Prepulse inhibition modulation by contextual conditioning of dopaminergic activity

When a neutral stimulus is repeatedly paired with a drug, an association is established between them that can induce two different responses: either an opponent response that counteracts the effect of the drug, or a response thatis similar to thatinduced by the drug. In this paper, we focus on the analysis ofthe associations that can be established between the contextual cues and the administration of dopamine agonists or antagonists. Our hypothesis suggests that repeated administration of drugs that modulate dopaminergic activity in the presence of a specific context leads to the establishment of an association that subsequently results in a conditioned response to the context that is similar to that induced by the drug. To test this hypothesis, we conducted two experiments that revealed that contextual cues acquired the property to modulate pre-pulse inhibition by prior pairings of such context with the dopamine antagonist haloperidol (Experiment 1), and with the dopamine agonist d-amphetamine (Experiment 2). The implications of these results are discussed both at a theoretical level, and attending to the possibilities that could involve the use of context cues for the therapeutic administration of dopaminergic drugs.Junta de Andalucía SEJ-02618Ministerio de Ciencia e Innovación de España PSI2012-3207

Startle response and prepulse inhibition modulation by positive- and negative-induced affect

The startle response, a set of reflex behaviours intended to prepare the organism to face a potentially threatening stimulus, can be modulated by several factors as, for example, changes in affective state, or previous presentation of a weak stimulus (a phenomenon termed Pre-Pulse Inhibition [PPI]). In this paper we analyse whether the induction of positive or negative affective states in the participants modulates the startle response and the PPI phenomenon. The results revealed a decrease of the startle response and an increase of the PPI effect when registered while the participants were exposed to pleasant images (Experiment 1), and an increase of the startle response and of the PPI effect when they were exposed to a video-clip of unpleasant content (Experiment 2). These data are interpreted considering that changes in affective states correlate with changes in the startle reflex intensity, but changes in PPI might be the result of an attentional processMinisterio de Economía y Competitividad de España PSI2012-32077Junta de Andalucía SEJ-0261

Effect of stress and attention on startle response and prepulse inhibition

The startle reflex magnitude can be modulated when a weak stimulus is presented before the onset of the startle stimulus, a phenomenon termed prepulse inhibition (PPI). Previous research has demonstrated that emotional processes can modulate PPI and startle intensity, but the available evidence is inconclusive. In order to obtain additional evidence in this domain, we conducted two experiments intended to analyze the effect of induced stress and attentional load on PPI and startle magnitude. Specifically, in Experiment 1 we used a between subject strategy to evaluate the effect on startle response and PPI magnitude of performing a difficult task intended to induce stress in the participants, as compared to a group exposed to a control task. In Experiment 2 we evaluated the effect of diverting attention from the acoustic stimulus on startle and PPI intensity. The results seem to indicate that induced stress can reduce PPI, and that startle reflex intensity is reduced when attention is directed away from the auditory stimulus that induces the reflex.Ministerio de Economía y Competitividad PSI2012-32077Ministerio de Economía y Competitividad PSI2015-64965-P/MINECO-FEDE

Disentangling the effects of context change and context familiarity on Latent Inhibition with a Conditioned Taste Aversion procedure

Contextual specificity of Latent Inhibition (LI) has been demonstrated using an ample range of experimental procedures. Context dependence has not been consistently obtained, however, when LI has been induced using a Conditioned Taste Aversion (CTA) procedure. This paper presents two experiments designed to analyze whether the context plays the same role in LI with a CTA paradigm as compared to other Pavlovian techniques. Experiment 1 compared the effect on LI of a context change between the conditioning and test stages as a function of whether the testing context was new or the animals’ home cage. The results of this experiment showed that using the animals’ home cage as context at testing enhanced the expression of LI. Experiment 2 manipulated context novelty and familiarity beforehand to introduce different context changes. The results indicate that, as compared to the no context change condition, the strength of LI increased when the conditioning context was different from that of preexposure and testing (ABA). Conversely, a context change from preexposure to conditioning/test stages (ABB) disrupted LI, but only when the animals had been pre-familiarized with the new context introduced at conditioning. These results are similar to those obtained with other conditioning procedures different from CTA.Junta de Andalucia SEJ-02618Ministerio de Ciencia e Innovación de España PSI2009-7536Ministerio de Ciencia e Innovación de España PSI2012-3207

Conditioned increase of locomotor activity induced by haloperidol

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase n locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.Ministerio de Economía, Industria y Competitividad PSI2015-64 965-

Calidad de prescripción de Captopril tableta 25 mg en pacientes Hipertensos de 30 a 70 años, atendidos en el Centro de Salud Francisco Morazán en el área ESAFC (Equipo de Salud de Atención Familiar Comunitario) en el período Enero-Julio 2017

