Adding Vitamins C and E to diet improves effectiveness of insulin

Adding antioxidants to therapy improves drug’s ability to reduce blood sugar

Boosting insulin with vitamins C and E may improve the drug’s effectiveness for treating diabetes.

A UC Irvine College of Medicine study has found that the popular antioxidant supplements not only enhance insulin’s ability to reduce blood sugar, but also lower the risks of organ damage that can occur despite insulin treatments. The study appears in the January issue of Kidney International.

Dr. Nick Vaziri, professor of medicine, and his team found that untreated diabetes raised blood pressure and increased the production of damaging oxidizing agents called free radicals. The free radicals converted sugars and proteins into harmful chemicals, increasing the risks of tissue damage often seen in untreated diabetes.

Treating the rats with insulin alone improved high blood pressure somewhat and partially spared the sugars and proteins from the free radicals’ assault. But it also added a new problem, as the free radicals turned their attack on nitric oxide, a ubiquitous molecule that usually protects the body from free radicals. This new attack results in yet more toxic chemicals, with the potential to inflict damage to tissues.

Adding vitamins C and E to insulin, however, spared the sugars, proteins and nitric oxide from attack.

“Blood pressure was lowered to normal, and free radicals were not in sufficient numbers to degrade the sugars, proteins and nitric oxide,” Vaziri said. “We think this shows that a diet rich in antioxidants may help diabetics prevent the devastating cardiovascular, kidney, neurological and other damage that are common complications of diabetes.”

Diabetes affects nearly 17 million Americans. Insulin is the predominant treatment, but patients eventually develop complications, like various forms of heart disease and nerve, liver and kidney damage. Studies would still have to be tested in humans, but Vaziri believes that adding vitamins C and E to an insulin-dependent diabetic’s diet should help treat the disease and perhaps prevent future organ damage.

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Andrew Porterfield
University of California – Irvine

The link between lack of sleep and obesity traced to brain cells

A possible link between lack of sleep (insomnia) and obesity has been traced to hypocretin/orexin cells in the hypothalamus region of the brain that are easily excited and sensitive to stress, Yale School of Medicine researchers report in the April 2005 issue of Cell Metabolism.

“If these neurons are over-activated by environmental or mental stress in daily situations, they may support sustained arousal, triggering sleeplessness, leading to overeating,” said lead author Tamas Horvath, associate professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences (Ob/Gyn) and Neurobiology at Yale School of Medicine. “The more stress you have, the lower the threshold becomes for exciting these hypocretin neurons.”

Horvath and co-author Xiao-Bing Gao, assistant professor in Ob/Gyn, studied hypocretin/orexin neurons in mice using electrophysiology and electron microscopy. They found a unique, previously un-described organization of inputs on hypocretin neurons in which excitatory nerve junctions outnumber inhibitory contacts by almost 10 fold. Stressors such as fasting further excite these neurons.

“This unique wiring and acute stress-induced plasticity of the hypocretin neurons correlates well with its involvement in the control of arousal and alertness, which are vital to survival,” said Horvath. “But it may also be an underlying cause of insomnia and associated metabolic disturbances, including obesity. In addition, insomnia is characteristic of perimenopause (early onset of menopause), which may lead to increased prevalence of obesity in postmenopausal women.”

Previous studies demonstrated the association between lack of sleep and obesity and suggested a good night’s sleep to help obesity. Horvath found that the neurological basis of the link between obesity and insomnia make them both independent and related products of the overactivated hypocretin system. Therefore, he said, “people with weight and sleep problems could benefit from cutting back on stressful aspects of their lives, rather than trying to specifically medicate either insomnia or obesity.”

Obesity and metabolic disorders are a major cause of death and illness in the United States, with one of the highest financial burdens on the health care system.

 —————————-
Article adapted by MD Only Weblog from original press release.
—————————-   

Contact: Karen N. Peart
Yale University

Citation: Cell Metabolism Vol. 1, Issue 4 (April 2005).

Low testosterone levels in men after 40 increase risk of death

Men who have a low testosterone level after age 40 may have a higher risk of death over a four-year period than those with normal levels of the hormone, according to a report in the August 14/28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Unlike women undergoing menopause, middle-aged men generally do not experience a dramatic decrease in the production of sex hormones, according to background information in the article. Testosterone levels gradually decline as a man ages, decreasing approximately 1.5 percent per year after age 30. The effects of low testosterone levels include decreased muscle mass and bone density, insulin resistance, decreased sex drive, less energy, irritability and feelings of depression.

