Wednesday, February 16, 2011

Hepatitis C Daily News;"Milk thistle"- IV silibin to have significant antiviral efficacy against HCV

Silibinin monotherapy prevents graft infection after orthotopic liver transplantation in a patient with chronic hepatitis C

From Jules@ NATAP: Many studies in the past few years conducted by Peter Ferenci have shown IV silibin to have significant antiviral efficacy against HCV.
So for patients who are peg/rbv nonresponders and for that matter responders as well IV silibin should be researched in combination with telaprevir and boceprevir as it might have a particular benefit for prior null responders and partial responders and perhaps most importantly for patients who are contraindicated for peg/rbv but could combine IV silibin with an HCV protease.
Jnl of Hepatology March 2011
Sandra Beinhardt1, Susanne Rasoul-Rocken
We read with great interest the letter by Neumann et al. [1] on the effect of Silibinin in preventing graft infection in a patient with cirrhosis due to chronic hepatitis C (HCV). We obtained the same result in a patient treated with intravenous (i.v.) Silibinin mono-therapy .. read more
New protease inhibitors for HCV - Help is on the way - Jnl of Hepatology March 2011Articles in PressUncorrected Proof Dahlene N. Fusco, Raymond T. ChungMassachusetts General Hospital, GI Unit, 55 Fruit Street, Warren 1007, Boston, MA 02114, USA " HCV DAAs (direct-acting antivirals in the development pipeline include inhibitors of the viral NS3/4A protease and the viral NS5B RNA-dependent RNA polymerase [2].
Inhibitors of the NS3/4A protease are particularly attractive, since these drugs may have the double-edged action of not only directly inhibiting HCV replication, but also abrogating HCV NS3/4A's subversion of the innate immune response [6]. The NS3/4A compounds currently furthest along in development, the linear protease inhibitors (PIs) boceprevir (Merck) and telaprevir (VX 950, Vertex)......represent an important step forward toward the eradication of HCV [19]. Their major contributions include potent antiviral effects with a lower pill burden and manageable side effect profiles. .....Great care will be necessary to counsel against unnecessary therapy in persons who have low likelihood of responding to PEG/RBV and a PI, including those persons with prior null response to PEG/RBV, and limited hepatic fibrosis....
Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting: 'prevalence 3-7 times higher than 1.6% reported by CDC'..... - pdf attached - Download the PDF here "risk-factor-based testing preferable...12% among African-Americans & Latinos...43% among substance abusers....3% among alcohol abusers....16% with psych illness....9% with STDs....34% among HIV+"

Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients - pdf attached - Download the PDF here Jnl of Hepatology March 2011 "Multivariate analysis revealed that lower age, HCV genotype 2, and the rs12979860 CC genotype were significantly associated with sustained virologic response.......The rapid virologic response (RVR) rates for the rs12979860 CC, CT, and TT genotypes were 87%, 77%, and 64%, respectively, but this failed to be statistically significant (p=0.17).
For SVR in patients who achieved an RVR, a significant correlation with the rs12979860 genotype was observed (p=0.05), while for SVR in non-RVR patients no association was found (p=0.48) (Fig. 4).....A higher HCV RNA concentration was significantly associated with the TT genotype of rs8099917, the CC genotype of rs12979860, and the AA genotype of rs12980275 for HCV genotype 1 and genotype 2/3 infected patients (Table 3). Finally, the rs8099917 TT genotype was significantly associated with a higher fibrosis stage in HCV genotype 1 infected patients (Table 3)."

Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b in Japan- pdf attached - We studied 719 Japanese patients with chronic hepatitis C (positive for HCV RNA for more than 6 months) who received interferon therapy with or without ribavirin between 2002 and 2008....In summary, we showed that the IL28B SNP genotype is an important predictive factor for SVR and early viral dynamics in patients with HCV genotypes 2a and 2b."

