Researchers discover molecular target for the bacterial infection brucellosis

Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 19 Aug 2013 - 1:00 PDT Current ratings for:
Researchers discover molecular target for the bacterial infection brucellosis

UC Davis scientists have uncovered a potential drug target for the development of an effective therapy against the debilitating, chronic form of the bacterial disease brucellosis, which primarily afflicts people in Mediterranean and Middle Eastern countries.

Brucellosis, which affects about 500,000 people worldwide each year, typically is caused by ingestion of unsterilized milk or close contact with body secretions from infected animals. Symptoms include intermittent or irregular fever of variable duration, headache, weakness, profuse sweating, chills, weight loss and generalized aching. It can also cause long-lasting or chronic symptoms such as recurrent fevers, joint pain and fatigue.

In a paper published online in the journal Cell Host & Microbe, the researchers reported that they have identified the cells that harbor the B. abortus bacteria during the persistent phase of the brucellosis. The cells, known as alternatively activated macrophages (AAMs), are a recently identified category of immune defense cells.

The researchers also determined that the biological pathway peroxisome proliferator activated receptor ?, abbreviated as PPAR?, is responsible for altering the metabolism of AAMs so that they supply B. abortus with the energy in the form of glucose that enables bacteria to survive and replicate and thereby sustain the chronic phase of the infectious disease. Other labs also have shown that PPAR? control a cell's metabolism.

"We found that PPAR? induces a metabolic shift in these cells that causes them to generate glucose," said Renee Tsolis, associate professor of medical microbiology and immunology at UC Davis who led the study.

"Starving the B. abortus bacteria by inhibiting the PPAR? pathway may be a new approach to eradicating the chronic, difficult-to-treat form of Brucellosis infection that usually occurs because antibiotic therapy was not used during the acute, or early, phase of the infection," said Tsolis.

Tsolis and her collaborators were the first to discover PPAR?'s role in brucellosis and to determine that AAMs harbor the bacteria during the chronic stage of the disease. The identification of the bacteria's niche is another important clue for the development of a more effective treatment, she said.

In a series of experiments, Tsolis and collaborators found that the gene encoding PPAR? is very active during chronic Brucellosis infection, but not during acute infection, and that the B. abortus bacteria did not survive in AAMs when deprived of glucose.

When the researchers inactivated the protein that normally transports glucose, the bacteria stopped reproducing, and the infection no longer was chronic, she said.

In mice infected with B. abortus, Tsolis and collaborators treated the animals with GW9662, a PPAR inhibitor. The researchers administered the inhibitor before the infection became chronic, or long lasting. The inhibitor significantly reduced the amount of AAMs and B. abortus bacteria in the mice.

"These results suggested that inhibition of PPARreduced the bacteria's survival by reducing the abundance of AAMs during chronic infection," said Tsolis.

Conversely, when the researchers treated the B. abortus-infected mice with Rosiglitazone, a drug that boosts PPAR activity, the bacteria increased by two-fold during the acute phase and four-fold during the chronic phase of infection. Rosiglitazone and other drugs that boost PPARare used to treat type 2 diabetes because they lower blood glucose by increasing cellular glucose uptake.

In other experiments, the researchers showed that AAMs, one of two categories of macrophages, are abundant in the spleen during chronic brucellosis but not during the acute, or initial, phase of the infection, which is dominated by classically activated macrophages (CAM), the second category of these immune cells.

In addition to profuse sweating, symptoms of brucellosis infection include joint and muscle pain. Among the complications of chronic infection are arthritis and endocarditis, a serious inflammation of one of the four heart valves. Brucellosis rarely occurs in the U.S., with about 100 to 200 cases reported each year, according to the U.S. Centers for Disease Control and Prevention.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject.

The title of the journal paper is “PPAR?-Mediated Increase in Glucose Availability Sustains Chronic Brucella abortus Infection in Alternatively Activated Macrophages.”

