Synthesis and biological evaluation of pyridin-2-one nucleosides

The synthesis of 1-(beta-D-ribofuranosyl)pyridin-2-one-3-carboxylic acid and the 3-carboxamide as well as a short series of 3N-carboxamides, prepared by TPTU/HOBt coupling of primary amines with 1-(beta-D-ribofuranosyl)pyridin-2-one-3-carboxylic acid, and their evaluation as anti-infective agents is described.     

Damage to Pseudomonas aeruginosa PAO1 bacteriophage F116 DNA by biocides

The mechanism of action of biocides against viruses has not been widely studied, although two main targets are viral proteins (capsids, enzymes) and the viral genome. This study was undertaken in order to investigate the efficacy of several disinfectants against the nucleic acid of the Pseudomonas aeruginosa PAO bacteriophage F116. Of all the biocides tested, only peracetic acid affected significantly the phage genome. However, it is not clear whether the nucleic acid was damaged inside the phage capsid or when released into the surrounding medium.     

Ventilatory adjustments during sustained resistive unloading in exercising humans

Effect of He-O2-breathing (79.1%:20.9%) compared to air-breathing on inspiratory ventilation (VI) and its different components [tidal volume (VT), the duration of the phases of each respiratory cycle (tI, tTOT)] as well as on inspiratory mouth occlusion pressure (P0.1) were studied in six normal men at rest and during 72 constant-load exercises (90 W) over a much longer period than in previous studies. Results showed that, irrespective of the order of administration of the two gases (7 min air----7 min He-O2 or vice versa): at rest, P0.1 decreased during He-O2 inhalation but no changes in VI and breathing pattern were detectable; during exercise, sustained He-induced hyperventilation was observed without any change in the absolute value of P0.1; increase in P0.1 between the resting period and exercise (delta P0.1) was significantly higher during He-O2-breathing than during air breathing; this He-induced hyperventilation was associated with a sustained increase in VT/tI, but with constant tI/tTOT. Helium-breathing during exercise cannot be a simple situation of resistance unloading, as has been suggested. We conclude that He-O2-breathing, after the initial compensation period, induces reflex changes in ventilatory control with an increase in inspiratory neural drive. Moreover, it appears that exercise P0.1 is not a legitimate index of inspiratory neural drive whenever rest P0.1 changes according to the nature of the inhaled gas mixture.     

Biomimetic liposomes and planar supported bilayers for the assessment of glycodendrimeric porphyrins interaction with an immobilized lectin

Photodynamic therapy is a potentially efficient treatment for various solid tumours, among which retinoblastoma. Its efficacy depends on the preferential accumulation of photosensitizers in the malignant tissues and their accessibility to light. The specificity of drugs for retinoblastoma cells can be improved by targeting a mannose receptor overexpressed at their surface. With the aim of assessing the recognition of newly synthesized glycodendrimeric porphyrins by such receptors, we have built and characterized an original synthetic biomimetic membrane having similar lipidic composition to that of the retinal cell membranes and bearing Concanavalin A, as a model of the mannose receptor. The interaction of the porphyrin derivatives with liposomes and supported planar bilayers has been studied by dynamic light scattering and quartz crystal microbalance with dissipation monitoring (QCM-D). Only mannosylated porphyrins interacted significantly with the membrane model. The methodology used proved to be efficient for the selection of potentially active compounds.     

Inflorescence of grapevine (Vitis vinifera L.): a high ability to distribute its own assimilates

The distribution of carbon (C) into whole grapevine fruiting cuttings was investigated during flower development to determine the relative contribution of inflorescence and leaf photoassimilates in the total C balance and to investigate their partitioning towards other plant organs. A (13)C labelling procedure was used to label C photoassimilates by leaves and inflorescences in grapevine. Investigations were carried out at various stages of flower/berry development, from separated cluster to fruit set, using grapevine fruiting cuttings with four leaves (Vitis vinifera L. cv. Chardonnay). This is the first study reporting that, during its development, (i) the carbon needs of the inflorescence were met by both leaf and inflorescence photosynthesis, and (ii) the inflorescence amazingly participated significantly to the total C balance of grapevine cuttings by redistributing an important part of its own assimilates to other plant organs. With regard to flowering, 29% of C assimilated by the inflorescence remained in the inflorescence, while partitioning towards the stem reached 42% and, as a lower proportion, 15% in leaves, and 14% in roots.     

Impact of benzalkonium chloride,benzethonium chloride and chloroxylenol on bacterial antimicrobial resistance

This review examined 3655 articles on benzalkonium chloride (BKC), benzethonium chloride (BZT) and chloroxylenol (CHO) aiming to understand their impact on antimicrobial resistance. Following the application of inclusion/exclusion criteria, only 230 articles were retained for analysis; 212 concerned BKC, with only 18 for CHO and BZT. Seventy-eight percent of studies used MIC to measure BKC efficacy. Very few studies defined the term ‘resistance’ and 85% of studies defined ‘resistance’ as <10-fold increase (40% as low as 2-fold) in MIC. Only a few in vitro studies reported on formulated products and when they did, products performed better. In vitro studies looking at the impact of BKC exposure on bacterial resistance used either a stepwise training protocol or exposure to constant BKC concentrations. In these, BKC exposure resulted in elevated MIC or/and MBC, often associated with efflux, and at time, a change in antibiotic susceptibility profile. The clinical relevance of these findings was, however, neither reported nor addressed. Of note, several studies reported that bacterial strains with an elevated MIC or MBC remained susceptible to the in-use BKC concentration. BKC exposure was shown to reduce bacterial diversity in complex microbial microcosms, although the clinical significance of such a change has not been established. The impact of BKC exposure on the dissemination of resistant genes (notably efflux) remains speculative, although it manifests that clinical, veterinary and food isolates with elevated BKC MIC carried multiple efflux pump genes. The correlation between BKC usage and gene carriage, maintenance and dissemination has also not been established. The lack of clinical interpretation and significance in these studies does not allow to establish with certainty the role of BKC on AMR in practice. The limited literature and BZT and CHO do not allow to conclude that these will impact negatively on emerging bacterial resistance in practice.