Insomnia Is Bad For The Heart; Increases Blood Pressure

Can't sleep at night? A new study published in the journal Sleep has found that people who suffer from insomnia have heightened nighttime blood pressure, which can lead to cardiac problems. The investigation, which measured the 24-hour blood pressure of insomniacs compared to sound sleepers, was conducted by researchers from the Université de Montréal, its affiliated Hôpital du Sacré-Cœur de Montréal Sleep Disorders Centre and the Université Laval."Over many years, chronic insomnia can have negative effects on the hearts of otherwise healthy individuals," says lead author Paola A. Lanfranchi, a professor in the Université de Montréal Faculty of Medicine and researcher at the Hôpital du Sacré-Cœur de Montréal Sleep Disorders Centre. "Whereas blood pressure decreases in regular sleepers and gives their heart a rest, insomnia provokes higher nighttime blood pressure that can cause long-term cardiovascular risks and damage the heart."

The findings are important given that insomnia, which is a chronic difficulty falling or staying asleep, affects up to 48 percent of the population at some point in their lives. As part of the study, the scientific team recruited 13 otherwise healthy chronic insomniacs and 13 good sleepers. Subjects spent 40 hours in the sleep laboratory: two nights for adaptation and one for monitoring followed by the intervening day.

"Blood pressure cycles are mainly linked to the sleep-wake cycle," says co-author Jacques Montplaisir, a professor in the Université de Montréal Department of Psychiatry and director of Hôpital du Sacré-Cœur de Montréal Disorders Center. "Since blood pressure is heightened among insomniacs, those with overt cardiac disease are particularly at risk for progression of the disease."

The article "Nighttime Blood Pressure in Normotensive Subjects With Chronic Insomnia: Implications for Cardiovascular Risk," published in Sleep was authored by Paola A. Lanfranchi, Marie-Hélène Pennestri, Lorraine Fradette, Marie Dumont and Jacques Montplaisir of the Université de Montréal and its affiliated Hôpital du Sacré-Cœur de Montréal, as well as Charles M. Morin of the Université Laval.

This study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Québec and the Fonds de Recherche en Santé du Québec.

How To Boost Value Of Alzheimer's-fighting Compounds

The polyphenols found in red wine are thought to help prevent Alzheimer's disease, and new research from Purdue University and Mount Sinai School of Medicine has shown that some of those compounds in fact reach the brain.Mario Ferruzzi, a Purdue associate professor of food science; Connie Weaver, Purdue's head of foods and nutrition; and Elsa Janle, a Purdue associate professor of foods and nutrition, found that the amount of polyphenols from grapeseed extract that can reach a rat's brain is as much as 200 percent higher on the 10th consecutive day of feeding as compared to the first. Many previous experiments, in which absorption was measured after single or sporadic doses, often found very little, if any, of the bioactive polyphenols reaching brain tissues. However, more chronic exposure appears to improve absorption.

"This shows that reasonable and chronic consumption of these products may be the way to go, rather than single, high doses, similar to drugs," said Ferruzzi, who collaborated on the research with Mount Sinai's Dr. Giulio Pasinetti. "It's like eating an apple a day, not a case of apples over two days every month."

A paper detailing the findings was published in the early online version of the September issue of the Journal of Alzheimer's Disease.

Polyphenols, compounds found in the skins and seeds of grapes, are thought to prevent the formation of beta-amyloid protein, which creates the plaque in the brain that causes Alzheimer's disease. Alzheimer's is a progressive brain disease that destroys memory and cognitive skills and affects as many as 4.5 million Americans, according to the National Institute on Aging.

Pasinetti, the Aidekman Family Professor in Neurology and director of the Center of Excellence for Novel Approaches to Neurotherapeutics, said discovering how polyphenols are absorbed and distributed to the brain can impact researchers' understanding of the amount of grape products or red wine a person would need to consume to most effectively combat Alzheimer's disease.

"The most important thing is that when we follow the repetitive administration of this compound, we were able to observe the transfer of the compound to the brain," Pasinetti said. "This may help us figure out the proper concentration necessary to get these chemicals to the brain."

