxins

per cubic meter (ng/m3).

In the May Environmental Health Perspectives (EHP), Kirkpatrick's team reports

that the

guards exhibited significantly more teary eyes, stuffy noses, and coughing on

red tide

days. However, the guards could still breathe deeply, even during 5 minutes of

mild

exercise on the beach. Moreover, their symptoms disappeared shortly after the

guards

entered an air-conditioned room.

On the other hand, red tide toxins can exert a choke hold on people with lung

disease,

Kirkpatrick's team reports in a second May EHP paper. The researchers evaluated

lung

function in 59 people who have asthma and take antiasthma drugs. Data were

collected

before and after these participants spent an hour on a beach with airborne

brevetoxin

concentrations of 3 to 36 ng/m3.

These volunteers reacted far more strongly to the algae's lung irritants than

did the

lifeguards, none of whom had asthma. While on the beach, the people with asthma

experienced not only the upper-airway effects seen in the guards, but also chest

tightness, wheezing, and reductions in lung airflow.

Some participants with asthma contacted Kirkpatrick after the testing to report

feeling

even worse on the day following their hour at the beach. Abraham says that he

isn't

surprised. He's seen similar persistent effects in sheep induced to have a

condition that

serves as a model of human asthma.

In one study, Abraham administered 20 breaths of air laced with a brevetoxin to

asthmatic

ewes on 4 consecutive days. Air concentrations of the toxin were at the low end

of what

the recruits encountered in Kirkpatrick's beach tests.

The exposures rendered the animals' airways " more twitchy than normal, " says

Abraham.

When the animals inhaled an irritant, the airways constricted erratically, he

reported in the

May EHP. This heightened responsiveness to brevetoxins lasted a week.

In people, such airway hypersensitivity contributes to a feeling of chest

tightness, he

explains.

Help is coming

Terrence P. Kane, a Sarasota, Fla., pulmonologist, and his colleagues have their

own way of

knowing when red tide toxins have become airborne. Beach residents with asthma,

emphysema, and bronchitis begin complaining that their prescribed drugs for

those

conditions aren't working. Kane says that the medications actually become

overwhelmed

by the onslaught of brevetoxins— " So, we may have to change their drug regimen. "

The sheep studies have identified at least four classes of drugs as especially

effective

against the toxins' bronchial symptoms.

In the May EHP, Abraham and his colleagues report that albuterol was the most

effective

agent that they tested. With this inhalable antiasthma drug, airway constriction

in the

sheep was about a quarter of what it was with no drug. Even the least effective

agent

tested, the antihistamine diphenhydramine, prevented about half the

constriction.

However, therapeutics that fight even more of brevetoxins' effects may be on the

horizon.

Their source could be K. brevis itself.

A couple of years ago, when Baden's team was isolating toxins from K. brevis

cells, it

turned up something new. In the January Journal of Natural Products, the

researchers

named the odd chemical brevenal. At the Society of Toxicology meeting, Baden

reported

isolating two additional variants of this chemical from the alga. What makes

these

brevenals interesting, says Baden, is that when administered to animals, all

three prevent

brevetoxins' damaging effects on nerves, lungs, and DNA.

These natural and strikingly potent antidotes bind to the same receptors on

cells that

brevetoxins target. " Receptor binding is dynamic, " Baden explains, with

compounds

continually attaching and then letting go. " It's like musical chairs, " the

biochemist says,

likening the receptors to the chairs. " So, the more brevenals you have relative

to toxin, the

less chance a toxin can get into one of those chairs " and harm cells.

Brevenals may also explain the decrease in the severity of health effects on

people and

animals in a coastal area during the course of a red tide. Algae tend to produce

more of

the antidotes as a bloom matures, Baden explains.

His team recently applied for a patent on brevenals, and " we're working with a

local

industry to move toward their clinical testing, " he says. The drug company,

aaiPharma of

Wilmington, N.C., foresees developing products to prevent the effects of the

brevetoxins in

people with compromised lungs. Workers, such as beach-cleanup or fishing crews,

who

endure regular exposure to red tide toxins might also benefit.