Palabras clave: Captopril 25 mg, Francisco Morazán, Hipertensión Arterial. Los Estudios de Utilización de Medicamentos tienen un objetivo de análisis en la comercialización, distribución, prescripción, dispensación y el uso de fármaco en una sociedad. Por ser esta investigación un estudio preferentemente cualitativo y de acuerdo con la clasificación de los EUM de Prescripción – Indicación con el objetivo de analizar la calidad de prescripción del captopril 25 mg tabletas en pacientes con hipertensión arterial en edad de 30 - 70 años atendidos en el centro de salud Francisco Morazán. Los parámetros evaluados para el desarrollo de esta investigación se realizaron mediante fichas de recolección de datos a partir de la revisión y análisis de los expedientes clínicos y perfiles farmacoterapéuticos de los pacientes en estudio, en donde esto nos permitirá conocer la utilización correcta de la captopril en pacientes hipertensos de 30 - 70 años. Los resultados que se obtuvieron de los pacientes hipertensos demostraron que algunos toman captopril 25 mg tabletas como tratamiento diario. El principal sexo de pacientes afectados con hipertensión arterial es el sexo femenino con un 65% de la muestra total en comparación con el sexo masculino equivalente al 35%, con respecto al peso el 28% de la muestra se encontró en la categoría de 61 - 71kg y respecto a la variable edad 51% de la muestra en estudio se encontraba entre 52 - 62 año

Different effects of unexpected changes in environmental conditions on prepulse inhibition in rats and humans

The reduction of the startle response to an auditory stimulus caused by the presentation of another stimulus of lower intensity closely preceding it, a phenomenon known as prepulse inhibition (PPI), can be modulated by changes in dopaminergic activity. Schmajuk, Larrauri, De la Casa, and Levin (2009) demonstrated that this dopaminergic modulation of PPI in rats can be influenced by manipulating the experimental context, specifically by introducing changes in the ambient lighting condition that include novel elements. In this paper we analyze the effects of introducing changes in context illumination on PPI in male rats (Experiment 1) and humans (Experiment 2). The results with rats showed a reduction of PPI when the illumination condition switched from dark to light, but not from light to dark. In the experiment with human participants the reduction of PPI occurred for both changes in illumination conditions. The animal experiment results are interpreted in terms of competing exploratory behavior that appear when the context is illuminated after the dark–light transition; while in the case of human participants a perceptual and/or attentional mechanism after both illumination transitions is proposed, which may result in a reduced processing of the prepulse and subsequent lower PPI.Junta de Andalucía SEJ-02618Ministerio de Ciencia e Innovación de España PSI2009-753

Basal VEGF-A and ACE Plasma Levels of Metastatic Colorectal-Cancer Patients Have Prognostic Value for First-Line Treatment with Chemotherapy Plus Bevacizumab

The identification of factors that respond to anti-angiogenic therapy would represent a significant advance in the therapeutic management of metastatic-colorectal-cancer (mCRC) patients. We previously reported the relevance of VEGF-A and some components of the renin–angiotensin-aldosterone system (RAAS) in the response to anti-angiogenic therapy in cancer patients. Therefore, this prospective study aims to evaluate the prognostic value of basal plasma levels of VEGF-A and angiotensin-converting enzyme (ACE) in 73 mCRC patients who were to receive bevacizumab-based therapies as a first-line treatment. We found that high basal VEGF-A plasma levels were significantly associated with worse overall survival (OS) and progression-free survival (FPS). On the other hand, low ACE levels were significantly associated with poor OS. Importantly, a simple scoring system combining the basal plasma levels of VEGF-A and ACE efficiently stratified mCRC patients, according to OS, into high-risk or low-risk groups, prior to their treatment with bevacizumab. In conclusion, our study supports that VEGF-A and ACE may be potential biomarkers for selecting those mCRC patients who will most benefit from receiving chemotherapy plus bevacizumab treatment in first-line therapy. Additionally, our data reinforce the notion of a close association between the RAAS and the anti-angiogenic response in cancer

The Combination of Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio with Liquid Biopsy Biomarkers Improves Prognosis Prediction in Metastatic Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly inflammatory microenvironment and liquid biopsy has emerged as a promising tool for the noninvasive analysis of this tumor. In this study, plasma was obtained from 58 metastatic PDAC patients, and neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), circulating cell-free DNA (cfDNA) concentration, and circulating RAS mutation were determined. We found that NLR was significantly associated with both overall survival (OS) and progression-free survival. Remarkably, NLR was an independent risk factor for poor OS. Moreover, NLR and PLR positively correlated, and combination of both inflammatory markers significantly improved the prognostic stratification of metastatic PDAC patients. NLR also showed a positive correlation with cfDNA levels and RAS mutant allelic fraction (MAF). Besides, we found that neutrophil activation contributed to cfDNA content in the plasma of metastatic PDAC patients. Finally, a multi-parameter prognosis model was designed by combining NLR, PLR, cfDNA levels, RAS mutation, RAS MAF, and CA19-9, which performs as a promising tool to predict the prognosis of metastatic PDAC patients. In conclusion, our study supports the idea that the use of systemic inflammatory markers along with circulating tumor-specific markers may constitute a valuable tool for the clinical management of metastatic PDAC patients

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients