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News - Week 15 - 2009

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ECAS launches its hotline on free movement

ECAS launches its hotline on how the EU Institutions and national authorities handle citizens’ complaints on free movement

There is a lot of debate in the Union about how to combat protectionism and zenophobia in the recession and guarantee the internal market freedoms. There is quite a debate in the Institutions about how to improve enforcement. However, as Alain Lamassure MEP points out in his recent report , no one bothers to ask the citizen. That’s where the hotline comes in. The background document (accessible HERE) sets the scene. It argues that with the increase in available information, citizens expect that someone will deal with their problem. Expectations have increased because the European Court of Justice has made free movement a fundamental right of Union citizenship and there is a much improved legal framework. So rarely do we need new European laws.

Frustration comes from the gap between the case-law and the legislation and what actually happens on the ground. People are not made to feel like European citizens with national authorities often applying, not the spirit of EU law, but the exceptions. What should be done? Do you or your organisation have experience of observing the application of EU law, sending complaints to the Commission, the European ombudsman or petitions to the European Parliament? How did you find the process in terms of ease of access, accountability, speed and results? Please email us at hotline @ ecas.org

This e-mail address is being protected from spam bots, you need JavaScript enabled to view it with your story, and fill in the questionnaire found HERE.

We would also be grateful if you could circulate the questionnaire widely in your network.

By collecting together the answers, ECAS will be able to add weight to the argument for the next European Parliament and the next Commission to show real political will not just to regulate, but to enforce regulation, and to put resources behind these efforts. The attached paper also argues that there is a need to strengthen the Commission’s powers of enforcement and create a European Commissioner for citizens and fundamental rights. The system of “infringement” dates back to 1957 and the institutional mechanisms are both under used and underperforming. Isn’t this an area ripe for reform to help keep Europe open and prepare to come out of the recession? The answers to the hotline will be gathered together in a new version of the background paper with fewer questions and more recommendations to the EU to be raised during the European election campaign .

Ditta

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Childhood Asthma and Exposures at Swimming Pools

Current evidence of an association between childhood swimming and new-onset asthma is suggestive but not conclusive. Important data gaps need to be filled, particularly in exposure assessment and characterization of asthma in the very young. Participants recommended that additional evaluations using a multidisciplinary approach are needed to determine whether a clear association exists.

Dioxin-like Compounds and Metabolic Syndrome

Environmental exposure to some persistent organic pollutants has been associated with metabolic syndrome in the United States. Uemura et al. (p. 568) conducted a cross-sectional study during 2002–2006 to evaluate associations between metabolic syndrome and body burden levels of dioxins and related compounds in Japan. They measured lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins, 7 polychlorinated dibenzofurans, and 12 dioxin-like polychlorinated biphenyls in fasting blood samples. Metabolic syndrome was assessed based on body mass index, high-density lipoprotein cholesterol, triglyceride, and hemoglobin A1c measurements, and measured or self-reported hypertension. The authors report that body burden levels of dioxins and related compounds were associated with metabolic syndrome, with high blood pressure, elevated triglycerides, and glucose intolerance most closely associated with these pollutants.

Lead Exposure and Cognition in Older Women

Chronic low-level exposure to lead has been associated with accelerated declines in cognition in older age, but few studies have included women, and none have reported results for women specifically. Weuve et al. (p. 574) examined tibia, patella, and blood lead levels in relation to performance on a battery of cognitive tests among 587 women 47–74 years of age. Levels of all three lead biomarkers were associated with worse cognitive performance for all tests combined, with stronger associations estimated for tibia bone lead, a measure of cumulative exposure over many years. Results suggest that a one-standard-deviation increase in tibia lead was associated with a reduction in cognitive scores, which was similar to that associated with a 3-year increase in age. The authors conclude that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age.

Exposure to BPA among Premature Infants in NICUs

Premature infants in neonatal intesive care units (NICUs) may be exposed to di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), and other phenols in medical products, but data on potential exposures are limited. Calafat et al. (p. 639) measured urinary levels of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben in 42 low-birth-weight infants from two NICUs in the Boston, Massachusetts, area. They found that the geometric mean urinary concentration (30.3 µg/L) of BPA among the study subjects was one order of magnitude higher than estimates for the general population, and that intensity of DEHP-containing product use was associated with total BPA concentration but not concentrations of any of the other phenols measured. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. In addition, urinary BPA concentrations differed substantially between the two institutions. The authors conclude that further studies are needed to determine specific source(s) of exposure to BPA among premature infants in NICUs.

Perfluorinated Chemicals and Fetal Growth

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are ubiquitous and persistent man-made contaminants in the environment, wildlife, and humans. These chemicals have been reported to interfere with fetal growth in humans, but results have been inconsistent. Washino et al. (p. 660) conducted a hospital-based prospective cohort study to investigate the association between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size among 428 women and infants in Sapporo, Japan. Characteristics of the mothers and infants were obtained from self-administered questionnaires and medical records. The authors report that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight in the study population.

Air Pollution and Lung Injury in Asthmatic Children

Air pollution has been associated with adverse respiratory outcomes, but the influence of air pollution on lung injury is unclear, in part because of a lack of appropriate noninvasive biomarkers of lung inflammation. Liu et al. (p. 668) measured fractional exhaled nitric oxide (FeNO), thiobarbituric acid reactive substances (TBARS), 8-isoprostane, and interleukin-6 in the breath condensate of 182 asthmatic children to investigate acute effects of air pollution on these markers of airway oxidative stress and inflammation. Interquartile-range increases in 3-day average ambient sulfur dioxide (5.4 ppb), nitrogen dioxide (6.8 ppb), and PM2.5 (particulate matter < 2.5 µm in aerodynamic diameter; 5.4 µg/m3) were associated with increases in TBARS and decreases in pulmonary function, with stronger associations estimated for children not taking corticosteroids. Results were consistent with an increase in airway oxidative stress and a decrease in small airway function in response to air pollution among asthmatic children. The authors conclude that TBARS in breath condensate may be a useful tool to investigate air pollution-related oxidative stress.

4 Promising Autism Treatments, From Vitamin B12 to Alzheimer’s Drug Namenda

MIND researchers recently tested injections of methyl B12 in a controlled trial on 30 children, since prior recent findings had shown that some children with autism have altered biomarkers for oxidative stress. The results weren’t statistically significant, but Hendren says nine of the children did improve in language and socialization, and those children had changes in biomarkers for oxidative stress. The institute will run a larger trial this summer with 50 children in an effort to figure out if the treatment really does have a benefit.

Beverage Consumption a Bigger Factor in Weight

When it comes to weight loss, what you drink may be more important than what you eat, according to researchers at the Johns Hopkins Bloomberg School of Public Health. Researchers examined the relationship between beverage consumption among adults and weight change and found that weight loss was positively associated with a reduction in liquid calorie consumption and liquid calorie intake had a stronger impact on weight than solid calorie intake. The results are published in the April 1, 2009, issue of the American Journal of Clinical Nutrition. “Both liquid and solid calories were associated with weight change, however, only a reduction in liquid calorie intake was shown to significantly affect weight loss during the 6-month follow up,” said Benjamin Caballero MD, PhD, senior author of the study and a professor with the Bloomberg School’s Department of International Health. “A reduction in liquid calorie intake was associated with a weight loss of 0.25 kg at 6 months and 0.24 kg at 18 months. Among sugar-sweetened beverages, a reduction of 1 serving was associated with a weight loss of 0.5 kg at 6 months and 0.7 kg at 18 months. Of the seven types of beverages examined, sugar-sweetened beverages were the only beverages significantly associated with weight change.”  Researchers conducted a prospective study of 810 adults aged 25-79 years old participating in the PREMIER trial, an 18-month randomized, controlled, behavioral intervention. Caballero along with colleagues from the Johns Hopkins School of Medicine; the National Heart, Lung, and Blood institute; Duke University; the Pennington Biomedical Research Center; the Kaiser Permanente Center for Health Research; the University of Alabama; and Pennsylvania State University measured participant’s weight and height using a calibrated scale and a wall-mounted stadiometer at both 6 and 18 months. Dietary intake was measured by conducting unannounced 24-hour dietary recall interviews by telephone. Researchers divided beverages into several categories based on calorie content and nutritional composition: sugar-sweetened beverages (regular soft drinks, fruit drinks, fruit punch, or high-calorie beverages sweetened with sugar), diet drinks (diet soda and other “diet” drinks sweetened with artificial sweeteners), milk (whole milk, 2 percent reduced-fat milk, 1 percent low-fat milk, and skim milk), 100 percent juice (100 percent fruit and vegetable juice), coffee and tea with sugar, coffee and tea without sugar and alcoholic beverages. They found that at 37 percent sugar-sweetened beverages were the leading source of liquid calories.

New storage system design brings hydrogen cars closer to reality

Researchers have developed a critical part of a hydrogen storage system for cars that makes it possible to fill up a vehicle's fuel tank within five minutes with enough hydrogen to drive 300 miles. The system uses a fine powder called metal hydride to absorb hydrogen gas. The researchers have created the system's heat exchanger, which circulates coolant through tubes and uses fins to remove heat generated as the hydrogen is absorbed by the powder. The heat exchanger is critical because the system stops absorbing hydrogen effectively if it overheats, said Issam Mudawar, a professor of mechanical engineering who is leading the research.

Health Benefits, Consequences of Folic Acid Dependent on Circumstances

For the past several decades, evidence has shown that greater dietary intake of the B-vitamin, folate, offers protection against the development of certain common cancers and reduces neural tube defects in newborns, opening new avenues for public health interventions that have a great impact on health. However, folate’s central role as an essential factor in DNA synthesis also means that abundant availability of the vitamin can enhance the development of pre-cancerous and cancerous tumors. Further, the intake of folic acid that results from consuming foods that are voluntarily fortified (e.g.: ready-to-eat cereals) in combination with the additional intake received from mandatory fortification of flour means that supplementary intake of folic acid is unnecessary for many segments of the population, and may even present a risk. Nevertheless, the issue is a complicated one since women of child-bearing age seem to benefit from supplemental folic acid in regard to its protection against birth defects. In the April issue of the journal Nutrition Reviews, two new articles by Omar Dary, Ph.D., and Joel B. Mason, M.D., assess the conditions under which folic acid can be beneficial and harmful and contribute to guidelines for the healthful intake of folic acid as a complement to dietary folate. The consequences of inadequate folate intake remain prevalent in many countries, even in industrial countries where specific interventions of folic acid have not been implemented. Moreover, there continues to be some concern—which, to date, lacks compelling scientific evidence—that the synthetic form of the vitamin, folic acid, might have adverse effects that do not exist with natural sources of folate. Under most circumstances, adequate intake of folate appears to assume the role of a protective agent against cancer, most notably colorectal cancer. However, in select circumstances in which an individual who harbors a pre-cancerous or cancerous tumor consumes too much folic acid, the additional amounts of folate may instead facilitate the promotion of cancer. In countries in which the fortification of flour with folic acid is working well, additional supplementation in the form of vitamin pills can lead to excessive intakes of the vitamin, which can then have undesirable adverse effects.

Prolactin reduces fat metabolism

The hormone prolactin is necessary for the production of breast milk, but it also affects adipose (fatty) tissue and the body’s metabolism. This has been shown by a thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden. Raised prolactin levels in a woman who is not pregnant or breast feeding reduces lipid (fat) metabolism. Over 30 000 Swedish men and women may have raised levels of prolactin. Women who are pregnant or breast feeding have naturally raised levels of prolactin, but stress, some medicines and benign brain tumours can also lead to raised levels of the hormone. In many cases doctors don’t know what causes the rise in hormone levels. In women, an abnormally high level can cause menstrual disturbances and infertility, and may also result in insulin resistance. “In recent years scientists have also recognised the role of prolactin in the development of obesity, but little research has been done into the precise mechanism by which prolactin regulates metabolism,” says Louise Nilsson.
In her thesis Louise Nilsson shows that there are receptors for the breast feeding hormone in human fatty tissue.

Diabetes Drug Class Linked to Vision-Threatening Complication

Treatment with the glitazone class of diabetes drugs leads to a "modest" increase in the risk of diabetic macular edema (DME)—a common complication that can lead to vision loss, reports a study in the April issue of the American Journal of Ophthalmology, published by Elsevier. Using a database of about 170,000 patients with diabetes, Drs. Donald S. Fong and Richard Contreras of Southern California Permanente Medical Group analyzed the link between glitazones and the development of DME. Diabetic macular edema is a common diabetes complication, with swelling and fluid build-up in the retina leading to progressive visual loss. The researchers identified 996 patients who were diagnosed with DME during 2006. Overall, patients who took glitazones were 2.6 times more likely to develop DME than patients not taking these drugs. Even after further adjustment for other factors, DME risk remained 60 percent higher for glitazone users. Previous studies have linked glitazones to problems related to fluid retention and edema (swelling), including heart failure. Fluid retention from heart failure or other diseases can worsen DME. Most of the glitazone users in the study were taking pioglitazone (Actos). Other studies have linked rosiglitazone (Avandia)—the only other approved glitazone drug—to a possible increase in the risk of myocardial infarction.

