Comparative pharmacokinetics of netobimin and albendazole in the one-humped camel (Camelus dromedarius)

Netobimin and albendazole were administered orally to camels (n = 5 + 5) at molecular equivalent dosages, 15.8 and 10.0 mg/kg body wt, respectively. The plasma profiles of the two main metabolites were investigated for 54 h by high performance liquid chromatography. The metabolism and the disposition of both anthelmintics in camels were similar to sheep rather than to cattle. These results indicate that netobimin and albendazole are likely to be excellent anthelmintics for camels.     

Effect of a nonsteroidal aromatase inhibitor on in vitro and in vivo secretion of estradiol and on the estrous cycle in ewes.

Three experiments were performed to study effects of decreased concentrations of estradiol-17β (E₂) on lifespan and function of ensuing ovine corpora lutea (CL). In experiment 1, 52 follicles were collected from 10 ewes and placed into individual culture with 0 or .01 μCi ³H-androstenedione (10 ng; ³H-A) and 0, 10⁻¹¹, 10⁻⁹, 10⁻⁷, or 10⁻⁵ M of a nonsteroidal aromatase inhibitor, CGS16949A (CGS). Concentrations of E₂ secreted into the medium, and synthesis of estrogens as estimated by formation of ³H-water from ³H-A were decreased by 10⁻⁵ and 10⁻⁷ (P<.01), but not 10⁻⁹ or 10⁻¹¹ M CGS. In experiment 2, luteolysis was induced in 24 ewes by injection of PGF₂ on days 5 to 10 of the estrous cycle (0 hr). Ewes received 0, 0.5, 1.0, 2.0 or 4.0 mg CGS per kg BW i.v. at −12, 0, 12 and 24 hr, and an ovulatory dose of hCG at 36 hr. Jugular (P<.001) and vena caval (P<.001) concentrations of E₂ were decreased by CGS at all doses tested for 8 to 10 hr, but had returned to levels similar to control ewes by the time of the next injection. Concentrations of E₂ around the time of the LH surge were similar in control and treated ewes. During the subsequent luteal phase, concentrations of progesterone (P₄) were similar in control and treated ewes. Thus, transient decreases in E₂ during the follicular phase were not deleterious to the subsequent luteal phase. In experiment 3, luteolysis was induced in 18 ewes by injection of PGF₂ on days 6 or 7 (0 hr) of the estrous cycle. Ewes received 0 or 1 mg CGS per kg BW i.v. every 8 hr from 0 to 40 hr. Ovulation was induced with hCG at 36 hr. CGS reduced jugular (P<.001) and vena caval (P<.001) concentrations of E₂, prevented an endogenous surge of LH (P<.05) and increased (P<.001) concentrations of FSH. All ewes had ovulated a marked follicle by 72 hr, but onset of the luteal phase, as assessed by concentrations of P₄, was delayed (P<.01) in ewes receiving CGS. Delayed luteal phases were not solely attributable to the presence of new CL or to luteinization of follicular cysts. When data were aligned according to the day ewes were observed in estrus, profiles of P₄ did not differ with treatment. Therefore, normal luteal function ensued following estrus whether or not ewes re-ovulated. In conclusion, decreased secretion of E₂ by the preovulatory follicle was not involved in the ontogeny of CL of short lifespan or subnormal function. Instead, adequate production of E₂ or precisely timed E₂ secretion may be required during follicular development for subsequent functional luteinization.     

The Marine-Derived Macrolactone Mandelalide A Is an Indirect Activator of AMPK

The mandelalides are complex macrolactone natural products with distinct macrocycle motifs and a bioactivity profile that is heavily influenced by compound glycosylation. Mandelalides A and B are direct inhibitors of mitochondrial ATP synthase (complex V) and therefore more toxic to mammalian cells with an oxidative metabolic phenotype. To provide further insight into the pharmacology of the mandelalides, we studied the AMP-activated protein kinase (AMPK) energy stress pathway and report that mandelalide A is an indirect activator of AMPK. Wild-type mouse embryonic fibroblasts (MEFs) and representative human non-small cell lung cancer (NSCLC) cells showed statistically significant increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in response to mandelalide A. Mandelalide L, which also harbors an A-type macrocycle, induced similar increases in phospho-AMPK (Thr172) and phospho-ACC (Ser79) in U87-MG glioblastoma cells. In contrast, MEFs co-treated with an AMPK inhibitor (dorsomorphin), AMPKα-null MEFs, or NSCLC cells lacking liver kinase B1 (LKB1) lacked this activity. Mandelalide A was significantly more cytotoxic to AMPKα-null MEFs than wild-type cells, suggesting that AMPK activation serves as a protective response to mandelalide-induced depletion of cellular ATP. However, LKB1 status alone was not predictive of the antiproliferative effects of mandelalide A against NSCLC cells. When EGFR status was considered, erlotinib and mandelalide A showed strong cytotoxic synergy in combination against erlotinib-resistant 11-18 NSCLC cells but not against erlotinib-sensitive PC-9 cells. Finally, prolonged exposures rendered mandelalide A, a potent and efficacious cytotoxin, against a panel of human glioblastoma cell types regardless of the underlying metabolic phenotype of the cell. These results add biological relevance to the mandelalide series and provide the basis for their further pre-clinical evaluation as ATP synthase inhibitors and secondary activators of AMPK.     

