Antioxidants and retinal degeneration

Antioxidants may slow vision loss

Scientists at Johns Hopkins have successfully blocked the advance of retinal degeneration in mice with a form of retinitis pigmentosa (RP) by treating them with vitamin E, alpha-lipoic acid and other antioxidant chemicals.

"Much more work needs to be done to determine if what we did in mice will work in humans," said Peter Campochiaro, the Eccles Professor of Ophthalmology and Neuroscience at The Johns Hopkins University School of Medicine. "But these findings have helped to solve a mystery."

In patients with RP, rod photoreceptors die from a mutation, but it has not been known why cone photoreceptors die. After rods die, the level of oxygen in the retina goes up, and this work shows that it is the high oxygen that gradually kills the cones. Oxygen damage is also called "oxidative damage" and can be reduced by antioxidants. So for the first time, scientists have a treatment target in patients with RP, added Campochiaro. His team's findings appeared in the July online edition of the Proceedings of the National Academy of Sciences.

Retinas in all mammals, from mouse to man, are made up of light-sensitive cells known as cones and rods, named for their shapes, which convert light into nerve signals that are then transmitted to the brain via the optic nerve. Cones are needed to see colors and make vision possible in bright light, whereas the far more numerous rods permit sight in low light. The human retina contains approximately 125 million rod cells and six million cone cells. In diseases like RP and age-related macular degeneration (AMD), these cells die off and eventually lead to blindness (in the case of RP) or legal blindness (in the case of AMD).

In earlier studies exposing mice to pure oxygen, the Hopkins scientists found that high levels of oxygen in the retina killed both rods and cones, said Campochiaro. "This was the clue that the high oxygen levels that occur naturally in the retina after rods die was the suspect regarding cone cell death. To test this, we used antioxidants, which protect cells from oxygen damage, and since they allowed many more cones to survive, it proves that the suspect is guilty."

In this mouse model of retinal degeneration, the rods have completely degenerated by the 18th day of age, and then the cones start to degenerate, with 85 percent of them dying off by the time the mice are 35 days old. Campochiaro and his team injected vitamin E, vitamin C, alpha-lipoic acid or an antioxidant similar to superoxide dismutase between the 18th and 35th day. In mice that received vitamin E or alpha-lipoic acid, 40 percent of the cones survived, about twice as many as in the control group or the groups treated with the other antioxidants, which had no identifiable effect.

"What's clear is the link between oxygen and photoreceptor damage, as well as the potential of antioxidant treatment," Campochiaro said. "These experiments suggest that an optimized regimen of antioxidants may help to protect patients with retinitis pigmentosa."

Campochiaro emphasized that even if found valuable, antioxidant treatment of RP, a group of inherited blinding diseases with complex genetic roots, would not cure the disease. But the salvaging of cones, which are concentrated in the retina's macula and are critical to central vision, could serve as a "maintenance therapy," he said. "That alone would be an enormous help."

RP affects only about 100,000 people in the United States. But the oxygen damage has also been implicated in other more pervasive eye diseases, like AMD and cataracts.

Antioxidants naturally occur in some fruits and vegetables, and are available as supplements, but Campochiaro said it remains unclear whether the amounts of antioxidants consumed in foods provided any benefit to people with these types of vision impairments.

Johns Hopkins Medical Institutions
http://www.brightsurf.com/news/

Posttraumatic Stress Disorder and Pregnancy Health

Posttraumatic Stress Disorder and Pregnancy Health: Preliminary Update and Implications

Leslie Morland, Psy.D., Deborah Goebert, D.P.H., Jane Onoye, Ph.D., LeighAnn Frattarelli, M.D., Chris Derauf, M.D., Mark Herbst, M.D., Courtenay Matsu, M.D., and Matthew Friedman, M.D., Ph.D.
From the Dept. of Psychiatry, John A. Burns School of Medicine, Univ. of Hawaii; the National Center for PTSD, Pacific Island Division, VA Pacific Island Healthcare System; the Dept. of Obstetrics, Gynecology, and Women’s Health, John A. Burns School of Medicine, Univ. of Hawaii; the Dept. of Pediatrics, John A. Burns School of Medicine, Univ. of Hawaii, and the National Center for PTSD, Executive Division, White River Junction, VT.

Posttraumatic stress disorder (PTSD) is pervasive among women of childbearing age.

