Sunday, January 2, 2011

VIR-576: Thwarts the AIDS virus and causes far fewer side-effects

New anti-AIDS drug goes after virus, avoids side-effects

German scientists have discovered a substance known as a peptide that thwarts the AIDS virus and causes far fewer side-effects than existing anti-HIV drugs, they said on Wednesday.

The breakthrough was reported in the science journal Science Translational Medicine after it had been tested on 18 AIDS patients.

But the scientists at Hanover university hospital or MHH in northern Germany said they are yet to find a way to put the substance, VIR-576, in a pill. All the test patients received it as an intravenous drip.

Variants of the new therapy could also be devised to fight measles, hepatitis C and Ebola disease, they said.

VIR-576 is a protein that smothers human immunodeficiency virus, stopping it docking with cells in the human body.

“It is a completely new therapy approach which we hope will reduce side effects,” said Mr Reinhold E Schmidt of MHH. Other existing medicines offered since the mid-1990s work by proofing cells of the body against the virus.

“Our peptide works on the virus, not on the cells, so some of the side-effects won’t happen at all,” he said.

Current anti-AIDS medications ensure an almost normal life span for HIV-infected people but raise the risk of strokes and liver damage. VIR-576 caused some diarrhoea, but no other major side effects, the tests suggested.

Mr Schmidt cautioned that it could take years before VIR-576 was available from pharmacies as a medicine.

See Full Press Release
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Saturday, January 1, 2011

Dangers of Toxoplasma Parasites: Harmful W-Suppressed Immune Systems

The parasite, Toxoplasma gondii, is thought to have been transmitted to approx half the people on the planet.

T. gondii is a species of parasitic protozoa that can be carried by all known mammals. It causes toxoplasmosis, a usually minor and self-limiting disease. It can, however, have serious or even fatal effects on an unborn foetus if the mother contracts toxoplasmosis during pregnancy.

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Toxoplasmosis and Cirrhosis
It is known that toxoplasmosis rarely leads to various liver pathologies, most common of which is granulomatose hepatitis in patients having normal immune systems. Patients who have cirrhosis of the liver are subject to a variety of cellular as well as immunity disorders. Therefore, it may be considered that toxoplasmosis can cause more frequent and more severe diseases in patients with cirrhosis and is capable of changing the course of the disease. Cirrhotic patients are likely to form a toxoplasma risk group.

Researchers Study the Dangers of Toxoplasma Parasites
Jan 4 2010

About one-third of the human population is infected with a parasite called Toxoplasma gondii, but most people don't know it. Although Toxoplasma causes no symptoms in most people, it can be harmful to individuals with suppressed immune systems, and to fetuses whose mothers become infected during pregnancy. Toxoplasma spores are found in dirt and easily infect farm animals such as cows, sheep, pigs and chickens. Humans can be infected by eating undercooked meat or unwashed vegetables.

Jeroen Saeij, an assistant professor of biology at MIT is investigating a key question: why certain strains of the Toxoplasma parasite (there are at least a dozen) are more dangerous to humans than others. He and his colleagues have focused their attention on the type II strain, which is the most common in the United States and Europe, and is also the most likely to produce symptoms. In a paper appearing in the Jan. 3 online edition of the Journal of Experimental Medicine, the researchers report the discovery of a new Toxoplasma protein that may help explain why type II is more virulent than others.

Toxoplasma infection rates vary around the world. In the United States, it's about 10 to 15 percent, while rates in Europe and Brazil are much higher, around 50 to 80 percent. However, these are only estimates — it is difficult to calculate precise rates because most infected people don't have any symptoms.

After an infection is established, the parasite forms cysts, which contain many slowly reproducing parasites, in muscle tissue and the brain. If the cysts rupture, immune cells called T cells will usually kill the parasites before they spread further. However, people with suppressed immune systems, such as AIDS patients or people undergoing chemotherapy, can't mount an effective defense.

"In AIDS patients, T cells are essentially gone, so once a cyst ruptures, it can infect more brain cells, which eventually causes real damage to the brain," says Saeij.
The infection can also cause birth defects, if the mother is infected for the first time while pregnant. (If she is already infected before becoming pregnant, there is usually no danger to the fetus.)

There are drugs that can kill the parasite when it first infects someone, but once cysts are formed, it is very difficult to eradicate them.
A few years ago, Saeij and colleagues showed that the Toxoplasma parasite secretes two proteins called rhoptry18 and rhoptry16 into the host cell. Those proteins allow the parasite to take over many host-cell functions.

In the new study, the MIT team showed that the parasite also secretes a protein called GRA15, which triggers inflammation in the host. All Toxoplasma strains have this protein, but only the version found in type II causes inflammation, an immune reaction that is meant to destroy invaders but can also damage the host's own tissues if unchecked. In the brain, inflammation can lead to encephalitis. This ability to cause inflammation likely explains why the type II strain is so much more hazardous for humans, says Saeij.

Saeij and his team, which included MIT Department of Biology graduate students Emily Rosowski and Diana Lu, showed that type II GRA15 leads to the activation of the transcription factor known as NF-kB, which eventually stimulates production of proteins that cause inflammation. The team is now trying to figure out how that interaction between GRA15 and NF-kB occurs, and why it is advantageous to the parasite.

