Что думают наркоманы?

Интересно о мнениях наркоманов о том, что они употребляют. Что опаснее - легальные или нелегальные вещества? Читаем: http://www.eurekalert.org/pub_releases/2009-11/ucl-duk112309.php
Drug users know their stuff

Drug users are well informed about the harms associated with the drugs they use, and perceive alcohol and tobacco to be amongst the most dangerous substances, according to a survey by UCL (University College London) and Imperial College London researchers. The findings, published in the Journal of Psychopharmacology, suggest that the current system of classifying psychoactive drugs in the UK may need to be revisited.

The study, led by Dr Celia Morgan and Professor Valerie Curran at UCL, surveyed 1,500 UK drug users via the website www.nationaldrugsurvey.org. Drug users were asked to rate twenty psychoactive substances on a 'rational' scale previously developed by Professor David Nutt, Imperial College London, who collaborated on this study. Heroin, crack and cocaine topped the list in terms of harm, but alcohol was rated fifth, solvents seventh and tobacco ninth. Ecstasy came 13th in the harm rating, LSD 16th and cannabis 18th. Thus, the survey found no relationship between the drug's legal status, based on the current classification system, and users' ratings of harm. In the UK, the Misuse of Drugs Act (1971) currently classifies psychoactive drugs as A, B or C, though alcohol and tobacco remain unclassified.

Dr Celia Morgan, UCL Clinical Psychopharmacology Unit, says: "Given that the Misuse of Drugs Act aims to signal to young people the harmfulness of drugs, this suggests a flaw with the current classification of drugs. We found that drug users rated legal substances such as alcohol and tobacco as more harmful than Class A substances like LSD and ecstasy. We found a high correlation between harm ratings by users and those made previously by scientific experts across all substances, suggesting users are well informed about the harms of drugs.

"The reported prevalence of use of each substance also suggests that the classification of drugs has little bearing on the choice of whether to use substances or not. For example ecstasy, a Class A substance, was the fourth most regularly used psychoactive drug, according to our survey.

"We also asked drug users about their perceived benefits of taking psychoactive substances, as this is clearly important in a person's decision of whether to take a drug or not. Psychoactive substances LSD, cannabis and ecstasy were consistently rated as having the highest short and long-term benefits. These findings add to the debate on the validity of the current classification of drugs in the UK.

"Worldwide, there are an estimated two billion alcohol users, 1.3 billion smokers and 185 million users of other drugs. Despite public health campaigns, levels of substance misuse continue to rise. One of the reasons for this may be the public's confusion about the actual risks of different drugs as they often receive conflicting messages from the legal system, the media and health campaigns. We recommend that future health campaigns consider whether to include the benefits of some drugs. By only citing harms, such campaigns likely represent – from a user's perspective – an unbalanced view and may mean that the overall message is more likely to be ignored."

The authors are following up the study with the launch of a new larger survey, in collaboration with the Beckley Foundation, hosted at www.internationaldrugsurvey.org.

Аминокислотная диета для мозга

Особая диета для выздоровления мозгов :)ЧИТАЕМ:
http://www.eurekalert.org/pub_releases/2009-12/chop-waa120209.php
May set stage for treating brain damage in people
Neurology researchers have shown that feeding amino acids to brain-injured animals restores their cognitive abilities and may set the stage for the first effective treatment for cognitive impairments suffered by people with traumatic brain injuries.

"We have shown in an animal model that dietary intervention can restore a proper balance of neurochemicals in the injured part of the brain, and simultaneously improves cognitive performance," said study leader Akiva S. Cohen, Ph.D., a neuroscientist at The Children's Hospital of Philadelphia.

The study appears today in the online issue of the Proceedings of the National Academy of Sciences.

If these results in mice can be translated to human medicine, there would be a broad clinical benefit. Every 23 seconds, a man, woman or child in the United States suffers a traumatic brain injury (TBI). The primary cause of death and disability in children and young adults, TBI also accounts for permanent disabilities in more than 5 million Americans. The majority of those cases are from motor vehicle injuries, along with a rising incidence of battlefield casualties.

Although physicians can relieve the dangerous swelling that occurs after a TBI, there are currently no treatments for the underlying brain damage that brings in its wake cognitive losses in memory, learning and other functions.

The animals in the current study received a cocktail of three branched chain amino acids (BCAAs), specifically leucine, isoleucine and valine, in their drinking water. Previous researchers had shown that people with severe brain injuries showed mild functional improvements after receiving BCAAs through an intravenous line.

BCAAs are crucial precursors of two neurotransmitters—glutamate and gamma-aminobutyric acid, or GABA, which function together to maintain an appropriate balance of brain activity. Glutamate excites neurons, stimulating them to fire, while GABA inhibits the firing. Too much excitement or, too little, and the brain doesn't work properly. A TBI upsets the balance.

In particular, a TBI frequently damages the hippocampus, a structure deep in the brain involved in higher learning and memory. In the current study, the researchers found that an injury to the hippocampus reduced levels of BCAAs. Although overall levels of glutamate and GABA were unchanged, the loss of BCAAs disturbed the critical balance of neurotransmitters in the hippocampus, making some localized regions more excitable and others less excitable. Cohen's team tested the hypothesis that providing dietary BCAAs would restore the balance in neural response.

In this study, Cohen's study team first created standardized brain injuries in mice, and one week later compared the animals' conditioned fear response to that of uninjured mice. A week after receiving a mild electric shock in a specific cage, normal mice tend to "freeze" when placed in the same cage, anticipating another shock. The brain-injured mice demonstrated fewer freezing responses—a sign that they had partially lost that piece of learning.

On the other hand, brain-injured mice that received a diet of BCAAs showed the same normal response as the uninjured mice. The BCAA cocktail had restored their learning ability.

In addition to the behavioral results, the team conducted electrophysiological experiments in slices of hippocampus from brain-injured and non-injured mice, and showed that BCAA restored a normal balance of neural activity. "The electrophysiological results were consistent with what we saw in the animals' functional recovery," said Cohen.

If the results in mice can be reproduced in people, patients with traumatic brain injuries could receive the BCAAs in a drink. Cohen suggests that BCAAs as a dietary supplement could have a more sustained, measured benefit than that seen when patients receive BCAAs intravenously, in which the large IV dose may flood brain receptors and have more limited benefits.

Although much work remains to be done to translate the finding into a therapy, Cohen expects to collaborate over the next year with other researchers in an early-phase clinical trial of dietary BCAAs in patients with mild to moderate TBI.


