A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Direct effect of p,p'- DDT on mice liver

ABSTRACT Contact with the pesticide dichlorodiphenyltrichloroethane (p,p′-DDT) can be the cause of various harmful effects in humans, wildlife, and the environment. This pesticide is known to be persistent, lipophilic, resistant to degradation, and bioaccumulive in the environment and to be slowly released into bloodstream. Growing evidence shows that exposure to DDT is linked to type 2 diabetes mellitus. Individuals exposed to elevated levels of DDT and its metabolite have an increased prevalence of diabetes and insulin resistance. To evaluate these possible relationships, experiments were performed on eight-week-old female mice, divided into three groups (n = 10 per group): Group 1 received a vehicle-control intraperitoneal (i.p.) injection of sesame oil; Groups 2 and 3 received an i.p. dose of 50 and 100 µg/g p,p′-DDT respectively, dissolved in sesame oil. All groups were treated once daily for four days. Real-time PCR analysis of several genes was undertaken. Additionally, biochemical parameters and histopathological changes were measured. NQO1, HMOX1, NR1I3 and NR3C1 were up-regulated in DDT-exposed animals compared to the vehicle control group, while only SREBP1 was down-regulated in the 100 µg/g group. MTTP and FABP5, not previously reported for DDT exposure, but involved in regulation of fatty acid fluxes, could also function as biomarkers cross-talking between these signaling pathways. These results suggest that beyond epidemiological data, there is increasing molecular evidence that DDT may mimic different processes involved in diabetes and insulin resistance pathways

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Caracterización del sistema neurosecretor de la hormona inhibidora de las gonadotrofinas (GnIH) en el lenguado senegalés, Solea senegalensis, y regulación del eje endocrino reproductor por factores ambientales y métodos de cultivo

Tesis llevada a cabo para conseguir el grado de Doctor por la Universidad de Cádiz.--2018-07-19.--Sobresaliente cum laudemEl cultivo de lenguado senegalés, Solea senegalensis, está actualmente en un gran proceso de expansión, aunque todavía persisten algunos problemas asociados a su cultivo, principalmente relacionados con el control deficiente de su reproducción, lo que limita el crecimiento definitivo en la acuicultura de esta especie. El principal problema reside en la incapacidad de los reproductores de cultivo (generación F1; nacidos en cautividad) de producir puestas de huevos fecundadas, lo que de momento se soluciona, a nivel industrial, con el uso de reproductores “salvajes” (obtenidos del medio natural y aclimatados a las condiciones de cautividad). El problema de los reproductores de cultivo está directamente relacionado con una inhibición del comportamiento reproductivo y, en general, con una depresión del sistema endocrino reproductor y en el desarrollo de los gametos. El hecho de que los juveniles de lenguado capturados en el medio natural (“salvajes”) y criados en cautividad en las mismas condiciones que los F1 hasta la edad adulta, sí sean capaces de producir puestas fecundadas, a diferencia de lo que ocurre con los F1, apunta a que el desarrollo temprano de los individuos en condiciones artificiales (cautividad) es el factor determinante de las diferencias observadas en la capacidad reproductiva entre ambas poblaciones. Así, la hipótesis de trabajo de esta tesis doctoral plantea que las condiciones ambientales (ciclos de luz y temperatura) durante el periodo embrionario y larvario son críticas para el desarrollo normal del sistema de regulación neuroendocrina de los lenguados, de forma que las condiciones inadecuadas de cría pueden determinar efectos negativos en las larvas que afecten al desarrollo del eje reproductivo y a sus características en la vida adulta. El esquema clásico de control neuroendocrino de la reproducción que ha estado vigente durante las últimas décadas se ha visto revolucionado recientemente por el descubrimiento de un nuevo neuropéptido inhibidor del eje reproductivo, perteneciente a la familia RF-amida, y denominado en base a sus funciones como hormona inhibidora de las gonadotrofinas o GnIH. La presencia de diferentes ortólogos de la GnIH se ha descrito en todos los grupos de vertebrados estudiados, incluidos los peces. Sin embargo, los avances científicos sobre la Gnih en peces son todavía escasos, contradictorios y poco concluyentes, y se conoce muy poco sobre cómo se expresa, cómo se regula y qué funciones desempeña la Gnih durante el desarrollo temprano. Por ello, en esta Tesis Doctoral, se ha planteado como objetivo principal progresar en el conocimiento del sistema neurosecretor de la Gnih del lenguado, Solea senegalensis, esclarecer su posible interacción con otros sistemas neuroendocrinos y endocrinos implicados en el control del ciclo reproductivo, determinar sus posibles funciones y caracterizar su regulación por factores ambientales (fotociclos, espectro de luz, termociclos diarios y estacionales) y de cultivo (cultivo en mesocosmos) durante la ontogenia y en ejemplares adultos del lenguado. Los resultados obtenidos en esta tesis doctoral nos han permitido identificar la presencia de un sistema Gnih funcional en el lenguado, caracterizar su distribución celular en el cerebro y en la hipófisis, y determinar sus efectos inhibidores sobre el eje reproductivo de esta especie. Asimismo, hemos puesto de manifiesto que tanto el sistema Gnih como otros factores neuroendocrinos y endocrinos implicados en el proceso reproductivo del lenguado se encuentran modulados por factores abióticos (fotociclos de luz azul, termociclos diarios y estacionales) y condiciones de cultivo (cultivo intensivo versus mesocosmos), en particular, en momentos críticos de la ontogenia como el desarrollo temprano, la metamorfosis y la diferenciación sexual, pero también en estadios adultos. Los resultados obtenidos en esta Tesis Doctoral refuerzan la importancia del uso de condiciones de cultivo del lenguado más próximas a las condiciones naturales (ciclos de luz-oscuridad de luz azul, termociclos diarios y estacionales naturales), en especial, durante los estadios tempranos del cultivo de esta especie.Peer reviewe