Coming face to face with autism

In the first study of its kind researchers will use video clips of spontaneously produced facial expressions in a real life social context to explore emotion recognition in autism. This research, carried out at The University of Nottingham, will go beyond the more artificial emotion recognition tasks that have previously been used. The eye movements of volunteers will also be tracked to find out which areas of the face were looked at while volunteers make spontaneous judgements. The study is being conducted by PhD student Sarah Cassidy who is a member of the Autism Research Team based in the School of Psychology. Her work has been funded through a PhD studentship from the Economic and Social Research Council. Her work will investigate if people with autism look at faces, particularly in the eye region, differently. If so, does this have any relationship with their ability to recognise emotions in others? What is their understanding of emotions in different social contexts? And as a consequence, how difficult is it for them to socialise and communicate with other people? Sarah said: “Previous research has suggested that people with autism have difficulty inferring emotion from faces due to lack of attention to the eyes and increased attention to the mouth. However not all studies have shown differences in emotion recognition and eye gaze. There is also little research asking what role reading emotion from the eyes plays in social communication difficulties in autism, with a few studies suggesting a relationship with social competence and responsiveness.”

Einstein scientists propose new theory of autism

Scientists at Albert Einstein College of Medicine of Yeshiva University have proposed a sweeping new theory of autism that suggests that the brains of people with autism are structurally normal but dysregulated, meaning symptoms of the disorder might be reversible. The central tenet of the theory, published in the March issue of Brain Research Reviews, is that autism is a developmental disorder caused by impaired regulation of the locus coeruleus, a bundle of neurons in the brain stem that processes sensory signals from all areas of the body. The new theory stems from decades of anecdotal observations that some autistic children seem to improve when they have a fever, only to regress when the fever ebbs. A 2007 study in the journal Pediatrics took a more rigorous look at fever and autism, observing autistic children during and after fever episodes and comparing their behavior with autistic children who didn't have fevers. This study documented that autistic children experience behavior changes during fever. "On a positive note, we are talking about a brain region that is not irrevocably altered. It gives us hope that, with novel therapies, we will eventually be able to help people with autism," says theory co-author Mark F. Mehler, M.D., chairman of neurology and director of the Institute for Brain Disorders and Neural Regeneration at Einstein. Autism is a complex developmental disability that affects a person's ability to communicate and interact with others. It usually appears during the first three years of life. Autism is called a "spectrum disorder" since it affects individuals differently and to varying degrees. It is estimated that one in every 150 American children has some degree of autism. Einstein researchers contend that scientific evidence directly points to the locus coeruleus–noradrenergic (LC-NA) system as being involved in autism. "The LC-NA system is the only brain system involved both in producing fever and controlling behavior," says co-author Dominick P. Purpura, M.D., dean emeritus and distinguished professor of neuroscience at Einstein. The locus coeruleus has widespread connections to brain regions that process sensory information. It secretes most of the brain's noradrenaline, a neurotransmitter that plays a key role in arousal mechanisms, such as the "fight or flight" response. It is also involved in a variety of complex behaviors, such as attentional focusing (the ability to concentrate attention on environmental cues relevant to the task in hand, or to switch attention from one task to another). Poor attentional focusing is a defining characteristic of autism.

MDC researchers prevent virus induced myocarditis

Life-threatening cardiac arrhythmia can be a consequence of myocarditis – an inflammation of the cardiac muscle that can be caused by the Coxsackievirus. In mice, Dr. Yu Shi, Chen Chen, and Professor Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now abolished the infection by blocking the receptor which is required for virus entry. "We did not detect a single cardiomyocyte that was infected by the virus. Inflammation of the heart muscle associated with this virus infection did not develop," Dr. Shi said. (Journal of American College of Cardiology, 2009; 53:1219-1226, doi:10.1016/j.jacc.2008.10.064).* The receptor used by the Coxsackievirus to infect the heart is the Coxsackie-adenovirus-receptor (CAR). It can be found in the cell membrane of myocardial fibers. Ulrike Lisewski, Dr. Shi, Michael Radke, and Prof. Gotthardt discovered only recently that CAR is necessary for a regular heart beat. In their current study, the researchers could demonstrate that genetically engineered mice without CAR were protected from cardiac infection caused by the Coxsackievirus. Moreover, the mice did not show any evidence of inflammatory cardiomyopathy. That is why Professor Gotthardt assumes – contrary to previous hypotheses – that the direct effects of the virus infection, and not the autoimmune response, primarily determine the disease process. This distinction is important in order to develop effective methods for future therapies of viral myocarditis. One therapeutic option could be to use CAR as a drug target and to block this receptor with a pharmacological agent.

Autism linked with stress hormone levels

Some of the symptoms of the autistic condition Asperger Syndrome, such as a need for routine and resistance to change, could be linked to levels of the stress hormone cortisol, suggests new research led by the University of Bath. Normally, people have a surge of this hormone shortly after waking, with levels gradually decreasing throughout the day. It is thought this surge makes the brain alert, preparing the body for the day and helping the person to be aware of changes happening around them. However, a study led by Dr Mark Brosnan and Dr Julie Turner-Cobb from the Department of Psychology at the University of Bath, and Dr David Jessop from the University of Bristol, has found that children with Asperger Syndrome (AS) do not experience this surge.The researchers believe these findings may help to explain why individuals with this condition have difficulties with minor changes to their routine or changes in their environment. The study has been published in the peer-reviewed journal Psychoneuroendocrinology. Dr Brosnan explained "Cortisol is one of a family of stress hormones that acts like a 'red alert' that is triggered by stressful situations allowing a person to react quickly to changes around them.
"In most people, there is a two-fold increase in levels of this hormone within 30 minutes of waking up, with levels gradually declining during the day as part of the internal body clock.
"Our study found that the children with AS didn't have this peak although levels of the hormone still decreased during the day as normal.

Some radiation therapy treatments can decrease fertility

In female cancer patients of reproductive age, radiation treatment directly to the ovaries should be avoided because there is a direct relationship between certain types of radiation therapy and fertility problems, according to a review in the April 1 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Radiation Oncology (ASTRO).
Radiation therapy to the pelvic region can cause ovarian failure or result in damage that makes the uterus unable to accommodate the growth of a fetus. These effects are not a great concern to cancer patients past their reproductive years, but due to the growing number of pediatric and young-adult cancer survivors, these effects are increasingly relevant. Researchers at the Harvard Radiation Oncology Program and the Department of Radiation Oncology at Brigham and Women's Hospital and Dana-Farber Cancer Institute, both in Boston, sought to review the impact of radiation therapy on fertility, pregnancy and neonatal outcomes among female patients and the effectiveness of ovarian transposition, or moving the ovaries out of the field of radiation, as a means of preserving fertility. The study authors reviewed the outcomes of past studies that reported fertility, pregnancy and neonatal outcomes as a result of cranio-spinal, abdominal and pelvic radiation and determined that cranio-spinal irradiation caused hormonal changes that affected a woman's ability to become pregnant later in life. Women who received abdominal or pelvic radiation had an increased risk of uterine dysfunction that lead to miscarriage, preterm labor, low birth weight and placental abnormalities. The study also determined that women who received low doses of ovarian radiation can suffer early menopause.

By Shutting Down Inflammation, Agent Reverses Damage from Spinal Cord Injury in Preclinical Studies

Researchers at Georgetown University Medical Center (GUMC) have been able to speed recovery and substantially reduce damage resulting from spinal cord injury in preclinical studies. Their research, published online in Annals of Neurology and led by Kimberly Byrnes, PhD, shows that inflammation following injury causes the neurotoxicity that leads to lasting nerve cell damage, and that an experimental agent is able to block this inflammatory reaction. “The findings we have made in this study may potentially be applicable to other neurological disorders, including stroke, head injury, Alzheimer’s disease and Parkinson’s disease,” says senior investigator Alan I. Faden, MD, a professor of neuroscience and director of the Laboratory for the Study of Central Nervous System Injury at GUMC. Faden says that the experimental agent they tested (CHPG), an activator of a type of glutamate receptor, is not ideal for human use because it cannot easily penetrate the blood-brain barrier. But he adds, “now that we know the biological target, a new drug could be designed that is better suited for clinical treatment of these neurodegenerative disorders.” CHPG shuts down activation of key immune cells in the brain known as microglia, which sense pathogens or damage in the spinal cord and brain. They helpfully foster the destruction of microbial invaders and clean up biological detritus that occurs after an injury, but researchers say they have a dark side as well – they can worsen the damage by releasing toxic inflammatory factors.

Physical activity may strengthen children's ability to pay attention

As school districts across the nation revamped curricula to meet requirements of the federal “No Child Left Behind” Act, opportunities for children to be physically active during the school day diminished significantly. Future mandates, however, might be better served by taking into account findings from a University of Illinois study suggesting the academic benefits of physical education classes, recess periods and after-school exercise programs. The research, led by Charles Hillman, a professor of kinesiology and community health and the director of the Neurocognitive Kinesiology Laboratory at Illinois, suggests that physical activity may increase students’ cognitive control – or ability to pay attention – and also result in better performance on academic achievement tests. “The goal of the study was to see if a single acute bout of moderate exercise – walking – was beneficial for cognitive function in a period of time afterward,” Hillman said. “This question has been asked before by our lab and others, in young adults and older adults, but it’s never been asked in children. That’s why it’s an important question.” For each of three testing criteria, researchers noted a positive outcome linking physical activity, attention and academic achievement. Study participants were 9-year-olds (eight girls, 12 boys) who performed a series of stimulus-discrimination tests known as flanker tasks, to assess their inhibitory control.

Genetic Link Uncovered in Disparate Colon Cancer Death

A new study reveals the first-ever genetic link to the reason African-Americans are at increased risk of dying from colon cancer. The discovery by researchers at the University of Alabama at Birmingham (UAB) is focused on a protein variant called Pro72 identified through genetic testing. In the study, African-Americans with a Pro72 protein variant had more than double the risk of dying from an advanced form of colon cancer compared to whites, the researchers said.The discovery boosts the scientific understanding of racial disparities in cancer and other diseases and adds new detail in the ongoing search for more personalized cancer-fighting therapies, said Upender Manne, Ph.D., an associate professor in the UAB Department of Pathology who led the study.

Light reveals breast tumor oxygen status

Light directed at a breast tumor through a needle can provide pathologists with biological specifics of the tumor and help oncologists choose treatment options that would be most effective for that individual patient. Duke University bioengineers have developed a light-based system that can quickly and easily provide important information about oxygen levels within a tumor while it is still in place. The new system, based on diffuse reflectance spectroscopy, gives researchers important clues about the tumor by interpreting how the light is either reflected back from the tumor or absorbed. Oxygen status is important, the researchers said, since past studies have shown that low levels of oxygen, or hypoxia, are more often associated with malignant tissue than healthy normal tissue. Tumors that thrive in these low-oxygen environments tend to be more difficult to treat, the researchers said. "We developed an easy-to-use fiber-optic probe that can provide immediate and non-destructive measurements of tumor oxygenation," said J. Quincy Brown, a fourth-year post-doctoral fellow in the laboratory of Nirmala Ramanujam, associate professor of biomedical engineering at Duke's Pratt School of Engineering. The results of the Duke experiments were published April 1 in the journal Cancer Research. "This new approach could be an important new tool for physicians in determining the aggressiveness of a specific tumor and which therapies might work best against it," Brown said. "Since this system is compatible with commonly used biopsy needles, we could make oxygen measurements at the time of a needle biopsy, providing immediate feedback about the tumor's oxygen concentration."

The More Oral Bacteria, the Higher the Risk of Heart Attack, UB study shows.

Several studies have suggested there is a connection between organisms that cause gum disease, known scientifically as periodontal disease, and the development of heart disease, but few studies have tested this theory. A study conducted at the University at Buffalo, where the gum disease/heart disease connection was uncovered, now has shown that two oral pathogens in the mouth were associated with an increased risk of having a heart attack, but that the total number of germs, regardless of type, was more important to heart health. Results of the study will be presented during a poster session at the International Association of Dental Research (IADR) General Session being held in Miami, Fla., from April 1-4. Oelisoa M. Andriankaja, D.D.S., Ph.D., conducted the study in UB's Department of Oral Biology in the School of Dental Medicine, as a postdoctoral researcher. She currently is an adjunct professor at the University of Puerto Rico's School of Dental Medicine. "The message here," said Andriankaja, "is that even though some specific periodontal pathogens have been found to be associated with an increased risk of coronary heart disease, the total bacterial pathogenic burden is more important than the type of bacteria.

Weight at birth tied to heart disease and diabetes risk in adulthood

Lower weight at birth may increase inflammatory processes in adulthood, which are associated with chronic diseases such as heart disease and diabetes, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM). Both the fetal and infancy periods are sensitive, critical stages of growth and development. Studies have previously suggested babies with lower weight at birth are at a higher risk for developing chronic diseases but until now, there has been little understanding to explain why. This study suggests an association between lower weight at birth and inflammation in adulthood may provide that explanation. Inflammation is a normal physiologic response of the body, and serves as a host defense which provides protective response to infection or tissue injury. If the source of infection or injury is not repressed, low-grade inflammation can persist and may promote the development of heart disease or diabetes. Earlier studies have found that babies born small for gestational age have weak immune systems, but at six years old have more white blood cells than babies born at a normal weight. White blood cells are cells of the immune system that defend the body against both infectious disease and foreign materials. These findings suggest that age might amplify the association between early growth and inflammatory processes. In this study, researchers followed 5,619 children born in 1966 and followed them up until they reached adulthood. As compared to children with 'normal' weight in the first year of life, researchers observed that babies born relatively smaller and gained the least weight during infancy had a higher number of white blood cells, an indicator of inflammation, in adulthood.

Balancing hormones may help prevent preterm births

The relationship between two different types of estrogen and a hormone produced in the placenta may serve as the mechanism for signaling labor, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM). This finding may help doctors intervene and prevent preterm birth much more effectively. "The trigger for the onset of labor in women has been a puzzle for a long time," says Dr. Roger Smith, MD, PhD, of John Hunter Hospital in Newcastle, Australia and lead author of the study. "Our findings show we may have an answer, and furthermore may be able to delay or advance labor." Humans have two types of estrogen called estradiol (E2) and estriol (E3). When E2 and E3 are in roughly equal amounts there is no drive to labor, but the opposite holds true once one becomes in greater excess than the other. This study evaluated the ratio of E3 to E2 in 500 pregnant women and found that it went up rapidly as labor approached indicating that E3 could stimulate the onset of labor. Dr. Smith and his colleagues then sought to understand what was causing the increase in E3 and they believe they found an answer. In a previous study they showed that a hormone in the placenta, called corticotrophin-releasing hormone (CRH), rises rapidly through pregnancy, peaking at the time of labor. CRH levels rise earlier in women who deliver prematurely and later in women who deliver late, forming a biological clock that regulates the length of pregnancy. Researchers also showed that CRH can act on the adrenal glands of the fetus to stimulate the production of a steroid hormone which the placenta uses to make E3. This study showed a strong relationship between CRH levels in the mother's blood in the weeks before birth and the levels of E3 supporting the view that CRH increases E3. "CRH may be the catalyst for the onset of labor, by driving steroid hormone production in the fetus, which then leads to an increase in E3 so that it exceeds E2," said Dr. Smith. "If this progression is correct, it may explain why women with a baby who dies in utero can still go into labor. In this scenario, levels of E3 would drop making E2 more dominant and triggering the onset of labor."

Researchers find marker for severity in adult brain cancer

Researchers at UT Southwestern Medical Center have identified a new biological indicator that may help identify which brain-cancer patients have the most aggressive forms of the disease. The researchers found that an inflammation-related molecule called RIP1 is commonly found in high levels in glioblastoma, the most common primary malignant brain tumor in adults. The protein RIP1 is a component of the complex NF-kB signaling network — a family of proteins that play a key role in inflammation-induced cancer.The study, available online and published in the April issue of Cancer Research, could provide a new target for therapeutic drugs for glioblastoma patients who have a high level of RIP1 in their tumors coupled with NF-kB activation. “This is the first report of high RIP1 levels being associated with any type of cancer,” said Dr. Amyn Habib, assistant professor of neurology at UT Southwestern and the study’s senior author. “Our data suggests that increased expression of RIP1 could serve as a marker to identify patients who have a significantly worse prognosis and who will likely be resistant to chemotherapy.”

Compassion fatigue - Impact on healthcare providers of caring for the terminally ill

Compassion fatigue in nurses, doctors and other front line cancer-care providers significantly impacts how they interact with patients, with patient families, with other healthcare workers, and with their own family, according to analysis by Indiana University School of Medicine and Regenstrief Institute researchers published in the March issue of the Journal of Health Psychology. "The healthcare field is becoming more aware of the profound emotional disturbances that occur in healthcare providers when they witness the suffering and pain of their patients in the face of an incurable disease, such as cancer. Healthcare providers are often partners in this journey, and the understanding of the effects of caring for the terminally ill on the caregiver is limited," the researchers wrote. They reviewed 57 studies to identify the prevalence of compassion fatigue among cancer-care providers, how to detect it and means of prevention and treatment. "Individuals who are drawn into healthcare careers may be more likely to develop compassion fatigue, based on their drive for perfection and to do their best for their patients. If you work in an environment where despite your very best efforts patients for whom you provide care will not survive, there is a set up for developing a sense of 'there is nothing I can do anymore,'" says the study's principal investigator Caroline Carney Doebbeling, M.D., associate professor of medicine and of psychiatry at the IU School of Medicine and a Regenstrief Institute research scientist. The term compassion fatigue was first coined in the 1990s to describe a syndrome experienced by a healthcare provider caring for individuals facing dire consequences as a result of their disease. Going beyond empathy or "feeling bad" for the person, it effects the nurse, doctor or other member of the healthcare team in a way that he or she often develops a distance from the patient as a way of self-protection.
Symptoms of compassion fatigue include chronic tiredness and irritability, lack of joy in life, engagement in behaviors which are fine in moderation, such as drinking, at a destructive level. Like individuals who have post traumatic stress disorder (PTSD), those with compassion fatigue often re-experience the deaths of their patients, according to Dr. Carney Doebbeling. Compassion fatigue can lead individuals to protect or insulate themselves by loss of compassion, cynicism, boredom, decreased productivity, more sick days and ultimately higher turnover. "How do you deal with compassion fatigue if you see patients every single day?" asks Dr. Carney Doebbeling. "In order to provide the best care to patients, the system, beginning with training in nursing and medical schools and residency, has to do a better job of helping those who go into cancer care learn what to expect and how to deal with it. On the job we need to create supportive work environments where supervisors and colleagues are aware that those who care for the sickest of the sick may be vulnerable to the triggers that could bring about compassion fatigue." While compassion fatigue has not been labeled a psychiatric disorder, it can lead to depression and anxiety disorders, according to Dr. Carney Doebbeling, a member of the Indiana University Melvin and Bren Simon Cancer Center, who is an internist and a psychiatrist as well as a health services researcher. "We are taught in medicine to be brave and to be strong, but there should also be a time and place for emotional expression, and perhaps even for crying. Doctors, nurses and other members of the healthcare team must be steady sources of support for patient. But when the patient encounter is over, at the end of the day, the doctor or nurse or social worker or clerk needs to be able to process everything they have seen and experienced. We need to support people who work with the sickest of the sick," she said.

Last step leading to blood cell formation elucidated

These new insights represent an important contribution to future clinical therapeutic approaches. The study was published in the prestigious science journal Nature and will be a central topic of the international symposium on the molecular mechanisms of hematopoiesis, which will take place in Munich from April 2nd to 4th. The findings on the molecular mechanisms of blood formation (hematopoiesis) will be presented in Munich at the international symposium "Molecular Mechanisms of Normal and Malignant Hematopoiesis" from April 2nd to 4th. A question that has puzzled researchers for decades could now be solved: How are the first blood cells generated in the embryo? In particular, Dr. Timm Schroeder, research group leader at the Institute of Stem Cell Research of Helmholtz Zentrum Muenchen and his team found out that a special type of endothelial cells exists that can transform themselves into blood cells. Endothelial cells line the interior surface of blood vessels. Dr. Timm Schroeder explained "It is extremely difficult to investigate the blood cell generation process. It occurs only very briefly, hidden from view in the embryo within the mother's uterus." The scientists first had to create the technical means to continually observe the transformation process of endothelial cells into blood cells on the single-cell level over a longer period of time. Dr. Schroeder and his colleagues developed novel bioimaging techniques with which the behavior of large numbers of individual cells can be recorded and tracked. They combined optimized microscopy, incubation and imaging technology as well as novel software programs to track individual cells in time-lapse videos with sophisticated cell purification and cell culture techniques. Thus, the scientists could observe the behavior of many differentiating mesodermal cells over a period of up to one week. By carefully analyzing thousands of cells and the molecules expressed by them, Dr. Schroeder and PhD student Hanna Eilken were able to detect several very rare endothelial cells that indeed transformed themselves into blood cells.

Blood protein may hold key to stopping tumor growth in cancer patients

A recent discovery by researchers at Wake Forest University School of Medicine could clear the way for a new drug that inhibits tumor growth in cancer patients and could potentially help in the healing of wounds.
The discovery stems from a study, recently published in the Proceedings of the National Academy of Sciences of the United States of America, in which researchers looked at angiogenesis – the body's formation of new blood vessels from existing blood vessels – and how some blood proteins are involved in that process and affect blood vessel growth. Researchers found that a protein called ferritin binds to and cripples the ability of another blood protein, called HKa, to shut down blood vessel growth. Because new blood vessels supply a steady stream of nutrients and oxygen that are essential for tumor growth, researchers found that the binding of the two proteins actually assists in new blood vessel formation by removing HKa's influence and therefore promotes tumor growth. The finding led researchers to the hypothesis that if they can somehow prevent the binding of ferritin and HKa, it will allow HKa to prevent new blood vessel growth and therefore block the growth of tumors. The finding also has possible implications for wound care. In order to heal, wounds need blood vessel growth. It is therefore possible that by increasing the binding of ferritin to HKa, one could increase the rate at which a serious wound heals.

Babies born to women with anxiety or depression are more likely to sleep poorly

A study in the April 1 issue of the journal SLEEP suggests that babies are more likely to have night wakings at both 6 months and 12 months of age if they are born to women who suffered from anxiety or depression prior to the pregnancy. Results indicate that preconceptional psychological distress – anxiety or depression - was a strong predictor of infant night waking, independent of the effects of postnatal depression, bedroom sharing and other confounding factors. Significant psychological distress prior to conception was associated with a 23-percent increased risk of infant night wakings at 6 months of age and a 22-percent increased risk at 12 months of age. According to the authors, frequent, disruptive night wakings in the latter period of the first year of life are clinically relevant because they predict sleep problems at three years of age, which in turn are associated with behavioral problems. During early childhood development, poor sleep quality also may affect learning abilities. Infant night wakings also disrupt a mother's sleep, which predicts maternal mood, stress and fatigue. The study involved 874 women between 20 and 34 years of age in the city of Southampton, U.K. Before becoming pregnant the women completed the General Health Questionnaire, a 12-question screening instrument that detects depression and anxiety disorders. Twenty-nine percent of the women were classified as having significant psychological distress. When their baby was 6 months and 12 months of age, the women reported how often their child had awakened on average between the hours of midnight and 6 a.m. each night during the last two weeks. The percentage of children who woke at least once each night was higher among women with psychological distress prior to the pregnancy, both at 6 months of age (52 percent vs. 43 percent) and 12 months of age (46 percent vs. 36 percent). According to the authors, untreated infant sleep problems can become chronic, with implications for the mental health and well-being of both the child and the mother. The difficulties of mothers who are already vulnerable to anxiety and depression will be exacerbated if they also are deprived of sleep. The authors conclude that recognizing and treating psychological distress before, during and after pregnancy may promote improved infant sleep.

Maternal smoking may alter the arousal process of infants, increasing their risk for SIDS

A study in the April 1 issue of the journal SLEEP shows that maternal smoking is associated with an impaired infant arousal process that may increase the risk for sudden infant death syndrome (SIDS). The authors suggest that maternal smoking has replaced stomach sleeping as the greatest modifiable risk factor for SIDS. Results show that the progression from sub-cortical activation to cortical arousal was depressed in smoke-exposed infants, who had lower proportions of full cortical arousals from sleep and higher proportions of sub-cortical activations than infants born to non-smoking mothers. The study also indicates that there is a dose-dependent relationship between cortical activation proportions and levels of infant urinary cotinine, a nicotine metabolite. Cortical arousals were lowest in babies with higher levels of smoke exposure.
According to senior investigator Rosemary Horne, PhD, scientific director of the Ritchie Centre for Baby Health Research at Monash University in Melbourne, Australia, decreased cortical arousals from sleep have been observed in victims of SIDS prior to death. "Our study suggests that maternal smoking can impair the arousal pathways of seemingly normal infants, which may explain their increased risk for SIDS," said Horne.
According to the authors, SIDS is the third-leading cause of infant mortality in the U.S. Although the exact cause is unknown, research suggests that an impairment of the arousal process from sleep in response to a life-threatening situation is involved. Autopsies of SIDS victims have revealed brainstem abnormalities in key areas that are required for arousal and cardiorespiratory control. The study involved 12 healthy, full-term infants born to mothers who smoked an average of 15 cigarettes per day. Their arousal responses during daytime sleep were monitored and compared with that of 13 healthy infants who were born to nonsmoking mothers.

Scientists identify new role for lung epithelial cells in sensing allergens in the air

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and at Ghent University in Ghent, Belgium, have identified a new role for certain lung cells in the immune response to airborne allergens. Many foreign substances, called antigens, are inhaled daily, but the lungs have mechanisms that usually prevent people from making unwanted immune responses to these materials. Sometimes, however, immune responses are generated to these substances, resulting in allergic responses and asthma. Scientists have been working to understand what triggers these undesirable airway responses. In this new study, conducted in mice, scientists discovered that special sensors called Toll-like receptors (TLRs), which dot the surface of epithelial cells that line the lungs, detect the presence of antigens and produce signals that activate immune cells. The researchers observed that a particular TLR, TLR4, promoted allergic airway responses to antigen mixtures containing bacterial material or a very common allergen from house dust mites. Previously, it was unclear whether TLRs on non-immune epithelial cells at mucosal surfaces such as those in the lungs were involved in antigen sensing, or if it was TLRs found on immune cells in these areas that were critical to these allergic responses. The research team observed that TLR4 on airway epithelial cells, not on immune cells, helped induce the initial immune response to antigens in the lungs. Eliminating TLR4 or blocking TLR4 function on the airway epithelial cells reduced the recruitment of immune cells to the lungs and the development of allergic disease. This study demonstrates that TLR4 found on non-immune cells in the lungs contributes to the immune response to airborne antigens. The new results suggest that targeting TLRs may be a research avenue for developing novel treatments for allergic diseases such as asthma.

