Zark's

Suffered a Stomach Bug this Year?

Transmission electron micrograph of the genus Norovirus, and the family Caliciviridae. They are a group of related, single-stranded RNA, nonenveloped viruses that cause acute gastroenteritis in humans.
Image Credit: CDC/ Charles D. Humphrey

Nasty, contagious norovirus is 'everywhere' now explains that one in fifteen Americans suffered an unpleasant stomach bug in the last year.  Although we describe most politely as the stomach flu, it is really a norovirus infection. 

Wikipedia reminds us that a norovirus is an RNA virus, which incidentally is responsible for 90 percent of the world's nonbacterial suffering of gastroenteritis.  Noroviruses are easily transmitted from person to person and only one to ten virus particles are necessary to infect the victim.  The infection begins in the small intestine and within one to two days, the stomach flu symptoms are present for up to 60 hours. 

In case you are fuzzy about RNA viruses, they can have one or two RNA strands. These are different from the larger class of viruses, those that have DNA as genetic material.  Some of the strains that result in gastroenteritis include the Norwalk, Hawaii, and Snow Mountain.  They have carbohydrate binding receptors which allows them to attach to food molecules.  Researchers are working on vaccines, but nothing is available yet.  Also, because the virus mutates rapidly, annual boosters will be required.

The CDC has a norovirus website with some tips on avoiding the infection and what to expect if you catch it.  As you probably know from experience, you don't obtain an immunity to the virus.  Because of the vomiting and diarrhea, dehydration can be a medical problem. 

Their suggestions on preventing the spread of norovirus: a) wash your hands (interestingly, the CDC says that alcohol-based hand sanitizers are not as good as washing with soap and water) b) proper hygiene in the kitchen, and don't prepare food if you are infected, c) clean and disinfect contaminated surfaces, and d) wash laundry throroughly.

Trial Drug MRK003 Shows Promise Against Pancreatic Cancer

Human tumor cells from the pancreas stained with an immunocytochemical stain with methyl green in the background and magnified to 400x.
Image Credit: Dr. Lance Liotta Laboratory, National Cancer Institute

The pancreas functions as both a digestive and endrocrine system.  It produces digestive enzymes that assists absorption of nutrients and digestion in the small intestine.  For the endocrine system, it produces several hormones including insulin, and glucagon. 

The National Cancer Institute estimates 43,920 new cases of pancreatic cancer in the United States for 2012.  Sadly, it also estimates 37,390 deaths.  The risk factors are: smoking (the largest risk factor), diabetes, family history, previous episode(s) of pancreatitis, and obesity. 

Pancreatic cancer: Trial drug MRK003 shows promise explains chemotherapy agent gemcitabine combined with MRK003 has been successful in killing cancer cells in mice.  They are currently testing about 60 patients in a clinical trial. 

Notch receptors are transmembrane receptors that help determine whether a cell continues reproducing, living, or even self-destructs.  There are four members of the Notch family that have been implicated with cancer.  Many cancers appear to depend upon Notch signaling survive.  MRK-003 is a γ-secretase inhibitor that can suppress this signaling.

Let's hope we have found a powerful weapon against this deadly cancer!

 

FDA Scrutinizes QNEXA

QNEXA
Image Credit: Vivus

In their advisory committee briefing, pharmaceutical company Vivus describes QNEXA as a one-a-day diet pill that contains immediate release phentermine hydrochloride (PHEN) and extended release topiramate.  The concept is to combine two types of weight control therapy - decreased hunger and increased satiety.  From a previous evaluation, the FDA expressed concern about potential birth defects and cardiovascular events.  After evaluation, the company agreed to remove the applicability of the drug for women of child bearing age.  (Basically any risk is unacceptable to that group is unacceptable.)

Vivus explains it believes the benefits of the new diet pill substantially outweigh the risks of obesity.  Their report explains the relative risk of diabetes increases 42 times in men and 93 times when the body mass index increases from normal to obese.  Their argument is that health care providers need another weapon in controlling obesity and QNEXA should be approved to be included in possible therapies.

