Estrogen analog may provide safer therapy

1
Estrogen analog may provide safer therapy A
synthetic estrogen has been shown to reverse bone
loss in both female and male mice without having
adverse effects on their reproductive systems, as
current hormone replacement therapies sometimes
do, suggesting that a potentially safer
osteoporosis drug for women and men may be in the
offing. Endocrinologists at the University of
Arkansas discovered last year that
4-estren-3a,17b-diol (estren) is bound by
receptor proteins in the pathway that helps
control bone density but not by receptors in the
pathway that helps regulate the size and function
of the uterus and prostate gland. Estradiol and
testosterone are active in both pathways. The
researchers show that estren provides greater
overall bone density and strength than estradiol
treatment in female mice and is equally effective
as testosterone at preserving bone density in
male mice. However, estren does not cause
abnormal growth of cells in the reproductive
tracts of mice, as do estradiol and testosterone.
2
Sulfanyl alcohols are culprits in smelly
armpits The typical smell associated with the
human armpit is caused by a witches brew of
molecules, including steroids, fatty acids, and
sulfur-containing compounds. The sulfur compounds
are the most malodorous, but little has been
known about them until now. Research groups at
two Swiss fragrance and flavor companies have
identified the compounds as sulfanyl alcohols. A
team at Firmenich found eight sulfanyl alcohols
in sweat from exercising volunteers, including
the major component (S)-3-methyl-3-sulfanylhexan-1
-ol, which has an onion-like smell that is likely
the most important contributor to the typical
and repulsive sweat malodor. A second team at
Givaudan Schweiz also identified this compound,
as well as three additional sulfanyl alcohols
with equally pungent odors. Both teams
identified Corynebacterium, Staphylococcus, and
other bacteria that dwell in the armpits and
produce enzymes that convert precursor compounds
in the initially odorless sweat to the stinky
compounds.
3
Butter flavoring harms popcorn producers Vapors
from artificial butter flavoring appear to be the
cause of the high incidence of lung disease among
employees at a microwave popcorn plant, according
NIOSH. Researchers have evaluated the vapors
impact on rats, and find that the vapors kill
portions of the lining epithelium of the nose and
large airways. The vapors include diacetyl
(2,3-butanedione), acetoin (3-hydroxy-2-butanone),
and acetic acid, among other compounds.
Preliminary data indicate that diacetyl by itself
can cause the damage. Diacetyl is classified as
generally recognized as safe, but that applies
to consumption of trace amounts rather than
inhalation of vapors. There is no indication of
risk from home popping, because consumers are
exposed to vapor concentrations that are many
times lower than those found in the production
plant.
4
Antibiotic secretions from deers' feet win U.S.
patent   Black-tailed deer have glands on their
feet that secrete compounds with antibiotic
properties, according to William Wood of Humboldt
State University, Arcata, CA. Wood has patented
synthetic versions of the compounds. The main
compound secreted by the black-tailed deer's feet
is 3-tridecen-2-one. It inhibits the growth of a
narrow range of organismsincluding bacteria and
fungithat live on the skin. It might be useful,
Wood believes, for treating acne, dandruff,
athlete's foot, and other conditions of human
skin. It doesn't kill beneficial skin bacteria,
Wood says, and it doesn't dissolve in water, so
it will sit on the skin for a long time. The
black-tailed deer antibiotics have not yet been
tried in animal tests.
5
Insect's Venom Eyed For Cancer Defense Camouflage
is not the only trick Madagascar walkingsticks
use to thwart their enemies. These insects also
spray a defensive fluid, and Arthur S. Edison of
the University of Florida and coworkers hope the
fluid's key component, parectadial (shown), will
ward off a human enemy cancer. The researchers
detail the discovery and characterization of
parectadial along with their development of a
synthetic route to the monoterpene. Parectadial
is structurally similar to perillyl alcohol, a
plant-derived compound that has been investigated
for anticancer activity. That structural
similarity prompted Edison and coworkers to test
parectadial's effect on tumor cells. Preliminary
unpublished results indicate that the compound
also has anticancer activity, leading the
researchers to file a patent on parectadial.
6
A Schiff base (or azomethine), named after Hugo
Schiff, is a functional group that contains a
carbon-nitrogen double bond with the nitrogen
atom connected to an aryl or alkyl groupbut not
hydrogen. Schiff bases are of the general formula
R1R2CN-R3, where R3 is an aryl or alkyl group
that makes the Schiff base a stable imine. Hugo
(Ugo) Schiff (1834 1915) was a German Chemist.