###

The National Institutes of Health provided funding for this study. Cohen's co-authors were Jeffrey Cole, Ph.D., Christina M. Mitala, Ph.D., Suhali Kundu and Itzhak Nissim, Ph.D., all of Children's Hospital; Jaclynn A. Elkind of the University of Pennsylvania; and Ajay Verma, M.D., Ph.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md. Cohen and Nissim are also on the faculty of the University of Pennsylvania School of Medicine.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 441-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

Об окислительном стрессе, маркерах и заболеваниях сердца

Очень интересная информация с http://www.eurekalert.org/pub_releases/2009-11/eu-moo111309.php
Marker of oxidative stress predicts heart disease outcomes
Judging from the number of juices and teas advertised as containing antioxidants, consumers are aware of the dangers of oxidative stress. But what is the best way to measure it – and fight it?

Doctors at Emory University School of Medicine have identified a substance in the blood that may be useful in predicting an individual's risk for heart disease. The substance is cystine, an oxidized form of the amino acid cysteine and an indirect measure of oxidative stress.

In a study of more than 1,200 people undergoing cardiac imaging at Emory because of suspected heart disease, people with high levels of cystine in the blood were twice as likely to have a heart attack or die over the next few years.

Riyaz Patel, MD, a postdoctoral researcher at Emory's Cardiovascular Research Group, is presenting the results Monday at the American Heart Association Scientific Sessions meeting in Orlando.

Patel was part of a team led by Arshed Quyyumi, MD, professor of medicine (cardiology) at Emory University School of Medicine.

When considered independently of variables such as the presence of diabetes, high levels of cystine still predicted future trouble, Patel says. In the current research, high levels means the quarter of the group of patients with the highest levels.

"Cystine could be a valuable marker of cardiovascular risk, but it also has a direct harmful effect on cells, so reducing it may be a valuable treatment strategy," he says. "What's exciting is there are already known ways to intervene and drive down cystine levels in patients."

For example, a previous study has shown that supplementing the diet with zinc can lower cystine levels, he says.

Several studies have shown that levels of oxidized cysteine in the blood tend to rise as people age. Smoking and alcohol consumption are also linked with higher levels of oxidized cysteine.

Cysteine is itself a short-lived precursor to glutathione, one of the main antioxidants found inside cells, says Dean P. Jones, PhD, professor of medicine and director of the Clinical Biomarkers Laboratory at Emory University School of Medicine.

"We need to have a continuous supply of cysteine, but it is too reactive for us to have very much at any one time," he says. "We are not sure why the oxidized form of cysteine accumulates with aging and disease. But our studies show that when it accumulates, it activates inflammation in cells."

Jones and his colleagues have shown that when white blood cells are exposed to high levels of cystine, they display signs of inflammation and become stickier. That makes them more likely to adhere to blood vessels in the heart, an event that contributes to the development of heart disease.

The team has found that levels of cystine do not correlate with C-reactive protein, a blood marker of inflammation other scientists have studied for a possible relationship with heart disease. The team's future plans include comparing cystine to other markers of inflammation and understanding the relationships between them.


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More about cysteine and oxidative stress:

http://whsc.emory.edu/home/news/releases/2009/03/targeting-oxidized-cysteine.html
http://whsc.emory.edu/home/publications/medicine/emory-medicine/summer2009/rejuggling-act.html

Reference:

Effects of long-term zinc supplementation on plasma thiol metabolites and redox status in patients with age-related macular degeneration.
SE Moriarty-Craige, KN Ha, P. Sternberg, M. Lynn, S. Bressler, G. Gensler, D.P. Jones. Am J Ophthalmol. 143(2):206-211 (2007)



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 the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has $2.3 billion in operating expenses, 18,000 employees, 2,500 full-time and 1,500 affiliated faculty, 4,500 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

Learn more about Emory's health sciences: http://emoryhealthblog.com - @emoryhealthsci (Twitter) - http://emoryhealthsciences.org

Хм. О летальности смеси кокаин+перечный газ

Отличная статья на http://www.newscientist.com/article/mg20427345.300-cocaine-and-pepper-spray--a-lethal-mix.html?DCMP=OTC-rss&nsref=online-news:
DEATHS in US police custody during the early 1990s may have been the result of an interaction between capsaicin, the key ingredient in pepper sprays, and psychostimulant drugs, an experiment in mice suggests.

If the two have a fatal interaction in people then police forces might have to rethink their use of pepper spray as a non-lethal weapon, says John Mendelson of the Addiction and Pharmacology Research Laboratory at St Luke's Hospital in San Francisco, who led the mouse research.

In the early nineties, anecdotal reports emerged in the US of people dying after being sprayed by police. "They seemed to die very quickly," says Mendelson. At post-mortem, many of these people showed signs of having taken cocaine, so Mendelson wondered if capsaicin and cocaine could interact fatally in the body.

To investigate, his team injected cocaine, capsaicin or both at once into the abdomens of several groups of about 30 mice. Injections allowed them to control the dose of capsaicin the mice received, which wouldn't have been possible if the mice were simply sprayed, says Mendelson.

In one group of mice, cocaine was injected at a dose of 60 milligrams per kilogram of mouse weight, which killed just a few of them. But when the researchers injected a group with the same dose of cocaine plus capsaicin, the death toll was about half. "The presence of capsaicin in mice makes smaller amounts of cocaine more lethal," Mendelson says. When the team gave another group of mice capsaicin along with a higher dose of cocaine - enough to kill half of the mice on its own - the death toll rose to 90 per cent (Forensic Toxicology, DOI: 10.1007/s11419-009-0079-9). "We don't actually know how capsaicin reacts with cocaine to produce a lethal effect," admits Mendelson.

However, his team also reviewed 26 autopsy reports and Californian police reports between 1993 and 1995 of people who died shortly after being subdued with pepper spray. They noted that 19 of them had evidence of psychostimulants in their blood and nine had cocaine. Mendelson suspects that a fatal interaction takes place in the brain between capsaicin and psychostimulants.

Toxicologists are intrigued, but say further evidence is needed. "In real-life situations, humans inhale pepper spray, whereas these mice had the substance injected directly into their abdominal cavities," says Andy Smith of the Medical Research Council in Cambridge, UK. Kathryn Cunningham of the Department of Pharmacology and Toxicology at the University of Texas in Galveston says we don't know how much of the capsaicin that is sprayed in someone's face makes it into their bloodstream.

Peter Bibring, an attorney at the American Civil Liberties Union in Los Angeles, says the study adds weight to the ACLU's concern that pepper spray could be fatal. "Police departments need to make adjustments to minimise the chance it will be used on those under the influence of cocaine."

Norm Leong, a sergeant at the Sacramento Police Department in California says this could be a tough call: "It's impossible to know if someone is under the influence of cocaine, some other drug", has mental issues, or is just resisting arrest.

