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Carnivorous Plant Inspires Coating That Resists Just About Any Liquids
http://www.sciencedaily.com/releases/2011/09/110921134526.htm
ScienceDaily (Sep. 22, 2011) — After a rain, the cupped leaf of a pitcher plant becomes a virtually frictionless surface. Sweet-smelling and elegant, the carnivore attracts ants, spiders, and even little frogs. One by one, they slide to their doom.
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Adopting the plant's slick strategy, a group of applied scientists at Harvard have created a material that repels just about any type of liquid, including blood and oil, and does so even under harsh conditions like high pressure and freezing temperatures.
The bio-inspired liquid repellence technology, described in the September 22 issue of Nature, should find applications in biomedical fluid handling, fuel transport, and anti-fouling and anti-icing technologies. It could even lead to self-cleaning windows and improved optical devices.
"Inspired by the pitcher plant, we developed a new coating that outperforms its natural and synthetic counterparts and provides a simple and versatile solution for liquid and solid repellency," says lead author Joanna Aizenberg, Amy Smith Berylson Professor of Materials Science at the Harvard School of Engineering and Applied Sciences (SEAS), Director of the Kavli Institute for Bionano Science and Technology at Harvard, and a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard.
By contrast, current state-of-the-art liquid repellent surfaces have taken cues from a different member of the plant world. The leaves of the lotus resist water due to the tiny microtextures on the surface; droplets balance on the cushion of air on the tips of the surface and bead up.
The so-called lotus effect, however, does not work well for organic or complex liquids. Moreover, if the surface is damaged (e.g., scratched) or subject to extreme conditions, liquid drops tend to stick to or sink into the textures rather than roll away. Finally, it has proven costly and difficult to manufacture surfaces based on the lotus strategy.
The pitcher plant takes a fundamentally different approach. Instead of using burr-like, air-filled nanostructures to repel water, the plant locks in a water layer, creating a slick coating on the top. In short, the fluid itself becomes the repellent surface.
"The effect is similar to when a car hydroplanes, the tires literally gliding on the water rather than the road," says lead author Tak-Sing Wong, a postdoctoral fellow in the Aizenberg lab. "In the case of the unlucky ants, the oil on the bottom of their feet will not stick to the slippery coating on the plant. It's like oil floating on the surface of a puddle."
Inspired by the pitcher plant's elegant solution, the scientists designed a strategy for creating slippery surfaces by infusing a nano/microstructured porous material with a lubricating fluid. They are calling the resulting bio-inspired surfaces "SLIPS" (Slippery Liquid-Infused Porous Surfaces).
"Like the pitcher plant, SLIPS are slippery for insects, but they are now designed to do much more: they repel a wide variety of liquids and solids," says Aizenberg. SLIPS show virtually no retention, as very little tilt is needed to coax the liquid or solid into sliding down and off the surface.
"The repellent fluid surface offers additional benefits, as it is intrinsically smooth and free of defects," says Wong. "Even after we damage a sample by scraping it with a knife or blade, the surface repairs itself almost instantaneously and the repellent qualities remain, making SLIPS self-healing." Unlike the lotus, the SLIPS can be made optically transparent, and therefore ideal for optical applications and self-cleaning, clear surfaces.
In addition, the near frictionless effect persists under extreme conditions: high pressures (as much as 675 atmospheres, equivalent to seven kilometers under the sea) and humidity, and in colder temperatures. The team conducted studies outside after a snowstorm; SLIPS withstood the freezing temperatures and even repelled ice.
"Not only is our bio-inspired surface able to work in a variety of conditions, but it is also simple and cheap to manufacture," says co-author Sung Hoon Kang, a Ph.D. candidate in the Aizenberg lab. "It is easily scalable because you can choose just about any porous material and a variety of liquids."
To see if the surface was truly up to nature's high standards, they even did a few experiments with ants. In tests, the insects slid off the artificial surface or retreated to safer ground after only a few timorous steps.
The researchers anticipate that the pitcher plant-inspired technology, for which they are seeking a patent, could one day be used for fuel- and water-transport pipes, and medical tubing (such as catheters and blood transfusion systems), which are sensitive to drag and pressure and are compromised by unwanted liquid-surface interactions. Other potential applications include self-cleaning windows and surfaces that resist bacteria and other types of fouling (such as the buildup that forms on ship hulls). The advance may also find applications in ice-resistant materials and may lead to anti-sticking surfaces that repel fingerprints or graffiti.
"The versatility of SLIPS, their robustness and unique ability to self-heal makes it possible to design these surfaces for use almost anywhere, even under extreme temperature and pressure conditions," says Aizenberg. "It potentially opens up applications in harsh environments, such as polar or deep sea exploration, where no satisfactory solutions exist at present. Everything SLIPS!"
Aizenberg is also Professor of Chemistry and Chemical Biology in the Department of Chemistry and Chemical Biology, and Susan S. and Kenneth L. Wallach Professor at the Radcliffe Institute for Advanced Study. Her co-authors included Tak-Sing Wong, Sung Hoon Kang, Sindy K.Y. Tang, Benjamin D. Hatton, and Alison Grinthal, all at SEAS, and Elizabeth J. Smythe, at the Schlumberger-Doll Research Center
Biomimetic Microsystems
http://wyss.harvard.edu/viewpage/100/biomimetic-microsystems
A flexible microfluidic organ-on-a-chip system. Learn more...
When scientists started fabricating microchips from silicon they opened doors to the modern age of electronics. Now, the Biomimetic Microsystems Platform is modifying these methods of miniaturization to build functional circuits with living cells as components. Researchers in this platform are building tiny, complex, three-dimensional models of human organs that can be used to treat patients, as well as replace costly and time-consuming animal studies that currently hamper drug development.
Human organs-on-a-chip
Cells normally exist in complex organ systems that are fed by blood vessels and affected by environmental changes, such as the expansion and contraction of lung tissues during inspiration and expiration. These conditions cannot be replicated in an ordinary Petri dish, so cells in culture do not behave as they would in the body, and cell-based research provides only limited information about the impact of a particular drug or toxin. To fill the gap, scientists normally rely on animal testing, but animal models are notoriously bad at predicting typical human responses to medications, and they are costly. The Biomimetic Microsystems team is addressing these shortcomings by replicating complex organ structures with patterns microetched into flexible biocompatible materials. These patterns can be shaped into channels containing blood capillaries that interface with neighboring epithelial tissues, like they do in living organs. These tissue-tissue interfaces distort and recoil elastically when stretched, and mimic other features of an organ's normal microstructure. This approach enables Wyss Institute scientists to engineer model 'organs-on-a-chip' that mimic normal the complex interactions between living tissues within an organ, as well as the physical cues that cells normally experience in the body. These systems, developed with human cells, are intended to make drug development and toxicology screening more reliable, while obviating the need for animal testing. Similar systems are being developed as therapeutic devices, such as an artificial spleen used to clear blood of pathogens in patients with sepsis.
Promoting low-cost diagnostics
A paper-based microfluidic analytical system. Learn more...
Whether in a village in India or a pharmaceutical laboratory, clinicians and researchers share a need for reliable, inexpensive tools that can be operated by untrained workers. Wyss researchers are developing screening tools based on coated paper that could be produced very cheaply and used in non-sterile environments to replace expensive laboratory equipment. These low-cost devices use polymers that repel water to steer blood or urine along tiny channels. There, the fluids interact with chemicals that change color if they detect disease indicators, such as the signature high glucose levels of diabetes. Results could be read by a layperson and called in by cell phone, allowing doctors to remotely diagnose and treat patients in impoverished rural areas. Institute scientists are exploring use of the same paper-based approach to create low-cost diagnostic devices and laboratory tools that incorporate living cells grown within the interstices of the paper in distinct three dimensional patterns that recreate complex tissue architecture and reconstitute tissue and organ level functions.
Initial target applications
•Human organs-on-a-chip
·Replacements for animal testing for drug discovery and toxicology
·Model systems for mechanistic analysis in physically relevant context
•Biochip-based therapeutics
·Extracorporeal devices for sepsis therapy, stem cell isolation, cancer therapy
·Implantable devices for replacement of organ function
•Low-cost diagnostics
·Disposable, inexpensive microfluidic systems for disease diagnosis and signal detection, including a Rapid Sepsis Diagnostic Device
Rapid Sepsis Diagnostic Device
http://wyss.harvard.edu/viewpage/234
A disposable Sepsis Diagnostic Device that can quantitatively identify pathogen class and type within one hour after blood collection
Critical Need for a Rapid Sepsis Diagnostic
Sepsis is a life-threatening infectious disease caused by blood-borne microbial pathogens. With more than 18 million cases occurring worldwide each year and more than 6 million deaths, sepsis is a huge clinical problem [Source: Frost & Sullivan]. The current standard of care involves culturing blood to identify the pathogen, while simultaneously initiating administration of broad-spectrum antibiotics. Unfortunately, treatment with the wrong antibiotic is often ineffective and, because anti-fungal drugs have significant toxicities, they are commonly not administered until a positive blood culture is reported (usually between 2 to 7 days). Thus, there is a critical unmet medical need for the rapid diagnosis of fungal and bacterial pathogens so that physicians can immediately choose the most effective therapy for immediate administration when sepsis is suspected.
