Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus

8 páginas, 2 figuras, 2 tablas.The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with Haemonchus contortus. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200 mg/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7 days at a dose of 120 mg/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants. © 2022, The Author(s).Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and MICINN/AEI (PID2020- 119035RB-100). EVG was funded by FPU17/00627, FPU17/05346; VCGA, MAB, MCP and LGP are recipients of Junta de Castilla y León (JCyL) (LE082-18, LE051-18, LE135-19, LE096-20, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y competitividad; MMV, RYC-2015-18368).Peer reviewe

Addressing the evolution of automated user behaviour patterns by runtime model interpretation

The final publication is available at Springer via http://dx.doi.org/10.1007/s10270-013-0371-3The use of high-level abstraction models can facilitate and improve not only system development but also runtime system evolution. This is the idea of this work, in which behavioural models created at design time are also used at runtime to evolve system behaviour. These behavioural models describe the routine tasks that users want to be automated by the system. However, users¿ needs may change after system deployment, and the routine tasks automated by the system must evolve to adapt to these changes. To facilitate this evolution, the automation of the specified routine tasks is achieved by directly interpreting the models at runtime. This turns models into the primary means to understand and interact with the system behaviour associated with the routine tasks as well as to execute and modify it. Thus, we provide tools to allow the adaptation of this behaviour by modifying the models at runtime. This means that the system behaviour evolution is performed by using high-level abstractions and avoiding the costs and risks associated with shutting down and restarting the system.This work has been developed with the support of MICINN, under the project EVERYWARE TIN2010-18011, and the support of the Christian Doppler Forschungsgesellschaft and the BMWFJ, Austria.Serral Asensio, E.; Valderas Aranda, PJ.; Pelechano Ferragud, V. (2013). Addressing the evolution of automated user behaviour patterns by runtime model interpretation. Software and Systems Modeling. https://doi.org/10.1007/s10270-013-0371-3SWeiser, M.: The computer of the 21st century. Sci. Am. 265, 66–75 (1991)Serral, E., Valderas, P., Pelechano, V.: Context-adaptive coordination of pervasive services by interpreting models during runtime. Comput. 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Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta

11 páginas, 5 figuras, 4 tablas.Gastrointestinal nematodes (GIN) infections are a serious problem in livestock production due to the great economic losses they cause. Their control is increasingly difficult because of the rapid development of drug resistance and the limited number of available drugs. Therefore, this study evaluated 18 aminoalcohol and 16 diamine derivatives against eggs, first and third stage larvae from a susceptible and a resistant isolate of Tela-dorsagia circumcincta collected from sheep. The effectiveness of the in vitro anthelmintic activity of the com-pounds was evaluated using three different procedures: Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT). Those compounds with activities higher than 90 % in the initial screening at 50 μM were selected to determine their half maximal effective concentration (EC50). In parallel, cytotoxicity assays were conducted on Caco2 and HepG2 cell lines to calculate Selectivity Indexes (SI) for each compound. The diamine 30 presented the best results in preventing egg hatching, displaying the lowest EC50 value (1.01 ±0.04 μM) of all compounds tested and the highest SI (21.21 vs. Caco-2 cells). For the LMIT, the diamine 34 showed the highest efficacy, with EC50 values of 2.67 ±0.08 and 3.02 ±0.09 μM on the susceptible and resistant isolate of the parasite, respectively.We are grateful to Dave Bartley, from Moredun Research Institute for providing the triple-resistant isolate of T. circumcincta. RE thank the RICET contract (E07D401988BR) EC Programs. Financial support came from MINECO: RETOS (AGL2016-79813-C2-1R/2R) and Junta de Castilla y León (JCyL) co-financed by FEDER, UE (LE020P17). EVG was funded by FPU16/03536; JV, VCGA and MAB are recipients of Junta de Castilla y Leon and European Social Found (ESF)’s Fellowships Scheme for Doctoral Training Programs. (JCYL-USAL35B, LE082-18, LE051-18, respectively) and MMV by the Spanish “Ramon y Cajal” Programme (Ministerio de Economía y Competitividad; RYC-2015-18368).Peer reviewe

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

New synthetic benzimidazole with potential anthelmintic activity

Póster presentado al: 2nd Working Groups Meeting COMBAR (Combatting Anthelmintic Resistance in Ruminants). León, 26-27 Septiembre 2018.Study funded by AGL2016-79813-C2-1/2-RPeer reviewe

Determinación de los niveles de IgA frente nematodos gastrointestinales como marcador de resistencia a la infección en el ganado ovino

Trabajo presentado al: XXII Congreso de Parasitología, SOCEPA. Madrid, julio 2022

New benzimidazole derivates as potential anthelmintic compounds

Trabajo presentado al: 27th International Conference of the World Association for the Advancement of Veterinary Parasitology. Abstract book, Oral Sesion OA36.08, pp. 135. Madison (USA). 7-11 julio 2019.Gastrointestinal nematode infections cause direct and indirect losses of great economic impact worldwide by decreasing productions yields and increasing health care cost in sheep. Thus, the aim of this study was to test the nematocidal e@ect of a new collection of benzimidazole derivatives against Teladorsagia circumcincta by in vitro methods. Compounds were tested in eggs, first stage larvae (L1) and thrid stage larvae (L3) by means of the Egg Hatch Assay, L1 Mortality Assay and the Larval Migration Inhibition Assay. An initial screening was done at a single concentration of 50 $M; those molecules that showed an activity higher than >90maximal e@ective concentration (EC50) and were tested again against a resistant strain. Finally, the anthelmintic e@ect was compared with their cytotoxicity in two digestive established cell lines, Caco-2 and HepG2, and their corresponding concentrations required to reduce cell viability by 50determined in order to establish a selective index (SI) for each molecules. Only 5 of the 18 compounds were able to arrest the hatching of eggs in the susceptible strain in more than 99$M and 4 of them were also able to produce a significant e@ect on the resistant strain used in the current study. Considering only those compounds that have a significant e@ect, their CC50 values were very homogeneous between Caco-2 and HepG2, which makes that SI values were comprised between 1.84 to 3.60 for Caco-2 cells and 1.53 and 2.73 for HepG2 cells. These results indicate that they could be good candidates for further studies to determine their in vivo activity.Study funded by AGL2016-79813-C2- 1-R, Junta de Castilla y León co-financed by FEDER [LE020P17], EVG by FPU17/00627 and MMV by RYC-2015-1836

In vivo toxicity and efficacy of two diamine and one benzimidazole derivatives against the gastrointestinal nematode Haemonchus contortus

Trabajo presentado al: 28th International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP). Dublín. Virtual meeting.MINECO (AEI, FEDER, UE): AGL2016-79813-C2-1R/2R and SAF2017-83575-R and Junta de Castilla y León (JCyL) cofinanced by FEDER, UE [LE020p17]. EVG is funded by JCyL and MMV by Ramón y Cajal Programme (RYC-2015-18368).Peer reviewe

Presencia de Leishmania infantum en distintas muestras biológicas de lobos ibéricos (Canis lupus signatus) de la provincia de Zamora

Trabajo presentado al: XXII Congreso de Parasitología, SOCEPA. Madrid, Julio. 2022