Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

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.

Qualidade microbiologica da carne de frango irradiada em embalagem convencional e a vácuo / Microbiological evaluation of chicken breast meat irradiated in conventional and vacuum package

Foram avaliados os efeitos da radiação gama nas doses de 1,5 e 3,0kGy, em peitos de frango embalados em embalagem convencional e a vácuo. As amostras embaladas foram submetidas à irradiação e estocadas sob refrigeração (4ºC) por 30 dias. A radiação mostrou-se eficiente na redução de mesófilos aeróbios estritos e facultativos viáveis, coliformes totais e termotolerantes, com destaque para Salmonella spp. Os bolores e leveduras mostraram-se bastante resistentes à radiação. Os resultados sugerem que a dose de 3,0kGy pode ser utilizada no controle da microbiota do peito de frango armazenado sob refrigeração, sendo uma alternativa para o aumento da vida de prateleira por até 10 dias, ao garantir a segurança do consumidor pela eliminação de possíveis patógenos.

The effects of gamma radiation doses of 1.5 and 3.0kGy on chicken breasts packed under conventional or vacuum atmosphere were evaluated. The packed samples were subjected to irradiation and stored under refrigeration (4ºC) for 30 days. The radiation was efficient in reducing strict and facultative aerobic mesophiles, total and fecal coliforms, and mainly Salmonella spp. The molds and yeasts were very resistant to radiation. The results suggest that gamma radiation at 3.0kGy can be used to control the microbiota in chicken breast stored under refrigeration, as an alternative to extend the shelf-life for more than ten days and ensure the food safety by eliminating potential pathogens.

Sildenafil delays the intestinal transit of a liquid meal in awake rats

Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25 percent (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95 percent CI: 4.1-152 nM) and cerulein (EC50: 58; 95 percent CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG) reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95 percent CI: 2.5-18 æM) in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 æM L-NOARG from 73 ± 5.1 to 19 ± 3.5 percent in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

Decreased gastric tone and delayed gastric emptying precede neutrophil infiltration and mucosal lesion formation in indomethacin-induced gastric damage in rats

Gastric antral dysmotility has been implicated in the pathogenesis of indomethacin-induced gastric damage, but the relationship between gastric motor abnormalities and mucosal lesions has not been extensively studied. We investigated whether changes in gastric tone and gastric retention correlate with mucosal lesions and neutrophil migration in indomethacin-induced gastric damage in rats. Indomethacin, either 5 or 20 mg/kg (INDO-5 and INDO-20), was instilled into the stomach, and then gastric damage, neutrophil migration, gastric tone and gastric retention were assessed 1 or 3 h later. Gastric damage was calculated as the sum of the lengths of all mucosal lesions, and neutrophil migration was measured by assaying myeloperoxidase activity. Gastric tone was determined by a plethysmometric method, and gastric retention of either saline or Sustacal« was evaluated by a scintigraphic method. Gastric damage was detectable 3 h after either INDO-5 or INDO-20, but not after 1 h. Neutrophil migration was significantly higher 3 h after INDO-20 as compared with INDO-5 or control group, but not after 1 h. Values of gastric tone 1 and 3 h after either INDO-5 (1 h = 1.73 ± 0.07 ml; 3 h = 1.87 ± 0.03 ml) or INDO-20 (1 h = 1.70 ± 0.02 ml; 3 h = 1.79 ± 0.03 ml) were significantly lower than in controls (1 h = 1.48 ± 0.05 ml; 3 h = 1.60 ± 0.06 ml). Gastric retention of saline was higher 1 h after INDO-5 (58.9 ± 3.3 percent) or INDO-20 (56.1 ± 3.1 percent) compared to control (45.5 ± 1.7 percent), but not after 3 h. There were no differences concerning gastric retention of Sustacal« between the various groups. Indomethacin induced decreased gastric tone and delayed gastric emptying, which precede mucosal lesion and neutrophil infiltration. These results indicate that there is no relationship between these gastric motor abnormalities and mucosal lesion in indomethacin-induced gastropathy

Methylmercury intoxication and histochemical demonstration of NADPH-diaphorase activity in the striate cortex of adult cats