Об ожидании наслаждения и допамине

Читаем на http://www.scientificblogging.com/news_articles/link_between_dopamine_and_expectation_pleasure_confirmed
Enhancing the effects of dopamine influences how people make life choices by affecting expectations of pleasure, according to new research from the UCL Institute of Neurology.

Published today in Current Biology, the study confirms an important role for dopamine in how human expectations are formed and how people make complex decisions. It also contributes to an understanding of how pleasure expectation can go awry, for example in drug addiction.

The study builds on earlier research which used brain imaging as participants imagined holiday destinations. An area of the brain called the straitum tracked expectations and the
scientists found that they could take that signal and predict what the participants would choose. The authors believed this was dopamine at work and set-up this study to further explore its role.

The research team examined estimated pleasure of future events before and after the administration of a drug called L-DOPA which is known to enhance dopamine function in the brain and is commonly used to treat patients with Parkinson's disease.

The 61 study participants were asked to rate their expectations of happiness if they were to holiday at each of 80 destinations, from Thailand to Greece. They were then given L-DOPA or a placebo and asked to imagine holidaying in those destinations.

The following day participants had to pick between a series of paired destinations that they had initially assigned with equal ratings, one member of the pair was imagined under L-DOPA the day before and the other under placebo. Finally, they rated the full set of 80 destinations again.

Ratings for particular destinations increased after they were imagined under L-DOPA's influence. That increase also affected the participants' selections the following day. Dr Sharot added: "We had reason to believe that dopamine would enhance expectations of pleasure in humans, but were surprised at the strength of this effect. The enhancement lasted at least 24 hours and was evident in almost 80 per cent of the subjects."

Citation: Tali Sharot, Tamara Shiner,Annemarie C. Brown, Judy Fan,Raymond J. Dolan, 'Dopamine Enhances Expectation of Pleasure in Humans', Current Biology Online 2009, doi:10.1016/j.cub.2009.10.025

Ген, ответственный за биполярное расстройство

О своём, о маниакально-депрессивном... На http://www.scientificblogging.com/news_articles/faulty_rorb_genes_may_explain_bipolar_disorder_children
A team of researchers said this week that they may have identified the genes responsible for bipolar disorder in children. Their study, published in BMC Psychiatry, implicates malfunctioning circadian clock genes, four alterations of the RORB gene to be specific, in the development of the disorder.

Scientists studied the RORA and RORB genes of 152 children with Bipolar and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. "Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder," explained co-author Alexander Niculescu.

RORB is mainly expressed in the eye, pineal gland and brain. Its expression is known to change as a function of circadian rhythm in some tissues, and mice without the gene exhibit circadian rhythm abnormalities.

According to Niculescu, "Bipolar disorder is often characterized by circadian rhythm abnormalities, and this is particularly true among pediatric bipolar patients. Decreased sleep has even been noted as one of the earliest symptoms discriminating children with bipolar disorder from those with attention deficit hyperactivity disorder (ADHD). It will be necessary to verify our association results in other independent samples, and to continue to study the relationship between RORB, other clock genes, and bipolar disorder".

Pediatric bipolar disorder is a controversial diagnosis characterized by alternating bouts of depression and mania in children, although it does not affect all young people in the same way and the duration and severity of the disorder can vary enormously.

Citation: Casey L McGrath, Stephen J Glatt, Pamela Sklar, Helen Le-Niculescu, Ronald Kuczenski, Alysa E Doyle, Joseph Biederman, Eric Mick, Stephen V Faraone, Alexander B Niculescu, Ming T Tsuang, 'Evidence for Genetic Association of RORB with Bipolar Disorder',
BMC Psychiatry 2009, doi:10.1186/1471-244X-9-70

Гипервитаминоз А

В детстве у меня был гипервитаминоз А - мама решила помочь мне справиться с трещинками на губах и помазала их витамином А из капсулки... Видимо - передоз. Потому что потом ещё неделю я ходила с распухшим, в красных пятнышках, личиком...
Вот и свежая статейка об эффектах витамина А при превышении дозы, читаю тут - http://www.biologynews.net/archives/2009/10/08/too_much_of_a_good_thing_scientists_explain_cellular_effects_of_vitamin_a_overdose_and_deficiency.html:

If a little vitamin A is good, more must be better, right? Wrong! New research published online in the FASEB Journal (http://www.fasebj.org) shows that vitamin A plays a crucial role in energy production within cells, explaining why too much or too little has a complex negative effect on our bodies. This is particularly important as combinations of foods, drinks, creams, and nutritional supplements containing added vitamin A make an overdose more possible than ever before.

"Our work illuminates the value and potential harm of vitamin A use in cosmetic creams and nutritional supplements," said Ulrich Hammerling, co-author of the study, from the Sloan-Kettering Institute for Cancer Research in New York. "Although vitamin A deficiency is not very common in our society, over-use of this vitamin could cause significant disregulation of energy production impacting cell growth and cell death."

Although the importance of vitamin A to human nutrition and fetal development is well-known, it has been unclear why vitamin A deficiencies and overdoses cause such widespread and profound harm to our organs, until now. The discovery by Hammerling and colleagues explains why these effects occur, while also providing insight into vitamin A's anti-cancer effects. The scientists used cultures from both human and mice cells containing specific genetic modifications of the chemical pathways involved in mitochondrial energy production. The cells were then grown with and without vitamin A, and scientists examined the impact on the various steps of energy production. Results showed that retinol, the key component of vitamin A, is essential for the metabolic fitness of mitochondria and acts as a nutritional sensor for the creation of energy in cells. When there is too much or too little vitamin A, mitochondria do not function properly, wreaking havoc on our organs.

"Beauty might be only skin deep, but vitamin A isn't. It goes to the nucleus of our cells and can affect our health for better or worse," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "Using too many products enriched with vitamin A could lead to negative, even fatal, consequences."

Source : Federation of American Societies for Experimental Biology

Безумие и гениальность

Читаем на http://www.eurekalert.org/pub_releases/2009-09/afps-mgs092809.php

Vincent van Gogh cut off his ear. Sylvia Plath stuck her head in the oven. History teems with examples of great artists acting in very peculiar ways. Were these artists simply mad or brilliant? According to new research reported in Psychological Science, a journal of the Association for Psychological Science, maybe both.

In order to examine the link between psychosis and creativity, psychiatrist Szabolcs Kéri of Semmelweis University in Hungary focused his research on neuregulin 1, a gene that normally plays a role in a variety of brain processes, including development and strengthening communication between neurons. However, a variant of this gene (or genotype) is associated with a greater risk of developing mental disorders, such as schizophrenia and bipolar disorder.

