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Archive for April 2009

Human Brain Makes Its Own ‘Marijuana’

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U.S. and Brazilian scientists have discovered that the brain manufactures proteins that act like marijuana at specific receptors in the brain itself. This discovery may lead to new marijuana-like drugs for managing pain, stimulating appetite, and preventing marijuana abuse.

Scientists made their discovery by first extracting several small proteins, called peptides, from the brains of mice and determining their amino acid sequence. The extracted proteins were then compared with another peptide previously known to bind to, but not activate, the receptor (THC) affected by marijuana. Out of the extracted proteins, several not only bound to the brain’s THC receptors, but activated them as well.

The FASEB Journal Published online before print April 20, 2009 as doi: 10.1096/fj.09-132142.

Novel endogenous peptide agonists of cannabinoid receptors
Ivone Gomes, Julia S. Grushko, Urszula Golebiewska, Sascha Hoogendoorn, Achla Gupta, Andrea S. Heimann, Emer S. Ferro, Suzanne Scarlata, Lloyd D. Fricker, and Lakshmi A. Devi

E-mail contact: lakshmi.devi@mssm.edu

Hemopressin (Hp), a 9-residue {alpha}-hemoglobin-derived peptide, was previously reported to function as a CB1 cannabinoid receptor antagonist (1). In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms of Hp containing either three (RVD-Hp{alpha}) or two (VD-Hp{alpha}) additional amino acids, as well as a {beta}-hemoglobin-derived peptide with sequence similarity to that of hemopressin (VD-Hp{beta}). Characterization of the {alpha}-hemoglobin-derived peptides using binding and functional assays shows that in contrast to Hp, which functions as a CB1 cannabinoid receptor antagonist, both RVD-Hp{alpha} and VD-Hp{alpha} function as agonists. Studies examining the increase in the phosphorylation of ERK1/2 levels or release of intracellular Ca2+ indicate that these peptides activate a signal transduction pathway distinct from that activated by the endocannabinoid, 2-arachidonoylglycerol, or the classic CB1 agonist, Hu-210. This finding suggests an additional mode of regulation of endogenous cannabinoid receptor activity. Taken together, these results suggest that the CB1 receptor is involved in the integration of signals from both lipid- and peptide-derived signaling molecules.—Gomes, I., Grushko, J. S., Golebiewska, U., Hoogendoorn, S., Gupta, A., Heimann, A. S., Ferro, E. S., Scarlata, S., Fricker, L. D., Devi, L. A. Novel endogenous peptide agonists of cannabinoid receptors.

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Written by huehueteotl

April 21, 2009 at 7:42 am

Posted in Neuroscience

Who I Am Depends on How I Feel

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Scientists have long been interested in the interplay of emotions and identity, and some have recently focused on cultural identity. One’s heritage would seem to be especially stable and impervious to change, simply because it’s been passed down generation after generation and is deeply ingrained in the collective psyche. But how deeply, exactly?

Psychologists Claire Ashton-James of the University of British Columbia, William W. Maddux from INSEAD, Adam Galinsky of Northwestern University, and Tanya Chartrand from Duke University decided to explore this intriguing question in the laboratory, to see if even something as potent as culture might be tied to normal mood swings. European cultures are known to value independence and individuality, whereas Asian cultures prize community and harmony. This fundamental East-West cultural difference is well established, and so offered the researchers an ideal test.

The volunteers consisted of students hailing from a number of different countries and the researchers unconsciously raised or lowered their moods via two different methods. In one study, the volunteers listened to some upbeat Mozart on the stereo to lift their moods, or some Rachmaninov to bring them down. In another study, the volunteers held pens in their mouths: Some held the pen with their teeth, which basically forces the face into a smile, which improves mood. Others held the pen with their lips, forcing a frown. Then the volunteers completed a variety of tests, each designed to measure the strength of their values. In one test, the volunteers were offered a choice of five pens, four blue and one red. In keeping with cultural values, Asians typically pick from the more common blue pens in this test — to be part of the group — while Westerners usually take the one red pen. In another test, the volunteers thought about the questions “Who am I?” and listed 20 answers. The lists were analyzed to see if they reflected predominantly individualistic or predominantly group values.

