Однако! http://www.biologynews.net/archives/2009/06/16/cannabis_alters_human_dna_new_study.html
A new study published by University of Leicester researchers has found "convincing evidence" that cannabis smoke damages DNA in ways that could potentially increase the risk of cancer development in humans.
Using a newly developed highly sensitive liquid chromatography-tandem mass spectrometry method, the University of Leicester scientists found clear indication that cannabis smoke damages DNA, under laboratory conditions.
They have now published the findings in the journal Chemical Research in Toxicology1.
The research was carried out by Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P. Steward, Dan Segerback and Peter B. Farmer from the Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine and Karolinska Institute, Sweden.
Raj Singh said: "Parts of the plant Cannabis sativa, also known as marijuana, ganja, and various street names, are commonly smoked as a recreational drug, although its use for such purposes is illegal in many countries.
"There have been many studies on the toxicity of tobacco smoke. It is known that tobacco smoke contains 4000 chemicals of which 60 are classed as carcinogens. Cannabis in contrast has not been so well studied. It is less combustible than tobacco and is often mixed with tobacco in use. Cannabis smoke contains 400 compounds including 60 cannabinoids. However, because of its lower combustibility it contains 50% more carcinogenic polycyclic aromatic hydrocarbons including naphthalene, benzanthracene, and benzopyrene, than tobacco smoke."
Writing in the journal Chemical Research in Toxicology, the scientists describe the development of a mass spectrometry method that provides a clear indication that cannabis smoke damages DNA, under laboratory conditions.
The authors added: "It is well known that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. Scientists were unsure though whether cannabis smoke would have the same effect. Our research has focused on the toxicity of acetaldehyde, which is present in both tobacco and cannabis."
The researchers add that the ability of cannabis smoke to damage DNA has significant human health implications especially as users tend to inhale more deeply than cigarette smokers, which increases respiratory burden. "The smoking of 3-4 cannabis cigarettes a day is associated with the same degree of damage to bronchial mucus membranes as 20 or more tobacco cigarettes a day," the team adds.
"These results provide evidence for the DNA damaging potential of cannabis smoke," the researchers conclude, "implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development."
Source : University of Leicester
п'ятниця, 19 червня 2009 р.
Продолжительность жизни и окислительный стресс
Такой вот спорный вопрос - этот окислительный стресс... Новая инфа на http://www.scienceblog.com/cms/how-oxidative-stress-may-help-prolong-life-21533.html
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins ? cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one ? covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 ? and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels ? and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway ? to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
###
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins ? cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one ? covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 ? and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels ? and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway ? to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
###
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.
п'ятниця, 5 червня 2009 р.
О счастье и мозге
Отличная статья на http://www.scienceblog.com/cms/blog/5634-happiness-%E2%80%93-theory-how-our-brains-lie-us-21534.html
Happiness – A Theory: How our Brains Lie to Us
May 29, 2009
The dialectic between descent with modification and the expanded cortex of the mammalian brain appears to have led to a kind of “house of mirrors” in humans. The smarter we get, it seems, the more we believe in our perceptions, while our brains work overtime to concoct a version of reality divorced from the evidence.
As part of the tangle of sophisticated circuitry enabled by our expanded cortex, we are able to associate any one thing with virtually any other thing, creating for ourselves an illusion of passive observation of what is actually happening in our present-time experience. We think of our brains as truth-seeking devices, but they deceive us without respite, and in staggeringly sophisticated ways.
Vision, for instance, is a projection of our minds, rather than the passive process that our brains might have us believe. Memory is fraught with error, but we adopt a false recollection with the fervor of a loving mother toward her child. We strive to acquire multiple choices, but we thrive where there are very few choices to be made, and suffer where there is a profusion. We are willing to diminish our own resources in order to punish someone we perceive as acting unfairly. We divide our fellows into “us” and “them” with regularity, despite the evidence that, in every meaningful way, we are just the same. We fret over a perceived threat that is little more than a dissenting opinion – i.e., something that would make us wiser, if we gave it shrift. We ruminate over real and imagined negatives, traumatizing ourselves more than would ever occur if we simply dealt with adversity as it arose. We set for ourselves the impossible goal of changing another person, then fall into a funk as the futility of the venture becomes apparent. We consider ourselves to be right in demanding that the world be different than it is. We perceive ourselves as victims, where the overwhelming evidence is that we are being treated to a truly unique experience in the universe. We expend energy in loathing others, when the evidence is that doing so is like taking poison. We think we are thinking when we have the perception that we are thinking, where the evidence is that our brains are whirring away 24/7, primarily in ways to which we have no access.
Recognizing that our brains lie – that we must cultivate a healthy skepticism of our own mental processes – is an important step in the pursuit of happiness.
Happiness – A Theory: How our Brains Lie to Us
May 29, 2009
The dialectic between descent with modification and the expanded cortex of the mammalian brain appears to have led to a kind of “house of mirrors” in humans. The smarter we get, it seems, the more we believe in our perceptions, while our brains work overtime to concoct a version of reality divorced from the evidence.
As part of the tangle of sophisticated circuitry enabled by our expanded cortex, we are able to associate any one thing with virtually any other thing, creating for ourselves an illusion of passive observation of what is actually happening in our present-time experience. We think of our brains as truth-seeking devices, but they deceive us without respite, and in staggeringly sophisticated ways.
Vision, for instance, is a projection of our minds, rather than the passive process that our brains might have us believe. Memory is fraught with error, but we adopt a false recollection with the fervor of a loving mother toward her child. We strive to acquire multiple choices, but we thrive where there are very few choices to be made, and suffer where there is a profusion. We are willing to diminish our own resources in order to punish someone we perceive as acting unfairly. We divide our fellows into “us” and “them” with regularity, despite the evidence that, in every meaningful way, we are just the same. We fret over a perceived threat that is little more than a dissenting opinion – i.e., something that would make us wiser, if we gave it shrift. We ruminate over real and imagined negatives, traumatizing ourselves more than would ever occur if we simply dealt with adversity as it arose. We set for ourselves the impossible goal of changing another person, then fall into a funk as the futility of the venture becomes apparent. We consider ourselves to be right in demanding that the world be different than it is. We perceive ourselves as victims, where the overwhelming evidence is that we are being treated to a truly unique experience in the universe. We expend energy in loathing others, when the evidence is that doing so is like taking poison. We think we are thinking when we have the perception that we are thinking, where the evidence is that our brains are whirring away 24/7, primarily in ways to which we have no access.
Recognizing that our brains lie – that we must cultivate a healthy skepticism of our own mental processes – is an important step in the pursuit of happiness.
Оксидативный стресс - подробности влияния
Я, как обычно, отслеживаю новости об окислительном стрессе. Вот - очередная: http://www.scientificblogging.com/news_articles/oxidative_stress_linked_aging_cancer_and_now_longer_life
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins – cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one – covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 – and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels – and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway – to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.
Kelley R, Ideker T (2009) Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide. PLoS Genet 5(5): e1000488. doi:10.1371/journal.pgen.1000488
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins – cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one – covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 – and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels – and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway – to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.
Kelley R, Ideker T (2009) Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide. PLoS Genet 5(5): e1000488. doi:10.1371/journal.pgen.1000488
п'ятниця, 29 травня 2009 р.
Новости о влиянии кокаина на допаминовый метаболизм
Очень интересно: http://www.eurekalert.org/pub_releases/2009-05/muhc-cpa051909.php
Contact: Isabelle Klingisabelle.kling@muhc.mcgill.ca514-843-1560McGill University Health Centre
Cocaine: Perceived as a reward by the brain?
Researchers at the MNI and the MUHC open up a new path for cocaine addiction research
This release is available in French.
Montreal, May 19th 2009 - Cocaine is one of the oldest drugs known to humans, and its abuse has become widespread since the end of the 19th century. At the same time, we know rather little about its effects on the human brain or the mechanisms that lead to cocaine addiction. The latest article by Dr. Marco Leyton, of the Montreal Neurological Institute (MNI), McGill University and the McGill University Health Centre, which was published in the journal Biological Psychiatry on May 15, 2009, not only demonstrates a link between cocaine and the reward circuits in the brain but also associates the susceptibility to addiction with these mechanisms.
The results of this study show that sniffing cocaine triggers high levels of dopamine secretion in a central region of the brain called the striatum. Dopamine is known to play a critical role in the brain's response to reward as well as in its response to addictive drugs.
This study was carried out in ten non-addicted users of cocaine, all of whom sniffed cocaine on one test day and placebo powder on another. Participants underwent blood tests before and after taking the drug, and dopamine release in the brain was measured using PET scans.
"The ability of cocaine to activate dopamine release varies markedly from person to person. Our study suggests that this is related to how much of the drug the person consumed in the past," explained Dr. Leyton. The more cocaine someone has used in his or her lifetime, the more the brain will secrete dopamine during subsequent cocaine use. "It's possible therefore that the intensity of the reward-circuit response is related to increased susceptibility to addiction," stated Dr. Leyton.
Although the relationship between the intensity of dopamine secretion and the frequency of drug use has been demonstrated, researchers still do not fully understand its mechanism of action. Is it the repeated stimulation of the reward circuit that leads to addiction, or is it an inherent sensitivity to addiction that leads to the increased secretion of dopamine? This question is not easy to answer, especially since other factors come into play, such as other aspects of the subject's personal history.
Whatever the answer, the relationship between dopamine and cocaine means that this hormone could be a potential target for treatment against addiction. More research is required before treatments are available, but this study opens a new door in this direction.
Contact: Isabelle Klingisabelle.kling@muhc.mcgill.ca514-843-1560McGill University Health Centre
Cocaine: Perceived as a reward by the brain?
Researchers at the MNI and the MUHC open up a new path for cocaine addiction research
This release is available in French.
Montreal, May 19th 2009 - Cocaine is one of the oldest drugs known to humans, and its abuse has become widespread since the end of the 19th century. At the same time, we know rather little about its effects on the human brain or the mechanisms that lead to cocaine addiction. The latest article by Dr. Marco Leyton, of the Montreal Neurological Institute (MNI), McGill University and the McGill University Health Centre, which was published in the journal Biological Psychiatry on May 15, 2009, not only demonstrates a link between cocaine and the reward circuits in the brain but also associates the susceptibility to addiction with these mechanisms.
