Thursday, December 31, 2009
Earlier this year, researchers showed that they could cut the lives of disease-carrying mosquitoes in half by infecting them with a bacterium they took from fruit flies. Now, a new report in the December 24th issue of Cell, suggests that their strategy might do one better: The Wolbachia bacteria also makes the mosquitoes more resistant to infection by viruses that are a growing threat to humans, including those responsible for dengue fever and Chikungunya.
Once infected with Wolbachia, Aedes aegypti mosquitoes also become less suitable as hosts for a form of malaria parasite that infects birds, said Scott O'Neill of The University of Queensland. (The mosquitoes under study aren't natural carriers of human malaria.)
"This might be very powerful in reducing pathogen transmission by Aedes aegypti to humans, particularly for dengue and Chikungunya," O'Neill said. "Together with the previously described life-shortening effects, the results suggest we might be able to have a major impact on disease." That's if it can be shown that the Wolbachia infection can invade natural mosquito populations, he added, a question his team is working on right now.
There is no vaccine or cure for dengue fever, which is a painful and debilitating disease suffered by some 50 million people worldwide every year. Dengue haemorrhagic fever, the more severe form of the disease, kills more than 40,000 people annually. Chikungunya usually isn't fatal, but can cause symptoms similar to dengue. Human epidemics of Chikungunya have been cited in Africa, Asia and more recently in Europe, according to the CDC.
Wolbachia is already rampant in nature; the bacterium is estimated to infect up to 60 percent of all insect species. They are passed from mother insect to daughter or son through the insect egg and readily spread to high frequency in many species of mosquito. The species that are the major carriers of human disease don't normally carry them, but that's something O'Neill aims to change.
"We are currently conducting a series of experiments in contained outdoor greenhouse settings that are examining the ability of the Wolbachia infection to spread into natural mosquito populations," he said. "If these prove successful, we hope to move to open field testing within the next one to two years."
The idea would be to seed the natural mosquito population with Wolbachia by releasing mosquitoes that had been purposefully infected in the laboratory. Wolbachia bacteria have a good 'trick' to help ensure their spread, O'Neill explained. They are responsible for a developmental defect that makes the would-be offspring of pairings between infected male mosquitoes and uninfected females inviable. Since the bacteria is passed from mothers to their offspring, that means that infected females can actually have a reproductive advantage over uninfected ones, encouraging Wolbachia's spread from one generation to the next.
O'Neill said his team is working on computational models to determine just how many infected mosquitoes would need to be released for the infection to take hold in the wild.
The researchers don't yet know exactly how Wolbachia protects the insects from human disease-causing viruses. They have some evidence to suggest that the bacterial symbiont primes the insects' immune system. Wolbachia may also outcompete the virus by limiting resources such as fatty acids inside the mosquitoes.
Even if the strategy works in a natural setting, there's a chance the mosquitoes or the viruses could become resistant to Wolbachia's influence over time.
" We can predict from evolutionary theory that selection will push the system in the direction of resistance, but we do not know the speed with which this might occur," O'Neill said. "Even if it was effective for a few decades it might have a major impact on human disease."
A Wolbachia Symbiont in Aedes aegypti Limits Infection with Dengue, Chikungunya, and Plasmodium
Luciano A. Moreira, Iñaki Iturbe-Ormaetxe, Jason A. Jeffery, Guangjin Lu, Alyssa T. Pyke, Lauren M. Hedges, Bruno C. Rocha, Sonja Hall-Mendelin, Andrew Day, Markus Riegler, Leon E. Hugo, Karyn N. Johnson, Brian H. Kay, Elizabeth A. McGraw, Andrew F. van den Hurk, Peter A. Ryan, Scott L. O'Neill
Cell, Volume 139, Issue 7, 1268-1278, 24 December 2009 doi:10.1016/j.cell.2009.11.042
Link to Cell abstract
Scientists at the University of California, Davis, have identified the dominant odor naturally produced in humans and birds that attracts the blood-feeding Culex mosquitoes, which transmit West Nile virus and other life-threatening diseases.
The groundbreaking research, published this week in the early online edition of the Proceedings of the National Academy of Sciences, explains why mosquitoes shifted hosts from birds to humans and paves the way for key developments in mosquito and disease control.
Entomology professor Walter Leal and postdoctoral researcher Zain Syed found that nonanal (sounds like NAWN-uh-nawl) is the powerful semiochemical that triggers the mosquitoes' keen sense of smell, directing them toward a blood meal. A semiochemical is a chemical substance or mixture that carries a message.
"Nonanal is how they find us," Leal said. "The antennae of the Culex quinquefasciatus are highly developed to detect even extremely low concentrations of nonanal." Mosquitoes detect smells with the olfactory receptor neurons of their antennae.
Birds, the main hosts of mosquitoes, serve as the reservoir for the West Nile virus, Leal said. When infected mosquitoes take a blood meal, they transmit the virus to their hosts, which include birds, humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels and domestic rabbits. Since 1999, the U.S. Centers for Disease Control and Prevention have recorded 29,397 human cases and 1,147 fatalities in the United States alone.
The UC Davis researchers tested hundreds of naturally occurring compounds emitted by people and birds. They collected chemical odors from 16 adult human subjects, representing multiple races and ethnic groups.
"We then determined the specificity and sensitivity of the olfactory receptor neurons to the isolated compounds on the antennae of the mosquitoes," Syed said.
