249 research outputs found
Comparison of a VLP‐based and GST‐L1‐based multiplex immunoassay to detect vaccine‐induced HPV‐specific antibodies in first‐void urine
No full textVaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P <= .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, r(s) = 0.85/0.86/0.91/0.79, P <= .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, r(s) = 0.86/0.83/0.89/0.53, P <= .0001; serum anti-HPV6/11/16/18, r(s) = 0.93/0.89/0.94/0.75, P <= .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection.Industrial Research Fund of the University of Antwerp, Belgium, Grant/Award Number: PS ID 32387Pattyn, J (reprint author), Campus Drie Eiken,Bldg R2,Univ Pl 1, B-12610 Antwerp, Belgium.
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Phenols from Origanum dictamnus L. and Thymus vulgaris L. and their activity against Malassezia globosa carbonic anhydrase
No full textMalassezia spp. are lipophilic fungi that are part of the normal flora of the human skin and are the etiological agents of dandruff and seborrheic dermatitis. β-Carbonic Anhydrases (CAs; EC 4.2.1.1) expressed from the pathogenic fungi are an alternative/complementary drug target. Previous work by our groups demonstrated that flavonoids and depsides can effectively inhibit Malassezia globosa β-CA (MgCA). In continuation of this study herein we report the inhibitory activity of a variety of phenols from Origanum dictamnus L. and Thymus vulgaris L. against β-MgCA, among them I4-II7-di-carvacrol, a new natural product. Structure elucidation of the compounds was performed by 1 D, 2 D NMR and spectrometric analyses. Xanthomicrol and rosmarinic acid were active in the (sub)micromolar range (KIS 0.6 and 2.2 μM, respectively vs 40.0 μM of the standard inhibitor acetazolamide). Finally, the compounds were not cytotoxic, but showed in vitro no activity against Malassezia furfur
Multicenter interlaboratory study of routine systems for the susceptibility testing of temocillin using a challenge panel of multidrug-resistant strains
No full textAccurate susceptibility result of temocillin (TMO) is important for treating infections caused by multidrug-resistant Enterobacterales. This multicenter study aimed to investigate the performance of routine temocillin testing assays against Enterobacterales challenging strains. Forty-seven selected clinical isolates were blindly analyzed by 12 Belgian laboratories using VITEK® 2 (n = 5) and BD Phoenix™ (n = 3) automated systems, ETEST® gradient strip (n = 3), and disk (3 brands) diffusion method (DD; n = 6) for temocillin susceptibility using standardized methodology. Results were interpreted using EUCAST 2023 criteria and compared to the broth microdilution (BMD; Sensititre™ panel) method used as gold standard. Methods' reproducibility was assessed by testing 3 reference strains in triplicate. A total of 702 organism-drug results were obtained against 33 TMO-susceptible and 14 TMO-resistant isolates. Excluding Proteae species (P. mirabilis and M. morganii), the essential agreement rates were excellent (91.5-100%) for all MIC-based methods. The highest category agreement was achieved by ETEST® (97.5%) followed by VITEK® 2 (93.2%), disk diffusion (91.6%), and BD Phoenix™ (88.5%). BD Phoenix™ and paper disk diffusion overcalled resistance (11.5% and 6.8% of major discrepancies, respectively), while ROSCO tablets diffusion and VITEK® 2 generated higher very major discrepancies (7.1% and 4.2% respectively). Inter-assay reproducibility was unsatisfactory using recommended E. coli ATCC 25922 strain but was excellent with E. coli ATCC 35218 and K. pneumoniae ATCC 700603 strains. This interlaboratory study suggests that routine testing methods provide accurate and reproducible TMO categorization results except for Proteae species.Funding
The study was funded by a specifc budget allocated by the National Antibiogram Committee through Federal Public Service. The Belgian National Reference Center is supported in part by the Belgian Ministry of Social Afairs through a fund within the national health insurance system (INAMI-RIZIV).
