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Comparative Pharmacokinetics of Intramuscular Artesunate and Artemether in Patients with Severe Falciparum Malaria. T. T. Hien, 2004.The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m . daily) and artemether (ARM; 3.2 mg/kg i.m . stat, followed by 1.6 mg/kg i.m . daily) were compared in Vietnamese adults with severe falciparum malaria . A total of 19 patients were studied; 9 received ARTS, and 10 received ARM . ARTS was absorbed very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter (median, 5,710 nmol/liter) within 20 min of injection and then declined with a median (range) half-life (t1/2) of 30 (3 to 67) min . ARTS was hydrolyzed rapidly and completely to the biologically active metabolite dihydroartemisinin (DHA) . Peak DHA concentrations in plasma ranged between 1,718 and 7,080 nmol/liter (median, 3,060 nmol/liter) and declined with a t1/2 of 52 (26 to 69) min . In contrast, ARM was slowly and erratically absorbed . The absorption profile appeared biphasic . Maximum ARM concentrations in plasma ranged between 67 nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred at a median (range) of 10 (1.5 to 24) h . There was relatively little conversion to DHA . After i.m . injection in cases of severe malaria, absorption of the water-soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and erratically absorbed, with relatively little conversion to the more active DHA . On the basis of this pharmacological study, parenteral ARTS is preferable to ARM as an initial antimalarial therapy, particularly in the most seriously ill patients . These findings should be formally assessed by a randomized clinical trial . Invasion of Spores of the Arbuscular Mycorrhizal Fungus Gigaspora decipiens by Burkholderia spp.. Avram Levy, 2003.Burkholderia species are bacterial soil inhabitants that are capable of interacting with a variety of eukaryotes, in some cases occupying intracellular habitats . Pathogenic and nonpathogenic Burkholderia spp., including B . vietnamiensis, B . cepacia, and B . pseudomallei, were grown on germinating spores of the arbuscular mycorrhizal fungus Gigaspora decipiens. Spore lysis assays revealed that all Burkholderia spp . tested were able to colonize the interior of G . decipiens spores . Amplification of specific DNA sequences and transmission electron microscopy confirmed the intracellular presence of B . vietnamiensis . Twelve percent of all spores were invaded by B . vietnamiensis, with an average of 1.5 x 106 CFU recovered from individual infected spores . Of those spores inoculated with B . pseudomallei, 7% were invaded, with an average of 5.5 x 105 CFU recovered from individual infected spores . Scanning electron and fluorescence microscopy provided insights into the morphology of surfaces of spores and hyphae of G . decipiens and the attachment of bacteria . Burkholderia spp . colonized both hyphae and spores, attaching to surfaces in either an end-on or side-on fashion . Adherence of Burkholderia spp . to eukaryotic surfaces also involved the formation of numerous fibrillar structures .
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