Leal and Syed found that nonanal acts synergistically with carbon dioxide, a known mosquito attractant. "We baited mosquito traps with a combination of nonanal and carbon dioxide and we were drawing in as many as 2,000 a night in Yolo County, near Davis," Syed said. "Nonanal, in combination with carbon dioxide, increased trap captures by more than 50 percent, compared to traps baited with carbon dioxide alone."
Acute olfactory response of Culex mosquitoes to a human- and bird-derived attractant
Zainulabeuddin Syed and Walter S. Leal
Proceedings of the National Academy of Sciences,November 3, 2009 vol. 106 no. 44 18803-18808
Link to PNAS article
Columbia University Mailman School of Public Health (December 30, 2009)
The presence of the Streptococcus pneumoniae in samples that can be easily obtained in clinics and emergency rooms may predict risk of severe disease in H1N1 pandemic influenza. Reports that H1N1 pandemic influenza in Argentina was associated with higher morbidity and mortality than in other countries led investigators in the Center for Infection and Immunity (CII) at the Mailman School of Public Health of Columbia University, their colleagues at Argentina's National Institute of Infectious Diseases (INEI), and Roche 454 Life Sciences to look for viral mutations indicative of increased virulence and for co-infections that could contribute to disease.
Complete genome sequencing of nasopharyngeal samples representing severe or mild disease revealed no evidence of evolution toward a more virulent phenotype or development of antiviral resistance. However, MassTag PCR, a method for sensitive, simultaneous surveillance and differential diagnosis of infectious diseases, found a strong correlation between the presence of Streptococcus pneumoniae and increased risk for severe disease. The findings, which suggest a new strategy for identifying and treating these patients, are currently online in the publication PLoS ONE.
The scientists examined nasopharyngeal samples representing 199 cases of H1N1 pandemic (H1N1pdm) influenza virus infections from Argentina. The sample set included 39 cases classified as severe and 160 cases categorized as mild.
"We used a combination of 454 pyrosequencing and classical Sanger sequencing methods to test for viral evolution toward increased virulence. Comparison of viral sequences from Argentina with those obtained from other parts of the world provided no clues to the increase in severity of disease," said Gustavo Palacios, PhD, assistant professor of epidemiology at CII, and a lead and corresponding author. "However, MassTag PCR allowed us to find a new risk factor, independent of obesity, asthma, diabetes or chronic illness. S. pneumoniae was present in the majority of severe cases."
Specimens were tested for the presence of 33 viral and bacterial respiratory pathogens. "The presence of Streptococcus pneumoniae in individuals between the age of 6 and 55, those most affected by the current pandemic, was associated with a 125-fold increased risk of severe disease," said Mady Hornig, MD, associate professor of epidemiology and a co-first author of the paper. "Whereas the association of S. pneumoniae with morbidity and mortality had been established in current and previous influenza pandemics, this study is the first to demonstrate that the diagnosis of S. pneumoniae, when it is still actionable, might have an impact on clinical management."
"Three practical implications emerge from our study," said CII Director W. Ian Lipkin, MD, John Snow Professor of Epidemiology, and professor of Neurology and Pathology at Columbia University. "First, S. pneumoniae is important in the pathogenesis and prognosis of H1N1pdm-associated disease. Whether this effect is associated with all S. pneumoniae or only with specific serotypes remains to be determined. Second, easily accessible samples such as nasopharyngeal swab samples may be used as an index to risk of severe disease. Third, multiplex diagnostic methods like MassTag PCR can enable rapid detection of a broad spectrum of viral and bacterial agents and inform clinical care."
Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza.
Gustavo Palacios, Mady Hornig, Daniel Cisterna, Nazir Savji, Ana Valeria Bussetti, Vishal Kapoor, Jeffrey Hui, Rafal Tokarz, Thomas Briese, Elsa Baumeister, W. Ian Lipkin
PLoS ONE, 2009; 4 (12): e8540 DOI: 10.1371/journal.pone.0008540
Link to PLoS ONE abstract
Wednesday, December 30, 2009
The timing of molar emergence and its relation to growth and reproduction in apes is being reported by two scientists at Arizona State University's Institute of Human Origins in the Dec. 28 online early edition of the Proceedings of the National Academy of Sciences (PNAS).
From the smallest South American monkeys to the largest African apes, the timing of molar development and eruption is closely attuned to many fundamental aspects of a primate's biology, according to Gary Schwartz, a researcher at the Institute of Human Origins and an associate professor in the School of Human Evolution and Social Change in ASU's College of Liberal Arts and Sciences.
"Knowing the age when the first molar appears in the mouths of most primates allows researchers to predict a host of life history attributes, such as gestation length, age at sexual maturity, birth spacing, and overall lifespan. Humans are unique among primates because our life histories are so slow and thus our molars emerge relatively late. Given that apes are our closest living relatives, understanding the broader context of when the characteristic slower development of humans evolved is of great interest," Schwartz explains.
"We've known quite a bit about the timing of molar development in chimpanzees, which is important because they are our closest living relative. However, we've known virtually nothing about when this important event occurs in other wild-living ape species -- until now," says lead author Jay Kelley, a research affiliate at ASU's Institute of Human Origins and an associate professor in the Department of Oral Biology at the University of Illinois, Chicago.
Because of the difficulties in obtaining tooth emergence ages from animals in the wild, Kelley opted for other means; he searched for specimens in museums. At the Zoologische Staatssammlung in Munich he found skulls of a wild-shot orangutan (Pongo pygmaeus pygmaeus) and gorilla (Gorilla gorilla gorilla) that preserved emerging first molars.
