Category: Steroids

Brain activity has been compared to a light bulb turning on in the head. Scientists at Washington University School of Medicine in St. Louis have reversed this notion, creating a drug that stops brain activity when a light shines on it.

The unexpected result, reported online in Nature Neuroscience, turned several lights on in researchers' heads.

"This is daydreaming at this point, but we might one day combine this drug with a small implanted light to stop seizures," says senior author Steven Mennerick, Ph.D. associate professor of psychiatry and of anatomy and neurobiology. "Some current experimental epilepsy treatments involve the implanting of an electrode, so why not a light?"

The new compound activates the same receptor used by many anesthetics and tranquilizers, making it harder for a brain cell to respond to stimulation. Mennerick and colleagues including lead author Larry Eisenman, M.D., Ph.D., assistant professor of neurology, tested the drug on cells in culture set up to behave like they were involved in a seizure, with the cells rapidly and repeatedly firing. When they added the new drug and shone a light on the cells, the seizure-like firing pattern calmed.

If the drug is adapted for epilepsy, Mennerick notes, it is most likely to help in cases where seizures consistently originate from the same brain region. Theoretically, doctors could keep a patient on regular doses of the new drug and implant a small fiber optic light in the dysfunctional region. The light would activate the drug only when seizure-like firing patterns started to appear.

Scientists in the laboratory of Douglas F. Covey, Ph.D., professor of molecular biology and pharmacology, created the drug by linking a steroid known to have anesthetic effects with a molecule, known as NBD, that fluoresces in response to blue light. Mennerick and colleagues were hoping to use the new compound, which they call the NBD-steroid, to trace the steroid's path in the nervous system.

To their initial disappointment, the researchers found that adding the fluorescent tag to the steroid had disabled it.

"Normally, the steroid keeps the cell quiet in the face of stimuli that would otherwise cause it to fire," Mennerick says. "That's why drugs like barbiturates and Valium, which act on the same receptor as the steroid, are sedatives–they quiet the nerve system down."

When dosed with NBD-steroid, nerve cells still responded to stimuli as readily as they had prior to exposure. Just to see where the modified steroid was going, though, researchers exposed the cells to light.

"All of a sudden, the response to the steroid was back, and the nerve cells were more reluctant to react to stimuli," Mennerick says. "And we knew we had found something very interesting."

To confirm what was happening, scientists dosed two of a nerve cell's many different branches with NBD-steroid. When they shone a light on one of the branches, its readiness to respond decreased, while the readiness of the branch not exposed to light remained the same.

Department of Anesthesiology colleagues tested the compound's effects on tadpoles.

"Tadpoles rapidly take up drugs through their skin, so they're frequently used to test potential anesthetics," Mennerick notes. "And of course, given that it's a photoactive drug, they make a nice test subject because they're mostly translucent."

Tadpoles swimming in a solution of NBD-steroid went to sleep at the bottom of their beaker when exposed to light.

Mennerick and his colleagues are currently seeking to identify or create an animal model of epilepsy that lets them test the NBD-steroid's potential as a therapeutic.

They are also looking for a new fluorescent tag that responds to longer wavelengths of light. Unlike many photoactive compounds, the NBD-steroid responds not to ultraviolet light but to light from the blue region of the electromagnetic spectrum. This helps because the longer wavelengths of blue light penetrate farther into tissue than ultraviolet light and are less damaging to it. Molecules that fluoresce in response to even longer wavelengths of light are available, and scientists are testing whether any of them can create the same effect when bound to the steroid.

Reference: Eisenman LN, Shu H-J, Akk G, Wang C, Manion BD, Kress GJ, Evers AS, Steinbach JH, Covey DF, Zorumski CF, Mennerick S. Anticonvulsant and anesthetic effects of a fluorescent neurosteroid analog activated by visible light. Nature Neuroscience, Feb. 25, 2007.

Funding from the Bantly Foundation and the National Institutes of Health supported this research.

NewsPsychology (Mar. 6, 2007) — A guideline developed by the American Academy of Neurology finds epidural steroid injections play a limited role in providing short-term pain relief for lower back pain that radiates down a leg, and do not provide long-term pain relief. The guideline is published in the March 6, 2007, issue of Neurology®, the scientific journal of the American Academy of Neurology.

To develop the guideline, the authors analyzed scientific studies on the topic.

According to the guideline, epidural steroid injections may provide some short-term pain relief between two and six weeks after injection, but the average amount of relief is small.

