Monthly Archives: January 2013

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Usually kept in check by the body, C. albicans can cause damage for those who are immunosuppressed

This is the second in a two-part series that began last week on two scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems.

Like the cracks in the sidewalk that we don’t notice most of the time, Candida albicans is everywhere. Mostly, though, it’s on and around us. While this fungus is harmless much of the time, it has a dark side.

After prolonged catheterization (tubes entering the body) or in people with weakened immune systems, Candida can enter the bloodstream, where it can cause significant damage.

“It’s considered to be the fourth most commonly acquired hospital infection,” explained James Konopka, a professor in molecular genetics and microbiology at Stony Brook Medical School. It often targets the kidney. Even with current state-of-the-art antifungal drugs, Candida can become life threatening.

In most people, Candida often can’t get past the skin or the lining of the gastrointestinal tract. That, however, changes when, for example, patients have surgical procedures.

“A tube going into a patient can provide a site for a biofilm and can get it across the skin,” Konopka explained.

This can also be compounded, he explained, by the use of antibacterial drugs, which eliminate the bacteria and give the fungus more room to grow.

Patients with weakened immune systems, through AIDS, cancer treatments or immunosuppressive therapies, can also be the target of fungal infections.

Konopka is looking from the outside of Candida in, trying to alter the cell wall, or plasma membrane. Everything in the membrane is not randomly moving around, he explained. There are specialized sensors that can be instrumental in its life cycle.

He’s been studying genes that are responsible for 30 proteins in the membrane. He has deleted the genes for most of these proteins and plans to pick the best candidates for more study and drug development.

“If we disrupt the function of those proteins, that leads to a global defect in how the membrane is organized,” he said.

One of the challenges in fungal research is that humans and fungi are more closely related, evolutionarily, than humans and bacteria. On the positive side, that means research into basic cellular mechanisms of fungi may provide information about human cells.

On the downside, however, it provides a tricky type of Venn diagram for medical treatment. Doctors and researchers have to find drugs that only affect fungi and that don’t harm human cells at the same time.

The existing therapies have limitations. As with bacteria, some fungal strains have developed resistance.

Even finding a specific therapy that targets and eliminates Candida could lead to another unintended consequence. Because Candida lives within most of us without causing problems, eliminating all of the fungus could create an opening for an infection from another type of bacteria or fungus.

“There’s been some suggestion that that possibility may be occurring in certain patients in long-term drug therapy,” Konopka acknowledged.

He’s not convinced that’s the case, but it has caused some researchers to think Candida might be filling a niche that keeps worse invaders out.

The ideal therapy may involve a short-term treatment that clears Candida from internal organs, but resets the relationship to where the fungus lives within humans without doing any damage.

At the University of Washington in Seattle, Konopka had been doing basic fungal research under the guidance of Leland Hartwell, who shared the Nobel Prize in 2001 for discovering protein molecules that control the division of cells. When Konopka moved to Stony Brook, he transitioned to studying Candida.

In 2008, he discovered that deleting the proteins in the plasma membranes caused the cell wall to grow backwards.

“There’s a layer of regulation that keeps the cell wall on the inside,” he explained.

Konopka lives in East Setauket with his life, Susan Watanabe, a scientist who is studying HIV, the virus that causes AIDS.

He said he wades out into the water at West Meadow Beach, where he catches bluefish and striped bass.

As for working with fungus, there is an upside: yeast. In the fall, he hosts an Oktoberfest party for his entire building, where he and his guests sample each other’s home-brewed beer. Last fall, the offerings included Strong Island Ale, Rye Smile and Midnight Spice. Konopka provided Hoppy Oktoberfest, a beer he describes as a “classic,” which has “the taste of fresh grown hops, but brings with it a fair amount of sweetness.”

 

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It is possible to overdo exercise for weight loss purposes

When we make our New Year’s resolutions to exercise regularly, the goal for many is to change body composition, to lose weight or at least to maintain weight, but is this reality or myth?

It is a hotly debated topic. You would think the answer would straightforward, since exercise helps us prevent and resolve a great many diseases. For example, in last week’s article, I wrote about the value of exercise before the flu shot in improving immunity.

At the same time, we hope exercise impacts our weight. Does it? This is something that we should know, and rightfully so, before we start exercising. It is important to manage our expectations. There are some new and intriguing studies that address whether exercise has an impact on weight management. The short answer is yes, however, not always in ways we might expect.

Then the questions become: what type of exercise should we be doing, how frequently and for how long? Let’s look at the evidence.

 

Duration

It makes sense that the more we exercise to lose weight, the better, or at least that is what we thought. In a recent small randomized controlled trial (RCT), the gold standard of studies, the results showed that the moderate group in terms of duration saw the most benefit for weight loss (Am J Physiol Regul Integr Comp Physiol. 2012 Sep 15;303(6):R571-R579). There were three groups in the study — a sedentary group (low), a group that did 30 minutes per day of aerobic exercise (moderate) and a group that did 60 minutes per day of aerobic exercise (high).

Perhaps obviously, the sedentary group did not see a change in weight. Surprisingly, though, the group that did 30 minutes of exercise per day experienced not only significantly more weight loss than the sedentary group, but also more than the 60-minute exercise group. The aerobic exercises involved biking, jogging or other perspiring activities. These were healthy young men that were overweight, but not obese, and the study duration was three months.

The authors surmise that the reason for these results is that the moderate group may have garnered more energy and moved around more during the remainder of the day, as sensors showed. The highest exercise group was sedentary through most of the rest of day, probably due to fatigue. Also, it seemed that the highest exercise group ate more than the moderate group, though the difference was not statistically significant. While this study is of impressive quality, it is small and of short duration. Nonetheless, its results are encouraging.

