Прозак может быть лекарством от рака?

Статья с http://scienceblogs.com/bushwells/2008/12/prozac_the_anticancer_drug.phpProzac, the anti-cancer drug?
Category: The Medical Tent
Posted on: December 22, 2008 9:46 AM, by Kevin Beck

It's common for cancer patients to be prescribed antidepressants as a means of helping them cope with an obviously traumatic diagnosis. But researchers in Israel have found that the selective serotonin-reuptake inhibitor Prozac (generic name fluoxetine) can increase the effectiveness of a common anti-cancer agent, doxorubicin, by tenfold.

A study [Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University] and his colleagues recently completed validates that Prozac dramatically enhances the effectiveness of a widely used anti-cancer drug.
"The good news is that the medical community won't have to wait - Prozac can be used for this purpose right away," says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.

"Prozac is a very interesting non-specific blocker of cancer resistance," says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.

In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.

In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.


It would be interesting to have more information on the exact mechanism of action involved here. At first I assumed that fluoxetine had been found to slow hepatic metabolism of doxorubicin or something like that, but it appears that fluoxetine's "wingman" effects on the anticancer agent are indeed direct.

The study results will be published in Cancer Letters.
Ещё, об этом же - http://www.scienceblog.com/cms/prozac-not-just-depression-anymore-18039.html
Prozac is regularly prescribed to ease the emotional pain of patients who are being treated for cancer. But can this common anti-depressant help to fight cancer itself?

Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University is proving that it can. A study he and his colleagues recently completed validates that Prozac (chemical name fluoxetine) dramatically enhances the effectiveness of a widely used anti-cancer drug.

“The good news is that the medical community won't have to wait — Prozac can be used for this purpose right away,” says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.

Fighting Drug Resistance in Colon Cancer Patients

“Prozac is a very interesting non-specific blocker of cancer resistance,” says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.

In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.

In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.

His research was just published in Cancer Letters, and his suggestions are now listed as recommendations in the latest version of Cancer Encyclopedia.

Working Backward to Make Great Advances

“Working with a major drug developer, we have validated Prozac's potential, and now Tel Aviv University can lead a humanitarian effort to save lives around the globe,” he says.

Since it is very hard to protect this patent because any clinician can prescribe Prozac, it is impossible for Tel Aviv University to commercialize its research, says Dr. Peer. Instead, he suggests that researchers join forces internationally to implement retrospective studies of all the types of cancer treatment in which Prozac was prescribed. And further clinical experiments to validate the use of Prozac with chemotherapy is also needed, he stresses.

“The next step is to take the files of chemo patients and determine whether they received Prozac for their depression,” says Dr. Peer. “This will streamline the understanding in the scientific community of whether, how and for which cancer-fighting drugs Prozac can be an effective partner. It will also give us invaluable information on how to design new drugs."

Dr. Peer's Tel Aviv University lab is also developing several new drug delivery nanotechnologies to bring novel therapeutics into breast, blood, pancreatic and brain cancers. A recent technological breakthrough to reprogram immune cells involved in ulcerative colitis and Crohn’s disease was reported in Science earlier this year and it is the basis of a new platform technology developed in his group.
http://www.aftau.org/site/News2?page=NewsArticle&id=8323

Кофеин сильнее влияет на мужчин...

Вот такое интересное исследование.
http://www.scientificblogging.com/news_releases/men_caffeine_more_effective_and_starts_working_10_minutesA study headed by researchers from the University of Barcelona (UB) shows that caffeine has a greater effect on men than women, and that these effects start just 10 minutes after it is drunk. In addition, contrary to what was previously thought, it has also been shown that decaffeinated coffee also produces an increased state of alertness.

“Numerous studies have demonstrated the stimulant effects of caffeine, but none of these have looked at their effects in terms of the consumer’s gender,” Ana Adan, lead author of the study and a researcher in the Psychiatry and Clinical Psychobiology Department of the UB, tells SINC.

Research into the effects of caffeine tends to be carried out using preparations in which the caffeine level is much higher than normal intake. According to Adan, the novelty of this study lies in “the difference seen in the effects on men and women, based on the quantities of caffeine people take in 99% of cases (espresso coffee and decaffeinated espresso coffee, containing 100mg and 5mg of caffeine, respectively)”.

