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Week Ending: September 19, 2009
Alan Franciscus
Editor-in-Chief
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This Issue:
September 12, 2009
Aspirin Could Diminish Hepatitis C Virus Replication
http://buscador.uanl.mx
Facultad de Medicina
By Lizbet Garcia Rodriguez
Doctor Ana Maria Guadalupe Rivas Estilla obtained the Research Award in the health area with her work “Acetylsalicylic inhibits the Hepatitis C virus replication through the ciclooxigenasa-2 signaling pathway.”
The infection with the Hepatitis C virus is one of the main causes of chronic hepatitis, cirrhosis, hepatocellular carcinoma and hepatic transplant. The enormous interest on the subject has led Doctor Ana Maria Guadalupe Rivas Estilla — from the Universidad Autonoma de Nuevo Leon’s School of Medicine — to deeply study it.
“For five years we have been implementing — at our school’s Molecular Infectology Laboratory — a research line to figure out the virus mechanisms when producing an infection that goes from an acute evolution to a chronic infection and finally it could lead to hepatic cancer.”
With the work entitled “Acetylsalicylic inhibits the Hepatitis C virus (HCV) replication through the ciclooxigenasa-2 signaling pathway,” Doctor Rivas and a team made up of doctors Karina Trujillo, Herminia Martinez, Javier Ramos, and Francisco Bosques, obtained the Research Award in the Health Sciences category.
“Previously, in the 2007 Award Edition, we were acknowledged for figuring out how ethanol favors the HCV replication. Now we are on the search for the replication and inhibition mechanisms. This year we demonstrated and published in an article of the The Hepatology magazine that aspirin is capable of diminishing the HCV´s replication and that the most probable mechanism proposed is the oxidizing stress modulation, which is one of the organism’s basic defense pathways to get rid of this type of virus.”
On a national scale, Hepatitis C affects around 0.8 per cent of the Mexican population and it is though that about 200 million people in the world are infected with this virus.
“The patient could be infected without realizing it. After five, ten, fifteen years he experiences a kidney infection, then a hepatic dysfunction, alterations in the hepatic profiles. Here is when he finally sees a doctor, but the disease’s state is quite advanced already.”
The researchers’ group challenge has been to discover what unchains it after having remained in silence after many years.
“We do know yet, that is why the research in our University is so important. To find out how does the virus silently survives for such a long time to later evolve into a chronic disease and even hepatic cancer. These types of diseases have a great impact, if we compare it to HIV for there are five times more people infected of HVC globally speaking.”
The problem is quite severe for there is no vaccine and Doctor Rivas believes there will be none in several years.
“This virus has the capacity to constantly mutate for it finds it easier to evade the immunological response; besides, there are no antiviral treatments either. For the HIV, for instance, there are a number of antiretroviral cocktails, proteases inhibitors that combine according to the different treatment schemas. However, with HCV the only available treatment is the pegylated interferon alpha combined with ribavirin. These are not antiviral but compounds that facilitate the virus elimination and they are very expensive for the patient.”
In the search for pathogenicity mechanisms of the virus the researchers try to propose new therapeutic targets to implement a better antiviral treatment.
“In this case our scientific contribution is that aspirin is capable of diminishing the virus replication and we are working on a pilot clinical study to see if the results are similar with the already infected patients.”
The also professor of the biochemistry, molecular biology, and molecular virology´ areas suggested that before any hepatic alteration we must see the doctor, determine our hepatic profile and check if we have antibodies against the virus.
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California bill would toughen training for tattoo artists
http://www.suntimes.com
The California legislature has passed a bill that imposes stricter training requirements, registration and safety rules on artists that tattoo or brand skin with a hot iron, pierce anything other than an earlobe or apply permanent cosmetics.
If signed by the governor, all body artists would be required to register and undergo sanitation and certified blood-borne pathogen training.
Artists must also be at least 18 years old, prove they are vaccinated against hepatitis B and show that they completed an accredited four-hour first aid and CPR course.
The number of California piercing and tattooing parlors is up 400 percent in the last decade.
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UPDATE 4-Dynavax shares soar as hepatitis B trials resume
www.reuters.com
By Toni Clarke
* FDA lifts clinical hold on Dynavax hepatitis B vaccine
* Could have product on the market by end of 2012
* Shares jump 45.7 percent (Updates with analyst comment, closing share price)
BOSTON, Sept 10 (Reuters) - Dynavax Technologies Corp (DVAX.O) said on Thursday that U.S. regulators have given it the green light to move forward with its experimental hepatitis B vaccine, sending the company's shares up nearly 46 percent.
The U.S. Food and Drug Administration placed the product on clinical hold 18 months ago due to safety concerns. Dynavax presented additional data to the agency, which has now given it the go-ahead to immunize patients with chronic kidney disease who do not respond well to an existing product.
The news surprised investors, who had largely written off the vaccine, Heplisav. Last November the company's shares fell to 15 cents, down from more than $10.00 in late 2006. They closed up 80 cents at $2.55 on Wednesday, having trading as high as $3.35 earlier in the day.
Hepatitis B is a chronic disease which can lead to cirrhosis of the liver. There is no cure for the condition. The only vaccine on the market is Engerix-B, made by GlaxoSmithKline Plc (GSK.L). Dynavax believes Heplisav is more effective and can be given in fewer doses than Engerix-B.
The FDA put Heplisav on hold last March after one patient developed a case of Wegener's granulomatosis, an inflammatory autoimmune disease that affects the small blood vessels and can cause extensive tissue damage.
Bret Holley, an analyst at Oppenheimer & Co, said the company may not have enough money to fund the trials required for approval and warned that any new safety concerns could derail its future.
"We believe sharp upside on today's news is appropriate but expect Dynavax to trade in line over the near- to mid-term with few upcoming catalysts," he said.
Heplisav combines a genetically engineered viral antigen with an adjuvant to create its vaccine. The adjuvant, designed to enhance the effectiveness of the antigen, targets Toll-like Receptor 9, a protein that tells the immune system to activate itself.
Dynavax, which is based in Berkeley, California, has completed a late stage trial of the vaccine, and said its next step is to enroll patients in a trial to compare vaccine made for commercial use with that made for use in clinical trials, to make sure they are the same.
Dynavax Chief Executive Dino Dina said the company expects to complete the process by end of 2011. If all goes well, the vaccine could reach the market by the end of 2012 or early 2013.
Dynavax is also using its adjuvant in a different form to develop a universal influenza vaccine that can be used for seasonal and pandemic flu. The vaccine is in pre-clinical development.
(Reporting by Toni Clarke; Editing by Matthew Lewis, Dave Zimmerman and Richard Chang)
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September 13, 2009
Interferon Gene Variant Predicts Response to Hepatitis C Treatment
www.medscape.com
Jacquelyn K. Beals, PhD
September 14, 2009 — Two new studies have found that gene IL28B variants are associated with the response of patients with chronic hepatitis C virus (HCV) infection to PEGylated interferon-α and ribavirin (PEG-IFN-α/RBV) therapy. The studies, based in Australia and in Japan, investigated the association in patients with genotype 1 HCV infections.
Published online September 13 in Nature Genetics, the studies demonstrated the genetic association in populations of European and Japanese origin. Genotype 1 chronic HCV is the most common strain in "developed countries." Although 6-month therapy produces a sustained virological response (SVR) in roughly three quarters of patients with other viral genotypes, a year's treatment is required to produce SVR in 50% or fewer patients with genotype 1 HCV.
"It is currently not known why genotype 1 is less treatment-responsive. Genotype 1 viruses appear to be better able to evade the human immune response when it is stimulated by PEG/IFN/RBV therapy," said senior author Jacob George, MD, from the Storr Liver Unit, Westmead Millennium Institute, University of Sydney, and Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia, in his email to Medscape Pathology & Lab Medicine.
Perhaps genotype 1 viruses are better at avoiding clearance through an IL28B-mediated mechanism. Or "[t]here is also a suggestion that, since HCV genotype 1 induces insulin resistance and the insulin signaling and interferon response pathways overlap, this may be a potential mechanism," Dr. George suggested. "However, the short answer is [that] no one is very sure."
