Anastrozole quantification in human plasma by high-performance liquid chromatography coupled to photospray tandem mass spectrometry applied to pharmacokinetic studies

A rapid, sensitive and specific method for quantifying the aromatase inhibitor (anastrozole) in human plasma using dexchlorpheniramine as the internal standard (I.S.) is described herein. The analyte and the I.S. were extracted from 200 microl of human plasma by liquid-liquid extraction using a mixture of diethyl ether:dichloromethane (70:30, v/v) solution. Extracts were removed and dried in the organic phase then reconstituted with 200 microl of acetonitrile:water (50:50; v/v). The extracts were analyzed by high performance liquid chromatography coupled with photospray tandem mass spectrometry (HPLC-MS-MS). Chromatography was performed isocratically on a Genesis, C18 4 microm analytical column (100 mm x 2.1mm i.d.). The method had a chromatographic run time of 2.5 min and a linear calibration curve ranging from 0.05-10 ng ml(-1). The limit of quantification (LOQ) was 0.05 ng ml(-1). This HPLC-MS-MS procedure was used to assess pharmacokinetic studies.     

Targeted proteomics on its way to discovery

For a long time, targeted and discovery proteomics covered different corners of the detection spectrum, with targeted proteomics focused on small target sets. This changed with the recent advances in highly multiplexed analysis. While discovery proteomics still pushes higher numbers of identified and quantified proteins, the advances in targeted proteomics rose to cover large parts of less complex proteomes or proteomes with low protein detection counts due to dynamic range restrictions, like the blood proteome. These new developments will impact, especially on the field of biomarker discovery and the possibility of using targeted proteomics for diagnostic purposes.     

Proteomic,metabolic and immunological changes in Biomphalaria glabrata infected with Schistosoma mansoni

Mansonic schistosomiasis is a neglected disease transmitted by Biomphalaria spp. snails. Understanding what happens inside the intermediate host is important to develop more efficient ways of reducing schistosomiasis prevalence. Our purpose was to characterize metabolic and immunological changes in Biomphalaria glabrata 24 h after exposure to Schistosoma mansoni. For this purpose, proteins were extracted from snails’ whole tissue with Tris-Urea buffer and digested with tripsin. Mass spectrometry was performed and analyzed with MaxQuant and Perseus software. Also, the hemolymph of five snails 24 h post exposure was collected, and the numbers of hemocytes, levels of urea, uric acid, nitric oxide, calcium, glycogen and alanine and aspartate aminotransferases activities were assessed. Snails were also dissected for measurement of glycogen content in the cephalopodal region and gonoda-digestive gland complex. Globin domain proteins were found to be up-regulated; also the number of circulating hemocytes was significantly higher after 24 h of exposure to the parasite. NO levels were higher 24 h post exposure. Several proteins associated with energy metabolism were found to be up-regulated. Glycogen analysis showed a significant decrease in the gonad-digestive gland complex glycogen content. We found several proteins which seem to be associated with the host immune response, most of which were up-regulated, however some were down-regulated, which may represent an important clue in understanding B. glabrata – S. mansoni compatibility.     

The omnivorous triggerfish Melichthys niger is a functional herbivore on an isolated Atlantic oceanic island

This study evaluated the functional role of the highly generalist omnivore Melichthys niger in the remote St. Peter and St Paul's Archipelago (SPSPA), Brazil, where grazing herbivorous fishes are very scarce. We analysed patterns of distribution from zero to 30 m deep during three time intervals during the day and sampled different aspects of their feeding behaviour, including diel feeding rate, feeding substrate and diet. The density of M. niger increased with depth (26–30 m) and decreased by the end of the day. Although M. niger did not present a typical herbivore diel feeding pattern, they targeted the epilithic algal matrix as their primary feeding substrate, ingesting predominantly algae and detritus. The characteristic Caulerpa racemosa var. peltata from SPSPA was ingested only as detached fronds. We suggest that in the isolated SPSPA, the single species M. niger may perform a unique role as a link between benthic primary production and higher levels. Further studies on the trophic ecology of omnivorous species are necessary to better understand their roles in a reef system, especially in impoverished areas where they are likely to play a crucial role.     

