Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation

Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and silybin B, which are insoluble in aqueous solution. A chemically modified and soluble version of silibinin, SIL, has been shown to potently reduce hepatitis C virus (HCV) RNA levels in vivo when administered intravenously. Silymarin and silibinin inhibit HCV infection in cell culture by targeting multiple steps in the virus lifecycle. We tested the hepatoprotective profiles of SIL and silibinin in assays that measure antiviral and anti-inflammatory functions. Both mixtures inhibited fusion of HCV pseudoparticles (HCVpp) with fluorescent liposomes in a dose-dependent fashion. SIL inhibited 5 clinical genotype 1b isolates of NS5B RNA dependent RNA polymerase (RdRp) activity better than silibinin, with IC50 values of 40–85 µM. The enhanced activity of SIL may have been in part due to inhibition of NS5B binding to RNA templates. However, inhibition of the RdRps by both mixtures plateaued at 43–73%, suggesting that the products are poor overall inhibitors of RdRp. Silibinin did not inhibit HCV replication in subgenomic genotype 1b or 2a replicon cell lines, but it did inhibit JFH-1 infection. In contrast, SIL inhibited 1b but not 2a subgenomic replicons and also inhibited JFH-1 infection. Both mixtures inhibited production of progeny virus particles. Silibinin but not SIL inhibited NF-κB- and IFN-B-dependent transcription in Huh7 cells. However, both mixtures inhibited T cell proliferation to similar degrees. These data underscore the differences and similarities between the intravenous and oral formulations of silibinin, which could influence the clinical effects of this mixture on patients with chronic liver diseases

Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006

The four dengue viruses (DENV) represent the most common human arbovirus infections in the world and are currently a challenging problem, particularly in the tropical and subtropical regions of Asia and the Americas. Infection with DENV may produce symptoms of varying severity. While access to care, appropriate interventions, host genetic factors, and previous exposure to DENV are all known to affect the outcome of the infection, it is not entirely understood why some individuals develop more severe disease. It has been hypothesized that the four dengue serotypes differ in disease severity and clinical manifestations. This analysis assessed whether there were significant differences in severity of disease caused by the dengue serotypes in a pediatric population in Thailand. We found significant and non-significant correlations between dengue serotype 2 infection and more severe dengue disease. We also found that individual serotypes varied in disease severity between study years, perhaps supporting the hypothesis that the particular sequences of primary and secondary DENV infections influence disease severity

A Review of the Clinical Applications of Artificial Intelligence in Abdominal Imaging

Artificial intelligence (AI) has been a topic of substantial interest for radiologists in recent years. Although many of the first clinical applications were in the neuro, cardiothoracic, and breast imaging subspecialties, the number of investigated and real-world applications of body imaging has been increasing, with more than 30 FDA-approved algorithms now available for applications in the abdomen and pelvis. In this manuscript, we explore some of the fundamentals of artificial intelligence and machine learning, review major functions that AI algorithms may perform, introduce current and potential future applications of AI in abdominal imaging, provide a basic understanding of the pathways by which AI algorithms can receive FDA approval, and explore some of the challenges with the implementation of AI in clinical practice

Clinical manifestations.

<p>*Percent of DENV-1 cases with ascites.</p><p>†Mean pleural effusion indexes (PEI) were significantly higher among DENV-2 compared to DENV-1.</p><p>‡Mean pleural effusion indexes (PEI) were significantly higher among secondary infections as compared to primary infections.</p

Serotype-specific data.

<p>Significant differences between study years within a serotype include:</p>*<p>p = 0.05 compared to 2004.</p>**<p>p = 0.02 compared to 2004.</p>†<p>p = 0.03 compared to 2006.</p>‡<p>p = 0.03 compared to 2006. Significant differences in disease severity between study years overall include:</p>§<p>most severe study year is used as reference.</p>##<p>least severe study year is used as reference.</p>#<p>Discrepancies in totals are due to the 7 cases that were not serotyped and the single case that did not receive a serological response profile.</p