In order to measure the effects, the scientists used a sample of 668 university students (238 male and 450 female) with an average age of 22 years. Measurements were taken before and after the caffeine was ingested (10, 20 and 30 minutes) and were carried out at mid-day (11am to 1pm) and in the afternoon (4pm to 6pm), to act as a control in case of possible differences caused by the time.

“Although both the men and women saw an improvement in their activity levels with the coffee, which increased in later measurements, we observed a greater impact among the males,” the Catalan researcher tells SINC.

When the decaffeinated version was introduced into the study, the authors also found a small subjective improvement in the participants’ state of alertness, which did not rise so strikingly in the later measurements. “Although we can’t say it is a placebo, we did note an effect resulting from drinking a decaffeinated coffee (at a quantity insufficient to actually affect mood),” adds Adan.

The results showed a small impact among both men and women who drank the decaffeinated coffee, although this time the effect was slightly more noticeable among the women. The effect of decaffeinated drinks on alertness had not been previously studied.

As the author says, “if a person cannot drink normal coffee, a decaffeinated one might provide some benefits. It remains to be evaluated whether these effects are simply subjective, or if they do have an impact on performance”.

Coffee produces fast-acting effects

Caffeine has an almost immediate effect. Previous studies had shown that alertness starts to increase 30-45 minutes after consumption, but the new study shows that the effects begin after as little as 10 minutes. According to the researcher “45 minutes is the time needed for maximum caffeine concentration to be reached in the blood, but levels reach half this concentration after just a few minutes”.

The experts say the effects of caffeine last for between two and three hours, although some authors extend this to up to four or five hours according to an individual’s particular sensitivity and metabolic rate, which varies greatly with age.

Article: Ana Adan, Gemma Prat, Marco Fabbri, Miquel Sánchez-Turet. “Early effects of caffeinated and decaffeinated coffee on subjective state and gender differences”. Progress in Neuro-Psychopharmacology&Biological Psychiatry 32 1698–1703 OCT 2008.

Ещё о пчёлах и кокаине. Видео.

В продолжение темы пчёлок-наркоманок. Видео, которое я откопала на http://scienceblogs.com/clock/2008/12/this_is_your_honeybee_and_this.php

http://www.youtube.com/watch?v=lE-8QuBDkkw&eurl=http://scienceblogs.com/clock/2008/12/this_is_your_honeybee_and_this.php&feature=player_embedded

Пчёлки любят кокс?!

Без комментариев... :) Читаем на scientificblogging.com/news_releases/honeybees_cocaine
Since its discovery in the 18th century, cocaine has been a scourge of western society. Strongly stimulating human reward centers in low doses, cocaine is extremely addictive and can be fatal in high doses.

But this potent compound did not evolve to ensnare humans in addiction, it is a powerful insect neurotoxin, protecting coca bushes from munching insects - without rewarding them.

Knowing that foraging honey bees are strongly motivated by rewards (they dance in response to the discovery of a rewarding nectar or pollen supply) and that this behavior is controlled by similar mechanisms to the ones that leave humans vulnerable to cocaine addiction, Andrew Barron from Macquarie University, Australia and Gene Robinson from the University of Illinois at Urbana-Champaign wondered whether bees may be vulnerable to cocaine's allure at the right dose.

Teaming up with Ryszard Maleszka at the Australian National University, Barron set about testing how honeybees respond to cocaine. They publish their results on 26th December 2008 in The Journal of Experimental Biology.

Setting up his hives on a farm just outside Canberra, Barron trained the insects to visit a feeder stocked with a sugar solution. Then he gently applied a tiny drop of cocaine solution to the insect's back, and waited to see how enthusiastically the foraging insects danced when returning to the hive.

Amazingly, low doses of the drug stimulated the insects to dance extremely vigorously. They behaved as if the sucrose solution was of a much higher quality than it really was. The cocaine seemed to be hitting the insects' reward centers, but were they really responding to the drug like humans or was the drug stimulating some other aspect of the insects' behavior to look as if they were becoming addicted?

Working with a team of undergraduate students, Barron tested whether cocaine stimulated the insects' locomotion centers by monitoring their movements after a dose of the drug. The insects behaved normally, so the drug probably doesn't affect their movements. However, when Paul Helliwell tested the bees' sensitivity to sugar solutions, the drugged bees responded more strongly than the undrugged insects, so cocaine was increasing their sugar sensitivity.