The results of this study show that sniffing cocaine triggers high levels of dopamine secretion in a central region of the brain called the striatum. Dopamine is known to play a critical role in the brain's response to reward as well as in its response to addictive drugs.
This study was carried out in ten non-addicted users of cocaine, all of whom sniffed cocaine on one test day and placebo powder on another. Participants underwent blood tests before and after taking the drug, and dopamine release in the brain was measured using PET scans.
"The ability of cocaine to activate dopamine release varies markedly from person to person. Our study suggests that this is related to how much of the drug the person consumed in the past," explained Dr. Leyton. The more cocaine someone has used in his or her lifetime, the more the brain will secrete dopamine during subsequent cocaine use. "It's possible therefore that the intensity of the reward-circuit response is related to increased susceptibility to addiction," stated Dr. Leyton.
Although the relationship between the intensity of dopamine secretion and the frequency of drug use has been demonstrated, researchers still do not fully understand its mechanism of action. Is it the repeated stimulation of the reward circuit that leads to addiction, or is it an inherent sensitivity to addiction that leads to the increased secretion of dopamine? This question is not easy to answer, especially since other factors come into play, such as other aspects of the subject's personal history.
Whatever the answer, the relationship between dopamine and cocaine means that this hormone could be a potential target for treatment against addiction. More research is required before treatments are available, but this study opens a new door in this direction.
понеділок, 25 травня 2009 р.
Счастливая наследственность?
Прочитано на http://www.scientificblogging.com/news_articles/can_you_inherit_happiness_endorphins_and_biochemistry_inheritance
As if you need another reason for parental guilt, a new article in Bioscience Hypotheses speculates that our feelings could impact our reproduction and affect our children.
Dr Alberto Halabe Bucay of Research Center Halabe and Darwich, Mexico, suggests that a wide range of chemicals that our brain generates when we are in different moods could affect 'germ cells' (eggs and sperm), the cells that ultimately produce the next generation. Such natural chemicals could affect the way that specific genes are expressed in the germ cells, and hence how a child develops.
In his article Halabe suggested that the hormones and chemicals resulting from happiness, depression and other mental states can affect our eggs and sperm, resulting in lasting changes in our children at the time of their conception.
Brain chemicals such as endorphins, and drugs, such as marijuana and heroin are known to have significant effects on sperm and eggs, altering the patterns of genes that are active in them.
"It is well known, of course, that parental behavior affects children, and that the genes that a child gets from its parents help shape that child's character." said Dr. Halabe Bucay. "My paper suggests a way that the parent's psychology before conception can actually affect the child's genes."
"This is an intriguing idea" commented Dr. William Bains, Editor of Bioscience Hypotheses. "We wanted to publish it to see what other scientists thought, and whether others had data that could support or disprove it. That is what our journal is for, to stimulate debate about new ideas, the more groundbreaking, the better."
Article: Alberto Halabe Bucay, 'Endorphins, personality, and inheritance: Establishing the biochemical bases of inheritance', Bioscience Hypotheses, In Press, Corrected Proof, Available online 7 May 2009 doi:10.1016/j.bihy.2009.03.003
As if you need another reason for parental guilt, a new article in Bioscience Hypotheses speculates that our feelings could impact our reproduction and affect our children.
Dr Alberto Halabe Bucay of Research Center Halabe and Darwich, Mexico, suggests that a wide range of chemicals that our brain generates when we are in different moods could affect 'germ cells' (eggs and sperm), the cells that ultimately produce the next generation. Such natural chemicals could affect the way that specific genes are expressed in the germ cells, and hence how a child develops.
In his article Halabe suggested that the hormones and chemicals resulting from happiness, depression and other mental states can affect our eggs and sperm, resulting in lasting changes in our children at the time of their conception.
Brain chemicals such as endorphins, and drugs, such as marijuana and heroin are known to have significant effects on sperm and eggs, altering the patterns of genes that are active in them.
"It is well known, of course, that parental behavior affects children, and that the genes that a child gets from its parents help shape that child's character." said Dr. Halabe Bucay. "My paper suggests a way that the parent's psychology before conception can actually affect the child's genes."
"This is an intriguing idea" commented Dr. William Bains, Editor of Bioscience Hypotheses. "We wanted to publish it to see what other scientists thought, and whether others had data that could support or disprove it. That is what our journal is for, to stimulate debate about new ideas, the more groundbreaking, the better."
Article: Alberto Halabe Bucay, 'Endorphins, personality, and inheritance: Establishing the biochemical bases of inheritance', Bioscience Hypotheses, In Press, Corrected Proof, Available online 7 May 2009 doi:10.1016/j.bihy.2009.03.003
Новое о механизмах эффектов экстази
Очень интересно... Как всегда грамотно написано на http://scienceblogs.com/drugmonkey/2009/05/waitcannabis_potentiates_the_e.php
Wait...Cannabis potentiates the effects of Ecstasy?
Category: Cannabis • MDMA
Posted on: May 15, 2009 5:35 PM, by DrugMonkey
Along with alcohol, caffeine and nicotine, the most-active ingredient in cannabis (Δ9-THC; "THC") is frequently co-ingested with MDMA by the Ecstasy user. There are, in fact, some suggestions that cannabis may be consumed in some cases specifically to assist with modulating the MDMA high.
Now, those that are aware of the tetrad test for cannabinoid action (necessary back before the first cannabinoid receptor was cloned in the early 90s) might think to themselves of a specific protective effect. One of the hallmarks of THC is that it reduces body temperature in rats. So if one of the problems with MDMA is that it results in high body temperature, it might be convenient if smoking a little dope had an action that reversed this physiological outcome.
This was supported by a paper by Morley et al (2004) which reported that yes indeed, if you inject a rat with 2.5 mg/kg THC i.p. it completely blocks the tympanic temperature elevation produced by 5 mg/kg MDMA i.p.
A recent study in humans suggests that caution is warranted.
Cannabis Coadministration Potentiates the Effects of "Ecstasy" on Heart Rate and Temperature in Humans. Dumont G, Kramers C, Sweep F, Touw D, van Hasselt J, de Kam M, van Gerven J, Buitelaar J, Verkes R. Clin Pharmacol Ther. 2009 May 13.
This study reports on the effects of 100 mg oral MDMA, three inhalations of about 6 mg THC (spaced at 90 min) and the combination in 13 human subjects. Plasma kinetics for the exogenous drugs, for norepinephrine and epinephrine and heart rate are reported. One of the more interesting bits, however, is reported in the following figure.
Tympanic temperature was increased by oral consumption of MDMA, reaching a peak about 90 minutes after ingestion (consistent with the plasma peak), as one might expect*. inhaling vaporized THC did not block this effect. The first inhalation of THC (timed to pill ingestion) looks to have delayed the onset of the temperature increase. However the second inhalation did not induce further delay and temperature ultimately reached a peak change approximately equal to the one after MDMA alone. The elevated temperature was sustained up to the end of the 300 min observation interval in the THC-MDMA combined condition compared with MDMA alone.
Hmm. Looking for differences here. The biggest thing would seem to be that this level of THC inhalation did not produce a reduction in body temperature by itself in humans. The doses that decrease body temperature in rodents are fairly high ones so what were these humans receiving? Well, the inhalation procedure in this study resulted in plasma levels of 60-80 ng/ml. This NHTSA site claims that 100-200 ng/ml of THC are "routinely" observed in cannabis smokers. See this, this, this for confirmation. So the present study was perhaps on the low side of things, but then speculating exactly how much cannabis an Ecstasy user might smoke is.....well, speculative. And the study did report about a 20-30 bpm elevation in heart rate after THC inhalation that appeared to be independent of MDMA (which itself elevated heart rate by about 20-30 bpm). So it was certainly in the range of physiological relevance.
Give that this study is in humans, given the doses seem more in line with what would be expected in the user population, I'd have to put more confidence in this study than in the Morley et al (2004) rat paper. Thus it appears unlikely that cannabis smoking in the recreational Ecstasy user provides any protection against MDMA-induced hyperthermia.
The prolongation of the elevated body temperature that was the excuse for using "Potentiates" in the title? Doesn't support a strong conclusion at this stage but it certainly brings up some other scenarios for risk with subsequent dosing.
__
*Actually it is not entirely true that one might expect this. This is well below the doses used in the clinical trials. One of the initial results seems to imply not just that mean temp did not significantly increase but that no individual experienced a 1 deg Celsius increase in temperature. Liechti and Vollenweider (2000) reported no effect of 1.5 mg/kg oral MDMA on axillary temperature. Nevertheless in a dedicated experiment using an ingested remote device to measure gastric ("core") temperature Freedman and colleagues (2005) found that 2 mg/kg oral MDMA did increase body temperature under cool and warm laboratory conditions.
п'ятниця, 15 травня 2009 р.
Курение поможет аллергикам???
Сенсационно! http://www.scientificblogging.com/news_articles/solution_allergies_cigarettes:
Smoking is bad for you, but it can also help with allergies, according to a new study which says that cigarette smoke can prevent allergies by decreasing the reaction of immune cells to allergens.
Smoking can cause lung cancer, pulmonary disease, and can even affect how the body fights infections but along with many harmful effects, smoking cigarettes has a surprising benefit: cigarettes can protect smokers from certain types of allergies. The new study says that cigarette smoke decreases the allergic response by inhibiting the activity of mast cells, the major players in the immune system's response to allergens.
Researchers at Utrecht University in the Netherlands found that treatment of primary cultured murine mast cells with a cigarette smoke-infused solution and activated with IgE and antigen or lipopolysaccharide (LPS) prevented the release of inflammation-inducing proteins in response to allergens, without affecting other mast cell immune functions.
The mast cells used in the study were derived from mice, but they say it is likely that the same anti-allergy effect will hold true in humans. While taking up smoking to cure allergies is unwise, Thomson concludes that the findings presented in this study are "consistent with a dampening of allergic responses in smokers."
