Janine Shepherd: A broken body isn’t a broken person
Cross-country skier Janine Shepherd hoped for an Olympic medal — until she was hit by a truck during a training bike ride. She shares a powerful story about the human potential for recovery. Her message: you are not your body, and giving up old dreams can allow new ones to soar.
BPA’s Real Threat May Be After It Has Metabolized
Chemical found in many plastics linked to multiple health threatsBisphenol A or BPA is a synthetic chemical widely used in the making of plastic products ranging from bottles and food can linings to toys and water supply lines. When these plastics degrade, BPA is released into the environment and routinely ingested.
New research, however, from the University of California, San Diego School of Medicine suggests it is the metabolic changes that take place once BPA is broken down inside the body that pose the greater health threat.
More than 90 percent of all Americans are believed to carry varying levels of BPA exposure.
In recent years, numerous studies have reported alarming associations between BPA exposure and myriad adverse health and development effects, from cancer and neurological disorders to physiological defects and, perhaps, a cause of childhood obesity.
Of particular concern is that BPA exposure is correlated with disruption of estrogen signaling. The chemical’s molecular structure is similar to that of estradiol, one of the human body’s three main estrogens, suggesting that BPA binds to estrogen receptors. The estrogen receptor is designed to grab and hold estradiol and related estrogens. Disparate chemicals, however, can share some structures found in estrogens, enabling them to bind to the estrogen receptor. When that happens, problems can occur.
In binding to the estrogen receptor, BPA can disrupt the body’s endocrine or hormone system, with consequences especially worrisome for fetuses, infants and young children. Earlier this year, the U.S. Food and Drug Administration banned BPA in baby bottles and sippy cups. Its use is more broadly banned elsewhere in the world.
In new research published in the October 4 online issue of the journal PLOS ONE, two scientists at UC San Diego School of Medicine say three-dimensional modeling suggests a metabolite of BPA – a molecule produced when BPA is metabolized or broken down by the body – actually binds to the estrogen receptor much more strongly than BPA itself. The finding could point the way to development of a new class of drugs designed to specifically inhibit excessive estrogen activity linked to disease.
According to Michael E. Baker, PhD, UCSD professor of medicine, and Charlie Chandsawangbhuwana, a graduate student in the UCSD Department of Bioengineering, several research labs have reported that BPA binds weakly to the estrogen receptor, suggesting that something else is interacting with this receptor.
In 2004, Shin’ichi Yoshihara, PhD, and colleagues at Hiroshima International University, discovered that another compound, dubbed MBP, was produced when BPA was metabolized. MBP has a 100-fold to 1,000-fold stronger bond to the estrogen receptor than BPA. However, the structural basis for MBP’s high affinity for the estrogen receptor was not investigated further.
In their PLOS ONE study, Baker and Chandsawangbhuwana revived Yoshihara’s research by creating three-dimensional, molecular models of MBP and BPA in the estrogen receptor and matching it against the crystal structure of estradiol in the estrogen receptor. They found that MBP’s longer structure allows both ends of the chemical to interact with the estrogen receptor in a way similar to estradiol. The shorter BPA molecule contacts the receptor at just one end, resulting in a weaker connection, providing an explanation for BPA’s lower affinity for the estrogen receptor.
“In other words, MPB is basically grabbing onto the estrogen receptor with two hands compared to just one hand for BPA,” said Baker. “Two contact points makes a much stronger connection.”
Baker said the 3D modeling supports the idea “that BPA is not the endocrine disruptor culprit. Instead, MBP is one (of perhaps several BPA metabolites) that causes disruption of estrogen signaling in humans and other animals.”
He said the research points to the need to measure MBP levels in urine and blood of patients suspected of BPA-mediated health effects, and may fuel development of a new therapeutic treatment for conditions linked to excessive estrogen levels and activity, such as some forms of breast and prostate cancers.
“One could use MBP, which has a novel structure, as a template to develop a new class of chemicals that could bind to the estrogen receptor with high affinity,” Baker said. “The goal would be to have these chemicals inhibit the action of estradiol instead of activating the estrogen response. These chemicals could control unwanted growth of estrogen-dependent tumors.”
Image: Contacts between the ends (red) of estradiol and the estrogen receptor are critical for biological activity. BPA is too short to have both contacts; MBP is longer and can mimic the sex hormone estradiol in the estrogen receptor.
Carpal tunnel syndrome: a Q & A with Reid Abrams, chief of hand and microvascular surgery
Carpal tunnel syndrome (CTS) is not a modern affliction. It has plagued workers since at least the Industrial Revolution and the dramatic rise in jobs requiring repetitive, physically stressing movements, from assembly-line workers to meat-cutters and machine operators.
There may be fewer of those jobs these days, but plenty of other ways to develop CTS, from dental hygienists and supermarket cashiers to bank tellers and baseball pitchers.
Women are three times more likely to develop CTS than men, according to the National Institutes of Health, though the reasons are unclear. Evidence suggests 3 percent of women and 2 percent of men will be diagnosed with CTS during their lifetime. Age is major risk factor. Peak prevalence for CTS occurs in women older than 55.
