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Publishing in Nature Medicine and showcased in Nature Research Highlights, the paper describes how working in mouse models the team were able to tip this balance to favour healthy tissue regeneration and block scarring by manipulating the actions of serotonin - the “happy” drug.
Manipulating serotonin can promote healthy repair in chronic liver disease
Publishing in the leading medical journal Nature Medicine, a team led by Newcastle University academics have identified serotonin receptors which can be targeted with drugs to enhance the natural healing properties of the liver.
In liver disease, extent of tissue damage depends on the balance between the generation of scar tissue and the regeneration of new liver cells. In a significant minority of people who get injury to their organs instead of repairing them, they form scars. This can progress to chronic liver disease and cirrhosis where the scarring is so extensive the liver is unable to clean blood or produce vital hormones and clotting factors. Liver scars also provide an ideal environment for the development of cancers.
Publishing in Nature Medicine and showcased in Nature Research Highlights, the paper describes how working in mouse models the team were able to tip this balance to favour healthy tissue regeneration and block scarring by manipulating the actions of serotonin - the “happy” drug. Normally when a liver is injured – by a virus such as Hepatitis C or B, by alcohol, environmental factors or by a metabolic or autoimmune condition – specialised blood cells known as platelets make general repairs and secrete serotonin. However, the team found that when scar-forming cells - Hepatic stellate cells (HSC) – are present they are instructed by the serotonin to make more scar tissue and switch off the healthy regeneration.
Identifying the receptor called 5-HT2B through which serotonin instructs the scar forming cells to switch off regeneration, they found that this resulted in less scarring and more regeneration. Of the work funded by the Medical Research Council and the Wellcome Trust, lead author, Professor Derek Mann said; “These are promising results in mouse models of liver disease and suggest that chemicals targeting 5-HT2B , which are currently in clinical trials for mood disorders and pulmonary hypertension might also have an application in the treatment of chronic liver disease.” The group believe the mechanism may also be found in other organs and offers an exciting opportunity for study in the future.
More information: Stimulating healthy tissues regeneration by targeting the 5-HT2B receptor in chronic liver disease, Derek A Mann et al. Nature Medicine.10.1038/10.1038/nm.2490
Provided by Newcastle University
HCV Worldwide
About 10 million people infected with Hepatitis- C in Pakistan
In Pakistan about 10 million people, which is about 6 per cent of the total population, is affected with hepatitis- C.
This was stated at a lecture jointly organised by Dr. Panjwani Centre for Molecular Medicine and Drug Research (PCMD).
It was pointed out that Hepatitis is an inflammation of the liver generally due to the viral infection or due to some metabolic abnormalities.
In his lecture Prof. Dr. Aqeel Ahmed of the Department of Microbiology, University of Karachi, expressed the apprehension that mortality rates due to hepatitis- C are expected to go up in future.
The Karachi University statement on Sunday said that the topic of his talk was ‘HCV: Disease and Prevention’.
It was jointly organised by PCMD and Virtual Education Project Pakistan (VEPP) as a part of series of popular lectures for public awareness on common diseases of Pakistan.
Health professionals, students, research scholars, NGO representatives and general public attended the lecture.
Prof Ahmed said that hepatitis is inflammation of the liver generally due to viral infection caused by hepatitis viruses; these unrelated viruses have different epidemiologic profiles and are transmitted through different routes which are either water-borne, or spread through the blood, blood products or unethical medical or social practices.
He said that Hepatitis viruses produce inflammation in the liver, resulting in clinical illness characterised by fever, and often non-specific symptoms like pain in abdomen, loss of appetite, nausea, vomiting and jaundice, he said, adding more than 70 per cent of HCV infected patients become chronic, which may lead to death of patient.
Prof. Ahmed said that this has immense financial implications, so early detection and treatment of Hepatitis- C is recommended.
Genotypes 3a and 3b, amongst 11 genotypes of hepatitis, are found to be the most common genotypes in some regions of the world.
He stated that patients with these genotypes also had good chances of response rate to the therapy.
There are some host-factors attributed to increased risk of HCV infection, including older age, male gender, co-infection with HIV, HBV.
Other factors such as alcohol consumption, iron overload and hepatotoxic medicines also have damaging effects.
Patients with chronic hepatitis ‘C’ can develop many extra hepatic symptoms like rheumatoid arteritis, keratoconjunctivitis sicca, glomerulonephritis and lymphoma which are probably due to altered immune response.
Psychological disorders like depression are seen in about 20 to 30 per cent patients.
Talking about prevention of the fatal disease, he said that there are some important preventive measures that include increasing awareness of disease; blood screening before transfusion; avoiding re-use of syringes and sharing common household items such as razors and tooth brushes; training of healthcare workers; treating Hepatitis- C patients with appropriate drugs including interferon and ribavirin.
A Hepatitis C epidemic has broken out in Woyang county in Bozhou, Anhui Province, and may have been caused by unsafe injections, said local health authorities.
According to a press release issued by the Anhui Provincial Health Bureau on Monday, 56 potential carriers of the virus were examined and 13 were tested positive.
Many of the Hepatitis C carriers are children, according to China National Radio, which reported parents in Woyang often take their kids to the nearby Miaoqian clinic in Maqiao, Henan Province, to see doctors.
After hearing rumors that some children in Maqiao, who go to the same clinic, contracted Hepatitis C, the parents in Woyang took their kids to local hospitals to get blood tests and found out their children are also infected.
According to the press release, the Anhui Provincial Health Bureau received a report from the Bozhou Health Bureau on Friday indicating a Hepatitis C epidemic had broken out. The initial investigation suggested the epidemic may have been caused by unsafe injections because all the carriers had intravenous injections at the private clinic in Henan Province.
"The number of the Hepatitis C virus carriers remains at 13 for the time being. We received the report from the Bozhou Health Bureau on Friday," said an employee at the public relations office in Anhui Province, who refused to give her name or reveal more details of the case. "We will have a meeting to discuss the public awareness strategy."
Hepatitis C is an infectious disease primarily affecting the liver. It usually spreads through contact with infected blood and there is no vaccine for it.
