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Anti-psychotic Drugs Could Help Fight Cancer

ScienceDaily (Aug. 13, 2009) — The observation that people taking medication for schizophrenia have lower cancer rates than other people has prompted new research revealing that anti-psychotic drugs could help treat some major cancers.
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A preliminary finding in the current online issue of the International Journal of Cancer reports that the anti-psychotic drug, pimozide, kills lung, breast and brain cancer cells in in-vitro laboratory experiments.

Several epidemiological studies have noted the low rate of cancer among schizophrenic patients. These studies found, for example, that these patients have lower rates of lung cancer than other people, even though they are more likely to smoke.

Genetic factors and the possibility of reduced cancer detection in patients have been considered and over the past decade anti-psychotic drugs have been suggested as possible mediators of this effect.

In the new study, pimozide was the most lethal of six anti-psychotic drugs tested by a team from UNSW and the University of Queensland. Rapidly-dividing cancer cells require cholesterol and lipids to grow and the researchers suspect that pimozide kills cancer cells by blocking the synthesis or movement of cholesterol and lipid in cancer cells.

Analysis of gene expression in test cancer cells showed that genes involved in the synthesis and uptake of cholesterol and lipids were boosted when pimozide was introduced.

To test the idea that pimozide acts by disrupting cholesterol homeostasis, the researchers combined pimozide with mevastatin, a drug that inhibits cholesterol production in cells. The two drugs were more lethal in combination against cancer cells than when either drug was used alone.

"The combination of pimozide and mevastatin increased cancer cell death," says UNSW researcher Dr Louise Lutze-Mann, a co-author of the study. "We needed a lower dose of each drug to kill the same amount of cells."

Although side-effects are associated with the use of high doses of these drugs – such as tremors, muscle spasms and slurred speech – these effects are considered to be tolerable in patients where other treatments have failed and the drugs will only be used short-term. These side-effects would be reduced if the drugs were used in combination with a lipid-lowering drug, such as mevastatin.

The researchers have also investigated the effects of olazapine , a "second-generation" antipsychotic drug, and found that it also kills cancer cells but has a better side-effect profile. When administered to patients, it accumulates in the lung, which suggests that it may prove to be most useful in treating lung cancer.

The researchers are now testing these drugs on tumour cells from brain cancers since these tumours are extremely difficult to treat and are frequently associated with poor patient prognosis. Patients diagnosed with glioblastoma, for example, survive less than one year.

The results are very promising as these drugs are greater than 50-fold more effective at killing glioblastoma cells than the chemotherapeutic drug currently in use. The researchers are also investigating the effects of these drugs on cells derived from drug-resistant childhood cancers where current chemotherapy has failed.

Another hopeful prospect is an investigation of another group of drugs, called SERMs, which are similar in structure to the antipsychotic drugs but have far fewer side-effects associated with them.
Adapted from materials provided by University of New South Wales, via EurekAlert!, a service of AAAS.
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Cognitive Testing, Gender And Brain Lesions May Predict Multiple Sclerosis Disease Progression Risk

ScienceDaily (Aug. 13, 2009) — Cognitive testing may help people with inactive or benign multiple sclerosis (MS) better predict their future with the disease, according to a study published in the July 29, 2009, online issue of Neurology®. Gender and brain lesions may also determine the risk of progression of MS years after diagnosis.
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By current definition, people with benign MS are those who remain "fully functional" after 15 or more years from disease onset. However, people with benign MS occasionally develop renewed disease activity or progression, and can experience severe symptoms.

For the study, researchers looked at the cognitive test results and brain scans of 63 people with benign MS during a period of five years. Of those, 43 were women and 20 were men.

The cognitive tests included verbal and visual memory, attention, concentration and the speed at which the participant processed information. Brain scans revealed the number of lesions associated with MS on the person's brain. Follow-up neurologic exams were done every six months.

The study found that nearly 30 percent of people with benign MS significantly worsened over the course of five years. People who failed more than two cognitive tests (out of 10 total) were 20 percent more likely to progress over time. Men with benign MS were nearly three times more likely to later experience signs of MS compared to women. People with more brain lesions detected on scans were also more likely to develop signs of the disease.