The results, published in Psychological Science, a journal of the Association for Psychological Science, were consistent for all of the tests: Feeling good did indeed encourage the volunteers — both European and Asian — to explore values that are inconsistent with their cultural norms. And elevated mood even shaped behavior, allowing volunteers to act “out of character.” These findings suggest that people in an upbeat mood are more exploratory and daring in attitude — and therefore more apt to break from cultural stereotype. That is, Asians act more independently than usual, and Europeans are more cooperative. Feeling bad did the opposite: It reinforced traditional cultural stereotypes and constrained both Western and Eastern thinking about the world.

The researchers note these results suggest that emotions may serve an important social purpose. They surmise that positive feelings may send a signal that it’s safe to broaden one’s view of the world — and to explore novel notions of one’s self. The researchers go on to indicate that negative feelings may do the opposite: They may send a signal that it’s time to circle the wagons and stick with the “tried and true.” They conclude that the findings also suggest that the “self” may not be as robust and static as we like to believe and that the self may be dynamic, constructed again and again from one’s situation, heritage and mood.

Psychological Science Volume 20 Issue 3, Pages 340 – 346 Published Online: 23 Feb 2009
Who I Am Depends on How I Feel: The Role of Affect in the Expression of Culture
Claire E. Ashton-James 1 , William W. Maddux 2 , Adam D. Galinsky 3 , and Tanya L. Chartrand 4
1 University of British Columbia, 2 INSEAD, 3 Northwestern University, and 4 Duke University
Address correspondence to Claire E. Ashton-James, University of British Columbia, School of Psychology, 2136 West Mall, Vancouver, British Columbia, Canada V6T 1Z4, e-mail: cajames@psych.ubc.ca.

ABSTRACT—We present a novel role of affect in the expression of culture. Four experiments tested whether individuals’ affective states moderate the expression of culturally normative cognitions and behaviors. We consistently found that value expressions, self-construals, and behaviors were less consistent with cultural norms when individuals were experiencing positive rather than negative affect. Positive affect allowed individuals to explore novel thoughts and behaviors that departed from cultural constraints, whereas negative affect bound people to cultural norms. As a result, when Westerners experienced positive rather than negative affect, they valued self-expression less, showed a greater preference for objects that reflected conformity, viewed the self in more interdependent terms, and sat closer to other people. East Asians showed the reverse pattern for each of these measures, valuing and expressing individuality and independence more when experiencing positive than when experiencing negative affect. The results suggest that affect serves an important functional purpose of attuning individuals more or less closely to their cultural heritage.

Written by huehueteotl

April 20, 2009 at 7:51 am

Posted in Psychology

Binge Eating: The Perfectionistm Model

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In everyday life, someone who takes a perfectionist’s approach to activities might be admired or even rewarded with a pat on the back.

These attitudes are tied to a commonly held, but mistaken, belief that perfectionism will ultimately produce achievement and social success. But a psychologist warns that perfectionism is not a healthy, or even effective, approach to life’s challenges.

“Perfectionism is a double-edged personality trait,” says Simon Sherry, assistant professor of psychology.

A newly-published study shows why individuals with a high degree of perfectionism are often setting themselves up for a host of physical, emotional and mental problems– particularly related to binge eating. Although less well recognized than anorexia or bulimia, binge eating is a serious disorder. Binge eating occurs when a person feels out of control and rapidly consumes a large amount of food in a short period of time. Binge eating elevates the risk of developing depression, obesity, diabetes and other problems.

Dr. Sherry, of Dalhousie University in Halifax Nova Scotia, has published “The Perfectionism Model of Binge Eating” in the Journal of Personality and Social Psychology, along with co-author Peter Hall of the University of Waterloo. By closely following the daily activities of a large group of undergraduates, the researchers believe that they’re the first to identify why perfectionism results in binge eating.

They have also honed in on the type of perfectionist who is most at risk–someone who believes that others are evaluating their performance critically (as opposed to someone who is self-critical). This kind of perfectionist concludes that a parent, a friend or a boss is being harshly judgmental of their performance and pressuring them to be perfect.

