Archive for the ‘Steroids’ Category

Research news from Journal of Mass Spectrometry

A new mass spectrometry test can help sports anti-drug doping officials to detect whether an athlete has used drugs that boost naturally occurring steroid levels. The test is more sensitive compared to previous alternatives, more capable of revealing specific suspicious chemical in the body, faster to perform, and could be run on standard drug-screening laboratory equipment. The new test is announced in a special issue of the Journal of Mass Spectrometry that concentrates on detecting drugs in sports.

One of the roles of the masculinising hormone testosterone is to increase muscle size and strength. Taking extra testosterone, or taking a chemical that the body can use to create extra testosterone, could therefore enhance an athlete’s performance. For this reason taking it is banned by the World Anti-Doping Agency (WADA).

The exact level of testosterone varies considerably between different people, so simply measuring total testosterone in an athlete’s urine can not show whether he or she has deliberately taken extra. There is, however, a second chemical in the body, epitestosterone, which is normally present in approximately equal proportions to testosterone. Comparing the ratio of testosterone to epitestosterone can then indicate whether testosterone or a precursor has been taken.

The problem is that it is not always easy to measure these two substances, particularly as they are only present in urine at very low concentrations.

A team of scientists the Sports Medicine Research and Testing Laboratory at the University of Utah have developed a test that makes use of liquid chromatography-tandem mass spectrometry. This method has incredibly high sensitivity (down to 1 ng/ml) and increases the power with which officials can search for both testosterone and epitestosterone within a sample.

“Our system means that we can determine the testosterone/epitestosterone ratio in a sample with greater confidence, and therefore be in a better position to spot doping violations without falsely accusing innocent athletes,” says lead investigator Dr Jonathan Danaceau.

“Not only is the test more sensitive, it is also faster to perform,” says colleague Scott Morrison.

“Having this sort of test available makes cheating harder and lets us take one more step towards enabling free and fair competition,” says Laboratory Director Dr Matthew Slawson.

This paper is part of a special issue for the Olympic Games from the Journal of Mass Spectrometry which focuses of drug use in sport. The issue is available free of charge online for one month at http://www.interscience.wiley.com/journal/jms. The other articles publishing in this issue are:

 

  • History of Mass Spectrometry at Olympic Games (DOI: 10.1002/jms.1445)
  • Nutritional supplements cross-contaminated and faked with doping substances (DOI: 10.1002/jms.1452)
  • Hair analysis of anabolic steroids in connection with doping control results from horse samples (DOI: 10.1002/jms.1446)
  • Mass spectrometric determination of Gonadotrophin releasing hormone (GnRH) in human urine for doping control purposes by means of LC-ESI-MS/MS (DOI: 10.1002/jms.1438)
  • Liquid chromatographic-mass spectrometric analysis of glucuronide-conjugated anabolic steroid metabolites: method validation and inter-laboratory comparison (DOI: 10.1002/jms.1434)
  • Mass Spectrometry of Selective Androgen Receptor Modulators (DOI: 10.1002/jms.1438)
  • Can glycans unveil the origin of glycoprotein hormones? – human chorionic gonadotropin as an example (DOI: 10.1002/jms.1448)
  • A High-Throughput Multicomponent Screening Method for Diuretics, Masking Agents, Central Nervous System Stimulants and Opiates in Human Urine by UPLC-MS/MS (DOI: 10.1002/jms.1436)
  • The application of carbon isotope ratio mass spectrometry to doping control (DOI: 10.1002/jms.1437)
  • Identification of zinc-alpha-2-glycoprotein binding to clone ae7a5 anti-human epo antibody by means of nano-hplc and high-resolution highmass accuracy esi-ms/ms (DOI: 10.1002/jms.1444)
  • Low LC-MS/MS Detection of Glycopeptides Released from pmol Levels of Recombinant Erythropoietin using Nanoflow HPLC-Chip Electrospray Ionization (DOI: 10.1002/jms.1439)
  • Introduction of HPLC/Orbitrap mass spectrometry as screening method for doping control (DOI: 10.1002/jms.1447)

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Article adapted by MD Sports from original press release.
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Contact: Jennifer Beal
Wiley-Blackwell

University Park, Pa. — Girls and boys are now equally caught up in the social pressure for a muscular body image currently lauded in popular culture. A Penn State researcher contends those pressures are leading girls and boys down unhealthy avenues such as the misuse of anabolic steroids.

