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2. Sex differences in β-N-Methylamino-L-alanine effects on zebrafish behavioral response

Author

Amaral, Nicoli R. do, Abreu, Murilo S. de, Zanella, Alexander, Poletto, Júlia P., Mello, Gabriel P. de, Croce, Marco A. da, Garbelotto, Larissa B., Bernardon, Manuela G., and Giacomini, Ana C.V.V.

Abstract

The β-N-methylamino-L-alanine (BMAA) is a neurotoxin produced by cyanobacteria and diatoms and related by triggered neurodegeneration. The exposure to neurotoxins has also been reported by causing emotional and neuroendocrine effects and these effects may be sex-specific. However, the effects of BMAA on emotions and pain, as well as neuroendocrine modulations remain poorly understood. Here, we evaluate potential sex differences in zebrafish behavioral responses to BMAA acute exposure on their anxiety and pain phenotypical behavioral repertoire and their neuroendocrine (cortisol) effects. Overall, sex differences in behavioral responses of adult zebrafish to BMAA exposure were demonstrated, as female fish reacted to it more strongly than males by altering their behavioral phenotype in both the novel tank and writhing -like behavior tests. In addition, sex differences were demonstrated in relation to time response, as male increased the writhing-like behavioral responses immediately after injection of BMAA, while female only 24-h after injection, reinforcing the painful stimulus caused by BMAA. However, the exposure to BMAA elevated the whole-body cortisol levels in both male and female zebrafish. Collectively, these findings emphasize the growing importance of studying sex differences in zebrafish, including the evaluation of neurotoxins effects on emotions and pain in this aquatic experimental model.

Published
2024
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4. Straightforward quantification of endogenous steroids with liquid chromatography-tandem mass spectrometry: Comparing calibration approaches

Author

Visconti, G., de Figueiredo, M., Salamin, O., Boccard, J., Vuilleumier, N., Nicoli, R., Kuuranne, T., and Rudaz, S.

Subjects
Female, Humans, Tandem Mass Spectrometry/methods, Calibration, Reproducibility of Results, Chromatography, Liquid/methods, Steroids, External calibration, Internal calibration, LC-MS, Quantification
Abstract

Different calibration strategies are used in liquid chromatography hyphenated to mass spectrometry (LC-MS) bioanalysis. Currently, the surrogate matrix and surrogate analyte represent the most widely used approaches to compensate for the lack of analyte-free matrices in endogenous compounds quantification. In this context, there is a growing interest in rationalizing and simplifying quantitative analysis using a one-point concentration level of stable isotope-labeled (SIL) standards as surrogate calibrants. Accordingly, an internal calibration (IC) can be applied when the instrument response is translated into analyte concentration via the analyte-to-SIL ratio performed directly in the study sample. Since SILs are generally used as internal standards to normalize variability between authentic study sample matrix and surrogate matrix used for the calibration, IC can be calculated even if the calibration protocol was achieved for an external calibration (EC). In this study, a complete dataset of a published and fully validated method to quantify an extended steroid profile in serum was recomputed by adapting the role of SIL internal standards as surrogate calibrants. Using the validation samples, the quantitative performances for IC were comparable with the original method, showing acceptable trueness (79%-115%) and precision (0.8%-11.8%) for the 21 detected steroids. The IC methodology was then applied to human serum samples (n = 51) from healthy women and women diagnosed with mild hyperandrogenism, showing high agreement (R 2 > 0.98) with the concentrations obtained using the conventional quantification based on EC. For IC, Passing-Bablok regression showed proportional biases between -15.0% and 11.3% for all quantified steroids, with an average difference of -5.8% compared to EC. These results highlight the reliability and the advantages of implementing IC in clinical laboratories routine to simplify quantification in LC-MS bioanalysis, especially when a large panel of analytes is monitored.

Published
2023

11. Evaluation of an in-capillary approach for performing quantitative cytochrome P450 activity studies

Author

Curcio, R., Nicoli, R., Rudaz, S., Veuthey, J.-L, Curcio, R., Nicoli, R., Rudaz, S., and Veuthey, J.-L

Abstract

An automated in-capillary assay requiring very small quantities of reagents was developed for performing in vitro cytochrome P450 (CYP450) drug metabolism studies. The approach is based on the following: (i) hydrodynamic introduction of nanoliter volumes of substrate and enzyme solutions in the sandwich mode, within a capillary; (ii) mixing the reagents by diffusion across the interfaces between the injected solutions; (iii) collection of the capillary content at the end of the in-capillary assay; and (iv) off-line analysis of the incubation mixture by ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After optimizing the injection sequence of the reagents, the in-capillary approach was applied to the quantitative determination of the kinetics of drug metabolism reactions catalyzed by three CYP450 isozymes involved in human drug metabolism: CYP1A2, CYP2D6, and CYP3A4. It was demonstrated that this in-capillary method was able to provide similar kinetic parameters for CYP450 activity (e.g., Michaelis constants and turnover values) as the classical in vitro method, with a drastic reduction of reagent consumption. Injection setups used for in-capillary CYP450 assays

