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094 Health Research Report 28 NOV 2010

#94

Health Technology Research Synopsis 94th Issue Date 28 NOV 10

Compiled By Ralph Turchiano

www.vit.bz

EditorsTopFive:

1.  Vitamin C: A potential life-saving treatment for sepsis 2.  Elderly can blame fractures and falls on low sodium

3.  Light at night causes changes in brain linked to depression 4.  High alpha-carotene levels associated with longer life

5.  Pomegranate juice: Beyond antioxidants, potential benefits for dialysis patients In this issue:

  1. 1.       Poor sleep quality increases inflammation, community study finds
  2. 2.       Stanford study suggests alternative to using preservatives in nasal spray
  3. 3.       How does the color of a pill affect its efficacy?
  4. 4.       Homeopathy consultations can benefit arthritis patients, say scientists
  5. 5.       Natural compound shows promise against Huntington’s disease
  6. 6.       Antibiotic treatment for ear infections in kids provides only modest benefits, study finds
  7. 7.       Light at night causes changes in brain linked to depression
  8. 8.       Low-allergenic wines could stifle sniffles and sneezes in millions of wine drinkers
  9. 9.       Vitamin C: A potential life-saving treatment for sepsis
  10. 10.   Pomegranate juice: Beyond antioxidants, potential benefits for dialysis patients
  11. 11.   Taking a break from osteoporosis drugs can protect bones
  12. 12.   Elderly can blame fractures and falls on low sodium
  13. 13.   High alpha-carotene levels associated with longer life
  14. 14.   Bacteria help infants digest milk more effectively than adults
  15. 15.   Danish researchers finally solve the obesity riddle
  16. 16.   Growth-factor gel shows promise as hearing-loss treatment
  17. 17.   New study reveals how cannabis suppresses immune functions

Public release date: 14-Nov-2010

Poor sleep quality increases inflammation, community study finds

People who sleep poorly or do not get enough sleep have higher levels of inflammation, a risk factor for heart disease and stroke, researchers have found.

Data from a recent study are scheduled to be presented Sunday, Nov. 14 at the American Heart Association Scientific Sessions in Chicago by Alanna Morris, MD, a cardiology fellow at Emory University School of Medicine.

The results come from surveying 525 middle-aged people participating in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study on their sleep quality and sleep duration. The META-Health study’s co-directors are Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and director of Emory’s Cardiovascular Research Center, and Gary Gibbons, MD, director of the Cardiovascular Research Institute at Morehouse School of Medicine. Donald Bliwise, MD, director of the Emory University Sleep Program, contributed additional guidance.

Acute sleep deprivation leads to an increased production of inflammatory hormones and changes in blood vessel function, but more research is needed on the physiological effects of chronic lack of sleep, Morris says.

“Most of the studies looking at the body’s response to lack of sleep have looked at subjects who have been acutely sleep deprived for more than 24 hours in experimental sleep laboratories,” she says. “Nothing of this sort has been investigated in epidemiologic studies.”

In the META-Health study, the researchers assessed sleep quality using the Pittsburgh Sleep Quality Index survey, where a score over six (based on the median sleep score of the study population) is considered poor. They also analyzed their data based on hours of sleep.

Individuals who reported six or fewer hours of sleep had higher levels of three inflammatory markers: fibrinogen, IL-6 and C-reactive protein. In particular, average C-reactive protein levels were about 25 percent higher (2 milligrams per liter compared to 1.6) in people who reported fewer than six hours of sleep, compared to those reporting between six and nine hours.

That difference was still significant even when the data is corrected for known risk factors such as smoking, blood pressure, diabetes and obesity, Morris says.

C-reactive protein is used extensively as a marker of inflammation and heart disease risk. People whose C-reactive protein levels are in the upper third of the population (above 3 milligrams per liter) have roughly double the risk of a heart attack, compared with people with lower C-reactive protein levels, according to the American Heart Association and Centers for Disease Control and Prevention.

“For people who got little sleep, the C-reactive protein levels were increased, but still in the range of what health authorities would consider low to intermediate risk,” she says. “However, our study population

represents a community-based population [as opposed to patients in the hospital or with known cardiovascular disease], so they have overall lower risk and lower C-reactive protein levels than many of the high risk populations in other studies.”

Inflammation may be one way poor sleep quality increases the risks for heart disease and stroke, Morris says.

“It remains uncertain whether short sleep duration contributes directly to cardiovascular mortality, or whether it is a mediating or moderating factor,” she says.

Previous research has shown that people who sleep between seven and eight hours per night live longest, and that especially short or especially long sleep durations bring higher mortality. Researchers find that short and long sleep durations are often seen together with high blood pressure, obesity, diabetes and psychological stress – all risk factors for heart disease and stroke.

Long sleep duration may reflect a compensation for sleep apnea, which the sleep quality survey does not directly address. However, in the META-Health study, people who slept for more than nine hours didn’t show significantly higher levels of inflammation markers.

In a separate poster, Morris is also presenting research on a difference between men and women in the interaction between sleep quality and arterial stiffness. Her results show that both men and women with poor sleep quality had higher blood pressures, but only men with poor sleep quality had a higher arterial stiffness, a lack of blood vessel flexibility which drives hypertension and puts more burden on the heart.

Public release date: 15-Nov-2010

Stanford study suggests alternative to using preservatives in nasal spray

STANFORD, Calif. — A preservative-free alternative to standard nasal sprays — which routinely use preservatives that can cause unwanted side effects, such as allergies or damage to the mucosal lining of the nose — was found to be both safe and well-tolerated, in a short-term study from the Stanford University School of Medicine.