The Australian genomewide association study evaluated samples from 293 patients with genotype 1 chronic HCV: 131 had responded to PEG-IFN-α/RBV therapy, and 162 were nonresponders. A single nucleotide polymorphism (SNP) on chromosome 19 between IL28A and IL28B was the only SNP significantly associated with treatment response at the genomewide level (P = 7.06 × 10−8; odds ratio [OR], 3.36; 95% confidence interval [CI], 2.15 – 5.35). IL28A and IL28B are lambda interferons — a family of cytokines highly expressed in macrophages and dendritic cells, whose receptors are especially prevalent in hepatocytes and epithelial cells.
The same SNP had the strongest association of 172 SNPs tested in the replication phase of the study. With discovery and replication cohorts combined, this SNP again demonstrated significant association with SVR (P = 9.25 × 10−9; OR, 1.98; 95% CI, 1.57 – 2.52). The authors report that the G allele "predicts nonresponse with 57% sensitivity and 63% specificity" and noted that the strongest effect on response to treatment was seen in patients homozygous for GG.
In a separate report, a Japanese genomewide association study identified the same SNP between IL28A and IL28B as highly associated (P = 3.11 × 10−15), with lack of virologic response to PEG-IFN-α/RBV therapy in 154 Japanese patients (72 responders, 82 nonresponders) with genotype 1 HCV. A second SNP near IL28B was also associated with treatment response at a genomewide level of significance (P = 1.93 × 10−13). Replication in an independent Japanese cohort of 122 responders and 52 nonresponders found that both SNPs achieved genomewide association study significance. This conclusion was supported by the combined P values for each SNP (P = 2.68 × 10−32; OR, 27.1; 95% CI, 14.6 – 50.3; and P = 2.84 × 10−27; OR, 17.7; 95% CI, 10.0 – 31.3, respectively).
"Our data strongly indicated that at least 85% of nonresponder HCV patients will be predicted before PEG-IFN-α/RBV therapy if our SNPs of IL28B are detected," said senior author Masashi Mizokami, MD, PhD, from the Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, and Research Center for Hepatitis and Immunology, International Medical Center of Japan Konodai Hospital, Ichikawa, Japan.
"PEG-IFN-α/RBV therapy is more powerful than other newly developed and developing drugs theoretically at present," continued his email to Medscape Pathology & Lab Medicine. "Most of the new drugs are targeting on HCV viral replication. But [the] nature of HCV is a very rapid mutation rate, 10−3/site/ year.... These data strongly suggest [it would] be easy to escape the new drugs," observed Dr. Mizokami. "Moreover, these new drugs cannot eradicate HCV RNA completely...and will only be a supportive role with PEG-IFN-α/RBV therapy. So I think that host factors for PEG-IFN-α/RBV therapy should be very important," he added.
Earlier identification of responders and nonresponders could save time and the expense of nonproductive therapy, as well as avoiding the adverse effects of PEG-IFN-α/RBV therapy in nonresponders who will gain no therapeutic benefit. Adverse effects include flu-like symptoms and hematologic and neuropsychiatric problems, often severe enough to mandate reduced dosage or early withdrawal from treatment.
The current studies "may increase the interest in developing interferon-lambda-based therapies for chronic HCV," suggests Thomas R. O'Brien, MD, MPH, from the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, in his "News and Views" commentary. He writes: "The observation that the outcome of treatment with interferon-alfa is associated with genetic variation affecting interferon-λ now suggests that interferon-λ is not simply an alternative means of inducing [the same] pathway."
Australian study author Dr. George cited other studies suggesting that interferon-α "induces expression of interferon-lambda genes and that interferon-lambda inhibits hepatitis C virus replication through a pattern...distinct from that of interferon-α."
In an email to Medscape Pathology & Lab Medicine, Dr. George added, "The new genetic studies...suggest that interferon-α and interferon-lambda may work together to suppress HCV, because genetic variants found near the interferon-lambda genes were associated with response to interferon-α. Together these studies suggest that combining both types of interferon might be more effective than either alone, but that is speculative," he admitted.
Clinical studies of interferon-lambda therapies are underway. "It remains to be seen whether interferon-lambda will prove clinically useful at all, either alone or in combination with interferon-α," Dr. George concluded.
Dr. George, Dr. Mizokami, and Dr. O'Brien have disclosed no relevant financial relationships.
Nat Genet. Published online September 13, 2009.
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September 15, 2009
Celsion and the American Liver Foundation Partner to Promote Awareness of Primary Liver Cancer and the ThermoDox Phase III Global HEAT Study to Patients and Physicians
http://www.reuters.com/
COLUMBIA, Md. & NEW YORK--(Business Wire)--Celsion Corporation (NASDAQ:CLSN) and the American Liver Foundation (ALF) announced today that they have formed a partnership to provide education to physicians and liver patients about the treatment options for hepatocellular carcinoma (commonly referred to as primary liver cancer) and Celsion`s on-going ThermoDox Phase III global HEAT clinical study.
The partnership is comprised of multiple programs that roll out over several months to increase patient and physician awareness. Collaboratively, the two organizations have developed a webinar geared toward physicians that covers recent advances in the treatment of hepatocellular carcinoma and features the ThermoDox HEAT clinical study. The alliance also includes outreach programs to increase awareness through regional ALF Divisions and patient support groups. On September 26, 2009, Celsion is sponsoring ALF`s Liver Life Walk in Los Angeles which reaches an audience of 50,000 people. Celsion and ALF have also developed an integrated media strategy that reaches internet communities, radio audiences, Health fair attendees, and physician networks. Information about the ThermoDox clinical trial is posted on ALF`s national website at: www.liverfoundation.org/education/info/livercancer
"We are very pleased to have formed a partnership with the American Liver Foundation who has been the voice for the 30 million Americans with liver disease and through the successful execution of its mission has made a measurable difference in the fight against liver disease," stated Michael H. Tardugno, President and Chief Executive Officer.
"We are enthusiastic to partner with Celsion to provide information about the ThermoDox clinical trial to our membership" stated Rick Smith, President and Chief Executive Officer of the ALF. "ThermoDox potentially provides an important new treatment option for primary liver cancer, an aggressive and difficult to treat cancer with a low five year survival rate".
Celsion is conducting a 600 patient ThermoDox global Phase III HEAT clinical study at up to sixty clinical sites under a Special Protocol Assessment with the U.S. Food and Drug Administration. The HEAT study is designed to evaluate the efficacy of ThermoDox in combination with radio frequency ablation (RFA) when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival. Celsion has received Orphan Drug designation in the United States for ThermoDox to treat primary liver cancer. Additional information on ThermoDox clinical studies can be found at: www.clinicaltrials.gov
About the American Liver Foundation
The American Liver Foundation is the nation`s largest non-profit organization promoting liver health and disease prevention. The ALF achieves it`s mission in the fight against liver disease by providing financial support for medical research, education for medical professionals, and advocacy and information for patients and their families, and by creating public awareness campaigns about liver wellness and disease prevention. Additional information on the ALF may be found at www.liverfoundation.org
About Primary Liver Cancer
Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States and is rapidly growing worldwide at approximately 1,000,000 cases per year, due to the high prevalence of Hepatitis B and C in developing countries. Among the standard treatment options for liver cancer is surgical resection of the tumor; however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasingly become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors.
About ThermoDox
ThermoDox is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers including breast cancer. ThermoDox is administered intravenously and in combination with hyperthermia has the potential to provide local tumor control and improve quality of life. Localized mild hyperthermia (39.5-42 degrees Celsius) releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumor.
ThermoDox is a registered trademark of Celsion Corporation
About Celsion
Celsion is dedicated to the development and commercialization of innovative oncology drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has licensed ThermoDox to Yakult-Honsha for the Japanese market and has a partnership agreement with Phillips Medical to jointly develop its heat activated liposomal technology in combination with high intensity focused ultrasound to treat difficult cancers. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the North Shore Long Island Jewish Health System.
For more information on Celsion, visit our website: http://www.celsion.com
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Editorial: Medical Inattention in New York Prisons
www.nytimes.com
Prison inmates are the sickest people in society, with infection rates for blood-borne viruses like H.I.V. and hepatitis C far higher than the general population. Failing to test, counsel and treat these inmates makes it more likely that they will spread infection once they are released and suffer catastrophic illnesses that shorten their lives and drive up public health costs.
