Friday, April 30, 2010
Chemists with the United States military have developed a set of ultra-strength cleaners that could be used in the aftermath of a terrorist attack. The new formulas are tough enough to get rid of nerve gas, mustard gas, radioactive isotopes, and anthrax. But they are also non-toxic, based on ingredients found in foods, cosmetics, and other consumer products.
A detailed evaluation of the cleansers appears in the American Chemical Society's journal Industrial Engineering and Chemistry Research.
George Wagner and colleagues explained that chlorine- and lye-based decontamination agents have serious drawbacks. In addition to being potentially hazardous, they can react with chemical weapons and materials in the environment to form new toxic substances. If the military needed to decontaminate a large area, the runoff could harm people and the environment. To solve that problem, military scientists developed the Decon Green suite of decontamination agents.
The main ingredients in each Decon Green formula are peroxides, the same substances that are in many household cleaners and whitening toothpaste. To bolster their effectiveness, the peroxides are mixed with bicarbonates or other non-toxic bases. That combination produces peroxyanions, highly reactive ions that can clean just about anything. It ensures that chemical weapons, like nerve gas, will break down completely.
Wagner describes putting the new cleaning agents through an exhaustive battery of tests. His team concluded that each formula can break down toxic chemicals, rather than just washing them away. They also showed that Decon Green is quite good at killing anthrax spores, and removing radioactive cesium and cobalt from smooth surfaces. One of the formulas that they tested can work in sub-zero temperatures. Another is a powder, which can be easily transported and mixed with water at the scene of an emergency. All but one of the ingredients in liquid Decon Green can be found in food, cosmetics, hygiene products, or vitamin pills.
All-Weather Hydrogen Peroxide-Based Decontamination of CBRN Contaminants.
George W. Wagner, Lawrence R. Procell, David C. Sorrick, Glenn E. Lawson, Claire M. Wells, Charles M. Reynolds, David B. Ringelberg, Karen L. Foley, Gregg J. Lumetta, David L. Blanchard.
Industrial & Engineering Chemistry Research, 2010; 49 (7): 3099 DOI: 10.1021/ie9019177
Link to IECS abstract
It is feasible to recruit and retain methamphetamine-dependent gay men in a pharmacologic drug-treatment program, US investigators report in the April 24th edition of AIDS.
The men participating in the study reduced their risky sexual behavior, and methamphetamine use declined; however, adherence to the study medication was poor.
“We demonstrated that it is feasible to enroll and retain actively using, high-risk, meth-dependent MSM [men who have sex with men] in a pharmacologic intervention trial…with excellent rates of participation in study visits, procedures, and follow-up evaluations,” comment the investigators.
Methamphetamine ('meth') is a highly addictive and potentially destructive drug. It is estimated that 0.5% of the US population use the drug, but much higher rates of usage have been observed in gay men. Some research suggests that use of the drug is contributing to the ongoing transmission of HIV in this population.
Pharmacologic therapies can help treat addiction to other illegal and legal drugs, such as heroin, nicotine and alcohol. Bupropion is currently being investigated as a possible drug therapy for meth dependence.
Given the high rates of meth use by gay men and the drug’s role in the transmission of HIV, investigators wished to see if it was possible to recruit and retain gay men who used the drug in a bupropion treatment program.
The investigators, encouraged by the results, conclude: “We must intensify our efforts to identify potential pharmacologic therapies for meth dependence, and to enroll high-risk populations, both to reduce meth-related morbidity and to further prevent HIV acquisition and transmission.”
Feasibility and acceptability of a phase II randomized pharmacologic intervention for methamphetamine dependence in high-risk men who have sex with men.
Das, Moupali; Santos, Deirdre; Matheson, Tim; Santos, Glenn-Milo; Chu, Priscilla; Vittinghoff, Eric; Shoptaw, Steve; Colfax, Grant N
AIDS 24: 991-1000, 2010. doi: 10.1097/QAD.0b013e328336e98b
Link to AIDS abstract
BBC News on line (April 30, 2010)
A "vaccine" which harnesses the body's own immune system to fight prostate cancer has been approved for use by US Food and Drug Administration.
