To their surprise, researchers at Georgetown University Medical Center (GUMC) have discovered that morphine (a derivate of the opium poppy that is similar to heroin) protects rat neurons against HIV toxicity - a finding they say might help in the design of new neuroprotective therapies for patients with the infection.
The discovery, being presented at the annual meeting of the Society of NeuroImmune Pharmacology, also helps explain why a subset of people who are heroin abusers and become infected with HIV through needle sharing don't develop HIV brain dementia. This brain disorder includes cognitive and motor abnormalities, anxiety and depression.
"We believe that morphine may be neuroprotective in a subset of people infected with HIV," says the study's lead investigator, Italo Mocchetti, PhD, Professor of neuroscience at GUMC. "That is not to say that people should use heroin to protect themselves - that makes no medical sense at all - but our findings gives us ideas about designing drugs that could be of benefit.
"Needless to say we were very surprised at the findings," he added. "We started with the opposite hypothesis - that heroin was going to destroy neurons in the brain and lead to HIV dementia."
The researchers conducted the study because they knew that a number of HIV-positive people are also heroin abusers, and because of that, some are at high risk of developing neurological complications from the infection. Others, however, never develop these cognitive problems, Mocchetti says.
Because little is known about the molecular mechanisms linking opiates and HIV neurotoxicity, Mocchetti and his team conducted experiments in rats. They found that in the brain, morphine inhibited the toxic property of the HIV protein gp120 that mediates the infection of immune cells. With further investigation, they concluded that morphine induces production of the protein CCL5, which they discovered is released by astrocytes, a type of brain cell. CCL5 is known to activate factors that suppress HIV infection of human immune cells. "It is known to be important in blood, but we didn't know it is secreted in the brain," says Mocchetti. "Our hypothesis is that it is in the brain to prevent neurons from dying."
They say morphine blocked HIV from binding to CCR5 receptors it typically uses to enter and infect cells. The researchers believe CCL5 itself attached to those receptors, preventing the virus from using it. In this way, it prevented HIV-associated dementia. This effect, however, only worked in the M-trophic strain of HIV, the strain that most people are first infected with. It did not work with the second T-trophic strain that often infects patients later.
"Ideally we can use this information to develop a morphine-like compound that does not have the typical dependency and tolerance issues that morphine has," says Mocchetti.
The study was funded by the National Institute on Drug Abuse, part of the National Institutes of Health. The authors declare no conflicts of interest.
Source:
Karen Mallet
Georgetown University Medical Center
вторник, 7 июня 2011 г.
понедельник, 6 июня 2011 г.
Low Doses Of Ecstasy Associated With Decline In Verbal Memory
Even low doses of Ecstasy may be associated with a decline in language-related memory, according to a report in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Ecstasy is an illicit recreational drug popular among young people, according to background information in the article. Research in both humans and animals suggests that the drug can harm the brain. Ecstasy may damage nerve cells that respond to the hormone serotonin, which is involved in mood, thinking, learning and memory.
Thelma Schilt, M.Sc., of the Academic Medical Center of the University of Amsterdam, the Netherlands, and colleagues recruited 188 volunteers (average age 22) who had not used Ecstasy but reported that they were likely to try it soon. Within three years of the initial evaluations, which took place between April 2002 and April 2004, 58 individuals began using Ecstasy. They were compared with 60 individuals who had the same age, sex and intelligence score but who did not use Ecstasy during the follow-up period. All participants took tests that assessed various types of memory - including attention, verbal memory for words and language, and visual memory for images - at the beginning and end of the study. Verbal memory was tested by memorizing a series of 15 words and repeating them immediately and again 20 minutes later.
"At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-na??ve subjects and future Ecstasy users," the authors write. "However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-na??ve subjects. There were no significant differences on other test scores."
In contrast to other studies, which have suggested that Ecstasy affects women more than men, there was no difference in the drug's effect between the sexes. Overall, test scores remained within the normal range for the general population.
The fact that Ecstasy appeared to affect only verbal memory points to specific brain areas and chemicals that may be affected by the drug, the authors note. "The main underlying factor seems to be a depletion of serotonin in Ecstasy users, a depletion that might be reversible," they write. "Serotonin is involved in several cognitive functions but might be especially relevant to learning and memory."
"In conclusion, our data indicate that low doses of Ecstasy are associated with decreased verbal memory function, which is suggestive for Ecstasy-induced neurotoxicity," the authors conclude. "Further research on the long-term effects of Ecstasy as well as on the possibility of additive effects of Ecstasy use on aging of the brain is needed."
