People have increasing opportunities to participate in genetic testing that can indicate their range of risk for developing a disease. Receiving these results does not appreciably drive up or diminish test recipients’ demand for potentially costly follow-up health services, according to a study performed by researchers at the National Institutes of Health and colleagues at other institutions.

The study in the May 17, 2012 early online issue of Genetics in Medicine was done by investigators with the Multiplex Initiative, a multi-center collaborative initiative involving investigators from the National Institutes of Health’s Intramural Research Program, Group Health Cooperative in Seattle, and the Henry Ford Health System in Detroit [1].

The tests are available from a growing number of commercial producers, and health care providers have been uncertain whether people who received information only about risk would follow up by demanding diagnostic testing to monitor for predicted illnesses.

The study is the first to use electronic health records (EHR) — rather than self-reported behavior — to measure the impact of genetic testing on the subsequent consumption of health services by commercially insured, healthy adults. Self reports, which can be affected by memory lapses and other problems, tend to be less accurate.

Dan Kastner, M.D., Ph.D., scientific director and head of the National Human Genome Research Institute’s (NHGRI) Division of Intramural Research, said:

We need to understand the impact of genomic discoveries on the health care system if these powerful technologies are going to improve human health. We are still learning how to integrate new genomic discoveries into clinical care effectively and efficiently.

Colleen McBride, Ph.D., chief of NHGRI’s Social and Behavioral Research Branch, said:

There are a lot of unanswered questions about how genetic test results can be used to guide people towards making positive lifestyle and health behavior changes. This study goes a long way towards bringing data to these debates and shows that people are not likely to make inappropriate demands of health delivery systems if they are properly informed about the limitations of genetic tests.

Genetic tests, such as those used in this study, can detect common variants of genes associated with modest alterations in the chances of developing particular diseases. The term multiplex refers to simultaneously performing multiple genetic tests on a single blood sample.

The study included 217 healthy people between the ages of 25 and 40 who elected to participate in genetic susceptibility testing offered by their health plan. The researchers analyzed healthcare usage by the participants in the 12 months before genetic testing and the 12 months following the testing. They also compared the test group’s behavior with a group of about 400 similar plan members who declined the testing offer.

The researchers counted the number of physician visits and laboratory tests or procedures the people received, particularly those services associated with four of the eight conditions tested by the multiplex panel. Most of the procedures or screening tests that were counted are not among those currently recommended for people in this age group who don’t have symptoms. The researchers found that participants in genetic testing did not change their overall use of healthcare services compared with those not tested.

All of the individuals who elected to undergo the multiplex test carried at least one at-risk genetic marker, with the majority carrying an average of nine at-risk variants. The tests performed for the Multiplex Initiative include a set of genetic variants reliably associated with an increase in disease risk and for which some corrective health behavior has been shown to prevent illness.

Having a risk version of one of the 15 genes on the multiplex genetic test does not mean that a person is certain to get the condition — only that he or she might have a slightly greater chance of developing the health condition, explained Dr. McBride. There are many things other than genetics that contribute to the risk of common diseases, including lifestyle factors such as diet, exercise, smoking and sun exposure.

Co-author Lawrence C. Brody, Ph.D., chief of NHGRI’s Genome Technology Branch, said:

Much is written about using genetics to personalize health care. Some think that this new generation of genetic tests will be a very positive addition to medicine; others believe they have the potential to make things worse.

Dr. Brody designed the panel of genetic tests used in the Multiplex Initiative, consisting of 15 genetic markers that play roles in eight common diseases, including type 2 diabetes, coronary heart disease, high blood cholesterol, high blood pressure, osteoporosis, lung cancer, colorectal cancer and melanoma.

The Multiplex Initiative was launched in May 2007 by the NHGRI Division of Intramural Research and the National Cancer Institute, both at NIH, along with Group Health Cooperative in Seattle and the Henry Ford Health System in Detroit. For the first two years of the study, the investigators accumulated data from 2,000 Detroit area residents who were offered a multiplex genetic test for eight common conditions.

Once enrolled, participants were asked to review information online about the multiplex genetic test and to decide whether they were interested in taking the test. Those who agreed to genetic testing met with a research educator, who provided more information about the risks and benefits of testing, and obtained the patient’s written consent. Test results were mailed to participants. Trained research educators called the participants to help them interpret and understand their results. The study also included follow-up interviews with participants three months after they received their results.

The Multiplex Initiative study team included Drs. McBride and Brody; Andy Baxevanis, Ph.D., associate investigator in NHGRI’s Genome Technology Branch; Sharon Hensley Alford, Ph.D., M.P.H., epidemiologist at the Henry Ford Health System; Eric B. Larson, M.D., M.P.H., executive director of Group Health Research Institute; and Robert Reid, M.D., Ph.D., associate investigator at Group Health Research Institute.

For more information about the Multiplex Initiative, go to multiplex.nih.gov.

Source: NIH News

References

1. Reid et al. Association between health-service use and multiplex genetic testing. Genet Med. 2012 May 17. doi: 10.1038/gim.2012.52. [Epub ahead of print]
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In early April, the Washington State Department of Health declared a pertussis (whooping cough) epidemic. The state has seen over 1,200 cases so far this year, and officials suspect there will be at least another few thousand cases before year’s end; levels that haven’t been seen in over 60 years. In response to the declared epidemic, the state has been working to make vaccines more accessible to uninsured patients. Additional response measures have included urging employers to encourage employee vaccination and instructing hospitals to vaccinate new parents.

Washington State Secretary of Health, Mary Selecky, said [1]:

We’re very concerned about the risk to infants, especially because of how quickly whooping cough is spreading. Whooping cough can be life threatening for infants, and they’re too young to get enough doses of vaccine to be protected. That’s why we want everyone else to make sure they’re vaccinated against whooping cough.

Pertussis is a very contagious respiratory infection caused by the Bordatella pertussis bacterium. Infected individuals experience severe, long-lasting coughing fits that leave them gasping for air. The prolonged coughing empties the lungs of air, which causes a gasping inhale that results in the characteristic “whooping” sound associated with pertussis. The disease is spread through the air; casual contact with an infected person is often sufficient to cause infection. Infants are particularly susceptible, and are also more likely than adults to become dangerously ill if infected; more than 50% of infants with pertussis require hospitalization, and of those, one in 100 will die.

Symptoms of early pertussis are similar to those of a cold, and last 1-2 weeks. The next stage of pertussis is more serious, and can last up to 10 weeks. It’s during this second stage that the paroxysmal coughing occurs. The coughing is often so protracted and violent that it results in vomiting and exhaustion. It takes an additional 2-3 weeks to recover from the illness, resulting in a total illness duration of up to three months.

There is a vaccine available for pertussis, which is generally given in combination with the vaccines for tetanus and diphtheria. The combined vaccine is called the TDaP (for adults) or the DTaP (for children). Children require a series of 5 DTaP shots starting at age 2 months to develop initial immunity; an incomplete series of shots does not provide adequate protection. Adults need a TDaP booster once every 10 years. Making sure adults are up to date on vaccination is a critical public health measure, as it helps to protect infants with whom they come into contact who are too young for immunization or have not yet completed their immunizations.

Reference

1. Whooping cough case count passes 1,000 cases in WA — epidemic continues. Washington State Department of Health. 2012 Apr 24.

More than 50 years ago, Mental Health America started the tradition of celebrating “May is Mental Health Month” to raise awareness of mental health conditions and mental wellness for all. For 2012, Mental Health America is addressing mental health conditions and mental wellness through two themes.

Do More for 1 in 4

Do More for 1 in 4 is a call to action for Americans to help the one-in-four American adults in their lives who are living with a diagnosable mental health condition. While mental health and substance conditions are common, they are extremely treatable and individuals go on to recover and lead full and productive lives.

Many people living with a mental health condition–as high as 50 percent–never seek or receive help due to shame, lack of information, cost or lack of health insurance coverage. Many people may be hesitant to ask for help or don’t know where to find it. But there are many community and national resources that can help people find support and treatment. [Download the Do More For 1in4 Toolkit from Mental Health America]

Does your 1 in 4 have AD/HD?

Although the condition is most often associated with children, Attention Deficit Hyperactivity Disorder (ADHD) can continue into adulthood for many people. Indeed, there are some adults who don’t know that they have the disorder. Adults who are living with the condition, and especially those who are undiagnosed and untreated, may experience a number of problems, some of which stem directly from the disorder and others that are the result of associated adjustment patterns.

The symptoms of ADHD can be constant or variable and situational. Some people with ADHD can concentrate if they are interested or excited. Others have difficulty concentrating under any circumstances. Some people eagerly seek stimulation, while others avoid it. Some people become hostile, ill-behaved and, later, antisocial; others may become fierce people-pleasers. Some people are outgoing, and others, withdrawn.

Symptoms of an adult with ADHD may include distractibility, chronic lateness, chronic boredom, anxiety, depression and mood swings. Some tips that adults with ADHD have found useful include using internal structure like date books, lists, notes to oneself, color coding, routines, reminders and files; choosing “good addictions,” for example, select exercise or other healthy activities for a regular structured “blow-out” time; becoming educated and an educator–read books, talk to professionals, talk to other adults who have ADHD, and let people who matter know about personal strengths and weaknesses related to ADHD.

Does Your 1 in 4 Have an Anxiety Disorder?

Most people experience feelings of anxiety before an important event such as a big exam, business presentation or first date. Anxiety disorders, however, are illnesses that cause people to feel frightened, distressed and uneasy for no apparent reason. Left untreated, these disorders can dramatically reduce productivity and significantly diminish an individual’s quality of life.

Anxiety disorders are among the most common mental illnesses in America; more than 40 million people are affected by these debilitating illnesses each year. Anxiety disorders include panic disorder, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD), phobia and generalized anxiety disorder.

• Panic disorder is characterized by panic attacks, which are sudden feelings of extreme fear that strike repeatedly without warning. Physical symptoms include chest pain, heart palpitations, shortness of breath, dizziness, abdominal discomfort, feelings of unreality, and fear of dying.
• Obsessive-compulsive disorder is characterized by repeated, intrusive and unwanted thoughts or rituals that seem impossible to control.
• Persistent symptoms of Post-Traumatic Stress Disorder occur after experiencing a traumatic event such as war, rape, child abuse, natural disasters, or being taken hostage. Nightmares, flashbacks, numbing of emotions, depression, and feeling angry, irritable, distracted and being easily startled are common.
• Phobia is an extreme, disabling and irrational fear of something that really poses little or no actual danger; the fear leads to avoidance of objects or situations and can cause people to limit their lives.
• Generalized anxiety disorder is characterized by chronic, exaggerated worry about everyday routine life events and activities, lasting at least six months; almost always anticipating the worst even though there is little reason to expect it. Generalized anxiety disorder is often accompanied by physical symptoms, such as fatigue, trembling, muscle tension, headache, or nausea.

Treatments, largely developed through studies conducted by research institutions, are extremely effective and often combine medication or specific types of psychotherapy.

Does Your 1 in 4 Have Bipolar Disorder?

Bipolar disorder, also known as manic depression, is an illness involving one or more episodes of great excitement and depression. The illness causes a person’s mood to swing from excessively “high” and/or irritable to sad and hopeless, with periods of a normal mood in between.

Bipolar disorder typically begins in adolescence or early adulthood and continues throughout life. It is often not recognized as an illness and people who have it may suffer needlessly for years. Bipolar disorder can be extremely distressing and disruptive for those who have this disease, their spouses, family mem- bers, friends and employers. Although there is no known cure, bipolar disorder is treatable, and recovery is possible. Individuals with bipolar disorder have successful relationships and meaningful jobs. The combi- nation of medications and psychotherapy helps the vast majority of people return to productive, fulfilling lives.

Bipolar disorder is often difficult to recognize and diagnose. It causes a person to have a high level of energy, unrealistically expansive thoughts or ideas, and impulsive or reckless behavior. These symptoms may feel good to a person, which may lead to denial that there is a problem.

Though there is no cure, treatment of bipolar disorder is critical for recovery. A combination of medica- tion, professional help and support from family, friends and peers help individuals with bipolar disorder stabilize their emotions and behavior. It is suggested that those with bipolar disorder receive guidance, education and support from a mental health professional to help deal with personal relationships, main- tain a healthy self-image and ensure compliance with his or her treatment.

Does Your 1 in 4 Have Depression?

Clinical depression is one of the most common mental illnesses, and affects more than 19 million Americans each year. This includes major depressive disorder, manic depression and dysthymia, a milder, longer-lasting form of depression.

Unfortunately, although about 70 percent of people with depression have a full remission of the disorder with effective treatment, fewer than half of those suffering from the illness seek treatment. Too many people resist treatment because they believe depression isn’t serious, that they can treat it themselves or that it is a personal weakness rather than a serious medical illness.

Symptoms of clinical depression include  persistent sad, anxious or “empty” mood, sleeping too much or too little, waking in the middle of the night or early morning, restlessness, irritability, difficulty concentrating, difficulty remembering or making decisions, fatigue or loss of energy, feeling guilty or worthless, thoughts of suicide or death.

Clinical depression is very treatable, with more than 80% of those who seek treatment showing improvement [1]. The most commonly used treatments are antidepressant medication, psychotherapy or a combination of the two.

Healing Trauma’s Invisible Wounds

The second theme, Healing Trauma’s Invisible Wounds, focuses on the devastating impact of traumatic events on physical, emotional, and mental well-being, and how therapeutic techniques based in neuroscience can mitigate these effects and create dramatic changes in people’s lives. It centers around asking the person-based question: “What happened to you?” [Download the Healing Trauma's Invisible Wounds Toolkit from Mental Health America]

A traumatic event–which threatens our lives, our safety or our personal integrity–can profoundly affect a person. Most people think that “trauma” refers to physical trauma that occurs as a result of a car accident or assault, but it’s much more than that. Trauma includes interpersonal violence such as abuse and bullying; social violence such as war and terrorism; natural disasters and accidents; serving in combat; stressors such as poverty and humiliation; and childhood trauma, which includes physical, emotional and sexual abuse, and difficult family relationships.

Trauma takes a huge toll on lives and health. It is the leading cause of the death of children in the U.S. The effect of trauma on productive life years lost exceeds that of any other disease. The economic cost of 50 million injuries in the year 2000, alone, was $406 billion. This includes estimates of $80 billion in medical care costs, and $326 billion in productivity losses. And the predicted cost to the health care system from interpersonal violence and abuse ranges between $333 billion and $750 billion annually, or nearly 17 to 37.5 percent of total health care expenditures.

When children or adults respond to traumas with fear, horror and/or helplessness, the extreme stress is toxic to their brains and bodies, and overwhelms their ability to cope. While many people who experience a traumatic event are able to move on with their lives without lasting negative effects, others may have more difficulty managing their responses to trauma.

Unresolved trauma can manifest in many ways, including anxiety disorders, panic attacks, flashbacks, obsessive-compulsive behaviors, Post-Traumatic Stress Disorder, addictions, self-injury and a variety of physical symptoms. Trauma increases health-risk behaviors such as overeating, smoking, alcohol abuse, and risky sex. Trauma survivors can also become perpetrators themselves. Unaddressed trauma can also significantly increase the risk of mental and substance use disorders, suicide, chronic physical ailments, as well as premature death.

The good news is that the invisible wounds caused by traumatic experiences can heal. With the proper treatment, support and self-care, recovery is possible for everyone.

References

1. National Institute of Mental Health, D/ART Campaign, “Depression: What Every Woman Should Know,” (1995). Pub No. 95-3871.

Scientists at the Children’s Hospital Oakland Research Institute (CHORI) Nutrition & Metabolism Center recently announced that they have developed a low-calorie, high-fiber, fruit-based vitamin and mineral nutrition bar called the CHORI-bar, which improves biomarkers linked to risk of cardiovascular disease, cognitive decline, and associated decline in antioxidant defenses.

After years of studying the interactions of vitamins and minerals with metabolic processes, Dr. Bruce Ames, professor of Biochemistry and Molecular Biology, University of California, Berkeley, and a senior scientist at CHORI, became convinced that modest deficiencies could be contributing to metabolic imbalances that increase risk of diseases associated with obesity and aging, such as diabetes, cancer, and heart disease. In 2006, Dr. Ames published a key article in the journal Proceedings of the National Academy of Sciences entitled ‘Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage’ [2]. In the article, Dr. Ames proposed the Triage theory, which postulated that DNA damage and late onset disease are consequences of a ‘triage allocation mechanism’ developed during evolution to cope with periods of micronutrient shortage.

Simply put, micronutrients, when scarce, are used for short-term survival at the expense of long-term survival.

The Triage theory helps explain why the quarter of the population that eats the fewest fruits and vegetables has double the cancer rate for most types of cancer compared with the quarter that eats the most fruits and vegetables.

In 2003, Dr. Ames and his colleague Mark Shigenaga, PhD, whose research focuses on the impact of food on gut function, began development of the CHORI-bar, an economical, low calorie, food supplement that could restore metabolic balance. Dr. Ames assembled a team of scientists and a started a collaboration with the Processed Foods Unit at the United States Department of Agriculture to assist in the production of a tasty and nutritious bar.

Intestinal health is now widely recognized to be an important determinant of overall health. Food components that benefit gut health, such as certain soluble fibers and polyphenols, were included in the bar along with DHA, insoluble fiber and a number of other ingredients, all aimed at helping to restore optimal nutrition. Since the project began, a series of bar formulations were developed, and to date 11 small pilot trials have been conducted to refine components and improve taste. Improvements are continuing to expand the number of disease risk biomarkers favorably impacted by the bar.

The first research report on the CHORI-bar appears in the August 2012 issue of the FASEB Journal (the Journal of the Federation of American Societies for Experimental Biology) [3]. The report details the results of a  2-week trial in 25 healthy adults with varied ages and body mass index (BMI). Participants ate two bars each day for 2-weeks. Changes in cardiovascular disease and diabetes risk biomarkers were measured at the end of the 2-week period and compared to levels taken at the beginning of the trial prior to CHORI-bar consumption.

A number of other assays (i.e. tests) were conducted to quantify specific compounds and metabolites, providing for a more more in depth look at biomarkers and clues to mechanisms underlying effects of the CHORI-bar.

The investigators found that following the 2-week program, plasma high density lipoprotein (HDL) (commonly called “good cholesterol”) increased 28%. HDL is a cholesterol transporter that carries cholesterol from cells in the body to the liver, where it is then excreted. Total plasma homocysteine decreased 19%. Homocysteine is a a non-protein amino acid that causes a number of issues, including endothelial damage and dysfunction (endothelial cells line the circulatory system, from small capillaries to veins and arteries to the heart) and free radical formation. Increased HDL and decreased homocysteine are associated with decreased risk of cardiovascular disease and cognitive decline. Total glutathione levels increased 20%. Increased glutathione reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed.

The metabolic changes are striking for two reasons. First, significant results were observed even though the trial lasted only two weeks, and two, comparable benefits were seen across a range of baseline BMIs and metabolic parameters. The researchers suggest that longer-term trials may result in a broader spectrum of favorable biomarker changes.

References

1. New Nutrition Bar Developed by CHORI Scientists Improves Metabolic Biomarkers Linked to Cardiovascular Disease, Cognitive Decline, and Anti-Oxidant Defenses in Only Two Weeks. Children’s Hospital & Research Center Oakland. 2012 May 10.
2. Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17589-94. Epub 2006 Nov 13.
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3. Mietus-Snyder et al. A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial. FASEB J. 2012 May 1. [Epub ahead of print]
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The National Institutes of Health recently unveiled a collaborative program that will match researchers with a selection of pharmaceutical industry compounds to help scientists explore new treatments for patients. NIH’s new National Center for Advancing Translational Sciences (NCATS) has partnered initially with Pfizer, AstraZeneca, and Eli Lilly and Company which have agreed to make dozens of their compounds available for this initiative’s pilot phase.

Health and Human Services Secretary Kathleen Sebelius said:

Americans are eagerly awaiting the next generation of cures and treatments to help them live longer and healthier lives. To accelerate our nation’s therapeutic development process, it is essential that we forge strong, innovative, and strategic partnerships across government, academia, and industry.