Provenge - which is designed to be used in men with advanced disease - is the first of its kind to be accepted by the FDA.
Each dose has to be individually tailored and it is an expensive treatment at $93,000 per patient.
It will add to, rather than replace, existing treatments, said experts.
Doctors have been working for decades on therapies that prompt the immune system to fight tumors.
Potential success stories include an experimental vaccine for melanoma which is in the late stages of development.
This latest therapy is made by collecting special blood cells from each patient that help the immune system recognize cancer as a threat.
These are then mixed with a protein found on most prostate cancer cells and a substance which kick-starts the immune response.
The drug is not a "cure" but is used in advanced prostate cancer that has spread to other sites in the body and is no longer responding to standard hormone treatment.
Clinical trials showed that the treatment extended the lives of patients by four months.
This compares with an average of three months with chemotherapy.
Dr Phil Kantoff, an oncologist at the Dana-Farber Cancer Institute who helped run the studies of Provenge said: "The big news here is that this is the first immunotherapy to win approval, and I suspect within five to ten years immunotherapies will be a big part of cancer therapy in general."
Thursday, April 29, 2010
Many women have no doubt been waiting a long time for this: the neuropeptide oxytocin enhances male empathy. This substance also increases sensitivity to so-called "social multipliers," such as approving or disapproving looks. This is revealed in a study conducted by scientists at Bonn University and the Babraham Institute of Cambridge, which appears in the Journal of Neuroscience.
48 healthy males participated in the experiment. Half received an oxytocin nose spray at the start of the experiment, the other half a placebo. The researchers then showed their test subjects photos of emotionally charged situations in the form of a crying child, a girl hugging her cat, and a grieving man. The test subjects were then invited to express the depth of feeling they experienced for the persons shown.
In summary, Dr. René Hurlemann of Bonn University´s Clinic for Psychiatry was able to state that "significantly higher emotional empathy levels were recorded for the oxytocin group than for the placebo group," despite the fact that the participants in the placebo group were perfectly able to provide rational interpretations of the facial expressions displayed. The administration of oxytocin simply had the effect of enhancing the ability to experience fellow-feeling. The males under test achieved levels which would normally only be expected in women. Under normal circumstances, the "weak" sex enjoys a clear advantage when it comes to the subject of "empathy."
Nasal Spray improves Learning
In a second experiment, the participants had to use their computers to complete a simple observation test. Correct answers produced an approving face on the screen, wrong ones a disapproving one. Alternatively, the feedback appeared as green (correct) or red (false) circles. "In general, learning was better when the feedback was shown in the form of faces," states Dr. Keith Kendrick of the Cambridge Babraham Institute in England. "But, once again, the oxytocin group responded clearly better to the feedback in the form of facial expression than did the placebo group."
In this connection, the so-called amygdaloid nucleus appears to play an important role. This cerebral structure, known generally to doctors as the amygdala, is involved in the emotional evaluation of situations. Certain people suffer from an extremely rare hereditary disease which progressively affects the amygdala. "We were lucky to be able to include two female patients in our study group who were suffering this defect of the amygdala," says Hurlemann. "Both women reacted markedly worse to approving or disapproving faces in the observation test than did other women in a control group. Moreover, their emotional empathy was also affected." Hence, the researchers suspect that the amygdala could bear some form of co-responsibility for the effect of the oxytocin.
One of the effects of the hormone oxytocin is that it triggers labor pains. It also strengthens the emotional bond between a mother and her new-born child. Oxytocin is released on a large scale during an orgasm, too. This neuropeptide is also associated with feelings such as love and trust. Our study has revealed for the first time that emotional empathy is modulated by oxytocin, and that this applies similarly to learning processes with social multipliers, says Hurlemann. This hormone might thus be useful as medication for diseases such as schizophrenia, which are frequently associated with reduced social approachability and social withdrawal.
Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans.