The Wyss Rapid Sepsis Diagnostic
The Wyss Sepsis Diagnostic Microdevice leverages recent developments in organ-on-chip microfluidic technologies that mimic the blood-cleansing functions of the human spleen. This microtechnology is based on the capture of pathogens from the blood sample flowing within a microfluidic device using magnetic microbeads coated with a recombinant human opsonin - Mannose Binding Lectin (MBL). This natural blood opsonin binds to carbohydrate components that are found in the cell walls of gram negative and positive bacteria, as well as fungi, viruses and parasites, but not in the cell membranes of mammalian cells. Once the pathogens have been captured and separated from the blood, they are identified using multiplexed reagents, including fluorescent dyes, antibodies and other molecular diagnostics. Novel tags generated using a new multiplicative labeling approach developed at the Wyss Institute allows identification of scores to hundreds of different pathogens simultaneously in a single fluorescence field of view within 1 hour after blood sampling.
Automated Instrument with Disposable Cassettes
The Wyss Rapid Diagnostic Device is an automated instrument with a disposable cassette. A Vacutainer tube containing a blood sample removed from a patient is inserted into the cassette, which is then placed within the benchtop read-out instrument. The instrument controls blood flow through the microfluidic channels, mixer and micromagnetic separator. A miniaturized, high resolution, auto-focusing, 5-channel fluorescence microscope contained within the instrument is used to detect the pathogens and quantitate their number. Integrated software and a user-friendly interface provide a simple readout indicating pathogen type and blood concentration. The device can be used to select appropriate antibiotic and antifungal therapies within hours after the patient enters the hospital, thus greatly decreasing hospital costs and saving lives.
Technical References
Micromagnetic-microfluidic blood cleansing device
Lab on a Chip. 2009 May 7.
The medical power of attraction
Highlights in Chemical Technology. 2009 Feb 25.
Contact us:
techinfo@wyss.harvard.edu
dannol48,
Thank you for sharing your thoughts.
When I had read about the DARPA project objective by Timothy Broderick, MD (Project Manager), I was amazed for a long time at what they had put together and what their expectations were for what they called DLTs. (It reminded me of a story of Steve Jobs when he had called for his first meeting about how he wanted a musical device with capacities and size unheard of before. People present thought he was unreasonable but he demanded it and subsequently Apple came out with the Ipod! It single handedly changed the fortunes of a sagging music industry) A lot of what they have asked for is already present in the market and looks like the system has to be tweaked and integrated to get to what is desired. Although it is a very formidable task, I do believe this will come to fruition.
Rereading Dr. Broderick's presentation also gave me a feeling that part of their idea of DLTs for "sepsis" is to diagnose and treat an infection before it reaches the sepsis stage. The presentation specifically emphasizes "Early detection and treatment of infection increases survival rate". There is also a mention of Bacteria doubling time being 300 minutes. A lot of patients come into a hospital and become septic because of a variety of conditions, either they have an infection already, they are immunocompromised, etc., during their hospital stay. Certain categories of patients may be considered high risk for sepsis and they may be candidates for the DLT pathway early in the process.
This is a much needed revolutionary concept which can change the whole paradigm of treating infections at different stages. Sepsis is a huge cost factor in healthcare all over the world. DARPA has this in mind beacause they very clearly mention statistics for civilian deaths because of sepsis in 2009 with the number being 215,000 and the associated cost - 16.7B. The goal is to save atleast 43,000 US lives and $3.3B annually!!!
I am assuming that AEMD will have to work with WYSS and integrate their expertise with the HP.
In the short term - Major validation for the company translating into more respect and interest for whatever they present including HIV/ HCV treatment, Cancer diagnosis and management etc.,
bbarry and Twister, welcome to the board.
About Aethlon (Updated website)-
The Aethlon Medical mission is to create innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT™ System is a revenue-stage technology platform that provides the basis for a new class of therapeutics that target the selective removal of disease enabling particles from the entire circulatory system. The Aethlon ADAPT™ product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer; HER2osome™ to address HER2+ breast cancer, and a medical device being developed under a contract with the Defense Advanced Research Projects Agency (DARPA) that would reduce the incidence of sepsis in combat-injured soldiers and civilians.
ELLSA™ Exosome Assay
To support our therapeutic advances to eliminate the presence of deleterious exosomes from circulation, our researchers needed to create a diagnostic tool that would provide greater detection sensitivity than other products available in the marketplace. The result was ELLSA™, an enzyme-linked lectin-specific assay that has demonstrated the ability to identify and quantify the presence of exosomes underlying human immunodeficiency virus (HIV), tuberculosis (TB), and all forms of cancer tested to date. As our focus is directed towards advancing the pipeline of Aethlon ADAPT™ system therapies, we plan to license or sell this technology to an organization already established in the research diagnostics field.
The Aethlon ADAPT™ System(From updated web site)
The Aethlon ADAPT™ system is an adaptive dialysis-like affinity platform technology that provides the foundation for an entirely new class of therapeutics that target the selective clearance of harmful agents from the entire circulatory system. Therapies that evolve from the Aethlon ADAPT™ system overcome the historic limitation of extracorporeal strategies that indiscriminately adsorb or remove particles solely by molecule size. In function, our device platform allows the immobilization of single or multiple affinity drug agents in the outer-capillary space of plasma membrane technologies as a means to provide rapid real-time clearance of corresponding targets without adding drug toxicity or interaction risks to established therapies. Beyond providing a novel regulatory and commercialization pathway for affinity drug agents, Aethlon ADAPT™ therapies can be implemented for use within the global infrastructure of dialysis machines and CRRT systems already located in hospitals and clinics.
At present, the Aethlon ADAPT™ product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer; HER2osome™ to target HER2+ breast cancer, and a medical device being developed under a $6.8 million contract with the Defense Advanced Research Projects Agency (DARPA) that would reduce the incidence of sepsis in combat-injured soldiers and civilians. As we advance our current pipeline of therapies toward market, we plan to further leverage our ADAPT™ system to generate new revenue sources through future government contracts or grants, and collaborations with organizations representing the pharmaceutical, biotechnology and medical device industry.
andy55q
Welcome to the board and thank you. I saw your post earlier on my cell phone. Finally!
dannol48-thank you EOM
Medical tourism: A faraway health fix
http://www.chicagotribune.com/health/sc-health-0803-medical-tourism-20110803,0,4286362,full.story
Medical Tourism in Asia
http://www.youtube.com/embed/xJCyaVkR7Lg
Targeted anticancers should mean smaller trials, researchers argue
http://www.pharmatimes.com/Article/11-09-27/Targeted_anticancers_should_mean_smaller_trials_researchers_argue.aspx
States Still Unclear on Health Insurance Exchanges (There seems to be more of Govt. involvement in the way health care is going to be practised. This may bode well for AEMD as it may potentially decrease the costs involved with treating chronic diseases.)
CRYSTAL CITY, Virginia (Reuters) Sep 21 - State health officials weighing the 2014 arrival of insurance exchanges heard little about the federally run option in a two-day meeting with U.S. health regulators.
States are facing three options in building the exchanges, a key aspect of President Barack Obama's healthcare overhaul passed last year: run one themselves, do it in a partnership with the federal government or let the Health and Human Services Department take over entirely.
"I haven't learned anything new about what the federal exchange would look like," said one state insurance official who attended the meeting that was closed to reporters.
Representatives from 46 states, the District of Columbia and two U.S. territories -- those that received federal grants to develop insurance exchanges -- gathered at a hotel here on Monday and Tuesday.
The exchanges are envisioned as open marketplaces where uninsured people and small businesses can band together to negotiate cheaper rates. With deadlines looming, there is concern about their smooth and timely roll-out, especially as many Republican governors seek to block implementation of the law supported largely by Democratic lawmakers.
According to slides posted online by the Centers for Medicare and Medicaid Services, which oversees progress on the exchanges, the federally-run exchanges will "look to state standards to harmonize rules inside and outside the exchanges" and could charge insurers user fees to run it.
It did become clear, three attendees said, that states partnering with the federal government would effectively give up authority over determining who is eligible to enroll in an exchange.
"That was an interesting thing to figure out, that wasn't something that a state could keep... at least initially," said April Todd-Malmlov, with Minnesota's Department of Health.
She said some states were concerned what that meant for their Medicaid programs for the poor, which have historically been managed at the state level.
Federal officials on Monday proposed more details on the partnership model, outlining some choices in what the federal government can do as a partner.
The partnership model, meant largely to help states transition into their own exchanges, offers three options. One lets states take the lead with participating insurance plans, another gives states the role of assisting consumers in understanding their options, and the third includes both.
A Medical Device Strategy To Inhibit HER2+ Breast Cancer Progression" Released by Aethlon Medical, Inc.
http://www.aethlonmedical.com/assets/001/5080.pdf
Viral hepatitis
Published Online First 19 September 2011
Impact of hepatitis C triple therapy availability upon the number of patients to be treated and associated costs in France: a model-based analysis
Results Compared with the 5100 G1 patients treated in 2010, the number of G1 patients receiving treatment in 2012 would be 15?000 in scenario 1, 18?300 in scenario 2 and 19?400 in scenario 3, among whom 2.5–3.7% may receive PEG-IFN/RBV and 96.3–97.5% PEG-IFN/RBV+PI. Costs associated with this regimen use ranged from 497 to 638 million Euros.
Conclusion These model-based estimates indicate that new anti-HCV treatments may result in a three- to fourfold increase in the number of G1 patients to be treated in France in 2012
dannol48
Some good thoughts there.