Ultimately, Saeij hopes to figure out how the parasite is able to evade the immune system and establish a chronic infection. Such work could eventually lead to new drugs that block the parasite from establishing such an infection, or a vaccine that consists of a de-activated form of the parasite.

MIT Department of Biology graduate students Emily Rosowski and Diana Lu are the paper's two first authors and contributed equally to the research. Other authors include MIT postdoc Kirk Jensen, lab technician Lindsay Julien, MIT undergraduate student Lauren Rodda, and Rogier Gaiser, a graduate student at Wageningen University in the Netherlands.
Reference: Strain-specific activation of the NF-kB pathway by GRA15, a novel Toxoplasma gondii dense granule protein, by Emily E. Rosowski, Diana Lu, Lindsay Julien, Lauren Rodda, Rogier A. Gaiser, Kirk D.C. Jensen, Jeroen P.J. Saeij. Journal of Experimental Medicine, 3 January 2011.



Credit: Image courtesy of E. Prandovszky and University of LeedsToxoplasma cyst outlined in red fluorescent cyst dye in mouse brain section. Hundreds of parasites are visible in cyst as blue dots (nuclei stained blue) and in surrounding brain tissue.
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Update March 23 2011

.Toxoplasmosis in a Patient who was Immunocompetent: A Case Report
Aneta K Taila; Ameet S Hingwe; Laura E Johnson
Authors and Disclosures
Posted: 03/23/2011; J Med Case Reports. 2011;5(1) © 2011 BioMed Central, Ltd.

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Case Presentation
A 20-year-old previously healthy man, a student by occupation and a non-smoker not on any medications, presented to his primary care physician with a history of swollen glands for a 'couple of months'. On further review it was found that for one month prior to presentation, our patient had noticed multiple enlarged cervical, occipital, and right inguinal lymph nodes. No constitutional symptoms were reported.

Our patient was of Middle Eastern heritage, but was born and raised in the USA. He had not travelled recently, nor had he had any recent contact with sick people or any occupational exposure. On physical examination, our patient was afebrile with normal vital signs. Enlarged, non-tender, freely mobile bilateral cervical and occipital lymph nodes were palpable and measured up to 4cm. His right inguinal lymph nodes were similarly enlarged.

The left palatine tonsil was slightly erythematous and enlarged. A monospot test was negative for Epstein-Barr virus infection. Given these findings, the primary care physician prescribed a course of antibiotics for a possible infectious etiology consisting of a three-day course of azithromycin followed by amoxicillin-clavulanate one week later due to persistent symptoms. Initial investigative tests showed normal blood counts and serum electrolytes. An HIV antibody enzyme-linked immunosorbent assay (ELISA) test was also negative.


Our patient returned to the clinic for re-evaluation. With the exception of the enlarged lymph nodes, he remained otherwise clinically asymptomatic. On physical examination, the lymph nodes appeared unchanged, and there were no newly involved nodal chains. Upon more thorough investigation, our patient indicated that approximately once month ago he ate raw kibbe, a Middle Eastern dish that consists of spiced uncooked beef or lamb with grains. Additional laboratory studies were ordered and are listed in Table 1.

Our patient was diagnosed with acute toxoplasmosis and counseled regarding dietary habits and risk factors. No specific treatment was administered, and close follow-up was planned to ensure resolution of the lymphadenopathy.

Discussion
Infection of humans with T. gondii is common worldwide, with the prevalence varying according to environment, eating habits, and age.[2] Contact with this obligate intracellular protozoan occurs through direct ingestion of food or water contaminated with cat feces containing oocysts, ingestion of tissue cysts in uncooked meat, transplacental infection of the fetus, white blood cell transfusion or organ transplantation. Our patient was probably exposed to T. gondii by eating raw lamb. Prior case reports have shown that the disease has a higher prevalence among men (79% versus 63.4% in women) and that age-dependent seroprevalence reaches > 92% in the age 40 to 50 group.[3] In seroepidemiological surveys in the USA, 11% of persons aged 6 to 49 are seropositive for T. gondii.[4]

Clinical presentation of T. gondii infection depends on the age and immune status of the patient. In the majority of patients who are immunocompetent, both adult and pediatric, primary infection is usually asymptomatic. In approximately 10% of this patient group, a non-specific and self-limiting illness is manifested most typically by isolated cervical or occipital lymphadenopathy lasting for less than four to six weeks. The lymph nodes are usually discreet, non-tender, and do not suppurate. Differential diagnoses include Epstein-Barr virus and other mononucleosis-like illnesses including cytomegalovirus and HIV with acute retroviral syndrome. Though not as common, hematological malignancies, cat scratch disease, leishmaniasis and syphilis can also cause lymphadenopathy. Very infrequently immunocompetent hosts might also suffer from myocarditis, polymyositis, pneumonitis, hepatitis, or encephalitis. After the acute phase, almost all patients will remain chronically infected with tissue cysts that are dormant and cause no clinical symptoms.