 

Postmenopausal women

As a group, postmenopausal women have considerable difficulty losing weight and maintaining weight loss. In a secondary analysis of a RCT, there were three aerobic exercise groups differentiated by the number of kcal/kg per week they burned: 4, 8 and 12 (Am J Prev Med. 2012;43(6):629-635). All of the groups saw significant reductions in waist circumference. Interestingly, however, a greater number of steps per day outside of the training, measured by pedometer, were primarily responsible for improved waistline circumference, regardless of the intensity of the workouts.

But it gets more intriguing because the group that exercised with the lowest intensity was the only one to see significant weight loss. More is not always better, and in the case of exercise for weight loss, less may be more. This study reinforces the suppositions made by the authors of the previous men’s study: exercise to a point where it is energy inducing and not beyond.

 

Premenopausal women

Not to ignore younger women, those who were premenopausal also saw a significant benefit with weight maintenance and exercise after having intentionally lost weight.

In a prospective (forward-looking) study, young women who did at least 30 minutes of exercise four to five days per week were significantly less likely to regain weight that they had lost, compared to those who were sedentary after losing weight (Obesity 2010;18(1):167-174).

Some of the strengths of this study were its substantially long six-year follow-up period and its large size, involving over 4,000 women between the ages of 26 and 45. Running and jogging were more impactful in preventing weight gain than walking with alacrity. However, all forms of exercise were superior to the sedentary group.

 

Aerobic exercise and resistance training

In another RCT with 119 overweight or obese adults, aerobic exercise four to five times a week for about 30 minutes each was most effective for weight loss and fat reduction, while resistance training added lean body mass. Lean body mass is very important. It does not cause weight reduction, but rather increased fitness (J Appl Physiol. 2012 Dec;113(12):1831-1837).

With weight loss, it’s important to delineate between thin and fit. Fitness includes a body composition of decreased body fat and increased lean muscle mass. To help achieve fit level, it’s probably best to have a combination of aerobic and anaerobic exercise (resistance training). Both contribute to achieving this goal.

In conclusion, exercise can play a significant role in weight, whether with weight reduction, weight maintenance or increasing lean body mass. It appears that 30 minutes of exercise four to five times a week is best. Longer is not necessarily better.

What is most important, however, is to exercise to the point where it energizes you, but doesn’t cause fatigue. This is because it is important not to be sedentary the rest of the day, but to remain active. We should also include a complete package of lifestyle modifications in general — diet, exercise and stress reduction — to get the most compelling results.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Long term goal is to find drugs that help immunocompromised individuals fight fungal diseases

One of them brews beer, while the other makes his own pizza. While it sounds like a great mealtime combination, what Maurizio Del Poeta and James Konopka do when they’re at work may one day help you or your friends and family.

The two are scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems. Del Poeta is studying Cryptococcus neoformans, a fungus that can kill if it reaches the brain, while Konopka is  working with Candida albicans, a fungus that normally lives with and on us but that can also do damage to internal organs, particularly the kidney.

Del Poeta, the pizza maker, has found a drug that targets a sphingolipid on the surface of Cryptococcus that clears the infection in the brains of mice. He recently applied to start testing that drug on humans. That process could take five years.

Konopka, the beer brewer, is targeting a 30-protein sequence in the cell wall of Candida. He is narrowing down the list of targets and hopes to start searching for effective drugs or therapies.

“These two men are superb,” said Jorge Benach, the chairman of the Department of Molecular Genetics and Microbiology. “They are sought after internationally and nationally” to address scientific audiences.

The Molecular Genetics and Microbiology department includes researchers who study viruses, bacteria and fungi. Benach said they are all aware of the potential medical benefit, even as they perform basic research to understand the way these pathogens work.

“It takes a while from what we do to the point where we can save lives,” he offered. “We are on that track. If you hit the ground running, you shorten that distance.”

The Times Beacon Record will profile the research of Konopka and Del Poeta in a two-part series. The Del Poeta feature will run today, while the Konopka story will run next week.

 

Maurizio Del Poeta loves stories. There’s the one about how he met his Italian wife when they were at Duke University. They were, he said with a laugh, two of the only three people originally from Italy at Duke.

He met her at a dinner party after he returned from a ski trip. The only complication: she was dating someone else.

“I was waiting for her to drop this guy,” he laughed. “He wasn’t good for her.”

Six months later, she became single and Del Poeta’s wait was over.

An avid reader, Del Poeta also has a story for a key insight into his research. While reading the late Michael Crichton’s anti-climate change novel “State of Fear,” an ironic choice given his findings, Del Poeta decided he had to test a fungus in a higher carbon dioxide environment, like that in the lung.

He was working with Cryptococcus neoformans, a fungus that is especially problematic in people who are immunocompromised — either through cancer treatments, drugs that suppress the immune system after organ transplants or in people with AIDS.

In the outside environment, a mutant type of this fungus grew normally, but “when you transfer it into the lung, it can’t grow anymore,” he explained.

When he studied it more closely, he found that a specific sphingolipid attached to the surface of the fungus in the mutant prevents it from growing in an environment that has 5 percent carbon dioxide (the concentration in the lung), compared with the approximately 0.4 percent in the atmosphere.

This sphingolipid and the genes and enzymes that lead to its production became a “fantastic target for developing drugs,” Del Poeta offered.

That discovery came in 2005. Del Poeta has spent the last seven years, including the last six months as a professor in the school of medicine at Stony Brook Medical School, looking for drugs that might target that sphingolipid.

He has found several that have worked. The survival rate of animals treated with these targeted drugs is 90 percent, compared with a 100 percent mortality rate when untreated.

Del Poeta submitted a grant to the National Institutes of Health for one of the drugs in February. It received a high score, he said, but it was not funded. After he conducted the promising mouse experiments this year, he resubmitted that grant in the middle of December. He hopes to hear back in the next few months.

The drug not only prevents the spread of an infection in the animal models but it clears the fungus from the brain. Currently in humans, there are no drugs that effectively eradicate the fungus in the brain.