At one time the thought had come to me about animal studies for another devise company I am invested in. I think the problem is that clinical studies even in animals would be far too expensive for a small startup company with limited financial resources, unless ofcourse they have fundings, grants etc., Cancer is very common in certain breeds of animals and if JJ can pull another research collaboration out of his hat it certianly may be a good source of revenue. Such research can possibly be a prologue to human studies also. I know quite a few people who have put their pets to sleep because of cancer and related issues.
Since 1970s, 'Unimagined Progress' Seen in Cancer Research
By Emily P. Walker, Washington Correspondent, MedPage Today
Published: September 20, 2011
The nation is in a "defining time" to defeat cancer given the "unimagined progress" in cancer research and treatment options, according to a new report from the American Association for Cancer Research (AACR).
The optimistic report on the much-feared disease that affects 1.6 million Americans each year trumpets the remarkable scientific advances made in the past few decades in cancer and biomedicine that are enabling a "scientific revolution" of personalized cancer treatments.
The report was released by the AACR to commemorate the 40th anniversary of the signing of the National Cancer Act in 1971. That law "set the Nation on a course to conquer cancer," according to the report authors, by laying the groundwork for funding research grant programs through the National Institutes of Health (NIH) and the National Cancer Institute.
Back in the 1970s, scientists had only a limited knowledge of cancer. For instance, "cancer" was at first thought to be one disease, but is now thought to be about 200 different diseases. Today, it is understood why and how cancer forms and spreads throughout the body, with mutations in genes being the cause of "most, if not all cancers," according to AACR.
"Previously the organ of origin, such as lung, brain, or breast, and so on, defined an individual's cancer; now it is defined by the intrinsic molecular changes driving the cancer, irrespective of its location," the report authors explained.
The Human Genome Project identified more than 290 genes related to the cause of cancer, and the list of cancer-related genes will continue to grow as projects supported by public funds identify the genomic changes in different types of cancer, the authors said.
Because of the knowledge of specific molecular defects that cause cancer, along with advances in biology, chemistry, and computational modeling, scientists can now identify and develop new drugs specifically targeted to block malfunctions that cause cancer cells to multiply.
There are now 32 FDA-approved targeted cancer drugs -- including imatinib (Gleevec) for myelogenous leukemia and trastuzumab (Herceptin) for HER2-positive breast cancer -- which are less toxic than cytotoxic chemotherapy drugs, which kill both cancerous and healthy cells.
In addition, advances in chemotherapy, surgery, radiation, and palliative care have been important improvements in patient care during the past four decades, the authors said. And, in some cases, new combinations of chemotherapy drugs have led to significant increases in survival rates and even to cures for some cancers such as childhood acute lymphoblastic leukemia, Hodgkin's disease, aggressive lymphomas, and testicular cancers.
The authors also point to advancements in public health -- such as anti-smoking policies -- as major drivers of lowering preventable cancer rates. In 1965, more than 40% of the U.S. population smoked, but today about 20% smoke, according to the AACR.
"This has saved millions of lives that would otherwise have been lost not only to lung cancer, but also to the 17 other types of cancer directly related to tobacco use," wrote the report authors.
In addition, screening for cancer also has led to five-year-survival rates for cervical, breast, and prostate cancers being over 90%, they said.
The field of "chemoprevention" is now robust, thanks to the growing understanding of the molecular basis of cancer. There are currently 150 chemoprevention trials under way, testing agents to reduce cancer incidence in high-risk populations.
To date, there more than 12 million cancer survivors in the U.S. and cancer mortality rates have steadily declined since 1990.
But despite advances in identifying cancer-causing genetic mutations, in many cases, cancer still confounds doctors, researchers, and patients, and continues to claim hundreds of thousands of lives each year.
Each year, 1.6 million Americans are diagnosed with cancer, and more 570,000 people die each year from the disease. One of every three women and one out of every two men will develop cancer in their lifetimes.
"Unfortunately, for all of these scientific successes, we are continually humbled by cancer's ability to defy expectations and change and adapt in response to treatment," the report authors wrote, adding, "Clearly, cancer's complexity still stands as a major challenge in cancer research."
Which is why additional research is needed, including developing a network of tissue banks and a massive infrastructure to store, manage, and analyze tissue as well as the vast amounts of genomic and molecular data already available, the AACR said.
Congress doubled the NIH's budget in 2003, but since then it has remained essentially flat. Currently, the NIH has a budget of $31.2 billion. The AACR recommends that Congress increase NIH's budget each year at 5% more than the inflation rate in the biomedical industry.
As for the future of cancer research, the authors said the field is evolving so fast, it's difficult to know what future technology will have the greatest impact on the field.
"Technology is moving at a dizzying pace," the authors said. Nanotechnology, stem cells, cancer metabolism, the microbiome, noncoding RNAs, to name a few, all could hold promise for banishing cancer as a disease that future generations will have to worry about.
"We live in an unprecedented time of scientific opportunities, and our commitment to prevent and cure cancer has never been stronger," the authors concluded.
Chronic hepatitis C in children - review of natural history at a National Centre
Abdel–Hady M et al. – Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of hepatitis C virus infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis
Targeting HIV's sugar coating ( Does this infringe on any patents which AEMD holds?)
http://www.eurekalert.org/pub_releases/2011-09/uou-ths092211.php
New microbicide may block AIDS virus from infecting cells
SALT LAKE CITY, Sept. 23, 2011 – University of Utah researchers have discovered a new class of compounds that stick to the sugary coating of the AIDS virus and inhibit it from infecting cells – an early step toward a new treatment to prevent sexual transmission of the virus.
Development and laboratory testing of the potential new microbicide to prevent human immunodeficiency virus infection is outlined in a study set for online publication by Friday in the journal Molecular Pharmaceutics.
Despite years of research, there is only one effective microbicide to prevent sexual transmission of HIV, which causes AIDS, or acquired immune deficiency syndrome. Microbicide development has focused on gels and other treatments that would be applied vaginally by women, particularly in Africa and other developing regions.
To establish infection, HIV must first enter the cells of a host organism and then take control of the cells' replication machinery to make copies of itself. Those HIV copies in turn infect other cells. These two steps of the HIV life cycle, known as viral entry and viral replication, each provide a potential target for anti-AIDS medicines.
"Most of the anti-HIV drugs in clinical trials target the machinery involved in viral replication," says the study's senior author, Patrick F. Kiser, associate professor of bioengineering and adjunct associate professor of pharmaceutics and pharmaceutical chemistry at the University of Utah.
"There is a gap in the HIV treatment pipeline for cost-effective and mass-producible viral entry inhibitors that can inactivate the virus before it has a chance to interact with target cells," he says.
Kiser conducted the study with Alamelu Mahalingham, a University of Utah graduate student in pharmaceutics and pharmaceutical chemistry; Anthony Geonnotti of Duke University Medical Center in Durham, N.C.; and Jan Balzarini of Catholic University of Leuven in Belgium.
The research was funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, the Catholic University of Leuven, Belgium, and the Fund for Scientific Research, also in Belgium.
Synthetic Lectins Inhibit HIV from Entering Cells
Lectins are a group of molecules found throughout nature that interact and bind with specific sugars. HIV is coated with sugars that help to hide it from the immune system. Previous research has shown that lectins derived from plants and bacteria inhibit the entry of HIV into cells by binding to sugars found on the envelope coating the virus.
However, the cost of producing and purifying natural lectins is prohibitively high. So Kiser and his colleagues developed and evaluated the anti-HIV activity of synthetic lectins based on a compound called benzoboroxole, or BzB, which sticks to sugars found on the HIV envelope.
Kiser and his colleagues found that these BzB-based lectins were capable of binding to sugar residues on HIV, but the bond was too weak to be useful. To improve binding, they developed polymers of the synthetic lectins. The polymers are larger molecules made up of repeating subunits, which contained multiple BzB binding sites. The researchers discovered that increasing the number and density of BzB binding sites on the synthetic lectins made the substances better able to bind to the AIDS virus and thus have increased antiviral activity.
"The polymers we made are so active against HIV that dissolving about one sugar cube's weight of the benzoboroxole polymer in a bath tub of water would be enough to inhibit HIV infection in cells," says Kiser.
Depending on the strain, HIV displays significant variations in its viral envelope, so it is important to evaluate the efficacy of any potential new treatment against many different HIV strains.
Kiser and his colleagues found that their synthetic lectins not only showed similar activity across a broad spectrum of HIV strains, but also were specific to HIV and didn't affect other viruses with envelopes.
The scientists also tested the anti-HIV activity of the synthetic lectins in the presence of fructose, a sugar present in semen, which could potentially compromise the activity of lectin-based drugs because it presents an alternative binding site. However, the researchers found that the antiviral activity of the synthetic lectins was fully preserved in the presence of fructose.
"The characteristics of an ideal anti-HIV microbicide include potency, broad-spectrum activity, selective inhibition, mass producibility and biocompatibility," says Kiser. "These benzoboroxole-based synthetic lectins seem to meet all of those criteria and present an affordable and scalable potential intervention for preventing sexual transmission in regions where HIV is pandemic."
Kiser says future research will focus on evaluating the ability of synthetic lectins to prevent HIV transmission in tissues taken from the human body, with later testing in primates. Kiser and his colleagues are also developing a gel form of the polymers, which could be used as a topical treatment for preventing sexual HIV transmission.
dannol48,
I do not understand the details company finances at all. You may be right about the financial situation with AEMD regarding to the DARPA contract. But given the fact that JJ knew in June about being selected for the contract, do you think he has had enough time to fix the issue?
