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Special Features
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Everyone Needs to Know
the Food Pyramid
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Nutritional Approaches
Hypothyroidism and thyroid hormone resistance are under-diagnosed
conditions that affect millions of Americans and significantly
contribute to the risk of cardiovascular disease and cancer.
The reason for under-diagnosis is twofold: first patients
believe that their symptoms are a normal part of aging and
second, physicians who take the time to investigate the
thyroid are misled into believing that if the TSH and other
lab values are normal, then function of thyroid hormones
is normal. Physicians are further persuaded by advertising
campaigns that Synthroid is the best treatment of low thyroid
when in fact it is probably the least effective method of
treatment. This paper will discuss the physiology of thyroid
hormones, diagnosis of hypothyroidism and thyroid resistance,
and the drug, nutritional and lifestyle strategies that
may be employed to improve function.
What are the
thyroid hormones and how are they produced?
The thyroid gland is composed of bundles of follicles enclosed
in fibrous capsules. The follicles secrete into the capsules
which store a colloid (suspension) of thyroid hormones and
their constituents such as thyroglobulin. Ribosomes in the
epithelial cells of the follicle walls secrete the carbohydrate-protein
compound called thyroglobulin. This compound is then packaged
in the golgi apparatus of the cells and secreted into the
colloid. The thyroid hormones actually form extracellularly
in the colloid rather than in the cells of the gland, making
thyroid hormone production unique among the endocrine glands.
The microvilli of the follicular cells produces an enzyme
called human thyroid peroxidase. This enzyme oxidises iodide
molecules trapped in the colloid into iodine (the active
form of the iodide molecule). This reaction produces peroxide
radicals which must be neutralized by antioxidants. The
iodine then combines with the amino acid Tyrosine to form
mono-iodotyrosine or T1. Then two of these molecules combine
to form di-iodotyrosine, T2. The peroxidase enzyme then
couples a T1 to T2 to form T3 or combines two molecules
of T2 to from T4. T3 and T4 are the thyroid hormones with
biological activity.
How is the
production of thyroid hormones stimulated?
When serum levels of iodine drop, the hypothalmus secretes
thyroid releasing hormone (TRH) from nerve endings in the
medial eminence of the hypothalmus. Another from of stimulation
that encourages the hypothalmus to produce TRH is prolonged
exposure to cold.
TRH in turn stimulates the anterior pituitary to produce
and release thyroid stimulating hormone or TSH. The anterior
pituitary cells that produce TSH are called thyrotrophs.
Thyrotrophs are the same cell type that produces human growth
hormone (HGH). TRH stimulates the production of TSH by promoting
the activity of phospholipase C. This enzyme catalyzes the
hydrolysis of phosphatidyl-inositol 4,5-bisphosphate to
insositol 1,4,5-bisphosphate and 1,2-diacylglycerol. The
1,2-diacylglycerol activates intracellular protein kinase
C which in turn stimulates the production of TSH. TSH in
turn stimulates the thyroid gland to produce and release
T3 and T4.
Calcium is a cofactor in the activation of TSH. In the thyroid
gland, TSH binds to TSH receptors and activates adenylate
cyclase enzyme. In the presence of magnesium, the activated
enzyme induces conversion of ATP to cyclic AMP. Cyclic AMP
activates the production of T3 and T4. There is a7-34% diurnal
variation in release of T4, with the peak at 12:00 noon
and the low at 2:00 AM.
How is the
production of thyroid hormones regulated?
Over-production of thyroid hormones is prevented by a negative
feedback loop. The greater the amount of circulating T3
and T4, the more inhibition of the hypothalmus and anterior
pituitary. Thyroid hormones directly suppress the production
of TRH in the hypothalmus. Thyroid hormones also increase
hypothalamic production of somatostatin, a hormone that
suppresses the pituitary's production of TSH and human growth
hormone (GH). Thyroid hormones also reduce the number of
TRH receptor sites on the somatotroph cells of the anterior
It should be noted that the major feedback loop for thyroid
hormone control is between the anterior pituitary and the
thyroid, the hypothalmus plays a smaller role in adjusting
the amount of thyroid hormone production and release. It
is also important to note that inactive isoforms of thyroid
hormones and even serum iodine can have a suppressive effect
on thyroid hormone production. Interactions with other hormones
will be discussed later.
How do thyroid
hormones get to the cells?
In order for the thyroid hormones to travel through the
blood to reach the cells, a transport protein is needed.
The three transport proteins are thyroxine-blinding globulin,
albumin and transthyretin (thyroxin-binding prealbumin).
All these transport proteins are produced by the liver,
though transthyretin is also produced in the choroid plexus
and thus is the main thyroxine-binding protein in the brain
and spinal cord. In the rest of the body, transthyretin
carries about 10% of the hormone while albumin binds around
15-20% and thyroxine-binding globulin carries about 70%
of the thyroid hormones. Protein malnutrition, alcoholism
and liver disease can impair the production of these carrier
proteins. T3 binds more weakly (is more easily released
into cells) than T4.
How does thyroid
hormone get into the cells?
Thyroid hormones are thought to easily penetrate cell membranes
however, some researchers believe that uptake may be regulated
by changes in the receptor-transporter interaction. The
interaction, "could be analogous to dimerisation of tyrosine
kinases after ligand binding" .
How does T4
become metabolically active in the cell?
The active form of thyroid hormone is T3 but the thyroid
gland releases 14 times more T4 than T3. Thus in the cell,
the T4 must be converted to T3 by type l 5"-deiodinase,
a selenium-dependent enzyme. (Selenium deficiency in rats
decreased enzyme activity by 90%). This enzyme is completely
inhibited by the drug propylthiourcil. Type ll 5"-deiodinase
is most active in the anterior pituitary, the central nervous
system, placenta and brown (high mitochondrial content)
fat. The drug propylthiourcil does not inhibit the type
ll enzyme.
T4 can also be converted to reverse T3 (rT3) by the enzyme,
5" deiodinase (especially type l 5' deiodinase in the liver).
Reverse T3 is an inactive form of the molecule. The production
of rT3 is thought to be a way the body prevents the accumulation
of excess T3. Both T3 and rT3 are further reduced to T2
(two iodine molecules), T1 (a single iodine molecule) and
T0 (thyronine without any iodine). The half-life of T3 is
one day while the half-life of T4 is about a week. The released
iodine and thyronine return to the thyroid gland for re-assembly
into T4 and T3.
How do the
thyroid hormones work inside the cell to stimulate metabolism?
Thyroid hormone (T3) increases transcription of beta-adrenergic
receptors and decreases transcriptions of alpha-adrenergic
receptors on the cell membrane. Beta-adrenergic receptors
bind with catacholamines such as norepinephrine which increase
metabolism. When catacholamines bind with alpha-adrenergic
receptors metabolism is reduced. By increasing B-adrenergic
receptors, T3 stimulates increased glycolysis and glycogenolysis,
thus increasing ATP production. In short, T3 encourages
the cell to convert fat and glucose into energy.
Thyroid hormone is an insulin antagonist. It stimulates
lipid turnover, free fatty acid release and cholesterol
synthesis. Thyroid maintains calcium mobilization and is
necessary for the contractility of myosin filaments in the
muscles. It is necessary for CNS, skeletal and sexual maturation.
Thyroid hormone is needed for protein synthesis, including
the apoenzymes. Thus T3 deficiency leads to a wide variety
of symptoms associated with reduced enzyme activity.
What is thyroid
Thyroid resistance, also called peripheral cellular resistance,
is the inability of the cell to accept and utilize circulating
thyroid hormone. This is similar to the plight of the NIDDM
patient. Circulating levels of the hormones are normal and
yet deficiency signs and symptoms abound. The mechanism
of action in most congenital cases of peripheral thyroid
resistance is an alteration in the c-erbAB gene. Mutations
in this gene can lead to as much as a 97% reduction in binding
of T3 to the nuclear receptor sites where transcription
of beta-adrenergic receptors occurs.
Resistance may also occur in the form of elevated cortisol.
High levels of cortisol can inhibit conversion of T4 to
T3 and promote conversion of T4 to r-T3 (the inactive form).
Dioxins and PCB's can also bind to transthyretin and presumably
to nuclear receptor for T3, thus competitively inhibiting
T3 binding. Other toxins that are known in animal models
to produce decreased serum levels of T4 and increased rT3
include chlorinated paraffins, polychlorinated biphenyl,
hexachlorobenzene, 3-methylcholanthrene, 3,3',4,4'-tetrachlorobiphenyl,
2,3,7,8-tetrachloro-p-dioxin and clofibrate. Drugs that
reduce T3 and increase rT3 include; dexamethasone, propylthiourcil,
iopanic acid (radiographic contrast agent), amiodarone,
propranalol. Down-regulation of T3 receptors also occurs
in animals under conditions of prolonged fasting or illness,
presumably to prevent catabolic wasting during periods of
caloric deficit. A similar post-receptor effector mechanism
defect is found in the ob/ob experimental mouse, leading
to ob/ob mouse obesity.
Symptoms of
low thyroid
What kinds of complaints characterize an under-active thyroid
system? Low energy and fatigue or tiredness, especially
in the morning. Difficulty losing weight, a sensation of
coldness--especially of the hands and feet, depression,
slowed thinking and reaction times, headaches, swelling
of the face or fluid retention in general, dry coarse skin,
brittle nails, chronic constipation, menstrual problems-such
as PMS and menstrual irregularities including heavy periods,
fertility problems, stiffness of joints, muscular cramps,
shortness of breath on exertion and chest pain are some
of the symptoms that can be seen in people with under-active
thyroid systems.
Other disorders associated with hypothyroidism include headaches,
migraines, sinus infections, post-nasal drip, visual disturbances,
frequent respiratory infections, difficulty swallowing,
heart palpitations, indigestion, gas, flatulence, constipation,
diarrhea, frequent bladder infections, infertility, reduced
libido and sleep disturbances, including the person requiring
12 or more hours of sleep at times. Other conditions include
intolerance to cold and/or heat, poor circulation, Raynaud's
Syndrome, which involves the hands and feet turning white
in response to cold, allergies, asthma, heart problems,
benign and malignant tumors, cystic breasts and ovaries,
fibroids, dry skin, acne, fluid retention, loss of memory,
depression, mood swings, fears, and joint and muscle pain.
What are the
lab tests for thyroid function?
The standard tests of thyroid function are serum levels
of TSH, total T4, Free T4, T3, T3 uptake, Free T3, the T4
to T3 ratio (also known as "T7"), anti-peroxidase and anti-microsomal
antibodies. Most physicians order a T4 as part of a general
metabolic panel (if they have any interest in the thyroid
at all). Physicians monitoring response to thyroid medication
generally watch the TSH as an indicator to direct the dosage
of Synthroid (T4) or other hormone replacements. Older tests
like protein-bound iodine and basal metabolic rate are rarely
used today. Another rare test, the TSH stimulation test
challenges the pituitary with an injection of TRH. A lack
of response indicates pituitary hypofunction or hypothalamus/pituitary
hypofunction. If this test is positive, imaging such at
CT and MRI are required along with other neurological tests
to look for anatomical lesions of the brain, pituitary and
hypothalmus. Uses for the tests are listed below:
A high TSH and low T4 and T3 indicate thyroid gland disease.
High T4 to T3 ratio (T7) or a high r-T3 (another rare test)
are suggestive of peripheral cellular resistance as these
levels indicate a decreased conversion of T4 to T3. Decreased
conversion may also be due to selenium deficiency or mercury
toxicity. If this ratio is high in conjunction with a high
serum or 24 hour urine cortisol, this may indicate cortisol-induced
decrease of T4 to T3 conversion.
Free (unbound) T4 is perhaps the best early indicator of
High free T3 is the best early indicator of hyperthyroidism.
T3 uptake and total T4 levels rise or fall together with
hyper or hypothyroidism. If the levels diverge, the cause
is more likely to be due to abnormalities in transport binding
High T4 and low T3 uptake indicates excess thyroid binding
Low T4 and high T3 uptake indicates low thyroid binding
R-T3 is abnormal in starvation, cirrhosis, insulin-dependent
diabetes and conditions of elevated cortisol such as Cushing's
FTI is calculated by multiplying T3 uptake by total T4.
This is used as a measure of Free T4.
The anti-peroxidase and anti-microsomal antibodies indicate