(Arch Gen Psychiatry. 2007;64:728-736.)
This study was supported by a grant from the Netherlands Organization for Health Research and Development as part of their Addiction Program. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Contact: Thelma Schilt
JAMA and Archives Journals
Ecstasy is an illicit recreational drug popular among young people, according to background information in the article. Research in both humans and animals suggests that the drug can harm the brain. Ecstasy may damage nerve cells that respond to the hormone serotonin, which is involved in mood, thinking, learning and memory.
Thelma Schilt, M.Sc., of the Academic Medical Center of the University of Amsterdam, the Netherlands, and colleagues recruited 188 volunteers (average age 22) who had not used Ecstasy but reported that they were likely to try it soon. Within three years of the initial evaluations, which took place between April 2002 and April 2004, 58 individuals began using Ecstasy. They were compared with 60 individuals who had the same age, sex and intelligence score but who did not use Ecstasy during the follow-up period. All participants took tests that assessed various types of memory - including attention, verbal memory for words and language, and visual memory for images - at the beginning and end of the study. Verbal memory was tested by memorizing a series of 15 words and repeating them immediately and again 20 minutes later.
"At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-na??ve subjects and future Ecstasy users," the authors write. "However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-na??ve subjects. There were no significant differences on other test scores."
In contrast to other studies, which have suggested that Ecstasy affects women more than men, there was no difference in the drug's effect between the sexes. Overall, test scores remained within the normal range for the general population.
The fact that Ecstasy appeared to affect only verbal memory points to specific brain areas and chemicals that may be affected by the drug, the authors note. "The main underlying factor seems to be a depletion of serotonin in Ecstasy users, a depletion that might be reversible," they write. "Serotonin is involved in several cognitive functions but might be especially relevant to learning and memory."
"In conclusion, our data indicate that low doses of Ecstasy are associated with decreased verbal memory function, which is suggestive for Ecstasy-induced neurotoxicity," the authors conclude. "Further research on the long-term effects of Ecstasy as well as on the possibility of additive effects of Ecstasy use on aging of the brain is needed."
(Arch Gen Psychiatry. 2007;64:728-736.)
This study was supported by a grant from the Netherlands Organization for Health Research and Development as part of their Addiction Program. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Contact: Thelma Schilt
JAMA and Archives Journals
воскресенье, 5 июня 2011 г.
U.N. Official Addresses Increasing Drug Addiction In Developing Countries
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_uacct = "UA-849615-1";
urchinTracker();
These are the most read articles from this news category for the last 6 months:
Alcohol Is Most Harmful Drug, Followed By Heroin And Crack
01 Nov 2010
Alcohol is the most damaging drug to the drinker and others overall, heroin and crack are the second and third most harmful, Professor David Nutt and colleagues wrote in the medical journal The Lancet today...
Giving Up Smoking Linked To Greater Happiness And Elevated Mood
05 Dec 2010
Energy Drinks: Is It Time To Tighten Regulation?
02 Nov 2010
USA's Drunkest Cities Are Milwaukee, Fargo And San Francisco
31 Dec 2010
Lock Up The Liquor; Parents Giving Children Alcohol
19 Feb 2011
_uacct = "UA-849615-1";
urchinTracker();
суббота, 4 июня 2011 г.
European Commission Adopts Communications On Reducing Alcohol Related Harm In Europe
The European Commission adopted a Communication on alcohol and health, setting out an EU strategy to support Member States in reducing alcohol related harm. The Communication addresses the adverse health effects of harmful and hazardous alcohol consumption in Europe, which is estimated to cause the deaths of 195,000 people a year in the EU.
The priorities identified in the Communication are:
to protect young people and children;
reduce injuries and deaths from alcohol-related road accidents;
prevent harm among adults and reduce the negative impact on the economy;
raise awareness of the impact on health of harmful alcohol consumption;
and help gather reliable statistics.
The Commission has identified areas where the EU can support and coordinate the actions of Member States to reduce alcohol related harm, such as financing projects through the Public Health and Research Programmes, exchanging good practice on issues such as curbing under-age drinking, exploring cooperation on information campaigns or tackling drink-driving and other Community initiatives. The Communication also maps out actions which Member States are taking, with a view to promoting good practice, proposes an Alcohol and Health Forum of interested parties and sets out areas where industry can make a contribution, notably in the area of responsible advertising and marketing.