Del Poeta said it may take five years before the drug goes through clinical testing to reach the pharmaceutical shelves.

While the drug is not toxic in animals, it’s unclear what reactions humans might have to it.

Del Poeta got involved in fungal research when he was a medical doctor at Duke. He observed that the patients he had who were immunocompromised, mostly because of AIDS, were dying because of this fungal infection.

He needed “to do something.” He consulted with his mentor John Perfect, who is now the director of the Division of Infectious Diseases at Duke, who suggested he choose between seeing patients and conducting research.

While he misses seeing patients, he finds his research satisfying, especially because of its potential practical impact.

In his research, he combines basic science with the search for drugs.

He explores the mechanism by which the sphingolipid limits the growth of the fungus. He is also looking at ways to boost other parts of the immune system that are not often weakened, even in immunocompromised individuals. He would like to raise the activity level of macrophages, neutrophils and Natural Killer (NK) cells.

A temporary resident of Port Jefferson, Del Poeta and his wife Chiara Luberto, who is studying leukemia at the cancer center at Stony Brook, recently bought a house in Mount Sinai. The couple have two young sons, Matteo and Francesco.

Del Poeta combined his passion for cooking and sharing amusing anecdotes in a cookbook called “Pasta con Amici.”

When he moved to South Carolina (a stop he made before landing at Stony Brook), he missed pizza so much that he built a brick oven with his father. He plans to build another one here, perhaps in 2013.

“I love stories,” he explained. “Behind a story, there is everything. Each of us has a fantastic story.”

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Exercise helps to boost the vaccine’s effect; green tea and hand sanitizers are also beneficial

If you have been on a distant planet, you may not know that we are in the middle of the flu season. The rest of us by now have had colleagues, friends, family members, and possibly ourselves, who have confronted the influenza virus.

If you think the flu season has been worse than in recent years, you’re right. The centers for disease control preliminary data indicate outpatient visits for the flu have been more than twice the baseline (CDC.gov). The good news is that the most recent comments from the director of the CDC, Dr. Thomas Frieden, suggest that we are over the hump.

According to the CDC the present vaccine is 62 percent effective. The statistic for this year’s vaccine is derived from a case study involving 1155 children and adults (MMWR Morb Mortal Wkly Rep. 2013;62). Though this is moderate, it is still reducing the risk by more than half. However, by no means is the vaccine’s coverage perfect.

I know some have hesitancy toward the vaccine because it contains eggs and thimerosal, a preservative that is organic mercury-based. A concern is that this preservative may increase neurotoxicity risk. There are trace amounts in the flu vaccine. Those with allergies to eggs should also not receive the standard vaccine.

If you are uncomfortable with the egg or thimerosal, there is good news. The FDA has recently approved a flu vaccine, Flublox, that is both eggless and does not contain the preservative thimerosal (www. FDA.gov). It uses a recombinant DNA technology that does not require inactivated virus. It is available this year in limited quantities and will be readily available for next year’s flu season. Currently, Flublox is approved for patients 18 to 49 years old.

So what can we do to decrease the chances of getting the virus following vaccination? Actually, there are several studies that show that exercise helps boost the vaccine’s effects.

 

Impact of exercise

We know that exercise plays an important role in altering and improving disease processes in general, but did you know that exercise may increase the effectiveness of the flu vaccine? In particular, elderly patients tend to have weaker immune responses to pathogens, such as the flu. In a study looking at the older population, those who walked with alacrity regularly for 10 months demonstrated higher antibody levels 24 weeks after getting the flu vaccine, compared to those who stretched and did balancing exercises (J Am Geriatr Soc. 2009 Dec;57(12):2183-91). This helped boost their immunity and improved the results from the vaccine.

So what if you haven’t exercised for almost a year and are not in cardiovascular shape? Is it too late for this year’s flu season? The answer is a resounding no.

Another study showed that people who did 20 minutes of eccentric exercise using the arm that would receive the vaccine on that same day also had higher titers of antibodies several weeks later, compared to those who were sedentary (Brain Behav Immun. 2007 Feb;21(2):209-17). Women had an increase in B-cell activity, part of the immune response, six and 20 weeks later. In men, there was an increase in cell-mediated activity, another part of the immune system, which includes T-cell activity, natural killer cells and phagocytes, with levels measured eight weeks after vaccination. Participants were given the vaccine six hours after exercising.

The exercises included several sets of weighted bicep curls and lateral arm raises for the shoulders. Eccentric exercises involve lowering weights, rather than lifting them. For example, if you are doing shoulder exercises, you slowly lower the weight from your shoulder to your side. This helps to elongate the muscles.

This was a randomized controlled trial, the gold standard of studies, in 60 young, healthy adult participants. The authors surmise that the inflammation due to exercises may have been the mechanism that helped boost the effect of the vaccine.

 

Green tea

The great thing about green tea is that it may have benefits for many diseases and their prevention. But, did you know that green tea may actually help prevent the influenza virus? In an observational study involving over 2,000 Japanese elementary schoolchildren, those who drank green tea at least six days a week were 40 percent less likely to get the flu than those who drank green tea three or fewer days per week (J. Nutr. 2011;141(10):1862-1870). Results were confirmed using an antigen test to detect the virus.

In a separate study, health care workers who took daily green tea supplements in an RCT saw a significant reduction in the incidence of the influenza virus than the placebo group (BMC Complement Altern Med. 2011 Feb 21;11:15). The supplements contained two compounds in green tea: 378 mg of catechins and 210 mg of theanine. There were 197 participants in the study.

Hand sanitizers

Many of us use hand sanitizers regularly. Are they beneficial or dangerous? It turns out that hand sanitizers may help reduce the transmission of the flu vaccine by breaking down the lipid envelope of the virus.