"Our findings strongly suggest that a person's gender, cognitive state and amount of lesions on the brain are important factors for predicting MS progression," said study author Maria Pia Amato, MD, with the University of Florence in Italy. "Our study highlights the importance of cognitively testing people with benign MS who appear to be healthy. This information might be important in tailoring the patient's treatment."

The study was supported by the Italian Multiple Sclerosis Association.
Adapted from materials provided by American Academy of Neurology.
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Older Drivers Unaware Of Risks From Medications And Driving

ScienceDaily (Aug. 13, 2009) — Most older drivers are unaware of the potential impact on driving performance associated with taking medications, according to new research from the Center for Injury Sciences at the University of Alabama at Birmingham (UAB). The findings, released by the AAA Foundation for Traffic Safety, indicate that 95 percent of those age 55 and older have one or more medical conditions, 78 percent take one or more medications, and only 28 percent have an awareness of the risks those medications might have on driving ability.
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The researchers surveyed 630 drivers ages 56 to 93. Only 18 percent reported receiving a warning from a health-care professional about potential driver-impairing (PDI) medications such as ACE inhibitors, sedatives and beta-blockers. The study found that such warnings do not increase with increasing numbers of medications used or increasing numbers of medical conditions.

"These findings indicate that health-care professionals need to take a more active role in educating their patients about the risks of PDI medications," said Paul MacLennan, Ph.D., assistant professor of surgery at UAB and the study's lead author. "Society needs to understand that PDI medications are a driving-safety issue, and there is a need for increased education geared at older drivers, their families and health professionals."

Studies have shown that certain medications are known to be associated with an increased risk for vehicle collision, according to MacLennan. Among survey respondents age 75 and older, 77 percent said they had no awareness of the risks presented from PDI medication and had not received any information on risk from health-care providers. Yet this group was most likely to have multiple medical conditions and be taking multiple medications.

"Increased knowledge and awareness by health professionals will enable them to offer suggestion on how older drivers can modify their behavior to reduce risks, such as reducing driving or increasing self-monitoring of PDI side-effects," said MacLennan. "Increased patient education by pharmacists also is a key component to addressing PDI medications and has been shown effective in increasing patient knowledge of medications."

MacLennan's collaborators on this study include Gerald McGwin, Ph.D., director of research for the UAB Center for Injury Sciences; Cynthia Owsley, Ph.D., professor of ophthalmology; and Loring Rue, M.D., chief of the section of trauma, burns and surgical critical care. Funding for the study came from the AAA Foundation for Traffic Safety.
Adapted from materials provided by University of Alabama at Birmingham.
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Oxygen Treatment Hastens Memory Loss In Alzheimer's Mice

ScienceDaily (Aug. 13, 2009) — A 65-year-old women goes into the hospital for routine hip surgery. Six months later, she develops memory loss and is later diagnosed with Alzheimer's Disease. Just a coincidence? Researchers at the University of South Florida and Vanderbilt University don't think so. They suspect that the culprit precipitating Alzheimer's disease in the elderly women may be a routine administration of high concentrations of oxygen for several hours during, or following, surgery – a hypothesis borne out in a recent animal model study.
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Dr. Gary Arendash of the Florida Alzheimer's Disease Research Center at USF and Dr. L. Jackson Roberts II at Vanderbilt University used mice genetically altered to develop abnormal levels of the protein beta amyloid, which deposits in the brain as plaques and eventually leads to Alzheimer's-like memory loss as the mice age. They found that young adult Alzheimer's mice exposed to 100-percent oxygen during several 3-hour sessions demonstrated substantial memory loss not otherwise present at their age. Young adult Alzheimer's mice exposed to normal air had no measurable memory loss, and neither did normal mice without any genetic predisposition for Alzheimer's disease.