Article: Mortaz E, Folkerts G, Engels F, Nijkamp FP, Redegeld FA, 'Cigarette smoke suppresses in vitro allergic activation of mouse mast cells', Clin Exp Allergy. 2009 May;39(5):679-87. Epub 2009 Mar 2
Smoking is bad for you, but it can also help with allergies, according to a new study which says that cigarette smoke can prevent allergies by decreasing the reaction of immune cells to allergens.
Smoking can cause lung cancer, pulmonary disease, and can even affect how the body fights infections but along with many harmful effects, smoking cigarettes has a surprising benefit: cigarettes can protect smokers from certain types of allergies. The new study says that cigarette smoke decreases the allergic response by inhibiting the activity of mast cells, the major players in the immune system's response to allergens.
Researchers at Utrecht University in the Netherlands found that treatment of primary cultured murine mast cells with a cigarette smoke-infused solution and activated with IgE and antigen or lipopolysaccharide (LPS) prevented the release of inflammation-inducing proteins in response to allergens, without affecting other mast cell immune functions.
The mast cells used in the study were derived from mice, but they say it is likely that the same anti-allergy effect will hold true in humans. While taking up smoking to cure allergies is unwise, Thomson concludes that the findings presented in this study are "consistent with a dampening of allergic responses in smokers."
Article: Mortaz E, Folkerts G, Engels F, Nijkamp FP, Redegeld FA, 'Cigarette smoke suppresses in vitro allergic activation of mouse mast cells', Clin Exp Allergy. 2009 May;39(5):679-87. Epub 2009 Mar 2
четвер, 14 травня 2009 р.
Больше думаем - сложнее выбор
Too much information: Process thinking can lead to difficult choices - отличная статья на http://www.eurekalert.org/pub_releases/2009-05/uocp-tmi051209.php
Choosing among products can be more difficult if you tend to think more about the process of using an item rather than the outcome of the purchase, according to a new study in the Journal of Consumer Research.
"Marketers often try to tempt consumers to buy their products by encouraging them to imagine themselves using the product," write authors Debora Viana Thompson (Georgetown University), Rebecca W. Hamilton (University of Maryland, College Park), and Petia K. Petrova (Dartmouth College). But this "process-oriented" thinking can lead to confusion.
"In this research, we show that when consumers are choosing among products, focusing on the process of using a product (versus on the outcomes) can increase decision difficulty and hinder consumers' motivation to subsequently implement their choices," the authors explain.
Consumer decisions often involve trade-offs between means and end benefits, such as weighing quality versus price, rewards versus risks, or enjoyment versus effort. Process-oriented thinkers tend to focus on both ends and means, making decisions more difficult.
For example, in one experiment, participants were asked to choose between a small apartment that required a short commute and one that was larger but required a longer commute. The researchers instructed participants to either think about how living in the apartment would affect their daily routine and habits (process-oriented thinking) or to think about what they would gain from living in the apartment (outcome-oriented thinking). "Process-oriented participants thought about both the size of the apartment and the length of the commute, were less likely to choose the larger apartment, and experienced more difficulty making the choice," the authors write.
"This experience of difficulty can have various negative consequences for consumers. It can lower consumer satisfaction with the decision process, increase willingness to postpone choices, increase the likelihood they will change their minds later and switch to a different option, and reduce motivation to implement the decision," the authors conclude.
###
Debora Viana Thompson, Rebecca W. Hamilton, and Petia K. Petrova. "When Mental Simulation Hinders Behavior: The Effects of Process-Oriented Thinking on Decision Difficulty and Performance." Journal of Consumer Research: December 2009 (published online April 9, 2009).
О влиянии кокаина на экспрессию генов
Новые исследования описаны на http://www.scientificblogging.com/news_articles/cocaine_regulates_gene_expression_and_has_longlasting_impact_behavior
New research sheds light on how cocaine regulates gene expression in a crucial reward region of the brain to elicit long-lasting changes in behavior. The study in Neuron provides insight into the molecular pathways regulated by cocaine and may lead to new strategies for battling drug addiction.
It is well established that addictive drugs induce persistent changes in the brain's reward circuits. Previous research has indicated that addiction to drugs such as cocaine is associated with altered gene expression in the nucleus accumbens (NAc), a region of the brain that is involved in motivation, pleasure, and reward.
"Although we have known for some time that changes in gene expression contribute to the long-lasting regulation of the brain's reward circuitry that is seen during drug addiction, how those specific genes are regulated is not well understood," explains senior study author, Dr. Eric J. Nestler from the Department of Neuroscience at the Mount Sinai School of Medicine.
Dr. Nestler and colleagues combined sophisticated and highly sensitive genetic isolation and screening techniques to study regulation of gene transcription in the mouse NAc, including regulation of chromatin structure, after repeated administration of cocaine. The results of this novel analysis significantly refined the understanding of cocaine-regulated gene transcription in general, and advanced knowledge of the specific role of two transcription factors known to play a prominent role in cocaine-induced addiction.
The researchers also identified a previously unrecognized family of genes, called the sirtuins, as being involved in cocaine addiction in the NAc. Chronic cocaine administration was linked with an increase in sirtuin gene transcription while increased sirtuin activity in NAc neurons was associated with a potentiation of the rewarding effects of cocaine. Importantly, pharmacological inhibition of sirtuins in the NAc reduced the rewarding effects of cocaine and the motivation to self-administer the drug.
Taken together, the results identify a subset of genes that are highly likely to be targets of cocaine and shed light on the specific mechanisms that underlie cocaine-induced changes in the NAc. "Our findings underscore the vast clinical potential of the many new gene targets identified in this study for the development of more effective treatments of cocaine and potentially other drug addictions," concludes Dr. Nestler.
The researchers include William Renthal, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Arvind Kumar, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Guanghua Xiao, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Matthew Wilkinson, Mount Sinai School of Medicine, New York, NY; Herbert E. Covington III, Mount Sinai School of Medicine, New York, NY; Ian Maze, Mount Sinai School of Medicine, New York, NY; Devanjan Sikder, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Alfred J. Robison, Mount Sinai School of Medicine, New York, NY; Quincey LaPlant, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, Mount Sinai School of Medicine, New York, NY; David M. Dietz, Mount Sinai School of Medicine, New York, NY; Scott J. Russo, Mount Sinai School of Medicine, New York, NY; Vincent Vialou, Mount Sinai School of Medicine, New York, NY; Sumana Chakravarty, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Thomas J. Kodadek, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Ashley Stack, Florida State University, Tallahassee, FL; Mohamed Kabbaj, Florida State University, Tallahassee, FL; and Eric J. Nestler, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, Mount Sinai School of Medicine, New York, NY.
New research sheds light on how cocaine regulates gene expression in a crucial reward region of the brain to elicit long-lasting changes in behavior. The study in Neuron provides insight into the molecular pathways regulated by cocaine and may lead to new strategies for battling drug addiction.
It is well established that addictive drugs induce persistent changes in the brain's reward circuits. Previous research has indicated that addiction to drugs such as cocaine is associated with altered gene expression in the nucleus accumbens (NAc), a region of the brain that is involved in motivation, pleasure, and reward.
"Although we have known for some time that changes in gene expression contribute to the long-lasting regulation of the brain's reward circuitry that is seen during drug addiction, how those specific genes are regulated is not well understood," explains senior study author, Dr. Eric J. Nestler from the Department of Neuroscience at the Mount Sinai School of Medicine.
Dr. Nestler and colleagues combined sophisticated and highly sensitive genetic isolation and screening techniques to study regulation of gene transcription in the mouse NAc, including regulation of chromatin structure, after repeated administration of cocaine. The results of this novel analysis significantly refined the understanding of cocaine-regulated gene transcription in general, and advanced knowledge of the specific role of two transcription factors known to play a prominent role in cocaine-induced addiction.
The researchers also identified a previously unrecognized family of genes, called the sirtuins, as being involved in cocaine addiction in the NAc. Chronic cocaine administration was linked with an increase in sirtuin gene transcription while increased sirtuin activity in NAc neurons was associated with a potentiation of the rewarding effects of cocaine. Importantly, pharmacological inhibition of sirtuins in the NAc reduced the rewarding effects of cocaine and the motivation to self-administer the drug.
Taken together, the results identify a subset of genes that are highly likely to be targets of cocaine and shed light on the specific mechanisms that underlie cocaine-induced changes in the NAc. "Our findings underscore the vast clinical potential of the many new gene targets identified in this study for the development of more effective treatments of cocaine and potentially other drug addictions," concludes Dr. Nestler.
The researchers include William Renthal, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Arvind Kumar, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Guanghua Xiao, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Matthew Wilkinson, Mount Sinai School of Medicine, New York, NY; Herbert E. Covington III, Mount Sinai School of Medicine, New York, NY; Ian Maze, Mount Sinai School of Medicine, New York, NY; Devanjan Sikder, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Alfred J. Robison, Mount Sinai School of Medicine, New York, NY; Quincey LaPlant, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, Mount Sinai School of Medicine, New York, NY; David M. Dietz, Mount Sinai School of Medicine, New York, NY; Scott J. Russo, Mount Sinai School of Medicine, New York, NY; Vincent Vialou, Mount Sinai School of Medicine, New York, NY; Sumana Chakravarty, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Thomas J. Kodadek, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Ashley Stack, Florida State University, Tallahassee, FL; Mohamed Kabbaj, Florida State University, Tallahassee, FL; and Eric J. Nestler, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, Mount Sinai School of Medicine, New York, NY.
середа, 6 травня 2009 р.
Снова о репарации ДНК
Отличная статья на http://www.biologynews.net/archives/2009/05/05/stopgap_dna_repair_needs_a_second_step.html
Оne can have a dream, two can make that dream so real, goes a popular song. Now a Weizmann Institute study has revealed that it takes two to perform an essential form of DNA repair.
Prof. Zvi Livneh of the Weizmann Institute's Biological Chemistry Department has been studying DNA repair for some two decades: 'Considering that the DNA of each cell is damaged about 20,000 times a day by radiation, pollutants and harmful chemicals produced within the body, it's obvious that without effective DNA repair, life as we know it could not exist. Most types of damage result in individual mutations – genetic 'spelling mistakes' – that are corrected by precise, error-free repair enzymes. Sometimes, however, damage results in more than a mere spelling mistake; it can cause gaps in the DNA, which prevent the DNA molecule from being copied when the cell divides, much like an ink blot or a hole on a book page interferes with reading. So dangerous are these gaps that the cell resorts to a sloppy but efficient repair technique to avoid them: It fills in the missing DNA in an inaccurate fashion. Such repair can save the cell from dying, but it comes at a price: this error-prone mechanism, discovered at the Weizmann Institute and elsewhere about a decade ago, is a major source of mutations.'