The New York State Legislature had this problem in mind when it passed a bill that requires the State Department of Health to ensure that prison H.I.V. and hepatitis programs are operating effectively and meet prevailing medical standards. Corrections officials, who tend to rebel against oversight of just about any kind, want Gov. David Paterson to veto this bill. He should ignore them and sign it.
The state correctional system has unquestionably improved medical care over the last several years. But a recent report by the Correctional Association of New York, which is authorized by the Legislature to monitor the prisons, found troubling inconsistencies in care in the state prison system, which is said to house 20 percent of the H.I.V.-infected inmates in the United States.
The report, based on state records, estimates that the state has identified through testing fewer than half of the H.I.V.-positive inmates and only about 70 percent of those with hepatitis C. The report finds that the number of people receiving treatment varies significantly from place to place, which is suspicious given that the population is fairly homogenous. The variation raises questions about the consistency and effectiveness of medical policies from prison to prison.
Prison medical officials argue that the treatment regime is fine and that oversight is unnecessary. But critics in the Legislature rightly point out that the prison health system is the only one in the state not overseen by the Health Department. The prison system, with about 4,000 infected inmates, is the largest provider of treatment for H.I.V., the virus that causes AIDS, in the state.
Other critics argue than the Health Department’s initiative would cost money at time when the state can’t afford it. But better diagnoses and treatment in prison would save more money than it would cost by preventing further infections and keeping many patients from moving on to costly, catastrophic illnesses.
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Physicians Are Talking About: The Million Med March on Washington
www.medscape.com
Nancy R. Terry
"I'm tired, mad as hell, and just not going to take it anymore," says Richard Chudacoff, MD, a gynecologist from Las Vegas. "I am going to Washington, DC. At noon, on Thursday, October 1, 2009, I will be on the Mall with a few other physicians."
Dr. Chudacoff is not talking about vacation plans. Rather, he intends to unite with other physicians in what he calls the Million Med March.
"We simply decided that we will not work that day and perhaps the day before and maybe even the day afterward," says Dr. Chudacoff. "Perhaps we will show the country that physicians are worth more than a $5 copay; that physicians are more important than a mid-level healthcare worker; and that our profession is needed, our services are required, and our practice is a calling to be respected, not a trade that is to be negotiated to the lowest bidder."
A letter posted by Dr. Chudacoff on www.obgyn.net in June has been spreading like wildfire across the Internet, finding its way to personal blogs, discussion groups, and professional forums. On June 23, it was posted to Medscape's Physician Connect (MPC), a physician-only discussion group, where it sparked a flurry of responses. A number of MPC postings suggest that Dr. Chudacoff will have plenty of company on October 1.
"Finally, something constructive," says a dermatologist. "I'll see you in DC on October 1. Some of the office staff, including our nurse, expressed a wish to be there too. Bring spouses and friends and anybody else who actually cares about healthcare in the US."
"I have cleared my schedule and plan to attend," responds a vascular surgeon. "I think this type of grassroots action, unaffiliated with hospitals, insurance companies, or the AMA, is likely to get the most sympathetic attention."
"This is the best proactive effort I have heard from physicians," says an MPC family medicine physician. "Actions speak louder than words."
"I can be there without changing my schedule," adds an anesthesiologist. "I was just terminated from my office-based practice where I have been for 7 years."
One physician's decision to take a stand and unite with his fellow colleagues has given doctors a simple way to show the public and elected officials that healthcare, for them, is not a political agenda. It is their life and livelihood. And in recent weeks, the partisan discussions in the Senate and House of Representatives on healthcare legislation have seemingly marginalized -- and at times even maligned -- physicians.
"I was for nationalized healthcare," says a family medicine physician, "but I thought that meant providing a safety net for needy Americans. But this monster of a bill is something quite different."
"Politicians and payers have turned our profession into a political football," retorts an anesthesiologist.
President Obama's recent tonsillectomy remark, in which he insinuated that doctors make medical decisions based on what they would be paid for a procedure rather than the best treatment for the patient, has further incensed physicians. "As a hard-working, conscientious physician, I am offended. It's like racial stereotyping. Only now it's about a group that is mostly overworked, tired, and saving people's lives," retorts a family medicine practitioner.
If the president is looking for greed within the healthcare system, Dr. Chudacoff suggests that he not take aim at primary care physicians. Chudacoff adds, "Medicine is going corporate, and we physicians are just flipping burgers so corporations have an improved bottom line."
Although fair compensation is an important issue among the organizers of the Million Med March, it is not the only issue. Medicine has become a toxic environment in which to work. Dr. Chudacoff underscores the situation. "Quality of care suffers with less time to see patients and less reimbursement received when we do see patients. We cannot do pro bono work as we have in the past because we have to see an ever increasing number of patients. This extra work is forced upon us when insurance companies, especially Medicare and Medicaid, constantly refuse to pay us in a timely fashion for our time and efforts. And then once we do see patients, our clinical acumen is stifled as we must follow a cookbook approach to patient care. It is time that we stand up for ourselves."
A vascular surgeon comments, "We can lead the way to real reform. Now is clearly the time to act, not just type."
On July 10, an MPC contributor and one of the supporters of the Million Med March launched a Website, www.millionmedmarch.com, to build support for the October event. The site announces a physician grassroots movement to re-establish honor, dignity, and worth to the medical profession. "The Million Med March movement has taken off, on so many sites, and within so many communities. Why now? The debate on national healthcare has forced this conversation, and this conversation has pushed us over the tipping point."
The mandate as stated on the Million Med March Website includes the following points:
- Services must be adequately reimbursed so that we may spend more time with our patients and not be forced to see an unsafe number of patients to pay for increased business costs.
- Less money must go into the hands of insurance companies' administrative costs, and more money must go towards patient care and medical research.
- We must abolish third-party payers or prevent a single-payer system for office visits and medical services; these services are costly to the patient, physician, and society as a whole.
- Our patients need access to brand-name drugs that are as affordable in the United States as in Canada and Mexico.
- We must have medical malpractice reform, with caps on all damages, so that we can practice without the fear of needless and unwarranted lawsuits that only benefit attorneys.
Some MPC contributors voice concern that the Million Med March scheduled for October will occur too late to have any meaningful impact on healthcare reform. "The health reform bill is going nowhere," says an anesthesiologist. "Let's make a major statement between its failure and the next attempt to marginalize the docs."
A plastic surgeon adds, "Stand up for our profession and come to DC."
The full discussion of the Million Med March is available at: http://boards.medscape.com/forums/.29f44f1b.
View this and other discussions in Physician Connect (physicians only; click here to learn more).
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Engineering Team To Design And Study Liver Mimics
www.medicalnewstoday.com
Virginia Tech College of Engineering researchers will use more than $1 million in grant funding to study engineered tissues that mimic the liver, one of the human body's most complex organs.
Padma Rajagopalan, an assistant professor in the department of chemical engineering, is designing liver mimics that eventually could form the basis for extracorporeal liver-assist devices. She is the principal investigator on three recent federal grants totaling $1,087,091 related to liver tissue engineering.
The liver plays a major role in the body's defense mechanisms and performs a multitude of functions including metabolism and detoxification. The deterioration in any one of the liver's functions can cause life-threatening health problems or death. Liver transplants are extremely expensive, may not be appropriate for patients at a high risk for surgery, or may simply not be possible due to a lack of suitable donors.
The primary research goal of these projects is to assemble 3D cellular structures that mimic the liver using the major cell types found in the liver. Rajagopalan's interest in this research began when she conducted studies on liver tissue engineering while she was a research associate at Massachusetts General Hospital, Harvard Medical School, from 2002 to 2004.
"Liver cells can regenerate inside the body, but lose this ability once removed," said Rajagopalan. "Therefore, researchers need to find a way to sustain cells in vitro. A critical aspect is capturing the precise spacing between different cell types in the liver." At Harvard Medical School, Rajagopalan developed a novel method that uses biocompatible, nanoscale polyelectrolyte scaffolds to replicate the spatial configuration within the liver.
A $419,230 grant from the National Institute of Health is for the project "3-D In Vitro Liver Sinusoids: Design and Detoxification Studies." This project will focus upon the detoxification pathways in 3D liver mimics.
A $365,000 grant from the National Science Foundation (NSF) is for the project "Self-Assembled Polymer Scaffolds for Liver Mimics." Richey Davis, a professor of chemical engineering, will collaborate with Rajagopalan on studying the mechanical properties of these scaffolds.