He has done an amazing job in making the multi-faceted product it is. I find it more fascinating as he is not even from the medical field. What comforts me is that the HP is a proven safe product. Drugs have to go through multiple trials to show safety before showing efficacy. In the HP we have one product which address some major medical issues all over the world. All we need are clinical trials showing the results. The health care industry is going through a tremendous phase of cost curtailment which I am sure is putting pressure at every level. A lot of this pressure is from the govt. This has actually made me more hopeful in terms of AEMD as I believe it can significantly cut the costs of treating some major diseases(and hopefully, if proven to be effective against some cancers, it may possibly change the paradigm of cancer care).
A few years back I would not have been hopeful about AEMD just on the basis of treating HCV as, even if it significantly decreases the viral load, I am not sure if it would have been accepted by the big pharmas. There are some very powerful groups out there which would have been difficult for AEMD to break into. But after reading Dr. T. Broderick's vision with DLT, I think the govt. has understood what it entails and they have big plans for DLT for the civilian population as well.
I am still not sure about the role of the HP in oncology, although am very hopeful. There are a lot of unanswered questions and it will still be a while before we get a clear picture of the role of the HP in this field. Having said that, if the HP is proven effective in being effective in some way (i.e with/without chemotherapy, decreasing exosome, etc.,) against even one tumor to start with then we know that will bring in a lot of new investigators and maybe funding. Improving cancer morbidity and mortality even by a few months is a major thing.
I hope you keep on posting when you feel it is appropriate. Thank you.
Dannol48
Welcome to the board. I had an extremely busy day and just saw your message. Initially when I read your message it came as a surprise that the govt. looks into the finances of a company before awarding a contract- but it does make a lot of sense.
Have you been following AEMD for a while?
Inner Workings of Virus Responsible for Rare Skin Cancer (Dr. Moore should be made aware of the HP)
http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=2436
• Merkel cell polyomavirus induces cell transformation in unexpected ways.
• Discoveries help narrow possible treatments.
• Virus functions differently than other cancer-related viruses.
SAN FRANCISCO — Scientists at the University of Pittsburgh Cancer Institute have begun to uncover how the virus that causes most Merkel cell carcinoma – a rare and aggressive skin cancer – operates, meaning that a rational chemotherapeutic target for this cancer could be developed in the near future.
Patrick Moore, M.D., M.P.H., an American Cancer Society professor in the laboratory of Yuan Chang and Patrick Moore at the University of Pittsburgh Cancer Institute in Pittsburgh, Pa., presented these study results at the Second AACR International Conference on Frontiers in Basic Cancer Research, held here Sept. 14-18, 2011.
Merkel cell carcinoma is a rare and highly aggressive cancer, the incidence of which has increased fourfold during the last 20 years, particularly in immunosuppressed populations, according to Moore.
“Unfortunately, Merkel cell carcinoma is difficult to treat and clinical trials of chemotherapeutics have been disappointing in affecting clinical course and survival,” he said. “Discovery of the molecular cause for this cancer provides opportunities to directly target the cellular pathways that are perturbed by the virus.”
In 2008, Moore and colleagues discovered Merkel cell polyomavirus (MCV), the virus that causes most Merkel cell carcinoma. Polyoma refers to the ability of some members of this family to produce multiple tumors in animal models. Their laboratory previously discovered the herpes virus that causes Kaposi’s sarcoma, cancer that commonly occurs in patients with AIDS.
“MCV is the first polyomavirus to be consistently associated with human cancer, and is believed to cause 80 percent of Merkel cell carcinoma,” Moore said.
MCV is a natural component of the human skin and is usually harmless, according to Moore. In fact, most adults carry the virus in some part of their skin cells. However, if someone becomes immunodeficient and the virus undergoes specific mutations, then it can generate Merkel cell carcinoma.
In the three years since they discovered MCV, this group has also discovered several of the unique characteristics of the virus. Most recently, their studies showed that MCV small T antigen protein is a new oncogene that can contribute to abnormal cell growth in both rodent and human cells. In addition, MCV does not act the same as other polyomaviruses that have served as classic models of cancer. These other polyomaviruses depend on viral interaction with the enzyme PP2A and heat-shock proteins; MCV interacts with them, but does not depend on them.
Moore and colleagues found that MCV could still cause the abnormal cell growth even after abolishing PP2A and heat-shock protein binding sites. The researchers hope to develop treatments that will directly target the cellular pathways affected by this virus.
“We are making headway on this approach now and have tested more than 1,350 drugs to identify better methods to treat this virus-caused cancer,” Moore said.
Avoiding Fatal Responses to Flu Infection (Applies to CTSO also)
http://www.sciencedaily.com/releases/2011/09/110915134410.htm
Exosomes in Alzheimer's!
http://viin.org.au/members/623/
Research Activities
The Hill lab focuses on neurodegenerative diseases caused by protein misfolding and aggregation, in particular Creutzfeldt-Jakob disease (CJD) and Alzheimer’s disease (AD).
Prion diseases are transmissible neurodegenerative disorders associated with a novel infectious agent known as a prion. We are interested in dissecting the pathways involved in the conversion of the normal cellular form of the prion protein (PrPC) to the abnormal, infectious disease associated isoform (PrPSc). Current work involves looking at cell to cell infection via exosomes, mutational analysis of specific motifs thought to play a role in protein misfolding, protein trafficking and identification of the toxic species involved in CJD and AD.
Our work on exosomes is also related to immunology fields as these vesicles are released by most cell types and have potential roles in antigenic signalling.
Techniques/Expertise
Our work involves cell culture, expression and purification of recombinant proteins, 2-dimensional gel electrophoresis, DIGE, site directed mutagenesis, confocal microscopy, real-time PCR, miRNA analysis, RNAi, exosome isolation.
Collaborations
A/Prof Roberto Cappai and A/Prof Kevin Barnham (Pathology/Bio21), A/Prof Steve Collins and Dr Vicki Lawson (Pathology), Dr Tony White (Centre for Neuroscience), Dr Paul Donnelly (Chemistry/Bio21). We also have collaborations with laboratories in Sydney, Melbourne, France, Brazil, and the UK.
Disease Models
Mouse models of prion disease (wild-type and transgenic).
Genetically Modified Organisms
Prion protein knockout and overexpressing mice.
Exosomes in Oncology
http://www.selectbiosciences.com/conferences/EO2012/
Welcome to the Exosomes in Oncology track of the Genomics Research conference and exhibition. This year's event will be held in Boston.
Other conference tracks at this event include RNAi & miRNA, Advances in qPCR, Epigenetics and Next Gen Sequencing. Registered delegates will have access to all five meetings ensuring a very cost-effective trip.
Register now and save up to $500!
Agenda Topics
To be announced
Sponsorship and Exhibition Opportunities
Aaron Woodley, Exhibition Manager
a.woodley@selectbiosciences.com
Call for Papers
Deadline: 21 October 2011
If you would like to be considered for an oral presentation at this meeting, submit an abstract for review now!
Call for Posters
Deadline: 12 March 2012
You can also present your research on a poster while attending the meeting. Submit an abstract for consideration now!
Diagnostic Applications of Exosomes
http://www.selectbiosciences.com/conferences/DAE2012/
Circulating tumor cell
From Wikipedia, the free encyclopedia
Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. CTCs may constitute seeds for subsequent growth of additional tumors (metastasis) in different tissues.
In 1869 Thomas Ashworth obeserved circulating tumor cells in the blood of a man with metastatic cancer. He postulated that “cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumours existing in the same person”. A thorough comparison of the morphology of the circulating cells to tumor cells from different lesions led Ashworth to conclude that “One thing is certain, that if they [CTC] came from an existing cancer structure, they must have passed through the greater part of the circulatory system to have arrived at the internal saphena vein of the sound leg”.[1] Cancer research has demonstrated the critical role circulating tumor cells play in the metastatic spread of carcinomas.[2] Technology with the requisite sensitivity and reproducibility to detect CTC in patients with metastatic disease was developed only recently.[3][4][5][6][7]
Contents
1 Frequency of CTC
2 Clinical utility
3 CellSearch Method
4 Morphological definition
5 Further characterisation of CTC
6 See also
7 References
Frequency of CTC
Figure 1: cell number of various blood cells in whole blood versus CTC
The detection of CTCs may have important prognostic and therapeutic implications but because their numbers can be very small, these cells are not easily detected.[8] Circulating tumor cells are found in frequencies in the order of 1-10 CTC per mL of whole blood in patients with metastatic disease. For comparison, a mL of blood contains a few million white blood cells and a billion red blood cells, see figure 1. This low frequency means that a key component of methods to detect CTC is the enrichment method.