“Young girls have always had to struggle against the media stereotypes of stick-thin models or voluptuous sexuality, but with the rising popularity of women sports, girls are bombarded with buffed body images,” says Dr. Charles Yesalis, professor of health policy and administration, and exercise and sports science at Penn State, and editor of the newest edition of the book “Anabolic Steroids in Sports and Exercise.” “Now, young boys face pop culture musclemen like The Rock and Steve Austin, given the influence of professional wrestling shows.”

“The current film ‘Charlie’s Angels’ sports karate-kicking women in cool clothes,” he added. “Today’s children look with envy at the physiques of actors Arnold Schwarzenegger, Jean-Claude Van Damme, Wesley Snipes, and Linda Hamilton, whose roles call for a muscular build. Hollywood stars are openly taking Human Growth Hormone (HGH) injections to combat aging.”

In addition, children are entering competitive sports at younger ages and many working families have children signed up in two or three sports. Parents, coaches and young athletes are facing growing violence in amateur athletics. The pressure to win at all costs continues to weigh heavily on children, Yesalis notes.

The concern is that many youths will take shortcuts to achieving a muscular build by using anabolic steroids. Female athletes also are pressured to achieve low body fat to excel in their sport. The Penn State researcher has seen evidence that the pressures are reaching down to young children. For example, the book cites figures from the Monitoring The Future Study, a national-level epidemiological survey conducted annually since 1975. Approximately 50,000 8th, 10th and 12 graders are surveyed each year.

The MTF data shows that during the 1990s, anabolic steroid use among 12 graders –both boys and girls – rose to an all-time high with more than 500,000 adolescents having cycled – an episode of use of 6 to 12 weeks – during their lifetime. And the percentage of girls alone doubled in the same period.

A 1998 study of 965 youngsters at four Massachusetts middle schools found that 2.7 percent admitted to taking illegal steroids for better sports performance. That included some boys and girls as young as 10 years old. “This year’s Olympic doping scandals and the epidemic of anabolic steroids in professional baseball just glorify and justify steroids to impressionable youths,” Yesalis notes. “The use of anabolic steroids has cascaded down from the Olympic, professional and college levels to high schools and junior high schools and now middle schools for athletes and non-athletes alike. ”

“Anabolic steroids are made to order for a female wanting to attain a lean athletic body. While most drug abuse has outcomes that tend to discourage use, females who use anabolic steroids may experience a decrease in body fat, increased muscle size and strength, and enhanced sports performance,” he says.

Girls and boys misusing anabolic steroids may win approval and rewards from parents, coaches and peers, but don’t realize there are long-term negative effects on their health, particularly girls, according to Yesalis. Young girls face potential permanent side effects of male hair growth or baldness, deepening of the voice, the enlargement of the clitoris as well as the known risks of heart and liver diseases.

Published by Human Kinetics, the book incorporates the latest research, experience and insights of 15 experts on the scientific, clinical, historical, legal and other aspects of steroid abuse and drug testing. New information looks at the effects of steroids on health, particularly that of women.

This year, trials of East German doctors, coaches and officials reveal records of systematic doping of young athletes without their own or parents’ knowledge. In 1974, officials’ plan to turn the tiny Communist nation into a superpower in sports included giving performance-enhancing drugs to all competing athletes including children as young as 10 years old. The indictments included 142 former East German athletes who now complain of health problems. In media reports, several female athletes report incidents of miscarriages, liver tumor, gynecological problems and enlarged heart, all showing up decades after the steroid misuse.

“Our society’s current strategy for dealing with the abuse of anabolic steroids in sport primarily involves testing, law enforcement and education,” Yesalis says. “But our efforts to deal with this problem have not been very successful. Unless we deal with the social environment that rewards winning at all costs and an unrealistic physical appearance, we won’t even begin to address the problem.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Vicki Fong
Penn State

By studying the genes of a German child born with unusually well developed muscles, an international research team has discovered the first evidence that the gene whose loss makes “mighty mice” also controls muscle growth in people.

Writing in the June 24 issue of the New England Journal of Medicine, German neurologist Markus Schuelke, M.D., and the team show that the child’s extra-large muscles are due to an inherited mutation that effectively silences the myostatin gene, proving that its protein normally keeps muscle development in check in people.

People with muscle-wasting conditions such as muscular dystrophy, and others just wanting to “bulk up,” have eagerly followed work on myostatin, hoping for a way to counteract the protein’s effects in order to build or rebuild muscle mass. But while research with mice has continued to reveal myostatin’s role and the effects of interfering with it, no one knew whether any of the results would be relevant to humans.

