Mystery Ingredient in Coffee Boosts Protection Against Alzheimer's Disease, Study Finds

Mystery Ingredient in Coffee Boosts Protection Against Alzheimer's Disease, Study Finds

  9:59:00 AM    Science Lover

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A yet unidentified component of coffee interacts with the beverage's caffeine, which could be a surprising reason why daily coffee intake protects against Alzheimer's disease. A new Alzheimer's mouse study by researchers at the University of South Florida found that this interaction boosts blood levels of a critical growth factor that seems to fight off the Alzheimer's disease process.

The findings appear in the early online version of an article to be published June 28 in the Journal of Alzheimer's Disease. Using mice bred to develop symptoms mimicking Alzheimer's disease, the USF team presents the first evidence that caffeinated coffee offers protection against the memory-robbing disease that is not possible with other caffeine-containing drinks or decaffeinated coffee.

Previous observational studies in humans reported that daily coffee/caffeine intake during mid-life and in older age decreases the risk of Alzheimer's disease. The USF researchers' earlier studies in Alzheimer's mice indicated that caffeine was likely the ingredient in coffee that provides this protection because it decreases brain production of the abnormal protein beta-amyloid, which is thought to cause the disease.

The new study does not diminish the importance of caffeine to protect against Alzheimer's. Rather it shows that caffeinated coffee induces an increase in blood levels of a growth factor called GCSF (granulocyte colony stimulating factor). GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice. A just-completed clinical trial at the USF Health Byrd Alzheimer's Institute is investigating GCSF treatment to prevent full-blown Alzheimer's in patients with mild cognitive impairment, a condition preceding the disease. The results of that trial are currently being evaluated and should be known soon.

"Caffeinated coffee provides a natural increase in blood GCSF levels," said USF neuroscientist Dr. Chuanhai Cao, lead author of the study. "The exact way that this occurs is not understood. There is a synergistic interaction between caffeine and some mystery component of coffee that provides this beneficial increase in blood GCSF levels."

The researchers would like to identify this yet unknown component so that coffee and other beverages could be enriched with it to provide long-term protection against Alzheimer's.

In their study, the researchers compared the effects of caffeinated and decaffeinated coffee to those of caffeine alone. In both Alzheimer's mice and normal mice, treatment with caffeinated coffee greatly increased blood levels of GCSF; neither caffeine alone or decaffeinated coffee provided this effect. The researchers caution that, since they used only "drip" coffee in their studies, they do not know whether "instant" caffeinated coffee would provide the same GCSF response.

The boost in GCSF levels is important, because the researchers also reported that long-term treatment with coffee (but not decaffeinated coffee) enhances memory in Alzheimer's mice. Higher blood GCSF levels due to coffee intake were associated with better memory. The researchers identified three ways that GCSF seems to improve memory performance in the Alzheimer's mice. First, GCSF recruits stem cells from bone marrow to enter the brain and remove the harmful beta-amyloid protein that initiates the disease. GCSF also creates new connections between brain cells and increases the birth of new neurons in the brain.



"All three mechanisms could complement caffeine's ability to suppress beta amyloid production in the brain" Dr. Cao said, "Together these actions appear to give coffee an amazing potential to protect against Alzheimer's -- but only if you drink moderate amounts of caffeinated coffee."

Although the present study was performed in Alzheimer's mice, the researchers indicated that they've gathered clinical evidence of caffeine/coffee's ability to protect humans against Alzheimer's and will soon publish those findings.

Coffee is safe for most Americans to consume in the moderate amounts (4 to 5 cups a day) that appear necessary to protect against Alzheimer's disease. The USF researchers previously reported this level of coffee/caffeine intake was needed to counteract the brain pathology and memory impairment in Alzheimer's mice. The average American drinks 1½ to 2 cups of coffee a day, considerably less than the amount the researchers believe protects against Alzheimer's.

"No synthetic drugs have yet been developed to treat the underlying Alzheimer's disease process" said Dr. Gary Arendash, the study's other lead author. "We see no reason why an inherently natural product such as coffee cannot be more beneficial and safer than medications, especially to protect against a disease that takes decades to become apparent after it starts in the brain."

The researchers believe that moderate daily coffee intake starting at least by middle age (30s -- 50s) is optimal for providing protection against Alzheimer's disease, although starting even in older age appears protective from their studies. "We are not saying that daily moderate coffee consumption will completely protect people from getting Alzheimer's disease," Dr. Cao said. "However, we do believe that moderate coffee consumption can appreciably reduce your risk of this dreaded disease or delay its onset."

The researchers conclude that coffee is the best source of caffeine to counteract the cognitive decline of Alzheimer's because its yet unidentified component synergizes with caffeine to increase blood GCSF levels. Other sources of caffeine, such as carbonated drinks, energy drinks, and tea, would not provide the same level of protection against Alzheimer's as coffee, they said.

Coffee also contains many ingredients other than caffeine that potentially offer cognitive benefits against Alzheimer's disease. "The average American gets most of their daily antioxidants intake through coffee," Dr. Cao said. "Coffee is high in anti-inflammatory compounds that also may provide protective benefits against Alzheimer's disease."

An increasing body of scientific literature indicates that moderate consumption of coffee decreases the risk of several diseases of aging, including Parkinson's disease, Type II diabetes and stroke. Just within the last few months, new studies have reported that drinking coffee in moderation may also significantly reduce the risk of breast and prostate cancers.

"Now is the time to aggressively pursue the protective benefits of coffee against Alzheimer's disease," Dr. Arendash said. "Hopefully, the coffee industry will soon become an active partner with Alzheimer's researchers to find the protective ingredient in coffee and concentrate it in dietary sources."