auto-immune diseases such as Grave's or Hashimoto's. Since
these conditions are associated with hyperthyroidism, I
will not discuss them here other than to point out that
following a hyperthyroid episode, these enzymes inhibit
the production of thyroxine. They also bind with cells of
the adrenals, pancreas and parietal cells of the stomach.
What other
tests can be used?
The most important single test for thyroid function is basal
temperature. The reason for this is that thyroid hormone
increases the conversion of ATP to ADP to power all the
metabolic functions of the cell. In that conversion, 50%
of the energy is released as heat. That heat is needed to
maintain bodily functions by maintaining the proper temperature
range for enzymatic activities necessary for life. Body
temperature is a good measure of basal metabolic rate and
is cheaper and simpler to perform than measuring the rate
of conversion of oxygen to carbon dioxide, which is the
"gold standard" measure of metabolic activity. Basal temperature
is taken by the patient in his or her own bed upon awakening
and before leaving the bed. A basal thermometer is retained
in the axilla and the results are charted in tenths of degrees
Fahrenheit. Daily measurement also provides many data points
by which to assess the effectiveness of therapy.
According to Broda Barnes, MD , if the average temperature
is below 97.8 Fahrenheit, then the diagnosis of a low functioning
thyroid system is likely. An average temperature between
97.8 and 98.2 is considered normal. An average temperature
above 98.2 is considered high and might reflect an infection
or a hyperthyroid condition. At least three days of measurement
are necessary for an average. The basal temperature in menstruating
women is most accurately measured on the 1st, 2nd, 3rd or
4th day of menses(preferably beginning on the 2nd day).
Males, pre-pubertal girls, and post-menopausal or non-menstruating
women may take basal temperatures any day of the month.
Women taking progesterone should not take the drug the day
before and the days when the basal temperatures are taken.
Other tests include Achilles heel reflex time, pulse rate
and reaction times. Physical signs such as dry skin and
hair, loss of the lateral third of the eyebrow may be observed
and a symptom survey can be used to measure thyroid associated
symptoms. Inability to lose weight, high cholesterol, lethargy,
fibromyalgia and sensitivity to cold are common signs and
symptoms. Myxedema appears in the later stages though mild
sub-dermal fat and water retention may be an early indicator
of thyroid hormone dysfunction (it may also indicate excess
steroid hormones such as progesterone).
What other
hormones interact with thyroid function?
Cortisol suppresses TSH production by reducing the sensitivity
of anterior pituitary thyrotrophs to T3. Cortisol also can
inhibit the conversion of T4 to T3 and promote the conversion
of T4 to reverse-T3, which is biologically inactive. Cortisol
clearance from the blood is decreased in hypothyroid patients.
Exogenous thyroid hormones may exacerbate adrenal insufficiency
by increasing metabolic demand. This can be tested with
the ACTH stimulation test. If ACTH (adrenal corticotropic
hormone) fails to stimulate the adrenals to make more cortisol,
then the adrenals are fatigued and would need support in
order to keep up with he effects of thyroid medication.
Estrogen, corticosteroids and prednisone decrease serum
levels of thyroid binding proteins. Exogenous estrogen (birth
control pills) also lower T3 uptake.
Thyroid hormones regulate dopamine synthesis by controlling
the concentration of it's precursor, DOPA. Thus hypothryoidism
results in low levels of dopamine. Dopamine is the main
neural mediator of pleasure.
strategies for hypothyroidism and thyroid resistance syndromes.
While the primary treatment of these conditions is T3 (Cytomel
or Armour), there are nutrition and lifestyle approaches
that may also be helpful.
Iodine and
Tyrosine � the biggest factors The two most important
nutrient deficiencies associated with hypothyroidism are
iodine and the amino acid Tyrosine. In this country, iodine
deficiency is rare as iodine is routinely added to salt
and the American diet is generally high in salt. In undeveloped
countries where iodine is deficient in the soil and little
fish and sea vegetables are consumed, iodine is a major
cause of goiter and a form of physical and mental retardation
known as Cretinism. Some 800,000,000 people worldwide suffer
from iodine deficiency and goiter. The RDA for iodine is
150 mcg per day for adults age 11 and above, 175 mcg per
day in pregnancy and 200 mcg during lactation. Lab tests
for iodine include plasma iodine (by neutron activation
analysis and urinary iodine. Hair trace mineral analysis
may also be used to screen for iodine deficiency. Excess
iodine may cause inhibition of TRH and TSH however. The
dietary intake of iodine in the United States is estimated
to be over 600 . Levels in excess of that amount are not
Tyrosine is the core of the thyroid hormone molecule. A
molecule of thyroglobulin contains 134 tyrosines, although
only a handful of these are actually used to synthesize
T4 and T3. Deficient intake, digestion or metabolism of
tyrosine may be a cause of hypothyroidism. Tyrosine is a
non-essential amino acid in that it can be made from phenylalanine.
However, some people have an enzyme deficiency and thus
have difficulty in converting phenylalanine to tyrosine.
Supplemental tyrosine may be taken in 500-1000 mg doses
Mercury and
Mercury toxicity can block the conversion of T4 to T3. Similarly
Selenium deficiency will also prevent the conversion of
T4 to T3. Selenium is a chelator of mercury and can be used
with dimercaptosuccinic acid to remove mercury toxicity
from the body.
Zinc supplementation re-established normal thyroid function
in hypothyroid disabled patients treated with anti-convulsants.
In a study, 9 of 13 patients with low free T3 and normal
T4 had mild to moderate zinc deficiency. After oral supplementation
with zinc sulfate (4-6 mg/kg body weight for 12 months),
levels of serum free T3 and T3 normalized, serum rT3 decreased
and TRH induced TSH reaction normalized. Since copper exerts
an antagonistic role, high copper may inhibit thyroid hormone
activity. A study of fourteen pre-adolescent hypothyroid
patients and a similar number of controls for serum zinc
levels revealed zinc levels were significantly lower in
the hypothyroid children before supplementation with thyroxine.
The authors suggest that there is an association with zinc
deficiency and thyroid function. A study of twelve hyperthyroid
and seven hypothyroid patients relative to zinc tolerance
found that high levels of zinc excretion were observed in
hyperthyroid cases and zinc deficiency was observed in hypothyroid
patients leading the authors to conclude that zinc levels
were a marker of thyroid function. Zinc and thyroid hormone
levels both decline with age and may be related. Children's
with Down's syndrome have many symptoms in common with hypothyroidism
and are also commonly deficient in zinc, suggesting an association.
Protein and
liver disease
Protein deficiency, starvation, cirrhosis or other liver
disease can reduce the amount of transport proteins available
to carry the T4 to the cell. In the case of liver disease,
overall nutrition and specifically, glutathione may be helpful
in promoting normal liver function.
Krebs cycle
At the level of cellular utillization, CoEnzyme Q10,
magnesium and B vitamins may be helpful as they play
roles in the Krebs cycle. B vitamins might have more direct
roles as well. In animals, B12 deficiency is associated
with slight reduction of type I 5'-deiodinase activity and
with significant reduction in serum T3. In a study of fifty-two
patients under psychiatric care for B-vitamin deficiencies,
it was observed that in the female patients where there
was depression and a low thyroid index, there was also a
deficiency of vitamin B2.
On the other hand, extreme doses of niacin (mean 2.6 grams
daily for an average duration of 1.3 years) revealed significant
decreases in serum T4, T3 and TBG with no alterations in
free T4 and TSH levels. Similarly, lipoic acid taken with
T4 resulted in a 57% reduction in the expected rise in T3
values in just 9 days, suggesting that lipoic acid should
not be taken with exogenous T4. Vitamins C and E only improved
hepatic 5' �deiodinization in conditions of increased lipid
peroxidation due to heavy metal toxicity.
Foods to avoid
Thiocyanate glucosides, substances found in vegetables from
the cabbage (brassica) family, have an antagonistic effect
on the binding of iodine in the thyroid. Persons with hypothryoidism
would do well to limit consumption of raw brussel sprouts,
cabbage, kale, broccoli and cauliflower. Cooking negates
this effect. Soy isoflavones also appear to exert a negative
effect on thyroid hormone activity. Animals fed soy protein
experienced a decline in T4, free T4 and T3 while experiencing
an increase in r-T3. In one study, 37 healthy adults consumed
30 grams of soybeans for 1-3 months. They experienced significantly
increased TSH levels and hypometabolic symptoms suggestive
of functional thyroid hormone deficiency (malaise, constipation,
sleepiness). Goiters appeared in half the subjects. Symptoms
disappeared after one month cessation of soy ingestion.
Dietary restriction
vs. vegetarianism
Caloric restriction should be avoided as this can reduce
metabolic rate up to 20% within 14 days even while exercising.
Decreases in T3, fT3, and increases in rT3 have been found
in a low carbohydrate, 800 Kcal per day diet. On the other
hand, a vegetarian diet can increase the resting metabolic
rate by 11%
Smoking has harmful effects on the thyroid. A study evaluating
one hundred thirty-five female hypothyroid patients and
a similar number of controls relative to cigarette smoking
observed a statistically significant relationship between
smoking and increased levels of hypothyroidism. The authors
conclude that smoking has both a goitrogenic effect and
other basic thyroid dysfunction influences.
Excessive alcohol consumption may be harmful to hypothyroid
patients. Low T3 and T4 levels are found in alcoholic cirrhosis
patients and animals exposed to ethanol have impaired hepatic
5'-deiodiniation, meaning that their liver's ability to
convert T4 to T3 is impaired.
helpful in the short term
Hypothyroidism causes an increase in three inhibitory molecules,
alpha adrenergic receptors, phosphodiesterase and G1 proteins
(the latter increases cellular sensitivity to adenosine
and adenosine receptor binding). Phosphodiesterase inactivates
cAMP. Adenosine activates an inhibitory GTP-binding protein
(G1) that also decreases cAMP formation. I have always advocated
avoidance of caffeine, especially in the form of coffee
however, caffeine in moderate doses inhibits these potent
enzymes phosphodiesterase and adenosine, which are both
metabolic inhibitors. Caffeine, theophylline and theobromine
are also adenosine receptor antagonists. Caffeine has a
half-life of 5.2 hours. It is a central nervous system stimulant
and thus for most people must be avoided before sleep. It
can also exacerbate osteoporosis and fibrocystic breast
disease. In large doses, tolerance develops and various
other disorder may develop, ranging from arrythmia to a
form of mania known as caffeineism. I recommend taking caffeine
in the form of green tea, and only in a dose that does not
overly stimulate the individual. When thyroid hormone levels
have been normalized, the dose of caffeine can be reduced.
Stress in the form of high cortisol can block the conversion
of T4 to T3, and in fact can promote the conversion of T4
to the inactive r-T3. Efforts must be made to get stress
under control. Many modalities such as Tai Chi, Yoga, meditation,
cognitive therapy, etc. can be employed to reduce the response
to stress. Deep breathing is one of the simplest ways to
change to a "rest and digest" metabolic state.
Sleep-deprivation produces elevations of T4, fT4, T3 and
rT3. The long-term implications of this are not clear but
it appears that the thyroid is responding to sleep-deprivation
as a stressful event.
Exercise creates a metabolic demand and is thus an essential
part of the treatment of hypothyroidism. Numerous studies
link both aerobic and anaerobic exercise with increases
in metabolism ranging from 6 to 11% Aerobic fitness, as
measured by VO2 Max has the strongest association with resting
metabolism. Hypothyroid patients must begin an exercise
program with care as stressful exercise (running as opposed
to walking for instance) can induce the release of catacholamines
such as epinephrine and norepinephrine. Hypothyroid patients
have increased alpha-adrenergic receptors and decreased
beta-adrenergic receptors. These hormones would bind to
the alpha-adrenergic receptors in the cell membranes, causing
a decrease in the cellular metabolism rather than the increase
needed to adapt to vigorous exercise. Moderation in all
We should all be aware of this common, under-diagnosed condition
and utilize basal temperature as a standard part of our
examination. While the primary treatment must be thyroid
hormone (a prescription item), we can provide considerable
support by eliminating adverse influences and normalizing
micronutrient status.
© 2000 DrWells.net All Rights Reserved


