Scientists create natural Alzheimer's-fighting compound in lab

Scientists at Yale University have developed the first practical method to create a compound called huperzine A in the lab. The compound, which occurs naturally in a species of moss found in China, is an enzyme inhibitor that has been used to treat Alzheimer's disease in China since the late 1990s and is sold in the U.S. as a dietary supplement to help maintain memory. Scientists believe it could also potentially combat the effects of chemical warfare agents.

Until now, researchers have only been able to derive small amounts of the compound directly from the Huperzia serrata plant, or had to resort to lengthy and cumbersome methods to synthesize it in the lab.

Now researchers at Yale have developed a practical and cost-effective method to synthesize huperzine A in the lab. The process requires just eight steps and produces a yield of 40 percent. Previously, the best synthetic techniques had required twice as many steps and achieved yields of only two percent.

"Being able to synthesize large amounts of huperzine A in the lab is crucial because the plant itself, which has been used in Chinese folk medicine for centuries, takes decades to grow and is nearing extinction due to overharvesting," said Seth Herzon, the Yale chemist who led the research, which is described in the Aug. 25 issue of the journal Chemical Science.

In some places, huperzine A can cost up to $1,000 per milligram. Herzon and his team produced several grams of the compound in their lab and are capable of creating much more. They believe they will be able to drive the cost down to just 50 cents per milligram (a projected typical dose is about one milligram per day), and have partnered with an industrial firm to help produce it on larger scales.

The firm plans to comprehensively evaluate the therapeutic potential of huperzine A by conducting clinical trials for several different neurological disorders in the U.S. In addition, the Herzon lab and the firm are working with the U.S. Army, which is interested in huperzine A's potential in blocking the effects of chemical warfare agents, he said. The compound has been shown to protect primates against chemical warfare agents, without side effects.

Other Alzheimer's treatments based on enzyme inhibitors are currently prescribed in the U.S., but huperzine A binds better, is more easily absorbed by the body and last longer in the body than other treatments, Herzon said.

"We believe huperzine A has the potential to treat a range of neurologic disorders more effectively than the current options available," Herzon said. "And we now have a route to huperzine A that rivals nature's pathway."

Provided by Yale University (news : web)

A 'nano,' environmentally friendly, and low toxicity flame retardant protects fabric

The technology in "fire paint" used to protect steel beams in buildings and other structures has found a new life as a first-of-its-kind flame retardant for children's cotton sleepwear, terrycloth bathrobes and other apparel, according to a report presented here today at the 242nd National Meeting & Exposition of the American Chemical Society (ACS).

"People are concerned about the potential toxicity of flame retardants that are currently used on a variety of products, especially children's pajamas and the foam in children's car seats," said Jaime C. Grunlan, Ph.D., who led the research. "The water-based ingredients in this new coating are much less toxic to humans than the so-called 'halogenated' or 'brominated' flame retardants used in the past, and they are more environmentally friendly."

Grunlan explained that flame retardants are used on cotton, the most popular fabric in the world, because it can catch fire easily and burns rapidly with a hot flame. Flame retardants make it more difficult for fabrics to ignite, make them burn slower and make fabrics self-extinguish when the flame is removed. That margin of safety is especially important for clothing fires, which can cause severe and disfiguring injuries. Flame retardants allow time to remove the clothing or put out the flames.

In responding to the need for more environmentally friendly flame retardants, Grunlan's team turned to a technology termed "intumescence," long used to fireproof exposed interior steel beams in buildings. At the first lick of a flame, an intumescent coating swells up and expands like beer foam, forming tiny bubbles in a protective barrier that insulates and shields the material below. The researchers are at Texas A&M University in College Station.

"This work is the first demonstration of a polymer-based 'nano intumescent'," said Grunlan. "We believe it has great potential for use as flame retardants on clothing and other materials in order to avoid some of the disadvantages of existing products."