New Alzheimer's diagnostic guidelines, now encompassing the full continuum of the disease from no overt symptoms to mild impairment to clear cognitive decline, could double the number of Americans with some form of the disease to more than 10 million. With the baby-boomer generation entering older age, these numbers will climb even more unless an effective preventive measure is identified.

"Because Alzheimer's starts in the brain several decades before it is diagnosed, any protective therapy would obviously need to be taken for decades," Dr. Cao said. "We believe moderate daily consumption of caffeinated coffee is the best current option for long-term protection against Alzheimer's memory loss. Coffee is inexpensive, readily available, easily gets into the brain, appears to directly attack the disease process, and has few side-effects for most of us."

According to the researchers, no other Alzheimer's therapy being developed comes close to meeting all these criteria.

"Aside from coffee, two other lifestyle choices -- physical and cognitive activity -- appear to reduce the risk of dementia. Combining regular physical and mental exercise with moderate coffee consumption would seem to be an excellent multi-faceted approach to reducing risk or delaying Alzheimer's," Dr. Arendash said. "With pharmaceutical companies spending millions of dollars trying to develop drugs against Alzheimer's disease, there may very well be an effective preventive right under our noses every morning -- caffeinated coffee."

This USF study was funded by the NIH-designated Florida Alzheimer's Disease Research Center and the State of Florida.

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Heart Valve Replacement without Opening the Chest Gives New Option for Patients with Untreatable, Non-Operative Condition

Heart Valve Replacement without Opening the Chest Gives New Option for Patients with Untreatable, Non-Operative Condition

  11:09:00 PM    Science Lover

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An innovative approach for implanting a new aortic heart valve without open-heart surgery is being offered at Rush University Medical Center to patients with severe aortic stenosis who are at high-risk or not suitable candidates for open heart valve replacement surgery.

"This breakthrough technology could save the lives of thousands of patients with heart valve disease who have no other therapeutic options," says Dr. Ziyad Hijazi, director of the Rush Center for Congenital and Structural Heart Disease and interventional cardiologist of the Rush Valve Clinic. The treatment is offered through a multi-center, phase IIb cohort study called the PARTNER II (Placement of AoRTic traNscathetER valves) trial.

Aortic valve stenosis (AS) is a type of valvular heart disease characterized by an abnormal narrowing of the aortic valve opening. It is a condition that affects nearly 1.5 million Americans. It causes hardening or thickening of the aortic valve leaflets, which limits leaflet motion and obstructs oxygen-rich blood flow from the heart to the rest of the body. Patients with severe AS may have symptoms of chest pain, fatigue, shortness of breath, lightheadedness or fainting. Although AS typically progresses slowly without symptoms, once symptoms occur, treatment is required. Fifty percent of patients may not survive beyond one to three years.

Traditionally, patients with symptomatic AS undergo aortic valve replacement during an open-heart surgery to alleviate symptoms, improve survival and improve quality of life. However, many patients who are at very high risk for surgery, such as elderly, frail individuals with multiple health concerns, are considered inoperable.

The PARTNER II trial will compare a pioneering technology called the Edwards SAPIEN XT valve, which is made of bovine pericardial tissue leaflets hand-sewn onto a metal frame, and a new catheter delivery system called the Edwards NovaFlex delivery system, which navigates the heart from a small incision to the femoral artery in a patient’s leg or through a small incision between the ribs and snaked up into the left ventricle. The Edwards NovaFlex delivery system positions the catheter inside the patient's original, collapsed valve, using a balloon to deploy the frame, which holds the artificial valve in place in order to restore normal blood flow. Both procedures are performed on a beating heart, without the need for open, cardiopulmonary bypass and its associated risks.



Annually, some 200,000 people in the U.S. need a new heart valve, but nearly half of them do not receive a new valve for a variety of reasons.

"Past study results show conclusively that transcatheter valve replacement is a safe and effective alternative to open surgery, which remains the 'gold standard' for most patients," says Hijazi.

Results from the first phase of the PARTNER trial showed that the rate of death from any cause at one year was 50.7 percent in the patients who received standard therapy, as compared to 30.7 percent of patients treated with transcatheter aortic valve replacement (TAVR).

The transcatheter valve procedures take about 90 minutes, compared with four to six hours for open-heart surgery. In open-heart surgery, the surgeon cuts through the breastbone, stops the heart, removes the valve and replaces it. Open-heart surgery can require a two- to three-month recovery period, compared to only a few days for the transcatheter approach.

The next generation Edwards SAPIEN XT valve in The PARTNER II trial was engineered to provide a better valve patterned after surgical heart valves and potentially decrease treatment complications.

The PARTNER trial is the world's first randomized, controlled trial of a transcatheter aortic heart valve. In this clinical phase IIb cohort, patients are randomized to receive either the new Edwards Sapien XT valve using the NovaFlex delivery system or the Edwards SAPIEN Transcatheter Heart Valve.

“The primary objective of the trial is to reduce death, major stroke and repeat hospitalization in these patients,” says Hijazi. “Additionally, we hope to improve quality-of-life indicators."

The PARTNER II trial is one of the three latest, nationwide clinical trials for minimally invasive heart valve replacement being offered through the Rush Valve Clinic, where a team of cardiac surgical and interventional experts address diseases of the aortic, mitral and pulmonary valves.

The three clinical trials include:

• PARTNER II trial for patients with aortic stenosis
• COMPASSION trial for patients with a dysfunctional conduit – A phase II clinical trial using the SAPIEN Transcatheter Heart Valve in patients who have a dysfunctional conduit between the right ventricle and the pulmonary artery
• EVEREST II trial for patients with mitral regurgitation – A continued access trial using the eValve MitraClip to treat a mitral valve leak.

For more information about the PARTNER trial or any of the other clinical trials at the Rush Valve Clinic, call 312-942-6800.

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Wireless Heart Implant Reduces HospitalizationsA pressure-sensing implant helps heart-failure patients stay healthy.

Wireless Heart Implant Reduces HospitalizationsA pressure-sensing implant helps heart-failure patients stay healthy.

  10:29:00 AM    Science Lover

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A wireless sensor developed by Atlanta-based CardioMEMS reduced the number of hospitalizations in patients with heart failure by 39 percent. The tiny implant monitors fluid pressure in the pulmonary artery and transmits the data wirelessly to physicians, who can adjust patients' medications accordingly.

Researchers say the sensor may significantly lower health-care costs and improve quality of life for people with congestive heart failure. The device is one of several prototypes being developed by CardioMEMS and other medical implant companies to provide continuous, personalized wireless monitors for such patients.

Pressure patrol: A new wireless sensor the size of a paper
clip measures fluid pressure in the pulmonary artery. The
metalloops on either end anchor the sensor to the artery
walls, while the self-contained transducer in the middle
takes pressure readings. The sensor is activated by radio
frequency, transmitting data wirelessly to physicians
via modem.Credit: OSU Medical Center/CardioMEMS

"I think the study shows this kind of device is incredibly useful in improving outcomes in patients and directing therapy," says Marc Jay Semigran, medical director of the Mass General Heart Failure and Cardiac Transplant Program, who was not involved in the study.

Hospitals admit 1.1 million adults each year for congestive heart failure, a condition in which pressure builds up in the circulatory system and the heart fails to pump blood adequately to the rest of the body. The American Heart Association estimates that the chronic condition costs the health-care system $29 billion per year. CardioMEMS aims to reduce that figure by providing an accurate way to continuously monitor patients after they've left the hospital.

The device is implanted in the pulmonary artery, an area that carries a low risk of clotting. It is smaller than other implants under development because it does not require a battery or a wire to take pressure readings. Two metal loops hold it to the sides of the artery, and a pressure transducer records the flow of fluids through the blood vessel. The sensor is powered externally by a receiver built into a pillow. When a patient lies on the pillow, the sensor is activated to take measurements and send them wirelessly to a computer, where physicians can review the data. In a large six-month clinical trial published this month in the Lancet, 550 patients from 64 centers across the United States were equipped with the device and instructed to take readings once a day. Patients were divided into two groups. The first took medication instructions from physicians who monitored the sensor data. The second took instructions from physicians who relied on traditional indicators like weight and blood pressure. Over the six months, patients in the first group experienced 39 percent fewer hospitalizations than those in the second.

Today, physicians often assess pulmonary pressure when initially evaluating a patient, but they do so far less frequently in follow-up evaluation. That's because the measurement requires doctors to snake a catheter into a patient's heart and inflate a balloon. However, fluid pressure changes by the day, and monitoring those fluctuations continuously is essential to treating heart failure effectively.

"Over the years, we found that pressures go up long before patients develop symptoms and call a doctor to say they're sick," says Philip Adamson, director of the Heart Failure Institute at Oklahoma Heart Hospital, the principal investigator in the CardioMEMS clinical trial. "By utilizing the pressure sensor information, we're given the ability to make changes in medications long before patients bring themselves to the doctor, and that's how we reduced hospitalizations."

Over the past few years, several companies have jockeyed to be first on the market with a continuous pressure-sensing cardiac implant. In 2007, Medtronic failed to get FDA approval for its sensor, a stopwatch-size, battery-powered implant wired to the heart. The device reduced hospitalizations by 22 percent, but FDA regulators did not consider that worth the risks associated with implanting it. Researchers also found that the wire connecting the sensor to the heart degraded over time.

CardioMEMS is currently seeking approval for its sensor from the U.S. Food and Drug Administration and has submitted results from the clinical study for FDA review. In the next two or three years, the company plans to integrate the sensor's receiver into a patient's cell phone, which will be able to instantly read pressure data and upload it for both physicians and patients to review.

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The Brain Speaks: Scientists Decode Words from Brain Signals

The Brain Speaks: Scientists Decode Words from Brain Signals

  10:15:00 AM    Science Lover

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In an early step toward letting severely paralyzed people speak with their thoughts, University of Utah researchers translated brain signals into words using two grids of 16 microelectrodes implanted beneath the skull but atop the brain.

This photo shows two kinds of electrodes sitting atop a severely epileptic patient's brain after part of his skull was removed temporarily. The larger, numbered, button-like electrodes are ECoGs used by surgeons to locate and then remove brain areas responsible for severe epileptic seizures. While the patient had to undergo that procedure, he volunteered to let researchers place two small grids -- each with 16 tiny "microECoG" electrodes -- over two brain areas responsible for speech. These grids are at the end of the green and orange wire bundles, and the grids are represented by two sets of 16 white dots since the actual grids cannot be seen easily in the photo. University of Utah scientists used the microelectrodes to translate speech-related brain signals into actual words -- a step toward future machines to allow severely paralyzed people to speak. (Credit: University of Utah Department of Neurosurgery)

"We have been able to decode spoken words using only signals from the brain with a device that has promise for long-term use in paralyzed patients who cannot now speak," says Bradley Greger, an assistant professor of bioengineering.