text:
Second City Comedy Improv
When Thursday October 18, 2012 @ 8:00 PM (1738 days ago)
Where JMU's Wilson Hall
Duration 1 hour
CAC is sponsoring a select number of tickets to go see Chicago's Second City comedy improv troupe at JMU. Tickets are only $5 with your EMU ID. You may purchase only 1 ticket per ID. General admission in JMU's Wilson Auditorium. You can purchase your ticket from Student Life starting Monday, October 8.
Event Web-site: http://info.jmu.edu/upb/promotion/the-second-city/
Intended Audience General Public

subset: commoncrawl


text:
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Great communication and quick service from start to finish - had MOT done - new cambelt, new water pump and new coolant bottle as my old one had cracked the day before. Very highly recommended and will be definitely use the garage for my servicing and MOT needs. Thanks team :-)
yes, He is exceptional.
Brilliant service from this garage, highly recommended. Replaced oxygen sensor and MOT
Yes, very good job. No issues, will use MC again.
Very good service all done on time to agreed price. Vehicle collected and returned on time.
Great service, extremely accommodating, gave me a lot of his time for good, honest and detailed advice. Recommended all around.


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After surreptitiously 3D scanning a museum artifact with Google Glass Todd Blatt is now playing the devil's advocate by providing a 3D printed cap to cover the lens of Google Glass and ensure the privacy of those around the wearer.
The GlassKap Kickstarter campaign is a range of accessories for Google Glass to either give those around the wearer privacy, or make explicit that the glass is 'On Air' and may be recording or even streaming what the wearer is currently seeing.
Along with the GlassKap, the product range also includes a few less functional and more fun items such as a wearable planter, pencil holder and laser sight. Although this is a playful response to the privacy issues surrounding google glass, it is also indicative of what is possible with 3D printing, to embed smart devices into almost any 3D printed product. Glass is starting to become a recognizable form that may indicate that you are being filmed, but what if someone were to 3D print a new housing and place the tell-tale form behind a polaroid lens.
You can support the Kickstarter campaign for as little as $1 and for as little as $20 you can put a Kap on that Glass.


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Lamb Chops with Lavender Salt
Slideshow: More Amazing Lamb Recipes
- Servings: 4
- 1 tablespoon dried lavender flowers (see Note)
- Coarse sea salt
- 1 tablespoon olive oil
- 3 garlic cloves, halved
- Eight 4- to 5-ounce lamb rib chops (1 inch thick)
- Freshly ground pepper
How to make this recipe
In a spice grinder, pulse the lavender flowers until finely ground. Transfer the ground flowers to a small bowl and toss with 1 tablespoon of sea salt.
Heat the olive oil in a large skillet. Add the garlic and cook over moderately high heat until golden, about 2 minutes. Discard the garlic. Season the lamb chops with salt and pepper, add them to the skillet and cook until browned outside and medium rare within, about 5 minutes per side. Transfer the chops to plates and serve the lavender salt on the side.
Lavender flowers are available at www.deandeluca.com.
One Serving Calories 260 kcal, Total Fat 15.9 gm, Saturated Fat 5.0 gm, Protein 27 gm, Carbohydrates 0 gm.


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Konrad J. Banaszak and Theodore K. Greenman—Landfills in Marion County— A Revisit
K.C. Kuo and T.R. West—Compression Strength Testing of the Springfield Coal,Coal V, Pike County, Indiana
Alan C. Samuelson— Interpretation of Glacial Geology and Groundwater Problems in East-central Indiana Using Improved Compilations of Water Well Driller's Records
J.R. Sans and CD. Potter—Three-dimensional Patterns of Biotic Composition within the Cloudy Pass Batholith, Washington
William L. Wilson and Donald W. Ash—Geology and Geomorphic History of the Garrison Chapel Cave System, Monroe County, Indiana


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Click here for the article of the Wall Street Journal, April 9, 2009
Web sites such as Cramster aim to revolutionize the way students study, much the way that networking sites like Facebook have changed the way people socialize.
Course Hero, launched last year primarily for college students, already holds a library of more than two million course documents, including homework, class notes and graded essays, uploaded by students enrolled at 3,000 different colleges. Koofers (a nickname at Virginia Tech for old tests passed around at fraternities) allows students from about 25 state universities to submit posts about the difficulty of courses taught by different instructors at their schools. It also offers average semester grades from instructors. Enotes, geared mainly to high-school students, allows peers to form discussion groups and pose questions to experts -- usually teachers -- who are paid by the Web site.


text: My back has been bothering me for months. My ortho just ordered an MRI of my back and hip. The pain wraps around from my back to my groin, and is quite painful. I cannot run my vacuum. It is one thing that immediately tightens up my back. Any ideas? I have found that Soma and a nap brings a lot of relief. Sitting in one position for too long really aggravates whatever it is that is unhappy!