Researchers have been studying CTS and other repetitive stress injuries for years, with clinical trials focusing on preventative measures and behaviors. We asked Reid Abrams, MD, professor of clinical orthopedic surgery at UC San Diego and chief of hand and microvascular surgery at the UC San Diego Medical Center, to talk about what’s known about CTS and how best to treat it.
Q: What is carpel tunnel?
A: The carpal tunnel is an oval-shaped canal at the base of the palm, about 1 ½ inches long and an inch wide. The tunnel is surrounded on three sides by bone and on the palm side by a thick ligament. All of the flexor tendons that control the fingers and thumb run through the tunnel, plus the median nerve. This is the nerve responsible for sensation in the thumb, index, middle and half of the ring finger, plus motor function for most of the muscles at the base of the thumb. CTS is what happens when the median nerve becomes compressed.
Q: How do you know you have CTS?
A: The condition produces a constellation of symptoms, including intermittent or constant numbness or tingling in the thumb, index, long and ring fingers. There can be hand numbness, tingling or burning at night, which awakens patients; swelling or stiffness in the hand; grip weakness; a tendency to drop things.Not all hand pain is caused by CTS. If the pain is not associated with hand tingling or numbness, it’s not CTS. Also, not all hand tingling or numbness is CTS. Other nerve problems originating in the hand, forearm, elbow, shoulder or neck can also cause these symptoms.
Q: What causes it?
A: CTS occurs when there is abnormally high pressure on the median nerve, so high that the nerve can’t function. That pressure can be the result of an injury that produces sudden swelling, like a wrist fracture, or something else in the canal crowding the nerve, like an engorged blood vessel or intruding muscle.Most often, the cause is idiopathic or unknown. It’s often activity-related because the dimensions of the carpel tunnel change with different positions of the wrist and fingers. Activities such as driving, tightly holding a book or newspaper while reading, jobs that entail sustained periods of wrist flexion or extension while gripping or pinching, such as maneuvers performed by a dental hygienist, mechanic or construction worker, can bring on symptoms. Some summer activities can set off CTS, such as carrying a surfboard for long distances, cycling or racket sports.
It’s a myth that keyboard use causes CTS. It’s been shown that intense keyboard users have the same incidence of CTS as the general population. This is not to say that symptoms of CTS can’t be brought on by keyboard use. If keyboarding is performed in a non-ergonomic fashion, with the wrists in hyper-flexion or extension, CTS symptoms could arise. Keyboarding can also be responsible for painful problems other than CTS.
Q: How is CTS treated?
A: In the mildest forms, keeping the wrist straight or wearing a splint at night may completely relieve symptoms. Avoiding extreme wrist positioning and repetitive or sustained heavy pinching and gripping can help. Cortisone injections into the carpal canal can also provide temporary relief, though severe CTS usually requires surgery.Carpal tunnel release surgery enlarges the carpal canal by cutting the transverse carpal ligament. We know the ligament heals with the canal 25 percent bigger. It’s highly successful with rare complications, failures or recurrences.
There are two basic techniques; both work. Endoscopic is done through one or two small incisions using a visualizing camera and a specialized small blade. It produces a modestly faster return to work, but has a three-fold higher incidence of transient median nerve injury. Open surgery through an incision in the palm has a slightly higher incidence of wound healing problems.
When macrophages take up massive amounts of cholesterol they form “foam cells,” characterized by multiple lipid droplets (stained red). Image courtesy of Marten Hoeksema, University of Amsterdam.
New Way of Fighting High Cholesterol Upends Assumptions
Atherosclerosis – the hardening of arteries that is a primary cause of cardiovascular disease and death – has long been presumed to be the fateful consequence of complicated interactions between overabundant cholesterol and resulting inflammation in the heart and blood vessels.
However, researchers at the University of California, San Diego School of Medicine, with colleagues at institutions across the country, say the relationship is not exactly what it appears, and that a precursor to cholesterol actually suppresses inflammatory response genes. This precursor molecule could provide a new target for drugs designed to treat atherosclerosis, which kills tens of thousands of Americans annually.
The findings are published in the September 28, 2012 issue of Cell.
Lurking within our arterial walls are immune system cells called macrophages (Greek for “big eater”) whose essential function is to consume other cells or matter identified as foreign or dangerous. “When they do that, it means they consume the other cell’s store of cholesterol,” said Christopher Glass, MD, PhD, a professor in the Departments of Medicine and Cellular and Molecular Medicine and senior author of the Cell study. “As a result, they’ve developed very effective ways to metabolize the excess cholesterol and get rid of it.”
But some macrophages fail to properly dispose of the excess cholesterol, allowing it to instead accumulate inside them as foamy lipid (fat) droplets, which gives the cells their particular name: macrophage foam cells.
These foam macrophages produce molecules that summon other immune cells and release molecules, signaling certain genes to launch an inflammatory response. Glass said conventional wisdom has long assumed atherosclerotic lesions – clumps of fat-laden foam cells massed within arterial walls – were the unhealthy consequence of an escalating association between unregulated cholesterol accumulation and inflammation.