In this study, the researchers recruited volunteers who considered themselves to be very creative and accomplished. They underwent a battery of tests, including assessments for intelligence and creativity. To measure creativity, the volunteers were asked to respond to a series of unusual questions (for example, "Just suppose clouds had strings attached to them which hang down to earth. What would happen?") and were scored based on the originality and flexibility of their answers. They also completed a questionnaire regarding their lifetime creative achievements before the researchers took blood samples.

The results show a clear link between neuregulin 1 and creativity: Volunteers with the specific variant of this gene were more likely to have higher scores on the creativity assessment and also greater lifetime creative achievements than volunteers with a different form of the gene. Kéri notes that this is the first study to show that a genetic variant associated with psychosis may have some beneficial functions. He observes that "molecular factors that are loosely associated with severe mental disorders but are present in many healthy people may have an advantage enabling us to think more creatively." In addition, these findings suggest that certain genetic variations, even though associated with adverse health problems, may survive evolutionary selection and remain in a population's gene pool if they also have beneficial effects.

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For more information about this study, please contact: Szabolcs Kéri (szkeri@phys.szote.u-szeged.hu)

Psychological Science is ranked among the top 10 general psychology journals for impact by the Institute for Scientific Information. For a copy of the article "Genes for Psychosis and Creativity" and access to other Psychological Science research findings, please contact Barbara Isanski at 202-293-9300 or bisanski@psychologicalscience.org

Активные формы Кислорода в сигнальных каскадах!

Немного новостей об АФК в новом функциональном свете на http://www.eurekalert.org/pub_releases/2009-09/uoc--roi092309.php

For years, health conscious people have been taking antioxidants to reduce the levels of reactive oxygen in their blood and prevent the DNA damage done by free radicals, which are the result of oxidative stress. But could excessive use of antioxidants deplete our immune systems?

Research at UCLA's Jonsson Comprehensive Cancer Center has raised that question.

It has been known for decades that reactive oxygen species (ROS) - ions or very small molecules that include free radicals - damage cells. But much to their surprise, Jonsson Cancer Center researchers found that in Drosophila, the common fruit fly, moderately elevated levels of ROS are a good thing.

These small molecules act as an internal communicator, signaling certain blood precursor cells, or blood stem cells, to differentiate into immune-bolstering cells in reaction to a threat. After the progenitor cells differentiate, the ROS levels return to normal, ensuring the safety and survival of the mature blood cells, said Utpal Banerjee, a Jonsson Cancer Center researcher and senior author of the study.

The study is published in the Sept. 24, 2009 issue of the peer-reviewed journal Nature.

The new finding was launched when Banerjee and his team set out to discover why fruit flies had naturally occurring, slightly elevated levels of ROS in their blood cell precursors, which is atypical of most other precursor cells.

"Reducing levels of reactive oxygen is usually the goal, and what we found was surprising," said Banerjee, professor and chairman of the molecular, cell, and developmental biology department at UCLA. "Most stem cells don't want to be damaged, so they have very low ROS levels. We wanted to know why this was different in the cells that we were investigating."

Banerjee discovered that when ROS was taken away in the blood stem cells, they failed to differentiate into the immune-bolstering cells, called macrophages. On the other hand, when levels of ROS were further increased by genetic means, the blood stem cells "differentiated like gang busters," Banerjee said, making a large number of macrophages.

But how did this happen? The ROS, Banerjee said, acted as a signaling mechanism that kept the blood stem cells in a certain state – when levels rose, it was a message to the cell to differentiate.

The implications from the finding are several fold, Banerjee said. The blood stem cells are stress sensing cells, their function is to sense conditions that increase oxidative stress and react with an immune response. Keeping their ROS levels slightly elevated puts the cells on alert, sensitized and ready to respond to any threat quickly.

That sparked a question: If fruit fly blood stem cells and mammalian blood stem cells operate in the same way, is it a good thing for people to be taking antioxidants? Are antioxidants dulling the immune system and its ability to react to threats?

"On the one hand, it's good to have antioxidants to reduce the amount of reactive oxygen in our body that causes DNA damage," Banerjee said. "But if we find that those blood stem cells aren't primed to respond because the ROS levels are reduced, that would not be a good thing. Our findings raise the possibility that wanton overdose of antioxidant products may in fact inhibit formation of cells participating in innate immune response."

It is known that certain types of mammalian blood stem cells, called common myeloid progenitors, do have elevated levels of ROS, but it isn't known whether those levels operate as messengers for differentiation. Studies of mammalian systems are needed to determine why ROS levels are elevated and what, if any, function that serves in the cell. It is interesting, however, that these types of blood progenitors in mammals also give rise to macrophages, Banerjee said.

"What we found is that the fruit fly keeps its own ROS levels in the blood stem cells slightly high for its own benefit," Banerjee said. "We do not have any direct evidence that this is true in humans, but our results suggest that further studies are needed to investigate a possible signaling role for ROS in the differentiation of precursor cells in mammalian myeloid cell development and oxidative stress response."

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UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2009, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

Новое лекарство от шизофрении

Интересно, как обычно на этом блоге! Статья с http://scienceblogs.com/corpuscallosum/2009/09/iloperidone_approved_for_treat.php?utm_source=combinedfeed&utm_medium=rss
The new drug is called iloperidone; the brand name in the USA will be Fanapt. It is yet another antipsychotic that blocks D2 and 5HT2 receptors. Although there is no universally accepted way of classifying drugs into families, it will be referred to as an atypical or second-generation antipsychotic. This designation will indicate a loose kind of similarity to risperidone, aripiperazole, ziprasidone, quetiapine, olanzapine, clozapine, and paliperidone.

It turns out that there is a Wikipedia page for iloperidone. It is not one of the better pages on Wikipedia.

Iloperidone is a monoamine directed towards acting upon and antagonizing specific neurotransmitters.

Iloperidone does act upon the transmitter. It blocks the receptor, which causes the transmitter to be ineffective, or less effective, at transmitting whatever message it otherwise would have transmitted.

There are several other quibbles I have with the Wikipedia page. If I were unemployed, I would edit it. But it is going to take a lot of work.

Anyway, I could write the kind of blog post that I usually have written when potentially-interesting new drugs come out. But it turns out that there is already a good, concise article in an open-access journal. It says all the things I would have said.

Iloperidone for schizophrenia
Peter J. Weiden, MD, and Jeffrey R. Bishop, PharmD, BCPP
Current Psychiatry Online
Vol. 8, No. 9 / September 2009

Iloperidone is a second-generation (atypical) antipsychotic the FDA approved in May 2009 for treating acute schizophrenia in adults (Table 1). Iloperidone is not a derivative (metabolite, isomer, or different formulation) of any other antipsychotic. Clinical trials have shown that iloperidone is efficacious and suggest that for some patients its side-effect profile may be more favorable than that of other antipsychotics.

