Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides

A novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Thirteen of the synthesized compounds showed a significant antileishmanial activity, with 50% effective concentration (EC50) values lower than that for the reference drug miltefosine (EC50, 2.84¿¿M). In addition, the derivatives 9, 11, 42, and 47, with EC50 between 1.1 and 1.95¿¿M, also displayed excellent selectivity (selectivity index ranged from 12.4 to 22.7) and were tested against infected macrophages. Compound 11, a derivative with a cyclohexyl chain, exhibited the highest activity against intracellular amastigotes, with EC50 values similar to those observed for the standard drug edelfosine. Structure-activity relationship analyses revealed that N-aliphatic substitution in urea and selenourea is recommended for the leishmanicidal activity of these analogs. Preliminary studies of the mechanism of action for the hit compounds was carried out by measuring their ability to inhibit trypanothione reductase. Even though the obtained results suggest that this enzyme is not the target for most of these derivatives, their activity comparable to that of the standards and lack of toxicity in THP-1 cells highlight the potential of these compounds to be optimized for leishmaniasis treatment.Comunidad de MadridMinisterio de Economía y CompetitividadFoundation for Applied Medical Investigatio

Monitorización de la frecuencia cardíaca en las labores de extinción de incendios forestales, para la prevención de riesgos laborales

P. 6-26Ante la previsión de aumento de incendios forestales en la zona meditarránea,TRAGSA y la Fraternidad Muprespa analizan los aspectos derivados de la frecuencia cardiaca en las labores de extinción de incendios forestales. El trabajo físico del personal especialista en extinción de incendios forestales durante la extinción de incendios se realiza a una intensidad de esfuerzo que es lo suficientemente alta como para conllevar un elevado coste energético, y que se corresponde a una carga de trabajo que requiere y exige una buena condición física para afrontarla con las suficientes garantías y con el menor riesgo para la salud.N

Low stocking density negatively affects growth, metabolism and stress pathways in juvenile specimens of meagre (Argyrosomus regius, Asso 1801)

The influence of culture density on growth, stress system and metabolism has been assessed in A. regius juveniles submitted to different initial stocking densities (3, 7, 10 and 13 g L− 1) for 40 days. On days 0, 12, 27 and 40 of the experiment, biometric parameters were measured. In addition, plasma, liver and muscle samples were taken for biochemical analysis at the end of experimental time. Our results showed better growth rates and feed utilization in those specimens held at high stocking densities when compared to those under low stocking densities. In addition, higher plasma cortisol, glucose and triglycerides levels found in the lowest stocking density tested suggest an activation of the stress system in fish held at this condition. Moreover, no changes in hepatic metabolites were observed, while values of muscle triglycerides, amino acids and lactate enhanced when stocking density increased. In conclusion, the culture of juvenile A. regius at higher initial densities (at least 13 g L− 1) ensures better growth and the optimization of the existing facilities, improving welfare of this species in aquaculture systems.Study funded by project AGL2013-48835-C2-1-R (Ministerio de Economía y Competitividad, Spain) awarded to J.M.M.Peer reviewe

Effects of sustained exercise on GH-IGFs axis in gilthead sea bream (Sparus aurata)

The endocrine system regulates growth mainly through the growth hormone (GH)/insulin-like growth factors (IGFs) axis and, although exercise promotes growth, little is known about its modulation of these factors. The aim of this work was to characterize the effects of 5 wk of moderate sustained swimming on the GH-IGFs axis in gilthead sea bream fingerlings. Plasma IGF-I/GH ratio and tissue gene expression of total IGF-I and three splice variants, IGF-II, three IGF binding proteins, two GH receptors, two IGF-I receptors, and the downstream molecules were analyzed. Fish under exercise (EX) grew more than control fish (CT), had a higher plasma IGF-I/GH ratio, and showed increased hepatic IGF-I expression (mainly IGF-Ia). Total IGF-I expression levels were similar in the anterior and caudal muscles; however, IGF-Ic expression increased with exercise, suggesting that this splice variant may be the most sensitive to mechanical action. Moreover, IGFBP-5b and IGF-II increased in the anterior and caudal muscles, respectively, supporting enhanced muscle growth. Furthermore, in EX fish, hepatic IGF-IRb was reduced together with both GHRs; GHR-II was also reduced in anterior muscle, while GHR-I showed higher expression in the two muscle regions, indicating tissue-dependent differences and responses to exercise. Exercise also increased gene and protein expression of target of rapamycin (TOR), suggesting enhanced muscle protein synthesis. Altogether, these data demonstrate that moderate sustained activity may be used to increase the plasma IGF-I/GH ratio and to potentiate growth in farmed gilthead sea bream, modulating the gene expression of different members of the GH-IGFs axis (i.e., IGF-Ic, IGF-II, IGFBP-5b, GHR-I, and TOR).E. J. Vélez and A. Millán-Cubillo are supported by a predoctoral fellowship from the Ministerio de Ciencia e Innovación (MICINN). This study was supported by the projects from the MICINN AGL2009-12427 and AGL2012-39768 to J. Gutiérrez, and the Xarxa de Refèrencia d’R+D+I en Aqüicultura and the SGR2009-00402 from the Generalitat de CatalunyaPeer reviewe

Cáncer de cabeza y cuello: proceso asistencial integrado

YesLa denominación de carcinomas de cabeza y cuello, o tracto aero-digestivo superior, supone un agrupamiento, no sólo por su mera localización anatómica, sino porque existen elementos comunes compartidos por estas neoplasias: etiología, epidemiología, histología, evolución clínica, procedimientos diagnósticos, enfoques terapéuticos, medidas de seguimiento. No obstante, la variabilidad en la localización, afectando órganos que participan en la fonación y la deglución, funciones fundamentales para el paciente, y su comportamiento evolutivo, exigen que los cánceres de cabeza y cuello sean abordados desde una perspectiva multidisciplinar, tanto en las actividades de detección precoz como en el diagnóstico y tratamiento, al estar implicados una gran variedad de profesionales tanto del ámbito de la Atención Primaria como de Atención Hospitalaria, siendo además imprescindible una perfecta coordinación que garantice la continuidad asistencial

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P <.001). Overall motor and cognitive performance (P <.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P <.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P <.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P <.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients