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Dokter_C
by Christina Dokter

Oddly enough, it was in a grassy field in Maine that a new class of antibiotic drug was discovered. Teixobactin was found by a team of scientists from Northeastern University, Massachusetts. Led by Kim Lewis, the Director of the Antimic Discovery Centre, the team found the antibiotic in a screen of soil bacteria using a new electronic technology, iChip. Tests of teixobactin against staphylococcus aureus (which cause “staph infections”) showed the compound to be very effective in killing this species of bacterium. Teixobactin is also said to treat infections caused by enterocooci and Mycobacterium tuberculosis.

This finding is significant not only as a new class of antibiotic, but also because there is now a perspective transformation about how scientists view inevitable bacterial resistance development in our society. The new method of using iChips allows scientists to tap into uncultured bacteria rather than creating synthetic antibiotics. This is welcome news, since more than 700,000 people die globally of antibiotic resistant infections annually.

Read more about it in:

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Flipping the Switch on Scleroderma [MSU Today, April 4, 2014]

Image

Dr. Richard Neubig

http://phmtox.msu.edu/news/2014-04/2014-04-04_Scleroderma.htm

“Scleroderma is a rare and often fatal disease, causing the thickening of tissue, that currently lacks a cure and any effective treatments. A group of researchers, including a Michigan State University professor, is looking to change that.”

Hollenberg

Dr. Steven Brody, Ethel Brody, Dr. Paul Hollenberg & Dr. J.R. Haywood

Hollenberg Awarded 2011 Theodore M. Brody Lectureship

Paul F. Hollenberg, PhD, Professor and Chair of the Department of Pharmacology at the University of Michigan Medical School Ann Arbor, MI was awarded the 2011 Theodore M. Brody Lectureship on November 14, 2011.

The topic of his seminar was:

MECHANISM-BASED INACTIVATORS OF CYTOCHROME P450:PROBES OF STRUCTURE AND FUNCTION


Nancy Kanagy

Dr. Kenneth E. Moore & Dr. Nancy Kanagy

Nan Kanagy: 2011 Kenneth E. Moore Distinguished Alumna Awardee and Recipient of the “Golden Sovereign”

Nancy Kanagy, PhD, Professor, Dept of Physiology & Cell Biology

U of New Mexico Health Sciences Center – Albuquerque, NM was awarded the Kenneth E. Moore Distinguished Alumna Award on November 14, 2011.
Following her presentation, Dr. Gregory Fink presented the Golden Sovereign to Dr. Kanagy.

Erika SparkenbaughSparkenbaugh Earns PhD, Accepts Post-Doc Position at UNC

Congratulations to Erica Sparkenbaugh on completing the requirements for a PhD and the successful defense of her dissertation.

Dr. Sparkenbaugh conducted her PhD research in Dr. Robert Roth’s laboratory.  She will be moving to the University of North Carolina in Chapel Hill to start a postdoctoral fellowship in the McAllister Heart Institute.


by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

cnn image of nuclear reactor

 

There is tremendous interest in the potential risks of radiation exposure that might come from  the earthquake and tsunami damaged Fukushima Daiichi nuclear plant in Japan.

Last week I discussed the mechanisms responsible for protection of the thyroid gland provided by potassium iodide tablets.  I want to clarify a few points about that blog.

  • Firstly, I provide basic information about the pharmacology and toxicology of drugs.  I focus on stories that appear in the popular press and my goal is to provide a little scientific background to these stories.  I do not and will not make any recommendations about what drugs readers should or should not take.
  • Secondly, readers need to understand that potassium iodide tablets provide very specific protection against one type of radiation danger.    Potassium iodide will only protect the thyroid gland against radiation exposure that would occur if the thyroid gland absorbs radioactive iodine emitted from the damaged reactor.

There is a wide range of the types of radiation that might be emitted and potassium iodide tablets do not protect against most radioactive emissions.

Advairby James J. Galligan,  Ph.D., Associate  Chair,
Department of Pharmacology and  Toxicology

The outcomes of recent studies of the long-term effects of asthma treatment medications that contain a steroid and a long acting beta agonist (LABA) have led the Food and Drug Administration to develop new guidelines for the use of these combination products.

These guidelines and the rationale behind them have been reported in the New England Journal of Medicine.  These new guidelines have also been the subject of numerous stories in the popular press and have raised concerns for asthmatics and their families.

While there are several components to these new recommendations, the bottom line is that LABA drugs should be used only by patients whose asthma can not be controlled adequately by other medications and LABA drugs should only be used in conjunction with another asthma control medication such as an inhaled steroid.  The new recommendations are based on studies showing a small but statistically significant increase in the number of serious asthma complications, including death, in patients using LABA drugs alone or in combination with a steroid.

What is the pharmacological basis for the concerns discussed above?

