Medicine Man

Women who receive a diagnosis of diabetes before they become pregnant are three to four times more likely to have a child with one or even multiple birth defects than a mother who receives a diagnosis of diabetes while pregnant or a mother who is not diabetic, according to a study by the Centers for Disease Control and Prevention (CDC), released in the American Journal of Obstetrics and Gynecology.

The article from the National Birth Defects Prevention Study (NBDPS), "Diabetes Mellitus and Birth Defects," shows that pregnant women with pre-gestational diabetes mellitus (pre-pregnancy diagnosis of diabetes, such as type 1 or type 2 diabetes) are more likely than a mother with no diabetes or a mother with gestational diabetes mellitus (pregnancy-induced diabetes) to have a child with various types of individual or multiple birth defects. This includes heart defects, defects of the brain and spine, oral clefts, defects of the kidneys and gastrointestinal tract and limb deficiencies. This study is the first to show the broad range and severity of birth defects associated with type 1 and type 2 diabetes.

"The continued association of diabetes with a number of birth defects highlights the importance of increasing the number of women who receive the best possible preconception care, especially for those women diagnosed with diabetes," says Adolfo Correa, M.D., M.P.H., Ph.D., lead author and epidemiologist at CDC's National Center on Birth Defects and Developmental Disabilities. "Early and effective management of diabetes for pregnant women is critical in helping to not only prevent birth defects, but also to reduce the risk for other health complications for them and their children."

Researchers also found that some of the pregnant women with gestational diabetes were more likely to have a child with birth defects. Because birth defects associated with diabetes are more likely to occur during the first trimester of pregnancy and before a diagnosis of gestational diabetes is made, the observed associations suggest that some of the mothers with it probably had undiagnosed diabetes before they became pregnant. However symptoms went unnoticed until pregnancy.

Further, the associations of gestational diabetes with various birth defects were noted primarily among women who had pre-pregnancy obesity, which is a known risk factor for both diabetes and birth defects. Preconception care also should be considered and promoted for women with pre-pregnancy obesity to prevent birth defects and reduce the risk for health complications.

The NBDPS is a population-based, case-control study that incorporates data from nine birth defect centers in the United States -- Arkansas, California, Georgia, Iowa, Massachusetts, New York, North Carolina, Texas and Utah. These centers have been working on the largest study of birth defects causes ever undertaken in the United States. Researchers have gathered information from more than 30,000 participants and are using this information to look at key questions on potential causes of birth defects.

Birth defects affect one in 33 infants and are a leading cause of infant mortality. For some birth defects, some risk factors or causes have been identified; however, for the majority of birth defects the causes remain unknown.

In the United States, the prevalence of gestational diabetes has been increasing in recent years and currently affects about seven percent of all pregnancies, resulting in more than 200,000 cases annually. While it is usually resolved shortly after delivery, women who have had gestational diabetes are at increased risk of developing type 2 diabetes in the future.

http://www.cdc.gov

After weeks of bed rest during pregnancy, new mothers need to rebuild muscles and strengthen their stamina. Now a group of women will test new interventions in aiding that recovery during a pilot study at Case Western Reserve University's Frances Payne Bolton School of Nursing.

"Putting people in bed is not a benign kind of thing," says Judith Maloni, a professor of nursing at the Bolton School. She has been studying the effects of bed rest for nearly two decades and aerospace research studies conducted by NASA have shown that bed rest changes every major organ system in the body and its function.

During her study, "Rebound: A Self-Management Intervention for Recovery from Ante-partum Bed Rest," Maloni will test a set of exercises and educational programs that help women learn to manage their recovery after both bed rest and birth.

The study is supported by the Bolton School's Center for Excellence for Self-Management Advancement through Research and Translation (SMART). It is among four projects the center is piloting to learn more about teaching individuals how to manage their own health care.

Nearly 1 million pregnant women annually are sent to bed near the end of their pregnancies to prevent preterm labor, premature rupture of membranes, placenta previa, incompetent cervix or placental abruption.

According to Maloni, many women leave the hospital and cannot understand why they suffer back problems and muscle aches and are fatigued while other new mothers seem to bounce back after giving birth.

Maloni said she would like bed-rest moms to understand that what they are experiencing is normal for women who have been on bed rest.

They may need physical therapy and other interventions to regain the strength to do normal activities like taking care of other children, doing household tasks or participating in activities in the community or with friends, said Maloni.

Following delivery, these women must overcome the long-term effects of bed rest. Other research has found these effects can be bone loss; decreases in body mass, fluid loss and plasma; depression; and muscle weakness.