A second NSF award, totaling $302,861, funds "Transcriptional Signatures in 3D Liver Mimetic Architectures" research. Through a combination of experimental and computational approaches, this project will study cell-cell communications in the liver mimics. T. M. Murali, an associate professor in the department of computer science, will develop algorithms to unravel gene networks activated within cells in the liver mimics. Rajagopalan and Murali collected the preliminary data for this project through seed funding obtained in 2007 from the Institute of Critical Technology and Applied Sciences (ICTAS).
Rajagopalan and her collaborators hope that designing liver mimics and studying them at the molecular and cellular levels will bring about a much improved understanding of the organ's structure, and thereafter, to potential breakthroughs in the design of tissue engineered livers. "Information gleaned from this project will provide a sound theoretical basis for the design of the next generation of tissue-engineered livers," said Rajagopalan.
These projects also include outreach to middle school students and to ethnically diverse female high school students. Through summer camps sponsored by Virginia Tech's Center for Enhancement in Engineering Diversity, Rajagopalan and her team will introduce students to the notion of interdisciplinary research and demonstrate how collaborative advances in engineering and computer science can have a direct impact on human health.
Source: Steven Mackay, Virginia Tech
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Aerobic Exercise Reduces Fatty Liver
http://www.hcvadvocate.org/news/Aerobic_exercise.html
Alan Franciscus
Readers of the HCV Advocate are familiar with my steady rap about exercise as a strategy for living well with hepatitis C. A study released earlier this month is adding to the growing body of knowledge on the benefits of exercise – at least from the standpoint of helping with fatty liver. While the study did not specifically address fatty liver and hepatitis C it seems like a no-brainer that this information can be translated into strategies that will help those living with hepatitis C.
The authors of the study wanted to find out what the effect of aerobic exercise was on liver fat. The study enrolled 15 males and 8 females. All 23 patients were obese (≥ 30 kg/m2), self-reported an inactive lifestyle (very little exercise) and low alcohol consumption (0-20 grams/day).
Nineteen patients were put on a supervised exercise program for 4 weeks. The exercise program consisted of an aerobic cycling exercise that was based on standard physical activity recommendations.
The remaining patients were put on a self-reported 30-minute stretching program for 4 weeks. The diet for both groups was not restricted and, in fact, all of the participants were encouraged to consume their usual diet.
The researchers then ran various tests (imaging techniques and blood work). At the end of the 4-week study period it was found that aerobic exercise significantly reduced visceral adipose tissue (body fat especially around the abdominal area) volume by 12% (P < 0.01) and hepatic triglyceride concentration (fat in the liver) by 21% (P < 0.05). This was also associated with a significant (14%) reduction in plasma free fatty acids (P<0.05).
Of note: exercise training in this study did not lower body weight or body mass index. In other words the aerobic exercise reduced the level of fat in the liver but without any weight loss. The authors concluded that regular exercise may diminish some of the consequences of obesity. The authors noted that, “Physical activity should be strongly promoted for the management of fatty liver, the benefits of which are not exclusively contingent upon weight loss.”
Source:
“Aerobic Exercise Training Reduces Hepatic and Visceral Lipids in Obese Individuals without Weight Loss,” Nathan A. Johnson, Toos Sachinwalla, David W. Walton, Kate Smith, Ashley Armstrong, Martin W. Thompson, and Jacob George Hepatology, Early View (Articles online in advance of print). Published Online: 15 Jun 2009.
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September 16, 2009
ChemDiv And IDialog Nominate Novel Inhibitor Of Hepatitis C For Clinical Development
www.medicalnewstoday.com
ChemDiv Inc. of San Diego, and iDialog (Intellektualniy Dialog) of Yaroslavl, Russia, announced today the successful completion of a pre-clinical development and the subsequent nomination of ID-12 as lead clinical development candidate for the treatment of chronic hepatitis C. This novel small molecule orally-bioavailable inhibitor of hepatitis C virus (HCV) blocks early stage of viral infection.
Vadim Bichko, Ph.D, ChemDiv's Vice President of Virology, stated: "We are very encouraged by the safety, potency, PK profile, and novel molecular mechanism of action, exhibited by iDialog's HCV inhibitor in the preclinical studies. We are quite excited by the ability of ID-12 to prevent spread of viral infection through cell-cell contact, which makes it superior to the neutralizing antibodies and other viral entry inhibitors. This mechanism of action is complimentary to that of other classes of HCV inhibitors currently on the market, or in late stage clinical development. Thus, ID-12 is a potentially important component of therapeutic cocktails for chronic hepatitis C."
The Phase I study is scheduled to begin in Q4 2009, and will be conducted in Russia. The objectives of the trial include assessment of safety, tolerability and pharmacokinetics. iDialog plans to present first clinical results at a scientific meeting in the second half of 2010. ChemDiv will continue supporting R&D programs of iDialog, including Proof of Concept Studies in man, through its Chemical Diversity Research Institute in Moscow, Russia.
Prof. Dr. Mikhail Dorogov, Director General of iDialog, confirmed: "We are happy that our discovery effort over last 3 years resulted in advancement of the candidate molecule to clinic. We shall strive in developing a successful new therapy for treatment of large population of hepatitis C patients worldwide. With its current financing iDialog is planning to complete the early development program to obtain clinical Proof of Concept. We are actively exploring options, which will allow us to accelerate the program with maximizing our shareholder's return on investment. We believe our approach is matching to innovative models of early partnering, co-development an co-investment established by pharma and investment community in the recent past."
About Hepatitis C
The U.S. Center for Disease Control and Prevention estimate that about 4.1 million persons in the United States have been infected with HCV, and 3.2 million of these people are chronic carriers. Russian Ministry of Health and Social Development estimates that over 7 million people in Russia have been infected with various types of Hepatitis and 2 million of them, chronically.
About ChemDiv
ChemDiv Inc. (Chemical Diversity) is a global contract research organization accelerating external discovery and development of novel therapies through comprehensive Discovery Outsource™ services, including discovery biology, medicinal and synthetic chemistry, pre-clinical and clinical development.
About iDialog
iDialog was established in 2006 as an innovative biopharma start up. It received over USD$3M of seed investment from Torrey Pines Investment in 2007 and subsequently won the research partnership award of over USD$3 from the Russian Federal Agency of Science and Innovation for development of novel anti-infective agents to match unmet needs in Russia. iDialog conducted and continues the broad program to discover novel therapies for Tuberculosis, hepatitis C and Influenza, in partnership with Moscow State University and other academic organizations. In 2008 iDialog established the R&D collaboration with ChemDiv's Chemical Diversity Research Institute for discovery and development of novel small molecule anti-infective agents, which is extended to 2011.
Source: ChemDiv Inc.
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Uninsured Americans hope reform brings health coverage
www.reuters.com
By Nick Carey
NEWARK, Ohio (Reuters) - As debate rages on how to reform the U.S. healthcare system, many of the one in six Americans now without medical insurance are hoping that reform brings at least one thing -- affordable coverage.
"I'd like to have some sort of health insurance I could actually afford," said Stuart Burrows, a Vietnam War veteran in Newark, a small town in central Ohio. "I stand to lose everything I ever worked for if I can't pay my medical bills."
Burrows, 61, said he was exposed in Vietnam to Agent Orange, a toxic mix of herbicides used by the U.S. military as a defoliant that has since been linked to numerous diseases.
He is retired on partial disability. But in March he had emergency surgery to remove blockages in his arteries and now owes tens of thousands of dollars in medical bills, since his veteran's disability only covers service-related health issues and he has no other insurance.
"I thought I had finally reached a point where I could relax and own something," Burrows said in the living room of his modest, five-room house. "But now I can't because they may take my house and throw me into the street."
Burrows is one of 46 million Americans -- in a population of 300 million -- without health insurance. Reforming the $2.5 trillion U.S. healthcare industry, including affordable coverage for the uninsured, is a top priority for President Barack Obama and a major test for his young presidency.
With unified opposition by most Republicans in Congress, the debate over healthcare reform has been heated and has left many Americans wary of Obama's desire for a "public option" -- a government-run non-profit insurer to offer coverage that private for-profit health insurers currently do not.
Many among the uninsured say they find the reform plans confusing, but believe the current system is unsustainable.
