(Ivanhoe Newswire) — Among patients receiving immunosuppressive therapy for severe aplastic anemia, a condition in which the bone marrow is unable to produce blood cells, the length of telomeres (chromosome markers of biological aging) was clearly associated with a higher rate of relapse and lower overall survival.

Severe aplastic anemia is characterized by life-threateningly low blood cell counts, but the condition can be treated by bone marrow transplant or immunosuppressive drugs. In older patients, or when an appropriate donor is not available, immunosuppression can be effective, although relapse can occur, as can chromosome abnormalities in bone marrow cells that accompany cancers in the blood ““ a condition referred to as clonal evolution.

Researchers have identified certain cell abnormalities as risk factors in bone marrow failure. “Mutations in telomerase complex genes resulting in extremely short telomeres have been described in some patients with apparently acquired severe aplastic anemia,” the authors were quoted as saying.

The telomere, a structure at the end of a chromosome that shortens with each cell division, functions as a protective cap to prevent erosion of genomic DNA during cell division.

Phillip Scheinberg, M.D., of the National Institutes of Health, Bethesda, MD., and colleagues conducted a study to determine the effect of telomere attrition in acquired severe aplastic anemia by measuring telomere length prior to immunosuppressive therapy. The study included 183 patients with severe aplastic anemia who were treated from 2000 to 2008.

Of the patients studied, 104 responded to immunosuppressive therapy. The researchers found that there was no correlation between telomere length and the probability of response to the therapy. The response rate for patients in the first quartile (shortest telomere lengths) was 56.5 percent; in the second quartile, 54.3 percent; in the third quartile, 60 percent; and in the fourth quartile, 56.5 percent.

Additional analysis, however, demonstrated that telomere length was associated with relapse, clonal evolution, and mortality. The shorter the telomere, the greater the probability of disease relapse. The probability of clonal evolution was higher in patients in the first quartile (24.5 percent) than in quartiles 2 through 4 (8.4 percent).

“Survival between these two groups differed, with 66 percent surviving 6 years in the first quartile compared with 83.8 percent in quartiles 2 through 4,” the researchers were quoted as saying.

“In conclusion, our data show that in a cohort of patients with severe aplastic anemia receiving immunosuppressive therapy, telomere length was not associated with response but was associated with risk of relapse, clonal evolution, and overall survival.”

SOURCE:  Journal of the American Medical Association (JAMA), September 22/29, 2010.

(Ivanhoe Newswire) ““ So far in 2010, 7,950 people have died from endometrial cancer and there are 43,470 new cases. Studies on animals showed that obese women, who are at a higher risk for endometrial cancer, should take vitamin D to reduce their risk.

The study showed that 25 percent of obese mice given vitamin D supplements in their diet developed endometrial cancer, while 67 percent of mice not given vitamin D developed cancer. Vitamin D did nothing for mice of normal weight, whether or not they took vitamin D supplements. All of the mice were already at an increased risk for cancer because they lost one of two PTEN tumor suppressor genes, and without both they are at a much higher risk for human endometrial cancer.

“Vitamin D has been shown to be helpful in a number of cancers, but for endometrial cancer, our study suggests it protects only against cancer that develops due to obesity,” the study’s lead investigator, Leena Hilakivi-Clarke, PhD, a Professor of Oncology was quoted as saying. “Still, if these results are confirmed in women, use of vitamin D may be a wonderfully simple way to reduce endometrial cancer risk.”

“Until further studies are done, I think the best advice for women concerned about their risk is to take vitamin D supplements or spend a few more minutes each week in the sun. This vitamin has shown many health benefits in addition to the promise suggested by our mouse study,” explains Dr. Leena Hilakivi-Clarke.

It is best for women to remain at a healthy weight, not only to prevent endometrial cancer, but maintaining a healthy weight has many other health benefits. “However, since over 50% of women in the US are overweight or obese, and losing weight is difficult, other means are needed to prevent endometrial cancer in these women. One way is to use progesterone, but it increases breast cancer risk. Vitamin D supplements are likely to be safer than, for example, progesterone,” says Dr. Leena Hilakivi-Clarke.

Previous studies have shown that obesity in women increases human endometrial cancer by two to six times. Recent research published by the National Institutes of Health on the protective effects of vitamin D on endometrial cancer showed no overall benefit, but the study did not investigate whether vitamin D was effective in obese women, Dr. Hilakivi-Clarke says. For that reason, researchers focused on weight and endometrial cancer.

They used the best animal model available to look at endometrial cancer ““ the PTEN knock-out mice. “Loss of PTEN is a common event in endometrial cancer in women,” Hilakivi-Clarke says. The mice were divided into four groups: one group was fed a normal diet, another was fed a normal diet with vitamin D supplements, another was fed a high-fat diet, and the last group was fed a high-fat diet with vitamin D supplements.

The study showed that of the mice fed a high-fat diet, 67 percent developed endometrial cancer, while only 25 percent fed high-fat diets along with vitamin D developed it. “In the obese mice, vitamin D offered a very strong, very significant protective effect,” Hilakivi-Clarke says.

The researchers aren’t sure as to why vitamin D reduces the chance of endometrial cancer in obese mice, but they presume that obese mice produce less osteopontin, which makes cancer more aggressive. They also believe the obese mice are producing more E-cadherin, which stops cancer form metastasizing.

“But we really don’t know why dietary vitamin D works so well in our obese mice,” Hilakivi says. “We are currently investigating the mechanisms, and we are hopeful that we can find an answer.”

SOURCE: Cancer Prevention Research, published online September 20, 2010

Press release from PLoS Medicine

Community Health Workers can safely and effectively provide integrated management of pneumonia and malaria to communities by dispensing amoxicillin to children with non-severe pneumonia and artemether-lumefantrine to children with malaria (after using rapid diagnostic tests). Furthermore, these activities result in a significant increase in the proportion of appropriately-timed antibiotic treatment for non-severe pneumonia and in a significant decrease in inappropriate use of antimalarials. These are the results from a study by Kojo Yeboah-Antwi from the Boston School of Public health, USA, and colleagues and published in this week’s PLoS Medicine.

The authors conducted their study in Zambia where 3125 children with fever and/or fast breathing were managed by community health workers over a 12-month period. Community health workers were matched and randomly allocated to the intervention arm (in which community health workers performed rapid diagnostic tests, treated rapid diagnostic test-positive children with the anti-malarial drug, artemether-lumefantrine, and treated children with non-severe pneumonia with amoxicillin) and the control arm (in which community health workers did not perform rapid diagnostic tests, treated all febrile children with artemether-lumefantrine and referred those with signs of pneumonia to the health facility, as per the Zambian Ministry of Health policy.

A significant proportion of children managed in the intervention arm [68.2% (247/362)] received appropriately-timed antibiotic treatment for non-severe pneumonia compared to 13.3% (22/203) in the control arm. There was also a significant decrease in inappropriate use of antimalarials when treatment was based on the results of rapid diagnostic tests. In the intervention group 27.5% (265/963) of children with fever received malaria treatment compared to 99.1% (2066/2084) of children in the control group.

The authors conclude: “The capacity of [community health workers] to use [rapid diagnostic tests], artemether-lumefantrine and amoxicillin to manage both malaria and pneumonia at the community level is promising and has the potential to reduce over usage of artemether-lumefantrine as well as to provide early and appropriate treatment to children with non-severe pneumonia.”

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On the Net:

• Public Library of Science
• PLoS Medicine

(Ivanhoe Newswire) ““ A specific region of the brain appears to be bigger in people who are good at tuning into their own thoughts and reflecting upon their decisions. Introspection, or “thinking about your thinking”, is a key aspect of human consciousness, but scientists have already discovered differences in people’s ability to introspect.

The researchers along with Prof. Geraint Rees from University College London, suggests that the volume of gray matter in the anterior prefrontal cortex of the brain, which lies right behind our eyes, is a strong indicator of a person’s introspective ability. They also believe that the white matter connected to this area is also playing a major role in introspective thinking. The scientists are unsure of how the tow matters and introspection work, however they are sure that people with more gray matter in that area tend to be more introspective.

In the future this knowledge may help doctors to understand what brain injuries will do to a person’s ability to introspectively think. Eventually, this could lead to tailored treatments for stroke victims or people who have had major head trauma or brain injury.

“Take the example of two patients with mental illness””one who is aware of their illness and one who is not,” Stephen Fleming, one of the authors of the study, from University College London was quoted as saying. “The first person is likely to take their medication, but the second is less likely. If we understand self-awareness at the neurological level, then perhaps we can also adapt treatments and develop training strategies for these patients.”

The study recruited 32 healthy human participants and showed them two screens, each having six patterned patches. One screen had one patch that was brighter than all the rest and the participants were to look at the screens then say which screen had the brighter patch and rate how confident there answer is. While the experiment was taking place their brains were being scanned by an MRI. The research team designed the task to be difficult, and for the participants to have to use introspection to correctly answer and judge their confidence. The researchers thought that those who were good at introspection would be confident after they knew their answer was right and unconfident when their answer was wrong. They altered the patches every time to.

“It’s like that show, ‘Who Wants to Be a Millionaire?'” Ramiona Weil, form the Wellcome Trust Center Neuroimaging at the University of London was quoted as saying. “An introspective contestant will go with his or her final answer when they are quite sure of it, and perhaps phone a friend when they are unsure. But, a contestant who is less introspective would not be as effective at judging how likely their answer is to be correct.”

“We want to know why we are aware of some mental processes while others proceed in the absence of consciousness,” said Fleming. “There may be different levels of consciousness, ranging from simply having an experience, to reflecting upon that experience. Introspection is on the higher end of this spectrum””by measuring this process and relating it to the brain we hope to gain insight into the biology of conscious thought.”

SOURCE: Science, published online September 16, 2010

Scientists reported new evidence on the effectiveness of that old folk remedy “” cranberry juice “” for urinary tract infections at the ACS’ 240th National Meeting. “A number of controlled clinical trials “” these are carefully designed and conducted scientific studies done in humans “” have concluded that cranberry juice really is effective for preventing urinary tract infections,” said Terri Anne Camesano, Ph.D., who led the study. “That has important implications, considering the size of the problem and the health care costs involved.”

Estimates suggest that urinary tract infections (UTIs) account for about 8 million medical visits each year, at a total cost of more than $1.6 billion. Camesano, who is with the Worcester Polytechnic Institute, said the study set out to shed light on how cranberry juice fights E. coli, the most common cause of UTIs. The study involved growing strains of E. coli in urine collected from healthy volunteers before and after consumption of cranberry juice cocktail. The scientists then tested the E. coli for their ability to stick together and form biofilms. Biofilms are thin, slimy layers that provide an environment for bacteria to thrive.

The scientists concluded that cranberry juice cocktail prevents E. coli from sticking to other bacteria and the surface of a plastic petri dish. E. coli that doesn’t stick has a better chance of being flushed out of the urinary track. The results suggest that the beneficial substances in cranberry juice could reach the urinary tract and prevent bacterial adhesion within 8 hours after consumption of cranberry juice.

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On the Net:

• American Chemical Society

A new report released Tuesday by the Brookings Institution finds that obesity costs the U.S. $215 billion annually in direct medical expenses and indirect productivity losses.

The study found that medical costs for obese adults are $147 billion dollars more per year than for those of normal weight.  For children, the added costs due to obesity are $14.3 billion per year.

