The Mystery Molecule Page: 2010

 December

A monoclonal antibody against this molecule will probably be approved by the FDA this month as the first major new treatment for systemic lupus erythematosus. Can you guess what it is?

Molecule of the Month December 2010

BAFF or BLyS
New B cells leave the bone marrow and, after further maturation, become follicular B cells in lymph nodes and spleen. Only about 10% of the new B cells become follicular B cells, however, and it is assumed that those that die do so because they may be auto-reactive B cells which have escaped central tolerance in the bone marrow but do not escape peripheral tolerance mechanisms. The nurturing of new B cells requires a number of factors, including a cytokine called B cell Activation Factor of the TNF (tumor necrosis factor) family (BAFF), or B Lymphocyte Stimulator (BLyS). Inactivating this factor may help prevent autoreactive B cells from maturing in patients with autoimmune disorders such as lupus. An FDA panel recently recommended approval for a monoclonal antibody against this cytokine (belimumab), but the final decision has been postponed until March 2011.


   

November

An AACC webinar this month will deal with biological variation and this commonly measured hormone is notorious for having significant diurnal variation. Can you guess what it is?

Mystery Molecule of the Month November 2010

Cortisol
Cortisol has many metabolic effects but, overall, its production appears to represent an adaptation to stress. Mammals have developed an internal rhythm for cortisol production: levels rise as we awaken, preparing us for the stress of the new day; levels fall as the day wanes, preparing us for sleep. This rhythm is influenced by sunlight, which activates production of pro-opiomelanocortin (POMC), the precursor of adrenocorticotropin (ACTH) in the anterior pituitary, which regulates production and secretion of cortisol by the adrenal gland. Although it was once common to draw cortisol levels at 8am (assuming that the patient had a conventional diurnal rhythm), most experts recommend a 24-hour urine collection to determine whether or not cortisol is elevated. Also, salivary cortisol, obtained by the patient at bedtime, is an excellent marker of the loss of the normal pattern of cortisol secretion seen in Cushing’s syndrome.


 

October

In an unusual (and controversial) move last month, drug regulators in both the U.S. and Europe acted to limit the distribution of this molecule. Can you guess what it is?

Mystery Molecule of the Month October 2010

Rosiglitazone (Avandia ©)
Oral hypoglycemic drugs can be divided into two major classes: secretagogues and non-secretagogues. The former all work by stimulating insulin production by the islet cells. The latter have a variety of effects but the majority work by decreasing insulin resistance. Biguanides such as metformin enhance glucose uptake by muscle and adipose tissue; thiazolidinediones also enhance uptake by the liver. One thiazolidinedione (troglitazone or Rezulin ©) has already been withdrawn from the market because of liver toxicity. Rosiglitazone has been shown to increase the risk of heart attacks. The recent severe restriction of the drug’s use by the FDA has been cited as evidence that the agency is taking a harder line on drug safety issues.


  

September

“Ex-Lax” (a non-prescription laxative) has been available since 1907 but the company that manufactures it recently replaced phenolphthalein, the original active ingredient, with this molecule. Can you guess what it is?

Mystery Molecule of the Month September

Senna glycoside
Anthraquinone derivatives and their glycosides from the seeds of cerain species of the genus Senna, a large group of tropical flowering plants, have been used as purgatives in herbal medicine for centuries. When Max Kiss originally developed a non-prescription laxative in New York in 1906, he used a combination of phenolphthalein and chocolate but the active ingredient is now senna. The market for digestive aids is enormous, and laxative sales alone reach almost $2 billion a year.

 


   

August

Many versions of this molecule (depending on the R-group) will be combining with skin proteins and putting a damper on camping trips this month. Can you guess what it is? 

August 2010 Mystery Molecule of the Month

Urushiol
Poison ivy and its relatives, including poison oak and sumac, produce an oil containing this compound, which combines with skin proteins and initiates a contact dermatitis in susceptible people (approximately 85% of the general population). A recent study suggests that poison ivy is becoming hardier (and making more urushiol) as a result of increased amounts of carbon dioxide in the atmosphere. We hope you had an enjoyable (and poison ivy-free) summer.

 


 

 

July

This molecule will be discussed during the presentation of the Wallace H. Coulter Lectureship plenary, which will open the 2010 AACC annual meeting in Anaheim this month. Can you guess what it is? 