In a recent study he conducted with graduate students Sigal Shachar and Omer Ziv, as well as researchers from the US and Germany, Livneh revealed how the error-prone repair works. The team found that such repair proceeds in two steps and requires two types of enzymes, belonging to the family of enzymes called DNA polymerases, which synthesize DNA. First, one repair enzyme, 'the inserter,' does its best to fit in a genetic 'letter' into the gap, opposite the damaged site in the DNA molecule; several enzymes can perform this initial step, which often results in the insertion of an incorrect genetic letter. Next, another enzyme, 'the extender,' helps to restore regular copying of DNA by attaching additional DNA letters after the damaged site; only one repair enzyme is capable of performing this vital second step. These findings were published recently in the EMBO Journal.
Оne can have a dream, two can make that dream so real, goes a popular song. Now a Weizmann Institute study has revealed that it takes two to perform an essential form of DNA repair.
Prof. Zvi Livneh of the Weizmann Institute's Biological Chemistry Department has been studying DNA repair for some two decades: 'Considering that the DNA of each cell is damaged about 20,000 times a day by radiation, pollutants and harmful chemicals produced within the body, it's obvious that without effective DNA repair, life as we know it could not exist. Most types of damage result in individual mutations – genetic 'spelling mistakes' – that are corrected by precise, error-free repair enzymes. Sometimes, however, damage results in more than a mere spelling mistake; it can cause gaps in the DNA, which prevent the DNA molecule from being copied when the cell divides, much like an ink blot or a hole on a book page interferes with reading. So dangerous are these gaps that the cell resorts to a sloppy but efficient repair technique to avoid them: It fills in the missing DNA in an inaccurate fashion. Such repair can save the cell from dying, but it comes at a price: this error-prone mechanism, discovered at the Weizmann Institute and elsewhere about a decade ago, is a major source of mutations.'
In a recent study he conducted with graduate students Sigal Shachar and Omer Ziv, as well as researchers from the US and Germany, Livneh revealed how the error-prone repair works. The team found that such repair proceeds in two steps and requires two types of enzymes, belonging to the family of enzymes called DNA polymerases, which synthesize DNA. First, one repair enzyme, 'the inserter,' does its best to fit in a genetic 'letter' into the gap, opposite the damaged site in the DNA molecule; several enzymes can perform this initial step, which often results in the insertion of an incorrect genetic letter. Next, another enzyme, 'the extender,' helps to restore regular copying of DNA by attaching additional DNA letters after the damaged site; only one repair enzyme is capable of performing this vital second step. These findings were published recently in the EMBO Journal.
Understanding how this major form of DNA repair works can have significant clinical implications. Since defects in this process increase the risk of cancer, clarifying its nuts and bolts might one day make it possible to enhance it in people whose natural DNA repair is deficient. In addition, manipulating this mechanism can improve the effectiveness of cancer drugs. Cancer cells can resist chemotherapy by exploiting their natural repair mechanisms, and blocking these mechanisms may help overcome this resistance, leading to a targeted destruction of the cancerous tumor.
Source : Weizmann Institute of Science
четвер, 9 квітня 2009 р.
О допамине и сексуальности :)
Приём агонистов допамина, даже при лечении болезни Паркинсона - влияет на поведенческие характеристики! Читаю на http://www.scientificblogging.com/erin039s_spin/hypersexual_compulsive_gambler_blame_dopamine_only_if_you_have_parkinsons_disease_too
According to a new study published by the Mayo Clinic, patients with Parkinson disease (PD) have another problem to deal with. Researchers have found that one in six patients taking therapeutic doses of
certain prescription drugs for management of PD have developed troubling behavioral symptoms. The most problematic symptoms include compulsive gambling and hypersexuality.
PD is one of the most common degenerative neurological disorders affecting 1.5 million people in the US. PD is characterized by the destruction of neurons responsible for the production of dopamine which allows coordinated function of muscles, movement and signals from the brain. Without dopamine, motor function becomes impaired and other signals from the brain are misinterpreted or not received at all. Tremors, slow movements, stiffness and imbalance are all symptoms of Parkinson’s and can severely impair normal life.
This study, published in the April issue of Mayo Clinic Proceedings, is based upon two previous case series from 2005, report a connection between dopamine agonist medications and the destructive symptoms. Dopamine agonists are compounds that activate dopamine receptors in the absence of dopamine. Dopamine agonists can then act as a dopamine substitute and manage signaling pathways and proper messaging which dopamine is the major mediator.
Dopamine agonists are a significant part of PD treatment and include drugs like pramipexole and ropinirole. In small doses, these drugs have other uses as well, and are also commonly prescribed for Restless Legs Syndrome (RLS). This class of medication stimulates specific brain circuits which are associated with substrates for emotional and reward centers in the brain and can cause an increase in hedonistic behaviors. Too much dopamine substitute may affect a PD patient’s brain chemistry and urge them to do “feel-good” behaviors to an extreme. Thus symptoms such as compulsive gambling and hyper-sexuality can arise.
"The 2005 case series alerted us that something bad was happening to some unfortunate people. This study was done to assess the likelihood that this effect would happen to the average Parkinson's patient treated with these agents," says J. Michael Bostwick, M.D., Mayo Clinic psychiatrist who spearheaded the new study.
Researchers analyzed a group of 267 patients, 66 of which were taking dopamine agonists as their primary medication for management of PD. They found that 7 of the patients experiences new onset of hedonistic behavioral gambling or hypersexuality. They also found that none of the other patients developed these symptoms, which included 28 patients taking lower doses of the dopamine agonists. Mayo physicians suggest that a lower dosage of these dopamine agonists be recommended for susceptible patients to reduce risk of unwanted side effects.
"It is crucial for clinicians prescribing dopamine agonists to apprise patients as well as their spouses or partners about this potential side effect. The onset can be insidious and overlooked until life-altering problems develop," says J. Eric Ahlskog, M.D., Ph.D., Mayo Clinic neurologist and co-author of the 2005 study. "It also is worth noting that the affected patients were all taking therapeutic doses. Very low doses, such as those used to treat restless legs syndrome, carry much less risk."
According to the National Parkinson’s Foundation, the disease affects 1 out of every 100 people over the age of 60. Globally, 2% of the population worldwide will develop Parkinson’s in their lifetime according to projections made by the Mayo Clinic.
According to a new study published by the Mayo Clinic, patients with Parkinson disease (PD) have another problem to deal with. Researchers have found that one in six patients taking therapeutic doses of
certain prescription drugs for management of PD have developed troubling behavioral symptoms. The most problematic symptoms include compulsive gambling and hypersexuality.
PD is one of the most common degenerative neurological disorders affecting 1.5 million people in the US. PD is characterized by the destruction of neurons responsible for the production of dopamine which allows coordinated function of muscles, movement and signals from the brain. Without dopamine, motor function becomes impaired and other signals from the brain are misinterpreted or not received at all. Tremors, slow movements, stiffness and imbalance are all symptoms of Parkinson’s and can severely impair normal life.
This study, published in the April issue of Mayo Clinic Proceedings, is based upon two previous case series from 2005, report a connection between dopamine agonist medications and the destructive symptoms. Dopamine agonists are compounds that activate dopamine receptors in the absence of dopamine. Dopamine agonists can then act as a dopamine substitute and manage signaling pathways and proper messaging which dopamine is the major mediator.
Dopamine agonists are a significant part of PD treatment and include drugs like pramipexole and ropinirole. In small doses, these drugs have other uses as well, and are also commonly prescribed for Restless Legs Syndrome (RLS). This class of medication stimulates specific brain circuits which are associated with substrates for emotional and reward centers in the brain and can cause an increase in hedonistic behaviors. Too much dopamine substitute may affect a PD patient’s brain chemistry and urge them to do “feel-good” behaviors to an extreme. Thus symptoms such as compulsive gambling and hyper-sexuality can arise.
"The 2005 case series alerted us that something bad was happening to some unfortunate people. This study was done to assess the likelihood that this effect would happen to the average Parkinson's patient treated with these agents," says J. Michael Bostwick, M.D., Mayo Clinic psychiatrist who spearheaded the new study.
Researchers analyzed a group of 267 patients, 66 of which were taking dopamine agonists as their primary medication for management of PD. They found that 7 of the patients experiences new onset of hedonistic behavioral gambling or hypersexuality. They also found that none of the other patients developed these symptoms, which included 28 patients taking lower doses of the dopamine agonists. Mayo physicians suggest that a lower dosage of these dopamine agonists be recommended for susceptible patients to reduce risk of unwanted side effects.
"It is crucial for clinicians prescribing dopamine agonists to apprise patients as well as their spouses or partners about this potential side effect. The onset can be insidious and overlooked until life-altering problems develop," says J. Eric Ahlskog, M.D., Ph.D., Mayo Clinic neurologist and co-author of the 2005 study. "It also is worth noting that the affected patients were all taking therapeutic doses. Very low doses, such as those used to treat restless legs syndrome, carry much less risk."
According to the National Parkinson’s Foundation, the disease affects 1 out of every 100 people over the age of 60. Globally, 2% of the population worldwide will develop Parkinson’s in their lifetime according to projections made by the Mayo Clinic.
References:
п'ятниця, 27 березня 2009 р.
Ещё - окислительный стресс и ДНК
Моей радости нет предела - ещё одна новость об оксидативном повреждении ДНК, на http://www.eurekalert.org/pub_releases/2009-03/eu-drm032609.php
Public release date: 26-Mar-2009
Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Public release date: 26-Mar-2009
Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Like doctors making house calls, some DNA repair enzymes can relocate to the part of the cell that needs their help, a collaborative team of scientists at Emory University School of Medicine has found.
The signal that prompts relocation is oxidative stress, an imbalance of cellular metabolism connected with several human diseases.