Melatonin may be served as a potential anti-fibrotic drug

In China, the incidence of liver cirrhosis is still high. Liver cirrhosis results from fibrosis. If treated properly at fibrosis stage, cirrhosis can be prevented. However, no effective antifibrosis drugs are available at present. Several lines of evidences suggest that oxidative stress plays an important role in the etiopathogenesis of hepatic fibrosis. Melatonin can protect cells, tissues, and organs against oxidative damage induced by a variety of free-radical-generating agents and processes. A research team led by Professor Jian-Ming Xu from the First Affiliated Hospital of Anhui Medical University, China evaluated the possible fibrosuppressant effect of melatonin in rat. Their study will be published on March 28, 2009 in the World Journal of Gastroenterology. In this study, hepatic fibrosis in rats was successfully induced by subcutaneous injection of sterile CCl4 twice weekly for a total of 12 wk. At the beginning of injection of CCl4, melatonin (2.5, 5, 10 mg/kg body weight) was intraperitoneally administered to the rats daily for 12 wk. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. The serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and glutathione peroxidase (GPx) in liver homogenates. Serum hyaluronic acid (HA), laminin (LN), and procollagen 3 N-terminal peptide (P3NP) were determined as serum markers of hepatic fibrogenesis.Their results suggested that treatment with melatonin (10 mg/kg) could decrease the scores of hepatic fibrosis grading, reduced the contents of HA, LN in serum and Hydroxyproline (HYP) in liver, treatment with melatonin (5,10 mg/kg ) could decrease serum levels of ALT, AST and blocked the increase in MDA in rats with hepatic injury caused by CCl4. Their result indicated melatonin could ameliorate CCl4-induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities. This may provide a basis for further studies on the potentially protective effect of melatonin on liver function in cirrhotic patients

Gene linked to lupus might explain gender difference in disease risk

In an international human genetic study, researchers at UT Southwestern Medical Center have identified a gene linked to the autoimmune disease lupus, and its location on the X chromosome might help explain why females are 10 times more susceptible to the disease than males. Identifying this gene, IRAK1, as a disease gene may also have therapeutic implications, said Dr. Chandra Mohan, professor of internal medicine and senior author of the study. “Our work also shows that blocking IRAK1 action shuts down lupus in an animal model. Though many genes may be involved in lupus, we only have very limited information on them,” he said.The study appears online this week in the Proceedings of the National Academy of Sciences. Locating IRAK1 on the X chromosome also represents a breakthrough in explaining why lupus seems to be sex-linked, Dr. Mohan said. For decades, researchers have focused on hormonal differences between males and females as a cause of the gender difference, he pointed out. “This first demonstration of an X chromosome gene as a disease susceptibility factor in human lupus raises the possibility that the gender difference in rates may in part be attributed to sex chromosome genes,” Dr. Mohan said. Systemic lupus erythematosus, or lupus for short, causes a wide range of symptoms such as rashes, fever or fatigue that make it difficult to diagnose. The multicenter study involved 759 people who developed lupus as children, 5,337 patients who developed it as adults, and 5,317 healthy controls. Each group comprised four ethnicities: European-Americans, African-Americans, Asian-Americans and Hispanic-Americans.

Cancer mutations in the heart of gene regulation?

Researchers have identified a new cancer gene - one that is common to many cancers and affects the most basic regulation of our genes. The new example - a gene on the X chromosome called UTX - is found in 10% of cases of multiple myeloma and 8% of oesophageal cancers. UTX plays a role in overall regulation of the activity of many genes and it is possible that other genes with similar roles will also be found to be involved in different tumour types. This is the first example of mutations in a gene of this functional class. The finding arose from a study of mutations in 4000 genes in kidney cancer. "UTX is an important component of the transcriptional control machinery - it influences some of the most fundamental mechanisms controlling gene activity in our cells," explains Dr Andy Futreal, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute. "Unlike many cancer genes, UTX does not appear to be directly involved in cell division or cell death but in basic gene regulation and shows the depths to which cancers will plumb in order to get themselves ready to go." The normal UTX protein modifies part of the structure holding DNA together in our cells. The composite DNA-protein structure, called chromatin, is not simply a scaffold, but plays an active role in controlling gene activity. The UTX protein alters a key organising subunit component of chromatin, called a histone. The protein is likely to be involved in both turning genes on and off, making it a key regulator of the yin-yang of gene control. In the massive DNA sequencing study, the team found rare mutations of the UTX gene in clear cell renal cancer - a type of kidney cancer. When they expanded the search they found mutations in many cancer types - including one in ten multiple myeloma and one in twelve oesophageal cancer cases. "This work shows that mutations in genes with different functions can be found in human cancer through systematic approaches. These results indicate that cancer genes are not restricted to 'classical' roles of survival and cell proliferation, but can affect a variety of other cellular mechanisms," explains Professor Victor Velculescu, Associate Professor of Oncology and Director of Cancer Genetics from the Ludwig Center at Johns Hopkins and co-Director of Cancer Biology, at Johns Hopkins Kimmel Cancer Center. "UTX wouldn't have been found without this high-throughput type of study and indicates the type of novel findings we might expect from the International Cancer Genome Consortium."

Tea tree oil and silver together make more effective antiseptics

In the fight against infected skin wounds, mixing tea tree oil and silver or putting them in liposomes, (small spheres made from natural lipids), greatly increases their antimicrobial activity and may minimise any side effects. Wan Li Low and colleagues from the University of Wolverhampton presented research at the Society for General Microbiology meeting in Harrogate today (30 March) which showed that although both tea tree oil and silver (in the form of silver nitrate) were effective against a range of micro-organisms, when low concentrations of the two agents were combined, their antimicrobial activity increased. They carried out laboratory tests on pathogens that are involved in skin infections. Bacteria such as Staphylococcus aureus (which is a common cause of skin infections and abscesses), and the yeast Candida albicans, which causes thrush, were killed. These positive findings led the researchers to use microscopic spherical bodies called liposomes, made of phospholipids, the naturally occurring lipids or fats in the cell wallsmembranes, to deliver the silver and tea tree oil mix to infected wounds the pathogens. This technique allows controlled release and therefore has the potential to use lower, less toxic, concentrations of the antimicrobial agents to treat infected wounds. This may also be of value to treat antibiotic resistant strains such as MRSA. Used alone, both silver and tea tree oil can cause side effects in patients. Over exposure to silver can cause a bluish-grey discolouration of the skin and applying unregulated amounts of tea tree oil externally can cause skin irritation. With increasing life expectancy, age related conditions such as chronic leg ulcers or bedsores are likely to become more common. Current treatments using traditional silver-based creams and dressings use relatively high metal concentrations. Creams containing lower amounts of the agents could provide safer and readily available over-the-counter antiseptic compounds for effective treatment without damaging the surrounding skin.

Spreading antibiotics in the soil affects microbial ecosystems

Antibiotics used extensively in intensive livestock production may be having an adverse effect on agricultural soil ecosystems. In a presentation to the Society for General Microbiology meeting at Harrogate International Centre, today (Monday 30 March), Dr Heike Schmitt from the University of Utrecht, the Netherlands described how antibiotics passed from the animals in manure that was then spread on farmland. Although higher organisms, such as earthworms, would only be affected at unrealistic concentrations of antibiotics, changes in soil bacterial communities have been found repeatedly using molecular microbiological techniques. Bacteria involved in the nitrogen cycle, which replenishes nutrients in the soil, seem to be particularly affected. The effects persisted over several weeks and were still seen even when the antibiotics had broken down significantly. In addition the microbial population of the soil changed as fungi replaced the bacteria suppressed by the antibiotics. "The antibiotic concentrations that to date have been found in agricultural soils are smaller than the concentrations at which the adverse effects start occurring", said Dr Schmitt, "However, this might not be the case for 'hot spots", for example, when manure is not mixed thoroughly in the soil."

Skin cancer study uncovers new tumor suppressor gene

National Institutes of Health (NIH) researchers have identified a gene that suppresses tumor growth in melanoma, the deadliest form of skin cancer. The finding is reported today in the journal Nature Genetics as part of a systematic genetic analysis of a group of enzymes implicated in skin cancer and many other types of cancer. The NIH analysis found that one-quarter of human melanoma tumors had changes, or mutations, in genes that code for matrix metalloproteinase (MMP) enzymes. The findings lay the foundation for more individualized cancer treatment strategies where MMP and other key enzymes play a functional role in tumor growth and spread of the disease. Tumor suppressor genes encode proteins that normally serve as a brake on cell growth. When such genes are mutated, the brake may be lifted, resulting in the runaway cell growth known as cancer. In contrast, oncogenes are genes that encode proteins involved in normal cell growth. When such genes are mutated, they also may cause cancer, but they do so by activating growth-promoting signals. Cancer therapies that target oncogenes usually seek to block or reduce their action, while those aimed at tumor suppressor genes seek to restore or increase their action. The new study may help to explain the disappointing performance of drugs designed to treat cancer by blocking MMP enzymes. Because members of the MMP gene family were thought to be oncogenes and many tumors express high levels of MMP enzymes, researchers have spent decades pursuing MMPs as promising targets for cancer therapies. However, when MMP inhibitors were tested in people with a wide range of cancers, the drugs failed to slow -- and in some cases even sped up -- tumor growth. Now, it turns out that one of the most often mutated MMP genes in melanoma is not an oncogene at all. In its study, the team led by researchers from the National Human Genome Research Institute (NHGRI) found that MMP-8 actually serves as a tumor suppressor gene in melanoma. Consequently, in the estimated 6 percent of melanoma patients whose tumors harbor a mutated MMP-8 gene or related tumor suppressor(s), it may not be wise to block all MMPs. The study suggests that a better approach may be to look for drugs that restore or increase MMP-8 function or for drugs that block only those MMPs that are truly oncogenes.

Autism skews developing brain with synchronous motion and sound

Individuals with autism spectrum disorders (ASD) tend to stare at people's mouths rather than their eyes. Now, an NIH-funded study in 2-year-olds with the social deficit disorder suggests why they might find mouths so attractive: lip-sync—the exact match of lip motion and speech sound. Such audiovisual synchrony preoccupied toddlers who have autism, while their unaffected peers focused on socially meaningful movements of the human body, such as gestures and facial expressions. "Typically developing children pay special attention to human movement from very early in life, within days of being born. But in children with autism, even as old as two years, we saw no evidence of this," explained Ami Klin, Ph.D., of the Yale Child Study Center, who led the research. "Toddlers with autism are missing rich social information imparted by these cues, and this is likely to adversely affect the course of their development." Klin, Warren Jones, Ph.D., and colleagues at Yale, report the findings of their study, funded in part by the National Institute of Health's National Institute of Mental Health, online March 29, 2009 in the journal Nature. For the first time, this study has pinpointed what grabs the attention of toddlers with ASDs," said NIMH Director Thomas R. Insel, M.D. "In addition to potential uses in screening for early diagnosis, this line of research holds promise for development of new therapies based on redirecting visual attention in children with these disorders."
A eureka moment in the research came when researchers followed up on a clue from children's responses to audiovisual synchrony embedded in a nursery rhyme cartoon. While it was known that people with autism do not spontaneously orient to social signals, it was unclear what early-emerging mechanism may contribute to that. Nor was it clear exactly what they were attending to instead. To find out, Klin, Jones and colleagues tracked the eye movements of two-year-olds with and without the disorder while they looked at cartoon animations on split-screen displays.The researchers borrowed a technique from the video game industry, called motion capture. They then reduced the movements to only points of light at each joint in the body, like animated constellations. These cartoons played normally – upright and forward – on one half of the screen, but upside-down and in reverse on the other half. The inverted presentation engages different brain circuits and is known to disrupt perception of biological motion in young children. The normal soundtrack of the actor's voice, recorded when the animations were made, accompanied the presentations.

Mayo Clinic researchers discover and manipulate molecular interplay that moves cancer cells

Based on research that reveals new insight into mechanisms that allow invasive tumor cells to move, researchers at the Mayo Clinic campus in Florida have a new understanding about how to stop cancer from spreading. A cancer that spreads elsewhere in the body, known as metastasis, is the process that most often leads to death from the disease. In the March 29 online issue of Nature Cell Biology, researchers say that a molecule known as protein kinase D1 (PKD1) is key to the ability of a tumor cell to "remodel" its structure, enabling it to migrate and invade. The researchers found that if PKD1 is active, tumor cells cannot move, a finding they say explains why PKD1 is silenced in some invasive cancers. During metastasis, invasive cancer cells respond to biological signals to move away from a primary tumor. Multiple research groups at Mayo Clinic in Florida are especially interested in this process. One team, led by cancer biologist Peter Storz, Ph.D., has been investigating a process known as actin remodeling at the leading edge - the most forward point - of these migrating tumor cells. "The events that reorganize the actin cytoskeleton at the leading edge are complex — a multitude of molecules act in concert," Dr. Storz says. "But it appears that PKD1 must be turned off if cancer cells are to migrate." Actin filaments help make up the cytoskeleton of cells. For cancer cells to move, the actin-based cell structure has to be continually reorganized, Dr. Storz says, and to do this, new actin filaments need to be generated to shift the cell forward. Dr. Storz' group discovered that PKD1 was critical to this process. The researchers found that PKD1 inhibits another protein known as slingshot, which regulates the severing of existing actin structures so that new actin filaments can be synthesized, an event that is essential for cell movement.