July 2010 Mystery Molecule of the Month

Beta-amyloid protein
Dr. John Trojanowski described progress in the identification of biomarkers for Alzheimer’s disease which may make early intervention (and delay in the onset of clinical symptoms) feasible. Two proteins in the cerebrospinal fluid (CSF) are directly linked to the two characteristic lesions found in the brains of Alzheimer’s patients. One is tau, whose elevation in CSF is associated with neurofibrillary tangles. The other is beta-amyloid protein, which decreases in the CSF as neuritic plaques form. Beta-amyloid protein appears to be the most useful marker of early neurodegeneration.


 

June 

This molecule is the cause of both the explosion of the Deepwater Horizon oil rig in the gulf of Mexico and the failure of BP’s initial “top hat” solution to the subsequent oil leak. Can you guess what it is?

June 2010 Mystery Molecule of the Month


Methane hydrate
This is called a "clathrate" because the gas molecule (methane) in encased in a cage of water molecules. The gulf area is known to contain large quantities of methane hydrate deposits, which are markedly compressed in the ocean bed. Rapid expansion of this gas probably destroyed the oil rig, and methane ice formation probably caused the initial capture device to clog shut. Ironically, if this form of methane could be harvested, it could be a major new source of energy.

 


 


May

This molecule, the first beta-blocker drug, was discovered by Dr. James Black (a Scottish pharmacologist who died recently) and the discovery earned him a Nobel prize. Can you guess what it is? 

May 2010 Mystery Molecule of the Month

Propanolol
In the late 1950s, Dr. Black was interested in the theory that there were two different types of adrenergic receptors: alpha and beta. He was trying to find an alternative to nitrates, at the time the only type of drug used to treat angina. He thought that a drug which decreased the heart’s requirement for oxygen would be effective. Propranol was the first “beta-blocker”, marketed as Inderal, which revolutionized cardiology. In the 1970s, he applied a similar approach to the problem of gastric acid secretion and developed an inhibitor to a second type of histamine receptor (cimetidine, marketed as Tagamet).

 



April

This molecule, and its new role in the diagnosis of diabetes, will be the focus of Dr. Larry Broussard’s discussion at our April local section meeting. Can you guess what it is?

 

Hemoglobin A1c
When a glucose molecule bumps into a free amino group (like the one on the terminal valine of the hemoglobin b chain), it forms an unstable aldimine which slowly rearranges into a stable ketoamine. This rearrangement turns glucose into fructose, so the resulting ketoamine is fructosamine. The amount of fructosamine formation in the red blood cell producing hemoglobin A1c is a reflection of the mean blood glucose over the preceding few weeks. A level of 8% or less is considered “good” glycemic control. The American Diabetes Association has recently recommended using hemoglobin A1c as a screening test for diabetes, instead of plasma glucose, with a diagnostic cut-off of 6.5%.


 
 


March

This is not a shamrock but it became a lucky charm to Howard Lotsof, who died recently, and he spent his life promoting its use as a cure for heroin addiction. Can you guess what it is? 

Ibogaine
This extract from a plant found primarily in Gabon (where it is used in puberty initiation rites) almost immediately cured teenaged Lotsof of his heroin addiction. He campaigned all of his life to have this drug accepted by the addiction treatment establishment, but to no avail. There have been no controlled studies, and the substance remains banned in the U.S. 



February

Dr. Catherine Hammett-Stabler, AACC’s new president, will discuss this molecule (and other narcotic analgesics) during her presentation at this month’s Northern California section meeting. Can you guess what it is?

 

Oxycodone
Dr. Hammett-Stabler’s review of pain management included the use and abuse of narcotic analgesics like oxycodone. There has been an increase in abuse of oxycodone in the last decade and its atypical structure (it differs from other opiates because it has a ketone group) presents some interesting testing issues. To see some pictures from our January Awards Dinner, visit the “Awards” section of our page.



January

This molecule was in the wrong place at the wrong time on Christmas Day and is now the focus of intense scrutiny. Can you guess what it is?

 

Pentaerythritol tetranitrate (PETN)
80 g of this explosive, commonly used in blasting caps or detonating devices, was found sewn into the charred underwear worn by Abdul Farouk Umar Abdulmutallab on-board a Northwest Airlines flight over Detroit. He had tried to ignite it but, happily, although it would have caused a blast powerful enough to tear a large hole in the plane’s fuselage, it is very difficult to detonate. Unhappily, it is a powder and would be difficult to detect using routine airport screening procedures. This incident has prompted authorities to consider expanding screening techniques, including the addition of whole body scanning.

 

 

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