The Making Of An Intestinal Stem Cell

Researchers have found the factor that makes the difference between a stem cell in the intestine and any other cell. The discovery reported in the March 6th issue of the journal Cell, a Cell Press publication, is an essential step toward understanding the biology of the stem cells, which are responsible for replenishing all other cells in the most rapidly self-renewing tissue in mammals. It may also have implications for colon cancer, according to the researchers.

The report finds evidence that a transcription factor called Achaete scute-like 2 (Ascl2) switches on the stem cell program in intestinal cells. Transcription factors are genes that control other genes.

“This transcription factor makes these stem cells tick,” said Hans Clevers of Hubrecht Institute-KNAW & University Medical Center Utrecht, The Netherlands. “It activates a small program of genes essential to gut stem cells.” In other words, if the Ascl2 gene turns on, any dividing cell in the intestine would turn into a stem cell capable of producing any other cell type in that tissue, he added.

The lining of the intestine is made up of peaks known as villi and valleys called crypts. The crypts contain stem cells and so-called Paneth cells, which serve to protect those stem cells.

Intestinal stem cells are rather unique among adult stem cells, Clevers said. In most tissues of the body, stem cells divide only rarely — perhaps once a month. That’s not true of the rapidly dividing stem cells of the intestine.

“Their entire life, intestinal stem cells make tissue every day,” he said. That’s because approximately every five days, the intestinal lining is replaced in its entirety, leaving only the stem cells and their Paneth cell defenders constant. The stem cells produce an impressive 200 to 300 grams of new cells every day, Clevers added.

“That’s an enormous buildup of tissue. These stem cells are responsible.”

While there has been some controversy in the field over the identity of intestinal stem cells, Clevers team earlier showed that tiny cells intermingled with the Paneth cells of the intestine do have the characteristics of stem cells. Each crypt bottom harbors around six of those cells, which divide daily to produce every other type of cell in the intestinal linings of mice over the course of their lifetimes. These cells are defined by the expression of a gene called Lgr5.

In the new study, the researchers wanted to further explore the genes that distinguish the Lgr5 stem cells from other intestinal cells. After examining 200 or so genes, they landed on a handful that differed between stem cells and all other cells. Of those, Clevers said Ascl2 was the only transcription factor, a class of genes that are generally important to setting the fates of cells.

When they induced the activity of the Ascl2 transcription factor throughout the intestinal lining of mice, it caused the overgrowth of crypts and the development of additional crypts on surfaces of the villi, they report. In intestines of adult mice lacking Ascl2, the Lgr5 stem cells disappeared within days. All together, those findings led the researchers to conclude that Ascl2 is the key to intestinal stem cell fate.

While he said the findings may not have any immediate practical implications, they could yet yield some insight into the cancer stem cells that give rise to other colon cancer cells.

“In colon cancer tumors, there are a very limited number of cells that express this transcription factor,” Clevers said. “It’s likely that the same gene turns cancer cells into cancer stem cells.”

The researchers include
Laurens G. van der Flier, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Marielle E. van Gijn, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Pantelis Hatzis, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands; Pekka Kujala, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands;
Andrea Haegebarth, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Daniel E. Stange, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Harry Begthel, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Maaike van den Born, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Victor Guryev, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Irma Oving, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Johan H. van Es, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Nick Barker, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
Peter J. Peters, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands;
Marc van de Wetering, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands;
and Hans Clevers, Hubrecht Institute-KNAW & University Medical Center Utrecht, Utrecht, The Netherlands.

Source:
Cathleen Genova
Cell Press

Effects Of Low Dose Arsenic On Development Shown By Dartmouth Researchers

A team of Dartmouth Medical School (DMS) researchers has determined that low doses of arsenic disrupt the activity of a hormone critical in development. The finding is further evidence that arsenic at low doses (at levels found in U.S. drinking water in some areas) can be harmful. The study appeared in the online edition of the journal Environmental Health Perspectives (EHP), and it will be published in a forthcoming issue of the journal.

“Arsenic is a natural, yet pervasive, chemical in the environment; we can’t seem to escape it,” says Joshua Hamilton, one of the authors on this study and the director of the Center for Environmental Health Sciences at Dartmouth and Dartmouth’s Superfund Basic Research Program on Toxic Metals. “By learning how it adversely affects biological processes and at what levels we should be concerned, we will hopefully someday be able to mitigate its impact on human health.” Hamilton is also a professor of pharmacology and toxicology at DMS.