"Like annual growth rings inside trees, the cells that produce teeth (both the enamel and underlying dentine) leave behind a trace of their presence, not as annual markers, but as growth lines that appear every day," says Kelley. By slicing the teeth in half, he and Schwartz were able to examine these incremental growth lines in ape individuals that died as their first molars were just erupting into their mouths.
"Because teeth preserve this phenomenal internal chronometer, we were able to count up how many days it took the first molars to form. In apes and monkeys, first molars start forming very close to the time of birth. As the first molars were still erupting in our specimens, development was incomplete and the final growth line was laid down on the day those animals died. Therefore, by counting backwards from the final growth line to the day of birth, we determined their age at death and thus the age at which that molar was erupting" says Schwartz.
Using this novel approach, the two scientists were able to mark the age of the gorilla's first molar emergence at 3.8 years, nearly identical to that of a wild chimpanzee's. The orangutan's age at first molar emergence was surprisingly much later, at 4.6 years, which falls closer to the age of approximately 6 years in modern humans.
"We were excited to discover this much older age for the orangutan, since orangutans have much slower life histories than the other two great apes," says Kelly.
However, he and Schwartz caution that though the later emergence age in these large Asian apes is closer to that for modern humans, these latest findings should not be taken to indicate some special evolutionary relationship between the two. "Rather, it is in keeping with what you would expect given the relatively slow pace of growth and long period of infant dependency that evolved separately in the lineage leading to orangutans and that leading to modern humans," says Schwartz.
The work by Kelley and Schwartz also has implications for understanding the evolution of human life history. "We can use the same techniques to calculate ages at first molar emergence from the fossils of early hominids that just happened to die while their first molars were erupting," says Kelley. "The close correspondence between age at first molar emergence and the timing of life history events that we found in great apes and modern humans means that we can have confidence that first molar emergence ages in the early hominids will provide equally accurate knowledge about their life histories."
Dental development and life history in living African and Asian apes
Jay Kelley and Gary T. Schwartz
PNAS published online before print December 28, 2009, doi:10.1073/pnas.0906206107
Link to PNAS abstract
Two gay men arrested in Malawi after getting engaged have pleaded not guilty to charges of gross public indecency. Homosexual acts carry a maximum prison sentence of 14 years in Malawi
Tiwonge Chimbalanga and Steven Monjeza appeared at a packed court in Malawi's biggest city Blantyre, where they will ask for bail on Monday.
The pair held a traditional engagement ceremony over the weekend - believed to be the first gay couple in Malawi to start the process of getting married.
The BBC's Raphael Tenthani in Blantyre says large crowds of onlookers went to see the couple in court. He says some people congratulated them but other shouted insults.
Prosecutors say they will send the pair to hospital to prove they have had sex together.
They face three charges of unnatural practices between males and gross indecency.
Mr Monjeza, 26, hinted that he may consider calling off the proposed wedding, as he was sent back to prison.
"I am sad I am going back to Chichiri Prison," he said. "The conditions are terrible there. People are exaggerating this thing. I may just as well dissolve this marriage."
Mr Chimbalanga, 20, dressed in women's clothes, refused to speak to journalists, beyond accusing them of writing "stupid" things.
They were arrested on Monday at the home they share.
Malawi is a deeply conservative society but recently a group of campaigners came together to form a gay rights organization, Centre for the Development of People (CEDEP).
CEDEP's executive director, Gift Trapence, says the laws used to arrest the couple are invalid because they are against the Bill of Rights enshrined in the 1995 constitution.
Correspondents say some voices in government have also started to call for more openness about homosexuality as the authorities try to tackle high rates of HIV/Aids.
Researchers from the Medical College of Wisconsin, the Children's Research Institute, and the Children's Hospital of Wisconsin have developed a rapid, automated system to differentiate strains of influenza.
In pandemic infection, such as the present H1N1 influenza outbreak, rapid automated tests are needed in order to make quick and effective public health decisions. Real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) is a sensitive and specific method for identifying flu substrains; however, technician and assay time are significantly longer than less accurate rapid influenza diagnostic tests.
A group led by Dr. Kelly J. Henrickson of the Medical College of Wisconsin has developed rapid semi- and fully-automated multiplex real-time RT-PCR assays to detect influenza A, influenza B, and respiratory syncytial virus (RSV). These assays can successfully detect human H1N1, H3N2, and swine-origin H1N1 viruses as well as distinguish these from influenza B and RSV infections. These assays could test large numbers of samples over a very short time, allowing for a significant decrease in both technician and assay time.
The researchers suggest that "this outbreak demonstrates the importance of having rapid, reliable, sensitive, and specific assays that allow clinicians and public health officials to react quickly and effectively during viral outbreaks."
Development of a rapid automated influenza A, influenza B, and RSV A/B multiplex real-time RT-PCR assay and its use during the 2009 H1N1 swine-origin influenza virus (S-OIV) epidemic in Milwaukee, Wisconsin.
Beck, ET, Jurgens LA, Kehl SC, Bose ME, Patitucci T, LaGue E, Darga, P, Wilkinson K, Witt LM, Fan J, He J, Kumar S, Henrickson KJ:.
Journal of Molecular Diagnostics, 2010, 12:74-81 First published online December 3, 2009; doi:10.2353/jmoldx.2010.090095
Link to LMD abstract
Tuesday, December 29, 2009
It is the ultimate goal in the treatment of cancer: tailoring a person's therapy based on his or her genetic makeup. While a lofty goal, scientists are steadily moving forward, rapidly exploiting new technologies. Researchers at Georgetown Lombardi Comprehensive Cancer Center report a significant advance in this field of research using a new chip that looks for hundreds of mutations in dozen of genes.
The goal of personalized medicine is to determine the best treatment and the optimal dose carrying the fewest side-effect, especially as new drugs are discovered and treatment options increase. Variations in our genes encode proteins, which impact how a drug is metabolized or taken in by the cells. This directly impacts the drug's effectiveness and the kinds of side-effects that may be caused by its toxicity.
"Currently, available genotyping tools test only a few genes at a time," explains John F. Deeken, a pharmacogentic researcher at Lombardi. "With a new chip called DMET, as many as 170 genes can be examined for more than a thousand variations. This type of turn-key testing, if validated, could eventually replace highly-specialized, time-consuming and labor-intensive testing -- thus allowing more institutes the opportunity to pursue genotyping and pharmocogenetic research. That alone would be a significant development for our field and for expediting the research many of us believe is the future of medicine."
Such a development is particularly critical for cancer research, both in terms of drug discovery and treatment. Genetic variability among patients in cancer clinical trials is not commonly taken into account, a factor that could skew dosage amounts and doom an otherwise promising new drug. A more simple and faster test could be readily incorporated into treatment trials.
In his paper published online December 29 in The Pharmacogenomics Journal, Deeken and colleagues report results of the new genotyping platform called DMET, or drug-metabolizing enzymes and transporters, (Affymetrix, Inc., Santa Clara, Calif.). The DMET "casts a wider net," screening for 1256 genetic variations in 170 genes involved in drug absorption, distribution, metabolism and excretion.
Deeken says one of the main obstacles facing pharmocogenetic researchers like himself is the lack of a proven and relatively quick technology for genotyping. "DMET appears to offer great promise in this field as a reliable test unveiling genetic variations that correlated with drug effectiveness and toxicity," says Deeken. "Still, DMET isn't yet ready for primetime in terms of having received FDA approval, but we're getting closer."
Deeken serves as a consultant to Sanofi-Aventis, the manufacturer of docetaxel, a drug involved in the current reported study. Three other authors are employees of Affymetrix, the manufacturer of the DMET platform. The study was done in part at the National Cancer Institute and supported by funding from the National Institutes of Health.
A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
J F Deeken, T Cormier, D K Price, T M Sissung, S M Steinberg, K Tran, D J Liewehr, W L Dahut, X Miao and W D Figg
The Pharmacogenomics Journal advance online publication, December 29, 2009; doi:10.1038/tpj.2009.57
Link to PJ abstract
The widely used herbal supplement Ginkgo biloba does not appear to slow the rate of cognitive decline in healthy older people or those with mild cognitive impairment according to a study that involved 3,069 people age 72 or older from four U.S. communities who were tracked for an average of six years. Half of them took twice-daily doses of 120 milligrams of extract from the leaves of the ginkgo tree and half received a placebo.
Compared with study participants who received a placebo, the use of Ginkgo biloba did not slow cognitive decline in those with normal conditions or those with mild cognitive impairment, the researchers wrote in the Journal of the American Medical Association.
The findings suggest that Ginkgo biloba -- one of the top-selling herbal supplements used with the aim of improving memory and preventing age-related cognitive decline -- had no effect on subtle changes associated with early symptoms of dementia or normal aging, the researchers said.
"The primary finding was no effect of the ginkgo extract over a relatively long period of time in older people in slowing down what we see as the normal changes of thinking function in aging," Dr. Steven DeKosky, dean of the University of Virginia School of Medicine and the study's leader, said in a telephone interview.
"If one thought that ginkgo might maintain cognition and prevent or delay decline in some thinking associated with aging, it did not do that," he said.
DeKosky and colleagues previously found that Ginkgo biloba was not effective in reducing the incidence of Alzheimer's dementia or dementia overall.
A supplements industry group, Council for Responsible Nutrition, said other studies suggest the herbal supplement can be effective in improving cognitive function.
"In an area where there are few other safe, affordable options, I would hate to see this study send the wrong message to consumers," Douglas MacKay, CRN vice president said in an email. "I would continue to recommend Ginkgo biloba to older adults as a safe, effective option for supporting cognitive health."
Ginkgo biloba for Preventing Cognitive Decline in Older Adults: A Randomized Trial
Beth E. Snitz, PhD;
Link to JAMA article
Scientists have created what appears to be a schizophrenic mouse by reducing the inhibition of brain cells involved in complex reasoning and decisions about appropriate social behavior.
Findings by Medical College of Georgia scientists, published Dec. 28 in the Proceedings of the National Academy of Sciences, elucidate the critical balance between excitation and inhibition of these cells that appears to go awry in schizophrenia. They also provide the first animal model for studying the disabling psychiatric disorder that affects about 1 percent of the population.
"We believe the mouse, which exhibits some of the same aberrant behavior as patients with this disorder, will help identify better therapies," said Dr. Lin Mei, a developmental neurobiologist who directs MCG's Institute of Molecular Medicine and Genetics. "We are doing testing to see if antipsychotic drugs already on the market are effective in treating the mouse."
MCG scientists made the mouse by deleting a candidate gene for schizophrenia, ErbB4, from interneurons, which are brain cells that help shower larger decision-making neurons, called pyramidal cells, with inhibition.
In their earlier work, they identified how ErbB4 and another candidate gene, neuregulin-1, work together to balance the activity of these pyramidal cells. They reported in Neuron in May 2007 that the two help keep a healthy balance between excitation and inhibition by increasing release of GABA, a major inhibitory neurotransmitter in the inhibitory synapses of the brain's prefrontal cortex. Seven years earlier, they showed the two also put a damper on excitatory synapses, communication points between neurons where the neurotransmitter glutamate excites cells to action.
To further test these findings, this time they altered the natural check and balance in cells directly involved with supplying pyramidal neurons with the inhibitor GABA. They did this by knocking out the ErbB4 gene in nearby chandelier and basket interneurons that supply GABA to pyramidal cells. "If we take out ErbB4 in these two interneurons, the neuregulin should have no effect because it can't promote GABA," Dr. Mei, Georgia Research Alliance Eminent Scholar in Neuroscience, said.
His postulation played out in the behavior of the mouse, who exhibited schizophrenia-like behavior including increased movement and impaired short-term memory. The scientists are still gathering data on the manic aspect of schizophrenia in their mice.
For example, both the normal and knockout mice learned they would find a food pellet in each arm of an eight-armed chamber but that if they went to the same arm for seconds, there were none. But the knockouts took longer to learn and finish the task. Knockouts also spent a lot more time sniffing and snooping around and revisiting empty arms.
In another test, knockouts couldn't -- or wouldn't -- make the connection that a relatively low noise would be followed by a slightly louder one. When they treated the knockouts with diazepam, an anti-anxiety medication, they responded similarly to the normal mice: the first sound prepared them for the second.
Dr. Mei suspects that if he could look at the chandelier and basket interneurons in the prefrontal cortex of schizophrenics, he would also find something wrong with their usual role of sensing the need for the inhibitor GABA and supplying it to the pyramidal cells. "In schizophrenia, the baseline of the excitatory neurotransmitter is probably high," he said.
Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons
Lei Wen, Yi-Sheng Lu, Xin-Hong Zhu, Xiao-Ming Li, Ran-Sook Woo, Yong-Jun Chen, Dong-Min Yin, Cary Lai, Alvin V. Terry, Jr., Almira Vazdarjanova, Wen-Cheng Xiong, and Lin Mei
Proceedings of the National Academy of Sciences published online before print December 29, 2009, doi:10.1073/pnas.0910302107
Link to PNAS abstract
Monday, December 28, 2009
BBC News on line (December 28, 2009)
Disinfectants could effectively train bacteria to become resistant to antibiotics, research suggests. Scientists know bacteria can become inured to disinfectant, but research increasingly shows the same process may make them resistant to certain drugs. This can occur even with an antibiotic the bacteria have not been exposed to.
Writing in Microbiology, the National University of Ireland team, who focused on a common hospital bacterium, urges a rethink of how infections are managed.
The scientists found that by adding increasing amounts of disinfectant to cultures of pseudomonas aeruginosa in the lab, the bacteria learnt to resist not only the disinfectant but also ciprofloxacin - a commonly-prescribed antibiotic - even without being exposed to it.
The researchers report the bacteria had adapted to pump out anti-microbial agents - be they a disinfectant or an antibiotic - from their cells.
The adapted bacteria also had a mutation in their DNA that allowed them to resist ciprofloxacin-type antibiotics specifically.
Pseudomonas aeruginosa can cause a wide range of infections, particularly among those with weak immune systems such as HIV or cancer patients, as well as people with severe burns, diabetes or cystic fibrosis.
Surface disinfectants are used to prevent its spread - but if the bacteria manage to survive and go on to infect patients, antibiotics are used to treat them.
Bacteria that could resist both these control points could be a serious threat to hospital patients, the study said.
At the high concentration levels generally employed this was unlikely to be a problem - but "in principle this means that residue from incorrectly diluted disinfectants left on hospital surfaces could promote the growth of antibiotic-resistant bacteria", said study author Dr Gerard Fleming.
"What is more worrying is that bacteria seem to be able to adapt to resist antibiotics without even being exposed to them."
There is an increasing body of research that raises concerns about the effects on antibiotic resistance of disinfectants and antiseptics.
An EU report published earlier this year stressed the importance of the "appropriate and prudent" use of disinfectants to minimize the risk that bacteria become resistant to both forms of defense.
It also emerged this year that treatments in hospitals in Brazil had been compromised by a bacterium, mycobacterium massiliense, which had developed resistance to a common sterilization fluid and a number of antibiotics used to treat the subsequent infections.
Research was published this year showing that the disinfecting wipes used to protect against MRSA could in fact spread the bug, as the solution contained was often not sufficient to kill all the bacteria picked up, and hospital staff often used the same wipe to clean more than one surface.
Effect of subinhibitory concentrations of benzalkonium chloride on the competitiveness of Pseudomonas aeruginosa grown in continuous culture
Paul H. Mc Cay,
Microbiology 156 (2010), 30-38; DOI 10.1099/mic.0.029751-0
Link to Microbiology abstract
Researchers from Thomas Jefferson University are one step closer to developing a vaccine against AIDS.
Led by Matthias J. Schnell, Ph.D., director of the Jefferson Vaccine Center, the researchers found that a rabies virus-based vaccine administered to monkeys protected against the simian equivalent of the HIV virus (SIV). The data were published in the journal Vaccine.
The researchers previously showed that a rabies-based vaccine expressing HIV and SIV antigens protective against a chimeric HIV/SIV virus in monkeys. In this study, they used highly attenuated rabies virus vaccine vectors to protect against challenge with the highly pathogenic SIVmac251. This type of SIV virus causes a more similar disease in monkeys compared to human infection with HIV-1. In addition, it is difficult to protect monkeys against AIDS-like disease after challenge with SIVmac251.
Two vaccine strategies were used: immunization with a recombinant rabies virus expressing SIVmac239GagPol, or a combination of that and a rabies virus expressing SIVmac239Env. Both strategies induced neutralizing antibody production, CD8+ T cell responses, and increased protection. Although the combination with Env helped immediately following the infection, the long-term benefits were minimal. However, it was surprising that the rabies-based vaccine was able to induce such potent anti-SIV humoral responses.
"Although we can't yet block the infection, we showed that we can protect against disease," said Dr. Schnell. "We also saw significant antibody activity against the virus, which is promising. In addition, this is a very simple approach that only took two immunizations."
Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFκB signaling pathway
Jianwei Li, James P. McGettigan, Milosz Faber, Matthias J. Schnell and Bernhard Dietzschold
Vaccine Volume 26, Issue 3, 17 January 2008, Pages 419-426
Sunday, December 27, 2009
Modern, couple-oriented treatment for male sexual dysfunction takes the psychosocial aspects of sex into account, as well as focusing on the purely physical aspects of the problem. The importance of this biopsychosocial approach, whether one looks at disorders of desire, arousal or orgasm, is supported by intercultural comparisons, among other data.
But sexual dysfunction can also arise as a consequence of a variety of diseases and their treatments, such as depression or diabetes, or can even be an early warning sign of serious physical illness such as heart disease. Hence an interdisciplinary approach, drawing on both medical and psychological techniques and insights, is essential.
In this week's Deutsches Ärzteblatt International, Urologist Dirk Rösing and coauthors present an overview of current thinking and practice in the area of male sexual dysfunction.
The authors use research on prostate cancer to underline the place of one important new development in German sex therapy, a form of the internationally familiar "couples" therapy called "syndiastic" therapy. Questionnaire surveys to men with prostate cancer show that while the importance of the genital aspects of sexuality decreased in importance following radical surgery, the relationship and physical intimacy remained as important as before.
"Syndiastic" sex therapy was introduced in Germany in 2004, and focused for the first time explicitly on fundamental psychosocial needs, in a wider way, rather than purely on sexual function itself. Derived from a word Aristotle uses, meaning a disposition to "live in pairs" or "belonging," this approach differs importantly from some other somatic or psychological treatments which focus mainly on restoring sexual function. Instead, it aims to broaden the understanding of sexuality, extend the range of physical experience, and improve overall satisfaction within the relationship.
Male Sexual Dysfunction: Diagnosis and Treatment From a Sexological and Interdisciplinary Perspective.
Rösing, D; Klebingat, K; Berberich, H J; Bosinski, H A G; Loewit, K; Beier, K M.
Deutsches Ärzteblatt International, 2009; 106: 821-8 DOI: 10.3238/arztebl.2009.0821
Link to DAI abstract
Saturday, December 26, 2009
Science Daily (December 24, 2009)
Antibiotic resistance in the natural environment is rising despite tighter controls over our use of antibiotics in medicine and agriculture, Newcastle University scientists have found.
Bacterial DNA extracted from soil samples collected between 1940 and 2008 has revealed a rise in background levels of antibiotic resistant genes.
Newcastle University's Professor David Graham, who led the research, said the findings suggest an emerging threat to public and environmental health in the future.
"Over the last few decades there has been growing concern about increasing antibiotic resistance and the threat it poses to our health, which is best evidenced by MRSA," explained Professor Graham, who is based in the School of Civil Engineering and Geosciences at Newcastle University.
"Despite increasingly stringent controls on our use of antibiotics, the background level of antibiotic resistant genes, which are markers for potential resistance, continues to rise in soils."
"This increases the chances of a resistant gene in a harmless bacteria being passed onto a disease-causing pathogen, such as a MRSA, with obvious consequences."
Published online this week in the academic journal Environmental Science and Technology, the report uses data taken from five sites in the Netherlands.
The team found that 78 per cent of genes from four classes of antibiotics showed increasing levels since 1940 -- despite continued efforts to reduce environmental levels.
Professor Graham said the next step would be to analyze soil samples from other parts of the world, although he expects to see similar results.
He adds: "The big question is that with more stringent European regulations and greater emphasis on conservative antibiotic use in agriculture and medicine, why are antibiotic resistant gene levels still rising?"
"Whatever the cause, this rise suggests an ever increasing risk of resistant genes being passed from environmental organisms to organisms of greater health concern."
Professor Graham contends that more complementary studies are desperately needed between environmental and public health researchers to determine whether this increasing 'pool' of resistance is actually contributing to harmful bacteria, such as MRSA.
Evidence of Increasing Antibiotic Resistance Gene Abundances in Archived Soils since 1940.
Charles W. Knapp, Jan Dolfing, Phillip A. I. Ehlert and David W. Graham
Environmental Science & Technology, published on line December 21, 2009DOI: 10.1021/es901221x
Link to EST abstract
Smoking is a risk factor for rheumatoid arthritis (RA), a new analysis of 16 studies confirms.
The effect is especially strong in men and heavy smokers, the researchers found. And men who tested positive for rheumatoid factor (RF), a self-attacking antibody found in about 80 percent of RA patients, were at even higher risk if they smoked.
Research over the past two decades has linked smoking to RA, especially in men, Dr. S. Kumagai of Kobe University Graduate School of Medicine in Kobe, Japan and his colleagues write. But findings on smoking and RA in women have been "inconsistent."
Clinical and epidemiological research: Extended report: Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies
D Sugiyama, K Nishimura, K Tamaki, G Tsuji, T Nakazawa, A Morinobu, S Kumagai
Annals of the Rheumatic Diseases, January 2010.;69:70-81 doi:10.1136/ard.2008.096487
Link to ARD abstract
Tumors can not only spread through the body by sending out tiny cells called seeds, but they can re-seed themselves. This may help explain why tumors grow back even after they are removed. It may also lead to the development of new drugs to stop the process of cancer spread, or metastasis.
"Circulating tumor cells can also colonize their tumors of origin, in a process that we call 'tumor self-seeding'," Joan Massague of the Memorial Sloan-Kettering Cancer Center in New York and colleagues wrote.
"Now we have found that tumors can recapture some of their most delinquent children, enriching themselves with the most aggressive metastatic cells, enabling them to grow faster and more robustly," Massague, a Howard Hughes Medical Institute researcher, said in a statement.
"Now we are thinking that in some cases, maybe treatment left inflamed tissue that had been a home for those cells that escaped and were residing somewhere temporarily, perhaps in the bone marrow.”.
"They may have re-entered the circulation in the weeks and months after surgery, and now, through the self-seeding process, have homed in on this tissue and reproduced the tumor."
Massague's team used mice, injecting them with human breast cancer cells that had been genetically engineered with a jellyfish protein to make them glow green under ultraviolet light.
They tracked these cells as they spread through the bodies of the mice.
Immune system signaling chemicals, including interleukin 6 and interleukin 8, appear to "call" the tumor cells home, Massague's team found.
Researchers are working on cancer vaccines that could harness the immune system to attack cancer cells more effectively. This study suggests it might also be necessary to tone down some aspects of the immune system.
Tumor Self-Seeding by Circulating Cancer Cells
Mi-Young Kim, Thordur Oskarsson, Swarnali Acharyya, Don X. Nguyen, Xiang H.-F. Zhang, Larry Norton and Joan Massagué
Cell, Volume 139, Issue 7, 1315-1326, 24 December 2009 doi:10.1016/j.cell.2009.11.025
Link to Cell abstract
Thursday, December 24, 2009
BBC News on line (December 24), 2009
Alzheimer's disease is associated with a reduced risk of cancer and vice versa, according to US researchers who followed 3,020 people aged 65 and above for the study, published in the journal Neurology.
Those who had Alzheimer's at the start of the study were 69% less likely to be admitted to hospital with cancer than those free of the disease at the start.
And those with cancer at the study's start were 43% less likely to develop Alzheimer's than the cancer free.
The researchers followed the subjects for an average of five years to see whether they developed Alzheimer's, and an average of eight years to see whether they developed cancer.
At the start of the study, 164 people (5.4%) already had Alzheimer's disease and 522 people (17.3%) already had a cancer diagnosis.
During the study, 478 people developed dementia and 376 people developed invasive cancer.
The researchers stressed that more work was needed before any firm conclusions could be drawn, and said the findings only seemed fully to apply to white people.
They found no association between cancer and another type of dementia, known as vascular dementia, which is thought to be caused by a lack of blood supply to the brain.
However, patients with this condition died earlier than people with Alzheimer's.
Lead researcher Dr Catherine Roe, of Washington University School of Medicine in St Louis, said this suggested the association between Alzheimer's and cancer was not simply due to people with those conditions dying before they could contract the other ailment.
"Discovering the links between these two conditions may help us better understand both diseases and open up avenues for possible treatments.”
"Alzheimer's disease and cancer are both characterized by abnormal, but opposing, cellular behavior.
"In Alzheimer's disease, excessive cell death occurs, whereas cancer is characterized by excessive cell growth.
"Other scientists have suggested that there are certain molecular pathways that may influence both Alzheimer's disease and cancer."
For instance, one specific enzyme has been shown to target a number of proteins, some of which are believed to stimulate cancer, some to suppress it, and others to be a hallmark of Alzheimer's.
Cancer linked to Alzheimer disease but not vascular dementia
C. M. Roe PhD, A. L. Fitzpatrick PhD, C. Xiong PhD, W. Sieh MD, PhD, L. Kuller MD, DrPH, J. P. Miller AB, M. M. Williams MD, R. Kopan PhD, M. I. Behrens MD, PhD, and J. C. Morris MD
Neurology, first published on line December 23, 2009 as doi: doi:10.1212/WNL.0b013e3181c91873
Link to Neurology abstract
A team of researchers working in a high containment laboratory at the Centers for Disease Control and Prevention in Atlanta, GA, have solved a fundamental mystery about smallpox that has puzzled scientists long after the natural disease was eradicated by vaccination. They know how it kills us. In a new research report appearing online in The FASEB Journal, researchers describe how the virus cripples immune systems by attacking molecules made by our bodies to block viral replication.
This discovery fills a major gap in the scientific understanding of pox diseases and lays the foundation for the development of antiviral treatments, should smallpox or related viruses re-emerge through accident, viral evolution, or terrorist action.
"These studies demonstrate the production of an interferon binding protein by variola virus and monkeypox virus, and point at this viral anti-interferon protein as a target to develop new therapeutics and protect people from smallpox and related viruses," said Antonio Alcami, Ph.D., a collaborator on the study from Madrid, Spain. "A better understanding of how variola virus, one of the most virulent viruses known to humans, evades host defenses will help up to understand the molecular mechanisms that cause disease in other viral infections."
Scientists produced the recombinant proteins from the variola virus and a similar virus that affects monkeys, causing monkeypox. The researchers then showed that cells infected with variola and monkeypox produced a protein that blocks a wide range of human interferons, which are molecules produced by our immune systems meant to stop viral replication.