Authors also include: Mariana N. Xavier, Maria G. Winter, Alanna M. Spees, Andreas B. den Hartigh, Kim Nguyen, Christelle M. Roux, Vidya L. Atluri, Tobias Kerrinnes, A. Marijke Keestra and Andreas J. Baumler of UC Davis; Denise M. Monack of Stanford University, Palo Alto, CA; and Paul A. Luciw, Richard A. Eigenheer, Renato L. Santos and Teane M.A. Silva of the Universidade Federal de Minas Gerais in Brazil. Cell Host & Microbe, Volume 14, Issue 2, 159-170, 14 August 2013; 10.1016/j.chom.2013.07.009

University of California - Davis Health System

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Vitamin D-related 'molecular switches' predict childhood bone mass

Main Category: Bones / Orthopedics
Also Included In: Nutrition / Diet;  Pregnancy / Obstetrics
Article Date: 19 Aug 2013 - 1:00 PDT Current ratings for:
Vitamin D-related 'molecular switches' predict childhood bone mass

Researchers at the MRC Lifecourse Epidemiology Unit, University of Southampton, have demonstrated that the degree to which a gene related to vitamin D action is switched on or off, when measured at birth, predicts bone density of the child at four years of age.

In the study, 230 boys and girls were assessed at 4 years as part of the Southampton Women's Survey (SWS), a large ongoing mother-offspring cohort. The children visited the Osteoporosis Centre at Southampton General Hospital for measurement of their bone size and density using a DXA scanner. The researchers were able to measure the extent to which a particular gene, RXRA, is switched on or off by measuring epigenetic marks on the DNA sequence of the gene in cells taken from umbilical cord tissue which had been collected at birth. They found that the less marking (which usually means greater gene activity), at birth, the greater the bone density of the child at four years old. Furthermore, one of the epigenetic marks was related to the mother's blood vitamin D concentrations in late pregnancy.

Dr Nicholas Harvey, Senior Lecturer at the MRC Lifecourse Epidemiology Unit, University of Southampton, who led this project said, "RXRA is essential for the action of vitamin D and several other hormones; taken together with the relationship we found between mothers' vitamin D levels and RXRA marking, this study provides further support for the potential importance of vitamin D in pregnancy. We are now testing whether mothers should be supplemented with vitamin D in pregnancy in a randomised controlled trial, the MAVIDOS Maternal Vitamin D Osteoporosis Study, which will report early next year."

Professor Cooper, Professor of Rheumatology and Director of the MRC Lifecourse Epidemiology Unit, University of Southampton and who oversaw this work, added "This study forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit and University of Southampton in which we are seeking to understand how factors such as diet and lifestyle in the mother during pregnancy, and of the child in early life, influence a child's body composition and bone development. This work should help us to design interventions aimed at optimising body composition in childhood and later adulthood and thus improve the health of future generations".

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our bones / orthopedics section for the latest news on this subject.

Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth.

Harvey NC, Sheppard A, Godfrey KM, McLean C, Garratt E, Ntani G, Davies L, Murray R, Inskip HM, Gluckman PD, Hanson MA, Lillycrop KA, Cooper C. J Bone Miner Res. 2013 Aug 1. DOI: 10.1002/jbmr.2056. [Epub ahead of print]

International Osteoporosis Foundation

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Siemens introduces the future of molecular imaging

Main Category: Radiology / Nuclear Medicine
Also Included In: Medical Devices / Diagnostics
Article Date: 16 Aug 2013 - 2:00 PDT Current ratings for:
Siemens introduces the future of molecular imaging

Siemens Healthcare has launched a new platform with the potential to change how molecular imaging is performed. The Symbia Intevo™ is the world's first xSPECT system. It combines the high sensitivity of single-photon emission computed tomography (SPECT) with the high specificity of CT, completely integrating the data from the two modalities, to generate high resolution and, for the first time, quantitative images[1]. The system demonstrates Siemens' innovation and competitiveness, key components of the Healthcare Sector's Agenda 2013 two-year initiative.