“This is the first evidence that myostatin regulates muscle mass in people as it does in other animals,” says Se-Jin Lee, M.D., Ph.D., professor of molecular biology and genetics in the Institute for Basic Biomedical Sciences at Johns Hopkins and co-author on the study. “That gives us a great deal of hope that agents already known to block myostatin activity in mice may be able to increase muscle mass in humans, too.”

Lee and his team discovered in 1997 that knocking out the myostatin gene led to mice that were twice as muscular as their normal siblings, lending them the moniker “mighty mice.” Later, others showed that naturally bulky cattle, such as Belgian Blues, got their extra muscles from lack of myostatin, too.

An unusual opportunity to examine myostatin’s role in humans arose when Schuelke examined a newborn baby boy, almost five years ago, and was struck by the visible muscles on the infant’s upper legs and upper arms. When ultrasound proved that the muscles were roughly twice as large as other infants’, but otherwise normal, Schuelke realized that a naturally occurring mutation in the child’s myostatin gene might be the cause.

Sequencing the myostatin gene from the boy and his mother, who had been a professional athlete, revealed a single change in the building blocks of the gene’s DNA. Surprisingly, the change was not in the gene regions that correspond to the resulting protein, but in the intervening regions that are used only to create protein-making instructions, thus changing the gene’s protein-building message.

“The mutation caused the gene’s message, the messenger RNA, to be wrong,” says Hopkins

neurologist Kathryn Wagner, M.D., Ph.D., who tested the genetic mutation’s effect in laboratory studies. “If the message had been used to make a protein, it would be much shorter than it should be. But we think the process doesn’t even get that far; instead the cells just destroy the message.”

Co-authors from Wyeth Research, Cambridge, Mass., analyzed samples of the child’s blood for evidence of the myostatin protein and found none. “Both copies of the child’s myostatin gene have this mutation, so little if any of the myostatin protein is made,” says Schuelke. “As a result, he has about twice the muscle mass of other children.”

Completely lacking myostatin, the boy is stronger than other children his age, and fortunately has no signs of problems with his heart so far, Schuelke says. But he adds that it’s impossible to know whether the lack of myostatin in that crucial muscle might lead to problems as the boy gets older.

While other family members — the boy’s mother and her brother, father and grandfather — were also reported to have been usually strong, only the mother’s DNA was available for analysis along with her son’s. Schuelke discovered that only one copy of the mother’s myostatin gene had the mutation found in both copies of her son’s myostatin gene. (We have two copies of each gene; one inherited from the mother and one inherited from the father.)

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Article adapted by MD Sports Weblog from original press release.
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 Contact: Joanna Downer
Johns Hopkins Medical Institutions

 

The Johns Hopkins researchers were funded by the National Institutes of Health and the Muscular Dystrophy Association. The German researchers were funded by the parents’ self-help group (Helft dem muskelkranken Kind).

Authors on the paper are Schuekle, Christoph Hubner, Thomas Riebel and Wolfgang Komen of Charite, University Medical Center Berlin, Germany; Wagner and Lee of Johns Hopkins; Leslie Stolz and James Tobin of Wyeth Research, Cambridge, Ma.; and Thomas Braun of Martin-Luther-University, Halle-Wittenberg, Germany.

*Under a licensing agreement between MetaMorphix Inc. and The Johns Hopkins University, Lee is entitled to a share of royalty received by the University on sales of products described in this article. Lee also is entitled to a share of sublicensing income from arrangements between MetaMorphix and American Home Products (Wyeth Ayerst Laboratories) and Cape Aquaculture Technologies. Lee and the University own MetaMorphix Inc. stock, which is subject to certain restrictions under University policy. Lee owns Cape Aquaculture Technologies stock, which is subject to certain restrictions under University policy. Lee has served as a paid consultant to MetaMorphix Inc. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

Researchers from the Division of Health Promotion & Sports Medicine at Oregon Health & Science University have found steroid use among teen girls is not limited to athletes and often goes hand in hand with other unhealthy choices, including smoking and taking diet pills. The study was published in the Archives of Pediatrics & Adolescent Medicine, a JAMA/Archives journal.Diane Elliot, M.D., professor of medicine (health promotion and sports medicine), OHSU School of Medicine, and colleagues analyzed findings from the Center for Disease Control’s Youth Risk Behavior Survey of 7,544 ninth- through 12th-grade girls from around the country. The questionnaire asked about sports participation, anabolic steroid and drug use, and other illegal or unhealthy behaviors. Approximately 5 percent of participants reported prior or ongoing anabolic steroid use.