Born in Frankfurt am Main, Schiff was a student
of Friedrich Wöhler in Göttingen. In 1879 he
founded the Chemical Institute of the University
of Florence. He discovered Schiff bases and other
imines, and was responsible for research into
aldehydes and had the Schiff test named after
him. He also worked in the field of amino acids
and the Biuret reagent. Schiff died in Florence.
7
Bill-collecting compound   In London, the British
company Bodywise revealed that it is offering a
product called Aeolus 7 to collection agencies
for 6000 per g. The active ingredient is a
pheromone, androstenone, from sweat secreted by
men from their armpits and groins. It appears to
act like magic on people who owe money.
Bodywise tried Aeolus 7 in Australia on bills
sent out by a mail-order cosmetics firm. Of 1000
bills, half were treated with Aeolus 7 and half
were not. The treated bills elicited 17 more
payments than the untreated bills.
8
Bill-collecting compound misspelled or
spurious   R.E. Juday of Missoula, MT, pointed
out that adrostenone does not appear in the Merck
Index. Juday suggested also that the pheromone in
question very likely was 5a-androst-16-en-3a-ol.
A major constituent of boar sweat that also has
been detected in human male axillary sweat.
Inquiries into the original news item have proved
fruitless, and Juday presumably is correct. Joe
Arrigo of Palatine, Ill., meanwhile recalled that
when the boar steroid was first found in human
male axillary sweat, in 1980, it was touted as a
human sex pheromone and used in a cologne billed
as the "first pheromone-based fragrance." No
frenzies resulted, Arrigo notes, and no magic
human sex pheromone had yet been found. It
wouldn't work anyway, he goes on. "Not since our
ancestors dwelled in caves have humans depended
on a keen sense of smell for their survival."
9
Pheromones from men affect women Exposure to male
armpit secretions reduces tension and enhances
relaxation in women, as well as altering hormone
pulses that may affect the length and timing of
the menstrual cycle, a recent study
shows. Researchers at the Monell Chemical Senses
Center have found that male armpit secretions
contain two types of pheromones a modulator,
which modifies mood, and a primer, which alters
endocrine responses. The change in womens mood
was gleaned from responses to a mood-rating
scale. The endocrine effect was measured through
pulsing of luteinizing hormone (LH). Bursts of LH
secretion precede ovulation and increase in
frequency as ovulation nears. On average,
exposure to male armpit extracts reduced the time
to the next burst by 20. Whether the emotional
and endocrine effects are due to the same or
different compounds is unknown. Chemical
characterization of the active components in the
extracts is under way.
10
Bombardier beetle fires defensive spray in
pulses   Thomas Eisner of Cornell University and
his colleagues report that a species of
bombardier beetle fires its defensive spray in
high-speed pulses rather than continuously, as
had been believed. The spray is generated by an
explosive chemical process. The group's
experimental subject was Stenaptinus insignis, a
relatively long bombardier beetle from Kenya. Its
body length is about 2 cm.   The beetle, when
disturbed, emits a jet-like spray from an
abdominal tip. The tip serves as a revolvable
turret that permits the beetle to aim the spray
in any direction. The emissions appear as a mist
and are accompanied by audible "pops". The spray,
whose active ingredients are p-benzoquinones,
fends off vertebrate and invertebrate predators.
11
S. insignis generates its spray in two large
glands that open at the abdominal tip. Each gland
has an inner chamber, or reservoir, containing
hydroquinones and hydrogen peroxide, and an
outer, or reaction, chamber containing the
oxidative enzymes catalase and peroxidases. The
reactants normally are kept apart by a valve
between the chambers. Sufficient aggravation
causes the beetle to compress the reservoir,
using muscles provided for the purpose, thus
forcing fluid through the valve and into the
reaction chamber. The resulting reaction produces
the p-benzoquinones explosively at the moment of
ejection. The spray is ejected at 100 C.
hydroquinone
benzoquinone
12
Definitive evidence for pulsed delivery was
obtained by high-speed cinematography, say Eisner
and his colleagues. They filmed 14 discharges
from seven beetles at 2670 and 4000 frames per
second. The films clearly resolved the burstlike
emissions that characterize the pulsations. The
pulse repetition rate averaged about 531 per
second. Spray emergence velocity was 1163 ? 330
cm per second. The beetle can spray about 30
times before it runs out of reactants it can
replenish its supply within a day.
13
Insight into activity of St. Johns
wort   Hyperforin, the putative antidepressant in
St. Johns wort, owes its activity to the
enolized b-diketone moiety. Luisella Verotta and
coworkers at the University of Milan, Italy,
reached this conclusion through
structure-activity studies of the compound.