After heart attack, bone marrow stem cells increase blood flow within heart

Patients treated with their own bone marrow stem cells after a heart attack experienced increased circulation within the heart, a study by Emory University School of Medicine physicians has found. Principal investigator Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine, presents the results Monday at the American College of Cardiology conference in Orlando. "These results show that treatment with a patient's own bone marrow stem cells has the potential to reduce long-term complications after a heart attack," Quyyumi says. "We are encouraged by these results and are planning to conduct a more extensive study." A severe enough heart attack can lead to remodeling of the heart muscle and increased risk of heart failure and other complications. Several groups of researchers around the world have reported clinical trials in which cells from the bone marrow are used to try to restore the heart's pumping power, with mixed results. This study was one of the first to use a preparation of bone marrow cells enriched for endothelial progenitor cells, which are thought to replenish the linings of blood vessels. Emory University, Vanderbilt University, The Lindner Research Center, Cincinnati, and Texas Heart Center in Houston participated. In the clinical trial, which began in June 2006, 31 patients were treated by angioplasty and stent placement after a heart attack. Within a week after their heart attacks, 16 of the patients had bone marrow cells infused into the coronary artery where a blockage caused the heart attack.

New brain analytical tool developed by Hebrew University scientists

An interdisciplinary team of scientists at the Hebrew University of Jerusalem has developed a new analytical tool to answer the question of how our brain cells record outside stimuli and react to them. Although much progress has been made in understanding the brain in recent decades, scientists still know relatively little about how these processes function. The two key problems in making progress in this field are that there will never be enough real data in terms of measuring what the brain actually does, and even if there were, there haven't been enough methods for analyzing such data and using them to answer the question of how neural coding actually takes place.
The analytical method developed by the Hebrew University researchers should be able to provide an indication, for example, of how many neurons encode a given stimulus such as reactions to a face or a movement and how they collaborate to do it. Current technology allows researchers only a very partial view of brain activity. For example, one cannot record the activity of more than a few hundred nerve cells from the cortex of a behaving animal. Methods like MRI imaging can map larger brain areas, but cannot be used to measure single neurons. A key question then remains of what one can learn from such a partial view. The Hebrew University researchers, headed by Dr. Amir Globerson of the Rachel and Selim Benin School of Computer Science and Engineering, have formulated the novel principle of Minimum Mutual Information (MinMI) to tackle the issue. An article detailing their findings has been published online in the Proceedings of the National Academy of Sciences (PNAS) in the US.

CT scans - Too much of a good thing can be risky

Patients who undergo numerous CT scans over their lifetime may be at increased risk for cancer, according to a study published in the April issue of Radiology. "We found that while most patients accrue small cumulative cancer risks, 7 percent of the patients in our study had enough recurrent CT imaging to raise their estimated cancer risk by 1 percent or more above baseline levels," said Aaron Sodickson, M.D., Ph.D., assistant director of Emergency Radiology at Brigham and Women's Hospital and researcher at the Center for Evidence-Based Imaging in Boston. "The techniques implemented in our study can be used to identify higher risk patients who might benefit from enhanced radiation protection efforts." CT has proven to be a valuable clinical tool, and its use has grown rapidly. According to a 2008 IMV Medical Information Division report, approximately 68.7 million CT exams were performed in the U.S. in 2007, up from 62 million in 2006. CT provides detailed images of internal organs and is a common technique used to make medical diagnoses and help guide medical treatment decisions. However, CT uses a higher radiation dose than most other imaging exams. For the study, the researchers developed new methodology to estimate cumulative CT radiation doses and associated radiation-induced cancer risks at the level of the individual patient, by extracting each patient's CT history from the electronic medical record and applying standard risk-estimation models that incorporate patient gender and age at exposure. The study group was comprised of 31,462 adult patients who had diagnostic CT scans at Brigham and Women's Hospital or the Dana-Farber Cancer Center in 2007 and had undergone a total of 190,712 CT exams over the prior 22 years. Approximately 33 percent of the patients underwent five or more lifetime CT exams, 5 percent underwent more than 22 exams, and 1 percent underwent more than 38 exams. Fifteen percent received estimated cumulative effective radiation doses of more than 100 millisieverts (mSv), equivalent to the dose one would receive from 1,000 chest x-rays. Four percent received over 250 mSv, and 1 percent received over 399 mSv. The researchers used the BEIR-VII (Biological Effects of Ionizing Radiation) risk model to estimate lifetime attributable risk (LAR) of cancer for each patient, based on their CT exposures. Approximately 7.3 percent of the study group had an estimated LAR of greater than 1 percent, meaning that due to cumulative CT radiation exposure, their risk of developing cancer increased by 1 percent above the baseline US cancer risk rate of 42 percent. Among the 315 patients in the top percentile of cumulative LAR, risk increased by 2.7 to 12 percent.

Eye cells believed to be retinal stem cells are misidentified

Cells isolated from the eye that many scientists believed were retinal stem cells are, in fact, normal adult cells, investigators at St. Jude Children's Research Hospital have found. If retinal stem cells could be obtained, they might provide the basis for treatments to restore sight to millions of people with blindness caused by retinal degeneration. Stem cells are immature cells capable of producing large numbers of adult cells, such as retinal cells. Researchers believe that stem cells offer the promise of regenerating tissue in organs such as the eye, brain and heart, damaged by trauma or disease.
The new findings suggest that research on cell therapies to restore blindness should not concentrate on these eye cells previously believed to be retinal stem cells. More promising, the scientists said, is research aimed at re-engineering stem cells to develop into the light-sensitive photoreceptor cells that are lost as a result of retinal degeneration. Such studies could lead to implantation of such engineered photoreceptor cells into the eye to restore sight. Led by Michael Dyer, Ph.D., the researchers published their findings March 30, 2009, in the online early edition of the Proceedings of the National Academy of Sciences. Dyer is a member of the St. Jude Department of Developmental Neurobiology. In studies reported in 2000, scientists proposed that the layer of ciliary epithelial cells lining the inside of the eye, contains retinal stem cells because when grown in culture dishes these cells formed tiny spheres of about a thousand cells, said Dyer, the paper's senior author. These spheres, in turn, could be cultured to give rise to more spheres, reminiscent of the self-renewing capability of stem cells. Also, the cultured sphere cells showed activation of genes characteristic of adult eye cells.
"The first clue that these cells were not stem cells was that they were pigmented," Dyer said. "Neural stem cells, in general, and retinal progenitor cells, in particular, are not pigmented. Nevertheless, the previous finding was met with a tremendous amount of enthusiasm because of the promise of introducing these cells into the eye to regenerate photoreceptors lost to blindness." In their studies, Dyer and his colleagues analyzed the sphere-forming cells in detail to determine whether they were really retinal stem cells. Painstaking microscopy studies of each cell in the spheres revealed all were pigmented and had features of ciliary epithelial cells. The researchers also compared the structure of the sphere-forming cells with those of confirmed stem cells and other immature cells in the developing retina called progenitor cells. That comparison revealed fundamental differences between the sphere-forming cells and established stem or progenitor cells.
The researchers also found that simply culturing the sphere-forming cells in the same growth medium as is used for stem cells caused them to activate genes characteristic of stem cells, yet remain adult ciliary epithelial cells.

New approach discovered to lowering triglycerides

Studies done with laboratory rats suggest that supplementation of their diet with lipoic acid had a significant effect in lowering triglycerides, which along with cholesterol levels and blood pressure are one of the key risk factors in cardiovascular disease.
In the lab animals, supplements of lipoic acid lowered triglyceride levels up to 60 percent. If the effect were the same in humans – which is not yet clear – that would be a greater impact than found with other dietary supplements, and similar to the effects of some prescription drugs. The results were just published in the Archives of Biochemistry and Biophysics, a professional journal. "The extent of triglyceride reduction was really dramatic, we didn't expect it to be this profound," said Regis Moreau, an assistant professor with the Linus Pauling Institute at Oregon State University. "The potential is good that this could become another way to lower blood triglycerides and help reduce the risk of atherosclerosis. It's pretty exciting." Lipoic acid is a natural compound found at low levels in some foods, including red meat and green leafy vegetables. A powerful antioxidant, it's been of considerable research interest in recent years for its apparent ability to reduce mitochondrial decay in cells and perhaps slow the process of aging. And it's been used in Europe for decades as a treatment for the neuropathic complications of diabetes. "Lipoic acid is known to influence glucose uptake, and bring down blood glucose by increasing its transport into skeletal muscle," Moreau said. "Less has been done to study its potential value in reducing triglycerides." Until about 10 years ago, Moreau said, high blood levels of triglycerides – basically a form of fat – were not thought to be as significant as cholesterol at predicting atherosclerosis and heart disease. That perspective has changed, he added, and most experts now see triglycerides as a third important risk factor for atherosclerosis, along with levels of "good" HDL and "bad" LDL cholesterol. Widely prescribed medications are often taken to influence all of these issues, especially when efforts to control them with diet, exercise, and proper weight have not been effective. However, some of these medications have unwanted side effects that remain a concern. In this research, it was found that supplements of lipoic acid appeared to affect triglyceride levels through two pathways. After eating, lipoic acid supplementation increased the rate of disappearance of triglycerides in the bloodstream. And supplements also reduced the genetic expression of enzymes in the liver that synthesize triglycerides.

A missing enzyme conveys major heart protection in pre-clinical work

Mice born without a certain enzyme can resist the normal effects of a heart attack and retain nearly normal function in the heart's ventricles and still-oxygenated heart tissue, according to a study by researchers at Duke University Medical Center. The findings raise the possibility of a therapy that could stimulate the growth of blood vessels and limit damage from a heart attack as well as prevent an attack from occurring at all, the scientists said. Normal mice that went through the same experiment had full heart attacks, suffering damage to their heart pumps and a lack of oxygen in their heart tissues, which are typical effects of a heart attack. The scientists found that in mice lacking the enzyme GNSOR (or S-nitrosoglutathione reductase) the blood was able to get around the blockage point that normally would cut off blood to the heart because of remarkable capillary growth in these animals. "There were blood vessels everywhere in these mice born without the enzyme," said Jonathan Stamler, M.D., a Duke professor of medicine and biochemistry and author of the study published in the Proceedings of the National Academy of Sciences online on March 27. "The hope is that this discovery someday could result in a therapy for new blood vessel growth that could be a sort of natural bypass in humans. Perhaps it could also benefit patients with peripheral artery disease, who cannot walk, for example, but who might be able to grow new blood vessels in their legs." Stamler said his research group might look into the question of improving peripheral artery disease.

Researchers discover link between schizophrenia and diabetes

People with schizophrenia are at increased risk for type 2 diabetes, Medical College of Georgia researchers have found. In a study of 50 people newly-diagnosed with schizophrenia or a related psychotic disorder with no other known risk factors, 16 percent had either diabetes or an abnormal rate of glucose metabolism, says Dr. Brian Kirkpatrick, vice chair of the MCG Department of Psychiatry and Health Behavior. In a similar size control group of people without schizophrenia, none had signs of or had developed the disease. People with diabetes cannot produce or properly use insulin, a hormone that converts glucose, starches and other food into energy. “These findings point toward there being some shared environmental factors or genetic factors between the development of schizophrenia and diabetes,” he says.

Stem cell breakthrough - Monitoring the on switch that turns stem cells into muscle

In a genetic engineering breakthrough that could help everyone from bed-ridden patients to elite athletes, a team of American researchers—including 2007 Nobel Prize winner Mario R. Capecchi—have created a "switch" that allows mutations or light signals to be turned on in muscle stem cells to monitor muscle regeneration in a living mammal. For humans, this work could lead to a genetic switch, or drug, that allows people to grow new muscle cells to replace those that are damaged, worn out, or not working for other reasons (e.g., muscular dystrophy). In addition, this same discovery also gives researchers a new tool for the study of difficult-to-treat muscle cancers. The full report containing details of this advance is available online in The FASEB Journal.
"We hope that the genetically-engineered mouse models we developed will help scientists and clinicians better understand how to make muscle stem cells regenerate muscle tissue," said Charles Keller, M.D., assistant professor at the University of Texas Health Science Center and a senior researcher involved in the work. "For our own work on childhood muscle cancers, we also hope to understand how tumors start and progress, and to develop therapies that are less toxic than chemotherapy."
The scientists made their discovery by breeding special mice with a specific gene, called "Cre," which, when activated, can trigger mutations in muscle stem cells. This Cre trigger is restricted to muscle stem cells and requires a special drug for it to be activated. In one part of the study, using fluorescent techniques, the researchers were able to visualize stem cells and their derivatives in order to pinpoint exactly where muscle tissue was being made. In another part of the study, the scientists were able to activate tumor-causing mutations in muscle stem cells, providing valuable insights into the origins of muscle tumors, which have been previously elusive.