In recent years, researchers have succeeded in identifying the causes of more than 4,500 diseases. But it has proven difficult to turn such knowledge into new therapies; effective treatments exist for only about 250 of these conditions. NCATS was established last year to help address this gap. It supports rigorous scientific research designed to reengineer elements of the development pipeline to move basic research findings into new treatments for patients.

Some compounds do not prove effective for the specific use for which they were developed; however, if additional research is conducted, they may succeed for a different therapeutic use. A prime example of a compound that did not prove effective for its initial use but succeeded for a different use is azidothymidine (AZT), which failed to show efficacy against cancer, but was later found to be the first medicine effective against HIV, the virus that causes AIDS.

NIH Director Francis S. Collins, M.D., Ph.D., said:

Clearly, we need to speed the pace at which we are turning discoveries into better health outcomes. NIH looks forward to working with our partners in industry and academia to tackle an urgent need that is beyond the scope of any one organization or sector.

The initiative, Discovering New Therapeutic Uses for Existing Molecules, will direct researchers’ attention to a part of the therapeutic pipeline that traditionally has been difficult for them to access: compounds that already have cleared several key steps in the development process, including safety testing in humans. The President’s fiscal year 2013 budget proposed $575 million for NCATS, of which approximately $20 million total will be provided to support research grants of up to three years duration for pre-clinical and clinical feasibility studies.  These studies will test more than 20 compounds from industry partners for their effectiveness against a variety of diseases and conditions. The companies will provide the researchers with access to the compounds and related data.

The pilot program incorporates innovative template agreements designed to streamline the legal and administrative process for participation by multiple organizations. These template agreements reduce time, cost, and effort, as well as allow greater participation than traditional partnerships.

The templates also provide a roadmap for handling intellectual property used in or developed through the program. Participating industry partners will retain the ownership of their compounds, while academic research partners will own any intellectual property they discover through the research project with the right to publish the results of their work.

For this pilot program, NIH is excited to have three participating companies. Additional companies may join and contribute their compounds for further investigation.

For more details about this program please see Notices (NOI and RFI) or visit www.ncats.nih.gov/research/reengineering/rescue-repurpose/therapeutic-uses/therapeutic-uses.html.

Quotes from representatives from participating companies:

Pfizer:
“Pfizer has a rich history of partnering with the academic and public sectors to discover and develop innovative medicines,” said Rod MacKenzie, Ph.D., group senior vice president, head of Pfizer PharmaTherapeutics Research and Development. “We believe that participating in this unique program, and making well researched molecules available to NIH’s broad network of researchers, is another important step in advancing a vibrant biomedical ecosystem.”

AstraZeneca:
“AstraZeneca strives to realize the full potential of its project portfolio by collaborating with the best clinical and pre-clinical research experts worldwide, leaving no stone unturned in our search for new and effective medicines,” said Menelas Pangalos, Ph.D., executive vice president, Innovative Medicines, AstraZeneca. “Partnering across government, academia andindustry is a critical way to spur additional scientific innovation and the delivery of new treatments for people who desperately need them.”

Eli Lilly and Company:
“We are pleased to see the significant progress made to date by the newly established NCATS under Dr. Collins’ leadership, especially given that we share a similar mission of speeding the delivering of innovative medicines to the patients who are waiting,” said Jan Lundberg, Ph.D., executive vice president, science and technology, and president, Lilly Research Laboratories. “Discovering and developing new medicines, regardless of the therapeutic area being studied, is a complex and expensive process and we look forward to collaborating with the NIH and academia for the benefit of the patients we all serve.”

Source: NIH News

Question: I’ve heard that nitrates in food are dangerous and that I should avoid them. What are nitrates, why are they a problem, and what foods contain them?

Answer: Nitrates are salts that contain the nitrate ion, which is a negatively charged particle made up of the elements nitrogen and oxygen. The most common nitrate salt is sodium nitrate. Another class of compounds, called nitrites, are closely related to the nitrates. Like nitrates, nitrites are salts. They contain the nitrite ion, which — like nitrate — is negatively charged and made up of the elements nitrogen and oxygen. The suffix -ite or -ate indicates a lesser or greater quantity of oxygen. For example, NO₂^? is nitrite, while NO₃^? is nitrate. Nitrate and nitrite are commonly added to foods as preservatives, because they help to prevent bacterial growth. Specifically, nitrate and nitrite inhibit the growth of Clostridium Botulinum, the bacterium which causes botulism. It is also gives cured meats that nice pink color and depth of flavor.

The reason nitrates are a problem in food is that the human body can convert them into nitrites. Nitrites (whether formed from nitrate or ingested) can then react with a class of compounds called secondary amines. Amino acids — the building blocks of protein — are secondary amines. Because protein is a major structural and functional component of every body cell, there is no shortage of secondary amines in the body. When nitrites react with secondary amines, the resulting compounds are called nitrosamines. These are carcinogenic — they cause cancer — in animals [1], and strong evidence suggests they’re carcinogenic in humans as well. While the Environmental Protection Agency (EPA)  doesn’t regulate the amount of nitrate and nitrite in food, they do make recommendations regarding consumption. The EPA suggests limiting nitrate and nitrite consumption to 1.6 mg/kg/day and 0.1 mg/kg/day respectively.

Nitrates and nitrites are also associated with methemoglobinemia, or “blue baby syndrome.” Because of their small size, infants under 6 months of age are most susceptible to this condition, which occurs when nitrites react with hemoglobin. Hemoglobin is the blood protein that carries oxygen to the tissues, and methemoglobin, the product of the reaction with nitrite, isn’t an efficient oxygen carrier. Generally speaking, infants who get blue baby syndrome have been exposed to excessive amounts of nitrate and nitrite in drinking water, which is most commonly the result of manure runoff getting into the water supply. Municipalities track nitrate and nitrite in the water and will issue “blue baby warnings” if levels get too high for safety.

While nitrates and nitrites are added to certain foods — especially bacon, ham, and lunch meat — as preservatives, there are natural sources of these compounds as well. Many vegetables, for instance, are nitrate-rich, particularly lettuce, spinach, beets and celery [2,3]. However, vegetables contain primarily nitrates as opposed to nitrites. While the human body can convert the former into the latter (nitrites being responsible for the disturbing chemistry), the conversion is very inefficient in adults. As such, vegetables are not a major source of nitrites. There is absolutely no reason to limit vegetable consumption out of concern for nitrates and nitrites. The most significant source of nitrites in the average diet is processed or cured meat. Reducing cured meat consumption to approximately three meals a week while maintaining a normal vegetable consumption is a very reasonable strategy for managing nitrate and nitrite intake.

Pregnant women may be advised to avoid cured meat altogether; this is partly due to the nitrates and nitrites, and is partly due to the fact that lunch meat can be contaminated with bacteria that are particularly problematic during pregnancy. Because nitrates and nitrites can cross the placenta into a fetus [4,5], it’s safest to avoid foods with added nitrates or nitrites during pregnancy. Again, however, there is no evidence to support avoiding vegetables, because of the inefficient conversion of nitrate to nitrite and because of the many health benefits associated with high vegetable consumption.

References

1. Swann et al. Nitrosamine-induced carcinogenesis. The alklylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate. Biochem J. 1968 Nov;110(1):39-47.
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2. van Velzen et al. The oral bioavailability of nitrate from nitrate-rich vegetables in humans. Toxicol Lett. 2008 Oct 1;181(3):177-81. Epub 2008 Aug 3.
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3. White, J. Relative significance of dietary sources of nitrate and nitrite. J Agric Food Chem. 1975 Sep-Oct;23(5):886-91 .
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4. Althoff et al. Transplacental effects of nitrosamines in Syrian hamsters: I. Dibutylnitrosamine and nitrosohexamethyleneimine. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976 May 3;86(1):69-75.
   View abstract
5. Gruener et al. Methemoglobinemia induced by transplacental passage of nitrites in rats. Bull Environ Contam Toxicol. 1973 Jan;9(1):44-8.
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Mitochondria are specialized subunits inside a cell that produce the cell’s energy and regulate its metabolism. Research suggests that mitochondria may play a central role in neuronal cell survival because they regulate both energy metabolism and cell death pathways. Using genetic mouse models of Alzheimer’s disease, researchers from Mayo Clinic have found that mitochondria in the brain are dysfunctional early in the disease. The findings were recently published in the open access journal PLoS ONE.

Using real time imaging, scientists examined mitochondria in live neurons from three different mouse models of Alzheimer’s disease. Each of the mouse models had a different gene mutation shown to cause familial, or early-onset, Alzheimer’s disease. To evaluate the the impact of a given mutation, mitochondrial motility, distribution, ultrastructure and function in neurons and brain tissue was examined early in mouse development until the age where mice began to display memory loss and amyloid deposits formed.

Researchers used a mitochondria-specific dye and monitored axonal trafficking (i.e. motion along axons or nerve fibers). The investigators found that mitochondrial axonal trafficking is inhibited in embryonic neurons afflicted with Alzheimer’s disease, well before mice showed any memory loss or amyloid plaque formation.
Indeed, inhibition of axonal trafficking was found to be a general defect that occurred in all three mouse models of Alzheimer’s disease and was not specific for mitochondria. Nevertheless, neurons with inhibited mitochondrial trafficking were found to be more susceptible to excitotoxic cell death, a pathological process wherein nerve cells are killed by excessive neurotransmitter stimulation.

In the brains of all three mouse models of Alzheimer’s disease, mitochondria tended to lose their integrity and subsequently stopped functioning. Importantly, dysfunctional mitochondria were detected at the synapses of neurons involved in maintaining memory, suggesting a direct linkage with Alzheimer’s disease.

The scientists also applied a method called metabolomics, which measures the chemical fingerprints of specific metabolic pathways in the cell such as sugars, lipids, nucleotides, amino acids and fatty acids. The approach takes a snapshot of what is happening in the body at a given time and at a hight level of detail, and provides insight into the cellular processes that underlie a disease. For this study, the metabolomic profiles showed changes in metabolites related to mitochondrial function and cellular energy metabolism, which further confirmed that altered mitochondrial energetics is fundamental to the disease process.