“It seems that as perfectionists go about their day-to-day lives, they generate a lot of friction,” says Dr. Sherry. “Because of their inflexibility and unrealistic expectations they also create problems in their relationships.”

Let’s imagine how a perfectionist might begin their day.

Today’s Goals

* Run faster than yesterday’s personal best.
* Drink coffee instead of having breakfast.
* Earn the highest grade in the class on that mid-term.
* Meet for group project at 3 p.m. sharp to fix presentation.
* Find the most original gift for friend’s birthday.

What happens when the day ends up looking more like this instead?

Today’s Failures

* Running time misses personal best altogether.
* Earned 89 on the midterm, so six others are ahead of me now.
* Manage to limit lunch to a salad.
* Group is late for meeting, so presentation is still boring.
* Friend is disappointed with birthday gift.

Chances are the next sequence of events will involve self-harm.

Today’s Secret

* Late in the day, lose control and binge eat.
* Feel a horrible ‘pit in the stomach.’
* Hide the evidence to keep the secret.
* Criticize and loathe myself.
* Dwell on being alone and isolated.

Binge eating becomes an effort to escape from being overwhelmed with feelings of loneliness, failure and sadness. To temporarily escape from a discouraging reality, it’s necessary to do away with higher order thought. The experience of eating–smelling, chewing, tasting–is immediate and visceral.

“Think about it–when was the last time that you were rapidly eating a pizza and pondering a major life decision at exactly the same time?” asks Dr. Sherry.

While binge eating banishes troubles and difficulties in the short term, it also generates powerful negative emotions of guilt and shame that are longer lasting.

“We want to improve the lives of perfectionists with patterns of disordered eating,” he says.

The intent is that this research will translate directly into better care, through improved assessment and treatment opportunities. Society does demand achievement, but perfectionism is often maladaptive–a conscientious and adaptable person who can modify goals and expectations is better able to excel.

Perfectionists are often not self aware and are reluctant to seek help, posing a conundrum: They don’t want to admit they’re imperfect.

“I’m hopeful that students will read about this and realize that there are effective interventions for binge eating, including some help for perfectionism–change is possible.”

Journal of Personality and Social Psychology. Vol 96(3), Mar 2009, 690-709.
The perfectionism model of binge eating: Tests of an integrative model.
By Sherry, Simon B.; Hall, Peter A.

This study proposes, tests, and supports the perfectionism model of binge eating (PMOBE), a model aimed at explaining why perfectionism is related to binge eating. According to this model, socially prescribed perfectionism (SPP) confers risk for binge eating by generating exposure to 4 triggers of binge episodes: interpersonal discrepancies, low interpersonal esteem, depressive affect, and dietary restraint. In testing the PMOBE, a daily diary was completed by 566 women for 7 days. Predictions derived from the PMOBE were supported, with tests of mediation suggesting that the indirect effect of SPP on binge eating through triggers of binge episodes was significant. Reciprocal relations were also observed, with certain triggers of binge episodes predicting binge eating (and vice versa). Results supported the incremental validity of the PMOBE over and above self-oriented perfectionism and neuroticism and the generalizability of this model across Asian and European Canadian participants. The PMOBE offers a novel view of individuals with high levels of SPP as active agents who raise their risk of binge eating by generating conditions in their daily lives that are conducive to binge episodes. (PsycINFO Database Record (c) 2009 APA, all rights reserved)

Written by huehueteotl

April 20, 2009 at 7:05 am

Posted in Psychology

Key for Learning And Learning-related Behavior – Dopamine

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Researchers at UT Southwestern Medical Center have shed light on how the neurotransmitter dopamine helps brain cells process important information.

Dopamine

Researchers found in a study of mouse cells that this neurotransmitter, one of the molecules used by nerve cells to communicate with one another, causes certain brain cells to become more flexible and changes brain-cell circuitry to process important information differently than mundane information.

“This can help one remember a new, important episode as distinct from any other episode, such as remembering where you parked your car today versus yesterday,” said Dr. Robert Greene, professor of psychiatry at UT Southwestern.

“If we can one day manipulate the way that salient information is processed, we might be able to not only improve learning, but also improve the learning needed to extinguish severe fear responsiveness, such as when a soldier can’t forget emotional war memories associated with post-traumatic stress disorder,” he said.