Because the method needs much more improvement and involves placing electrodes on the brain, he expects it will be a few years before clinical trials on paralyzed people who cannot speak due to so-called "locked-in syndrome."

The Journal of Neural Engineering's September issue is publishing Greger's study showing the feasibility of translating brain signals into computer-spoken words.

The University of Utah research team placed grids of tiny microelectrodes over speech centers in the brain of a volunteer with severe epileptic seizures. The man already had a craniotomy -- temporary partial skull removal -- so doctors could place larger, conventional electrodes to locate the source of his seizures and surgically stop them.

Using the experimental microelectrodes, the scientists recorded brain signals as the patient repeatedly read each of 10 words that might be useful to a paralyzed person: yes, no, hot, cold, hungry, thirsty, hello, goodbye, more and less.

Later, they tried figuring out which brain signals represented each of the 10 words. When they compared any two brain signals -- such as those generated when the man said the words "yes" and "no" -- they were able to distinguish brain signals for each word 76 percent to 90 percent of the time.

When they examined all 10 brain signal patterns at once, they were able to pick out the correct word any one signal represented only 28 percent to 48 percent of the time -- better than chance (which would have been 10 percent) but not good enough for a device to translate a paralyzed person's thoughts into words spoken by a computer.

"This is proof of concept," Greger says, "We've proven these signals can tell you what the person is saying well above chance. But we need to be able to do more words with more accuracy before it is something a patient really might find useful."

People who eventually could benefit from a wireless device that converts thoughts into computer-spoken spoken words include those paralyzed by stroke, Lou Gehrig's disease and trauma, Greger says. People who are now "locked in" often communicate with any movement they can make -- blinking an eye or moving a hand slightly -- to arduously pick letters or words from a list.

University of Utah colleagues who conducted the study with Greger included electrical engineers Spencer Kellis, a doctoral student, and Richard Brown, dean of the College of Engineering; and Paul House, an assistant professor of neurosurgery. Another coauthor was Kai Miller, a neuroscientist at the University of Washington in Seattle.

The research was funded by the National Institutes of Health, the Defense Advanced Research Projects Agency, the University of Utah Research Foundation and the National Science Foundation.

Nonpenetrating Microelectrodes Read Brain's Speech Signals

The study used a new kind of nonpenetrating microelectrode that sits on the brain without poking into it. These electrodes are known as microECoGs because they are a small version of the much larger electrodes used for electrocorticography, or ECoG, developed a half century ago.

For patients with severe epileptic seizures uncontrolled by medication, surgeons remove part of the skull and place a silicone mat containing ECoG electrodes over the brain for days to weeks while the cranium is held in place but not reattached. The button-sized ECoG electrodes don't penetrate the brain but detect abnormal electrical activity and allow surgeons to locate and remove a small portion of the brain causing the seizures.

Last year, Greger and colleagues published a study showing the much smaller microECoG electrodes could "read" brain signals controlling arm movements. One of the epileptic patients involved in that study also volunteered for the new study.

Because the microelectrodes do not penetrate brain matter, they are considered safe to place on speech areas of the brain -- something that cannot be done with penetrating electrodes that have been used in experimental devices to help paralyzed people control a computer cursor or an artificial arm.

EEG electrodes used on the skull to record brain waves are too big and record too many brain signals to be used easily for decoding speech signals from paralyzed people.

Translating Nerve Signals into Words

In the new study, the microelectrodes were used to detect weak electrical signals from the brain generated by a few thousand neurons or nerve cells.

Each of two grids with 16 microECoGs spaced 1 millimeter (about one-25th of an inch) apart, was placed over one of two speech areas of the brain: First, the facial motor cortex, which controls movements of the mouth, lips, tongue and face -- basically the muscles involved in speaking. Second, Wernicke's area, a little understood part of the human brain tied to language comprehension and understanding.

The study was conducted during one-hour sessions on four consecutive days. Researchers told the epilepsy patient to repeat one of the 10 words each time they pointed at the patient. Brain signals were recorded via the two grids of microelectrodes. Each of the 10 words was repeated from 31 to 96 times, depending on how tired the patient was. Then the researchers "looked for patterns in the brain signals that correspond to the different words" by analyzing changes in strength of different frequencies within each nerve signal, says Greger.

The researchers found that each spoken word produced varying brain signals, and thus the pattern of electrodes that most accurately identified each word varied from word to word. They say that supports the theory that closely spaced microelectrodes can capture signals from single, column-shaped processing units of neurons in the brain.

One unexpected finding: When the patient repeated words, the facial motor cortex was most active and Wernicke's area was less active. Yet Wernicke's area "lit up" when the patient was thanked by researchers after repeating words. It shows Wernicke's area is more involved in high-level understanding of language, while the facial motor cortex controls facial muscles that help produce sounds, Greger says.

The researchers were most accurate -- 85 percent -- in distinguishing brain signals for one word from those for another when they used signals recorded from the facial motor cortex. They were less accurate -- 76 percent -- when using signals from Wernicke's area. Combining data from both areas didn't improve accuracy, showing that brain signals from Wernicke's area don't add much to those from the facial motor cortex.

When the scientists selected the five microelectrodes on each 16-electrode grid that were most accurate in decoding brain signals from the facial motor cortex, their accuracy in distinguishing one of two words from the other rose to almost 90 percent.

In the more difficult test of distinguishing brain signals for one word from signals for the other nine words, the researchers initially were accurate 28 percent of the time -- not good, but better than the 10 percent random chance of accuracy. However, when they focused on signals from the five most accurate electrodes, they identified the correct word almost half (48 percent) of the time.

"It doesn't mean the problem is completely solved and we can all go home," Greger says. "It means it works, and we now need to refine it so that people with locked-in syndrome could really communicate."

"The obvious next step -- and this is what we are doing right now -- is to do it with bigger microelectrode grids" with 121 micro electrodes in an 11-by-11 grid, he says. "We can make the grid bigger, have more electrodes and get a tremendous amount of data out of the brain, which probably means more words and better accuracy."

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Biosynthetic Corneas Restore Vision in Humans

Biosynthetic Corneas Restore Vision in Humans

  10:26:00 AM    Science Lover

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A new study from researchers in Canada and Sweden has shown that biosynthetic corneas can help regenerate and repair damaged eye tissue and improve vision in humans. The results, from an early phase clinical trial with 10 patients, are published in the August 25th, 2010 issue of Science Translational Medicine.

Dr. May Griffith displays a biosynthetic cornea that can be implanted into the eye to repair damage and restore sight. (Credit: Photo courtesy of the Ottawa Hospital Research Institute)

"This study is important because it is the first to show that an artificially fabricated cornea can integrate with the human eye and stimulate regeneration," said senior author Dr. May Griffith of the Ottawa Hospital Research Institute, the University of Ottawa and Linköping University. "With further research, this approach could help restore sight to millions of people who are waiting for a donated human cornea for transplantation."

The cornea is a thin transparent layer of collagen and cells that acts as a window into the eyeball. It must be completely transparent to allow the light to enter and it also helps with focus. Globally, diseases that lead to clouding of the cornea represent the most common cause of blindness. More than a decade ago, Dr. Griffith and her colleagues began developing biosynthetic corneas in Ottawa, Canada, using collagen produced in the laboratory and moulded into the shape of a cornea. After extensive laboratory testing, Dr. Griffith began collaborating with Dr. Per Fagerholm, an eye surgeon at Linköping University in Sweden, to provide the first-in-human experience with biosynthetic cornea implantation.

Together, they initiated a clinical trial in 10 Swedish patients with advanced keratoconus or central corneal scarring. Each patient underwent surgery on one eye to remove damaged corneal tissue and replace it with the biosynthetic cornea, made from synthetically cross-linked recombinant human collagen. Over two years of follow-up, the researchers observed that cells and nerves from the patients' own corneas had grown into the implant, resulting in a "regenerated" cornea that resembled normal, healthy tissue. Patients did not experience any rejection reaction or require long-term immune suppression, which are serious side effects associated with the use of human donor tissue. The biosynthetic corneas also became sensitive to touch and began producing normal tears to keep the eye oxygenated. Vision improved in six of the ten patients, and after contact lens fitting, vision was comparable to conventional corneal transplantation with human donor tissue.

"We are very encouraged by these results and by the great potential of biosynthetic corneas," said Dr. Fagerholm. "Further biomaterial enhancements and modifications to the surgical technique are ongoing, and new studies are being planned that will extend the use of the biosynthetic cornea to a wider range of sight-threatening conditions requiring transplantation."

This research was supported by grants from the Canadian Stem Cell Network, the Swedish Research Council and County of Östergötland and a European Union Marie Curie International Fellowship. Initial work in developing the biosynthetic corneas was supported by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research. Recombinant human collagen type III used in formulating the biosynthetic corneas for the clinical study was provided by FibroGen, Inc., San Francisco, CA, U.S.A.

Dr. May Griffith is a Senior Scientist at the Ottawa Hospital Research Institute, Professor at the University of Ottawa (Faculty of Medicine) and Professor of Regenerative Medicine and Director of the Integrative Regenerative Medicine Centre at Linköping University. Dr. Per Fagerholm is a Professor of Ophthalmology at Linköping University. Dr. Neil Lagali is a senior lecturer at Linköping University. Other authors are listed in the paper.

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Drink Water to Curb Weight Gain? Clinical Trial Confirms Effectiveness of Simple Appetite Control Method

Drink Water to Curb Weight Gain? Clinical Trial Confirms Effectiveness of Simple Appetite Control Method

  7:38:00 AM    Science Lover

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Has the long-sought magic potion in society's "battle with the bulge" finally arrived? An appetite-control agent that requires no prescription, has no common side effects, and costs almost nothing? Scientists report results of a new clinical trial confirming that just two 8-ounce glasses of the stuff, taken before meals, enables people to shed pounds. The weight-loss elixir, they told the 240th National Meeting of the American Chemical Society (ACS), is ordinary water.

Drinking more water before meals can help promote weight loss, new research suggests. (Credit: iStockphoto/Lise Gagne)

"We are presenting results of the first randomized controlled intervention trial demonstrating that increased water consumption is an effective weight loss strategy," said Brenda Davy, Ph.D., senior author on the study. "We found in earlier studies that middle aged and older people who drank two cups of water right before eating a meal ate between 75 and 90 fewer calories during that meal. In this recent study, we found that over the course of 12 weeks, dieters who drank water before meals, three times per day, lost about 5 pounds more than dieters who did not increase their water intake."

"People should drink more water and less sugary, high-calorie drinks. It's a simple way to facilitate weight management."

Davy pointed out that folklore and everyday experience long have suggested that water can help promote weight loss. But there has been surprisingly little scientific information on the topic. Previous studies hinted that drinking water before meals reduces intake of calories. Lacking until now, however, has been the "gold-standard" evidence from a randomized, controlled clinical trial that compares weight loss among dieters who drink water before meals with those who do not.