But was it only increasing their sensitivity to sugar, or increasing their response to all rewards? Barron offered the drugged insects pollen to see if cocaine increased their sensitivity to other floral rewards and found that the foragers were equally overenthusiastic, dancing as if the pollen quality was much better than it really was.

Finally Barron and Helliwell wondered whether bees that had been on cocaine for a few days had become dependent and went into withdrawal when the drug was withheld. Testing the insects' ability to learn to distinguish between lemon and vanilla scents, they found that the bees were fine so long as their cocaine supply was maintained. But as soon as the drug was withdrawn the bees had difficulty learning the task, just like humans going into withdrawal.

Barron is confident that honeybees are as susceptible to cocaine's allure as humans, and is keen to find out more about the drug's effects. He hopes to identify the neural pathways that it targets to find out more about the mechanisms involved in human addiction and to find out whether the drug has as devastating an effect on honey bee society as it does on human society.

Новый способ детекции активных форм Кислорода.

Активные формы Кислорода, окислительный стресс - это одни из наиболее интересующих меня проблем. Занятная статья об использовании нового флюоресцентного красителя для определения наличия АФК на http://www.biologynews.net/archives/2008/12/16/researchers_create_new_class_of_fluorescent_dyes_to_detect_reactive_oxygen_species_in_vivo.html
Researchers have created a new family of fluorescent probes called hydrocyanines that can be used to detect and measure the presence of reactive oxygen species. Reactive oxygen species are highly reactive metabolites of oxygen that have been implicated in a variety of inflammatory diseases, including cancer and atherosclerosis.

"We've shown that the hydrocyanines we developed are able to detect the reactive oxygen species, superoxide and the hydroxide radical, in living cells, tissue samples, and for the first time, in vivo," said Niren Murthy, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Details of the hydrocyanine synthesis process and experimental results showing the ability of the dyes to detect reactive oxygen species in cells, tissues and mouse models were reported on December 8 in the online version of the journal Angewandte Chemie International Edition. This research is supported by the National Institutes of Health and the National Science Foundation.

The researchers have created six hydrocyanine dyes to date – hydro-Cy3, hydro-Cy5, hydro-Cy7, hydro-IR-676, hydro-IR-783 and hydro-ICG – but say that there are potentially 40 probes that could be created. The dyes vary in their ability to detect intracellular or extracellular reactive oxygen species and by their emission wavelength – from 560 to 830 nanometers.

Fluorescing at higher wavelengths allows the hydrocyanine dyes to be used for deep tissue imaging in vivo, a capability that dihydroethidium (DHE), the current "gold standard" for imaging reactive oxygen species, does not have. The dyes also have other advantages over DHE.

"When DHE comes into contact with reactive oxygen species, it oxidizes into ethidium bromide, a common mutagen, which means it's toxic and can't be injected inside the body," explained Murthy. "DHE also auto-oxidizes in the presence of aqueous solutions, which creates high levels of background fluorescence and interferes with reactive oxygen species measurements."

Hydrocyanines are also simple and quick to synthesize, according to Coulter Department postdoctoral fellow Kousik Kundu. Sodium borohydride is added to commercially available cyanine dyes and the solvent is removed – the one-step process takes less than five minutes.

W. Robert Taylor, a professor in the Coulter Department and Emory's Division of Cardiology, and Emory postdoctoral fellow Sarah Knight, tested the ability of the dyes to detect reactive oxygen species inside of cells and animals.

For their first experiment, they tested the ability of hydro-Cy3, which has an emission wavelength of 560 nanometers, to detect reactive oxygen species production in the aortic smooth muscle cells of rats. They incubated the cells with hydro-Cy3 and angiotensin II, which is a stimulator of reactive oxygen species that is implicated in the development of atherosclerosis and hypertension.

Results showed that cells incubated with angiotensin II and hydro-Cy3 displayed intense intracellular fluorescence, whereas control cells incubated with hydro-Cy3 and phosphate buffer saline displayed significantly lower fluorescence. When they introduced TEMPOL, a molecule that intercepts the reactive oxygen species so that they cannot interact, the cells treated with angiotensin II and hydro-Cy3 displayed a dramatic decrease in fluorescence.