“While some pain relief is a positive result in and of itself, the extent of leg and back pain relief from epidural steroid injections, on the average, fell short of the values typically viewed as clinically meaningful,” said lead author Carmel Armon, MD, MHS, Chief, Division of Neurology, with Baystate Medical Center in Springfield, Massachusetts, and Professor of Neurology at Tufts University School of Medicine in Boston, Massachusetts. Armon is also a Fellow member of the American Academy of Neurology.

The guideline also found epidural steroid injections usually did not help patients “buy time” to avoid surgery, or provide long-term pain relief beyond three months. Their routine use for these purposes is not recommended.

“The use of epidural steroid injections to treat chronic back pain is increasing over time despite limited quality data,” said Armon. “Recent figures show 1999 Medicare Part B claims for lumbar epidural steroid injections were $49.9 million, for 40.4 million covered individuals.”

In addition, the authors also found insufficient evidence to use epidural steroid injections to treat radicular cervical pain, or neck pain.

Armon says the review was limited by the small number of high-quality scientific studies on epidural steroid injections, and further well-designed studies are needed to determine their effectiveness.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by American Academy of Neurology.

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NewsPsychology (Feb. 7, 2007) — Interrupting nerve signals to the liver can prevent diabetes and hypertension in mice, according to scientists at Washington University School of Medicine in St. Louis. The finding is reported in the February issue of the journal Cell Metabolism.

The research team surgically removed the vagus nerve in mice and found the procedure prevented or reversed the development of insulin resistance and high blood pressure in mice primed to develop these disorders through treatment with glucocorticoids.

“So at least in mice, we’ve shown we can prevent the development of diabetes and hypertension by interrupting vagal nerve signaling,” says senior investigator Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology. “We don’t know whether the same will hold true for humans, but we think somehow altering vagal nerve activity could provide a novel approach for treating these common metabolic disorders.”

Previously, the research team had shown that a nuclear receptor called PPAR-alpha (Ppara) was necessary for the induction of both diabetes and hypertension when mice were treated with glucocorticoids, also known as steroids.

“Mice that can’t make Ppara don’t develop diabetes or hypertension in response to glucocorticoids,” says Semenkovich, who also is chief of the Division of Endocrinology, Metabolism and Lipid Research. “The use of steroids is very common in medicine. People with asthma, arthritis, organ transplants and others rely on those steroid drugs, and many of them go on to develop insulin resistance that can advance to diabetes and hypertension.”

But in these most recent experiments, the researchers showed that both Ppara and the vagus nerve seem to play important roles in the development of these disorders.

“If the vagus nerve has been surgically removed, the mice won’t develop diabetes or hypertension in response to glucocorticoids, even if they have Ppara,” says first author Carlos Bernal-Mizrachi, M.D., an assistant professor of medicine in the Division of Endocrinology, Metabolism and Lipid Research. “The process seems to be mediated by communication between the liver cells, the liver branch of the vagus nerve and its signals to the brain.”

Actually, the vagus nerve communicates with just about everything. Its name is taken from the Latin word meaning “wanderer.” Early neuroanatomists chose the name because it seemed whenever they looked at an organ in the body, they also found fibers from the vagus. It extends from the base of the brain, through the chest where it innervates part of the heart. It also sends nerve signals to other internal organs, including the liver, and eventually connects to the intestine. In these studies, however, the researchers were interested mainly in the connection between the vagus nerve coming from the liver and its communication with the brain.

When mice are treated with glucocorticoids, Ppara in the liver communicates with the vagus nerve, which signals the brain. Then the brain uses the vagal pathway to feed back instructions to the liver and kidneys. The brain instructs the liver to increase glucose production and the kidney to alter fluid metabolism, elevating blood pressure.

The same sort of process can occur in people who are obese. Semenkovich says a modest elevation of glucocorticoids is associated with obesity. Those elevated levels can initiate Ppara activity in the liver, which then will communicate with the vagus nerve to signal the brain and, in turn the brain will signal the liver and kidneys, contributing to diabetes and hypertension.

“We think obesity is probably initiating a similar process to the one we’ve interrupted in the mice,” says Semenkovich. “An environmental influence — such as treatment with glucocorticoids or excess caloric intake that causes obesity — engenders a signal started by Ppara, which then is transmitted from the liver, along the vagus nerve.”

That cascade of communication along the vagal nerve pathway has made the investigators think that they may be able to help people with diabetes and hypertension by interrupting normal vagal signaling. And there may be a ready-made population to study because many people already have surgically implanted devices that alter the signaling of the vagus nerve.

