суббота, 21 мая 2011 г.

Fluorescence Used To Develop Method For Detecting Mercury In Fish, Dental Amalgam

Researchers at the University of Pittsburgh have developed a simple and quick method for detecting mercury in fish and dental samples, two substances at the center of public concern about mercury contamination. The technique involves a fluorescent substance that glows bright green when it comes into contact with oxidized mercury, the researchers report in the current online edition of the Journal of the American Chemical Society. The intensity of the glow indicates the amount of mercury present.



Developed in the laboratory of Kazunori Koide (Ko-ee-deh), a chemistry professor in Pitt's School of Arts and Sciences, the new method can be used onsite and can detect mercury in 30 to 60 minutes for dental fillings (or amalgams) or 10 to 30 minutes for fish, Koide explained. "Our method could be used in the fish market or the dentist office," he said. "We have developed a reliable indicator for mercury that a person could easily and safely use at home."



The fluorescence results from the reaction of mercury ions with hydrocarbons called alkynes - the alkyne is converted into a ketone and creates a fluorescent molecule. Koide's method differs from similar mercury indicators in that it withstands the oxidation process mercury samples must undergo prior to testing, Koide said. The mercury species found in most fish and dental amalgams - such as the toxic methyl mercury - must be converted into a safer variety of mercury with an oxidizing agent. Other fluorescent detectors are often not compatible with samples that have been oxidized.



In testing fish, Koide and his team oxidized a piece of salmon (about the size of a fingertip) in water mixed with a chlorine solution similar to household bleach. The conversion process is safe and relatively simple, Koide said. Afterward, the team added the alkyne solution and the mixture glowed bright green.



The Pitt researchers also tested for mercury leaching from dental amalgam, a common tooth filling composed primarily of mercury mixed with smaller amounts of other metals. Concern exists about the mercury seeping from a filling into a person's body and about the disposal of unused amalgam by dentist offices (which is not federally regulated in the United States). To test for leaching, the team pressed a cloth to a tooth with an amalgam filling for one minute; the sample glowed when exposed to the mercury-detecting agent. They also submerged two amalgam-filled teeth in the amino acid cysteine to mimic sulfur-rich foods, which are thought to increase mercury seepage from amalgam. Again, the cysteine solution turned bright green when the indicator was added, suggesting that Koide's method can also be used to monitor mercury leaching caused by sulfur-rich food.



In terms of amalgam disposal, Koide suggested that his method could be used to test dentist office wastewater for mercury content onsite without sending samples to analytical laboratories.







The current paper can be found on the JACS Web site at pubs.acs/doi/abs/10.1021/ja805678r



Source: Morgan Kelly


University of Pittsburgh

A Warm Sensor Maintains Skin Barrier

Japanese research group led by Prof. Makoto Tominaga and Dr. Takaaki Sokabe (National Institute for Physiological Sciences: NIPS) found that TRPV4 ion channel in skin keratinocytes is important for formation and maintenance of barrier function to prevent dehydration. Their finding was reported in the Journal of Biological Chemistry.



TRPV4 is one of the temperature-sensitive Ca2+-permeable channels, namely "thermoTRPs". It is expressed in skin, acting as a warm sensor (>27oC) to choose preferred environmental temperatures in mammals. The research group sought the alternative function of TRPV4, since skin keratinocytes express another thermoTRP named TRPV3, which also functions as a warm sensor.



TRPV4 was found to interact with b-catenin, an adaptor protein between actin filaments and E-cadherin in cell-cell junction complex. When TRPV4 was genetically removed from keratinocytes, Ca2+-induced cell-cell junction formation was delayed and immature, resulting in leaky junctions. Consistently, intercellular junction-dependent skin barrier in TRPV4-deficient mice became weak (leaky intercellular pathway) compared to wild-type mice. Interestingly, these phenotypes were TRPV4-specific, but not TRPV3-dependent.



Dr. Sokabe said, "TRPV4 may utilize skin temperature to provide Ca2+ for cell-cell junction complexes to reinforce their tightness. For instance, dried skin in cold seasons or regions could be due to low activity of TRPV4 caused by low skin temperature. Development of chemicals modulating TRPV4 activity would be useful for barrier repair of damaged skin."



Source:

Dr. Takaaki Sokabe


National Institute for Physiological Sciences

An "Elegant" Idea Proves Its Worth 25 Years Later

The simple notion of copying the body's own natural "waste disposal" chemistry to mop up potentially toxic nitrogen has saved an estimated 80 percent of patients with urea cycle disorders --- most of them children according to a report in this week's New England Journal of Medicine summarizing a quarter century of experience with the treatment.