"This test demonstrated that the cellular fluorescence was due to intracellular reactive oxygen species production," said Murthy. "What was even more exciting was that we saw that once the hydrocyanine dye was oxidized, it stayed in the cell and the fluorescence was not extinguished by cellular metabolism, which is what happens with DHE."

The researchers also investigated the ability of hydro-Cy3 to image reactive oxygen species production in live mouse aorta tissue, which exhibit a physiological environment that closely resembles in vivo conditions. Explants were incubated with hydro-Cy3 and either lipopolysaccharide endotoxin (LPS), an inflammatory molecule that binds to aortic cells and causes reactive oxygen species to be produced, or the control saline solution.

Samples treated with hydro-Cy3 and LPS showed fluorescence intensity almost four times greater than explants treated with hydro-Cy3 and saline. Once more, adding TEMPOL to the sample with hydro-Cy3 and LPS decreased the fluorescence to a level comparable to the control saline explants.

After the successful cell culture and tissue experiments, the researchers progressed to in vivo mouse imaging studies. Hydro-Cy7 was selected for the in vivo tests because of its higher emission wavelength of 760 nanometers. LPS-treated mice showed twofold greater fluorescence intensity in the abdominal area than those treated with saline.

"Given their ability to detect reactive oxygen species in living cells, tissue samples and in vivo, we believe these dyes will enhance the ability of researchers to measure reactive oxygen species," noted Murthy.

The researchers' ultimate goal, though, is to use the dyes in clinical applications.

"We want to use these hydrocyanine dyes to detect overproduction of reactive oxygen species at an early stage inside the body so that we can identify patients who are more likely to suffer from these inflammatory diseases," added Murthy.

Source : Georgia Institute of Technology Research News

О генах и моноаминооксидазе.

Отличная статья. О полиморфизме генов, кодирующих МАОА, и связанных с этим нарушениях поведения. http://www.eurekalert.org/pub_releases/2008-12/ace-aaa120808.php

Contact: Roope Tikkanen, M.D.
roope.tikkanen@helsinki.fi
358-9-471-63760
University of Helsinki

Alcoholism: Clinical & Experimental Research
Alcohol and a polymorphism of the monoamine oxidase A gene predict impulsive violence

The monoamine oxidase A (MAOA) gene is an outer membrane mitochondrial enzyme that breaks down monoamines such as serotonin, noradrenalin and dopamine. A common polymorphism in MAOA results in high- or low-activity MAOA, and both genotypes have been linked to aggression and violence. A Finnish study has found that drinking and high-activity MAOA can predict the risk of impulsive violence, while aging may decrease this risk.

Results will be published in the March issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Alcoholism, alcohol consumption and violence are clearly related," said Roope Tikkanen, a researcher in the department of psychiatry at Helsinki University Central Hospital and corresponding author for the study. He noted that crime statistics show that most impulsive homicides occur among adolescent and middle-aged groups rather than among the elderly, and habitually violent-impulsive offenders are often expected to "grow out of their difficulties" with increasing age. "Surprisingly little accurate information, however, is available on this aging-impulsive aggression issue," he said.

Tikkanen and his colleagues decided to look at the MAOA gene, alcohol consumption and aging as predictors for recidivism in impulsive violent behavior among a sample of 174 Finnish alcoholic male offenders originally recruited between 1990 and 1998. Each offender was given a psychiatric assessment; in addition, their alcohol consumption was measured, their violent behavior was assessed, and they were genotyped for polymorphisms of MAOA.

"Increased alcohol consumption and aging seem to predict violence," said Tikkanen, "although these risk factors 'work' in opposite directions, and only concern individuals who have been given by nature a high-activity variant of MAOA." On the other hand, he added, additional research has suggested that individuals with low-activity MAOA seem to be at risk for criminality and violence after exposure to severe childhood maltreatment.

"People react quite differently to acute alcohol exposure," Tikkanen continued. "Most individuals become relaxed and talkative, while some – particularly persons who are introverted while sober – become expansively extroverted and aggressive. A dramatic change from a normally introverted personality to extroverted aggressiveness and uncontrolled behaviors under the influence of alcohol was formerly called 'pathological intoxication' in Finland."

Regarding the decline in impulsive-aggressive behavior with aging among high-activity MAOA offenders, Tikkanen hypothesized that it may be due to a correction of low central serotonin levels in the central nervous system.