In a small study, healthy participants were subjected to the flu H1N1 strain on their fingertips. They were then randomly given wipes, foam or gels that contained at least 60 percent alcohol (Am J Infect Control. 2012 Nov;40(9):806-9). It did not matter which vehicle was used to deliver the sanitizer, they all worked equally well to reduce the viral load significantly.

Be careful not to overutilize sanitizers as they may dry out the skin and cause cracking, allowing pathogens to invade the body. Sanitizers should not replace washing your hands with soap and water, but rather be an additional defense.

Although this year’s flu season seems like it is one of the more dramatic, there are ways to reduce the risk. Exercise is a great way to improve your immunity, particularly in combination with the vaccine. It may also help those who are obese, and thus may have decreased immune functioning. And drinking green tea should be easy, since flu season is during the cold weather.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Physical factors, such as exercise and even vibrating platforms may have profound health benefits

One way to shake up an immune system may be, in fact, to shake up the immune system.

Clinton Rubin, the chairman of the Department of Biomedical Engineering at Stony Brook, has been studying the effects of low intensity vibrations as substitutes for physical activity on bone growth in animal models. He’s found, for example, that older sheep standing on a platform that’s vibrating at a level that’s barely noticeable show bone growth.

His latest finding is that these same slightly moving platforms can also raise the level of immune cells, including T cell and B cell levels, in an obese mouse.

While it’s early to extend this to humans, the findings present the possibility that these small vibrations may help contain or even prevent significant health problems that often threaten or damage the lives of people who are significantly overweight.

“Obesity makes you susceptible to a number of disorders,” explained Rubin, who is also the director at the Center for Biotechnology. “We hope that some day, if we are able to extrapolate these findings in mice to people, that these low magnitude mechanical signals can help mitigate the health complications that arise in those that are obese.”

Rubin cautioned that these signals would not be a substitute for a healthy diet, exercise and active interaction with a physician’s advice.

Ever since he arrived at Stony Brook University in 1987, Rubin has been studying how physical factors influence the musculoskeletal system, to understand, for example, how exercise can generate a profound health benefit. He has also looked at how the removal of these physical factors, through bed rest, extended time in space, and spinal cord injuries, can affect these systems. These low intensity vibrations have served as surrogates for typical mechanical loading signals.

Recently, he has studied the effects of these small vibrations on mesenchymal stem cells (or MSC). These cells can become bone cells, cartilage or fat cells. Low intensity vibrations for as little as 10 minutes a day can bias these cells away from becoming fat cells.

Rubin suggests the process may involve a signaling pathway that mimics the way muscles move bones. Muscles are generally inefficient motors, shaking as they contract (as anyone who has challenged themselves to do a few extra push ups or do a few more reps with weights can attest). The vibrations from these plates may provide a substitute signal for the muscle vibrations.

Rubin is the chief scientific advisor for a company called Marodyne Medical, which hopes to translate his science into a medical device that can address such problems as bone wasting, muscle wasting, obesity and diabetes.

Rubin readily recognizes he has a potential conflict of interest because of his involvement with a company he hopes will one day sell a product that could offer a nonpharmaceutical alternative for people with various bone or muscle challenges.

“Do I look at this stuff with rose-colored glasses?” he asked. “As a scientist, I hope not. I try to insulate myself as much as possible from the subjects in evaluating the data.”

Rubin said the university helps him address these concerns by ensuring he provides full disclosure, in publications, grants and lectures and by informing any human subject who participates in his studies of his dual roles.

He does not interact with potential subjects in his studies and all his scientific methods are performed in a double blind fashion. That means he doesn’t know which animal received which treatment when he records results.

As for the immune system response, the benefit from these low intensity vibration is through another class of cells, called the hematopoietic stem cells (HSC).

“If these bone marrow are influenced by mechanical signals, why not HSCs?” Rubin reasoned.

Rubin and his wife, Jennifer Sigler, live in Port Jefferson with their 16-year-old son Jasper. Sigler works as an architect for the building department in their village. Jasper, meanwhile, has kept his own musculoskeletal system active by playing right defensive back for the Port Jefferson Royals, who have won back-to-back New York state class C soccer championships.

Rubin, who has been at Stony Brook since 1987, said he struggles on the Port Jefferson golf courses, but that hasn’t kept him from the links.

Rubin appreciates the support and talent of his colleagues at Stony Brook, including Assistant Professor Meilin Ete Chang and senior doctoral students Danielle Green and Ben Adler.

His work, he said, suggests that even supporting weight can send the right signals to their bodies.

“When people ask me what they should do if they can’t run or walk, I tell them stand up,” he offered.

 

Cast call

Cast is sought by Star Playhouse, Suffolk Y JCC, 74 Hauppauge Road, Commack for their upcoming play, “Dirty Rotten Scoundrels.” All roles are open; ages 17 and up. Prepare to sing 32 bars of contemporary theater music. Bring sheet music in the proper key and be prepared for dance audition. Call 462-9800, ext. 136, or go to starplayhouse.com for further information.

Free Irish language classes

The Gerry Tobin Irish Language School will be offering free Irish language classes beginning on Wednesday, Feb. 6, at the Ancient Order of Hibernians Hall, 27 Locust Ave., Babylon. Classes include “Mommy, Daddy and Me,” for young children and their parents. Classes for new and advanced students are also available. Call 521-1227 or go to www.scoilgaeilge.org for further information.

Seamanship course

The U.S. Coast Guard Auxiliary Flotilla 2204 will be offering a boating and seamanship course beginning on Thursday, Feb. 7, at 7 pm. Classes will be held at the Smithtown Library, 1 North Country Road, Smithtown, and runs for seven sessions.

Upon completion of the course a certificate will be awarded, satisfying the Suffolk County boaters requirements and the New York PWC operators certificate; this also covers the young boaters requirements for those under 18 years of age. Additionally, boat owners may be eligible for an insurance discount.