“The overall economic impact of obesity in the US appears to be substantial,” wrote researchers Ross Hammond and Ruth Levine of the Brookings economic studies program.

“Medical costs appear to have increased dramatically over the last decade and may continue to grow with future increases in rates of overweight and obesity in US adults and children, perhaps substantially,” they wrote in the journal Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.

In addition to the direct costs of obesity, the indirect costs include absenteeism, lost productivity, disability and premature death.

The researchers also found that transportation costs may be higher due to the added weight of obese travelers.

“Total productivity costs are likely substantial, perhaps as high as 66 billion dollars annually for the US,” the researchers wrote.

Although previous research has examined the costs of obesity, it did not focus specifically on the potential external effects, such as transportation and environmental effects.

“Increases in body weight among Americans mean that more fuel and, potentially, larger vehicles are needed to transport the same number of commuters and travelers each year,” the researchers wrote.

“This produces a direct cost (in the form of greater spending on fuel), as well as potential indirect costs in the form of greater greenhouse gas emissions.”

Obesity may also have “human capital” costs, such as a diminished ability to attain higher levels of education.  However, these effects are hard to calculate.

“Women who had been obese in the baseline survey had significantly fewer years of school completed (0.3 year on average),” the researchers said.

“Likewise, they were less likely to be married, had lower household incomes, and higher rates of poverty. For men, the only statistically significant correlation was for marital status.”

The report found that obesity has grown into a significant global epidemic, with some half a billion people worldwide classified as overweight in 2002.

In the United States, more than two-thirds of adults are now overweight.  This includes one-third of the U.S. adult population that are now considered obese.

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On the Net:

• Brookings Institution
• The full report, entitled “The economic impact of obesity in the United States”, can be downloaded here

A new Iowa State University study has found that corn bred to contain increased levels of beta-carotene is a good source of vitamin A. The discovery gives added support to the promise of biofortified corn being developed through conventional plant breeding as an effective tool to combat vitamin A deficiency in developing countries.

Beta-carotene is converted in the body to vitamin A. The researchers found that the beta-carotene in the corn was converted to vitamin A at a higher rate than what’s predicted for corn, and higher than the rate for beta-carotene in vegetables – including spinach and carrots, among others.

Wendy White, an ISU associate professor of food science and human nutrition, led the six-week study conducted at Iowa State’s Nutrition and Wellness Research Center. The results validate the promise of ‘orange’ maize that will soon be released to combat vitamin A deficiency in sub-Saharan Africa.

According to a 2009 World Health Organization estimate, vitamin A is deficient in more than half of the world’s countries, with Africa and Southeast Asia having the highest deficiencies. Medical researchers have reported vitamin A deficiency to be one of the most serious causes of malnutrition in developing countries and can cause blindness, poor immune function and even premature death — particularly in young children.
Working with HarvestPlus on biofortified corn

The effort to biofortify corn with beta-carotene is being led by HarvestPlus (http://www.harvestplus.org/) – a global research initiative directed, in part, by the Washington, D.C.-based International Food Policy Research Institute.

“Biofortification is a revolutionary approach to combating micronutrient malnutrition in developing countries and it has the potential to be self-sustaining,” White said. “The seeds are bred by plant breeders to be naturally high in key micronutrients, such as vitamin A, zinc and/or iron. And then the seeds will ultimately be distributed to poor farmers in developing countries and they’ll be able to reproduce the seeds so they can share them with their communities.

“This study answered a major feasibility concern for the biofortification program because plant breeders were quickly successful in ramping up the beta-carotene content in the corn, but then the question was, ‘Would it be available to be absorbed and utilized by people?,'” she continued. “So what we’ve shown is the beta-carotene is bioavailable to be converted to vitamin A in the body, and much more so than previously expected.”

The study was posted online this month by the American Journal of Clinical Nutrition, which is published by the American Society for Nutrition. Iowa State graduate students Shanshan Li and Angela Nugroho, and Purdue University researcher Torbert Rocheford — who was at the University of Illinois at Urbana-Champaign at the time the research was conducted — collaborated with White on the study. An abstract is available at: http://www.ajcn.org/cgi/content/abstract/ajcn.2010.29802v1.

The researchers had their six healthy female subjects, between the ages of 18 and 30, consume 250-gram portions of maize porridge three times at two-week intervals. Each subject consumed the beta-carotene biofortified maize porridge, as well as two white maize control porridges that were naturally devoid of beta-carotene, but contained known amounts of added beta-carotene or vitamin A. Blood samples were drawn after they ate each porridge to determine the amount of vitamin A that was absorbed in the blood.
An important step in fighting malnutrition

White says the study’s findings provide an important step in the process of making the biofortified corn available to the people who desperately need vitamin A in their diets.

“These [their subjects] were mostly graduate students based in the U.S. who were screened for excellent health. So this study was conducted under ideal conditions,” White said. “And so the next step — knowing that under ideal conditions the beta-carotene can be well absorbed — is to take it into a more field setting.”

White reports that there is already a pilot program being conducted in Zambia to feed the beta-carotene, biofortified maize to young children to increase their vitamin A intake. HarvestPlus is conducting that project and supported the development of the maize for the Iowa State study.

The HarvestPlus Challenge Program was launched when it became the first recipient of funding for biofortification research granted by the Bill and Melinda Gates Foundation.

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On the Net:

• Iowa State University

The practice of giving infants a small amount of sugar when performing invasive procedures does not reduce the amount of pain they feel, and could actually lead to brain damage, according to a new study published Wednesday in the medical journal The Lancet.

Previous studies, including a 2001 series of clinical trials performed by doctors, found that by giving one-tenth of a gram of sucrose to babies before completing a procedure such as installing an antibiotic drip or taking a blood sample would have an analgesic effect.

