Archive for July, 2008
July 31st, 2008 -- Posted in Arthritis / Joint Pain, Brain Food, Life Extension, Mental Health, Physical Health |
If Bruce Lipshutz has his way, you may soon be buying bottles of water brimming with the life-sustaining coenzyme CoQ10 at your local Costco.
Lipshutz, a professor of chemistry at UC Santa Barbara, is the principal author of an upcoming review, “Transition Metal Catalyzed Cross-Couplings Going Green: in Water at Room Temperature,” which will be published in Aldrichimica Acta in September. In it, Lipshutz and post-doctoral researcher Subir Ghorai discuss how recent advances in chemistry can be used to solubilize otherwise naturally insoluble compounds like CoQ10 into water.
Never heard of CoQ10? Lipshutz says you’re not alone. “If you don’t know anything about it,” Lipshutz said during a recent interview, “that’s not surprising to me. Much of the public hasn’t heard of it.” But he’s on a mission to correct what he views as a major oversight. “In a sense, I’m just a messenger. People need to not only know about CoQ10, they need to take it.”
Like vitamin C, CoQ10 is a compound that’s vital to our survival. It’s a coenzyme that our cells synthesize, albeit in 21 steps, and it’s in every cell. This contrasts with a vitamin, such as vitamin C, which is not made by the body. Both CoQ10 and vitamin C are “compounds of evolution,” Lipshutz said. “Everybody accepts the importance of vitamin C. The reason the public does not fully appreciate it is that there’s no Linus Pauling for CoQ10. There is no champion.”
Pauling, a Nobel Prize-winning scientist, was also an advocate for greater consumption of vitamin C. “CoQ is not really in that category of public awareness yet,” Lipshutz said.
While the body produces its own CoQ10, that production decreases with age. “Nature gave us, through 2.5 billion years of evolution, a number of fundamental anti-aging, free-radical scavengers that helped us to survive, on average, only to about 40 years of age, until modern medicine came along,” Lipshutz said.
A large percentage of the body is made up of water, “but there are also the lipophilic portions of our cells that make up the non-aqueous part,” Lipshutz explained. At some point in our evolution, the water-soluble antioxidant vitamin C was produced in vivo, or what would technically be “coenzyme C.” Eventually, “a mutation took place that now prevents humans from making it,” he said. “However, evolution chose not to mutate out CoQ10.”
If one doesn’t get vitamin C, the consequences can be dire. “It’s essential for several cellular processes. For example, everyone knows about scurvy,” Lipshutz said. “You can last 30 days, maybe 60 days, as your cells deteriorate.”
On the other hand, CoQ10 – much of which is in the mitochondria of our cells – is essential for cellular respiration and ATP (adenosine triphosphate) production. “You wouldn’t last 30 minutes without CoQ10,” he said. “Thus, evolution teaches us that CoQ10 is as important as vitamin C. But who’s teaching this to our aging population? Nobody.”
Lipshutz has a history of CoQ10 research at UCSB. Initially, he retooled the chemistry that would produce the supplement via synthesis instead of fermentation, which is what Japan used to become the world leader in CoQ10 production. But China’s entry into the CoQ10 market only a few years ago changed everything.
“The price of CoQ for over 30 years was about $1,600 per kilo as produced by the Japanese,” Lipshutz said. “The Chinese came along and, for the time being, have dramatically altered the market by deciding at the government level that they were going to own this important area of dietary supplements. CoQ10 can now be purchased for as little as $400 a kilo, which in principle is great news for consumers.”
When the supply of CoQ10 grew faster than demand, Lipshutz went into the lab to study what else could be done with this life-enriching compound. After all, CoQ is now readily available. At Costco or drug stores, you can buy CoQ10 formulated into softgels that deliver the nutrient in various strengths. It’s marketed as helping to provide a boost in energy as well as a healthy heart. But, Lipshutz notes, you absorb only10-15 percent of CoQ10 in the softgel form. How, he asked, could this become more available and bioefficient?
“The future is not about access to CoQ10 anymore,” he said. “It’s not about, ‘Do we have the best synthesis?’ or ‘Can we compete with the Chinese?’ It’s about getting it into water, so that we can get it into our mitochondria.”
Quite a challenge since CoQ10 is water insoluble. The answer? Go nano.