Tikkanen cautioned against genetic testing for individuals who may be worried for one reason or another about their risk. "Even though whole genome scans will one day be affordable, the average person probably has very many factors that differ from the violent offenders in the study," he said. "For instance, the average Finnish consumption is two drinks a day or 10 kg pure alcohol per year, whereas the upper 10 percent of violent offenders drink approximately one 0.75 liter bottle of liquor a day or around 100 kg pure alcohol a year."

Tikkanen and his co-authors suggest that high-activity MAOA offenders may be helped to control their violent behaviors by coaching to maintain alcohol abstinence, and possibly by psychopharmacological treatment to increase central serotonin levels.

"In some countries, prison sentences may be very long – even a lifetime or more – and the reason for the sentence may be an accumulation of minor convictions committed in a drunken state," said Tikkanen. "In such cases, it could perhaps benefit all parties to decrease the length of the sentence. Our results suggest that the risk for new violent crimes decreases by 150 percent when high-activity MAOA individuals become 20 years older. Perhaps we could increase the efficacy of addiction rehabilitation by focusing resources particularly on younger heavy-drinking high-activity MAOA individuals."

###

Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Effects of MAOA-genotype, Alcohol Consumption, and Ageing on Violent Behavior," were: Richard L. Sjöberg of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism, the Center for Clinical Research at Uppsala University in Västerås, Sweden, and the Department of Neurosurgery at University Hospital in Umeå, Sweden; Francesca Ducci of King's College in London; Davie Goldman of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism; Matti Holi and Matti Virkkunen of the Department of Psychiatry in the Institute of Clinical Medicine at the University of Helsinki; and Jari Tiihonen of the Department of Forensic Psychiatry and Clinical Physiology at the University of Kuopio, Finland. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the Olle Engkvist Byggmästare foundation.

Однозначно - за! Лекарства для улучшения работы мозга.

Одна из самых животрепещущих тем - допинг для мозга. Статья на http://blog.wired.com/wiredscience/2008/12/brain-enhancing.html:
If drugs can safely give your brain a boost, why not take them? And if you don't want to, why stop others?

In an era when attention-disorder drugs are regularly — and illegally — being used for off-label purposes by people seeking a better grade or year-end job review, these are timely ethical questions.

The latest answer comes from Nature, where seven prominent ethicists and neuroscientists recently published a paper entitled, "Towards a responsible use of cognitive-enhancing drugs by the healthy."

In short: Legalize 'em.

"Mentally competent adults," they write, "should be able to engage in cognitive enhancement using drugs."

Roughly seven percent of all college students, and up to 20 percent of scientists, have already used Ritalin or Adderall — originally intended to treat attention-deficit disorders — to improve their mental performance.

Some people argue that chemical cognition-enhancement is a form of cheating. Others say that it's unnatural. The Nature authors counter these charges: Brain boosters are only cheating, they say, if prohibited by the rules — which need not be the case. As for the drugs being unnatural, the authors argue, they're no more unnatural than medicine, education and housing.

In many ways, the arguments are compelling. Nobody rejects pasteurized milk or dental anesthesia or central heating because it's unnatural. And whether a brain is altered by drugs, education or healthy eating, it's being altered at the same neurobiological level. Making moral distinctions between them is arbitrary.

But if a few people use cognition-enhancing drugs, might everyone else be forced to follow, whether they want to or not?

If enough people improve their performance, then improvement becomes the status quo. Brain-boosting drug use could become a basic job requirement.

Ritalin and Adderall, now ubiquitous as academic pick-me-ups, are merely the first generation of brain boosters. Next up is Provigil, a "wakefulness promoting agent" that lets people go for days without sleep, and improves memory to boot. More powerful drugs will follow.

As the Nature authors write, "cognitive enhancements affect the most complex and important human organ and the risk of unintended side effects is therefore both high and consequential." But even if their safety could be assured, what happens when workers are expected to be capable of marathon bouts of high-functioning sleeplessness?

Most people I know already work 50 hours a week and struggle to find time for friends, family and the demands of life. None wish to become fully robotic in order to keep their jobs. So I posed the question to Michael Gazzaniga, a University of California, Santa Barbara, psychobiologist and Nature article co-author.

"It is possible to do all of that now with existing drugs," he said. "One has to set their goals and know when to tell their boss to get lost!"

Which is not, perhaps, the most practical career advice these days. And University of Pennsylvania neuroethicist Martha Farah, another of the paper's authors, was a bit less sanguine.