First evidence indicates that CTC markers applied in human medicine are conserved in other species. Five of the more common markers including CK19 are also useful to detect CTC in the blood of dogs with malignant mammary tumors.[9]
[edit] Clinical utility
Figure 2: Kaplan Meier Analysis of overall survival before starting a new line of therapy for patients with metastatic breast, colorectal and prostate cancer. Patients were divided into those with Favorable and Unfavorable CTC (Unfavorable: >5 CTC/7.5mL for breast and prostate, >3 CTC/7.5mL for colon) [10]
To date, a variety of research methods have been developed to isolate and enumerate CTC.[11] The only U.S. Food and Drug Administration (FDA) cleared methodology for enumeration of CTC in whole blood is the CellSearch system.[12] Extensive clinical testing done using this method shows that presence of CTC is a strong prognostic factor for overall survival in patients with metastatic breast, colorectal or prostate cancer, see figure 2 [13][14][15][16][17][18][19]
CellSearch Method
Blood is sampled in an EDTA tube with an added preservative. Upon arrival in the lab, 7.5mL of blood is centrifuged and placed in a preparation system. This system first enriches the tumor cells immunomagnetically by means of ferrofluidic nanoparticles conjugated to epithelial cell adhesion molecule (EpCAM). Subsequently it stains the sample with a nuclear stain, and fluorescent antibody conjugates against CD45 and cytokeratin 8, 18 and 19 (CK). The sample is scanned on an analyzer, which takes images of the nuclear stain, the cytokeratin stain and the CD45 stain. A trained operator looks at the images of cells to identify those cells that are positive for the nuclear stain and the cytokeratin stain and negative for the CD45 stain. If the cell meets these criteria, the operator judges whether the morphology is suitable for a tumor cell. If the total number of tumor cells found is 5 or more, a sample is positive. In studies done on prostate, breast and colon cancer patients, median survival of metastatic patients with positive samples is about half the median survival of metastatic patients with negative samples.
Morphological definition
Morphological appearance is judged by human operators and is therefore subject to large inter operator variation.[20] Several CTC enumeration methods exist which use morphological appearance to identify CTC, which may also apply different morphological criteria. A recent study in prostate cancer showed that many different morphological definitions of circulating tumor cells have similar prognostic value, even though the absolute number of cells found in patients and normal donors varied by more than a decade between different morphological definitions.[21]
Further characterisation of CTC
Some drugs are particularly effective against cancers which fit certain requirements. For example Herceptin is very effective in patients who are Her2 positive, but much less effective in patients who are Her2 negative. Once the primary tumor is removed, biopsy of the current state of the cancer through traditional tissue typing is not possible anymore.[22] Often tissue sections of the primary tumor, removed years prior, are used to do the typing. Further characterisation of CTC may help determining the current tumor phenotype. FISH assays has been performed on CTC to as well as determination of IGF-1R, Her2, Bcl-2, [ERG (gene)|ERG], PTEN, AR status using immunofluorescence.
World Circulating Tumor Cells Summit
http://ctc-summit.com/
The application of CTCs as a predictive biomarker and non-invasive cancer diagnostic holds great promise for drug developers; and the technologies enabling you to achieve this are advancing rapidly.
But there is still a need for increased collaboration and understanding if the industry is to use CTCs to improve cancer survival rates and provide significant cost-savings.
Designed by thought leaders at Centocor, AstraZeneca, Veridex, Eli Lilly, Massachusetts General Hospital and Genentech, the 3rd World Circulating Tumor Cells Summit will focus on how you can practically apply CTCs in the clinic and move one step closer to realizing their commercial potential.
Why Attend?
Building on the huge success of our previous World CTC Summits, this unique industry gathering will again bring together leaders from pharma, biotech and academia, as well as the most innovative technology developers and pioneering clinicians.
If you’d like to go straight to the conference agenda, click here. Or to find out more about the key learning points you will take away from the event, read on…
Richard J. Cote, Professor and Chair, Department of Pathology & Director, Biomedical Nanoscience Institute, University of Miami will show you cutting edge gene expression and sequencing techniques for capturing, counting and characterizing CTCs.
Elizabeth Punnoose, Scientist, Development Oncology Diagnostics, Genentech will reveal the results of recent clinical trials, where CTCs were used as an exploratory marker for lung cancer.
Abraham Tzou, Division of Immunology and Hematology Devices, FDA will discuss regulatory considerations for developing a CTC-derived diagnostic assay.
Nicolo Manaresi, Chief Technology Officer, Silicon Biosystems and David Nelson, President & CEO, Epic Sciences will be among the platform providers showcasing their next-generation technologies and demonstrating their proven utility in the clinic.
Monica Motwani, Director, Oncology Biomarkers, GlaxoSmithKline will explain how CTCs can drive your oncology drug development and be used to make better patient decisions.
To find out what other key issues will be addressed at the meeting, click here to see the agenda and list of speakers.
Here’s What Delegates at Last Year’s Event Had to Say:
“Very valuable, well organized, good diversity of speakers.”
Daiichi-Sankyo
“Groundbreaking.”
Siemens Diagnostics
“I really enjoyed the wealth of knowledge on CTCs. The networking session was of great benefit. As a person new to CTCs, it was wonderful networking with the other attendees.”
Pfizer
“Excellent snapshot on the current status of CTC research, both in clinic as well as in the pharma industry.”
Roche Diagnostics
“A nice balance of vendors, clinicians and researchers in well established, as well as emerging companies. Very useful for key contacts.”
Biofluidica Microtechnologies
Attend the 3rd World Circulating Tumor Cells Summit and be a part of the only purely CTC-focused meeting that brings together all the key stakeholders and provides real solutions to the key challenges in this field.
Pharmaceutical Competitive Intelligence and New Product Planning Conference
http://www.q1productions.com/RXCI/
FDA Announces New Staff Training For Medical Device Reviewers
September 12, 2011
Training a key step to improving device review program, strategic priorities
The U.S. Food and Drug Administration recently announced two new training programs designed to improve the consistency of medical device reviews by enhancing the skills of those reviewing premarket applications at the Center for Devices and Radiological Health (CDRH).
The Reviewer Certification Program, which began as a pilot in April 2010 with participants from CDRH's Division of Anesthesia, General Hospital, and Infection Control and Dental Devices, will launch this month and is intended to include all new device reviewers.
The program includes up to 18 months of training, aimed at complementing the skills and knowledge that new reviewers bring to CDRH from fields such as biomedical engineering and health care. Reviewers in the program will complete online training modules, instructor-led courses, and obtain practical experience in the medical device review process. Courses include medical devices, food and drug law and regulatory requirements, the CDRH review process, device design, and the impact of human factors.
"We are investing resources so that new device reviewers at CDRH are equipped to handle the range of issues that arise during the premarket device reviews," said CDRH director Jeffrey Shuren, M.D. "This investment will improve the quality of submission review and make the process more consistent and predictable."
CDRH is also developing a pilot Experiential Learning Program for premarket reviewers. The program will include visits to academic institutions, manufacturers, research organizations, and health care facilities and is intended to give reviewers a better understanding of how medical devices are designed, manufactured and used. The program will also help new medical device reviewers understand the challenges of technology development and the impact of medical devices on patient care.
"Providing our review staff with opportunities to experience medical device development and use from outside the agency will provide new reviewers with a broader view of the regulatory process for medical devices," Shuren said.
The Experiential Learning Program is in the design stage and scheduled to begin as a pilot program in 2012.
Enhancing staff training is one of the 25 action items listed in the FDA's Plan of Action for Implementation of 510(k) and Science Recommendations announced earlier this year to increase the predictability and transparency of regulatory pathways and to strengthen the 510(k) process. The 510(k) is the most common pathway to market for medical devices.
For more information: CDRH Plan of Action for 510(k) and Science(http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/ucm239448.htm)
About FDA
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
SOURCE: U.S. Food and Drug Administration
Gender, Insurance Type Tied To HPV Infection In Laryngeal Cancer Patients
Main Category: Cervical Cancer / HPV Vaccine
Article Date: 15 Sep 2011 - 1:00 PDT
(Just like in patients with HIV and HCV combo where the HP would theoretically kill 2 birds with one stone if the HP would also eradicate HPV and control the cancer also)
Healthcare Prof:
The human papillomavirus (HPV) is more likely to be found in tumors of laryngeal cancer patients who are male and those with private health insurance, according to a new study from researchers at Henry Ford Hospital.
The study also reveals that laryngeal cancer patients with Medicare, who tend to be 65 and older, have a lower prevalence of HPV, suggesting that HPV infection may be closely tied to age and changes in sexual behavior with younger generations.
"Our study is an important step forward in learning more about HPV trends, and ultimately learning how HPV positive status could impact screening and treatment for laryngeal cancer patients," says study lead author Josena Stephen, M.D., a research scientist investigator in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford.
"This is relevant because HPV positive patients, particularly those with oropharyngeal cancer, have improved survival. For laryngeal cancer this remains to be established."
Results from the study will be presented Wednesday, Sept. 14 in San Francisco at the American Academy of Otolaryngology Head & Neck Surgery Foundation Annual Meeting. The research was funded by a NIH grant.
In 2010, an estimated 12,700 new cases of laryngeal cancer cancers that start in the voice box were diagnosed, according to the National Cancer Institute. Like other head and neck cancers, risk factors include smoking, alcohol consumption. HPV is a risk factor in some head and neck cancers, such as oropharyngeal cancer.
Prior HPV-related research for head and neck cancer has been focused on oropharyngeal cancer, which includes the base of the tongue, the tonsils, the soft palate (back of the mouth), and the walls of the pharynx (throat).
In those studies, HPV-positive patients with oropharyngeal cancer were shown to have a reduced risk of death and respond better to treatment. With laryngeal cancer, little is known about HPV prevalence and how HPV might impact survival.
The Henry Ford study takes a closer look at HPV prevalence based on race, gender and insurance type, as well as stage and survival for laryngeal cancer patients.
The study group included information and tissue samples for 79 patients, of which 60 were male and 19 were female. The patients were categorized into two groups: no treatment and treatment (radiation and/or chemotherapy).