The cascade of behavioral health and neuroendocrine changes commonly associated with PTSD may adversely affect perinatal health.

The authors examined the relationship between PTSD and perinatal health in a sample of 101 women seeking prenatal care on the island of Oahu, Hawaii.

Trauma, PTSD, and psychological and behavioral health were assessed during prenatal care. Pregnancy health, labor and delivery information, and birth outcomes were abstracted from medical records post-partum.

Findings suggest that women with PTSD entering pregnancy are at increased risk for engaging in high-risk health behaviors, such as smoking, alcohol consumption, substance use, poor prenatal care, and excessive weight gain.

Authors discuss clinical and research implications. Full Text

Psychosomatics 48:304-308, August 2007

© 2007 Academy of Psychosomatic Medicine

Green tea protected cancerous bladder cells

Green tea may protect the bladder from becoming inflamed

Herbal agents could be used to treat inflammatory bladder diseases, according to a preliminary study that looked at the ability of green tea to protect bladder cells from inflammation. The University of Pittsburgh School of Medicine study, being presented at the annual meeting of the American Urological Association (AUA) in Anaheim, Calif., found that components of green tea protected bladder cells from damage in culture. The study is Abstract 299 in the AUA proceedings.

Green tea, reported to have many health benefits, is rich in powerful antioxidants that make it a possible remedy for many medical conditions. It is comprised of catechins - plant metabolites that provide it with many anti-oxidative properties.

"We discovered that catechins found in green tea protected both normal and cancerous bladder cells from inflammation when we exposed the cells to hydrogen peroxide," said Michael B. Chancellor, M.D., professor of urology and gynecology at the University of Pittsburgh School of Medicine. "Although further studies are needed, these results indicate herbal supplements from green tea could be a treatment option for various bladder conditions that are caused by injury or inflammation."

In the study, normal and cancerous bladder cells were exposed to two major catechin components of green tea, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), for 23 hours. Both significantly protected cell lines from exposure to hydrogen peroxide, which damages or kills cells. The concentrations of EGCG and ECG used in the study were at levels that may be achieved through dietary intake.

University of Pittsburgh Schools of the Health Sciences
http://www.brightsurf.com/news/

Green tea: Protect against autoimmune disease

Green tea may help prevent autoimmune diseases

Green tea may help protect against autoimmune disease, Medical College of Georgia researchers say.

Researchers studied an animal model for type I diabetes and primary Sjogren's Syndrome, which damages the glands that produce tears and saliva.

They found significantly less salivary gland damage in a group treated with green tea extract, suggesting a reduction of the Sjogren's symptom commonly referred to as dry mouth. Dry mouth can also be caused by certain drugs, radiation and other diseases.

Approximately 30 percent of elderly Americans suffer from degrees of dry mouth, says Dr. Stephen Hsu, a researcher in the MCG School of Dentistry and lead investigator on the study. Only 5 percent of the elderly in China, where green tea is widely consumed, suffer from the problem.

"Since it is an autoimmune disease, Sjogren's Syndrome causes the body to attack itself and produce extra antibodies that mistakenly target the salivary and lacrimal glands," he says.

There is no cure or prevention for Sjogren's Syndrome.

Researchers studied the salivary glands of the water-consuming group and a green tea extract-consuming group to look for inflammation and the number of lymphocytes, a type of white blood cells that gather at sites of inflammation to fend off foreign cells.

The group treated with green tea had significantly fewer lymphocytes, Dr. Hsu says. Their blood also showed lower levels of autoantibodies, protein weapons produced when the immune system attacks itself, he says.

Researchers already know that one component of green tea - EGCG - helps suppress inflammation, according to Dr. Hsu.

"So, we suspected that green tea would suppress the inflammatory response of this disease. Those treated with the green tea extract beginning at three weeks, showed significantly less damage to those glands over time."

These results, published in a recent issue of Autoimmunity, reinforced findings of a 2005 study showing a similar phenomenon in a Petrie dish, Dr. Hsu says.

Researchers also suspect that the EGCG in green tea can turn on the body's defense system against TNF-alpha - a group of proteins and molecules involved in systemic inflammation.

TNF-alpha, which is produced by white blood cells, can reach out to target and kill cells.

"The salivary gland cells treated with EGCG had much fewer signs of cell death caused by TNF-alpha," Dr. Hsu says. "We don't yet know exactly how EGCG makes that happen. That will require further study. In some ways, this study gives us more questions than answers."