But Baden says that the company's primary interest in brevenals goes beyond

concerns

about red tides. People with cystic fibrosis and chronic obstructive pulmonary

disease

experience a slowdown of lung-mucus clearance similar to that in

brevetoxin-exposed

sheep. The company is designing drugs to restore normal mucus clearance from the

lungs, as the brevenals do.

These algal agents or drugs derived from them might also find use combating

algal toxins

far beyond southwest Florida. Baden's group recently showed that an alga

unrelated to K.

brevis produces brevetoxins. The alga, currently known as Chattonella cf.

verruculosa, was

initially isolated in Delaware waters 5 years ago during a massive fish kill.

Scientists have recently identified ia species other than K. brevis in

Japan and New

Zealand. Although their toxicity is only beginning to be tested, Baden says that

in

experiments on asthmatic sheep, agents from at least one of the species induce

bronchoconstriction and respiratory distress.

Such findings suggest that brevetoxins might pose health risks—and that

brevenals may

be useful to combat them—around the world.

Marine Mystery

Die-offs of manatees and dolphins in red tides prove perplexing

<PHOTO>

Manatees, the shy and docile mascots of towns around Florida's Gulf Coast, are

experiencing a serious die-off. The current body count—55—is roughly 4 percent

of

southwest Florida's population of these endangered marine mammals. Most of the

deaths

are being attributed to an ongoing red tide of ia brevis.

TRAPPED BY TOXINS. Manatees often can't evade brevetoxins when red-tide algae

infest

the warm haunts that the marine mammals need to survive during the winter.

Fish and Wildlife Res. Inst., Fla. Fish & Wildlife Conserv. Comm.

This bloom began last January in the Gulf of Mexico off Tampa. Currents moved it

to

coastal inlets, bays, and the mouths of rivers, where boaters began reporting

dead

manatees in March. K. brevis blooms in Florida can last from 30 days to 18

months.

The state retrieves each manatee carcass to study the cause of death. Because

most bodies

were recovered in areas hit by the algal bloom, observes Elsa M. Haubold of the

State of

Florida's Fish and Wildlife Research Institute, her team had little doubt what

it would find:

classic but nonspecific internal damage, such as tissues weeping blood. She

notes that this

occurs because the blood often doesn't coagulate in brevetoxin-poisoned

manatees.

An antibody-based test for brevetoxins is confirming the poisons' presence in

vital

manatee tissues and body fluids. Physicians use similar antibody-based tests to

diagnose

various diseases in people.

Still, understanding how the algal compounds kill remains a challenge, notes

veterinarian

Greg Bossart of Harbor Branch Oceanographic Institution in Fort Pierce, Fla.,

who

developed the brevetoxin test. He and other scientists used to think that

disorientation

triggered by nerve damage might be drowning the manatees. Bossart now reports

that the

algal poisoning isn't only neurological.

In many instances, chronic inhalation of brevetoxins contributes to the

destruction of red

blood cells, resulting in severe anemia. This can lead to lung hemorrhages

during which

the animals " drown in their own fluids, " Bossart says. He likens the condition

to the human

infection known as toxic shock syndrome.

However, inhalation is hardly the only route of poisoning. In 2002, months after

a red tide

had come and gone, nearly 3 dozen manatees died after entering their spring

feeding

grounds south of Sarasota, Fla. Some of them died abruptly, with their mouths

still full of

sea grass.

Leanne Flewelling of the state's Fish and Wildlife Research Institute headed a

team that

used Bossart's then-new antibody test to identify large amounts of brevetoxins

adhering

to sea grass the manatees had been eating.

The researchers' findings, reported in the June 9 Nature, might explain some

manatee

deaths this year. Several animals succumbed while eating sea grass.

The 2002 study also found high concentrations of brevetoxins in fish swimming in

an area

that was previously a red tide zone. " Until now, " the authors note, " it was

uncertain

whether live fish could accumulate and transfer [lethal amounts of]

brevetoxins, " because

even relatively low concentrations of these poisons usually kill fish.

The finding of brevetoxins in fish offers a dietary explanation for the deaths

last year of

107 bottlenose dolphins off Florida's Panhandle. Flewelling and her colleagues

propose

that tainted fish poisoned the dolphins.

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