Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents

Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50 values of 24.3 and 27.9 mu M, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 mu M, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC50 value of 20.4 mu M. Moreover, relevant cytotoxicity against MCF-7 cells (IC50 = 13.3 mu M) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 mu M) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters. (C) 2017 Elsevier Masson SAS. All rights reserved.Peer reviewe

Development of separation and detection techniques to analyze organic and organometallic pollutants in environmental samples

La Directive Cadre sur l'Eau (DCE) (2000/60) a mis en place une liste de 33 substances prioritaires, avec des normes qualité de l'environnement (NQE) pour chaque substance, et leur concentration dans les milieux aquatiques qui ne doivent pas dépasser c es NQE. De plus, elle exige des performances analytiques spécifiques pour ces méthodes: la limite de quantification doit être au moins aussi basse que 30% des NQE et l'incertitude de la méthode au niveau de la NQE doit être inférieure à 50%, pour k = 2. Par conséquent, le défi analytique actuel est de mesurer de faibles concentrations de ces polluants dans les matrices parfois difficiles. Ceci peut être réalisé en améliorant la technique d'extraction utilisée pour obtenir un extrait de l'échantillon plus concentré et plus propre. Dans ce contexte, les trois méthodes d'analyse ont été mises au point pour déterminer les composés musqués, alkylphénoliques et organométalliques dans les matrices environnementales. Ces techniques d'extraction et de pré-concentration innovantes ont ensuite été appliquées pour l’évaluation de la présence de ces composés dans les stations d'épuration locales et dans les cours d'eau récepteurs. Enfin, les niveaux de concentrations de fond au niveau national ont été mises à jour pour les composés organométalliques.The ambitious Water Framework Directive (WFD) (2000/60) set up a list of 33 priority substances, with Environmental Quality Standards (EQS) for each substance, and their concentration in aquatic environments should not go beyond the EQS. Additionally, it requires specific analytical method performances: the limit of quantification must be at least as low as 30 % of the EQS and the uncertainty of the method at the EQS level must be inferior to 50 %, for k=2. Therefore, the current analytical challenge is to measure low concentrations of these pollutants in sometimes difficult matrices. This can be achieved by improving the extraction technique used to obtain a more concentrated and cleaner sample extract. In this context, 3 analytical methods were developed to determine musk, alkylphenols and organometallic compounds in environmental matrices. Recent extraction and pre-concentration techniques were applied and later the occurrence of these compounds in the local WWTPs and in the receiving water bodies where they are discharged was evaluated. Additionally, updated French background concentrations were established for organometallic compounds