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The How-To Lounge: Buying a Bra that Fits!
According to Susan Nethero, an expert bra fitter, 85% of women in America wear the wrong size bra. Odds are, this means you. Are you still buying the same size bra you wore in college? Are you wearing bras you owned before your pregnancy? Is it time for you to go bra shopping? Hopefully I can help you make the best choices.
To see some helpful tips
- Get measured by a professional. Go to any department store's lingerie department (as you know, I'm a big fan of Nordies) and ask for a proper bra fitting
- The band (the part that goes around your back) of your bra provides 90% of the support, so make sure to measure your ribcage carefully. You can wear your clothing to take this measurement, but don't wear bulky clothes. It's better, really, to not wear any clothes at all. These ladies have seen it all; don't fret
- Make sure to secure the bra on the last hook (the loosest notch) when trying it on, because your bra will stretch with wear and you'll need the ability to tighten it. Make sure the band fits snugly, but not so that it creates a back roll
- Slip back on your shirt or blouse so you can be certain the bra looks and fits well under your clothing
- When determining your cup size, bend over at the waist and shimmy your way into the bra. This will evenly distribute your weight into cups
- If the band of your bra rides up your back, it's the wrong size. The straps of your bra should not slip from your shoulders or dig into them. Straps should be about 10% of the support; remember, 90% of the support comes from the band
While there's a time and a place for sexy lingerie, your everyday bra should be about comfort and support. If you're wearing a bra that's too small and you spill out of the cup, you could be causing a loss of firmness. Don't smash your breast tissue, ladies. If you're wearing a bra that you can't fill out, you could be causing stretchmarks on your breasts.
Happy shopping, and don't forget to bring along these tips. Good luck!


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ANADA 200-028 Evict® DS and Lassie® DS Liquid Wormer plus Vet's Own™ DS Canine Anthelmintic Suspension - supplemental approval (June 4, 1997)
Approval Date: June 4, 1997
Division of Carter-Wallace, Inc.
Half Acre Road
P.O. Box 1001
Cranbury, New Jersey 08512-0181
Generic Name:
pyrantel pamoate
Trade Name:
Evict® DS and Lassie® DS Liquid Wormer plus Vet's Own™ DS Canine Anthelmintic Suspension
Marketing Status:
Over the Counter (OTC)
Effect of Supplement:
Provides for a double strength pyrantel pamoate suspension.
Amount of Active Ingredients: Each mL contains 4.54 mg of pyrantel base as pyrantel pamoate
Route of Administration: Oral with or without food
Species: Canine (puppies and dogs)
Labeled Dosage/Indications for Use: To prevent reinfection of Toxacara canis in puppies and adult dogs and in lactating bitches after whelping. For removal of large roundworms (Toxacara canis and Toxacaris leonia) and hookworms (Ancylostoma caninum and Uncinaria stenocephala) in dogs and puppies.
Pharmacological Category: Anthelmintic
- Pioneer Product NENEX-2™, NADA 100-237, Pfizer Inc.
Effect of supplement: To provide for a double strength pyrantel pamoate suspension
Under the provisions of the Federal Food, Drug and Cosmetic Act, as amended by the Generic Animal Drug and Patent Term Restoration Act (53 FR 50460, December 15, 1988, First GADPTRA Policy Letter) an abbreviated new animal drug application (ANADA) may be submitted for a generic version of an approved new animal drug (pioneer product).
For certain dosage forms, the agency grants a waiver from conducting an in vivo bioequivalence study (55 FR 24645, June 18, 1990: fifth GADPTRA Policy Letter). In lieu of bioequivalence testing, the safety and efficacy of the generic product are based on the demonstrated chemical equivalence to the pioneer product.
Based upon the formulation characteristics of the generic product, Lambert-Kay, Division of Carter-Wallace, Inc. was granted a waiver from conducting an in vivo bioequivalence study with pyrantel double strength. The generic and pioneer products are suspensions with the same active and similar inactive ingredients.
Human Safety Relative to Food Consumption: Regarding consumption of drug residues in food, human safety data were not required for approval of this ANADA. The drug is to be labeled for use in dogs and puppies.
Human Safety Relative to Possession, Handling and Administration: Labeling contains adequate caution/warning statements
This is an Abbreviated New Animal Drug Application (ANADA) filed under Section 512(b)(2) of the Federal, Food, Drug and Cosmetic (FFD&C) Act.
Safety and effectiveness for this generic animal drug, pyrantel pamoate suspension, were established by demonstration of chemical equivalence to the pioneer product, Pfizer, Inc. Nemex-2™ (NADA 100-237).
This generic product and the pioneer product have identical labeling indications for use. The route and method of administration of the two drugs are identical. Both drugs are orally administered. The generic and pioneer products are both suspensions that contain the same active in the same concentration and similar inactive ingredients. Therefore, consistent with FDA policy implementing Section 512(b)(2) of the FFD&C Act, no additional safety, efficacy, or in vivo bioequivalency studies were necessary or required.
This ANADA satisfies the requirements of section 512 of the Act and demonstrates that pyrantel pamoate double strength oral suspension (EVICT® DS and LASSIE® DS Liquid Wormer plus VET'S OWN™ DS), when used under proposed conditions of use, are safe and effective for labeled indications.
Generic Labeling:
- 2 oz. bottle and carton
- 4 oz. bottle and carton
- 8 oz. bottle and carton
- 16 oz. bottle and package insert
- 2 oz. bottle and carton
- 4 oz. bottle, carton and package insert
- 2 oz. bottle and carton
- 4 oz. bottle and carton
- 8 oz. bottle
- 16 oz. bottle and package insert
Pioneer Labeling:
- Nemex-2™: 2 oz. bottle, carton and package Insert
- D-Worm™ 120: package Insert
Copies of applicable labels may be obtained by writing to the:
Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855


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Table of contentsChapter 1: WithholdingChapter 1: WithholdingFilling out your W-4See all stories »Chapter 2: Forms and filingChapter 2: Forms and filingFiling your returnSee all stories »Chapter 3: DeductionsChapter 3: DeductionsDeductions: cutting your tax billSee all stories »Chapter 4: CreditsChapter 4: CreditsTax credits: Cut your tax billSee all stories »Chapter 5: Life events and taxesChapter 5: Life events and taxesYour changing tax lifeSee all stories »Chapter 6: Closing detailsChapter 6: Closing detailsTaking care of tax detailsSee all stories »
Bartering your services won't help, either. The value of noncash items must be determined and then counted as income. Putting your money in a foreign bank to earn interest won't cut your tax bill either. If it's in your name and you can get to it, it's considered income. Even that $50 bill you found at the bus stop counts.
And don't think for a minute you can get away with some underhanded ways to make a few extra bucks without paying up. The IRS says that embezzlement and swindling proceeds are taxable, too. The tax folks don't care if you steal it, as long as they get their piece of the action.
Bankrate wants to hear from you and encourages thoughtful and constructive comments. We ask that you stay focused on the story topic, respect other people's opinions, and avoid profanity, offensive statements, illegal contents and advertisement posts. Comments are not reviewed before they are posted. Bankrate reserves the right (but is not obligated) to edit or delete your comments. Please avoid posting private or confidential information, and also keep in mind that anything you post may be disclosed, published, transmitted or reused. We do not permit the inclusion of hyperlinks in comments and may remove any comment that includes a hyperlink.
By submitting a post, you agree to be bound by Bankrate's terms of use. Please refer to Bankrate's privacy policy for more information regarding Bankrate's privacy practices.


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Carroll reflects on difficult cut-down weekend - Sept. 2, 2013
Fullback Michael Robinson #26 of the Seattle Seahawks during the season opener against the Arizona Cardinals at the University of Phoenix Stadium on September 9, 2012 in Glendale, Arizona. The Cardinals defeated the Seahawks 20-16. (Photo by Christian Petersen/Getty Images)
by Curtis Crabtree
KJR reporter
Twitter: @Curtis_Crabtree
RENTON - Head coach Pete Carroll and general manager John Schneider have built a team full of quality depth across the board. The downside was it meant several quality players being let go over the weekend.
FB Michael Robinson, CB Antoine Winfield, DT Clinton McDonald and TE Sean McGrath were perhaps the four most surprising cuts during the purge from 75 players to 53.
Carroll said the moves weren't easy to make.
"It's been a very challenging weekend as we knew going in," Carroll said.
The decisions with Robinson and Winfield were perhaps the toughest to make. Robinson had developed into a team leader and Pro Bowl fullback in hist time with Seattle. Ultimately, his salary become problematic for the team and was the likely reason he was let go.
"We had a lot of tough decisions and Mike was one of them," Carroll said. "Mike had been with us for a long time. All these guys hurt us, in a sense, when they left because they had bought in and given us everything that they had and Mike was a very instrumental guy on this football team as we were coming along."
Carroll said FB Derrick Coleman played well enough to allow the Seahawks to take a bit of a chance with the release of Robinson.
"He just came through in a big way and sent a big message to us in special teams. Hes had a great camp in special teams. He's one of the core guys there," Carroll said.
"We know that he can carry the ball too if we need him to, he catches the ball very well, and he's learning the system as a fullback. He outlasted his competition to go into the opener as a starter. That's a big accomplishment for Derrick [Coleman] and we are really excited about him."
Winfield took less money to sign with Seattle because he wanted to chase a Super Bowl. Instead, the Seahawks were going to release him and he elected to retire. Carroll said Winfield did everything they hoped he would do and that he's still playing at a high level. However, Carroll said CB Walter Thurmond just had an outstanding training camp and essentially earned the job.
"As much as I love Antoine, I'm really excited for Walter to have come through like he did and we have all been waiting for him and he just needed to get healthy and he finally is and it showed," Carroll said.
One of the more curious decision was to part with McGrath.
McGrath and TE Luke Willson were the top two tight ends for nearly the entirety of training camp as TE Zach Miller remained on the physically unable to perform list. Seattle has regularly kept at least three tight ends on the roster but elected to go with just two and let McGrath go. McGrath was claimed off waivers by the Kansas City Chiefs.
Carroll said they have total faith in Miller and Willson and that T Michael Person can also work as an extra tight end at times. He played in Seattle's jumbo packages the last two weeks of the preseason.
Seattle made the decision to release fourth-round pick WR Chris Harper over the weekend and actually signed him back to the practice squad on Sunday. However, the San Francisco 49ers signed Harper to their active roster.
"We were fortunate to get him back on the practice squad, that's how you go about it and the gamble that you take, and they picked up a good football player," Carroll said.
"We were hoping that he would be with us and bring him along. But that's how it goes."
It was the only player Seattle lost to other teams. McGrath, DT Jaye Howard and CB Ron Parker were all claimed off waivers by the Chiefs. S Winston Guy was claimed by the Jacksonville Jaguars.