Most notably, 41% percent of the study group was African American, and the majority of the study group (95%) had a history of smoking. The study found HPV-positive status for laryngeal cancer to be significantly tied to gender, with 34% of men and 5% of women having HPV.
Insurance type also was associated with HPV status. The majority of private insurance patients were found to have HPV, while the Medicare group had far more HPV-negative patients than HPV-positive patients.
HPV had a lower prevalence in African American patients. It was detected in 16% of African Americans as compared to 33% of Caucasian in the study.
"It's very revealing what's embedded in this study, particularly for African American patients," says co-author Maria J. Worsham, Ph.D., director of research in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford.
"We know that African Americans are disproportionately diagnosed with late-stage cancer and have worse outcomes than Caucasians. This study really builds on sexual behavioral lifestyle-related evidence that may be contributing to outcomes, especially since there's a significant difference between HPV status in African Americans and Caucasian populations."
The study results also suggest that, similar to oropharyngeal cancer research, laryngeal cancer patients with HPV have better survival and tend to respond better to chemotherapy and radiation treatments than patients who do not have HPV.
The researchers say, however, that this pattern needs to be further studied to confirm such results, and they plan to do so using a larger group of patients.
New Synthetic Regulatory Circuit Can Identify and Kill Cancer Cells
By Anna Azvolinsky, PhD | September 13, 2011
http://www.cancernetwork.com/cancer-genetics/content/article/10165/1948479
Collaborating scientists at the Department of Biological Engineering at MIT and the Center for Systems Biology at Harvard University have created an engineered biological system that senses and integrates multiple inputs and can precisely regulate the biology of a living cell. This type of approach could be useful to engineer anti-cancer therapies that are able to distinguish a cancer from a non-cancer cell, inducing apoptosis in the cancerous cells.
Geniom RT Analyzer for microRNA quantification analysis for biomarkers of disease progression
Zhen Xie and Professor Ron Weiss of MIT, Yaakov Benenson of Harvard and the ETH Zurich Institute and their colleagues have demonstrated how a “transcriptional synthetic regulatory circuit” can sense the expression levels of endogenous microRNAs within a cell and trigger an engineered cellular response. The research is published in Science (Xie et al. Science Sept. 2, 2011 333: 1307-1311). The applications of this system include cancer and other disease treatment as well as further elucidating important biological processes.
To induce cancer cell-killing, the researchers designed a logic circuit made up of genes that detect molecules that are specific to the HeLa cervical cancer cell line. The gene circuit is delivered to cells and if a specific set of endogenous molecules are present at a particular level, the apoptotic protein, Bcl-2–associated X protein (hBax) is expressed from the circuit and apoptosis is induced. If the molecules are not detected, nothing happens.
The circuit senses microRNAs, and essentially functions as a “classifier” of a specific cell type, executing the pre-specified output of apoptosis. CancerNetwork spoke with Professor Ron Weiss of MIT about the development of this system. “He explained that the circuit is made up of three essential components: the sensing component, the computational component, and the actuation component. The sensing component is comprised of several sensors that can detect levels of microRNA of interest in the cell; microRNA that has been identified as being indicative of the presence of cancer. The sensors then feed into the computational portion or the logic processing portion of the circuit. That portion of the circuit integrates multiple pieces of information from the sensors and makes the decision about whether the profile is indicative of the cancer that we hope to eliminate; it does this by looking at the sensor levels and computing “and” or “not” operations. The sensors are fed into this computational core, which then determines whether the levels of the sensors, looked upon as a group, are actually indicative of the cancer. Weiss went on to explain that "If the answer is yes, then the computational core causes a production of a killer protein – the hBax protein – which ends up killing the cell. If the answer is no then that protein is not expressed and eventually the genetic circuit just goes away."
The published research brings together two important concepts to create a system that has high utility. The first is tissue-specific signaling, which has previously been used to restrict, or at least partially restrict, a therapeutic agent’s action specifically to cancer cells. The second is the demonstration that multi-input information processing can work in living cells.
The researchers chose a set of low and high expression HeLa microRNAs whose expression is drastically different from a healthy, wild-type cell as markers. To decide which markers to use to differentiate cancerous from normal cells, the researchers created a mathematical model and experimentally derived responses of the individual sensors to their microRNA inputs. Multiple combinations of microRNAs were tested until an efficient output in HeLa cancerous cells, but not in normal cells was achieved.
The selective output of hBax expression followed by apoptosis in HeLa cells but not in the control normal cells was demonstrated by quantitating the level of apoptosis. This was done by using a fluorescent reporter assay; the protein was expressed when apoptosis is induced and this allowed a quantitative measure of apoptosis. Importantly, the system was demonstrated as being both specific and selective in a heterogenous cell population consisting of HeLa and non-cancerous, reference cells. A difference in the level of a single microRNA profile was enough to prevent the cell death output. However, further evolution and optimization of this circuit system is still necessary, to decrease false-positive cell detection and false-negative cell death in normal cells.
There are clearly therapeutic applications for this type of synthetic modulation of biological cell function. The new technology offers the possibility of designing a system to selectively induce cell death of any cancer type, without adverse effects on the surrounding healthy tissue. Because the circuit can be easily manipulated by adding any gene of interest, it may yield new treatments or diagnostics nobeyond cancer.
"This is a general technology for disease-state detection," says Professor Weiss. “We can basically target any biomarker. Certain existing therapies may utilize a small molecule that has to bind to a specific enzyme that's involved in the progression of cancer--it has to interfere with the progression of the cancer itself, whereas our system is actually a very different approach: We’re not interfering with the pathways that are responsible for the cancer, we're creating a circuit that reacts to the changes in the cell, and then we kill the cell,” professor Weiss explained.
The approach is not limited to targeting microRNA levels, which lends further flexibility to the potential uses of this type of system. However, the authors note that microRNAs make great markers and also because the data on micro RNA expression in cancer cells is readily available.
There are also potential in vitro applications of this type of system, including drug screening and the monitoring of developmental processes, as the authors suggest in the paper. The in vitro applications will likely be developed in a much shorter time frame compared to therapeutic applications.
The researchers are currently creating new circuits to identify other cell types, with the idea of moving this approach into a pre-clinical animal system. The original choice of using HeLa cells was based on the availability and ease of culture of these cells, and because this cell line is a “good testing ground”. They are also modulating the output. “In this case hBAX worked for us so we decided to use, it but we’re certainly exploring others, either separately or in conjunction with hBAX” Weiss said.
“We’re asking ourselves, how much we need to optimize this current circuit before we’re actually able to test this in a mouse model?” said Weiss. One of the current limitations is the efficient delivery of the DNA circuit to cells and the body. The groups is currently looking into different methods to package and deliver the DNA that makes up the circuit, using vesicles or a virus.
The ultimate goal is to advance this technology to therapeutic in-human trials. “We are planning animal testing in the near term," says Dr. Yaakov Benenson of Harvard. "We also need to solve the issue pertaining to efficient in vivo DNA delivery, as well perform additional circuit optimization that will be required for successful in vivo function. We have to wait for animal testing results to say anything about clinical potential."
HHS awards $94 million to develop broad-spectrum antibiotic (How about acknowledging the HP as a broad spectrum agent for HIV, HCV, H1N1, other viral diseases, cancer diagnosis and possibly treatment etc.,!)
Broad-spectrum antibiotic, training for food testing, H5N1 in ducks, malaria control
Sep 7, 2011
The federal government yesterday awarded a contract to GlaxoSmithKline (GSK) for up to $94 million for advanced research and development of a broad-spectrum antibiotic that researchers hope can be used against both bioterror agents and Gram-negative bacteria. The contract, awarded by the Department of Health and Human Services' (HHS's) Biomedical Advanced Research and Development Authority (BARDA), is for advancing GSK2251052, which GSK has been developing to treat ventilator-associated pneumonia, complicated urinary tract infections, and complicated postoperative intra-abdominal infections. If approved for its designed purpose it would become the first new class of antibacterial to treat Gram-negative infections in 30 years. The contract is for $38.5 million for the first 2 years and can be extended for a total of 4 years and $94 million. Under the contract, BARDA will provide technical and financial support for GSK2251052 development. The funds support studies to evaluate efficacy against bioterror threats such as plague and tularemia, phase 2 clinical trials for ventilator-associated pneumonia, and phase 3 clinical trials involving complicated intra-abdominal infections. In addition, the funds will support initial lab testing to determine if the drug also protects against multidrug-resistant pathogens, including those containing the New Delhi metallo-beta-lactamase-1 (NDM-1) resistance gene.
Sep 6 HHS news release
FDA collaboration trains foreign lab workers on food-testing methods
The University of Maryland and the US Food and Drug Administration (FDA) are launching a program on Sep 12 to teach foreign laboratory workers who test food about US lab methods, standards, and technology, as well as what acceptable alternatives they can use if they don't have the same high-technology lab equipment. The program, called the International Food Safety Training Laboratory, is based at the University of Maryland's Joint Institute for Food Safety and Applied Nutrition. The Waters Corp. is helping build, equip, and design the new lab. Janie Dubois, PhD, who directs the new lab, said in a press release, "The more we can get foreign food facilities to harmonize their procedures and their work with US requirements, the greater the likelihood of safe imported foods reaching American consumers." The program aims to enable about 200 foreign lab technicians each year to learn microbiological and chemical analysis methods directly from regulators from the FDA and other federal agencies. The first class is made up of Chinese students who will learn methods to test for pesticide contamination in fresh produce.