"I've heard a lot of crazy things about health reform and I'm worried about how the country will pay for it," said Moira McKamey, 52, an unemployed worker in southwestern Ohio who is retraining as a medical assistant. "But healthcare is in a critical state and something must be done."
'NO INSURER WILL COVER ME'
Many of the uninsured say they would pay for affordable coverage and many are angry at private health insurers.
But according to opinion polls, Americans are divided over plans to reform the healthcare industry. A Washington Post-ABC News poll released on September 14 showed 46 percent of respondents in favor of Obama's healthcare reform plans and 48 percent opposed. A CNN/Opinion Research Corporation poll released the same day showed 51 percent in favor and 46 percent opposed.
Polls of the uninsured are rare. But a May 2009 survey by Rasmussen Reports of uninsured voters showed 56 percent described the U.S. healthcare system as poor and 48 percent said health costs had caused them to miss credit card or mortgage payments.
"Healthcare in this country sucks," said Charlotta Shepherd, 54, who runs a beauty salon near Oconto Falls, Wisconsin and cannot afford health insurance.
"If countries like Canada and Germany can provide affordable healthcare to everyone, why can't we?"
One reason is the hot-button social issues that critics and opponents have included in the complex debate, whether factual or not. In a nationally televised speech to Congress on October 9, Obama assailed the "scare tactics" of his opponents, such as claims of death panels to decide the fate of senior citizens or free healthcare for illegal immigrants.
"We have already have death panels," said Gloria Smith, Stuart Burrows' partner. "They're called insurance companies."
The country's 12 million or more illegal immigrants have been a special target of the attacks on Obama's reform plans.
Samuel Rolden, 33, an illegal immigrant in Phoenix, Arizona, said he could probably afford a low-cost public option healthcare plan.
"If they offered me a medical insurance plan that cost $100 for my family, I'd pay it. But if they want $250 to $450 a month, I can't pay it," he said. "How are we going to be able to eat or pay the rent?"
There are also those like Devin Baty, 32, a former music teacher in the Cleveland suburb of Lakewood. He is unable to work because of an "organic tick disorder," which sounds innocuous. But when he has an attack his entire upper body shakes violently in a way that is painful to watch.
He has just become eligible for coverage under the government's Medicare program because he is disabled, but this does not include medications, which cost him $400 a month. He spent years without any coverage and said that "without financial help from my mother we would have lost our house."
Baty said he is now skeptical of private insurers.
"No insurer will cover me because of my condition," Baty said. "I don't know what Americans feel they would be giving up with a public option. But just from a philosophical standpoint you will never convince me that someone making a profit from my healthcare would make the best decisions on how to treat me."
(Additional reporting by Tim Gaynor; Editing by Eric Walsh)
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Hepatitis myths put Canadians at risk, survey warns
http://www.montrealgazette.com
By Meagan Fitzpatrick,
Canwest News Service
According to a new poll by the Canadian Liver Foundation released Wednesday, the majority of Canadians believe common myths about food-related illnesses and may have a false sense of security when it comes to food safety. This includes believing that hepatitis A and B are mostly diseases contracted outside Canadian borders.
According to a new poll by the Canadian Liver Foundation released Wednesday, the majority of Canadians believe common myths about food-related illnesses and may have a false sense of security when it comes to food safety. This includes believing that hepatitis A and B are mostly diseases contracted outside Canadian borders.
Thirteen years ago, Samantha Spencer ate a handful of fresh strawberries and wound up with hepatitis A, a virus that infects the liver and is commonly associated with eating contaminated food while on vacation.
But Spencer was not away at a tropical, all-inclusive resort — she was 15 years old and at a summer camp near Toronto.
"It was a shock," the 28-year-old woman says now, looking back on what she calls a "traumatic" experience. "I never suspected that I could get it in Toronto."
Spencer is like the majority of Canadians who, according to a new poll by the Canadian Liver Foundation released Wednesday, believe common myths about food-related illnesses and may have a false sense of security when it comes to food safety.
The survey conducted by the charity found that most Canadians erroneously believe that where they eat and where they shop will help protect them from such food-related illnesses as hepatitis A.
They also falsely believe that hepatitis A and hepatitis B are mostly diseases contracted outside Canadian borders, notes the report.
"Most tend to think of these as travel-related diseases when, in fact, the majority of patients who pick up hepatitis A pick up their disease in Canada. This is true of hepatitis B as well," Dr. Morris Sherman, chairman of the Canadian Liver Foundation, said in an interview.
Sixty-five per cent of Canadians surveyed said they knew they could be exposed to hepatitis A when eating on holiday, but only 35 per cent recognized there are risks in Canada. Almost 60 per cent said they were not worried about contracting a food-related disease because they buy their fresh produce from a reputable store and 63 per cent said they felt safe because they eat at reputable restaurants. Just over half of those polled — 53 per cent — said they try to purchase local fruits and vegetables and, therefore, they don't need to be concerned.
"Canadians really are not fully aware of the risks of acquiring either hepatitis A or B," Sherman said.
Leger Marketing questioned 1,521 Canadians. The survey has a confidence level of 2.5 per cent, 19 times out of 20.
Hepatitis A is usually acquired by ingesting contaminated water or food that was grown in contaminated soil or washed with contaminated water from areas with poor sanitation standards. It's also spread by food service workers who fail to wash their hands properly after going to the bathroom.
In some cases, such as Spencer's, symptoms don't immediately show up, but when they do, they can last a few weeks to several months.
Spencer noticed she was feeling ill about a month after eating the contaminated fruit, and thought she had the flu. She was fatigued, lost her appetite, dropped nearly seven kilograms in two weeks, and then, her skin turned yellow — a classic symptom of a liver disorder. A blood test confirmed Spencer had hepatitis A, along with three other campers who also ate the strawberries.
"You can't sleep, you're itchy, you're so uncomfortable, weak, tired, and you don't want to go out in public because you're bright yellow," said Spencer, who was sick for about six weeks.
While she feels her digestive system never fully recovered from her bout with the virus, Spencer has a clean bill of health.
In the wake of her illness, the young woman said she is extra cautious about what she eats.
"For a while, I felt like I had to become hyper-vigilant about how my food was prepared and what I was eating," she said.
Proper hygiene and food handling can help reduce the risk of infection, but Sherman, a liver specialist at Toronto General Hospital, advises Canadians to get vaccinated against both hepatitis A and B.
Hepatitis B is spread through blood and bodily fluids and risk factors include having unprotected sex and getting a tattoo or piercing, a pedicure, manicure or a dental or medical procedure with inadequately sterilized instruments. It has similar symptoms to hepatitis A but can keep recurring. An estimated 250,000 Canadians are living with chronic hepatitis B, which can cause scarring of the liver, liver cancer and organ failure.
The Liver Foundation survey also revealed that Canadians are not taking the proper precautions to protect themselves from liver diseases. Only 49 per cent said they always wash their produce and only 43 per cent said they do not re-wash their frozen or bagged fruits and vegetables. Only one-third believe they are vaccinated against hepatitis A and 37 per cent think they are vaccinated against hepatitis B.
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September 17, 2009
Genetic Hint for Ridding the Body of Hepatitis C
www.medicalnewstoday.com
More than seventy percent of people who contract Hepatitis C will live with the virus that causes it for the rest of their lives and some will develop serious liver disease including cancer. However, 30 to 40 percent of those infected somehow defeat the infection and get rid of the virus with no treatment. In this week's Advanced Online Publication at Nature, Johns Hopkins researchers working as part of an international team report the discovery of the strongest genetic alteration associated with the ability to get rid of the infection.
"If we knew why some people got rid of the disease on their own, then maybe we could figure out ways to help other people who didn't," says David Thomas, M.D., professor of medicine and director of infectious diseases at Johns Hopkins. "Or maybe even help prevent infections entirely."
A previous study led by David Goldstein at Duke University had found a variation in a single chemical of DNA, known as a single-nucleotide polymorphism, or SNP, near the IL28B gene, which while poorly understood, is thought to help the immune response to Hepatitis C viral infection. People infected with Hepatitis C, who carried the C/C variation SNP near their IL28B gene, were found more likely to respond to hepatitis C treatment, which can rid some patients of the virus.