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Return to Top
Admissions · Advising · Catalog · Financial Aid · Registrar · Scholarships
Academic Prerequisites for Optometry School
There is only one college of optometry in the State of Texas, the University of Houston College of Optometry located in the city of Houston. For admission into the program, a baccalaureate degree is required.
The prerequisite academic courses are listed below.
|Biological Sciences
|8 hours General Biology
4 hours Microbiology
8 hours Human Anatomy and Physiology
3 hours Biochemistry
|8 hours General Chemistry
4 hours Organic Chemistry
|3 hours College Math
3 hours Calculus
3 hours Statistics & Research Design
|8 hours College Physics
|6 hours English Composition
6 hours English Literature
|3 hours General Psychology
Optometry Schools in Texas
For additional information on Optometry schools, see the Association of Schools and Colleges of Optometry.


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E.L.I—The Israel Association for Child Protection
The Jaffa Institute
The Jewish Women International, The Children's Home in Israel
Orr Shalom
Israel Women's Network
Israel National Council for the Child
Orr Shalom
View the agency's website
Homes for children, staffed by caring, competent people, change the lives of children far more constructively than large, impersonal institutions manage to do. Ten children reside in each home along with Orr Shalom house parents. "These are homes for the most neglected children in Israel and many of the most abused! Children ages 8-18 from all over Israel are brought to the Orr Shalom homes. One of their facilities is called Friendship House and it houses and treats adolescent juvenile delinquent boys whose difficulties are so severe that no other setting is appropriate for them."
"Orr Shalom's proven success has led to calls for it to expand the number of its facilities and programs. That takes funding! It takes help from us, from the souls who direct funds to Orr Shalom through Amcha For Tsedakah!"


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Estes-Park.com Blog
It's Time You Stopped!
A recent visitor to the Rock n' River Resort said, "I've been driving past your covered, wooden bridge on Hwy 36 for years, but never stopped in. I'm so glad I know this is here!"
Tucked into a canyon of shady cottonwood trees and the rushing sounds of the St Vrain River, Rock n' River Resort is an ideal spot to get away from it all! Located just 3.5 miles west of Lyons on the way up to Rocky Mountain National Park and the town of Estes Park, Rock n' River Resort is a convenient drive for folks coming from the Front Range. With 18 acres to explore, stocked trout ponds, a winery, and spa on site, you won't want to leave! But if you want to explore, just a short drive away you'll discover the many outdoor delights and activities of spectacular Rocky Mountain National Park.
Guests will enjoy the comfortable amenities of an authentic, yet updated western style resort. Accommodating up to 50 guests, the resort would be the perfect spot to host an intimate wedding or a family reunion. Imagine the joy of watching a young guest catching their first fish, while nearby adults enjoy a sampling of onsite Ciatano Winery's delightful wines, cheese, and smoked trout, as everyone takes in the stunning views of the canyon.
After a day of hiking, you can pamper yourself to one of the variety of treatments offered at La Bellezza Day Spa, or turn-in for a quiet evening in your comfortable king sized bed. All rooms are furnished with king sized beds, a convenient kitchen, and a stylish bathroom, and they even have a few family suites if you want to bring the kids. We can't wait to go!
If you want more information on booking a stay at Rock n' Resort, visit their website here . And for great planning tips on how to enjoy nearby Rocky Mountain National Park, be sure to visit www.RockyMountainNationalPark.com.
The Surprising Role of Lichen: How RMNP was Made
Perhaps one of the most under-appreciated lifeforms in Rocky Mountain National Park are the large variety of lichens growing on the rocks and trees. Not only are lichen colorful and an important food source for the park's beloved elk, but they actually played an important role in creating RMNP as we know it.
Lichen are an amazing combination of fungus and algae that take in nutrients from the air, as well as through photosynthesis. But it is the role lichens played approximately 16,000 years ago that we owe a little respect. At that time, the glaciers receded from the lower parts of the park. Lichens were some of the original colonizers on the newly exposed rocks. Over time, lichens' small threads (called hyphe) that attach them to their rocks grow into the smallest cracks in the rock. Gradually these cracks get larger and allow water to freeze and thaw thousands of times. This process is what eventually breaks the largest rocks into tiny pebbles. Breaking down rocks this way is what allows plants and tress to move into an area that was previously barren rock.
Even though lichens play a vital role in the ecosystem by creating soil and providing a hospitable environment for plants, and essential nutrients to many of the park's fauna, most people won't give them a second glance. Maybe next time you are out exploring Rocky Mountain National Park, you'll take a moment to appreciate the beauty and power of the humble lichen.
Blog post and photo provided by Jared Gricoskie of Yellow Wood Guiding. Find out how you can book your own guided tour of RMNP by visiting YWGuiding.com.


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- Prescription Drug Abuse Slideshow: Facts and Statistics
- OTC and Prescription Drug Abuse Slideshow Pictures
- Health Risks of Alcohol Abuse Slideshow Pictures
- Patient Comments: Cocaine and Crack Abuse - Personal Experience
- Find a local Psychiatrist in your town
- Cocaine and crack abuse facts
- What is cocaine? What is crack?
- How is cocaine abused?
- What are cocaine's effects on the body and the mind?
- What causes and prevents cocaine abuse and addiction?
- What are symptoms and signs of cocaine abuse and addiction?
- How do health-care professionals diagnose cocaine addiction?
- What is the treatment for cocaine and crack addiction?
- What are symptoms and signs of cocaine withdrawal?
- What are the long-term effects and the prognosis for cocaine and crack addiction?
- Where can people find more information about cocaine and crack abuse?
What causes and prevents cocaine abuse and addiction?
Like most other mental-health problems, cocaine-use disorder has no single cause, but there are biological, psychological, and social risk factors that can increase a person's risk of developing a chemical use disorder. The frequency that substance-use disorders occur within some families tends to be higher than can be explained by the addictive environment of the family. Therefore, most substance-abuse professionals recognize an inherited risk of drug addiction. This is particularly true for cocaine dependence.
Symptoms of mental illness that can be caused by cocaine-use disorder include mood disorders like depression, anxiety, or bipolar disorder, as well as personality disorders like antisocial personality disorder. Social risk factors for drug addiction include male gender, being 18 to 44 years of age, Native American heritage, single marital status, and lower socioeconomic status. Statistics by state indicate that people living in the West tend to be at higher risk for chemical-use disorder. Consistent with substance abuse in general, prevention of cocaine-use disorder is increased by circumstances like receiving adequate supervision, as well as clear indications from family members that cocaine use is not acceptable.


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MFS International New Discovery
Category: Foreign Small/Mid Growth
Fund Return for 2012: 18.81%
Category Return for 2012: 16.65%
Assets Under Management: $3.3 billion
Foreign equities have been a rough play this year thanks to the issues hampering Europe and Asia. Still, foreign small- and mid-cap companies have been able to grow, and thus have produced some nice winners.
Just look at MFS International New Discovery (MUTF:MIDCX). The fund has top notch portfolio managers — which include David Antonelli, Peter Fruzzetti, Jose Luis Garcia and Robert Lau — who scour the world looking for bargains, especially companies with strong moats and healthy cash flow prospects. The fund has a long-term approach, reflected in its low 44% turnover ratio.
MIDCX's top holdings include Bunzl (U.K.), Amadeus IT Holding SA (Spain) and Swedish Match.
You can avoid an initial sales charge through Discovery's C shares, but if you redeem your shares within the first year, you may be subject to a contingent deferred sales charge of 1%. Expenses are a hefty 2.17% on C shares, however. MIDCX requires a $1,000 minimum investment.
Tom Taulli runs the InvestorPlace blog IPOPlaybook, a site dedicated to the hottest news and rumors about initial public offerings. He also is the author of "All About Short Selling" and "All About Commodities." Follow him on Twitter at @ttaulli. As of this writing, he did not hold a position in any of the aforementioned securities.