Some people with seizure disorders and treatment-resistant depression already have implanted electrodes that stimulate the vagus nerve to help alleviate their symptoms. Semenkovich believes the new mouse study suggests a similar approach might help people with insulin resistance or hypertension. They plan to follow patients who already have stimulators to see if signals from the stimulators affect susceptibility to diabetes, insulin resistance or hypertension.

“We used surgery to interrupt all signaling from the vagal nerve pathway,” Bernal-Mizrachi says. “But it might actually be possible to change very specific signaling patterns to provide benefit to people who are at risk for hypertension or diabetes.”

Some available drugs might be able to attack the problem in other ways. A class of medications called fibrate drugs can modulate the activity of Ppara. Those drugs are used to lower triglycerides and to elevate levels of HDL (good) cholesterol. Some studies have indicated the drugs provide a modest benefit, but other studies have suggested that such drugs might be harmful. So for now, the researchers are focusing more on the potential of the vagus nerve.

“I would argue that you can clearly produce a major impact by stimulating this nerve because it carries signals to so many organs,” Semenkovich says. “We know the vagal pathway can influence seizures, depression and other disorders. This study suggests it affects diabetes and hypertension, too.”

Bernal-Mizrachi C, Xiaozhong L, Yin L, Knutsen RH, Howard MJ, Arends JJA, DeSantis P, Coleman T, Semenkovich CF. An afferent vagal nerve pathway links hepatic PPAR? activation to glucocorticoid-induced insulin resistance and hypertension. Cell Metabolism, vol. 5:2, pp. 91-102, Feb. 2007 DOI 10.1016/j.cmet.2006.12.010

This work was funded by grants from the National Institutes of Health and by an American Diabetes Association mentor-based postdoctoral fellowship.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Washington University School of Medicine.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

NewsPsychology (Nov. 8, 2006) — Stanford University neuroscientists have designed a gene that enhances memory and learning ability in animals under stress. Writing in the Nov. 8 issue of the Journal of Neuroscience, the Stanford team says that the experimental technique might one day lead to new forms of gene therapy that can reduce the severe neurological side effects of steroids, which are prescribed to millions of patients with arthritis, asthma and other illnesses.

“Steroids can mess up the part of the brain involved in judgment and cognition,” said neuroendocrinologist Robert Sapolsky, co-author of the study. “In extreme cases it’s called steroid dementia. Ideally, if you could deliver this gene safely, it would protect the person from some of these cognitive side effects, while allowing the steroid to do whatever helpful thing it should be doing elsewhere in the body.”

Sapolsky, the John A. and Cynthia Fry Gunn Professor of Biological Sciences and a professor of neurology and neurological sciences at Stanford, has conducted numerous experiments on the damaging physiological effects of stress and has written extensively on the subject, including a 1995 book, “Why Zebras Don’t Get Ulcers.”

Hormonal effects

In the Journal of Neuroscience study, Sapolsky and his colleagues focused on the effect of stress on the hippocampus, a part of the brain that’s important for learning and memory. Nerve cells throughout the hippocampus contain numerous receptors that respond to a group of steroid hormone called glucocorticoids, which are secreted from the adrenal glands in male and female rats during times of stress. When high levels of these corticoids bind to the hippocampal receptors, they can trigger a destructive biochemical cascade that damages nerve cells in the hippocampus and ultimately impairs memory and learning.

But not all hormones are bad. Estrogen, the primary female sex hormone, enhances memory and can therefore block the negative cognitive effects of the corticoids.

“Estrogen protects memory against stress,” said former Stanford postdoctoral fellow Andrea Nicholas, lead author of the study, who was recently named an adjunct professor at St. Mary’s College. “In women, there are long-term protective effects of estrogen in the brain. As people age, females often fare better than males cognitively, in part because they have that estrogenic protection.”

In a 2004 study, Sapolsky and his co-workers showed that gene therapy could be used to neutralize the deleterious effects of stress in laboratory rats. The idea behind gene therapy is eventually to cure a disease or repair an injury by injecting a beneficial gene into the patient’s DNA. For the experiment, Sapolsky and his team created what geneticists call a chimera–an experimental strand of DNA made with two genes stitched together, in this case a glucocorticoid-receptor gene from a rat combined with an estrogen-receptor gene from a human.

When this new chimeric gene was injected into the hippocampus of a rat, the result was dramatic. The gene produced new protein receptors that quickly converted stress-inducing glucocorticoids into beneficial estrogen signals.