Hyperforin inhibits serotonin uptake, while
non-enolizable analogs do not. A. Douglas
Kinghorn, a professor of pharmacognosy at the
University of Illinois notes that the work comes
at a time of heightened awareness of the adverse
interactions of St. Johns wort with various
drugs. The analogs prepared for this study will
have great value for additional biological
tests, he says.
14
Strawberry flavonoid enhances memory Neurotrophic
factors are polypeptides that promote the
well-being of nerve cells, but their clinical use
for, say, sustaining memory is limited because
the compounds have trouble getting past the
blood-brain barrier. Pamela Maher of the Salk
Institute for Biological Studies and colleagues
have now identified the flavonoid fisetin (shown)
as a small molecule that has several properties
of a neurotrophic factor and can be taken orally.
The researchers report that fisetin, which is
found in strawberries and other foods, enhances
memory in mice by increasing activation of the
transcription factor CREB (cAMP response
element-binding protein), which is involved in
the physical changes in the brain underlying the
development of long-term memory. Chowing down on
strawberries isn't a feasible memory-enhancing
regimen, Maher warns, since a person would have
to eat 10 lb of the fruit per day to obtain a
beneficial effect.
15
Plant Pathogen Guides Cancer Research The
bacterium Pseudomonas syringae is infamous for
the brown rot spots it leaves on apples, pears,
and many other crops. Now, a team of U.S. and
European researchers report the mechanism behind
this plant pathogen's virulence and propose that
this mechanism could inform cancer drug
development. The bacterium produces a peptide
virulence factor called syringolin A (shown) that
facilitates infection by inhibiting the plant
cell's proteasome. The proteasome is essential
for regulating many cellular functions in both
plant and human cells. A hydroxyl group on one of
the proteasome's threonine residues does a
Michael-type 1,4-addition to syringolin A's
a,ß-unsaturated carbonyl (shown in red), forming
a covalent bond. Because the proteasome is a
promising anticancer target and syringolin A has
been shown to thwart ovarian andneuroblastoma
cancer cells,the authors note that this
novelmechanism could guide thedesign of new
proteasomeinhibitors.
16
Ad draws fire Roy W. King of Gainesville, FL, who
confesses to a low tolerance for bafflegab and
quackery, sent in an ad for an all-natural
product that significantly clears discoloration
of toenails and fingernails caused by fungal
infection. The product is said to eliminate
keratin debris under the nails and lower the
nails pH. The key ingredient is ethanoic acid.
The cost is 29.99 per bottle one 4-oz bottle,
the ad says, lasts three to four months.
Maybe it takes a chemist, King fumes, to realize
that ethanoic acid also comes in a bottle of
all-natural vinegar.
17
Vinegaroon The whipscorpion, or vinegaroon, has
survived for 300 million years by defending
itself with a discharge that is 84 percent acetic
acid. Its spray also includes caprylic acid
(octanoic acid), a foul-smelling spreading agent
that promotes penetration. The creature has
excellent aim and can fire many times in
succession.
18
acetabulum definition n. pl. acetabula (-l )
1. Anatomy The cup-shaped cavity at the base of
the hipbone into which the ball-shaped head of
the femur fits. 2. Zoology The cavity in the body
of an insect into which the leg fits. 3. Zoology
A cup-shaped structure, such as the sucker of a
tapeworm or leech. acetabulum etymology Latin
acetabulum, vinegar cup, from acetum, vinegar
see acetum.
19
Peruvian wound treatment explained Trials with
mice confirm that a traditional Peruvian medicine
can help heal wounds, report researchers based in
Kentucky and Peru (J. Nat. Prod.). Peruvians use
an infusion of a plant called Anredera diffusa to
wash wounds. They also use the wet leaves of the
plant, which is commonly known as lloto, as a
wound dressing. Gerald B. Hammond of the
University of Louisville, Abraham J. Vaisberg of
Cayetano Heredia University in Lima, and their
colleagues found that an ethanolic extract ofthe
plant's leaves and stems showed wound-healing
activity inmice and was nontoxic. After
hydrolyzing and fractionatingthe extract, the
team determined that the wound-healingfraction
contained oleanolic acid (shown). Theresearchers
found that wounds treated withthe compound heal
significantly fasterthan untreated wounds.
Oleanolicacid is an inexpensive,
commerciallyavailable product that is
currentlyused in skin care products.