Most of those infected have no symptoms until the virus causes liver damage, which can take 10 or more years to occur.
Though some people can fight off the virus, most Hepatitis C infections become chronic. Without treatment, chronic Hepatitis C can scar the liver and lead to liver cancer or liver failure.
The outbreak comes one year after a cholera epidemic in Anhui, which infected 33 people.
In August 2010, health authorities in Mengcheng, Anhui Province, withheld the statistics of the cholera epidemic for 12 days.
The county said the numbers were delayed because it was not at liberty to release them.
Wang Jianjun, a vice director of the Anhui Center for Disease Prevention and Control, said people will become indifferent to epidemics if they publicize each infection case immediately.
And the decision on whether or not to notify the public was also based on a discussion with the Ministry of Heath, according to the Southern Metropolis Daily.
In Case You Missed It
Hep C Protease Inhibitors May Not Be Cost-Effective For Some First-Time Treatment Takers
Hepatitis C virus (HCV) protease inhibitors are not cost-effective for first-time treatment takers with HCV genotype 1 and the IL-28B CC genotype, according to analysis conducted by Ziad Gellad, MD, MPH, of Duke University Medical Center in Durham, North Carolina, and his colleagues. They reported their findings on Monday, November 7, at the 62nd annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco. According to the study authors, people with the IL-28B CC genotype are more likely to be cured with pegylated interferon and ribavirin alone than people with the IL-28B CT or TT genotypes, for whom the addition of either Incivek (telaprevir) or Victrelis (boceprevir) may be more cost effective.
A 24- to 48-week course of pegylated interferon and ribavirin ranges from $18,000 to $30,000. As Gellad noted, “adding Incivek (telaprevir) or Victrelis (boceprevir)”—both recently approved HCV protease inhibitors—“more than doubles the cost of therapy, to a range of $48,000 to $85,000.” Read More Here
MT MRI Contrast No Help in Cirrhosis Diagnosis
Magnetization transfer (MT) contrast-prepared magnetic resonance imaging is “unlikely to be of clinical utility” in diagnosing cirrhosis, according to a study published online Nov. 23 in the journal Radiology. The study did confirm the ability of MT contrast prepared MRI to help distinguish substances of varying protein concentration, according to New York University researchers led by radiologist Andrew B. Rosenkrantz, MD. Researchers studied 20 patients with cirrhosis and portal hypertension and 20 healthy volunteers with no known liver disease. Rosenkrantz and colleagues had previously optimized the MT sequence using agar phantoms with protein concentrations ranging from 0 percent to 4 percent. The subjects underwent liver MR imaging that included eight separate breath-hold MT contrast sequences, each performed by using a different MT pulse frequency offset (range, 200–2500 Hz). Regions of interest were then placed to calculate the MT ratio for the liver, fat, and muscle in the volunteer group and for the liver in the cirrhosis group. The MT ratio was nearly identical between healthy (26.0 percent to 80.0 percent) and cirrhotic livers (26.7 percent to 81.2 percent) for all frequency offsets. But as has been showed with previous studies, MT ratio can indeed differentiate tissue types. MT ratio increased with decreasing MT pulse frequency offset for each of the four phantoms and the assessed in vivo tissues, consistent with previous reports. At all frequency offsets, MT ratio increased with increasing phantom protein concentration. In volunteers, at frequency offsets greater than 400 Hz, the MT ratio was significantly greater for muscle (34.4 percent to 54.9 percent) and much lower for subcutaneous fat (10.3 percent to 12.6 percent), compared with that for the liver (22.8 percent to 46.9 percent).
From Journal of Viral Hepatitis
HIV and HCV Health Beliefs in an Inner-city Community
Posted: 11/27/2011; J Viral Hepat. 2011;18(11):785-791.
© 2011 Blackwell Publishing
HIV and HCV Health Beliefs in an Inner-city Community
This study underscores the importance of public health interventions to educate the public about the dangers of hepatitis C, especially in vulnerable inner-city communities.
Journal of Viral Hepatitis, November 2011
Discussion Only
Click Here For Full TextIn this study of inner-city adults from a community at high risk for HIV and HCV, participants were more likely to have inaccurate health beliefs about risks factors for causes, sequelae and control of HCV than of HIV. Overall, our results demonstrate that study participants have accurate health beliefs for HCV only 58% of the time. Furthermore, as hypothesized, our study population demonstrated significantly less accurate health beliefs about HCV than about HIV, despite the fact that participants were recruited from a community with higher prevalence of HCV than of HIV. This discrepancy in health beliefs for the two infections was present for several key domains within the Common Sense Model.
Results of our study also highlight specific health belief inaccuracies that might be important targets for public health interventions. When compared to HIV, fewer participants accurately believed that HCV could be prevented, fewer believed that HCV could be transmitted by sharing needles, and less than half accurately believed that it is a potentially life-long infection. The fact that beliefs were more accurate for HIV than for HCV in our study suggests that lessons might be learned from successful HIV interventions to improve similar health beliefs about the risk for and long-term consequences of HCV.
In contrast with HIV that cannot yet be cured, HCV treatments are curative (defined as sustained viral response 6 months after completing treatment). While treatment with pegylated interferon and ribavirin is involved and often arduous, a sustained viral response can be obtained in 40–80% of treated cases of chronic HCV, depending on viral genotype and certain patient characteristics. Furthermore, the advent of new therapies suggests that cure rates may rise in the near future. Yet, only 25% of our study participants believed there to be a potential cure for HCV infection. In general, low uptake of HCV treatment poses a persistent challenge – despite the possibility of SVR, 20–30% of patients with HCV initiate and complete therapy.[26,27] The decision to initiate treatment for HCV is complex and health beliefs may pose an important component. The commonly held belief among patients in our study that HCV is not curable may stem in part from limited knowledge about treatment options. It is also possible that treatment side effects or treatment failures have been disproportionately represented in our survey community, thus contributing to the belief that HCV is not curable.