“That experiment showed that gene therapy works at the molecular level,” Nicholas said. “We then wanted to see if the chimeric gene would actually alter the behavioral effects that we know stress hormones cause in live rats.”

Water maze

To find out, Nicholas and her colleagues set up a Morris Water Maze experiment, a procedure widely used by neuroscientists to test spatial memory in rats. The maze consists of a round pool about 5 feet wide and filled with about 2 feet of water. A hidden platform is placed just below the surface. When an untrained rat is released into the pool, it swims around looking for an exit, until it finally discovers the platform and climbs out of the water.

“When the animals first go in, they’re pretty clueless,” Nicholas said. “It usually takes them about a minute to locate the platform, but over time, they get very efficient at finding it. Once they learn where it is, they’ll swim directly to it in about 5-10 seconds. Then we remove the platform from the water and watch what they do.”

A key part of the water maze procedure involves counting the number of times a rat swims across the spot where the platform was originally located. “It’s a measure of their persistence,” Nicholas explained. “If they know it really well, they’re going to keep going over and over the platform area, as if saying to themselves, ‘I know it’s got to be here.'”

Stress tests

The goal of the study was to see if rats treated with gene therapy would perform differently than normal rats during the water maze tests following exposure to stress. To administer gene therapy, the researchers anesthetized the rodent, inserted a syringe into its hippocampus and injected a genetically engineered virus with DNA containing the chimeric gene.

Once injected, individual copies of the virus penetrate the hippocampal neurons, thereby delivering the chimeric gene and activating it in the rat’s brain. The new gene then transforms harmful corticoids into helpful estrogens–a process that should hypothetically block the animal’s negative behavioral response to stress.

To make sure that natural estrogen wasn’t a factor, the experiment was restricted to male rats only. Every rat was trained to find the hidden platform. To raise corticoid levels in the animal’s bloodstream, the rats were subjected to a variety of stresses, such as immobilization or cold temperature, then released into the water, where observers counted how quickly and how often they swam to the area above the missing platform.

Stress tests were conducted before the animal received training, immediately after training and 24 hours later. “This taps into three different domains and three different timings–the effects of stress on learning, on storing learned information as memory and on retrieving that memory,” Sapolsky explained. The results were clear: When stress was applied 24 hours after training, the rats infected with the chimeric gene swam to the area of the missing platform faster, and spent significantly more time looking for it, than the normal rats did.

“These results are pretty fantastic, ” Nicholas said. “They suggest that this gene therapy not only blocks the deleterious effects of glucocorticoids but actually enhances spatial memory and learning through estrogen-controlled events, even in the presence of stress. Seeing this enhancement effect was pretty exciting. It’s the best we could have hoped for.”

Gene therapy

These findings also demonstrate the potential value of gene therapy for people who suffer severe cognitive side effects from taking large doses of corticoids to treat multiple sclerosis, rheumatoid arthritis and other diseases, Sapolsky said.

“Potentially it could be used to protect the brain when you’re taking tons of this stuff for some disease,” he explained. “People who take high doses of these steroids can also get clinically depressed. In principle, you could use gene therapy to protect them as well.”

However, this type of gene therapy will not be medically available until scientists figure out a way to safely deliver the chimeric gene to humans, Sapolsky said. He also noted that the treatment should be used to prevent severe neurological side effects caused by medication and should not be given to those who simply want to enhance their short-term memory and learning skills. “You can’t drill into people’s heads and inject a virus just because somebody has a big exam coming up, ” he said.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Stanford University.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

— The use of anabolic androgenic steroids may be associated with an antisocial lifestyle involving several types of crime, including weapons offenses and fraud, but did not appear to be associated with violent crimes or crimes against property, according to an article in the November issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Non-prescription steroid use has been linked to a number of psychiatric conditions and changes in behavior, according to background information in the article. "Case reports or survey studies of groups using anabolic androgenic steroids (e.g., bodybuilders) have described hypomania or manic episodes, depression or suicide, psychotic episodes and increased aggressiveness and hostility," the authors write. "This aggressiveness appears to occasionally trigger violent behavior, sometimes even including homicide."

Fia Klötz, M.D., Uppsala University, Sweden, and colleagues studied the associations between criminality and steroid use in 1,440 Swedish residents tested for the drugs between 1995 and 2001. Individuals were referred for such testing from inpatient and outpatient clinics, including substance abuse facilities, as well as police and customs stations. Of those screened, 241 (average age 20.5) tested positive and 1,199 (average age 20) tested negative and served as controls. Identifying information gathered at the drug-testing laboratory was used to collect criminal records of all the subjects. Offenses for which participants were convicted were divided into five categories: violent crime, including homicide, assault and robbery; weapons offenses; property crimes, including theft and receiving stolen goods; fraud; and sexual offenses.