The ontogeny of sole (Solea senegalensis) neuroendocrine systems is affected by environmental and culture conditions

Trabajo presentado en el 10º Congreso de la Asociación Ibérica de Endocrinología Comparada (AIEC), celebrado en Castellón (España), del 23 al 25 de septiembre de 2015Aquaculture of sole is seen as an excellent choice for diversification and economic expansion of the European aquaculture. Reproduction of wild sole breeders in captivity is successful whilst sole specimens from F1 generation present reproductive dysfunctions. Fish farming in captivity introduces variations in environmental conditions compared to natural ecosystems, which could affect the ontogeny of the brain and neuroendocrine systems and, therefore, the reproductive performance and behavior. However, information on how environmental and culture conditions affect the establishment of fish reproductive systems is rather scarce. For this purpose, sole larvae were exposed to: 1) daily thermocycle and blue light (18-21ºC; TCblue) or, 2) constant temperature and white light (19.5ºC; cteW; routine aquaculture conditions). In addition, and to determine a potential sensitive period, the TCblue conditions were applied in different time frames: 1) until metamorphosis (0-12 days post-hatching or dph), 2) post-metamorphosis (0-30 dph) or, 3) gonad differentiation (0-100 dph). In other experiment, development of sole embryo and larvae under routine aquaculture conditions and mesocosm conditions was compared. Effects were determined by analyzing gonadotropin-releasing hormone (GnRH), kisspeptin and gonadotropin-inhibitory hormone (GnIH) gene expression by qPCR. The results obtained demonstrated that under routine aquaculture conditions, developing sole exhibited higher GnIH transcript levels in critical ontogenetic periods (sex differentiation) compared to specimens reared under natural thermocycles and blue lights. Mesocosm culture conditions also affected GnIH, sGnRH and kisspeptin ontogenetic expression patterns. Our results evidence that routine conditions used in aquaculture practice can disturb the natural organization of sole neuroendocrine systems, reinforcing the importance of mimicking natural environmental conditions during fish rearing.Funded by MINECO (AGL2010-22139-C03-03 and AGL2013-49027-C3-2-R grants to JAM-C and BES-2011-047276 Fellow to MA-G)Peer reviewe

