Leishmania: role of P glycoprotein in drug resistance and reversion strategies

Protozoan parasites are important causative agents of morbidity and mortality throughout the world--a problem further complicated by the emergence of drug resistance in these parasites. Mechanisms of drug resistance include the following: decreased uptake of the drug into the cell, loss of drug activation, alterations in the drug target, and over-expression of a well-known multiple drug transporter proteins. In this review, two critical components of resistance are stressed: (1) the role of ATP binding cassette proteins, such as P-glycoproteins, in mediating drug resistance in Leishmania and other protozoans, followed by development of cross-resistance to many structurally and functionally unrelated drugs, and (2) some concepts concerning the reversal mechanism of multidrug resistance by drugs and natural products. Several modulators or chemosensitizers alter the capacity of P-glycoproteins to maintain subtoxic intracellular drug concentrations. Calcium channel blockers such as verapamil act in this mode; however, high concentrations are required for an efficient and effective inhibition and, in addition, produce undesirable side effects. The discovery of new, natural product modulators of P-glycoproteins is stressed. This category of modulators offer potentially improved efficacy and lowered toxicity for the mammalian host.     

Organisation of the lamprey (Lampetra fluviatilis) embryonic brain: insights from LIM-homeodomain, Pax and hedgehog genes

To investigate the embryonic development of the central nervous system of the lamprey Lampetra fluviatilis, we have isolated and analysed the expression patterns of members of the LIM-homeodomain, Pax, Hedgehog and Nkx2.1 families. Using degenerate RT-PCR, single representatives of Lhx1/Lhx5, Lhx2/Lhx9, Pax3/Pax7 and Hedgehog families could be isolated in L. fluviatilis. Expression analysis revealed that the lamprey forebrain presents a clear neuromeric pattern. We describe the existence of 4 embryonic diencephalic prosomeres whose boundaries can be identified by the combined and relative expressions of LfPax37, LfLhx15 and LfLhx29. This suggests that the embryonic lamprey and gnathostome forebrain are patterned in a highly similar manner. Moreover, analysis of the LfHh gene, which is expressed in the hypothalamus, zona limitans intrathalamica and floor plate, reveals the possible molecular origin of this neuromeric brain pattern. By contrast, LfHh and LfNkx2.1 expressions suggest major differences in patterning mechanisms of the ventral telencephalon when compared to gnathostomes. In summary, our findings highlight a neuromeric organisation of the embryonic agnathan forebrain and point to the possible origin of this organisation, which is thus a truly vertebrate character. They also suggest that Hh/Shh midline signalling might act as a driving force for forebrain evolution.     

Micromolar HgCl2 concentrations transitorily duplicate the ATP level in Saccharomyces cerevisiae cells

Low concentrations of HgCl2 elicited, in Saccharomyces cerevisiae, a transitory increase in the ATP level followed by a decrease of its concentration, until almost disappearance. At 1 microM HgCl2, the increase in ATP lasted for about 30 min, while at 10 microM the increase was only observed in the first 5 min of treatment. The initial burst of ATP was accompanied by a decrease in the level of hexose phosphates, whereas during the decrease of ATP an increase in the inosine and hexose phosphates levels took place. The treatment with HgCl2 inhibited the plasma membrane proton ATPase but not the activities of hexokinase or 6-phosphofructokinase.     

Disruption of pheromone communication in Tecia solanivora (Lepidoptera: Gelechiidae): flight tunnel and field studies

The moth Tecia (Scrobipalpopsis) solanivora Povolny (Lepidoptera: Gelechiidae) is the most important pest of potato, Solanum spp., in Central America and adjacent South American countries. Insecticide treatments are not sufficiently effective; therefore, we investigated the feasibility of pheromone-mediated mating disruption for control of T. solanivora. Pheromone dispensers were formulated with 70 mg of the three sex pheromone compounds (E)-3-dodecenyl acetate, (Z)-3-dodecenyl acetate, and dodecyl acetate, in a ratio of 100:56:100, respectively. Male attraction to these compounds is optimal at a ratio of 100:1:20, thus the mating disruption dispensers contained an off-blend, which attracted only a few males. Nonetheless, one mating disruption dispenser suppressed male attraction to calling females in a flight tunnel and reduced male activation in response to female pheromone. Communication disruption is accordingly due to camouflage of the female signal and possibly due to a reduction of male responsiveness by sensory imbalance. Only a few males were observed in a 3-ha potato field treated with 84 g pheromone/ha, compared with an untreated control field. During 2 mo, male attraction to traps baited with calling females or synthetic pheromone was strongly reduced. This reduction confirms the potential of mating disruption for management of T. solanivora. The efficacy of the pheromone treatment can be further improved by earlier dispenser application, by increased dispenser load, and by treatment of larger fields to reduce immigration of mated females.     

Parasites of the Central American tapir Tapirus bairdii (Perissodactyla: Tapiridae) in Chiapas, Mexico

We analyzed 19 samples of Baird's tapir feces from La Sepultura Biosphere Reserve, collected between March and July 1999. We also took samples directly from a male tapir captured at the Montes Azules Biosphere Reserve. Both reserves are in Chiapas, Mexico. We used five techniques: flotation, MacMaster, micrometric, Ritchie's sedimentation and Ferreira's quantitative. In addition, we collected ectoparasites from animals captured in both reserves and from a captive couple from Tuxtla Gutierrez, Chiapas. These nematodes and protozoans were found: Agriostomun sp., Lacandoria sp., Neomurshidia sp., Trichostrongylus sp., Strongylus sp., Brachylumus sp, and an unidentified species of ancilostomaide. We also found Eimeria sp. and Balantidium coli, as well as the mites Dermacentor halli, Dermacentor latus, Amblyomma cajannense, Amblyomma coelebs, Amblyomma ovale, Anocentor nitens and Ixodes bicornis.