However, according to Guardian Health Correspondent Denis Campbell, the new study–which was funded by the Medical Research Council and completed at University College London (UCL)–discovered that previous research was “flawed” because the researchers involved “relied on the change in the baby’s facial expression upon receiving the sugar, from puckered-up to relaxed, as proof that it works.”

The UCL team, was led by Dr. Rebeccah Slater from the school’s Neuroscience, Physiology and Pharmacology departments, simulated drawing blood samples from 59 newborns by pricking their heels with a small blade. The subjects were given either sterile water or a solution of concentrated sugar, delivered orally through a small syringe, and the researchers monitored pain activity in the brain and spine by using electrodes. They observed no noticeable difference in the two groups, according to Campbell’s September 2 report.

“The absence of evidence for an analgesic action of sucrose in this study, together with uncertainty over the long-term benefits of repeated sucrose administration, suggest that sucrose should not be used routinely for procedural pain in infants without further investigation,” Slater’s team said, according to Wednesday reports from French news agency AFP.

“Our findings indicate that sucrose is not an effective pain relief drug. This is especially important in view of the increasing evidence that pain may cause short and long-term adverse effects on infant neurodevelopment,” Slater also told Campbell. “While we remain unsure of the impact sucrose has, we suggest that it is not used routinely to relieve pain in infants without further investigation.”

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On the Net:

• The Lancet
• Medical Research Council
• University College London (UCL)

US health regulators are working out possible restrictions on popular cough suppressants in hopes to stop cases of abuse that send thousands of people to the hospital each year.

The Food and Drug Administration posted its review on Tuesday of dextromethorphan, an ingredient found in over a hundred non-prescription medications that is often abused for its euphoric effects. “Robotripping,” as it is known among abusers, involves taking more than 25 times the recommended dosage of a cold medicine. The problem is most often associated with teenagers.

High doses of the drug can cause increased blood pressure, heart rate and fever. Abusers can also suffer side effects from other ingredients found in cough medicines, such as acetaminophen, which is linked to liver damage.

The drug is typically viewed as a safe, easy-to-use medication. But the psychoactive effects it can cause, “is sought after by those seeking to alter their mental state,” states the FDA in a review.

Inappropriate use of the ingredient was linked to roughly 8,000 emergency room visits in 2008, according to the FDA. That number was up by more than 70 percent from 2004.

Analysis by the FDA concluded that dextromethorphan is abused less often than the popular painkiller codeine, but, more often than pseudophedrine, a cold medicine ingredient that can be processed into methamphetamine.

The FDA is now looking to reconsider how it regulates the drug after the Drug Enforcement Agency raised concerns about the increasing abuse among adolescents.

The FDA will ask a panel of outside experts on September 14 whether dextromethorphan should be available only as a prescription. The agency is not required to follow the panel’s advice, though it usually does.

Mandating a prescription for cough suppressants that have dextromethorphan would be a major upset for over-the-counter drug makers, which use the drug in dozens of cold medications.

Brands such as Wyeth’s Dimetapp, Bayer’s Alka-Seltzer Flu Plus and Proctor and Gamble’s Vicks cough medicines all contain dextromethorphan. The drug is available in pills, capsules, liquids and other forms.

Most industry experts do not believe the FDA will impose a prescription on those products due to the enormous workload it would create for doctors and pharmacists.

A possible alternative would be to place such medicines behind the counter, although the FDA review did not disclose any specific proposals.

The over-the-counter industry supports the prohibition of sales of the medicines to people under the age of 18. Such age restrictions would require legal changes, and the industry’s trade association has lobbied on the issue at the state and federal levels.

The Consumer Healthcare Products Association has been working to reduce abuse of over-the-counter drugs since 2003 by sponsoring educational campaigns that target parents, teenagers and school nurses, a spokeswoman for the agency told the Associated Press.

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On the Net:

• FDA
• Drug Enforcement Agency
• Consumer Healthcare Products Association

Aug. 28-Sept. 1, 2010, Amsterdam, the Netherlands

Mental disorders, such as depression, anxiety disorders, addiction and schizophrenia are the core challenge of most health care systems around the world. In the EU alone, each year 27% of the total adult population ““ this corresponds to 83 Million citizens ““ suffer from mental disorders. Depression alone affects almost 20 million ranking in the EU as the most disabling disorder of all diseases. Unless appropriately treated, mental disorders are typically associated with a wide range of complications and sequelae for the subjects affected, their partners and families as well as society as a whole, and they can be lethal. Suicide ““ a frequent complication of depression and other mental disorders ““ is a major cause of premature death in Europe with over 160.000 completed suicides every year; rates of attempted suicides are at least 10 times higher. Nevertheless ““ despite the tremendous suffering and burden of mental disorder and the fact that mental disorders are treatable ““ the majority of persons with mental disorders in the EU remain untreated.

The EU over the past three years has recognized with increasing emphasis the urgent need to change this, calling for concerted mental health action on all levels: science and research, improved public health and outreach activities and improved policies in its member states. The 2008 ‘European Pact for Mental Health and Well-being’ reflects the EU’s strong commitment for this mission, highlighting that mental health and well-being in the population is a key resource for the success of the EU as a knowledge-based society and economy. Confronting the high and increasing prevalence of mental disorders and their currently deficient care in many areas, health care systems and schemes are encouraged to act, striving for improved early recognition and diagnosis and ensuring the provision of adequate and state of the art treatment and comprehensive rehabilitation programmes for all.

