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•Zenkersterone is described for the first time as natural products.•Absolute configuration as well as X-Ray data of penianthic acid methyl ester are also described for the first ...time.•We evaluated the antibacterial and cytotoxic activities of the extracts, fractions and compounds.•We reported the chemotaxonomic relevance of the isolated compounds.
A phytochemical investigation of the roots and twigs of Penianthus zenkeri Diels led to the identification of twenty four compounds including one previously undescribed C-28 ecdysteroid (1) and previously described phytosteroids (2–5, 20, 22, 23), phenolic compounds (6–8, 12), diterpenoids (9–11), alkaloids (13,14, 18, 19), a dipeptide (15), ursane type triterpenoids (16–17), a carbohydrate (21) and a fatty alcohol (24). Three semi-synthetic derivatives (5b, 5a, 17a) obtained from acetylation and acetonidation of rubrosterone (5), and allylation of ursolic acid (17), respectively, are also reported. The chemical structures of the compounds were determined using 1D and 2D NMR spectral data, mass spectrometry and by comparison with the data reported in the literature. The absolute configuration of compound 9 was established using X-Ray and ECD analysis. Different extracts of the twigs and roots, compounds 2–4, 6–11, 15, and 17–21 were evaluated for their antibacterial, and cytotoxic activities. The twigs extract showed an antibacterial activity with an MIC of 62.5 μg/mol against Staphylococcus aureus ATCC 4300, while ursolic acid exhibited a moderate cytotoxicity with an IC50 of 50.9 μM. The chemotaxonomic relevance of the isolated compounds is discussed.
Objective
To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis ...(JIA).
Methods
In this phase III, open‐label, international, multicenter, single‐arm study, patients with polyarticular JIA (cohort 1, ages 6–17 years and cohort 2, ages 2–5 years) in whom treatment with ≥1 disease‐modifying antirheumatic drug was unsuccessful received weight‐tiered SC abatacept weekly: 10 to <25 kg (50 mg), 25 to <50 kg (87.5 mg), ≥50 kg (125 mg). Patients who had met the JIA–American College of Rheumatology 30% improvement criteria (achieved a JIA‐ACR 30 response) at month 4 were given the option to continue SC abatacept to month 24. The primary end point was the abatacept steady‐state serum trough concentration (Cminss) in cohort 1 at month 4. Other outcome measures included JIA‐ACR 30, 50, 70, 90, 100, and inactive disease status, the median Juvenile Arthritis Disease Activity Score in 71 joints using the C‐reactive protein level (JADAS‐71–CRP) over time, safety, and immunogenicity.
Results
The median abatacept Cminss at month 4 (primary end point) and at month 24 was above the target therapeutic exposure (10 μg/ml) in both cohorts. The percentage of patients who had achieved JIA‐ACR 30, 50, 70, 90, or 100 responses or had inactive disease responses at month 4 (intent‐to‐treat population) was 83.2%, 72.8%, 52.6%, 28.3%, 14.5%, and 30.1%, respectively, in cohort 1 (n = 173) and 89.1%, 84.8%, 73.9%, 58.7%, 41.3%, and 50.0%, respectively, in cohort 2 (n = 46); the responses were maintained to month 24. The median (interquartile range) JADAS‐71–CRP improved from baseline to month 4: cohort 1, from 21.0 (13.5, 30.3) to 4.6 (2.1, 9.4); cohort 2, from 18.1 (14.0, 23.1) to 2.1 (0.3, 4.4). Improvements were sustained to month 24, at which time 27 of 173 patients (cohort 1) and 11 of 22 patients (cohort 2) had achieved JADAS‐71–CRP remission. No unexpected adverse events were reported; 4 of 172 patients (2.3%) in cohort 1 and 4 of 46 (8.7%) in cohort 2 developed anti‐abatacept antibodies, with no clinical effects.
Conclusion
Weight‐stratified SC abatacept yielded target therapeutic exposures across age and weight groups, was well tolerated, and improved polyarticular JIA symptoms over 24 months.
The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro chromosome aberration test. ...The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the chromosome aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the 14 positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration–related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially, when cells in metaphasis and multinucleated cells are also scored and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro chromosome aberration test to be used in the standard genotoxicity battery.
Ce volume réunit un ensemble de contributions en hommage à Nicole Jacques-Lefèvre qui a été une figure majeure du développement de la recherche en Lettres à l’ENS de Fontenay-Saint-Cloud dans le ...dernier quart du xxe siècle. Ces contributions, toutes signées par d’anciens élèves de Nicole Jacques-Lefèvre, témoignent du rayonnement de son enseignement, de la valeur séminale des pistes et des méthodes de recherche qu’elle a développées, et de la place importante occupée aujourd’hui par sa pensée dans l’université littéraire française, par l’intermédiaire des enseignants-chercheurs qu’elle a contribué à former. Cet ouvrage n’est donc pas seulement un volume d’hommages : il offre aussi l’image dynamique d’un courant actuel des études littéraires qui forge ses outils et définit ses champs de recherches au contact de l’anthropologie et de l’histoire culturelle.
The archaeon Methanosarcina thermophila expresses large amounts of a small basic protein, called MC1 (methanogen chromosomal protein), which was previously identified as a DNA‐binding protein ...possibly involved in DNA compaction in some methanogenic species. We have investigated the binding of MC1 to various kinds of branched DNA molecules whose double helix axis is severely kinked. We show that MC1 is able to distinguish and to bind preferentially to four‐way junctions. This preferential binding is observed in the absence and presence of divalent cations. However, we find that MC1 has a low affinity for bulged DNA structures. These results show how MC1 is able to discriminate between different deformations of the DNA double helix.
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