U.S. to Review Diet Treatment Once Rejected tells that although the pill was rejected in 2010, docs have been prescribing the two ingredients independently, achieving the same thing. Perhaps as much as 70 percent of docs treating obesity.  Draft Questions for the February 22, 2012 Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee give some hints on what the FDA is thinking.  They are concerned about cleft lip defects and cardiovascular impacts.  The panel of doctors will make a recommendation on whether the new diet pill should be approved and then the FDA will make a final determination in April.

If you are interested, The National Institutes of Healthy has chart to help you determine whether you fall into the Overweight or Obesity category.  They explain the primary cause is a lack of energy balance - you are consuming too many calories for the amount of calories your body is burning.  There are other factors - inactive life style, environment (work schedules, access to healthy food), genes and family history, and health conditions, among others.

Almost as Good as Starving

Red seedless grape, Flame Seedless
Image Credit: Scott Bauer, USDA

I have blogged previously about calorie restriction (not that I practice it).  Research has shown that reducing calorie intake slows the aging process in animals and some fungi. 

Wikipedia tells that reducing the calories consumed by rats can nearly double their lifespans.  It can also prevent aging diseases such as type 2 diabetes and heart disease.

Resveratrol is a complex molecule produced by several fruits and plants with some controversial claims appearing the literature, such as longevity increasing, cancer prevention, etc. 

One of the best sources of resveratrol is in the skin of red grapes, and despite some popular writing, red wine contains surprisingly little of the compound.  It has been synthesized, although the marketed nutritional supplement comes from Japanese knotweed.

Scientists find target for resveratrol tells that the molecule mimics calorie restriction.  Researchers have discovered that reservatrol activates the same biochemical pathways as a low-calorie diet, by inhibiting the production of PDE4, which raises the levels of cAMP.  This is a signal sent to the cells of the body indicating that blood sugar levels are low. 

In laboratory mice testing, rolipram, a compound similar to resveratrol which restricts PDE4, protected the mice from a high-fat diet.  (Otherwise they would have developed glucose intolerance, similar to type 2 diabetes.) 

Researchers believe this regimen has the potential of therapies in diabetes, Alzheimer's and other aging diseases.  They are planning clinical trials.

Mmm.  Can you imagine a film titled, "The Man Who Lived Too Long"?

 

 

Does a Cancer Drug Reverse Alzheimer's Disease?

Unhealthy protein and tangles result in isolated neurons
Image Credit: National Institute on Aging

We can’t wait: Administration announces new steps to fight Alzheimer’s disease tells that 5.1 million Americans suffer from Alzheimer's disease.  By 2050, that number could double.  To counter this looming crisis, the government is identifying $130M in additional funding for 2012 and 2013 for research on the disease.

Bexarotene is a skin cancer medicine sometimes also prescribed for lung cancer, breast cancer, and Kaposi's sarcoma. 

New Attack on Alzheimer's tells that researchers have discovered that bexarotene has the ability to melt away the protein and tangles for mice with Alzheimer's symptoms. 

It may seem strange that a skin cancer drug would be effective in melting protein, but similar to fighting fire with fire, a protein named ApoE (Apolipoprotein E) has a special property of dissolving amyloid-beta proteins, correlated with Alzheimer's disease.  Coincidentally, bexarotene has the ability to switch on the production of ApoE. 

Scientists at Case Western Reserve University have shown startling cognitive improvements in mice with amyloid protein plaque.  Prior to the treatment, they were completely unable to create a nest.  After treatment with bexarotene, they regain their natural ability to make a nest.

The Wall Street Journal reports that bexarotene is marketed under the trade name of Targretin by Japan's Eisai Company.  Here is the good news - patents begin to expire on the drug this year. 

Case Western research doctors hope to begin human trials in only a few weeks.

 

Stem Cells Triggered by Exercise

Mesenchymal stem cells (green) accumulate in skeletal muscle following exercise
Image Credit: Marni Boppart, University of Illinois

Something that always puzzled researchers is why runners rarely develop the arthritis and muscle deterioration that you might expect from years of exercise.  Since entropy always increases (roughly translated - things wear out), you might expect runners could hardly walk at all by the time they are fifty or sixty.

