Antioxidants in Pecans May Contribute to Heart Health and Disease Prevention

Naturally occurring antioxidants in pecans may helpcontribute to heart health and disease prevention.

A new research study from Loma Linda University (LLU) demonstrated that naturally occurring 1) ___ in pecans may help contribute to heart health and disease prevention. The results were published in the January 2011 issue of The Journal of Nutrition.


Pecans contain different forms of the antioxidant vitamin 2) ___ – known as tocopherols, plus numerous phenolic substances, many of them with antioxidant abilities. The nuts are especially rich in one form of vitamin E called gamma-tocopherols. The findings illustrate that after eating pecans, gamma-tocopherol levels in the body doubled and unhealthy oxidation of LDL (bad) cholesterol in the blood decreased by as much as 33%. Oxidized LDLs may further contribute to 3) ___ in the arteries and place people at greater risk of cardiovascular problems.


“Our tests show that eating pecans increases the amount of healthy antioxidants in the body,” says LLU researcher Ella Haddad, DrPH, associate professor in the School of Public Health department of nutrition. “This protective effect is important in helping to prevent development of various diseases such as cancer and 4) ___ disease.”


The findings are from a research project designed to further evaluate the health benefits of 5) ___, according to Dr. Haddad. She analyzed biomarkers in blood and urine samples from study participants (a total of 16 men and women between the ages 23 and 44) who ate a sequence of three diets composed of whole pecans, pecans blended with water, or a control meal of equivalent nutrient composition. The pecan meals contained about three ounces of the nut. Samples were taken prior to meals and at intervals up to 24 hours after eating.


Following the test meals composed of whole pecans and blended pecans, researchers found that amounts of gamma-tocopherols (vitamin E) in the body doubled eight hours after both meals, and oxygen radical absorbance capabilities (ORAC – a scientific method for measuring antioxidant power in the blood) increased 12% and 10% respectively two hours after the meals. In addition, following the whole-pecan meal, oxidized LDL cholesterol 6) ___ by 30% (after 2 hours), 33% (after 3 hours), and 26% (after 8 hours).


“This study is another piece of evidence that pecans are a healthy food,” says Dr. Haddad. “Previous research has shown that pecans contain antioxidant factors. Our study shows these antioxidants are indeed absorbed in the body and provide a 7) ___ effect against diseases.”


Research from Loma Linda University published earlier in the Journal of Nutrition showed that a pecan-enriched diet lowered levels of LDL cholesterol by 16.5% – more than twice the American Heart Association’s Step I diet, which was used as the control diet in that study. Similarly, the pecan-enriched diet lowered total 8) ___ levels by 11.3% (also twice as much as the Step I diet).


ANSWERS: 1) antioxidants; 2) E; 3) inflammation; 4) heart; 5) pecans; 6) decreased; 7) protective; 8) cholesterol



Penicillin, the first antibiotic ever discovered, helped revolutionize the medical field during the twentieth century. Knowledge of this important and powerful antibiotic began with Alexander Fleming, who in 1928 observed by chance that the growth of bacteria he was attempting to culture in his laboratory was inhibited by a contaminating mold (Penicillium). Fleming correctly deduced that the mold was producing a substance, which he termed penicillin, produced this unusual effect, but was unable to isolate the material. During World War II, an increased necessity for finding ways of treating infections suffered by wounded members of the military resulted in increased interest in penicillin research. The first to isolate and chemically characterize the substance were pathologist Howard Florey and biochemist Ernst Chain, whose achievements led to the ability of generating sizable quantities of the antibiotic, which quickly became a widespread form of medical treatment.


The chemotherapy of bacterial infections dates back to 1935, when the synthetic group of drugs commonly known as sulfonamides, or sulfa drugs, was introduced. Examination of mortality rates in England and Wales from that time onwards indicates that these drugs reduced the mortality from hemolytic streptococcal infections (typified by puerperal fever), pneumonia, and cerebrospinal fever. Though often referred to as antibiotics due to their bacteria-fighting ability, sulfonamides are not derived from living organisms and should not, therefore, be classified as such according to traditional usage of the term. It was not until several years after sulfonamides became available that true antibiotics derived from, or produced by, fungi, bacteria, and other organisms, were added to the arsenal of medicinal weapons available for combating bacterial diseases.

Today, there are hundreds of derivatives of penicillin that have been developed, including the semi-synthetic compound ampicillin that appears on the banner above, as well as a wide range of other antibiotics. Indeed, shortly after the introduction of penicillin to the world, René Dubos, an American scientist, found that a soil bacterium was able to render pneumococcus bacteria innocuous, and his further efforts revealed that a substance dubbed tyrothricin derived from the bacterium was actually able to combat an impressive array of infectious bacteria. Around the same time, American microbiologists Selman Waksman and Albert Schatz isolated streptomycin and a variety of other bacteria-fighting agents from the microbe Streptomyces griseus. These and additional antibiotics that have since been developed are responsible for saving innumerable lives and improving the quality of life for countless others.