UW-Madison study reveals new options for people with PKU

For people with the genetic condition known as phenylketonuria (PKU), diet is a constant struggle. They can eat virtually no protein, and instead get their daily dose of this key macronutrient by drinking a bitter-tasting formula of amino acids. Yet drink it they must; deviating from this strict dietary regimen puts them at risk of developing permanent neurological damage.In the near future, fortunately, a better option may become available. In April, a team of University of Wisconsin-Madison researchers will publish the second of two key papers showing that a unique protein derived from whey — known as glycomacropeptide, or GMP — is safe for people with PKU to eat. GMP is the first known natural protein that is safe for this group, and these findings are poised to revolutionize the PKU diet. Already, Cambrooke Foods, a Massachusetts company that specializes in the manufacture of medical foods, is in the process of developing GMP-fortified snack foods for commercial sale. "It's so important to individuals on the PKU diet to have new options, to have their diet liberalized. It's a quality-of-life issue," says Denise Ney, a professor of nutritional sciences who led the two studies. "Adolescents have an especially difficult time [staying on the diet], but it's so critical that they do." People with PKU are born without the enzyme responsible for breaking down phenylalanine, one of the 20 major amino acids that form the proteins we eat in everyday foods. While small amounts of phenylalanine are essential for PKU patients, excess amounts stay in their bodies indefinitely and interfere with brain function. Those who go off-diet often suffer from concentration problems and depression. Some even sustain permanent brain damage. The GMP protein isolated from whey, on the other hand, is the only known dietary protein that contains only trace amounts of phenylalanine; absolutely pure GMP, in fact, is completely phenylalanine-free. The first GMP human feeding trial was published in February in the Journal of Inherited Metabolic Disorders. In it, Ney and her team describe the experience of an individual with PKU who volunteered to consume an all-GMP diet for 10 weeks. As the paper explains, not only did the subject enjoy the GMP-fortified snack bar, pudding and sports beverage that supplied most of his daily protein, but the amount of phenylalanine in his blood actually starting going down after he ate these items for a couple of weeks.

Study examines the use of light in medical therapy

A study published in a special issue of Photochemistry and Photobiology examines the emerging practice of drug delivery systems which use the application of light to activate medications in the body. The process uses biocompatible materials that are sensitive to certain physiological variables or external physicochemical stimuli. Changes in external or internal body conditions can be used to achieve control of the delivery. There are drug delivery systems that can respond to small changes in light, temperature, pH or the concentration of specific substances. Current research on the drug delivery systems is focused on developing systems capable of delivering the adequate dose of drug at the target site, avoiding collateral effects and enhancing the therapeutic efficiency. In the case of cancer, light-sensitive systems are particularly useful for direct treatment of malignant cells and minimizing damage to healthy cells.External control of drug delivery offers a number of advantages. The process enables an easy and precise control of the medication. Switching the light on and off also triggers or stops the release of medication. This can often be done by the patient. "Near-infrared (NIR) light is particularly useful as an agent capable of triggering the drug release," says Carmen Alvarez-Lorenzo, co-author of the study. "NIR is innocuous, does not cause significant heating in the area of its application and can be useful in the difficult to access areas of the body."

Time of conception linked to birth defects in United States

A study published in the April 2009 issue of the medical journal Acta Pædiatrica is the first to report that birth defect rates in the United States were highest for women conceiving in the spring and summer. The researchers also found that this period of increase risk correlated with increased levels of pesticides in surface water across the United States. Studying all 30.1 million births which occurred in the U.S. between 1996 and 2002, the researchers found a strong association between the increased number of birth defects in children of women whose last menstrual period occurred in April, May, June or July and elevated levels of nitrates, atrazine and other pesticides in surface water during the same months. While many of these chemicals, including the herbicide atrazine which is banned in European countries but permitted in the U.S., are suspected to be harmful to the developing embryo, this is the first study to link their increased seasonal concentration in surface water with the peak in birth defects in infants conceived in the same months. The correlation between the month of last menstrual period and higher rates of birth defects was statistically significant for half of the 22 categories of birth defects reported in a Centers for Disease Control database from 1996 to 2002 including spina bifida, cleft lip, clubfoot and Down's syndrome. "Elevated concentrations of pesticides and other agrochemicals in surface water during April through July coincided with significantly higher risk of birth defects in live births conceived by women whose last menstrual period began in the same months. While our study didn't prove a cause and effect link, the fact that birth defects and pesticides in surface water peak during the same four months makes us suspect that the two are related," said Paul Winchester, M.D., Indiana University School of Medicine professor of clinical pediatrics, the first author of the study. "Birth defects, which affect about 3 out of 100 newborns in the U.S., are one of the leading causes of infant death. What we are most excited about is that if our suspicions are right and pesticides are contributing to birth defect risk, we can reverse or modify the factors that are causing these lifelong and often very serious medical problems," said Dr. Winchester, a Riley Hospital for Children neonatalogist. Birth defects are known to be associated with risk factors such as alcohol, smoking, diabetes or advanced age. However, the researchers found that even mothers who didn't report these risk factors had higher overall birth defect rates for babies conceived from April to July. The study relies on findings by U.S. Geological Survey, the U.S. Environmental Protection Agency and other agencies on the seasonal variations in nitrates, atrazine and other pesticides in the surface water.

Team identifies a molecular switch linking infectious disease and depression

Researchers at the University of Illinois report that IDO, an enzyme found throughout the body and long suspected of playing a role in depression, is in fact essential to the onset of depressive symptoms sparked by chronic inflammation. Their study, just published online in the Journal of Immunology, is the first to identify IDO (indoleamine 2,3 dioxygenase) as a molecular switch that induces depressive symptoms in some cases of chronic inflammation. Doctors have known for decades that patients with chronic inflammation, such as that linked to coronary heart disease or rheumatoid arthritis, are more likely than others to become depressed. Some pro-inflammatory drugs, such as interferon-alpha, which is used to treat Hepatitis C and a cancer known as malignant melanoma, also induce symptoms of depression in a significant number of patients. In the new study, mice were exposed to Bacille Calmette–Guérin (BCG), a vaccine used in many parts of the world to prevent tuberculosis. BCG produces low-grade, chronic inflammation in mice, which can be detected by measuring levels of certain immune system proteins, called inflammatory cytokines, in the blood and brain. Mice exposed to BCG display the normal symptoms of illness (lack of appetite, reduced activity), but after these symptoms fade the mice continue to exhibit depressive-like behaviors that can be reversed with antidepressants, said animal sciences and pathology professors Keith Kelley and Robert Dantzer, who led the study. Even after they recover from their sickness, the BCG-infected mice are much more passive than non-infected mice when in an inescapable situation. When placed in a bucket of water for a few minutes, for example, they struggle less to escape and spend more time floating passively, the researchers report. "The mice that we're calling depressed give up more quickly. While physically able, the mice quit trying to escape," said animal sciences professor Jason O'Connor, first author on the study. "But if you give them anti-depressants, the depressive-like behavior goes away," Kelley said. "So the next question is, how can this be?" Dantzer said. "What is the biological molecular switch which makes them go from sickness to depression?" The researchers knew that infection causes immune cells to produce cytokines, signaling proteins that help the body fight infection. These proteins also activate IDO in the body and brain. IDO degrades the amino acid tryptophan, producing metabolites that affect animal and human behavior. Previous studies have found a strong correlation between an increase in these metabolites and the depressive symptoms seen in some patients.An analysis of gene regulation in the mouse brains showed that exposure to BCG increased expression of IDO and two cytokines known to induce IDO: tumor necrosis factor-alpha and interferon-gamma. Because IDO degrades tryptophan, which is the precursor of serotonin, a brain chemical known to positively influence mood, scientists have hypothesized that the depression seen in patients with inflammatory disease was due to a decrease in serotonin in the brain. But a check of serotonin in the brains of mice with depressive-like behavior showed otherwise, Dantzer said. "The brain is able to compensate for the decrease in tryptophan," he said.

A mother's criticism causes distinctive neural activity among formerly depressed

Formerly depressed women show patterns of brain activity when they are criticized by their mothers that are distinctly different from the patterns shown by never depressed controls, according to a new study from Harvard University. The participants reported being completely well and fully recovered, yet their neural activity resembled that which has been observed in depressed individuals in other studies. The study, which appears in the current issue of the journal Psychiatry Research: Neuroimaging, was led by Jill M. Hooley, professor of psychology in the Faculty of Arts and Sciences at Harvard. Hooley's co-authors were Holly Parker, also of Harvard, and Staci Gruber, Julien Guillaumot, Jadwiga Rogowska and Deborah Yurgelun-Todd of McLean Hospital in Belmont, Mass. "We found that even though our formerly depressed participants were fully well, had no symptoms, and felt fine, different things were happening in their brains when they were exposed to personal criticism," says Hooley. "What's interesting to us about these findings is that although these women were fully recovered, at the level of the brain they were not back to normal." The study included 23 female participants, 12 of whom had no history of depression or any other mental illness and 11 of whom had previously experienced one or more depressive episodes, but had reported no symptoms for an average of 20 months. To an observer, both the control group and the formerly depressed appeared completely healthy. While inside an fMRI scanner, the participants listened to 30-second audio recordings of remarks from their mother. Some comments were praising, some were critical and others were neutral in content. The comments were previously recorded over the telephone with the permission of the mothers. The participants were also asked to rate their mood on a scale from one to five after hearing the different kinds of remarks.

Blood test for brain injuries gains momentum

A blood test that can help predict the seriousness of a head injury and detect the status of the blood-brain barrier is a step closer to reality, according to two recently published studies involving University of Rochester Medical Center researchers. News stories about tragic head injuries – from the death of actress Natasha Richardson to brain-injured Iraq war soldiers and young athletes – certainly underscore the need for a simpler, faster, accurate screening tool, said brain injury expert Jeffrey Bazarian, M.D., M.P.H., associate professor of Emergency Medicine, Neurology and Neurosurgery at URMC, and a co-author on both studies.
The S-100B blood test recently cleared a significant hurdle when a panel of national experts, including Bazarian, agreed for the first time that it could be a useful tool for patients with a mild injury, allowing them to safely avoid a CT scan. Previous studies have shown the S-100B serum protein biomarker to increase rapidly after an injury. If measured within four hours of the injury, the S-100B test accurately predicts which head injury patients will have a traumatic abnormality such as hemorrhage or skull fracture on a head CT scan. It takes about 20 minutes to get results and could spare many patients unnecessary radiation exposure.
Physicians at six Emergency Departments in upstate New York, including the ED at Strong Memorial Hospital in Rochester, this year will continue to study the accuracy of the test among 1,500 patients. Scientists plan to use the data to apply for U.S. Food and Drug Administration approval. "The S-100B blood test is an important part of the tool set we need to improve our treatment of patients with brain injuries," Bazarian said. "It's not the ultimate diagnostic test, but it may make things easier for patients, and it will help doctors sort through difficult clinical decisions." The test is used routinely in 16 European countries as a screening device. If a person falls and gets a head injury in Munich, Germany, during Oktoberfest, for example, a neurosurgeon is on duty within 500 meters of the beer tent, ready to administer the blood test, Bazarian said.

New insights into how brain responds to viral infection

Scientists at Columbia University Mailman School of Public Health have discovered that astrocytes, supportive cells in the brain that are not derived from an immune cell lineage, respond to a molecule that mimics a viral infection using cellular machinery similar to that used by classical immune cells in the blood. While scientists have been aware of the capacity of astrocytes to trigger an innate immune response when encountering a foreign agent, this work provides a new understanding of the complex mechanisms responsible for induction and regulation of inflammation in the brain and has significant implications for both the diagnosis and treatment of brain infections. The study is published as the cover article in the April 2009 issue of The FASEB Journal (http://www.fasebj.org). In the course of trying to contain and neutralize a virus that has breached the protective barrier of the central nervous system, immune mediators secreted by astrocytes may injure other cells and tissues in the vicinity and cause additional life-threatening inflammation.
By defining the nature of inflammatory responses by brain astrocytes, this study has implications for both the diagnosis of chronic infections of the central nervous system, as well as the treatment of acute and chronic brain infections. Viral infections of the brain are associated with extremely high morbidity and mortality; in most cases, the specific microbial cause is unknown. Even when a viral cause is clear, the specific antiviral tools at our disposal remain limited. This work provides a means for implementation of a more general therapeutic approach to viral brain infections that may be effective across a wide range of viruses, or even where a virus is suspected but the offending agent cannot be identified."Studies such as this take us one step closer to understanding both the risk and benefit associated with antiviral immune response and may lead to new treatment strategies," said W. Ian Lipkin, MD, senior author of the paper, director of the Mailman School of Public Health's Center for Infection and Immunity, John Snow Professor of Epidemiology, and professor of Neurology and Pathology. The researchers compared two methods of exposing a cell to this virus-like challenge—one from outside the cell and the other by direct delivery into the cell's cytoplasm. By culturing the supportive cells known as astrocytes obtained from the brains of newborn mice and exposing them to a virus-like molecule (called Poly I:C) from the outside and the inside, the scientists were able to show for the first time the differences between extracellular and intracellular immune response in these supportive brain cells.