European Health and Consumer Protection Commissioner Markos Kyprianou said: "Binge drinking, under-age drinking and drink-driving are real public health issues in Europe, especially among young people. The Commission is not targeting moderate alcohol consumption, but seeks to actively support Member States measures to reduce the harm caused by alcohol abuse. This Communication aims to promote discussion and cooperation at European level more actively by creating fora to exchange good practices. I also believe that industry can do more to reduce alcohol harm, promote responsible drinking and improve consumer information. The Commission is committed to supporting this process by bringing the relevant actors together, promoting cooperation and funding projects in this area."
A major health and economic impact
Fifty-five million adults are estimated to drink to hazardous levels in the EU. Harmful and hazardous alcohol consumption is a net cause of 7.4 % of all ill-health and early death in the EU. Absenteeism due to hazardous alcohol use, drinking during working hours, or working with a "hangover" all have a negative impact on work performance, and thereby on competitiveness and productivity. In the age group of 15-29 years over 10% of female mortality and around 25% of male mortality are due to hazardous alcohol consumption. This is also the cause in 16% of cases of child abuse and neglect. Exposure to alcohol during pregnancy can impair brain development and is associated with intellectual deficits. Approximately one accident in four can be attributed to alcohol consumption, and about 10,000 people are killed in alcohol-related road accidents in the EU each year.
Commission action
In cooperation with Member States and stakeholders, the Commission will develop strategies aimed at curbing under-age drinking, by exchanging good practice on issues like selling and serving, marketing, and the image of alcohol use conveyed through the media. Through its Public Health Programme, the Commission will support projects that will contribute to reduce alcohol-related harm in the EU, and especially the harm suffered by children and young people, as well as gathering and disseminating data. It will support the monitoring of young people's drinking habits, with a focus on the increased drinking of alcohol among girls and binge-drinking.
The Commission will explore, in cooperation with Member States and stakeholders, the usefulness of developing efficient common approaches throughout the Community to provide adequate consumer information. Such reflections are particularly important as some Member States are planning to introduce warning labels (e.g. on alcohol and pregnancy). It will support Member States and stakeholders in their efforts to develop information and education programmes on the effect of harmful drinking. Through the EU Research Framework Programme, the Commission will launch research on young people's drinking in order to analyse current trends and motivations for drinking, as well as the wider determinants of youth drinking.
Mapping out national action with a view to promoting good practice
Member States have the main responsibility for national alcohol policy. The Commission's role is to encourage cooperation and coordination between Member States, and to complement their activities, for example through the funding of projects. The Communication maps out measures adopted by Member States to tackle alcohol related harm, which can facilitate the dissemination of good practice across the EU. Examples of national measures identified in the Communication include: action to improve consumer information at point of sale, on products or at the workplace; action to better enforce age limits for selling and serving alcohol; education of young people and parents; introducing a zero blood alcohol concentration limit for young or inexperienced drivers, and for professional drivers; and enforcing counter-measures against drink-driving.
Follow-up and consistency with other policies
The Commission will also set up:
-- an "Alcohol and Health Forum" by June 2007, to support, provide input and monitor the implementation of the strategy outlined in the Communication. The Forum will focus on topics such as research, information and data collection, and education. a working group to coordinate drink-driving and road safety actions including those supported by the Public Health Programme and the Action Plan on Road Safety, to help reduce alcohol-related road accidents, and with a particular view to combating drink-driving. The group will in particular address the issue of novice and young drivers.
-- a group of stakeholders for co-operation on responsible commercial communication and sales. The group will inter alia support EU and national/local Government actions to reduce irresponsible marketing of alcoholic beverages, and examine data about trends in advertising. It will develop codes of conduct for commercial communications.
The Commission considers that its main contribution to the strategy should be based on the existing approach of complementing national strategies in this area and therefore does not intend to implement the strategy through legislative proposals. The Commission invites Member States to report back regularly on the implementation of measures to tackle harmful and hazardous alcohol consumption as well as on the impact of the EU strategy set out in this Communication.
ec.europa.eu
The priorities identified in the Communication are:
to protect young people and children;
reduce injuries and deaths from alcohol-related road accidents;
prevent harm among adults and reduce the negative impact on the economy;
raise awareness of the impact on health of harmful alcohol consumption;
and help gather reliable statistics.