Glass and colleagues wanted to know exactly how cholesterol accumulation led to inflammation, and why the macrophages failed to do their job. Using specialized mouse models that produced abundant macrophage foam cells, they made two unexpected discoveries that upend previous assumptions about how lesions form and how atherosclerosis might be more effectively treated.
“The first is that foam cell formation suppressed activation of genes that promote inflammation. That’s exactly the opposite of what we thought happened,” said Glass. “Second, we identified a molecule that helps normal macrophages manage cholesterol balance. When it’s in abundance, it turns on cellular pathways to get rid of cholesterol and turns off pathways for producing more cholesterol.”
That molecule is desmosterol – the final precursor in the production of cholesterol, which cells make and use as a structural component of their membranes. In atherosclerotic lesions, Glass said the normal function of desmosterol appears to be “crippled.”
“That’s the next thing to study; why that happens,” Glass said, hypothesizing that the cause may be linked to overwhelming, pro-inflammatory signals coming from proteins called Toll-like receptors on macrophages and other cells that, like macrophages, are critical elements of the immune system.
The identification of desmosterol’s ability to reduce macrophage cholesterol presents researchers and drug developers with a potential new target for reducing the risk of atherosclerosis.
Glass noted that a synthetic molecule similar to desmosterol already exists, offering an immediate test-case for new studies. In addition, scientists in the 1950s developed a drug called triparanol that inhibited cholesterol production, effectively boosting desmosterol levels. The drug was sold as a heart disease medication, but later discovered to cause severe side effects, including blindness from an unusual form of cataracts. It was pulled from the market and abandoned.
“We’ve learned a lot in 50 years,” said Glass. “Maybe there’s a way now to create a new drug that mimics the cholesterol inhibition without the side effects.”
Eating Your Way Healthy: how diet and exercise can help you fight cancer
Recent reports on NPR and MSNBC are highlighting the benefits of healthy eating and exercise for cancer patients based on several new research papers. The Healthy Eating & Living Program at UC San Diego Moores Cancer Center has promoted healthy eating since conducting the Women’s Healthy Eating & Living (WHEL) Study between 1995 and 2006.
We’ve asked Vicky Newman, MS, RD, associate clinical professor in the UC San Diego School of Medicine’s Department of Family & Preventive Medicine three questions about how nutrition can affect cancer patients.
Question: How far ahead of the American Cancer Society’s recommendations was the Healthy Eating Program?
Answer: The UCSD Healthy Eating & Living Program has been helping cancer patients change to a healthier diet since 1995. While the primary focus of the WHEL Study was on diet, the focus of the Healthy Eating & Living Program has broadened to include exercise and weight control as all of these lifestyle factors are increasingly being shown through research to influence risk of breast cancer recurrence.
Q: In the MSNBC article, Dr. Kucuk of Emory University states that when it comes to dealing creating a course of treatment for cancer patients “Usually the last thing on their (the doctor’s) mind is to talk about diet and exercise.” At what point do patients at Moores Cancer Center enter The Healthy Eating Program – is it an integral part of their treatment plan?
A: At Moores, patients are encouraged to attend an introductory lecture offered each month called “Fighting Cancer with Your Fork.” Participants learn about dietary factors that strengthen the body’s immune and detoxification systems, and are provided with practical tips for optimizing intake of protective plant foods with BIG color and STRONG flavors because these contain the most plant protectors. Moores patients are also encouraged to attend monthly cooking classes in our Healing Food Kitchen where they learn to prepare and are able to taste delicious health-promoting recipes. During treatment, patients are encouraged to consult with the Oncology Dietitian. And after treatment, patients are encouraged to enroll in our Healthy Eating & Living Program, which provides the support and guidance of their own personal coach by telephone to help them make long-term changes to a healthier diet and more active lifestyle that will not only support their health, but also help them to maintain a healthy weight.
Q: What advice do you have for someone facing a cancer diagnosis about where to begin thinking about their diet and exercise?
A: The literature clearly shows that a healthy diet and regular physical activity are both important in reducing the risk of recurrence, and in supporting quality of life during treatment so the best advice is to begin working toward the diet and physical activity guidelines right away. Just remember, slow and steady in the right direction. This is where coaching can really help in setting short-term, attainable goals that are reachable and then to keep building on those. If you are at three vegetable servings daily, make a goal to get to four servings. When you have adjusted to that goal, consider increasing the goal to five vegetable servings daily. And begin adding BIG color and STRONG flavor vegetables and fruits as soon as possible because these are the ones with most health-promoting benefits.
With regard to exercise, think of wearing a pedometer. Start by recording usual steps daily. Set a goal for increasing your daily steps by 1,000 daily until you get to the 10,000 steps recommended. Even if fatigued during treatment, move as much as possible. Just walking around the house during each commercial break from your favorite television program is better for your body than continual sitting. And some very interesting research is being reported showing the health benefits of many small bouts of exercise being even more protective of health than sitting all day and only exercising vigorously once.
For more information on our research, programs, and services, visit our website www.healthyeatingucsd.org