In contrast, toxoplasmosis in patients who are immunocompromised can be a life-threatening infection. In this population, toxoplasmosis almost always occurs as a result of reactivation of chronic disease and most typically affects the central nervous system. Toxoplasmic encephalitis has a varied clinical presentation, ranging from an acute confusional state with or without focal neurological deficits evolving over days to a subacute gradual process evolving over weeks. Other presentations of toxoplasmosis in patients who are immunocompromised include chorioretinitis, pneumonitis, or multi-organ failure.

Diagnosis of T. gondii infection can be made via a number of methods, both directly via polymerase chain reaction (PCR), hybridization, isolation, and histology and indirectly via serological methods. In our patient, serology was helpful. In patients who are immunocompetent, indirect serological methods are more widely used as they are readily available, faster, and cheaper. However, testing for IgG antibodies to T. gondii should also be performed in asymptomatic patients who are immunocompromised, as this allows identification of those at risk for reactivation of latent infection. Additionally, an absence of IgG antibodies in pregnant women allows identification of those at risk of acquiring infection during gestation.
Serological methods used to detect antibodies include the Sabin-Feldman dye test, immunofluorescent antibody test, ELISA, IgG avidity test, and agglutination tests. Assays for functional affinity of these antibodies have become standard as they help discriminate between recently acquired and more chronologically distant infections. The presence of high avidity antibodies essentially excludes infection acquired in the past three to four months; however, low avidity antibodies may persist beyond three months of infection and therefore do not necessarily indicate recent infection.[5]

In patients who are immunocompromised, direct methods of detection must be employed. Body fluids and tissues can be subjected to PCR amplification of T. gondii genes (specifically, the B1 gene). Assuming appropriate sample collection, handling, and storage, sensitivity is no greater than 50% but highly specific.[6] Isolation of T. gondii directly from blood or body fluids is indicative of acute infection, whether newly acquired or reactivation of latent infection. Direct diagnosis can also be made with tissue sections or body fluid smears that demonstrate tachyzoites.

Treatment with pyrimethamine, sulfadiazine and folinic acid is usually reserved for patients who are immunocompromised and those patients who are immunocompetent who have severe or persistent symptoms. Duration of treatment varies from two to four months depending upon resolution of clinical signs and symptoms. Alternatively, trimethoprim/sulfamethoxazole is equivalent to pyrimethamine/sulfadiazine.[7] Maintenance therapy should be started after the acute phase has resolved and should consist of the same regimen as in the acute phase but at half dose. This should continue for the life of the patient or until the immunosuppression has resolved.[8]

Conclusion
We present a case of acute toxoplasmosis manifesting as generalized lymphadenopathy with the leading risk factor in this case being the consumption of raw meat. For the general internist, a broad differential should be kept in mind when patients present with lymphadenopathy and appropriate testing should be performed. When the diagnosis is made, treatment is rarely required for asymptomatic patients who are immunocompetent. Proper education and counseling regarding risk factors can reduce the incidence and risk of acquiring the infection.

See Full Data At Medscape

Abstract and Introduction
Discussion
Conclusion

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Toxoplasmosis Parasite May Trigger Schizophrenia And Bipolar Disorders

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Science Daily - Scientists have discovered how the toxoplasmosis parasite may trigger the development of schizophrenia and other bipolar disorders. The team from the University of Leeds' Faculty of Biological Sciences has shown that the parasite may play a role in the development of these disorders by affecting the production of dopamine -- the chemical that relays messages in the brain controlling aspects of movement, cognition and behaviour. Toxoplasmosis, which is transmitted via cat faeces (found on unwashed vegetables) and raw or undercooked infected meat, is relatively common, with 10-20% of the UK population and 22% of the US population estimated to carry the parasite as cysts.

Most people with the parasite are healthy, but for those who are immune-suppressed -- and particularly for pregnant women -- there are significant health risks that can occasionally be fatal. Dr Glenn McConkey, lead researcher on the project, says: "Toxoplasmosis changes some of the chemical messages in the brain, and these changes can have an enormous effect on behaviour. Studies have shown there is a direct statistical link between incidences of schizophrenia and toxoplasmosis infection and our study is the first step in discovering why there is this link."

The parasite infects the brain by forming a cyst within its cells and produces an enzyme called tyrosine hydroxylase, which is needed to make dopamine. Dopamine's role in mood, sociability, attention, motivation and sleep patterns are well documented and schizophrenia has long been associated with dopamine, which is the target of all schizophrenia drugs on the market. The team has recently received $250,000 (£160,000) to progress its research from the US-based Stanley Medical Research Institute, which focuses on mental health conditions and has a particular emphasis on bipolar illnesses. Dr McConkey says: "It's highly unlikely that we will find one definitive trigger for schizophrenia as there are many factors involved, but our studies will provide a clue to how toxoplasmosis infection - which is more common than you might think - can impact on the development of the condition in some individuals. "In addition, the ability of the parasite to make dopamine implies a potential link with other neurological conditions such as Parkinson's Disease, Tourette's syndrome and attention deficit disorders, says Dr McConkey. "We'd like to extend our research to look at this possibility more closely."
Source
Updated March 23 2011

Certain Type Of HIV Reduces Breast Cancer Risk Among HIV-Infected Women

Study Finds That A Certain Type Of HIV Reduces Breast Cancer Risk Among HIV-Infected Women
By Meerat Oza and Courtney McQueen

Results of a recently published study have shown that women infected with a certain type of HIV may have a significantly lower risk of breast cancer compared to women with other strains of HIV, possibly because this type of HIV effectively targets and kills breast cancer cells.

The study authors stated that the results need to be confirmed by additional studies, but may explain results showing women with HIV are at lower risk for breast cancer than women without HIV.

HIV is often associated with increased rates of several types of malignant cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, cervical cancer, and anal cancer.

However, studies have shown that women with HIV may be at decreased risk of breast cancer. Between 1980 and 2002, the risk of breast cancer was found to be 31 percent lower in HIV-infected women as compared to uninfected women.

Researchers have speculated that this may be because a type of cell protein that HIV sometimes uses to infect immune system cells is also found on the surface of breast cancer cells.

In order to infect healthy white blood cells, HIV binds to certain proteins on their surface, called CCR5 or CXCR4. Most HIV, especially early in infection, uses CCR5 for infection. However, later in infection HIV will sometimes switch to using CXCR4 or a combination of the two proteins.

One hypothesis for why HIV-positive women may be at reduced risk for breast cancer is that the CXCR4 protein is also found on the surface of breast cancer cells. This protein is not found on normal breast cells and may be used by the cancer cells to grow and spread. Scientists have shown that in the laboratory, HIV that binds to breast cancer cells kills them.

If this hypothesis is correct, then women with HIV that uses the protein CXCR4 for infection should be at lower risk of developing breast cancer.

To test their hypothesis, the researchers in this study identified 23 HIV-infected women who had breast cancer and compared them to 69 HIV-positive women without breast cancer who were of similar age.

Results showed that only 9 percent of the women with breast cancer had CXCR4-dependent HIV, compared to 28 percent of the women without breast cancer.

Further analysis revealed that women with CXCR4-dependent HIV were only 10 percent as likely to have breast cancer as women infected with CCR5-dependent HIV.

Menopause was the only other factor that affected the risk of developing breast cancer. CD4 (white blood cell) count, viral load (amount of HIV in the blood), antiretroviral therapy regimen, ethnicity, and other lifestyle factors such as use of alcohol or contraceptives did not correlate with risk.

The researchers concluded that CXCR4-dependent HIV has a protective effect against breast cancer in women, and they speculated that CXCR4-dependent HIV may account for the lower risk of breast cancer in women with HIV.

They suggested that their findings could lead to new methods for trying to combat breast cancer.

Since the study was small, the researchers noted that their results will need to be confirmed by further studies with larger groups of women.

Also, while they presume the lower risk of breast cancer arises from CXCR4-dependent HIV infecting and killing breast cancer cells, they suggested further study on the exact mechanism by which CXCR4-dependent HIV protects against breast cancer.
http://www.aidsbeacon.com/news/2011/01/04/study-finds-that-a-certain-type-of-hiv-reduces-breast-cancer-risk-among-hiv-aids-infected-women/

Morning Hep C News and Letters


Lifesaving change for transplant checklist
TRANSPLANT patients are being given the healthy organs of pack-a-day smokers, heavy drinkers and the elderly to give more people on the waiting list a chance of survival.
Surgeons are also transplanting the unaffected body parts of cancer patients and have begun a new registry for donors with hepatitis C.
While donor rates in NSW have risen by a quarter this year - due to reforms and a public awareness campaign - Australia still lags behind many countries, leading doctors to extend the criteria for acceptable donors.
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Thelma Thiel, CEO of the Hepatitis Foundation International explains the functions of the liver and risk behaviors that can cause liver disease on CBS 6 - Good Morning Virginia program. Check out the video of the interview entitled "Hepatitis Awareness"
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January 2011 HEPC Bull Newsletter

Read the hepc.bull -our online monthly newsletter (.pdf)
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IN This Issue:

More AASLD 2010 News
My Story (Daryl) / PHCN Conference Report
Hep C & Me
Hep C on the Internet
Conferences
PegCARE/PegAssist/Neupogen/Compensation
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HEPATITIS C NUTRITION: Foods that Bite, Foods that Fight
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Inside Look
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More AASLD 2010 News

SVR 20 YEARS LATER

We often think our goal is an SVR(Sustained Viral Response), but the long term goal is to prevent Hep-C related deathor disability. This study looked at 103 successfully-treated patients treated beginning in 1984. Biopsies and blood tests were compared before and after. Patients seen since 2007 were evaluated by elastography, a type of liver scan. Three of the original patients had relapsed between just over a half a year up to 6 ½ years after treatment. Of the other100, 45% had GT1, and 53% had GT2 or 3.2% had other genotypes. There was no liver failure or liver cancer. ALTs were 27 U/Land ASTs were 24 U/L, average. All other markers remained good, as well. There were no liver-related deaths, and 97% had maintained their SVR. The study concluded that “SVR is associated with both short term and long-term benefits.”
Source:
www.natap.org/2010/AASLD/AASLD_25.htm
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BMS-790052 + BMS-650032
Bristol-Myers presented results from their protease + NS5A inhibitor trial. The drugs were tested with and without standard therapy, on GT1 null-responders. At 12weeks of therapy, 6 out of 11 patients experienced breakthrough. All were GT-1a. However, the other 5 patients remained undetectable with the two oral drugs alone. It appears that the patients with breakthrough............
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HEPATITIS C NUTRITION:
At one point scientific studies stated that there was no notable harm in taking milk thistle but also did not see any benefit. However new work has demonstrated that at the very least milk thistle is a powerful antioxidant providing benefits to cell health. While milk thistle has more therapeuticpotential than first imagined when refined and administered intravenously, there are some new indications that taking it orally likely reduces fibrosis as well as raising QoL.

Any improvement in QoL is going to increase your chances of fighting HCV. However if there is a potential for negative health consequences from a food or drug it is said to be a contraindication. For example when you take interferon and eat high fat food, fat is going to be a contraindication for the interferon since fat temporarily fertilizes the virus we are trying to fight. Also fat deposits in the liver have been shown to hamper treatment success and it is especially harmful to those with HIV coinfection.......

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From NATAP
(12/30/10)

New York Magazine Top Infectious Disease Doctors in NYC 2010 List -

More Hep C Articles...

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Ten Neglected Points
by Articleman

12/31/2010
The Silent Hepatitis C Crisis. Hepatitis C is rampant among American prison inmates. While the general population has it at an incidence of roughly 2%, prison populations have it at rates ranging from 28% to 30% to 40%, depending on who you ask or read. To be sure, the percentage of inmates who enter prison with it is substantially higher than the percentage of infections among the general public. But many are infected in prison, and given the lack of treatment in prison, we are seeing long-term catastrophic liver failures and illnesses among persons late in their prison terms and after they are released back into society. While treatment on the front end is expensive, it is more expensive on the back end, when livers and lives are destroyed, and when the ill person can go on to infect others as well. This is a huge public health problem that no one can be bothered to discuss.

Last update 01/01/2011 11:00:00 AM (GMT+7)


Vietnam successfully conducts second liver transplantation for adult

VietNamNet Bridge – Hanoi-based Vietnam-Germany Hospital has successfully performed liver transplantation for a 44-year-old man from the central city of Da Nang in a 13-hour surgery.

The liver donor is the patient’s cousin, who is 34 years old.

Vietnam has carried out many liver transplantations but all of them were on children. This is the second liver transplantation on an adult in Vietnam, according to Dr. Nguyen Tien Quyet, director of the Vietnam-Germany Hospital.

Liver transplantation for adults is much more complicated and risky than for children because doctors have to take up at least half of the liver of the donor while it is only one third for children.

The first adult liver transplantation was in late 2007, also conducted at the Vietnam-Germany Hospital

“Besides the harmony of indexes between the donor and the recipient, the weight of liver is very important. In some case, the weight of liver of the donor is not enough for the recipient,” Quyet said.

The patient has recovered after the operation.

In May 2010, this hospital successfully performed liver, kidney and heart valve transplantations, using donated organs of a dead person.

Quyet said that Vietnam’s viscera transplantation technique is not behind any country in the world. Notably, the cost for viscera transplantation in Vietnam is very cheap, equivalent to one third of the region and the world.

However, the common problem is the scarcity of viscera for transplantation. In the world, up to 90 percent of viscera come from dead people while 90 percent of viscera for transplantation in Vietnam come from the living people.

Vietnam is about to build a centre to coordinate viscera transplantation.

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Stem Cells
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Scripps Scientists home in on chemicals to reprogramme cells news
Breaking new groundScientists have known for at least 50 years that a cell's identity is reversible if given the right signal - cells go forward to become mature, functional cells or they can go backward to become primitive cells. In order for cellular reprogramming to be safe and practical enough to use in cell therapy, researchers have sought an efficient, reliable way to trigger the reprogramming process


What Are Stem Cells ?
Yesterday, December 31, 2010, 7:35:06 PM


• All stem cells can divide many times without turning into specialized cells. In a laboratory, a small batch of stem cells can multiply over many months and yield millions of cells.

• Embryonic stem cells can develop into any of the more than 200 types of cells found in the human body.

• Embryonic stem cells can be produced fairly easily in the laboratory, by cell division.

• Adult stem cells (also called somatic stem cells) are found in specific tissues of the body. Usually, they develop only into the type of cells needed in those tissues. Adult stem cells have been found in the brain, bone marrow, blood, skeletal muscle, skin, teeth, heart, and liver.

• Adult stem cells are difficult to isolate from the surrounding specialized cells, and scientists haven’t yet learned how to grow them in the laboratory. This makes them less promising for therapies that would involve replacing damaged tissues with tissues grown from stem cells. However, certain adult stem cells are already being used in medical therapy: for example, in bone marrow transplants for leukemia patients. (Bone marrow contains stem cells that produce blood cells.)


Liver: Stem Cells Updates and News 2011
Yesterday, December 31, 2010, 7:21:52 PM
Patients who are displaying symptoms of liver cirrhosis are involved in the trial Once harvested, the cells are purified, so that a high concentration of the right type of stem cells can be injected back into the patient's blood stream. The Repeated Autologous Infusions of Stem Cells in Cirrhosis, or 'Realistic' trial, will compare the current standard treatment to both the effect of giving GCSF injections on their own and giving the injections, collecting the stem cells and putting them back into the bloodstream. Dr Philip Newsome, from the Centre for Liver Research at Birmingham University, is the clinical leader for the trial.