The course is free; there is a nominal charge for course materials. Family participation is encouraged. Call 732-3562 for further information and to register.

Pysanky Easter egg workshop

The third annual traditional Ukrainian Easter Egg (Pysanky) decorating workshop will be held on Sundays, March 10 and 17, at the Resurrection Byzantine Catholic Church, Edgewater and Mayflower avenues, Smithtown. All levels of experience are welcome. Cost of the class is $20; each participant must bring a candle in holder, pencils and roll of paper towels. Registration is required by Feb. 8. Call 246-5669.

 

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Iron deficiency without anemia may cause fatigue

This week, I thought it would appropriate to talk about the significance of low iron, since I wrote about iron overload last week. The major causes of low iron are anemia of chronic disease, iron deficiency anemia, sideroblastic anemia and thalassemia. Of these, iron deficiency anemia is the most common.

However, there is a much less known, but not uncommon, form of low iron. This is called iron deficiency without anemia. Unlike iron deficiency anemia, the straightforward CBC (complete blood count) that is usually drawn cannot detect this occurrence since the typical indicators, hemoglobin and hematocrit, are not yet affected.

So how do we detect iron deficiency without anemia? Not to despair, since there is a blood test done by major labs called ferritin. What is ferritin? I mentioned in my pervious article that ferritin is a protein that is involved in iron storage. When ferritin is less than 10 to 15 ng/ml, the diagnosis of iron deficiency is most likely indicated. Even healthy people with ferritin slightly higher than this level may also have iron deficiency (Br J Haematol. 1993;85(4):787-798). The normal range of ferritin is 40-200 ng/ml.

You should be asking at this point, who does low ferritin affect and what are the symptoms? Women and athletes are affected primarily, and low ferritin levels may cause symptoms of fatigue. It is also seen with some chronic diseases such as restless leg syndrome (RLS) and attention deficit hyperactivity disorder (ADHD) in children.

 

Effect on women

In a prospective (forward-looking) study done in 1993 looking at primary care practices, it was determined that 75 percent of patients complaining of fatigue were women (BMJ 1993;307:103). Interestingly, less than 10 percent of these women had abnormal lab results when routine labs were drawn, most probably without a ferritin level. Many of them had experienced these symptoms for at least three months.

There was a recent randomized controlled trial (RCT), the gold standard of studies, that showed women who were suffering from fatigue and low or low normal ferritin levels (less than 50 ng/ml), but who did not have anemia, benefited from iron supplementation (CMAJ. 2012;184(11):1247-1254). When comparing women with these ferritin levels, many of those that were given 80 mg of oral prolonged release ferrous (iron) sulfate supplements daily saw a significant improvement in their fatigue symptoms when compared to those women who were not given iron.

Almost half the women taking iron supplements had a significant improvement in fatigue symptoms. The results were seen in a very short 12-week period. This is nothing to sneeze at, since fatigue is one of main reasons people go the doctor. Also, although this was a small study, there were 198 women involved, ranging from 18 to 53 years old.

There are caveats to these study results. There was no improvement in depression or anxiety symptoms, nor in overall quality of life. Even though it was blinded, stool changes occur when a patient takes iron. Therefore, the women taking supplements may have known. Nonetheless, the study results imply that physicians should check ferritin level, not only a CBC, when a premenopausal woman complains of fatigue. Note that all of the women in the study were premenopausal. This is important to delineate, since postmenopausal women are at much higher risk of iron overload, rather than deficiency. They are no longer menstruating and therefore do not rid themselves of significant amounts of iron.

 

Athletes

According to a recent article, athletes’ endurance may be affected by iron deficiency without anemia (Am J Lifestyle Med. 2012;6(4):319-327). Low ferritin levels are implicated, as in the previous study. Iron is important for exercise motivation and may play a role in peak mental functioning, as reported in “Iron: Nutritional and Physiological Significance.” In animal studies, iron deficiency without anemia is associated with reduction in endurance, because of a decrease in oxygen-based enzymatic activity within the cells. However, this has not been shown definitively in human athletes and remains an interesting, but yet to be proven hypothesis.

Interestingly, female endurance athletes are more likely to be affected by iron deficiency without anemia, which occurs in about 25 percent of this population, according to studies (J Am Diet Assoc. 2005;105:975–978). Low ferritin is not seen as much in male athletes. This difference in gender may be due to the fact that women not only menstruate, losing iron on a regular basis, but also their intake of dietary iron seems to be lower (J Pediatr. 1989;114:657–663).

However, male athletes are not immune. At the end of the season for high school runners, 17 percent had iron deficiency without anemia (J Adolesc Health Care. 1987;8:322–326).

Do not take iron supplements without knowing your levels of hemoglobin and ferritin and without consulting a doctor. Studies are mixed on the benefits of iron supplementation without anemia for athletes.

 

Impact on restless leg syndrome

Iron deficiency with a ferritin level lower than 50 ng/ml affects approximately 20 percent of patients who suffer from restless leg syndrome (Am Fam Physician. 2000;62(4):736). Restless leg syndrome (RLS), classified as a neurologic movement disorder, causes patients to feel like they need to move their legs, most commonly about a half hour after going to bed. In a very small study, patients with restless leg syndrome who had ferritin levels lower than 45 ng/ml saw significant improvement in symptoms within eight days with iron supplementation (Sleep Med. 2012;13(6):732-735). Before you get too excited, the caveat is that 75 percent of restless leg patients have high ferritin levels.

Ferritin levels — both high and low — may play a role in a number of diseases and symptoms. If you are suffering from fatigue, a CBC blood test may not be enough to detect iron deficiency. You may want to suggest checking your ferritin level. Though iron supplementation may help those with symptomatic iron deficiency without anemia, it is very important not to take iron supplements without the direct supervision of your physician.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Long Baseline Neutrino Experiment seeks to understand why matter triumphed over antimatter

If two armies of twins fought against each other with identical protective gear and equally fatal weapons, the result would likely be fatal for every one of them. At least, that’s how particle physicists see it when they look at the early universe.