The effects of methylmercury (MeHg) on histochemical demonstration of the NADPH-diaphorase (NADPH-d) activity in the striate cortex were studied in 4 adult cats. Two animals were used as control. The contaminated animals received 50 ml milk containing 0.42 µg MeHg and 100 g fish containing 0.03 µg MeHg daily for 2 months. The level of MeHg in area 17 of intoxicated animals was 3.2 µg/g wet weight brain tissue. Two cats were perfused 24 h after the last dose (group 1) and the other animals were perfused 6 months later (group 2). After microtomy, sections were processed for NADPHd histochemistry procedures using the malic enzyme method. Dendritic branch counts were performed from camera lucida drawings for control and intoxicated animals (N = 80). Average, standard deviation and Student t-test were calculated for each data group. The concentrations of mercury (Hg) in milk, fish and brain tissue were measured by acid digestion of samples, followed by reduction of total Hg in the digested sample to metallic Hg using stannous chloride followed by atomic fluorescence analysis. Only group 2 revealed a reduction of the neuropil enzyme activity and morphometric analysis showed a reduction in dendritic field area and in the number of distal dendrite branches of the NADPHd neurons in the white matter (P<0.05). These results suggest that NADPHd neurons in the white matter are more vulnerable to the long-term effects of MeHg than NADPHd neurons in the gray matter.

Characterization of nerve-induced relaxation of gastrointestinal sphincteric smooth muscle in a South American opossum (Didelphis albiventris)

The presence of inhibitory nonadrenergic noncholinergic (NANC) intrinsic innervation of the circular muscle of the gastrointestinal sphincters of the South American (SA) opossum was investigated in vitro. Isolated circular muscle strips from the esophagogastric and ileocolonic junctions but not from the gastroduodenal (pylorus) region developed spontaneous tension. Tetrodotoxin (TTX, 1 muM) augmented the spontaneous tension only in the ileocolonic junction strips. Electrical field stimulation of esophagogastric and ileocolonic junction strips caused frequency-dependent responses consisting of a relaxation at lower frequencies (<1 Hz) and a biphasic response or contraction at higher frequencies. In the strips from the pyloric region electrical field stimulation abolished the spontaneous activity at lower frequencies and induced contractions at higher frequencies. The responses elicited by electrical field stimulation in the three sphincters were abolished by TTX (1 muM). Electrical field-induced contractions were reduced while relaxations were enhanced by atropine (1 muM). In the presence of atropine (1 muM) and guanethidine (3 muM), electrical field stimulation, nicotine and ATP induced frequency-or concentration-dependent relaxations of the three sphincters that were abolished by TTX (1 muM). Isoproterenol and sodium nitroprusside caused concentration-dependent relaxations which were TTX-resistant. These findings indicate that the sphincteric circular muscle of the SA opossum gastrointestinal tract is relaxed by the activation of intrinsic NANC nerves and therefore can be used as a model for the study of the mechanisms involved in these responses.

Uma nova proposta para o estudo do trânito esofagiano através das técnicas biomagnéticas e cintilográficas / New proposal for esophageal transit study by biomagnetic and scintigraphic techniques

Apresentamos neste trabalho os resultados iniciais de uma nova proposta de aparato para o estudo do tempo de trânsito esofagiano em voluntários assintomáticos de um bolus de alimento-teste AT (10 ml de iogurte) marcado com 5g de pó de ferrita (estudo biomagnético, B) e com 350 MBq de (99m)Tc (estudo cintilográfico, C). Para B este novo aparato consiste de uma configuração de espiras em oposição de fase excitada por um sinal senoidal de 10 kHz. O sinal de resposta é obtido quando o AT passa entre os arranjos de bobinas posicionadas sobre as regiões de interesse (ROIs) do esôfago (fúrcula, F, e apêndice xifóide, X) produzindo um sinal de tensão medido por um amplificador lock-in Stanford SR530. Para C marcamos as ROIs com reparos posicionados sobre F e X. Usamos uma câmara de circulação Orbiter Siemens para as aquisições dinâmicas de deglutição. A análise dos dados foi feita em um microcomputador PC 386. Os resultados foram (4.1+0.7)s para B e (3.7+0.9) s para C (R=0.6, P<0.07)