Molly M. Shores, M.D., and colleagues at the VA Puget Sound Health Care System and University of Washington, Seattle, studied the relationship between hormone levels and death in a total of 858 male veterans older than age 40 years. All participants received care in the VA Puget Sound Health Care System and had their testosterone levels checked at least twice between 1994 and 1999, with at least one week and no more than two years elapsing between tests. The men were followed for an average of 4.3 years and a maximum of eight years, through 2002.

About 19 percent (166) of the men had a low testosterone level; 28 percent (240) had an equivocal testosterone level, meaning that their tests revealed an equal number of low and normal levels; and 53 percent (452) had normal testosterone levels. One-fifth (20.1 percent) of the men with normal testosterone levels died during the course of the study, compared with 24.6 percent of men with equivocal levels and 34.9 percent of those with low levels. Men with low testosterone levels had an 88 percent increase in risk of death compared with those who had normal levels. When the researchers considered other variables that may influence risk of death, such as age, other illnesses and body mass index, the association between low testosterone levels and death persisted.

Previous studies have found that testosterone levels may dramatically decrease one to two days after surgery, trauma or critical illness–all factors that can increase the risk of death. To eliminate these effects, the authors reanalyzed the data excluding men who had died within the first year of follow-up. Men with low testosterone levels were still 68 percent more likely to have died. “The persistence of elevated mortality risk after excluding early deaths suggests that the association between low testosterone and mortality is not simply due to acute illness,” they write. “Large prospective studies are needed to clarify the association between low testosterone levels and mortality.” (Arch Intern Med. 2006;166:1660-1665. (http://www.jamamedia.org.)

—————————-
Article adapted by MD Only Weblog from original press release.
—————————- 

Contact: Clare Hagerty
JAMA and Archives Journals

Editor’s Note: This study was supported by the Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System; the Royalty Research Fund of the University of Washington (Dr. Shores); and a VA merit review grant (Dr. Matsumoto). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Caffeine Boosts Blood Pressure and Stress Hormones All Day

People who drink four or five cups of coffee throughout the morning have slightly elevated blood pressure and higher levels of stress hormones all day and into the evening, creating a scenario in which the body acts like it is continually under stress, according to a group of Duke University Medical Center scientists.In a study of 72 habitual coffee drinkers, the researchers found that subjects produced more adrenaline and noradrenalin and had higher blood pressure on days when they drank caffeine compared with days they abstained. The two stress hormones are vital to helping the body react quickly in times of danger or stress, but they can damage the heart over a lifetime of heightened production, said James Lane, associate research professor of psychiatry at Duke.

Lane prepared results of his study, funded by the National Heart, Lung and Blood Institute, for presentation Thursday to a meeting of the 1999 Society of Behavioral Medicine.

“Moderate caffeine consumption makes a person react like he or she is having a very stressful day,” Lane said in an interview before the meeting. “If you combine the effects of real stress with the artificial boost in stress hormones that comes from caffeine, then you have compounded the effects considerably.”

During the two-week study, the subjects experienced, on average, a 32 percent increase in adrenalin and a 14 percent increase in noradrenaline on days when they consumed caffeine. Their blood pressure rose an average of 3 points.

Lane’s study builds on smaller ones in which he found that caffeine boosted blood pressure, heart rate and stress hormones in subjects who drank 4 to 5 cups of caffeine per day. In the current study, Lane replicated those findings and added to them by showing that subjects’ blood pressures and stress hormone levels stayed elevated until bedtime, even though they last consumed caffeine between noon and 1 p.m.

Occasional surges of stress hormones temporarily raise heart rate, blood pressure and mental acuity — long enough to accomplish the task at hand. But an excess of stress hormones has been shown to compromise health in a variety of ways, from damaging blood vessels to weakening the immune system.