Hamilton and his team, in previous work, have learned that arsenic at low doses appears to suppress the ability of all critical steroid receptors, including those for estrogen and testosterone, to respond to their normal hormone signals. Chemicals that disrupt steroid hormone receptor signaling are called endocrine disruptors. Arsenic can disrupt these hormone pathways at extremely low doses equivalent to what many people in the U.S. have in their drinking water.

This study set out to see whether arsenic can also disrupt the activity of two hormone receptors that are involved in normal development – the retinoic acid receptor and the thyroid hormone receptor, two important members of the larger nuclear hormone receptor family. While the researchers studied the impact on frog development, these two hormone receptors are also vital to human development.

“I believe this is the first demonstration in an animal model that arsenic actually disrupts a developmental process that is regulated by hormones, and it does this at extremely low doses that are directly relevant to human exposures of concern,” says Hamilton.

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The work is funded by grants to Dartmouth from the National Institute of Environmental Health Sciences, a component of the National Institutes of Health. Other researchers on the paper include Jennifer C. Davey, Athena P. Nomikos, Manida Wungjiranirun, Jenna R. Sherman, Liam Ingram, Cavus Batki, and Jean P. Lariviere, all with, or formerly with, the Department of Pharmacology and Toxicology at DMS.

Source: Sue Knapp

Dartmouth College

Reading Gets Stroke Support, UK

The Stroke Association is launching its first support service for the people of Reading. Stroke survivors and carers will meet on Wednesday 20 January at Greyfriars Church, 10am to 2.30pm, to mark the launch and listen to talks from various local organisations.

The Stroke Survivors and Carers Support Group is co-ordinated by Claire Chapman from The Stroke Association and is run in partnership with Reading Borough Council and Berkshire West PCT. Claire says:

“All stroke survivors and their carers in the Reading area are invited to our launch day. It’s important that people who may feel isolated know that there are lots of others in a similar boat and there is some excellent support available to them. If they come along to our launch they will find everyone here under the one roof. I have already had over 100 referrals since May.”

As well as stroke survivors, the group aims to provide support to carers – whose needs can often be forgotten in the aftermath of a loved one suffering a stroke.

It has been proven that people who provide over 50 hours of care per week are twice as likely to be in poor health themselves; so the training, advice and assistance that this support group can help provide will prove invaluable.

The group will then continue to meet once a month after the launch.

CASE STUDY: Chris Goodall, 68, from Reading had a stroke in 1999. Chris was a journalist for over 30 years on the Islington Gazette in London before his stroke left him with communication difficulty and semi-paralysis. Chris would be happy to speak to any media and will be attending the Stroke Survivors and Carers Support Group opening ceremony on Wednesday 20 January.

The opening ceremony will take place at the Greyfriars Church, Friar Street, Reading, RG1 1EH on the 20 January at 10.30am – 2.30pm. Lunch and refreshments will be provided.

The agenda will include:

- Claire Chapman, The Stroke Association (Family and Carer Support Co-ordinator for Reading)
- Heather Priestley (Community Stroke Rehab Nurse)
- Catherine Sykes (Community Based Neuro Rehab Team)
- Reading Borough Council’s Direct Payments Team and an interactive voting session with Angela Todd, from the Strategy Team for housing and community care.
- Adrianne Kop from Inspired Health Solutions who will set the scene for a Health and Wellness afternoon.
- Mini Tai Chi and seated exercise sessions, Indian head massage and mini beauty and physiotherapy massages for stroke survivors and their carers.

There will also be stalls run by The Princess Royal Carers Trust, Ryder Cheshire Volunteers, Physiocare, The Stroke Association and a few others yet to be confirmed.

Notes

The Stroke Association is the only UK charity solely concerned with combating stroke in people of all ages.

The charity funds research into prevention, treatment, better methods of rehabilitation and helps stroke patients and their families directly through its community services which include communications support, family and carer support, information services, welfare grants, publications and leaflets.

The Stroke Association also campaigns, educates and informs to increase knowledge of stroke at all levels of society acting as a voice for everyone affected by stroke.