The alternative acidified solution also maintained sterility in the applicator bottle without the use of the chemical preservatives, according to the study, which will be published Nov. 15 in the Archives of Otolaryngology-Head & Neck Surgery.

“There is another way that you can preserve nasal sprays that is safe for consumer use,” said Peter Hwang, MD, professor of otolaryngology and co-author of the study. “This also has potential for eye drops, medicated sprays, eardrops.”

Stanford researchers decided to test the safety of the new method of maintaining sterility, which is patented by an ophthalmologist in Los Altos, Calif., as an alternative to the wide use of preservatives in     everything from over-the-counter nasal sprays to medicated sprays and eye drops. Scientific evidence has shown that the preservatives used, such as benzalkonium chloride and phenylcarbinol, can damage human and animal tissues.

Researchers compared the use of a saline nose spray that had been acidified by hydrochloric acid to a pH of 2.5 and then buffered by low concentrations of citric acid with the commonly used over-the-counter saline nose spray Ocean Spray, which contains both benzalkonium chloride and phenylcarbinol.

Twenty healthy subjects used the preservative-free saline spray in each nostril twice a day for a week followed by a weeklong “washout period” and then another weeklong use of the over-the-counter

commercial product. Each subject underwent a nasal endoscopic exam and filled out an extensive questionnaire — the Sino-Nasal Outcome Test, or SNOT — at the end of each week of nasal spray use.

The open-applicator bottle was also tested for bacterial growth. None was found in either of the spray solutions. No differences were found in symptom reporting or in the endoscopy findings between the preservative-free versus the preservative-containing spray.

“Of those analyzed, we believe that the most important symptoms for determining the safety and tolerance of the preservative-free acidified solution nasal spray are nasal burning, smell disturbance, taste disturbance, nasal bleeding, purulent rhinorrhea [runny nose with pus], sore throat, need to blow nose, sneezing, runny nose, postnasal discharge, thick nasal discharge, ear fullness, ear pain and facial pain or pressure,” the authors write. “There were no discernible differences in these symptoms between the two nasal sprays used.”

Public release date: 15-Nov-2010

The color of medicine

How does the color of a pill affect its efficacy?

According to recent research the color, shape, taste and even name of a tablet or pill can have an effect on how patients feel about their medication. Choose an appropriate combination and the placebo effect gives the pill a boost, improves outcomes and might even reduce side effects. Now, researchers at the University of Bombay, New Mumbai, India, have surveyed users of over-the-counter (OTC) medication to find out  just how much the color of a tablet influences patient choice.

Writing in the International Journal of Biotechnology, R.K. Srivastava and colleagues report that red and pink tablets are preferred over other colors. Their survey of 600 people showed that for three quarters of people the color and shape of their tablets act as a memory tag for compliance. Strangely, they found   that 14 percent of people think of pink tablets as tasting sweeter than red tablets whereas a yellow tablet is perceived as salty irrespective of its actual ingredients. 11% thought of white or blue tablets as tasting bitter and 10% said orange-colored tablets were sour.

Twice as many middle-aged people preferred red tablets as younger adults and more women chose red tablets as were chosen by men. Color seems to be integral component of an OTC product, the team says.

Patients may trust their doctor or pharmacist, but this does not mean they will take the bitterest pill. “Patients undergo a sensory experience every time they self-administer a drug, whether it’s swallowing a tablet or capsule, chewing a tablet, swallowing a liquid, or applying a cream or ointment,” the team says. “The ritual involving perceptions can powerfully affect a patient’s view of treatment effectiveness.” The researchers suggest that it might be possible to ensure that all the sensory elements of given medication work together to create positive perceptions that complement the medical attributes. They point out, however, that surprisingly little attention has been paid to this aspect of pharmaceutical formulation.

The research has implications for marketing OTC medication to different age groups and to men and women. However, given that compliance in taking medication strongly depends on the patient’s perception of that medication the study could also have important connotations for improving effects. If patients are disinclined to take a tablet they consider bitter or sour or because they simply do not like the color, then a change of aesthetics might be needed. The same research might apply equally to prescription medicines.

Public release date: 15-Nov-2010

Homeopathy consultations can benefit arthritis patients, say scientists

In a study published today in the journal Rheumatology, researchers found that arthritis patients significantly benefited when they received homeopathy alongside conventional treatment over a period of 6 months

New evidence that homeopathic consultations can reduce the symptoms of rheumatoid arthritis has been revealed by scientists from the University of Southampton.

In a study published today in the journal Rheumatology, researchers found that arthritis patients significantly benefited when they received homeopathy alongside conventional treatment over a period of 6 months, but this improvement was due to homeopathy’s consultation process and not its remedies.

“Although previous trials have shown homeopathy may help patients with rheumatoid arthritis, this is the first time that we have scientific evidence that these benefits are specifically due to its unique consultation process,” comments lead author Dr Sarah Brien, a senior research fellow in complementary medicine at the University of Southampton.

“Homeopathic consultations differ from those in conventional medicine in that homeopaths focus on treating the patient, whereas conventional doctors tend to treat the illness. The homeopathic consultation process improves the health of these arthritis patients based on standard rheumatology measurements and does so safely and without side effects.

“What we don’t yet know is if it is possible to introduce some of the techniques or approaches used within these consultations into conventional medicine.”