As conceções de amizade das crianças de uma sala de Jardim de Infância

Relatório da Prática Profissional Supervisionada II apresentado à Escola Superior de Educação de Lisboa para obtenção de grau de mestre em Educação Pré-EscolarO presente relatório decorre da Prática Profissional Supervisionada II, integrada no plano de estudos do 2º ano do Mestrado em Educação Pré-escolar, da Escola Superior de Educação de Lisboa. A prática decorreu entre os dias 7 de outubro de 2019 e 31 de janeiro de 2020 e foi concretizada num Jardim de Infância público, com um grupo de dezanove crianças, com idades compreendidas entre os quatro e os seis anos. Neste relatório, inicialmente, apresento uma caracterização do contexto socioeducativo, sobre a qual refleti e que, posteriormente, me permitiu descrever, fundamentar, analisar e avaliar a minha prática pedagógica. Esta foi desenvolvida no contexto de Jardim de Infância, em que contactei com profissionais que me deram a oportunidade de desenvolver diversas competências e adquirir conhecimentos, fundamentais para a construção da minha identidade profissional. A componente investigativa também se encontra presente neste relatório, em que através de uma observação cuidada e atenta do contexto socioeducativo, especificamente, do grupo de crianças da sala A, surgiu a problemática – As conceções de Amizade das Crianças de uma Sala de Jardim de Infância. Desta forma, recorrendo à observação direta e à realização de entrevistas às crianças e à equipa educativa da sala A, pretendia (i) analisar as conceções das crianças sobre o conceito de amizade; (ii) analisar as relações de amizade deste grupo de crianças; e (iii) analisar as conceções da equipa educativa sobre as relações de amizade entre as crianças. Assim, a partir da análise dos dados, constatei que as crianças caracterizam a amizade como uma relação afetuosa, em que se transmitem afetos e em que a partilha é fundamental. As crianças associaram a este conceito sentimentos, como, alegria, felicidade e amor, mas também o relacionaram com o brincar e com o facto de ter/fazer amigos. Com esta investigação, consegui também analisar as suas relações de amizade, em que as crianças nomearam os seus amigos, demonstrando preferência por determinados pares e verifiquei que é através do brincar que se criam e mantêm as relações de amizade. Em suma, a amizade na infância exerce um papel fulcral no desenvolvimento holístico das crianças. Por fim, relativamente à construção da minha identidade profissional, no decorrer da PPS II refleti sobre a minha prática e priorizei alguns aspetos que considero relevantes para a concretização de uma prática de qualidade enquanto Educadora de Infância.ABSTRACT The present report is part of the Supervised Professional Practice II, integrated in the study plans of the 2nd year Master’s Degree in Preschool Education, from “Escola Superior de Educação de Lisboa”. The internship took place from the 7th of October 2019 to 31st of January 2020 in a public kindergarten with a group of nineteen children, with ages between four and six years. In this report, initially, I´m going to illustrate the socio-educational context which I ponder and then allowed me to describe, fundament, analyze, and evaluate my pedagogical method. This method was developed in the context of kindergarten, in which I come in contact with professionals that gave me a chance to improve several skills and acquire knowledge, fundamental to the construction of my professional identity. This research component is also present in this report, in which through a detailed and attentive observation of the socio-educational context, especially of the children in classroom A, the problem surged – The Conceptions of Friendship of Children in a Kindergarten Room. This way, using direct observation and conducing interview with the children and the faculty team of classroom A, I intended to (i) analyze the conceptions of the children about friendship; (ii) analyze the relationship of this group of children; and (iii) analyze the conceptions of the faculty team about the friendship relations among the children. From my data research, I concluded the children describe friendship as a loving relationship, in which the transmission of affection and sharing is fundamental. The children associated this concept to feelings like joy, happiness and love, but also for playing and making friends. With this investigation, I also manage to analyze their friendships, in which the children nominated their friends showing preference for specific peers and verified that it is throwing playing around with each other that that they create and maintain their friendships. In summary, friendships in early age have a key role in the global development of the children. In conclusion, going back to the construction of my professional identity, during the “PPS II” course I reflected about my practice and prioritize some aspects that I consider relevant for the concretization of a quality practice as a kindergarten teacher.N/

Synthetic musk in seafood products from south Europe using a quick, easy, cheap, effective, rugged and safe extraction method

International audienceThis study aims at developing a method for the determination of 9 synthetic musk compounds in seafood products by combining the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and determination by gas chromatography mass spectrometry (GC-EI-MS). Method detection limits (MDL) ranging between 0.001 and 1.94 ng g-1 were obtained. The linearity is higher than 0.9899 in the range MDL - 100 ng g-1 with precision below 18% and recoveries between 46% and 120% were obtained. The method was applied to quantify musk compounds in seafood products from the European southwest coast (oysters, mussels, salmon organs, glass eels). Galaxolide and Tonalide exhibited the highest concentration levels ranging between MDL - 96.4 ng g-1 and MDL - 6.85 ng g-1, respectively. Contamination levels observed for the two nitro musks (musk xylene and musk ketone) are significantly lower ranging between MDL - 0.6 ng g-1 and MDL - 0.09 ng g-1, respectively. Analysis of different organs of salmons showed higher concentrations in liver and gonad than in muscle tissues. © 2016 Elsevier Ltd. All rights reserved

Organotin persistence in contaminated marine sediments and porewaters: In situ degradation study using species-specific stable isotopic tracers

International audienceThis paper provides a comprehensive study of the persistence of butyltins and phenyltins in contaminated marine sediments and presents the first data on their degradation potentials in porewaters. The study's aim was to explain the different degradation efficiencies of organotin compounds (OTC) in contaminated sediments. The transformation processes of OTC in sediments and porewaters were investigated in a field experiment using species-specific, isotopically enriched organotin tracers. Sediment characteristics (organic carbon content and grain size) were determined to elucidate their influence on the degradation processes. The results of this study strongly suggest that a limiting step in OTC degradation in marine sediments is their desorption into porewaters because their degradation in porewaters occurs notably fast with half-lives of 9.2 days for tributyltin (TBT) in oxic porewaters and 2.9 ± 0.1 and 9.1 ± 0.9 days for dibutyltin (DBT) in oxic and anoxic porewaters, respectively. By controlling the desorption process, organic matter influences the TBT degradation efficiency and consequently defines its persistence in contaminated sediments, which thus increases in sediments rich in organic matter. © 2015 Elsevier B.V