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This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Metformin, an anti-diabetic drug, exerts cardioprotection against ischemia-reperfusion (IR) through the activation of AMPK. However, the molecular mechanisms underlying these beneficial effects remain elusive. In this study, we examined the role of PPARα in mediating cardioprotective effects of metformin on mitochondria. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to IR in the presence or absence of metformin and the PPARβ inhibitor, GW6471. IR reduced cardiac function and compromised the structural integrity of cardiac cells evidenced by increased LDH release from the hearts. In addition, IR induced mitochondrial dysfunction as evidenced by reduced respiration and increased mitochondrial permeability transition pore (PTP) opening. However, metformin-treated hearts demonstrated improved post-ischemic recovery of cardiac function and reduced cell death that were associated with increased state 3 respiration at complexes I and II (by 27% and 32%, respectively, both
Cardiac ischemia/reperfusion (IR) is associated with metabolic alterations including the generation of reactive oxygen species (ROS), calcium overload, ATP depletion, low myofibrillar activity, and cell death [
The protective effects of AMPK on mitochondria may be mediated through several downstream targets, one of which is peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1α (PGC-1α). Existing studies provide strong evidence that AMPK and a superfamily of transcriptional activators including PGC-1α and PPARα are key players of a cascade that coordinate energy metabolism in the heart [
In the current study, we examined the possible role of the AMPK/PPARα/mitochondria pathway in the cardioprotective effects of metformin during acute IR in rats. Our results demonstrated that PPARα is a critical signaling molecule that mediates AMPK-induced signaling to mitochondria and improves recovery of cardiac function after IR in the heart.
Male Sprague-Dawley rats weighing 250–275 g were purchased from Charles River (Wilmington, MA, USA). All experiments were performed according to protocols approved by the University Animal Care and Use Committee and conform to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).
To determine cardiac function, isolated rat hearts were perfused by the Langendorff mode as previously described [
To isolate mitochondria, the ventricles were cut, weighed and homogenized with a Polytron homogenizer in 5 mL of ice-cold sucrose buffer containing 300 mM sucrose, 10 mM Tris-HCl, and 2 mM EGTA; pH 7.4. The volume was made up to 40 mL with buffer containing 5 mg/mL BSA. Mitochondria were isolated from the homogenate by centrifugation at 2000× g for 2 min in a benchtop centrifuge to remove cell debris, followed by centrifugation of the supernatant at 10,000× g for 5 min to sediment the mitochondrial suspension. The pellet was then washed two times at 10,000× g for 5 min in 40 mL of BSA-free sucrose buffer. The final pellet was resuspended in 300 μL of sucrose buffer. The yield of mitochondria was 12.1 ± 0.9 mg of protein per mL. A 200-μL sample of the suspension was then used for measurement of mitochondrial respiration rates and PTP opening. A 100-μL sample was retained for assay of citrate synthase activity and protein expression.
Measurement of mitochondrial respiration was performed at 30 °C using a YSI Oxygraph (Yellow Springs, OH, USA) model 5300 equipped with a Clark-type oxygen electrode [
Swelling of de-energized mitochondria as an indicator of PTP opening in the presence or absence of Ca2+ was determined by monitoring the decrease in light scattering at 520 nm as described previously [
Protein concentration in homogenate and mitochondria was determined by the Bradford protein assay (Bio-Rad, Hercules, CA, USA). Equal amounts of homogenate or mitochondrial protein were resolved by SDS-PAGE, and transferred onto Amersham Hybond ECL nitrocellulose membranes (GE Healthcare Bio-Sciences Corp., Piscataway, NJ, USA). The membranes were immunoblotted with AMPK, P-AMPKα1 Thr172, voltage-dependent anion channel (VDAC), LKB1, P-LKB1Ser428 (Cell Signalling, Boston, MA, USA), cyclophilin D (CyP-D), adenine nucleotide translocase (ANT), PPARα (Santa Cruz Biotechnology, Santa Cruz, CA, USA), PGC-1α (Abcam, Cambridge, MA, USA) or actin (Sigma-Aldrich, St. Louis, MO, USA) antibodies followed by secondary antibodies. The signals were visualized using Thermo Scientific Pierce ECL Western Blotting Detection reagents (Thermo Scientific, Rockford, IL, USA) at the VersaDoc 3000 Gel Imaging System (Bio-Rad).
Protein samples were incubated with anti-PPARα antibodies (1 μg per 100 μg protein samples) overnight at 4 °C and the immunoprecipitates were harvested by protein A/G-agarose beads (Santa Cruz Biotechnology) for 3 h [
Data are presented as means ± SEM of 6–8 experiments per group. The statistical differences between groups were calculated by two-tailed Student's
First, we examined the cardioprotective effects of metformin on hearts subjected to IR in the presence or absence of the PPARα antagonist GW6471. IR exerted detrimental effects on cardiac performance. Hearts subjected to IR exhibited low LVDP values at reperfusion when compared to pre-ischemia (
Overall, the results of these experiments show that metformin attenuated cardiac dysfunctions associated with preserved structural integrity of cardiac cells and mitochondria during acute IR in rats. The cardioprotective action of metformin was prevented in the presence of the PPARα antagonist, GW6471.
In the next set of experiments, we examined whether the cardioprotective effects of metformin on mitochondria are mediated through PPARα. Mitochondria isolated from IR hearts with or without metformin and/or GW6471 treatment were used to determine respiration rates at complexes I, II and IV. Results demonstrated that basal respiration (state 2) of mitochondria at both complexes I and II was not affected in any of our experimental groups (not shown). IR markedly reduced state 3 respiration, and respiratory control index (RCI), which indicates a decrease in the efficiency of respiratory coupling and ATP synthesis. In metformin-treated hearts, state 3 respiration at complexes I and II was 31% and 51% greater (
Altogether, these experiments demonstrate that the beneficial effects of metformin on mitochondria respiration rates in hearts subjected to IR are mediated through PPARα.
The extent of mitochondrial PTP opening was determined by measuring Ca2+-induced light scattering of mitochondria isolated from hearts after Langendorff perfusion. In addition, a direct effect of metformin was determined
In the following groups of experiments, co-immunoprecipitation was performed to clarify whether PPARα interacts with the PTP components, VDAC, ANT and CyP-D. As shown in
In the next group of experiments we investigated the effects of metformin on protein levels of AMPK and PPARα. Homogenates were isolated from the IR hearts treated with metformin and/or GW6471 and then subjected to SDS-PAGE followed by immunoblotting. Results demonstrated that metformin increased phosphorylation of AMPK at Thr172 in the hearts subjected to IR (
Thus, the present study demonstrated that metformin improved recovery of cardiac contractility after acute ischemia in Langendorff-perfused rat hearts, and that the cardioprotective effects were associated with attenuation of mitochondrial dysfunction. Pharmacological inhibition of PPARα by GW6471 abrogated the beneficial effects of metformin on cardiac performance and mitochondrial function. Metformin is a biguanide drug that is broadly used in clinical practice to prevent hyperglycemia in patients with diabetes mellitus. In addition to its anti-hyperglycemic action, metformin also exerts cardioprotective effects and improves clinical outcomes during IR and heart failure [
Several mechanisms can be responsible for the AMPK/PPARα-mediated improvements of mitochondrial function in IR hearts. The main function of mitochondria to produce ATP from FFA in the heart is controlled, in part, at the level of expression of nuclear genes encoding enzymes that catalyze FAO. PPARα is the key transcriptional regulator of genes of FAO enzymes in the heart and its upregulation stimulates ATP synthesis [
Our study demonstrates that metformin exerts cardioprotection against acute IR by improving mitochondrial function through activation of AMPK and its downstream signalling molecule, PPARα. Most likely, the effects of the AMPK/PPARα pathway activation in mitochondria are not associated with direct interactions with the PTP complex. Further studies are required for understanding the precise molecular mechanisms underlying the cardioprotective effects of the AMPK/PPARα/mitochondria pathway against acute IR damages. This study emphasizes the role of metformin-induced activation of PPARα as a potential target for the development of new therapeutic strategies aimed at the prevention of IR-induced cardiac dysfunction.
The authors thank Miriam Castro for her invaluable technical assistance in performing of experiments. This work was supported by a grant of the University of Puerto Rico School of Medicine, and in part, by the grant 2G12-RR003051 from the National Center for Research Resources, National Institutes of Health. G. Barreto-Torres is the recipient of the Porter Physiology Predoctoral Fellowship from the American Physiological Society.
None declared.
Perfusion protocols for Langendorff heart preparation. Experimental groups: (1) IR, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; (2) IR+Met, hearts subjected to global ischemia followed by reperfusion in the presence of 2 mM metformin (Met); (3) IR+GW, hearts subjected to global ischemia followed by reperfusion in the presence of 0.30 μM GW6471 (GW); (4) IR+Met+GW, hearts subjected to global ischemia followed by reperfusion in the presence of 2 mM metformin and 0.30 μM GW6471.
The effects of metformin (Met) on post-ischemic recovery in hearts in the presence or absence of GW6471 (GW). (
Lactate dehydrogenase (LDH) activity in eluates from hearts collected during reperfusion (
Respiration rates of mitochondria isolated from the IR hearts treated with metformin (Met) in the presence or absence of GW6471 (GW). (
Ca2+-induced mitochondrial swelling as an indicator of PTP opening in the IR hearts treated
The effects of metformin (Met) on phosphorylation of AMPKα1 Thr172 (


