Détection colorimétrique des toxines diarrhéiques par inhibition des protéines phosphatases préparées extemporanément

Depuis la première mise en évidence des toxines diarrhéiques en 1978 et la mise au point d'un bioessai sur souris pour les détecter, de très nombreuses recherches ont été menées pour améliorer ce test ou développer de nouvelles méthodes. L'acide okadaïque principale toxine produite par les dinoflagellés du genre Dinophysis peut se concentrer dans les bivalves et provoquer des gastro-entérites chez les consommateurs. La méthode proposée est une détection colorimétrique de l'acide okadaïque basée sur l'activité enzymatique des protéines phosphatases. L'activité de ces enzymes est mise en évidence par la réaction du paranitrophénylphosphate incolore qui est transformé par des protéines phosphatases en paranitrophénol jaune. Les protéines phosphatases utilisées proviennent de différentes sources (filets de volailles, filets de poissons et invertébrés marins) et sont préparées extemporanément.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Aspergillose cérébrale : une infection opportuniste émergente chez les patients traités par ibrutinib pour leucémie lymphoïde chronique ?

International audienceIbrutinib is a novel oral covalent inhibitor of Bruton's tyrosine kinase (BTK). It has been approved for the treatment of relapsing chronic lymphocytic leukemia (CLL), or CLL with high-risk cytogenetic abnormalities. Several cases of invasive aspergillosis have recently been reported in ibrutinib-treated patients. We report two cases of cerebral aspergillosis in CLL patients treated with ibrutinib

Synthesis and antiproliferative activity of ligerin and new fumagillin analogs against osteosarcoma

International audienceLigerin is a natural chlorinated merosesquiterpenoid related to fumagillin exhibiting a selective antiproliferative activity against osteosarcoma cell lines and an in vivo antitumor activity in a murine model. Semisynthesis of ligerin analogs was performed in order to study the effects of the C3-spiroepoxide substitution by a halogenated moiety together with the modulation of the C6 chain. Results showed that all derivatives exhibited an in vitro antiproliferative activity against osteosarcoma cell lines and that chlorohydrin compounds were equally or more active than their spiroepoxy analogs. Among semisynthetic analogs, the parent compound 1 was the best candidate for further studies since it exhibited higher or equivalent activity compared to TNP470 against SaOS2 and MG63 human osteosarcoma cells with a four times weaker toxicity against HFF2 human fibroblasts. Quantitative videomicroscopy analysis was conducted and allowed a better understanding of the mechanism of its antiproliferative activity

Coronary angioplasty is associated with a better neurological outcome in the era of modern management of out-of-hospital cardiac arrest.: Angioplasty and neurologic outcome of cardiac arrest

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Ligerin, an antiproliferative chlorinated sesquiterpenoid from a marine-derived Penicillium strain.

International audienceA new chlorinated sesquiterpenoid analogue of fumagillin, ligerin (1), was isolated from a marine-derived strain of Penicillium, belonging to the subgenus Penicillium, along with the known compounds penicillic acid (2), orcinol, and orsellinic acid. Chemical structures were established by an interpretation of spectroscopic data including IR, UV, and HRESIMS, together with analyses of 1D and 2D NMR spectra and X-ray analysis for the determination of the absolute configuration. Ligerin (1) displayed strong inhibitory activity against an osteosarcoma cell line. This is the first report of the isolation of a fumagillin analogue from a marine-derived Penicillium strain

Meconium concentrations of pesticides and risk of hypospadias: a case–control study in Brittany, France

International audienceBackground: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role environmental risk factors suspected, including prenatal exposure to pesticides. Objectives: To study of hypospadias association with multiple pesticide measurements meconium samples. Methods: The Brittany Registry Congenital Anomalies (France) conducted case–control between 2012 and 2018. Cases were hypospadias, ascertained by pediatrician pediatric surgeon, excluding genetic conditions, following EUROCAT guidelines (N=69). Controls (N=135) two infants without congenital anomaly born after each case same maternity unit. Mothers units completed self-administered questionnaire, we collected medical data from hospital records, staff We performed chemical analysis 38 pesticides (parent compound and/or metabolite) UHPLC/MS/MS strict quality assurance/quality control criteria blind status. carried out logistic regression accounting frequency-matching variables major factors. Results: Among measured, 16 (42%) never detected samples, 18 (47%) andl

2b80 − Hydroxybisphosphonate Linked Doxorubicin: Bone Targeted Strategy for Treatment of Osteosarcoma

International audienceTo reply to as yet unmet medical needs to treat osteosarcoma, a form of primary bone cancer, we conceived the 12b80 compound by covalently conjugating antineoplastic compound doxorubicin to a bone targeting hydroxybisphosphonate vector and turned it into a prodrug through a custom linker designed to specifically trigger doxorubicin release in acidic bone tumor microenvironment. Synthesis of 12b80 was thoroughly optimized to be produced at gram scale. 12b80 was evaluated in vitro for high bone support affinity, specific release of doxorubicin in acidic condition, lower cytotoxicity, and cellular uptake of the prodrug. In vivo in rodents, 12b80 displayed rapid and sustained targeting of bone tissue and tumor-associated heterotopic bone and permitted a higher doxorubicin payload in tumor bone environment compared to nonvectorized doxorubicin. Consequently, 12b80 showed much lower toxicity compared to doxorubicin, promoted strong antitumor effects on rodent orthotopic osteosarcoma, displayed a dose-response therapeutic effect, and was more potent than doxorubicin/zoledronate combination

Ligerin, an Antiproliferative Chlorinated Sesquiterpenoid from a Marine-Derived <i>Penicillium</i> Strain

A new chlorinated sesquiterpenoid analogue of fumagillin, ligerin (<b>1</b>), was isolated from a marine-derived strain of <i>Penicillium</i>, belonging to the subgenus <i>Penicillium</i>, along with the known compounds penicillic acid (<b>2</b>), orcinol, and orsellinic acid. Chemical structures were established by an interpretation of spectroscopic data including IR, UV, and HRESIMS, together with analyses of 1D and 2D NMR spectra and X-ray analysis for the determination of the absolute configuration. Ligerin (<b>1</b>) displayed strong inhibitory activity against an osteosarcoma cell line. This is the first report of the isolation of a fumagillin analogue from a marine-derived <i>Penicillium</i> strain

Ligerin, an Antiproliferative Chlorinated Sesquiterpenoid from a Marine-Derived <i>Penicillium</i> Strain

A new chlorinated sesquiterpenoid analogue of fumagillin, ligerin (<b>1</b>), was isolated from a marine-derived strain of <i>Penicillium</i>, belonging to the subgenus <i>Penicillium</i>, along with the known compounds penicillic acid (<b>2</b>), orcinol, and orsellinic acid. Chemical structures were established by an interpretation of spectroscopic data including IR, UV, and HRESIMS, together with analyses of 1D and 2D NMR spectra and X-ray analysis for the determination of the absolute configuration. Ligerin (<b>1</b>) displayed strong inhibitory activity against an osteosarcoma cell line. This is the first report of the isolation of a fumagillin analogue from a marine-derived <i>Penicillium</i> strain