Methylmercury effects on migratory behaviour in glass eels (Anguilla anguilla) : an experimental study using isotopic tracers

International audienceThe effect of methylmercury (MeHg) on glass eels' propensity to migrate, mitochondrial activity and antioxidative defence systems was investigated. Marine glass eels were first sorted in an experimental flume according to their response to dusk. Fish responding to the decrease in light intensity by ascending in the water column and moving with or against the flow were considered as having a high propensity to migrate (migrant). Glass eels still sheltering at the end of the 24 h catching period were considered as having a low propensity to migrate and were called non-migrant. Migrant and non-migrant glass eels were then individually tagged and exposed to isotopically enriched 201MeHg (50 ng L− 1) for 11 days. The effect of contamination was studied on muscle fibre structure, and the expression level of genes involved in mitochondrial activity and antioxidative defence systems. To investigate the effect of MeHg on glass eel behaviour, migrant and non-migrant glass eels were sorted again and the bioaccumulation of 201MeHg and its demethylation product (201Hg(II)) were determined for each individual. MeHg exposure increased activity in non-migrant glass eels but not migratory behaviour. Contamination affected mitochondrial structure and metabolism and suggests a higher oxidative stress and activation of antioxidative defence systems in non-migrant glass eels. Overall, our results suggest that exposure to MeHg might induce an increase in energy expenditure and a higher vulnerability to predation in non-migrant glass eels in the wil

Assessment of background concentrations of organometallic compounds (methylmercury, ethyllead and butyl- and phenyltin) in French aquatic environments

International audienceThe aim of this work is to estimate background concentrations of organometallic compounds, such as tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPhT), diphenyltin (DPhT), monophenyltin (MPhT), methylmercury (MeHg), inorganic mercury (iHg) and diethyllead (Et2Pb) in the aquatic environment at the French national scale.Both water and sediment samples were collected all over the country, resulting in 152 water samples and 123 sediment samples collected at 181 sampling points. Three types of surface water bodies were investigated: rivers (140 sites), lakes (19 sites) and coastal water (42 sites), spread along the 11 French river basins. The choice of sites was made on the basis of previous investigation results and the following target criteria: reference, urban sites, agricultural and industrial areas. The analytical method was properly validated for both matrices prior to analysis, resulting in low limits of quantification (LOQ), good precision and linearity in agreement with the Water Framework Directive demands. The results were first evaluated as a function of their river basins, type of surrounding pressure and water bodies. Later, background concentrations at the French national scale were established for both water and sediment matrices, as well as their threshold, i.e., the concentration that distinguishes background from anomalies or contaminations. Background concentrations in water are ranging between <0.04-0.14 ng Hg. L-1 for MeHg, <0.14-2.10 ng Hg. L-1 for iHg, <1.0-8.43 ng Pb. L-1 for Et2Pb and 0.49-151 ng Sn. L-1, <0.08-3.04 ng Sn. L-1 and <0.08-0.25 ng Sn. L-1 for MBT, DBT and TBT, respectively. For sediments, background concentrations were set as <0.09-1.11 ng Hg. g-1 for MeHg, <0.06-24.3 ng Pb. g-1 for Et2Pb and <1.4-13.4 ng Sn. g-1, <0.82-8.54 ng Sn. g-1, <0.25-1.16 ng Sn. g-1 and <0.08-0.61 ng Sn. g-1 for MBT, DBT, TBT and DPhT, respectively. TBT occurs in higher concentrations than the available environmental protection values in 24 and 38 sampling sites for both water and sediment samples, respectively. Other phenyltins (MPhT and TPhT) did not occur above their LOQ and therefore no background was possible to establish. Throughout this work, which is the first assessment of background concentrations for organometallic compounds at the French national level ever being published, it was possible to conclude that over the last 10-20 years organotin concentrations in French river basins have decreased while MeHg concentration remained stable

Ovarian follicular dynamics in beef cows treated with three protocols of synchronization of ovulation