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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9%
At the time of transition from the fetal to neonatal pattern of circulation, blood vessels in the neonatal pulmonary vasculature are acutely exposed to mechanical forces such as shear stress from the movement of circulating blood, intra-luminal stretch determined by pressure from heart propulsions, and extra-luminal stretch induced by respiratory cycles. Cyclic stretch (CS) alters intracellular signaling, leading to changes in vascular tone, often by the production of vasoactive molecules. Physiologic levels of cyclic stretch can also promote vascular remodeling by inhibiting apoptosis in the vascular endothelium and causing mitotic arrest of vascular smooth muscle cells. Recent reports suggest that pathologic levels of stretch increase production of reactive oxygen species (ROS)
Nitric oxide (NO), a well-studied vasodilator molecule in the pulmonary vasculature, is produced by nitric oxide synthase (NOS) by conversion of L-arginine to L-citrulline, and activates soluble guanylate cyclase (sGC) to increase levels of cyclic guanine monophosphate (cGMP), ultimately causing vasorelaxation. Three distinct isoforms of NOS have been identified: neuronal NOS (nNOS, NOS I), inducible NOS (iNOS, NOS II) and endothelial NOS (eNOS, NOS III). Past studies presumed eNOS to be the predominant source of NO production in the pulmonary vasculature; however, more recent studies suggest that iNOS is an important isoform in generating the NO-mediated fall in pulmonary vascular resistance during the transition of pulmonary circulation from fetal to neonatal life [
Recent studies from a lamb model of persistent pulmonary hypertension of the newborn (PPHN) suggest that pulmonary vascular sGC activity is diminished [
Previous studies have suggested that fetal and neonatal lambs with chronic intrauterine pulmonary hypertension exhibit increased ROS in their pulmonary arteries [
To determine if the stretch-induced ROS would directly impact sGC activity, we measured both oxidative stress and sGC activity in the presence of the antioxidant, rhSOD. rhSOD blocked stretch-induced cytosolic oxidative stress (
Previous studies in adult systemic SMC and in fetal and lamb resistance pulmonary arteries suggest that elevated ROS are associated with decreased sGC expression and activity [
We have previously demonstrated that lambs with chronic intrauterine pulmonary hypertension have increased iNOS expression, and others have previously shown mechanical stretch can induce iNOS expression and activity in bronchial or synovial cells [
The specific iNOS inhibitor, 1400 W, led to a 30% decrease in sGC activity in PASMC exposed to 24 h of cyclic stretch
The exposure of blood vessels to mechanical stress is thought to play an important role in vascular remodeling in both normal physiologic adaptation, such as the neonatal transition to ex-utero life, and in pathological conditions, such as hypertension, atherosclerosis and diabetes [
Vascular stretch has also been shown to stimulate the generation of ROS by activation of redox-sensitive signaling pathways [
The NO-sGC-cGMP signaling pathway has been implicated in many physiological processes including cell growth and proliferation and vascular homeostasis. sGC contains a prosthetic ferrous heme group that binds NO with very high affinity. When NO binds to the enzyme's heme moiety, a conformational change occurs, leading to a 200-fold increase in the enzyme's production of cGMP, which then acts as a second messenger to mediate vascular relaxation through the activation of a cGMP-specific protein kinase [
Thus, based on the ample evidence for increased ROS and decreased sGC activity in intact lambs with PPHN [
Since stretch-induced sGC activity was not dependent on ROS in our PASMC, we sought to determine what might be upstream of sGC. sGC expression and activity is well-known to be regulated by NO derived from eNOS [
Primary cultures of ovine PASMC from healthy sheep were isolated and grown to confluence and maintained in DMEM with glucose (Mediatech, Herndon, VA, USA), 10% fetal bovine serum (Hyclone, Logan, UT, USA), antibiotics and antimycotics (Mediatech) at 37 °C in 21% O2–5% CO2. All experiments were carried out using cells that were less than passage 8, and all experiments were performed with cells isolated from multiple different animals [
PASMC were cultured on Bioflex plates as described above. For transfection assay, 10 μL of an iNOS-specific siRNA (50 μM stock diluted in nuclease-free water, Invitrogen) or scrambled control (50 μM stock diluted in nuclease-free water, Invitrogen) was incubated with 17.5 μL Lipofectamine RNAimax reagent (10 μM stock diluted in nuclease-free water, Invitrogen) in 1.4 mL serum-free DMEM for 20 min at room temperature. Each well of cells received 200 μL of either the iNOS-specific siRNA-transfection mixture or the scrambled control and 500 μL serum-free DMEM such that the final concentration of siRNA or scrambled control was 100 nM; cells were incubated with this transfection mixture for 4–6 h. The cells were then incubated with complete DMEM, and 48 h after transfection, cells were changed to serum-free DMEM with antibiotics and antimycotics and subjected to either cyclic stretch or maintained in static conditions at 37 °C in 21% O2–5% CO2 for 24 h. PASMC were then harvested, and sGC activity and iNOS expression were measured as described below.
PASMC were infected with 100 PFU/cell of a cytosolic roGFP adenoviral construct. RoGFP is a previously characterized ratiometric fluorescent probe sensitive to cellular oxidative stress [
PASMC were harvested using 1× Mg-lysis buffer (Upstate, Charlottesville, VA, USA) along with protease inhibitor (Sigma) and phosphatase inhibitor (EMD Biosciences, San Diego, CA, USA) as previously described [
PASMC were harvested using 1× Mg-lysis buffer, cell extracts were sonicated, and protein concentration determined as described above. Total protein (40 μg) was used to perform Western blots as previously published [
PASMC steady state cGMP content was measured by enzyme linked immunoassay in duplicate using a commercially available kit (Cayman Chemical) as previously described [
PASMCs were harvested, and protein was prepared as described above. Free phosphate was removed from protein extracts by passing extracts over a Centri-Spin 10 column (Princeton Separations, Adelphia, NJ, USA). Protein concentration was determined using the Bradford method. Total protein (5 μg) was assayed for cGMP hydrolytic activity using a commercially available colorimetric cyclic nucleotide phosphodiesterase assay kit (Enzo, Farmingdale, NY, USA) with and without sildenafil (Sigma) as described previously [
PASMC were harvested for RNA utilizing the Aurum Total RNA Mini Kit (BioRad, Hercules, CA, USA), and RNA was quantified using the Quant-it RiboGreen assay (Molecular Probes/Invitrogen, Carlsbad, CA, USA). cDNA was prepared from total RNA utilizing the iScript cDNA Synthesis Kit (BioRad). Real-time PCR was performed using the iQ SYBR Green Supermix (BioRad) with the iCycler iQ real-time PCR detection system (BioRad) with 38 cycles of real-time data collection using 95 °C for 10 s and 60.5 °C for 45 s, followed by melt curve analysis to verify the presence of a single product. Primers were designed using commercially available software and are based on ovis aries iNOS mRNA accession number AF223942.1: forward 5′-TGAGAATGGCAGCTACTGGGTCAA and reverse 5′-TGGTGATGTCCAGGAAATGGGTGA. Relative iNOS amounts were normalized to β-actin expression using the ΔΔCT method [
All data are expressed as the mean ± SEM. Results were analyzed by student's
In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in fetal PASMC. The mechanism is not yet known, but does not appear to involve activation by ROS. The increase in sGC expression and activity may represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. This compensation may be lost over time with ongoing cyclic stretch and/or stretch-induced oxidative injury. Therefore, a better understanding of how to preserve sGC activity as well as a better understanding of the interplay between stretch-mediated oxidative injury and the iNOS-sGC pathway in PASMC could provide key insights into future avenues to treat infants with pulmonary hypertension.
This work was supported by the Northwestern University Flow Cytometry Facility and a Cancer Center Support Grant (NCI CA060553), as well as by NIH grants: HL104681 (M.R. Shah), HL035440 (P.T. Schumacker), HL054705 (R.H. Steinhorn), HL086715 (K.N. Farrow) and HL109478 (K.N. Farrow). The authors thank Keng Jin Lee for assistance in completing experiments for the revised manuscript.
The authors declare no conflict of interest.
Pulmonary artery smooth muscle cells (PASMCs) exposed to 24 h cyclic stretch have increased oxidative stress in the cytosol. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
Recombinant human superoxide dismutase (rhSOD) abrogates stretch-induced cytosolic oxidative stress but not soluble guanylate cyclase (sGC) activity in PASMC. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
PASMC exposed to 24 h cyclic stretch have increased sGC expression and activity. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
PASMC exposed to 24 h of cyclic stretch have increased inducible nitric oxide synthase (iNOS) mRNA and protein expression. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
An iNOS inhibitor, 1400 W, decreased sGC activity in PASMC exposed to 24 h of cyclic stretch. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
An iNOS-specific siRNA decreased sGC activity in PASMC exposed to 24 h of cyclic stretch. Ovine PASMC were isolated from healthy lambs and exposed to cyclic stretch
Proposed model for effects of cyclic stretch on ROS and sGC in PASMC. Cyclic stretch increases both cytosolic ROS and sGC expression and activity. The stretch-induced increase in ROS is blocked by rhSOD. The stretch-induced increase in sGC activity is attenuated by 1400 W, a selective iNOS inhibitor, and iNOS-specific siRNA but not rhSOD, suggesting that the stretch-induced changes in sGC are dependent on iNOS and independent of cytosolic ROS.


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- Analia's Achievements
- Analia's Poems
Poet Laureate
Fan Favorite
Poet's Friend
Published Poet
Poetry Promoter
The Master Badge represents the total amount of points that you have earned from participating in the poetry.com community
I'm a sophomore in High school and I love writing. All my poems are raw, I don't edit or revise. I hope you enjoy :D


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Which celebrity is due for a comeback?
Boy howdy, you guys really miss the '80s. Most e-mail
I received last week took me back to a time when Rob
Stone oozed sex appeal and Christopher Cross reigned supreme as a
lite-rockin' mack daddy. My own pick also gained fame during the Velcro Age:
I think it's high time we saw singer Siouxsie Sioux back in action, don't
Some of your comeback wishes:
"John Schneider. Who could resist Bo Duke in tight jeans?"
Meredith Prince, Lowell, Mass.
"I would like to see Rerun from What's Happening!! make
a comeback. Is he still alive?"
Steve Freeto, Elkhart, Ind.
"I would love to see Dana Delany back in a television series. I
was/am a big fan of China Beach I have all the shows on tape,
for cryin' out loud. Since Marg Helgenberger has made a comeback on television
with C.S.I., I think it's high time that they give Dana her series."
Pamela Acree
"Jerry Mathers should return as a child molester on Judging
Rob LaHood, Washington, D.C.
"Urkel. Was he a genius?"
Patric Beno
"Frankly, I'd like to see both Jimmy and Kristy McNichol
pop up on the small screen again. Maybe they could do an Afterschool Special
or Lifetime Moment of Truth movie in which they play adult siblings and parents
of drug-addicted or sex-addicted youngsters. Joining the cast as the drug/grief
counselor could be Philip McKeon (aka "Tommy" from Alice). And
while we're at it, why not have Beth Howland ("Vera" from Alice)
step in as Kristy and Jimmy's mom? Shall I continue?"
Patrick Fogerty
"Not sure if he should or would, but I would love to see Isaac the
Bartender pop up on TV again!"
Barrie J. Mand, Fort Lauderdale
"Lee Majors."
Anthony Rossi
"The Wacky '70s Celebrity ... You know who I mean, people
with no real talent but were somehow famous anyway. The concept needs to be
revived. Alec Baldwin's impersonation of Charles Nelson Reilly on Saturday
Night Live last month made me long for the days of the "goofballs" who were
good to cast as game show participants and Love Boat/Fantasy Island
fodder. Reilly, Phyllis Diller, Charo, Rip Taylor, Rich
Little, the ventriloquist from Soap, Paul Williams, Ruth
Buzzi, Artie Johnson, etc."
Mike Quinlan
"How about a little Webster reunion episode? My Fridays have never
been complete since the Papadapolis family left us in 1987. I am willing to
bet that Emmanuel Lewis looks the same, Katherine (Susan Clark)
still has the terribly dyed red hair, and George (Alex Karras) is about
512 pounds."
Edward A. Hoffman, Chicago
"What about Lisa Bonet? She could be in a bizarre hemp sitcom where
she's a pierced and tattooed bohemian in love with a budding rocker."
Phil Launer, Portland, Ore.
"After the disappointing string of Problem Child movies, I'd almost
given up hope on John Ritter. But Sling Blade made a believer
out of me. Who knew this pratfalling comedian could be so convincing in a dramatic
role? I was surprised he didn't make a huge comeback after that film, but I
am still hoping. He certainly has the talent and experience."
Nicole Bradshaw Jackson, Miss.
"Leonard Nimoy. Without eartips and with wrinkles and different
hair, he has many non-Spock character roles in the near future."
Don Evans
"Rick Astley. He had it all the looks, the voice, the style.
I LOVED him!"
Dawn Bailey, Las Vegas


