BACKGROUND & AIMS: Nucleic acid polymers (NAPs) inhibit assembly and secretion of hepatitis B virus (HBV) subviral particles. We performed an open-label, phase 2 study of the safety and efficacy of the NAPs REP 2139 or REP 2165 combined with tenofovir disoproxil fumarate (TDF) and pegylated interferon alfa-2a (pegIFN) in patients with chronic HBV infection who were negative for hepatitis B e antigen. METHODS: Following 24 weeks TDF therapy, 40 patients were randomly assigned to groups that received 48 weeks of experimental therapy (TDF þ pegIFN þ REP 2139-Mg or REP 2165-Mg) or 24 weeks of control therapy (TDF þ pegIFN) followed by 48 weeks of experimental therapy. Patients were then followed for a treatment-free period of 48 weeks. Primary outcomes were the safety and tolerability of REP 2139-Mg or REP 2165-Mg in combination with TDF þ pegIFN compared with TDF þ pegIFN alone through the first 48 weeks of therapy and subsequently throughout 48 weeks of NAP-based combination therapy (treatment weeks 24-72 in the experimental group and weeks 48-96 in the control group). Secondary outcomes were reductions in hepatitis B surface antigen (HBsAg) in control and experimental groups over the first 48 weeks of the study and throughout 48 weeks of combination therapy and virologic control (HBsAg positive, HBV DNA below 2000 IU/mL, normal level of alanine aminotransferase) or functional cure (HBsAg below 0.05 IU/mL, HBV DNA target not detected, normal level of alanine aminotransferase) after removal of all therapy. RESULTS: Levels of HBsAg, anti-HBs, and HBV DNA did not differ significantly between the groups given REP 2139 vs REP 2165. PegIFN-induced thrombocytopenia (P ¼ .299 vs controls) and neutropenia (P ¼ .112 vs controls) were unaffected by NAPs (REP 2139 vs REP 2165). Increases in levels of transaminases were significantly more frequent (P < .001 vs controls) and greater (P ¼ .002 vs controls) in the NAP groups (but did not produce symptoms), correlated with initial decrease in HBsAg, and normalized during therapy and follow-up. During the first 24 weeks of TDF and pegIFN administration, significantly higher proportions of
In this work, the surface treatment of poly(ethylene terephtalate) (PET) films in a low frequency (70 kHz) discharge in helium-oxygen mixtures is investigated. Optical emission spectroscopy and mass spectrometry are used to analyze the gas phase. Surface properties are analyzed via the X-ray photoelectron spectroscopy (XPS) technique and contact angle measurements. The treatment conditions are optimized in order to obtain a surface functionalization, which would show a reduced ageing effect. The stability of the treated surface via the crosslinking process seems to be closely correlated to the presence of the helium metastable species in the discharge. A very good stability with the ageing time is obtained for samples treated in gaseous mixtures that contain less than 5% O 2 , conditions for which the oxidized polymeric structure seems to be formed on a reinforced crosslinked layer. The very efficient loss of He excited species, for amounts of O 2 higher than a few percent, affects the surface crosslinking. For high quantities of oxygen introduced in the reactor (more than about 50%), a balance is established between the introduction of oxygenated groups and the ablation of the surface. In this case, the surface degradation has, as a consequence, the ageing effect.
Films of poly(ethylene terephthalate) (PET) have been subjected to a low frequency (70 kHz) helium discharge, with a non-symmetrical configuration of electrodes, in order to study the treatment conditions for which the 'ageing' effect is slowed down. Treatments were made for different gas flow rates (40, 70 and 100 sccm) and different exposure times (1, 10 and 30 s). Emission spectroscopy and mass spectrometry were used to characterize the discharge plasma. The resulting modifications to the polymer surface were analysed via contact angle measurements and the XPS technique. It is pointed out that treatments on an He discharge induce both a functionalization and a cross linking of the uppermost layers of the polymer film. The residual oxygen, which partially originates within the polymer, induces surface oxidation. The cross-linked content critically depends on the residence time and concentration of implicated species. It seems that a change in the surface work function takes place as a result of a surface restructuring in the earliest stages of the reactions. This could involve an increase in the rate constant for the surface de-excitation of the helium metastables in the presence of the polymer. A contribution to the understanding of the competitive processes of cross linking and functionalization, as a function of the helium flow rate, is accomplished.
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