Instituto Murciano Of Investigacion Biosanitaria

Murcia, Spain

Instituto Murciano Of Investigacion Biosanitaria

Murcia, Spain
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Canovas S.,University of Murcia | Canovas S.,Instituto Murciano Of Investigacion Biosanitaria | Ivanova E.,Babraham Institute | Romar R.,University of Murcia | And 13 more authors.
eLife | Year: 2017

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT. © Canovas et al.


Garcia-Perez D.,University of Murcia | Garcia-Perez D.,Instituto Murciano Of Investigacion Biosanitaria | Laorden M.L.,University of Murcia | Laorden M.L.,Instituto Murciano Of Investigacion Biosanitaria | And 2 more authors.
Molecular Neurobiology | Year: 2017

Pleiotrophin (PTN) and midkine (MK) are secreted growth factors and cytokines, proposed to be significant neuromodulators with multiple neuronal functions. PTN and MK are generally related with cell proliferation, growth, and differentiation by acting through different receptors. PTN or MK, signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), lead to the activation of extracellular signal-regulated kinases (ERKs) and thymoma viral proto-oncogene (Akt), which induce morphological changes and modulate addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines. In the present work, we studied the effect of acute morphine, chronic morphine, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the ventral tegmental area (VTA). Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were upregulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminergic neurons expressed RPTPβ/ζ. Interestingly, p-ERK 1/2 levels during chronic morphine and morphine withdrawal correlated RPTPβ/ζ expression. All these observations suggest that the neuroprotective and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by these cytokines. © 2016, Springer Science+Business Media New York.


Popovic N.,University of Murcia | Popovic N.,Instituto Murciano Of Investigacion Biosanitaria | de Bejar V.G.,Instituto Murciano Of Investigacion Biosanitaria | de Bejar V.G.,Santa Lucía University | And 4 more authors.
Frontiers in Pharmacology | Year: 2017

The purpose of the present study was to examine the effects of the phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, verapamil (1.0, 2.5, 5.0, or 10 mg/kg i.p.), administered immediately after the acquisition task, on memory consolidation of the open field habituation task, in male Wistar rats. On the 48 h retested trial, all tested parameters (ambulation in the side wall and in the central areas, number of rearing, time spent grooming and defecation rate) significantly decreased in the saline treated animals. A significant decrease of rearing was observed in all verapamil treated groups. On the retention day, the ambulation in the side wall and central areas significantly decreased in the animals treated with 1 mg/kg and 10 mg/kg of verapamil, while the time spent grooming and the defecation rate significantly decreased only in the group treated with 1 mg/kg of verapamil. According to the change ratio scores that correct the individual behavioral baseline differences during initial and final sessions, habituation deficit was found in animals treated with verapamil as follows: ambulation along the side wall area (1, 2.5, and 5 mg/kg), number of rearing (all used dose) and time spent grooming (2.5, 5, and 10 mg/kg). In conclusion, the present data suggest that the post-training administration of verapamil, parameter- and dose-dependently, impairs the habituation to a novel environment. © 2017 Popovic, Giménez de Béjar, Caballero-Bleda and Popovic.


Sanchez-Navarro J.P.,University of Murcia | Sanchez-Navarro J.P.,Instituto Murciano Of Investigacion Biosanitaria | Maldonado E.F.,University of Malaga | Martinez-Selva J.M.,University of Murcia | And 3 more authors.
Psychophysiology | Year: 2012

We studied the changes in salivary alpha-amylase (sAA) and other psychophysiological indices (heart rate, skin conductance, and corrugator supercilii activity) elicited by sustained exposure to affective pictures. Thirty-nine subjects viewed five blocks of pictures depicting mutilations, human attack, neutral scenes, sport/adventure, and erotica. Each block comprised 12 pictures of the same content. Saliva samples were collected before and after each block of pictures. The results showed that mutilation pictures promoted the greatest increase in sAA activity and output, as well as greater corrugator supercilii activity than pleasant pictures. Skin conductance response did not differ among high arousal picture contents. Changes in sAA varied with the affective valence but not with the arousal ratings of the pictures. Our results point to sAA as an index directly related to the unpleasantness elicited by sustained exposure to affective stimuli. © 2012 Society for Psychophysiological Research.