Ferruzzi said the study dealt with polyphenols, but also could be important for determining proper doses of other compounds or drugs for patients. Testing of a pharmaceutical, for example, could show that the drug is too potent when given repetitively; whereas that might not be apparent if the drug is administered on non-consecutive days or weeks.

"It could become important in terms of side effects," Ferruzzi said. "You could be overdosing because the body is adapting and absorbing or metabolizing these compounds differently over time."

Pasinetti is the principal investigator for the Center of Excellence for Research and Complementary and Alternative Medicine in Alzheimer's Disease grant from the National Institutes of Health that funded the work. Ferruzzi said further studies will focus on the mechanisms that control absorption of compounds during chronic consumption.

Vitamin C Deficiency Impairs Early Brain Development, Guinea Pig Study Finds

New research at LIFE – Faculty of Life Sciences at University of Copenhagen shows that vitamin C deficiency may impair the mental development of new-born babies.In the latest issue of the well-known scientific journal The American Journal of Clinical Nutrition, a group of researchers headed by professor Jens Lykkesfeldt shows that guinea pigs subjected to moderate vitamin C deficiency have 30 per cent less hippocampal neurones and markedly worse spatial memory than guinea pigs given a normal diet. Like guinea pigs, human beings are dependent on getting vitamin C through their diet, and Jens Lykkesfeldt therefore speculate that vitamin C deficiency in pregnant and breast-feeding women may also lead to impaired development in foetuses and new-born babies.

The brain retains vitamin C

Several factors indicate that the neonatal brain, in contrast to other tissue, is particularly vulnerable to even a slight lowering of the vitamin C level. The highest concentration of vitamin C is found in the neurons of the brain and in case of a low intake of vitamin C, the remaining vitamin is retained in the brain to secure this organ. The vitamin thus seems to be quite important to brain activity. Tests have shown that mouse foetuses that were not able to transport vitamin C develop severe brain damage. Brain damage which resembles the ones found in premature babies and which are linked to learning and cognitive disabilities later in life.

Widespread vitamin C deficiency

In some areas in the world, vitamin C deficiency is very common – population studies in Brazil and Mexico have shown that 30 to 40 per cent of the pregnant women have too low levels of vitamin C, and the low level is also found in their foetuses and new-born babies. It is not yet known to what extent new-born babies in Denmark or the Western World suffer from vitamin C deficiency but a conservative estimate would be 5 to 10 per cent based on the occurrence among adults.

“We may thus be witnessing that children get learning disabilities because they have not gotten enough vitamin C in their early life. This is unbearable when it would be so easy to prevent this deficiency by giving a vitamin supplement to high-risk pregnant women and new mothers" says Jens Lykkesfeldt whose research group is currently studying how early in pregnancy vitamin C deficiency affects the embryonic development of guinea pigs and whether the damage may be reversed after birth.

Discovery Of Novel Genes Could Unlock Mystery Of What Makes Us Uniquely Human

Humans and chimpanzees are genetically very similar, yet it is not difficult to identify the many ways in which we are clearly distinct from chimps. In a study published online in Genome Research, scientists have made a crucial discovery of genes that have evolved in humans after branching off from other primates, opening new possibilities for understanding what makes us uniquely human.The prevailing wisdom in the field of molecular evolution was that new genes could only evolve from duplicated or rearranged versions of preexisting genes. It seemed highly unlikely that evolutionary processes could produce a functional protein-coding gene from what was once inactive DNA.

However, recent evidence suggests that this phenomenon does in fact occur. Researchers have found genes that arose from non-coding DNA in flies, yeast, and primates. No such genes had been found to be unique to humans until now, and the discovery raises fascinating questions about how these genes might make us different from other primates.

In this work, David Knowles and Aoife McLysaght of the Smurfit Institute of Genetics at Trinity College Dublin undertook the painstaking task of finding protein-coding genes in the human genome that are absent from the chimp genome. Once they had performed a rigorous search and systematically ruled out false results, their list of candidate genes was trimmed down to just three. Then came the next challenge. "We needed to demonstrate that the DNA in human is really active as a gene," said McLysaght.

The authors gathered evidence from other studies that these three genes are actively transcribed and translated into proteins, but furthermore, they needed to show that the corresponding DNA sequences in other primates are inactive. They found that these DNA sequences in several species of apes and monkeys contained differences that would likely disable a protein-coding gene, suggesting that these genes were inactive in the ancestral primate.

The authors also note that because of the strict set of filters employed, only about 20% of human genes were amenable to analysis. Therefore they estimate there may be approximately 18 human-specific genes that have arisen from non-coding DNA during human evolution.

This discovery of novel protein-coding genes in humans is a significant finding, but raises a bigger question: What are the proteins encoded by these genes doing? "They are unlike any other human genes and have the potential to have a profound impact," McLysaght noted. While these genes have not been characterized yet and their functions remain unknown, McLysaght added that it is tempting to speculate that human-specific genes are important for human-specific traits.

Scientists from the Smurfit Institute of Genetics, Trinity College Dublin (Dublin, Ireland) contributed to this study.

This work was supported by a President of Ireland Young Researcher Award from Science Foundation Ireland.

New iPhone App 'Outbreaks Near Me' Locates H1N1 (Swine Flu), Infectious Diseases

A new iPhone application, created by researchers at Children's Hospital Boston in collaboration with the MIT Media Lab, enables users to track and report outbreaks of infectious diseases, such as H1N1 (swine flu), on the ground in real time.The application, "Outbreaks Near Me," builds upon the mission and proven capability of HealthMap, an online resource that collects, filters, maps and disseminates information about emerging infectious diseases, and provides a new, contextualized view of a user's specific location – pinpointing outbreaks that have been reported in the vicinity of the user and offering the opportunity to search for additional outbreak information by location or disease.

Additional functionality of Outbreaks Near Me is the ability to set alerts that will notify a user on their device or by e-mail when new outbreaks are reported in their proximity, or if a user enters a new area of activity.

"We hope individuals will find the new app to be a useful source of outbreak information – locally, nationally, and globally," says HealthMap co-founder John Brownstein, PhD, assistant professor in the Children's Hospital Informatics Program (CHIP). "As people are equipped with more knowledge and awareness of infectious disease, the hope is that they will become more involved and proactive about public health."

The new application also features an option for users to submit an outbreak report. This will enable individuals in cities and countries around the world to interact with the HealthMap team and participate in the public health surveillance process. Users may take photos – of situations and scenarios of, and/or leading to, disease – with their iPhone and submit them to the HealthMap system for review and eventual posting as an alert on the worldwide map.

"This is grassroots, participatory epidemiology," says HealthMap co-founder Clark Freifeld, a PhD student at the MIT Media Lab and research software developer at CHIP. "In releasing this app we aim to empower citizens in the cause of public health, not only by providing ready access to real-time information, but also by encouraging them to contribute their own knowledge, expertise, and observations. In enabling participation in surveillance, we also expect to increase global coverage and identify outbreaks earlier."

HealthMap was founded in 2006 and mines the Internet – searching disparate data sources such as news reports, curated personal accounts, official alerts, blogs and chat rooms – to track and map infectious disease outbreaks. While the data have been shown to provide early information on new outbreaks, users are encouraged to interpret the data appropriately as it is drawn from both official and unofficial sources.

The HealthMap Web site (http://www.healthmap.org) averages 10,000 unique visits a day, including regular users from the World Health Organization, the CDC, and the European Centre for Disease Prevention and Control. During the peak of H1N1 swine flu this spring, visits to the site rose substantially, with as many as 150,000 visitors coming to the Web site to search for information.

Outbreaks Near Me was developed with support from Google.org and is available at no cost for download in the iTunes App Store. For more information on Outbreaks Near Me, visit: http://healthmap.org/iphone.php.

We Are All Mutants: Measurement Of Mutation Rate In Humans By Direct Sequencing

An international team of 16 scientists today reports the first direct measurement of the general rate of genetic mutation at individual DNA letters in humans. The team sequenced the same piece of DNA - 10,000,000 or so letters or 'nucleotides' from the Y chromosome - from two men separated by 13 generations, and counted the number of differences. Among all these nucleotides, they found only four mutations.In 1935 one of the founders of modern genetics, J. B. S. Haldane, studied men in London with the blood disease haemophilia and estimated that there would be one in 50,000 incidence of mutations causing haemophilia in the gene affected - the equivalent of a mutation rate of perhaps one in 25 million nucleotides across the genome. Others have measured rates at a few further specific genes or compared DNA from humans and chimpanzees to produce general estimates of the mutation rate expressed more directly in nucleotides of DNA.