Further study could help determine green tea's protective role in other autoimmune diseases, including lupus, psoriasis, scleroderma and rheumatoid arthritis, he says.

Medical College of Georgia
http://www.brightsurf.com/news/

SIDS: association with lethal arrhythmias

Heart rhythm genes possible factors in SIDS

Nearly 10 percent of sudden infant death syndrome (SIDS) victims have mutations or variations in genes associated with potentially lethal heart rhythms (arrhythmias), according to two newly published studies involving Vanderbilt researchers.

The findings indicate that arrhythmia-susceptibility genes represent important genetic contributors to SIDS, said Alfred L. George Jr., M.D., senior author on one of the studies. The studies appear in the early online edition of the journal Circulation.

According to the Centers for Disease Control and Prevention, approximately 2,200 deaths each year in the United States are attributed to SIDS, making it the third leading cause of death among all infants, but the leading cause of mortality in infants age 1 month to 1 year. Several behavioral and environmental factors - such as prone (stomach) sleeping position and exposure to cigarette smoke - are known risk factors. Campaigns to educate parents about these potential dangers may explain the decrease in SIDS since the early 1990s.

However, SIDS continues to be a leading cause of infant mortality in developed countries, and the underlying basis of the condition remains unclear. A popular theory proposes that SIDS occurs because of a combination of risks including abnormal physiological state, environmental factors and developmental vulnerabilities. Genetic factors have also been proposed to be important.

"SIDS is not one disease," said George, the Grant W. Liddle Professor of Medicine and director of the Division of Genetic Medicine. "Multiple conditions can increase the risk of sudden death in an infant. Some have been identified, but many have not."

Anecdotal evidence previously suggested that some SIDS victims carry mutations in genes associated with conditions such as the long QT syndrome (LQTS) that predispose individuals to life-threatening arrhythmias and sudden death. But the proportion of SIDS cases that carry such mutations was not clear.

George's collaborators, Peter Schwartz, M.D., in Italy, and Torleiv Rognum, M.D., Ph.D., in Norway, led the efforts to screen seven arrhythmia-associated genes in 201 SIDS cases from Norway - the largest ever genetic survey of a SIDS cohort. The results showed that 9.5 percent of SIDS victims harbored mutations in genes associated with inherited forms of cardiac arrhythmia, such as LQTS.

The researchers identified mutations and variations in several genes, including the gene that encodes the cardiac sodium channel - a protein that regulates the electrical properties of heart cells. George's lab then performed studies to understand the physiological consequences of mutations in the cardiac sodium channel gene, called SCN5A, which has previously been associated with LQTS and several other conditions that cause unstable heart rhythms and sudden death.

"We observed a pattern of SCN5A dysfunction that is reminiscent of what's been observed in LQTS. That gives us confidence that the mutations observed in SIDS victims are not benign genetic variants - but rather could increase the risk of potentially lethal arrhythmias," he said. The researchers have similar evidence, to be published separately, demonstrating that mutations in heart potassium channels are also contributing factors in SIDS.

The findings also suggest that there may be strategies to identify whether infants are a carrier of one of these mutations before the tragic event of their death, George said.

"We are not recommending that a population-wide genetic screening be done, but there may be simpler, cost-effective measures that should be investigated further, perhaps performing ECG (electrocardiogram) screening of infants, although this idea is controversial."

Inherited arrhythmias are manageable conditions that can be treated with medications or implantable devices, George said.

"There's potentially an infant death every other day in the U.S. due to this problem (arrhythmias)," he said. "Exactly how best to identify this risk and prevent arrhythmia-related death during infancy needs to be determined."

George and colleagues are continuing to analyze other arrhythmia-linked genes identified in the Norwegian SIDS cohort. They are also planning studies to determine if the parents of SIDS victims carry the same mutations.

"This is critical because knowing how often mutations are transmitted from parents rather than occur spontaneously, will help establish the risk to siblings of SIDS victims," he said.

George hopes that eventually, all of the causes of SIDS - environmental, developmental and genetic factors - will be identified.

"Many years from now, 'SIDS' may not be a term we use anymore because we will understand all causes of sudden infant death," George said. "But right now, SIDS is a bona fide disease category, and we should strive to understand it fully."

Vanderbilt University Medical Center
http://www.brightsurf.com/news/