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Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

https://doi.org/10.1590/1414-431x2023e13258

SCREENER, an educational game for teaching the Drug Discovery and Development process
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Noël, F.

; Xexéo, G.

; Mangeli, E.

; Mothé, A.

; Marques, P.

; Kritz, J.

; Blanchard, F.

; Vermelho, H.

; Paiva, B. de

Brazilian Journal of Medical and Biological Research

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2021, Volume 54 Nº 12 elocation e11786

Resumo: En | Texto: En | PDF: En

Although the use of games as an educational strategy is an important current trend, there is practically no option available for training people on the Drug Discovery and Development (DDD) process. To fill this gap, we designed “SCREENER”, a science game that is intended to be educational, but also challenging and interesting enough to ensure player engagement. Our main target audience is students of postgraduate programs in pharmacology, medicinal chemistry, pharmacy, and medicine. This game could also be of interest to the pharmaceutical industry and regulatory and patent agencies for training new employees. We discuss the creation of SCREENER, a hybrid of board and card games, and present its components with some examples of cards and resources, as well as the dynamics of the game. SCREENER mimics the process of drug discovery and development from validating a target to registering the new drug with the regulatory agency, and can be played individually (self-learning) or with the help of a monitor who assists up to six players/teams. Briefly, 29 task cards categorized in four major areas (efficacy, safety, pharmacokinetics, and pharmaceutical development) must be purchased sequentially. Classic characteristics of games such as decision making and challenge have been incorporated. More in-depth information on the tasks and technical terms is available through QR codes. The vagaries of the DDD process are mimicked by the bonus/setback cards. The evaluation of our first test with students is presented and supports the usefulness of this new tool.

https://doi.org/10.1590/1414-431x2021e11786 1 downloads

ADME studies and preliminary safety pharmacology of LDT5, a lead compound for the treatment of benign prostatic hyperplasia
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Noël, F.

; Nascimento-Viana, J.B.

; Romeiro, L.A.S.

; Silva, R.O.

; Lemes, L.F.N.

; Oliveira, A.S.

; Giorno, T.B.S.

; Fernandes, P.D.

; Silva, C.L.M.

Brazilian Journal of Medical and Biological Research

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2016, Volume 49 Nº 12 elocation e5542

Resumo: En | Texto: En | PDF: En

This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in rat and human plasma, human liver microsomes and hepatocytes, but unstable in rat liver microsomes and hepatocytes (half-life of 11 min). LDT5 is highly permeable across the MDCK-MDR1 monolayer (Papp ∼32×10-6 cm/s), indicating good intestinal absorption and putative brain penetration. LDT5 is not extensively protein-bound and is a substrate of human CYP2D6 and CYP2C19 but not of CYP3A4 (half-life >60 min), and did not significantly influence the activities of any of the human cytochrome P450 isoforms screened. LDT5 was considered safe albeit new studies are necessary to rule out putative central adverse effects through D2, 5-HT1A and 5-HT2B receptors, after chronic use. This work highlights the drug-likeness properties of LDT5 and supports its further preclinical development.

https://doi.org/10.1590/1414-431x20165542 2562 downloads

Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors
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Barreto, F.

; Rezende, D.C.

; Scaramello, C.B.V.

; Silva, C.L.M.

; Cunha, V.M.N.

; Caricati-Neto, A.

; Jurkiewicz, A.

; Noël, F.

; Quintas, L.E.M.

Brazilian Journal of Medical and Biological Research

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Mai 2010, Volume 43 Nº 5 Páginas 500 - 505

Resumo: En | Texto: En | PDF: En

The regulatory function of α1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a significant increase in the activity of the thapsigargin-resistant (PMCA) to thapsigargin-sensitive (SERCA) ratio was detected. Neither Na+/K+-ATPase activity nor the expression of α1 and α2 subunit isoforms was changed in CAMα1B-AR mouse hearts. Moreover, immunoblot assays did not provide evidence for an enhanced activation of the three mitogen-activated protein kinases studied in this stage of hypertrophy. Therefore, these findings indicate that chronic cardiac α1B-AR activation in vivo led to mild hypertrophy devoid of significant signs of adaptive modifications concerning primary intracellular calcium control and growth-related proteins, suggesting a minor pathophysiological role of this adrenergic receptor in mouse heart at this stage of development.