Researchers recruited 83 people with rheumatoid arthritis from clinics in Southampton, Poole and Winchester for the study. Each patient received a series of homeopathy consultations over a 24 week period between January 2006 and July 2008, while continuing their conventional treatment. Patients and doctors reported significant reductions in a variety of symptoms including reduced ‘disease activity scores’,      fewer swollen joints, reduced pain and improved mood.

The team now plans to conduct more research into identifying which elements of the consultation process are most beneficial and if homeopathy is a cost effective treatment.

Public release date: 15-Nov-2010

Natural compound shows promise against Huntington’s disease

LA JOLLA, CA-Fisetin, a naturally occurring compound found in strawberries and other fruits and vegetables, slows the onset of motor problems and delays death in three models of Huntington’s disease, according to researchers at the Salk Institute for Biological Studies. The study, published in the online edition of Human Molecular Genetics, sets the stage for further investigations into fisetin’s neuroprotective properties in Huntington’s and other neurodegenerative conditions.

Huntington’s disease (HD) is an inherited disorder that destroys neurons in certain parts of the brain and slowly erodes victims’ ability to walk, talk and reason. It is caused by a kind of genetic stutter, which leads to the expansion of a trinucleotide repeat in the huntingtin protein. When the length of the repeated  section reaches a certain threshold, the bearer will develop Huntington’s disease. In fact, the longer the repeat, the earlier symptoms develop and the greater their severity.

One of the intracellular signaling cascades affected by mutant huntingtin is the so-called Ras/ERK

pathway. It is activated by growth factors and is particularly important in brain development, learning, memory and cognition.

In earlier studies, Pamela Maher, Ph.D., a senior staff scientist in the Salk Cellular Neurobiology Laboratory, had found that fisetin exerted its neuroprotective and memory-enhancing effects through the activation of the Ras/ERK signaling pathway. “Because Ras/ERK is known to be less active in HD, we thought fisetin might prove useful in the condition,” Maher says.

Maher and her team began their study by looking at a nerve cell line that could be made to express a mutant form of the huntingtin protein. Without treatment, about 50 percent of these cells will die within a few days. Adding fisetin, however, prevented cell death and appeared to achieve it by activating the Ras- ERK cascade.

The researchers then turned their attention to Drosophila. In collaboration with J. Lawrence Marsh, Ph.D., a professor of developmental and cell biology at the University of California, Irvine, Maher tested fisetin in fruit flies overexpressing mutant huntingtin in neurons in the brain. The affected flies don’t live as long as normal flies and also have defective eye development. When they were fed fisetin, however, the HD flies maintained their life span and had fewer eye defects.

Finally, Maher and her team tested fisetin’s effects in a mouse model of HD. HD mice develop motor defects early on and have much shorter life spans than normal control animals. When Maher and her team fed them fisetin, the onset of the motor defects was delayed, and their life span was extended by about 30 percent.

“Fisetin was not able to reverse or stop the progress of the disease,” Maher notes, “but the treated mice retained better motor function for longer, and they lived longer.”

Fisetin, which also has anti-inflammatory properties and maintains levels of glutathione, a major cellular antioxidant that plays a key role in protecting against different types of stress in cells, has not yet been tested in humans. But Maher’s findings suggest that the compound may be able to slow down the progression of Huntington’s disease in humans and improve the quality of life for those who have it.

While she cautions that it won’t necessarily be effective for people already in the advanced stages of the disease, for those in the early stages or who are presymptomatic, fisetin might help.

Furthermore, once their safety and efficacy are proved in humans, the advent of substances like fisetin might prompt more people to be tested for the mutation. “Cells are damaged and dying before there are overt symptoms,” Maher says. “If patients know they have the mutation, then they could potentially start treatment before they start showing symptoms, which might be more effective than waiting for the symptoms to appear, as many do now.”

Maher’s lab has developed a variety of fisetin derivatives that are more potent in cell-based assays than the fisetin used in the study, and she plans further tests to see which combination is most effective in HD and other neurodegenerative disorders.

In the meantime, does she recommend eating a lot of strawberries to gain fisetin’s benefits? “It probably couldn’t hurt,” she says.

Public release date: 16-Nov-2010

Antibiotic treatment for ear infections in kids provides only modest benefits, study finds

Using antibiotics to treat newly diagnosed acute ear infections among children is modestly more effective than no treatment, but comes with a risk of side effects, according to a new study designed to help advise efforts to rewrite treatment guidelines for the common illness.

Researchers found no evidence that name-brand antibiotics work any better in general than generic antibiotics and that careful examination of the eardrum by a clinician for signs of infection is critical for accurate diagnosis of acute ear infections. The study is published in the Nov. 17 edition of the Journal of the American Medical Association.

“Our findings reinforce the existing knowledge that the best antibiotic treatment for common childhood  ear infections may be no antibiotic treatment at all,” said lead author Dr. Tumaini R. Coker, a pediatrician at Mattel Children’s Hospital UCLA and a researcher at the RAND Corporation, a nonprofit research organization.

“Prescribing antibiotics early may help cure ear infections a little bit faster, but also raises the risk that children will suffer antibiotic-related side effects such as a rash or diarrhea,” Coker said. “Parents and their children may value these different outcomes differently.”

Researchers from the Southern California Evidence-Based Practice Center conducted the study by examining previously published research about the diagnosis and treatment of acute ear infections among children. The review was requested by the American Academy of Pediatrics as part of its effort to update practice guidelines for treating acute ear infections among young children.