René Hurlemann, Alexandra Patin, Oezguer A. Onur, Michael X. Cohen, Tobias Baumgartner, Sarah Metzler, Isabel Dziobek, Juergen Gallinat, Michael Wagner, Wolfgang Maier, and Keith M. Kendrick
Journal of Neuroscience, 2010; 30 (14): 4999 DOI: 10.1523/JNEUROSCI.5538-09.2010
Link to Journal of Neuroscience abstract
Science Daily (April 29, 2010)
A study published in the journal Science offers a long-awaited explanation for the link between HIV infection and susceptibility to life-threatening nontyphoidal strains of Salmonella. The research, funded by the Wellcome Trust and GlaxoSmithKline, goes on to identify targets that could be pursued for vaccine development.
Nontyphoidal strains of Salmonella (NTS) usually cause vomiting and diarrhea in high-income countries and are mainly contracted by consuming infected foods, such as uncooked meat and eggs. NTS can also cause fatal bloodstream infections in people with compromised immunity, such as HIV-infected individuals, and children under two years of age or with malaria, anemia or malnutrition.
This is a particular problem in Africa where Salmonellae are the most common bacteria to infect the blood. Such bloodstream infections can be treated with antibiotics, but drug resistance is on the increase and there is currently no vaccine available.
"The association between HIV infection and fatal cases of nontyphoidal Salmonella disease has been known since the onset of the AIDS pandemic 26 years ago, but this is the first time we've been able to offer a scientific explanation why," said Dr Cal MacLennan from the University of Birmingham, who led the research.
In an earlier study of African children, the team of researchers working at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, at the University of Birmingham and the University of Malawi's College of Medicine, had shown that protective Salmonella-specific antibodies generated in the first two years of life are critical for controlling the infection.
In the new study, the researchers turned their attention to immunity in African adults. While blood samples from HIV-uninfected adults killed Salmonella without difficulty, those from many HIV-infected Africans could not kill Salmonella. Since HIV causes significant defects in the immune system, the team examined whether a lack of these antibodies might account for the absence of killing and explain why HIV-infected adults are particularly susceptible to Salmonella infections.
Contrary to expectations, the team found that blood from HIV-infected adults harbored high levels of antibodies to Salmonella, molecules that normally help the immune system to fight infections. However, unlike the antibodies in healthy adults, these antibodies were unable to kill Salmonella. In fact, antibodies from these people actually stopped the antibodies from healthy adults from killing Salmonella.
The team went on to show that this difference in ability to kill Salmonella is due to the part of the Salmonella that the antibodies bind to. The protective 'killing' antibodies bind to structures on the surface of the bacteria known as outer membrane proteins. This then allows the immune system to destroy the Salmonella bacteria.
On the other hand, large numbers of antibodies in HIV-infected Africans bind to a structure that sticks out from the surface of the Salmonella known as LPS (lipopolysaccharide). These 'blocking' antibodies appear to divert the immune system away from the surface of the bacteria and stop the killing antibodies from doing their job.
When the researchers specifically removed the blocking antibodies from HIV-infected blood samples, they found killing antibodies present in the blood that could once again kill the bacteria. This shows that people infected with HIV still have the protective killing antibodies generated in the first two years of life that can control Salmonella infection, but the excess of blocking antibodies stops the killing antibodies from working.
"We normally think of HIV patients as being more susceptible to bacterial infections because of deficiencies in their immune systems, and often they have problems making antibodies when given vaccinations. In the present study, we found that it's actually an excess of antibodies that causes the problem," explained Dr MacLennan.
"The findings are important because LPS is currently being investigated as a potential target for a vaccine. Our observations that antibodies targeting LPS can actually impede the protective immune response to Salmonella would caution against this, suggesting that such a vaccine could do more harm than good."
Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults.
C. A. MacLennan, J. J. Gilchrist, M. A. Gordon, A. F. Cunningham, M. Cobbold, M. Goodall, R. A. Kingsley, J. J. G. van Oosterhout, C. L. Msefula, W. L. Mandala, D. L. Leyton, J. L. Marshall, E. N. Gondwe, S. Bobat, C. Lopez-Macias, R. Doffinger, I. R. Henderson, E. E. Zijlstra, G. Dougan, M. T. Drayson, I. C. M. MacLennan, M. E. Molyneux.