Mental disorders are “complex disorders of the brain”, bound to the way we perceive, think, feel and behave. Understanding such brain dysfunctions in mental disorders is of core relevance for their prevention and their treatment. The interdisciplinary field of neuropsychopharmacology links the core disciplines of neuroscience, psychology and pharmacology and is devoted to this aim. It covers basic and clinical neuroscience from the molecule to system approaches over the establishment of improved diagnostic and treatment standards to fostering their implementation in the health care system for patients with neurological and mental disorders. The European College of Neuropsychopharmacology (ECNP) is Europe’s largest and most comprehensive interdisciplinary forum in this field, dedicated to translating new knowledge on fundamental disease mechanisms into clinical practice, paving the way for improved pharmacological and non drug treatments for the prevention and treatment of all mental disorders and disorders of the brain in general.

The 23rd ECNP Congress 2010 in Amsterdam is Europe’s leading and largest scientific meeting on mental health in Europe, providing insight into the latest achievements in brain research and treatment, providing a unique and stimulating forum for scientists and clinicians in the mental health field.

Mental health: an ever-changing challenge

Mental disorders cause immense suffering for individuals, families and communities, and represent over all and by far the leading cause of disability-associated burden in the EU of all diseases. Across the EU, pressure is being put on the health, the social welfare and the educational systems as well as the labour market, employers and economy in general. Due to the financial and economic crisis, the situation since 2008 has aggravated and poses even more and new challenges to these systems.

In its communication ‘Driving European recovery’, the European Commission highlights the need of supporting the EU population through the crisis and of reducing its human cost [1]. A key aspect in this context is to minimise its harmful impact on mental health, which is based on a complex interaction between neuropsychopharmacological and psychosocial factors. The crisis is not only believed to have a harmful effect on the provision of the already deficient health care system, but is also believed to be associated with a deterioration of several socio-economic determinants of mental health and well-being. While protective psychosocial factors, such as a stable professional and social life, get weakened, risks increase: impaired social contacts due to unemployment, social isolation, financial hardship, lack of personal recognition, fear and uncertainty about the future, etc. The European Union, therefore, has identified specific challenges and called for action in five priority areas: prevention of depression and suicide, mental health in youth and education, mental health in older people, mental health in workplace settings, and combating stigma and social exclusion.

The human brain, the most complex structure ever investigated by science, is the basis of our behaviour, mental functions and inner life. Over the past decades, new techniques of investigation of brain structure and function have become available, allowing further penetration of the mysteries of human feelings, thoughts, and emotions, and consequently even human values, relationships, and belief. Today scientists are truly beginning to learn about the structure and function of the human brain, which is physically shaped by contributions from our genes as well as from our experience. This understanding strengthens the view that mental disorders are both caused and can be treated by biological and experiential processes, working together. As the breathtaking progress in modern neuropsychopharmacology begins to integrate knowledge from biological as well as behavioural sciences, a fundamental realisation is taking place that treatment of mental disorders works ““ whether in the form of a somatic intervention such as a medication, or a psychosocial intervention such as psychotherapy ““ by actually changing the brain.

In recent decades, a wealth of information has become available about brain function and dysfunction in neuropsychiatric disorders. As a consequence, many people have benefited from treatments that have arisen from our understanding of how the brain works and how it may be disordered in neuropsychiatric illnesses.

Neuropsychopharmacology: a comprehensive, interdisciplinary approach

Neuropsychopharmacology is the trans-disciplinary field of science that is of core relevance for examining and understanding how the brain works and functions. As such it includes many disciplines: the neurosciences (e.g. molecular biology, genetics, chronobiology, neuroimmunology, brain imaging), the psychological sciences (e.g. cognition, emotion, behaviour and environmental interactions), psychopharmacology (neurochemistry, pharmacodynamics and drug action), and the respective applied clinical fields (psychiatry, psychotherapy, clinical psychology and neurology.

The goal of neuropsychopharmacology is to understand (1) how the brain works and functions and how and why it may get dysfunctional promoting disorders of the brain. (2) Moreover it is the field that allows the derivation of effective pharmacological interventions, to treat and to prevent mental disorders. This implies to develop specific therapeutic agents to regulate the neurobiological mechanisms of mental disorders, understanding the causes of mental disorders and the investigation of the effect of drugs on the central nervous system (CNS), respectively their use in treating disorders such as anxiety, mania, depression, schizophrenia, dementia, addictive and neurological disorders in the most rational and empirical manner.

Clinical advances: from molecules to effective treatments

The pharmacological progress achieved in recent decades is based on fundamental biochemical and physiological discoveries, translated into clinical practice through randomised, double-blind and placebo-controlled drug studies.

Progress in neuropsychopharmacology has contributed in a crucial way to the fundamental transformation of our mental health systems, allowing in particular patients with severe mental disorders such as psychotic disorders and schizophrenia as well as recurrent and chronic depression to avoid long-term hospitalization and disability and to live and function independently in the community. So-called atypical antipsychotics were the outcome of a search for efficacious drugs for psychotic disorders showing a better tolerability profile than conventional neuroleptics, especially with regard to limiting motor side effects such as tardive dyskinesia improving significantly the prognosis and quality of life of patients affected. Similarly, the introduction of new antidepressants, including the generations of new selective serotonin reuptake inhibitors (SSRIs) that have fewer adverse effects and pose less danger in overdose than older agents, have improved dramatically the situation and prognosis of patients with anxiety and depressive disorders allowing the majority of patients to live without significant impairment and disability.

However, research in neuropsychopharmacology has also informed exciting non-pharmacological developments. One example are chronotherapeutics, which comprise direct manipulations of sleep (e.g. wake therapies) as well as controlled exposure to environmental cues (e.g. light therapy) in order to achieve therapeutic effects in patients with mental disorders. Normalisation of circadian rhythms by chronotherapeutics represents a promising new direction in the search for novel non-pharmacological and pharmacological treatments that might avoid the limitations of current drug treatments in this field. Benefits through chronotherapeutic applications have been achieved for a broad range of patients with depression, bipolar disorder, seasonal affective disorder (SAD), premenstrual dysphoric disorder, bulimia nervosa, attention-deficit/hyperactivity disorder (ADHD), dementia, Parkinson´s disease, and shift and jet lag disturbances [7].