It is expected to be available later this year. It is not possible for me, or anyone else, to say exactly when this will be.

The high points are: oral bioavailability 95%, half-life about 18 hours, protein binding about 95%, high affinity for D2 and 5HT2A, low for H1, minimal for muscarinic, and moderate for NEα1. The cost will be too high, but I don't know exactly how high. The manufacturer, Vanda Pharmaceuticals, reportedly is working on a long-acting injectable product.

The one sort of interesting thing has to do with the alpha-1 antagonism. This is a nuisance sometimes, because it can cause orthostatic hypotension (dizziness upon standing up, due to drop in blood pressure). This is a side effect, which may or may not happen in a given individual. It is potentially an adverse effect.

Prazosin is an antihypertensive drug that blocks alpha-1 receptors. Prazosin has been used, off-label, to reduce nightmares in persons with PTSD.

Could iloperidone have a similar effect? If so, it would be a side effect, but not an adverse effect. It would be a beneficial side effect. It remains to be seen whether this will turn out to be the case. In general, it is tricky to anticipate clinical effects, based upon the in vitro pharmacology of a drug, when it comes to the effects in the brain.

Несколько весёлостей из научных новостей о сексе

Здесь - о сексе и оргазме. Всегда ли одно не возможно без другого?
Здесь - о полезности здоровой сексуальной жизни для самочувствия женщин.

Об эффективности обогащённой тромбоцитами плазмы

Ещё один объект моего изучения и тестирования попал сегодня в сводку новостей с научных фронтов. Прочитала на http://www.biologynews.net/archives/2009/10/01/plateletrich_plasma_does_it_work.html:

Platelet -rich plasma (PRP) is currently used as an alternative treatment method for several common orthopaedic-related sports medicine conditions. According to a new study in the October issue of the Journal of the American Academy of Orthopaedic Surgeons (JAAOS), early outcomes of PRP appear promising; however, larger clinical studies are still needed to determine the benefits of its use.

"Some believe that PRP may catalyze the body's repair mechanisms at areas of injury, improve healing and shorten recovery time," said study co-author Michael Hall, MD, a senior orthopaedic surgery resident at the NYU Hospital for Joint Diseases in New York. "However, there currently is minimal evidence of this clinically and more research must be performed."

A Simple Process and Procedure

• Obtaining and utilizing PRP is a relatively simple process: a patient's own blood is placed into a centrifuge that rotates at high speed.
• This procedure separates the red blood cells from the platelets, which are blood cells that release growth factors that help the body heal itself.
• Next, the physician takes the platelet-rich portion of this blood (PRP) and injects it directly into the patient's injured area and the treatment is complete.

PRP Used Primarily for Chronic Conditions

PRP treatments have been used for the past two decades to improve wound healing and bone grafting procedures by plastic and maxillofacial (mouth, jaw and neck) surgeons. It is only in recent years that orthopaedic surgeons and sports medicine specialists have utilized this technology.

PRP use in sports medicine primarily has been for the treatment of chronic tendon conditions, but also for acute muscle injuries and for the augmentation of tendon repair in the operating room.

The most common applications include:

• tennis elbow (lateral epicondylitis);
• Achilles tendonitis (inflammation and swelling of the Achilles tendon);
• patellar tendonitis (inflammation of the patellar tendon, also called "Jumper's Knee"); and
• rotator cuff tendonopathy.

Should I Have PRP Treatment?

According to Dr. Hall, PRP use has increased in recent years, and it has become a popular topic of discussion because the process is "simple, quick and relatively safe for patients."

"Use of PRP has increased, in large part due to new devices that enable fast preparation in the outpatient setting. A patient gives a blood sample and 30 minutes later can receive their injection," he explained. "There is always a risk of infection with any injection, and some have reported increased pain or inflammation at the injection site, but otherwise the risks with PRP appear minimal."

Questions to Ask Your Doctor

Each patient and injury is unique; therefore it is important to discuss any treatment with an orthopaedic surgeon. If PRP treatment is recommended, Dr. Hall suggests asking your doctor the following to help determine if it is right for you:

1. What is your experience in administering PRP? (Precise placement of PRP injection into the area of injury is important for it to be effective, therefore physicians with more experience may be best.)
2. What are possible side effects? (Examples include increased pain or inflammation at the injection site.)
3. How many injections will I receive? (Several studies have reported using multiple injections, but the benefit of this is unknown.)
4. Will there be any restrictions? (Generally, patients are asked to avoid strenuous activity or sports for a short period of time after the injection to aid in the healing process.)
5. Will my insurance cover treatment? (Currently, most insurance companies do not cover treatment.)

Also, before embarking on PRP, Dr. Hall suggests trying conventional treatments, such as anti-inflammatory medications, physical therapy, massage, activity modification, bracing and even cortisone injections.

"The bottom line is that there are some studies indicating that PRP may be beneficial in the healing process. Does it really have a positive effect clinically? We don't know," said Dr. Hall. "The good news is that there are a tremendous amount of studies underway. Hopefully, in the next few years, we will be able to help determine the true benefit of PRP."

Source : American Academy of Orthopaedic Surgeons

Конопля без каннабиноидов

До чего дошла наука... Читаем на http://www.biology-blog.com/blogs/permalinks/9-2009/drug-free-cannabis-plant.html
Drug-free Cannabis plant
In a first step toward engineering a drug-free Cannabis plant for hemp fiber and oil, University of Minnesota scientists have identified genes producing tetrahydrocannabinol (THC), the psychoactive substance in marijuana. Studying the genes could also lead to new and better drugs for pain, nausea and other conditions. The finding is reported in the recent issue of the Journal of Experimental Botany Main author is David Marks, a professor of plant biology in the College of Biological Sciences. The study revealed that the genes are active in tiny hairs covering the flowers of Cannabis plants. In marijuana, the hairs accumulate high amounts of THC, whereas in hemp the hairs have little. Hemp and marijuana are difficult to distinguish apart from differences in THC. With the genes identified, finding a way to silence themand thus produce a drug-free plant comes a step closer to reality. Another desirable step is to make drug-free plants visually recognizable. Since the hairs can be seen with a magnifying glass, this could be accomplished by engineering a hairless Cannabis plant. The scientists are currently using the methods of the latest study to identify genes that lead to hair growth in hopes of silencing them. "We are beginning to understand which genes control hair growth in other plants, and the resources created in our study will allow us to look for similar genes in Cannabis sativa," said Marks. "Cannabis genetics can contribute to better agriculture, medicine, and drug enforcement," said George Weiblen, an associate professor of plant biology and a co-author of the study. As with Dobermans and Dachshunds, marijuana and hemp are different breeds of the same species (Cannabis sativa), but marijuana contains much more THC than hemp, which is a source of industrial fiber and nutritious oil. Hemp was raised for its fiber which is similar to cotton but more durable in the United States until legislation outlawed all Cannabis plants because they contain THC. Today, marijuana contains as much as 25 percent THC, whereas hemp plants contain less than 0.3 percent. Hemp was once a popular crop in the upper Midwest because it tolerates a cool climate and marginal soils that won't support other crops but, after drug legislation, hemp fiber was replaced by plastic and other alternatives. Recent popular demand for hemp products has led some states to consider the economic and environmental benefits of hemp. North Dakota legislation aims to reintroduce it as a crop, and Minnesota is considering similar legislation. At the same time, California and other states permit the medicinal use of marijuana. "I can't think of a plant so regarded as a menace by some and a miracle by others," says Weiblen, who is one of the few scientists in the United States permitted to study Cannabis genetics. In 2006, Weiblen and his colleagues developed a DNA "fingerprinting" technique capable of distinguishing among Cannabis plants in criminal investigations. Posted by: Erica Source