Dr. Greene said the research also could have implications for addictions and schizophrenia, because those conditions are associated with alterations in dopamine in the brain.

Researchers have known that dopamine is released in the brain in association with experiencing “important” events and remembering salient acts, such as learning to avoid a hot stove or that a good grade is rewarded. The current research focused on how dopamine operates on the cells associated with this type of memory formation.

Dr. Greene, director of the National Clozapine Coordinating Center at the Dallas Veterans Affairs Medical Center, and his research team isolated slices of the hippocampus region of the animals’ brains and then electrically stimulated the cells. To simulate what happens in the brain in response to a memory-worthy event, they then exposed the cells to a selective dopamine-like neurotransmitter agent and repeated the stimulation. By comparing the effects of the stimulation with and without the dopamine agent, they could identify changes in NMDA receptor responses. NMDA receptors are proteins that mediate synaptic plasticity when activated.

“The NMDA responses changed to increase the cells’ plasticity, and we think that this facilitates learning and memory,” Dr. Greene said.

In addition, the changes in NMDA responses to dopamine agents changed the functional circuitry of the cells. These changes made the cells more responsive to electrical impulses coming from an indirect route through three processing “stations” before they reached the output region of the hippocampus. Without the presence of dopamine, Dr. Greene said, the cells tend to respond instead to impulses traveling by a route that is more direct and requires less processing. Information sent by this direct route may reflect what is already known and is less likely to change the animal’s behavior.

“While the current study involved isolated mouse brain tissue containing the memory circuits, the human brain likely works the same way,” Dr. Greene said. “You don’t want to have interference from yesterday. You need to know where you parked your car today, and dopamine may help to ensure that information from today will be remembered as distinct from yesterday.”

The researchers next will study how dopamine modulation affects learning and memory-related behavior and will investigate further exactly how dopamine acts on cells and their circuits.

Adapted from materials provided by UT Southwestern Medical Center.

J. Neurosci., Mar 2009; 29: 3109 – 3119 ; doi:10.1523/JNEUROSCI.4746-08.2009
D1/D5 Modulation of Synaptic NMDA Receptor Currents
Juan A. Varela, Silke J. Hirsch, David Chapman, Leah S. Leverich, and Robert W. Greene

Correspondence should be addressed to Robert W. Greene, 5323 Harry Hines Boulevard, Dallas, TX 75390. Email: robertw.greene@utsouthwestern.edu

Converging evidence suggests that salience-associated modulation of behavior is mediated by the release of monoamines and that monoaminergic activation of D1/D5 receptors is required for normal hippocampal-dependent learning and memory. However, it is not understood how D1/D5 modulation of hippocampal circuits can affect salience-associated learning and memory. We have observed in CA1 pyramidal neurons that D1/D5 receptor activation elicits a bidirectional long-term plasticity of NMDA receptor-mediated synaptic currents with the polarity of plasticity determined by NMDA receptor, NR2A/B subunit composition. This plasticity results in a decrease in the NR2A/NR2B ratio of subunit composition. Synaptic responses mediated by NMDA receptors that include NR2B subunits are potentiated by D1/D5 receptor activation, whereas responses mediated by NMDA receptors that include NR2A subunits are depressed. Furthermore, these bidirectional, subunit-specific effects are mediated by distinctive intracellular signaling mechanisms. Because there is a predominance of NMDA receptors composed of NR2A subunits observed in entorhinal–CA1 inputs and a predominance of NMDA receptors composed of NR2B subunits in CA3–CA1 synapses, potentiation of synaptic NMDA currents predominates in the proximal CA3–CA1 synapses, whereas depression of synaptic NMDA currents predominates in the distal entorhinal–CA1 synapses. Finally, all of these effects are reproduced by the release of endogenous monoamines through activation of D1/D5 receptors. Thus, endogenous D1/D5 activation can (1) decrease the NR2A/NR2B ratio of NMDA receptor subunit composition at glutamatergic synapses, a rejuvenation to a composition similar to developmentally immature synapses, and, (2) in CA1, bias NMDA receptor responsiveness toward the more highly processed trisynaptic CA3–CA1 circuit and away from the direct entorhinal–CA1 input.

