Ugly Aging

Wellness and the buzz about General Metabolic Syndrome (GMS)
By Michael W. Loes, M.D.

We all want to live well and reasonably long – and without pain. We quest for great health, even optimal, enviable health, a term I like to call salubrity. Should our time come to die, most of us would prefer to die quickly, quietly, and comfortably.

Sounds nice, but in reality this is not what generally happens. We, as a society, are not aging gracefully. In fact, we are degenerating at a remarkably fast rate. The life expectancy tables look pretty stable but in reality ugly aging is out of control.

We go for a check-up and your doctor gives you the bad news. You – yes you - have one or more of the following:

* Diabetes – Type I or Type II
* Arthritis – Mostly Osteoarthritis, but Rheumatoid is on the rise
* Heart Disease & Stroke – Atherosclerosis
* Lung Disease – Bronchitis, Asthma, Emphysema
* Deep Venous Phlebitis – Blood Clots in your Legs
* Liver Disease – Cirrhosis and Fatty Liver
* Kidney Disease – Fibrosis and Chronic Renal Failure
* Cancer – Usually Lung, Colon, Breast, Uterus, Ovarian

All of these illnesses start with soft symptoms called “dys-ease.” You don’t feel great –but you are not sure why. The new buzz word for this is General Metabolic Syndrome (GMS). There is hardly a journal that crosses my desk that does not discuss this, mainly because this is the new concept that physicians are now examining, particularly as it relates to the avalanche of early diabetes that we now see. Doctors are able to identify GMS early if they are actively looking for it, and perhaps in doing so, warn you to wake up and change. What you need to understand is that if you have GMS, you are at risk for the whole gamut of degenerative diseases listed above.

There are various blood markers that are helpful in identifying GMS, such as homocysteine, glyco-hemoglobin (also known as HbA1C), ferritin, asymmetric-methyl-D-aspartate (AMDA), total and LDL cholesterol, sedimentation rates and C-reactive protein (CRP). The markers often show up early. You may be at the top of your life activity, experiencing only minor symptoms. You may be comfortably seated, like a child at the top of a slide, experiencing merriment. But, if you have GMS, the descent is likely into the chaos of chronic disease.

Does this scare you? It should. In 2004, more than 35% of Americans were more than 30 pounds overweight. The British come in second at 23%, followed by the Finnish at 19% and the Spaniards are 13%. While weight alone is not the main expressed risk factor for GMS, it factors into what is known as the body mass index (BMI), a combined measure of your weight, height and girth. When this merged number is high, the recipe for disaster is cooking. As this number goes up, you are losing the grip on your life.

In the United States, the incidence of GMC is now 24%.1 Can GMS be prevented? Of course it can, but it’s tough. We all know that losing weight is very hard, but it can be done. Surgical treatment of obesity can be effective when required. Structured supervised diet programs, some using medications for obesity, may be necessary when coupled with accountability measures.

Start doing what the “doctor within you” tells you that you must do to get back on track. Watch the food. Take your exercise program seriously. Consider taking some supplements that may be helpful such as anti-oxidants, herbal anti-inflammatories, and agents to reduce or stabilize blood sugar. Be sure and ask your doctor first.

And then you walk, and walk some more and do it again. I tell patients to exercise eight days a week and keep that pedometer on (a little device that counts steps). Try to get in 4000-5000 steps per day. Please understand that every one of the aging diseases can cause pain. Take this advice very seriously. Learn about healing and enhance your healing response by taking care of yourself.

1. Statistics from the Journal of the American Medical Association as reported in American Journal of Family Practice

Research - Potent Pain Reliever

A New Target for Painkillers

Snail Toxins Reveal Novel Way to Fight Severe Nerve Pain

Nov. 13, 2006 -- A brand new approach to treating severe nerve pain – by aiming drugs at a previously unrecognized molecular target – has been discovered by University of Utah scientists who study the venoms of deadly, sea-dwelling cone snails.

"We found a new way to treat a chronic and debilitating form of pain suffered by hundreds of millions of people on Earth," says J. Michael McIntosh, a University of Utah research professor of biology, and research director and professor in the Department of Psychiatry. "It is a previously unrecognized mechanism for treating pain."

The findings are being published the week of Nov. 13 in the online edition of the journal Proceedings of the National Academy of Sciences.

The study in rats found that cone snail toxins named RgIA and Vc1.1 can treat nerve hypersensitivity and pain by blocking a molecule in cells known as the "alpha9alpha10 nicotinic acetylcholine receptor."

