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Resistance Problem (resistance + problem)
Selected AbstractsThe resistance of metallothionein to proteolytic digestion: An LC-MS/MS analysisELECTROPHORESIS, Issue 16 2007Rongying Wang Abstract Metallothioneins (MTs) are a family of cysteine-rich metalloproteins which strongly bind to heavy metals, such as Cd(II), Zn(II), and Cu(I). Previous works by other group using gel electrophoresis and fluorescence showed MTs were resistant to proteolytic digestion by a variety of enzymes, raising the difficulties in proteomic identification of MTs. The present work was attempted to analyze the resistance of MTs to trypsin using LC with MS/MS (LC-MS/MS), which was able to determine the sequences of the produced peptides and thus precisely characterize the cleavages. The results showed that metal-saturated MTs were completely resistant to trypsin. This resistance problem could be overcome by the addition of EDTA to MT samples, which rendered MTs readily digested into peptides and identified by MS/MS. Interestingly, the partially metal binding MTs were digested into peptides predominantly with miss cleavages which were well dependent on the amount of heavy metals bound to MTs. An explanation for these observations was proposed. The potential applications of the MT's resistance to trypsin in isolation and identification of MTs in complex mixtures such as cultured cells was demonstrated. The preliminary data also showed the same proteomic approach of proteolytic digestion followed by MS/MS analysis may provide information on metal binding status of MTs, along with the identification of MTs in a mixture. [source] Pollen beetle in the UK; the start of a resistance problem?EPPO BULLETIN, Issue 1 2008D. M. Richardson In 2003, the first report of poor control of pollen beetle Meligethes aeneus at a site in South East England in the UK was investigated but resistance to pyrethroid insecticides was not confirmed in subsequent laboratory testing. Bioassays of 26 UK samples of M. aeneus collected in 2004 with the pyrethroid lambda-cyhalothrin showed little or no divergence from the response expected of a fully susceptible strain. In 2006 samples of pollen beetle from the UK were sent to Germany, and again these were shown to be fully susceptible. In 2007 using test kits supplied by Udo Heimbach, BBA, 19 samples of pollen beetle were tested, again from across the UK. Results indicated that a small number of individuals were fully resistant, surviving the highest dose of lambda-cyhalothrin tested (0.375 microg/L) after 5-h exposure at 4 sites, and after 24-h exposure at 2 of these sites. [source] Current therapy of HIVJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2010Anja Verena Potthoff Summary Antiretroviral therapy has improved continuously. Almost every year a new drug has been approved. Nucleoside analogs still build the backbone of antiretroviral therapy. They inhibit reverse transcriptase and thus the transcription of RNA to DNA. They are combined with non-nucleoside reverse transcriptase inhibitors or protease inhibitors. New therapeutic approaches are attachment or entry inhibitors, integrase inhibitors and maturation inhibitors. Multiple prospective multicenter studies have proven the life prolonging effect of antiretroviral therapy. With the optimal therapy life expectancy of HIV patients is only slightly reduced, similar to that of those with chronic diseases such as diabetes mellitus. One result of the higher age of HIV patients is an increase in concomitant diseases and medications. Drug interactions have to be considered and avoided. There has been a long discussion about the best time point to start antiretroviral therapy. In the late 1990s, every infected patient was treated hoping to eliminate the virus, ignoring the CD4+ cell count and viral load. This caused multiple (long-term) side effects and a rising resistance problem. The guidelines now recommend starting therapy at about 350/,l CD4 lymphocytes. Due to its complexity antiretroviral therapy should be initiated and monitored in specialized centers. [source] A precise boundary element method for macromolecular transport propertiesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2004Sergio Aragon Abstract A very precise boundary element numerical solution of the exact formulation of the hydrodynamic resistance problem with stick boundary conditions is presented. BEST, the Fortran 77 program developed for this purpose, computes the full transport tensors in the center of resistance or the center of diffusion for an arbitrarily shaped rigid body, including rotation-translation coupling. The input for this program is a triangulation of the solvent-defined surface of the molecule of interest, given by Connolly's MSROLL or other suitable triangulator. The triangulation is prepared for BEST by COALESCE, a program that allows user control over the quality and number of triangles to describe the surface. High numerical precision is assured by effectively exact integration of the Oseen tensor over triangular surface elements, and by scaling the hydrodynamic computation to the precise surface area of the molecule. Efficiency of computation is achieved by the use of public domain LAPACK routines that call BLAS Level 3 hardware-optimized subroutines available for most processors. A protein computation can be done in less than 10 min of CPU time in a modern Pentium IV processor. The present work includes a complete analysis of the sources of error in the numerical work and techniques to eliminate these errors. The operation of BEST is illustrated with applications to ellipsoids of revolution, and Lysozyme, a small protein. The typical numerical accuracy achieved is 0.05% compared to analytical theory. The numerical precision for a protein is better than 1%, much better than experimental errors in these quantities, and more than 10 times better than traditional bead-based methods. © 2004 Wiley Periodicals, Inc. J Comput Chem 9: 1191,1205, 2004 [source] Translesion Synthesis of 1,3-GTG Cisplatin DNA LesionsCHEMBIOCHEM, Issue 11 2010Sabine Schneider Dr. Low-fidelity polymerases: Cells can copy genetic material even in the presence of DNA lesions. Here we show that this bypass process is also possible for the strongly helix disturbing cisplatin 1,3-GTG lesion. A key polymerase involved in the translesion synthesis (TLS) process is Pol ,. The results have implication for the resistance problem associated with cisplatin chemotherapy. [source] Review article: nucleoside analogues for the treatment of chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2004H. M. Younger Summary Current accepted treatment for chronic hepatitis B uses either the immunomodulator interferon alpha or nucleoside analogues lamivudine or adefovir. Interferon has side effects which mean it is often poorly tolerated. Long-term use of lamivudine is associated with increasing viral resistance for each year it is taken and the rebound viraemia that can occur when the drug is stopped is also of concern to many. Adefovir appears to have less of the resistance issues of lamivudine but is still a relatively new drug and at present its use is principally limited to patients with lamivudine-resistant disease. A number of other nucleoside analogues are currently being developed with some now at the stage of early clinical trials. A proportion share the significant resistance problems of lamivudine but many appear to have more potent anti-viral effect than the drugs currently available. If some of these newer anti-viral agents are approved for use in chronic hepatitis B, the potential for prolonged suppression of hepatitis B virus replication with resultant stabilization or improvement in liver disease may be achieved. [source] | ||||||||||||||||