The study found that a major limitation of efforts to improve the treatment of acute ear infections is that there is no one definitive test for making the diagnosis. The use of an otoscope to look into the ear for signs of infection is a key component of any diagnosis and improving clinicians’ ability to conduct this exam may help improve the accuracy of diagnosis, researchers said.

Acute ear infections are the most common childhood illness in the United States where antibiotics are routinely prescribed. A 2006 study estimated that it costs about $350 to treat each episode of the illness, with yearly national costs totaling $2.8 billion.

The new study reviews published data from 1999 to 2010 about the treatment of acute ear infections among children. This systematic review of the literature found that prescribing antibiotics early for acute ear infections had a modest benefit. Of 100 average-risk children with acute ear infections, about 80 would be expected to get better within about three days without antibiotics. If all were treated with antibiotics immediately at diagnosis, evidence suggests an additional 12 would improve, but three to 10 children would develop a rash and five to 10 would develop diarrhea, according to the study.

“Early prescribing of antibiotics offers a slight benefit and poses a slight risk,” said the study’s senior author, Dr. Glenn Takata, a pediatrician and researcher at Children’s Hospital Los Angeles. “Clinicians will have to take these modest benefits and risks into consideration when deciding whether to treat with antibiotics or not.”

Researchers also found no evidence that using newer, name-brand antibiotics to treat uncomplicated acute ear infections in normal-risk children offers an advantage over generic antibiotics, namely the commonly- used amoxicillin. Despite these findings, the higher-priced antibiotics are often prescribed for uncomplicated acute ear infections. Savings could be substantial if physicians used amoxicillin as the first line of defense against uncomplicated acute ear infections, according to researchers.

Public release date: 17-Nov-2010

Light at night causes changes in brain linked to depression

COLUMBUS, Ohio – Exposure to even dim light at night is enough to cause physical changes in the brains of hamsters that may be associated with depression, a new study shows.

Researchers found that female Siberian hamsters exposed to dim light every night for eight weeks showed significant changes in a part of the brain called the hippocampus.

This is the first time researchers have found that light at night, by itself, may be linked to changes in the hippocampus.

These alterations may be a key reason why the researchers also found that the hamsters exposed to dim light at night showed more depressive symptoms when compared to hamsters in a standard light-dark cycle.

“Even dim light at night is sufficient to provoke depressive-like behaviors in hamsters, which may be explained by the changes we saw in their brains after eight weeks of exposure,” said Tracy Bedrosian, co- author of the study and doctoral student in neuroscience at Ohio State University.

Bedrosian and her colleagues presented the results Nov. 17 in San Diego at the annual meeting of the Society for Neuroscience.

The results are significant because the night-time light used in the study was not bright: 5 lux, or the equivalent of having a television on in a darkened room, said Randy Nelson, co-author of the study and professor of neuroscience and psychology at Ohio State.

“You would expect to see an impact if we were blasting these hamsters with bright lights, but this was a very low level, something that most people could easily encounter every night,” said Nelson, who is also a member of Ohio State’s Institute for Behavioral Medicine Research.

The study involved female Siberian hamsters, which had their ovaries removed to ensure that hormones produced in the ovary would not interfere with the results.

Half were housed in a standard light-dark cycle of 16 hours of light (at 150 lux) and eight hours of total darkness. The other half were housed in 16 hours of daylight (150 lux) and eight hours of dim light (5 lux).

After eight weeks in their lighting condition, they were tested for depressive-like behaviors. These tests are the same ones used by pharmaceutical companies to test anti-depressive and anti-anxiety drugs in animals before they are used in humans.

One depression test, for example, measured how much sugar water the mice drank. Mice generally like the drink, but those with depressive-like symptoms will not drink as much, presumably because they don’t get as much pleasure from activities they usually enjoy.

Results showed that hamsters that lived in the dim light at night showed more symptoms of depression compared to the hamsters in the standard light-dark cycle.

At the end of the experiment, the researchers examined the hippocampus area of the hamsters’ brains.

Results showed that mice that lived in the dim light had a significantly reduced density of dendritic spines – hairlike growths on brain cells, which are used to send chemical messages from one cell to another.

“The hippocampus plays a key role in depressive disorders, so finding changes there is significant,” Bedrosian said.

The researchers found no difference between the two groups of hamsters in terms of concentrations of the stress hormone cortisol. That’s important because hormones like cortisol have been linked to changes in the hippocampus.

“To the best of our knowledge, this is the first study to document that light at night is a sufficient stimulus to induce changes in the hippocampus, without changes in cortisol levels,” Nelson said.

How is light at night causing the changes in the hippocampus? The researchers believe it is related to production of the hormone melatonin. Light at night suppresses secretion of melatonin, which is involved in how the body knows it is nighttime.

The lower levels of melatonin at night may be the cause of the lower density of dendritic spines in the hippocampus, Bedrosian said.

The researchers are continuing this work by investigating the exact role of melatonin in the findings of this study.

These results are consistent with an earlier study by Nelson and his colleagues which found that constant bright light at night is linked to depressive symptoms in male mice. In another recent study, they found that light at night is also linked to weight gain in mice.

Public release date: 17-Nov-2010

Low-allergenic wines could stifle sniffles and sneezes in millions of wine drinkers

Scientists have identified a mysterious culprit that threatens headaches, stuffy noses, skin rash and other allergy symptoms when more than 500 million people worldwide drink wine. The discovery could help winemakers in developing the first low allergenic vintages — reds and whites with less potential to trigger allergy symptoms, they say. The new study appears in ACS’ monthly Journal of Proteome Research.