"The re-emergence of pox viruses has potentially devastating consequences for people worldwide, as increasing numbers of people lack immunity to smallpox," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Understanding exactly how pox viruses disrupt our immune systems can help us develop defenses against natural and terror-borne pox viruses."
The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.
María del Mar Fernández de Marco, Alí Alejo, Paul Hudson, Inger K. Damon, and Antonio Alcami
The FASEB Journal, 2009; DOI: 10.1096/fj.09-144733
Link to FASEB abstract
Wednesday, December 23, 2009
Scientists have identified a strain of antibiotic-resistant tuberculosis that thrives in the presence of rifampin, a front-line drug in the treatment of tuberculosis. The bacterium was identified in a patient in China and is described in a study by researchers at the Johns Hopkins Bloomberg School of Public Health, Chongqing Pulmonary Hospital, Lanzhou University and Fudan University. The researchers determined that the bacteria grew poorly in the absence of the antibiotic rifampin and better in the presence of the drug. They also observed that the patient's condition grew worse with treatment regimens containing rifampin, before being cured with rifampin-free regimens.
The World Health Organization (WHO) estimates that tuberculosis kills approximately 2 million people worldwide each year. Multidrug-resistant tuberculosis (MDR-TB) is becoming an increasing problem in many parts of the world, largely due to poor patient adherence to the six-month tuberculosis chemotherapy. About 5 percent of all TB cases are MDR-TB that is resistant to isoniazid and rifampin, two main drugs used to treat the disease.
"Rifampin-dependent tuberculosis is an unrecognized and potentially serious treatment issue," said Ying Zhang, MD, PhD, senior author of the study and professor in the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology. "Rifampin resistance is ominous. Our study highlights the potential dangers of continued treatment of MDR-TB with rifamycins that occur frequently due to delayed or absent drug susceptibility testing in the field. Further studies are urgently needed to determine how common such rifampin-dependent MDR-TB is in field conditions and if it contributes to the worsening of the disease in MDR patients and treatment failures."
Zhang adds that rifampin-dependent tuberculosis is difficult to detect and may be a bigger problem than we currently realize, since the bacteria do not grow well in the culture medium unless rifampin is added. The study authors urge timely detection of rifampin-dependent or -enhanced bacteria in patients with treatment failure by including rifampin in culture media and removing of rifampin from the treatment regimen once rifampin dependency or enhancement are detected. However, the researchers note that drug susceptibility testing is time-consuming and not easily performed in resource-poor settings where tuberculosis is frequently more common.
For the study, the research team documented the treatment of a 35-year-old Chinese man with tuberculosis. The man failed to respond to the WHO's thrice-weekly treatment regimen, which includes rifampin and other first-line tuberculosis drugs. The patient's condition worsened following an additional treatment regimen with rifampin and other second-line agents. Further testing detected the rifampin-dependency/enhancement. The patient fully recovered once rifampin was removed from his treatment regimen.
An interesting case of rifampicin-dependent/-enhanced multidrug-resistant tuberculosis.
Zhong, M.; Zhang, X.; Wang, Y.; Zhang, C.; Chen, G.; Hu, P.; Li, M.; Zhu, B.; Zhang, W.; Zhang, Y.
The International Journal of Tuberculosis and Lung Disease, Volume 14, Number 1, January 2010 , pp. 40-44(5)
Link to IJTLD abstract
An estimated 25,000 Americans develop severe fungal infections each year, leading to 10,000 deaths despite the use of anti-fungal drugs. The associated cost to the U.S. health care system has been estimated at $1 billion a year.
Now two Syracuse University scientists have developed new brominated furanones that exhibit powerful anti-fungal properties.
The most virulent fungus is Candida albicans, which is carried by about 75 percent of the public. Typically the fungus is harmless but, in individuals with HIV or otherwise compromised immune systems, it can cause candidiasis, which has a high mortality rate. The fungi can also form biofilms that attach to surfaces and are up to 1,000 times more resistant to anti-fungals.
"These new furanones have the potential to control such infections and save lives," says assistant professor Dacheng Ren of the Department of Biomedical and Chemical Engineering in SU's L.C. Smith College of Engineering and Computer Science. "In our tests, they reduced fungal growth by more than 80 percent, and we hope to improve on that going forward."
Ren and his collaborator, chemistry professor Yan-Yeung Luk of SU's College of Arts and Sciences, have filed a non-provisional patent application. They have also published related results in the Journal of Applied Microbiology and Biotechnology.
Over the past 20 years, pathogenic fungi have developed growing resistance to anti-fungal drugs. This stimulated a strong demand for more effective drugs and led to the successful research at Syracuse. The researchers' genomic study suggests that furanones have different genetic targets than current anti-fungal agents and thus may avoid drug resistance acquired in the past. The research team has also shown previously that these furanones inhibit bacterial biofilm formation; thus they may help control chronic infections where biofilms often appear, on surgical, dental and other implants.
Ongoing furanones research at Syracuse University will investigate a broad spectrum of other potential capabilities, ranging from diverse medical uses, such as controlling bacterial and fungal biofilms, to anti-fungal wood preservatives for the building materials market
Inhibition of Candida albicans growth by brominated furanones
Miao Duo, Mi Zhang, Yan-Yeung Luk and Dacheng Ren
Journal of Applied Microbiology and Biotechnology 10.1007/s00253-009-2174-6
Link to JAMB abstract