20
Wild ox bugs mosquitoes The gaur, a wild ox
native to Southeast Asian regions plagued by
mosquitoes and other biting flies, has a short
velvety coat that glistens with an oily
secretioon, according to Chris Wemmer, director
of the Smithsonian National Zoos Conservation
Research Center. When he learned that his
colleague, vertebrate biologist Paul J. Weldon,
was investigating the insect repellant qualities
of vertebrate skin secretions, he suggest that
Weldon include gaur gunk in his studies. They
obtained sample of the greasy gaur hair and
separated the waxy material from the hair and
fractionated it. Tests with a mosquito colony
established that a novel 18-carbon acid isolated
from the mixture acts as a landing and feeding
deterrent for the yellow fever mosquito. The
compound was identified using NMR and mass
spectrometry, and enantioselective synthesis is
being carried out to determine the compounds
absolute configuration, which was tentatively
assigned by analogy to the configuration a
related compound.
21
Healthy oils turn toxic in fryer When it comes to
deep frying, highly unsaturated vegetable oils,
such as soybean, sunflower, and corn oils, may
soon lose their reputation as healthy
alternatives to saturated animal fats and
partially hydrogenated oils. Unlike their
saturated counterparts, these vegetable oils
dont increase levels of bad cholesterol, and
theyve been considered heart-healthy because
they contain high levels of linoleic acid.
However, food chemists A. Saari Csallany and
Christine Seppanen report that when these oils
are heated at frying temperatures (365F) for 30
minutes or longer, the healthy linoleic acid
oxidizes to the highly toxic compound
(E)-4-hydroxy-2-nonenal (HNE). This toxic
aldehyde has been linked to a number of diseases,
including Parkinsons and Alzheimers. The
University of Minnesota researchers also found
that the concentration of HNE in fried foods is
directly proportional to its concentration in the
cooking oil. The toxin accumulates with each
heating cycle, underscoring the importance of not
reusing these oils for frying.
22
Queen mandibular pheromone   Last summer,
scientists at Simon Fraser University, Burnaby,
British Columbia, reported their work on the
queen bee's pheromonal control of her troops.
Mark Winston and Keith Slessor have figured out
the composition of the secretion involved and
have explored possible commercial applications.
Bee scientists have recognized for more than 30
years that the queen's pheromones mediate worker
and colony reproduction and influence broad
aspects of foraging and other activities.
Scientists have also identified certain active
elements of the pheromones, but realized that
they did not have the full picture. Analyses of
crushed bee heads produced laundry lists of
chemical, but none proved active. In 1985, the
Canadian investigators quite by accident put a
glass lure coated with queen mandibular extract
on a lab bench next to some stray worker bees.
The worker bees immediately formed a retinue
around the lure, indicating that it was coated
with the real McCoy or something close to it.
Winston, Slessor, and their colleagues
eventually found that queen mandibular pheromone,
as it is called, is a mixture of five molecules
(E)-9-keto-2-decenoic acid both enantiomers of
(E)-9-hydroxy-2-decenoic acid methyl
p-hydroxy-benzoate and 4-hydroxy-3-methoxy-phenyl
ethanol.
23
Several uses of queen mandibular pheromone are
near commercialization, say Winston, and Slessor.
One use permits packages of worker bees to be
shipped without queens, for example, and may also
be useful as an attractant for swarms. The most
valuable use, however, may be in promoting
pollination. Trees and berries experimentally
sprayed with queen mandibular pheromone nearly
always attract up to twice the normal number of
worker bees. Increases in yield and quality are
more variable, but very promising. . .
24
Bee Brainwashing   Using chemicals to prevent
someone from forging bad memories smacks of
brainwashing, but this is precisely what a queen
bee does to the young worker bees that tend to
her. Queen bees keep their young servants happy
by means of homovanillyl alcohol (HVA). It is one
of several pheromones a queen uses to maintain
control of her hive. Its been known for a while
that the queen's pheromones block ovary
development in worker bees and inspire the worker
bees to clean and feed her but the big discovery
is that HVA is directly influencing brain
chemistry. Researchers found that when young bees
were exposed to HVA, they were incapable of
learning to associate a nasty experience with a
smell, a process that neurobiologists call
aversive learning. HVA did not prevent the
association of a good experience with a smell,
so-called appetitive learning. The social perk
achieved by preventing these young nursebees
from developing aversive memories againstodors
in the hiveincluding the queen's own odoris
colony security. Thwarting bad memories
reducesaggressive behavior among the masses deep
within a hive.
HVA
25
Female elephants, moths signal mates with same
compound   As different as elephants are from
moths, they share a mating ritual the females
release the volatile ester (Z)-7-dodecen-1-yl
acetate to signal their readiness to mate. Many
insects, especially moths, excrete this ester in
their pheromone mixtures. In work that may find
use in the breeding of elephants in captivity, L.
