Shareware Overload/ShartewareOverload.cdr/games/fireside.zip/PIGS

Text File | 1987-07-31 | 10KB | 208 lines

Copyright 1987 by Michael Finley Writing Services * 612/646-4642




OF PIGS AND PEOPLE:

Research Links Human Drug Reaction
To Swine Metabolic Disorder

By Michael Finley

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People were dying on the operating table, and pigs were dying in
trucks.  It turns out that there's a direct link between the two
occurrences, and research at the University's Schools of Veterinary
Medicine and Nursing is helping to further connect problems facing
very separate populations.

OF PEOPLE

The human health problem is called malignant hypothermia, and it
is a reaction some individuals experience while in surgery under
the most common anesthesia, the drug halothane.  Though somewhat
rare, affecting only 1 in 40,000 adults, or 1 in 12,000 children,
the consequences are extremely serious.

The body begins to heat up, the whole metabolism goes "crazy" in
a very few seconds, and the muscle tissue of the body stiffens, almost
like rigor mortis.  Unless caught immediately and taken off halothane
and given its antidote, a drug called dantrolene, the individual
dies.

The disorder was first written about in 1960 when a young man with
a broken leg worried out loud to doctors because 10 of his 24 relatives
had died under general anesthesia.  He, too, developed malignant
hypothermia under anesthesia, but survived.

Though an unusual reaction to halothane, malignant hypothermia is
common enough that anesthetists routinely keep dantrolene on hand
in surgery, just in case. And non-triggering anesthetics exist which
can be used as an alternative to halothane.  Still, it is the anesthesiological
profession which has pushed the hardest for research into the nature
and prevention of malignant hypothermia.  It is a horrible thing
to experience any fatality, but especially so during something as
routine as a tonsillectomy!

OF PIGS

Sometime in the 1950s, a new phenomenon was attracting the attention
of hog farmers, slaughterhouses, and veterinary doctors.  Large numbers
of animals were dying -- in trucks, in pens, even in the serene confines
of the barnyard.  Drivers pulling up to the stockyards would open
the gates and see as many as three-quarters of the swine lying dead
and stiff-legged in back.

Examination of the muscle tissue of dead pigs revealed an unappetizing
pale drippiness to the flesh.  Farmers lost a lot of money because
of this trait, tagged PSE, for pale-soft-*exudative flesh.  The cause
of death was labeled Porcine Stress Syndrome.

The connection?  Porcine stress syndrome (PSS) and malignant hypothermia
(MH) are one and the same thing.

THE TEAM

And so researchers at the University began to explore the nature
of this twin-barreled problem.  At the School of Veterinary Science
in St. Paul, Bill Remple began breeding a herd of swine particlularly
vulnerable to porcine stress syndrome.  This herd of select pietrain
pigs took years to breed -- today it is the only 100% porcine stress
syndrome-susceptible pigs in the world, and researchers everywhere
are begging to borrow a cupful of pigs.  Remple can remember when
having all those pigs didn't automatically translate into popularity.

While
Remple has been examining pigs as a whole, researcher Esther Gallant
has been trying to understand what happens in their muscles better.
 Her experiments remind one of those frog-dissection lessons from
high school biology, where electric shock made the frog legs jump
anew.  She tests the muscle tissue of PSS-susceptible pigs against
the tissue of normal pigs.

Researcher Charles Louis looks even more deeply into PSS, by examining
the phenomena of muscle distress at the microbiological level.

And across town, at the University's School of Nursing, co-researcher
Sue Donaldson has been examining the pig/people connection, and working
with Esther Gallant to determine what happens in the muscle to cause
this catastrophic chain reaction in the two species.

The objective of all this looking and breeding and probing and electrifying?
 On the swine side, to find a way to separate the lean, well-muscled
body type of pork preferred in today's diets from the high susceptibility
to PSS.  Achieving that will mean less loss  and higher profits for
farmers and producers, and higher-quality, high-protein pork for
consumers.

The human side, of course, is to use the pigs as guinea pigs to
understand what mechanism triggers the metabolic catastrophe of malignant
hypothermia, develop a more reliable diagnostic tool than simply
asking the patient whether any relatives have died in surgery before,
and ultimately to eliminate surgical fatalities caused by this genetic
disorder.