Those who tested positive for steroid use were about twice as likely to have been convicted of a weapons offense and one and a half times as likely to have been convicted of fraud. There was no difference in the rate of violent crimes, sexual offenses or crimes against property between those who tested positive for steroids and those who tested negative.

When individuals referred to testing from substance abuse centers were excluded, the association between steroid use and weapons offenses remained significant. "One possible explanation for this finding might be that criminals involved in heavy types of crime, such as armed robbery or collection of crime-related debts, derive an advantage from being muscular and/or having a heavy build," the researchers write. "The well-documented increase in aggressiveness associated with anabolic androgenic steroid use might also be advantageous in carrying out premeditated crimes against people." Also in this analysis, the association between steroid use and fraud disappeared, and the risk for crimes against property became lower among those testing positive for steroids than among those testing negative.

Although steroids are primarily associated with violent outbursts of anger and impulsive behavior, these results suggest that they may also be linked to crimes involving preparation and advance planning, the authors conclude. However, additional research is required to assess the motives behind and effects of steroid use by criminals.

A Yale School of Medicine study shows for the first time that a high level of testosterone, such as that caused by the use of steroids to increase muscle mass or for replacement therapy, can lead to a catastrophic loss of brain cells.

Taking large doses of androgens, or steroids, is known to cause hyperexcitability, a highly aggressive nature, and suicidal tendencies. These behavioral changes could be evidence of alterations in neuronal function caused by the steroids, said the senior author, Barbara Ehrlich, professor of pharmacology and physiology.

"Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad, just take a deep breath and realize that it might not be his fault," said Ehrlich.

Testosterone is the main male hormone and it plays fundamental roles in development, differentiation, and cellular growth. In neurons, testosterone acts as a neurosteroid and can induce changes at the cellular level, which in turn lead to changes in behavior, mood and memory. Both neuroprotective and neurodegenerative effects of androgens have been reported.

The researchers showed that high levels of testosterone triggered programmed cell death in nerve cells in culture. Cell death, or apoptosis, is critical in many life processes, including development and disease. It is characterized by membrane instability, activation of caspases, which are the executioner proteins in apoptosis, change in membrane potential, and DNA fragmentation.

"In the present study we have demonstrated for the first time that the treatment of neuroblastoma cells with elevated concentrations of testosterone for relatively short periods, six to 12 hours, induces a decrease in cell viability by activation of a cell death program," Ehrlich said. "Low concentrations of testosterone had no effects on cell viability, whereas at high concentrations the cell viability decreased with incremental increases in hormone concentration."

The testosterone-induced apoptosis described in this study occurs through overactivation of intracellular Ca2+ signaling pathways. Overstimulation of the apoptotic program in neurons has been associated with several neurological illnesses, such as Alzheimer disease and Huntington disease.

Co-authors include Manuel Estrada, now continuing his work at the University of Chile in Santiago, and Anurag Varshney, now working at Ranbaxy, a drug discovery company in New Delhi, India.

Researchers at UT Southwestern Medical Center, working with mice, have shown how the body's own natural stress hormone can help lastingly decrease the fearful response associated with reliving a traumatic memory.

Days after experiencing a traumatic event — a mild electrical shock — mice in the study still showed a fearful response when re-exposed to the place where it happened, a condition that could be a model for post-traumatic stress disorder in humans. But mice receiving the hormone corticosterone at the time they "relived" the event experienced a significant drop in that fear.

"Corticosterone appears to enhance new memories that compete with the fearful memory thereby decreasing its negative emotional significance," said Dr. Craig Powell, senior author and assistant professor of neurology and psychiatry at UT Southwestern. "When an animal or human is exposed to or relives an aversive scenario, a process called extinction creates a competing memory."

"We're not erasing memories," said Dr. Robert Greene, professor of psychiatry at UT Southwestern and another author of the study. "What the steroid does is attenuate the fear memory by helping the mice to learn that these contexts should no longer be perceived as dangerous."

The study is being published online and in the Sept. 13 issue of the Journal of Neuroscience.

While other researchers have tested such steroids clinically with some success for patients with disorders of emotional memories such as post-traumatic stress disorder (PTSD) and phobias, those studies did not control for a number of variables and were not designed to address the mechanism of the drug's action, Dr. Greene said.