E. L. (Bets) Rasmussen, associate professor of
chemistry at Oregon Graduate Institute of Science
Technology, and colleagues at three other
institutions recently identified the compound in
the urine of preovulatory elephants. Very few
vertebrate pheromones have previously been
identified. The feat comes 14 years after
Rasmussen and other coworkers observed that
something in the urine of a cow elephants elicits
a specific behavior in malesthe Flehmen
response. A bull elephant detects the ester by
touching the urine or urogenital orifice of a
female. If the compound is present, the bull then
inserts the tip of its trunk into ductal orifices
leading to a chemoreceptive organ found on the
roof of its mouth. Bulls display this behavior
frequently when the female is in heat, and the
response correlates with penile erections.
26
Antifrog pesticide   Harry Ako and his colleagues
at the University of Hawaii are battling the
coquí, a tiny tree frog imported inadvertently
from Puerto Rico. The dinky frog, Ako writes,
has a pleasant chirp in the laboratory and in
Puerto Rico. In Hawaii, however, the frog has no
natural enemies. Population densities have been
estimated at 8,000 frogs per acre, and the racket
the frogs produce has been measured at 90 to 100
decibels.   Aki and his coworkers hope to reduce
the coquí frogs population densities to
reasonable levels. They plan to use caffeine and
pyrethrum, a pesticide derived from
chrysanthemums, or perhaps another pesticide.
They also hope to do enough physiological and
biochemical work to earn somebody a masters
degree.
27
Herbal remedy relieves hay fever   An herbal
extract has been shown in a clinical study to be
as effective at treating hay fever as the
antihistamine fexofenadine (Allegra or Telfast).
The finding could boost the fledgling
phytopharmaceutical industry, which scrutinizes
natural remedies for efficacy and safety and
hopes to develop them at lower cost than
traditional pharmaceuticals. In the study, led by
Andreas Schapowal at the Allergy Clinic in
Landquart, Switzerland, patients took a placebo,
Telfast, or Tesalin, a prescription drug prepared
from an extract of the butterbur plant. Butterbur
roots have been used in herbal remedies for
centuries. The most prevalent compound, petasine,
and its isomers are thought to inhibit synthesis
of leukotrienes, which along with histamine and
other compounds are synthesized as part of the
immune response to an allergen.
petasine
28
Sunless tanning with forskolin Using a mouse
model of "redheads," David E. Fisher of the
Dana-Farber Cancer Institute, Boston, and his
coworkers have shown that the natural
skin-tanning pathway can be jump-started by
topical application of the plant-derived natural
product forskolin, shown. Tanning is a protective
response of the skin to ultraviolet radiation,
and the pigment pathway resulting in a tan is
often defective in people with fair hair and
skin, such as redheads. The researchers found
that mice genetically engineered to lack the
melanocortin 1 receptor, which is normally
located on the surface of pigment cells, produced
no pigment in response to UV light. But the mice
progressively became so dark in response to
forskolin that they looked like naturally dark
mice. The pigment produced in this manner acts
just like naturally produced pigment, collecting
in umbrella-like arcs over the nuclei of skin
cells known askeratinocytes. The
forskolin-treated mice werethus protected
against potential skin damage orcancer that can
be caused by UV exposure.Studies are currently
under way to identifydrugs that may have similar
activity inhuman skin, Fisher says.
29
A test for red pepper   "People eat red pepper
exclusively for the sensory pain it arouses,"
according to Marianne Gillette and Silvia King.
The two are sensory specialists at McCormick
Co., the big spice company in Baltimore,
MD. Naturally, the authors say, people have
differing appetites for painsome like it hot, so
to speak, others not so much. But whatever the
desired level of heat, they note, it must be
"measured and controlled in order to deliver the
appropriate sensory dose." To do so, spice people
now can rely on ASTM E 1083, Test Method of
Materials and Products. Both Gillette and King
are members of the committee. The new method, say
the McCormick duo, correlates very well with
instrumental analyses of the level of
capsaicinoids, the hot chemicals in red pepper, a
fruit of the genus Capsicum. The instrumental
method, using high-pressure liquid
chromatography, is Method 21.1 of the American
Spice Trade Association.
 
capsaicin
30
Molecule selectively kills cancer
cells   Apoptosis, or programmed cell death, is
an attractive target for cancer therapeutics.
However, most apoptosis-inducing small molecules
dont distinguish between cancerous and normal
cells. Paul J. Hergenrother, an assistant
professor at the University of Illinois, has
identified an amide that selectively induces
apoptosis in cancer cells. Compounds in a library
based on a natural product from a kind of mint
plant were screened for their ability to cause
death in two different cancer cell lines.