The material is "nano," or ultra-small, built up from layers of alternating positively and negatively charged polymers so thin that almost 50,000 would fit across the width of a human hair. Size has an advantage, Grunlan explained. Because these layers are so thin, the polymer liquid seeps deep into cotton fabric and onto each individual cotton fiber. Existing flame retardants, in contrast, simply settle on fiber bundles like armor and slow the spread of flames, but the fabric still burns and turns black. When the new nano coating is exposed to a flame, it expands slightly and stops the fire from igniting and burning the fabric — which remains white, except for the small area where the cotton directly touches the flame.

Grunlan noted that the new flame retardant addresses public concerns about the potential toxicity of flame retardants now used on a variety of products, especially children's pajamas and the foam inside children's car seats and toys, and pointed out that the water-based polymers used in the nanocoating are much less toxic to humans than other flame retardants used today.

Would clothing coated with the nano intumescent be stiff and dull? "The look and texture of the fabric would depend on the thickness of the coating and also on the specific polymer we use," Grunlan pointed out. The nanocoating is deposited in alternate layers of positively and negatively charged polymers; swapping one of those polymers out for a different one in the recipe could offer similar anti-flammable protection while making the fabric softer.

Grunlan's team is in the process of optimizing the flame retardant so that it remains on cotton fabrics despite frequent laundering. "We haven't done anything yet to protect the coating, but we believe that with further research, we could make this an almost permanent addition to the fabric," he explained.

They also plan to test the coating on other materials, such as polyester and foam, possibly with commercial partners.

Provided by American Chemical Society (news : web)

Iron 'veins' are secret of promising new hydrogen storage material

 With a nod to biology, scientists at the National Institute of Standards and Technology have a new approach to the problem of safely storing hydrogen in future fuel-cell-powered cars. Their idea: molecular scale "veins" of iron permeating grains of magnesium like a network of capillaries. The iron veins may transform magnesium from a promising candidate for hydrogen storage into a real-world winner.

Hydrogen has been touted as a clean and efficient alternative to gasoline, but it has one big drawback: the lack of a safe, fast way to store it onboard a vehicle. According to NIST materials scientist Leo Bendersky, iron-veined magnesium could overcome this hurdle. The combination of lightweight magnesium laced with iron could rapidly absorb—and just as importantly, rapidly release—sufficient quantities of hydrogen so that grains made from the two metals could form the fuel tank for hydrogen-powered vehicles.

"Powder grains made of iron-doped magnesium can get saturated with hydrogen within 60 seconds," says Bendersky, "and they can do so at only 150 degrees Celsius and fairly low pressure, which are key factors for safety in commercial vehicles."

Grains of pure magnesium are reasonably effective at absorbing hydrogen gas, but only at unacceptably high temperatures and pressures can they store enough hydrogen to power a car for a few hundred kilometers—the minimum distance needed between fill-ups. A practical material would need to hold at least 6 percent of its own weight in hydrogen gas and be able to be charged safely with hydrogen in the same amount of time as required to fill a car with gasoline today.

The NIST team used a new measurement technique they devised that uses infrared light to explore what would happen if the magnesium were evaporated and mixed together with small quantities of other metals to form fine-scale mixtures. The team found that iron formed capillary-like channels within the grains, creating passageways for hydrogen transport within the metal grains that allow hydrogen to be drawn inside extremely fast. According to Bendersky, the magnesium-iron grains could hold up to 7 percent hydrogen by weight.

Bendersky adds that the measurement technique could be valuable more generally, as it can reveal details of how a material absorbs hydrogen more effectively than the more commonly employed technique of X-ray diffraction—a method that is limited to analyzing a material's averaged properties.

More information: Z. Tan, et al. Thermodynamics, kinetics and microstructural evolution during hydrogenation of iron-doped magnesium this films. International Journal of Hydrogen Energy, 36 (2011), pp. 9702-9713, DOI: 10.1016/j.ijhydene.2011.04.196

Provided by National Institute of Standards and Technology (news : web)

New skin test determines age of wild animals to help control nuisance animals

A new skin test can determine the age of wild animals while they are still alive, providing information needed to control population explosions among nuisance animals, according to a report here today at the 242nd National Meeting & Exposition of the American Chemical Society (ACS).