Giuseppe Palmisano and colleagues note growing concern about the potential of certain ingredients in red and white to cause allergy-like symptoms that range from stuffed up noses to headaches to difficulty breathing. So-called wine allergies occur in an estimated 8 percent of people worldwide. Only 1 percent of those involve sulfites, sulfur-containing substances that winemakers add to wine to prevent spoilage and also occur naturally. But the wine components that trigger allergies in the remaining 7 percent are unclear. Studies suggest that glycoproteins — proteins coated with sugars produced naturally as grapes         ferment — may be a culprit. However, scientists knew little about the structure and function of these substances in wine.

Their analysis of Italian Chardonnay uncovered 28 glycoproteins, some identified for the first time. The scientists found that many of the grape glycoproteins had structures similar to known allergens, including proteins that trigger allergic reactions to ragweed and latex. The discovery opens to door to development of wine-making processes that minimize formation of the culprit glycoproteins and offer consumers low-allergenic wines.

Public release date: 17-Nov-2010

Vitamin C: A potential life-saving treatment for sepsis

Physicians caring for patients with sepsis may soon have a new safe and cost-effective treatment for this life-threatening illness. Research led by Dr. Karel Tyml and his colleagues at The University of Western Ontario and Lawson Health Research Institute have found that vitamin C can not only prevent the onset of sepsis, but can reverse the disease.

Sepsis is caused by a bacterial infection that can begin anywhere in your body. Your immune system goes into overdrive, overwhelming normal processes in your blood. The result is that small blood clots form, blocking blood flow to vital organs. This can lead to organ failure. Babies, the elderly and those with weakened immune systems are most likely to get sepsis. But even healthy people can become deathly ill from the disease.

According to Dr. Tyml, a professor at Western’s Schulich School of Medicine & Dentistry, patients with

severe sepsis have a high mortality rate, nearly 40 percent, because there is no effective treatment.

“There are many facets to sepsis, but the one we have focused on for the past 10 years is the plugging of capillaries,” says Dr. Tyml. Plugged capillaries prevent oxygenation and the supply of life-supporting materials to your organ tissue and stop the removal of metabolic waste product. Plugged capillaries are seen in organs of septic patients. These organs may eventually fail, leading to multiple organ failure and death. Dr. Tyml’s lab was the first to discover this plugging by using intravital microscopy, a technique Dr. Tyml pioneered in Canada.

According to Dr. Tyml’s most recent publication, oxidative stress and the activated blood clotting pathway are the major factors responsible for the capillary plugging in sepsis. Through his research, Dr. Tyml  has discovered that a single bolus of vitamin C injected early at the time of induction of sepsis, prevents capillary plugging. He has also found that a delayed bolus injection of vitamin C can  reverse plugging by restoring blood flow in previously plugged capillaries.

“Our research in mice with sepsis has found that early as well as delayed injections of vitamin C improves chance of survival significantly,” explains Dr. Tyml. “Furthermore, the beneficial effect of a single bolus injection of vitamin C is long lasting and prevents capillary plugging for up to 24  hours post-injection.”

Dr. Tyml and his colleagues are eager to find appropriate support to move this research from the bench to the bedside to see if these findings translate to patients with sepsis.

The potential benefit of this treatment is substantial. “Vitamin C is cheap and safe. Previous studies have shown that it can be injected intravenously into patients with no side effects,” says Dr. Tyml. “It has the potential to significantly improve the outcome of sepsis patients world-wide. This could be especially beneficially in developing countries where sepsis is more common and expensive treatments are not affordable

Public release date: 18-Nov-2010

Pomegranate juice: Beyond antioxidants, potential benefits for dialysis patients

Pomegranate juice reduces damage to tissues, inflammation and infections

Studies in recent years have claimed multiple health benefits of pomegranate juice, including that it is a good source of antioxidants and lowers both cholesterol and blood pressure, especially in diabetic and

hypertensive patients. A preliminary study now suggests that it can ward off a number of complications in kidney disease patients on dialysis, including the high morbidity rate due to infections and cardiovascular events, according to a paper being presented at the American Society of Nephrology’s 43rd Annual Meeting and Scientific Exposition in Denver, CO.

Batya Kristal, MD, FASN (Western Galilee Hospital, in Nahariya, Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel), PhD candidate, Lilach Shema, and colleagues studied 101 dialysis patients who received either pomegranate juice or another placebo drink at the beginning of each dialysis session, three times a week for one year.

Laboratory tests showed that patients who drank pomegranate juice experienced reduced inflammation and the damage of oxidative stress caused by free radicals, was minimized. Furthermore, pomegranate juice drinkers were less likely to be hospitalized due to infections. These findings support other studies that suggest pomegranate juice has potent antioxidant properties.

Recent analyses of data not included in this abstract, revealed that those who drank pomegranate juice also showed an improvement in cardiovascular risk factors, such as reduced blood pressure, improvement in lipid profile and fewer cardiovascular events, suggesting that they had better heart health. These results are in agreement with other studied populations and particularly important for hemodialysis patients, because most kidney disease patients die either from cardiovascular-related causes or infections.

The authors say their findings suggest that drinking a controlled amount of pomegranate juice with a safe and monitored content of potassium may help reduce the complications that often occur in dialysis patients. It is important to consider the risk involved in potassium overload, especially in chronic kidney disease (CKD) patients with dietary potassium restriction.