The study included 48 adults aged 55-75 years, divided into two groups. One group drank 2 cups of water prior to their meals and the other did not. All of the subjects ate a low-calorie diet during the study. Over the course of 12 weeks, water drinkers lost about 15.5 pounds, while the non-water drinkers lost about 11 pounds.

Davy said water may be so effective simply because it fills up the stomach with a substance that has zero calories. People feel fuller as a result, and eat less calorie-containing food during the meal. Increased water consumption may also help people lose weight if they drink it in place of sweetened calorie-containing beverages, said Davy, who is with Virginia Tech in Blacksburg, Va.

Diet soda pop and other beverages with artificial sweeteners may also help people reduce their calorie intake and lose weight, Davy said. However, she advised against using beverages sweetened with sugar and high-fructose corn syrup because they are high in calories. A 12-ounce can of regular soda pop, for instance, contains about 10 teaspoons of sugar.

Davy noted that that nobody knows exactly how much water people should drink daily. The Institute of Medicine, an agency of The National Academies, which advises the Federal Government on science, says that most healthy people can simply let thirst be their guide. It does not specify exact requirements for water, but set general recommendations for women at about 9 cups of fluids -- from all beverages including water -- each day, and men at about 13 cups of fluids.

And it is possible to drink too much water, a situation that can lead to a rare, but serious, condition known as water intoxication, Davy pointed out.

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Drugs Encased in Nanoparticles Travel to Tumors on the Surface of Immune-System Cells

Drugs Encased in Nanoparticles Travel to Tumors on the Surface of Immune-System Cells

  10:53:00 PM    Science Lover

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Clinical trials using patients' own immune cells to target tumors have yielded promising results. However, this approach usually works only if the patients also receive large doses of drugs designed to help immune cells multiply rapidly, and those drugs have life-threatening side effects.

pouches (yellow) to the surfaces of cells. 
(Credit: Darrell Irvine and Matthias Stephan)

Now a team of MIT engineers has devised a way to deliver the necessary drugs by smuggling them on the backs of the cells sent in to fight the tumor. That way, the drugs reach only their intended targets, greatly reducing the risk to the patient.

The new approach could dramatically improve the success rate of immune-cell therapies, which hold promise for treating many types of cancer, says Darrell Irvine, senior author of a paper describing the technique in the Aug. 15 issue of Nature Medicine.

"What we're looking for is the extra nudge that could take immune-cell therapy from working in a subset of people to working in nearly all patients, and to take us closer to cures of disease rather than slowing progression," says Irvine, associate professor of biological engineering and materials science and engineering and a member of MIT's David H. Koch Institute for Integrative Cancer Research.

The new method could also be used to deliver other types of cancer drugs or to promote blood-cell maturation in bone-marrow transplant recipients, according to the researchers.

To perform immune-cell therapy, doctors remove a type of immune cells called T cells from the patient, engineer them to target the tumor, and inject them back into the patient. Those T cells then hunt down and destroy tumor cells. Clinical trials are under way for ovarian and prostate cancers, as well as melanoma.

Although immune-cell therapy is a promising approach to treating cancer, success has been limited by difficulties in generating enough T cells that are specific to the cancer cells and getting those T cells to function properly in the patient.

To overcome those obstacles, researchers have tried injecting patients with adjuvant drugs that stimulate T-cell growth and proliferation. One class of drugs that has been tested in clinical trials is interleukins -- naturally occurring chemicals that help promote T-cell growth but have severe side effects, including heart and lung failure, when given in large doses.

Irvine and his colleagues took a new approach: To avoid toxic side effects, they designed drug-carrying pouches made of fatty membranes that can be attached to sulfur-containing molecules normally found on the T-cell surface.

In the Nature Medicine study, the researchers injected T cells, each carrying about 100 pouches loaded with the interleukins IL-15 and IL-21, into mice with lung and bone marrow tumors. Once the cells reached the tumors, the pouches gradually degraded and released the drug over a weeklong period. The drug molecules attached themselves to receptors on the surface of the same cells that carried them, stimulating them to grow and divide.

Within 16 days, all of the tumors in the mice treated with T cells carrying the drugs disappeared. Those mice survived until the end of the 100-day experiment, while mice that received no treatment died within 25 days, and mice that received either T cells alone or T cells with injections of interleukins died within 75 days.

Irvine's approach to delivering the adjuvant drugs is both simple and innovative, says Dranoff. "The idea of modifying T cells in the lab to make them work better is something many people are exploring through more complicated approaches such as gene modification," he says. "But here, the possibility of just attaching a carefully engineered nanoparticle to the surface of cells could be a much simpler procedure."

While he is now focusing on immune-cell therapy, Irvine believes his cell pouches could be useful for other applications, including targeted delivery of chemotherapy agents. "There are lots of people studying nanoparticles for drug delivery, especially in cancer therapy, but the vast majority of nanoparticles injected intravenously go into the liver or the spleen. Less than 5 percent reach the tumor," says Irvine, who is also a Howard Hughes Medical Institute Investigator.

With a new way to carry drugs specifically to tumors, scientists may be able to resurrect promising drugs that failed in clinical trials because they were cleared from the bloodstream before they could reach their intended targets, or had to be given in doses so high they had toxic side effects.

Irvine and his colleagues also demonstrated that they could attach their pouches to the surface of immature blood cells found in the bone marrow, which are commonly used to treat leukemia. Patients who receive bone-marrow transplants must have their own bone marrow destroyed with radiation or chemotherapy before the transplant, which leaves them vulnerable to infection for about six months while the new bone marrow produces blood cells.