The Commission has identified areas where the EU can support and coordinate the actions of Member States to reduce alcohol related harm, such as financing projects through the Public Health and Research Programmes, exchanging good practice on issues such as curbing under-age drinking, exploring cooperation on information campaigns or tackling drink-driving and other Community initiatives. The Communication also maps out actions which Member States are taking, with a view to promoting good practice, proposes an Alcohol and Health Forum of interested parties and sets out areas where industry can make a contribution, notably in the area of responsible advertising and marketing.
European Health and Consumer Protection Commissioner Markos Kyprianou said: "Binge drinking, under-age drinking and drink-driving are real public health issues in Europe, especially among young people. The Commission is not targeting moderate alcohol consumption, but seeks to actively support Member States measures to reduce the harm caused by alcohol abuse. This Communication aims to promote discussion and cooperation at European level more actively by creating fora to exchange good practices. I also believe that industry can do more to reduce alcohol harm, promote responsible drinking and improve consumer information. The Commission is committed to supporting this process by bringing the relevant actors together, promoting cooperation and funding projects in this area."
A major health and economic impact
Fifty-five million adults are estimated to drink to hazardous levels in the EU. Harmful and hazardous alcohol consumption is a net cause of 7.4 % of all ill-health and early death in the EU. Absenteeism due to hazardous alcohol use, drinking during working hours, or working with a "hangover" all have a negative impact on work performance, and thereby on competitiveness and productivity. In the age group of 15-29 years over 10% of female mortality and around 25% of male mortality are due to hazardous alcohol consumption. This is also the cause in 16% of cases of child abuse and neglect. Exposure to alcohol during pregnancy can impair brain development and is associated with intellectual deficits. Approximately one accident in four can be attributed to alcohol consumption, and about 10,000 people are killed in alcohol-related road accidents in the EU each year.
Commission action
In cooperation with Member States and stakeholders, the Commission will develop strategies aimed at curbing under-age drinking, by exchanging good practice on issues like selling and serving, marketing, and the image of alcohol use conveyed through the media. Through its Public Health Programme, the Commission will support projects that will contribute to reduce alcohol-related harm in the EU, and especially the harm suffered by children and young people, as well as gathering and disseminating data. It will support the monitoring of young people's drinking habits, with a focus on the increased drinking of alcohol among girls and binge-drinking.
The Commission will explore, in cooperation with Member States and stakeholders, the usefulness of developing efficient common approaches throughout the Community to provide adequate consumer information. Such reflections are particularly important as some Member States are planning to introduce warning labels (e.g. on alcohol and pregnancy). It will support Member States and stakeholders in their efforts to develop information and education programmes on the effect of harmful drinking. Through the EU Research Framework Programme, the Commission will launch research on young people's drinking in order to analyse current trends and motivations for drinking, as well as the wider determinants of youth drinking.
Mapping out national action with a view to promoting good practice
Member States have the main responsibility for national alcohol policy. The Commission's role is to encourage cooperation and coordination between Member States, and to complement their activities, for example through the funding of projects. The Communication maps out measures adopted by Member States to tackle alcohol related harm, which can facilitate the dissemination of good practice across the EU. Examples of national measures identified in the Communication include: action to improve consumer information at point of sale, on products or at the workplace; action to better enforce age limits for selling and serving alcohol; education of young people and parents; introducing a zero blood alcohol concentration limit for young or inexperienced drivers, and for professional drivers; and enforcing counter-measures against drink-driving.
Follow-up and consistency with other policies
The Commission will also set up:
-- an "Alcohol and Health Forum" by June 2007, to support, provide input and monitor the implementation of the strategy outlined in the Communication. The Forum will focus on topics such as research, information and data collection, and education. a working group to coordinate drink-driving and road safety actions including those supported by the Public Health Programme and the Action Plan on Road Safety, to help reduce alcohol-related road accidents, and with a particular view to combating drink-driving. The group will in particular address the issue of novice and young drivers.
-- a group of stakeholders for co-operation on responsible commercial communication and sales. The group will inter alia support EU and national/local Government actions to reduce irresponsible marketing of alcoholic beverages, and examine data about trends in advertising. It will develop codes of conduct for commercial communications.
The Commission considers that its main contribution to the strategy should be based on the existing approach of complementing national strategies in this area and therefore does not intend to implement the strategy through legislative proposals. The Commission invites Member States to report back regularly on the implementation of measures to tackle harmful and hazardous alcohol consumption as well as on the impact of the EU strategy set out in this Communication.
ec.europa.eu
пятница, 3 июня 2011 г.