“Considering the expected epidemic of CKD in the next decade, further clinical trials using pomegranate juice aimed at reducing the high cardiovascular morbidity of CKD patients and their deterioration to end- stage renal disease should be conducted,” said Dr. Kristal.

Public release date: 18-Nov-2010

Taking a break from osteoporosis drugs can protect bones

MAYWOOD, Ill. — Taking time off from certain osteoporosis drugs may be beneficial to bone health, according to a study conducted at Loyola University Health System. Researchers found that bone  density remained stable for three years in patients who took a drug holiday from bisphosphonates, a popular class of osteoporosis drugs that can cause fractures in the thigh bones and tissue decay in  the jaw bone.

“These drugs are potentially harmful when taken for long durations, yet little has been known until now about the length of time osteoporosis patients should go without treatment for this debilitating condition,” said Pauline Camacho, MD, study investigator and director of the Loyola University Osteoporosis and Metabolic Bone Disease Center. “Our study demonstrated that bones can remain stable for a number of years after these drugs are discontinued.”

Doctors recommend that patients take drug holidays from bisphosphonates after four to five years. These drugs continue to stabilize bones and reduce the risk for bone loss after treatment ceases.

The study’s goal was to identify the optimal drug holiday length after prolonged use of bisphosphonates based on changes in bone mineral density and bone loss. The study evaluated 139 patients (123 females, 16 males) with osteoporosis and osteopenia, the precursor to the disease. Patients took a bisphosphonate

an average of 6.8 years before beginning a drug holiday from 2005 to 2010. Over three years, five fractures occurred, but bone mineral density did not change significantly. However, bone loss did start to increase at six months. The type of bisphosphonate and the duration of treatment did not affect bone mineral density.

“While further research is needed to adequately assess the optimal duration of the drug holiday, we do know that patients can relatively safely discontinue their treatment for at least three years,” Dr. Camacho said. “However, patients who fracture during their drug holiday should notify their physician right away so osteoporosis therapy can be resumed. Patients also should continue to see their physician to regularly monitor their bone health.”

Public release date: 19-Nov-2010

Elderly can blame fractures and falls on low sodium

But increase in fractures isn’t explained by osteoporosis

Older adults with even mildly decreased levels of sodium in the blood (hyponatremia) experience increased rates of fractures and falls, according to a study presented at the American Society of Nephrology’s 43rd Annual Meeting and Scientific Exposition. Falls are a serious health problem for the elderly and account for about 50 percent of deaths due to injury in the elderly.

“Screening for a low sodium concentration in the blood, and treating it when present, may be a new strategy to prevent fractures,” comments Ewout J. Hoorn, MD, PhD (Erasmus Medical Center, Rotterdam, the Netherlands). However, hyponatremia does not appear to affect the risk of osteoporosis, as defined by low bone mineral testing, so more research is needed to understand the link between sodium levels and fracture risk.

The study included more than 5,200 Dutch adults over age 55, all with initial information on sodium levels and six-year follow-up data on fractures and falls. “A number of recent studies suggested a relationship between hyponatremia, falls, osteoporosis, and fractures,” Hoorn explains. The authors’ goal was to confirm these possible associations using prospective, long-term follow-up data.

About eight percent of the study participants, all community dwelling adults, had hyponatremia. This group of older participants had a higher rate of diabetes and was more likely to use diuretics (water pills) than those with normal sodium levels. Subjects with hyponatremia had a higher rate of falls during follow-up: 24 versus 16 percent. However, there was no difference in bone mineral density between groups, so hyponatremia was not related to underlying osteoporosis.

Nevertheless, the group with low sodium levels had a higher rate of fractures. With adjustment for other risk factors, the risk of vertebral / vertebral compression fractures was 61 percent higher in the older adults with hyponatremia. The risk of non-spinal fractures, such as hip fractures, was also significantly increased: a 39 percent difference.

The relationship between hyponatremia and fracture risk was independent of the increased rate of falls in the low-sodium group. Subjects with hyponatremia also had a 21 percent increase in the risk of death during follow-up.

Hyponatremia is the most common electrolyte disorder, usually developing because the kidneys retain too

much water. “Although the complications of hyponatremia are well-recognized in hospitalized patients, this is one of the first studies to show that mild hyponatremia also has important complications in the general population,” says Hoorn.

Further study will be needed to clarify the mechanism by which low sodium levels increase fracture risk. In the meantime, “Screening older adults for and treatment of hyponatremia in older adults may be an important new strategy to prevent fractures,” adds Hoorn.

Public release date: 22-Nov-2010

High alpha-carotene levels associated with longer life

High blood levels of the antioxidant alpha-carotene appear to be associated with a reduced risk of dying over a 14-year period, according to a report posted online today that will be published in the March 28 print issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Oxygen-related damage to DNA, proteins and fats may play a role in the development of chronic diseases like heart disease and cancer, according to background information in the article. Carotenoids—including beta-carotene, alpha-carotene and lycopene—are produced by plants and microorganisms and act as antioxidants, counteracting this damage. Carotenoids in the human body are obtained mainly through eating fruits and vegetables rich in the nutrients, or through antioxidant supplements.

Although studies suggest eating more fruits and vegetables is associated with lower risk of chronic diseases, randomized controlled trials have not shown any benefit for beta-carotene supplements, the authors note. “Therefore, carotenoids other than beta-carotene may contribute to the reduction in disease risk, and their effects on risk of disease merit investigation,” the authors write.