Antibiotics are not only utilized as a form of medical treatment for humans, however. The drugs are also frequently included in the diet of cattle and other farm animals. This controversial practice, which is often carried out even for healthy livestock, is intended to increase the weight of the animals, which correspondingly increases their economic value. For similar monetary reasons, antibiotics are also widely used to treat a number of plant diseases caused by bacterial infections, often enabling farmers to avoid significant crop losses. Yet, although utilization of antibiotics for such purposes may make short-term economic sense, many are skeptical and believe long-term concerns about the increasing immergence of antibiotic-resistant strains of bacteria, which common exposure to antibiotics promotes, should take precedence. For similar reasons, many in the scientific community also find the everyday use of antibiotic soaps and lotions that has arisen among the general public in recent years problematic.

The development of bacteria that are resistant to antibiotics essentially occurs due to the evolutionary process and natural selection. More precisely, when a group of bacteria are exposed to an antibiotic, only those that exhibit a certain trait or mutation can survive. These remaining bacteria reproduce and pass the same characteristic to their offspring, resulting in an entire generation of microbes that are resistant to that particular compound. Antibiotic-resistant bacteria were discovered as early as the 1960s, when strains of both pneumonia-causing pneumococcus and the Neisseria gonorrhoeae bacterium that is responsible for gonorrhea were discovered. Some of the other common bacteria that have since been found to be unaffected by antibiotics that were formerly effective in rendering them harmless include Salmonella, Streptococci, and Escherichia coli.

Many strains of bacteria have become, in fact, resistant to multiple antibiotics. These remarkable microorganisms are commonly referred to as “superbugs” due to the incredible difficulty in combating them. As more and more multiresistant bacteria evolve, the faster pharmaceutical companies must race to develop new antibiotics to fight them. If they are unable to meet the challenge, illnesses that came to be considered trifling occurrences in the twentieth century may once again become a cause for alarm.


Electron Microscopy Credit: Michael W. Davidson, The Florida State University and Optical Microscopy at the National High Magnetic Field Laboratory



Risks of Combination Therapy with ACE Inhibitor and ARB

Combination therapy with an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin-receptor blocker (ARB) improves outcomes compared with monotherapy in patients with diabetic nephropathy or advanced systolic left ventricular dysfunction. However, several randomized trials have shown an increased risk of renal dysfunction in patients treated with combination therapy as opposed to either agent alone. As a result, a study published online (March 21, 2011) in the Canadian Medical Association Journal was designed to determine the safety of combination therapy with these two drugs in clinical practice.


The study was a population-based longitudinal analysis using linked administrative and laboratory data for elderly patients who were new users of an ACE inhibitor, an angiotensin-receptor blocker or a combination of both medications between May 1, 2002, and Dec. 31, 2006. Outcomes were compared in patients given combination therapy versus patients given monotherapy using Cox proportional hazards analyses with adjustment for baseline characteristics.


Of the 32,312 new users of either medication (mean age 76.1 years, median creatinine level 92 µmol/L), 1,750 (5.4%) received combination therapy. Of these patients, 86.4% did not have baseline indications of heart failure or proteinuria. Results showed that renal dysfunction was more common among patients given combination therapy (5.2 events per 1,000 patients per month) than among patients given monotherapy (2.4 events per 1,000 patients per month) (adjusted hazard ratio [HR] 2.36). Hyperkalemia (increased potassium) was also more common among patients given combination therapy (2.5 events per 1000 patients per month) vs. 0.9 events (adjusted HR 2.42). Most patients took combination therapy for only a short time, median of three months, before at least one agent was stopped.


According to the authors, combination therapy was frequently prescribed for patients without established indications and was associated with an increased risk of adverse renal outcomes when compared with monotherapy and these results mirrored data from randomized controlled trials. In addition, renal dysfunction and hyperkalemia occurred twice as often in older patients treated with both an ACE inhibitor and an ARB than with either agent alone.

Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients with Suspected Acute Coronary Syndrome

Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve clinical outcomes in patients with suspected acute coronary syndrome (ACS). As a result, a study published in the Journal of the American Medical Association (2011;305:1210-1216), was performed to determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes.


The study included all consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, in a study evaluating a diagnostic with a lowered threshold of detection of troponin 1 for myocardial necrosis from 0.20 to 0.05 ng/mL. The study population was stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and >0.20 ng/mL).