The effectiveness of sodium phenylacetate and sodium benzoate, two chemicals the body already makes to carry nitrogen for disposal in urine "just knocked my socks off from the moment we first tried them," recalls Saul Brusilow, M.D., professor emeritus of pediatrics at Hopkins who first had the notion to use the drugs. "In all my years I never came across another disease where patients come in near-comatose and you stick a needle in them and lo and behold, they wake up just like that. It was just astonishing," he says.


"His elegant idea was to give patients chemicals they already make in small amounts in large doses to make up for the missing urea cycle enzyme they inherited," says Ada Hamosh, M.D., M.P.H, clinical director of the McKusick-Nathans Institute of Genetic Medicine. "Sodium phenylacetate and sodium benzoate already know how to eliminate nitrogen in urine, so having more in the body carries more nitrogen out and reduces the toxic effects of excess nitrogen accumulation."


Excess nitrogen yields ammonia, which is poisonous and in the case of urea cycle disorders, causes brain damage, retardation, coma and even death.


Despite the immediate clinical success of the treatment, the drug combination was finally approved by the U.S. Food and Drug Administration only in 2005.


Brusilow, Hamosh, and colleagues at Stanford University, University of Minnesota, Thomas Jefferson University and the Medical College of Wisconsin looked back at 299 urea cycle disorder patients with a total of 1,181 hyperammonemia "episodes" from 118 hospitals around the United States from August 1980 until March 2005.


The regimen consisted of high-dose intravenous sodium phenylacetate and sodium benzoate for two hours followed by "maintenance infusions" until blood ammonia levels were normal. The patients' overall survival rate was 84 percent, and 96 percent survived episodes of severe ammonia poisoning.


An estimated one in 40,000 live births is a child with a urea cycle disorder, according to Hamosh, who says early and accurate detection can now assure prompt treatment.


"We're teaching all medical students at Hopkins to consider hyperammonemia and immediately do blood tests when they see a combative, lethargic or comatose newborn or child," she says. "The longer the hyperammonemia lasts, the higher the risk for brain damage."


"This is a happy story," says Brusilow. "It isn't too often in genetic medicine that we can intuitively develop a treatment with already available chemicals and save lives."


The research was funded by the Johns Hopkins University General Clinic Research Centers, Children's Hospital of Philadelphia, Children's National Medical Center, the National Institute of Child Health and Human Development, the Food and Drug Administration, and the National Center for Research Resources.


Authors on the paper are Gregory Enns of Stanford University, Susan Berry of the University of Minnesota, Gerald Berry of Thomas Jefferson University, William Rhead of the Medical College of Wisconsin, and Brusilow and Hamosh, both of Hopkins.


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NIMBioS Hosts 200 Undergraduates At National Research Conference

Nearly 200 undergraduates and faculty from more than 40 academic institutions in North America will gather Oct. 23-24 in Knoxville for the first annual Undergraduate Research Conference at the Interface of Biology and Mathematics sponsored by the National Institute for Mathematical and Biological Synthesis (NIMBioS).



Undergraduates in biology, mathematics, computer science and related fields will give talks and present posters on topics ranging from modeling diseases to using mathematics to understand population dynamics and biological phenomena. The conference, which will be held at the University of Tennessee's Conference Center in downtown, Knoxville, features 40 student talks and 40 student posters.



Keynote speakers include Lisa J. Fauci, professor of mathematics at Tulane University, who will discuss the dynamics of cilia and flagella, and Paul E. Super, science coordinator at the Great Smoky Mountains National Park (GSMNP), who will talk about research, inventories, and monitoring used in protection efforts at GSMNP.



The conference also includes a panel discussion with university faculty on career opportunities at the interface of mathematics and biology.



"This conference is an excellent opportunity for undergraduate students to present their research to a large audience and to learn about possible career paths that combine both the mathematical and the biological disciplines," said Suzanne Lenhart, professor of mathematics at the University of Tennessee-Knoxville and NIMBioS Associate Director of Education, Outreach and Diversity.



Source:
Catherine Crawley


National Institute for Mathematical and Biological Synthesis (NIMBioS)

Biological Sensors Are The Future Of Personalized Treatment

Informatics is the foundation of research into biomedicine and nanomedicine


In the future, explained Peter Ghazal, Chair of Edinburgh University's Department of Molecular Genetics and Biomedicine, biological sensors, the product of the integration of biology and electronics will be used to detect infections and prescribe personalized treatments. He was speaking at the International Symposium on Research in Grid/Nano/Bio/Medical Informatics (Bioinforsalud 2009), held at Madrid last month.


Ghazal also clarified that research in the fields of molecular genetics and biomedicine targets personalized medicine. Not all patients respond to drugs in the same way, and, because of this, each patient's profile needs to be identified to be able to treat them with a specific drug.