Delivering drugs that accelerate blood-cell production along with the bone-marrow transplant could shorten the period of immunosuppression, making the process safer for patients, says Irvine. In the Nature Medicine paper, his team reports successfully enhancing blood-cell maturation in mice by delivering one such drug along with the cells.

Irvine is now starting to work on making sure the manufacturing process will yield nanoparticles safe to test in humans. Once that is done, he hopes the particles could be used in clinical trials in cancer patients, possibly within the next two or three years.

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New Drug Delivery Technique: Nanoblasts from Laser-Activated Nanoparticles Move Molecules, Proteins and DNA Into Cells

New Drug Delivery Technique: Nanoblasts from Laser-Activated Nanoparticles Move Molecules, Proteins and DNA Into Cells

  2:39:00 PM    Science Lover

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Using chemical "nanoblasts" that punch tiny holes in the protective membranes of cells, researchers have demonstrated a new technique for getting therapeutic small molecules, proteins and DNA directly into living cells.

A field of human prostate cancer cells is shown after exposure to laser-activated carbon nanoparticles. The cell membranes have been stained red to assist in visualization. Each of the red circles is a single cell. (Credit: Credit: Prerona Chakravarty)

Carbon nanoparticles activated by bursts of laser light trigger the tiny blasts, which open holes in cell membranes just long enough to admit therapeutic agents contained in the surrounding fluid. By adjusting laser exposure, the researchers administered a small-molecule marker compound to 90 percent of targeted cells -- while keeping more than 90 percent of the cells alive.

The research was sponsored by the National Institutes of Health and the Institute of Paper Science and Technology at Georgia Tech. It will be reported in the August issue of the journal Nature Nanotechnology.

"This technique could allow us to deliver a wide variety of therapeutics that now cannot easily get into cells," said Mark Prausnitz, a professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. "One of the most significant uses for this technology could be for gene-based therapies, which offer great promise in medicine, but whose progress has been limited by the difficulty of getting DNA and RNA into cells."

The work is believed to be the first to use activation of reactive carbon nanoparticles by lasers for medical applications. Additional research and clinical trials will be needed before the technique could be used in humans.

Researchers have been trying for decades to drive DNA and RNA more efficiently into cells with a variety of methods, including using viruses to ferry genetic materials into cells, coating DNA and RNA with chemical agents or employing electric fields and ultrasound to open cell membranes. However, these previous methods have generally suffered from low efficiency or safety concerns.

With their new technique, which was inspired by earlier work on the so-called "photoacoustic effect," Prausnitz and collaborators Prerona Chakravarty, Wei Qian and Mostafa El-Sayed hope to better localize the application of energy to cell membranes, creating a safer and more efficient approach for intracellular drug delivery.

Their technique begins with introducing particles of carbon black measuring 25 nanometers -- one millionth of an inch -- in diameter into the fluid surrounding the cells into which the therapeutic agents are to be introduced. Bursts of near-infrared light from a femotosecond laser are then applied to the fluid at a rate of 90 million pulses per second. The carbon nanoparticles absorb the light, which makes them hot. The hot particles then heat the surrounding fluid to make steam. The steam reacts with the carbon nanoparticles to form hydrogen and carbon monoxide.

The two gases form a bubble which grows as the laser provides energy. The bubble collapses suddenly when the laser is turned off, creating a shock wave that punches holes in the membranes of nearby cells. The openings allow therapeutic agents from the surrounding fluid to enter the cells. The holes quickly close so the cell can survive.

The researchers have demonstrated that they could get the small molecule calcein, the bovine serum albumin protein and plasmid DNA through the cell membranes of human prostate cancer cells and rat gliosarcoma cells using this technique. Calcein uptake was seen in 90 percent of the cells at laser levels that left more than 90 percent of the cells alive.

"We could get almost all of the cells to take up these molecules that normally wouldn't enter the cells, and almost all of the cells remained alive," said Prerona Chakravarty, the study's lead author. "Our laser-activated carbon nanoparticle system enables controlled bubble implosions that can disrupt the cell membranes just enough to get the molecules in without causing lasting damage."

To assess how long the holes in the cell membrane remained open, the researchers left the simulated therapeutics out of the fluid when the cells were exposed to the laser light, then added the agents one second after turning off the laser. They saw almost no uptake of the molecules, suggesting that the cell membranes resealed themselves quickly.

To confirm that the carbon-steam reaction was a critical factor driving the nanoblasts, the researchers substituted gold nanoparticles for the carbon nanoparticles before exposure to laser light. Because they lacked the carbon needed for reaction, the gold nanoparticles produced little uptake of the molecules, Prausnitz noted.

Similarly, the researchers substituted carbon nanotubes for the carbon nanoparticles, and also measured little uptake, which they explained by noting that the nanotubes are less reactive than the carbon black particles.

Experimentation further showed that DNA introduced into cells through the laser-activated technique remained functional and capable of driving protein expression. When plasmid DNA that encoded for luciferase expression was introduced into the cancer cells, production of luciferase increased 17-fold.

For the future, the researchers plan to study use of a less expensive nanosecond laser to replace the ultrafast femtosecond instrument used in the research. They also plan to optimize the carbon nanoparticles so that nearly all of them are consumed during the exposure to laser light. Leftover carbon nanoparticles in the body should produce no harmful effects, though the body may be unable to eliminate them, Prausnitz noted.

"This is the first study showing proof of principle for laser-activation of reactive carbon nanoparticles for drug and gene delivery," he said. "There is a considerable path ahead before this can be brought into medicine, but we are optimistic that this approach can ultimately provide a new alternative for delivering therapeutic agents into cells safely and efficiently."