Written by huehueteotl

April 15, 2009 at 7:53 am

Posted in Neuroscience

Is There A Seat Of Wisdom In The Brain?

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Researchers at the University of California, San Diego School of Medicine have compiled the first-ever review of the neurobiology of wisdom – once the sole province of religion and philosophy.

The study by Dilip V. Jeste, MD, and Thomas W. Meeks, MD, of UC San Diego’s Department of Psychiatry and the Stein Institute for Research on Aging, is published in the Archives of General Psychiatry.

“Defining wisdom is rather subjective, though there are many similarities in definition across time and cultures,” said Jeste, who is the Estelle and Edgar Levi Chair in Aging, professor of psychiatry and neuroscience and chief of geriatric psychiatry at UC San Diego. “However, our research suggests that there may be a basis in neurobiology for wisdom’s most universal traits.”

Wisdom has been defined over centuries and civilizations to encompass numerous psychological traits. Components of wisdom are commonly agreed to include such attributes as empathy, compassion or altruism, emotional stability, self-understanding, and pro-social attitudes, including a tolerance for others’ values.

“But questions remain: is wisdom universal, or culturally based?” said Jeste. “Is it uniquely human, related to age? Is it dependent on experience or can wisdom be taught?”

Empirical research on wisdom is a relatively new phenomenon. Meeks and Jeste noted that in the 1970s, there were only 20 peer-reviewed articles on wisdom, but since 2000, there have been more than 250 such publications. However, the researchers found no previous studies using the keyword “wisdom” in combination with the terms neurobiology, neuroimaging or neurotransmitters.

In order to determine if specific brain circuits and pathways might be responsible for wisdom, the researchers examined existing articles, publications and other documents for six attributes most commonly included in the definition of wisdom, and for the brain circuitry associated with those attributes.

Meeks and Jeste focused primarily on functional neuroimaging studies, studies which measure changes in blood flow or metabolic alterations in the brain, as well as on neurotransmitter functions and genetics. They found, for example, that pondering a situation calling for altruism activates the medial pre-frontal cortex, while moral decision-making is a combination of rational (the dorsolateral prefrontal cortex, which plays a role in sustaining attention and working memory), emotional/social (medial pre-frontal cortex), and conflict detection (the anterior cingulate cortex, sometimes also associated with a so-called “sixth sense”) functions.

Interestingly, several common brain regions appear to be involved in different components of wisdom. The UC San Diego researchers suggest that the neurobiology of wisdom may involve an optimal balance between more primitive brain regions (the limbic system) and the newest ones (pre-frontal cortex.) Knowledge of the underlying mechanisms in the brain could potentially lead to developing interventions for enhancing wisdom.

“Understanding the neurobiology of wisdom may have considerable clinical significance, for example, in studying how certain disorders or traumatic brain injuries can affect traits related to wisdom,” said Jeste, stressing that this study is only a first step in a long process.

Arch Gen Psychiatry. 2009;66(4):355-365. DOI: 10.1001/archgenpsychiatry.2009.8
Neurobiology of Wisdom. A Literature Overview.
Thomas W. Meeks, MD; Dilip V. Jeste, MD

Context Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology.

Objective To discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field, ie, prosocial attitudes/behaviors, social decision making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgment of and dealing effectively with uncertainty.

Data Sources Literature focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants.

Study Selection Studies involving functional neuroimaging or neurotransmitter functioning, examining human (rather than animal) subjects, and identified via a PubMed search using keywords from any of the 6 proposed subcomponents of wisdom were included.

Data Extraction Studies were reviewed by both of us, and data considered to be potentially relevant to the neurobiology of wisdom were extracted.

Data Synthesis Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (eg, emotional regulation, decision making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), influenced by several genetic polymorphisms, is critical to certain subcomponents of wisdom such as emotional regulation (including impulse control), decision making, and prosocial behaviors.

Conclusions We have proposed a speculative model of the neurobiology of wisdom involving frontostriatal and frontolimbic circuits and monoaminergic pathways. Wisdom may involve optimal balance between functions of phylogenetically more primitive brain regions (limbic system) and newer ones (prefrontal cortex). Limitations of the putative model are stressed. It is hoped that this review will stimulate further research in characterization, assessment, neurobiology, and interventions related to wisdom.