Another example is the identification of areas in the central nervous system that correlate with pathological mood states, suggesting targets for novel therapeutic interventions. Through modern imaging techniques including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuronal activity in psychiatric conditions can be monitored and measured. Modern imaging studies of the brain circuitry underlying normal and pathological behaviours may contribute to a better understanding of the neural basis of mental disorders and identify novel targets for pharmacological treatment. Brain imaging has revealed a breakdown in normal patterns of emotional processing that impairs the ability to suppress negative emotional states. Mood disturbances thus may reflect the exaggeration of emotional responses or abnormalities in emotional processing. Recent findings have identified an extended neural network during self-referential processing in the brain, contributing to the exploration of the concrete neural bases of the depressive self [3]. Imaging researchers are also studying depression-related circuits to see how they may arise from genetic variations known to put people at risk for depression. Imaging genetics is a novel research strategy that attempts to identify gene effects with regard to the brain and has provided significant contributions to the understanding of the complex impact of hereditary factors on psychiatric illness.

Clinical advances based on neuropsychopharmacological research are enabling people struck with mental disorders to make the way from isolation back to social reintegration.

Neuropsychopharmacology: mental disorders and beyond

In recent years, neuropsychopharmacology has expanded its interdisciplinary focus, and dialogues with other medical fields such as internal medicine have been initiated. The interaction between mental disorders and somatic disease is explored thoroughly, and the role of mental disorders in increasing vulnerability to physical morbidity and poorer outcomes is well documented [8] [9]. Mental disorders are frequently associated with metabolic disorders and cardiovascular disease, with evidence for reciprocal pathways and interactions. For example, chronic depression increases the risk for diabetes; conversely, in adult diabetics depression is much more frequent compared to metabolically healthy subjects [6]. Furthermore, research has shown links between depression and anxiety, and cardiovascular and cerebrovascular diseases. The influence of specific psychiatric disorders in contributing to adverse cardiac disease trajectories and death has been established, and depression has been identified as a risk factor for the development and progression of coronary artery disease [4].

In addition, the risk for metabolic syndrome in patients with schizophrenia and mood disorders is increased compared to the general population. Even the single components of the metabolic syndrome (overweight, hypertension, hyperlipidemia) are significantly more frequent in schizophrenia and mood disorders. Whether these metabolic and cardiovascular conditions are primarily due to the illness or secondarily induced by psychopharmacological treatment is subject to current research. Since metabolic and cardiovascular risk in long-term psychopharmacological treatment has been evaluated extensively, cardio-metabolic risk factors in patients with severe mental illness, especially when treated with antipsychotic agents, are now much better recognised, and efforts to ensure improved physical health screening and prevention are becoming established [2].

Psychopharmacologic approaches have increasingly expanded the boundaries to treat numerous other disorders not traditionally part of practice including obesity, hypoactive sexual desire disorder, fibromyalgia, perimenopausal vasomotor symptoms, numerous dementias, pain management, and even gambling [5]. Increasing evidence for the intrinsic analgesic effect of antidepressants and the antidepressant efficacy of neurological treatments in patients with Morbus Parkinson has opened up the way to new treatments. In the future, neuropsychopharmacologic approaches will have to increasingly deal also with non-pharmacologic devices, including not only classical electroconvulsive therapy but also vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation.

Neuropsychopharmacology is a dynamic field that is continuously expanding the boundaries of research and practice. New developments in neuropsychopharmacology are improving the interdisciplinary health care and patient management.

European College of Neuropsychopharmacology (ECNP)

The European College of Neuropsychopharmacology (ECNP) is Europe’s largest and leading forum for the exchange and dissemination of interdisciplinary research on the brain and brain dysfunction. ECNP is an independent scientific association founded in 1987 by European scientists and clinicians working in neuropsychopharmacology and related disciplines to encourage innovative research across the neurosciences and to translate new knowledge on fundamental disease mechanisms into clinical applications.

ECNP serves as a uniquely broad interdisciplinary platform, which strongly emphasises the complementary nature of research at the bench and at the bedside or clinic. This so-called ‘translational research’ is target-oriented, promoting the development of diagnostic procedures and laboratory outcomes in the service of discoveries that will result in improved patient care [10].

To achieve its objectives, ECNP has established a number of activities and programmes stimulating interdisciplinary forces designed to promote the communication and cross-fertilisation of research results and ideas in the field of neuropsychopharmacology. These include the ECNP Congresses, the largest high-level scientific meeting on neuropsychopharmacology and mental disorders in Europe, Regional Meetings, Seminars and Consultation Meetings, as well as activities for young scientists. The scientific journal of ECNP, European Neuropsychopharmacology (ENP), publishes original findings from basic and clinical research. Recently the ECNP School of Neuropsychopharmacology has been established with the aim of teaching junior clinicians high-standard practice in neuropsychopharmacology and to involve them in the development of local good practice in teaching and training. The second ECNP School of Neuropsychopharmacology has been held in Oxford, UK, from 11 to16 July 2010.

Through all its activities, ECNP aims to increase the understanding of brain disorders, helping to pave the way to improved treatments, and to promote the development of common standards in Europe.