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Contact Lenses Loaded With Vitamin E May Treat Glaucoma

Contact Lenses Loaded With Vitamin E May Treat Glaucoma

  1:30:00 AM    Science Lover

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The popular dietary supplement vitamin E, loaded into special medicated contact lenses, can keep glaucoma medicine near the eye -- where it can treat that common disease -- almost 100 times longer than possible with current commercial lenses, scientists report.

Contact lenses containing vitamin E like the one above can treat glaucoma, the second leading cause of blindness, and other eye conditions, scientists are reporting. (Credit: Anuj Chauhan, Ph.D.)

In a presentation at the 239th National Meeting of the American Chemical Society (ACS) in San Francisco, they described use of vitamin E to develop contact lenses that may deliver more medication for glaucoma and perhaps other diseases to the eye.

Anuj Chauhan, Ph.D., who headed the research team, explained that glaucoma is second only to cataracts as the leading cause of vision loss and blindness in the world. It affects almost 67 million people. Eye drops that relieve the abnormal build-up of pressure inside the eye that occurs in glaucoma, are a mainstay treatment.

"The problem is within about two to five minutes of putting drops in the eye, tears carry the drug away and it doesn't reach the targeted tissue," said Chauhan, who is with the University of Florida in Gainesville. "Much of the medicine gets absorbed into the bloodstream, which carries it throughout the body where it could cause side effects. Only about one to five percent of drugs in eye drops actually reach the cornea of the eye."

Chauhan and colleagues have developed a new extended-release delivery approach incorporating vitamin E into contact lenses. The invisible clusters, or aggregates, of vitamin E molecules form what Chauhan describes as "transport barriers." that slow down the elusion of the glaucoma medication from the lens into the eye. The drug released from the lens into the eye stays in the tears far longer than the 2-5 minutes with eye drops, leading to more effective therapy.

"These vitamin structures are like 'nano-bricks'," Chauhan said. "The drug molecules can't go through the vitamin E. They must go around it. Because the nanobricks are so much bigger than the drug molecules -- we believe about a few hundred times bigger -- the molecules get diverted and must travel a longer path. This increases the duration of the drug release from the lenses."

In research with laboratory animals, the lenses containing vitamin E nanobricks administered drugs up to 100 times longer than most commercial lenses. The lenses could be designed for continuous wear for up to a month, Chauhan said. In addition to treating glaucoma, the contacts could help other eye conditions, such as cataract and dry eye. Cataract is a clouding of the lens of the eye, and dry eye involves decreased production of tears. It affects about 2 in 10 people and can lead to more severe eye problems.

"Vitamin E is a proven nutraceutical that in small amounts is good for the eye because of its ant-oxidant properties. Also Vitamin E presence in the contact lenses blocks UV radiation, leading to increased protection against the UV light. Our research has shown that the vitamin can be loaded into the lenses without any reduction in transparency. We believe it could be helpful in disease treatment and in prevention as well," he said.

Chauhan said that clinical trials of the new lenses could begin within a year to 2 years.

Here is an excerpt from Chauhan's ACS presentation:

"We have developed a novel approach of extending the duration of drug release from contact lenses by including nanosized aggregates of Vitamin E in the lenses. The Vitamin E nano-aggregates force the drug molecules to travel in a tortuous path leading to increased drug release durations. Another benefit of Vitamin E incorporation is that Vitamin E is known to be an anti-oxidant, whose slow release from lenses could also help in prevention of ophthalmic diseases like cataract and glaucoma. Furthermore, Vitamin E blocks UV radiation, leading to reduced ocular damage from the UV light. Our research has shown that Vitamin E can be loaded into the lenses without any reduction in transparency. The drug release durations from Vitamin E loaded lenses are about 100 times longer than from commercial lenses for several ophthalmic drugs including glaucoma drug timolol, anti-inflammatory drug dexamethasone, and anti-viral drug flucanozole. Thus, Vitamin E loaded lenses could be highly effective in synergistic prevention and treatment of ophthalmic diseases through extended delivery of the desired drugs and the nutraceutical Vitamin E. Animal studies in beagle dogs are ongoing to explore glaucoma treatment through Vitamin E laden contact lenses."

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Potential Treatment for Huntington's Disease

Potential Treatment for Huntington's Disease

  1:58:00 AM    Science Lover

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Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease. In contrast, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins' deadly effects.

Normal synaptic activity in nerve cells protects the brain from the misfolded proteins associated with Huntington's disease, researchers have discovered. (Credit: iStockphoto/Sebastian Kaulitzki)

Researchers also found that the drug Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity. The research was published in the journal Nature Medicine on November 15.

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Gene Therapy Can Improve Muscle Mass And Strength In Monkeys, Research Suggests

Gene Therapy Can Improve Muscle Mass And Strength In Monkeys, Research Suggests

  12:51:00 AM    Science Lover

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A study appearing in Science Translational Medicine puts scientists one step closer to clinical trials to test a gene delivery strategy to improve muscle mass and function in patients with certain degenerative muscle disorders.

Cynomolgus macaque. New research in these primates suggests that a gene delivery strategy that produces follistatin can improve muscle mass and function. 

(Credit: iStockphoto/Anna Yu)

Severe weakness of the quadriceps is a defining feature of several neuromuscular disorders. Researchers at Nationwide Children's Hospital have shown that a gene delivery strategy that produces follistatin -- a naturally occurring protein that inhibits myostatin, a growth factor expressed specifically in skeletal muscle -- directly to the quadriceps of non-human primates results in long-term gene expression with muscle enhancing effects, including larger muscles with greater strength.

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