Роль активных форм Кислорода в формировании метастазов

Читаю на http://www.eurekalert.org/pub_releases/2009-09/bi-ror091509.php Reactive oxygen's role in metastasis
LA JOLLA, Calif., September 15, 2009 -- Researchers at the Burnham Institute for Medical Research (Burnham) have discovered that reactive oxygen species, such as superoxide and hydrogen peroxide, play a key role in forming invadopodia, cellular protrusions implicated in cancer cell migration and tumor metastasis. Sara Courtneidge, Ph.D., professor and director of the Tumor Microenvironment Program at Burnham's NCI-designated Cancer Center, and colleagues have found that inhibiting reactive oxygen reduces invadopodia formation and limits cancer cell invasion. The study was published on September 15 in the journal Science Signaling.
In a companion paper, published in the same issue of Science Signaling, Gary Bokoch, Ph.D., of The Scripps Research Institute, in collaboration with Dr. Courtneidge, found that the proteins Tks4 and Tks5, commonly expressed in cancer cells, are functionally related to p47phox, a protein found in phagocytes that is part of a complex that is instrumental in producing reactive oxygen to mount an immune response.
"Reactive oxygen has a complex cellular role," said Dr. Courtneidge. "Normal cells use reactive oxygen to signal, grow and move. Immune cells, such as neutrophils, produce reactive oxygen to destroy bacteria. Now we find that reactive oxygen is necessary for invadopodia formation, which allows cancer cells to become metastatic."
Invadopodia facilitate cancer cell migration by breaking down the extracellular matrix that normally keeps cells in place. In previous research, Dr. Courtneidge discovered that Tks5 is crucial for invadopodia formation. The structural similarities between Tks5 and p47phox, which is part of the NADPH oxidase (Nox) system, led Dr. Courtneidge to consider the role reactive oxygen plays in invadopodia formation.
Using invadopodia-rich mouse fibrosarcoma cells, the Courtneidge laboratory tested a number of antioxidants and found both a marked reduction in invadopodia formation and invasive behavior. In addition, the team inhibited expression of Nox family enzymes with siRNA and had similar results, demonstrating that NADPH oxidases are involved in invadopodia formation. The scientists repeated these experiments with human melanoma, head and neck and breast cancer cell lines and also saw a marked reduction in invadopodia formation.
With the discovery of reactive oxygen's role in invadopodia formation, researchers have additional possibilities for drug intervention. Future research and drug development may focus on inhibiting NADPH oxidase activity and limiting invadopodia formation to prevent cancer cell migration.

При повреждениях ДНК срабатывает сигнализация!

Интересные новости с http://www.biologynews.net/archives/2009/08/13/raising_the_alarm_when_dna_goes_bad.html:

Our genome is constantly under attack from things like UV light and toxins, which can damage or even break DNA strands and ultimately lead to cancer and other diseases. Scientists have known for a long time that when DNA is damaged, a key enzyme sets off a cellular 'alarm bell' to alert the cell to start the repair process, but until recently little was known about how the cell detects and responds to this alarm. In a study published today in Nature Structural and Molecular Biology, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have identified a whole family of proteins capable of a direct response to the alarm signal.

Our genome is a huge repository of information guiding the construction and function of all the cells in our bodies. Cells sustain many hits to their DNA every day, which can lead tomutations, so they maintain a fleet of DNA repair machinery that can be rapidly mobilised and sent to damaged sites in an emergency.

Because our DNA is so long and unwieldy, it needs to be packaged up with proteins and organised into a complex structure called chromatin. Scientists have known for 50 years that one component of chromatin, an enzyme known as PARP1, is activated by DNA damage and produces a molecular signal, called PAR, which raises the alarm at the site of the damage. In recent weeks, scientists have for the first time worked out how PAR is rapidly detected by the cell; in their Nature Structural and Molecular Biology paper, the group of Andreas Ladurner and their colleagues at EMBL have identified a whole family of proteins that respond to this signal by binding to it directly.

What these proteins share is a special region called a macrodomain. By using a laser to reproduce DNA damage in the lab, the scientists were able to follow fluorescently-labelled macrodomain proteins in cells and observed that they quickly move to the site of DNA damage. A high-resolution image, obtained by X-ray crystallography, shows how the macrodomain forms a 'pocket' fitting the PAR signal exactly.

Among the members of the family the researchers found a protein called histone macroH2A1.1. "This was very surprising. Histones play a major role in assembling chromatin and keeping it together, but they don't usually have macrodomains," says Ladurner. "The finding is particularly relevant, because it turns out that cancer cells don't have macroH2A1.1. The fact that one member of the rapid response team that detects DNA damage is missing could contribute to the disease."

Because macroH2A1.1 is embedded in chromatin, when it recognises PAR at DNA damage sites, it drags the complex but highly-organised tangle of chromatin with it. As a result, macroH2A1.1 condenses the chromatin environment around the damaged area.

The scientists are now trying to understand why this happens. One plausible explanation could be that by temporarily compacting the DNA, the broken ends of the DNA molecule are kept closer together. This should increase the chances of being able to repair it.

"With these findings we've opened up completely new perspectives to a fifty-year-old field of research," says Ladurner. "We're very excited of what lies ahead and hope that we'll soon be much closer in understanding how PARP1 and macrodomains together maintain a healthy genome."