Molecules that showed cytotoxicity were evaluated
to determine if the cells died via apoptosis,
which can be determined by measuring the activity
of caspase-3, a protease known to be involved in
apoptosis. The selectivity of molecules for
cancerous cells was determined by comparing
apoptosis in lymphoma cells versus noncancerous
splenocytes. Hergenrothers team is working to
determine the biological pathway responsible for
the selectivity.
31
Beetle-eating frogs may pose dietary
hazard  Biologist Thomas Eisner of Cornell
University and a group of scientists from
Cornell, the University of Michigan, and the
University of Missouri warn us of a hazard of
eating frog legs. The hazard is not genericthe
frogs have to have been eating meloid beetles not
long before their legs are served. Eisner and
his colleagues were drawn to the topic by reports
in the medical literature of 1861 and 1893. The
first was by a French physician, M. Vezien, who
observed French Legionnaires in a North African
field hospital suffering from priapism. On being
questioned, the soldiers admitted having eaten
the legs of nonregulation frogs captured locally.
Vezien found a site nearby that was stiff with
frogs that proved, when dissected, to be full of
meloid beetles. He connected the priapism with
the beetles and rushed into print. A second
military doctor in North Africa, J. Meynier,
reported a similar case 32 years later. The
Eisner group followed up these findings. They
knew that meloid beetles are the source of
Spanish fly, whose active ingredient is
cantharidin. The compound is a cellular poison,
Eisner says taken internally it can have
"drastic, irreversible effects on the urogenital
system." The lethal dose to humans is somewhere
between 10 and 100 mg, and one meloid beetle can
contain several milligrams.
 
32
The beetles are found in this country and many
other parts of the world. The cantharidin they
produce evidently protects them and their eggs
against predators like ants and carabid beetles,
but not against frogs. The authors fed leopard
frogs meloid beetles collected from tomato
plants. Frogs that ate 13 to 95 beetles over
spans of three to 12 days showed cantharidin
levels of 0.03 to 0.05 mg per g of thigh muscle.
A half pound to a pound of frog legs at that
loading could be fatal, and sublethal amounts can
do serious damage. The group doesn't generalize
on the hazard, having no notion of how many
meloid beetles are eaten, and where, by frogs
eaten by humans worldwide. But it seems clear,
they say, that field-collected frogs from regions
teeming with beetles are best not wolfed soon
after capture.
33
A turn of the century remedy for hiccoughs   A
cure for hiccoughs reported here prompted Helen
Stanbro to send in a copy of a page from a book
that my grandmother used to raise her family at
the beginning of the century, "The Household
Physician" (Woodruff Publishing Co., Boston,
1905). Stanbro, who hails from Los Alamos, NM,
says, "It amazes me that anyone survived."   The
page in question gives the authors' cure for
hiccoughs, described as "a sudden jerking spasm
of the midriff, occurring every few moments in
bad cases, causing the air to be driven out of
the lungs with such suddenness as to produce a
noise like the involuntary yelp of a puppy." The
authors recommend several cures, but the one that
caught Stanbro's attention was "cocaine,
one-eighth grain every fifteen minutes is a very
simple remedy." (A grain for those not in touch,
is .002285 oz or 0.0648 gram.)   When the
hiccoughs were severe, Stanbro notesfor example,
in the last stages of yellow feverthe authors
recommended adding brandy and strychnine to the
cocaine. The patient, she says in so many words,
probably didn't care whether the cure worked.
34
Cocaine free base oily liquid insoluble in H2O
35
Caution urged with urine tests as screen for
drugs James Abelson of the University of Michigan
has written a cautionary letter on screening
people for drugs by urine analysis. He reports
the case of a 26-year-old woman who responded to
an advertisement for normal subjects for a
research project to be conducted by him and his
colleagues. The woman went through the physical
examination with flying colors until a urine test
for illicit drugs came out positive for opiates.
Gas chromatography-mass spectroscopy showed
morphine and codeine. The woman "convincingly
denied" any known use of opiates, so they
reviewed her recent oral intake. The problem, it
developed, was a lemon poppy seed muffin the
woman had eaten five hours before the urine test.
A test run six days after she ate the muffin was
negative for opiates. She then ate a second
muffin and, five hours later, her urine again
tested positive for opiates. With this, she was
cleared of hanky-panky and accepted the research
project. The Michigan scientists learned from a
literature search that "the ability of poppy
seeds to produce positive urine tests for
morphine and codeine is will established." A
survey of colleagues in the departments of
psychiatry and internal medicine showed that only
a few knew of the poppy seed problem. The
director of the drug analysis lab was aware of
it, but doubted that one muffin could do the job.