A number of additional associations deserve comment. First, only one quarter of our survey participants accurately believed that both HIV and HCV can cause cancer. These are concerning results as HCV continues to represent the leading cause of liver transplantation in the United States, contributing significantly to growing rates of cirrhosis and hepatocellular carcinoma.[28] Similarly, since the advent of HAART, rates of cancer – in particular non-AIDS malignancies – continue to rise in the HIV-infected population.[29,30] It may be difficult for individuals to modify perceptions of HIV and HCV as infectious diseases that are capable of resulting in long-term, even chronic, health consequences. Interventions to improve health beliefs about HIV and HCV might highlight the growing overlap of infectious disease elements with long-term, chronic disease characteristics within these illnesses. Helping patients understand that engaging in healthier behaviours related to HIV and HCV may prevent not just the infection, but also the development of chronic disease and cancer, may prove to be a compelling public health strategy. Sylvestre et al.,[31] for example, have demonstrated that peer-based educational interventions have successfully engaged members of an urban community of drug users in care, with subsequent increases in HCV testing and treatment uptake. Broader application of these techniques might serve to improve health beliefs and HCV health outcomes in additional at-risk communities.
Second, the association between female gender and accurate health beliefs about HIV deserves some exploration. Perhaps this association reflects the fact that women, more often then men, participate in the health care system and in accessing community-based health information – either in caring for themselves or as caregivers for others.[32–34] As a result, women may come into contact more often with accurate health information, may be more motivated themselves to seek screening and treatment in general, and may be more likely to encounter others seeking screening and treatment for HIV. These factors may subsequently contribute to more accurate HIV health beliefs.
To our knowledge, at present there are no studies formally comparing health beliefs about HIV and HCV in an at-risk community in the United States, using the Self-Regulation model. Several limitations of our study are worth noting. The overall sample size and response rate were modest. Yet the sociodemographics of participants in our study were representative of the clinic population in general, and the high rate of Medicaid insurance was reflective of the study community at large. In addition, our study was conducted in a single, hospital-based, academic internal medicine practice, and findings should therefore be interpreted carefully in the context of other settings. Interviews for this study were conducted in-person, which may have resulted in some response bias because of the highly personal and sensitive nature of some of the survey questions. Less-public approaches to asking them, such as audio computer assisted self-interviews, might have been more effective at eliciting some participants' health beliefs. In addition, 'history of sex without a condom with a person at risk for HCV' was included as an independent variable in our regression model. Use of this variable as a predictor is ambiguous, as evidence in the time period since this study was conducted demonstrates that HCV is not a sexually transmitted infection in the traditional sense, given that its mode of transmission is blood borne. Finally, our study suggests that further research might explore health beliefs compared to health knowledge in a similar population.
Prominent public health messages about HIV appear to have largely been received and remembered by this at-risk population. This does not appear to have been the case with HCV in this same population, despite shared risk factors. This deficit, therefore, is likely not due to underlying low health literacy of this population. Instead, it may reflect that our study population has not been effectively exposed to detailed HCV public health messages or that these messages simply do not exist. As Klein et al. describe, despite the creation of the National Hepatitis C Prevention Strategy in 2001, federal funding for HCV in the United States through the Centers for Disease Control and Prevention Division of Viral Hepatitis has been limited to supporting HCV coordinators on a State level. Thus, federal funding has not been sufficient for the development of sustainable HCV public health prevention programmes or services implementation.[35] Furthermore, if HCV public health messages have been created on a local level, they may not have effectively connected with our study population. As the burden of HCV infection continues to mount in the United States and promising new therapies become available to combat it, screening and treatment must increase beyond their current, disappointingly low rates. The Institute of Medicine recently acknowledged this need when it issued its Report on Hepatitis Prevention and Control, which recommends the development of national public health strategies to improve awareness of HCV in at-risk communities and in the general population.[3] Disseminating accurate information about HCV may be a key element to modifying patient behaviour and may subsequently result in better health outcomes for patients. Educational efforts should extend beyond providing correct health information to improve knowledge and should also address specific socio-cultural experiences that influence the development of health beliefs to perhaps foster healthier behaviours.
Hepatitis B
| Liver cancer occurs in immigrants with Hep B younger than screening guidelines | |
| Antigens and not genotypes predict viral load in Hep B |
Liver Transplants
Novel score improves guidelines for allocation in liver transplants
The latest Annals of Surgery reports on a novel score targeting justice and utility in the Model for End-Stage Liver Disease era.
Dr Philipp Dutkowski and colleagues designed a new score on risk assessment for orthotopic liver transplantation based on both donor and recipient parameters.
The balance of waiting list mortality and posttransplant outcome remains a difficult task in the era of the model for end-stage liver disease (MELD).
Using the United Network for Organ Sharing database, a risk analysis was performed in adult recipients of orthotopic liver transplantation in the United States of America between 2002 and 2010.
Living donor-, partial-, or combined-, and donation after cardiac death liver transplants were excluded.
Predictors included recipient MELD score and recipient age
Annals of Surgery
The research team then calculated a risk score on the basis of logistic regression factors, and validated using our own orthotopic liver transplantation database.
Finally, the team compared the new score with other prediction systems including donor risk index, survival outcome following liver transplantation, donor-age combined with MELD, and MELD score alone.
The team identified 6 strongest predictors of posttransplant survival.
The predictors were recipient MELD score, cold ischemia time, recipient age, donor age, previous orthotopic liver transplantation, and life support dependence prior to transplant.
The researchers found that the new balance of risk score stratified recipients best in terms of patient survival in the United Network for Organ Sharing data, as in the European population.
Dr Dutkowski's team concluded, "The BAR system provides a new, simple and reliable tool to detect unfavorable combinations of donor and recipient factors, and is readily available before decision making of accepting or not an organ for a specific recipient."
"This score may offer great potential for better justice and utility, as it revealed to be superior to recent developed other prediction scores."