Large Family Study Pinpoints Genetic Linkage In Drug Addiction
Based on data obtained from one of the largest family sets of its kind, Yale School of Medicine researchers have identified a genetic linkage for dependence on drugs such as heroin, morphine and oxycontin.
The lead author, Joel Gelernter, M.D., professor in the Department of Psychiatry, said the researchers recruited a sample of 393 small families, most with at least two individuals with opioid dependence. They then searched genetic signposts throughout the entire genome in an effort to identify markers that, within the same family, would show that individuals who share the illness also share marker alleles, or gene variants.
This information allowed the team to identify where genes influencing opioid dependence are located. Gelernter said the researchers found evidence of gene linkage for opioid dependence. They also found strong evidence of linkage in the family groups for the symptom cluster traits characterized by dependence on substances other than opioids, specifically, alcohol, cocaine and tobacco.
"These results provide a first basis to identify genes for opioid dependence from a genome-wide investigation," Gelernter said. "Research in the laboratory now is focused on finding specific genes that modify risk for opioid dependence."
He said that although environment plays a significant role, it is well established that substance dependence risk is also genetically influenced. Understanding the genetic factors that influence opioid dependence risk would represent major progress toward understanding the basic biology of the disorder.
"Once specific genes that increase or decrease risk are known, we will be in a better position to figure out exactly what the environmental factors might be and, perhaps, how they can be modified to protect people who are genetically at risk," Gelernter said.
The study was a collaborative effort involving investigators at Yale, the University of Connecticut Health Center, McLean Hospital in Boston, the Medical University of South Carolina, and Boston University. The National Institute on Drug Abuse supported the study.
The American Journal of Human Genetics: (Published online March 16, 2006. DOI 10.1086/503631)
Yale News Releases are available via the World Wide Web at:
yale/opa
View drug information on OxyContin.
The lead author, Joel Gelernter, M.D., professor in the Department of Psychiatry, said the researchers recruited a sample of 393 small families, most with at least two individuals with opioid dependence. They then searched genetic signposts throughout the entire genome in an effort to identify markers that, within the same family, would show that individuals who share the illness also share marker alleles, or gene variants.
This information allowed the team to identify where genes influencing opioid dependence are located. Gelernter said the researchers found evidence of gene linkage for opioid dependence. They also found strong evidence of linkage in the family groups for the symptom cluster traits characterized by dependence on substances other than opioids, specifically, alcohol, cocaine and tobacco.
"These results provide a first basis to identify genes for opioid dependence from a genome-wide investigation," Gelernter said. "Research in the laboratory now is focused on finding specific genes that modify risk for opioid dependence."
He said that although environment plays a significant role, it is well established that substance dependence risk is also genetically influenced. Understanding the genetic factors that influence opioid dependence risk would represent major progress toward understanding the basic biology of the disorder.
"Once specific genes that increase or decrease risk are known, we will be in a better position to figure out exactly what the environmental factors might be and, perhaps, how they can be modified to protect people who are genetically at risk," Gelernter said.
The study was a collaborative effort involving investigators at Yale, the University of Connecticut Health Center, McLean Hospital in Boston, the Medical University of South Carolina, and Boston University. The National Institute on Drug Abuse supported the study.
The American Journal of Human Genetics: (Published online March 16, 2006. DOI 10.1086/503631)
Yale News Releases are available via the World Wide Web at:
yale/opa
View drug information on OxyContin.
четверг, 2 июня 2011 г.
High Resolution 'snapshots' Detail Dynamics Of A Cocaine Antibody
Cocaine-binding antibodies have shown some promise in their ability to neutralize cocaine toxicity, but their binding ability is severely impaired by high concentrations of the drug. A catalytic monoclonal antibody such as 7A1, on the other hand, has the ability to regenerate after each new dose of the drug, making it far more effective than others in metabolizing cocaine.
The study, which will be published in the February issue (Volume 14 Issue 2) of the journal Structure, was led by Ian A. Wilson, D.Phil., of Scripps Research Department of Molecular Biology and The Skaggs Institute for Chemical Biology, and Kim D. Janda, Ph.D., of Scripps Research Departments of Chemistry and Immunology and The Skaggs Institute for Chemical Biology.