At Bioinforsalud 2009, Martin Fritts, Principal Scientist at the US National Cancer Institute's Nanotechnology Characterization Lab, explained that the key objective of his research is to speed up the application of nanotechnology concepts to treat cancer in clinical research. He added that there are already tens of clinical trials on cancer involving nanomedicine.


Another point he made is that informatics is a key aspect of this research, as regards both knowledge discovery and transfer to clinical research. The first standardized protocols for characterizing nanoparticles are already out and the first interdisciplinary laboratory using these protocols to conduct research is now operational.


Finally, he noted that the success of the development of nanomedicine-based treatments and diagnoses will depend on how well we understand the interactions between nanoparticles and their environments be they organs, tissues, a cell or infracellular bodies at the molecular level. The informatics infrastructure, he concluded, is an essential part of research underlying nanomedicine and its applications to personalized medicine.


Bioinforsalud 2009 was organized by ACTION-Grid, the first European Commission-funded initiative for analysing and linking three fields: biomedical informatics, grid technologies and nanotechnology. The organizing committee was chaired by VГ­ctor Maojo, Director of the Universidad PolitГ©cnica de Madrid School of Computing's Biomedical Informatics Group and by Fernando MartГ­n SГЎnchez, Director of the Medical Bioinformatics Department of the Instituto de Salud Carlos III in Madrid.


ACTION-Grid's aim is to exchange results and encourage cooperation in these scientific fields between Latin America, the Balkans and North Africa. One of ACTION-Grid's fields of interest is nanoinformatics in medicine. In this respect, ACTION-Grid is the first European Commission-funded project addressing the field of nanoinformatics, a new informatics discipline, and its applications to medicine or nanomedicine.


Bioinforsalud 2009 is part of the implementation of ACTION-Grid and brought together twenty experts from different regions of the world, including Peter Ghazal and Martin Fritts, to discuss nanotechnology and the personalization of medicine.


Source: Facultad de InformГЎtica de la Universidad PolitГ©cnica de Madrid

Rhode Island Hospital Awarded $11 Million, 5-Year Renewal

Rhode Island Hospital has received an $11 million renewal of a National Institutes of Health (NIH) grant to fund its Center of Biomedical Research Excellence (COBRE) Center for Cancer Research Development (CCRD). Rhode Island Hospital's COBRE CCRD offers cancer researchers access to the latest technologies in molecular pathology and the emerging field of proteomics. The 5-year grant from the NIH's National Center for Research Resources (NCRR), awarded after an extremely competitive peer review process, guarantees that the laboratory-based cancer research program will continue through the year 2013.



"Rhode Island Hospital has done outstanding work in this field, and I am pleased it will continue to receive federal funds to support cancer research. This federal investment will help Rhode Island Hospital transform lab discoveries into patient treatment and attract more elite researchers to the state," says U.S. Senator Jack Reed, who supported the program and serves on the Appropriations subcommittee which oversees federal funding for NIH programs.



One area within the COBRE CCRD is proteomics -- the identification and quantification of proteins with the goal of determining how they interact, how their expression changes by disease and how they are modified by environmental change. This type of basic research has the potential to go from "bench to bedside," by identifying breakthroughs that will translate to changes in the treatment of patients with cancer. Another area within the COBRE CCRD is molecular pathology, which deals with the characterization of the molecular and cellular events critical to the development of cancer, with the goal of identifying biomarkers with diagnostic and prognostic potential.



Peter Snyder, Lifespan's vice president of research, says, "The renewal of this grant shows the NIH's recognition of the valuable research being performed here at Rhode Island Hospital's CCRD. In addition, it helps to solidify our role of supporting the Rhode Island economy by increasing the research and biotechnology being done locally."



Under the leadership of principal investigator Douglas Hixson, PhD, the center received its first grant in 2003. Hixson says, "Over the past five years we have established an infrastructure and the technology to support basic research in the area of gastrointestinal cancer and to engage investigators in developing new research initiatives centered around the role of adult stem cells in the genesis of cancer." He further notes, "This year we also received a $500,000 economic stimulus fund grant that allowed our proteomics core to purchase a state-of-the art imaging mass spectrometer. By allowing investigators to identify proteins differentially expressed in malignant and normal cells by directly scanning tissue sections, this exciting new technology will accelerate the identification of biomarkers by directly linking the fields of proteomics and molecular pathology."



"This award will enable these investigators to continue to build their capacity to perform state-of-the-art research in specific cancers, such as in gastrointestinal tumors," said NCRR Director Barbara Alving, MD. "The center will also provide excellent opportunities to train new generations of biomedical researchers."