In addition, even the small boost in blood pressure seen in this study — an average of 3 points during the day and evening — can have clinical significance, Lane said. A review of nine major studies of blood pressure and heart-disease risk showed that a 5-point difference in diastolic blood-pressure — the lower number used to assess health risk — was associated with at least a 34 percent increase in stroke and a 21 percent increase in the incidence of coronary heart disease

While researchers have long known that caffeine can boost stress hormones and blood pressure, Lane said most studies have been conducted in a laboratory setting under tightly controlled circumstances where a single dose of caffeine is compared to none in a short time span. Lane said his body of research is unique because it measures blood pressure, heart rate and stress hormone levels at timed intervals during normal working conditions, while subjects are exposed to a range of moods and activities.

“You can measure how caffeine affects people in the laboratory, but that doesn’t tell you what effects the drug has in the real world when people are exposed to normal stressors and activities,” he said.

In the current study, Lane also studied the effects of caffeine on women taking oral contraceptives, since previous research suggested that this population might be more responsive to the negative effects of caffeine. But Lane found no such effect. In fact, women taking oral contraceptives showed slightly less of a stress response to caffeine than a control group of women.

Lane’s next study will measure the effects of eliminating caffeine from the diets of people with high blood pressure. The goal is to see if stopping caffeine use can be a useful therapy in reducing hypertension, along with diet, exercise and salt reduction.

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Rebecca A. Levine
Duke University Medical Center

High sugar, low caffeine drink make you sleepy

An hour after consuming a high sugar, low caffeine drink you will tend to have slower reactions and experience more lapses in concentration than if you had simply drunk a decaffeinated, nil carbohydrate drink.

This was the finding of research performed at the University of Loughborough and published in Human Psychopharmacology: Clinical and Experimental.

Ten healthy adults had volunteered to restrict their sleep to 5 hours on the day before participating in the trial. An hour after eating a light lunch they were given either an energy drink (42g sugar + 30mg caffeine) or an identically tasting zero-sugar drink. They then performed a monotonous 90-minute test during the afternoon ‘dip’ that assessed their sleepiness and ability to concentrate.

For the first 30 minutes there was no difference in the reaction times or error rates, but 50 minutes after consuming the drinks, the performance of those who had had the energy drink started to slip, and they became significantly sleepier.

Other researched work shows that high energy drinks that contain caffeine will boost concentration.(1)

“A ’sugar rush’ is not very effective in combating sleepiness – so avoid soft drinks that contain lots of sugar but little or no caffeine,” explains Professor Jim Horne, who runs the Sleep Research Centre at the University of Loughborough. “A much better way to combat sleepiness is to have a drink that contains more useful amounts of caffeine and combine this with a short nap”.

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Polly Young
John Wiley & Sons, Inc.

Notes to Editors

• Physiology & Behavior, 2002, 75: 331-335.

• Full citation: C. Anderson & J.A. Home. A high sugar content, low caffeine drink does not alleviate sleepiness but may worsen it. Hum Psychopharmacol Clin Exp 2006; 21: 1-5

• Human Psychopharmacology: Clinical and Experimental provides a forum for the evaluation of clinical and experimental research on both new and established psychotropic medicines. Experimental studies of other centrally active drugs, including herbal products, in clinical, social and psychological contexts, as well as clinical/scientific papers on drugs of abuse and drug dependency are also be considered. While the primary purpose of the journal is to publish the results of clinical research, the results of animal studies relevant to human psychopharmacology are welcome. The journal’s co-editors are Professor Stephen Curran of the University of Huddersfield, UK and Professor C. Lindsay DeVane of the Medical University of South Carolina, Charlestown, USA. Human Psychoparmacology can be accessed at: http://www.interscience.wiley.com/journal/hup

Nanodiamonds Sparkle Delivering Drugs Without Side Effects

Northwestern University researchers have shown that nanodiamonds — much like the carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale — are very effective at delivering chemotherapy drugs to cells without the negative effects associated with current drug delivery agents.

Their study, published online by the journal Nano Letters, is the first to demonstrate the use of nanodiamonds, a new class of nanomaterials, in biomedicine. In addition to delivering cancer drugs, the model could be used for other applications, such as fighting tuberculosis or viral infections, say the researchers.

Nanodiamonds promise to play a significant role in improving cancer treatment by limiting uncontrolled exposure of toxic drugs to the body. The research team reports that aggregated clusters of nanodiamonds were shown to be ideal for carrying a chemotherapy drug and shielding it from normal cells so as not to kill them, releasing the drug slowly only after it reached its cellular target.