Despite intensive research, cocaine abuse continues to be a major public health problem, so far eluding efforts at developing an effective therapeutic agent to counter the craving, addiction, and overdose of the drug. To date, no treatment has been approved by the Food and Drug Administration (FDA).
Commenting on the new findings, Xueyong Zhu, Ph.D., the primary author of the study and a staff scientist in the Wilson laboratory said, "Development of effective therapies for cocaine abuse has been a long-standing goal, and a number of medications under study do show some promise. Immunopharmacotherapy has been proposed as a way to neutralize the drug outside the central nervous system- basically soaking up the drug before it has a chance to cross the blood brain barrier-as a potentially effective new approach to treat cocaine abuse."
Using a monoclonal antibody endowed not only with high binding ability, but also with sufficient catalytic activity to metabolize cocaine, would have potentially enhanced therapeutic effects, Zhu said. This antibody could intercept cocaine in the blood stream before it reaches the central nervous system-stopping the drug cold. Because cocaine has a half life of approximately 30 minutes inside the human body, a cocaine catalytic antibody would basically have to out-run the body's natural metabolism process to have any serious impact on the psychoactive effects of the drug.
Generated by x-ray crystallography, pictures of the conformational changes that occur during the antibody's complete catalytic cycle show the molecular basis for catalysis and reveal possible mutations that could increase catalytic proficiency. This, Zhu pointed out, provides a foundation for the humanization and mutagenesis of the antibody to enhance its cocaine-hydrolyzing activity and make future human clinical trials feasible. "Given the fact that catalytic antibodies have been produced with the same levels of efficiency as natural enzymes, it seems well within the realm of possibility," he added.
To reach this ambitious goal, however, it may be necessary to explore new incremental approaches for optimizing the efficiency of such catalytic activity. Novel functional groups could be introduced into first generation antibody catalysts by multiple rounds of mutagenesis and selection to produce improvements. In essence, this would allow scientists to dramatically accelerate the evolutionary process, producing improvements in the immune system in weeks or months that previously took billions of years.
"The structural insights into antibody catalysis that we have shown with 7A1 Fab' are critical for any future improvement of effective biocatalysts," Zhu said. "One of the main goals of our lab has been to focus on catalytic antibodies that will have a direct impact on public health issues. With the snapshots of the complete cycle of the cocaine antibody catalytic reaction, we have shed new light on the sequence of events in an antibody-mediated reaction and provided a rare glimpse of the structural dynamics involved. With this information, it's possible to move onto the next step in the development of a treatment for cocaine abuse and addiction."
Other authors of the study include Tobin J. Dickerson, Claude J. Rogers, Gunnar F. Kaufmann, Jenny M. Mee, and Kathleen M. McKenzie.
Support for the study was provided by grants from the National Institutes of Health, The Skaggs Institute for Chemical Biology and Scripps Research.
About The Scripps Research Institute
The Scripps Research Institute, headquartered in La Jolla, California, in 18 buildings on 40 acres overlooking the Pacific Ocean, is one of the world's largest independent, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.
Scripps Florida, a 364,000 square-foot, state-of-the-art biomedical research facility, will be built in Palm Beach County. The facility will focus on basic biomedical science, drug discovery, and technology development. Palm Beach County and the State of Florida have provided start-up economic packages for development, building, staffing, and equipping the campus. Scripps Florida now operates with approximately 160 scientists, technicians, and administrative staff at 40,000 square-foot lab facilities on the Florida Atlantic University campus in Jupiter.
Contact: Keith McKeown
kmckeownscripps
Scripps Research Institute
The study, which will be published in the February issue (Volume 14 Issue 2) of the journal Structure, was led by Ian A. Wilson, D.Phil., of Scripps Research Department of Molecular Biology and The Skaggs Institute for Chemical Biology, and Kim D. Janda, Ph.D., of Scripps Research Departments of Chemistry and Immunology and The Skaggs Institute for Chemical Biology.
Despite intensive research, cocaine abuse continues to be a major public health problem, so far eluding efforts at developing an effective therapeutic agent to counter the craving, addiction, and overdose of the drug. To date, no treatment has been approved by the Food and Drug Administration (FDA).
Commenting on the new findings, Xueyong Zhu, Ph.D., the primary author of the study and a staff scientist in the Wilson laboratory said, "Development of effective therapies for cocaine abuse has been a long-standing goal, and a number of medications under study do show some promise. Immunopharmacotherapy has been proposed as a way to neutralize the drug outside the central nervous system- basically soaking up the drug before it has a chance to cross the blood brain barrier-as a potentially effective new approach to treat cocaine abuse."