A stroke is a brain attack which causes brain damage. A stroke can be diagnosed by using FAST – Facial weakness, Arm weakness, Speech problems, Time to call 999. If any of these symptoms are present call an ambulance straight away.

About stroke

A stroke happens when the blood supply to part of the brain is disrupted. Most strokes occur when a blood clot blocks the flow of blood to the brain. Some strokes are caused by bleeding in or around the brain from a burst blood vessel. When the blood supply is disrupted, parts of the brain become damaged or destroyed. Some strokes are fatal whist others can cause permanent or temporary disabilities such as paralysis to one side of the body and loss of the ability to speak, read or write. Recovery may be slow and can vary from person to person.

Strokes can be prevented through lifestyle factors such as a healthy diet – particularly reducing salt intake, drinking alcohol in moderation, not smoking and taking regular exercise

Stroke statistics:

- Each year an estimated 150,000 people in the UK have a stroke.
- Stroke is the third biggest killer and the leading cause of disability.
- Of all people who suffer from a stroke, about a third are likely to die within the first 10 days, about a third are likely to make a recovery within one month and about a third are likely to be left disabled and needing rehabilitation.
- At least 300,000 people in England are living with moderate to severe disabilities as a result of a stroke.
- A stroke can happen to any one at any time. Around a quarter of strokes happen to those aged under 65, with around 1000 happening to those under 30.

Source
The Stroke Association

IT Employed To Allocate Stormwater Runoff, Leading To Cleaner Waters

Streams, lakes, and bays may soon be cleaner thanks to an innovative approach to managing stormwater runoff being developed at Virginia Tech and funded by the U.S. Environmental Protection Agency (EPA).

A novel software application will help engineers and planners select the most efficient and site specific methods — called “Best Management Practices” (BMPs) — of controlling the amount of pollutants that enter the receiving waters through stormwater runoff.

Pollutants are washed off the roads, parking lots, or other surfaces by stormwater, and include toxic motor oil, pesticides, metals, bacteria, and trash. The Congressional Research Service reported in 2007 that up to 50 percent of water pollution problems in the United State are attributed to stormwater runoff.

The application is the product of collaboration between faculty and researchers from Virginia Tech’s Virginia Water Resources Research Center (vwrrc.vt.edu), the Center for Geospatial Information Technology in the College of Natural Resources (cgit.vt.edu), and the Via Department of Civil and Environmental Engineering in the College of Engineering (cee.vt.edu).

The new BMPs selection approach, called Analytical Hierarchy Process (AHP), will factor in dozens of site-specific criteria such as soil types, land slopes, or maintenance accessibility before choosing the optimal BMPs for a particular location.

“This technique is expected to drastically reduce the BMP selection time and will also eliminate the human error from such a complex process,” says project coordinator Tamim Younos, water center associate director and research professor of water resources in the Department of Geography in the College of Natural Resources. Other project leaders include Randy Dymond, CGIT co-director, and David Kibler, professor of civil and environmental engineering.

Traditionally, the selection of BMPs has been done only by proficient stormwater experts guided by little more than vaguely written regulations, experience, and intuition. “They rely heavily on past knowledge, tradition, or even personal preference for particular methods of controlling stormwater runoff,” explains Kevin Young, research associate at CGIT.

Young adds that all too often personal bias has led to “cookie-cutter” solutions to very complex stormwater management needs, resulting in poor control of the pollutants.

A widely used, conventional BMP is to build detention ponds near commercial or residential areas, regardless of the actual construction site needs and conditions. “The stormwater is directed to a detention pond where gravity takes over, depositing sediment and some pollutants onto the bottom,” says Younos. “Pond overflow that still may contain dissolved pollutants reaches streams, rivers, and lakes, and possibly groundwater.”

Other types of BMPs are trenches and porous pavement that allow the stormwater to infiltrate the ground, vegetated wetlands, and sand filters that help sift the pollutants, or proprietary stormwater technologies such as hydrodynamic separators.

The new tool will be pilot-tested on Town of Blacksburg’s storm water system and the local Stroubles Creek watershed. The AHP software will be used by the research team to select BMPs within the watershed contributing runoff to Stroubles Creek, the town’s main receiving water body. Two existing computer models will then be used to simulate how efficient the selected BMPs are at removing the stormwater runoff pollutants.