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Control of calcium homeostasis in Schistosoma mansoni
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Noël, F

; Cunha, VMN

; Silva, CLM

; Mendonça-Silva, DL

Memórias do Instituto Oswaldo Cruz

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Set 2001, Volume 96 Páginas 85 - 88

Resumo: En | Texto: En | PDF: En

Calcium signalling is fundamental for muscular contractility of Schistosoma mansoni. We have previously described the presence of transport ATPases (Na+,K+-ATPase and (Ca2+-Mg2+)-ATPase) and calcium channels (ryanodine receptors - RyR) involved in control of calcium homeostasis in this worm. Here we briefly review the main technics (ATPase activity, binding with specific radioligands, fluxes of 45Ca2+ and whole worm contractions) and results obtained in order to compare the distribution patterns of these proteins: thapsigargin-sensitive (Ca2+-Mg2+)-ATPase activity and RyR co-purified in P1 and P4 fractions mainly, which is compatible with a sarcoplasmic reticulum localization, while basal ATPase (along with Na+,K+-ATPase) and thapsigargin-resistant (Ca2+-Mg2+)-ATPase have a distinct distribution, indicative of their plasma membrane localization. Finally we attempt to integrate these contributions with data from other groups in order to propose the first synoptic model for control of calcium homeostasis in S. mansoni.

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Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum
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Noël, F.

; Geurts, M.

; Maloteaux, J.-M.

Brazilian Journal of Medical and Biological Research

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Fev 2000, Volume 33 Nº 2 Páginas 237 - 240

Resumo: En | Texto: En | PDF: En

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

1950 downloads

(Ca2+-Mg2+)ATPase in Schistosoma mansoni: evidence for heterogeneity and resistance to praziquantel
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Cunha, VMN

; Noël, F

Memórias do Instituto Oswaldo Cruz

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1998, Volume 93 Supl. 1 Páginas 181 - 182

Resumo: En | Texto: En | PDF: En

1353 downloads

Evidence for functional ryanodine receptors in Schistosoma mansoni and their putative role in the control of calcium homeostasis
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Silva, CLM

; Mendonça-Silva, DL

; Noël, F

Memórias do Instituto Oswaldo Cruz

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1998, Volume 93 Supl. 1 Páginas 269 - 270

Resumo: En | Texto: En | PDF: En

1051 downloads

Portal veins of mice infected with Schistosoma mansoni exhibit an increased reactivity to 5-hydroxytryptamine
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Silva, CLM

; Morel, N

; Noël, F

Memórias do Instituto Oswaldo Cruz

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1998, Volume 93 Supl. 1 Páginas 153 - 155

Resumo: En | Texto: En | PDF: En

In chronic severe infection with Schistosoma mansoni, portal hypertension and related vascular alterations usually develop as a consequence of granulomatous response to eggs. In order to investigate a putative direct effect of worms on the reactivity of their host portal vein, mice infected only with male worms were used in the present study. An higher reactivity to 5-hydroxytryptamine (5-HT) characterized by an increase in the maximal contraction and sensitivity was observed in portal vein from infected mice compared to healthy mice. Blockade of NO-synthase with l-NAME induced a small increase in 5-HT potency in portal vein from non-infected mice without changing the amplitude of the contractions, whereas it did not alter the reactivity of veins from infected mice. The present results show that unisexual infection of mice with male S. mansoni increased the reactivity of the portal vein to 5-HT which seems to be partially related to an alteration in the nitric oxide release by endothelium.

1509 downloads

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