Highlights of the 23rd ECNP Congress 2010

From 28 August to 1 September 2010, renowned experts and 7,000 anticipated participants will meet in Amsterdam to present, discuss and evaluate the latest achievements and future perspectives in the fields of schizophrenia, depression, bipolar disorder, drugs and addiction, Alzheimer´s disease, chronopsychiatry, eating disorders, autism spectrum disorders, as well as basic and clinical neuroscience and psychopharmacology. Great emphasis will be put on clear take-home messages that can easily be translated into clinical practice by medical professionals.

The scientific programme includes more than 35 sessions to be presented by more than 150 speakers from 20 countries, and will comprise, among others, the following topics:

    * The neural basis of the depressive self
    * Gene-environment interactions in psychosis
    * Circadian rhythms: their role and dysfunction in affective disorder
    * Predictors of relapse in alcohol dependence
    * Avenues to novel antipsychotics: moving to exploratory strategies
    * Fear memory and extinction: options for new treatments
    * Stress and affective disorders
    * Neuroprotective therapies: common potential targets in multiple sclerosis, stroke and neurodegenerative disease

The educational update sessions at the ECNP Congress will deal with the neurobiology and neuropharmacology of compulsivity in addictive behaviour, pain and neuropsychopharmacology, the placebo in psychiatry, neurostimulation techniques in mood disorders, metabolic and cardiovascular risks in the long-term psychopharmacological treatment of patients with psychiatric disorders, as well as psychiatric symptoms and their treatment in neurological disorders. Three poster sessions with in total more than 750 poster presentations from scientists from all over the world will offer an exciting insight into the research activities of (young) scientists.

Furthermore, ECNP is proud to present the results of the ECNP Consultation Meeting 2010 on ´The future of the placebo in clinical trials in brain diseases´. Through annual Consultation Meetings on specific topics, ECNP aims to facilitate the dialogue and exchange of advice between the participating parties, i.e. scientists, regulatory authorities and the pharmaceutical industry.

Invitation: meet the scientists!

Experts will be available for questions by journalists in the course of press conferences at the 23rd ECNP Congress. Please refer to the detailed schedule of press conferences in the enclosed ´press information and procedures´.

The 23rd ECNP Congress will once again present a high-calibre and balanced scientific programme, in which the latest achievements and future perspectives in neuropsychopharmacology and related disciplines of virtually all disorders of the brain are discussed, including the various aspects of pharmacotherapy in order to improve the life of patients with psychiatric and neurological disorders.

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On the Net:

• European College of Neuropsychopharmacology

Prohibited from using television, radio, and newspapers for advertising their products, tobacco companies may have taken their marketing to YouTube and other popular online media outlets, according to a study published in the online journal Tobacco Control on Wednesday.

Authors Lucy Elkin, George Thomson, and Nick Wilson, all members of the Department of Public Health from the University of Otago in Wellington, New Zealand, conducted their research at YouTube, and conducted searches featuring five of the top cigarette brands internationally: Marlboro, L&M, Benson and Hedges, Winston, and Mild Seven.

They then looked at the thematic content of a total of up to 40 of the most popular videos per brand–a total of 163. Of those, “a majority”¦ (71.2%, 95% CI 63.9 to 77.7) had pro-tobacco content, versus a small minority (3.7%) having anti-tobacco content (95% CI 1.4 to 7.8),” the researchers note.

“Most of these videos contained tobacco brand content (70.6%), the brand name in the title (71.2%) or smoking imagery content (50.9%),” they added. “One pro-smoking music video had been viewed over 2 million times. The four most prominent themes of the videos were celebrity/movies, sports, music and ‘archive’, the first three of which represent themes of interest to a youth audience.”

According to an August 25 press release from Tobacco Control parent British Medical Journal, tobacco companies have long “vehemently denied advertising on the Internet,” and several top manufacturers voluntarily agreed to restrict direct advertising online by the end of 2002. In the press release, the trio of researchers state that 20 of the 163 videos appeared to be “very professionally made,” and that each of the videos averaged 100,000 views, with one topping the two million view plateau.

Furthermore, according to AFP, “Many of the videos included old TV advertising and posters, which are outlawed in many countries”¦ There were also scenes from films with popular actors and a cigarette whose brand was visible, extracts of tobacco-sponsored sporting events, and TV footage from the 1950s and 1960s, including The Flintstones, The Beverly Hillbillies and even the Beatles.”

“Pro-tobacco videos have a significant presence on YouTube, consistent with indirect marketing activity by tobacco companies or their proxies,” Elkin, Thomson, and Wilson conclude in their study. “Since content may be removed from YouTube if it is found to breach copyright or if it contains offensive material, there is scope for the public and health organizations to request the removal of pro-tobacco content containing copyright or offensive material.”

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On the Net:

• Tobacco Control
• University of Otago

Whole-body magnetic resonance imaging (MRI), which is highly accurate at detecting soft-tissue abnormalities, may play a role in detecting child abuse in infants.

Currently, the diagnosis of abuse relies heavily on the presence of skeletal injuries, and high-quality skeletal surveys (a series of X-rays of all the bones in the body) are recommended to visualize the often subtle high-specificity fractures seen in infant abuse. Bruises are the most common sign of physical abuse, but subcutaneous tissue and muscle injuries are not currently evaluated with a global imaging technique in living children.

A study performed at Children’s Hospital Boston and Harvard Medical School in Boston, MA, included 21 infants who underwent whole-body MRI for the evaluation of suspected child abuse. Summary skeletal survey and whole-body MRI identified 167 fractures or areas of skeletal signal abnormality.

“Although our study results revealed that whole-body MRI is insensitive in the detection of classic metaphyseal lesions and rib fractures, we found it did identify soft-tissue injuries such as muscle edema and joint effusions that, in some cases, led to identifying additional fractures,” lead author Jeannette M. Perez-Rossello, MD, was quoted as saying.