“The best part about conducting a pilot test on Blacksburg is that the town will be able to implement our recommendations,” says Younos. “We are very pleased by the town’s enthusiasm and support for this project.” Other stakeholders include the New River Planning District Commission, Virginia Department of Environmental Quality, and Virginia Department of Conservation and Recreation.

Young discussed the principles of this novel approach to managing stormwater runoff in his Master’s thesis, under the guidance of the late professor G. V. Loganathan.

The software, expected to be available next year, will be free for use by all interested engineers and planners, localities, and BMP review authorities, and will be applicable in other states with geographic and climatic environments similar to Virginia.

###

Source: Ana Constantinescu

Virginia Tech

Youth Smoking Rates At Lowest Rates Ever, Canada

Smoking rates among Canadian youth are at their lowest ever, the most recent Canadian Tobacco Use Monitoring Survey shows.

The results, which came from data collected between February and December 2006, show a significant decrease in the smoking rates among youth aged 15-19 years over the past 12 months, with 15% of youth reporting smoking in 2006, down from 18% for the same period one year ago.

“I am extremely pleased to see that our governments’ efforts in tobacco control have made such a positive impact, especially among our younger Canadians,” said Health Minister Tony Clement. “These results encourage us to continue to work collectively towards reducing smoking rates in Canada.”

The 2006 survey found that fewer than five million Canadians, representing 19% of the population aged 15 years or older, were current smokers. Results indicate that, between 1985 and 2006, smoking rates have fallen by almost one-half, from 35% to 19%.

While the achievements so far are impressive, much remains to be done. Smoking is still the most preventable cause of disease and premature death in Canada. More than 37,000 people will die prematurely each year in Canada due to tobacco use, including at least 800 non-smokers who will die from exposure to second-hand smoke.

Understanding Canadian trends in tobacco use helps to effectively develop, implement and evaluate national tobacco control strategies, policies and programs.

For more information on Health Canada’s tobacco control efforts, and complete results from the 2006 Canadian Tobacco Use Monitoring Survey, please visit Gosmokefree!

hc-sc.gc

Sleep Apnea, Blood Pressure Linked

Full-night sleep studies and echocardiography may need to be incorporated into routine assessments of patients with difficult-to-treat high blood pressure, suggests UAB researcher Monique Pratt-Ubunama, M.D.

“And those who are resistant to treatment and are found to have sleep apnea may benefit from mineralocorticoid receptor antagonists, since levels of aldosterone were high in study patients; and continuous positive airway pressure (CPAP) should be encouraged,” she said.

Ubunama’s suggestions are based on results of a study funded by the National Heart, Lung and Blood Institute and presented last month at the American Heart Association annual meeting.

“We found a direct relationship between the severity of sleep apnea and cardiovascular changes associated with high blood pressure.”

University of Alabama at Birmingham
701 20th St. S., AB 1320
Birmingham, AL 35294-0113
United States
uab.edu/news

New Therapy For Chronic Fatigue Syndrome To Be Tested At Stanford

A preliminary study suggests there may be hope in the offing for some sufferers of chronic fatigue syndrome with a new therapy being tested by researchers at the Stanford University School of Medicine.

JosГ© Montoya, MD, associate professor of medicine (infectious diseases), and postdoctoral scholar Andreas Kogelnik, MD, PhD, have used the drug valganciclovir – an antiviral often used in treating diseases caused by human herpes viruses – to treat a small number of CFS patients.

The researchers said they treated 25 patients during the last three years, 21 of whom responded with significant improvement that was sustained even after going off the medication at the end of the treatment regimen, which usually lasts six months. The first patient has now been off the drug for almost three years and has had no relapses. A paper describing the first dozen patients Montoya and Kogelnik treated with the drug was published in the December issue of Journal of Clinical Virology.

“This study is small and preliminary, but potentially very important,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, who was not involved in the study. “If a randomized trial confirmed the value of this therapy for patients like the ones studied here, it would be an important landmark in the treatment of this illness.”

Montoya has received a $1.3 million grant from Roche Pharmaceutical, which manufactures the drug under the brand name Valcyte, to conduct a randomized, placebo-controlled, double-blind study set to begin this quarter at Stanford. The study will assess the effectiveness of the drug in treating a subset of CFS patients.

Montoya is speaking about his efforts at the biannual meeting of the International Association for Chronic Fatigue Syndrome in Fort Lauderdale on Jan. 11 and 12.

Chronic fatigue syndrome has baffled doctors and researchers for decades, because aside from debilitating fatigue, it lacks consistent symptoms. Although many genetic, infectious, psychiatric and environmental factors have been proposed as possible causes, none has been nailed down. It was often derided as “yuppie flu,” since it seemed to occur frequently in young professionals, though the Centers for Disease Control and Prevention says it’s most common in the middle-aged. But to those suffering from it, CFS is all too real and its effects are devastating, reducing once-vigorous individuals to the ranks of the bedridden, with an all-encompassing, painful and sleep-depriving fatigue.

More than 1 million Americans suffer from the disorder, according to the CDC. The disease often begins with what appears to be routine flulike symptoms, but then fails to subside completely – resulting in chronic, waxing and waning debilitation for years.

Valganciclovir is normally used against diseases caused by viruses in the herpes family, including cytomegalovirus, Epstein-Barr virus and human herpes virus-6. These diseases usually affect patients whose immune systems are severely weakened, such as transplant and cancer patients. Montoya, who had used the drug in treating such patients for years, decided to try using it on a CFS patient who came to him in early 2004 with extremely high levels of antibodies for three of the herpes family viruses in her blood. At the time, she had been suffering from CFS for five years.

When a virus infects someone, the levels of antibodies cranked out by the immune system in response typically increase until the virus is overcome, then slowly diminish over time. But Montoya’s patient had persistently high antibodies for the three viruses. In addition, the lymph nodes in her neck were significantly enlarged, some up to eight times their normal size, suggesting her immune system was fighting some kind of infection, even though a comprehensive evaluation had failed to point to any infectious cause.

Concerned about the unusual elevations in antibody levels as well as the swelling of her lymph nodes, Montoya decided to prescribe valganciclovir. “I thought by giving an antiviral that was effective against herpes viruses for a relatively long period of time, perhaps we could impact somehow the inflammation that she had in her lymph nodes,” said Montoya.

Within four weeks, the patient’s lymph nodes began shrinking. Six weeks later she phoned Montoya from her home in South America, describing how she was now exercising, bicycling and going back to work at the company she ran before her illness. “We were really shocked by this,” recalled Montoya.

Of the two dozen patients Montoya and Kogelnik have since treated, the 20 that responded all had developed CFS after an initial flulike illness, while the non-responders had suffered no initial flu.

Some of the patients take the drug for more than six months, such as Michael Manson, whose battle with CFS has lasted more than 18 years. The former triathlete was stricken with a viral infection a year after his marriage. After trying unsuccessfully to overcome what he thought were lingering effects of the flu, he had no choice but to drastically curtail all his activities and eventually stop working.

During his longest period of extreme fatigue, 13 1/2 weeks, Manson said, “My wife literally thought I was passing away. I could hear the emotion in her voice as she tried to wake me, but I couldn’t wake up to console her. That was just maddening.”

Now in his seventh month of treatment, Manson is able to go backpacking with his children with no ill after-effects. Prior to starting the treatment, Manson’s three children, ages 9 to 14, had never seen him healthy.

Montoya and Kogelnik emphasized that even if their new clinical trial validates the use of valganciclovir in treating some CFS patients, the drug may not be effective in all cases. In fact, the trial will assess the effectiveness of the medication among a specific subset of CFS patients; namely, those who have viral-induced dysfunction of the central nervous system.

“This could be a solution for a subset of patients, but that subset could be quite large,” said Kristin Loomis, executive director of the HHV-6 Foundation, which has helped fund a significant portion of the preparatory work for the clinical trial. “These viruses have been suspected in CFS for decades, but researchers couldn’t prove it because they are so difficult to detect in the blood. If Montoya’s results are confirmed, he will have made a real breakthrough.”

“What is desperately needed is the completion of the randomized, double-blind, placebo-controlled clinical trial that we are about to embark on,” Montoya said.

###

People interested in participating in the clinical trial must live in the San Francisco Bay Area. More information about the clinical trial is available online at vicd/clinicaltrial.html.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at mednews.stanford.edu/.