“We do it with nano-micelle-forming technology,” Lipshutz said. He starts by putting a known, inexpensive molecule called PTS into water, which spontaneously forms a nanosphere about 25 nanometers (one nanometer is equal to one billionth of a meter) in diameter. This sphere has a lipophilic portion tied to a hydrophilic portion through a linker. The lipophilic portion, which is actually vitamin E, goes to the center. “The vitamin E portion associates in the middle with itself because it doesn’t have any solubility, any energy-lowering interactions, with the water around it,” Lipshutz said. “But the external or hydrophilic portion associates with water.
“So, on the outside is the water-loving portion, while the lipophilic, or grease-loving portion, is on the inside. When you add the CoQ, it says, ‘Where would I rather be?’ Since like dissolves like, the CoQ10 goes inside the micelle. It’s 25 nanometers and it’s crystal clear. And, it’s stable at room temperature.”
That’s nanotechnology. It delivers twice the amount of the compound into the bloodstream, and the concentration in water can be adjusted, he said. This approach can be applied to a broad range of nutraceuticals, including omega-3s, carotenoids like lutein and beta-carotene, and resveratrol. “We can also take pharmaceuticals, like Taxol, an anti-tumor agent, and put them into just water or saline using this PTS,” he said.
By taking advantage of this micellar technology, synthetic chemistry can also be done inside the nano-containers. That translates into doing chemistry in pure water, and at room temperature. “That’s green chemistry,” Lipshutz said.
The amount of heat usually needed in reactions, and the waste created by organic solvents, are dramatically reduced. Lipshutz hopes that when his processes are looked at on a much larger scale, a savings of metric tons of solvent, currently released into the environment, will be realized.
“We aim to get organic solvents out of organic reactions,” he said. “And we’re already looking into next-generation possibilities. All of our green chemistry has come out of being able to put CoQ10 and other dietary supplements into water.”
Lipshutz sees this as his most significant contribution to an already illustrious career as an organic chemist.
“It’s an opportunity to affect every person on the planet,” he says proudly.
July 31st, 2008 -- Posted in Life Extension, Physical Health |
Genetics, not wear and tear, may be the true cause of aging, according to a study by School of Medicine researchers.
Led by Developmental Biology and Genetics Prof. Stuart Kim, the study looked at 20,000 genes in C. elegans, a millimeter-long worm. Researchers monitored discrepancies in gene function over the course of the worms’ lives. They found that 1,254 genes had different levels of function depending on the worm’s age.
This suggests that certain genes, especially transcription factors — the “on-and-off-switch” genes that regulate the function of other genes — play important roles in regulating the process of aging cells. Transcription factors in worms were found to gradually disrupt the balance in cell regulation, over time turning more genes “off,” than were being turned “on.”
But the new theory doesn’t explain everything. A gene-based explanation of aging doesn’t account for vast differences in the life spans of species — this is better explained by the old molecular damage theory.
“The [old theory] is that there is damage to the proteins,” Kim said. “The differences in life spans must be how well you tolerate or repair the damage to your cells. There is a huge variation in life spans, all dependent on the same chemical reactions.” In the molecular damage theory, oxygen free radicals gradually break down the molecules within the cells of species, and this wear and tear contributes to a gradual breakdown in their ability to function.
Kim and his colleagues sought to gauge just how much genetics can affect life span when they conducted the study — the researchers took steps to find how much deterioration and genetics contributed to aging, respectively.
“We rebalanced the system [stopping altogether the function of the transcription factors],” Kim explained. “Worms lived 50 percent longer [as a result]. I don’t have the tools yet to really balance it — all I can do is knock it out.”
With the power to alter transcription factors might come the power to extend life. [KH1]Scientists could inhibit genes’ ability to control the function of cell regulation and thus control the amount of time a individual possesses a balance in cell regulation. The longer amount of time balance is achieved, the longer life is sustainable.
“Here is the next experiment,” Kim said. “Let a worm grow old so the pathways are unbalanced, and then balance the pathways [by controlling changes in transcription factors over time] and see what happens. Ask yourself the question that perhaps you not only slowed down the process of aging but you reversed it. It’s a really fascinating process, and I think we can understand it.”