Ann Surg 2011: 254(5): 745–754
28 November 2011
Nonalcoholic steatohepatitis (NASH)
From Medscape Medical News
More Nonalcoholic Steatohepatitis Requiring Transplant
"NASH is increasingly an indication for liver transplant," said Danielle Brandman, MD, from the University of California at San Francisco. "Factors for this include the addition of NASH as a diagnosis in the UNOS [United Network for Organ Sharing] database, and increased awareness of NASH as a cause of end-stage liver disease." Up to half of all cases of cryptogenic cirrhosis are likely a result of unrecognized NASH, although Dr. Brandman noted that there are no uniform diagnostic criteria to define cryptogenic cirrhosis caused by NASH.
To identify the NASH-related risk factors driving this increase, the researchers conducted a comparison of pre- and post-MELD score measures.
The findings suggest that steep increases in the incidence of obesity and insulin resistance are the culprits, as opposed to the recorded rates of hypertension and dyslipidemia, which have remained essentially stable since 2002.
In addition to these changes occurring over time in the general population, "we must think about how patients with NASH undergoing liver transplant may be changing over time," said Dr. Brandman. This study is an investigation of changes in the characteristics of liver transplant recipients secondary to NASH over time, as well as patient survival after transplantation for NASH.
The data for this retrospective investigation were drawn from the UNOS database. The inclusion criteria included being 18 years or older and undergoing liver transplantation from 2002 to 2009. Exclusion criteria included retransplantation, HIV positivity, fulminant hepatic failure, and rare liver diseases.
Cases of NASH and "probably NASH" were combined for the analysis. NASH was determined using primary diagnostic code at liver transplantation, and probably NASH was defined as preliver transplant diabetes mellitus, preliver transplant hypertension, and/or a body mass index (BMI) of 40 kg/m² or higher.
After reviewing 30,182 charts, Dr. Brandman's team identified 1355 cases of NASH and 1537 cases of probably NASH. In the probably NASH group, 70% had diabetes, 32% were hypertensive, and 9% had a BMI of 40 kg/m² or higher. Many patients had more than 1 condition, and half of the remaining liver transplant recipients were positive for hepatitis C virus infection.
There were more females in the NASH/probably NASH group than in the no NASH group (43% vs 29%), more patients with a BMI of 40 kg/m² or higher (31.7% vs 27.5%), more white patients (31.7 vs 27.5), more preliver transplant diabetes (67% vs 19%), and more hypertension (43% vs 16%). Patients in the NASH/probably NASH group had a low prevalence of hepatocellular carcinoma but a high requirement for renal replacement therapy just before transplantation.
Five-year survival rates after liver transplantation in the 2 groups were the same (81.1%).
Matching temporal trends of these measures to risk and outcome has been problematic. "Since 2002, NASH is an increasing indication for liver transplant; it was responsible for just over 4% of transplants in 2002 and more than 12% in 2009," said Dr. Brandman. "At the same time, those identified as having NASH/probably NASH exhibited less preliver transplant diabetes and pretransplant hypertension over time, despite increases in these conditions in the general population."
Dr. Brandman surmises that the selection criteria for liver transplantation are likely being applied. "Additional studies are needed to determine what these criteria are, and which are the strongest predictors of outcome."
There's Something Happening Here
"NASH can definitely kill an individual," said Arun Sanyal, MD, chair of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University in Richmond. Patients with NASH have a 15% to 20% risk of progressing to cirrhosis and end-stage liver disease, and there is increasing evidence that NASH may be connected to the development of hepatocellular carcinoma, even in the absence of cirrhosis. "That has huge public health implications because this cancer has one of the fastest rising incidences in the country."
Dr. Sanyal concurs with Dr. Brandman that the factors driving the increase in NASH are not clear.
"The increasing incidence of obesity and insulin resistance are 2 factors certainly." Other suggested contributors are the consumption of high-fructose corn syrup and environmental exposure to pollution. "There are studies that have linked exposure to various hydrocarbons to the development of fat in the liver — one of the defining characteristics of NASH."
Genetics also play a role. "We know that African Americans have a high incidence of hypertension and diabetes, but seem to be protected from fatty liver disease. In contrast, Hispanics have a high rate of metabolic syndrome and fatty liver disease," Dr. Sanyal said.
What is the clinician to do for the obese or hypertensive patient regarding NASH? "This is an emerging trend, so we're not quite there yet with a general clinical recommendation." There is no set diagnostic criteria for the disease, and other than lifestyle interventions, there is no approved treatment, although vitamin supplements can help. "We published a study last year showing that vitamin E at 800 units/day reverses NASH in roughly 40% of patients [N Engl J Med. 2010;362:1675-1685]," Dr. Sanyal noted.
Dr. Brandman and Dr. Sanyal have disclosed no relevant financial relationships.
The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 12. Presented November 8, 2011.
Journalist
Neil Canavan
Neil Canavan is a freelancer for Medscape.
Read More Here
More Stories Skin Deep
Rob Norman
This is part two of Stories On The Skin: The Life and Times of Tattoos, Piercings, and Modifications.Tattoos had been used in ancient Greece and Rome to mark ownership of slaves and as punishment for criminals.
Excerpt;
Health Considerations
What about the piercing and tattoo scene and where is it headed? Both forms of adornment have their dangers. The American Dental Association opposes oral (tongue, lip, or cheek) piercing and calls it a public health hazard. The American Academy of Dermatology has taken a position against all forms of body piercing with one exception: the ear lobe.
People piercing their bodies should concern themselves with more than just sensitivity and allergic reactions. One of the biggest problems many of us see is keloid formation. Although the ear lobe is made of fatty tissue and has a good blood supply, it does not protect you from the wrath of keloids and other disfiguring growths that can sprout up in response to piercing.
A keloid is a large scar or raised portion of abnormal skin. I have removed horrendous keloids on those that have had ear piercings including one recently that had grown to the size of a small tomato on the right ear of an African-American man.
The tattooing procedure involves a variable amount of pain and a small amount of bleeding. The medical complications can be classified as either infectious or noninfectious. Noninfectious include scarring (common), skin allergies to the jewelry metals, urticarial (hive-like) reactions, and prolonged bleeding. Malignant melanoma, basal cell carcinoma, squamous cell carcinoma, psoriasis, sarcoidosis and lupus have been attributed to tattoos.