So the Hopkins-and-National-Institutes-of-Health-led team wondered if the C/C variation as opposed to the C/T or T/T alternatives also played a role in some peoples' ability to get rid of the virus without the help of medication. To do this, they assembled information from six different studies that had over many years collected DNA and Hepatitis C infection information from people all over the world. The team then analyzed DNA at the IL28B gene from a total of 1008 patients: 620 persistently infected and 388 who had been infected but no longer carried any virus. DNA analysis revealed that of the 388 patients who no longer carried virus, 264 have the C/C variation.
"This is the strongest clue to date to understanding what would constitute a successful immune response," says Thomas. "We don't yet know the significance of this C variant, but we know we need to do more work to find out what it means and whether it might be helpful to halting the disease."
In addition to confirming that the C/C variant correlates with the ability to get rid of the virus once infected, the researchers also noticed an intriguing trend: the C/C variant does not appear equally in all populations.
To investigate further, they analyzed DNA from more than 2300 people worldwide in order to further examine distribution of the C/C variant in different populations. Of the 428 samples from Africa, only 148 carried the C/C genotype. In contrast, of the European samples 520 out of 761 carried the C/C variant. The most striking were the DNA samples from Asia, where 738 of 824 samples carried C/C.
"We wonder if this SNP also explains some of the genetic basis for the population difference of Hepatitis C clearance," says Chloe Thio, M.D., associate professor of medicine. "It's been reported that African-Americans are less likely to clear the disease than Caucasians."
The team plans to pursue this research further to better understand why some populations become chronically infected. Says Thio, "This is an exciting step towards better understanding of what the immune response is against the virus so we can improve our therapies."
This study was principally funded by the National Institutes of Drug Abuse and the National Cancer Institute of the National Institutes of Health.
Authors on the paper are Thomas, Thio, and Gregory Kirk of Johns Hopkins; Maureen Martin, Ying Qi, Colm O'hUigin and Mary Carrington of SAIC-Frederick, Inc. and Ragon Institute; Dongliang Ge and David Goldstein of Duke University; Judith Kidd and Kenneth Kidd of Yale University School of Medicine; Salim Khakoo of Imperial College, London; Graeme Alexander of University of Cambridge; James Goedert of the National Cancer Institute; Sharyne Donfield of Rho, Inc.; Hugo Rosen of University of Colorado Health Sciences Center; Leslie Tobler and Michael Busch of Blood Systems Research Institute; and John McHutchison of Duke University School of Medicine.
Source: Johns Hopkins Medicine
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Are HBV Genotype B/B3 and C/C1 the Major Genotypes in Indonesia?
www.medicalnewstoday.com
Previous studies revealed that HBV genotypes as well as mutations in the core promoter, precore or HBx gene have been shown to have an association with the clinical outcome of liver disease, however, this is still controversial. It is likely that this depends on the HBV genotype distribution in certain region. So far, there is no such data from Indonesia, which is a big country with a big population and a relatively high HBV carrier rate.
A research article published in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Utama from Mochtar Riady Institute for Nanotechnology, used samples from HBV-associated liver disease patients [chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC)]collected from several centers, to study the association between HBV genotype and mutations and clinical outcome of liver disease.
The study demonstrated that only HBV genotype B and C were detected among HBV-associated liver disease patients in Indonesia, and genotype B was predominant. It was found that HBV genotype, as well as the serotype, might not be associated with an increased risk of HCC. The double mutation (A1762T/G1764A) was associated with progression of liver disease, while T1753V mutation could be used as an indicator of liver cirrhosis rather than HCC.
Reference:
Utama A, Purwantomo S, Siburian MD, Dhenni R, Gani RA, Hasan I, Sanityoso A, Miskad UA, Akil F, Yusuf I,Achwan WA, Soemohardjo S, Lelosutan SAR, Martamala R, Lukito B, Budihusodo U, Lesmana LA, Sulaiman A, Tai S. Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia. World J Gastroenterol 2009; 15(32): 4028-4036 http://www.wjgnet.com/1007-9327/15/4028.asp
Source: Lai-Fu Li, World Journal of Gastroenterology
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New Micro-Bland Embolization Technique with Embozene(TM) Microspheres to Be Presented at the International Medical Conference in Lisbon, Portugal
www.medicalnewstoday.com
CeloNova BioSciences, Inc. announced that Franco Orsi, MD, PhD, will make two presentations at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) conference about "micro-bland embolization" which has demonstrated excellent clinical results in treating liver cancer. Professor Orsi and his colleagues at the European Institute of Oncology in Milan, Italy have developed a technique to cut off the blood supply inside liver tumors and liver metastases that leads to effective tumor control and reduced recurrence of tumors without the use of chemotherapy drugs.
"Embolic particles should be size-calibrated with a small bandwidth in diameter variations because during administration, larger particles within the same vial or syringe may occlude micro-vessels more proximally and prevent a deeper penetration of the smaller ones," reports Professor Orsi, whose findings will be presented at the CIRSE medical conference September 19-23 and published in the September edition of Vascular Disease Management.
"We are gratified that Dr. Orsi has developed this micro-bland embolization technique and demonstrated that the unique and very precise calibration of Embozene(TM) Microspheres leads to superior clinical findings in the treatment of liver cancer," said Thomas A. Gordy, President and Chief Executive Officer, CeloNova Biosciences. "Embozene(TM) Microspheres, unlike other embolics, are precisely calibrated so that larger spheres do not prevent the deepest possible penetration of tumors. Patients with liver cancer treated in this new way can experience a longer life and a better quality of life."
About Embozene(TM) Microspheres
Embozene(TM) Microspheres are the first and only microspheres to be color-enhanced with a different color for each size for increased procedural safety, efficiency and visibility. They are also available in a wider range of sizes than any other spherical embolic on the market. CeloNova's Embozene(TM) Microspheres consist of a hydrogel core and an exterior shell made from Polyzene(R)-F, CeloNova's proprietary polymer which is known to be anti-inflammatory and bacterial-resistant. Four design features distinguish Embozene(TM) Microspheres from other spherical embolics: biocompatibility, precise calibration, stable suspension, and structural stability.
About CeloNova BioSciences, Inc.
Headquartered in Newnan, Georgia, CeloNova BioSciences, Inc., is a developer of novel medical devices that are enhanced by one of the Company's proprietary materials, Polyzene(R)-F, a highly lubricious, anti-thrombotic, anti-inflammatory, and bacterial-resistant making it an ideal surface treatment for implanted medical devices. The Company's current products include Embozene(TM) Color-Advanced Microspheres and the CATANIA(TM) Coronary Stent System with NanoThin Polyzene(R)-F. Both products are CE marked and Embozene(TM) Color Advanced microspheres have been approved by the US FDA.
Source: CeloNova BioSciences, Inc
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Pa. approves over-the-counter syringe sales
http://www.philly.com/
The Associated Press
HARRISBURG, Pa. - Over-the-counter sales of syringes are now legal in Pennsylvania.
The rule change went into effect Saturday after approval from the state Board of Pharmacy.
Pennsylvania Department of State spokeswoman Leslie Amoros says the board acted to increase access to clean needles and help slow the spread of blood-borne diseases including HIV, AIDS and hepatitis.
State law previously required a prescription to buy needles and syringes. Under the new rules they still must be kept behind the pharmacy counter and sold under the supervision of a pharmacist.
According to the AIDS Law Project of Pennsylvania, New Jersey and Delaware are the only remaining states that require a prescription to buy syringes.
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Sticking it to the myths about hepatitis C
http://blogs.westword.com/
By Alan Prendergast
This week's cover story, "Going Viral," looks into how one drug-seeking hospital worker probably infected dozens of Colorado surgery patients with hepatitis C -- and the emotional fallout of Kristen Parker's recklessness for the patients, several of whom are speaking out here for the first time. Just confronting the fact that you've been injected with a potentially deadly virus is the shock of a lifetime; at the same time, many of the patients are learning quickly that the greatest challenge of having hep C is facing all the unknowns of the virus, which can affect people in radically different ways -- or not at all.
Twenty years ago, no one had even heard of hep C. It was known in medical circles as "non-A, non-B hepatitis" and among a few media alarmists as "the silent killer." But considerable research has gone into the disease over the past two decades, and there are now a range of treatment options and more promising medications in the pipeline. What hasn't gone away is the stigma associated with the virus, which is usually acquired through shared needles among intravenous drug users and convicts. But as the debacle at Rose Medical Center demonstrates, it can also be acquired unwittingly in what most people would assume is a safe and sterile setting.
