Hydrolysis and transesterification reactions of candesartan cilexetil observed during the solid phase extraction procedure

Candesartan cilexetil is an angiotensin receptor antagonist widely used in the treatment of high blood pressure. This prodrug is metabolised into candesartan, which blocks the receptors AT1 for angiotensin II decreasing the blood pressure levels. During the development of a solid phase extraction procedure for the chromatographic determination of eight antihypertensive compounds, lack of linearity and reproducibility was observed only for candesartan cilexetil. Due to this fact, a stability study for this prodrug was performed. It showed that the lack of linearity and reproducibility was based on hydrolysis and transesterification processes which occurred during the drying step after elution with methanol into glass tubes. These phenomena could be reproduced artificially under basic conditions, which demonstrated the presence of basic residues in glass tubes. The study of this potential hydrolysis and transesterification reactions is very important to assure that labile drugs containing ester groups remain unaffected.     

The manifold characters of orbicules: structural diversity,systematic significance,and vectors for allergens

In the anthers of flowering plants, gymnosperms, and seed ferns, tiny (±1?μm) granules might occur on the radial and innermost tangential wall of secretory tapetum cells. These sporopollenin granules develop simultaneously with the pollen exine and are called orbicules or Ubisch bodies. The present paper focuses on two quite different topics associated with orbicules.

The morphological and ultrastructural diversity of orbicules in the order Gentianales is summarized, and it is demonstrated that orbicules are a plesiomorphic feature in the order. Furthermore, orbicule characters seemed to be correlated with evolutionary trends in pollen dispersal unit and tapetum type features.

In the second part, we report on our investigation of Corylus avellana L. (Hazel) pollen, using immunogold electron microscopy to gain an insight into the possible role that orbicules may play as a vector of pollen allergens. During the pollen season orbicules are dispersed into the atmosphere along with Hazel pollen grains. The localisation of homologues of the new birch pollen allergen Bet v 7 was studied at the subcellular level in Hazel anthers. The results of this study indicate that orbicules and pollen of Hazel might act as very effective vectors for homologues of Bet v 7 and that debris of Hazel anthers represent vectors of allergens after the pollen season.     

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.     

Comparison of two birnavirus-rhabdovirus coinfections in fish cell lines

Aquabirnaviruses, such as the infectious pancreatic necrosis virus (IPNV), Novirhabdoviruses, such as the infectious hematopoiteic necrosis virus (IHNV) and the viral hemorrhagic septicemia virus (VHSV), cause considerable losses to the salmonid industry worldwide. Coinfections of 2 viruses have been described, but the interactions between rhabdoviruses and birnaviruses have not been examined closely. Using virus titration, flow cytometry and RT-PCR assays, we compared the effect of IPNV on the replication of IHNV and VHSV in tissue culture cells. RT-PCR assays indicated that simultaneous infection of IPNV with VHSV does not affect the replication of the rhabdovirus either in the first or successive passages; the infective titers were similar in single and double infections. In contrast, coinfection of IPNV with IHNV induced a fall in infectivity, with reduced expression of IHNV viral antigens in BF-2 cells from Lepomis macrochirus and a loss of 4.5 log10 units of the infective titer after 3 successive passages. It was possible to stimulate BF-2 cells to produce significant interferon-like activity against IHNV but not against VHSV.     

Climate change impacts on biodiversity in Switzerland: A review

A noticeable increase in mean temperature has already been observed in Switzerland and summer temperatures up to 4.8 K warmer are expected by 2090. This article reviews the observed impacts of climate change on biodiversity and considers some perspectives for the future at the national level.The following impacts are already evident for all considered taxonomic groups: elevation shifts of distribution towards mountain summits, spread of thermophilous species, colonisation by new species from warmer areas and phenological shifts. Additionally, in the driest areas, increasing droughts are affecting tree survival and fish species are suffering from warm temperatures in lowland regions. These observations are coherent with model projections, and future changes will probably follow the current trends.These changes will likely cause extinctions for alpine species (competition, loss of habitat) and lowland species (temperature or drought stress). In the very urbanised Swiss landscape, the high fragmentation of the natural ecosystems will hinder the dispersal of many species towards mountains. Moreover, disruptions in species interactions caused by individual migration rates or phenological shifts are likely to have consequences for biodiversity. Conversely, the inertia of the ecosystems (species longevity, restricted dispersal) and the local persistence of populations will probably result in lower extinction rates than expected with some models, at least in 21st century. It is thus very difficult to estimate the impact of climate change in terms of species extinctions. A greater recognition by society of the intrinsic value of biodiversity and of its importance for our existence will be essential to put in place effective mitigation measures and to safeguard a maximum number of native species.     

Deoxyribonucleic acid relatedness inYersinia enterocolitica andYersinia enterocolitica-like organisms

Yersinia enterocolitica andY. enterocolitica-like strains were characterized by DNA relatedness. These strains formed four distinct DNA relatedness groups: (i) the 5 classical biotypes ofY. enterocolitica sensu stricto as designated by Wauters; (ii) strains that are rhamnose positive and also positive in tests for melibiose, α-methyl-d-glucoside, raffinose, and Simmons' citrate; (iii) strains that are rhamnose positive but negative in tests for melibiose, α-methyl-d-glucoside, and raffinose; (iv) sucrose-negative, Voges-Proskauer-negative, trehalose-positive strains.     

Analyses of the Temporal Dynamics of Fungal Communities Colonizing the Healthy Wood Tissues of Esca Leaf-Symptomatic and Asymptomatic Vines

Esca, a Grapevine Trunk Disease (GTD), is of major concern for viticulture worldwide. Our study compares the fungal communities that inhabit the wood tissues of vines that expressed or not foliar esca-symptoms. The trunk and rootstock tissues were apparently healthy, whether the 10 year-old plants were symptomatic or not. The only difference was in the cordon, which contained white rot, a typical form of esca, in 79% of symptomatic plants. Observations over a period of one year using a fingerprint method, Single Strand Conformation Polymorphism (SSCP), and the ITS-DNA sequencing of cultivable fungi, showed that shifts occurred in the fungal communities colonizing the healthy wood tissues. However, whatever the sampling time, spring, summer, autumn or winter, the fungi colonizing the healthy tissues of asymptomatic or symptomatic plants were not significantly different. Forty-eight genera were isolated, with species of Hypocreaceae and Botryosphaeriaceae being the most abundant species. Diverse fungal assemblages, made up of potentially plant-pathogenic and -protective fungi, colonized these non-necrotic tissues. Some fungi, possibly involved in GTD, inhabited the non-necrotic wood of young plants, but no increase in necrosis areas was observed over the one-year period.     

A focused antibody library for selecting scFvs expressed at high levels in the cytoplasm

Background  

Intrabodies are defined as antibody molecules which are ectopically expressed inside the cell. Such intrabodies can be used to visualize or inhibit the targeted antigen in living cells. However, most antibody fragments cannot be used as intrabodies because they do not fold under the reducing conditions of the cell cytosol and nucleus.