Source: Stanford Daily (http://daily.stanford.edu/article/2008/7/31/studyFindsPossibleSecretOfAging)
July 28th, 2008 -- Posted in Life Extension, Mental Health |
Researchers show direct pathway that could be targeted for drug therapy
A new genetic finding from a group of researchers at Brigham and Women’s Hospital (BWH), the University of Wisconsin School of Medicine and Public Health (SMPH), and the University of Ottawa may help pave the way for the discovery of therapies that could effectively treat Parkinson’s disease (PD). Clemens Scherzer, a neurologist and researcher at BWH, along with collaborators, showed that the buildup of a certain protein is responsible for controlling the production of the gene, alpha-synuclein, which is a cause of PD. These findings appeared online in the Proceedings of the National Academy of Science during the week of July 21 and will be published in a later print edition of the journal.
“This discovery is exciting because it allows for a paradigm shift in how researchers can search for a cure for Parkinson’s disease. So far, research has focused on ways to get rid of excess alpha-synuclein that is built up in the brain of patients with Parkinson’s. Now, we can look for ways to lower the production of alpha-synuclein upfront,” Scherzer said.
Patients with PD have clumps of alpha-synuclein in their brains, and high levels of this protein kill off dopamine neurons and cause tremors and other symptoms of PD. While looking at blood tests for Parkinson’s disease, the researchers noticed high levels of alpha-synuclein in the blood. Because alpha-synuclein was thought previously to be a gene found in the brain, its presence in the blood was surprising. Seeking to uncover the reason for the presence of this gene in blood, the researchers used gene chips to look at whether or not any of the thousands of other genes active in blood was linked to alpha-synuclein. They discovered that there are actually three genes, called heme genes, which are responsible for carrying oxygen and transporting electrons through the blood, whose activity was in lock step with the activity of the alpha-synuclein gene.
“In the middle of this noisy picture of gene expression in blood, we were able to uncover a very clear pattern of activity with these four genes,” said Scherzer. “By recognizing that pattern, we then deduced that there must be a switch, or mechanism that was responsible for controlling the activity of these genes.”
The next step for researchers was to discover what was controlling the activity of these genes in the blood. For this, Scherzer and Michael Schlossmacher, who leads the University of Ottawa research team, turned to Emery Bresnick, an SMPH professor of pharmacology, and an expert in GATA transcription factors. A transcription factor is a dial that turns the activity of genes up or down. Through this collaboration, researchers discovered that the transcription factor GATA-1 was responsible for controlling the functions of these four genes in the blood and that a relative of GATA-1, the transcription factor GATA-2 – which is highly present in the brain regions affected by PD – may be responsible for the activity of alpha-synuclein in the brain.
“We were able to show that the GATA-2 transcription factor directly sticks to the alpha-synuclein gene and when GATA-2 was knocked down in dopamine cells, the levels of alpha-synuclein went down as well,” said Schlossmacher.
This discovery illustrates the direct regulation of the gene by GATA factors, but researchers emphasize that further research is needed to understand if this pathway can be used for the development of drug therapies to tailor treatment strategies.
Source: Harvard News (http://www.news.harvard.edu/gazette/2008/07.24/00-parkinsons.html)
July 24th, 2008 -- Posted in Mental Health |
We all know people who are tense and nervous and can’t relax. They may have been wired differently since childhood.
New research done by the HealthEmotions Research Institute and Department of Psychiatry at the School of Medicine and Public Health (SMPH) indicates that the brains of those suffering from anxiety and severe shyness in social situations consistently respond more strongly to stress and show signs of being anxious even in situations that others find safe.
Ned Kalin, chair of the UW-Madison Department of Psychiatry and director of the HealthEmotions Research Institute, in collaboration with graduate student Andrew Fox and others, has published a new study on anxious brains on the Public Library of Science (PLoS One) Web site today (July 2).
The study looked at brain activity, anxious behavior and stress hormones in adolescent rhesus monkeys, which have long been used as a model to understand anxious temperament in human children. Anxious temperament is important because it is an early predictor of the later risk to develop anxiety, depression and drug abuse related to self-medicating. The researchers found that those individuals with the most anxious temperaments showed higher activity in the amygdala, a part of the brain that regulates emotion and triggers reactions to anxiety, such as the fight or flight response. These anxious monkeys had more metabolic activity in the amygdala in both secure and threatening situations.
“The brain machinery underlying the stress response seems to be always on in these individuals,” says Kalin, “even in situations that others perceive as safe and secure.”
Rhesus monkeys were graded on their anxious temperament, then exposed to situations that ranged from being secure at home with their cage-mates to being alone to being confronted by an unfamiliar person. (This unknown person presented her facial profile to the monkey while avoiding any eye contact.)
The adolescent monkeys received an injection of FDG, a radioactive substance similar to glucose that lights up the active parts of the brain when the monkeys are imaged with positron emission tomography (PET). Whether in a secure environment or a more uncertain and possibly scary one, the nervous monkeys had more brain activity in the amygdala and surrounding “stress response” parts of the brain. This corresponded to higher levels of “freezing” behavior, fewer vocalizations and higher levels of the stress hormone cortisol in the anxious monkeys.
When the monkeys were retested a year and a half later, the results were the same: the anxious monkeys still were more stressed out than their calmer peers when judged by the behavioral and physiological measures.
“We’re looking for better ways to diagnose and treat mental illness,” explains Kalin about his ongoing work at HealthEmotions. “We’re trying to understand how the brain influences mood, reactions to stress and physical health.”
Kalin, who has long been an advocate of screening children for mental health problems, says the newest brain research refutes the idea that severely shy or anxious children will just “grow out of it” without help.
Psychiatrists have long known that an anxious temperament in childhood is a risk factor for developing anxiety disorders, depression and substance abuse, so intervention at a young age makes sense.
One thing’s certain: Telling someone with an anxious temperament to “calm down” probably won’t work. They’re just not wired that way.
Source:University of Wisconsin-Madison (http://www.news.wisc.edu/15363)
July 23rd, 2008 -- Posted in Arthritis / Joint Pain, Osteoporosis / Bone Health, Physical Health |
Patients suffering from severe arthritis now have an option for total ankle replacement that offers increased mobility and pain relief without permanent metal implants. Pioneered by Daniel K. Lee, D.P.M., F.A.C.F.A.S., at UC San Diego Medical Center, this technique is the first in the U.S to offer arthritis sufferers a non-metal, biological ankle replacement.
“Up until now, patients have had two options for replacing their ankle joints: metal implants or fusion of the joints,” said Lee, director of foot and ankle surgery at UCSD Medical Center. “Now there is an option that actually restores the ankle with an FDA-approved biologic material that is similar to the collagen found in cartilage.”
During a two hour minimally-invasive surgical procedure, Lee, a podiatric foot and ankle surgeon, removes the damaged cartilage around the ankle joint through a four centimeter incision. The collagen material is then molded into the joint where it adapts to the contour of the patient’s ankle.
“Unlike a metal device, the advantage to this material is that the implant can be customized in size and contour for every patient’s individual need,” said Lee. “No matter how the patient’s ankle is shaped, the collagen is a perfect fit.”
The biologic material, processed from either human or animal collagen sources, has been used for more than 10 years in plastic and abdominal surgery and heart valve replacement. Since it is non-allergenic and sterile in nature, there is no risk of rejection or need for the patient to take immunosupressors.
To allow the material to integrate fully with the ankle joint, a temporary external device is used to stabilize the joint area while keeping it “distracted” or open for a period of 4-6 weeks. Attached by small pins, the cylinder-shaped device serves as a shock system to keep the joint free from friction and movement until healing is complete. The device is then removed entirely, which keeps the patient’s ankle free from any metal parts.
“Within 3 weeks after surgery, we see an incorporation of tissue onto the damaged cartilage,” said Lee. “The idea here is to avoid fusion of the ankle and to add longevity to the joint. We want to give patients as much mobility as possible so they can get back to the activities they love the most.”
Lee’s patient’s range in age from 30-85. Robert Adams, 82, a retired professor, received the ankle replacement after repeated attempts at physical therapy.
“My ankle collapsed on me,” said Adams. “I didn’t like the idea of a fusion with no motion or opening up my ankle for a metal device. Following this surgery, I no longer have sharp or stabbing pains. I am continuing to improve and can get around better.”
For years, patients have had the option of total joint replacement in the hips, knees, and ankle with titanium and other metal devices. While the implants are well suited for hips and knees, metal replacements for the ankle show a high level of failure and unwanted complications such as metal collapse and breakage. Once an ankle is replaced with metal, options for revision surgery are little to none.
According to the Centers for Disease Control, an estimated 46 million U.S. adults, approximately 1 in 5, report doctor-diagnosed arthritis. As the U.S. population ages, these numbers are likely to increase sharply. The number of adults with arthritis is projected to increase to 67 million by 2030, and a good proportion of U.S. adults will have limited activity as a result. Nearly two-thirds of people with arthritis are younger than 65.
This novel technique for ankle replacement and results of a study will be described in late 2008 in the Journal of Foot & Ankle Surgery.
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