Levels of serum markers of liver inflammation and fibrosis in patients with chronic hepatitis C virus infection according to HIV status and antiretroviral use.

Liver disease in patients with chronic hepatitis C virus (HCV) infection has an accelerated course in the presence of human immunodeficiency virus (HIV) coinfection. Some data suggest that HIV suppression achieved with highly active antiretroviral therapy (HAART) ameliorates HCV-related liver disease progression. The aim of this study was to test if there is overexpression of serum markers of liver inflammation and fibrosis in HIV-HCV-coinfected patients and if the effect is counteracted by HAART. In a pilot, cross-sectional, and comparative study serum markers of liver inflammation (CK-18 and HGF) and fibrosis (HGF, MMP-2, and TIMP-1) were measured via ELISA in HIV-infected patients off and on HAART, HCV monoinfected, HIV-HCV coinfected off and on HAART, and controls (10 per group). HIV-HCV-coinfected off HAART patients with low CD4 counts had higher levels of M30, HGF, and MMP-2 than HIV-HCV-coinfected on HAART. HCV coinfection predicted higher levels of MMP-2 [B 65.82 (95% CI 3.86-127.78); p = 0.04], HGF [B 520.22 (95% CI 123.65-916.78); p = 0.01] and M30 [B 128.02 (95%CI 16.39-239.64); p = 0.03]. HAART use was a predictor of lower levels of MMP2 [B -83.18 (95%CI (-146.8) - (-19.52)); p = 0.01] and M30 [B -112.9 (95% CI (-221.3) - (-4.52)); p = 0.04]. Other factors analyzed including alcohol intake ware not associated with the studied markers. In conclusion, serum markers of hepatic inflammation and fibrosis are overexpressed in HIV-HCV-coinfected patients with advanced immunosuppression, while HAART has a "protective" effect.

Arachidonic acid-induced gene expression in colon cancer cells.

It is well documented that arachidonic acid (AA) and its metabolites are intimately linked to cancer biology. However, the downstream mechanism(s) that link AA levels to cancer cell proliferation remain to be elucidated. Initial experiments in the current study showed that exogenous AA and inhibitors of AA metabolism that lead to the accumulation of unesterified AA are cytotoxic to the colon cancer cell line, HCT-116. Additionally, exogenous AA and triacsin C, an inhibitor of AA acylation, induced apoptosis and related caspase-3 activity in a transcriptionally dependent manner. Gene array analysis revealed that both exogenous AA and triacsin C alter the expression of similar genes in HCT-116 cells. For example, both downregulate several genes with well-documented roles in cell survival and apoptotic resistance. Conversely, both upregulate genes encoding activator protein-1 (AP-1) transcription factors, which have known roles in inducing apoptosis, and genes that counteract ras (Erk/MAPK) growth signaling pathways. Real-time polymerase chain reaction and immunoblotting demonstrated that mRNA and protein levels of one of the major AP-1 transcription factors, c-Jun, is markedly elevated by exogenous AA and triacsin C. Additionally, the cyclooxygenase inhibitor, sulindac sulfide, increases c-Jun mRNA levels. Together, these studies reveal that the generation of intracellular AA and its subsequent impact on gene expression probably represents a critical step that regulates colon cancer cell proliferation.

Age-related changes in cell surface and senescence markers in the spleen of DBA/2 mice: a flow cytometric analysis.

In murine studies of immune senescence cell preparations from whole organs, e.g. splenocytes, are frequently reported. However, age-related changes in spleen cell types have been poorly defined throughout the spectrum of adult age or across murine strains. The aim of this study was to use flow cytometry to more fully characterize cell types within the spleen of DBA/2 mice, a strain available from the National Institute of Aging (NIA), across the entire adult age spectrum. In advanced age, B cells comprise a greater percentage of the total splenocyte population, and there is a decline in the percentage of gammadelta+T cells in the spleen. The percentage of memory CD4+T cells increases in middle age with a corresponding decrease in the percentage of naïve CD4+T cells. Expression of the co-stimulatory molecule CD28 on splenic CD4+ and CD8+T cells increases with age, but CD28 expression on peripheral blood T cells does not change. The senescence marker p16INK4a increases in B cells and CD8+T cells within the spleen and can be measured by flow cytometry.