“Although our study indicates that whole-body MRI is currently unsuitable as a primary global skeletal imaging tool for suspected imaging abuse,” said Perez-Rossello, “it may be useful as a supplement to the skeletal survey in selected cases, particularly with regard to soft tissue injuries.”

SOURCE:  American Journal of Roentgenology, September, 2010.

Scientists fear that a global shortage of radioactive isotopes, required for the 20 million medical scans and treatments done each year, could jeopardize patient care and drive up health care costs.

Medical isotopes are used to diagnose and treat a variety of diseases. Isotopes injected into the body can enable doctors to determine whether the heart has adequate blood flow or whether cancer has spread to a patient’s bones. Isotopes help diagnose gallbladder, kidney, and brain disorders. When delivered into a malignant tumor, isotopes can kill the cancer cells while minimizing damage to nearby healthy tissue.

The shortage of radioactive isotopes also threatens basic and environmental research, oil exploration, and nuclear proliferation.

“Although the public may not be fully aware, we are in the midst of a global shortage of medical and other isotopes,” Robert Atcher, Ph.D., MBA, director of the National Isotope Development Center (NIDC), the U.S. Department of Energy unit responsible for production of isotopes nationwide, was quoted as saying. “If we don’t have access to the best isotopes for medical imaging, doctors may be forced to resort to tests that are less accurate, involve higher radiation doses, are more invasive, and more expensive.”

The shortage already is forcing some doctors to reduce the number of imaging procedures they order for patients, Atcher added.

Each day more than 50,000 patients in the U.S. receive diagnostic and therapeutic procedures using medical isotopes, particularly individuals with heart problems and cancer. Eight out of every 10 procedures require the isotope technetium-99m, which has a half-life of only six hours. Thus, technetium-99m cannot be stockpiled. It must constantly be made fresh and distributed quickly to medical facilities.

Wolfgang Runde, Ph.D., who works with Atcher at the Los Alamos National Laboratory in New Mexico, was quoted as saying that an unexpected shutdown of a major isotope production facility in Chalk River, Ontario, Canada, in 2009 precipitated the shortage. The Chalk River facility produces 50 percent of the U.S. supply of the isotope used to make technetium-99m. Simultaneous production problems at other isotope facilities compounded the problem. Remaining suppliers have not been able to make up the resulting shortage, leaving the U.S. in an isotope supply crunch. The Chalk River facility, which was scheduled to restart this summer, remained closed as of early August.

“Shortage of this key medical isotope makes it more difficult to carry out important medical procedures, such as finding out whether cancer has spread to the bones,” said Atcher. “Doctors have been trying everything they can think of to meet the needs of patients, including the use of other less-than-ideal isotopes, but it has been a real struggle.”

Atcher noted that the U.S. is highly dependent on foreign suppliers of medical isotopes. Only about 10 to15 percent of medical isotopes are produced domestically. The nuclear medicine community has been pressuring the U.S. government to develop improved domestic capability for producing these materials to reduce this dependence.

“The challenge we have is to produce enough materials to meet commercial needs as well as needs of the research community “” from nuclear physics, to environmental research, to medical research “” amid increasing demands and fewer isotope sources,” Atcher said. “The long-term solution to this crisis remains to be seen.”

SOURCE:  Presented at the National Meeting of the American Chemical Society, Boston, August 22, 2010.

A daily dose of an old antibiotic may help diabetics avoid a stroke or at least minimize its damage, Medical College of Georgia researchers report.

Minocycline, a drug already under study at MCG for stroke treatment, may help diabetics reduce remodeling of blood vessels in the brain that increases their stroke risk and help stop bleeding that often follows a stroke, said Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies.

“We know that diabetes is bad and that diabetics have more strokes and that when they have a stroke they do more poorly,” said Ergul, corresponding author on the study published in the Journal of Cerebral Blood Flow and Metabolism. Nearly 70 percent of the estimated 24 million Americans with diabetes list a major vascular event such as a stroke or heart attack as a cause of death, according to the American Diabetes Association.

To figure out why, the researchers focused on the blood vessels of diabetic rats, finding that even moderately elevated blood glucose levels can result in thicker, twisted blood vessels that tend to leak, resulting in the bleeding that can follow a stroke. Clot-based strokes are the most common type while hemorrhagic strokes tend to be most lethal. But diabetics are at risk for a sort of combination in which a clot causes the stroke and leaking from the blood vessels follows ““ called hemorrhagic transformation ““ a scenario that can dramatically worsen the stroke’s effect, Ergul said.

Much of the bad vascular remodeling that occurs in diabetes results from elevated glucose activating matrix metalloproteinases or MMPs. “They break down things and allow for cells to move so blood vessels change shape,” Ergul said. They also destroy the basement membrane of blood vessels, allowing the destructive bleeding that often follows a diabetic stroke. On the good side, MMPs help clean up damage to enable repair and recovery.

One way minocycline works is by blocking MMPs. Less directly, diabetes drugs like metformin, used to lower blood sugar, also reduce MMP levels.

Another MCG research team, led by Dr. David Hess, stroke specialist and chairman of the Department of Neurology, is showing that minocycline given alone or with tPA, the clot dissolver that is the only FDA-approved stroke treatment, can also work after a stroke to help minimize damage. One great synergy about the pair is that tPA increases bleeding risk and minocycline decreases it.

That could particularly benefit diabetics who already are at increased risk for bleeding, particularly when oxygen is restored to that area of the brain. This damage ““ called a reperfusion injury ““ is a primary reason that a diabetic stroke may look small on a magnetic resonance image but can have a devastating, effect, Ergul also has found.

Some of her next studies will include giving both tPA and minocycline to diabetic rats to study bleeding and the impact of the two drugs on blood vessels, particularly the tiny ones that are tightly connected to brain cells.

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• Medical College of Georgia