The study integrated the expertise of three Emory groups and resulted in a new level of understanding of the cell's response to genetic damage. The finding could lead to new targets for anti-cancer drugs that interfere with DNA repair, says Paul Doetsch, PhD, professor of biochemistry, radiation oncology, and hematology and oncology at Emory University School of Medicine.
The results were published in the February 1 issue of Molecular and Cellular Biology. The journal's editors chose an image of yeast cells with fluorescent DNA repair enzymes for the cover.
"DNA damage and oxidative stress are very closely related," Doetsch says. "For example, the way radiation inflicts most of its damage on DNA is through oxidative stress. The more we know about how cells respond to oxidative stress, the more chances there could be to influence those responses for diagnostic or therapeutic purposes."
The DNA inside cells is continually under assault by heat, radiation and oxygen. Cells have an extensive set of repair enzymes that comb through DNA, continually excising and re-copying damaged segments. To complicate matters, mitochondria (cells' miniature power plants) have their own DNA.
Working with Doetsch, Emory graduate students Lyra Griffiths and Dan Swartzlander, and biochemists Anita Corbett and Keith Wilkinson, genetically modified strains of yeast so that two different DNA repair enzymes would be fluorescent. They were able to follow the enzymes around the cell when yeast was exposed to hydrogen peroxide, causing oxidative stress, or to other chemicals causing DNA damage.
One DNA repair enzyme they studied, Ntg1, moves to the nucleus or the mitochondria depending on where DNA damage is concentrated, the authors found. In contrast, a related enzyme, Ntg2, stays in the nucleus under all conditions.
Cells appear to direct Ntg1's relocation by briefly attaching a small protein called SUMO to what needs to be moved around, the authors found. SUMO is found in fungi, plants and animals and is already being investigated by several research groups as a possible target for anti-cancer drugs.
###
The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; the Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.
неділя, 22 березня 2009 р.
И снова о депрессии
Об очень интересном исследовании мне довелось прочитать на http://www.scienceblog.com/cms/depressed-people-have-trouble-learning-good-things-life-19595.html, оказывается, восприятие позитивной и негативной информации отличается у людей в депрессии и нормальных...
COLUMBUS, Ohio - While depression is often linked to negative thoughts and emotions, a new study suggests the real problem may be a failure to appreciate positive experiences.
Researchers at Ohio State University found that depressed and non-depressed people were about equal in their ability to learn negative information that was presented to them.
But depressed people weren't nearly as successful at learning positive information as were their non-depressed counterparts.
"Since depression is characterized by negative thinking, it is easy to assume that depressed people learn the negative lessons of life better than non-depressed people - but that's not true," said Laren Conklin, co-author of the study and a graduate student in psychology at Ohio State.
The study appears in the March issue of the Journal of Behavior Therapy and Experimental Psychiatry.
Researchers tested 34 college students, 17 of whom met criteria for clinical depression and 17 of whom were not depressed.
This study is one of the first to be able to link clinical levels of depression to how people form attitudes when they encounter new events or information, said Daniel Strunk, co-author of the study and assistant professor of psychology at Ohio State.
Strunk said the key to conducting this study was the use of a computer game paradigm co-developed at Ohio State in 2004 by Russell Fazio, a professor of psychology and co-author of this new study. Fazio and his collaborators, Natalie Shook, a PhD graduate of Ohio State now at Virginia Commonwealth University and J. Richard Eiser of the University of Sheffield (England) have used the game in many studies examining differences in the development of positive and negative attitudes.
The developers affectionately call the game "BeanFest." It involves people encountering images of beans on the computer screen. The beans could be good or bad, depending on their shape and the number of speckles they had.
Good beans earned the players points, while bad beans took points away. The goal was to earn as many points as possible.
While the game may seem trivial to a naive audience, Strunk said it offers a unique and powerful way to measure how people learn new attitudes.
"Before, if researchers wanted to investigate how people formed new attitudes, it was very difficult to do," Strunk said. If researchers asked about real-life issues, the problem is that prior learning and attitudes may impact how people respond to new information. But in this game, participants don't have any prior knowledge or attitudes about the beans so researchers could learn how they formed their attitudes in a novel situation, without interference from past experiences.
In the game phase of this study, participants had to choose whether they would accept a bean when it appeared on the screen. If they accepted the bean, the points were added or deducted from their total. If they rejected the bean, they were still told how many points they would have earned or lost if they had accepted it.
Each of the 34 beans was shown three times during the game phase, giving the participants a good opportunity to learn which beans were good and which were bad.
Then, in the test phase, participants had to indicate whether beans they learned about in the game phase were "good" (choosing it would increase points) or "bad" (choosing it would decrease points). The researchers tallied how well participants did in correctly identifying positive and negative beans.
The non-depressed students correctly identified 61 percent of the negative beans, which was about the same as the depressed students, who correctly identified 66 percent of the "bad" beans.
But while the non-depressed students correctly identified 60 percent of the positive beans, depressed students correctly classified only 49 percent of these good beans. Non-depressed students identified the good beans better than the depressed students, who failed to identify good beans better than chance.
"The depressed people showed a bias against learning positive information although they had no trouble learning the negative," Strunk said.
One of measures researchers used in the study classified whether the depressed participants were currently undergoing a mild, moderate or severe episode of depression. In the study, those undergoing a severe depressive episode did more poorly on correctly choosing positive beans than those with mild depression, further strengthening the results.
While more research is needed, Conklin and Strunk said this study suggests possible ways to improve treatment of depressed people.
"Depressed people may have a tendency to remember the negative experiences in a situation, but not remember the good things that happened," Conklin said. "Therapists need to be aware of that."
For example, a depressed person who is trying out a new exercise program may mention how it makes him feel sore and tired - but not consider the weight he has lost as a result of the exercise.
"Therapists might focus more on helping their depressed clients recognize and remember the positive aspects of their new experiences," Strunk said.
вівторок, 17 березня 2009 р.
Тромбоциты и сепсис
Тема тромбоцитов сейчас меня особо интересует, поэтому советую почитать статейку на http://www.eurekalert.org/pub_releases/2009-03/cnmc-cnr031009.php
Contact: Jennifer Leischerjleische@cnmc.org202-476-4500Children's National Medical Center
Children's National research links platelets to sepsis-related organ failure
Conventionally thought to be the bloodstream's 'innocent bystanders,' platelets may actually play a more sinister role in organ failure caused by severe sepsis
WASHINGTON, DC—Scientists at Children's National Medical Center have identified a previously unknown contributor to organ failure in patients suffering from sepsis: platelets.
The finding, published in the American Journal of Respiratory and Critical Care Medicine, is the first time doctors have looked at and linked platelets to poor outcomes from this often fatal infection.
"Despite many medical advances over the last few decades, mortality rates for sepsis have not really improved," said Robert Freishtat, MD, MPH, of the Center for Genetic Medicine Research at Children's National Medical Center, who led the study. "But now that we know that platelets, which we previously believed to be merely 'innocent bystanders,' can actually contribute to the development of fatal complications from sepsis, we can use this knowledge to better gauge someone's risk of dying and to design new interventions."
Sepsis is the tenth leading cause of death in the United States. More than 40 percent of sepsis cases are fatal, and in most, the resulting organ failure, not the underlying infection, is the primary cause of death. Through gene and protein analyses in both septic mice and humans, scientists found that cases of severe sepsis featured a unique attribute: the genes within platelets were triggered to produce a protein known as granzyme B, which has been shown in previous studies to contribute to cell death as part of the body's immune response to cancer and viruses. During sepsis, platelets collect within major organs including the spleen, an important infection-fighting organ. As they collect and come into contact with the organ's cells, the granzyme B, if present, will cause the organ's cells to die. Previous research has shown that that this factor may be a major contributor to organ failure. Granzyme B was only detected in humans and mice with the most severe sepsis.
"Detection of granzyme B in platelets could be a huge step forward in battling sepsis," said Dr. Freishtat. "First, as a prognostic indicator, the protein's presence could show more aggressive treatments are needed right off the bat. Eventually, perhaps this knowledge will help us find a way to prevent organ failure by targeting interventions directly at the platelets and granzyme B production."
###
The study was funded by the National Institutes of Health and Children's National Medical Center.
The full manuscript, "Sepsis Alters the Megakaryocyte-Platelet Transcriptional Axis Resulting in Granzyme B-mediated Lymphotoxicity" is available on the journal's website.
About Children's National Medical Center
Children's National Medical Center, located in Washington, DC, is a proven leader in the development of innovative new treatments for childhood illness and injury. Children's has been serving the nation's children for more than 135 years. Children's National is proudly ranked among the best pediatric hospitals in America by US News & World Report and the Leapfrog Group. For more information, visit www.childrensnational.org. Children's Research Institute, the academic arm of Children's National Medical Center, encompasses the translational, clinical, and community research efforts of the institution. Learn more about our research programs at www.childrensnational.org/research.
Contact: Jennifer Leischerjleische@cnmc.org202-476-4500Children's National Medical Center
Children's National research links platelets to sepsis-related organ failure
Conventionally thought to be the bloodstream's 'innocent bystanders,' platelets may actually play a more sinister role in organ failure caused by severe sepsis
WASHINGTON, DC—Scientists at Children's National Medical Center have identified a previously unknown contributor to organ failure in patients suffering from sepsis: platelets.
The finding, published in the American Journal of Respiratory and Critical Care Medicine, is the first time doctors have looked at and linked platelets to poor outcomes from this often fatal infection.
"Despite many medical advances over the last few decades, mortality rates for sepsis have not really improved," said Robert Freishtat, MD, MPH, of the Center for Genetic Medicine Research at Children's National Medical Center, who led the study. "But now that we know that platelets, which we previously believed to be merely 'innocent bystanders,' can actually contribute to the development of fatal complications from sepsis, we can use this knowledge to better gauge someone's risk of dying and to design new interventions."
Sepsis is the tenth leading cause of death in the United States. More than 40 percent of sepsis cases are fatal, and in most, the resulting organ failure, not the underlying infection, is the primary cause of death. Through gene and protein analyses in both septic mice and humans, scientists found that cases of severe sepsis featured a unique attribute: the genes within platelets were triggered to produce a protein known as granzyme B, which has been shown in previous studies to contribute to cell death as part of the body's immune response to cancer and viruses. During sepsis, platelets collect within major organs including the spleen, an important infection-fighting organ. As they collect and come into contact with the organ's cells, the granzyme B, if present, will cause the organ's cells to die. Previous research has shown that that this factor may be a major contributor to organ failure. Granzyme B was only detected in humans and mice with the most severe sepsis.