This study focused on a mechanism called extinction, in which a memory gradually diminishes, but can be re-established by a small reminder of the original event.

"Our studies show that glucocorticoids work specifically to enhance the extinction of fear memory, as opposed to other mechanisms affecting recall, such as eliminating the memory entirely," said Dr. Greene. "This provides a proof of principle, and is an essential step in advancing this therapeutic approach."

A UT Southwestern study is now under way in collaboration with the Dallas VA Medical Center with veterans suffering from PTSD to see if receiving a stress hormone while reliving their memories can reduce their disabling fear responses to their traumatic memories.

"The natural release of stress hormones during recall of a fearful memory may be a natural mechanism to decrease the negative emotional aspects of the memory," said Dr. Jacqueline Blundell, a postdoctoral fellow in neurology at UT Southwestern and one of the paper's co-lead authors. "Conversely, patients with post-traumatic stress disorder have blunted stress hormone responses and thus may not decrease fearful memories normally over time."

In the published study, mice were placed in a plastic box and given an electrical shock to the feet equal to the standard protocol for this type of research. The shock, Dr. Powell said, is similar to a static electricity shock people experience when wearing socks on carpet and then touching metal. "Except that instead of a brief spark, it persists for two seconds," he said. "It's more than enough to scare you, makes you react briskly, and makes you hesitant to touch the door handle again."

The mice were returned to the box two days later, and their fear, gauged by how long they "froze" in place, remained high. A few minutes later, they were injected with the stress hormone corticosterone.

The day after the injection, when they were returned to the box, the mice showed significantly less fear. The strength of this effect depended on the dosage of the hormone given.

In order for the effect to work, the corticosterone had to be given after the mice were returned to the site of the initial trauma, causing the memory to be re-activated. Giving it beforehand or giving it without placing the mice in the box had no effect when tested a day later.

However, when the injections were given over four days, the timing became less important — giving the steroid either before or after secondary exposure to the box reduced fear.

Other UT Southwestern researchers involved in the study were Dr. Wen-Hui Cai, assistant professor of psychiatry; and Jie Han, research assistant in psychiatry.

The work was supported by the National Institute of Mental Health, the Conte Center, the National Alliance for Research on Schizophrenia and Depression, and the Department of Veterans Affairs.

 Women are not the only ones in American society who feel pressure to achieve the perfect body.

New research suggests that men feel pressure to have muscular bodies, and that influence can lead some to symptoms of eating disorders, pressure to use steroids, and an unhealthy preoccupation with weightlifting.

“Men see these idealized, muscular men in the media and feel their own bodies don't measure up,” said Tracy Tylka, author of the study and assistant professor of psychology at Ohio State University 's Marion campus.

“For some men, this can lead to unhealthy and potentially dangerous behaviors to try to reach that ideal.”

Tylka presented her research at a symposium August 10 in New Orleans at the annual meeting of the American Psychological Association.

Of course, women have been pressured for decades to achieve a thin ideal, but this is a more recent phenomenon for men, Tylka said.

“Instead of seeing a decrease in objectification of women in society, there has just been an increase in the objectification of men. And you can see that in the media today,” she said.

To test how this emphasis on muscularity has affected men, Tylka studied 285 college men. She asked them a variety of questions to determine how much pressure to be muscular that they felt from family, friends, romantic partners and the media.

The findings showed that the more pressure the men felt, the more they felt they had to live up to the ideals.

“They start to believe that the only attractive male body is a muscular one. And when they internalize that belief, they judge themselves on that ideal and probably come up short, because it is not a realistic portrayal of men,” she said.

While other studies have suggested men can become preoccupied with their muscles, Tylka said this research shows men are also very worried about their body fat.

“Not only are men being targeted to be muscular, but they also feel they have to be very lean to show off their muscularity.”

And the more dissatisfied that men in the study felt with their muscularity and body fat, the more they engaged in unhealthy behaviors, findings showed.

For example, men who were not happy with their muscles were more likely to say that their weight-training schedule interfered with other parts of their life, that others think they work out too much, that they used protein supplements, and even that they thought about using steroids.

Men who were dissatisfied with their body fat were more likely to report symptoms of eating disorders, such as avoiding certain foods, being terrified about being overweight, and being preoccupied with a desire to be thinner.

Tylka said there is a difference between men who exercise and watch their diet for their health, and those who do so because they feel pressure to change their bodies.

“It is good to exercise, to lift weights, and to eat the foods that make your body function well,” she said.