Over the years, Westword has explored the impact of hep C on Colorado citizens in several ways. For a primer on the virus, see Steve Jackson's "The Hep C Generation" and follow-up coverage. For a report on how the virus has reached epidemic proportions inside American prisons, see my story about Colorado inmate Terry Akers, "The Needle and the Damage Done."
Akers died of cirrhosis not long after that story was published. For many hep C patients, the prognosis isn't as grim. But the stigma remains, despite the fact that exposure can occur in unexpected ways -- as the angry patients at Rose know all too well.
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Researchers Isolates Liver Cancer Stem Cells Prior to Tumor Formation
http://www.sciencedaily.com
ScienceDaily (Sep. 18, 2009) — Penn State College of Medicine researchers, in collaboration with colleagues at the University of Southern California, have taken an important step in understanding the role of stem cells in development of liver cancer. Using a unique approach that involves study of individual cells, the team, led by C. Bart Rountree, M.D., has demonstrated for the first time a population of cancer stem cells in the liver prior to tumor formation.
The research, published in the journal Stem Cells, shows a potential link between liver stem cells and liver cancer.
Using a liver-specific PTEN (phosphatase and tensin homolog deleted on chromosome 10) mouse model allowed Rountree and his colleagues to study the microenvironment of the liver without affecting the rest of the mouse.
"The PTEN knock-out mouse is one model of chronic liver injury that ultimately leads to liver cancer. During chronic injury, liver stem cells proliferate, and at times of healthy liver, the liver stem cells are very rare," Rountree said. "We were initially looking for what is driving liver stem cell proliferation during chronic liver injury.
"We started investigating liver stem cells in many different liver injury models with the idea we may be able to help people with liver disease, but we discovered that some cells we isolated were malignant," Rountree said. "It was quite a surprise for us because there were not any tumors in the mice when we isolated the cells."
The liver is the only organ in the body that is able to fully regenerate itself. The cells of the liver, including hepatocytes and cholangiocytes, can divide and repopulate themselves. With chronic liver injury, including by a virus or alcoholism, the hepatocytes lose the ability to make more of themselves. In that setting, liver stem cells proliferate and can make either of the cell types. However, patients with chronic injury also develop liver cancer, opening the possibility that the stem cells are involved in tumor formation.
"There's been a groundswell of interest in understanding the role of specific stem cells in the development of liver cancer," Rountree said. "There is a cancer stem cell lurking out there that may be very bad. It has stem cell properties and is malignant, resistant to chemotherapy. These properties make it harder to treat these cancers.
"What we ended up doing was shifting our understanding of liver stem cells and their role in malignancy," Rountree said. "All work previously done was looking at patients, animal models or cell lines after the tumor already developed. What we did was identify malignant stem cells before there is evidence of the primary tumor. This gave us a new perspective on not only what the potential of stem cells for therapy is, but also in terms of what's driving cancer formation. Imagine treating a cancer before a primary malignancy forms."
Researchers created ten cell lines to study using a single-cell isolation technique. Cells that make a unique surface protein called CD133 were separated by placing them in a liquid medium and running through a flow cytometer. Once identified, a robot took a single CD133-positive cell and placed it in a single drop into one well of a culture dish. Doing this several hundred times, the cell lines were established.
These single cells, when expanded up, had stem cell characteristics, having markers of both hepatocytes and cholangiocytes. When these lines were injected into a mouse with a deficient immune system, the tumors then formed.
Rountree said there is interest in targeting these stem cells with malignant potential. "Can we target these cells in patients with hepatitis B or C, either before or after their cancer forms?" Rountree said. "The broader implication is very powerful. If you look at a patient with chronic injury and find a way to specifically target cells with malignant potential, you may be able to prevent liver cancer in the first place."
Other researchers involved in the study are Wei Ding, M.D., Ph.D., Penn State College of Medicine; and Lina He and Bangyan Stiles, Ph.D., of University of Southern California, Los Angeles. This study was funded by the National Institute of Health and the American Gastroenterological Association.
Adapted from materials provided by PennStateHersheyMedicalCenter, Penn State College of Medicine, via EurekAlert!, a service of AAAS.
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September 18, 2009
Study links 45,000 U.S. deaths to lack of insurance
www.reuters.com
By Susan Heavey
WASHINGTON (Reuters) - Nearly 45,000 people die in the United States each year -- one every 12 minutes -- in large part because they lack health insurance and can not get good care, Harvard Medical School researchers found in an analysis released on Thursday.
"We're losing more Americans every day because of inaction ... than drunk driving and homicide combined," Dr. David Himmelstein, a co-author of the study and an associate professor of medicine at Harvard, said in an interview with Reuters.
Overall, researchers said American adults age 64 and younger who lack health insurance have a 40 percent higher risk of death than those who have coverage.
The findings come amid a fierce debate over Democrats' efforts to reform the nation's $2.5 trillion U.S. healthcare industry by expanding coverage and reducing healthcare costs.
President Barack Obama's has made the overhaul a top domestic policy priority, but his plan has been besieged by critics and slowed by intense political battles in Congress, with the insurance and healthcare industries fighting some parts of the plan.
The Harvard study, funded by a federal research grant, was published in the online edition of the American Journal of Public Health. It was released by Physicians for a National Health Program, which favors government-backed or "single-payer" health insurance.
An similar study in 1993 found those without insurance had a 25 percent greater risk of death, according to the Harvard group. The Institute of Medicine later used that data in its 2002 estimate showing about 18,000 people a year died because they lacked coverage.
Part of the increased risk now is due to the growing ranks of the uninsured, Himmelstein said. Roughly 46.3 million people in the United States lacked coverage in 2008, the U.S. Census Bureau reported last week, up from 45.7 million in 2007.
Another factor is that there are fewer places for the uninsured to get good care. Public hospitals and clinics are shuttering or scaling back across the country in cities like New Orleans, Detroit and others, he said.
Study co-author Dr. Steffie Woolhandler said the findings show that without proper care, uninsured people are more likely to die from complications associated with preventable diseases such as diabetes and heart disease.
Some critics called the study flawed.
The National Center for Policy Analysis, a Washington think tank that backs a free-market approach to health care, said researchers overstated the death risk and did not track how long subjects were uninsured.
Woolhandler said that while Physicians for a National Health Program supports government-backed coverage, the Harvard study's six researchers closely followed the methodology used in the 1993 study conducted by researchers in the federal government as well as the University of Rochester in New York.
The Harvard researchers analyzed data on about 9,000 patients tracked by the U.S. Centers for Disease Control and Prevention's National Center for Health Statistics through the year 2000. They excluded older Americans because those aged 65 or older are covered by the U.S. Medicare insurance program.
"For any doctor ... it's completely a no-brainer that people who can't get health care are going to die more from the kinds of things that health care is supposed to prevent," said Woolhandler, a professor of medicine at Harvard and a primary care physician in Cambridge, Massachusetts.
(Editing by Xavier Briand)
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Give your kidneys a break: lose some weight
www.reuters.com
NEW YORK (Reuters Health) - Shedding some excess weight through diet, exercise or surgery may help obese adults with kidney disease ward off further decline in kidney function, research hints.
The kidneys filter waste products from the blood and excrete them in the urine. When damaged, their ability to perform these vital functions is reduced.
More than a third of US adults are either overweight or obese, putting them at increased risk for kidney trouble, not to mention heart trouble and diabetes. Weight loss has been shown to improve control of diabetes, lower blood pressure and cholesterol levels, and reduce the effects of heart disease.
To see if losing weight might also help protect the kidneys, Dr. Sankar Navaneethan, from Ohio's Cleveland Clinic, and colleagues pooled data from 13 studies that examined the impact on kidney function of weight loss achieved through diet, exercise, or surgery. They report their findings in an upcoming issue of the Clinical Journal of the American Society Nephrology.
The researchers found that, in obese adults with kidney disease, losing weight through diet and exercise reduced one hallmark of kidney damage - namely, excess excretion of protein in the urine - what doctors call "proteinuria."
Diet- and exercise-induced weight loss may also prevent additional decline in kidney function in obese adults with kidney disease, the researchers found.