"First the early adopters use the enhancements to get an edge. Then, as more people adopt them, those who don't, feel they must just to stay competitive with what is, in effect, a new higher standard," she said.

Citing the now-normal stresses produced by expectations of round-the-clock worker availability and inhuman powers of multitasking, Farah said, "There is definitely a risk of this dynamic repeating itself with cognition-enhancing drugs."

But people are already using them, she said. Some version of this scenario is inevitable — and the solution, she said, isn't to simply say that cognition enhancement is bad.

Instead we should develop better drugs, understand why people use them, promote alternatives and create sensible policies that minimize their harm.

As Gazzaniga also pointed out, "People might stop research on drugs that may well help memory loss in the elderly" — or cognition problems in the young — "because of concerns over misuse or abuse."

This would certainly be unfortunate collateral damage in the 21st century theater of the War on Drugs — and the question of brain enhancement needs to be seen in the context of this costly and destructive war. As Schedule II substances, Ritalin and Adderall are legally equivalent in the United States to opium or cocaine.

"These laws," write the Nature authors, "should be adjusted to avoid making felons out of those who seek to use safe cognitive enhancements."

After all, according to the law's letter, seven percent of college students and 20 percent of scientists should have done jail time — this journalist, too.

Towards responsible use of cognitive-enhancing drugs by the healthy [Nature]

Гены и плацебо

Всё в нашем организме зависит от экспрессии генов. Оказывается, и эффективность таблеток-пустышек - тоже. Описан интересный эксперимент. Нашла - на http://www.scienceblog.com/cms/genes-determine-whether-placebos-work-17920.html

It is a well-known fact in drug trials that individuals can respond just as well to placebos, sugar pills, as to the active drug. On the other hand, it is difficult to explain why only certain people get better from placebos. A team of researchers from Uppsala University and Gothenburg University have now found gene variants that can impact the placebo effect and a mechanism in the brain that characterizes those who respond to placebos.

The study, published in Journal of Neuroscience, examined 108 individuals suffering from social phobia using a brain camera (PET, positron emission tomography). The individuals were participating in a treatment study looking into how anxiety-moderating drugs affect brain activity. Just under one fourth of the subjects were given a placebo instead of a drug. This was a double-blind study, meaning that neither the subjects nor the research team know who was taking the drug or the sugar pill.

Before and after an eight-week period of treatment, the participants were asked to give a stressful oral presentation while their brain activity was monitored. When all the metering was finished and the study was decoded, it turned out that 40 percent of the placebo group had received the same degree of anxiety relief from the sugar pill as other groups got from a drug.

Those who responded well to the placebo had a significant reduction in activity in the amygdala in the temporal lobe, while this reduction was not found in the others. In previous research the amygdala has stood out as a key structure for emotional reactions. Both serotonin-active drugs (SSRI preparations) and cognitive behavioral therapy moderate activity in this area.

"Thus, successful placebo treatment works through the same mechanism in the brain," says Tomas Furmark at the Uppsala University Department of Psychology, who directed the study.

The study also analyzed two genes that influence the reabsorption and synthesis of serotonin in the brain (the serotonin transporter gene and the tryptophan hydroxylase-2 gene). The findings showed that only individuals who had certain variants, alleles, of these genes had a moderation of activity in the amygdala. Above all, the tryptophan hydroxylase-2 genes variants could predict the degree of relief from anxiety achieved by the placebo pill as well as the moderation of the amygdala.

Statistical analyses showed that it is a genetic effect on the activity in the amygdala that influences the propensity to respond to a placebo, that is, a path from the gene, via the brain, to behavior.

The study shows for the first time that genes influence the placebo effect by regulating the propensity to react in an area of the brain that is important for our feelings.

This could have significant consequences for all drug testing and other treatment studies that use a placebo.

"The findings show that the possibilities of demonstrating that an active treatment functions better than a placebo can be affected by the gene variants in the trial subjects. It is also possible that genes can explain why certain people respond well or poorly to anxiety-moderating drugs and psychotherapy respectively," says Tomas Furmark.
http://www.uu.se

Повреждения ДНК и старение

Как вы уже поняли, повреждения ДНК - моя любовь. А их роль в процессах старения - одна из интереснейших тем... Поэтому не могу не запостить заметку, прочитанную на http://www.scientificblogging.com/news_releases/did_these_researchers_discover_universal_mechanism_aging
Researchers have discovered that DNA damage decreases a cell's ability to regulate which genes are turned on and off in particular settings. This mechanism, which applies both to fungus and to us, might represent a universal culprit for aging.