The twins in the primordial battle are matter and antimatter. Matter includes positively charged protons and negatively charged electrons (which are also called baryons). The antimatter equivalent are negatively charged protons and positively charged electrons.

Somehow, when these two armies mixed in something akin to a soup, matter wiped out its antimatter counterpart.

But why, physicists wonder, did matter win? Could the battle, which physicists believe lasted mere microseconds, have ended the other way, or could the two sides have left nothing behind?

Physicists, including Milind Diwan of Brookhaven National Laboratory, believe neutrinos may provide the answer. Almost as plentiful in the universe as particles of light, neutrinos are so small that a trillion of them pass through our bodies each second. Not only are they harmless, they barely interact with anything else, because, while they do have mass, they are spectacularly small.

The sun, stars and even the Earth produce them and, thanks to particle accelerators, humans can, too. Diwan is part of a collaboration of 350 scientists, mostly from American universities, who are teaming up in a program called the Long Baseline Neutrino Experiment (LBNE) to use these nearly massless particles to try to understand the early triumph of matter over antimatter.

In the LBNE, the scientists hope to shoot neutrinos and antineutrinos 800 miles through the Earth — the experiment wouldn’t require any tunnels — from the Fermilab accelerator outside of Chicago to a research facility in a former gold mine, now called the Sanford Underground Research Facility in Lead, South Dakota.

The effort suffered a funding setback this past summer, when the Department of Energy praised the goals but asked the scientists to return with a plan that was affordable. The LBNE researchers broke the project up in phases. After the LBNE team made the suggested revisions, they received approval in early December from the DOE.

Diwan and his colleagues anticipate that the LBNE will provide evidence of how matter and antimatter behave differently as neutrinos make the long journey underground to a receptor in what was once the Homestake Mine, which was, up until it closed in 2002, the largest and deepest gold mine in North America.

Neutrinos have three different types, changing readily from muon to tau to electron. It is over these distances that these oscillations, as the changes are called, may help unlock the key to the asymmetry between matter and antimatter.

“If you measure their properties in this far-away detector, there will be differences,” Diwan predicts. “I suspect those differences will be quite large and … can be directly linked to the way the universe evolved in its first few microseconds” when antimatter was annihilated.

“We have been struggling to understand this miraculous event,” Diwan explained. “This is one of the key problems in all of science.”

While scientists plan to send the neutrinos on a long journey through the Earth, the researchers themselves are expecting their own long trek.

Based on the current plan, the LBNE will start producing data in 2022. By then, would-be scientists who are planning to graduate from high school this year may contribute to the research.

While that might seem like a slow build for a long range project, there are competitive time pressures.

“Japanese physicists want to perform a similar experiment with a shorter distance and Europeans want to perform a bigger experiment with almost the same experimental features,” Diwan explained. “At this point, there is agreement that in terms of planning, we are ahead of them.”

A resident of Port Jefferson Station, Diwan and his wife Sucheta, an engineer at Hauppauge-based Parker Hannifin, have a 14-year old daughter, Renuka, and a 10-year old son, Yashodhan.

His wife’s job is “much more important than mine,” he offers. Her company makes fuel gauges for jumbo jets.

As for his work, Diwan has been in the physics department at BNL since 1994. He is eager to see the LBNE project through.

“I feel very fortunate that I am working on a question that is important,” he offered. “It is extraordinary that we have the tools to actually perform this experiment.”

 

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Yet another reason to avoid red meat; focus on a plant-based diet

Iron is contained in most of the foods that we eat. It is needed for proper functioning of the body and plays an integral role in such processes as DNA synthesis and adenosine triphosphate (ATP) production, which provides energy for cells (Proc Natl Acad Sci USA. 1997;94:10919–10924). It is very important to maintain iron homeostasis, or balance.

When we think of iron, we associate it with reducing fatigue and garnering energy. In fact, many of us think of the ironman triathlons — endurance and strength come to mind. If it’s good for us, then the more we get the better right? It depends on the circumstances. But for many of us, this presumption is not grounded in reality.

Iron in excess amounts is dangerous. It may contribute to a host of diseases, including diabetes, diabetic retinopathy, age-related macular degeneration (AMD), glaucoma, Parkinson’s disease and even heart disease. These diseases are perpetuated because when we have excess iron it may cause reactive oxygen species, or free radicals, which cause breakdown of DNA and tissues, ironically, the very things that iron homeostasis tends to preserve (Clin Haematol. 1985;14(1):129).

So what helps us differentiate between getting enough iron and iron overload? It is a good question and depends on the type of iron we ingest. There are two main types: heme iron and nonheme iron. Dietary heme, or blood, iron primarily comes from red meat and is easily absorbed into the gut. Dietary nonheme iron comes from other sources, such as plants and fortified foods, which are much more difficult sources to absorb. By focusing on the latter source of dietary iron, you may maintain homeostasis, since the gut tends to absorb 1-2 mg of iron, but also excretes 1-2 mg of iron through urine, feces and perspiration.

Not only does it matter what type of iron we consume, but also the population that ingests the iron. Age and gender are critical factors. Let me explain. Women of reproductive age, patients who are anemic and children may require more iron. However, iron overload is more likely to occur in men and postmenopausal women because they cannot easily rid the body of excess iron.

Let’s investigate some of the research that shows the effects of iron overload on different chronic diseases.

Impact on diabetes

In a recent meta-analysis (a group of 16 studies), results showed that both dietary heme iron and elevated iron storage (ferritin) may increase the risk of type 2 diabetes (PLoS One. 2012;7(7):e41641). When these ferritin levels were high, the risk of diabetes increased 66 percent to 129 percent. With heme iron, the group with the highest levels had a 39 percent increased risk of developing diabetes. There were over 45,000 patients in this analysis. You can easily measure ferritin with a simple blood test. Also these levels are modifiable through blood donation and avoidance of heme iron. Thus, reducing the risk of iron overload.