Source : European Molecular Biology Laboratory

Новое о курении марихуаны

Нашла на http://www.eurekalert.org/pub_releases/2009-08/acs-geo_1080509.php

In a finding that challenges the increasingly popular belief that smoking marijuana is less harmful to health than smoking tobacco, researchers in Canada are reporting that smoking marijuana, like smoking tobacco, has toxic effects on cells. Their study is scheduled for the Aug. 17 issue of ACS' Chemical Research in Toxicology, a monthly journal.

Rebecca Maertens and colleagues note that people often view marijuana as a "natural" product and less harmful than tobacco. As public attitudes toward marijuana change and legal restrictions ease in some countries, use of marijuana is increasing. Scientists know that marijuana smoke has adverse effects on the lungs. However, there is little knowledge about marijuana's potential to cause lung cancer due to the difficulty in identifying and studying people who have smoked only marijuana.

The new study begins to address that question by comparing marijuana smoke vs. tobacco smoke in terms of toxicity to cells and to DNA. Scientists exposed cultured animal cells and bacteria to condensed smoke samples from both marijuana and tobacco. There were distinct differences in the degree and type of toxicity elicited by marijuana and cigarette smoke. Marijuana smoke caused significantly more damage to cells and DNA than tobacco smoke, the researchers note. However, tobacco smoke caused chromosome damage while marijuana did not.

###

ARTICLE #2 FOR IMMEDIATE RELEASE
"The Genotoxicity of Mainstream and Sidestream Marijuana and Tobacco Smoke Condensates"

DOWNLOAD FULL TEXT ARTICLE: http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/tx9000286

Кортинко улыбнуло

Весёленькая пикча. :) Отсюда - ianheath653.wordpress.com/category/humor/page/8/

Немного о болевой чувствительности

Отличная заметка в блоге у http://scienceblogs.com/neurophilosophy/2009/07/swearing_increases_pain_tolerance.php

Category: Neuroscience • Psychology
Posted on: July 13, 2009 1:02 PM, by Mo

SWEARING OCCURS IN most cultures - people swear to let off steam, or to shock or insult others. It is also a common response to a painful experience. We've all done it: after stubbing our toe, or hitting our thumb with a hammer, we draw a sharp breath and mutter a swear word. Until now, though, whether swearing actually alters our perception of pain had not been investigated. But according to a new study due to be published next month in the journal NeuroReport, swearing increases pain tolerance, enabling us to withstand at least one form of pain for longer.

Some pain theorists regard our tendency to swear after hurting ourselves to be a form of "pain-related catastrophising" - an exaggerated negative mind set which is brought to bear during a painful experience. As such, swearing is thought of as a maladaptive response, which contributes to the intensity of the pain and emotional distress. Given that it is such a common response, Richard Stephens and his colleagues at the Keele University School of Psychology set out test the hypothesis that swearing would decrease pain tolerance and increase pain perception.

They recruited 67 undergraduates, and asked to make two short lists of words - one containing five words they might use after hitting themselves on the thumb with a hammer, the other containing five words they might use to describe a table. The participants submerged one of their hands into room temperature water for three minutes, to provide a standardized starting point, then transferred it to a container of cold water and instructed to keep it submerged for as long as they could. In one condition, they were told to repeat the first swear word they had included in their list; in another, they repeated one of the words describing a table.

The researchers measured how long the participants kept their hands submerged in cold water, and asked them to rate the amount of pain they felt. Their heart rates were also recorded after they had submerged their hands in room temperature water as well as after the submersion in cold water. Contrary to their hypothesis, they found that swearing actually reduced the amount of pain felt. The participants kept their hands submerged in the cold water longer for longer, and also reported experiencing less pain, when they repeated a swear word than when they repeated a word describing a table. Swearing was also associated with increased heart rate.

Swearing therefore enabled the participants to tolerate to the cold temperature for longer, and also caused a reduction in their perception of the pain felt. A difference between males and females was observed. Swearing led to a greater reduction in pain perception and a bigger increase in heart rate in females. Most interestingly though, the effect of swearing in females occurred regardless of their tendency to catastrophise their pain. On the other hand, in the males, catastrophising was found to diminish the effects of swearing on the felt pain. This is interesting in light of other findings which show that men generally catastrophise less, but swear more often, than women.

This study shows that swearing appears to have an analgesic effect under certain conditions. Exactly how is unclear, but the authors suggest that it is because swearing induces negative emotions. It is well known that pain has a strong emotional aspect to it. Fear of pain, for example, is known to enhance pain perception, possibily by activating pathways which descend from the brain and modulate noxious stimuli entering the spinal cord. Swearing, too, is known to induce negative emotions (according to Steven Pinker, it taps into the "deep and ancient parts of the emotional brain"). It may therefore trigger a physiological alarm reaction known as the fight or flight response, which accelerates the heart rate and reduces sensitivity to pain.

Клетки с повреждённой ДНК общаются между собой :)

Здорово! Читаю на http://www.biologynews.net/archives/2009/07/13/dnadamaged_cells_communicate_with_neighbors_to_let_them_know_theyre_in_trouble.html
When cells experiencing DNA damage fail to repair themselves, they send a signal to their neighbors letting them know they're in trouble. The discovery, which shows that a process dubbed the DDR (DNA Damage Response) also controls communication from cell to cell, has implications for both cancer and aging. The findings appear in the July 13 online edition of the Nature Cell Biology.
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When a cell experiences DNA damage, its first response is to try to repair the damage. If that doesn't work the cell, hopefully, either commits suicide or stops dividing, two intrinsic mechanisms for preventing cancer according to Judith Campisi, PhD, lead author of the study and a faculty member at the Buck Institute for Age Research. The discovery of the extracellular signaling mechanism, which sets off an inflammatory response, explains how unsuccessful DNA repair at the cellular level impacts tissues, which are the vital units of function in complex organisms like humans, she said.
"With regard to cancer, we found that if there is a mutant and potentially cancerous cell in the vicinity of the damaged cell, the signals from the damaged cell can encourage that mutant cell to behave more aggressively cancerous," said Campisi. "With regard to aging, we think the inflammatory signals from damaged cells propagate an aging 'field' whereby damage builds up over time, impacting not only the individual damaged cells, but the function of the tissue itself." When Buck scientists disabled particular proteins involved in the DDR, the cell-to-cell communication was cut off.
Buck Institute scientist Francis Rodier, PhD, led the team that did the research in the Campisi lab. He was surprised to find that even though the DDR signaling process was activated inside the cultured human cells within minutes of the DNA damage, it took 24 to 48 hours for the damaged cells to start secreting the inflammatory signals.
"We think the cell is giving itself time to repair its DNA before alerting the immune system that there's a problem," said Rodier. He added that scientists were also surprised to discover that the damage-induced communication signaling pathway bypasses a powerful tumor suppressor gene known as p53. That finding gives scientists a target to shut down the inflammatory process without hampering the activity of p53, which is essential to prevent cancer. It also explains why cancerous tumors are still able to secrete inflammatory signals when p53 has mutated and lost its tumor suppressing capabilities.
"Inflammation is a hallmark symptom of cancer," said Rodier. "Inflammation also promotes cancer, so this helps us begin to understand what's involved in that process."
The findings also help explain the aging process Campisi said. The immune system, which destroys damaged cells (such as skin cells whose DNA has been exposed to UV radiation), is not perfect, she said. "Damaged cells that survive the activity of the immune system are sending out continuous danger signals to surrounding cells. That constant alarm drives inflammation, which helps drive aging." Campisi added, "Now we have a target to focus on that could stop those damaged cells from sending out the inflammatory signals."
Source : Buck Institute for Age Research