ACS, the world largest scientific society with more than 163,000 members, is holding the meeting through Thursday at the Colorado Convention Center and downtown hotels. With 7,500 reports on new advances in science and more than 12,000 scientists and others expected in attendance, it will be one of 2011’s largest scientific gatherings.

Randal Stahl, Ph.D., said that the improved method will provide important information about the health and stability of herds, flocks and other populations of wild animals, which lack the established birthdates of prized cattle, horses, and many household pets.

“Determining the age of wild animals is important for a number of reasons,” Stahl explained. “We are in the midst of population explosions of some animals that have negative impacts on people, property and other animals. Wildlife management programs have been established to cope with the situation. Some of these programs, for instance, seek to maintain healthy numbers of breeding pairs. The new skin test will help us tell how many animals in a wild population are of breeding age.”

Stahl is a scientist with the National Wildlife Research Center (NWRC) in Fort Collins, CO. The center is the research arm of the U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services program.

The test detects pentosidine, a biomarker for so-called advanced glycation end products (AGEs), substances that form in the body as a result of aging; the amounts can indicate an animal’s age. Those substances also form in humans, and have been linked to a range of chronic disorders, including type 2 diabetes, cancer and Alzheimer’s disease.

Tests for AGEs already exist and have been used in both animals and humans. At the ACS meeting, Stahl and colleagues described development of a more sensitive version of the animal test. That test involves taking a biopsy, or sample, of the animal’s skin. In the past, scientists needed such a large skin sample — about the size of a postage stamp — that scientists usually could do the test only on dead animals. The new version of the test requires a skin sample only the size of a pea.

“We improved the sensitivity of the pentosidine test so we can detect very small amounts of it,” Stahl said. “The advance will enable scientists to capture a few individuals, take a small skin sample without harming the animal and then release it back into the wild. With this approach, we can sample a population repeatedly over time without having an effect on the size of the population.”

Stahl’s group is currently studying double-crested cormorants, large fish-eating birds that have become a nuisance due to population explosions. Federal and state agencies in the Great Lakes region, and other areas, are trying to manage cormorant populations to reduce the birds’ adverse impacts on vegetation, other water birds, private property, fish farming, sports fishing and risks of collisions with aircraft. Those efforts involve maintaining the number of breeding pairs of cormorants at environmentally healthy levels. And the new skin test will enable scientists to gauge the number of birds that are of breeding age.

Collaborating with the NWRC field station in Mississippi, the researchers also developed a technique of handling cormorants to obtain samples with little harm to the birds. They place a small hollow metal cylinder called a biopsy punch on the bird’s skin to remove the sample and then put an adhesive on the wound to prevent infection and promote healing, just like a Band-Aid. No anesthesia is needed.

Stahl plans to use the skin analysis method to study other wild populations, such as invasive species of snakes and lizards in Florida. And because of recent coyote attacks on humans in populated areas, such as the suburbs of New York City and in California, Stahl’s team also will use the method to determine the demographics of these urban coyote populations during management activities.

Provided by American Chemical Society (news : web)

Research from Everest: Can leucine help burn fat and spare muscle tissue during exercise?

Research on Mt. Everest climbers is adding to the evidence that an amino acid called leucine — found in foods, dietary supplements, energy bars and other products — may help people burn fat during periods of food restriction, such as climbing at high altitude, while keeping their muscle tissue. It was one of two studies reported here today at the 242nd National Meeting & Exposition of the American Chemical Society (ACS) on the elite corps of men and women who have tackled the highest peak on Earth, mountaineering’s greatest challenge.

In a pilot study of the feasibility of supplementing the diet of climbers with the branch chain amino acid, leucine, scientists studied 10 climbers for 6-8 weeks as they ascended Mt. Everest, which towers 29,000 feet above sea level. Since Sir Edmund Hillary and Sherpa guide Tenzing Norgay made the first successful climb in 1953, over 2,500 people have scaled Mt. Everest in the Himalayas. Thousands more tried and failed, with more than 216 deaths. The researchers were studying the physiological benefits of adding leucine to the climbers’ diets to help them stay healthy. The researchers are from the University of Utah.