Description of a new Brazilian species of Mycodrosophila (Diptera,Drosophilidae) with emphasis on the morphology of phallic sclerites

Mycodrosophila is a cosmopolitan genus of Drosophilidae that comprises approximately 130 species with mycophagous habitats. In this study, we described a new species of Mycodrosophila based on morphological traits and included details of the male terminalia. The holotype is from Eugênio Lefévre, locality in Campos do Jordão municipality, SP, Brazil, located in the Atlantic rainforest biome and was sampled in the 1930s.     

Human Semaphorin 3 Variants Link Melanocortin Circuit Development and Energy Balance

1. Download high-res image (164KB)
2. Download full-size image

     

NEOSQUIRREL: a data set of ecological knowledge on Neotropical squirrels

相似文献   

Synthesis and larvicidal activity of indole derivatives against Aedes aegypti (Diptera: Culicidae)

In light of the challenges to control Aedes aegypti and the critical role that it plays as arbovirus vector, it is imperative to adopt strategies that provide fast, efficient and environmentally safe control of the insect population. In the present study, we synthesized six indole derivatives (C1‐C6) and examined their larvicidal activity and persistence against Ae. aegypti larvae, as well as their toxicity towards Raw 264.7 macrophages, Vero cells, Chlorella vulgaris BR017, Scenedesmus obliquus BR003, Caenorhabditis elegans N2 and Galleria mellonella. Among the bioactive compounds (C1, C2, C4 and C5), C2 exerted the strongest larvicidal activity against Ae. aegypti, with LC50 = 1.5 μg/ml (5.88 µM) and LC90 = 2.4 μg/ml (9.50 µM), indicating that the presence of chlorine or bromine groups in the aromatic ring improved the larvicidal activity of the indole derivatives. C1, C2, C4 and C5 did not reduce viability of RAW 264.7 macrophages, Vero cells, C. elegans N2 and G. mellonella. Compounds C1, C2 and C5 did not affect the growth of C. vulgaris BR017 and S. obliquus BR003. Analysis of larvicidal persistence under laboratory conditions revealed that the effect of compounds C1, C2, C4 and C5 lasted for 30 days and caused 100% of larvae mortality within few hours. Altogether, our findings demonstrate that the indole derivatives C1, C2, C4 and C5 effectively control Ae. aegypti larvae population, without clear signs of toxicity to mammalian cells, algae, C. elegans and G. mellonella.     

The ecology of the banded civet (Hemigalus derbyanus) in Southeast Asia with implications for mesopredator release,zoonotic diseases,and conservation

Habitat loss and degradation threaten forest specialist wildlife species, but some generalist mesopredators exploit disturbed areas and human‐derived food, which brings them into closer contact with humans. Mesopredator release is also important for human health for known zoonotic disease reservoirs, such as Asian civets (Viverridae family), since this group includes the intermediator species for the SARS‐CoV‐1 outbreak. Here we use camera trapping to evaluate the habitat associations of the widespread banded civet (Hemigalus derbyanus) across its range in Southeast Asia. At the regional scale, banded civet detections among published studies were positively associated with forest cover and negatively associated with human population. At the local scale (within a landscape), hierarchical modeling of new camera trapping showed that abundance was negatively associated with forest loss and positively associated with distance to rivers. These results do not support mesopredator release and suggest a low likelihood overlap with humans in degraded habitats and, therefore, a low risk of zoonotic disease transmission from this species in the wild. We also estimate that banded civet distribution has contracted to under 21% of its currently recognized IUCN Red List range, only 12% of which falls within protected areas, and a precipitous recent decline in population size. Accordingly, we suggest the banded civet''s Red List status should be re‐evaluated in light of our findings.