In addition to greater substance use, young female steroid users were more likely to have had sexual intercourse before age 13; have been pregnant; drink and drive or have ridden with a drinking driver; carry a weapon; have been in a fight on school property; have feelings of sadness or hopelessness almost every day for at least two weeks; and have attempted suicide. Those reporting anabolic steroid use were less likely to participate in team athletics.

Overall, more than two-thirds of those surveyed reported trying to change their weight. Girls who used steroids were more likely try extreme weight-loss techniques, such as vomiting and laxative use.

Adolescent girls reporting anabolic steroid use had significantly more other health-harming behaviors, Elliot explained, “They were much more likely to use other unhealthy substances, including cigarettes, alcohol, marijuana and cocaine.”

“Across all grades, these seem to be troubled adolescents with co-occurring health-compromising activities in the domains of substance use, sexual behavior, violence and mental health,” Elliot said. “Anabolic steroid use is a marker for high-risk girls. High-risk young women have received less attention than young men, perhaps reflecting that their actions are less socially, albeit more personally, destructive. Further study is needed to develop effective interventions for these young women.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Tamara Hargens
Oregon Health & Science University

Baseball team owners, players and fans seem to agree on the importance of drug testing for steroids, according to current reports, but the entire scope of performance-enhancing substances available for all athletes is vastly broader and many of the drugs employed by athletes are not easily detectable, says a Penn State researcher.”The use, misuse and abuse of drugs have long shaken the foundations of amateur and professional sports–baseball, football, track and field, gymnastics and cycling, to name just a few,” says Dr. Charles Yesalis, Penn State professor of exercise and sport science and health policy and administration. “The problem is not new. But like the rest of technology, doping in sport has grown in scientific and ethical complexity. In addition to drugs, we have natural hormones, blood doping, diuretics, nutritional supplements, social and recreational drugs, stimulants and miscellaneous substances, some of which may not even be on any list of banned substances.”

While drug testing technology struggles to keep up, an array of new and emerging technologies has arrived or is on the horizon with potential for abuse by athletes including gene transfer therapy, stem cell transplantation, muscle fiber phenotype transformation, red blood cell substitutes and new drug delivery systems, says Yesalis

“It is not too hard to imagine the day when muscles can be selectively enlarged or contoured,” according to the book. “Just imagine the consequences of a kinesiologist isolating specific muscles and selectively injecting designer genes into those muscles to maximize their function.”

The new book brings together the latest and most comprehensive scientific information about performance-enhancing substances, as well as discussion of drug testing, legal and social issues, and future directions by sports governing organizations.

“Sport has a responsibility to maintain a level playing field for the trial of skill,” Yesalis says. “The use of chemical and pharmacologist agents is cheating – just like using a corked baseball bat. But unlike the bat, doping is shrouded in mystery. Athletes and their advisors are constantly seeking ‘gray areas” surrounding the rules, and if something is not explicitly banned, then why not try it. This slippery slope of rationalization is treacherous and appealing to a player or team seeking glory and money rewards.”

In one chapter, “Drug Testing and Sport and Exercise,” author R. Craig Kammerer suggests that improvement in current tests and developments in new methods will assist future policymaking by athletic federations. However, effective testing must become more widespread and include unannounced testing outside of competition. Sanctions against athletes must be more fairly and uniformly applied, with thorough investigation to avoid false positive results and ruin an athlete’s career.

The difficulty of detecting and preventing the abuse of performance enhancing substances by adult athletes may seem futile but remains necessary as part of the effort to discourage abuse by youths who emulate professional athletes and also seek a winning advantage, Yesalis notes.

A recent government study of adolescent drug use shows an alarming increase in anabolic steroid use among middle school youths from 1998-1999 with an estimated 2.7 percent of eighth graders saying they have used the drugs. A larger survey by Blue Cross and Blue Shield estimates that one million U.S. children between the ages of 12 and 17 may have taken performance-enhancing substances including creatine, according to the book.

“Children and teens can seriously harm their future health by misusing these substances,” Yesalis says. “For example, steroids alone can cause scarring acne, hair loss and testicular atrophy, and may increase the risk of stroke and heart disease. It is just as important to note that little is known about the health consequences of many of the other substances used to enhance performance. Yet some coaches and parents look the other way and even actively encourage the use of performance-enhancing substances in pursuit of scholarships and winning.