Impact of <Emphasis Type="Italic">Erysiphe alphitoides</Emphasis> on transpiration and photosynthesis in <Emphasis Type="Italic">Quercus robur</Emphasis> leaves

Oak powdery mildew, (Erysiphe alphitoides) causes one of the most common diseases of oaks. We assessed the impact of this pathogen on photosynthesis and water relations of infected leaves using greenhouse-grown oak seedlings. Transpiration of seedlings infected by oak powdery mildew was also investigated. Altogether, E. alphitoides had a low impact on host gas exchange whether at the leaf or whole plant scale. Maximal stomatal conductance of infected leaves was reduced by 20–30% compared to healthy controls. Severely infected seedlings did not experience any detectable change of whole plant transpiration. The reduction in net CO₂ assimilation, A_n, was less than proportional to the fraction of leaf area infected. Powdery mildew reduced both the maximal light-driven electron flux (J_max) and the apparent maximal carboxylation velocity (Vc_max) although Vc_max was slightly more impacted than J_max. No compensation for the infection occurred in healthy leaves of partly infected seedlings as the reduced photosynthesis in the infected leaves was not paralleled by increased A_n levels in the healthy leaves of the seedlings. However, E. alphitoides had a strong impact on the leaf life-span of infected leaves. It is concluded that the moderate effect of E. alphitoides on oak might be related to the small impact on net CO₂ assimilation rates and on tree transpiration; nevertheless, the severe reduction in leaf life-span of heavily infected leaves may lead to decreased carbon uptake over the growth season.     

A general method to filter out defective spatial observations from yield mapping datasets

Yield maps are recognized as a valuable tool with regard to managing upcoming crop production but can contain a large amount of defective data that might result in misleading decisions. These anomalies must be removed before further processing to ensure the quality of future decisions. This paper proposes a new holistic methodology to filter out defective observations likely to be present in yield datasets. The notion of spatial neighbourhood has been refined to embrace the specific characteristics of such on-the-go vehicle based datasets. Observations are compared with their newly-defined spatial neighbourhood and the most abnormal ones are classified as defective observations based on a density-based clustering algorithm. The approach was conceived to be as non-parametric and automated as far as possible to pre-process a growing number of datasets without supervision. The proposed approach showed promising results on real yield datasets with the detection of well-known sources of errors such as filling and emptying times, speed changes and non-fully used cutting bar.     

Measurement of plasma leucine flux in rainbow trout (Salmo gairneri R.) using osmotic pump. Preliminary investigations on influence of diet

A method for the direct measurement of plasma amino acid flux, in rainbow trout, using the continuous infusion of L-[U-¹⁴C]-leucine with ALZET mini-osmotic pumps implanted into the peritoneal cavity, was developed. The fish were fed successively on three different diets (a commercial control diet, a semi-purified diet and a purified diet) during the 4 weeks of experiment. The amounts of radioactivity in the free pool and the protein of both the plasma and skin mucus were measured in these fish. The total flux of leucine was calculated either from the specific activity of leucine in the plasma (61.8 mg leucine. 100 g^-1.d^-1) or from the amounts of labelled and unlabelled leucine flowing into the skin mucus protein (61.5 mg leucine. 100g^-1.day^-1). The total plasma flux was not affected by changes in the diet. The contributions of total leucine oxidation and whole body protein turnover to plasma leucine flux (80% and 20% respectively) were estimated in fish fed the semi-purified diet.     

Application of leaf,soil, and tree ring chemistry to determine the nutritional status of sugar maple on sites of different levels of decline