First, we need to understand a little about asthma and control of airways.  The airways are composed partly of smooth muscle.  When the muscle contracts airway resistance increases and this makes breathing more difficult.  When the muscle relaxes, airway resistance decreases and it is easier to breathe.  Airway muscle is supplied by sympathetic nerves which release norepinephrine.  The adrenal gland is also part of the sympathetic nervous system and it releases epinephrine into the blood stream.  Norepinephrine and epinephrine act on beta adrenergic receptors in airway muscle to cause the muscle to relax.  The sympathetic nervous system becomes active during the “fight or flight response” which in the old days helped us to escape predators but now helps us to exercise more efficiently.  Increased sympathetic nerve activity relaxes airway muscle making it easier to suck in huge volumes of air while we run a marathon.

The LABA drugs mimic the effects of epinephrine and norepinephrine by relaxing airway muscle; they can do this for up to 12 hours after a single dose.  Asthma is an inflammatory disease in which the airways are chronically inflamed.  Chronic inflammation can cause the airway wall to become thicker and more rigid.  This causes an increase in airway resistance.  Inflamed airways are also hypersensitive and things like emotional stress or breathing cold air can cause the airways to constrict precipitating an asthma attack.  Corticosteroids are great drugs for suppressing inflammation and this is why inhaled corticosteroids are a frontline treatment for many asthma patients.

Why is the FDA concerned?

The LABA drugs used either alone or in combination products (Advair contains the steroid, fluticasone and the LABA, salmeterol) can hide inflammation-induced thickening of the airway wall.  The patient may not be aware that his or her asthma is actually getting worse.  Then, when the patient does experience an acute asthma attack it becomes a very severe episode that can require hospitalization.

The new recommendations support use of LABA containing medications during the time required for the patient to get their asthma under control.  Then the patient should reduce use of LABA drugs gradually to the point where they are only using an inhaled steroid to maintain control.  This will reduce the risk of a severe attack that results from the chronic but undetectable inflammatory changes that can occur in many asthma patients.

Dr. Mark Roth

Dr. Mark Roth

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

You may have seen a recent news article about near death experiences on CNN.  Associated with this report was a story about the potential life saving effects of the supposedly toxic gas, hydrogen sulfide (H2S).  This is the gas that gives rotten eggs their characteristic smell and it was long thought that H2S was not only foul smelling but a deadly gas.  However, the CNN story goes on to discuss the work of Dr. Mark Roth who is studying the potentially protective and life saving effects of H2S.

Dr. Roth has shown in laboratory animals that H2S may protect cells and tissues against the toxic effects of ischemia (low oxygen supply to tissues and cells).  Ischemica occurs during a heart attack or stroke which block blood flow to the heart or brain respectively.  H2S may protect cells against the dangerous chemical reactions that occur in cells when their oxygen supply is reduced.

Hydrogen Sulfide 3d

Hydrogen Sulfide 3d

This is an interesting story as it highlights a potential function of one of the so-called gasotransmitters that are synthesized in cells of animals and humans.  These gasotransmitters include nitric oxide (NO) (not to be confused with nitrous oxide, “Laughing gas”), carbon monoxide (CO) (yes, the carbon monoxide that is the toxic component of automobile exhaust and the carbon monoxide detected by your in home carbon monoxide detector) and H2S.

NO is produced by the enzyme nitric oxide synthase and NO is produced in the nervous system, in blood vessels and by immune cells.  NO functions as a neurotransmitter in the brain and in the gastrointestinal tract.  NO also relaxes blood vessels to increase blood flow to tissues and it is released by immune cells as part of their defense mechanism against invading bacteria and viruses.

CO is produced by the enzyme heme oxygenase (HO) and CO is also a signaling molecule in the brain, the gastrointestinal tract and in blood vessels.  H2S is produced by three different enzymes: cystathionine-b-synthase (CBS), cystathionine-g-lyase (CGL), and 3-mercaptopyruvate sulfurtransferase (3MST).  H2S is also a signaling molecule in the brain, gut and blood vessels.  H2S is an antioxidant that reduces levels of the dangerous oxygen radicals that are paradoxically produced during ischemia and particularly during reperfusion of tissues when the blood supply is restored.  The oxygen radicals activate apoptosis (the programmed cell death mechanism) that is responsible for the permanent tissue injury that occurs during ischemia and subsequent reperfusion.  H2S may act as an endogenous anti-oxidant but, as Dr. Roth’s work has shown, exogenous H2S may also be a good anti-oxidant.

This story also points out the importance of basic research.  No one would have predicted that the foul smelling and toxic rotten egg gas would have the potential to be a life saving treatment.  However, basic laboratory science revealed the complexity of the H2S system and how its activation could protect tissues against ischemic injury.  The emerging H2S story is another example of how new drugs or other treatments for human disease can come from the most unlikely sources.

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