Infectious agents include Hepatitis B and C, tetanus, syphilis, leprosy, tuberculosis, warts, fungus, HIV, and pyogenic Staphylococcus and Streptococcus infections (cellulitis and gangrene necessitating amputation). One must even be cautious of the benign, pretty tattooed butterfly, for it may be a vector of mycobacteria.
Make sure that wherever you go for piercing is a reputable place. It’s important to ask what tools and devices they are using and whether they’re going to check for allergic reactions.
Both the U.S. and Canadian Red Cross will give you a year’s deferment if you’ve been pierced or tattooed except at a state-licensed shop. Why? Both procedures can transmit dangerous blood-borne diseases. Beyond the immediate pain and suffering of the procedure, other factors including the risk of chronic infection including abscesses or boils, prolonged bleeding, scarring, Hepatitis B and C, Tetanus, skin allergies to the jewelry that’s used, permanent holes, chipped or broken teeth, choking from mouth jewelry, and a speech impediment.
Tattoos require appropriate aftercare, including keeping them clean while they heal, usually 5-10 days. Once they’re healed, sunscreen is strongly recommended, both because the skin is more susceptible to the rays of the sun and to prevent fading.
Read More Here
AIDS
Compound dissolves HIV on contact
November 28, 2011
TEXAS A&M (US) — Researchers are closer to developing a topical compound that stops HIV by dissolving the virus on contact.
The ability of the synthetic compound known as “PD 404,182″ to break apart the AIDS-causing virus before it can infect cells was discovered by Zhilei Chen, assistant professor of chemical engineering at Texas A&M University, and her team of researchers. Their findings appear in the journal Antimicrobial Agents and Chemotherapy.
“This is a virucidal small-molecule compound, meaning that it has the ability to kill a virus; in this case that virus is HIV,” Chen says. “Basically, it acts by breaking the virus open. We found that when HIV comes in contact with this compound, it breaks open and loses its genetic material.
“In a sense, the virus ‘dissolves,’ and its RNA becomes exposed. Since RNA is pretty unstable, once it is exposed it’s gone very quickly and the virus is rendered non-infectious.”
In other words, the compound works by quickly ripping open the virus before it can inject its genetic material into a human cell. What’s more—and perhaps even more important—the compound, Chen explains, achieves this by acting on something within the virus other than its viral envelope protein, meaning that the virus can’t alter its proteins to bolster its resistance—something that’s made HIV notoriously difficult to treat.
“We believe this compound is not working on the viral protein of the viruses but on something else common in all the viruses on which we tested it—some cellular material common in these viruses,” Chen notes. “Because this compound is acting on a component that is not encoded by the virus, it will be difficult for the virus to evolve resistance against this compound.”
While not a cure for HIV, the compound demonstrates significant potential for use as a preventative, specifically in the form of a topical gel that could be applied in the vaginal canal, Chen explains.
“We conducted a number of tests to demonstrate that this compound remains active in vaginal fluid and is not rendered ineffective,” Chen says. “In the form of a vaginal gel, the compound would serve as a barrier, acting almost instantaneously to destroy the virus before it could infect a cell, thereby preventing HIV transmission from one person to another.”
Surprisingly, Chen and her team did not set out to discover an HIV preventative. Instead, they were conducting screenings of molecules for use in potential drug therapies targeting hepatitis C virus, which causes the dangerous and often fatal disease of the liver. Employing a screening system developed by Chen, the team screened thousands of molecular compounds, in search of those that could block aspects of the HCV life cycle.
During the course of the screenings, the team made an interesting discovery—not only was PD 404,182 an HCV inhibitor, it also worked on lentiviruses (the group’s negative control in its experimental procedures). Intrigued by that finding, Chen then tested PD 404,182 on HIV, which itself is a lentivirus and found the compound to be even more effective on HIV than on HCV.
“We believe PD 404,182 acts through a unique and important mechanism,” Chen notes. “Most of the known virucidal compounds interact with the virus membrane, but our compound does not appear to interact with the virus membrane. Instead, it bypasses interaction with the membrane and still compromises the structural integrity of the virus.”
The ability of the compound to avoid interaction with the virus membrane is important because human cells have similar membranes, Chen notes. If the compound were to disrupt the structure of the virus membrane, it could also disrupt and ultimately kill human cells. PD 404,182 doesn’t interact with these membranes and is therefore a more attractive option for clinical treatment.
As is the case with any potential pharmaceutical, several key steps are still needed before it winds up on drug store shelves. In addition to several rounds of animal studies to ensure the compound is safe for humans, further collaborations with chemists are needed to continue to improve the efficiency of the compound. Chen says.
Chen also plans to further explore the mechanism by which PD 404,182 breaks apart HIV. Collaborators include scientists at the Scripps Research Institute.
More news from Texas A&M University: http://tamutimes.tamu.edu
Global Fund halts new funding until 2014
Crossposted from Nature's news blog
The Global Fund to Fight AIDS, Tuberculosis and Malaria has cancelled its 11th funding round because of the current economic crisis.
“Substantial budget challenges in some donor countries, compounded by low interest rates have significantly affected the resources available for new grant funding,” the fund said in a statement on 23 November.
It will still provide some funding to existing projects to keep them going over the next couple of years, but will award no new grants before 2014. The fund, a public-private partnership supported by around 150 donor countries, also announced that it would create a new general manager position, taking management responsibility away from executive director
Continue reading on Nature's news blog.
Vitamin D Benefits: Hope or Hype?
By Michael Smith, North American Correspondent, MedPage Today
Published: November 27, 2011
In the past few months, deficiency in the substance has been linked to chronic obstructive pulmonary disease, tuberculosis, spinal inflammatory diseases, age-related macular degeneration ... and the list goes on.
On the other hand, taking high doses of vitamin D didn't help patients with multiple sclerosis, MedPage Today reported, and it was of no benefit in reducing left ventricular mass in patients with chronic kidney disease.