The researchers identified a panel of metabolomic biomarkers. According to Eugenia Trushina, Ph.D., Mayo Clinic pharmacologist and senior investigator on the study [2]:

We are not looking at the consequences of Alzheimer’s disease, but at very early events and molecular mechanisms that lead to the disease. We expect to validate metabolomic changes in humans with Alzheimer’s disease and to use these biomarkers to diagnose the disease before symptoms appear — which is the ideal time to start treatment.

The researchers conclude by stating that Alzheimer’s disease can be viewed as a mitochondrial movement disorder with evolving energetic deficit represented by the panel of metabolomic biomarkers and that mitochondrial dysfunction is an underlying event in Alzheimer’s disease progression.

References

1. Trushina et al. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer’s disease. PLoS One. 2012;7(2):e32737. Epub 2012 Feb 29.
   View abstract
2. Mitochondrial Dysfunction Present Early in Alzheimer’s, Before Memory Loss. Mayo Clinic News. 2012 Feb 29.

World Asthma Day (WAD) takes place each year on the first Tuesday in May. The annual event, organized by the Global Initiative for Asthma (GINA), raises asthma awareness and care around the world. Continuing last year’s positive theme, the WAD 2012 theme is “You Can Control Your Asthma”. The campaign emphasizes asthma control as described in the latest version of the GINA guideline documents [1]. Asthma control is also the focus of GINA’s Asthma Control Challenge, a five-year campaign to reduce asthma hospitalizations worldwide by fifty percent.

According to a recent editorial published in the European Respiratory Journal by GINA leaders, hospitalizations are highly responsive to interventions and decrease as access to care and controller treatment is improved [2]. They note that programs targeting improved education, pharmacotherapy, and follow-up have reduced asthma-related hospitalizations as much as 68% in certain countries.

For WAD 2012, GINA is calling for increased collaboration and encouraging all World Asthma Day participants to bring the Challenge to the community of asthma patients, health care workers, educators, and advocates in their area. Tari Haahtela, MD, a member of the GINA Board of Directors who has conducted research on how countries and health care systems can reduce the burden of asthma, suggests [3]:

We should personalize the Challenge, and find out those local professionals whom we already know and who could create help with collecting data or other activities related to the effort.

The GINA Asthma Control Challenge organizes working groups — including public health authorities, government representatives, NGOs, and respiratory societies — at the local or national level to collect baseline data on hospitalizations, develop and carry out strategies to improve asthma control, and measure the results. The GINA Hospitalization Survey is a repository of data that provides a baseline and benchmark for progress in the campaign.

Control your asthma

GINA recommends five interrelated components of therapy for asthma management [1]:

1. Develop the patient/doctor partnership with the aim of guided self-management (i.e. give people with asthma the ability to control their own condition with guidance from health care professionals).
2. Take measures to prevent the development of asthma, asthma symptoms, and asthma exacerbations by avoiding or reducing exposure to risk factors.
3. Assess, treat, and monitor asthma with the goal of achieving and maintaining clinical control.
4. Manage asthma exacerbations through repetitive administration of rapid-acting inhaled bronchodilators, the early introduction of systemic glucocorticosteroids, and oxygen supplementation.
5. Special considerations should be made for various health conditions such as pregnancy, obesity, surgery, sinusitis, etc.

Although World Asthma Day only runs one day, May is also National Asthma and Allergy Awareness Month. It’s a peak season for asthma and allergy sufferers, and a perfect time to educate everyone about these diseases.

Asthma facts

Asthma is a chronic inflammatory disorder of the airways.  Asthma presents with wheezing, coughing, chest tightness and shortness of breath, caused by mild to life-threatening episodes of airway narrowing and obstruction. Asthma affects more than 230 million people worldwide, including more than 17 million American adults and 7 million children under 18 years of age.

Asthma is the most common chronic disease among children. Over the past thirty years, rates of asthma have risen sharply, particularly among children ages 5 to 14. Asthma disproportionately affects minorities, people with lower incomes, females, and children.

The strongest risk factors for developing asthma are exposure to indoor allergens such as house dust mites in bedding, carpets and stuffed furniture; pollution and pet dander; outdoor allergens such as pollens and moulds; tobacco smoke and chemical irritants in the workplace. Asthma triggers can include cold air, extreme emotional arousal such as anger or fear, and physical exercise.

Asthma is often under-diagnosed and under-treated, creating a substantial burden to individuals and families and possibly restricting individuals’ activities for a lifetime. Although there is no cure for asthma, daily preventive treatment plans according to individual symptoms can enable people to manage their symptoms and lead active lives.

References

1. GINA Report, Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA). Updated 2011.
2. Fitzgerald et al. The GINA Asthma Challenge: reducing asthma hospitalisations. Eur Respir J. 2011 Nov;38(5):997-8. Epub 2011 Sep 6.
   View abstract
3. Connect with your Network to Improve Asthma Control. GINA press release. 2012 May 1.