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American Association of Railroad Superintendents
Overview / Responsibilities
Amec Foster Wheeler Environment & Infrastructure is currently seeking an experienced Geotechnical / Materials Technician to join our team in Sudbury, ON. This positon is will begin with a probationary period followed by the potential to move to regular part-time or fulltime based on performance and project needs.
As is characteristic of large corporations, it is impossible to quantify all job activities and expectations. While the request for an experienced position is technically focused, our expectations are that you become quickly familiar with Amec Foster Wheeler's core principles of providing high-caliber professional services in a fully integrated manner across our operating business units and divisions.
Work Location
Sudbury with travel throughout Northern Ontario
Key Responsibilities
You will work with an integrated team of professionals and undertake a variety of tasks that may include:
Skills / Qualifications
We are an equal opportunity employer that recognises the value of a diverse workforce. All suitably qualified applicants will receive consideration for employment on the basis of objective criteria and without regard to the following (which is a non-exhaustive list): race, colour, age, religion, gender, national origin, disability, sexual orientation, gender identity, protected veteran status, or other characteristics in accordance with the relevant governing laws.


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Israel-News Today
Week in Review
Court Bans Tal Law for Religious Exemptions from IDF (INN) ISRAEL NATIONAL NEWS) By Tzvi Ben Gedalyahu 02/22/12)
Source: http://www.israelnationalnews.com/News/News.aspx/153020#.T0SXhYeO2So
INN} ISRAEL NATIONAL NEWS Articles-Index-Top
Almost all political leaders have welcomed the High Court decision Tuesday night that the Tal Law for religious exemptions from the IDF is illegal.
The law was named after the Tal Committees suggestion, adopted in law in 2002, allowing young men to learn in yeshiva with a deferral from enlisting until the age of 22, when they can decide whether to serve in the army or continue to learn. Those who opted to go to work were obligated to four months of army duty or one year of civilian service.
The government admitted several years ago that the law did not achieve its aim of significantly increasing the enlistment of those who wanted to forego army service altogether in favor of learning in yeshiva.
The High Court ruled by a 6-3 vote that the law is unconstitutional because it violates the principle of equality. The justices said the law can remain on the books for the time being but cannot be extended when its time limit expires in several months.
There was no unified bloc of justices on either side of the decision. Among those in favor of striking down the law were outgoing court president Dorit Beinisch, a declared secular justice who has consistently ruled against Jewish outposts in Judea and Samaria, and Neil Hendel, a graduate of Yeshiva University and who is known to have national religious views.
Voting against declaring the Tal Law unconstitutional were Asher Dan Grunis, who will replace Beinisch next month as president and who is religious, and Edna Arbel, another secular justice who has not been favorable to a Jewish presence in Judea and Samaria.
The majority of justices concluded that the government failed to implement the law, creating a situation of inequality.
Justice Grunis wrote in his dissension that the judicial system has not done any better than the government to encourage the enlistment of hareidi religious Jews.
Prime Minister Binyamin Netanyahu, who has said he wanted to extend the law in altered form, said after the ruling that the government will present a new law within six months to lead to a more just share of the burden of military service among Israelis.
Leaders of almost all parties except for Shas and United Torah Judaism welcomed the ruling. Foreign Minister Avigdor Lieberman, heads of the Yisrael Beiteinu party, has made the elimination of the Tal Law a principle of his partys platform.
Kadima also praised the ruling. Party leader Tzipi Livni accused the government of "enslaving Israel future´s in favor of a minority.
Foreign Minister Avigdor Lieberman, chairman of senior coalition partner Yisrael Beiteinu, welcomed the ruling. Opposition from his party and the Independence faction to the laws extension led Netanyahu to back away last month from his plan to advance the law without change.
Defense Minister Ehud Barak, who was on the Tal committee that recommended the law, said that it has not met expectations and should be eliminated. (IsraelNationalNews © 2012 02/22/12)
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|Information for:
|Campus Communicators
Acclaimed writer and historian David McCullough discusses the critical role of history in education, life and citizenship at Auburn University on Oct. 15.
Two-time Pulitzer Prize-winning author and historian David McCullough shared his message about the role of history in education, life and citizenship with a crowd of more than 2,000 people at Auburn University on Tuesday.
"History is about life. It's not about boring textbooks. It shouldn't be taught with boring textbooks. It isn't just about dates and quotations from obscure treaties and the like; it's about people," McCullough said.
"History is human when in the course of human events – our great founding document begins, "When in the Course of human events," – and it shouldn't be understood or retaught, in my opinion, as it's all about politics and the military and social issues. Yes, a great deal of it is about politics and the military and social issues, but you can't leave out music or art, or finance or medicine, or money or love, or tragedy or evil, or opportunity or freedom or the path to the truth."
McCullough shared stories about Harry Truman and a series of letters between Truman and his sister Mary Jane. McCullough received his first Pulitzer in 1993 for "Truman," a biography of the 33rd president.
He also spoke of the critical role of books and reading in the lives of John Adams and Theodore Roosevelt and how Americans should appreciate the opportunities we have to study history.
"Leadership calls on, not just the reading of anything, but history," he said. "There's no better training facility, no better major, if you will, for leadership in any field than history. Why? First of all, it is about people, and any leader has to deal with people. It's about cause and effect. … Whatever we do, there are going to be consequences. Also, if you are a student of history, you learn to love history, you take history as part of the experience of being alive, which it is; why should we limit our time on earth, as it were, to our own rather brief biological span when we can be involved in the whole realm, experience, of the human being on earth all the way back as far as history goes? History also injects the realization that it isn't just behind us, it's right now and it's going to be tomorrow, and that we are going to be judged by history. … How will we measure up?"
"Today's lecture by David McCullough was riveting and inspiring," said Jay Lamar, director of special programs for the associate provost for undergraduate studies. "He touched on so many topics – what makes good teaching, libraries as the gateway to learning and how history informs leadership. He addressed the young people in the audience with advice that all of us can appreciate: 'follow your heart about what interests you,' he said, 'and stay curious.' One audience member said afterward, 'That is the kind of message that can change lives.'"
McCullough is a 2006 winner of the Presidential Medal of Freedom. His books also include the Pulitzer Prize-winning biography "John Adams," which was published in 2001 and is one of the most praised and widely read American biographies of all time. He has written histories of the Johnstown flood, the Panama Canal and the Brooklyn Bridge. His "1776," which covers a year in the life of George Washington and the American Revolution, is a classic.
"Mr. McCullough is a legend, of course," Lamar said, "but he was so warm and funny – though it was a large crowd, I think every one of us felt he was talking directly to us."
McCullough's talk was made possible by the support of Merchant Capital LLC of Montgomery and is sponsored by the Auburn University Office of the Provost and Office of Undergraduate Studies, in partnership with the Littleton-Franklin Lectures.
— By Carol Nelson, Office of Communications & Marketing
Last Updated: Oct. 15, 2013


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Choppy weather, leaky tents, and delicious looking spiced meats on the pristine shores of Lake Superior. When you resign yourself to the whim of the Great Lake, luck and misfortune are your tour guides. These boys certainly seem to have the grit to endure, but what surprises lay in the waiting for them on their epic journey? Will they see fingers of lighting scratch across the skies? Will they run short of food as the fish stop biting? Will the bears smell the menstruation? Will the "superior dream" transform without warning into the North Shore nightmare? Stay tuned friends. See if you can guess the next unfortunate event that befalls these Northern Water Warriors. Best of luck on your journey, gentlemen.
Learn more at www.superiordream.com.


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- {{matchup.date.fullday}}{{matchup.date.month + ' ' + matchup.date.day}}
NCAAB Basketball - Preview
The fans at Kirby Center will be treated to a game between the Yale Bulldogs and the Lafayette Leopards when they take their seats on Tuesday.
In their last action, Yale was an 81-54 loser on the road against Mercer.
Lafayette was a 91-88 loser in its last match on the road against NJIT.
Team record: 2-3 SU, 1-1 ATS
is 7-18 SU in its last 25 games on the road
When playing on Tuesday are 7-3
Before playing Hartford are 6-4
After a loss are 7-3
Team record: 0-4 SU, 0-0 ATS
Current streak: lost 4 straight games.
Next up:
Yale at Hartford, Saturday, November 30
Lafayette home to Pennsylvania, Saturday, November 30


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Oakley sunglasses - brand new frame
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Oakley sunglasses - brand new frame
For Sale:
Older model Oakley Straight Jacket sunglasses. Earpiece cracked about 2 years ago, finally sent back to Oakley a couple months ago, they replaced the entire frame (entire frame & 2 earpieces are BRAND NEW). Only the lenses are original. They cost me about $135 a few years ago...paid extra for the irridium coated lenses. Lenses have a couple very very minor marks from use, not cracks or deep scratches. I have a nice pair of polarized Bolle's that I wear now and these Oakleys have just been sitting around for years. I have NOT worn them since frame was replaced.
Make me an offer. Should only cost a few bucks to ship. I can email more pics if you want to provide an email address.
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