The authors suggest that people genetically predisposed to Alzheimer's disease or with excessive amounts of beta amyloid in their brains are at increased risk of developing the disease earlier if they receive high concentrations of oxygen, known as hyperoxia. Their study is published online this month in NeuroReport.

"Although oxygen treatment beneficially increases the oxygen content of blood during or after major surgery, it also has several negative effects that we believe may trigger Alzheimer's symptoms in those destined to develop the disease," said USF neuroscientist Arendash, the study's lead author. "Our study suggests that the combination of brain beta amyloid and exposure to high concentrations of oxygen provides a perfect storm for speeding up the onset of memory loss associated with Alzheimer's Disease."

While postoperative confusion and memory problems are common and usually transient in elderly patients following surgery, some patients develop permanent Alzheimer's-like cognitive impairment that remains unexplained. Recent studies have indicated that general anesthesia administered during surgery may increase a patient's risk of Alzheimer's disease, but the laboratory studies did not use animals or people predisposed to develop the disease.

"Postoperative memory loss can be a fairly common and devastatingly irreversible problem in the elderly after major surgical procedures," said Roberts, an MD who holds an endowed chair in Pharmacology at Vanderbilt University School of Medicine. "There has been much speculation as to the cause of this memory loss, but the bottom line is that no one really knows why it happens. If all it takes to prevent this is reducing the exposure of patients to unnecessarily high concentrations of oxygen in the operating room, this would be a major contribution to geriatric medicine."

The USF-Vanderbilt study looked at 11 young adult mice genetically modified to develop memory problems as they aged, mimicking Alzheimer's disease. After behavioral tests confirmed the mice had not yet developed memory impairment at age 3 months – about age 40 in human years – the researchers exposed half the Alzheimer's mice to 100-percent oxygen for three hours, three times over the next several months. The protocol was intended to replicate initial and supplemental exposures of elderly patients in hospital operating rooms and recovery suites to high concentrations of oxygen. The other half of the mice were exposed to 21-percent oxygen, the concentration of oxygen in typical room air.

When researchers retested the mice after the final gas exposure, they found that Alzheimer's mice exposed to 100-percent oxygen performed much worse on tests measuring their memory and thinking skills than the Alzheimer's mice exposed to normal room air. In fact, the Alzheimer's mice exposed to room air demonstrated no memory loss. Moreover, exposure of young adult mice without beta amyloid protein deposited in their brains to 100-percent oxygen did not adversely affect their memories. This is consistent with studies in humans showing that exposure of young adults to high concentrations of oxygen has no harmful effects on memory.

The researchers also demonstrated that even a single 3-hour exposure to 100-percent oxygen caused memory deficits in the Alzheimer's mice. Furthermore, when they examined the brains of these mice, they found dramatic increases in levels of isofurans, products of oxygen-induced damage from toxic free radicals. The increase was not present in the brains of normal control mice exposed to the single hyperoxia treatment.

How might high concentrations of oxygen hasten memory impairment in those destined to develop Alzheimer's disease? The researchers suggest the striking increase of isofurans during surgery may be one triggering mechanism, particularly in cardiac bypass surgery where very high blood oxygen levels are routinely attained and permanent memory loss often occurs months after the surgery. Secondly, exposure to high concentrations of oxygen prompts abnormal swelling of brain cell terminals that transmit chemical messages from one brain cell to another and may further disrupt already frayed nerve cell connections in those at risk for Alzheimer's. Third, high concentrations of oxygen combined with beta amyloid plaques constricts blood vessels and decreases blood flow to the brain more than either one alone.

The authors caution that the study in mice may or may not accurately reflect the effects of hyperoxia in human surgery patients.

"Nonetheless, our results call into question the wide use of unnecessarily high concentrations of oxygen during and/or following major surgery in the elderly," Roberts said. "These oxygen concentrations often far exceed that required to maintain normal hemoglobin saturation in elderly patients undergoing surgery."