36
Chocolate cures cough A new study brings more
good news for chocolate fans. Theobromine,
cocoa-derived compound, shows promise as a
suppressant for persistent coughs. Volunteers
participating in a study at Imperial College
London were given tablets containing theobromine,
codeine, or a placebo. They were then asked to
inhale a gas containing capsaicin in order to
induce coughing. Those who were given enough
theobromine to equal two cups of cocoa needed
about a third more capsaicin to induce coughing
that those given codeine. Theobromine, unlike
codeine, which can cause drowsiness and
constipation, seems to be free of side effects.
Theobromine (from theobroma cacao)
37
Swine-farm odor under attack Simon Davies, an
agricultural engineer at Michigan State
University, is systematically identifying each
odorous compound in swine manure. The work is one
step in an attack on swine-farm odor, which is
caused by a mixture of perhaps 10 to 20 fragrant
compounds Major groups of odorous compounds,
Davies says, include sulfur compounds, phenols,
indoles, alcohols, and fatty acids. Some are
formed inside the hog and excreted in the manure
others are formed by microbes as they decompose
manure. Some odorous compounds, such as skatole
and indole, are attacked by oxidizing agents,
such as ozone others including fatty acids, are
not. Davies and his colleagues plan to associate
specific odors with specific compounds. They will
use gas chromatography/mass spectrometry (GC/MS)
and GC/olfactometry. Gases from the GC column
will be collected and sniffed if they have a
perceptible odor, the guilty compounds will be
identified by MS. The results will comprise the
groundwork needed to find ways to destroy
swine-farm odors.
38
Better chemistry for the armpits The active
ingredients in most antiperspirants today are
aluminum salts that act by forming a plug that
blocks the flow of sweat from the sweat duct to
the skin. Quaternary ammonium anticholinergics,
on the other hand, block the activation of sweat
glands by binding to receptors that trigger sweat
formation. These compounds were introduced in the
1960s as drugs to treat peptic ulcers. The
compounds use in treating hyperhidrosisexcessive
sweatinghas been well known, but their safe
application to ordinary sweating and higher
efficacy compared to aluminum salts has just
recently been shown in a clinical trial with
glycopyrrolate (below). The compounds do not
leave residues on the skin or clothing. The
current market for antiperspirants worldwide is
about 4 billion.
39
Berberine cuts cholesterol Berberine is a plant
alkaloid with manifold biological effects. Now,
it has been shown to be a cholesterol-lowering
agent in humans that acts via a mechanism
different from that of statins. According to
Jian-Dong Jiang of the Chinese Academy of Medical
Sciences, berberine increases the activity of
extracellular-regulated protein kinase (ERK),
with the end result that more receptors of
low-density lipoproteins (LDLs) are formed on the
surface of liver cells. With more receptors,
removal of LDLs and the cholesterol the
containthe bad cholesterolis enhanced. Statins
also increase the number of LDL receptors, but
they do so through their effect on sterol
regulatory element-binding proteins. Noting that
ERK could be a new target for lowering
cholesterol, Jiang has applied for patent
protection of this discovery.
40
Joe Betz of Wheaton, MD, saw in a local business
newspaper a story about a new biotechnology
product, a "right-handed sugar that is
metabolized by humans to produce energy not fat."
The inventing company, the story said, is still
working on a "left-handed sugar (so named because
it worked on the left side of the brain which did
not recognize it as sugar and thus did not
metabolize it in the body)."
41
Sweetness in fine detail The subunits of the
sweet taste receptorT1R2 and T1R3have distinct
affinities for different saccharides, according
to a new study. Although it has been known that
the nonsaccharide sweetener aspartame binds only
to T1R2 and cyclamate only to T1R3, which subunit
interacts with saccharides was not known until
now. The study by Graeme Conn, University of
Manchester, and Steven Munger, University of
Maryland, indicates that both T1R2 and T1R3 bind
saccharides with different affinities. They show
that sucrose and the low-calorie sweetener
sucralose interact with both subunits.
Furthermore, sucralose binds with either subunit
with greater affinity than does sucrose.
sucrose
sucralose
42
Taste receptor responds to only one class of
bitter molecules At least 24 human taste
receptors are believed to mediate the perception
of bitterness. Researchers at the German
Institute of Human Nutrition show that one of
these receptors, known as TAS2R16, recognizes
only one class of bitter compounds. When
expressed in cell cultures and presented with
compounds that are closely related structurally,
TAS2R16 responds specifically to
b-glucopyranosides such as salicin, a bitter
compound from willow bark that has long been
known as an analgesic. A b-glycosidic bond
between glucose and a large hydrophobic group,
such as phenyl, benzyl, or naphthyl, appears to
be required for receptor binding. Thus, TAS2R16
doesnt respond to phenyl-b-D-galactopyranoside,
phenyl-a-D-glucopyranoside, or methyl-b-D-glucopyr
anoside. The finding opens opportunities to
modify human perception of bitter tasting
compounds.