Background: Artificial insemination is an established and viable technique to accelerate the genetic advancement and economic return of the cattle. However, compromises the efficiency of detection of estrus results in low insemination rates. To avoid these problems in beef herd, synchronization protocols have been developed that allow inseminate large number of animals within a set period of time. These treatments are known as protocols for synchronization of ovulation for fixed-time artificial insemination (FTAI). There are several slow-release progesterone or progestins devices on the market for use in synchronization of estrus/ovulation programs in cattle, but these devices have a high cost, which results in less use of these protocols by farmers . This study aimed to determine the follicular dynamic of a low cost protocol to synchronize ovulation, which uses vaginal sponges impregnated with medroxy-progesterone acetate (MPA; group 1) and compare it with two trade protocols (groups 2 and 3). Materials, Methods & Results: Nine Braford cows, multiparous non-lactating, cyclic and BCS > 3 (BCS = 1 extremely lean cows and BCS = 5 obese cows) where used in these trial. The animals were divided into three treatments, which all animals went for three treatments in four replicates. (Continue0 Group 1 (n = 14), animals received on day 0, a vaginal sponge impregnated with 250 mg MPA and an intramuscular (i.m.) application of 2 mg of estradiol benzoate (EB); on day 8, the vaginal sponge was removed and applied i.m. 0.5 mg cloprostenol and 24 h latter was applied i.m. 1 mg of EB. Group 2 (n = 7), the animals received on day 0, a silicone vaginal implant with 1 g of progesterone and an application i.m. of 2 mg of EB; on day 8, the implant was removed and applied i.m. 0.5 mg cloprostenol and 24 h latter was applied i.m. 1 mg of EB. Group 3 (n = 8), the animals received on day 0, a silicone ear implant impregnated with 3 mg norgestomet and an application i.m. of 3 mg norgestomet and 5 mg of estradiol valerate; on the 9th day the implant was removed. From day 0, animals were examined daily by trans-rectal ultrasound with an 8 MHz linear transducer to monitor follicular and luteal dynamics. After removal of the implant in group 3 and after application of 1 mg EB in the other groups, the animals were evaluated by ultrasound two times per day until ovulation was detected. In group 1, seven animals lost a vaginal sponge impregnated with MPA and the data were removed from analysis. The emergence of follicular wave for groups 1, 2 and 3 occurred, respectively, 3.7 ± 1.1, 3.7 ± 0.7 and 4.9 ± 1.1 days, with a statistical trend (P < 0.06) to occur earlier in groups 1 and 2 than in group 3. There was no statistical difference between groups in other variables. The interval between wave emergence and ovulation occurred in 7.4 ± 0.9, 7.3 ± 0.7 and 7.6 ± 1.3 days (P = 0.82); the interval between implant removal and ovulation occurred in 66 ± 12, 66 ± 0 and 70.5 ± 12.7 hours (P = 0.62); the dominant follicle diameter at implant removal was 10.9 ± 2.6, 12.7 ± 2.1 and 10.3 ± 2.1 mm (P = 0.13); and the larger diameter of the dominant follicle was 15.3 ± 2.9, 16.6 ± 1.3 and 15.9 ± 1.5 mm (P = 0.49) for groups 1, 2 and 3 respectively. Discussion: In this experiment, the protocols used in groups 1, 2 and 3 were effective in promoting the emergence of a synchronized new follicular wave and promote synchronized ovulation of a follicle with few days of dominance and an appropriate diameter. It was observed that numerical variations on the emergence of the new follicular wave numerically influenced in the timing ovulations. A study with a larger number of animals per group should be performed to confirm these differences between the groups

Dynamics of particulate organic matter in a coastal system characterized by the occurrence of marine mucilage – A stable isotope study

International audienceIn coastal systems, particulate organic matter (POM) originates from various autochthonous and allochthonous organic matter sources. Also, some coastal systems are characterized by the occurrence of large amounts of mucilaginous material of biologic origin (i.e. phytoplankton, bacteria), which aggregates and potentially traps other organisms and particles present in the water column. This study focuses on POM origin and spatio-temporal dynamics in the South-East coast of the Bay of Biscay, an area subject to mucilage occurrence. In order to investigate POM quantitative and qualitative (C and N elemental and isotopic ratios) characteristics, sampling was performed over an annual cycle at two sites experiencing different mucilage occurrence and river influence. Contribution of phytoplankton, terrestrial POM and anthropogenic POM to coastal-POM composition was calculated using a three-sources mixing model. Overall, phytoplankton dominated the coastal-POM composition at all seasons, sites and most of the depths (71.6 ± 24.2%). Terrestrial-POM contribution was moderate (22.7 ± 21.8%) and anthropogenic-POM contribution was usually negligible (5.7 ± 7.4%). Both sites mainly exhibited similar vertical and temporal variations in terms of POM origin and dynamics: terrestrial-POM contribution increased with depth and was higher in winter at all depths and in autumn in bottom waters, compared to other seasons. The main differences between both sites were related to the vertical dynamics of the terrestrial contribution to the coastal POM. Horizontal, vertical and temporal variation of POM composition was linked to processes driving the sedimentary hydrodynamics: the river flow, the direction of the river plume and events of sediment resuspension/deposition. During the study period, the mucilage occurred only as flocs (small aggregates). The mucilage was of autochthonous origin and did not trap detectable amount of allochthonous material. © 2016 Elsevier B.V

