Trypanosoma brucei: An evaluation of salicylhydroxamic acid as a trypanocidal drug

The chemotherapeutic potential of salicylhydroxamic acid (SHAM) was studied in adult rats infected with a strain of Trypanosoma brucei that kills the rats in about 100 hr. The median lethal dose, administered intraperitoneally in a carboxymethyl-cellulose suspension, is approximately 820 mg/kg body weight for male and 850 mg/kg for female rats. The apparent cause of death is severe depression of the central nervous system.Half-maximal inhibition of O₂ uptake by trypanosomes in vitro requires 15 μM SHAM, whereas 100 μM inhibits over 90%. This inhibitory effect on trypanosome respiration was used as a biological assay for the effective SHAM concentration in rat plasma. After administration of a sublethal SHAM dose to rats, the effective plasma SHAM concentration rose rapidly to about 500 μM and then fell to about 10 μM at 4 hr. Nevertheless, this dose did not significantly affect the survival time of rats infected with T. brucei. Even if, by repeated SHAM administration, the plasma SHAM concentration was kept at around 100 μM for more than 4 hr, no therapeutic effect was observed.These results show that O₂ uptake is not essential for the survival of trypanosomes in rats and they support the idea that bloodstream trypanosomes have an alternative pathway for glycolysis, allowing energy production in the absence of respiration.The possibility that SHAM or other inhibitors of trypanosome respiration could stilll be trypanocidal if used in conjunction with another inhibitor of glycolysis is discussed.     

Alcohol dehydrogenase-coupled spectrophotometric assay of plasmalogenase

Plasmalogenase has been assayed by conversion of the fatty aldehydes, released by hydrolysis of the vinyl ether bond of plasmalogens, to long-chain alcohols by horse liver alcohol dehydrogenase. The reaction was followed spectrophotometrically by measuring the oxidation of NADH. The assay is sufficiently sensitive to enable plasmalogenase activity to be determined in isolated oligodendroglia and derived membranes and in brain microsomal membranes using 50-250 micrograms protein.     

Elevated serum and hepatic tyrosine aminotransferase in voles chronically infected with Trypanosoma brucei gambiense.

Chronic infections of voles (Microtus montanus) with Trypanosoma brucei gambiense result in marked elevations in both serum and hepatic tyrosine aminotransferase. Serum enzyme levels correlate poorly with hepatic levels but well with parasitemia. Because the trypanosome itself contains high levels of this same enzyme, it is hypothesized that lysis of extravascular parasites, possibly due to agglutination by variant-specific antibody, releases parasite enzymes into host tissues, resulting in the observed increase in serum enzyme levels. The possible role of increased tyrosine transamination in the behavioral syndrome of trypanosome-infected voles is considered.     

The method matters: A guide for indicator aggregation in ecological assessments

Ecological assessment requires the integration of many physical, chemical, and/or biological quality elements. The choice of the aggregation method of such partial assessments into an overall assessment can considerably affect the assessment outcome – an issue that has been controversially discussed within the scientific community for the last decade. Current practice often considers only two different aggregation methods, the weighted arithmetic mean (additive aggregation) and the one-out, all-out method (minimum aggregation). However, both have important drawbacks. Additive aggregation compensates a bad status of one quality element by a number of elements featuring good status. Minimum aggregation can lead to overly pessimistic assessment results, since only the quality element in the worst status is considered. Here, we introduce a toolbox containing current and new aggregation methods, demonstrate and discuss their properties with simple, didactical examples, and suggest in which situations best to use them. Then, we illustrate the consequences of selected aggregation schemes for ecological river assessment with the case study of the Swiss Modular Concept of stream assessment (SMC), which we apply to ten river reaches in the Mönchaltdorfer Aa catchment in Switzerland. To be able to do so, we used multi-criteria decision analysis, i.e., multi-attribute value theory, to arrange the SMC quality elements into an objectives hierarchy, and to translate their individual assessments into value functions. Our case study revealed that choosing the most appropriate aggregation method particularly matters, if objectives with significantly different qualities are aggregated. We argue that redundant objectives (i.e., quality elements), often found at the lower levels of the objectives hierarchy, should best be aggregated additively allowing for compensation to increase the statistical significance of the results. Further, we suggest that complementary sub-objectives that often occur at higher levels may be optimally aggregated with a mixture of additive and minimum aggregation. Such a mixed method will allow some compensation, but nevertheless penalize for very bad states. Since here we compare commonly used aggregation methods with some which we believe have never been discussed in an assessment context before, our study concurrently informs ecological assessment in theory and in practice.     

δ-Aminolevulinate dehydratase from Raphanus sativus cotyledons

Phytochrome induces δ-aminolevulinate dehydratase (ALAD) activity in radish seedling cotyledons under continuous far red light. Analysis of the enzymatic activity in etioplasts vs total activity shows a constant ALAD level in these organelles (10 %) in etiolated seedlings. In far red irradiated seedlings, the percentage of enzyme detected into etioplasts increases up to 45 % of the total. Comparative kinetic studies of ALAD activity detected in the cytoplasm and the etioplasts indicate an increase in both compartments with a maximum value reached respectively at 96 and 120 hr from sowing. Treatment with cycloheximide shows a very fast abolition of cytoplasmic ALAD activity which is always correlated to an etioplast decrease with a time shift of ca 24 hr. Erythromycin acts only on the cytoplasmic level of ALAD, and only for far red irradiated seedlings, with an increase of activity twice the level detected in untreated ones. This unexpected effect is discussed.     

Mutations to azaguanine resistance induced in cultured diploid human fibroblasts by the carcinogen, N-acetoxy-2-Acetylaminofluorene

The ability of the carcinogen, N-acetoxy-2-acetylaminofluorene (N-AcO-AAF), to induce mutations to azaguanine resistance in diploid human cells was quantitatively investigated and shown to be dose-dependent. The 8-azaguanine (AG) resistance was shown to be heritable in the absence of mutagen or selective agent and the cells of the mutant clones were shown to retain normal sensitivity to N-AcO-AAF.     

Gap analysis revealed a low efficiency of Natura 2000 network for the conservation of endemic species in Mediterranean temporary freshwater habitats

Listed and rare species are abundant in temporary freshwater habitats. Among them, the endemic contingent represents a crucial conservation target particularly in the areas characterized by abundant endemic flora for which the local administrations have a high level of responsibility. The aim of this research was to test how the endemic plants found in Mediterranean temporary ponds were represented in Natura 2000 network in a biodiversity hotspot of the Mediterranean region. The results of our research at regional scale pointed out that the existing Nature 2000 sites provide a limited degree of protection and that the gap analysis should be taken into account when conservation priorities are set.