"Detection of granzyme B in platelets could be a huge step forward in battling sepsis," said Dr. Freishtat. "First, as a prognostic indicator, the protein's presence could show more aggressive treatments are needed right off the bat. Eventually, perhaps this knowledge will help us find a way to prevent organ failure by targeting interventions directly at the platelets and granzyme B production."
###
The study was funded by the National Institutes of Health and Children's National Medical Center.
The full manuscript, "Sepsis Alters the Megakaryocyte-Platelet Transcriptional Axis Resulting in Granzyme B-mediated Lymphotoxicity" is available on the journal's website.
About Children's National Medical Center
Children's National Medical Center, located in Washington, DC, is a proven leader in the development of innovative new treatments for childhood illness and injury. Children's has been serving the nation's children for more than 135 years. Children's National is proudly ranked among the best pediatric hospitals in America by US News & World Report and the Leapfrog Group. For more information, visit www.childrensnational.org. Children's Research Institute, the academic arm of Children's National Medical Center, encompasses the translational, clinical, and community research efforts of the institution. Learn more about our research programs at www.childrensnational.org/research.
Работа над ошибками (белки в клетке) :)
Отличная новость!!! http://www.biologynews.net/archives/2009/03/12/cells_get_two_chances_not_just_one_to_fix_their_mistakes.html
Оказывается, клетки имеют не один шанс исправить ошибки!!!
Cells have two chances to fix the same mistake in their protein-making process instead of just one – a so-called proofreading step – that had previously been identified, according to new research.
Proteins are essential to life and do most of the work in cells, so avoiding mistakes during their production is a critical way to prevent a variety of harmful conditions that result when mutations cause damage or when cells die.
Better knowledge of the mechanism behind these occasional mistakes could increase understanding of various disease processes, especially in neurodegenerative disorders, some of which scientists suspect are associated with mutated proteins, Ohio State University researchers say.
The discovery of this second step also gives drug-makers a new target to consider, especially in the development of antibiotics. Drugs designed to interfere with the enzymes that make, find and repair the mistakes during protein production could be powerful agents in stopping bacterial cell growth.
One key enzyme involved in cell quality control is called phenylalanyl-tRNA synthetase (PheRS). This enzyme's job within the cell is to correctly select one of the amino acids that will be strung together into a molecule to make a protein.
"We're describing a pretty simple process where the cell says, 'I think I'll have one more look at that,'" said Michael Ibba, senior author of the study and an associate professor of microbiology at Ohio State. "It looks at the building blocks and checks that they're right before it makes the protein."
The research is published in the March 13 issue of the journal Molecular Cell.
In past examinations of this mechanism in the cell, Ibba's lab had identified a single quality-control measure cells take as they produce proteins. The researchers initially thought that this proofreading step was the only check during the protein-making process.
"There was a step at which we thought, now it's done, and if a mistake gets through here, it's irreversible and is going to end up as a mistake. But it turns out there is yet another step at which the cell has another look. It's checking itself," Ibba said. "The bottom line is we must have been missing something."
Previous research has suggested that cells, on average, make one error during protein production for every 10,000 amino acids strung together.
"What we do is try to find out where that error rate number comes from," said Ibba, also an investigator in Ohio State's Biochemistry Program and its Center for RNA Biology. "Understanding where the mistakes come from means you can try to predict conditions that will either raise or lower the frequency of mistakes."
Within the cell, PheRS is one member of a family of enzymes responsible for selecting amino acids that will be attached to an adapter molecule that facilitates the protein-building process. The amino acids must be attached to the appropriate adapter to ensure the genetic code is deciphered properly.
Ibba's lab has been studying this enzyme's activities for years. After observing over time what appeared to be a second quality-control step, the scientists had to devise a method they could use to prove the second step occurred. So the researchers first generated the mistake synthetically, and then introduced other enzymes that would normally be present later in protein production to see if they could then observe the second quality check.
The researchers discovered that the same enzyme that makes the mistake, PheRS, also checks and cleans up after itself in a process that removes the incorrect amino acid and attaches the correct one in its place. And the enzyme can do this even after an initial check misses the mistake and allows the protein-building process to continue.
"The enzyme is two catalysts, one that can make the mistake and one that can correct the mistake. It can let the mistake go and grab it back. Nothing tells it to do this. It figures it out on its own," Ibba said.
These experiments were conducted using E. coli bacterial cells, which are a preferred model for many cell studies. But understanding this mechanism can be particularly useful in the design of antibiotics because many such drugs specifically target the protein-production process to halt the growth of bacteria.
"We're trying to understand the process which in the past has proven to be very fruitful as a target for antibiotics," Ibba said. "The hope is when you target protein synthesis in general, either you stop it completely or make the process too inaccurate so the cell can't grow."
This very same quality-control process, involving a different enzyme, is being targeted in the development of an antifungal agent that is currently being tested in humans to treat toenail fungus, Ibba noted.
Even with this second editing step identified, there is still plenty to learn. For example, these enzymes do not act alone. Their interactions with other enzymes in the cell affect their behavior. And exactly what happens when mutant proteins slip through the quality-control system remains poorly understood, as well.
"Sometimes mistakes do get in, and that's what we're still uncertain about. Even in some neurodegenerative disorders, we can see that there are almost certainly errors, but the frequency is impossible to know at present," Ibba said. "If we know more about the mechanism, then if we find mutations, we'll have a much better chance of finding what the consequences of those mutations are."
Source : Ohio State University
неділя, 15 березня 2009 р.
Соль - антидепрессант!
Прочитала новую статью на http://www.scienceblog.com/cms/study-suggests-salt-might-be-natures-antidepressant-19352.html и призадумалась...
Most people consume far too much salt, and a University of Iowa researcher has discovered one potential reason we crave it: it might put us in a better mood.
UI psychologist Kim Johnson and colleagues found in their research that when rats are deficient in sodium chloride, common table salt, they shy away from activities they normally enjoy, like drinking a sugary substance or pressing a bar that stimulates a pleasant sensation in their brains.
"Things that normally would be pleasurable for rats didn't elicit the same degree of relish, which leads us to believe that a salt deficit and the craving associated with it can induce one of the key symptoms associated with depression," Johnson said.
The UI researchers can't say it is full-blown depression because several criteria factor into such a diagnosis, but a loss of pleasure in normally pleasing activities is one of the most important features of psychological depression. And, the idea that salt is a natural mood-elevating substance could help explain why we're so tempted to over-ingest it, even though it's known to contribute to high blood pressure, heart disease and other health problems.
Past research has shown that the worldwide average for salt intake per individual is about 10 grams per day, which is greater than the U.S. Food and Drug Administration recommended intake by about 4 grams, and may exceed what the body actually needs by more than 8 grams.
Johnson, who holds appointments in psychology and integrative physiology in the College of Liberal Arts and Sciences and in pharmacology in the Carver College of Medicine, published a review of these findings in the July issue of the journal Physiology & Behavior with Michael J. Morris and Elisa S. Na, UI graduate students. In addition to reporting their own findings, the authors reviewed others' research on the reasons behind salt appetite.
High levels of salt are contained in everything from pancakes to pasta these days, but once upon a time, it was hard to come by. Salt consumption and its price skyrocketed around 2000 B.C. when it was discovered as a food preservative. Roman soldiers were paid in salt; the word salary is derived from the Latin for salt. Even when mechanical refrigeration lessened the need for salt in the 19th century, consumption continued in excess because people liked the taste and it had become fairly inexpensive. Today, 77 percent of our salt intake comes from processed and restaurant foods, like frozen dinners and fast food.
Evolution might have played an important part in the human hankering for salt. Humans evolved from creatures that lived in salty ocean water. Once on land, the body continued to need sodium and chloride because minerals play key roles in allowing fluids to pass in and out of cells, and in helping nerve cells transfer information throughout the brain and body. But as man evolved in the hot climate of Africa, perspiration robbed the body of sodium. Salt was scarce because our early ancestors ate a veggie-rich diet and lived far from the ocean.
"Most of our biological systems require sodium to function properly, but as a species that didn't have ready access to it, our kidneys evolved to become salt misers," Johnson said.
Behavior also came to play a key role in making sure we have enough salt on board. Animals like us come equipped with a taste system designed to detect salt and a brain that remembers the location of salt sources -- like salt licks in a pasture. A pleasure mechanism in the brain is activated when salt is consumed.
So the body needs salt and knows how to find it and how to conserve it. But today scientists are finding evidence that it's an abused, addictive substance -- almost like a drug.
One sign of addiction is using a substance even when it's known to be harmful. Many people are told to reduce sodium due to health concerns, but they have trouble doing so because they like the taste and find low-sodium foods bland.
Another strong aspect of addiction is the development of intense cravings when drugs are withheld. Experiments by Johnson and colleagues indicate similar changes in brain activity whether rats are exposed to drugs or salt deficiency.
"This suggests that salt need and cravings may be linked to the same brain pathways as those related to drug addiction and abuse," Johnson said.
Most people consume far too much salt, and a University of Iowa researcher has discovered one potential reason we crave it: it might put us in a better mood.
UI psychologist Kim Johnson and colleagues found in their research that when rats are deficient in sodium chloride, common table salt, they shy away from activities they normally enjoy, like drinking a sugary substance or pressing a bar that stimulates a pleasant sensation in their brains.
"Things that normally would be pleasurable for rats didn't elicit the same degree of relish, which leads us to believe that a salt deficit and the craving associated with it can induce one of the key symptoms associated with depression," Johnson said.
The UI researchers can't say it is full-blown depression because several criteria factor into such a diagnosis, but a loss of pleasure in normally pleasing activities is one of the most important features of psychological depression. And, the idea that salt is a natural mood-elevating substance could help explain why we're so tempted to over-ingest it, even though it's known to contribute to high blood pressure, heart disease and other health problems.
Past research has shown that the worldwide average for salt intake per individual is about 10 grams per day, which is greater than the U.S. Food and Drug Administration recommended intake by about 4 grams, and may exceed what the body actually needs by more than 8 grams.