Contact: Louis Bergeron

Stanford University Medical Center

View drug information on Valcyte.

New Research Study: Statins May Stave Off Septic Lung Damage

Statins may be best known for their ability to reduce cholesterol, but a research report appearing in the May 2011 issue of the Journal of Leukocyte Biology shows that these same drugs could also play a crucial role in the reduction of lung damage resulting from severe abdominal sepsis and infection.

“We hope that this study will not only provide new knowledge about the complicated pathophysiology behind abdominal sepsis, but also form the basis for more effective and specific treatment options for patients with severe infections,” said Henrik Thorlacius, M.D., Ph.D., a researcher involved in the workfrom the Department of Surgery at Skane University Hospital at Lund University, Malmo, Sweden.

To make this discovery, the researchers studied mice with a punctured intestinal bowel and treated half with a statin drug, simvastatin, and the others with only water. The animals treated with simvastatin had much less lung injury than those only given water. Additionally, the simvastatin-treated group demonstrated significantly fewer inflammatory cells in the lung, as well as reduced levels of pro-inflammatory substances. These findings suggest that treatment with statins may be of clinical value for patients with severe abdominal infections.

“Sepsis is a serious medical problem for which few good treatments exist,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “This research is very exciting because statins are readily available and have a well established safety profile, making them a prime candidate for efficacy testing.”

According to the National Institute of General Medical Sciences, NIH, Sepsis is a major challenge in the intensive care unit, where it is one of the leading causes of death. It is caused when immune chemicals released into the blood to combat infection trigger widespread inflammation, resulting in impaired blood flow, which damages the body’s organs by depriving them of nutrients and oxygen. In the worst cases, the heart weakens and multiple organs – lungs, kidneys, liver – may quickly fail and the patient can die. Each year, severe sepsis strikes about 750,000 Americans, and as many as half die, which is more than the number of U.S. deaths from prostate cancer, breast cancer and AIDS combined.

Source:
Cody Mooneyhan
Federation of American Societies for Experimental Biology

Pine Bark Naturally Decreases Severe Chronic Venous Insufficiency Study Shows

Recent findings published in the journal of Clinical and Applied Thrombosis/Hematosis show a significant symptom reduction of chronic venous insufficiency (CVI) in patients after supplementing with Pycnogenol® (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree. Over 35 years of research on Pycnogenol® demonstrate the antioxidant’s ability to improve blood flow and strengthen venous walls. Published results from this study showed Pycnogenol® to be more effective in reducing edema (leg swelling), tight calves, skin alterations, pain during walking and swelling limbs than Daflon®, a combination of diosmin and hesperidin and a commonly prescribed drug used to treat CVI.

About 500,000 people in the United States develop leg ulcers due to CVI. If left untreated, leg and ankle swelling can lead to dangerous conditions such as deep vein thrombosis (DVT). Previous studies have shown Pycnogenol® to be effective in encouraging improved circulation and helping to prevent travel-related DVT. Like varicose veins, spider veins also develop if edema is left untreated.

“Chronic venous insufficiency is caused when leg veins cannot pump enough blood back into the heart. When people are not active, blood pools in their leg veins, legs and ankles can become swollen,” said Peter Rohdewald, Ph.D. and researcher of the study. “Eventually, some of the valves cannot hold the weight of excessive blood, which then adds more pressure onto the next valve further downwards. Ultimately, the inability to prevent the liquid in the blood from seeping into the tissue is what causes edema, a common condition of CVI.”

Researchers at L’Aquila University in Italy conducted a comparative analysis by supplementing 86 patients with severe CVI with Pycnogenol® and Daflon®. Each group supplemented daily for eight weeks. Patients who supplemented with Pycnogenol® received either 150 mg or 300 mg, while Daflon® patients supplemented with 1000 mg.

Ankle swelling was measured before 10 a.m. to avoid the swelling effect of standing and again after 30 minutes of resting with feet elevated. Measurements were taken at the beginning of the study and after four and eight weeks of treatment. A composite, analogue score based on signs and symptoms (edema, pain, restless limbs, subjective swelling, and skin alterations/redness) was recorded by patients. A second evaluation of edema was made by another physician.

