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Objective Chronic viral infections, HCV and HIV, are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods We studied seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than two years and had suppressed plasma HIV levels (<50 copies/ml). Two patient groups: HCV+/HIV+, HCV−/HIV+, and a control group comprised of healthy volunteers (n=20) were examined. Markers of systemic inflammation (IL-6, IP-10, sTNF-RI, and sTNF-RII), monocyte/macrophage activation (sCD163, sCD14, and neopterin), intestinal epithelial barrier loss (I-FABP and LPS), and coagulation (D-dimers) were analyzed. CD4+ naïve T cells and CD4+ recent thymic emigrants (RTE) were enumerated. Results Plasma levels of IP-10, neopterin, and sCD163 were higher in HCV/HIV co-infection than in HIV monoinfection and were positively correlated with indices of hepatic damage (AST, ALT, and APRI). Levels of I-FABP were comparably increased in both HIV monoinfection and HIV/HCV co-infection but LPS concentrations were highest in HCV/HIV co-infection suggesting impaired hepatic clearance of LPS. Plasma HCV levels were related to no inflammatory indices but for sCD163. In co-infected subjects, a previously recognized relationship of CD4+ naïve T cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusion Hepatocellular injury in HCV/HIV co-infection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4+ naïve T cells and recent thymic emigrants also merits further exploration.

Whereas we could find no relationship between HCV infection and most indices of CD4⁺ T-cell homeostasis or activation, CD4⁺ RTEs are diminished in the circulation of HCV coinfected persons and appear to be related to indices of ongoing hepatic damage or inflammation.

Background:The cause-effect relationships between physicochemical properties of amphiphilic [60]fullerene derivatives and their toxicity against bacterial cells have not yet been clarified. In this study, we report how the differences in the chemical structure of organic addends in 10 originally synthesized penta-substituted [60]fullerene derivatives modulate their zeta potential and aggregate's size in salt-free and salt-added aqueous suspensions as well as how these physicochemical characteristics affect the bioenergetics of freshwater Escherichia coli and marine Photobacterium phosphoreum bacteria. Dynamic light scattering, laser Doppler micro-electrophoresis, agarose gel electrophoresis, atomic force microscopy, and bioluminescence inhibition assay were used to characterize the fullerene aggregation behavior in aqueous solution and their interaction with the bacterial cell surface, following zeta potential changes and toxic effects.Results: Dynamic light scattering results indicated the formation of self-assembled [60]fullerene aggregates in aqueous suspensions. The measurement of the zeta potential of the particles revealed that they have different surface charges. The relationship between these physicochemical characteristics was presented as an exponential regression that correctly described the dependence of the aggregate's size of penta-substituted [60]fullerene derivatives in saltfree aqueous suspension from zeta potential value. The prevalence of DLVO-related effects was shown in salt-added aqueous suspension that decreased zeta potential values and affected the aggregation of [60]fullerene derivatives expressed differently for individual compounds. A bioluminescence inhibition assay demonstrated that the toxic effect of [60]fullerene derivatives against E. coli cells was strictly determined by their positive zeta potential charge value being weakened against P. phosphoreum cells in an aquatic system of high salinity. Atomic force microscopy data suggested that the activity of positively charged [60]fullerene derivatives against bacterial cells required their direct interaction. The following zeta potential inversion on the bacterial cells surface was observed as an early stage of toxicity mechanism that violates the membrane-associated energetic functions. Conclusions:The novel data about interrelations between physicochemical parameters and toxic properties of amphiphilic [60]fullerene derivatives make possible predicting their behavior in aquatic environment and their activity against bacterial cells.