Maloni will recruit 80 women who have had good physical and mental health and had at least 21 days or more of bed rest prior to their baby's birth.

These women will be evaluated two days into the study with follow-ups after two months and three months. At the end of testing, Maloni will offer the new intervention to the women in the control group.

The new intervention is a set of cardiovascular and strength exercises developed for the elderly, who, like new mothers, may be in a state of physical deterioration.

Women in this group will be tested for their physical capabilities during a six-minute walk, 30 seconds of sit-stands and two minutes of stepping in place.

In a prior study on the ability of bed-rest mothers to function after childbirth, Maloni reported that women who were given the exercises from the Rikkli Jones Senior Fitness Test walked an average of 217 feet in 4.8 minutes. This was the same level of performance as women in the 70-75 age group.

Maloni has studied the postpartum conditions of bed-rest moms until six weeks and found that many of them are still fatigued. By following the women to the third month, she hopes to discover if longer intervention is need to help women regain lost strength and stamina.

http://www.case.edu/

A London, Canada scientist studying cystic fibrosis (CF) has successfully corrected the defect which causes the overproduction of intestinal mucous in mice.

This discovery by Dr. Richard Rozmahel, a scientist with the Lawson Health Research Institute, affiliated with The University of Western Ontario, has clear implications to understanding and treating this facet of the disease in humans. CF is a fatal, genetic disease characterized by an overproduction of mucous in the lungs and digestive system.

Rozmahel and his colleagues are identifying secondary genes that could contribute to CF, and measuring their impact on the disease. More specifically, they are investigating the potential of a gene found in mice, mCLCA3, which is similar to one in humans that exhibits abnormal levels in CF. The mCLCA3 gene is expressed by cells that produce and secrete mucous.

The researchers discovered that mCLCA3 plays an important role in the property of mucous, thereby allowing it to be cleared rather than result in the blockages that underlie CF. By correcting the abnormal levels of mCLCA3 in CF mice they were able to overcome the mucous lesions. Whereas CF mice normally do not survive more than 4 weeks as a consequence of the mucous disease, the animals where mCLCA3 levels were corrected could live a normal lifespan.

"It's my hope to understand what is causing the exaggerated mucous production and secretion in CF patients," says Dr. Rozmahel. "From there, we can figure out ways to correct it."

Rozmahel is a Lawson scientist at the Children's Health Research Institute and the London Regional Cancer Program at the London Health Sciences Centre. He's also an associate professor of Biochemistry, Pediatrics and Oncology at the Schulich School of Medicine & Dentistry at The University of Western Ontario.

CF is a chronic inherited disease affecting 70,000 children and adults worldwide. In the late 1930's, CF was usually recognized only after a child had died, often as a result of malnutrition or pneumonia. Medical awareness of CF has increased tremendously over the years, and doctors are now able to diagnose most patients within the first year of life. Thanks to advances in research and clinical care, growing numbers of children with CF are surviving into adulthood, compared to the 1960's, when most patients died by age four. Now the median age of survival is 37 years.

http://www.uwo.ca

Estrogen treatments may sharpen mental performance in women with certain medical conditions, but University of Florida researchers suggest that recharging a naturally occurring estrogen receptor in the brain may also clear cognitive cobwebs.

The discovery suggests that drugs can be developed to offset "senior moments" related to low estrogen levels, as well as to protect against neurological diseases, all while avoiding the problems associated with adding estrogen to the body.

Writing online in Molecular Therapy in July, scientists with UF's McKnight Brain Institute describe how they improved thought processes in female mice bred with the inability to produce estrogen receptor-alpha, a protein apparently necessary for healthy learning and memory.

"We were able to restore function in these animals, not by dosing them with estrogen, but by enabling them to use the estrogen that was naturally present in their bodies," said Tom Foster, Ph.D., the Evelyn F. McKnight chair for brain research in memory loss at the UF College of Medicine. "We discovered that you can affect the estrogen receptor directly in the hippocampus, right where it's needed to address memory and spatial learning."

Changes in the estrogen receptor have been associated with age-related memory deficits and an increased incidence of Alzheimer's disease among women. In addition, previous studies have shown estrogen replacement may improve cognition in postmenopausal women and younger women with low estrogen levels. Estrogen also appears to protect against Alzheimer's disease and dementia.

The downside is that estrogen is a powerful hormone that has far-reaching effects throughout the body. It has been associated with a slight increase in women's risk for breast cancer, heart disease in patients with existing cardiovascular problems, and stroke.