After eight weeks of treatment, patients who supplemented with Pycnogenol® experienced decreased ankle swellings by 35 percent, while Daflon treatment decreased ankle swelling by 19 percent. A composite score for edema including pain, restless legs, feeling of heavy swollen legs, and skin alterations was found to be decreased with Pycnogenol® by 64%, whereas Daflon® was only half as effective, lowering the composite edema score by 32%.

The transdermal oxygen and carbon dioxide concentration in the lower legs was estimated with small sensors attached to the skin. Pycnogenol® treatment was found to significantly increase tissue oxygen and lower CO2, suggesting a considerable improvement in blood circulation to the legs. Daflon®, in contrast, did not yield any significant effect on the tissue oxygenation and apparently does not improve blood circulation to the legs.

“Interestingly, this study demonstrated that supplementation with a very high dosage of 300 mg Pycnogenol® a day did not yield significantly better effects than treatment with 150 mg PycnogenolпїЅ, with the exception of the composite edema score, which improved better with the higher dosage,” said Rohdewald.

Continuous stretching from CVI permanently enlarges veins. Past studies have shown that treating edema with Pycnogenol® prevents the development of spider veins. Pycnogenol® also helps prevent existing spider veins from getting larger and more prominent. When edema is successfully treated, the increased pressure on veins gets normalized, preventing the veins from further increasing in size.

“Pycnogenol® has demonstrated its efficacy and safety in several clinical trials and symptoms of CVI have been reduced significantly by Pycnogenol® in controlled studies. We were pleased to see that not only did Pycnogenol® decrease CVI symptoms, but the results were significantly more successful then the prescription drug used for treating CVI,” said Rohdewald.

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Pycnogeno®: is a natural plant extract originating from the bark of the Maritime pine that grows along the coast of southwest France and is found to contain a unique combination of procyanidins, bioflavonoids and organic acids, which offer extensive natural health benefits. The extract has been widely studied for the past 35 years and has more than 220 published studies and review articles ensuring safety and efficacy as an ingredient. Today, Pycnogenol® is available in more than 400 dietary supplements, multi-vitamins and health products worldwide. For more information or a copy of this study, visit pycnogenol/.

Natural Health Science Inc., (NHS) based in Hoboken, New Jersey, is the North American distributor for Pycnogenol® (pic-noj-en-all) brand French Maritime Pine Bark Extract on behalf of Horphag Research. Daflon® is a registered trademark of Biofarma / Laboratoires Servier, France. PycnogenolпїЅ is a registered trademark of Horphag Research Ltd., Guernsey, and its applications are protected by U.S. patents #5,720,956 / #6,372,266 and other international patents. NHS has the exclusive rights to market and sell Pycnogenol® in North America and benefits from more than 35 years of scientific research assuring the safety and efficacy of PycnogenolпїЅ as a dietary supplement. For more information about Pycnogenol® visit our web site at pycnogenol/.

Contact: Melanie Nimrodi

MWW Group

Wisconsin Governor Signs Law On Umbilical Cord Blood Donations

Wisconsin Gov Jim Doyle (D) on Thursday signed into law a bill (AB 270) requiring health care providers to inform pregnant women they can donate their infants’ umbilical cord blood to a state-approved blood bank after delivery, the AP/Janesville Gazette reports (AP/Jansville Gazette, 12/16). The legislation was approved by the Assembly in June and unanimously approved by the state Senate in September. Umbilical cord blood contains stem cells that have been used to treat a variety of diseases and medical conditions, including leukemia (Kaiser Daily Women’s Health Policy Report, 9/29). “As governor, I am doing all that I can to encourage the cutting-edge scientific research happening here in Wisconsin,” Doyle said in a statement. State Rep. Steve Wieckert (R) and state Sen. Joe Leibham (R), who were sponsors of the bill, said the measure seeks to prevent shortages of cord blood in the state. Wieckert after the signing said, “We are going to save kids’ lives with this” (Appleton Post-Crescent, 12/16). Doyle said stem cell research using umbilical cord blood should not replace embryonic stem cell research, adding, “I believe they can complement one another, with umbilical cord research providing just another weapon in the arsenal of scientists who are trying to conquer diseases that have affected millions around the world” (AP/Janesville Gazette, 12/16).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.