“But it is not good to be preoccupied with gaining muscle mass. Those that are preoccupied are not working out to get healthier, they are working out to bulk up. They are not eating healthy, they are cutting out major food groups like carbohydrates and eating massive amounts of protein.”

While men in American society are feeling increasing pressures to achieve the perfect body, Tylka said women still get a disproportionate share of the pressure.

“Women still get objectified more than men, but men are feeling the pressure too.”

ANN ARBOR, Mich. — Our immune system protects us from disease, destroying invading microbes with a swarm of attacking cells. But it can also go haywire for no apparent reason, ganging up on normal tissues in our body and wreaking havoc.

In thousands of people each year, the immune system attacks the inner ear, home to the tiny, delicate structures that allow us to hear. Without warning, in days or weeks, patients lose the ability to hear in one or both ears. Some might get part or all of their hearing back if they take steroid medicines, but many are left to cope with partial or total deafness without knowing what caused it. And no one knows why it happens.

Now, new research based at the University of Michigan's Kresge Hearing Research Institute may help more patients find out quickly if steroids could help them, or if they can be spared the drugs' harsh side effects. It may also expand the definition of the condition, known as autoimmune sensorineural hearing loss or AISNHL, and help more people get a firm diagnosis of what's causing their mysterious hearing loss.

In the August issue of the Archives of Otolaryngology — Head and Neck Surgery, researchers reports results from a study of 63 people with rapidly progressing hearing loss in Michigan, Pennsylvania and Indiana, and 20 people with normal hearing. The patients were suspected of having an auto-immune cause for their hearing loss, and all received steroids, but they hadn't been formally diagnosed.

The researchers found that more than half of the hearing-loss patients had antibodies against a protein found in the inner ear, called IESCA for inner-ear supporting cell antigen. This is a sign their immune systems recognized it as foreign.

"In all, 28 of the 63 patients experienced improvement in their hearing after steroid treatment, and 35 did not. But the vast majority, 89 percent, of those who improved had a positive immunofluorescence test for an antibody to IESCA that we have studied at U-M for years," says senior author Thomas Carey, Ph.D., a professor and distinguished research scientist at the U-M Medical School and department chair in the School of Dentistry. "The results strongly suggest that a direct test for antibodies could accurately predict which patients will regain hearing with steroid treatment." Such a test, he notes, is still several years away from being available to patients.

The new findings also may be important to people with systemic autoimmune disorders such as lupus or rheumatoid arthritis. Such people may be prone to losing all or part of their hearing due to an overzealous autoimmune reaction. All eight study participants who had systemic autoimmune diseases showed signs of antibodies against IESCA. Six of them regained hearing after steroid treatment.

U-M researchers have been studying IESCA for several years in animals and have found that it may be a main target of the immune system's deafening attack on the inner ear. IESCA is found in the supporting cells that help make up the organ of Corti, a tiny but crucial structure inside the cochlea, or inner ear.

Inside the organ of Corti are the ultra-sensitive hair cells, whose movement in response to vibrations creates the nerve signals that are fed to the brain and interpreted as sounds and speech. Damage to the organ of Corti and hair cells, whether due to immune system attack, loud noise, trauma or medications, can diminish or destroy hearing.

The U-M team has developed a monoclonal antibody, called KHRI-3, that attaches to IESCA in the inner ear, and can be detected in living animal systems and cell cultures. It has allowed them to study IESCA's role in hearing loss in animal models, and show that damage to the inner ear caused by antibodies to IESCA can destroy hearing. The KHRI-3 antibody creates a staining pattern that resembles a line of tiny wine glasses when it binds to IESCA in the organs of Corti of guinea pigs.

The U-M has patent applications pending in the U.S. and abroad pertaining to KHRI-3, IESCA and AISNHL. The University, Carey and several colleagues stand to profit if tests or treatments based on these patents are developed. The development of a clinical test for patient antibody to IESCA will take time, Carey says.

In previous papers, Carey and his colleagues have shown that IESCA has about the same molecular weight as — but is distinct from — a protein that serves as the basis for a currently available commercial AISNHL test. That test, based on a protein-separation test known as Western blot, is known to give accurate results only some of the time. The U-M team reported in previous paper in the Journal of Neuroscience that IESCA is identical to a protein called CTL2, or choline transport-like protein 2.

In the new study, the researchers tested blood from the 63 patients and 20 normal controls with two tests: a Western blot test and an immunofluorescence (IF) test based on KHRI-3. They correlated the results of those two tests with patients' response to steroid treatment, based on standard criteria and the results of hearing tests performed before and after treatment. They also considered patients' other autoimmune diseases, the length and pace of hearing loss progression before treatment, and age and gender.

Thirty of the patients were female, and 33 male; their average age was 47, reflecting the young age at which AISNHL typically begins. Twenty-six had lost hearing in both ears, the rest in the left or right ear. They had no known cause for hearing loss, and most had lost their hearing gradually over weeks, though eight had lost it over hours or days. Many also had dizziness, ringing or a sensation of fullness in their ears. In all, half regained some or all of their hearing after steroid treatment.

Seventy-five percent of the patients had "wine glass" staining with IF testing, and 68 percent had positive Western blot results for the same size protein as is used in the commercial test.

The two different blood tests weren't always consistent – – results were the same in 47 patients (both positive or both negative) but different in 16. But the IF test appeared give a more specific response to steroid treatment: patients who had a positive IF test result were three times more likely to improve after steroid treatment than those with negative IF results.

The two tests combined were even more predictive: 54 percent of those who had positive results on both tests improved after steroid, compared with 10 percent of those who had two negative results.

Interestingly, Carey notes, nearly all of the patients who had sudden hearing loss over hours or days had antibodies, and nearly all improved with steroids.

Since this kind of rapid-onset hearing loss has historically been excluded from the formal definition of AISNHL, Carey suggests the definition may need re-examining in light of this strong evidence for an immune-system cause in these patients.

In addition to Carey, who is associate chair for research of the Department of Otolaryngology at the U-M Medical School, the paper's other U-M authors are Otolaryngology/Kresge members Hisham Zeitoun, MPhil., FRCS, the lead author; H. Alexander Arts, M.D.; Dawn E. Denny; Michael J. Disher, M.D.; Hussam El-Kashlan, M.D.; David S. Lee, M.D.; Thankam S. Nair, M.S.; Anna Ramakrishnan, M.S.; and Steven Telian, M.D. Co-authors from outside U-M are Jennifer Gray Beckman, JD; Christopher D. Lansford, M.D.; Robert Sataloff, M.D.; and Susan G. Fisher, Ph.D.

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The research was funded by the Autoimmune Sensorineural Hearing Loss Research Fund, the Ruth and Lynn Townsend Fund, a gift from the Holden Foundation, the Deafness Research Foundation and the National Institutes of Health.

Special note for hearing-loss patients: The new findings, while exciting, are laboratory results and cannot be immediately applied to human treatment. It will take several years to develop a test that could be used in patients who have recently developed hearing loss. If you have recently begun to experience hearing loss that is progressing, seek immediate attention from an otolaryngologist, sometimes called an ear, nose and throat (ENT) doctor. He or she can advise you on immediate and long-term treatment options.

If you would like to help support U-M research into autoimmune sensorineural hearing loss, visit https://cgi.www.umich.edu/cents-bin/cents-open/mcado2 to make a secure on-line donation; please note that you would like the donation to go to the Autoimmune Hearing Loss Research Fund of the Kresge Hearing Research Institute.

— A variety of biomedical technologies are being developed that can be used for purposes other than treating disease. Such "enhancement technologies" can be used to improve our appearance and regulate our emotions, with the goal of feeling "better than well." While these technologies can help people adapt to their rapidly changing lifestyles, their use raises important ethical issues.

In a provocative debate in this month's PLoS Medicine, the premier open-access medical journal, two of America's foremost medical ethicists, Arthur Caplan and Carl Elliott, lay out the pros and cons respectively of these new enhancement technologies.

Caplan, who chairs the Department of Medical Ethics at the University of Pennsylvania School Of Medicine, says that "nobody is perfect–but why not try to be better?" He argues that it is in our human nature to strive for self-improvement and he sees real value in using technology to "enhance our vision, memory, learning skills, immunity, or metabolism." What's more, says Caplan, "putting the brakes on biologically driven human betterment would have real consequences for science. Some lines of research would be slowed or restricted." There is no reason why we "should not try to improve the biological design with which we are endowed."

But Elliot, Associate Professor at the Center for Bioethics at the University of Minnesota, and author of the book Better Than Well, worries "about the larger social effects of embracing medical enhancement technologies too enthusiastically." For example, athletes taking steroids may improve their own ability but they set off "a steroid arms race" that could destroy their sport. Manufacturers of enhancement technologies "will usually exploit the blurry line between enhancement and treatment in order to sell drugs." Citing the story of the diet drug Fen-Phen, Elliot says that "an alarming number of supposedly risk-free enhancements have later been associated with unanticipated side effects."