But overall, vitamin D gets pretty good press. The trouble is that hard evidence to back up the vitamin's benefits is lacking, according to Clifford Rosen, MD, of the Maine Medical Center Research Institute in Scarborough. "There's no data," Rosen told MedPage Today. "It's all weak association studies."
Benefit Beyond the Bones
At the American Heart Association meeting earlier this month, several studies suggested associations between low vitamin D and various aspects of heart disease.
But as one observer said at the time, there are no clinical trials yet that show improving vitamin D status does anything to reduce cardiovascular risk.
One study, the Vitamin D and Omega-3 (VITAL) trial, may shed some light on the issue. It is a randomized trial that is enrolling some 20,000 patients to see if daily vitamin D supplements prevent cancer and cardiovascular disease.
It will be one of the few randomized trials -- if not the only one -- to look at the issue directly, according to JoAnn Manson, MD, of Brigham and Women's Hospital in Boston, who is the principal investigator.
Although other randomized trials have produced evidence for a vitamin D benefit in several important clinical categories, Manson told MedPage Today it was mostly as an afterthought.
"Many of the randomized trials people have heard about were trials designed to look at the effect of vitamin D on fractures and falls," she said, with other effects as secondary outcomes.
It's in the nature of statistics, she pointed out, that if researchers look at enough outcomes, some will be significant just on the basis of chance.
The vast mass of the evidence for any kind of nonskeletal benefit is observational, and therefore suspect until confirmed by a properly designed, randomized trial, Manson said.
Among other things, a host of confounding factors -- obesity, poor nutrition, lack of exercise -- might play a role. No matter how carefully an observational study is done, she said, confounding is always possible. "Correlation does not prove causation," Manson reminded.
She noted that randomized trials have demolished observational evidence many times in the past, notably in the cases of such former fads as beta-carotene and selenium.
According to Rosen, there is reasonable evidence that improved vitamin D status leads to better bone health and some evidence that supplements reduce all-cause mortality in elderly women.
For almost everything else, he said, hard evidence is missing.
Biologically Active D
Measuring exposure to vitamin D is relatively easy -- it's a simple matter of serum levels of a compound called 25-hydroxyvitamin D, or 25(OH)D, Rosen said.
But the relationship between circulating 25(OH)D and the active form of the vitamin, 1,25-dihydroxycholecalciferol, is not clear. It's entirely possible, he said, to have low levels of 25(OH)D and yet have a perfectly adequate amount of the hormonally active form.
Indeed, Manson said, the Institute of Medicine (IOM) recently estimated that the average requirement of 25(OH)D is really only 16 nanograms per milliliter -- a level that would in most cases ensure adequate amounts of the active vitamin.
"It's extremely variable," she noted, "and there is much that isn't known about vitamin D and metabolism."
"So the tissues and cells may be seeing adequate amounts of biological active vitamin D and adequate stimulation of the vitamin D receptor even in those who have lower blood levels," she said.
So the question of how much vitamin D is enough is a vexing one. But doctors and their patients still want an answer.
The IOM last year released new guidelines for vitamin D, which say that healthy people should aim to have at least 20 nanograms of 25(OH)D per milliliter of serum.
That can be achieved, the IOM said, by taking 600 IU a day of a vitamin D supplement if people are between ages 1 and 70, and 800 a day if they are 70 or older.
Manson, who along with Rosen was part of the IOM panel, said that "relatively modest amount" of vitamin D will keep 97.5% of the general population in good bone health.
And, she noted, the IOM really was only concerned about bone health, because there's such a dearth of evidence for benefits in other areas.
But even if there's no evidence for a benefit, is there any harm in taking a bit extra? Well, possibly.
One of the functions of vitamin D is to regulate calcium and phosphorus; too much can lead to hypercalcemia. The IOM set the tolerable upper limit at between 2,500 and 4,000 IU per day, depending on age.
The institute also cautioned, Manson said, that there is some evidence of a U-shaped curve for vitamin D -- too little is bad and so is too much.
In particular, the IOM reported that, although the evidence is weak, more than 4,000 IU a day of the vitamin might increase the risk of cardiovascular disease, some cancers, and all-cause mortality.
"There's no evidence that more is better, so why use more?" Rosen asked.
On a day to day basis, most people can ensure they have enough vitamin D by eating certain foods – fatty fish like salmon, for example – and taking a multivitamin, Manson said.
But there's no need to screen the healthy population for vitamin D levels at least until there's more evidence that it matters, the IOM concluded.
On the other hand, the Endocrine Society has called for regular screening for groups at risk for vitamin D deficiency such as the obese, African Americans, and pregnant women.
Low Prevalence of Testing Despite High Prevalence of Insufficiency
By David Wild
Nov 9th 2011
Chicago—Retrospective findings presented at the 2011 Digestive Disease Week meeting revealed that 64% of patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have low levels of vitamin D (abstract Su1302). In light of the results, researchers are urging clinicians to monitor vitamin D levels in all patients with chronic viral hepatitis.
“If we treat vitamin D deficiency, we can potentially decrease the high rate of osteopenia and osteoporosis in this population, including bone loss related to some of the antiviral therapies” said co-investigator Maya Gambarin-Gelwan, MD, assistant professor of clinical medicine, Weill Cornell Medical College, New York City.
Up to 53% of patients with viral hepatitis–related cirrhosis develop osteoporosis. Given the risk for bone loss associated with low levels of serum 25-hydroxyvitamin D (25[OH]D), investigators set out to determine the prevalence of vitamin D deficiency and insufficiency among patients with HBV and HCV treated at Weill Cornell Medical Center. They defined vitamin D deficiency as serum 25[OH]D less than 20 ng/mL and vitamin D insufficiency as levels between 20 and 30 ng/mL.
Among 2,312 patients with chronic viral hepatitis seen at the center between 2007 and 2009, only 17% (395 of 2,312) had been tested for vitamin D levels. Of those who underwent vitamin D testing, 31% (122 of 395) were vitamin D insufficient and 33% (132 of 395) were vitamin D deficient. The prevalence of vitamin D insufficiency was similar among the 29% (115 of 395) of patients with chronic viral hepatitis who had cirrhosis and those who did not (26% vs. 33%, respectively; P=0.10). However, the difference in vitamin D deficiency among patients with cirrhosis and those without cirrhosis was significant (44% vs. 29%; P=0.01).