Written by huehueteotl

April 8, 2009 at 7:54 am

Posted in Neuroscience

D-1mT May Help HIV Patients Not Responding To Treatment In The Future

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Monkeys with the simian form of HIV treated with a molecule called D-1mT alongside Anti-Retroviral Therapy (ART) reduced their virus levels in the blood to undetectable levels.

Simian Immunodeficiency Virus (SIV) is very similar to Human Immunodeficiency Virus (HIV) and it is used to study the condition in animal models. In both HIV and SIV, the level of virus in the blood, or ‘viral load’, is important because when the viral load is high, the disease progresses and it depletes the patient’s immune system. This eventually leads to the onset of Acquired Immune Deficiency Syndrome (AIDS), where the patient cannot fight infections which would be innocuous in healthy individuals.

Currently, the ‘gold standard’ treatment for HIV is Highly Active Anti-Retroviral Therapy (HAART), a cocktail of drugs that reduces the viral load by stopping the virus from replicating. HAART can increase the life expectancy of an HIV-positive patient substantially if it works well. However, the treatment is not effective for around one in ten patients, partly because some develop resistance to the drugs used in HAART. The researchers, from Imperial College London, the National Cancer Institute, Bethesda, and Innsbruck Medical University, hope their study could ultimately lead to a new treatment that will help HAART to work more effectively in these people.

In the new study, researchers gave daily doses of a modified amino acid called D-1mT to 11 rhesus macaques infected with SIV. All of the macaques had been treated with ART for at least four months. Eight of the macaques had higher viral loads (reaching up to 100,000 copies of the virus per millilitre of blood), because they were not responding completely to the treatment. However, three had undetectable viral loads (fewer than 50 copies of the virus per millilitre of blood), because ART was working well.

The researchers took blood samples at six and 13 days. After six days, only three of the macaques had detectable SIV levels and after 13 days the virus could only be found in two of them, at very low levels (below 1,000 copies of the virus per millilitre of blood). The researchers repeated the research in eight macaques that were not being treated with ART but this time they found no change in viral load over 13 days.

Dr Adriano Boasso from Imperial College London said: “HIV can have a devastating effect on people’s lives but with advances in Anti-Retroviral Therapy it is becoming a more chronic, manageable disease. Unfortunately, treatment does not work for everyone – some people develop resistance to the drugs and when that happens, we start to run out of options for treating them and delaying the onset of AIDS.

“Our early findings suggest that D-1mT could be used alongside antiretroviral therapy to stop the virus from replicating. The disease can only progress if the virus is replicating, so if we can slow replication down we can reduce the impact of the disease on the patient’s life. We still need to figure out how D-1mT is working, then we can think about developing this as a potential treatment for HIV,” added Dr Boasso.

The results of the new study surprised the researchers because D-1mT did not appear to work in the way they had expected. They had believed it might reactivate the immune system, because D-1mT is able to block an enzyme called IDO, which HIV and SIV use to hold the immune system back. In healthy people, IDO prevents the immune system from attacking the body. HIV and SIV hijack the machinery that makes IDO and use it to stop the immune system from attacking them.

In the new study, the researchers could find no evidence that D-1mT reactivated the immune response against SIV, although they do not exclude this possibility. They are now keen to carry out further research to explore how D-1mT is working.

“The effect D-1mT seemed to have on viral load was really encouraging but it was a surprise to us – we didn’t expect D-1mT to work only in macaques that were already being treated with ART. It seems that D-1mT synergises with ART and we would really like to find out how this works,” said Dr Boasso.

In healthy people, the IDO enzyme controls allergic reactions and autoimmune diseases and it also stops the foetus from being rejected in pregnancy. As D-1mT blocks IDO, the researchers say that its effects may need to be tested in SIV-infected macaques over a longer time, to determine if taking the drug could increase the risk of these conditions.

D-1mT is currently in Phase I clinical trials to test its safety and potential efficacy as a treatment for cancer, which should indicate whether the drug is suitable for treating human patients. The researchers hope that if D-1mT proves safe in the initial trials for cancer and shows further promise for treating HIV, trials for using D-1mT as a treatment for HIV could begin as early as 5 years from now.