Sep 6 University of Maryland press release
Indonesian backyard poultry survey finds H5N1 differences in ducks
A study today profiling H5N1 avian flu viruses in Indonesia's backyard farms found that ducks were more likely than chickens to survive their infections. Also, the Australian and Indonesian researchers found no evidence of major antigenic variants. They conducted the longitudinal survey between March 2007 and March 2008 at 96 small duck farms in four Java province districts. Every 2 months they collected oropharyngeal and cloacal swabs from individually banded ducks and from chickens they were in contact with on the farms. Viral samples were also collected from dead and live birds during the investigation of outbreaks at the study farms. Researchers ran molecular and virologic tests to explore relationships between the circulating viruses. Of 132 samples collected, the group found viable H5 viruses in 84. All belonged to clade 2.1 and fell into three virus sublineages. They found no major amino acid mutations of the hemagglutinin and neuraminidase sites. Multiple variants were found on different farms and at different times on single farms. The proportion of virus isolated from surviving ducks was higher than that of chickens, suggesting that ducks may be more resistant to infection and may play a role in maintaining Indonesia's H5N1 lineages.
Sep 7 Virol J abstract
Two studies detail benefits of malaria-control efforts in Africa
Two recent studies illustrated the benefits of malaria-control efforts like insecticide-treated nets (ITNs) in Africa. In the first study, US and Zambian researchers analyzed data from seven surveys in seven sub-Saharan African nations and found that ITNs reduced the prevalence of malaria parasites in the bloodstream by 20% and death by 23% in children under 5 years old. Using data from six malaria indicator surveys and one demographic and health survey, the scientists used matched logistic regression to assess the association between household ITN ownership or use in children under 5 and the prevalence of parasitemia and death. They found a 20% reduction in parasitemia in households that owned an ITN and a 24% reduction in children who slept under one, as well as a 23% reduction in death in that age-group in ITN households. In a press release yesterday, the authors say, "These findings suggest that the recent scale-up in ITN coverage has likely been accompanied by significant reductions in child mortality and that additional health gains could be achieved with further increases in ITN coverage in populations at risk of malaria." In an accompanying editorial, two US malaria experts caution, however, that ITNs alone are insufficient to eliminate malaria transmission.
Sep 6 PLoS Med study
Sep 6 Public Library of Science press release
Sep 6 PLoS Med editorial
In the second study, Wellcome Trust researchers from Kenya, Britain, and Ghana found that measures such as ITNs to control malaria will also lower the incidence of bacteremia in children 3 months to 13 years of age. The researchers first conducted a matched case-control study involving 292 cases and 528 controls from a district hospital in Kilifi, Kenya, to determine that sickle cell trait, which is known to protect patients from malaria, was also associated with lower bacteremia incidence. To ascertain whether the lower incidence was due to genetics or to the lower incidence of malaria, they then conducted a 9-year longitudinal case-control study of 1,454 cases and 10,749 controls from the same hospital. During the study period, which coincided with increased malaria-prevention efforts such as ITNs, antimalarial drugs, and mosquito control, the incidence of hospitalization for malaria decreased from 28.5 to 3.45 cases per 1,000 child-years. In addition, hospitalizations for bacteremia fell from 2.59 to 1.45 cases per 1,000 child-years. The team found that 62% of bacteremia cases—including meningitis, pneumonia, and sepsis—were attributable to malaria. They conclude, "Interventions to control malaria will have a major additional benefit by reducing the burden of invasive bacterial disease."
BARDA contracts will expand the tools available to protect the nation in a bioterrorism attack
Novel anthrax vaccine and antitoxin being developed with federal support
The advanced development of a novel next-generation anthrax vaccine and a new type of anthrax antitoxin have received support through new contracts funded the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA).
Vaccines prevent illness by boosting the body's ability to make antibodies so the body recognizes and eliminates a bacteria or virus; with antitoxins, antibodies are injected directly into the body to neutralize the bacteria or virus.
The vaccine being developed under today’s contract could be administered as a spray in the nose and given by non-medical personnel, making administration easier and potentially increasing the number of people who could be vaccinated against this potentially fatal infection.
Similarly, the new anthrax antitoxin medication could be administered by conventional injection, making the medication much easier and faster to administer than current anthrax antitoxins, which must be administered intravenously. This would greatly facilitate antitoxin administration in an emergency.
The vaccine development contract was awarded to Vaxin Inc. of Rockville, Md., for $14.7 million over two years and could be extended for a total of up to four years and $21.7 million. The contract for the new antitoxin was issued to Elusys Therapeutics Inc. of Pine Brook, N.J., for two years and $26.5 million, and can be extended for a total of five years and up to $68.9 million.
Under the contract, Vaxin will conduct studies and develop manufacturing processes for the vaccine, AdVAV. In part these studies will determine whether the vaccine can protect against anthrax with fewer doses than the currently licensed vaccine, which requires five doses over 18 months with annual boosters to protect against anthrax. In addition, Vaxin will optimize and validate commercial-scale manufacturing processes for the AdVAV vaccine.
Under the antitoxin contract, Elusys will conduct studies to evaluate the efficacy of its medication, Anthim, when administered before or after exposure to anthrax.
“These are promising medical countermeasure candidates. The new vaccine candidate has attractive attributes – ease of administration, the possibility of fewer doses, and technology that can be used to make vaccines for other diseases – and the new anthrax antitoxin candidate may enable a life-saving therapy to be available to more people sooner in an anthrax attack,” said BARDA Director Robin Robinson, Ph.D. “Through these contracts, we are helping develop new tools to protect the public in an emergency and at the same time helping industry manage the costs of these products over their life cycle.”
BARDA currently supports the advanced development of three other next-generation anthrax vaccines known as recombinant protein antigen (rPA)-based vaccines, as well as development of a new formulation of the currently licensed anthrax vaccine, Anthrax Vaccine Absorbed (AVA), that may require less antigen (the active vaccine ingredient) and fewer doses to be effective. AVA is approved by the U.S. Food and Drug Administration only for use before exposure to anthrax. BARDA is also supporting the expansion of AVA manufacturing capacity.
In addition, BARDA previously funded the development and acquisition of two anthrax antitoxin drugs that reside in the Strategic National Stockpile. These drugs could be authorized for use in an emergency. BARDA continues to support the late-stage development of these drugs toward full approval by the FDA.
BARDA is seeking additional proposals for vaccines, antitoxins, and therapeutics that potentially protect against anthrax infection. Proposals are accepted through the Broad Agency Announcement BARDA-CBRN-BAA-11-100-SOL-00009 at www.fbo.gov.
BARDA, an agency within the HHS Office of the Assistant Secretary for Preparedness and Response, provides a comprehensive integrated portfolio approach to the advanced research and development, innovation, acquisition, and manufacturing infrastructure for vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products for public health emergency threats. These threats include chemical, biological, radiological, and nuclear threats, pandemic influenza, and emerging infectious diseases.
For more information about BARDA and the advanced research and development of medical countermeasures, visit www.phe.gov. Contract opportunities and awards are announced at www.fbo.gov.
ping_pow_princess
Thank you for the info. Some awards were announced yersterday also.
BARDA contracts support new anthrax countermeasures
http://www.cidrap.umn.edu/cidrap/content/bt/anthrax/news/sep1511anthrax.html
Thank you.
New DSO Director--Scientist, Engineer and Physician--Brings Unique Perspective to Agency (Very impressive bio. Can be a visionary who may/can appreciate the true potential of the HP in the big scheme if he gets involved with it)
September 07, 2011
Acceptance of risk cited as key to success
Defense Sciences Office (DSO) programs bridge the gap from fundamental science to applications by identifying and pursuing some of the most promising ideas within the science and engineering research communities and transforming these ideas into new Department of Defense capabilities. It makes sense then that its new director would have a background steeped in engineering yet equally rooted in biological sciences and fundamental research.
Dr. Jay Schnitzer, who joined DARPA this week as director, DSO, has a background that is a composite of experience in basic research, medicine, surgery, trauma, burns, medical devices and international healthcare work. A Doctor of Philosophy in chemical engineering from Massachusetts Institute of Technology and a Medical Doctor from Harvard Medical School give Schnitzer a unique perspective in his work.
"We are pleased to have Dr. Schnitzer on the DARPA technogeek team,” said DARPA Director, Regina E. Dugan. His entire career is characterized by work at the intersection of basic science and application—DARPA’s power lane. He knows Pasteur’s quadrant, because he’s lived it. He’s got the experience, the skill and the nerve to help DARPA fulfill its mission."
“I think my engineering and quantitative science training have combined to shape my research over the years. It has always been a part of how I work,” said Schnitzer. This approach to problem solving will assist Schnitzer as he watches over DSO’s programs, which cover a range of fields from physical science to materials to biology to mathematics.
DARPA’s mission to create and prevent strategic surprise requires agile, rapid innovation so that technologies may be brought to bear quickly to serve the warfighter. Schnitzer believes his medical background will help provide for agile yet informed decisions. “Being comfortable making decisions when data is sparse because it hasn’t been done before is critical to big innovation. It helps if you come from a background where you’re comfortable thinking in those terms,” he said.
This risk equation thrives at DARPA. According to Schnitzer, “DARPA is the leading agency perhaps in the entire Federal Government in terms of doing really, truly advanced and revolutionary science. I think that having an appropriate risk appetite is really crucial to maintaining that position within the federal government.”