Ovarian follicular dynamics in beef cows treated with three protocols of synchronization of ovulation

Background: Artificial insemination is an established and viable technique to accelerate the genetic advancement and economic return of the cattle. However, compromises the efficiency of detection of estrus results in low insemination rates. To avoid these problems in beef herd, synchronization protocols have been developed that allow inseminate large number of animals within a set period of time. These treatments are known as protocols for synchronization of ovulation for fixed-time artificial insemination (FTAI). There are several slow-release progesterone or progestins devices on the market for use in synchronization of estrus/ovulation programs in cattle, but these devices have a high cost, which results in less use of these protocols by farmers . This study aimed to determine the follicular dynamic of a low cost protocol to synchronize ovulation, which uses vaginal sponges impregnated with medroxy-progesterone acetate (MPA; group 1) and compare it with two trade protocols (groups 2 and 3). Materials, Methods & Results: Nine Braford cows, multiparous non-lactating, cyclic and BCS > 3 (BCS = 1 extremely lean cows and BCS = 5 obese cows) where used in these trial. The animals were divided into three treatments, which all animals went for three treatments in four replicates. (Continue0 Group 1 (n = 14), animals received on day 0, a vaginal sponge impregnated with 250 mg MPA and an intramuscular (i.m.) application of 2 mg of estradiol benzoate (EB); on day 8, the vaginal sponge was removed and applied i.m. 0.5 mg cloprostenol and 24 h latter was applied i.m. 1 mg of EB. Group 2 (n = 7), the animals received on day 0, a silicone vaginal implant with 1 g of progesterone and an application i.m. of 2 mg of EB; on day 8, the implant was removed and applied i.m. 0.5 mg cloprostenol and 24 h latter was applied i.m. 1 mg of EB. Group 3 (n = 8), the animals received on day 0, a silicone ear implant impregnated with 3 mg norgestomet and an application i.m. of 3 mg norgestomet and 5 mg of estradiol valerate; on the 9th day the implant was removed. From day 0, animals were examined daily by trans-rectal ultrasound with an 8 MHz linear transducer to monitor follicular and luteal dynamics. After removal of the implant in group 3 and after application of 1 mg EB in the other groups, the animals were evaluated by ultrasound two times per day until ovulation was detected. In group 1, seven animals lost a vaginal sponge impregnated with MPA and the data were removed from analysis. The emergence of follicular wave for groups 1, 2 and 3 occurred, respectively, 3.7 ± 1.1, 3.7 ± 0.7 and 4.9 ± 1.1 days, with a statistical trend (P < 0.06) to occur earlier in groups 1 and 2 than in group 3. There was no statistical difference between groups in other variables. The interval between wave emergence and ovulation occurred in 7.4 ± 0.9, 7.3 ± 0.7 and 7.6 ± 1.3 days (P = 0.82); the interval between implant removal and ovulation occurred in 66 ± 12, 66 ± 0 and 70.5 ± 12.7 hours (P = 0.62); the dominant follicle diameter at implant removal was 10.9 ± 2.6, 12.7 ± 2.1 and 10.3 ± 2.1 mm (P = 0.13); and the larger diameter of the dominant follicle was 15.3 ± 2.9, 16.6 ± 1.3 and 15.9 ± 1.5 mm (P = 0.49) for groups 1, 2 and 3 respectively. Discussion: In this experiment, the protocols used in groups 1, 2 and 3 were effective in promoting the emergence of a synchronized new follicular wave and promote synchronized ovulation of a follicle with few days of dominance and an appropriate diameter. It was observed that numerical variations on the emergence of the new follicular wave numerically influenced in the timing ovulations. A study with a larger number of animals per group should be performed to confirm these differences between the groups