"Estrogen may act as a growth agent for cancer, but in the brain, it appears to maintain health and counteract stress," Foster said. "We wanted to come back and enhance the signaling pathway that makes estrogen functional. We used a gene therapy technique that enables us to target the brain, but ultimately there could be a pharmaceutical that enhances the signaling pathway solely in the brain."

The mice had unusually low levels of estrogen because their ovaries were removed at an early age. However, scientists were still able to rescue learning ability by delivering the correct gene to produce estrogen receptor-alpha directly to the hippocampus.

Mice that lacked the estrogen receptor showed poor ability to locate a platform hidden in a small swimming tank over a training period of several days. After receiving the gene, the mice learned to locate the platform in two days of training.

"This research shows that when the estrogen receptor-alpha is restored to adult mice that have been missing it their entire lives, it is still possible to enhance memory and learning," said John H. Morrison, Ph.D., dean of basic sciences and the Graduate School of Biological Sciences at Mount Sinai School of Medicine, who did not participate in the research. "This is good news for moving forward to develop clinical interventions and therapeutics because it appears critical damage was not done to brain circuitry during early development. There has also been debate about which of at least two estrogen receptors is key to synaptic health. Clearly estrogen receptor-alpha plays a critically important role in hippocampal organization and function."

Recordings made from the brain tissue of treated mice showed signals were strongly communicated across the gaps, or synapses, between hippocampal cells, similar to what would happen with estrogen replacement.

"Investigating the impact of genetically replacing the estrogen receptor at the cellular, synaptic and behavioral levels is a scientific tour de force which provides a strong foundation for the role of estrogen receptor alpha in mediating estrogen action in the hippocampus to restore select types of memory function," said Roberta Diaz Brinton, Ph.D., a professor of pharmacology and pharmaceutical sciences and biomedical engineering at the University of Southern California, who was not involved in the study. "From a technology perspective, their technique to transfect the estrogen receptor is an exciting advance for researching steroid receptors in the brain."

Studying the effects of increasing the estrogen receptor in other brain regions may shed additional light on memory processes.

"The research brings up the idea that local activation of non-nuclear estrogen receptor-alpha is important for regulating memory processes in the hippocampus," said Teresa A. Milner, Ph.D., a professor of neuroscience at Weill Cornell Medical College, who also was also not involved in the research.

http://www.ufl.edu/

While scientists and physicians know what happens if you don't get six to eight hours of shut-eye a night, investigators have long been puzzled about what controls the actual need for sleep.

Researchers at the University of Pennsylvania School of Medicine might have an answer, at least in fruit flies. In a recent study of fruit flies, they identified a gene that controls sleep.

"We spend -- or should spend -- a third of our lives sleeping," says Amita Sehgal, PhD, Professor of Neuroscience and an Investigator with the Howard Hughes Medical Institute (HHMI). "The idea that so much time is spent in sleep is intriguing. Also, sleep deprivation has serious health consequences and impairs cognitive function."

This study was published in the latest Science.

Fruit flies typically sleep 12 hours a day. Sehgal and her team studied 3,500 fruit flies and found mutants that survived on little to no sleep - one to two hours a day or none at all. The sleepless flies had a mutation of a gene that Sehgal and her team have named Sleepless. They believe the Sleepless gene encodes a protein that affects whether potassium ion channels in the brain stay open or closed. When the channels are open, the brain is connected and working - the fly is awake. When closed, the channel shuts down and the fly sleeps. The insomniac fruit flies had less of the Sleepless-produced protein.

The lack of sleep didn't come without consequences. The Sleepless fruit flies lived about half as long as fruit flies that did not carry the mutation. They also experience impaired coordination and restlessness in their few hours of sleep.

Sleep is regulated by two processes: circadian and homeostatic. Circadian regulation affects the timing of sleep, and the homeostatic mechanism affects the need for sleep. The Sleepless gene affects the homeostatic mechanism.

Sleep isn't just for humans - it's been observed in everything from flies to dogs to people, indicating that it's essential to life. Insufficient and poor-quality sleep is an increasing problem in industrialized nations. In the U.S. alone, about 70 million people suffer from chronic sleep problems, which reduce workplace productivity, affect quality of life and can even be lethal.

"In the long term, we hope that human equivalents of our gene will be isolated and will not only further our understanding of human sleep, but perhaps also serve as drug targets to promote sleep or treat insomnia," says Sehgal.

http://www.med.upenn.edu/