Johnson, who holds appointments in psychology and integrative physiology in the College of Liberal Arts and Sciences and in pharmacology in the Carver College of Medicine, published a review of these findings in the July issue of the journal Physiology & Behavior with Michael J. Morris and Elisa S. Na, UI graduate students. In addition to reporting their own findings, the authors reviewed others' research on the reasons behind salt appetite.
High levels of salt are contained in everything from pancakes to pasta these days, but once upon a time, it was hard to come by. Salt consumption and its price skyrocketed around 2000 B.C. when it was discovered as a food preservative. Roman soldiers were paid in salt; the word salary is derived from the Latin for salt. Even when mechanical refrigeration lessened the need for salt in the 19th century, consumption continued in excess because people liked the taste and it had become fairly inexpensive. Today, 77 percent of our salt intake comes from processed and restaurant foods, like frozen dinners and fast food.
Evolution might have played an important part in the human hankering for salt. Humans evolved from creatures that lived in salty ocean water. Once on land, the body continued to need sodium and chloride because minerals play key roles in allowing fluids to pass in and out of cells, and in helping nerve cells transfer information throughout the brain and body. But as man evolved in the hot climate of Africa, perspiration robbed the body of sodium. Salt was scarce because our early ancestors ate a veggie-rich diet and lived far from the ocean.
"Most of our biological systems require sodium to function properly, but as a species that didn't have ready access to it, our kidneys evolved to become salt misers," Johnson said.
Behavior also came to play a key role in making sure we have enough salt on board. Animals like us come equipped with a taste system designed to detect salt and a brain that remembers the location of salt sources -- like salt licks in a pasture. A pleasure mechanism in the brain is activated when salt is consumed.
So the body needs salt and knows how to find it and how to conserve it. But today scientists are finding evidence that it's an abused, addictive substance -- almost like a drug.
One sign of addiction is using a substance even when it's known to be harmful. Many people are told to reduce sodium due to health concerns, but they have trouble doing so because they like the taste and find low-sodium foods bland.
Another strong aspect of addiction is the development of intense cravings when drugs are withheld. Experiments by Johnson and colleagues indicate similar changes in brain activity whether rats are exposed to drugs or salt deficiency.
"This suggests that salt need and cravings may be linked to the same brain pathways as those related to drug addiction and abuse," Johnson said.
понеділок, 2 березня 2009 р.
О каинатных рецепторах
Интересные новости о стрессе и депрессии нашла я на http://www.scienceblog.com/cms/protein-found-linking-stress-and-depression-18947.html
Stress, the ever-present threat to health and happy living, is tough on the brain. If the strain goes on too long, it can lead to debilitating psychological problems.
Part of the reason, according to scientists at The Rockefeller University, may have to do with a little-known family of proteins called kainate receptors that has recently been implicated in major depression. New research in rats may help explain one mechanism by which stress reshapes the brain: namely, by ramping up production of a particular part of these proteins.
“We’ve recently seen large human studies that suggest kainate receptors are targets for response to certain antidepressants and are also involved in major depression and the susceptibility to suicidal thoughts,” says Richard Hunter, a postdoctoral fellow in Bruce S. McEwen’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller. “We are trying to build up a molecular understanding of what is going on here.”
In experiments published recently in a special issue of PLoS ONE, Hunter and his colleagues homed in on one of five subunits of the kainate receptor called KA1. Performing a series of experiments exploring the impact of stress and steroids on rats, they found that stress, simulated by restraining the rats for six hours a day for three weeks, caused the genes to send instructions — messenger RNA — to increase production of KA1 subunits in particular parts of the hippocampus, a highly plastic brain structure involved in learning and memory.
The lab produced a similar result by injecting unstressed rats with hormones called corticosteroids, suggesting that an increase in these hormones is largely responsible for the stress response in rats. But the researchers also found that the dose is critical. While a moderate amount of corticosteroids increased KA1 messenger RNA, a high dose of the steroids did not. The relationship between the hormone and its impact is an inverted U response, a pattern familiar to biologists.
“The body seeks to maintain ideal levels, whether it is salts in the blood or any number of other things like KA1,” Hunter says. “Deviations to either side of these levels can cause pathologies or changes. The body adapts to changing circumstances to keep the levels healthy.”
Stress and depression are known to cause a reversible retraction of dendrites in certain brain cells, particularly in the hippocampus, that McEwen and colleagues refer to as “adaptive plasticity.” The new research suggests that an increase in KA1, caused by the corticosteroid response in rats, may trigger this retraction. The finding follows recent work by Rockefeller’s Sidney Strickland, head of the Laboratory of Neurobiology and Genetics, that showed that KA1 production explodes in the hippocampus during simulated stroke in mice, driving a cell-death cascade that begins when part of the brain is deprived of blood. Combined, the work suggests that the relatively understudied KA1 subunit plays an important role in a key area of the brain in both causing damage in an uncontrolled trauma such as a stroke and in protecting the brain from damage under the more controlled circumstances of chronic stress.
McEwen and colleagues have shown that healthy brains are remarkably resilient in the face of stress — brains replace their retracted neurons once the stress is removed. Perhaps, the researchers say, the same will prove true for depression. “One of the great hopes is that these changes in the hippocampus that happen with prolonged depression may not be signs of permanent irreversible damage but they may actually be signs of plasticity that we can treat with appropriate medications and also behavioral therapies,” McEwen says.
http://newswire.rockefeller.edu
Stress, the ever-present threat to health and happy living, is tough on the brain. If the strain goes on too long, it can lead to debilitating psychological problems.
Part of the reason, according to scientists at The Rockefeller University, may have to do with a little-known family of proteins called kainate receptors that has recently been implicated in major depression. New research in rats may help explain one mechanism by which stress reshapes the brain: namely, by ramping up production of a particular part of these proteins.
“We’ve recently seen large human studies that suggest kainate receptors are targets for response to certain antidepressants and are also involved in major depression and the susceptibility to suicidal thoughts,” says Richard Hunter, a postdoctoral fellow in Bruce S. McEwen’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller. “We are trying to build up a molecular understanding of what is going on here.”
In experiments published recently in a special issue of PLoS ONE, Hunter and his colleagues homed in on one of five subunits of the kainate receptor called KA1. Performing a series of experiments exploring the impact of stress and steroids on rats, they found that stress, simulated by restraining the rats for six hours a day for three weeks, caused the genes to send instructions — messenger RNA — to increase production of KA1 subunits in particular parts of the hippocampus, a highly plastic brain structure involved in learning and memory.
The lab produced a similar result by injecting unstressed rats with hormones called corticosteroids, suggesting that an increase in these hormones is largely responsible for the stress response in rats. But the researchers also found that the dose is critical. While a moderate amount of corticosteroids increased KA1 messenger RNA, a high dose of the steroids did not. The relationship between the hormone and its impact is an inverted U response, a pattern familiar to biologists.
“The body seeks to maintain ideal levels, whether it is salts in the blood or any number of other things like KA1,” Hunter says. “Deviations to either side of these levels can cause pathologies or changes. The body adapts to changing circumstances to keep the levels healthy.”
Stress and depression are known to cause a reversible retraction of dendrites in certain brain cells, particularly in the hippocampus, that McEwen and colleagues refer to as “adaptive plasticity.” The new research suggests that an increase in KA1, caused by the corticosteroid response in rats, may trigger this retraction. The finding follows recent work by Rockefeller’s Sidney Strickland, head of the Laboratory of Neurobiology and Genetics, that showed that KA1 production explodes in the hippocampus during simulated stroke in mice, driving a cell-death cascade that begins when part of the brain is deprived of blood. Combined, the work suggests that the relatively understudied KA1 subunit plays an important role in a key area of the brain in both causing damage in an uncontrolled trauma such as a stroke and in protecting the brain from damage under the more controlled circumstances of chronic stress.
McEwen and colleagues have shown that healthy brains are remarkably resilient in the face of stress — brains replace their retracted neurons once the stress is removed. Perhaps, the researchers say, the same will prove true for depression. “One of the great hopes is that these changes in the hippocampus that happen with prolonged depression may not be signs of permanent irreversible damage but they may actually be signs of plasticity that we can treat with appropriate medications and also behavioral therapies,” McEwen says.
http://newswire.rockefeller.edu
неділя, 15 лютого 2009 р.
О новом рецепторе галлюциногенов
Нашла на http://www.scienceblog.com/cms/hallucinogen-activates-mysterious-receptor-18609.html
A hallucinogenic compound found in a plant indigenous to South America and used in shamanic rituals regulates a mysterious protein that is abundant throughout the body, University of Wisconsin-Madison researchers have discovered.
The finding, reported in the Feb. 13 issue of Science, may ultimately have implications for treating drug abuse and/or depression. Many more experiments will be needed, the researchers say.
Scientists have been searching for years for naturally occurring compounds that trigger activity in the protein, the sigma-1 receptor. In addition, a unique receptor for the hallucinogen, called dimethyltryptamine (DMT), has never been identified.
The UW-Madison researchers made the unusual pairing by doing their initial work the "old-fashioned," yet still effective, way. They diagrammed the chemical structure of several drugs that bind to the sigma-1 receptor, reduced them to their simplest forms and then searched for possible natural molecules with the same features. Biochemical, physiological and behavioral experiments proved that DMT does, in fact, activate the sigma-1 receptor.
"We have no idea at present if or how the sigma-1 receptor may be connected to hallucinogenic activity," says senior author Arnold Ruoho, chair of pharmacology at the UW-Madison School of Medicine and Public Health. "But we believe that the National Institute on Drug Abuse (NIDA) may be interested in biological mechanisms underlying psychoactive and addictive drug action."
In addition to being a component of psychoactive snuffs and sacramental teas used in native religious practices in Latin America, DMT is known to be present in some mammalian tissues, and it has also been identified in mammalian blood and spinal fluid. Elevated levels of DMT and a related molecule have been found in the urine of schizophrenics.
Ruoho speculates that the hallucinogen's involvement may mean that the sigma-1 receptor is connected in some fashion to psychoactive behavior. When his team injected DMT into mice known to have the receptor, the animals became hyperactive; mice in which the receptor had been genetically removed did not.