Science, 2010; 328 (5977): 508 DOI: 10.1126/science.1180346
Link to Science abstract
Limited success in modeling the behavior of the complex, unusual and unpredictable HIV virus has slowed efforts to develop an effective vaccine to prevent AIDS.
A new improved modeling system, developed by Chinese researchers, which attempts to incorporate more of the virus random behavioral dynamics, suggests that a particular type of T cell could be useful in the development of an AIDS vaccine.
New research published April 29 in New Journal of Physics (co-owned by the Institute of Physics and German Physical Society), describes how physicists and biologists from Xiamen University have been able to incorporate random patterns in the virus mutation, and the way the virus responds to antibodies, into their model.
Gratifyingly, they have found that the new model, and the projections made by the new model for development of disease, mirror real-life, clinical behavior of the virus.
Clinical trials show that the HIV virus behaves quite normally during the acute first phase of human infection, normally 2-6 weeks after HIV enters the host body, during which time the strength of the virus increases and our immune systems deploy killer T cells, CD4+ T cells, to battle against it.
Outwardly, we would experience flu like symptoms and would, when we started to feel better, imagine that we are over the infection but this is not so with the HIV virus which somehow avoids total annihilation and manages to spend years rebuilding strength, slowly chipping away at our immune system.
Researchers suspect that HIV's ability to avoid annihilation has to do with its own mutating properties and its ability to preferentially target CD4+ T cells, the master regulators of our immune system.
The model-makers from Xiamen University have created a simulation which takes a wider range of variables into consideration and while they are in agreement that both HIV's mutating and T-cell targeting ability are crucial to the virus' devastating success rate, they have found a possible chink in the virus armor.
To date, no models have been able to discern between the behavioral patterns of two different types of T-cells, both of which are involved in our internal fights against HIV.
These are CD4+ T and CD8+ T cells. Patterns emerging from these new models now suggest that CD8+T cells could be used to stimulate a stronger response against the virus.
This particular type of T-cell does not appear to be as preferentially targeted by HIV as its counterpart and also appears to be more actively involved in putting the virus down during the first acute phase of the infection.
As the researchers write, "We assess the relative importance of various immune system components in acute phase and have found that the CD8+ T cells play a decisive role to suppress the viral load. This observation implies that stimulation of a CD8+T cell response might be an important goal in the development of an effective vaccine against AIDS."
A stochastic spatial model of HIV dynamics with an asymmetric battle between the virus and the immune system.
Hai Lin and J W Shuai.
New Journal of Physics, 2010; DOI: 10.1088/1367-2630/12/4/043051
Link to IOP’s post of the article
Wednesday, April 28, 2010
Science Daily (April 27, 2010)
Long-term anabolic steroid use may weaken the heart more than previously thought and may increase the risk of heart failure, according to research reported in Circulation: Heart Failure, an American Heart Association journal.
Anabolic-androgenic steroids mimic the naturally occurring testosterone, a muscle-building hormone that promotes male sexual characteristics.
"Anabolic steroids, in addition to being illegal, have important health consequences," said Aaron L. Baggish, M.D., lead author of the study and instructor in the Department of Medicine at Massachusetts General Hospital in Boston. "I think for the first time we're starting to realize that the heart is one of the organs that is negatively impacted by long-term steroid use."
In the small study, investigators found that the left ventricle, the heart's main pumping chamber, was significantly weaker during contraction (systolic function) in participants who had taken steroids compared to a group of similar non-steroid users.
A healthy left ventricle pumps out 55 percent to 70 percent of the blood that fills the heart (a measurement known as ejection fraction). Eighty-three percent of steroid users in the 12-person study had a low pumping capacity (ejection fraction less than 55 percent) that previous studies have linked to increased risk of heart failure and sudden cardiac death. In contrast, only one of the non-steroid users had a low ejection fraction.
Steroid users also exhibited impaired diastolic function, which is when the left ventricle relaxes and fills with blood. The researchers showed that ventricle relaxation among steroid users, as demonstrated by the left ventricle's ratio of early-to-late blood filling, was reduced by almost half (0.93 compared with 1.80 among non-users). The left ventricle's structure was similar in both steroid-users and non-users.
Baggish and his co-investigators used a technique known as Doppler echocardiography to examine the left ventricle's function and structure. The test uses high-frequency sound waves, or ultrasound, to create moving pictures of the heart and its blood flow.
The steroid-using group included 12 male weight lifters, average age 40, who reported taking about 675 milligrams of steroids per week for nine years. The control group was seven age-matched, male weight lifters who reported no steroid exposure. Both groups had similar durations of past and current weight lifting and other physical activity, as well as similar cardiac risk factors other than steroid use. Although the users and non-users had comparable body-mass indices and body-surface areas, the steroid users had more muscle mass than the non-users.
Despite the small sample size, the statistically significant differences in heart function suggest a strong link between steroid use and heart impairment, said investigators who are conducting further studies to confirm their findings.
In previous studies, the precise effects of steroid use on heart dysfunction have been unclear. Part of the problem with conducting studies of steroid-related heart injury is that illegal anabolic steroid use is relatively recent. In the United States, these drugs first became widespread among athletes in the 1980s; so many steroid users from that era are now reaching the age when heart problems often surface.
"What we hope is that people start recognizing steroid use as a potential cause of heart disease and a cause of otherwise unexplained heart dysfunction in young people," Baggish said.
Long Term Anabolic-Androgenic Steroid Use is Associated with Left Ventricular Dysfunction.
Aaron L. Baggish, Rory B. Weiner, Gen Kanayama, James I. Hudson, Michael H. Picard, Adolph M. Hutter Jr., and Harrison G. Pope Jr.
Circulation: Heart Failure, 2010; DOI: 10.1161/CIRCHEARTFAILURE.109.931063
Link to CHF abstract
Science Daily (April. 26, 2010)
Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have developed an imaging protocol that allows them to visualize the activity of the brain's reward circuitry in both normal individuals and those addicted to drugs. The technique could lead to better insight into why people take recreational drugs as well as help determine which treatment strategies might be most effective.
Drug addiction is a complex process that involves numerous biological and environmental factors, but a central element is how the drugs affect the activity of dopamine, the chemical that regulates pleasure and reward in the brain.
To get a real-time sense of dopamine activity, Joanna Fowler and her colleague Gene-Jack Wang at Brookhaven, along with Nora Volkow, Director of the National Institute on Drug Abuse, combined positron emission tomography (PET), a medical imaging technology useful for identifying brain diseases, with special radioactive tracers that bind to dopamine receptors. The PET scan highlights the movement of the tracers in the brain, and can be used to reconstruct real-time 3D images of the dopamine system in action.
The scientists tested this procedure on several drug-addicted volunteers as well as age-matched healthy control subjects and found that people with addictions in general have 15-20 percent fewer dopamine receptors than normal and thus cannot bind to a lot of the dopamine released in response to the drugs or natural reinforcers like food.
"These addicted individuals all had a blunted dopamine response," noted Fowler, a senior scientist in Brookhaven's medical department. "This reinforces the idea that drug addicts experience diminished feelings of pleasure, which drives their continual drug use."
Fowler added that the study looked at multiple recreational drugs and found similar results. "So, while various drugs operate by unique mechanisms, they all share a commonality in that the dopamine receptors in the brains of addicted individuals show an under-stimulated reward system."
In an interesting correlation, Fowler noted that Gene-Jack Wang also used the dopamine PET scans on obese individuals and found highly similar patterns of low dopamine receptors-validating that at least in some cases, obesity can also be considered a disease of addiction.
A potential valuable application of observing dopamine activity in real-time, Fowler noted, involves not looking at addicted individuals while they use drugs, but rather when they don't.
"We can examine individuals as they use different coping strategies to try to suppress their desires for drugs or food," she said, "and see in the scans which approach work best."
"We still have a lot of research to do before we fully understand why people take drugs," Fowler continued, "but with this new PET scan application, we might help more people stop."
The highlights of this study were recently presented in Fowler's talk, "Imaging Brain Chemistry in Diseases of Addiction," at the American Society for Biochemistry and Molecular Biology's annual meeting, which took place April 26 in Anaheim, CA.