The gonadotropin-inhibitory hormone system of sole, Solea senegalensis

Resumen del trabajo presentado en el 11th International Symposium on Reproductive Physiology of Fish, celebrado en Manaus (Brasil) del 03 al 08 de junio de 2018.Gonadotropin-inhibitory hormone (GnIH) belongs to the RFamide family of neuropeptides and exhibits orthologs in different vertebrate groups, including fish, which inhibits the synthesis and/or release of gonadotropin-releasing hormone and gonadotropins. The Senegalese sole, Solea senegalensis, is a flatfish species with increasing interest for Mediterranean aquaculture. However, reproductive problems exhibited by F1 generation of cultured soles are limiting the development of the aquaculture of this species. Therefore, the aim of this study was to obtain pioneer information on this inhibitory GnIH system and elucidate its distribution, function and daily/seasonal regulation in the sole. [Methods]: The distribution of GniH in the brain and pituitary of sole was determined by RT-PCR and immunohistochemistry by using specific antibodies generated against sole GnIH-1 (ssGnIH-1), GnIH-2 (ssGnIH-2) and GnIH-3 (ssGnIH-3). Moreover, ssGnIH-2 and ssGnIH-3 were injected intramuscularly (0.1 and 1 ¿g/g bw) and the effects of both peptides on the expression of gnrh-1, gnrh-2, gnrh-3, kiss2, fsh¿, lh¿ and gh were determined by real time quantitative PCR. Finally, the daily and seasonal expression of gnih was determined by real time quantitative PCR. [Results and Discussion]: The expression of gnih was particularly evident in the diencephalon, but also in the olfactory bulbs/cerebral hemispheres, optic tectum/tegmentum, retina, and pituitary. We showed the presence of ssGnIH-immunoreactive cell bodies in the olfactory bulbs, ventral telencephalon, caudal preoptic area, dorsal tegmentum and rostral rhombencephalon. The ssGnIH fibers innervated the brain and pituitary of sole profusely. Intramuscular injection of ssGnih-3 provoked a significant reduction in gnrh-3 and lh¿ expression. Daily rhythms in gnih expression were found after the completion of metamorphosis, peaking at the beginning of the night. Seasonal variations were also observed in F1 male and female adult specimens, with high levels in April/May, which corresponded with the maturation and spawning season. [Conclusion]: Our results reveal the existence of a functional GnIH system in sole, which could represent an important inhibitory factor, underlying the reproductive dysfunctions observed in this flatfish species. The existence of daily and seasonal variations in the expression of gnih could reflect a role of this neuropeptidergic system in the mediation of the effects of environmental factors

Cardioprotection with halogenated gases: how does it occur?