PubMed | Instituto Murciano Of Investigacion Biosanitaria, Servicio de Planificacion y Financiacion Sanitaria and Centro Regional Of Estadistica
Type: Comparative Study | Journal: Salud publica de Mexico | Year: 2015

To compare the self-perceived health, use of health services and unmet need for health care (UNHC) among immigrants and native populations of Southeast Spain.Cross-sectional study of two representative samples of 1150 immigrants, and 1303 native participants from the National Health Survey. A single database was created with specific weights for each sample, and prevalence ratios (PR) were estimated by multivariate regression.Moroccans, Ecuadorians and Eastern Europeans (EE) reported poorer health than the native population (PRs [CI95%]: 2.45 [1.91-3.15]; 1.51 [1.28-1.79] and 1.44 [1.08-1.93], respectively). Immigrants made greater use of emergencies that natives (except for EE) and had lower use of medication. Moroccan showed the greatest difference in the frequency of UNHC (PR [CI95%]:12.20 [5.25 - 28.37]), mainly because of working limitations (46%).The health status and use of health services among immigrants differ significantly from those of natives. Results highlight the higher frequency of UNHC among immigrants, especially high in Moroccans.


Cruzado J.,Instituto Murciano Of Investigacion Biosanitaria | Sanchez F.I.,University of Murcia | Abellan J.M.,University of Murcia | Perez-Riquelme F.,Instituto Murciano Of Investigacion Biosanitaria | Carballo F.,University of Murcia
Best Practice and Research: Clinical Gastroenterology | Year: 2013

Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed once common economic evaluation standards are established in order to alleviate the methodological heterogeneity prevailing in study results. © 2013 Elsevier Ltd. All rights reserved.


Garcia-Garcia E.,University of Murcia | Garcia-Garcia E.,Instituto Murciano Of Investigacion Biosanitaria | Gomez-Gonzalez N.E.,University of Murcia | Meseguer J.,University of Murcia | And 2 more authors.
Developmental and Comparative Immunology | Year: 2014

Histamine is stored inside hemocytes of the tunicate Styela plicata (Chordata, Tunicata, Ascidiacea), but no evidence on its role in the regulation of the immune response of this species has been reported. We examined whether histamine participated in the regulation of inflammation and host defense in S. plicata. The presence of histamine inside S. plicata hemocytes was confirmed by flow cytometry, and histamine release was detected by ELISA, after in vitro hemocyte stimulation with different PAMPs. In vitro hemocyte treatment with histamine, or specific histamine-receptor agonists, reduced their phagocytic ability. Injection of histamine into the tunic recruited hemocytes to the site of injection. Systemic injection of histamine, or the histamine-releasing agent compound 48/80, decreased the phagocytic ability of hemocytes. Histamine promoted the constriction of tunic hemolymph vessels in vivo, having a direct effect on vasoconstriction in tunic explants. These results provide for the first time clear evidence for the involvement of histamine in the regulation of inflammation and host defense in tunicates. © 2014 Elsevier Ltd.


Garcia-Perez D.,University of Murcia | Garcia-Perez D.,Instituto Murciano Of Investigacion Biosanitaria | Nunez C.,University of Murcia | Nunez C.,Instituto Murciano Of Investigacion Biosanitaria | And 4 more authors.
Addiction Biology | Year: 2016

Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real-time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH+ neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine-withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug-reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal-induced alterations of DA neurons activity in the mesolimbic pathway. Dopamine is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. © 2014 Society for the Study of Addiction.


Garcia-Perez D.,University of Murcia | Garcia-Perez D.,Instituto Murciano Of Investigacion Biosanitaria | Laorden M.L.,University of Murcia | Laorden M.L.,Instituto Murciano Of Investigacion Biosanitaria | And 2 more authors.
International Journal of Neuropsychopharmacology | Year: 2016

Background: Most classes of addictive substances alter the function and structural plasticity of the brain reward circuitry. Midkine (MK) and pleiotrophin (PTN) are growth/differentiation cytokines which, similarly to neurotrophins, play an important role in repair, neurite outgrowth, and cell differentiation. PTN or MK signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), leads to the activation of extracellular signal-regulated kinases and thymoma viral proto-oncogene. This activation induces morphological changes and modulates addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines. Methods: In the present work we studied the effect of acute morphine administration, chronic morphine administration, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the nucleus accumbens. Results: Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were up-regulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminoceptive neurons expressed RPTPβ/ζ. Conclusions: All these observations suggest that the neurotrophic and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by cytokines. © The Author 2015.


PubMed | Instituto Murciano Of Investigacion Biosanitaria
Type: Journal Article | Journal: Best practice & research. Clinical gastroenterology | Year: 2013

Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed once common economic evaluation standards are established in order to alleviate the methodological heterogeneity prevailing in study results.

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