A case of so-called “mad cow disease” was found in a California dairy cow last week. The disease, known to veterinary scientists as bovine spongiform encephalopathy (BSE), is fatal, and can be transmitted from cow-to-cow or cow-to-human through the ingestion of contaminated tissue. There is no evidence BSE spreads to humans — the human form of the disorder is called Creutzfeldt-Jakob disease — through drinking milk. As such, authorities claim that the infected animal (which is being held and will be destroyed) posed no risk to humans.

While a BSE-infected dairy cow is somewhat less distressing than a BSE-infected meat cow, there are nevertheless serious issues raised by this discovery. BSE isn’t caused by a virus or by bacteria. Instead, it’s a prion disease (a prion is a misfolded protein). Proteins are major components of all cells. They’re made up of long chains of smaller molecules, and are folded into specific shapes. The folded shape of a protein determines its function; a misfolded protein acts differently than a properly folded protein. Strangely enough, prions — misfolded proteins — possess the ability to cause normal proteins that they encounter to misfold; this is how they propagate themselves. They are not living, however, and they can’t be “killed.” This is one of the reasons that prions in the food supply are so concerning; unlike bacterial contamination, the threat of which is mitigated by cooking, prions are heat-resistant. A person who eats thoroughly cooked, BSE-contaminated meat can still get Creutzfeldt-Jakob disease.

Prion diseases like BSE can’t be transmitted thorough the air or through animal-to-animal or animal-to-human contact. They are transmitted only through consuming infected animal material. One might reasonably assume, therefore, that a case of BSE in a cow would be an isolated incident, as cows are not normally cannibals. Unfortunately, common cattle husbandry practices in the U.S. do, in fact, produce cow cannibalism. It used to be common for waste products left over from cattle slaughter (the brain and spinal cord, for instance) to be ground up and added back into cattle feed. This practice created optimal conditions for transmission of prion disease. The practice was banned by the FDA in 1997, but it’s currently legal to use cattle products in chicken feed, as it’s not possible to transmit BSE to a chicken. Conversely, it’s currently legal to use chicken litter (the swept-up scraps off the floor of a chicken coop that include feces, feathers, and so forth) in cattle feed. This creates a problem, however; chickens scatter (cow part-containing) chicken feed on the floor, which is swept up and fed back to cows. The vehicle for cow-to-cow BSE transmission is still in place in conventional cattle operations in the United States.

Symptoms of Creutzfeldt-Jakob disease include loss of muscle control, hallucinations, and dementia. Infected individuals do not develop symptoms for many years, but once symptoms occur, death inevitably follows within about 13 months. There is no known treatment for prion disease. Because cooking does not render prion-infected meat safe, the safest route for avoiding infection is to avoid cattle raised on chicken litter-containing feed. Such cattle include those that are exclusively grass-fed and those labeled “certified organic.”

We are all familiar with the negative consequences of getting too little sleep, but they may be more serious than just feeling a bit groggy. A new study published in the journal Science Translational Medicine has shown that sleep restriction, along with a disruption of one’s internal body clock, can raise the risk of obesity and type 2 diabetes [1]. This could explain the increased rates of these conditions in shift workers and others who work at night.

Researchers at Harvard disrupted the study subjects’ circadian rhythms by adjusting their sleep/wake cycles and feeding schedules to 28 hour “days” in lieu of 24 hour ones. Subjects were kept in a dimly lighted room so their internal clocks did not adjust to external light and dark cues, but rather maintained their normal 24 hour cycles. In addition to this circadian disruption, subjects were permitted only 5.6 hours of sleep per 24 hours for three weeks. Twenty-one subjects completed the study.

When undergoing this regimen, study participants had a reduced resting metabolic rate and increased plasma glucose concentrations after eating. The latter effect is because their pancreas’ were not secreting enough insulin to clear the glucose out of the blood. Levels of ghrelin -– the hormone that makes you hungry — were higher during sleep restriction, while levels of leptin –- the hormone that makes you feel full -– were lower. These effects were independent of gender and of age, which ran counter to the researchers’ expectations since older people often experience dramatic changes in both sleep patterns and circadian rhythms. After nine days of recovery sleep, the levels of these parameters reverted back to normal.

The authors note that their results accord with a number of studies showing that sleep deficiency impairs glucose metabolism by decreasing insulin sensitivity. They go on to say that the number of hours we sleep each night, as well as the length of days or weeks we are subjected to inadequate sleep, probably both contribute to increasing our risk of diabetes. Circadian disruption, such as that occurring during jet lag or shift work, also adversely affects glucose metabolism.

These results were highlighted in The New York Times, along with those from an unrelated study claiming that children with attention deficit hyperactivity disorder (ADHD) symptoms may in fact be sleep deprived [2-3]. So in these busy times, it is as important as ever for everyone, young and old, to carve out the time for a decent night’s sleep.

References

1. Buxton et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012 Apr 11;4(129):129ra43.
   View abstract
2. http://www.nytimes.com/2012/04/17/health/research/curtailed-sleep-raises-risk-of-obesity-and-diabetes.html”>Risks: More Signs of Rest’s Regulatory Powers NYTimes. 2012 Apr 16.
3. Attention Problems May Be Sleep-Related. Well Blog – NYTimes.com. 2012 Apr 16.