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Pharmaceutical News

Roche acquires Marcadia Biotech
Roche beat the end of year holiday rush yesterday by acquring Marcadia Biotech - probably the last pharma deal of 2010. Marcadia is located in Carmel, IN and was founded by former Lilly executives.
Roche acquires Marcadia Biotech Indianapolis Business Journal IBJ.com.

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New Drugs 2010 - Fewest FDA Approvals since 2007
Here's a piece republished in its entirety from Bloomberg.
Twenty-one new drugs were approved in the U.S. this year, the fewest since 2007, as the Food and Drug Administration showed more willingness to delay or reject medicines with potential safety risks.
The tally, compiled by Bloomberg from an FDA database, compares with 25 approvals last year and 24 in 2008, according to the FDA’s website. Nineteen new drugs were cleared in 2007, the fewest in 24 years.

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New Year !

The List: Top New Year's resolutions

Telaprevir Makes The List: New year, new science

2011: Good News For Hepatitis C Patients

Scripps Research scientists identify key interaction in hepatitis C virus

http://hepatitiscnewdrugs.blogspot.com/2010/12/getting-ready-for-2011-hepatitis-c-new.html

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Infectious Disease

Who Knew ?

Deer-Associated Parapoxvirus Infection Identified
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Parapoxvirus infection, attributable to a unique strain, diagnosed in two deer hunters
THURSDAY, Dec. 30 (HealthDay News) --
Parapoxvirus infections were identified in two deer hunters in 2009 and, with deer populations on the rise, the potential for deer-associated parapoxvirus infections may also be increasing, according to a report published in the Dec. 30 issue of the New England Journal of Medicine. Amira A. Roess, Ph.D., of the U.S. Centers for Disease Control and Prevention in Atlanta, and colleagues describe the clinical and pathological features of parapoxvirus infection and the phylogenetic relationship of a unique strain of parapoxvirus diagnosed in two deer hunters to other parapoxviruses. Both hunters had cut their fingers while field-dressing deer. DNA sequence analysis revealed that the parapoxvirus infections identified in these deer hunters were likely due to a unique strain of the virus. Individuals with parapoxvirus infection typically present three to seven days after exposure with erythematous maculopapular lesions on the hands that progress over four to eight weeks. The histopathological appearance of the lesions is characterized predominantly by epidermal hyperplasia, with occasional cytoplasmic inclusions, prominent vascular proliferation and dilatation, and mixed inflammatory-cell infiltrates. The authors note that, because the deer population is increasing in the United States, the potential for parapoxvirus infection may be increasing as well. "Anecdotal data suggest that imiquimod may be effective in the treatment of parapoxvirus infection in patients with underlying health conditions, to prevent the spread of virus, autoinoculation, and the need for surgical d├ębridement," the authors write. One author disclosed financial relationships with pharmaceutical and medical companies.
Full Text (subscription or payment may be required)

Upcoming Events:

4th Paris Hepatitis ConferenceParis, France Jan. 17 – Jan. 18, 2011

http://www.colloquium.eu/site/-Homepage,1724-


EASLBerlin, GermanyMarch 30 – April 3, 2011

http://www.easl.eu/


DDWChicago, ILMay 7 – May 10, 2011

http://www.ddw.org/wmspage.cfm?parm1=679


HCV 2011 SymposiumSeattle, WA Sept. 8 – 11, 2011

http://www.hcv2011.org/


AASLDSan Francisco, CA Nov. 4 – 8, 2011

http://www.aasld.org/lm/Pages/default.aspx

Hepatitis C and B : Cirrhosis etiology a major factor in cancer risk

Last Updated: 2010-12-30 18:55:16 -0400 (Reuters Health)

By Scott Baltic

NEW YORK (Reuters Health) - Patients with cirrhosis are at a significantly higher risk of cancer - not just hepatocellular carcinoma (HCC) but extrahepatic cancers (EHC) too - and a new study by U.S. researchers adds to what's already known about those risks.

One of the study's most striking findings was that cirrhosis etiology was a major factor in cancer risk.

Patients with hepatitis B or C cirrhosis (with or without alcohol use) had a five-year risk of HCC of 11.2%. Those with primary biliary cirrhosis, primary sclerosis cholangitis, alpha-one antitrypsin deficiency-related cirrhosis or alcohol-related liver disease, however, had only a 3.4% five-year probability of HCC.

In contrast, the risk of EHC was highest in patients with primary biliary cirrhosis or alcoholic cirrhosis.

For analysis of EHC risk, the researchers followed 952 patients with cirrhosis; for HCC risk, they followed 797 (after excluding patients who were positive for HCC on index CT screening or who were found to have HCC within six months of enrollment).

Overall, the cirrhotic patients had a risk of HCC that was 186 times higher than in the general population. Point estimates of HCC incidence at one, three and five years after a first negative CT scan were 1.2%, 4.4% and 7.8%, respectively, according to lead author Dr. Ken Berman of the University of Colorado School of Medicine, Denver and colleagues.