J. Immunol., Apr 2009; 182: 4313 – 4320. doi:10.4049/jimmunol.0803314
Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques
Adriano Boasso, Monica Vaccari, Dietmar Fuchs, Andrew W. Hardy, Wen-Po Tsai, Elzbieta Tryniszewska, Gene M. Shearer, and Genoveffa Franchini

Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-D-tryptophan (D-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). D-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, D-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, D-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-β mRNA expression in lymph nodes of ART-treated macaques after D-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by D-1mT, which may account for the lack of effect on plasma Kyn. Finally, D-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, D-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which D-1mT inhibited SIV replication in vivo.

Written by huehueteotl

April 8, 2009 at 7:48 am

Posted in HIV

You Wear Me Out: Self-control Is Exhausting

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Exerting self-control is exhausting. In fact, using self-control in one situation impairs our ability to use self-control in subsequent, even unrelated, situations. What about thinking of other people exerting self-control?

Earlier research has shown that imagining actions can cause the same reactions as if we were actually performing them (e.g., simulating eating a disgusting food results in a revolting face, even if no food has been eaten) and psychologists Joshua M. Ackerman and John A. Bargh from Yale University, along with Noah J. Goldstein and Jenessa R. Shapiro from the University of California, Los Angeles explored what affect thinking about other people’s self-control has on our own thoughts and behavior.

Participants were presented with a story about a hungry waiter who was surrounded by delicious food, but was not allowed to sample any, for fear of being fired. Half of the participants simply read the story and the other half were told to imagine themselves in the waiter’s shoes. Next, all of the participants were shown images of mid- to high-priced items (e.g., cars and TVs) and were to indicate how much they would pay for them. In a follow-up experiment, some of the participants read the same story and others read a similar story in which the waiter was not hungry and did not have to use self-control. Just as in the first experiment, some of the participants read the story while others imagined themselves as the waiter. All of these volunteers then participated in a word game and a memory task.

The results, reported in Psychological Science reveal that the participants who imagined themselves in the waiter’s position were more willing to spend greater amounts of money on the luxury items – they had exhausted their capacity for self-control and restraint, leading them to spend more money. In the follow-up experiment, the volunteers who read and imagined the story of the waiter who was not hungry performed much better on the word game and memory task. Overall, the group that imagined themselves as the waiter from the original story, who exercised self-control and did not eat any food, performed the worst on the word game and memory tasks.

These findings suggest that our own self-control can be worn out simply by mentally simulating another person acting with self-control. The authors note, for example, that imagining someone else’s self-control “could result in small breakdowns of self-control, such as employees speaking out improperly during a meeting, to catastrophic ones, such as police officers responding to an emotionally charged encounter with deadly force.”

Psychological Science, 2009; 20 (3): 326 DOI: 10.1111/j.1467-9280.2009.02290.x
You Wear Me Out: The Vicarious Depletion of Self-Control.
Joshua M. Ackerman, Noah J. Goldstein, Jenessa R. Shapiro, and John A. Bargh

Address correspondence to Joshua Ackerman, Yale University, Department of Psychology, P.O. Box 208205, New Haven, CT 06520-8205, e-mail: joshua.ackerman@yale.edu.

ABSTRACT—Acts of self-control may deplete an individual’s self-regulatory resources. But what are the consequences of perceiving other people’s use of self-control? Mentally simulating the actions of others has been found to elicit psychological effects consistent with the actual performance of those actions. Here, we consider how simulating versus merely perceiving the use of willpower can affect self-control abilities. In Study 1, participants who simulated the perspective of a person exercising self-control exhibited less restraint over spending on consumer products than did other participants. In Study 2, participants who took the perspective of a person using self-control exerted less willpower on an unrelated lexical generation task than did participants who took the perspective of a person who did not use self-control. Conversely, participants who merely read about another person’s self-control exerted more willpower than did those who read about actions not requiring self-control. These findings suggest that the actions of other people may either deplete or boost one’s own self-control, depending on whether one mentally simulates those actions or merely perceives them.

Written by huehueteotl

April 7, 2009 at 7:55 am

Posted in Psychology