Abstract - This work shows the initial results for a new apparatus to study the esophageal transit time in assymptomatic persons for a yogurt bolus ( 1 O mi) uniformely labeled with 5g of ferrite powder (biomagnetic study. B) or 350MBq of 99mTc (scintigraphic study, C). For the B study the detection is made by means two pair of coils in opposite phase excited by a 1 O kHz sinusoidal voltage. We obtainted the signal response when the bolus traverses the coils placed on the regions-of-interest (RO!s) of the esophagus (furcula, F, and xiphoid process, X) and produces a signal voltage that is measured by a lock-in amplifier Stanford SR530. For C studies an Orbiter Siemens scintilation camera is used linked to a computer. The data analysis shows a (4.1±0.7)s in B studies and (3.7±0.9) s in C studies ( R=0.6, P<0.07 )

Estudos em magnetogastrografia / Study in magnetogastrography

O registro da atividade elétrica doo estômago, através da detecção do campo magnético associado foi detectado. A comparação desta atividade através do registro simultâneo do sinal elétrico e magnético foi feita através da função de correlação, análise de Fourier e testes estatísticos. A medida desta atividade pode auxiliar no diagnóstico de patologias do trato gastrointestinal. O método magnético apresenta a vantagem de ser completamente não invasivo.

Abstract - This work shows the study of the stomach electrical activity by the measurement of the magnetic field produced by the electrical currents generated at the stomach. A comparison between the electric and magnetic measurements was performed by the correlation function, Fourier analysis and statistical tests. These measurements can help on diagnostic of gastric-intestinal pathologies. This method has the advantage of the being non invasive

Tempo de trânsito faringeano medido através dos métodos cintilográfico e biomagnético / Pharyngeal transit time measured by of scintilographic and biomagnetic methods

Apesar do método Cintilográfico se mostrar o melhor estabelecido para o estudo do trânsito digestivo, recentemente o método Biomagnético vem sendo utilizado, possuindo algumas vantagens em relação ao Cintilográfico. O objetivo deste estudo é comparar ambos os métodos para a medida de tempo de trânsito faringeano. Foram estudados 3 voluntários, obtendo-se valores consideravelmente diferentes do método Cintilográfico, possivelmente devido a resolução do detetor biomagnético.

Abstract - The Scintigrafic method is well established to study the digestive tract motility. Nevertheless, the Biomagetic method has recently been employed and it does have some advantages over the Scintigraphic one. The aim of this study is to compare pharyngeal transit time measured by both methods. Our preliminary results indicate that there is a difference between the values obtained with each method, probabily due to the Biomagnetic detector resolution

Evidence for the participation of the L-arginine-nitric oxide pathway in neurally induced relaxation of the isolated rat duodenum

1. Electrical field stimulation (EFS) of intrinsic nerves in the rat proximal duodenum induces a frequency-dependent non-adrenergic-non-cholinergic (NANC) relaxation response. 2. The inhibitors of L-arginine-NO synthase L-NG-nitro arginine methyl-ester (L-NAME) and L-NOARG (L-NG-nitro arginine) reduced the NANC relaxations elicited by EFS in a dose- and time-dependent manner; L-NOARG was two times more potent than L-NAME (IC50 = 14.3 vs 25.2 microM) and these effects were partially reverted by the addition of 300-1000 microM L-arginine but not of 300-1000 microMD-arginine. Relaxation caused by vasoactive intestinal peptide (VIP; 0.1 microM) or ATP (20 microM) was not blocked by L-NAME or L-NOARG. 3. The magnitude of the blockade caused by L-NAME and L-NOARG was dependent on the frequency of stimulation. At low frequencies (below 1 Hz) both L-NAME and L-NOARG abolished the relaxations, while at 2 to 8 Hz only partial inhibition was observed (maximal inhibition: 44.6 per cent +/- 5.2 and 63.4 per cent +/- 3.4, respectively) 4. The basal tonus of the duodenum was increased by 10-300 microM L-NAME and 10-300 microM L-NOARG and this effect was blocked by 1 mM L-arginine. 5. Nitric oxide generated from acidified NaNO2 caused a dose-dependent (EC50 = 2.75 microM) relaxation of the duodenum which was not affected by 100 microM L-NAME, 100 microM L-NOARG or 1 microM tetrodotoxin (TTX). 6. NADPH-diaphorase positive neurons and fibers identified by histochemistry were present in the myenteric plexus and along both circular and longitudinal muscle fibers indicating that nitric oxide could be synthetized by these neural structures