"Hyperactive behavior is often associated with drug use or psychiatric problems," says Ruoho. "It's possible that new, highly selective drugs could be developed to inhibit the receptor and prevent this behavior."
The study revealed an additional neurologic link by confirming that the sigma-1 receptor and some compounds that bind to it inhibit ion channels, which are important for nerve activity. Work by many researchers — including some from UW-Madison — initially showed this relationship in earlier studies.
Some studies have also linked the receptor to the action of antidepressant drugs, and National Institutes of Health (NIH) scientists recently found that it appears to serve as a "chaperon," helping proteins to fold properly.
The Wisconsin researchers found that DMT is derived from the naturally occurring amino acid tryptophan and is structurally related to the neurotransmitter serotonin. This finding, Ruoho says, illustrates the mantra often used in the biological processing of natural molecules: Nothing goes to waste.
"Our findings support the idea that biochemical alterations of molecules such as tryptophan can produce simple compounds such as DMT that may target other regulatory pathways served by sigma-1 receptors," he says.
DMT may also reflect the presence of an even larger family of natural compounds that arise from other structurally related amino acids that may further regulate the receptor, Ruoho adds.
"It may well be that these different, naturally derived chemical forms regulate the sigma-1 receptor in tissue and organ-specific ways," he says.
A hallucinogenic compound found in a plant indigenous to South America and used in shamanic rituals regulates a mysterious protein that is abundant throughout the body, University of Wisconsin-Madison researchers have discovered.
The finding, reported in the Feb. 13 issue of Science, may ultimately have implications for treating drug abuse and/or depression. Many more experiments will be needed, the researchers say.
Scientists have been searching for years for naturally occurring compounds that trigger activity in the protein, the sigma-1 receptor. In addition, a unique receptor for the hallucinogen, called dimethyltryptamine (DMT), has never been identified.
The UW-Madison researchers made the unusual pairing by doing their initial work the "old-fashioned," yet still effective, way. They diagrammed the chemical structure of several drugs that bind to the sigma-1 receptor, reduced them to their simplest forms and then searched for possible natural molecules with the same features. Biochemical, physiological and behavioral experiments proved that DMT does, in fact, activate the sigma-1 receptor.
"We have no idea at present if or how the sigma-1 receptor may be connected to hallucinogenic activity," says senior author Arnold Ruoho, chair of pharmacology at the UW-Madison School of Medicine and Public Health. "But we believe that the National Institute on Drug Abuse (NIDA) may be interested in biological mechanisms underlying psychoactive and addictive drug action."
In addition to being a component of psychoactive snuffs and sacramental teas used in native religious practices in Latin America, DMT is known to be present in some mammalian tissues, and it has also been identified in mammalian blood and spinal fluid. Elevated levels of DMT and a related molecule have been found in the urine of schizophrenics.
Ruoho speculates that the hallucinogen's involvement may mean that the sigma-1 receptor is connected in some fashion to psychoactive behavior. When his team injected DMT into mice known to have the receptor, the animals became hyperactive; mice in which the receptor had been genetically removed did not.
"Hyperactive behavior is often associated with drug use or psychiatric problems," says Ruoho. "It's possible that new, highly selective drugs could be developed to inhibit the receptor and prevent this behavior."
The study revealed an additional neurologic link by confirming that the sigma-1 receptor and some compounds that bind to it inhibit ion channels, which are important for nerve activity. Work by many researchers — including some from UW-Madison — initially showed this relationship in earlier studies.
Some studies have also linked the receptor to the action of antidepressant drugs, and National Institutes of Health (NIH) scientists recently found that it appears to serve as a "chaperon," helping proteins to fold properly.
The Wisconsin researchers found that DMT is derived from the naturally occurring amino acid tryptophan and is structurally related to the neurotransmitter serotonin. This finding, Ruoho says, illustrates the mantra often used in the biological processing of natural molecules: Nothing goes to waste.
"Our findings support the idea that biochemical alterations of molecules such as tryptophan can produce simple compounds such as DMT that may target other regulatory pathways served by sigma-1 receptors," he says.
DMT may also reflect the presence of an even larger family of natural compounds that arise from other structurally related amino acids that may further regulate the receptor, Ruoho adds.
"It may well be that these different, naturally derived chemical forms regulate the sigma-1 receptor in tissue and organ-specific ways," he says.
п'ятниця, 30 січня 2009 р.
Новое в изучении репарации ДНК
Процесс репарации ДНК зафиксирован! Информация с http://www.eurekalert.org/pub_releases/2009-01/uoc--hdr012809.php по ссылке есть картинка и видео для заинтересовавшихся. :)
Contact: Liese Greensfelder
lgreensfelder@ucdavis.edu
University of California - Davis
Human DNA repair process recorded in action
Fluorescent microscopy captures the repair protein Rad51 as it assembles into a filament on DNA
A key phase in the repair process of damaged human DNA has been observed and visually recorded by a team of researchers at the University of California, Davis. The recordings provide new information about the role played by a protein known as Rad51, which is linked to breast cancer, in this complex and critical process.
The breakthrough comes a decade after Stephen Kowalczykowski, a distinguished professor of microbiology and the study's principal investigator, and Ron Baskin, professor emeritus of molecular and cellular biology, first began developing methods of labeling molecules with fluorescent markers and observing them at work using optical trapping of individual DNA molecules and advanced microscopy techniques. In 2006, the researchers recorded a portion of the bacterial DNA repair process, a system considerably less complex than its human counterpart. The new study was published in the Proceedings of the National Academy of Sciences on Jan. 13.
Human DNA is under constant assault from harmful agents such as ultraviolet sunlight, tobacco smoke and a myriad of chemicals, both natural and man-made. Because damage can lead to cancer, cell death and mutations, an army of proteins and enzymes are mobilized into action whenever it occurs.
Rad51 takes a leading role in the action. Always on call in the cell, molecules of the protein assemble into a long filament along a damaged or broken segment of DNA, where they help stretch out the coiled strands and align them with corresponding segments on the cell's second copy of the chromosome, which serves as a template for reconstruction. Because this protein is regulated by a gene linked to increased risk of breast cancer, BRCA2, it is also thought to play a role in suppression of that disease.
With the ability to watch the assembly of individual filaments of Rad51 in real time, Kowalczykowski's team made a number of discoveries. Among those are that, in contrast to their bacterial counterparts, Rad51 filaments don't grow indefinitely. This indicates that there is an as-yet undiscovered mechanism that regulates the protein's growth, Kowalczykowski said.
Another surprising difference between the human and bacterial processes, Kowalczykowski said, is that Rad51 doesn't fall away from the DNA when repair is complete. Instead, proteins that motor along DNA are required to dislodge it.
"From a practical point of view, being able to record these single molecules gives us insightful information regarding the assembly process," the researcher said. "Now we're able to measure this in a quantifiably meaningful way."
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Other contributors to the study were postdoctoral scholars Jovencio Hilario and Ichiro Amitani.
The research was supported by the National Institutes of Health and a Susan G. Komen Postdoctoral Fellowship.
The paper and supporting materials can be viewed online at http://www.pnas.org/.
About UC Davis
For 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has 31,000 students, an annual research budget that exceeds $500 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges -- Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science -- and advanced degrees from five professional schools: Education, Law, Management, Medicine, and Veterinary Medicine. The UC Davis School of Medicine and UC Davis Medical Center are located on the Sacramento campus near downtown.
Contact: Liese Greensfelder
lgreensfelder@ucdavis.edu
University of California - Davis
Human DNA repair process recorded in action
Fluorescent microscopy captures the repair protein Rad51 as it assembles into a filament on DNA
A key phase in the repair process of damaged human DNA has been observed and visually recorded by a team of researchers at the University of California, Davis. The recordings provide new information about the role played by a protein known as Rad51, which is linked to breast cancer, in this complex and critical process.
The breakthrough comes a decade after Stephen Kowalczykowski, a distinguished professor of microbiology and the study's principal investigator, and Ron Baskin, professor emeritus of molecular and cellular biology, first began developing methods of labeling molecules with fluorescent markers and observing them at work using optical trapping of individual DNA molecules and advanced microscopy techniques. In 2006, the researchers recorded a portion of the bacterial DNA repair process, a system considerably less complex than its human counterpart. The new study was published in the Proceedings of the National Academy of Sciences on Jan. 13.
Human DNA is under constant assault from harmful agents such as ultraviolet sunlight, tobacco smoke and a myriad of chemicals, both natural and man-made. Because damage can lead to cancer, cell death and mutations, an army of proteins and enzymes are mobilized into action whenever it occurs.
Rad51 takes a leading role in the action. Always on call in the cell, molecules of the protein assemble into a long filament along a damaged or broken segment of DNA, where they help stretch out the coiled strands and align them with corresponding segments on the cell's second copy of the chromosome, which serves as a template for reconstruction. Because this protein is regulated by a gene linked to increased risk of breast cancer, BRCA2, it is also thought to play a role in suppression of that disease.
With the ability to watch the assembly of individual filaments of Rad51 in real time, Kowalczykowski's team made a number of discoveries. Among those are that, in contrast to their bacterial counterparts, Rad51 filaments don't grow indefinitely. This indicates that there is an as-yet undiscovered mechanism that regulates the protein's growth, Kowalczykowski said.
Another surprising difference between the human and bacterial processes, Kowalczykowski said, is that Rad51 doesn't fall away from the DNA when repair is complete. Instead, proteins that motor along DNA are required to dislodge it.
"From a practical point of view, being able to record these single molecules gives us insightful information regarding the assembly process," the researcher said. "Now we're able to measure this in a quantifiably meaningful way."
###
Other contributors to the study were postdoctoral scholars Jovencio Hilario and Ichiro Amitani.
The research was supported by the National Institutes of Health and a Susan G. Komen Postdoctoral Fellowship.
The paper and supporting materials can be viewed online at http://www.pnas.org/.
About UC Davis
For 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has 31,000 students, an annual research budget that exceeds $500 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges -- Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science -- and advanced degrees from five professional schools: Education, Law, Management, Medicine, and Veterinary Medicine. The UC Davis School of Medicine and UC Davis Medical Center are located on the Sacramento campus near downtown.
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