"This is the first potentially fundamental, root cause of aging that we've found," says Harvard Medical School professor of pathology David Sinclair. "There may very well be others, but our finding that aging in a simple yeast cell is directly relevant to aging in mammals comes as a surprise."

Their findings appear in the November 28 issue of the journal Cell.

For some time, scientists have know that a group of genes called sirtuins are involved in the aging process. These genes, when stimulated by either the red-wine chemical resveratrol or caloric restriction, appear to have a positive effect on both aging and health.

Nearly a decade ago, Sinclair and colleagues in the Massachusetts Institute of Technology lab of Leonard Guarente found that a particular sirtuin in yeast affected the aging process in two specific ways—it helped regulate gene activity in cells and repair breaks in DNA. As DNA damage accumulated over time, however, the sirtuin became too distracted to properly regulate gene activity, and as a result, characteristics of aging set in.

"For ten years, this entire phenomenon in yeast was considered to be relevant only to yeast," says Sinclair. "But we decided to test of this same process occurs in mammals."

Philipp Oberdoerffer, a postdoctoral scientist in Sinclair's Harvard Medical School lab, used a sophisticated microarray platform to probe the mammalian version of the yeast sirtuin gene in mouse cells. The results in mice corroborated what Sinclair, Guarente, and colleagues had found in yeast ten years earlier.

Oberdoerffer found that a primary function of sirtuin in the mammalian system was to oversee patterns of gene expression (which genes are switch on and which are switch off). While all genes are present in all cells, only a select few need to be active at any given time. If the wrong genes are switched on, this can harm the cell. (In a kidney cell, for example, all liver genes are present, but switched off. If these genes were to become active, that could damage the kidney.) As a protective measure, sirtuins guard genes that should be off and ensure that they remain silent. To do this, they help preserve the molecular packaging—called chromatin—that shrink-wraps these genes tight and keeps them idle.

The problem for the cell, however, is that the sirtuin has another important job. When DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.

During this unguarded interval, the chromatin wrapping may start to unravel, and the genes that are meant to stay silent may in fact come to life.

For the most part, sirtuins are able to return to their post and wrap the genes back in their packaging, before they cause permanent damage. As mice age, however, rates of DNA damage (typically caused by degrading mitochondria) increase. The authors found that this damage pulls sirtuins away from their posts more frequently. As a result, deregulation of gene expression becomes chronic. Chromatin unwraps in places where it shouldn't, as sirtuin guardians work overtime putting out fires around the genome, and the unwrapped genes never return to their silent state.

In fact, many of these haplessly activated genes are directly linked with aging phenotypes. The researchers found that a number of such unregulated mouse genes were persistently active in older mice.

"We then began wondering what would happen if we put more of the sirtuin back into the mice," says Oberdoerffer. "Our hypothesis was that with more sirtuins, DNA repair would be more efficient, and the mouse would maintain a youthful pattern gene expression into old age."

That's precisely what happened. Using a mouse genetically altered to model lymphoma, Oberdoerffer administered extra copies of the sirtuin gene, or fed them the sirtuin activator resveratrol, which in turn extended their mean lifespan by 24 to 46 percent.

"It is remarkable that an aging mechanism found in yeast a decade ago, in which sirtuins redistribute with damage or aging, is also applicable to mammals," says Leonard Guarente, Novartis Professor of Biology at MIT, who is not an author on the paper. "This should lead to new approaches to protect cells against the ravages of aging by finding drugs that can stabilize this redistribution of sirtuins over time."

Both Sinclair and Oberdoerffer agree with Guarente's sentiment that these findings may have therapeutic relevance.

"According to this specific mechanism, while DNA damage exacerbates aging, the actual cause is not the DNA damage itself but the lack of gene regulation that results," says Oberdoerffer. "Lots of research has shown that this particular process of regulating gene activity, otherwise known as epigenetics, can be reversed—unlike actual mutations in DNA. We see here, through a proof-of-principal demonstration, that elements of aging can be reversed."