The main outcome measure was event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations.


Results showed that plasma troponin concentrations were less than 0.05 ng/mL in 1,340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase of the study, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P < 0.001) or 0.20 ng/mL or more (P = 0.007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; P = 0.01).


According to the authors, in patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.

Gene Identified That Suppresses Cell’s Immune Activation

One of the main problems in treating cancer, by vaccine or immunotherapy, is that tumors often evade the body’s immune response – and one of their tricks is to create an environment where immunity is inhibited or suppressed. According to a study reported online in the Journal of Clinical Investigation (23 March 2011), a gene, FOXO3, has been shown to suppress activation of cells related to immunity and thus leads to a reduced immune response against prostate cancer. By identifying a gene that makes immune cells suppressive, the study may have found a new target for enhancing immune responses to cancer tumor cells.


The cells isolated and examined in this study were dendritic cells. These cells normally initiate an immune response to disease by presenting a foreign protein (or antigen) in a way that it is recognized by an invader-killing T cell. In tumor-associated dendritic cells, however, this stimulating immune response is often suppressed.


To overcome the problem associated with tumor-associated dendritic cells, a series of experiments were conducted aimed at enhancing immunity to tumors. As a result, it was discovered that prostate tumors from mice contained a population of dendritic cells that express FOXO3 at high levels. These dendritic cells no longer activated T cells. Instead, they muted the immune response, which caused the T cells to become tolerant of tumor cell antigens, to lose their ability to target and kill tumor cells, and even to suppress the activity of other T cells. Under certain conditions, elimination of the suppressive dendritic cells led to reduced tumor size. The findings made in mice then led the research team to examine human prostate tumors in the lab where they found similar dendritic cells with high FOX03 levels.


In past studies, the research team worked to identify how tumors evade recognition by the immune system. Their results showed that, in the same mouse model of prostate cancer, T cells become tolerant upon entering a tumor and acquire the ability to suppress other T cells. In the present study, the authors demonstrated not only that dendritic cells isolated from tumors were poor at initiating immune responses, but also that these cells were responsible for inducing T cell tolerance and converting them to suppressor T cells. Using microarray technology, a technique that allows for the examination of expression of thousands of genes simultaneously, the study compared the genes expressed by the tumor-associated dendritic cells to those expressed by dendritic cells in normal tissue. Among the genes that were overexpressed in the tumor-associated dendritic cells, FOXO3 was an appealing candidate for an immune modulator because it was known to be a regulator associated with dendritic cell function. When FOXO3 gene expression was silenced in the tumor-associated dendritic cells, the study found that these cells no longer had an immune suppressive function but rather initiated appropriate immune responses.


This work has led to the submission of a patent application by the NIH on behalf of Hurwitz and Watkins to target FOXO3 as a way to boost immune responses in cancer and to silence excessive immune responses in autoimmune diseases. While waiting for patent approval, the scientists will study how tumors, or the tumor microenvironment, induce FOXO3 expression as well as how FOXO3 induces this suppressive activity.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.



FDA Approves New Melanoma Treatment



The FDA has approved Yervoy (ipilimumab; Bristol-Myers Squibb) to treat patients with late-stage (metastatic) melanoma. Melanoma is the leading cause of death from skin disease, and according to the National Cancer Institute, an estimated 68,130 new cases of melanoma were diagnosed in the US during 2010 and about 8,700 people died.


Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body’s immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously.


Yervoy’s safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed.


The study was designed to measure overall survival, the length of time from when this treatment started until a patient’s death. The randomly assigned patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone. Results showed that those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.


Common side effects that can result from autoimmune reactions associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). Severe to fatal autoimmune reactions were seen in 12.9% of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.


Due to the unusual and severe side effects associated with Yervoy, the therapy is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy’s potential side effects.


For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.



Target Health Inc.
261 Madison Avenue
24th Floor
New York, NY 10016

P:   212-681-2100
F:   212-681-2105



Saturday March 26th was sunny and a gorgeous day to be in the Park.  The forsythia is beginning to bloom and it is magnificent.

Science Weekly podcast: Mathematics special + Brian Cox = science2

Filed Under Uncategorized | Comments Off on Science Weekly podcast: Mathematics special + Brian Cox = science2

Bowing to popular demand, here’s our mathematical special. No calculators allowed. As an added bonus, physicist and star of the small screen Brian Cox dropped by




An On-Off Switch for Anxiety

Light control: Scientists use fiber optics to control genetically engineered neurons in the brains of animals (as shown here).    Credit: Deisseroth lab



Researchers discover a brain circuit that can instantly dampen—or exacerbate—anxiety in mice.