Interestingly, vitamin D insufficiency was more prevalent among those infected with HBV than among those infected with HCV (73% vs. 60%, respectively; P=0.01). Although she suspects that ethnicity may play a role in this difference, Dr. Gambarin-Gelwan said that her data set did not include adequate information on ethnicity to draw a conclusion.
Zobair Younossi, MD, MPH, a liver specialist who was not involved in the study, said that prior studies have shown low vitamin D levels tend to be more common in patients with advanced stage fibrosis and cirrhosis. “However, this study shows insufficiency can also be seen in non-cirrhotic patients with hepatitis B and C, and particularly in those with chronic hepatitis B,” said Dr. Younossi, vice president for research, Inova Health System, and chairman, Department of Medicine, Inova Fairfax Hospital, Falls Church, Va.
Dr. Gambarin-Gelwan said that she hopes her research will spur clinicians to routinely monitor vitamin D levels in patients with chronic HBV and HCV infection. She said the small percentage of patients who were screened for vitamin D levels demonstrates that “gastroenterologists and hepatologists are paying too little attention to vitamin D levels.”
Source
Caucasians who avoid sun more likely D-deficient
Palo Alto, Calif. — Light-skinned people who avoid the sun are twice as likely to have vitamin D deficiency as those who do not — and, surprisingly, the use of sunscreen does not significantly affect blood levels of the vitamin, a new study suggests.
Stanford University School of Medicine researchers led by dermatologist Eleni Linos, M.D., Ph.D., analyzed data from the National Health and Nutrition Examination Survey of nearly 6,000 people collected by the Centers for Disease Control and Prevention from 2003 to 2006. The survey asked respondents about their sun-protection behavior — such as whether they wore long sleeves, hats and sunscreen — and whether they sought shade on sunny days. Data also included each respondent’s race and blood levels of 25-hydroxyvitamin D.
Investigators found that blood levels of vitamin D in Caucasians who avoided the sun with clothing or stayed in the shade were about 3.5 and 2.2 nanograms per milliliter lower than levels for those who did not report such behavior. In contrast, the association between sun avoidance and reductions in vitamin D levels in Hispanic or African-American survey-takers was not statistically significant.
Respondents with blood levels of 20 nanograms per milliliter or below were considered to be vitamin D-deficient. Researchers found that though about 40 percent of all survey participants were deficient, the prevalence increased to 53 and 56 percent among those who wore long sleeves and stayed in the shade.
Caucasians who wore long sleeves and stayed in the shade were twice as likely to be vitamin D-deficient as those who did not.
According to a university news release, researchers were surprised that reported use of sunscreen did not significantly affect vitamin D levels. Because sunscreens block the UV rays that trigger vitamin D production, investigators expected to find lower levels. The release quotes Dr. Linos as saying, “People are probably not applying (sunscreen) often or thickly enough. Often, people use sunscreen when they anticipate getting a lot of sun exposure, unlike others who spend time in the shade in order to avoid the sun.”
Dr. Linos says sun protection is “not as simple as telling everyone to wear sunscreen. We may instead need to begin tailoring our recommendations to the skin tones and lifestyles of individual patients. It’s clearly a very complex issue.”
Study results notwithstanding, Dr. Linos cautions against wholesale use of vitamin D dietary supplements until more is known. She notes that two large, randomized clinical trials are under way to test the health effects of relatively high doses of vitamin D.
The study was published online Nov. 4 in Cancer Causes and Control.
By Emily Main
A nutrient-poor diet filled with added sugars and unhealthy trans fats is known to cause high cholesterol, so it sure makes sense try and fix the problem with healthy food.
Although 25 percent of adults over the age of 45 take cholesterol-lowering drugs called statins -- which can sap your energy and cause problems for your sex life -- a new study reveals that changes to your diet might actually do a better job without the energy-sapping, sex-killing side effects.
A new study in the Journal of the American Medical Association followed 345 people with high cholesterol who were placed on one of two vegetarian low-cholesterol diets for six months. The first was a low-saturated-fat diet and participants were told simply to eat low-fat dairy and get more fruits and vegetables into their meals. The second group had help from nutritionists to incorporate specific cholesterol-lowering foods into their meals, including soy proteins, nuts, oats, peas, and beans. That group saw a drop in cholesterol three times higher than the group on the regular low-saturated-fat diet, and both diets proved to be at least as successful as early trials of statins.
If you've been battling high cholesterol, try some of these swaps for a tasty, low-cholesterol diet:
Breakfast: The low-fat group ate Raisin Bran cereal for breakfast, but the second group ate oat-bran cereal with strawberries and jam. For a seasonal twist, try this recipe for a Peachy Oat Breakfast and chase it down with a glass of soy milk, as those in the study did.
Mid-Morning Snack: For a cholesterol-lowering hunger fix, grab another peach (or some cantaloupe, grapes, nectarines, or apricots also in season now) and a handful of almonds when hunger strikes, and chase them down with another glass of soy milk. Or throw all your fruit, soy milk, and nuts, along with a little ice, into a blender to make something like the Women's Health Immunity Builder smoothie.
Lunch: For lunch, the low-cholesterol group downed sandwiches made with oat-bran bread, tofu slices, lettuce, tomato, and cucumber, accompanied by Spicy Black Bean Soup. The tofu slices provided the soy protein that proved so successful at lowering cholesterol, but if that doesn't tempt your palate, replace tofu with avocado, as in this Roasted Bell Pepper and Avocado Sandwich and have another glass of soy milk instead.
Mid-Afternoon Snack: The healthy dieters had more almonds and fresh fruit in the afternoon, but with an added dose of psyllium, a form of soluble fiber made from ground up psyllium seeds. Psyllium may not be very appetizing, so to get your fill of fiber, try these Banana, Yogurt, and Walnut Muffins; the bananas and oatmeal both contain high levels of soluble fiber.