Nutrient concentrations and D.R.I.S. indices of leaves, soil chemistry and dendrochronological changes of elemental concentrations in sugar maple (Acer saccharum Marsh.) were used to determine its nutritional status on three sites of contrasting levels of decline. We hypothesized that the ratio of Al to base cations in tree rings would increase more at the most severely declining site, and that the ratios of K⁺ to divalent cations (Ca²⁺ and Mg²⁺) would increase slower or decrease more rapidly over time than at the less severely declining sites. Forest health, based on percentage of foliage missing, and leaf K and Mg concentrations of the three sites were ranked as follows: Morgan Arboretum > Saint-Hippolyte > Entrelacs. Soil pH, Ca, Mg, E.C.E.C. and percentage of base saturation were highest at the Morgan Arboretum, and exchangeable Al in the organic horizon was highest at Entrelacs. Concentrations of K, Ca, Mg and Al, and ratios of these elements in wood were determined for each of the following periods: 1940–1956, 1957–1973 and 1974–1989. Variations in tree ring chemistry among sites were significant for K and Al and all elemental ratios except K:Mg. Al concentration and the ratios of Al to base cations in wood were all significantly higher at Entrelacs (7.0 vs 2.6 and 2.8 mg Al kg^?1 for the other two sites, respectively). Weak relationships were generally observed between leaf and soil elemental concentrations, and wood elemental concentrations. The D.R.I.S. K index and soil exchangeable K and Al showed good concordance with wood concentrations. With the exception of Mg, Al and Al:Mg, the effect of period was significant for all other elements and ratios of elements. The most severely declining stand (Entrelacs) differed from the healthiest stand by decreasing K:Ca and increasing A1:K from the 1940–1956 to the 1957–1973 period.     

Chiral behaviour of the metabolite albendazole sulphoxide in sheep, goats and cattle

Three sheep, three goats and three cattle were dosed orally with 5.0, 7.5 and 10 mg albendazole kg-1 bodyweight, respectively. Blood samples were taken at intervals for 48 hours after administration. The enantiomeric ratio of the metabolite albendazole sulphoxide (SO.ABZ) was determined by liquid chromatography on chiral stationary phases. At To, the plasma concentration ratio (+)SO.ABZ/(-)SO.ABZ was estimated at 3.0 in sheep, 1.5 in goats and 4.0 in cattle. The proportion of the (+) enantiomer then increased linearly as a function of time during the course of the kinetics. In comparison to the area under the curve for total SO.ABZ, the (+) enantiomer represented 86 per cent in sheep, 80 per cent in goats and 91 per cent in cattle. The specific behaviour of the two enantiomers is probably the result of the enantioselectivity of the flavine adenosine dinucleotide and cytochrome P450 dependent enzymatic systems which are involved in the sulphoxidation and the sulphonation of ABZ.     

Butterfly assemblages in residential gardens are driven by species’ habitat preference and mobility

Context

Understanding the factors contributing to maintaining biodiversity is crucial to mitigate the impact of anthropogenic disturbances. Representing large proportions of green area in highly modified landscapes, residential gardens are often seen as local habitats that can contribute to larger networks of suitable environments at the landscape scale.

Objectives

We investigated the impact of the landscape context on butterfly communities observed in residential gardens, taking into account garden characteristics, land-use types and presence of linear features in the surrounding landscape. We examined how species traits affected butterflies’ response to landscape context and habitat quality.

Methods

We performed a cross-scale study, based on citizen science data documenting butterfly species composition and abundance in 920 gardens across France. We examined the effect of garden quality, the area of different land-use types and the length of linear elements measured at three scales within the surrounding landscape. Species were grouped according to their habitat preference and mobility.

Results

Urbanization negatively affected total species richness and the abundance of butterfly in each group. This was related to declining habitat quality and reduced area of suitable habitat in the surrounding landscape. The magnitude of this effect, however, was negatively correlated with mobility, a trait related to habitat preference. The spatial scale at which landscape context best explained variation in butterfly abundance changed with species’ habitat preference.

Conclusions

This study highlights the importance of preserving high quality habitats in altered landscapes and considering species’ mobility and habitat preference when assessing the impact of landscapes on butterfly communities.

     

New strategy for the survey of Toxoplasma gondii in meat for human consumption

Monitoring of Toxoplasma infection in animals destined for human consumption is a great challenge for human toxoplasmosis prevention. This study aimed to compare results obtained from a naturally infected population of sheep using different tests and targeting an original matrix: meat samples and muscle fluids collected at the slaughterhouse. A commercial ELISA test was performed on diaphragm fluids from 419 ovine carcasses collected at the slaughterhouse. A MAT (modified agglutination test) was performed on heart fluids obtained from the same animals. In addition, all hearts were bioassayed in mice. Serological test agreement, the relative sensitivity of ELISA MAT and mouse bioassay as well as a correlation between titres and parasite isolation probability were statistically evaluated. The overall agreement (kappa coefficient=0.64) of ELISA on diaphragm fluids and MAT on heart fluids is substantial and subsequently both tests can be used for epidemiological studies. Relative sensitivity was higher for MAT performed on cardiac fluids (90%) than ELISA on diaphragm fluid (61%). For both serological tests, relative sensitivity is lower in lambs younger than 12 months. Relative sensitivity of mouse inoculation was 42%. A significant correlation was obtained between increasing MAT titres and probability to isolate live parasite from the heart. When the fluid titre was higher than 1:16, parasites were isolated in 65% of cases. When it was lower, isolation failed in 95% of the cases. According to our results, cardiac fluids appear to be a relevant matrix for toxoplasmosis survey in meat.