Atomic Force Microscopy and High Resolution Scanning Electron Microscopy Investigation of Zeolite A Crystal Growth. Part 2: In Presence of Organic Additives

The nanoscopic details of the crystal growth of zeolite A in the presence of the organic modifiers diethanolmaine (DEA) and triethanolamine (TEA) has been determined using a combination of atomic force microscopy (AFM) and high-resolution scanning electron microscopy (HRSEM) coupled with Monte Carlo simulations. Crystallization of zeolite A in the presence of TEA was faster than when the growing solution contained DEA. In addition, the morphology of the final zeolite A crystals depended on the type of organic molecule, with TEA producing crystals bound only by {100} facets and DEA leading to the formation of relatively large {110} faces. These features can be explained in terms of the relative Si/Al in the growing medium and its control due to the different affinity of the organic molecules to Al. In addition, synthesis performed at 90 °C showed the appearance of {211} facets. Careful review of the HRSEM and AFM images, in addition to comparison with the MC simulations, reveals that these are in fact pseudofacets, products of the slow dissolution of the metastable zeolite A crystals. This proves that the final habit of the LTA crystals can be governed by very small changes in saturation of the growing medium, and control of this parameter can prove advantageous when designing crystals for industrial applications

Cross-Resistance Testing of Antihepadnaviral Compounds Using Novel Recombinant Baculoviruses Which Encode Drug-Resistant Strains of Hepatitis B Virus

Long-term nucleoside analog therapy for hepatitis B virus (HBV)-related disease frequently results in the selection of mutant HBV strains that are resistant to therapy. Molecular studies of such drug-resistant variants are clearly warranted but have been difficult to do because of the lack of convenient and reliable in vitro culture systems for HBV. We previously developed a novel in vitro system for studying HBV replication that relies on the use of recombinant baculoviruses to deliver greater than unit length copies of the HBV genome to HepG2 cells. High levels of HBV replication can be achieved in this system, which has recently been used to assess the effects of lamivudine on HBV replication and covalently closed circular DNA accumulation. The further development of this novel system and its application to determine the cross-resistance profiles of drug-resistant HBV strains are described here. For these studies, novel recombinant HBV baculoviruses which encoded the L526M, M550I, and L526M M550V drug resistance mutations were generated and used to examine the effects of these substitutions on viral sensitivity to lamivudine, penciclovir (the active form of famciclovir), and adefovir, three compounds of clinical importance. The following observations were made: (i) the L526M mutation confers resistance to penciclovir and partial resistance to lamivudine, (ii) the YMDD mutations M550I and L526M M550V confer high levels of resistance to lamivudine and penciclovir, and (iii) adefovir is active against each of these mutants. These findings are supported by the limited amount of clinical data currently available and confirm the utility of the HBV-baculovirus system as an in vitro tool for the molecular characterization of clinically significant HBV strains