"The numerous analgesic compounds currently available are largely ineffective" for chronic nerve pain, McIntosh and colleagues write. "Our findings not only suggest a previously unrecognized molecular mechanism for the treatment of neuropathic pain, but also demonstrate the involvement of alpha9alpha10 nicotinic receptors" in nerve injury.

McIntosh emphasized neither substance will be on the market soon. Vc1.1, also known as ACV1, is being developed by an Australian company, Metabolic, and is undergoing trials of its effectiveness in human patients. While Metabolic has said the drug targets nicotinic receptors, McIntosh says alpha9alpha10 nicotinic receptors have not been reported previously as a target for any kind of painkilling medication. McIntosh says Vc1.1 is administered by subcutaneous (under the skin) injection.

McIntosh hopes the new findings make it feasible to develop a painkiller based on RgIA that could be taken orally, but he believes that will take at least 10 years.

McIntosh co-authored the study with two colleagues in the University of Utah Center for Neuropeptide Pharmacology – Baldomero "Toto" Olivera, a distinguished professor of biology, and Michael Ellison, a postdoctoral fellow in biology – and with Michelle Vincler, Shannon Wittenauer and Renee Parker at the Wake Forest University School of Medicine in Winston-Salem, N.C.

The research was funded by the National Institutes of Health.

A Pain in the Nerves

The study dealt with what is known as neuropathic pain, which is chronic pain due to injury to the nerves, spinal cord or brain.

Such pain can result from diabetes damage to nerves in the feet or elsewhere, spinal injury, degenerative disc disease, alcoholism, failed low-back surgery, tumors compressing nerves, spinal tumors, repetitive motion disorders, multiple sclerosis, infection, stroke, traumatic brain injury, shingles, nerve toxins and electrical or other damage to peripheral nerves. Sometimes, doctors are unable to find a cause.

Symptoms can include numbness and pain that feels like constant burning, "pins and needles," sharp shooting pain, electricity or electrical shock, or tingling. People with neuropathic pain often are hypersensitive to previously innocuous stimuli – for example, feeling pain from a foot rubbing against the inside of a shoe – and feel an exaggerated response to things that are painful.

Common pain medicines like aspirin, ibuprofen and acetaminophen often fail to relieve neuropathic pain. Morphine-like opiods such as oxycodone sometimes are used, but can cause constipation, nausea and a spaced-out feeling.

Anticonvulsant drugs for epilepsy sometime are used to reduce the pain by decreasing nerve cell excitability, but have side effects such as lethargy, fatigue, clouding of mental state and weight gain, McIntosh says. Antidepressants and muscle relaxants have been used, but they can cause weight gain, nausea and sexual dysfunction.

Topical treatments include capsicum cream derived from chili peppers, but they usually are not very effective.

"There really is no highly effective treatment available for this kind of severe pain, so having a new way to treat it is exciting," McIntosh says. If the new discovery eventually leads to a new pain drug that is combined with existing treatments, "you may be able to reduce the pain to a lower level than ever before. No one drug is going to fully treat all pain, so having a new way is like having a backup catcher if the first catcher misses the ball."

How the Study was Performed

The toxins in the study come from two cone snail species that eat worms, unlike relatives that eat fish or snails and occasionally deliver a fatal sting to a human fisherman.

* RgIA is from the species Conus regius, which measures 1.6 to 2.8 inches in length and lives from Georgia southward along Central America to Brazil's central coast.
* Vc1.1 is from the species Conus victoriae, which measures 1.4 to 2.8 inches long and lives off portions of Australia.

RgIA and Vc1.1 fit like keys into lock-like alpha9alpha10 nicotinic acetylcholine receptors, which are found on nerve cells and are in the family of receptors activated by nicotine from cigarette smoking.

Alpha9alpha10 nicotinic receptors are found in a variety of body tissues, including white blood cells and the dorsal root ganglia – a group of nerve cells near the spine and involved in pain transmission.

The new study showed alpha9alpha10 nicotinic receptors provide a previously unknown route to pain relief. McIntosh says a patent is pending on this new mechanism.

One form of severe nerve pain is known as sciatica, and occurs when a herniated disk in the lower back causes pain to one or both sciatic nerves, which extend from the lower back to the hips, buttocks and back of the thighs.