Wayne Askew, Ph.D., and his co-investigator, Stacie Wing-Gaia, Ph.D., who headed the leucine study, explained that the extreme weather conditions, low oxygen levels, treacherous terrain and strenuous exercise during such climbs create a huge nutritional challenge. Weight loss at high altitude is exactly the opposite problem that is on the minds of millions of people in the United States and other countries who are trying to shed excess weight. Climbers often cannot or do not eat enough calories, failing to replenish their bodies with important nutrients. They lose both fat and muscle during an arduous climb, endangering their strength and motor coordination. At high altitudes, fat and muscle loss occurs not only when they are climbing, but also at rest.

“The significant part about this weight loss is that a disproportionate amount comes from the muscle mass,” said Askew. “This can be a problem on long expeditions at high altitude because the longer climbers are there and the higher they go, the weaker they get. The body breaks down the muscle for energy, so climbers don’t have it available for moving up the mountain.

“We knew that leucine has been shown to help people on very low-calorie, or so-called ‘calorie-restricted diets’, stay healthy at sea level,” said Askew. “It’s one of the components, the building blocks, of protein. But no one had tested whether leucine would help people stay healthy and strong at high altitudes, so we added leucine to specially prepared food bars that we gave to the climbers.”

Askew didn’t climb Mt. Everest, but members of his research team, Dr. Wing-Gaia and Dr. Rodway, went to base camp and measured expedition members’ fat and muscle by using an ultrasound device placed on the skin. They are currently examining the data to see whether climbers who ate the leucine bar retained more muscle than those who ate a bar without leucine. One finding that was apparent early on in the study was that the food item in which the leucine was delivered was critically important. The Everest climbers had difficulties consuming the three food bars per day that contained the additional leucine. Askew stressed that this was a small pilot study to test the feasibility of leucine supplementation at altitude, so definitive conclusions of its benefits at altitude await the results of a more controlled clinical study. The researchers plan to improve the palatability of the leucine food vehicle in consultation with military food product developers at Natick Research Development and Engineering Center and conduct a more controlled study at high altitude, possibly with the U.S. Army Institute of Environmental Medicine at their laboratory on Pike’s Peak.

Askew pointed out that the findings also could help people at lower altitudes who want to lose weight while preserving their lean body mass, or who are elderly and don’t eat or exercise enough to maintain their strength. He predicts that consumers might one day see leucine-rich bars on grocery store shelves, especially at high-altitude locations, such as Aspen and Denver, where high-altitude skiing and climbing activities are popular.

In the other Everest report, John Finley, Ph.D., described a study in which he gave Mt. Everest climbers a type of fat called “medium-chain triglycerides” in their cookies and hot chocolate. They also took an aspirin every day.

“We tried to improve climbers’ performances by feeding them medium-chain triglycerides — fat that we thought would be metabolized better as quick energy,” said Finley, who is with Louisiana State University.

At high altitudes, the air pressure is low and the oxygen is less dense — making less oxygen available for breathing. In response, the body makes more oxygen-carrying red blood cells. This thickens the blood and puts a strain on the heart and lungs, increasing the risk of potentially dangerous blood clots. That’s why Finley also had the climbers take aspirin, which is known for thinning the blood and reducing the risks of having a heart attack or stroke. “We found that we could reduce the risk factors involved in having more viscous blood at high altitudes by giving the climbers aspirin,” he said.

Finley himself went on the climb and collected urine and fecal samples. The climbers who consumed the medium-chain triglycerides lost less weight and performed better than others on the expedition. The data also suggested that fats aren’t absorbed well at high altitudes when the body is losing a lot of weight, possibly because too little bile is produced by the liver to dissolve the fats, he explained.

Finley doesn’t have plans to commercialize the medium-chain triglyceride hot chocolate and cookies, but suggests that people going to high-altitude locations talk with their health-care providers about taking a daily aspirin.

Provided by American Chemical Society (news : web)