Remarkably, the new research, recently published in Current Biology, shows that these early estimates were spot on - in total, we all carry 100-200 new mutations in our DNA. This is equivalent to one mutation in each 15 to 30 million nucleotides. Fortunately, most of these are harmless and have no apparent effect on our health or appearance.

"The amount of data we generated would have been unimaginable just a few years ago," says Dr Yali Xue from the Wellcome Trust Sanger Institute and one of the project's leaders. "But finding this tiny number of mutations was more difficult than finding an ant's egg in the emperor's rice store."

Team member Qiuju Wang recruited a family from China who had lived in the same village for centuries. The team studied two distant male-line relatives - separated by thirteen generations - whose common ancestor lived two hundred years ago.

To establish the rate of mutation, the team examined an area of the Y chromosome. The Y chromosome is unique in that, apart from rare mutations, it is passed unchanged from father to son; so mutations accumulate slowly over the generations.

Despite many generations of separation, researchers found only 12 differences among all the DNA letters examined. The two Y chromosomes were still identical at 10,149,073 of the 10,149,085 letters examined. Of the 12 differences, eight had arisen in the cell lines used for the work. Only four were true mutations that had occurred naturally through the generations.

We have known for a long time that mutations occur occasionally in each of us, but have had to guess exactly how often. Now, thanks to advances in the technology for reading DNA, this new research has been possible.

Understanding mutation rates is key to many aspects of human evolution and medical research: mutation is the ultimate source of all our genetic variation and provides a molecular clock for measuring evolutionary timescales. Mutations can also lead directly to diseases like cancer. With better measurements of mutation rates, we could improve the calibration of the evolutionary clock, or test ways to reduce mutations, for example.

Even with the latest DNA sequencing technology, the researchers had to design a special strategy to search for the vanishingly rare mutations. They used next-generation sequencing to establish the order of letters on the two Y chromosomes and then compared these to the Y chromosome reference sequence.

Having identified 23 candidate SNPs - or single letter changes in the DNA - they amplified the regions containing these candidates and checked the sequences using the standard Sanger method. A total of four naturally occurring mutations were confirmed. Knowing this number of mutations, the length of the area that they had searched and the number of generations separating the individuals, the team were able to calculate the rate of mutation.

"These four mutations gave us the exact mutation rate - one in 30 million nucleotides each generation - that we had expected," says the study's coordinator, Chris Tyler-Smith, also from The Wellcome Trust Sanger Institute. "This was reassuring because the methods we used - harnessing next-generation sequencing technology - had not previously been tested for this kind of research. New mutations are responsible for an array of genetic diseases. The ability to reliably measure rates of DNA mutation means we can begin to ask how mutation rates vary between different regions of the genome and perhaps also between different individuals."

This work was supported by the Joint Project from the NSFC and The Royal Society, and the Wellcome Trust.

How Alcohol Blunts Ability Of Hamsters To 'Rise And Shine'

Chronic alcohol consumption blunts the biological clock’s ability to synchronize daily activities to light, disrupts natural activity patterns and continues to affect the body’s clock (circadian rhythm), even days after the drinking ends, according to a new study with hamsters.The study describes the changes that drinking can produce on the body’s master clock and how it affects behavior. The research provides a way to study human alcoholism using an animal model, said researcher Christina L. Ruby.

The study appears in the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. Christina L. Ruby, Allison J. Brager, Marc A. DePaul, and J. David Glass, all of Kent State University, and Rebecca A. Prosser of the University of Tennessee, conducted the study. The American Physiological Society published the research.