Acknowledgements
We thank the staf of the laboratories who participated this study and the members of the Belgian National Antimicrobial susceptibility testing Committee for their scientifc and logistic support: Jerina Boelens, Laetitia Brassinne, Lucy Catteau
[Sciensano], Pieter-Jan Ceyssens, Julie Descy, Stefanie Desmet, Sarah Gils, Katrien Latour [Sciensano], Bénédicte Lissoir, Koen Magerman, Veerle Matheeussen, Cécile Meex, Hector Rodriguez-Villalobos, Sarah Vandamme [Universitaire Ziekenhuis Antwerpen], Anne-Marie Van den Abeele, Aline Vilain [Sciensano], Kris Vernelen, Ingrid Wybo [Universitaire Ziekenhuis Brussels], Harun Yaras [Belgian Antibiotic Policy Coordination Commission], Nicolas Yin [Laboratoire Hospitalier Universitaire de Bruxelles]
Chemical and Pharmacological Potential of Coccoloba cowellii, an Endemic Endangered Plant from Cuba
No full textCoccoloba cowellii Britton (Polygonaceae) is an endemic and critically endangered plant that only grows in Camagüey, a province of Cuba. In this study, a total of 13 compounds were identified in a methanolic leaf extract, employing a dereplication of the UHPLC-HRMS data by means of feature-based molecular networking (FBMN) analysis in the Global Natural Products Social Molecular Network (GNPS), together with the interpretation of the MS/MS data and comparison with the literature. The major constituents were glucuronides and glycosides of myricetin and quercetin, as well as epichatechin-3-O-gallate, catechin, epicatechin and gallic acid, all of them being reported for the first time in C. cowellii leaves. The leaf extract was also tested against various microorganisms, and it showed a strong antifungal effect against Candida albicans ATCC B59630 (azole-resistant) (IC50 2.1 μg/mL) and Cryptococcus neoformans ATCC B66663 (IC50 4.1 μg/mL) with no cytotoxicity (CC50 > 64.0 μg/mL) on MRC-5 SV2 cells, determined by the resazurin assay. Additionally, the extract strongly inhibited COX-1 and COX-2 enzyme activity using a cell-free experiment in a dose-dependent manner, being significantly more active on COX-1 (IC50 4.9 μg/mL) than on COX-2 (IC50 10.4 μg/mL). The constituents identified as well as the pharmacological activities measured highlight the potential of C. cowellii leaves, increasing the interest in the implementation of conservation strategies for this species
In vitro screening of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives as antiprotozoal agents and docking studies on Trypanosoma cruzi CYP51
No full textSterol 14a-demethylase (CYP51) is a key enzyme involved in the survival and virulence of many parasite
protozoa, such as Trypanosoma and Leishmania species, thus representing a valuable drug target for the
treatment of Kinetoplastid diseases. A set of azole-based compounds selected from an in-house compound
library was in vitro screened against different human protozoan parasites. Several compounds
showed selective activity against Trypanosoma cruzi, with compound 7 being the most active
(IC50 40 nM). Given the structural similarity between the compounds here reported and known CYP51
inhibitors, a molecular docking study was performed to assess their binding with protozoal target and to
rationalize the biological activity data
Antifungal Activity of Extracts, Fractions, and Constituents from <i>Coccoloba cowellii</i> Leaves
No full textCoccoloba cowellii Britton (Polygonaceae, order Caryophyllales) is an endemic and critically endangered plant species that only grows in the municipality of Camagüey, a province of Cuba. A preliminary investigation of its total methanolic extract led to the discovery of promising antifungal activity. In this study, a bioassay-guided fractionation allowed the isolation of quercetin and four methoxyflavonoids: 3-O-methylquercetin, myricetin 3,3′,4′-trimethyl ether, 6-methoxymyricetin 3,4′-dimethyl ether, and 6-methoxymyricetin 3,3′,4′-trimethyl ether. The leaf extract, fractions, and compounds were tested against various fungi and showed strong in vitro antifungal activity against Cryptococcus neoformans and various Candida spp. with no cytotoxicity (CC50 > 64.0 µg/mL) on MRC-5 SV2 cells, determined by a resazurin assay. A Candida albicans SC5314 antibiofilm assay indicated that the antifungal activity of C. cowellii extracts and constituents is mainly targeted to planktonic cells. The total methanolic extract showed higher and broader activity compared with the fractions and mixture of compounds
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