The new Symbia Intevo xSPECT system reconstructs both the SPECT and CT portions of an image into a much higher frame of reference than other systems for precise, accurate alignment facilitating the extraction and deep integration of medically relevant information. This ability is the basis for differentiating between tissue boundaries in bone imaging. With xSPECT Bone clinicians can potentially provide additional support for detection and distinguishing between cancerous lesions and degenerative disorders. The Symbia Intevo's precise alignment of SPECT and CT provides clinicians with essential volumetric information from the CT scan, enabling accurate and consistent quantitative assessment meaning the clinician can apply quantitative information to assess whether a patient's condition has regressed, stabilised or progressed.

SPECT and CT integrated.

The Symbia Intevo uses more CT data than ever before, but Siemens is still able to limit patient dose by offering Combined Applications to Reduce Exposure (CARE). The system uses AUTOFORM collimator, capturing up to 26 more counts, helping boost image acquisition time and patient throughput.

"Siemens Healthcare anticipates the new Symbia Intevo technology will improve the quality of care, while helping to reduce costs," states Lawrence Foulsham, Molecular Imaging Product Manager at Siemens Healthcare. "Siemens recognises that these two elements must go hand-in-hand, and with our new molecular imaging solutions, we can demonstrate our commitment to true innovation leadership by overcoming the limitations of conventional SPECT systems to help provide answers to the toughest clinical questions in the safest and most efficient way possible."

Article adapted by Medical News Today from original press release. Source:

1. Pending 510(k) clearance,

Siemens

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1. Pending 510(k) clearance,

Siemens

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'Molecular flashlight' developed that illuminates brain tumors in mice

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology;  Pediatrics / Children's Health
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
'Molecular flashlight' developed that illuminates brain tumors in mice

In a breakthrough that could have wide-ranging applications in molecular medicine, Stanford University researchers have created a bioengineered peptide that enables imaging of medulloblastomas, among the most devastating of malignant childhood brain tumors, in lab mice.

The researchers altered the amino acid sequence of a cystine knot peptide - or knottin - derived from the seeds of the squirting cucumber, a plant native to Europe, North Africa and parts of Asia. Peptides are short chains of amino acids that are integral to cellular processes; knottin peptides are notable for their stability and resistance to breakdown.

The team used their invention as a "molecular flashlight" to distinguish tumors from surrounding healthy tissue. After injecting their bioengineered knottin into the bloodstreams of mice with medulloblastomas, the researchers found that the peptide stuck tightly to the tumors and could be detected using a high-sensitivity digital camera.

The findings are described in a study published online in the Proceedings of the National Academy of Sciences.

"Researchers have been interested in this class of peptides for some time," said Jennifer Cochran, PhD, an associate professor of bioengineering and a senior author of the study. "They're extremely stable. For example, you can boil some of these peptides or expose them to harsh chemicals, and they'll remain intact."

That makes them potentially valuable in molecular medicine. Knottins could be used to deliver drugs to specific sites in the body or, as Cochran and her colleagues have demonstrated, as a means of illuminating tumors.

For treatment purposes, it's critical to obtain accurate images of medulloblastomas. In conjunction with chemotherapy and radiation therapy, the tumors are often treated by surgical resection, and it can be difficult to remove them while leaving healthy tissue intact because their margins are often indistinct.

"With brain tumors, you really need to get the entire tumor and leave as much unaffected tissue as possible," Cochran said. "These tumors can come back very aggressively if not completely removed, and their location makes cognitive impairment a possibility if healthy tissue is taken."

The researchers' molecular flashlight works by recognizing a biomarker on human tumors. The bioengineered knottin is conjugated to a near-infrared imaging dye. When injected into the bloodstreams of a strain of mice that develop tumors similar to human medullublastomas, the peptide attaches to the brain tumors' integrin receptors - sticky molecules that aid in adhesion to other cells.

But while the knottins stuck like glue to tumors, they were rapidly expelled from healthy tissue. "So the mouse brain tumors are readily apparent," Cochran said. "They differentiate beautifully from the surrounding brain tissue."

The new peptide represents a major advance in tumor-imaging technology, said Melanie Hayden, MD, a neurosurgeon at the Stanford Brain Tumor Center and a lead author of the paper. The most common extant technique employs a high-contrast dye that is injected intravenously shortly before or during an operation. Tumors absorb some of the dye, and can be identified on a magnetic resonance imaging scan.

"But that has limitations," Hayden said. "When you're using dye and an MRI scan, you're basically working off a snapshot. And the brain can sometimes shift during an operation, so there's always the possibility you may not be precisely where you want to be. The great advantage of this new approach is that you're illuminating the tumor in real time - you're seeing it directly under your scope instead of relying on an image that was taken earlier." An important next step will be to translate these results from mice to human patients.

Though the team's research focused on medulloblastomas, Hayden said it's likely the new knottins could prove useful in addressing other cancers.

"We know that integrins exist on many types of tumors," she said. "The blood vessels that tumors develop to sustain themselves also contain integrins. So this has the potential for providing very detailed, real-time imaging for a wide variety of tumors."

And imaging may not be the only application for the team's engineered peptide.

"We're very interested in related opportunities," Cochran said. "We envision options we didn't have before for getting molecules into the brain." In other words, by substituting drugs for dye, the knottins might allow the delivery of therapeutic compounds directly to cranial tumors - something that has proved extremely difficult to date because of the blood/brain barrier, the mechanism that makes it difficult for pathogens, as well as medicines, to traverse from the bloodstream to the brain.

"We're looking into it now," Cochran said.

A little serendipity was involved in the peptide's development, said Sarah Moore, a recently graduated bioengineering PhD student and another lead author of the study. Indeed, the propinquity of Cochran's laboratory to co-author Matthew Scott's lab at Stanford's James H. Clark Center catalyzed the project. "Our labs are next to each other," Moore said. "We had the peptide, and Matt had ideal models of pediatric brain tumors - mice that develop tumors in a similar manner to human medulloblastomas. Our partnership grew out of that."

Scott, PhD, professor of bioengineering and of developmental biology, credits the design of the Clark Center as a contributor to the project. The building is home to Stanford's Bioengineering Department, a collaboration between the School of Engineering and the School of Medicine, and Stanford Bio-X, an initiative that encourages communication among researchers in diverse scientific disciplines.

"So in a very real sense, our project wasn't an accident," Scott said. "In fact, it's exactly the kind of work the Clark Center was meant to foster. The lab spaces are wide and open, with very few walls and lots of glass. We have a restaurant that only has large tables - no tables for two, so people have to sit together. Everything is designed to increase the odds that people will meet and talk. It's a form of social engineering that really works."

Scott said he is gratified by the collaboration that led to the team's breakthrough, and observed that the peptide has proved a direct boon to his own work. About 15 percent of Scott's mice develop the tumors requisite for medulloblastoma research. The problem, he said, is that the cancers are cryptic in their early stages.

"By the time you know the mice have them, many of the things you want to study - the genesis and development of the tumors - are past," Scott said. "We needed ways to detect these tumors early, and we needed methods for following the steps of tumor genesis."

Ultimately, Scott concluded, the development of the new peptide can be attributed to Stanford's long-established traditions of openness and relentless inquiry.

"You find not just a willingness, but an eagerness to exchange ideas and information here," Scott said. "It transcends any competitive instinct, any impulse toward proprietary thinking. It is what makes Stanford - well, Stanford."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

Other Stanford co-authors were postdoctoral scholar Jamie Bergen, PhD; medical student Yourong Sophie Su; and life science research assistant Helen Rayburn.

Stanford University Medical Center

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'Molecular flashlight' developed that illuminates brain tumors in mice

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology;  Pediatrics / Children's Health
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
'Molecular flashlight' developed that illuminates brain tumors in mice

In a breakthrough that could have wide-ranging applications in molecular medicine, Stanford University researchers have created a bioengineered peptide that enables imaging of medulloblastomas, among the most devastating of malignant childhood brain tumors, in lab mice.

The researchers altered the amino acid sequence of a cystine knot peptide - or knottin - derived from the seeds of the squirting cucumber, a plant native to Europe, North Africa and parts of Asia. Peptides are short chains of amino acids that are integral to cellular processes; knottin peptides are notable for their stability and resistance to breakdown.