Dinner: Dieters who shed the most cholesterol swapped pasta for pearled barley and an omelet for a tofu bake with ratatouille. To jazz up plain barley, make a Creamy Barley Risotto or add asparagus and cucumbers and top with a yogurt-dill dressing. Then add some tofu to this recipe for Easy Ratatouille. Just be sure your tofu is organic; nonorganic tofu has been found to contain high levels of cancer-causing hexane.
Really? The Claim: Coffee Can Prevent Some Medications From Working
Coffee and espresso can have consequences in people taking certain medications, by either blocking their absorption or enhancing their effects.
In many cases, the interactions are caused by caffeine. But other compounds in coffee may also play a role. Studies show that more than a dozen medications — as varied as antidepressants, estrogen and thyroid and osteoporosis drugs — can be affected by coffee consumption.
A study in 2008, for example, found that people who drank coffee shortly before or after taking levothyroxine, a common thyroid medication, experienced a reduction of up to 55 percent in absorption of the drug. Read More Here
Big Pharma
November 28, 2011 - The Wall Street Transcript has just published Biotechnology and Pharmaceuticals Report offering a timely review of the sector. This Special Report contains expert industry commentary through in-depth interviews with public company CEOs, Equity Analysts and Money Managers. Please find an excerpt below.
TWST: What about on the liver side? Who are your favorites there?
Dr. Nash: The liver side is a different space, where all the companies tend to be affected by similar events because they are all on the same market. Here, these are companies that are developing drugs to treat the virus, hepatitis C. Fortunately, unlike hepatitis B and HIV, hepatitis C is curable. If you don't treat patients, it can lead to hepatocellular carcinoma as well as cirrhosis. But if you do treat them with the current regimens, you get about 75% cure rate, which is better than the 40% to 50% cure rate we saw last year before some new drugs came out. There are a whole host of new drugs coming out which are aspired to being able to cure hepatitis C without the use of interferon.
The most advanced one is a drug PSI-7977, which is being developed by a company I do not cover, Pharmasset (VRUS). Their market cap is about $6 billion. That drug keeps showing fairly astonishing data. There are four main classes of drugs that are directed to HCV, and this drug is in a class called nucleotides. Over the course of 2011, nucleotides have distinguished themselves as the single most promising class by far. At the moment, it is assumed that Pharmasset will play a very large role in therapy for HCV for the future.The market is very big. It's probably about 3 million people in the United States with a chronic HCV, cost of therapy is roughly $80,000. So for the full U.S. market, you are talking over $200 billion, although it's very unlikely we will get anywhere near full penetration.
Instead, the total revenues will probably be somewhere in the tens of billions of dollars. For every one American who has HCV, there are 40 foreigners who have HCV, although many of these foreign countries are very poor and don't have the ability to afford expensive drugs. But needless to say, this could be a very lucrative market. While Pharmasset is very well positioned, there are a host of other companies out there whose position and ability to capitalize on this market is far more tenuous. Read More Here
FDA, Adulterated Drugs And Industry Silence
The various scandals involving adulterated drugs and pet food in recent years prompted some members of Congress to ask the US General Accountability Office to review how the FDA oversees product safety to prevent and respond to economic adulteration. Not surprisingly, the GAO found that the increasing complexities of the global supply chain pose significant challenges - particularly, tracking ingredients back to their original sources.
Recalled
Several recalls were issued over the Thanksgiving holiday.
Perhaps, most notable on the list was Ocean Spray’s recall of its dried cranberries. The FDA’s notice stated that Ocean Spray announced it has taken the precautionary measure of voluntarily recalling certain production lots of its Original Flavor Craisins® Dried Cranberries product in 5-ounce, 10-ounce and 48-ounce packages as well as bulk sweetened dried cranberries in 10-pound packages due to the possible presence of very small hair-like metal fragments that are unlikely to cause consumer injury.
The recalled product lots (only dates followed by the letter M are affected) are:
—5-oz. Craisins UPC: 00293-000 Best By Dates/Letter: Oct 27 2012 M
—10-oz. Craisins UPC: 29456-000 and 29464-000 Best By Dates/Letter: Oct 27 2012 M, Oct 28 2012 M, Oct 29 2012 M
—48-oz. Craisins UPC: 00678-318 Best By Dates/Letter: Oct 27 2012 M, Oct 28 2012 M, Nov 3 2012 M, Nov 4 2012 M, Nov 5 2012 M, Nov 6 2012 M, Nov 7 2012 M, Nov 10 2012 M, Nov 11 2012 M.
—10-lb. bulk ingredient & foodservice UPC: 03477-000 Best By Dates/Letter: 30 Oct 2013 M, 31 Oct 2013 M, 1 Nov 2013 M, 5 Nov 2013 M.
There is no indication of the size of the recall or how the issue was discovered by the company. To date, it has not received any reports of consumer complaints relating to this recall. No injuries or adverse effects have been reported regarding these products to date. Ocean Spray issued the voluntary recall out of an abundance of caution to ensure the safety of our consumers.
The product labels are below:
Viral Hepatitis - 2011 HCV Symposium - Welcome
The promise of highly efficacious drugs soon to be made available drives the impetus to screen for and detect active and incident HCV infection. CDC is organizing a symposium entitled “Identification, Screening and Surveillance of HCV Infections in the Era of Improved Therapy for Hepatitis C,” which will be held on December 1st and 2nd at CDC’s Roybal Campus in Atlanta. A unique array of international experts will present their latest perspectives and findings, and there will be ample opportunity for an exchange of ideas including roundtable discussions. You are cordially invited to participate. No registration fee is required.
Dates: December 1st & 2nd, 2011
Program: Schedule of events and speakers
Location: Tom Harkin Global Communication Center, Roybal Campus, 1600 Clifton Road, Centers for Disease Control and Prevention, Atlanta, GA 30333
Accommodations: For those coming from outside the Atlanta area, here is a list of local hotels, including directions to the Symposium from the more remote ones.
Registration: The registration page was closed, as of November 14.
This event is hosted by the Division of Viral Hepatitis, CDC
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