Role of Glucocorticoid Receptor in the Relation between Stress and Opiate Addiction

Stressful situations can result in relapse in dependent or abstinent causing reinstatement of drug-seeking. In fact, it has been suggested that activation of the brain stress system results in glucocorticoid release that affects the dopaminergic pathways. Also, the noradrenergic system innervates the extrahypothalamic BSS from the nucleus of tractus solitarius (NTS), resulting in a feedforward loop between the corticotropin-releasing factor (CRF) and noradrenaline (NA) crucial in drug addiction and relapses. Glucocorticoids interact with two receptors: mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) which bind to a GRE site located in tyrosine hydroxylase (TH), resulting in the upregulation of TH synthesis and, finally, increasing dopamine (DA) release in the nucleus accumbens. TH upregulation depends on the phosphorylation of serine 31 and/or serine 40. Previous research has shown that protein kinase C (PKC) activates extracellular signal-regulated kinase (ERK) pathway and in turn phosphorylates serine 31 in the NTS. Besides, cAMP response element binding protein (CREB) is regulated by PKA and PKC. The results shown after pretreating morphine-withdrawn rats with mifepristone and spironolactone (GR and MR antagonists, respectively) suggest that glucocorticoids have a prominent role in addiction because GR would activate ERK and CREB in the NTS, phosphorylating serine 31 and activating TH and indeed noradrenergic release in the paraventricular nucleus (PVN)

Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence

©2021. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published version of a Published Work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https://doi.org/ 10.3390/ijms222413488Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients

Formar para integrar o integrar para formar

Es un tópico decir que cualquier proceso de cambio educativo conlleva, necesariamente, a un proceso previo y/o en paralelo de preparación-formación por parte de quienes tienen la responsabilidad última de llevarlo a la práctica. En este sentido, las teorías actuales sobre cambio educativo nos informan del papel que ejercen los profesores en la realización del cambio en la escuela y en sus aulas. Puede decirse que gran parte de la credibilidad de cualquier intento de cambio y mejora educativa está en función del modo en que en la misma se defina y se desarrolle el profesorado y, consiguientemente, su formación. Como muy bien apunta ESCUDERO (1988), los proyectos de cambio educativo y la formación de los profesores representan dos caras de una misma realidad

Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys.

©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published, version of a Published Work that appeared in final form in Movement Disorders. To access the final edited and published work see https://doi.org/10.1002/mds.27958ABSTRACT: Background: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson’s disease. However, the role of cardiac sympathetic nerves still needs to be elucidated. Objectives: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys. Methods: Adult male monkeys were divided into 1 of the following 3 groups: controls, 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine–treated monkeys, and 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine+levodopa–treated animals. Noradrenaline, its metabolite normetanephrine, and phospho-Heat shock proten 27 (p-Hsp27) at erine 82 levels were analyzed in the left and right ventricles of the heart. Tyrosine hydroxylase immunohistochemistry was performed in the ventral mesencephalon. Results: The results were the following: (1) 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine intoxication significantly increased normetanephrine levels and decreased noradrenaline turnover in the right ventricle without changes in the left ventricle; however, (2) levodopa treatment decreased noradrenaline levels and enhanced the normetanephrine/noradrenaline ratio in parallel with a very significant increase of Hsp27 activity in both ventricles. Conclusions: Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. © 2019 International Parkinson and Movement Disorder Societ

Sobre el año europeo contra el racismo y el actual plan de acción

The present article deals with racism and the origen, development and results of the celebration of the European Year against Racism in 1997. It also deals with the present action plans. The educative dimension is emphasized in a special way.El presente artículo reflexiona sobre el racismo y sobre el origen, desarrollo y resultados de la celebración de 1997 como Año Europeo contra el Racismo. Igualmente trata de los actuales planes de acción derivados de dicha celebración. Se destaca, de manera especial, la dimensión educativa

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Automatismo cardiaco in vitro : efectos de bloqueantes dopaminérgicos, antidepresivos tricíclicos y antiarrítmicos / María Luisa Laorden Carrasco ; dirigida por José S. Serrano Molina.

Tesis - Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 21

Conditioned aversive memory associated with morphine withdrawal increases brain-derived neurotrophic factor in dentate gyrus and basolateral amygdala.

Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone-precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of corticotropin-releasing factor (CRF)/CRF1 receptor signalling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone-induced morphine-withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic-pituitary-adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre- treatment with the CRF1 receptor antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition, the increased corticosterone plasma levels and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether present results suggesting a clear connexion between HPA axis and BDNF in the formation and extinction of aversive memory

Conditioned aversive memory associated with morphine withdrawal increases brain derived neutrophic factor in dentate gyrus and basolateral amygdala

Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone-precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of corticotropin-releasing factor (CRF)/CRF1 receptor signalling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone-induced morphine-withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic-pituitary-adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre- treatment with the CRF1 receptor antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition, the increased corticosterone plasma levels and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether present results suggesting a clear connexion between HPA axis and BDNF in the formation and extinction of aversive memory

Perfil demográfico-sociológico de los enfermos con dolor crónico: unidad de tratamiento del dolor (U.T.D.) Hospital Virgen de la Arrixaca, años 1988-90 / Ernesto Robles García ; directores Mª Luisa Laorden Carrasco, Fernando S. Miralles Pardo.

Tesis-Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 437.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1258