Taking cues - Sometimes environmental cues can activate thrifty behavior

Consumers are constantly bombarded with subtle and even subconscious cues from their environment. A new study in the Journal of Consumer Research examines whether these cues activate goals that affect behavior in the long term or momentary desires that fade away.Authors Aner Sela and Baba Shiv (both Stanford Graduate School of Business) investigated the difference between goals that influence behavior and semantic activation, which has no lingering effect on behavior."Passing mindlessly by a discount store on the way to the mall might activate the goal of being frugal, which can sustain for a relatively long duration and influence subsequent purchases at the mall," explain the authors. "Alternatively, the same discount store may simply bring to mind the semantic notion of frugality, without actually activating the lingering motivation to behave frugally."The difference between the two outcomes, the authors believe, depends on the degree to which the primed concept (like frugality) is perceived as discrepant from the consumer's self-concept. In other words, a person who does not see himself as frugal who is exposed to a prime is more likely to activate a goal of frugality and to pursue that goal until he feels he has fulfilled it. But someone who already believes she is frugal is more likely to respond to the prime in a short-term fashion.In the experiments, the authors asked a large group of university students to rate the extent to which they saw themselves as physically fit. Then the authors exposed the participants to quick flashes of words related to physical fitness (primes) without participants being aware of the exposure. Finally the participants were asked to select and drink one of two energy beverages: They were told one boosted mental acuity and the other boosted fitness.

What's in your water? Disinfectants create toxic by-products

Although perhaps the greatest public health achievement of the 20th century was the disinfection of water, a recent study now shows that the chemicals used to purify the water we drink and use in swimming pools react with organic material in the water yielding toxic consequences. University of Illinois geneticist Michael Plewa said that disinfection by-products (DBPs) in water are the unintended consequence of water purification. "The reason that you and I can go to a drinking fountain and not be fearful of getting cholera is because we disinfect water in the United States," he said. "But the process of disinfecting water with chlorine and chloramines and other types of disinfectants generates a class of compounds in the water that are called disinfection by-products. The disinfectant reacts with the organic material in the water and generates hundreds of different compounds. Some of these are toxic, some can cause birth defects, some are genotoxic, which damage DNA, and some we know are also carcinogenic." The 10-year study began with an EPA grant to develop mammalian cell lines that would be used specifically to analyze the ability of these compounds to kill cells, or cytotoxicity, and the ability of these emerging disinfection by-products to cause genomic DNA damage. "Our lab has assembled the largest toxicological data base on these emerging new DBPs. And from them we've made two fundamental discoveries that hopefully will aid the U.S. EPA in their regulatory decisions. The two discoveries are somewhat surprising," Plewa said. The first discovery involves iodine-containing DBPs. "You get iodine primarily from sea water or underground aquifers that perhaps were associated with an ancient sea bed at one time. If there is high bromine and iodine in that water, when you disinfect these waters, you can generate the chemical conditions necessary to produce DBPs that have iodine atoms attached. And these are much more toxic and genotoxic than the regulated DBPs that currently EPA uses," he said. Plewa said that the second discovery concerns nitrogen-containing DBPs. "Disinfectant by-products that have a nitrogen atom incorporated into the structure are far more toxic and genotoxic, and some even carcinogenic, than those DBPs that don't have nitrogen. And there are no nitrogen-containing DBPs that are currently regulated." In addition to drinking water DBPs, Plewa said that swimming pools and hot tubs are DBP reactors. "You've got all of this organic material called 'people' -- and people sweat and use sunscreen and wear cosmetics that come off in the water. People may urinate in a public pool. Hair falls into the water and then this water is chlorinated. But the water is recycled again and again so the levels of DBPs can be ten-fold higher than what you have in drinking water." Plewa said that studies were showing higher levels of bladder cancer and asthma in people who do a lot of swimming - professional swimmers as well as athletic swimmers. These individuals have greater and longer exposure to toxic chemicals which are absorbed through the skin and inhaled. "The big concern that we have is babies in public pools because young children and especially babies are much more susceptible to DNA damage in agents because their bodies are growing and they're replicating DNA like crazy," he said.

Childhood abuse associated with onset of psychosis in women

Researchers at the Institute of Psychiatry, King's College London have published new research which indicates that women with severe mental illness are more likely to have been abused in childhood that the general population. But the same association has not been found in men. The researchers believe their findings point to differences in the way boys and girls respond to traumatic and upsetting experiences. The paper which is published in the April issue of the British Journal of Psychiatry compared two groups of adults with all the participants were aged between 16 and 64, and lived in either south-east London or Nottingham.
Those in the first group had experienced psychotic symptoms, such as hallucinations or delusions and received treatment for depression, mania or schizophrenia. Those in the second group had no mental health problems, and acted as a control sample. Both groups were asked whether they experienced physical or sexual abuse during their childhood. Women with psychosis were twice as likely to report either physical or sexual abuse compared to healthy women. But no such association was found in men. The researchers suggest that one explanation for this is that girls are more likely to 'internalise' difficulties than boys. In other words, girls who are abused may distance themselves from other people, and become overly suspicious of other people's behaviour. This may put them at greater risk of psychotic symptoms in the future, such as paranoid delusions. In contrast, boys may be more likely to 'act out' following physical abuse and potentially be at greater risk for antisocial behaviour.

Bad mix of bacterial remnants and genetics leads to arthritis

Here's another reason to hate leftovers. A research study appearing in the April 2009 issue of the Journal of Leukocyte Biology (http://www.jleukbio.org) sheds light on one cause of arthritis: bacteria. In the study, scientists from the United States and The Netherlands show that a specific gene called NOD2 triggers arthritis or makes it worse when leftover remnants of bacteria cell walls, called muramyl dipeptide or MDP, are present. This discovery offers an important first step toward new treatments to prevent or lessen the symptoms of inflammatory arthritis."Despite recent advances in the treatment of arthritis, none target its cause," said Michael Davey, Associate Chief of Staff for Research at the Portland Oregon Veteran's Affairs Medical Center and one of the researchers involved in the study. "Our work with MDP and NOD2 is a step toward understanding the root cause of arthritis which one day may allow certain forms of arthritis to be prevented altogether." Davey and colleagues made this discovery through experiments using two groups of mice, one group was normal and the other had been genetically modified so that their NOD2 gene was deactivated (commonly referred to as "knocked out"). Then they administered MDP to the joints of mice in each group, and unlike the normal group of mice, the mice with the deactivated NOD2 gene did not experience signs of arthritis. This may also be an important advance in the understanding and treatment of Blau Syndrome, a rare genetic disease characterized by granulomatous arthritis (arthritis caused by bacteria), uveitis (inflammation in the middle layer of the eye), skin rash and cranial neuropathy (a disorder affecting nerves that control sight, eye movement, hearing, and taste). "Now that we know that bacterial products can activate this NOD2 pathway and that this signal contributes to arthritis," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, "the next step is to find treatments that either rid the body of this inflammatory signal or mask it. Either way, the net effect would be the same: people would be spared from a very crippling disease. "

New evidence explains poor infant immune response to certain vaccines, says MU researcher

For years, researchers and physicians have known that infants' immune systems do not respond well to certain vaccines, thus the need for additional boosters as children develop. Now, in a new study from the University of Missouri, one researcher has found an explanation for that poor response. In the study, the MU scientist found evidence that the immune systems of newborns might require some time after birth to mature to a point where the benefits of vaccines can be fully realized. Habib Zaghouani, a professor of molecular microbiology and immunology and child health at the MU School of Medicine, recently found that a slowly maturing component of the immune system might explain why newborns contract infections easily. In his work, Zaghouani studied newborn mice and how their immune systems reacted when they were repeatedly exposed to an antigen that simulates a virus. Zaghouani found that while the antigen would prompt a response of the immune system, it was not the expected response. In the adult immune system, two major types of cells, known as T-helper 1 (Th-1) and T-helper 2 (Th-2) cells, are instrumental in the development of an effective immune response. Typically, Th-1 cells respond when dangerous microbes enter the body. The Th-1 cells then work to help destroy the foreign microbes. When an antigen from a vaccine enters a body with a mature immune system, Th-1 cells respond and, after destroying the invader, the Th-1 cells "remember" how to fight the antigen for future battles. Th-2 cells typically develop when the body is exposed to allergens. The responses of Th-2 cells are usually strong and manifest in the form of allergic reactions. When Zaghouani gave the newborn mice an antigen shortly after birth, he noticed the presence of both Th-1 and Th-2 cells. However, when he gave the antigen a second time, he noticed an abundance of Th-2 cells that responded to the antigen instead of Th-1 cells. Zaghouani was surprised to notice that the Th-2 cells worked to destroy the small contingent of Th-1 cells that had responded to the antigen given at birth. "Perhaps we should test vaccines at a very early age in animals to establish a regimen with the most effectiveness," Zaghouani said.

UC Davis researchers identify a protein that may help breast cancer spread, beat cancer drugs

New research from UC Davis Cancer Center shows that a protein called Muc4 may be the essential ingredient that allows breast cancer to spread to other organs and resist therapeutic treatment. The study, which appears in the April 1 issue of Cancer Research, is one of the first to characterize the role of Muc4 in the disease. Kermit Carraway, senior author of the study, knew that Muc4 was not always expressed in primary breast cancer tumors, yet it could be present in lymph node metastases. He suspected that it may have a specialized function in the process of metastasis. "Breast cancer deaths are caused by metastasis, not by the primary tumor," explained Carraway, an associate professor of biochemistry and molecular medicine. "It's at that point that the disease also becomes difficult to treat. We think that Muc4 may be packing a one-two punch by promoting the release of breast cancer cells from the primary tumor and then inhibiting their death." Muc4 is member of a group of proteins called mucins, which are commonly found in fluids such as tears and mucus. They have a known role in protecting epithelial cells, from which breast cancer cells are derived. When separated from their surrounding cell matrix, epithelial cells tend to die. Metastasizing breast cancer cells, however, can survive this detachment. "Because breast cancer cells can lose their adhesive properties and still thrive, we suspected that Muc4 may be somehow allowing them to leave their cellular framework, travel to secondary sites and withstand treatment," Carraway explained. To test his suspicions, Carraway and his team conducted two experiments. They started by comparing breast cancer cells that express Muc4 with those for which Muc4 production is blocked. The researchers then exposed both types of cells to chemotherapy drugs. The Muc4-producing cells survived. They repeated the experiment with breast cancer cells and epithelial cells that do not naturally express Muc4 but were engineered to do so. Both sets of cells avoided cell death and effectively resisted chemotherapy."Our results lead us to believe that Muc4 is somehow disrupting normal links between epithelial cells," said UC Davis graduate student Heather Workman, lead author of the study. "We now need to refine our understanding of this disruption process in order to find ways to interfere with it. There currently are no drugs that target Muc4, and this research will help change that."

Researchers reveal how the brain processes important information

Researchers at UT Southwestern Medical Center have shed light on how the neurotransmitter dopamine helps brain cells process important information.
Researchers found in a study of mouse cells that this neurotransmitter, one of the molecules used by nerve cells to communicate with one another, causes certain brain cells to become more flexible and changes brain-cell circuitry to process important information differently than mundane information. “This can help one remember a new, important episode as distinct from any other episode, such as remembering where you parked your car today versus yesterday,” said Dr. Robert Greene, professor of psychiatry at UT Southwestern and senior author of the study published in the March 11 issue of the Journal of Neuroscience.“If we can one day manipulate the way that salient information is processed, we might be able to not only improve learning, but also improve the learning needed to extinguish severe fear responsiveness, such as when a soldier can’t forget emotional war memories associated with post-traumatic stress disorder,” he said.Dr. Greene said the research also could have implications for addictions and schizophrenia, because those conditions are associated with alterations in dopamine in the brain. Researchers have known that dopamine is released in the brain in association with experiencing “important” events and remembering salient acts, such as learning to avoid a hot stove or that a good grade is rewarded. The current research focused on how dopamine operates on the cells associated with this type of memory formation.

Intestinal cancer in spite of screening

Only every second patient with colorectal carcinoma had taken part in an early detection program within the last ten years. This is the result, at least for a group of 212 colorectal cancer patients whose screening behavior is examined in the current edition of Deutsches Ärzteblatt International (Dtsch Arztebl Int 2009; 106[12]: 195 ) by Konrad Schoppmeyer and his colleagues from Leipzig University Hospital.  The authors have performed a retrospective analysis of the data on screening examinations for the ten years before the diagnosis of colorectal cancer. In 83% of patients, the colorectal carcinoma was discovered after symptoms had developed. In 17% of patients, the diagnosis was made during screening. In the 10 years before the diagnosis, 51% of the colorectal cancer patients had used screening tests for early recognition. The most frequent of these was the test for fecal occult blood—although this was mostly not in accordance with the guidelines. 25 patients had undergone colonoscopy, 20 of these within the five years before diagnosis. The most frequent reason that screening tests were not used was that patients were unaware of what was available. Schoppmeyer et al. therefore advocate that doctors should provide their patients with more detailed advice. Moreover, procedures should be in accordance with the guidelines.

Can periodontal disease act as a risk factor for HIV-1?

Today, during the 87th General Session of the International Association for Dental Research, convening at the Miami Beach Convention Center, a group of scientists from Nihon University (Tokyo, Japan) will present findings suggesting that periodontal disease could act as a risk factor for reactivating latent HIV-1 in affected individuals. Latently infected cells harbor HIV-1 proviral DNA genomes integrated with heterochromatins, allowing for the persistence of transcriptionally silent proviruses. Hypoacetylation of histone proteins by histone deacetylases (HDACs) is primarily involved in the maintenance of HIV-1 latency by repressing transcription from HIV-1 provirus. On the other hand, periodontal diseases, caused by infection with the bacterium Porphyromonas gingivalis (P. gingivalis), are found worldwide and are among the most prevalent microbial diseases of mankind. The investigators demonstrated the effects of such periodontopathic bacteria on HIV-1 replication. They found that P. gingivalis could strongly facilitate HIV-1 reactivation via chromatin modification. The bacteria produced high concentrations of butyric acid, a potent inhibitor of HDACs, and induced acetylation of histones, leading to reactivation of HIV-1 in latently infected cells. These results suggest that periodontal disease could act as a risk-factor for HIV-1 reactivation in latently infected individuals, and might contribute to the systemic dissemination of the virus causing clinical progression of acquired immunodeficiency syndrome (AIDS). The findings emphasize the essential role of maintaining oral hygiene and controlling oral diseases for the prevention of AIDS.