“There is too much fame and fortune to be gained by being a winner in sports,” he notes. “It’s interesting to see that baseball fans being polled support drug testing and a ban on steroids, but it will take fans of all major sports to take a stand by turning off their TV sets or not buying a ticket to sports events before adult athletes, coaches and team owners stop trying to cheat. And, that’s probably not going to happen.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Vicki Fong
Penn State

And it increases endurance to run a mile and decreases inflammation

The Salk Institute scientist who earlier discovered that enhancing the function of a single protein produced a mouse with an innate resistance to weight gain and the ability to run a mile without stopping has found new evidence that this protein and a related protein play central roles in the body’s complex journey to obesity and offer a new and specific metabolic approach to the treatment of obesity related disease such as Syndrome X (insulin resistance, hyperlipidemia and atherosclerosis).

Dr. Ronald M. Evans, a Howard Hughes Medical Investigator at The Salk Institute’s Gene Expression Laboratory, presented two new studies (date) at Experimental Biology 2005 in the scientific sessions of the American Society for Biochemistry and Molecular Biology. The studies focus on genes for two of the nuclear hormone receptors that control broad aspects of body physiology, including serving as molecular sensors for numerous fat soluble hormones, Vitamins A and D, and dietary lipids.

The first study focuses on the gene for PPARd, a master regulator that controls the ability of cells to burn fat. When the “delta switch” is turned on in adipose tissue, local metabolism is activated resulting in increased calorie burning. Increasing PPARd activity in muscle produces the “marathon mouse,” characterized by super-ability for long distance running. Marathon mice contain altered muscle composition, which doubles its physical endurance, enabling it to run an hour longer than a normal mouse. Marathon mice contain increased levels of slow twitch (type I) muscle fiber, which confers innate resistance to weight gain, even in the absence of exercise.

Additional work to be reported at Experimental Biology looks at another characteristic of PPARd: its role as a major regulator of inflammation. Coronary artery lesions or atherosclerosis are thought to be sites of inflammation. Dr. Evans found that activation of PPARd suppresses the inflammatory response in the artery, dramatically slowing down lesion progression. Combining the results of this new study with the original “marathon mouse” findings suggests that PPARd drugs could be effective in controlling atherosclerosis by limiting inflammation and at the same time promoting improved physical performance.

Dr. Evans says he is very excited about the therapeutic possibilities related to activation of the PPARd gene. He believes athletes, especially marathon runners, naturally change their muscle fibers in the same way as seen in the genetically engineered mice, increasing levels of fat-burning muscle fibers and thus building a type of metabolic ‘shield” that keeps them from gaining weight even when they are not exercising.

But athletes do it through long periods of intensive training, an approach unavailable to patients whose weight or medical problems prevent them from exercise. Dr. Evans believes activating the PPARd pathway with drugs (one such experimental drug already is in development to treat people with lipid metabolism) or genetic engineering would help enhance muscle strength, combat obesity, and protect against diabetes in these patients.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Sarah Goodwin
Federation of American Societies for Experimental Biology

When given extra shots of the plant steroid brassinolide, plants “pump up” like major league baseball players do on steroids. Tracing brassinolide’s signal deep into the cell’s nucleus, researchers at the Salk Institute for Biological Studies have unraveled how the growth-boosting hormone accomplishes its job at the molecular level.The Salk researchers, led by Joanne Chory, a professor in the Plant Molecular and Cellular Biology Laboratory and a Howard Hughes Medical Institute investigator, published their findings in this week’s journal Nature.

“The steroid hormone brassinolide is central to plants’ growth. Without it, plants remain extreme dwarfs. If we are going to understand how plants grow, we need to understand the response pathway to this hormone,” says Chory. “This study clarifies what’s going on downstream in the nucleus when brassinolide signals a plant cell to grow.”

Brassinolide, a member of a family of plant hormones known as brassinosteroids, is a key element of plants’ response to light, enabling them to adjust growth to reach light or strengthen stems. Exploiting its potent growth-promoting properties could increase crop yields or enable growers to make plants more resistant to drought, pathogens, and cold weather.

Unfortunately, synthesizing brassinosteroids in the lab is complicated and expensive. But understanding how plant steroids work at the molecular level may one day lead to cheap and simple ways to bulk up crop harvests.