Arendash published initial evidence in 1987 that Alzheimer's disease starts in the brain several decades before memory loss occurs. His research focuses on developing promising therapeutics in Alzheimer's mice that can quickly be transferred to human clinical trials. Roberts, an expert on the role of free radicals and oxidative injury in disease, has discovered novel products of free radical damage that may be associated with several age-related brain dysfunctions. Also participating in the hyperoxia study were Dr. Takashi Mori of Saitama Medical University (Japan) and Dr. Kenneth Hensley of the Oklahoma Medical Research Foundation.

The study was supported by grants within the Florida Alzheimer's Disease Research Center, a statewide project sponsored by the National Institute on Aging, and a National Institutes of Health Merit Award to Dr. Roberts.

An estimated 10 million baby boomers will develop Alzheimer's disease in their lifetime. The disease usually begins after age 60, and risk rises with aging. The direct and indirect cost of Alzheimer's disease in the United States is a staggering $150 billion a year, according to the national Alzheimer's Association.
Adapted from materials provided by University of South Florida Health.
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Female Supervisors More Susceptible To Workplace Sexual Harassment

ScienceDaily (Aug. 13, 2009) — Women who hold supervisory positions are more likely to be sexually harassed at work, according to the first-ever, large-scale longitudinal study to examine workplace power, gender and sexual harassment.
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The study, which will be presented at the 104th annual meeting of the American Sociological Association, reveals that nearly fifty percent of women supervisors, but only one-third of women who do not supervise others, reported sexual harassment in the workplace. In more conservative models with stringent statistical controls, women supervisors were 137 percent more likely to be sexually harassed than women who did not hold managerial roles. While supervisory status increased the likelihood of harassment among women, it did not significantly impact the likelihood for men.

"This study provides the strongest evidence to date supporting the theory that sexual harassment is less about sexual desire than about control and domination," said Heather McLaughlin, a sociologist at the University of Minnesota and the study's primary investigator. "Male co-workers, clients and supervisors seem to be using harassment as an equalizer against women in power."

McLaughlin and her co-authors examined data from the 2003 and 2004 waves of the Youth Development Study (YDS), a prospective study of adolescents that began in 1988 with a sample of 1,010 ninth graders in the St. Paul, Minnesota, public school district and has continued near annually since. Respondents were approximately 29 and 30 years old during the 2003 and 2004 waves. The analysis was supplemented with in-depth interviews with a subset of the YDS survey respondents.

The sociologists found that, in addition to workplace power, gender expression was a strong predictor of workplace harassment. Men who reported higher levels of femininity were more likely to have experienced harassment than less feminine men. More feminine men were at a greater risk of experiencing more severe or multiple forms of sexual harassment (as were female supervisors).

In a separate analysis examining perceived and self-reported sexual orientation, study respondents who reported being labeled as non-heterosexual by others or who self-identified as non-heterosexual (gay, lesbian, bisexual, unsure, other) were nearly twice as likely to experience harassment.

Researchers also found that those who reported harassment in the first year (2003) were 6.5 times more likely to experience harassment in the following year. The most common scenario reported by survey respondents involved male harassers and female targets, while males harassing other males was the second most frequent situation.

McLaughlin co-authored the study with sociologists Christopher Uggen, chair of the University of Minnesota's sociology department and a distinguished McKnight professor of sociology, and Amy Blackstone, associate professor of sociology at the University of Maine. The multi-method research was supported by grants from the National Institutes of Mental Health and the National Institute of Child Health and Human Development.