The team used their invention as a "molecular flashlight" to distinguish tumors from surrounding healthy tissue. After injecting their bioengineered knottin into the bloodstreams of mice with medulloblastomas, the researchers found that the peptide stuck tightly to the tumors and could be detected using a high-sensitivity digital camera.

The findings are described in a study published online in the Proceedings of the National Academy of Sciences.

"Researchers have been interested in this class of peptides for some time," said Jennifer Cochran, PhD, an associate professor of bioengineering and a senior author of the study. "They're extremely stable. For example, you can boil some of these peptides or expose them to harsh chemicals, and they'll remain intact."

That makes them potentially valuable in molecular medicine. Knottins could be used to deliver drugs to specific sites in the body or, as Cochran and her colleagues have demonstrated, as a means of illuminating tumors.

For treatment purposes, it's critical to obtain accurate images of medulloblastomas. In conjunction with chemotherapy and radiation therapy, the tumors are often treated by surgical resection, and it can be difficult to remove them while leaving healthy tissue intact because their margins are often indistinct.

"With brain tumors, you really need to get the entire tumor and leave as much unaffected tissue as possible," Cochran said. "These tumors can come back very aggressively if not completely removed, and their location makes cognitive impairment a possibility if healthy tissue is taken."

The researchers' molecular flashlight works by recognizing a biomarker on human tumors. The bioengineered knottin is conjugated to a near-infrared imaging dye. When injected into the bloodstreams of a strain of mice that develop tumors similar to human medullublastomas, the peptide attaches to the brain tumors' integrin receptors - sticky molecules that aid in adhesion to other cells.

But while the knottins stuck like glue to tumors, they were rapidly expelled from healthy tissue. "So the mouse brain tumors are readily apparent," Cochran said. "They differentiate beautifully from the surrounding brain tissue."

The new peptide represents a major advance in tumor-imaging technology, said Melanie Hayden, MD, a neurosurgeon at the Stanford Brain Tumor Center and a lead author of the paper. The most common extant technique employs a high-contrast dye that is injected intravenously shortly before or during an operation. Tumors absorb some of the dye, and can be identified on a magnetic resonance imaging scan.

"But that has limitations," Hayden said. "When you're using dye and an MRI scan, you're basically working off a snapshot. And the brain can sometimes shift during an operation, so there's always the possibility you may not be precisely where you want to be. The great advantage of this new approach is that you're illuminating the tumor in real time - you're seeing it directly under your scope instead of relying on an image that was taken earlier." An important next step will be to translate these results from mice to human patients.

Though the team's research focused on medulloblastomas, Hayden said it's likely the new knottins could prove useful in addressing other cancers.

"We know that integrins exist on many types of tumors," she said. "The blood vessels that tumors develop to sustain themselves also contain integrins. So this has the potential for providing very detailed, real-time imaging for a wide variety of tumors."

And imaging may not be the only application for the team's engineered peptide.

"We're very interested in related opportunities," Cochran said. "We envision options we didn't have before for getting molecules into the brain." In other words, by substituting drugs for dye, the knottins might allow the delivery of therapeutic compounds directly to cranial tumors - something that has proved extremely difficult to date because of the blood/brain barrier, the mechanism that makes it difficult for pathogens, as well as medicines, to traverse from the bloodstream to the brain.

"We're looking into it now," Cochran said.

A little serendipity was involved in the peptide's development, said Sarah Moore, a recently graduated bioengineering PhD student and another lead author of the study. Indeed, the propinquity of Cochran's laboratory to co-author Matthew Scott's lab at Stanford's James H. Clark Center catalyzed the project. "Our labs are next to each other," Moore said. "We had the peptide, and Matt had ideal models of pediatric brain tumors - mice that develop tumors in a similar manner to human medulloblastomas. Our partnership grew out of that."

Scott, PhD, professor of bioengineering and of developmental biology, credits the design of the Clark Center as a contributor to the project. The building is home to Stanford's Bioengineering Department, a collaboration between the School of Engineering and the School of Medicine, and Stanford Bio-X, an initiative that encourages communication among researchers in diverse scientific disciplines.

"So in a very real sense, our project wasn't an accident," Scott said. "In fact, it's exactly the kind of work the Clark Center was meant to foster. The lab spaces are wide and open, with very few walls and lots of glass. We have a restaurant that only has large tables - no tables for two, so people have to sit together. Everything is designed to increase the odds that people will meet and talk. It's a form of social engineering that really works."

Scott said he is gratified by the collaboration that led to the team's breakthrough, and observed that the peptide has proved a direct boon to his own work. About 15 percent of Scott's mice develop the tumors requisite for medulloblastoma research. The problem, he said, is that the cancers are cryptic in their early stages.

"By the time you know the mice have them, many of the things you want to study - the genesis and development of the tumors - are past," Scott said. "We needed ways to detect these tumors early, and we needed methods for following the steps of tumor genesis."

Ultimately, Scott concluded, the development of the new peptide can be attributed to Stanford's long-established traditions of openness and relentless inquiry.

"You find not just a willingness, but an eagerness to exchange ideas and information here," Scott said. "It transcends any competitive instinct, any impulse toward proprietary thinking. It is what makes Stanford - well, Stanford."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

Other Stanford co-authors were postdoctoral scholar Jamie Bergen, PhD; medical student Yourong Sophie Su; and life science research assistant Helen Rayburn.

Stanford University Medical Center

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14 Aug. 2013. APA

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''Molecular flashlight' developed that illuminates brain tumors in mice'

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All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

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Study suggests role for adenosine in molecular processes involved in epilepsy

Main Category: Epilepsy
Article Date: 29 Jul 2013 - 0:00 PDT Current ratings for:
Study suggests role for adenosine in molecular processes involved in epilepsy

Silk has walked straight off the runway and into the lab. According to a new study published in the Journal of Clinical Investigation, silk implants placed in the brain of laboratory animals and designed to release a specific chemical, adenosine, may help stop the progression of epilepsy. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), which are part of the National Institutes of Health.

The epilepsies are a group of neurological disorders associated with recurring seizures that tend to become more frequent and severe over time. Adenosine decreases neuronal excitability and helps stop seizures. Earlier studies have suggested abnormally low levels of adenosine may be linked to epilepsy.

Rebecca L. Williams-Karnesky, Ph.D. and her colleagues from Legacy Research Institute, Portland, Ore., Oregon Health and Sciences University (OHSU), Portland, and Tufts University, Boston, looked at long-term effects of an adenosine-releasing silk-implant therapy in rats and examined the role of adenosine in causing epigenetic changes that may be associated with the development of epilepsy.

The investigators argue that adenosine's beneficial effects are due to epigenetic modifications (chemical reactions that change the way genes are turned on or off without altering the DNA code, the letters that make up our genetic background). Specifically, these changes happen when a molecule known as a methyl group blocks a portion of DNA, affecting which genes are accessible and can be turned on. If methyl groups have been taken away (demethylated), genes are more likely to turn on.

The results reported in the paper provided evidence that changing adenosine levels affects DNA methylation in the brain. Specifically, greater amounts of adenosine were associated with lower levels of DNA methylation. The investigators also demonstrate that rats induced to develop epilepsy have higher levels of methylated DNA. Of particular note, epileptic rat brains that had received the adenosine-releasing silk implants exhibited DNA methylation levels close to brains of normal rats and this significantly lessened the worsening of the epilepsy over time.

"We know that there are mutations that are associated with epilepsy. However, there are few people such as Dr. Detlev Boison who are doing this type of work, focusing not just on genetic mutations but how the genes are regulated," said Vicky Whittemore, Ph.D., program director at NINDS.

One mechanism involved in a specific type of epilepsy is an increase in mossy fiber sprouting - the formation of new excitatory circuits in the part of the brain where seizures commonly originate. At the end of the experiment, animals that had been treated with the adenosine-releasing silk implant showed less sprouting than animals that were not given the drug. "Based on our findings that 10 days of adenosine delivery prevented the sprouting of mossy fibers for at least three months in rats, we predict that the benefits of our adenosine therapy may extend even longer. However, this assumption needs to be validated in long-term experiments that go beyond three months," said Dr. Boison, senior author of the paper from Legacy Research Institute and OHSU.