Since its opening in 2003, the center has already made discoveries that have broadened knowledge of different types of cancer. Hixson explains, "We've identified a new mode of transmitting signals regulating the growth and spread of cancer, a new gene that determines sensitivity to anti cancer drugs, another gene elevated by acid reflux that increases the risk of esophageal cancer and two novel tumor suppressor genes whose loss elevates the risk of stomach cancer.



"The renewal of our grant provides us with an outstanding potential for groundbreaking research in our center," he comments. Over the next five years, the center will focus its efforts on generating new avenues of research by facilitating collaboration among cancer investigators within the CCRD and at other universities and hospitals in Rhode Island. Hixson says, "Of particular interest will be research aimed at identifying characteristics of cancer stem cells that could serve as therapeutic targets. We also expect our new imaging mass spectrometer to become a catalyst for collaborative interactions aimed at developing novel clinical and basic research applications for this largely unexplored technology."



Snyder concludes, "Not only are we helping to fuel our local economy, but overall, our research may someday prove to be the key to unlocking medical breakthroughs that may completely change the course of cancer treatment to improve outcomes. We look forward to that day."



Source:
Nancy Jean


Lifespan

Future Type 2 Diabetes Research May Be Inspired By Genetic 'Roadblock'

A team of Mount Sinai Hospital researchers has found that a "genetic roadblock" identified in a recent study could pave the way toward novel treatments for type 2 diabetes.



In the study, researchers from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital found the first genetic evidence that the elimination of the gene for glycogen synthase kinase-3 (GSK-3) in mice sensitizes the animals to insulin.



Insulin is a hormone that helps control sugar (glucose) levels in the blood. In people with type 2 diabetes, the pancreas does not produce enough insulin, or it is not properly used. As a result, sugar accumulates in the blood rather than being absorbed, stored or burned for energy. The study found that by eliminating GSK-3 in mouse models, more sugar became stored in the liver in response to increased insulin sensitivity, indicating that insulin had become more effective.



The study from the laboratory of Dr. Jim Woodgett, Director of the Lunenfeld, and the first scientist to isolate the GSK-3 genes in 1990, made the cover of the October 3 edition of Cell Metabolism.



"We created a 'genetic roadblock' by knocking out this particular gene and this made the mice far more efficient in their ability to use insulin to regulate their blood-sugar levels," said Dr. Woodgett. "Research creates the best medicine and while potential human treatments are likely still years down the road, this study provides strong evidence that chemical inhibitors of this enzyme will be useful for increasing the effective potency of insulin."



The study was co-authored by Drs. Katrina MacAulay and Bradley Doble. Dr. MacAulay was inspired to become a medical researcher specializing in diabetes because her sister, Ailsa MacAulay, suffers from this disease.



"I hope our findings will inspire other researchers around the world to develop treatments that will reduce symptoms of this epidemic disease as well as its associated complications, such as heart disease, liver disease or limb amputation," said Dr. MacAulay.



Currently, more than two million people in Canada suffer from diabetes. It is one of the fastest growing diseases in the country with more than 60,000 new cases diagnosed each year.



Type 2 diabetes makes up about 90 per cent of all cases, with most evidence suggesting that it could be prevented or delayed by maintaining a healthy lifestyle.



"With this research, another piece in the puzzle has been put in place. It advances our understanding of how the complex mechanisms activated by insulin work. Understanding the details of this picture is central to developing new drugs that can help people with diabetes control their blood sugar," says Dr. Diane T. Finegood, Scientific Director of the CIHR-Institute of Nutrition, Metabolism and Diabetes.







The health-care costs associated with diabetes are estimated at more than $1.6 billion by the Public Health Agency of Canada. This study was supported by funding from the Banting and Best Diabetes Centre and the Canadian Institutes of Health Research.



About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital



The Samuel Lunenfeld Research Institute is a recognized leader in the world's research community, with a reputation for top-quality investigators and scientific excellence. It has an extensive impact on scientific advancement and is home to many of Canada's outstanding biomedical researchers.



About Mount Sinai Hospital



Mount Sinai Hospital is an internationally recognized academic health centre affiliated with the University of Toronto. It is known for excellence in the provision of compassionate patient care, innovative education and world-leading research. Our Centres of Excellence are Women's and Infants' Health; Surgery and Oncology; Acute and Chronic Medicine; Laboratory Medicine and Infection Control; and the Samuel Lunenfeld Research Institute. Mount Sinai Hospital brings together Bright Minds and Big Hearts to provide The Best Medicine.



About the Canadian Institutes of Health Research



The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 11,000 health researchers and trainees across Canada.



Source: Noemie Wiggett


Samuel Lunenfeld Research Institute