Another advantage of the material, confirmed by a series of genetic studies also reported in the paper, is that nanodiamonds do not cause cell inflammation once the drug has been released and only bare diamonds are left. Materials currently used for drug delivery can cause inflammation, a serious complication that can predispose a patient to cancer, block the activity of cancer drugs and even promote tumor growth.

“There are a lot of materials that can deliver drugs well, but we need to look at what happens after drug delivery,” said Dean Ho, assistant professor of biomedical engineering and mechanical engineering at Northwestern’s McCormick School of Engineering and Applied Science, who led the research. “How do cells react to an artificial material left in the body? Nanodiamonds are highly ordered structures, which cells like. If they didn’t, cells would become inflamed. From a patient’s perspective, this is very important. And that’s why clinicians are interested in our work.”

“Novel drug delivery systems, such as the one being developed by Dean and his team, hold great promise in cancer therapeutics,” said Steven Rosen, M.D., director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and Genevieve E. Teuton Professor of Medicine at Northwestern’s Feinberg School of Medicine. “We anticipate they will allow for more sophisticated means of targeting cancer cells while sparing healthy cells from a drug’s toxicity.”

To make the material effective, Ho and his colleagues manipulated single nanodiamonds, each only two nanometers in diameter, to form aggregated clusters of nanodiamonds, ranging from 50 to 100 nanometers in diameter. The drug, loaded onto the surface of the individual diamonds, is not active when the nanodiamonds are aggregated; it only becomes active when the cluster reaches its target, breaks apart and slowly releases the drug. (With a diameter of two to eight nanometers, hundreds of thousands of diamonds could fit onto the head of a pin.)

“The nanodiamond cluster provides a powerful release in a localized place — an effective but less toxic delivery method,” said co-author Eric Pierstorff, a molecular biologist and post-doctoral fellow in Ho’s research group. Because of the large amount of available surface area, the clusters can carry a large amount of drug, nearly five times the amount of drug carried by conventional materials.

Liposomes and polymersomes, both spherical nanoparticles, currently are used for drug delivery. While effective, they are essentially hollow spheres loaded with an active drug ready to kill any cells, even healthy cells that are encountered as they travel to their target. Liposomes and polymersomes also are very large, about 100 times the size of nanodiamonds — SUVs compared to the nimble nanodiamond clusters that can circulate throughout the body and penetrate cell membranes more easily.

Unlike many of the emerging nanoparticles, nanodiamonds are soluble in water, making them clinically important. “Five years ago while working in Japan, I first encountered nanodiamonds and saw it was a very soluble material,” said materials scientist Houjin Huang, lead author of the paper and also a post-doctoral fellow in Ho’s group. “I thought nanodiamonds might be useful in electronics, but I didn’t find any applications. Then I moved to Northwestern to join Dean and his team because they are capable of engineering a broad range of devices and materials that interface well with biological tissue. Here I’ve focused on using nanodiamonds for biomedical applications, where we’ve found success.

“Nanodiamonds are very special,” said Huang. “They are extremely stable, and you can do a lot of chemistry on the surface, to further functionalize them for targeting purposes. In addition to functionality, they also offer safety — the first priority to consider for clinical purposes. It’s very rare to have a nanomaterial that offers both.”

“It’s about optimizing the advantages of a material,” said Ho, a member of the Lurie Cancer Center. “Our team was the first to forge this area — applying nanodiamonds to drug delivery. We’ve talked to a lot of clinicians and described nanodiamonds and what they can do. I ask, ‘Is that useful to you?’ They reply, ‘Yes, by all means.’”

For their study, Ho and his team used living murine macrophage cells, human colorectal carcinoma cells and doxorubicin hydrochloride, a widely used chemotherapy drug. The drug was successfully loaded onto the nanodiamond clusters, which efficiently ferried the drug inside the cells. Once inside, the clusters broke up and slowly released the drug.

In the genetic studies, the researchers exposed cells to the bare nanodiamonds (no drug was present) and analyzed three genes associated with inflammation and one gene for apoptosis, or cell death, to see how the cells reacted to the foreign material. Looking into the circuitry of the cell, they found no toxicity or inflammation long term and a lack of cell death. In fact, the cells grew well in the presence of the nanodiamond material.

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Megan Fellman
Northwestern University