The paper, "A Longitudinal Analysis of Gender, Power and Sexual Harassment in Young Adulthood," will be presented on Saturday, Aug. 8, at the American Sociological Association's 104th annual meeting.
Adapted from materials provided by American Sociological Association, via EurekAlert!, a service of AAAS.
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Power And Sexual Harassment -- Men And Women See Things Differently (Apr. 6, 2007) — In the hands of the wrong person, power can be dangerous. That's especially the case in the workplace, where the abuse of power can lead to sexual ... > read more
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Women Experience More Sexual Harassment In Work Groups With Male, Female Balance (Nov. 12, 2008) — Despite common assumptions, new research suggests that women are not more likely to be sexually harassed when they are the minority or majority in a work group. Instead, researchers found that in ... > read more
Both Boys And Girls Negatively Affected By Sexual Harassment (May 13, 2008) — A new study in Psychology of Women Quarterly explored the outcomes of sexual harassment on both boys and girls. While girls were harassed more frequently, boys were indirectly yet negatively affected ... > read more
Sexual Harassment 10 Times More Likely In Casual And Contract Jobs (Sep. 11, 2008) — Women employed in casual and contract jobs are up to 10 times more likely to experience unwanted sexual advances than those in permanent full time positions, a University of Melbourne study has ... > read more
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ScienceDaily: Your source for the latest research news and science breakthroughs -- updated daily
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Scientists Find A Common Link Of Bird Flocks, Breast Milk And Trust

ScienceDaily (Aug. 13, 2009) — What do flocks of birds have in common with trust, monogamy, and even breast milk? According to a new report in the journal Science, they are regulated by virtually identical neurochemicals in the brain, known as oxytocin in mammals and mesotocin in birds.
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* Oxytocin

Neurobiologists at Indiana University showed that if the actions of mesotocin are blocked in the brains of zebra finches, a highly social songbird, the birds shift their social preferences. They spend significantly less time with familiar individuals and more time with unfamiliar individuals. The birds also become less social, preferring to spend less time with a large group of same-sex birds and more time with a smaller group. Conversely, if birds are administered mesotocin instead of the blocker, the finches become more social and prefer familiar partners.

Perhaps most striking is the fact that none of the treatments affect males -- only females.

According to James Goodson, lead author on the study, the sex differences in birds provide important clues to the evolutionary history of oxytocin functions in humans and other mammals. "Oxytocin is an evolutionarily descendant of mesotocin and has long been associated with female reproductive functions -- things such as pair bonding with males, giving birth, providing maternal care and ejecting milk for infants," said Goodson.

Goodson and colleagues have found hints of similar processes in fish, and he speculates that oxytocin-like neuropeptides have played special roles in female affiliation ever since the peptides first evolved. That was sometime around 450 million years ago, about the same time that jaws evolved.

"The ancient properties of this system appear to be retained in all major vertebrate groups, and date back to our common ancestor with sharks," says co-author Marcy Kingsbury, associate scientist at IU Bloomington.

But if all vertebrates possess similar neuropeptide circuits, why don't they all live in big groups -- flocks, schools or herds? A possible answer to that question is provided in the second part of the Science study. The authors speculated that the behavioral actions of mesotocin may differ across species depending upon the distribution of "receptors" for the chemical in the brain -- that is, places where mesotocin can attach to brain cells and alter their activity.

Using a radioactive compound that attaches to oxytocin-like receptors, the authors mapped the distribution of receptors in three finch species that form flocks and two species that are territorial and highly aggressive. What they found was that the flocking species had many more receptors in a part of the brain known as the lateral septum. And when they blocked those receptors in female zebra finches, the birds became less social.

According to Goodson, these findings suggest that it is actually the concentration and location of receptors that determines whether an individual prefers spending time in large groups. Natural selection could act to increase the number of receptors expressed by certain lateral septum neurons, or by altering the regions where receptor genes are expressed, depending on whether female sociality is favored or not among the individuals of a species.

If Goodson's discovery holds true for other birds and even mammals, the concentration of receptors for mesotocin (and oxytocin) in the lateral septum could accurately predict whether an individual is naturally gregarious.

"The lateral septum is structurally very similar in reptiles, birds and mammals," Goodson said. "To our knowledge, it plays an important role in the social and reproductive behaviors of all land vertebrates."

What might be next for Goodson's research group?

"We still don't understand why mesotocin and oxytocin are so potent in females, but not always in males," Goodson said. "And we also don't fully understand how the lateral septum functions to influence sociality." But he is convinced that his group's ongoing studies of songbirds will soon provide the answers.
Adapted from materials provided by Indiana University.
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Zebra finches in congress. (Credit: Photo copyright Graeme S. Chapman; Courtesy of Indiana University)

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