Media Queries
Telaprevir-Incivek-Allows Shorter Hepatitis Therapy for Some
(The question is how much time does the HP cut off from the SOC or the new SOC therapies? This becomes more pertinent with the gov. taking more interest in curtailing health care costs esp. for chronic diseases)
Wednesday, September 14, 2011
Posted by New HCV Drugs
File Under telaprevir-incivek
New Drug Allows Shorter Hepatitis Therapy for Some
By Michael Smith, North American Correspondent, MedPage Today
Published: September 14, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Response-guided therapy with the protease inhibitor telaprevir (Incivek) can cut the treatment period for hepatitis C (HCV) in half, researchers reported.
In an open-label randomized trial, 24 and 48 weeks of standard therapy – each combined with telaprevir for the first 12 weeks – had equivalent efficacy among patients who responded early and strongly, according to Kenneth Sherman, MD, PhD, of the University of Cincinnati College of Medicine, and colleagues.
But those getting the shorter therapy had significantly fewer adverse events, they reported in the Sept. 15 issue of the New England Journal of Medicine.
Action Points
Note that in this study, the investigators evaluated the efficacy of shorter treatment duration to decrease the risk of exposure of patients to adverse events associated with the 48-week use of peginterferon and ribavirin.
Point out that a regimen of peginterferon–ribavirin for 24 weeks was noninferior to the same regimen for 48 weeks in patients with extended rapid virologic response, and was associated with significantly less discontinuation of all the study drugs based on adverse events.
Telaprevir was approved earlier this year to be used in combination with standard HCV therapy with pegylated interferon and ribavirin. It is one of two new medications -- the other is boceprevir (Victrelis) -- that target the virus directly, in contrast to the standard therapy, which boosts the immune system.
Both the standard therapy and telaprevir are associated with a range of adverse events that can lead patients to stop therapy, the researchers noted, so that a shorter course would have important advantages.
To test the idea, they enrolled 540 patients with genotype 1 HCV -- the most difficult to treat -- who had not previously had therapy. All patients were given the three drugs for the first 12 weeks, followed by 12 weeks of peg-interferon and ribavirin alone.
At week 24, patients who had what the researchers called an "extended rapid virologic response" were randomly assigned to stop treatment or to have another 24 weeks of peg-interferon and ribavirin.
Patients who did not have an extended rapid response – defined as undetectable HCV RNA at both weeks four and 12 of treatment – were non-randomly assigned to the longer treatment arm.
The main goal of the analysis was to see if there was a difference in the rate of sustained virologic response -- defined as undetectable HCV both at the end of treatment and 24 weeks later – among the randomized patients.
The study was designed as a non-inferiority trial, with the margin of non-inferiority set at minus 10.5%, the researchers noted.
Among the 540 patients, the overall rate of sustained virologic response was 72%.
A total of 352 patients -- 65% -- had an extended rapid virologic response, 30 dropped out before randomization, and the rest were randomly assigned to a study group. Among those randomized:
149 of 162 patients in the short arm – or 92% -- had a sustained virologic response, compared with 140 of 169 (or 88%) in the long arm. The absolute difference of four percentage points with a 95% confidence interval from minus two to 11 established non-inferiority.
Among the patients who did not have an extended rapid virologic response and were assigned to the long arm, 76 (or 64%) had a sustained virologic response.
Adverse events included rash in 37% of patients that was severe in 5% and anemia in 39% that was severe in 6%.
Overall, 18% of patients stopped all study drugs because of adverse events.
After randomization, however, only 1% of those assigned to the short arm dropped out, compared with 12% of those in the long arm, a difference that was significant at P<0.001.
The researchers concluded that the results support the notion of using early response to guide treatment duration.
The study was supported by Vertex Pharmaceuticals and Tibotec. Sherman reported financial links with Vertex, Tibotec, Merck, SciClone, GSK, Three Rivers, J&J, Regulus, Valeant, Anadys, Schering, Baxter, Astellas, Boehringer Ingelheim, UBC Healthcare, Roche /Genentech, Gilead, BMS, MedPace, and Pfizer.
Primary source: New England Journal of Medicine
Source reference:
Sherman KE, et al. "Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection." N Engl J Med 2011; 365:1014-1024.
Hepatitis B and C Coinfection among HIV Positive People in the U.S. ( Once again this is a subset where the HP may be ideal)
Details Category: HIV/HBV Coinfection Published on Monday, 12 September 2011 00:00 Written by Liz Highleyman
© Russell Kightley
Liver disease and coinfection with hepatitis B or C are common among people with HIV, according to a recent analysis, leading researchers to recommend that viral hepatitis screening, vaccination, and treatment should be considered a priority for HIV positive individuals.
Since the advent of effective antiretroviral therapy (ART), liver disease -- often related to hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection -- has become a leading cause of illness and death among people with HIV.
As described in the April 14, 2011, World Journal of Gastroenterology, Susan Buskin from the Seattle and King County Department of Public Health and colleagues evaluated trends and risk factors for liver disease and viral hepatitis among HIV positive people age 13 and older.
The analysis included 29,490 participants in the Adult/Adolescent Spectrum of HIV-related Diseases Project, a multicenter review sponsored by the Centers for Disease Control and Prevention (CDC) that looked at medical records of HIV patients at more than 100 medical facilities in Atlanta, Dallas, Denver, Detroit, Houston, Los Angeles, New Orleans, New York City, Puerto Rico, San Antonio, and Seattle.
The project started collecting information in 1990, but the present analysis was restricted to data obtained data between 1998 and 2004 (not long after the widespread adoption of combination ART).
Every 6 months researchers collected data about presentation, treatment, and outcomes of HIV disease and associated conditions, including presence of liver disease, hepatitis screening, and hepatitis diagnosis. Participants were followed for 2.4 years on average, contributing a total 69,487 person-years of observation.
Results
Overall, 3% of cohort participants were diagnosed with liver disease, 8% with chronic hepatitis B, and 19% with hepatitis C; 2% had both hepatitis B and C.
25% had a liver disease diagnosis at baseline (first record examined), while 75% developed new liver disease during follow-up.
The rate of chronic hepatitis B diagnosis showed a small but significant rise, from 7% in 1998 to 9% in 2004.
The rate of hepatitis C diagnosis nearly tripled over the same period, from 9% to 24%.
832 participants diagnosed with liver disease had the following conditions:
31% with non-alcoholic cirrhosis (or alcohol not specified as a cause);
20% with alcoholic cirrhosis;
3% with a primary liver cancer;
3% with liver failure not otherwise specified;
29% with other liver disease.
Over the course of follow-up, the rate of new or incident liver disease was 0.9 cases per 100 person-years.
The incidence of chronic hepatitis B was 1.8 per 100 person-years, and the rate for hepatitis C was 4.7 per 100 person-years.
Significant risk factors for new chronic hepatitis B diagnosis included male sex, men having sex with men, lower nadir (lowest-ever) CD4 T-cell count, injection drug use, alcohol use, and triple infection with HCV.
Significant risk factors for new hepatitis C diagnosis included male sex, older age, white or Latino race/ethnicity, triple infection with HBV, injection drug use (4.7-fold higher risk), and hemophilia (7-fold higher).
In a multivariate analysis, independent predictors of liver disease included:
Older age, history of injection drug users, heavy alcohol consumption, and diagnosis of AIDS (CD4 T-cell count < 200 cells/mm3) was associated with greater risk.
Black patients had a lower rate than other racial/ethnic groups.
Neither ART use overall nor use of specific antiretroviral drugs was positively or negatively associated with liver disease after controlling for other factors including HBV and HCV.
25 participants were diagnosed with liver cancer, including 15 with hepatocellular carcinoma; 2 of these patients were lost to follow-up and the rest died.
13 patients with liver cancer had HCV and 10 had chronic HBV (including 2 people with both).
Mortality was much higher among people diagnosed with liver disease, 57% compared with 15% for the study population overall.
10% of all deaths occurred among participants with liver disease.
An estimated 1% of all deaths may have had liver disease as a cause or contributing factor, rising to 2% among people with HBV or HCV.
The likelihood of HBV and HCV screening increased significantly during the study period -- from less than 20% to more than 60% -- but repeat screening was uncommon, even for people with ongoing risk of infection.
Less than one-third of people without prior hepatitis B had a record of HBV vaccination, although this increased from 10% to 28% during the study period.
The researchers noted that despite care guidelines calling for HBV vaccination and hepatitis B and C screening for people with HIV, these were not universally performed (or if done, were not documented).
Based on these findings, they concluded, "Due to high rates of incident liver disease, viral hepatitis screening, vaccination, and treatment among HIV-infected individuals should be a priority."
"Although HBV vaccination rates have improved and screening rates for HBV and HCV have climbed steadily, they are still inadequate, and efforts are needed to improve vaccination and screening rates," they elaborated in their discussion.
"The high rates of incident HCV (5/100 person-years) indicate that individuals at risk should be screened and while remaining at risk, re-screened on a regular basis. Similarly, a sizable HBV incidence (2/100 person-years) supports improved screening and vaccination," they continued.
"Until better data are available, annual screenings for HCV and HBV vaccination discussions are suggested," they recommended. "Treatment of HBV and HCV should be considered for all HIV co-infected individuals."
Investigator affiliations: Public Health, Seattle and King County, WA; University of Washington, Seattle, WA; Harborview Medical Center, Seattle, WA; Virginia Mason Medical Center, Seattle, WA.
9/13/11