Likewise, since low brassinolide levels are associated with dwarfism, manipulating hormone levels during dormant seasons may allow growers to control the height of grasses, trees or other plants, thereby eliminating the need to constantly manicure gardens.

Based on earlier studies, the Salk researchers had developed a model that explained what happens inside a plant cell when brassinolide signals a plant cell to start growing.

But a model is just a model. Often evidence in favor of a particular model is indirect and could support multiple models. Describing the components of the signaling cascade that relays brassinolide’s message into a cell’s nucleus, postdoctoral researcher and lead author of the study Grégory Vert, now at the Centre national de la recherche scientifique (CNRS) in Montpellier, France, said, “All the players are old acquaintances and we knew from genetic studies that they were involved in this pathway. But when we revisited the old crew it became clear that we had to revise the original model.”

When brassinosteroids bind a receptor on the cell’s surface, an intracellular enzyme called BIN2 is inactivated by an unknown mechanism. Previously, investigators thought that inactivation of BIN2, which is a kinase, freed a second protein known as BES1 from entrapment in the cytoplasm, the watery compartment surrounding a cell’s nucleus, and allowed it to migrate or “shuttle” into the nucleus where it tweaked the activity of genes regulating plant growth.

A closer inspection, however, revealed that BIN2 resides in multiple compartments of a cell, including the nucleus, and it is there–not in the cytoplasm–that BIN2 meets up with BES1 and prevents it from activating growth genes. “All of a sudden the ‘BES1 shuttle model’ no longer made sense,” says Vert, adding that it took many carefully designed experiments to convince himself and others that it was time to retire the old model.

A new picture of how brassinosteroids stimulate plant growth now emerges based on those experiments: steroid hormones are still thought to inactivate BIN2 and reciprocally activate BES1, but instead of freeing BES1 to shuttle into the nucleus, it is now clear that the crucial activation step occurs in the nucleus where BES1 is already poised for action. Once released from BIN2 inhibition, BES1 associates with itself and other regulatory factors, and this modified form of BES1 binds to DNA, activating scores of target genes.

Referring to the work of Vert and other members of the brassinosteroid team, Chory says, “The old model may be out, but Greg’s new studies, together with those of former postdocs, Yanhai Yin and Zhiyong Wang, have allowed us to unravel the nuclear events controlling brassinosteroid responses at the genomic level. This turns our attention to the last mystery: the gap in our understanding of the events between steroid binding at the cell surface and these nuclear mechanisms.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Gina Kirchweger
Salk Institute

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today. Genetic research into athletic ability should be encouraged for its potential benefits in both sport and public health, a leading group of scientists meeting at the University of Bath said today.

However, ethical concerns, such as whether seeking information about differences between ethnic groups could be perceived as racist research, need to be properly addressed, they warn.

Their recommendations are published in a ‘position stand’ on genetic research and testing launched at the British Association of Sport & Exercise Sciences annual meeting today.

They call for more genetic research in the sport and exercise sciences because of the anticipated benefits for public health, but want researchers to take a more active role in debating the implications of their work with the public.

“If a powerful muscle growth gene was identified, on the one hand this could help develop training programmes that increase muscle size and strength in athletes, but even more importantly the knowledge could be used to develop exercise programmes or drugs to combat muscle wasting in old age,” said Dr Alun Williams from Manchester Metropolitan University, one of the report’s authors.

“We, as scientists investigating genetics, acknowledge a public concern about some genetic research and we believe scientists need to engage in public in debates about the potential benefits of their research.

“Research into the athletic success of East African distance runners or sprinters of West African ancestry might be perceived as unethical.

“But understanding the limits of human exercise capacity in sport could lead to the development of treatments for a range of diseases like cancer and cardiovascular disease.”

The potential applications of genetic testing in sport and exercise also raise some ethical concerns, for example in identifying potential athletic ability before birth.

An Australian company already offers the first genetic performance test (for the ACTN3 gene) which has been linked to sprint and power performance.

The report authors are sceptical about whether this test is useful but anticipate that more advanced versions of these tests will be available in future.

“We are not yet at a point where we can identify a potential future Olympic champion from genetic tests but we may not be very far away,” said Dr Williams, who wrote the report with Drs Henning Wackerhage (Aberdeen University), Andy Miah (University of Paisley), Roger Harris (University of Chichester) and Hugh Montgomery (University College London).