THE CALCIUM CONNECTION

Esther, Gallant, Remple and Louis agree that the cause of this catastrophe
has something to do with calcium release in the tissue of ordinary
muscle tissue cells.  In the ordinary conduct of business, most muscle
cells have a choice of being long and skinny (the relaxed state)
or getting tight and bunched up (contracting).

Cells make this choice depending upon electrical stimulation by
one cell membrane upon the next, and on and on, until we make a fist,
lift a cup of coffee, or pat the baby.

But a chemical exchange also occurs involving intracellular calcium.
 Every cell has a sac or organelle (called the sarcoplasmic reticulum)
containing a supply of ionized or activated calcium.  When the cell
gets the news to contract, the sac releases its calcium into the
cell, the calcium bonds instantaneously with the protein molecules
in the cell, and the cell clenches with incredible rapidity.  Given
the opposite signal, the calcium un-bonds and returns to its organelle
sac, to be used and reused a thousand times again that day.

That's the ideal.  In the cells of people susceptible to MH, and
in pigs susceptible to PSS, something less than ideal occurs, and
vastly greater amounts of calcium are shunted into the cell proper.
 The result is a blow-out, with the creation of massive amounts of
lactic acid, and a tremendous increase in cell heat.

Gallant and Louis and Donaldson aren't sure what that "something"
is -- no one knows.  Gallant is trying to learn what the "signal"
or electrical or chemical event is that sets this dynamic into action.


Louis wants to learn more about the calcium uptake phenomenon --
why so much more calcium is ushered along the transverse tubular
channel of select individuals' muscle cells, why things go completely
haywire there.

The pigs/people model is a pleasant opportunity for researchers.
 Physiologists have long known that pigs and humans were remarkably
similar in many ways metabolically.
It is also known that similar stress syndromes occur in other species.
 Racehorses are known to "tie up" during a race and die.  Dogs collapse
and die during fights.  These and other animal stress deaths may
appear to be "heart bursting" events, or endocrine explosions.  But
they are not.  It is likely they are instances of genetic defect
in the muscle similar to those experienced by pigs and by people.
 But Bill Remple's pigs are still the best model in the world for
PSS and for MH.

As for dantrolene, the customary antidote for people suffering attacks
of malignant hypothermia, it is expensive and difficult to administer,
with many "maybes" and not near enough "certainlys."  You either
have to anticipate troubles before surgery and administer it orally,
or else inject it intravenously during the event itself.

It is a remarkable drug -- it goes right to the heart of the muscle
contraction debate and calms the commotion there.  "It is thought
of in an almost mystical manner -- it is a pure prophylactic, reversing
muscle activity immediately," said Louis.

For that reason it is used quite commonly for people with muscle
spasticity problems, and helps explain why Louis' research has been
unwritten in part by the Muscular Dystrophe Association.


WHAT NEXT?

It is known that PSS was unreported before the current day of the
leaner pig.  An educated guess is that something in the breeding
process that created the "Mr. Pig Universe" physique also led to
the stress susceptibility.  (There is, by the way, no similar correlation
for humans between "porkiness" and MH -- football players and other
big athletic types have no greater susceptibility to the disorder.)
 We know that every protein in the body is specified at conception
by the parents' DNA.  If a common protein such as troponin is aberrant
from birth, it is an achilles' heel for the life of that pig, or
that person.

"So the search for that one errant protein goes on," says Louis.
 "It's this way in research for every genetic disease -- find the
errant protein for Cystic Fibrosis, Huntington's Chorea, or Muscular
Dystrophe, and you will finally understand those diseases."  The
problem then, however, is the search for a cure -- pigs can be bred
for the "right stuff" at the cellular level, but people cannot.

Louis has discovered that the introduction of the drug ryanodine
produces startling amounts of calcium binding in the sarcoplasmic
reticulum -- ryanodine may be the "smoking gun" that genetic detectives
are ever on the lookout for.

Just another tale of research at the University of Minnesota.  Lots
of what-ifs, plenty of dead-ends, and no shortage of what-does-this-mean?

But
at the end of this elusive rainbow are several pots of gold -- one
for the pigs and Minnesota's $250 million pork industry, one for
medicine and its mandate to make surgery more safe, and a third for
the rest of us, who need to eat leaner meat, and who have no desire
to leave this world just because we inhaled the wrong gas.

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