Chaoyang Li, M.D., Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues assessed the relationship between alpha-carotene and the risk of death among 15,318 adults age 20 and older who participated in the Third National Health and Nutrition Examination Survey Follow-up Study. Participants underwent a medical examination and provided blood samples between 1988 and 1994, and were followed through 2006 to determine whether and how they died.

Over the course of the study, 3,810 participants died; the risk for dying was lower with higher levels of alpha-carotene in the blood. Compared with individuals with blood alpha-carotene levels between 0 and 1 micrograms per deciliter, the risk of death during the study period was 23 percent lower among who had concentrations between 2 and 3 micrograms per deciliter, 27 percent lower with levels between 4 and 5 micrograms per deciliter, 34 percent lower with levels between 6 and 8 micrograms per deciliter and 39 percent lower with levels of 9 micrograms per deciliter or higher.

Higher alpha-carotene concentration also appeared to be associated with lower risk of dying from cardiovascular disease or cancer individually, and of all other causes. “The association between serum alpha-carotene concentrations and risk of death from all causes was significant in most subgroups stratified by demographic characteristics, lifestyle habits and health risk factors,” the authors write.

Alpha-carotene is chemically similar to beta-carotene but may be more effective at inhibiting the growth of cancer cells in the brain, liver and skin, they note. “Moreover, results from a population- based case-control study of the association between the consumption of fruits and vegetables and risk of lung cancer suggest that consumption of yellow-orange (carrots, sweet potatoes or pumpkin and winter squash) and dark-green (broccoli, green beans, green peas, spinach, turnips greens, collards and leaf lettuce) vegetables, which have a high alpha-carotene content, was more strongly associated with a decreased risk of lung cancer than was consumption of all other types of vegetables,” the authors write.

The results support increasing fruit and vegetable consumption as a way of preventing premature death, and suggest a need for clinical research into the health benefits of alpha-carotene, they conclude.

Public release date: 22-Nov-2010

Bacteria help infants digest milk more effectively than adults

Infants are more efficient at digesting and utilizing nutritional components of milk than adults due to a difference in the strains of bacteria that dominate their digestive tracts. Researchers from the University of California, Davis, and Utah State University report on genomic analysis of these strains in the November 2010 issue of the journal Applied and Environmental Microbiology identifying the genes that are most likely responsible for this difference.

“Human milk oligosaccharides (HMOs) are the third-largest solid component of milk. Their structural complexity renders them non-digestible to the host,” say the researchers. “Bifidobacterium longum strains often predominate the colonic microbiota of exlusively breast-fed infants. Among the three recognized subspecies, B. longum subsp. infantis achieves high levels of cell growth on HMOs and is associated with early colonization of the infant gut.”

In the study the researchers used whole-genome microarray comparisons to associate genotypic biomarkers among 15 B. longum strains exhibiting various HMO utilization patterns. They identified 5 distinct gene clusters on B. longum that were conserved (showed little or no variation) across all strains capable of growth on HMOs and have also diverged in strains incapable of growing on HMOs.

The results of this study suggest that B. longum has at least 2 distinct subspecies: B. longum subsp. infantis, adapted to ultilize milk carbon and found primarily in the digestive tract of children, and B. longum subsp. longum, specialized for plant-derived carbon metabolism and associated with the adult digestive tract.

“Although early gut colonization is likely dependent on a multitude of dietary and nondietary factors, the delivery of complex oligosaccharides through milk creates an ideal and unique nutrient niche for the establishment of, and colonization by, B. longum subsp. infantis strains,” say the researchers. “During weaning, a gradual transitioning from milk-based to plant-based diets generates a shift in carbon availability in the gastrintestinal tract favorable for the expansion and formtion of an adult-like gastointestinal tract microbiota.”

Public release date: 24-Nov-2010

Danish researchers finally solve the obesity riddle

Researchers at the Faculty of Life Sciences (LIFE), University of Copenhagen, can now unveil the results of the world’s largest diet study: If you want to lose weight, you should maintain a diet that is high in proteins with more lean meat, low-fat dairy products and beans and fewer finely refined starch calories such as white bread and white rice. With this diet, you can also eat until you are full without counting calories and without gaining weight. Finally, the extensive study concludes that the official dietary recommendations are not sufficient for preventing obesity.

The large-scale random study called Diogenes has investigated the optimum diet composition for preventing and treating obesity. The study was conducted by eight European research centres and headed by Thomas Meinert Larsen, PhD, and Professor Arne Astrup, DrMedSc and Head of Department at the Faculty of Life Sciences (LIFE) and is funded by an EU grant of EUR 14.5 million.

The results were recently published in the distinguished New England Journal of Medicine and have already attracted considerable international attention.

The objective of the Diogenes study has been to compare the official dietary recommendations in Europe, including the Danish recommendations, with a diet based on the latest knowledge about the importance of proteins and carbohydrates for appetite regulation. A total of 772 European families participated, comprising 938 adult family members and 827 children. The overweight adults initially followed an 800 kcal/day diet for eight weeks, losing an average of 11 kg. They were then randomly assigned to one of five different low-fat diet types which they followed for six months in order to test which diet was most effective at preventing weight regain. Throughout the project, the families received expert guidance from dieticians and were asked to provide blood and urine samples.

The five diet types

The design comprised the following five diet types:

•A low-protein diet (13% of energy consumed) with a high glycemic index (GI)*

•A low-protein, low-GI diet

•A high-protein (25% of energy consumed), low-GI diet

•A high-protein, high-GI diet

•A control group which followed the current dietary recommendations without special instructions regarding glycemic index levels

A high-protein, low-GI diet works best

A total of 938 overweight adults with a mean body mass index (BMI) of 34 kg/sq m were initially placed on an 800-kcal-per-day diet for eight weeks before the actual diet intervention was initiated. A total of 773 adult participants completed this initial weight-loss phase and were then randomly assigned to one of five different diet types, where 548 participants completed the six-month diet intervention (completion rate of 71%).