Diabetic retinopathy

Diabetic retinopathy is a complication of diabetes that occurs when glucose, or sugar, levels are not tightly controlled. It affects the retina, or the back of the eye. Iron excess and its free radicals can have detrimental effects on the retina (Methods Enzymol. 1990;186:1-85). This is potentially caused by oxidative stress resulting in retinal tissue damage (Rev Endocr Metab Disord. 2008;9(4):315-327).

So how is iron related to uncontrolled glucose levels? In vitro studies (preliminary lab studies) suggest that high glucose levels may perpetuate the breakdown of heme particles and subsequently raise the level of iron in the eye (Biophysical Chemistry. 2003;105:743-755). In fact, those with diabetic retinopathy tend to have iron levels that are 150 percent greater than those without the disease (Indian J Ophthalmol. 2004;52:145-148). Diets that are plant-based and, therefore, nutrient-dense are some of the most effective ways to control glucose levels and avoid diabetic retinopathy.

Age-related macular degeneration (AMD)

Continuing with the theme of retinal damage, excessive dietary iron intake may increase risk of AMD according to the Melbourne Collaborative Cohort Study (Am J Epidemiol. 2009;169(7):867-876). AMD is the number one cause of blindness for people 65 and older. People who consumed the most iron from red meat increased their risk of early AMD by 47 percent, however, due to the low incidence of advanced AMD among study participants, the results for this stage were indeterminate.

I have been frequently asked if unprocessed red meat is better than processed meat. Well, this study showed that both types of red meat were associated with an increased risk. This was a large study with over 5,000 participants ranging in age from 58 to 69.

Cardiovascular disease

Though we have made considerable headway in reducing the risk of cardiovascular disease and even deaths from these diseases, there are a number of modifiable risks that need to be addressed. One of these is iron overload. In the Japan Collaborative Cohort, results showed that men who had the highest amount of dietary iron were at a 43 percent increased risk of stroke death, compared to those who ate the least amounts. And overall increased risk of cardiovascular disease death, which includes both heart disease and stroke, was increased by 27 percent in men who consumed the most dietary iron. There were over 23,000 Japanese men who were between the ages of 40 to 79 that were involved in this study.

In conclusion, we should focus on avoiding heme iron, especially for men and postmenopausal women. Too much iron creates a plethora of free radicals that damage the body. Therefore, the best way to circumvent the increased risk of chronic diseases with iron overload is prevention. Significantly decreasing red meat consumption and donating blood on a quarterly basis, assuming that one is not anemic, may be the most effective strategies for not falling into the trap of iron overload.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

 

Milind Diwan

Continued from page B15

“If you measure their properties in this far-away detector, there will be differences,” Diwan predicts. “I suspect those differences will be quite large and … can be directly linked to the way the universe evolved in its first few microseconds” when antimatter was annihilated.

“We have been struggling to understand this miraculous event,” Diwan explained. “This is one of the key problems in all of science.”

While scientists plan to send the neutrinos on a long journey through the Earth, the researchers themselves are expecting their own long trek.

Based on the current plan, the LBNE will start producing data in 2022. By then, would-be scientists who are planning to graduate from high school this year may contribute to the research.

While that might seem like a slow build for a long range project, there are competitive time pressures.

“Japanese physicists want to perform a similar experiment with a shorter distance and Europeans want to perform a bigger experiment with almost the same experimental features,” Diwan explained. “At this point, there is agreement that in terms of planning, we are ahead of them.”

A resident of Port Jefferson Station, Diwan and his wife Sucheta, an engineer at Hauppauge-based Parker Hannifin, have a 14-year old daughter, Renuka, and a 10-year old son, Yashodhan.

His wife’s job is “much more important than mine,” he offers. Her company makes fuel gauges for jumbo jets.

As for his work, Diwan has been in the physics department at BNL since 1994. He is eager to see the LBNE project through.

“I feel very fortunate that I am working on a question that is important,” he offered. “It is extraordinary that we have the tools to actually perform this experiment.”

 

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Councilman Steve Fiore-Rosenfeld and Cumsewogue Historical Society President Jack Smith on a recent trip to the Gentlemen’s Driving Park in Terryville. Photo by Elana Glowatz

It’s been some 130 years, but the half-mile loop the horses raced is still visible, though it’s coated in layers of leaves.

The path in the woods is all that remains of the Gentlemen’s Driving Park in Terryville, where local bettors once gathered to watch men race in carts called sulkies behind horses, or compete on bicycles or even on foot.

Cumsewogue Historical Society President Jack Smith said the track is one of the last known of its kind in the Northeast. He discovered the hidden gem a couple of years ago using Google Earth: After hearing rumors that such a track existed off Canal Road, Smith looked at an aerial view of the hamlet and quickly noticed a faint oval shape cut into the woods. He visited the spot with his wife, Pam, the next day and walked the length of the track.

Brookhaven Town has already acquired about half of the 11-acre plot since Smith alerted Councilman Steve Fiore-Rosenfeld about the track and an effort to preserve it began two years ago. Fiore-Rosenfeld (D-East Setauket) said the other half is owned entirely or almost entirely by one family, and the town is discussing an acquisition with them so it can preserve the site.

Starting in the 1880s, horses would race in heats throughout an entire afternoon at the Terryville site and the attendees would gamble modest amounts. The horses would take a few minutes to go counterclockwise twice around the half-mile track, which was part of a larger circuit of driving parks. It was adjacent to the Comsewogue stables, of which Robert L. Davis, a well-known area horse trainer, took ownership. The stables are now the Davis Professional Park.