Evidence for the involvement of nitric oxide in the electrically induced relaxations of human lower esophageal sphincter and distal pylorus

The aim of the present study was to investigate in vitro the effect of Ng-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on neurogenic relaxation of human lower esophageal sphincter (LES) and distal pylorus (DP) circular muscle strips induced by electr4ical field stimulation (EFS). Muscle strips obtained from 5 patients who underwent total gastrectomy were suspended in 10-ml organ baths containing Krebs solution for recording isometric tension. L-NAME(30 uM) reduced the amplitude of the EFS-induced relaxation by 85 ñ 9% (N=3) in the LES and by 52 ñ 16% (N=3) in the DP but did not affect sodium nitroprusside-induced relaxation. L-Arginine (300 uM) partially reversed the L-NAME inhibition in the LES and totally in the DP. These findings suggest a role for L-arginine-derived NO in the nerve-mediated NANC relaxation of the human LES and DP

Use of isosorbide dinitrate for the symptomatic treatment of patients with Chagas' disease achalasia: a double-blind, crossover trial

1. A randomized, double-blind, placebo-controlled trial was carried out to determine the efficacy of isosorbide dinitrate (ISD) on diasphagia in patients with Chagasic achalasia. 2. Twenty-three patients with Chagas' disease and dysphagia entered the study ans 20 (87%) complelted the two 7-day treatment periods. Subjects were given either 5 mg ISD (12 patients) or placebo (11 patients) by the sublingual route for the first 7 days. On the 8 th day, patients crossed over and began another 7-days period during which they received the opposite, identical-appearing tablets. 3. Scores attributed by uniformed investigators for the frequency and severity of dysphagia were signidicantly lower (P,0.05) following ISD treatment than after the placebo period or for the pretreatment condition. A significantly higher degree of improvement of dysphagia was experienced by the patients during ISD treatment than during the placebo period. Fourteen patients experienced meal-related headaches during ISD, but not placebo treatment. The extent of improvement in general well-being due to ISD was the same when the drug given in the first or second test period. 4. Our results indicate that ISD, 5 mg by the sublingual route, is effective in alleviating dysphagia in patients with Chagasic achalasia but its usefulness is limited by the high rate of headache as a side effect

Diferenca de comprometimento do peristaltismo entre a parte superior e inferior do esofago na doenca de Chagas. / Difference of involvement of peristalsis between the upper and the lower part of the esophagus in Chagas disease

Os autores estudaram manometricamente o peristaltismo esofagico em 16 pacientes com esofagopatia chagasica com poucas alteracoes radiologicas. Em 6 foram observadas ondas peristalticas em todo o esofago e em 6 ondas sincronas. Em 4 pacientes observou-se ondas peristalticas na parte superior e ondas sincronas na parte inferior. A exemplo do que acontece em outras patologias que comprometem a motilidade esofagica, tambem na esofagopatia chagasica a perda do peristaltismo e mais precoce na parte inferior que na superior

Pericardite constritiva causando perda anormal de proteínas pelo tubo digestivo. Relato de 2 casos / Constrictive pericarditis causing abnormal protein-losing through digestive tube. Report of 2 cases

Os autores descrevem dois casos de pericardite constrictiva cronica causando perda anormal de proteinas pelo tubo digestivo. No primeiro caso, coexistiram varias das alteracoes clinicas e laboratoriais descritas na sindrome, todas com elevada intensidade. A correcao cirurgica da constriccao pericardica foi seguida por regressao incompleta e transitoria da anormalidade. Esta irreversibilidade foi atribuida a concomitancia de obstrucao da drenagem linfatica abdominal, possivel sequela de lesao ganglionar tuberculosa, que foi demonstrada radiologicamente. No segundo caso, estavam presentes apenas alteracoes laboratoriais sugestivas da gastrenteropatia perdedora de proteinas. Apos a pericardiectomia houve regressao completa e pemanente do disturbio. Os possiveis mecanismos geradores de perda intestinal de proteinas na insuficiencia cardiaca congestiva, as anormalidades clinicas e laboratoriais decorrentes do defeito, bem como os meios diagnosticos e terapeuticos da perda de proteinas sao comentados