New Adult Model Of Rett Syndrome

An IRSF funded study published in the journal Science has shown that the childhood disorder Rett syndrome, can be reestablished in adult animals by "switching off" a critical disease causing gene in healthy adult animals. The gene was "switched off" in adult mice by use of a sophisticated genetic trick, resulting in the appearance of behaviors typically seen in Rett syndrome. The leading author Christopher McGraw, MD/PhD student, carried out the study in the laboratory of Dr. Huda Zoghbi, a renowned neuroscientist based at Baylor College of Medicine, and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital in Houston TX.



In 1999 Dr. Zoghbi's laboratory made a central discovery, identifying the causative link between mutations in the gene methyl-CpG-binding protein 2 (MeCP2) and Rett syndrome. This work led to other studies showing that MeCP2 protein is critical for the proper functioning of nerve cells during development and into adulthood. In 2007 a further study conducted by Dr. Adrian Bird, at Edinburgh University in the UK, showed the neurological symptoms of Rett syndrome can be reversed by reactivating MeCP2 in an adult mouse where the disease is already established. This work provided a critical proof of concept that symptoms of the disorder may be reversible in humans; however, to-date it was not known whether the early developmental period was important in establishing the course of the disease. This new study argues that early expression of the gene does not protect against the development of symptoms if the disease gene is later inactivated.



Commenting on the study, Dr. Zoghbi said "We did this experiment to see if providing MeCP2 early on in life, during critical periods of brain maturation, would be partially protective from loss of this protein in the adult brain. We were surprised to see that the nervous system had no detectable protection when MeCP2 was lost in adulthood. This affirmed that brain cells must have MeCP2 at all times to function normally."



There have been no effective pharmacological treatments developed to treat the disorder although new therapeutic trials are currently underway. This work suggests that therapies for Rett syndrome may need to be continuously maintained throughout the course of an individual's life.



Funding for this work was jointly provided by the National Institutes of Health, the Baylor College of Medicine Research Advocates for Student Scientists, the International Rett Syndrome Foundation, the Simons Foundation and the Rett Syndrome Research Trust.



About Rett Syndrome



Rett syndrome (RTT), a developmental neurological disorder, occurs almost exclusively in females. RTT results in severe movement and communication problems following apparently normal development for the first six to 18 months of life. Characteristic features of the disease include loss of speech and purposeful hand use, repetitive hand movements, abnormal walking, abnormal breathing, slowing in the rate of head growth and increased risk of seizures. Current treatment for girls with RTT includes physical and occupational therapy, speech therapy, and medication for seizures. There is no known cure for RTT. In 2007, researchers heralded a major breakthrough by reversing RTT symptoms in mouse models. RTT is considered a "Rosetta Stone" that is helping scientists understand multiple developmental neurological disorders, and shares genetic links with other conditions such as autism and schizophrenia.



Source:

Steve Bajardi


International Rett Syndrome Foundation

How Bisphenol A Induces Epigenetic Changes In Pregnant Mice That Cause Hormonal Imbalance In The Later Life Of Female Progeny

Here's more evidence that "safe" plastics are not as safe as once presumed: New research published online in The FASEB Journal (fasebj) suggests that exposure to Bisphenol A (BPA) during pregnancy leads to epigenetic changes that may cause permanent reproduction problems for female offspring. BPA, a common component of plastics used to contain food, is a type of estrogen that is ubiquitous in the environment.



"Exposure to BPA may be harmful during pregnancy; this exposure may permanently affect the fetus," said Hugh S. Taylor, Ph.D., co-author of the study from Yale University School of Medicine in New Haven, Connecticut. "We need to better identify the effects of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors."



Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses. Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically "programmed" the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants.



"The BPA baby bottle scare may be only the tip of the iceberg." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We'd better watch out for BPA, which seems to carry similar epigenetic risks across the generations. "



Source:

Cody Mooneyhan

Federation of American Societies for Experimental Biology

Public Citizen Petitions FDA To Ban Birth Control Pills Containing Hormone Desogestrel

The consumer advocacy group Public Citizen on Tuesday released a petition calling on FDA to ban oral contraceptives containing the hormone desogestrel because studies have shown they are twice as likely to cause blood clots without boosting protection against pregnancy, USA Today reports (Rubin, USA Today, 2/7). The pills cited in the petition include Ortho-McNeil's Ortho-Cept; Watson Pharmaceuticals' Reclipsen; Organon's Desogen; Barr Pharmaceuticals' Mircette, Velivet, Kariva and Apri-28; and some generic pills, according to Reuters (Heavey, Reuters, 2/6). The petition says many studies back to 1995 indicate that oral contraceptives containing desogestrel cause about 30 blood clot cases per 100,000 users annually, compared with 15 cases per 100,000 users of other oral contraceptives annually. More than 7.5 million prescriptions for oral contraceptives containing desogestrel were filled as of last year, according to the petition. Sidney Wolfe, director of Public Citizen's health research group, said that on the pills' labels, under the heading "Risks of Taking Oral Contraceptives," there is a warning "in barely perceptible four-point type" stating that the blood-clot risk might be higher in oral contraceptives that contain desogestrel than in other low-dose oral contraceptives (USA Today, 2/7). "By banning [desogestrel-containing] oral contraceptives, the FDA will potentially save hundreds of young women a year from developing venous thrombosis and its disabling and sometimes fatal consequences," the petition said (Reuters, 2/6). Public Citizen is posting a video explaining the petition on YouTube to spread its message to younger pill users. FDA spokesperson Susan Cruzan said the agency "will carefully review the petition" (AP/San Diego Union-Tribune, 2/6). Barr in a statement responding to the petition said, "The labeling that accompanies the company's oral contraceptive products provides all the necessary warnings and precautions for the appropriate use of the products." Ortho-McNeil in a statement said, "When used as labeled, Ortho-Cept is a safe and effective birth control choice" (USA Today, 2/7).