43
Deodorizing gum  A new chewing gum from Japan can
freshen your body as it freshens your breath,
according to a post on www.dailycandy.com. Pop a
stick of the gum into your mouth, and in about an
hour, your body should start emitting a fragrant
aroma. The scents, due to aroma chemicals such as
geraniol and linalool, are released from the skin
after being consumed with the gum. Fuwarinka gum
is available through www.compactimpact.com and
comes in three flavors fresh citrus, fruity
rose, and rose menthol.
44
Caterpillar makes its own bug repellant   Look
closely at that caterpillar chomping on your
cabbage plants. The drops of oily fluid on the
tips of the hairs running down its body contain a
family of compounds that repel ants and perhaps
other insects as well. That homegrown insect
repellant may help explain how the European
cabbage butterfly has spread so widely throughout
North America, Australia, and elsewhere. Chemist
Jerrold Meinwald and chemical ecologist Thomas
Eisner of Cornell University and their coworkers
observed ants that contact the caterpillars back
away and clean themselves. The researchers found
that the fluid consists largely of a series of
unsaturated lipids derived from
11-hydroxylinolenic acid, which they call
mayolenes. The mixture is dominated by compounds
containing hexadecanoyl and octadecanoyl groups.
45
Contributed anonymously is the following packing
tip from the March American Way, American
Airlines in-flight magazine Medication,
glasses, contacts I make sure they are packed
and one other salt. Remember high school
science? Salt is a protein, and proteins get out
proteins. So that coffee, blood, or ink stain
that happened right before a big meeting is
easily removed with a touch of water and salt.
46
Cat food chemistry   Jan N. Zonjee of Zaandam,
the Nederlands, writes that he was puzzled
recently by a mailing-list mention of taurine, an
amino acid that cats cannot synthesize for
themselves. Zonjee sought further data on the
Internet. He found a Web page that spoke of
buying taurine supplements to be used in
preparing cat food at home. It explained in part
that most taurine supplements are labeled
L-taurine. However, there is no difference
between taurine and L-taurine. The L of
L-taurine stands for levo, which means that the
groups at the lowest numbered asymmetric carbon
atom are placed at the lefta description of the
configuration of the molecular structure of
taurine. In other words All taurine is
L-taurinethe L is simply bonus
information. Says Zonjee, Bonus information?
Bogus information, surely. Taurine, he says, is
aminoethanesulfonic acid and has no chance of
being chiral.
47
Asparagus revelation 200 years ago
Asparagus, white or green, boiled or steamed, is
a tasty and nutritionally valuable vegetable. It
has few calories, no fat, and is a good source of
folic acid, a vitamin of the B complex that is
needed for nucleic acid synthesis. Lack of the
vitamin causes anemia. The vegetable has also
proven its value in another way - in the history
of science. Two hundred years ago, French
pharmacists Louis Nicolas Vauquelin (1763-1829)
and Pierre-Jean Robiquet (1780-1840) reported the
crystallization of the nonessential amino acid
asparagine from asparagus juice (Ann. Chim. 1806,
57, 88). It was the first amino acid to be
discovered in plants.
48
FDA approves new sweetener   Nutrasweet Co. has
received FDA approval for neotame, a new
nonnutritive sweetener that is structurally
similar to the firms Nutrasweet aspartame
product. Neotame is about 10,000 times sweeter
than sugar and approximately 20 to 30 times
sweeter than aspartame. Neotame is a white,
water-soluble, crystalline powder that is heat
stable and can be used as a table-top sweetener
or in cooking. FDA says the product has
negligible if any calories. In determining that
neotame is safe, the agency reviewed more than
100 animal and human studies, including some that
checked for cancer-causing, reproductive, and
neurological effects.
49
Peptide puts female rats in the mood
Researchers first noticed that PT-141, a cyclic
heptapeptide that mimics the action of
a-melanocyte-stimulating hormone (a-MSH), causes
erections in men. But James G. Pfaus of Concordia
University wondered whether the neuropeptide also
affects females. He and his team observed that
female rats on PT-141 initiate sex more by
hopping, darting, and enticing males to chase
them. This is the first time that a melanocortin
receptor has been linked to sexual desire, Pfaus
says. Unlike other erectile enhancers such as
Viagra, which relaxes vascular smooth-muscle
cells and increases blood flow to the penis,
PT-141 targets receptors in the brain. The
finding could lead to a new drug for women, who
currently have no pill for sexual disorders.