Batteries not included

Alcohol consumption affects the master clock, located in the suprachiasmatic nucleus (SCN) section of the brain. This clock controls the circadian cycle, a roughly 24-hour cycle, which regulates sleeping and waking, as well as the timing of a variety of other physiological functions, such as hormonal secretions, appetite, digestion, activity levels and body temperature. The SCN synchronizes physiological functions so that they occur at the proper times and keeps these functions synchronized with daylight. Disruption of the clock dramatically increases the risks of developing cancer, heart disease, and depression, among other health problems.

The researchers used hamsters to find out how alcohol affects circadian rhythms. Although hamsters are nocturnal, light synchronizes their clocks, just as with humans. The animals were divided into three groups, differing only on what they drank. The control group received water only. A second group received water containing 10% alcohol and the third group received water containing 20% alcohol. Hamsters, when given a choice, prefer alcohol, which they metabolize quickly.

The animals drank as much as they wanted and lived in an environment that provided 14 hours of light and 10 hours of darkness each day.

Sleeping in

The researchers recorded the activity levels of the three groups throughout the day. Late in the dark cycle, about three hours before the nocturnal animals would normally be settling in to sleep, the researchers put on a low-level light for 30 minutes. The light was similar to the dim light of dawn. At another time, the groups received a brighter light, akin to the light in an office building. Hamsters exposed to the light late in their active cycle will normally settle down to sleep at the same time, but will wake up earlier. In effect, the light pushes their circadian clock forward.

In addition, the researchers tracked how long it takes alcohol to travel to the master clock in the brain. They also took regular readings of subcutaneous alcohol levels, which are akin to blood alcohol levels. In the final phase of the experiment, the hamsters that received alcohol were switched to regular water to examine the effects of withdrawal.

The study found that:

* The hamsters that drank alcohol had the hardest time shifting their rhythms after exposure to the dim light, and the more alcohol they drank, the harder it was to adjust. Exposure to dim light caused the water-only hamsters to wake up 72 minutes earlier than they normally would. The 10% alcohol group woke up 30 minutes earlier and the 20% alcohol group woke up only 18 minutes earlier.
* Exposure to bright light helped the alcohol-consuming hamsters to wake up sooner, greatly reducing the difference in wake up times among the groups. The control animals woke up 102 minutes earlier compared to the 20% alcohol group that woke up 84 minutes earlier.
* Total time spent active during the 24-hour period was the same for all three groups. However, the hamsters that consumed alcohol had fewer bouts of activity that lasted longer than the water-consuming controls. The control group had more bouts of activity over the course of the day.
* When the hamsters were withdrawn from alcohol for 2-3 days and then exposed to the same light treatment again, they woke up much earlier than the animals that had drunk only water. The hamsters that were withdrawn from alcohol woke up 126 minutes sooner compared to the water drinking controls, who advanced 66 minutes. This exaggerated response persisted even up to three days later, when the experiment ended.
* The hamsters drank the most heavily shortly after the beginning of the dark cycle, when they would naturally be most active. A peak in alcohol reached the suprachiasmatic nucleus in the brain 20 minutes later.

Human applications?

The researchers aim to apply the research to people, who also show circadian disruptions from drinking. Specifically, the study suggests the following:

* People who drink alcohol, particularly late into the night, may not respond to important light cues to keep their biological clocks in synch with daylight over the next 24 hours. Even low levels of alcohol may impair the response to light cues, said Ruby.
* After the first 24 hours, the circadian cycle continues to be affected, even without further consumption of alcohol.
* Exposure to bright light in the morning may reduce the disruption of alcohol to the biological clock.
* Chronic drinking continues to affect the biological clock even after withdrawal from alcohol. The hamsters withdrawn from alcohol woke up much earlier in response to light than they normally would, just like people who are trying to stop drinking. Getting a person’s circadian rhythm back in line after quitting may be why staying abstinent is so difficult.
* Chronic drinking may affect activity patterns, making drinkers less active at times of the day when they should be active and more active when they should not be, such as late at night.

Journal reference:

1. Christina L. Ruby, Allison J. Brager, Marc A. DePaul, Rebecca A. Prosser and J. David Glass. Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster. AJP Regulatory Integrative and Comparative Physiology, 2009; 297 (3): R729 DOI: 10.1152/ajpregu.00268.2009