Thursday, July 06, 2006

 

Taking A Close Look At HepB



June 26, 2006


Filed under: in the news...
Using some of the latest investigational techniques, scientists at the Scripps Research Institute have discovered pretty amazing functional morphology of the Hepatisis B virus:
Hepatitis B virions, also known as Dane particles, are approximately 40 nanometers in size, and the capsid is surrounded by a membrane envelope. While the structure of the hepatitis B capsid has been studied intensively in vitro, until this study little was known about the structure and assembly of native capsids present in infected cells in vivo, and even less was known about the structure of mature virions.
"We used cryomicroscopy and image analysis to examine the native structure of HBV [hepatitis B virus ] capsids from transgenic mice and virions isolated from patient blood samples," Yeager said. [Mark Yeager, M.D., Ph.D. is a professor at Scripps -ed.] "By rapidly freezing the samples we were able to use cryo-electron microscopy to image the particles while they were maintained at the temperature of liquid nitrogen--around--300° F--which preserves them in a state close to what exists in vivo. Image processing allowed us to derive 3-D maps that revealed for the first time how the outer lipid envelope interacts with the capsid shell. "
The 3-D maps showed that in terms of molecular size, hepatitis B virus is enormous--nearly 10 times larger than a hemoglobin molecule. Like the human genome, the genome of the hepatitis B virus is formed by double-stranded DNA and enclosed by the capsid, which has icosahedral symmetry, resembling the geometric structure of a geodesic dome. The capsid itself is contained within an outer envelope formed by a lipid bilayer, similar to the membranes that enclose all human cells. The membrane of hepatitis B virus is studded with glycoprotein spikes, which bind to receptors on liver cells that mediate infection.
In hepatitis B-infected liver cells, transcription of the viral DNA produces a type of RNA that is packaged into capsids. Within the capsid, reverse transcription produces a single-strand DNA copy that serves as the template for second strand DNA synthesis. The resulting particles bud through membranes of the endoplasmic reticulum--the part of the cell involved with protein folding, assembly, and transport--to acquire the outer membrane envelope of the virus, a step that confers infectivity.
"In the transgenic mice, we found two types of capsids with different densities," Yeager said. "While both types of capsids were assembled as similar icosahedral structures, we found that the lower density capsids did not contain any viral DNA or viral RNA, while the higher density capsids contained viral DNA intermediates. It seems likely that these lower density capsids were released from the cell nucleus. These results may offer new clues how the virus replicates in vivo."

 

Statins Stop Hepatitis C Virus Replication ...




Japanese scientists say they've found statins, typically used as anti-cholesterol medications, can inhibit the replication of the hepatitis C virus.

The findings mean statins might be able to replace ribavirin in combination therapy with interferon. There are 170 million people worldwide infected with HCV. The standard HCV treatment is a combination therapy of interferon and ribavirin, which is effective in about 55 percent of patients. The remaining 45 percent face a threat of the disease progressing to cirrhosis and liver cancer. Aware of recent studies showing one statin, lovastatin, inhibits HCV replication, researchers led by Masanori Ikeda of Okayama University tested other statins in search of a more effective anti-HCV therapy. They evaluated the anti-HCV activities of five statins: atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin.


When the statins were tested alone, all except pravastatin inhibited HCV replication, with fluvastatin having the strongest effect; atorvastatin and simvastatin had moderate effects and lovastatin had a weak effect. The findings are reported in the July issue of the journal Hepatology.

Copyright 2006 by United Press International




Wednesday, July 05, 2006

 

Clinical Trials for Natural Hepatitis C Remedy Looking Good


June 28, 2006

What can interferon non-responders do about Hepatitis c? What about people who cannot or will not tolerate the devastating side effects of interferon therapy? Find out about the positive preliminary results from a medical study of a natural Japanese prescription medicine that's available to patients now.
Progressive Alternative Medicine Solution Undergoes Clinical Trials and Holds Promise of Benefiting Millions of Americans with Hepatitis CSource: HepCare Inc. Tuesday, May 23An estimated five million Americans have been infected with hepatitis C virus (HCV) according to a study published at the Liver Meeting by the American Association for the Study of Liver Diseases (AASLD) in November 2005. Chronic hepatitis C is associated with significant morbidity (liver cirrhosis and hepatocellular carcinoma) and mortality. Current treatment is based on interferon and ribavirin. However, treatment options are limited for patients who are not candidates for interferon-based therapy, particularly for those who suffer from HCV genotype 1 infection.

Sho-saiko-to (SST), a standardized herbal formula, is under a clinical phase II trial by a leading New York Cancer Research Institute to determine its effect on hepatitis C patients. The research group has reported the preliminary results of 15 patients at the 2nd Society of Integrative Oncology Conference in San Diego on November 10, 2005. This study is titled "Sho-saiko-to for Patients with Chronic Hepatitis C Who Are Intolerant to or Have Contraindication to Interferon-Based Therapy: A Phase II Study." SST is know to have anti-fibrotic effect by inhibition of lipid peroxidation in hepatocytes and stellate cells in animal studies. It has also been shown to reduce aminotransferase levels and the incidence of hepatocellular carcinoma in hepatitis and liver cirrhosis patients.

According to the design of the clinical trial, 31 patients will receive SST daily for 52 weeks. Fifteen patients have completed the treatment and the preliminary results have been reported. No serious adverse events have been attributed to SST among any patients who enrolled in the trial. Among the 15 patients who completed the study, reductions in alanine aminotransferase (ALT) were observed in 11 patients and aspartate aminotransferase (AST) in 10 patients. In 10 patients, the liver biopsy showed 20% improvement on histological assessment of the liver. This is consistent with the findings by the Japanese researchers for its anti-inflammatory effect. More interestingly, the majority of the patients whom participated in the clinical trial were genotype 1 infection.For more information about the herbal remedy, Sho-saiko-to, visit www.shosaikoto.com.


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