Weight loss achieved through surgery, on the other hand, seems to help normalize the rate at which the kidneys filter waste products in obese adults with abnormally high filtration rates - a well-known risk factor for the development of kidney disease.
Currently more than 20 million Americans have chronic kidney disease and it's estimated that by 2015 there will be more than 700,000 people with the most advanced form of kidney disease known as end-stage renal disease or ESRD.
"The health care costs that are associated with this increase are staggering," Navaneethan and colleagues note.
In obese adults, weight loss may offer real benefits in terms of the kidneys, in addition to the heart-related benefits of shedding excess pounds, they conclude.
SOURCE: Clinical Journal of the American Society Nephrology, 2009.
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Cases of Liver Cancer Reduced in a Younger Population Vaccinated for HBV
www.medicalnewstoday.com
A 20-year follow-up study revealed a dramatic drop in liver cancer cases among 6- to 19-year-olds who were vaccinated for the hepatitis B virus at birth, according to a study published online September 16 in the Journal of the National Cancer Institute.
In July 1984, a universal vaccination program was initiated among newborn children in Taiwan to prevent the hepatitis B virus infection, which can predispose to the development of hepatocellular carcinoma, a primary malignancy of the liver.
For this study, Mei-Hwei Chang, M.D., of the Department of Pediatrics, National Taiwan University Hospital in Taipei, and colleagues collected data from almost 2,000 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004. Age- and sex-specific incidence were compared among vaccinated and unvaccinated birth cohorts with regression models.
Sixty-four cases of hepatocellular carcinoma were found among people vaccinated in almost 38 million person-years vs. 444 cancers among unvaccinated people in almost 80 million person-years.
A few individuals have developed liver cancer despite the program. Analysis of their records shows that most of these patients, however, were not given enough doses of the vaccine, or were insufficiently protected when they were born to hepatitis B-infected mothers, according to the study.
"These data suggest that the effectiveness of the universal HBV immunization program to prevent hepatocellular carcinoma has extended beyond childhood and into young adulthood over the past two decades," the authors write.
Source: Steve Graff, Journal of the National Cancer Institute
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Prime Minister Bayar Diagnosed to Have Hepatitis C
http://ubpost.mongolnews.mn
Written by Ch.Sumiyabazar
The Prime Minister of Mongolia S.Bayar, who left the country for a medical trip to South Korea to treat his old injury, was diagnosed to have viral Hepatitis C that affects the liver and can cause further hardening of liver which needs hospitalized treatment, according to a press statement by Minister of Health S.Lambaa, who quickly returned to Ulaanbaatar from his trip to Arkhangai province to clarify latest media reports. “Necessary treatments are now being made to the prime minister. We expect the Prime Minister S.Bayar to return home country on September 21 after his treatment ends,” Lambaa said.
“No medical treatment, except liver protection measures such as consumption of vitamins, was being received by Prime Minister S.Bayar. He had very tight work schedule that kept him busy all the time. He had no time to get proper hospitalized treatments,” Lambaa said.
Bayar was reported to have the viral infectious disease of Hepatitis C before he took office of prime minister. He said that the Prime Minister took a holiday of five working days only since he assumed office in November 2007. In Seoul, Lambaa said, Prime Minister Bayar is now receiving “interferon-based therapy”.
He denied recent media reports that said Bayar’s prior injury in his backbone and legs was caused by a road accident. He said that the prime minister will remain under control of a state medical institution after his return.
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ICAAC: Hepatitis E Virus Finally Gets Some Respect
http://www.medpagetoday.com
By Crystal Phend, Senior Staff Writer, MedPage Today
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
SAN FRANCISCO -- Hepatitis E virus, known for decades but given little attention, is gaining recognition as a public health problem, particularly for pregnant women and transplant recipients.
"Now we're beginning to recognize that this is an important virus," Kenrad Nelson, MD, of Johns Hopkins Bloomberg School of Public Health, told attendees at the Interscience Conference on Antimicrobial Agents and Chemotherapy.
Hepatitis E causes outbreaks, largely in the developing world, through waterborne transmission. But it's endemic in the U.S. as well. Nelson's group analyzed the 1990-1992 National Health and Nutrition Examination Survey and found antibodies to the virus in 21% of Americans, more likely because of food-borne infection.
The first large epidemic of what is now known as hepatitis E struck at least 30,000 people in Dehli, India, after monsoon rains in 1955. The outbreak was predominantly among adults, which raised suspicions of a new virus, since the only hepatitis known at the time -- hepatitis A -- affected mainly infants and children.
It wasn't until the 1980s -- after the discovery of other viruses that caused hepatitis -- that this theory was proven by a Soviet scientist who mixed a stool sample with yogurt and drank it for want of a better mode of transportation to his lab from the remote central Asian site of the outbreak.
Since then, hepatitis E has been characterized, cloned, and sequenced. Researchers even developed a vaccine to prevent it, Nelson said.
Although the vaccine was 95% effective in preventing clinical hepatitis E, GlaxoSmithKline abandoned it because of what it regarded as an untenable commercial market -- predominantly monsoon areas such as India, Burma, and Pakistan, Nelson said.
Now annual outbreaks strike tens of thousands in the developing world each year, with a 10% to 20% death rate for infected women in their last trimester of pregnancy, Nelson said.
"This is a public health emergency that's not being dealt with," he declared.
In industrialized nations, a threat is emerging among immunosuppressed patients, which is changing the way epidemiologists regard hepatitis E, Nelson said.
One study from England showed hepatitis E infection became chronic in eight of 14 infected solid organ transplant recipients, a condition that can lead to later cirrhosis and organ failure. One chronic case has been reported in an HIV patient as well.
"There are just a couple of papers because nobody has really looked so far," Nelson said. Elevated liver enzymes in these patients are often attributed to the phalanx of drugs they receive, so they rarely are tested for the virus, he explained.
Public health researchers have attempted to interest the Bill & Melinda Gates Foundation and other international aid groups in further development of the vaccine, without success so far, Nelson noted.
"Clearly it's indicated in areas where these huge epidemics occur, and particularly in pregnant women," he said.
Other likely candidates for inoculation against hepatitis E would be patients anticipating organ transplantation before they go on immunosuppressive drugs, he said, though it's not clear if the antibodies would be protective while on immunosuppression.
Nelson reported no conflicts of interest.
Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy
Source reference: Nelson KE "Hepatitis E: Emerging issues worldwide and among transplant recipients" ICAAC 2009; Session 055(L1).
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September 19, 2009
University Hospital Coventry unveils life-saving liver scanner
http://www.coventrytelegraph.net
by Warren Manger, Coventry Telegraph
COVENTRY’S University Hospital has unveiled a high-tech new scanner which will help save the lives of patients with liver damage.
The £62,000 scanner at University Hospital in Walsgrave will allow doctors to check for liver damage without having to risk the complications involved in carrying out a liver biopsy.
It will be a vital tool in the fight against Hepatitis C, which can cause fatal cirrhosis of the liver.
Consultant liver specialist John Wong said: “Until now, the only way we’ve been able to check the extent of Hepatitis C-related liver damage is by carrying out a biopsy – removing a small sample of someone’s liver and checking it under the microscope.
“Liver biopsy is associated with potential complications which put people off getting tested and assessed for Hepatitis C treatment.
“The new scanner works like an ultrasound machine, in a similar way as those used during pregnancy. It is completely painless and safe and allows us to assess for any liver damage far quicker.”
The unveiling of the new scanner coincides with the launch of a campaign to encourage people in Coventry who are most at risk from Hepatitis C to get tested.
Around four in every five people who have contracted it do not realise they have the condition as they have no symptoms.
Anyone who has ever injected illegal drugs like heroin is being urged to see their GP, even if they have only done it once because two out of every five injecting drug users have contracted the virus.
Other people at risk of Hepatitis C include anyone who has had a tattoo or piercing done with unsterile equipment and people who have received medical or dental care in parts of the world where infection control is poor, such as Asia and Africa.
The campaign has been funded by the Coventry Community Safety Partnership and will include buses bearing promotional artwork.
Coun Andrew Williams, cabinet member with responsibility for community safety, said: “Hepatitis C is a major health risk which can lie undetected for many years.
“Anyone who has injected drugs, even if only once or a long time ago, is at risk and should request testing from their GP. Treatment is available but is less successful the longer the virus is left undiagnosed.”
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