The petition is available online.

"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.


View drug information on Mircette.

True Weight Underestimated By Obese And Overweight Mothers And Their Children

Overweight and obese mothers and their children think they weigh less than their actual weight, according to research reported at the American Heart Association's Nutrition, Physical Activity and Metabolism/Cardiovascular Disease Epidemiology and Prevention 2011 Scientific Sessions.



In the study of women and children in an urban, predominantly Hispanic population, most normal weight women and children in the study correctly estimated their body weight, but most obese women and children underestimated theirs.



"Obesity is a well-known risk factor for the development of many diseases, including heart disease and diabetes," said Nicole E Dumas, M.D., lead author and an internal medicine resident at Columbia University Medical Center in New York City. Dumas and colleagues surveyed women and their pre-adolescent children attending an urban, primary care center in New York City. They asked the subjects about their age, income, heart disease risk factors, and perceptions of their body size using silhouette images that corresponded to specific body mass index (BMI) types - for example, underweight, normal and overweight.



The researchers also recorded participants' height, weight and BMI, which is a measurement of body weight based on height. A BMI of 25-29 is overweight, and a BMI over 30 is obese.



The researchers found:
65.8 percent of the mothers surveyed were overweight or obese.
38.9 percent of children surveyed were overweight or obese.
81.8 percent of obese women underestimated their weight compared to 42.5 percent of overweight and 13.2 percent of normal weight women; similarly, 86 percent of overweight or obese children underestimated their weight compared to 15 percent of normal weight children.
Of mothers with overweight or obese children, almost half (47.5 percent) thought their children were of normal weight.
Children selected larger body images than those chosen by their mothers to describe an "ideal" or "healthy" body image for a woman.
41.4 percent of the children in the study thought their moms should lose weight.

"These findings imply that not only is obesity prevalent in urban America, but that those most affected by it are either unaware or underestimate their true weight," she said. "In addition, obesity has become an acceptable norm in some families. Strategies to overcome the obesity epidemic will need to address this barrier to weight loss."



Future research should include interventions that study the effect of increased accuracy of body image perception on weight loss among families.


Notes:


Co-authors are Robert R Sciacca, Eng.Sc.D.; Jennifer Decolongon, M.D.; Juviza K. Rodriguez, B.A.; and Elsa-Grace V Giardina, M.D.



Author disclosures are on the manuscript. The study was funded by the Department of Health and Human Services and the Arlene and Joseph Taub Foundation.



Source:

Darcy Spitz

American Heart Association

Progress Against Child Deaths Will Lag Until Family, Community Care Prioritized

Global efforts to tackle millions of preventable child and maternal deaths will fail to extend gains unless world leaders act now to pour more healthcare resources directly into families and communities, according to a new World Vision report launched recently.



"The Missing Link: Saving children's lives through family care" examines how the resources invested to achieve Millennium Development Goals (MDGs) 4 and 5 can go further toward saving the more than 8 million children under the age of five and 350,000 mothers who die each year, mostly from preventable causes. Undertaken by the international child-focused organization World Vision, the analysis distills several decades of field-based experience and research to recommend investing directly in care for families and the communities where they live.



"With only five years to go until the MDG target deadline, no one can afford to waste time or resources," said Kevin Jenkins, president and CEO of World Vision International. "Efforts will falter for the world's most impoverished, vulnerable children and their mothers until we focus our energies on bringing health care directly where they need it most - right to their homes and communities."



In 2000, world leaders adopted eight ambitious yet achievable goals aimed at halving extreme poverty and its effects. Known as the MDGs, their target deadline is 2015. Next week, world leaders, governments and NGOs convening for the 2010 UN General Assembly in New York will highlight progress, examine gaps and lessons learned and revitalize efforts on the MDGs, with Secretary General Ban Ki-Moon putting a special focus on women's and children's health.



MDGs 4 and 5, targeting the reduction of maternal and child mortality, lag far behind the other goals. This is in part because the people who most need care can't access it, say the authors of the World Vision report.



"Millions of children live and die beyond the reach of formal health services and clinics, of diseases that are easily prevented and treated when families are able to access effective, basic interventions as close to their homes as possible," said Martha Newsome, Global Director of Health and Nutrition for World Vision International. "This deadly gap makes family and community care a critical link in saving millions from preventable deaths, and an essential component required to strengthen health systems adequately."



World Vision's Child Health Now campaign, drawing upon lessons learned from the Christian humanitarian organization's 1,600+ community programs, encourages communities to express their rights to quality health care, and press local and national governments to meet their responsibilities for promoting health and ending preventable child deaths.



Although the number of deaths among children under the age of five has declined in recent years, the rate of decline - an estimated one-third reduction over 20 years - is insufficient to meet MDG 4, particularly in the regions of Sub-Saharan Africa, Southern Asia and Oceania, where most child deaths occur, according to estimates released today by UNICEF.



The results are dismal given that evidence shows millions of babies and toddlers could be saved from death each year through a small number of proven, cost-effective interventions such as skilled birth attendants, immunizations, mosquito nets and oral rehydration therapy.



"We know what works, why it works and how to do it," says Jenkins. "What we need to do now is to mobilize the necessary political will to put mothers, children, their families and communities front and centre of global development."



"Otherwise, too many children born today into poor, under-served communities won't survive the five years to the 2015 deadline, simply because they and their families don't have access to basic health services," said Jenkins.



A PDF of the report and multimedia resources (PSA on malnutrition, VNR and b-roll) are available here.



Source:

Geraldine Ryerson-Cruz

World Vision