Recent findings by Chu-Xia Deng of the National Institute of Diabetes, Digestive and Kidney Diseases, has also found that mice that lack sirtuin are susceptible to DNA damage and cancer, reinforcing Sinclair's and Oberdoerffer's data.

Пингвины-геи крадут яйца у птиц-натуралов! :)

Вот такие реалии животного гомосексуализма... :) Читаю на http://scienceblogs.com/zooillogix/2008/12/gay_penguins_steal_straight_co.phpGay Penguins Steal Straight Couples' Eggs
Category: penguins
Posted on: December 1, 2008 8:02 PM, by Benny Bleiman

A pair of gay penguins at Polar Land in Harbin, north east China has taken to stealing the eggs of straight couples and leaving rocks in place to fool their victims. The penguins, named Anderson Cooper and Clay*** by the zoo keepers, have been outed by their fellow penmates and have since been ostracized by the flock. Fearing for the stress levels of the flock, keepers have taken Anderson and Clay out of their enclosure and segrated them alone in a pen of their own.


"Did you see little miss happy feet the other day? That new bleak gloss was a travesty against all things good in this world!..." "Um, I KNOW it. I mean, wooo-ooooh, wooo-ooooh, someone call the Antarctic Fashion Police!"

When asked about the decision to separate the gay penguin couple, one keeper told the Austrian Times newspaper as reported in the Daily Telegraph, "It's not discrimination. We have to fence them separately, otherwise the whole group will be disturbed during hatching time."

Either way, 51 percent of Californians applauded the zoo's decision. "When it comes to penguin rights, separate but equal sounds good to us," a spokesman for the Church of Jesus Christ of Latter Day Saints from nearby Utah was quoted as saying.

Instances of animal homosexuality are recorded all over the science kingdom (including by us), and prove, once and for all, that when you don't believe in genes, evolution or science, homosexuality is merely a choice of lifestyle.

***The names Anderson Cooper and Clay may not have actually been used by the keepers at the zoo, and may in fact have been invented by me.

Псевдоэфедрин и дети!

Детки часто кушают псевдоэфедрин... и много... http://www.eurekalert.org/pub_releases/2008-12/bu-puc120108.phpPublic release date: 1-Dec-2008

Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8491
Boston University

Pseudoephedrine use common among young children
Boston, MA—Researchers from Boston University's Slone Epidemiology Center have found that exposure to pseudoephedrine, a decongestant found in many cough-and-cold and allergy medications, has been common among U.S. children, especially those under the age of two years who are at the highest risk for toxicity and for whom safe dosing recommendations are lacking. These findings appear in the December issue of the journal Pediatrics.

Pseudoephedrine has been associated with deaths and adverse events in young children. However, the absolute risks of pediatric pseudoephedrine use are difficult to determine because the number of children exposed to this medication and typical patterns of use are unknown. In addition, use may be changing because of the Combat Methamphetamine Act of 2005, a law which limited availability of pseudoephedrine-containing products.

To define the frequency and patterns of use, the researchers analyzed data from 1999 through 2006 on pseudoephedrine use among 4,267 children, aged 0 to 17 years, who were enrolled in the Slone Survey, a national random-digit-dial telephone survey of medication use in the U.S.

The researchers found 4.9 percent of children took pseudoephedrine in a given week. Use was highest in children under two years of age (8.1 percent). Sixteen children (7.5 percent of users) took more than one pseudoephedrine-containing product within the same week, including six children under two years old. Of the pseudoephedrine products used, most were multiple-ingredient liquids (58.9 percent) and multiple-ingredient tablets (24.7 percent). Fifty-two subjects (25 percent of users) took pseudoephedrine for longer than one week, including seven children under two years of age. Perhaps reflecting reduced availability, use in 2006 (2.9 percent) was significantly lower than in 1999-2005 (5.2 percent).

Concerning patterns of use identified in the study include taking more than one pseudoephedrine-containing product at the same time and using pseudoephedrine for long periods of time. Pediatric pseudoephedrine use appears to be declining since the institution of the 2005 Combat Methamphetamine Act. "Pseudoephedrine exposure, mostly in the form of multiple-ingredient products, is common among U.S. children and needs to be monitored closely because of the potential for this medication to cause harm, particularly to children under two" said lead author Louis Vernacchio, MD, MSc, an assistant professor of epidemiology and pediatrics at Boston University School of Medicine.