They highlight two dangers of genetic performance tests. Firstly, genetic performance tests might later be linked to disease. For example, a muscle growth gene may later be linked to cancer growth.

“Not all people may want to know, while young that they are at increased risk of cancer by early middle age, but they might inadvertently become aware of that just because they had a ‘sport gene’ test,” said Dr Williams.

Secondly, genetic performance tests can be performed even before birth and this may lead to the selection of foetuses or to abortions based on athletic potential.

The report recommends genetic counselling and that the testing should be confined to mature individuals who fully understand the relevant issues.

Genetic tests might also be used to screen for health risks during sport such as genes that are linked to sudden cardiac death.

Genetic tests for sudden cardiac death are already available but the report recommends that such testing should not be enforced on athletes.

Problems with mandatory testing are highlighted by the case of the basketball player Eddy Curry, who had an irregular heart beat.

Curry was asked by his club, the Chicago Bulls, to perform a predictive genetic test for a heart condition. The athlete refused and was traded to the New York Knicks who did not make such a demand.

In future, genetic tests might be used to identify those that respond with the biggest drop in cholesterol, blood pressure or glucose to exercise.

In a personalised medicine approach, such tests could be used to select subjects for therapeutic exercise programmes but scientists are concerned that this might undermine the ‘exercise for all’ message that already seems difficult to get across to the public.

The authors say that genetic testing might also be used to detect gene doping, which may be a real threat by the time of the London Olympics in 2012, or to show that positive doping tests are the result of a genetic mutation in an athlete.

The report recommends that genetic testing should be used for anti-doping testing as long as the genetic samples are destroyed after testing.

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Article adapted by MD Sports Weblog from original press release.
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Contact: Andrew McLaughlin
University of Bath

A team of researchers, led by scientists at Dartmouth Medical School and Dartmouth College, have identified and tested a gene that dramatically alters both muscle metabolism and performance. The researchers say that this finding could someday lead to treatment for muscle diseases, including helping the elderly who suffer from muscle deterioration and improving muscle performance in endurance athletes.

The researchers report that the enzyme called AMP-activated protein kinase (or AMPK) is directly involved in optimizing muscle activity. The team bred a mouse that genetically expressed AMPK in an activated state. Like a trained athlete, this mouse enjoyed increased capacity to exercise, manifested by its ability to run three times longer than a normal mouse before exhaustion.

One particularly striking feature of the finding was the accumulation of muscle glycogen, the stored form of carbohydrates, a condition that many athletes seek by “carbo-loading” before an event or game. The study appears in the Nov. 14 online issue of the American Journal of Physiology: Endocrinology and Metabolism.

“Our genetically altered mouse appears to have already been an exercise program,” says Lee Witters, the Eugene W. Leonard 1921 Professor of Medicine and Biochemistry at Dartmouth Medical School and professor of biological sciences at Dartmouth College. “In other words, without a prior exercise regimen, the mouse developed many of the muscle features that would only be observed after a period of exercise training.”

Witters, whose lab led the study, explains that this finding has implication for anyone with a muscle disease and especially for the growing proportion of the population that is aging. Deteriorating muscles often make the elderly much more prone to fall, leading to hip and other fractures. According to Witters, there is tremendous interest in the geriatric field to find ways to improve muscle performance.

“We now wonder if it’s possible to achieve elements of muscular fitness without having to exercise, which in turn, raises many questions about possible modes of exercise performance enhancement, including the development of drugs that could do the same thing as we have done genetically,” he says. “This also might raise to some the specter of ‘gene doping,’ something seriously being talked about in the future of high-performance athletes.”

Witters says that the carbohydrate, glucose, is a major fuel that powers muscles, and this contributes directly to a muscle’s ability to repetitively contract during exercise. The activated AMPK in the Dartmouth mouse appears to have increased glycogen content by actually switching on a gene that normally synthesizes liver glycogen.

“The switching on of this liver gene in muscles,” he says, “is a shift in the conception of the biochemistry of muscle metabolism, since many enzyme genes are thought to only be active in just one tissue.”

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Article adapted by MD Sports Weblog from original press release.
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Contact: Sue Knapp
Dartmouth College

Other authors on the paper include Laura Barré, Christine Richardson, and Steven Fiering, all at Dartmouth; Michael Hirshman and Laurie Goodyear of Joslin Diabetes Center in Boston; Joseph Brozinick with Eli Lilly and Company; and Bruce Kemp of the St. Vincent’s Institute in Australia.

This research is funded by the National Institutes of Health.