“This was not some backwoods, good ol’ boy, local kind of thing. This was a big deal for its time,” Smith said. He called it the NASCAR of its day and said, “This was an era when the horse was king. The horse was everything to everyone,” including transportation, sport and work.

 A ticket to a race at the Gentlemen’s Driving Park in Terryville on July 4, 1892. Photo by Elana Glowatz

A ticket to a race at the Gentlemen’s Driving Park in Terryville on July 4, 1892. Photo by Elana Glowatz

Eventually, however, the excitement petered out — the automobile was likely the track’s downfall.

“People were more enamored and more excited with racing automobiles than they were with racing horses,” Smith said.

At least through the mid-1950s, local kids raced jalopies around the 25-foot-wide track, which helped preserve it, preventing it from becoming completely overgrown.

“A lot of this has just been pure luck,” Smith said, referring to the fact that the track was still visible and he was able to find it. He pointed out that if the Google Earth satellite image had been taken not in the winter but during the summer, when the trees had leaves, he would not have been able to see through them to the track beaten into the ground and would not have known it was there.

It was also by luck that Smith found a pair of Victorian-era field glasses. He had been searching for horseshoes with a metal detector near the finish line on the west side of the track when he came upon them. They were broken, likely dropped near the finish line and trampled.

Smith said he cleaned them using toothbrushes and compressed air.

Other artifacts he has are a ticket from a July 4, 1892, race and news articles that mention the track. He does not have photos of the track in use, but he believes they are out there somewhere.

Fiore-Rosenfeld said during a visit to the track that one reason he is interested in preserving the driving park is to make a place where residents can recreate. With it abutting the Woodcrest Estates apartments, he said, it is a natural place to create a public space.

The councilman said, “It’s a miracle that it’s still here” and it’s mostly whole.

In addition to the track being overgrown, a Long Island Power Authority right of way cuts into its southwestern curve. Hurricane Sandy also tore some trees out of the ground, so there are a few obstacles in the way of those who wish to walk it.

As the town waits to acquire the remainder of the track to ensure its future, Smith pieces together its history. A stump could have been part of a guard rail on the border of the track and the infield — inside the racing loop — was clear of trees so viewers could see across to the other side.

It’s hard to picture the Victorian-era scene, Smith said, “but these were local guys and horse racing was their passion.”

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With ‘veto power,’ chandelier cells are theorized to keep order in the nervous system

Someone whose opinion he trusted told him he was going in the wrong direction. Every indication for years suggested success was as elusive four years after failing as it had been during his first unsuccessful attempt.

“It didn’t look very good,” confided Z. Josh Huang, a scientist at Cold Spring Harbor Laboratories. In those first years, he wondered if he should do something else.

Sticking with it, however, paid off, especially in the last few years. Huang and his team have made important discoveries about a type of neuronal cell in the cerebral cortex called chandelier cells.

Huang has not only been able to label these cells and watch them in action, but he has also figured out where and when they develop, before they move to their position inside the cerebral cortex (the part of the brain that is responsible for processing sensory information, for thinking and reasoning and for directing movement).

These chandelier cells are likely to be the most powerful cells in the cerebral cortex. They are only found in the cerebral cortex and humans appear to have more of them than other mammals, including monkeys and mice.

They got their name from the way their branches jut out from the main body of the cell. Their axon arbor looks like a chandelier light. Researchers believe they serve an important role in keeping order in the nervous system, quieting other nerve cells from vying for attention all at once.

Francis Crick, who won the Nobel Prize in 1962 for discovering the double-helical nature of DNA with James Watson, first suggested four decades ago that these cells had “veto” power, according to Huang.

“When the chandelier cell ‘speaks,’ it is like the president. All these other cells will be quiet, regardless of their urge to speak,” Huang explained.

While that metaphor hasn’t been proven precisely yet, Huang said the evidence is mounting to support Crick’s original contention. Huang’s research is testing this specific assertion.

Some medical challenges, including schizophrenia and epilepsy, have been linked to problems with chandelier cells.

“A variety of molecular markers were altered or reduced in the pre-frontal cortex in schizophrenia patients,” Huang explained. “That has been a very reliable finding from many labs.”

The possible explanation is that if these cells are compromised, the excitatory neurons will not function coherently. Some treatments are looking at ways to boost the output of the chandelier cells by enhancing the so-called GABA receptor.

GABA, named for the neurotransmitter gamma amino-butyric acid, is the only inhibitory neurotransmitter in the brain. GABAergic inhibitory cells, including chandelier cells, organize neuronal populations into groups that guide behavior.

Some of Huang’s early work, which proved so challenging, involved following the pathway of these chandelier cells, which develop outside the cortex and move to their central locations during development. When he started looking for ways to track these cells, scientists were using dyes, which weren’t reliable.

Huang built a better animal model system to track these cells. Now, he can see them every time they are active.

“You can activate them or silence them and see the consequence,” he explained. “It’s extremely powerful.”

In the latest finding, Huang discovered that these important cells start out in a region of the embryonic brain he called the ventral germinal zone. This part of the brain didn’t have a name because it wasn’t clear what types of cells it produced.

Chandelier cells are “born” after another region that is responsible for producing different neurological inhibitor cells disappears.

Huang’s work was published last month in the journal Science. Earlier this year, he also served as co-author on three papers in Nature, another prestigious scientific journal.

“This has been an amazing year,” he concedes. “It took us four years to fail, to build this experimental system” to make these findings.

Huang, who has been at Cold Spring Harbor for a dozen years, lives in Woodbury with his wife May Lim, a radiation oncologist in Queens, and his two daughters, Vivien, 12, and Julienne, 8.

In graduate school, he added the first name “Josh” because it has some phonetic resemblance to his Chinese first name.

In terms of his research, Huang said he received supportive advice from colleagues and advisors along the way, much of which he took to heart during the years that weren’t quite as productive as this one.

“What I came away with is to do something that is very fundamentally important and to stay the course,” he offered.

 

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