Using a monoclonal antibody endowed not only with high binding ability, but also with sufficient catalytic activity to metabolize cocaine, would have potentially enhanced therapeutic effects, Zhu said. This antibody could intercept cocaine in the blood stream before it reaches the central nervous system-stopping the drug cold. Because cocaine has a half life of approximately 30 minutes inside the human body, a cocaine catalytic antibody would basically have to out-run the body's natural metabolism process to have any serious impact on the psychoactive effects of the drug.
Generated by x-ray crystallography, pictures of the conformational changes that occur during the antibody's complete catalytic cycle show the molecular basis for catalysis and reveal possible mutations that could increase catalytic proficiency. This, Zhu pointed out, provides a foundation for the humanization and mutagenesis of the antibody to enhance its cocaine-hydrolyzing activity and make future human clinical trials feasible. "Given the fact that catalytic antibodies have been produced with the same levels of efficiency as natural enzymes, it seems well within the realm of possibility," he added.
To reach this ambitious goal, however, it may be necessary to explore new incremental approaches for optimizing the efficiency of such catalytic activity. Novel functional groups could be introduced into first generation antibody catalysts by multiple rounds of mutagenesis and selection to produce improvements. In essence, this would allow scientists to dramatically accelerate the evolutionary process, producing improvements in the immune system in weeks or months that previously took billions of years.
"The structural insights into antibody catalysis that we have shown with 7A1 Fab' are critical for any future improvement of effective biocatalysts," Zhu said. "One of the main goals of our lab has been to focus on catalytic antibodies that will have a direct impact on public health issues. With the snapshots of the complete cycle of the cocaine antibody catalytic reaction, we have shed new light on the sequence of events in an antibody-mediated reaction and provided a rare glimpse of the structural dynamics involved. With this information, it's possible to move onto the next step in the development of a treatment for cocaine abuse and addiction."
Other authors of the study include Tobin J. Dickerson, Claude J. Rogers, Gunnar F. Kaufmann, Jenny M. Mee, and Kathleen M. McKenzie.
Support for the study was provided by grants from the National Institutes of Health, The Skaggs Institute for Chemical Biology and Scripps Research.
About The Scripps Research Institute
The Scripps Research Institute, headquartered in La Jolla, California, in 18 buildings on 40 acres overlooking the Pacific Ocean, is one of the world's largest independent, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.
Scripps Florida, a 364,000 square-foot, state-of-the-art biomedical research facility, will be built in Palm Beach County. The facility will focus on basic biomedical science, drug discovery, and technology development. Palm Beach County and the State of Florida have provided start-up economic packages for development, building, staffing, and equipping the campus. Scripps Florida now operates with approximately 160 scientists, technicians, and administrative staff at 40,000 square-foot lab facilities on the Florida Atlantic University campus in Jupiter.
Contact: Keith McKeown
kmckeownscripps
Scripps Research Institute
среда, 1 июня 2011 г.
Finding may explain link between alcohol and certain cancers
Drinking alcoholic beverages has been linked to an increased risk of upper gastrointestinal cancer and other types of cancer. Researchers looking for the potential biochemical basis for this link have focused on acetaldehyde, a suspected carcinogen formed as the body metabolizes alcohol. In the journal Nucleic Acids Research, scientists from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute of Standards and Technology (NIST) report that polyamines - natural compounds essential for cell growth - react with acetaldehyde to trigger a series of reactions that damage DNA, an event that can lead to the formation of cancer.
"We've long suspected acetaldehyde's role in the carcinogenicity of alcohol beverage consumption, but this study gives us important new clues about its involvement," says Ting-Kai Li, M.D., director of the NIAAA, part of the National Institutes of Health. "This work provides an important framework for understanding the underlying chemical pathway that could explain the association between drinking and certain types of cancer."
The research team, led by P.J. Brooks, Ph.D., of NIAAA and Miral Dizdaroglu, Ph.D., of NIST, examined acetaldehyde's reaction with polyamines, small molecules found in all cells. "Polyamines are usually considered 'good guys,' because they have been shown to protect DNA from oxidative damage," says Dr. Brooks. Yet the researchers found the polyamines facilitated the conversion of acetaldehyde into crotonaldehyde (CrA), an environmental pollutant that has been shown to cause cancer in animals. This chemical in turn altered DNA, generating an abnormal, mutagenic DNA base called a Cr-PdG adduct. Dr. Brooks says, "We concluded that polyamines stimulated the formation of Cr-PdG adducts from acetaldehyde, and this may provide a mechanism to explain how alcohol consumption increases the risk of some types of cancer."