Steroid use by a Major League Baseball slugger may produce only modest increases in muscle mass and bat and ball speed but still boost home run production by 50 percent or more, according to a new study by Tufts University physicist Roger Tobin.

Tobin, a specialist in condensed matter physics with a long-time interest in the physics of baseball, will publish his paper “On the potential of a chemical Bonds: Possible effects of steroids on home run production in baseball” in an upcoming issue of the American Journal of Physics.

As Tobin’s paper notes, Babe Ruth’s record of 60 home runs in a single season stood for 34 years until Roger Maris hit 61 homers in 1961. For the next 35 years, no player hit more than 52 home runs in one season. But between 1998 and 2006, players hit more than 60 home runs in a season six times. Barry Bonds hit 73 home runs in 2001 — topping Maris’ mark by an astonishing 20 percent.

According to Tobin, the explosion in home runs coincides with the dawn of the “steroid era” in sports in the mid-1990s, and that surge quickly dropped to historic levels in 2003, when Major League Baseball instituted steroid testing.

While the increase in home runs has been clouded by suspected use of performance-enhancing steroids, many have wondered why home-running hitting would be particularly vulnerable to performance enhancement. They have also asked if it is even physically and physiologically plausible that steroids could produce effects of the magnitude observed. The answer to both questions, says Tobin, is “yes.”

Home Runs Disproportionately Affected

“A change of only a few percent in the average speed of the batted ball, which can reasonably be expected from steroid use, is enough to increase home run production by at least 50 percent,” he says. This disproportionate effect arises because home runs are relatively rare events that occur on the “tail of the range distribution” of batted balls.

“In most any statistical distribution — of people’s heights, SAT scores, or how far baseballs are hit — there’s a large bump where most of the values fall, with the graph falling rapidly as you move away from that region in either direction toward the rarer values,” explains Tobin. “It’s a well-known statistical property of such distributions that a relatively small shift in the center point of the distribution can produce a much larger proportional change in the number of values well above or below the center. Because the distribution’s ‘tail’ is particularly sensitive to small changes in the peak and/or width, home run records can be more strongly affected by steroid use than other athletic accomplishments.”

Muscle Mass Boosts Bat and Ball Speed

Tobin reviewed previous studies of the effect of steroid use and concluded that muscle mass, the force exerted by those muscles and the kinetic energy of the bat could each be increased by about 10 percent through the use of steroids. According to his calculations, the speed of the bat as it strikes the pitched ball will be about 5 percent higher than without the use of steroids and the speed of the ball as it leaves the bat will be about 4 percent higher.

To determine the ultimate impact on home run production, Tobin then analyzed a variety of models for trajectory of the baseball, accounting for gravity, air resistance and lift force due to the ball’s spin. While there was considerable variation among the models, “the salient point,” he says, “is that a 4 percent increase in ball speed, which can reasonably be expected from steroid use, can increase home run production by anywhere from 50 percent to 100 percent.”

What About the Pitchers?

Tobin applied a similar, though less extensive, mechanical analysis to pitching and found that smaller impacts were possible. He calculated that a 10 percent increase in muscle mass should increase the speed of a thrown ball by about 5 percent, or four to five miles per hours for a pitcher with a 90 mile per hour fastball. That translates to a reduction in earned run average of about 0.5 runs per game.

“That is enough to have a meaningful effect on the success of a pitcher, but it is not nearly as dramatic as the effects on home run production,” says Tobin. “The unusual sensitivity of home run production to bat speed results in much more dramatic effects, and focuses attention disproportionately on the hitters.”

A Reasonable Suspicion

Tobin is quick to acknowledge that athletes in many sports today achieve at a higher level than athletes of the past, and that this trend is not evidence of cheating. He also points out that many other changes, including adjustments in ballpark dimensions, league expansions, entry of African-American athletes, and lowering of the pitcher’s mound, could affect major league batting — although he says that none of those changes coincide with the sudden burst of home run production in the mid-1990s.

“Physics cannot tell us whether a particular home run was steroid-assisted, or even whether an extraordinary individual performance indicates the use of illicit means,” says Tobin.

But analysis of the physics, combined with physiology, yields telling results. “These results certainly do not prove that recent performances are tainted, but they suggest that some suspicion is reasonable,” he concludes.

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Article adapted by MD Sports Weblog from original press release.
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Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville, and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university’s schools is widely encouraged.

Source: Kim Thurler
Tufts University