Several nucleoside analogues (penciclovir, lobucavir, dioxalane guanine [DXG], 1-beta-2,6-diaminopurine dioxalane [DAPD], L-FMAU, lamivudine) and acyclic nucleoside phosphonate analogues (adefovir, tenofovir) that are in clinical use, in clinical trials or under preclinical development for the treatment of hepatitis B virus (HBV) infections, were evaluated for their inhibitory effect on the replication of a la- mivudine-resistant HBV variant containing the methionine --> valine substitution (M550V) in the polymerase nucleoside-binding domain. The antiviral activity was determined in the tetracycline-responsive HepAD38 and HepAD79 cells, which are stably transfected with either a cDNA copy of the wild-type pregenomic RNA or with cDNA containing the M550V mutation. As expected, lamivudine was much less ( approximately 200-fold) effective at inhibiting replication of the M550V mutant virus than the wild-type virus. In contrast, adefovir, tenofovir, lobucavir, L-FMAU, DXG and DAPD proved almost equally effective against both viruses. A second objective of this study was to directly compare the antiviral potency of the anti-HBV agents in HepG2 2.2.15 cells (which are routinely used for anti-HBV drug-screening purposes) with that in HepAD38 cells. HepAD38 cells produce much larger quantities of HBV than HepG2 2.2.15 cells, and thus allow drug screening in a multiwell plate format. All compounds were found to be almost equally effective at inhibiting HBV replication in HepAD38 cells (as in HepG2 2.2.15 cells), except for penciclovir, which was clearly less effective in HepAD38 cells.
Stem base disease (eyespot, sharp eyespot and brown foot rot) was assessed visually and by the polymerase chain reaction (PCR) technique on single plants sampled at four-week intervals in two crops of winter wheat grown in the UK in 1992-3. PCR assays were conducted for Fusarium avenaceum, F. culmorum, both varieties of Microdochium nivale, both eyespot-causing species of Tapesia and Rhizoctonia cerealis. PCR diagnoses were compared with visual diagnoses at each time point. Eyespot was caused principally by T. acuformis (R-type) and developed rapidly late in the season. Visual diagnoses of eyespot were largely confirmed by PCR but T. acuformis was detected in many plants lacking eyespot symptoms. R. cerealis was detected at relatively low incidences on both sites, and sharp eyespot visual diagnoses did not correlate with the incidence of any of the pathogens assayed by PCR. Brown foot rot, caused principally by Microdochium nivale var. majus, accumulated earlier in the season than eyespot. Overall, visual diagnoses of stem base disease coincided poorly with PCR data until after growth stage (GS) 30.
Two polyacid-modified composite resins, Dyract and Compoglass, have been studied for water-uptake on storage in three aqueous media, namely pure water, 0.9% NaCl and 1 M NaCl at 37 degrees C, and the results compared with those of a conventional composite resin, Pekafill. The equilibrium water-uptake of Dyract and Compoglass varied depending on time of cure and ionic strength of the storage medium. This latter finding contrasted with that for Pekafill, where equilibrium water content showed almost no variation with ionic strength of the storage medium. Uptake of water was always greater in Dyract and Compoglass than in Pekafill, reflecting the role of water in promoting the later neutralization reaction in these materials and its further role in hydrating the ionic products of that reaction. Despite this and other evidence of neutralization, specimens of Dyract and Compoglass stored in wet conditions (0.9% NaCl) showed no change in compressive strength on storage from 24 h to 30 days, a result similar to that reported previously for Dyract alone for flexural strength for times up to 1 year. By contrast, specimens of Dyract and Compoglass stored in dry air at 37 degrees C, and therefore unable to undergo any neutralization, showed an increase in compressive strength of between 40 and 70 MPa by 30 days that was significant at P < 0.01.
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