Previous studies had shown acetaldehyde could be converted to mutagenic Cr-PdG, but those studies used very high acetaldehyde concentrations. "We were able to demonstrate that these reactions can take place with acetaldehyde concentrations that have been measured in human saliva during alcohol consumption," says Dr. Brooks.
An important part of this research was a new chemical analysis method developed at NIST. According to Dr. Dizdaroglu, "This novel chemical assay is a powerful method that accurately measures the Cr-PdG adduct."
George Kunos, M.D., Ph.D., director of NIAAA's Division of Intramural Clinical and Biological Research, says, "These findings also have significant implications for researchers seeking to understand how genes affect the risk for cancer." Many studies have shown that certain genetic variants that affect alcohol and acetaldehyde metabolism can also affect individual susceptibility to alcohol-related gastrointestinal cancer. Dr. Kunos adds, "This work could serve as a roadmap for future studies to investigate other genetic factors, particularly those that influence DNA repair pathways, in relation to alcohol consumption and cancer."
To arrange an interview with Dr. Brooks, contact the NIAAA press office at 301-443-3860.
The National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health, U.S. Department of Health and Human Services, conducts and supports approximately 90 percent of U.S. research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to science, practitioner, policy making and general audiences. Additional alcohol research information and publications are available at niaaa.nih.
Gregory Roa
greg.roanih
301-443-3860
NIH/National Institute on Alcohol Abuse and Alcoholism
niaaa.nih
"We've long suspected acetaldehyde's role in the carcinogenicity of alcohol beverage consumption, but this study gives us important new clues about its involvement," says Ting-Kai Li, M.D., director of the NIAAA, part of the National Institutes of Health. "This work provides an important framework for understanding the underlying chemical pathway that could explain the association between drinking and certain types of cancer."
The research team, led by P.J. Brooks, Ph.D., of NIAAA and Miral Dizdaroglu, Ph.D., of NIST, examined acetaldehyde's reaction with polyamines, small molecules found in all cells. "Polyamines are usually considered 'good guys,' because they have been shown to protect DNA from oxidative damage," says Dr. Brooks. Yet the researchers found the polyamines facilitated the conversion of acetaldehyde into crotonaldehyde (CrA), an environmental pollutant that has been shown to cause cancer in animals. This chemical in turn altered DNA, generating an abnormal, mutagenic DNA base called a Cr-PdG adduct. Dr. Brooks says, "We concluded that polyamines stimulated the formation of Cr-PdG adducts from acetaldehyde, and this may provide a mechanism to explain how alcohol consumption increases the risk of some types of cancer."
Previous studies had shown acetaldehyde could be converted to mutagenic Cr-PdG, but those studies used very high acetaldehyde concentrations. "We were able to demonstrate that these reactions can take place with acetaldehyde concentrations that have been measured in human saliva during alcohol consumption," says Dr. Brooks.
An important part of this research was a new chemical analysis method developed at NIST. According to Dr. Dizdaroglu, "This novel chemical assay is a powerful method that accurately measures the Cr-PdG adduct."
George Kunos, M.D., Ph.D., director of NIAAA's Division of Intramural Clinical and Biological Research, says, "These findings also have significant implications for researchers seeking to understand how genes affect the risk for cancer." Many studies have shown that certain genetic variants that affect alcohol and acetaldehyde metabolism can also affect individual susceptibility to alcohol-related gastrointestinal cancer. Dr. Kunos adds, "This work could serve as a roadmap for future studies to investigate other genetic factors, particularly those that influence DNA repair pathways, in relation to alcohol consumption and cancer."
To arrange an interview with Dr. Brooks, contact the NIAAA press office at 301-443-3860.
The National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health, U.S. Department of Health and Human Services, conducts and supports approximately 90 percent of U.S. research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to science, practitioner, policy making and general audiences. Additional alcohol research information and publications are available at niaaa.nih.
Gregory Roa
greg.roanih
301-443-3860
NIH/National Institute on Alcohol Abuse and Alcoholism
niaaa.nih
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