Fewer participants in the high-protein, low-GI groups dropped out of the project than in the low-protein, high-GI group (26.4% and 25.6%, respectively, vs. 37.4%; P = 0.02 and P = 0.01 for the two comparisons, respectively). The initial weight loss on the 800-kcal diet was an average of 11.0 kg.

The average weight regain among all participants was 0.5 kg, but among the participants who completed the study, those in the low-protein/high-GI group showed the poorest results with a significant weight gain of 1.67 kg. The weight regain was 0.93 kg less for participants on a high-protein diet than for those         on a low-protein diet and 0.95 kg less in the groups on a low-GI diet compared to those on a high-GI diet.

The children’s study

The results of the children’s study have been published in a separate article in the American medical journal Pediatrics. In the families, there were 827 children who only participated in the diet intervention. Thus, they were never required to go on a diet or count calories – they simply followed the same diet as their parents. Approx. 45% of the children in these families were overweight. The results of the children’s study were remarkable: In the group of children who maintained a high-protein, low-GI diet the prevalence of overweight dropped spontaneously from approx. 46% to 39% – a decrease of approx. 15%.

Proteins and low-GI foods ad libitum – the way ahead

The Diogenes study shows that the current dietary recommendations are not optimal for preventing weight gain among overweight people. A diet consisting of a slightly higher protein content and low-GI foods ad libitum appears to be easier to observe and has been documented to ensure that overweight people who

have lost weight maintain their weight loss. Furthermore, the diet results in a spontaneous drop in the prevalence of overweight among their children.

Public release date: 24-Nov-2010

Growth-factor gel shows promise as hearing-loss treatment

A new treatment has been developed for sudden sensorineural hearing loss (SSHL), a condition that causes deafness in 40,000 Americans each year, usually in early middle-age. Researchers writing in the open access journal BMC Medicine describe the positive results of a preliminary trial of insulin-like growth factor 1 (IGF1), applied as a topical gel.

Takayuki Nakagawa, from Kyoto University, Japan, worked with a team of researchers to test the gel in 25 patients whose SSHL had not responded to the normal treatment of systemic gluticosteroids. He said, “The results indicated that the topical IGF1 application using gelatin hydrogels was safe, and had equivalent or superior efficiency to the hyperbaric oxygen therapy that was used as a historical control; this suggests that the efficacy of topical IGF1 application should be further evaluated using randomized clinical trials”.

At 12 weeks after the test treatment, 48% of patients showed hearing improvement, and the proportion increased to 56% at 24 weeks. No serious adverse events were observed. This is the first time that growth factors have been tested as a hearing remedy. According to Nakagawa, “Although systemic glucocorticoid application results in hearing recovery in some patients with SSHL, approximately 20% show no recovery. Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for these patients”.

Public release date: 24-Nov-2010

New study reveals how cannabis suppresses immune functions

Cannabis compounds found to trigger unique immune cells which promote cancer growth

An international team of immunologists studying the effects of cannabis have discovered how smoking marijuana can trigger a suppression of the body’s immune functions. The research, published in the European Journal of Immunology, reveals why cannabis users are more susceptible to certain types of cancers and infections.

The team, led by Dr Prakash Nagarkatti from the University of South Carolina, focused their research on cannabinoids, a group of compounds found inside the cannabis plant, including THC (delta-9 tetahydrocannabinol) which is already used for medical purposes such as pain relief.

“Cannabis is one of the most widely used drugs of abuse worldwide and it is already believed to suppress immune functions making the user more susceptible to infections and some types of cancer,” said Dr Nagarkatti. “We believe the key to this suppression is a unique type of immune cell, which has only recently been identified by immunologists, called myeloid-derived suppressor cells, MDSCs.”

While most immune cells fight against infections and cancers to protect the host, MDSCs actively suppress the immune system. The presence of these cells is known to increase in cancer patients and it is believed that MDSCs may suppress the immune system against cancer therapy, actually promoting cancer growth.

Dr Nagarkatti’s team demonstrated that cannabinoids can trigger a massive number of MDSCs through activation of cannabinoid receptors. This research reveals, for the first time, that marijuana cannabinoids

may suppress the immune system by activating these unique cells.

“These results raise interesting questions on whether increased susceptibility to certain types of cancers or infections caused from smoking marijuana results from induction of MDSCs,” said Nagarkatti. “MDSCs seem to be unique and important cells that may be triggered by inappropriate production of certain growth factors by cancer cells or other chemical agents such as cannabinoids, which lead to a suppression of the immune system’s response.”

In a related study, also published in the European journal of Immunology, Dr Christian Vosshenrich from the Institut Pasteur in Paris, reveals that when cancer cells grow they produce a molecule called interleukin-1 β (IL-1β), which also triggers MDSCs. This study identifies how MDSCs produced during cancer growth also weaken the ability of immune cells to kill cancer cells.

“Marijuana cannabinoids present us with a double edged sword,” concluded Dr Nagarkatti. “On one hand, due to their immunosuppressive nature, they can cause increased susceptibility to cancer and infections.

However, further research of these compounds could provide opportunities to treat a large number of clinical disorders where suppressing the immune response is actually beneficial.”

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