69 research outputs found

    Modification and re-validation of the ethyl acetate-based multi-residue method for pesticides in produce

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    The ethyl acetate-based multi-residue method for determination of pesticide residues in produce has been modified for gas chromatographic (GC) analysis by implementation of dispersive solid-phase extraction (using primary–secondary amine and graphitized carbon black) and large-volume (20 ΌL) injection. The same extract, before clean-up and after a change of solvent, was also analyzed by liquid chromatography with tandem mass spectrometry (LC–MS–MS). All aspects related to sample preparation were re-assessed with regard to ease and speed of the analysis. The principle of the extraction procedure (solvent, salt) was not changed, to avoid the possibility invalidating data acquired over past decades. The modifications were made with techniques currently commonly applied in routine laboratories, GC–MS and LC–MS–MS, in mind. The modified method enables processing (from homogenization until final extracts for both GC and LC) of 30 samples per eight hours per person. Limits of quantification (LOQs) of 0.01 mg kg−1 were achieved with both GC–MS (full-scan acquisition, 10 mg matrix equivalent injected) and LC–MS–MS (2 mg injected) for most of the pesticides. Validation data for 341 pesticides and degradation products are presented. A compilation of analytical quality-control data for pesticides routinely analyzed by GC–MS (135 compounds) and LC–MS–MS (136 compounds) in over 100 different matrices, obtained over a period of 15 months, are also presented and discussed. At the 0.05 mg kg−1 level acceptable recoveries were obtained for 93% (GC–MS) and 92% (LC–MS–MS) of pesticide–matrix combinations

    Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp

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    Gis-assisted Coastal Zone Planning

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    In this paper we opine that a geographic information system can provide essential and much needed support to integrate coastal and marine resource management, provided, however, that a number of preconditions have been met. Detailed and highly accurate geo-referenced digital data are available to the coastal zone manager. If required, sub meter accuracy can be introduced into the planning process. We would, however, like to propound that the most effective mapping scale for integrated coastal and marine resource management (in Indonesia) is 1:250.000, which would hardly warrant sub-meter accuracy. The necessity to include the motivations and activities of multitude of stakeholders further diminishes the need for detailed and sophisticated systems, as their disorderly, random and often haphazard behavior defies attempts at accurate modeling. We therefore believe that GIS for coastal resource management is best used as a system to monitor events, and to interpret the results there through querying the database by way of algorithmic as well as visual methods and techniques. The resulting information should then be presented as an easily accessible and friendly decision support tool to the coastal zone managers. A GIS, in other world, should be a management support tool, not a device to spout answers (decisions) derived from mathematical calculations performed on a “model” of the marine and coastal zone. By designing the system to monitor events and change at scale of 1:250.000, the managers would be forced to concentrate on the main trends and developments, and see the coastal zone in its relation to its wider surroundings. They would moreover avoid the collection and loading of superfluous details, which generally result in data-overload and system slow-downs, if not failures. And most importantly, a manager would be forced to use his creativity and imagination in guiding, directing and cotrolling the utilization of marine and coastal resource

    A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis:a comparison with neutralization of mouse TNF alpha

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    BACKGROUND AND PURPOSE: The p38 kinase regulates the release of proinflammatory cytokines including tumour-necrosis factor-α (TNFα) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762-0, we investigated the therapeutic potential of p38 inhibition and compared this to anti-mouse (m)TNFα antibody treatment in murine collagen-induced arthritis (CIA). EXPERIMENTAL APPROACH: Pharmacological profiles of Org 48762-0 were characterized in kinase assays, cellular assays and in lipopolysaccharide (LPS)-induced inflammation in mice. The effects of Org 48762-0 and of mTNFα-neutralization on established arthritis were examined in murine CIA. KEY RESULTS: Org 48762-0 potently inhibited p38α kinase with a high degree of kinase selectivity. In cellular assays, Org 48762-0 reduced LPS-induced TNFα release. Oral administration of Org 48762-0 in mice showed drug-like pharmacokinetic properties and inhibited LPS-induced cytokine production. These pharmacological characteristics of Org 48762-0 prompted a comparison of therapeutic efficacy with mTNFα-neutralization in CIA. Org 48762-0 and anti-mTNFα antibody treatment equally inhibited development of arthritis when evaluated macroscopically. Radiological analyses revealed protection against bone damage for both treatments, although statistical difference was reached with Org 48762-0 treatment only. Further, micro-computed tomographical and histopathological analyses confirmed the protective effects of Org 48762-0 on joint damage. CONCLUSIONS AND IMPLICATIONS: Pharmacological targeting of p38 kinase provided good protection against joint tissue damage in CIA. In our experiments, neutralization of mTNFα produced less prominent suppression of bone damage. Our data suggest a therapeutic potential for selective and potent p38 inhibitors in RA
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