Search

Unlabelled: Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult-to-cure hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is unknown. One hundred and one HBeAg-negative patients (92% genotype D) with compensated CHB (84% males, 46 years; hepatitis B virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% with cirrhosis) were followed up for a median of 11 years (range, 1-17) after a median of 23 months (range, 10-48) of either standard or pegylated (Peg)-IFN-alpha therapy. A post-treatment response was defined as hepatitis B surface antigen (HBsAg) clearance with or without antibody to hepatitis B surface antigen (anti-HBs) seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays (Applied Biosystems, Carlsbad, CA). During a median of 11 years of post-treatment follow-up, 21 patients (21%) cleared serum HBsAg, including 15 who developed>10 IU/mL of anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) had CT, and 11 (11%) had TT, with the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC, genotype carriers (P=0.039). Baseline HBV DNA levels<6 log cp/mL (odds ratio [OR], 11.9; 95% confidence interval [CI]: 2.8-50.6; P=0.001), ALT levels>136 IU/L (OR, 6.5; 95% CI: 1.8-22.5; P=0.003), duration of IFN (OR, 1.16; 95% CI: 1.02-1.31; P=0.021), and genotype CC (OR, 3.9; 95% CI: 1.1-13.2; P=0.025) independently predicted HBsAg clearance., Conclusions: IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in the pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of HBV., (Copyright © 2012 American Association for the Study of Liver Diseases.)

The photodynamic activity of a carrier-sensitizer system consisting of heterotopic colloidal nanoparticles (diameter 100-1000 nm) of a cationic amphiphilic cyclodextrin, heptakis(2-omega-amino-O-oligo(ethylene oxide)-6-hexylthio)-beta-CD (SC6CDNH2) encapsulating the anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin (TPPS) is investigated by an interdisciplinary approach involving the combination of time-resolved absorption and emission techniques with in vitro studies on cultured tumor cells. In a range of TPPS:SC6CDNH2 molar ratios between 1:10 and 1:50 these nanoparticles preserve the photodynamic properties of the entrapped photoactive agent. In fact, the triplet state of TPPS is efficiently populated, very long-lived and, as a consequence, able to produce singlet oxygen (the essential species for the photodynamic action) with quantum yield comparable to the free TPPS. Photodynamic efficacy of the carrier/sensitizer system is proven by in vitro studies on tumor Hela cells treated with TPPS:SC6CDNH2 at different molar ratio, showing significant cells death upon illumination with visible light.

Isoxazolidinyl polycyclic aromatic hydrocarbons (isoxazolidinyl-PAHs) have been synthesized in good yields by 1,3-dipolar cycloaddition methodology promoted by microwave irradiation. The structures of the obtained cycloadducts have been determined by NOE experiments and supported by computational studies at the AM1 level. The cytotoxicity and antiviral activity of the synthesized compounds have been investigated. In particular, compounds 7c and 7e show high levels of cytotoxicity on MOLT-3 leukemia cells; 7e exerts a remarkable enhancing activity on apoptosis caused by anti-fas antibody addition. Furthermore, compounds 7b and 8b exhibit specific antiviral effects against the Punta Toro virus.

Crude extracts of the coelenterate Aiptasia mutabilis (Anthozoa, Aiptasiidae) nematocysts have been tested for their cytotoxicity of Vero and HEp-2 cells monolayers. The results indicate that the nematocyte venom contains one or more toxins with an extremely powerful cytolytic activity. An extract containing the equivalent of as little as 0.6 nematocysts/microL is sufficient to induce significant cellular necrosis, and IC50 can be estimated to be ca. 2 nematocysts/microL on Vero cells. These values are 1-2 orders of magnitude lower than those reported so far for other sea anemone venoms. The extreme potency is accompanied by poor stability of the venom that is readily inactivated by moderate heat and by buffers at non-neutral pH values. The extract is unstable even when kept for short times at 4 degrees C, or after storage at -20 degrees C. Separation of crude venom by affinity chromatography on ConA-Sepharose allowed us to identify two main components with molecular masses of 95 and 31 kDa, respectively, as responsible for the cytolytic properties of A. mutabilis nematocyst extract.

The synthesis of 4'-alpha-C-branched N,O-nucleosides has been described, based on the 1,3-dipolar cycloaddition of nitrones with vinyl acetate followed by coupling with silylated nucleobases, The obtained compounds have been evaluated for their activity against HSV-1, HSV-2, HTLV-1. Cytotoxicity and apoptotic activity have been also investigated: compound 10c shows moderate apoptotic activity in Molt-3 cells.