I will save the discussion for whether a living organism can reverse entropy for another day, but University of Illinois researchers have discovered that Exercise triggers stem cells in muscle.

If you recall, embryonic stems cells can differentiate, or turn into, any type of cell in the human body.  We still don't know how to switch an embryonic stem cell into say, a liver cell, but when an embryo is developing, that differentiation takes place naturally.  Less capable stem cells are more limited in the types of cells they can produce.  For example, the mesenchymal stem cells pictured above can produce connective tissue, but not blood cells. 

The University of Illinois researchers discovered that Mesenchymal stem cells (MSCs) respond to mechanical strain.  In studies of laboratory mice, they observed that large MSC accumulation in the muscle tissue occurs after vigorous excercise.  Even though MSCs do not immediately produce new muscle fiber, they produce signals for the muscle cells to generate new muscle tissue.  The study results are important, because they suggest therapies for healing damaged muscle tissue.

A challenge though, is how to induce these MSCs to signal for individuals that cannot exercise and generate the MSCs naturally. 

 

 

Clues to the Addiction of Cigarettes

Map of fiber pathways in the brain
Image Credit: National Institutes of Health

Cigarette smokers know their habit is harmful, but quitting is difficult.  35 million a year attempt quitting, but are unsuccessful.  An individual cigarette contains 10 mg of nicotine, but realistically, only about 1 to 2 mg is obtained in a single smoke. 

It isn't the nicotine that damages the lungs and increases the risk of cancer, but tar.  Carbon monoxide produced by the burning tobacco is harmful to the cardiovascular system and is responsible for the increased risk of heart disease.

The reason for the addiction is that nicotine activates reward pathways in the brain and increases the levels of dopamine.  This is a chemical that has complex effects within the brain.  One of the more notable is what gives pleasure also gives unhappiness when the expected reward does not arrive.

Resting brain studies shed new light on vulnerabilities provides new information on nicotine addiction.  They reveal that nicotine does increase cognitive pathways temporarily which explains the mental boost that some smokers claim.  A provocative finding is that nicotine patches and other nicotine replacement therapies do not activate the same circuits of the brain as smoking.  Perhaps that explains the poor success rate of nicotine replacements. 

A fascinating article, Siblings brain study sheds light on the roots of addiction explains that some chemical addictions such as marijuana, amphetamines, prescription drugs, and so on, damage the medial orbitofrontal cortex (OFC) of the brain.  What happens is that a normal person will stop placing money in a vending machine when nothing happens due to the braking action of the OFC.  When this is damaged, the person will keep placing money in the vending machine, expecting reward.  Researchers think this is why addicted people keep pursuing their devil long after it no longer gives them the pleasure it once did.  They have damaged their brakes.

 

Can Bingo Keep Alzheimer's Disease Away?

Amid a network of blood vessels and star-shaped support cells, neurons in the brain signal each other.
Image Credit: Kim Hager and Neal Prakash, University of California, Los Angeles

Alzheimer's Disease (AD) is going to become an urgent problem as last year the first of America's baby boomers began reaching their 65th birthday.  The disease itself began receiving increased attention in the 1970s, although the principal contributors of the disease, high levels of amyloid and tau proteins in the brain have been known for almost 100 years.

Brain amyloid: Is it ever benign? explains that the proteins are correlated with poor mental acuity.  (Memory, language, vision, and navigation.)   Healthy brains don't have abnormal levels of proteins - it isn't that some people become immune to them.  You can think of the tangles as simply shorting out the brain.

Researchers are developing drugs and therapies, but so far, they have not discovered a magic bullet.  Untangling the Mysteries of Alzheimer's tells that scientists have identified some elementary building blocks of these proteins and tangles. 

Cellular Changes in Alzheimer’s Disease explains that researchers also know that gene changes, specifically —presenilin-1 and presenilin-2 can cause early-onset AD.  They have also been identified the abnormal tau protein invades cell walls and boundaries that healthy protein does not.  Penetration into the dendrites disrupts chemical messaging and reception.

Brain imaging shows lifetime cognitive activity may influence Alzheimer’s disease risk explains that just as researchers have correlated the proteins with AD, they have also correlated lower levels of protein with higher levels of cognitive activity.  In other words, people who stay mentally alert with games, reading, and writing, have lower amyloid and tau protein levels. 

 

 

The Scientists Who Know Too Much

General influenza virus
Image Credit: CDC/ Doug Jordan, M.A.

Perhaps you don't remember the Alfred Hitchcock film, "The Man Who Knew Too Much", but you would probably recognize the theme song, "Que Sera, Sera".  The title though, says it all - is there knowledge that we shouldn't have? 

Think back to 1939.  Would the world be better today without the Manhattan Project's successful conclusion with the atomic bomb?  (The morals of the bomb are a completely separate discussion.  I had an uncle who was deployed in the Pacific at the end of World War II.  Henry claimed he would have been killed on the beaches of Japan during an invasion without the weapon's success.)

But would the world be better off today without the knowledge of atomic energy?  Although I am an advocate of atomic energy, I must confess that it has been more of a distraction than positive benefit for the world. 

Caution Urged for Mutant H5N1 Avian Flu Work explains that a collection of flu researchers have declared a 60 day pause in creating lab variants of the influenza.  During this pause they are urging governments and policy makers to develop a strategy on how such genetic engineering can be monitored and regulated.  There is urgency, because a research team in the Netherlands published a paper showing how only 5 mutations of H5N1 resulted in a virus that would spread rapidly among ferrets.  Under pressure from the U.S. government, the publisher withheld the scientific details, fearing genetic proliferation.

Scientists argue they will learn valuable information about protection against pandemics if they proceed.  (I can imagine teenagers arguing that they could learn something from playing with dynamite.) 

Mmm.  Remember Dr. Ian Malcom's declaration from the film, Jurassic Park:

I'll tell you the problem with the scientific power you're using here: it didn't require any discipline to attain it. You read what others had done, and you took the next step. You didn't earn the knowledge for yourselves, so you don't take any responsibility for it. You stood on the shoulders of geniuses to accomplish something as fast as you could, and before you even knew what you had, you, you've patented it, and packaged it, you've slapped it on a plastic lunchbox, and now you're selling it.
(From IMDb.)

It seems counter-intuitive, doesn't it?  As knowledge has become cheap or inexpensive, civilization has become more vulnerable.

 

Is the Fountain of Youth a Treadmill?

Runner in a Georgia Recreational Park
Image Credit: CDC/ Amanda Mills

I must confess, I am an exercise addict.  As a long-time runner, I crave beta-endorphins perhaps more than a drug addict. We know that exercise fights diseases such as dementia, heart attacks, and dementia.  But why?

Exercise and longevity: Worth all the sweat explains that researchers at the University of Texas Southwestern Medical Centre may have discovered the primary reason.  Beth Levine's research specialty is Autophagy. This is a process in which a functioning cell decides to discard portions of the cell and regenerate them. It has been known since the 60s, but how and why it works is a mystery.

Piecing things together, it appears to be a survival strategy or technique for living organisms.  The word autophagy, after all, is derived from the Greek, for 'self-eating'. 

As the Economist article tells, Levine's insight was that exercise promotes autophagy.  So in other words, exercise forces the body to renew itself. 

In experiments with laboratory mice, they discovered that if the mice were prone to diabetes, exercise would stimulate the mouse's body to correct the diabetes.  But if the mice were fed a diet that induced diabetes, the exercise had no benefit. (Implying that exercise can heal our bodies naturally, but cannot undue bad lifestyle choices.)

Also, as I have blogged previously in Strategizing for a Longer Life, reducing calorie intake by 30 percent extends the lives of other organisms.  Although there are some die-hards out there, starving themselves, most of us would prefer a higher quality of life.  But Levine and the other researchers speculate that exercise can achieve the same thing without the starvation.

Levine has recently purchased a treadmill.

(Beta-endorphins are chains of 37 amino acids that can actually bind to same neuro-receptors as opioids.  Think oxycodones.  Does this give you any ideas?)