Jose Luis Guerrero-Orriach,1–3 Juan Jose Escalona Belmonte,1 Alicia Ramirez Fernandez,1 Marta Ramirez Aliaga,1 Manuel Rubio Navarro,1 Jose Cruz Mañas1 1Department of Cardioanesthesiology, Virgen de la Victoria University Hospital, 2Instituto de Investigación Biomédica de Málaga (IBIMA), 3Department of Pharmacology and Pediatrics, University of Malaga, Malaga, Spain Abstract: Numerous studies have studied the effect of halogenated agents on the myocardium, highlighting the beneficial cardiac effect of the pharmacological mechanism (preconditioning and postconditioning) when employed before and after ischemia in patients with ischemic heart disease. Anesthetic preconditioning is related to the dose-dependent signal, while the degree of protection is related to the concentration of the administered drug and the duration of the administration itself. Triggers for postconditioning and preconditioning might have numerous pathways in common; mitochondrial protection and a decrease in inflammatory mediators could be the major biochemical elements. Several pathways have been identified, including attenuation of NFκB activation and reduced expression of TNFα, IL-1, intracellular adhesion molecules, eNOS, the hypercontraction reduction that follows reperfusion, and antiapoptotic activating kinases (Akt, ERK1/2). It appears that the preconditioning and postconditioning triggers have numerous similar paths. The key biochemical elements are protection of the mitochondria and reduction in inflammatory mediators, both of which are developed in various ways. We have studied this issue, and have published several articles on cardioprotection with halogenated gases. Our results confirm greater cardioprotection through myocardial preconditioning in patients anesthetized with sevoflurane compared with propofol, with decreasing levels of troponin and N-terminal brain natriuretic peptide prohormone. The difference between our studies and previous studies lies in the use of sedation with sevoflurane in the postoperative period. The results could be related to a prolonged effect, in addition to preconditioning and postconditioning, which could enhance the cardioprotective effect of sevoflurane in the postoperative period. With this review, we aim to clarify the importance of various mechanisms involved in preconditioning and postconditioning with halogenated gases, as supported by our studies. Keywords: sevoflurane, preconditioning, postconditioning, mechanisms, enzyme&nbsp

Gonadotropin inhibitory hormone down-regulates the brain-pituitary reproductive axis of male European sea bass (dicentrarchus labrax)

Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II- 2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide.The research leading to these results has received funding from the Junta de Andalucía (P10-AGR-05916), the European Union’s Seventh Framework Programme (FP7/2007-2013, grant agreement no. 331964) to J.A.M.C. and Generalitat Valenciana (PROMETEOII/2014/051) to S.Z. J.A.P.-S. is a fellow FPI from the Junta de Andalucı´a. M.C. was a recipient of a Marie Curie contract from UEPeer reviewe

Exposure of sole (Solea senegalensis) larvae to different environmental conditions affect the synthesis of reproductive hormones

Trabajo presentado en el 10º Congreso de la Asociación Ibérica de Endocrinología Comparada (AIEC), celebrado en Castellón (España), del 23 al 25 de septiembre de 2015In fish, environmental factors have profound effects on larval development. In sole, we have recently shown that daily thermocycles, compared to constant temperatures, affect gonad differentiation (GD) and change sex ratios. Also, blue light affects positively several metabolic and reproductive parameters, compared to other light spectra. The mechanisms involved in the integration of environmental signals in fish larvae and the early establishment of the reproductive axis are largely unknown. This study investigated the combined effects of light and temperature during early development. Sole larvae were exposed to, 1) daily thermocycle and blue light (18-21ºC; TCblue) or, 2) constant temperature and white light (19.5ºC; cteW; routine aquaculture conditions). In addition, and to determine a potential sensitive period, the TCblue conditions were applied in different time frames, 1) until metamorphosis (0-12 days post hatching (dph)), 2) post-metamorphosis (0-30 dph) or, 3) gonad differentiation (0-100 dph). Effects were studied by analyzing steroid levels (ELISA) and gonadotropin gene expression (qPCR). Body weight was similar in all TCblue groups and, from 30 dph onwards, higher than in cteW larva. Metamorphosis happened at 13-20 dph in all groups. Expression of follicle-stimulating hormone beta (fshb) and luteinizing hormone beta (lhb)) subunits increased at metamorphosis, but only under TCblue; they peaked again at GD and, in most sampling points, expression was higher in TCblue groups than cteW. Levels of estradiol, testosterone and 11-ketotestosterone increased at metamorphosis and GD, whereas the progestrogen 17,20ß-P increased after metamorphosis and was maintained high until 138 dph; no clear effect of treatments was evident. The results showed a significant synthesis of reproductive hormones during larval ontogeny and GD which was influenced by light and temperature regimes.Work funded by the Spanish Ministry of Economy and Competitiveness (AGL2010-22139-C03-02 and AGL2013-49027-C3-3-R).Peer reviewe