MIT Technology Review, March 24, 2011, by Emily Singer  —  With the flick of a precisely placed light switch, mice can be induced to cower in a corner in fear or bravely explore their environment. The study highlights the power of optogenetics technology—which allows neuroscientists to control genetically engineered neurons with light—to explore the functions of complex neural wiring and to control behavior.


In the study, Karl Deisseroth and collaborators at Stanford University identified a specific circuit in the amygdala, a part of the brain that is central to fear, aggression, and other basic emotions, that appears to regulate anxiety in rodents. They hope the findings, published today in the journal Nature, will shed light on the biological basis for human anxiety disorders and point toward new targets for treatment.


“We want to conceptualize psychiatric disease as real physical entities with physical substrates,” says Deisseroth. “Just like people who have asthma have reactive airways, people with anxiety disorders may have an underactive projection in the amygdala.”


The researchers engineered mice to express light-sensitive proteins in specific cells in the amygdala that send out neural wires, known as axons, to different substructures. Using a specially designed fiber-optic cable implanted in the animal’s brain, researchers found that aiming the light to activate one specific circuit had an immediate and potent effect on the animal’s behavior.


“I’ve never seen anything like it,” says Kay Tye, a postdoctoral researcher in Deisseroth’s lab and lead author on the study. Mice are naturally fearful of exploring open areas, she explains. Under normal circumstances, the animal “will poke its nose out and then scurry into a corner,” says Tye. “But when you turn on the light, the animal begins exploring the platform with no visible signs of anxiety. Then you turn the light off, and it scurries back in to the corner.”


The researchers could induce the opposite effect using a light-sensitive protein that silences the cells instead of activating them.


Shining light on the bodies of the cells, which in turn activates axons in multiple circuits, had no effect on the animals’ behavior, highlighting how important it is to be able to target individual circuits in the brain.




New research bring scientists one step closer to isolating the mechanisms by which the brain compensates for disruptions and reroutes neural functioning — which could ultimately lead to treatments for cognitive impairments in humans caused by disease and aging. (Credit: iStockphoto/Vasiliy Yakobchuk)




University of Michigan Health System, March22, 2011  —  When Geoffrey Murphy, Ph.D., talks about plastic structures, he’s not talking about the same thing as Mr. McGuire in The Graduate. To Murphy, an associate professor of molecular and integrative physiology at the University of Michigan Medical School, plasticity refers to the brain’s ability to change as we learn.

Murphy’s lab, in collaboration with U-M’s Neurodevelopment and Regeneration Laboratory run by Jack Parent, M.D., recently showed how the plasticity of the brain allowed mice to restore critical functions related to learning and memory after the scientists suppressed the animals’ ability to make certain new brain cells.

The findings, published online this week in the Proceedings of the National Academy of Sciences, bring scientists one step closer to isolating the mechanisms by which the brain compensates for disruptions and reroutes neural functioning — which could ultimately lead to treatments for cognitive impairments in humans caused by disease and aging.

“It’s amazing how the brain is capable of reorganizing itself in this manner,” says Murphy, co-senior author of the study and researcher at U-M’s Molecular and Behavioral Neuroscience Institute. “Right now, we’re still figuring out exactly how the brain accomplishes all this at the molecular level, but it’s sort of comforting to know that our brains are keeping track of all of this for us.”

In previous research, the scientists had found that restricting cell division in the hippocampuses of mice using radiation or genetic manipulation resulted in reduced functioning in a cellular mechanism important to memory formation known as long-term potentiation.

But in this study, the researchers demonstrated that the disruption is only temporary and within six weeks, the mouse brains were able to compensate for the disruption and restore plasticity, says Parent, the study’s other senior author, a researcher with the VA Ann Arbor Healthcare System and associate professor of neurology at the U-M Medical School.

After halting the ongoing growth of key brain cells in adult mice, the researchers found the brain circuitry compensated for the disruption by enabling existing neurons to be more active. The existing neurons also had longer life spans than when new cells were continuously being made.

“The results suggest that the birth of brain cells in the adult, which was experimentally disrupted, must be really important — important enough for the whole system to reorganize in response to its loss,” Parent says.

Additional Authors: Benjamin H. Singer, Ph.D., Amy E. Gamelli, Ph.D., Cynthia L. Fuller, Ph.D., Stephanie J. Temme, all of U-M

The research was supported by grants from the National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke. Temme is a National Science Foundation Graduate Research Fellow and was also supported by a U-M Rackham Merit Fellowship.

Journal Reference:

1.                         B. H. Singer, A. E. Gamelli, C. L. Fuller, S. J. Temme, J. M. Parent, G. G. Murphy. Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1015425108


← Previous PageNext Page →