The rats did not receive the implants until they had experienced a number of seizures. The researchers noted that many studies investigating anti-epileptic drugs often test the treatments too early. "If the therapy interferes with the trigger for epilepsy development then the trigger is weakened and subsequent epilepsy is less severe. However, this is not necessarily indicative of a stop in the progression of the disease," said Dr. Boison. They found that the adenosine-releasing silk did not completely abolish seizures in their animal model but reduced them four-fold.

"To avoid interference with the epilepsy-triggering mechanisms, we waited until all animals developed an early stage of epilepsy. In this model, the disease is life-long: seizures become more frequent and worsen with time. Therefore, we challenged ourselves to attempt treatment at a stage where epilepsy had already been established," Dr. Boison continued.

The findings show that the implants are safe to use in rats and suggest that they may one day be used in the clinic. "Adenosine-releasing silk is a biodegradable implant. The release of adenosine occurs for 10 days and then the silk will completely dissolve. This is an ideal set-up for a transient preventative treatment," said Dr. Boison. "Clinical applications could be the prevention of epilepsy following head trauma or the prevention of seizures that often - in about 50 percent of patients - follow conventional epilepsy surgery. In this case, adenosine-releasing silk might be placed into the resection cavity in order to prevent future seizures."

However, before the silk implants are ready for their close-up, future studies will need to determine their optimal use and safety in humans. According to Dr. Boison, "We need to look into the efficacy of different doses of adenosine, the duration of adenosine release, and various time points of intervention."

Future studies also need to demonstrate how long the effects of the adenosine-releasing silk implant will last.

"This work is important because 25-30 percent of people with epilepsy do not have effective therapies. This research may help us to prevent epilepsy in people who suffer some event that places them at risk for the disorder, such as individuals who have experienced head trauma," said Dr. Whittemore.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our epilepsy section for the latest news on this subject.

This study was supported by grants from NINDS (NS061844, NS070359), NIBIB (EB002520), and the U.S. Department of Defense (W81XWH-12-1-0283).

Rebecca L. Williams-Karnesky et al. "Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis." J Clin Invest. doi:10.1172/JCI65636, July 25, 2013.

NIH/National Institute of Neurological Disorders and Stroke

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Laser-controlled molecular switch turns blood clotting on, off on command

Main Category: Blood / Hematology
Article Date: 24 Jul 2013 - 14:00 PDT Current ratings for:
Laser-controlled molecular switch turns blood clotting on, off on command

Researchers have designed tiny, light-controlled gold particles that can release DNA controls to switch blood clotting off and on. The results are reported July 24 in the open access journal PLOS ONE by Kimberly Hamad-Schifferli and colleagues from the Massachusetts Institute of Technology.

The two-way switch for blood clotting relies on the ability of two gold nanoparticles to selectively release different DNA molecules from their surface under different wavelengths of laser excitation. When stimulated by one wavelength, one nanorod releases a piece of DNA that binds the blood protein thrombin and blocks clot formation. When the complementary DNA piece is released from the other nanorod, it acts as an antidote and releases thrombin, restoring clotting activity.

Natural blood clotting is precisely synchronized to occur at the right time and place. Wound healing, surgery and other conditions require manipulation of this process, typically through the use of anticoagulants like heparin or warfarin. However, these drugs are inherently one-sided as they can only block clotting, and reversing their effects depends on removing them from the bloodstream. The methods described in this research open up new possibilities for more precise, selective control of the blood clotting process during therapy.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our blood / hematology section for the latest news on this subject.

de Puig H, Cifuentes Rius A, Flemister D, Baxamusa SH, Hamad-Schifferli K (2013) Selective Light-Triggered Release of DNA from Gold Nanorods Switches Blood Clotting On and Off. PLoS ONE 8(7): e68511. doi:10.1371/journal.pone.0068511

PLOS ONE

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