Регулярный секс и повреждения ДНК

Занятно! Читаю на http://www.biologynews.net/archives/2009/06/30/daily_sex_helps_to_reduce_sperm_dna_damage_and_improve_fertility.html

Daily sex (or ejaculating daily) for seven days improves men's sperm quality by reducing the amount of DNA damage, according to an Australian study presented today (Tuesday) to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.

Until now there has been no evidence-based consensus amongst fertility specialists as to whether or not men should refrain from sex for a few days before attempting to conceive with their partner, either spontaneously or via assisted reproduction.

Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said: "All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF.

"I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range."

To investigate this hypothesis, Dr Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI). Men who had a more than 15% of their sperm (DFI >15%) damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15% DFI for excellent quality sperm, 15-24% DFI for good, 25-29% DFI for fair and more than 29% DFI for poor quality; but other laboratories can have slightly different ranges.

The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15% and 98% DFI, with an average 34% DFI when measured after three days' abstinence. When the men's sperm was re-assessed on the seventh day, Dr Greening found that 96 men (81%) had an average 12% decrease in their sperm DNA damage, while 22 men (19%) and an average increase in damage of nearly 10%. The average for the whole group dropped to 26% DFI.

Dr Greening said: "Although the mean average was 26% which is in the 'fair' range for sperm quality, this included 18% of men whose sperm DNA damage increased as well as those whose DNA damage decreased. Amongst the men whose damage decreased, their average dropped by 12% to just under 23% DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.

"In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.

"Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates.

"The optimal number of days of ejaculation might be more or less than seven days, but a week appears manageable and favourable. It seems safe to conclude that couples with relatively normal semen parameters should have sex daily for up to a week before the ovulation date. In the context of assisted reproduction, this simple treatment may assist in improving sperm quality and ultimately achieving a pregnancy. In addition, these results may mean that men play a greater role in infertility than previously suspected, and that ejaculatory frequency is important for improving sperm quality, especially as men age and during assisted reproduction cycles."

Dr Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species – very small molecules, high levels of which can damage cells. "The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage," he concluded.

Source : European Society for Human Reproduction and Embryology

Восстановление функций мозга после метамфетаминовой абстиненции

Интересно написано на http://www.biologynews.net/archives/2009/06/29/brain_functions_that_can_prevent_relapse_improve_after_a_year_of_methamphetamine_abstinence.html
Іn a study published online by the Journal of Substance Abuse Treatment, UC Davis researchers report that it takes at least a year for former methamphetamine users to regain impulse control. The results tell recovering substance abusers, their families and drug-treatment specialists that it can take an extended period of time for the brain functions critical to recovery to improve.

"Recovery from meth abuse does not happen overnight," said Ruth Salo, lead author of the study and a UC Davis assistant professor of psychiatry and behavioral sciences. "It may take a year — or even longer — for cognitive processes such as impulse control and attentional focus to improve. Treatment programs need to consider this when monitoring recovering addicts' progress during their early periods of abstinence."

Salo specializes in the behavioral, neuropsychiatric and cognitive outcomes of methamphetamine addiction — a particularly difficult condition to treat, primarily due to prolonged, intense cravings for the drug. During her career, she has worked with hundreds of methamphetamine addicts.

"All of them want to know if there is hope," Salo said. "We used to think most, if not all, effects of meth addiction were permanent. This study adds to the growing evidence that this assumption is not true. I can confidently tell patients that the longer they stay in a structured rehabilitation program and remain drug free, the more likely it is that they will recover some important brain functions."

For the current study, Salo used the widely-validated, computer-based Stroop attention test to measure the abilities of 65 recovering methamphetamine abusers to use cognitive control — or direct their attention to specific tasks while ignoring distractors. Study participants had been abstinent for a minimum of three weeks and a maximum of 10 years, and they had previously used the drug for periods ranging from 24 months to 28 years. The data for the 65 individuals were compared to Stroop attention test data from 33 participants who had never used methamphetamine.

"The test taps into something people do in everyday life: make choices in the face of conflicting impulses that can promote a strong but detrimental tendency," Salo explained. "For meth users, impairments in this decision-making ability might make them more likely to spend a paycheck on the immediate satisfaction of getting high rather than on the longer-term satisfaction gained by paying rent or buying groceries."

The study analyzed cognitive control in terms of the amount of time since methamphetamine was last used as well as total time spent using the drug. The researchers found that those who were recently abstinent (three weeks to six months) performed significantly worse on the Stroop test than those who had been abstinent one year or longer. In addition, there was no statistical difference between test results for those abstinent at least one year and non-drug using controls. Longer-term methamphetamine use was associated with worse test scores. Similarly, longer-term abstinence was connected to improved test performance.

According to Salo, the new study mirrors previous magnetic resonance imaging (MRI) studies she and her colleagues published in 2005 showing a partial normalization of chemicals in selected brain regions after one year of methamphetamine abstinence.

"Together, the studies provide strong evidence that, eventually, meth abusers in recovery may be able to make better decisions and regain the impulse control that was lost during their drug use period," she said.

Salo said that more research is needed to determine just how the brain recovers from methamphetamine addiction and if behavioral treatments can hasten that recovery. She plans to continue neuroimaging studies to further define the brain functions affected by the drug. Her ultimate goal is to provide information essential to refining treatment programs for this population of drug users.

"Meth use worldwide is pandemic," she said, referring to the estimated 35 million people who have used the neurotoxic stimulant or similar drugs. "Recovery is difficult, but possible. The point of my research is to better understand the neural and behavioral consequences of this toxic drug along with the brain and behavior changes that are possible with long-term abstinence."

Source : University of California - Davis - Health System

Повреждения ДНК и марихуана

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

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.

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.

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

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.

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

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.