The cohort's risk of EHC was nearly double that of the general population. Point estimates of EHC incidence at one, three and five years were 2.2%, 4.5% and 6.8%, respectively. The most common EHCs were breast cancer, lung cancer and lymphoma, the research team reported online December 21st in the American Journal of Gastroenterology.

The results do not support "enhanced screening for any particular EHC in an otherwise asymptomatic patient with cirrhosis," Dr. Berman told Reuters Health by e-mail. But, he added, they do suggest a need for "heightened awareness for early warning signs of cancer in these patients."

The researchers say theirs is the first study to evaluate EHC risk in a cohort of patients with cirrhosis of all etiologies in the United States.

Both male patients and older patients were significantly more likely to be diagnosed with HCC during follow-up.

SOURCE: http://link.reuters.com/pyg34r

Am J Gastroenterol 2010.

Steady Hepatitis C mortality rates disappoint in Australia

Last Updated: 2010-12-31 17:52:24 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - In Australia in the past few years, death rates in patients with hepatitis C virus have not increased - but they haven't improved, either, researchers say.

"Although treatment strategies have improved over the past decade," Dr. Gregory J. Dore told Reuters Health by email, "stable rates of liver disease-related mortality among people with hepatitis C reflect low treatment uptake and poor treatment outcomes in the setting of advanced liver disease."

Dr. Dore of The University of New South Wales, Sydney and colleagues analyzed data from 1992 to 2006 on more than 42,000 people with hepatitis B monoinfection and roughly 82,000 with hep C monoinfection.

Compared to the general population there, the group with hepatitis B had a marginally elevated age- and sex adjusted overall mortality rate. But for hepatitis C patients, that rate was around two and half times higher than in the general public, the authors reported online December 9th n the Journal of Hepatology.

Over the study period, the hepatitis B group had a decrease in non-hepatoma deaths - but the hepatitis C group did not.

This finding in the hepatitis B group "suggests that even in the setting of relatively low antiviral therapy uptake, the potential use and improved potency of therapy in those with advanced liver disease is having an impact," Dr. Dore said.

The research team also found that HIV co-infection (present in 0.2% of the hepatitis B group and 0.5% of the hepatitis C group) increased overall mortality by 10-fold in hep B patients vs threefold in hep C patients.

Patients were at higher risk for liver-related death with hepatitis B (standardized mortality ratio 10.0) and hepatitis C (SIR 15.8) compared to the general population,

The hepatitis C group also had a higher risk for drug-related death (SMR 15.4). This group's drug-related mortality in 2002, however, was approximately half that in years prior to 2000, and rates have remained low since. This, say the investigators, is most likely due to the Australian heroin shortage in which both supply and purity decreased while the price increased markedly.

In fact, said Dr. Dore, "Among people with hepatitis C, liver disease has overtaken drug-related causes as the major contributor to mortality."

But, he concluded, "Improved antiviral therapy uptake and outcomes are required to reduce liver disease related mortality among people with hepatitis C."

SOURCE: http://link.reuters.com/xuc44r

J Hepatol 2010

Rifaximin improves cognition in minimal hepatic encephalopathy

Rifaximin improves cognition in minimal hepatic encephalopathy

Last Updated: 2010-12-29 15:25:07 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - By restoring cognitive function in patients with minimal hepatic encephalopathy (MHE), rifaximin treatment also improves their quality of life, investigators in India report.

The broad-spectrum antibiotic rifaximin (Xifaxan) is a nonabsorbable gut-specific antibiotic. It is thought to improve hepatic encephalopathy by depleting the supply of gut-derived bacterial ammonia associated with cirrhosis.

In March of this year, the U.S. Food and Drug Administration approved rifaximin for preventing recurrent hepatic encephalopathy. At the same time, the New England Journal of Medicine reported that rifaximin cut recurrence of overt hepatic encephalopathy by more than half. (See Reuters Health story of March 24, 2010).

"MHE is not widely tested for in clinical practice, but it's apparent to the patients and their families," Dr. Nathan M. Bass told Reuters Health. "They're 'off their game' in terms of work, particularly jobs with significant intellectual demand, and it impacts day-to-day skills, such as the ability to drive."

Dr. Bass, from the University of California, San Francisco, was the lead author of the NEJM article, but he was not involved in the present research.

Researchers at Dayanand Medical College and Hospital in Ludhiana, Punjab, led by Dr. Sandeep Singh Sidhu, studied the use of rifaximin in adults with MHE. A diagnosis of MHE required impairment on at least two of five neuropsychometric tests.

The investigators screened 281 patients with liver cirrhosis without overt hepatic encephalopathy and diagnosed 115 (41%) with MHE. Of the 94 who agreed to participate, 49 were randomized to oral rifaximin 400 mg three times daily for 8 weeks, and 45 were randomized to placebo. (Study drugs were provided by LUPIN Ltd.)

In the intent-to-treat analysis, patients taking rifaximin showed significantly greater rates of MHE reversal at two weeks (57% vs 18%) and at eight weeks (76% vs 20%), p < 0.0001 for both times, the researchers reported online December 14th in the American Journal of Gastroenterology.

The mean number of abnormal tests fell from 2.35 to 0.81 between baseline and eight weeks in the rifaximin group, and from 2.31 to 1.97 in the placebo group.

Rifaximin, but not placebo, was also associated with significant improvement in health-related quality of life, assessed with the Sickness Impact Profile (SIP) Questionnaire. Higher scores denote greater dysfunction. At baseline, mean total SIP scores were 2.12 in patients without MHE and 10.71 in those with MHE.

After 8 weeks, total SIP score had fallen by 4.61 points in the rifaximin group and by 0.88 in the placebo group. Rifaximin also led to significant improvements in six of 12 SIP scales, and in total psychosocial and physical sub-scores.

When the authors looked at potential confounders -- age, education, sex, residence, duration of cirrhosis and its etiology, esophageal varices and ascites - only the presence of MHE significantly affected total SIP score.

"Thus," Dr. Sidhu and colleagues conclude, "MHE has a significant impact on (a) patient's overall quality of life, and it deserves screening and treatment."

In e-mail to Reuters Health, Dr. Sidhu added, "Lactulose remains the standard of care in MHE. But if rifaximin proves to be as effective as and better tolerated than lactulose in future trials, it will become the standard of care."

His team is now planning to study the combination of rifaximin and lactulose for MHE patients nonresponsive to either drug alone. He said it will also be important to study the natural history of MHE at six months or one year after patients stop taking it.

"This study is well designed and quite impressive," Dr. Bass said. "Now we need to consider how best to test patients for MHE. Possibilities would be computer-based assessment tests or short psychometric protocols."

He noted that rifaximin is better tolerated than lactulose, and it does not appear to promote antibiotic resistance or propensity to infection with Clostridium difficile.

The one problem is cost: If used at the dose in this study, one month's supply of rifaximin could cost nearly $1600.

Neomycin and metronidazole - favored by insurance carriers, Dr. Bass said - are available as generics and cost much less. "But they're also much more toxic, and can cause hearing loss, nephrotoxicity, and peripheral neuropathy."

"If you're going to use an antibiotic for hepatic encephalopathy, I'd choose rifaximin, both for safety and proven efficacy," he said.

SOURCE: http://link.reuters.com/zut52r

Am J Gastroenterol 2010.

Hepatitis C Genotype 4 Spread To Egypt and Africa into Europe

HCV -4 spreads from Egypt and Africa into Europe

Last Updated: 2010-12-31 18:00:24 -0400 (Reuters Health)

By C. Vidya Shankar MD

NEW YORK (Reuters Health) - Hepatitis C virus (HCV) genotype 4, previously limited to Egypt and other parts of Africa, has now spread to southern Europe and other parts of world, an international panel says in a review published online December 9th in the Journal of Hepatology.

Genotype 4, or the Egyptian genotype, now accounts for roughly 20% of HCV infections in Europe and worldwide.

This strain is more difficult to treat than genotypes 2 and 3, which have traditionally been relatively more common in Europe, said Dr. Stephen Harrison, a panelist from the Brooke Army Medical Center, Houston, Texas, in email to Reuters Health.

Still, he said, "We approach the treatment of (HCV 4) the same way we do (HCV 1). Current standard of care is 48 weeks of pegylated interferon and weight based ribavirin."

HCV is classified into six genotypes based on nucleotide sequences. While type 4 is uncommon in the U.S., with a prevalence of 1%, it accounts for 90% of HCV infections in Egypt, according to the review.

Along with lead author Dr. Mahmoud A. Khattab, from the University of Minia, Egypt, Dr. Harrison and colleagues point out in the article that the HCV-4 epidemic in Egypt probably traces its origins to an anti-schistosomiasis campaign that involved parenteral injections on a large scale. Whereas sexual transmission and traditional medical practices like scarification were responsible for its spread through Africa and Middle East, immigration and intravenous drug use may have spread the virus worldwide, they say.

Though the clinical features and microscopy findings are similar to that of other genotypes, co-existent schistosomiasis hastens hepatic fibrosis and reduces the odds of spontaneous resolution. Severe steatosis without sinusoidal fibrosis is a typical finding on liver biopsy, the panelists said.

HCV-4, like the other types, is a major cause of chronic liver disease. "A possible association had been suggested between HCV-4 and hepatocellular carcinoma (HCC) based on the similarity of distribution of HCC and HCV-4 in Egypt," the authors wrote.

Dr. Sam Lee, a panelist from the University of Calgary, Canada, told Reuters Health that of all the HCV genotypes, 1, 4 and 6 "appear to be the most resistant to treatment, with success rates of about 50% in viral clearance with a longer course of treatment." This compares to "much more favorable" success rates of about 70-85%, with shorter treatment, in patients with genotypes 2 and 3, he said.

"About 5-35% of patients stop treatment prematurely due to side effects," Dr. Lee added.

HIV co-infection, cirrhosis and high initial viral load are the main predictors of a delayed treatment response, according to the panelists. Response-guided therapy is the accepted standard, they say; while patients who have virological clearance within four weeks can benefit from a 24 week regimen, delayed responders may need a longer course.

Newer drugs like nitazoxanide (NTZ) and the cyclophillin inhibitor Debio 025 show promise and need further trials, the panelists concluded.

SOURCE: http://link.reuters.com/tad44r

J Hepatol 2010.