Liver Cancer
New ray of hope to treat liver cancer’
Published: Wednesday, Feb 16, 2011, 11:49 IST
Liver is a common site for cancer — both primary cancer that originates in the liver as well as secondary cancer that originates elsewhere. Until recently, patients with liver cancer were considered to have a dismal prognosis without any useful treatment options. However, a significant proportion of such patients can expect considerable prolongation of life and even complete cure. Dr Sanjay Govil, hepatobiliary surgeon, Healthcare Global (HCG), spoke to DNA about this disease and the treatment.
What are the latest developments in the treatment of liver cancer?
The potential treatments include combinations of surgery, chemotherapy and ablative therapies such as radio frequency ablation, arterial chemoembolisation and cyber-knife radiotherapy. Surgery of the liver has become safer, with the risk of peri-operative death falling to one to two per cent in patients with normal liver function and 5-10% in those with jaundice or cirrhosis. The average hospital stay is about 10 days.
Can patients with liver cancer get back quality life?
The increasing safety of liver surgery permits more patients to benefit from tumour resection. In some patients with primary liver cancers and cirrhosis, resection may risk post-operative liver failure from a poorly functioning liver remnant. These patients are candidates for liver transplantation, which, though expensive, is now widely available in our country. Far from being a hopeless situation, many patients with liver cancer can look forward to many years of productive life.
Who are at risk of developing liver cancer?
Patients with liver cirrhosis and chronic Hepatitis B or C carriers are at a particularly high risk of developing cancer. These patients should be screened every six months with liver ultrasound and serum alphafetoprotein. While this will not detect all cancers, those that are picked up are usually small with a better chance of cure.
Is a combination of treatments a safe approach?
Other modalities of treatment may be combined with surgery to increase the number of patients who become eligible for operation. These include radio frequency ablation (RFA) and Trans-arterial Chemoembolisation (TACE) in particular. Moreover, laproscopic surgery reduces the trauma of surgery without compromising safety.
Healthy You

An analysis of data including more than 500,000 adults indicates that levels in the blood of bilirubin (a compound produced by the breakdown of hemoglobin from red blood cells) in the normal range but relatively higher were associated with a reduced risk of lung cancer, chronic obstructive pulmonary disease and all-cause death, according to a study in the February 16 issue of JAMA.

Serum total bilirubin is routinely measured in the primary care setting to identify hepatobiliary (liver, gall bladder and bile ducts) and blood diseases. Bilirubin may have cytoprotective (cell protective) properties, including antioxidant and anti-inflammatory effects, according to background information in the article. “Experimental studies using animal models support a protective effect of increased bilirubin against respiratory injury by environmental stressors. The epidemiological relationship between bilirubin level and the risk of respiratory disease is not well characterized,” the authors write.

Laura J. Horsfall, M.Sc., of University College London, and colleagues examined the association between serum bilirubin levels and the incidence of chronic obstructive pulmonary disease (COPD), lung cancer and all-cause death in a large population-based group of patients from the United Kingdom. The study included 504,206 adults from a U.K. primary care research database (the Health Improvement Network) with levels of serum bilirubin recorded between January 1988 and December 2008.

After various analyses and adjustment for several important health indicators, the researchers found that moderately higher levels of bilirubin within the range considered normal were associated with reduced risk of respiratory disease and all-cause mortality. Estimates for the incidence rate of lung cancer per 0.1-mg/dL increase in bilirubin level were an 8 percent decrease for men and an 11 percent decrease for women. The estimate for COPD in men per 0.1-mg/dL increase in bilirubin level was a 6 percent decrease, and for mortality in men was a 3 percent decrease. The results for COPD and mortality in women were similar.
“Based on our findings, bilirubin levels within the normal range appear to capture information about patients that may reflect a combination of environmental and genetically determined susceptibility to respiratory diseases,” the authors write. “Further research is needed to investigate causal associations between bilirubin levels and respiratory outcomes. A fuller understanding of these mechanisms may lead to the potential use of targeted clinical treatments that mildly suppress UGT1A1 [liver enzyme uridine diphosphate-glucuronosyltransferase activity and moderately increase bilirubin levels.”
Source: JAMA and Archives Journals

University of Tennessee, Knoxville, researchers have found that blue-green algae may be responsible for producing an estrogen-like compound in the environment which could disrupt the normal activity of reproductive hormones and adversely affect fish, plants and human health. Previously, human activities were thought solely responsible for producing these impacts.
Theodore Henry, an adjunct professor for UT Knoxville's Center for Environmental Biotechnology and faculty at the University of Plymouth, and his colleagues looked into blue-green algae, or cyanobacteria, and their effects on zebrafish. They discovered the algae may add a new harmful element into the way they understand and investigate alga blooms in aquatic systems.

Using funding from the National Oceanic and Atmospheric Administration (NOAA) Ecology of Harmful Algal Blooms (ECOHAB), the scientists uncovered how exposure to the blue-green algae called Microcystis induced a response consistent with exposure to estrogen-like compounds in larval fish.
The research can be found in the article "Global Gene Expression Profiling in Larval Zebrafish Exposed to Microcystin-LR and Microcystis Reveals Endocrine Disrupting Effects of Cyanobacteria" in the American Chemical Society's journal, Environmental Science & Technology.

Researchers compared groups of larval zebrafish exposed to Microcystis cells with those exposed to just the well-studied toxin they produce and found that only the fish in contact with the blue-green algal cells tested positive for a well-studied estrogenic biomarker. This led them to conclude the algal blooms were producing a previously unrecognized substance which is an estrogen-like compound that acts as an endocrine disruptor.

"The induction of these genes is consistent with presence of an estrogen and it is possible that many adverse affects may occur in fish populations," said Henry, "from physical feminization of male fish to behavioral changes, increased environmental estrogen levels can impact male territorial defending and even their nest-building habit. Environmentally released estrogen has not been shown to affect reproduction, but studies are still being conducted on the subject."
Possible human health effects include skin rashes, fever and liver damage. Henry and colleagues note that harmful blooms of toxin-producing algae occur in waters throughout the world and are a growing health and environmental concern. As a result, the scientists are calling for a revision of environmental monitoring programs to watch for these new substances.

Diabetes Treatment: New Approach with No Insulin
February 16, 2011 at 7:28 am

New research for diabetes treatment has pointed to possible future treatments that are free from insulin injections. A new report in Nature Medicine online by Dr. Umut Ozcan from Children’s Hospital in Boston MA demonstrates that diabetes may be controlled by artificially activating a protein in the liver. Ozcan is now researching ways to safely do this in his Ozcan laboratory.

In this new study, Ozcan and his colleagues demonstrate that a regulatory protein called XBP-1 regulates blood sugar by causing the degradation of the FoxO1 protein, which is responsible for increasing glucose output from the liver while stimulating the brain’s feeding behavior. The degradation of the FoxO1 protein is independent of XBP-1’s effect on the system that signals insulin.

Activating the XBP-1 may be another approach at controlling type 2 diabetes (decreased sensitivity to insulin). Ozcan Labs is now looking for practical means to implement the activation of the XBP-1 protein that can lead to a clinical development. While there are drugs available for type 2 diabetes, the disease is difficult to control
Ozcan Laboratory primary objective is to delineate the molecular mechanisms of endoplasmic reticulum stress originated pathologies focusing on insulin and leptin receptors. The ultimate goal of the lab is to find a cure for treatment of obesity and obesity related diseases. The study was funded by Children’s Hospital in Boston MA. Umut Ozcan received his MD from the University of Istanbul and completed his research training at the Joslin Diabetes Center and Harvard School of Public Health.;

;. Stem Cells

OCEANSIDE, Calif. -- International Stem Cell Corporation (OTCBB:ISCO), together with colleagues from ViaCyte (formerly Novocell), announced the successful derivation from its human parthenogenetic stem cells (hpSCs) of enriched cultures of definitive endoderm (DE). DE can be further developed into pancreas or liver cells. These new results create a platform for the development by ISCO of therapeutic products that have great potential to overcome the problem of rejection of transplanted cells by the patient’s own immune system.

The results are described in a new article that will appear in Differentiation, the official journal of the International Society of Differentiation, published by Elsevier. The article concludes that, “Creation of the definitive endoderm lineages from hpSC represents the critical first step toward the development of hpSC-based cellular therapies for diseases of the liver or pancreas.”
Off The Cuff
Blogging at Medpage
Celebrity Diagnosis
Michele Berman and her physician husband, Mark Boguski, co-founded Celebrity Diagnosis with a dual mission: to report on common diseases affecting uncommon people and to provide the medical facts behind the headlines. From 1988 to 2000, Dr. Berman had a pediatric practice in Washington, D.C., where she authored a monthly column for Washington Parent magazine. She is also a medical Internet pioneer, having established one of the first medical practice websites in 1997. She and her husband have trained and taught at some of the top medical schools in the country including Harvard, Johns Hopkins, and Washington University in St. Louis.
By: Michele R. Berman, MD February 14, 2011
Last Thursday, Dr. Mark Boguski and I delivered an invited lecture at the Harvard School of Public Health. In our presentation, entitled "Health Communication at the Nexus of Social Media and Popular Culture," we described and defined the Goody-Gaga Effect, which is the phenomenon of sharply increased volume of search engine traffic for specific diseases or medical conditions that correlates with a celebrity association with that disease or condition.
By: Peggy Peck February 15, 2011
I was in Los Angeles last week when the diet soda bomb exploded. About five years ago I was in Anaheim when hot dogs and spam (that's Spam in a can) came under fire.
A Few Of The Best Medical and Patient's Blogs Online.......
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