For the study, the North Carolina co-authors tied sutures loosely around one of each rat's two sciatic nerves to mimic nerve compression and injury from sciatica. That made the rats overly sensitive to touch on one hind paw but not the other. Each rat's sensitivity was assessed by measuring how much pressure could be applied to a hind paw with a blunt Teflon tip before the rat pulled away the paw.

Normal rats could withstand 4.7 times more pressure before withdrawing their paws, compared with rats with sciatica. When cone snail toxin RgIA was injected, the rats with sciatica were able to tolerate a stronger touch from the tip – both four hours and 24 hours after the drug was given. The highest dose completely reversed the hypersensitivity caused by sciatica, with no adverse effects. Daily injections "produced a sustained analgesic effect," the researchers wrote.

RgIA was such a potent pain reliever that "about 10 billionths of an ounce reversed the hypersensitivity to pain," McIntosh says.

Vc1.1 had a similar effect – replicating studies by other researchers – allowing rats with sciatica to tolerate touch with greater pressure.

The new study is not McIntosh's first involving chronic pain. As an incoming college freshman working in Olivera’s lab in 1979, McIntosh discovered in cone snails the natural form of a drug now used against severe nerve pain. It is Prialt, which must be injected into fluid surrounding the spinal cord as a treatment for severe pain due to cancer, AIDS, injury, failed back surgery and certain nervous system disorders.

The shell of the sea-dwelling cone snail Conus regius, which uses its venom to kill worms so it can capture and eat them. A toxin from Conus regius venom helped University of Utah researchers identify an entirely new way to treat severe pain caused by injury to the nervous system.

Research - Opiates

Prolonging Painkillers
By Mary Beckman

Morphine and other opiates dull pain, but they don't stick around for long. Almost immediately, a class of enzymes known as peptidases burst onto the scene and degrade these painkillers. Now researchers have identified a naturally occurring molecule in humans that blocks this process, prolonging the effect of opiates. The findings, say the researchers, may lead to new ways to combat pain.

Three years ago, researchers got their first hint that animals could block opiate-destroying enzymes. When neuroendocrinologists stressed rats, they found a small protein or peptide called sialorphin inhibited the action of neutral endopeptidase (NEP), which breaks down a natural opiate known as enkephalin. Do humans make a similar peptide?

Neuroendocrinologist Catherine Rougeot of the Institut Pasteur in Paris suspected so. Previous work hinted that people secrete a mystery molecule in their mouths that could inhibit NEP, so Rougeot and colleagues started isolating peptides from saliva. The team identified a peptide that was five amino acids long and could block NEP in a test tube. Calling it opiorphin, the team modified it slightly to make it easier to work with in rats, naming the new peptide YQRFSR. Then the researchers injected YQRFSR into the bloodstreams of rats and, 15 minutes later, injected a compound that stimulates painful inflammation into the rats' hind paws. Rodents without YQRFSR licked their paws in discomfort for more than 2 minutes, but rats that got the small molecule only tended their paws for a little over a minute and a half, indicating less pain.

© 2006 American Association for the Advancement of Science

Depression & Osteoporosis - A Study

October 31, 2006

Feeling down? Depression may cause bone loss. Scientists say antidepressants could offer treatment for osteoporosis

“The new findings ... point for the first time to depression as an important element in causing bone mass loss and osteoporosis,” Hebrew University professor Raz Yirmiya, who took part in the study, said in a statement.

JERUSALEM - Depression can lead to brittle bones, Israeli scientists found in a new study released on Monday that also suggested antidepressant drugs could be used to treat osteoporosis.

The scientists, at Jerusalem’s Hebrew University, said mice that were given drugs to induce behavior similar to human depression suffered from a loss of mass in their bones, mainly their hips and vertebrae.

After being given antidepressants, the bone density of the mice increased, along with their level of activity and social interaction, the scientists said.

Depression activates the “sympathetic nervous system”, which responds to impending danger or stress, causing the release of a chemical compound called noradrenaline that harms bone-building cells, the study showed.

Antidepressant drugs block noradrenaline and reverse its negative effects, according to the findings, which will be published this week in the American journal PNAS (Proceedings of the National Academy of Sciences).

A study published earlier this month by the Forsyth Institute in Boston found that fluoxetine, used in the popular anti-depressant drug Prozac, also increased bone mass in mice.

Osteoporosis weakens bones and makes them more likely to fracture. It is treatable but affects millions and is most prevalent among postmenopausal women.

Copyright 2006 Reuters Limited