Published
2018

14. Il tedesco in una facoltà di economia. Bilancio e prospettive

Author

Brambilla, M, Missaglia, F, Neiger G, Nicoli, R, Crestani, V, Vogler, SK, Taino, P, Dusi, M, Gobber, G, Vogler, S, VOGLER, STEFANIE KARIN, Brambilla, M, Missaglia, F, Neiger G, Nicoli, R, Crestani, V, Vogler, SK, Taino, P, Dusi, M, Gobber, G, Vogler, S, and VOGLER, STEFANIE KARIN

Abstract

Nell’Unione Europea si contano ca. 90 milioni persone di madrelingua tedesca che costituiscono il gruppo linguistico più forte. Il tedesco è lingua nazionale in Germania, Svizzera e Austria ed esistono minoranze di lingua tedesca in Francia, Lussemburgo, Belgio e in Italia. La Germania si colloca come una delle più importanti economie non solo all’interno dell’Unione Europea ma anche a livello mondiale, e tra l’Italia e la Germania esistono stretti legami culturali e rapporti commerciali consolidati nel corso della storia di entrambi i paesi. Tuttavia in molte facoltà non umanistiche degli atenei italiani si registra ormai da anni una flessione del numero degli studenti che decidono di includere nel loro piano di studi la lingua tedesca. La stessa tendenza si osserva anche nella facoltà di economia dell’Università degli Studi di Milano-Bicocca (di seguito Università di Milano-Bicocca). Questa tendenza dovrebbe però far riflettere, alla luce del fatto che la Lombardia ha particolari legami commerciali ed industriali con la Germania e che anche geograficamente si trova vicino all’aerea di lingua tedesca. Dopo una breve rassegna delle più importanti modifiche ai piani di studi dei differenti corsi di laurea di economia presso l’Università di Milano-Bicocca e dopo l’analisi dei dati relativi agli studenti che decidono di apprendere il tedesco oppure di approfondire le loro conoscenze della stessa lingua precedentemente acquisite, si individuano i fattori che condizionano la scelta degli studenti a favore di una lingua diversa dal tedesco. Infine si formulano delle proposte relative alle misure adottabili per incoraggiare gli studenti ad inserire nel loro piano di studi anche il tedesco.

Published
2014

21. Les biocénoses dulcaquicoles de la Corse cristalline

Author

Nicoli, R., Nicoli, J., Quilici, M., and Rioux, Jean-Antoine

Abstract

Nicoli René-Marie,Nicoli J.,Quilici M.,Rioux Jean-Antoine. Les biocénoses dulcaquicoles de la Corse cristalline. In: La Terre et La Vie, Revue d'Histoire naturelle, tome 17, n°2, 1963. pp. 140-163.

Published
1963
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22. Evaluation of an in-capillary approach for performing quantitative cytochrome P450 activity studies

Author

Curcio, R., Nicoli, R., Rudaz, S., Veuthey, J.-L, Curcio, R., Nicoli, R., Rudaz, S., and Veuthey, J.-L

Abstract

An automated in-capillary assay requiring very small quantities of reagents was developed for performing in vitro cytochrome P450 (CYP450) drug metabolism studies. The approach is based on the following: (i) hydrodynamic introduction of nanoliter volumes of substrate and enzyme solutions in the sandwich mode, within a capillary; (ii) mixing the reagents by diffusion across the interfaces between the injected solutions; (iii) collection of the capillary content at the end of the in-capillary assay; and (iv) off-line analysis of the incubation mixture by ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After optimizing the injection sequence of the reagents, the in-capillary approach was applied to the quantitative determination of the kinetics of drug metabolism reactions catalyzed by three CYP450 isozymes involved in human drug metabolism: CYP1A2, CYP2D6, and CYP3A4. It was demonstrated that this in-capillary method was able to provide similar kinetic parameters for CYP450 activity (e.g., Michaelis constants and turnover values) as the classical in vitro method, with a drastic reduction of reagent consumption. Injection setups used for in-capillary CYP450 assays

38. Notes et informations

Author

Mazzotti, Luis, primary, Chabaud, Alain-G., additional, Nicoli, R.-M., additional, di Campo, A., additional, Quilici, M., additional, and Ribeiro, Henrique, additional

Published
1962
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