Pregnancy and tobacco a 'smoking gun' for baby

Monash University researchers have shown that babies born to a mother who smokes are more likely to be slower to wake or respond to stimulation – and this may explain their increased risk of Sudden Infant Death Syndrome (SIDS). Scientific director of the Ritchie Centre for Baby Health Research Associate Professor Rosemary Horne and PhD student Heidi Richardson compared babies of mothers who smoked both during the pregnancy and after the baby was born, with babies who lived in a smoke-free environment. Professor Horne said the study suggested that maternal smoking can impair a baby's ability to respond to external stimuli, which may explain their increased risk of SIDS. "Those babies whose mothers smoked did not have as many arousals overall and the progression of the arousal response through the brain was also impaired. Mothers who smoked while pregnant and continued to smoke afterward significantly increased their baby's chances of succumbing to SIDS," Professor Horne said.
Although the exact cause of SIDS is unknown, research suggests that an impairment of the arousal process from sleep in response to a life-threatening situation is involved. Autopsies of SIDS victims have revealed brainstem abnormalities in key areas that are required for arousal and cardio respiratory control. The study involved 12 healthy, full-term infants born to mothers who smoked an average of 15 cigarettes per day. Their arousal responses during daytime sleep were monitored and compared with that of healthy infants who were born to non-smoking mothers. The study was performed on each child on three occasions: at two to four weeks, two to three months and five to six months. Arousals were induced without compromising the infants' natural sleep cycles by delivering a pulsatile air-jet for five seconds at the infants' nostrils through a hand-held cannula.

Naturally fluorescent molecules may serve as cancer biomarker

Excess amounts of a naturally fluorescent molecule found in all living cells could serve as a natural biomarker for cancer, according to bioengineers. NADH, or nicotinamide adenine dinucleotide, is a key coenzyme -- a non-protein molecule necessary for the functioning of an enzyme -- found mostly in the inner membrane of a cell's power plant, or mitochondria. It fuels a series of biochemical reactions that involve various enzymes to produce ATP, the major energy source in cells. In the event of disease or a metabolic disorder, these enzymes and their related reactions can become disabled, causing a buildup of unused NADH. "Dysfunctional enzymes in the mitochondria are known to be associated with serious health problems such as cancer and neurodegenerative diseases," said Ahmed Heikal, associate professor of bioengineering, Penn State. "By detecting the level of NADH and its distribution inside living cells, we should be able to monitor the mitochondrial activity and thus the integrity of any given cell, without adding potentially toxic dyes or actually destroying the cell." According to Heikal, one of the main challenges in cancer diagnosis is the ability to differentiate cancer cells from normal ones at the early stages of tumor progression. To tease apart the critical difference between normal and cancerous cells, the researchers used the fluorescence of natural NADH. Using a combination of state-of-the-art spectroscopy and microscopy techniques, the researchers were able to convert such fluorescence into an accurate measure of NADH concentration in live cells. Heikal and Yu, graduate student, bioengineering, have found that the average concentration of NADH in breast cancer cells is about twice that in normal breast cells.

JHU researcher discovers brain cells have 'memory'

As we look at the world around us, images flicker into our brains like so many disparate pixels on a computer screen that change every time our eyes move, which is several times a second. Yet we don't perceive the world as a constantly flashing computer display. Why not? Neuroscientists at The Johns Hopkins University think that part of the answer lies in a special region of the brain's visual cortex which is in charge of distinguishing between background and foreground images. Writing in a recent issue of the journal Neuron, the team demonstrates that nerve cells in this region (called V2) are able to "grab onto" figure-ground information from visual images for several seconds, even after the images themselves are removed from our sight. "Recent studies have hotly debated whether the visual system uses a buffer to store image information and if so, the duration of that storage," said Rudiger von der Heydt, a professor in Johns Hopkins' Zanvyl Krieger Mind-Brain Institute, and co-author on the paper. "We found that the answer is 'yes,' the brain in fact stores the last image seen for up to two seconds."
The image that the brain grabs and holds onto momentarily is not detailed; it's more like a rough sketch of the layout of objects in the scene, von der Heydt explains. This may elucidate, at least in part, how the brain creates for us a stable visual world when the information coming in through our eyes changes at a rapid-fire pace: up to four times in a single second. The study was based on recordings of activity in nerve cells in the V2 region of the brains of macaques, whose visual systems closely resemble that of humans. Located at the very back of the brain, V2 is roughly the size of a wristwatch strap.

Lead in the blood increases women's mortality

Lead concentrations in the blood are associated with an increased risk of death from coronary heart diseases (CHD). A study of 533 American women, published in BioMed Central's open access journal Environmental Health, has shown that those with blood lead concentrations above 8?g/dL were three times more likely to die of CHD.
Naila Khalil worked with a team of researchers from the University of Pittsburgh and the University of Maryland to study the effects of lead on the mortality of a group of 65-87 year old women who had joined an earlier study between 1986 and 1988. These women have been followed ever since and their causes of death recorded. Khalil said, "Despite population-wide declines in blood lead concentrations during the past 30 years, environmental lead exposure continues to be a public health concern. Lead is a toxic metal, and our results add to the existing evidence of adverse affects of lead on health as seen in an older cohort who experienced greater historic environmental lead exposure".
The average population blood lead concentration in the most recent US National Health and Nutrition Examination Survey (2001-2002) had declined to 1.45?g/dL. The women studied in Dr. Khalil's research, however, were alive while lead was still used in paints, water systems and as a gasoline additive. They had an average blood concentration of 5.3?g/dL, with some women showing levels as high as 21?g/dL. According to Khalil, "Women with a blood lead concentration above 8?g/dL had a 73% increased risk of dying. In particular, blood lead was associated with almost three-fold risk in CHD mortality". This study shows that environmental toxicants, such as lead, may account for some of the burden of cardiovascular disease, which is the leading cause of mortality worldwide. It kills nearly half a million women in the United States every year, more than the next five causes of death combined and nearly twice as many as all forms of cancer, including breast cancer. The authors conclude, "While the damage may already have been done for some older people, it is important that we recognize the harm that environmental exposure to lead can cause. We must remain vigilant and ensure that lead pollution is minimized for the sake of future generations' health".

Alzheimer's disease linked to mitochondrial damage

Investigators at Burnham Institute for Medical Research (Burnham) have demonstrated that attacks on the mitochondrial protein Drp1 by the free radical nitric oxide—which causes a chemical reaction called S-nitrosylation—mediates neurodegeneration associated with Alzheimer's disease. Prior to this study, the mechanism by which beta-amyloid protein caused synaptic damage to neurons in Alzheimer's disease was unknown. These findings suggest that preventing S-nitrosylation of Drp1 may reduce or even prevent neurodegeneration in Alzheimer's patients. The paper was published in the April 3 issue of the journal Science. The team of scientists, led by neuroscientist and clinical neurologist Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research, showed that S-nitrosylated Drp1 (SNO-Drp1) facilitates mitochondrial fragmentation, damaging regions of nerve cell communication called synapses. Mitochondria are the energy storehouses of the cell, and their compromise by excessive fragmentation causes synaptic injury and eventual nerve cell death. Synapses are critical for learning and memory and their impairment leads to the dementia seen in Alzheimer's patients. "We now have a better understanding of the mechanism by which beta-amyloid protein causes neurodegeneration in Alzheimer's disease," said Dr. Lipton. "We found that beta-amyloid can generate nitric oxide that reacts with Drp1. By identifying Drp1 as the protein responsible for synaptic injury, we now have a new target for developing drugs that may slow or stop the progression of Alzheimer's." Drp1 is an enzyme that mediates fission or fragmentation of mitochondria. The Burnham researchers showed that excessive production of nitric oxide caused S-nitrosylation of Drp1 and induced excessive fragmentation of mitochondria in cultured nerve cells or neurons. The scientists also showed that beta-amyloid protein multimers, which had been previously implicated in Alzheimer's disease, induced formation of SNO-Drp1. Importantly, elevated SNO-Drp1 levels were also found in human brains of Alzheimer's patients, but not in those with Parkinson's disease or controls who didn't have neurodegenerative diseases.
Molecular modeling performed by the team suggested that S-nitrosylation of Drp1 causes dimerization of the protein and activation of enzymatic activity that induces mitochondrial fragmentation. To confirm this hypothesis, the scientists showed that RNA interference to knock down Drp1 or a mutation that prevented Drp1 activity inhibited excess mitochondrial fragmentation and protected the neurons. Finally, the researchers showed that a mutated Drp1, lacking the nitrosylation site, did not induce mitochondrial fragmentation and also prevented neuronal damage. Taken together, these findings suggest that multimers of beta-amyloid protein induce generation of nitric oxide, which reacts with Drp1 to cause excessive mitochondrial fragmentation and in turn neuronal damage.

Protein protects neurons in brain from damage due to inflammation

A research team from the University of California, San Diego School of Medicine and the Salk Institute for Biological Studies in La Jolla has identified a protein in the brain of mice that protects neurons from excessive inflammation, which can lead to neurodegenerative disorders such as Parkinson's disease. Their study, which identifies the protective function of a protein called Nurr1 and defines the pathway by which it works, will be published in the April 3 edition of the journal Cell. Nurr1 is a transcription factor that has been known for some time to play an essential role in the generation and maintenance of dopaminergic neurons in the brain. Rare mutations in Nurr1 are associated with familial Parkinson's disease, and the loss of dopaminergic neurons – which are the main source of dopamine in the central nervous system – is associated with the disease. Dopamine helps control multiple brain functions such as movement, attention, pleasure, emotion and motivation. The new findings have uncovered a second and previously unexpected role of the Nurr1 protein in two other cell types in the brain – microglia and astrocytes. The brain's microglia are macrophage-like cells that are active components of the immune defense in the central nervous system, while astrocytes are large star-shaped cells that normally play important support functions in the brain. Working in mice, researchers in the Laboratory of Genetics headed by Fred H. Gage, PhD, professor at the Salk Institute, reduced the expression of Nurr1 in the brain to see how it affected the inflammatory stimulus when the brain was infused with either bacterial lipolysaccharide (LPS) – a potent activator of microglia – or with a mutant form of alpha synuclein that is associated with an early form of familial Parkinson's disease. They found that, in the absence of Nurr1, inflammation was increased in the region where dopaminergic neurons are found, resulting in a toxic effect on those neurons. "LPS won't normally kill neurons, but the neurons died when Nurr1 was removed, so we realized that another cell type in the brain must be responding to LPS to cause this toxic effect," Gage said.

Sleep may help clear the brain for new learning

A new theory about sleep's benefits for the brain gets a boost from fruit flies in this week's Science. Researchers at Washington University School of Medicine in St. Louis found evidence that sleep, already recognized as a promoter of long-term memories, also helps clear room in the brain for new learning.The critical question - How many synapses, or junctures where nerve cells communicate with each other, are modified by sleep? Neurologists believe creation of new synapses is one key way the brain encodes memories and learning, but this cannot continue unabated and may be where sleep comes in."There are a number of reasons why the brain can't indefinitely add synapses, including the finite spatial constraints of the skull," says senior author Paul Shaw, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "We were able to track the creation of new synapses in fruit flies during learning experiences, and to show that sleep pushed that number back down." Scientists don't yet know how the synapses are eliminated. According to theory, only the less important connections are trimmed back, while connections encoding important memories are maintained. Many aspects of fly sleep are similar to human sleep; for example, flies and humans deprived of sleep one day will try to make up for the loss by sleeping more the next day. Because the human brain is much more complex, Shaw uses the flies as models for answering questions about sleep and memory. Sleep is a recognized promoter of learning, but three years ago Shaw turned that association around and revealed that learning increases the need for sleep in the fruit fly. In a 2006 paper in Science, he and his colleagues found that two separate scenarios, each of which gave the fruit fly's brain a workout, increased the need for sleep. The first scenario was inspired by human research linking an enriched environment to improved memory and other brain functions. Scientists found that flies raised in an enhanced social environment—a test tube full of other flies—slept approximately 2-3 hours longer than flies raised in isolation. Researchers also gave male fruit flies their first exposure to female fruit flies, but with a catch—the females were either already mated or were actually male flies altered to emit female pheromones. Either fly rebuffed the test fly's attempts to mate. The test flies were then kept in isolation for two days and exposed to receptive female flies. Test flies that remembered their prior failures didn't try to mate again; they also slept more. Researchers concluded that these flies had encoded memories of their prior experience, more directly proving the connection between sleep and new memories. Scientists repeated these tests for the new study, but this time they used flies genetically altered to make it possible to track the development of new synapses, the junctures at which brain cells communicate. "The biggest surprise was that out of 200,000 fly brain cells, only 16 were required for the formation of new memories, " says first author Jeffrey Donlea, a graduate student. "These sixteen are lateral ventral neurons, which are part of the circadian circuitry that let the fly brain perform certain behaviors at particular times of day."

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