El dolor tiene una gran relevancia en el nivel socioeconómico y de salud, ya que es un síntoma muy común que lleva a pacientes a consultar centros hospitalarios. Sin embargo, siendo tan común, su tratamiento dista de ser óptimo y holístico, es por ello que el objetivo general de esta investigación es: Determinar prácticas y barreras en el manejo no farmacológico del dolor por profesionales enfermeros en un hospital público de Chiclayo, 2023. Este estudio tuvo un diseño cuantitativo, descriptivo y transversal. La población estuvo conformada por 62 enfermeras asistenciales que laboran en los servicios de hospitalización del Hospital las Mercedes de Chiclayo. La muestra fue censal y el muestreo no probabilístico por conveniencia. Se aplicó de manera presencial el cuestionario Prácticas y barreras en el manejo no farmacológico del dolor por profesionales enfermeros en un hospital público de Chiclayo, 2023. Este cuestionario tiene una validez de V de Aiken de 0,99 y un alfa de cronbach de 0.74. El procesamiento, análisis, e interpretación de datos se realizó en Excel. Las variables (práctica y barrera) se calcularon hallando la frecuencia relativa y absoluta. El resultado más resaltante en la variable práctica es que 90,32% de los profesionales enfermeros siempre aplican el método restricción de movimiento /descanso al paciente y en la variable barrera es que 88.71% es la escasa capacitación en los métodos no farmacológicos. Esta investigación se basó en los principios éticos básicos en la investigación científica: autonomía, no maleficencia, beneficencia y justicia. / Pain has great relevance in the socioeconomic and health level, since it is a very common symptom that leads patients to consult hospital centers. However, being so common, its treatment is far from optimal and holistic, which is why the general objective of this research is: Determine practices and barriers in the non-pharmacological management of pain by nursing professionals in a public hospital in Chiclayo, 2023 This study had a quantitative, descriptive and cross-sectional design. The population was made up of 62 care nurses who work in the hospitalization services of the Las Mercedes de Chiclayo Hospital. The sample was census and non-probability sampling for convenience. The questionnaire Practices and barriers in the nonpharmacological management of pain by nursing professionals was applied in person at a public hospital in Chiclayo, 2023. This questionnaire has a validity of Aiken's V of 0.99 and a Cronbach's alpha of 0.74. Data processing, analysis, and interpretation was performed in Excel. The variables (practice and barrier) were calculated by finding the relative and absolute frequency. The most outstanding result in the practice variable is that 90.32% of the nursing professionals always apply the movement/rest restriction method to the patient and in the barrier variable is that 88.71% is the lack of training in non-pharmacological methods. This research was based on the basic ethical principles in scientific research: autonomy, non-maleficence, beneficence and justice.

Generation of Ca 2+ signals in cells involves regulation by multiple components controlling Ca 2+ release from the internal stores, Ca 2+ influx across the plasma membrane (PM), elicitation of Ca 2+ sensitive processes and finally the removal of Ca 2+ from the cell. One such mode of facilitating Ca 2+ entry is called store-operated Ca 2+ entry (SOCE) mediated by the store operated Ca 2+ channels (SOCs). SOCE, wherein the depletion of internal Ca 2+ stores triggers the influx of Ca 2+ across the PM, not only plays a vital role in refilling the Ca 2+ stores, but also regulates a multitude of downstream Ca 2+ regulated signalling events. Despite recent advances in elucidating the entry pathway, its molecular identity, biophysical properties and store-depletion signal remains undefined. The most potent inducer of SOCE, thapsigargin (TG), fails to induce Ca 2+ influx in the NG115-401L (401L) cells. This unusual phenotype of the cell makes it a useful model to study the mechanisms and components underlying the SOCE pathway. Although TG failed to induce SOCE in the 401L cells, we report that the activation of intracellular release channels such as the inositol-1,4,5-trisphosphate (fP3Rs) and ryanodine receptors (RyRs) were able to activate Ca 2+ influx upon store depletion. This is in keeping with mechanisms proposed to explain SOCE, namely the conformational coupling hypothesis, wherein depletion of the ER stores signals the release channels to physically interact with the PM SOCs. We found that disrupting the communication between the ER and the PM channels induced by actin disassembly affected both Ca 2+ release and influx. Our study shows that Ca 2+ release and influx is dependent on cortical actin organization and that the RyR mediated release is less regulated by cortical actin than the IP3R induced Ca 2+ release. Studies conducted using 2-aminoethoxy diphenylborate (2-APB), a commonly used SOC blocker, revealed that 2-APB stimulated Ca 2+ release in the 401L cells. This release of Ca 2+ was also found to be dependent on the conformational coupling between the ER and PM SOCs. We also studied the effect of overexpressing various isoforms of the transient receptor potential (TRP) channels. We found that protein kinase C (PKC) differentially regulated the activity of the TRP channels in the 401L cells. PKC activation prolonged the Ca 2+ influx in the wild type cells while attenuating the same in the TRP transfected cells. We also found that influx of surrogate cations (Ba 2+ ) is augmented in the TRPC transfected cells. Our studies reveal that the activation of ER release channels followed by conformational coupling with the PM channels may be a mechanism by which the 401L cells or neurons in general maintain a rigid control over intracellular Ca 2+ concentrations and thus regulate Ca 2+ homeostasis.

No description available.

Bakgrund: Preoperativ oro förekommer hos över hälften av alla barn som ska genomgå kirurgiska ingrepp. Oron inför den kommande operationen orsakar ett stort lidande för barnet. Detta kan orsaka både fysiologiska och psykologiska symtom till följd av oron. Dessutom får dessa barn en ökad risk för postoperativa komplikationer, vilket innebär fortsatt lidande för barnen men även en ökad belastning för sjukvården. Lekterapi har visat ha en lindrande effekt på känslor hos barn och därför syftar denna studie på att undersöka om lekterapin även kan lindra den preoperativa oron.  Syfte: Detta arbetets syfte var att undersöka om lekterapi har effekt på preoperativ oro hos barn i åldrarna 0-18 som ska genomgå kirurgiska ingrepp.  Metod: En litteraturstudie gjordes med en deskriptiv design med en kvantitativ ansats. Denna studie baserades på 11 experimentella kvantitativa studier som undersökte lekterapins effekt på preoperativ oro. Artiklarna kvalitetsgranskades utifrån Fribergs granskningsmall.  Resultat: Studien använde Popenoe et al.s guide för dataanalys och resultatet delades in i tre kategorier: terapeutisk lek, teknologisk lek och strukturerad lek. Gemensamt för alla tre kategorier var att de visade på en reducerande effekt på preoperativ oro hos barn.  Slutsats: Lekterapi verkar ha en reducerande effekt på den preoperativa oron hos barn. Vilken typ av lek som lekterapin baseras på tycks inte påverka effekten av interventionen. Lekterapi bör därmed kunna användas som preoperativ förberedelse av barn i kombination med den rutinmässiga förberedelsen. / Background: Preoperative anxiety is prevalent in over half of all children undergoing invasive procedures. This may cause great suffering for the child which can lead to both physiological and psychological symptoms. Additionally these children face an increased risk of postoperative complications, which only leads to more suffering for the children but also an additional burden on the healthcare system. Studies have shown that play therapy has an alleviating effect on emotions in children, therefore this study aims to explore if play therapy also could have an alleviating effect on preoperative anxiety. Aim: To examine play therapy’s effect on preoperative anxiety in children undergoing invasive procedures.  Method: A literature review using a descriptive design with a quantitative approach. This study was based on 11 experimental quantitative studies examining the effect of play therapy on preoperative anxiety. The articles were reviewed based on Friberg’s quality review template. Results: This study used Popenoe et al.’s guide for data analysis and the results were categorized into three groups: therapeutic play, technological play and structured play. Common across all three categories was that they showed a reduction in preoperative anxiety in children.  Conclusion: Play therapy appears to have an alleviating effect on preoperative anxiety in children. What type of play that was carried out in play therapy does not seem to matter. Therefore, play therapy should be considered as part of the preoperative preparation for children, in conjunction with general surgery preparation.

<p>Teza istražuje mogućnost kori&scaron;ćenja kopule u finoj analizi međusobne zavisnosti kardiovaskularnih signala. U tu svrhu kori&scaron;ćene su različite GoF (Goodness of Fit) tehnike i matematički alati bazirani na kopuli. Predložena metoda određuje nivo zavisnosti kao funkciju vremenskog ka&scaron;njenja signala pulsnog intervala u odnosu na signal sistoličkog krvnog pritiska i omogućuje uvid u mehanizme otkucaj-po-otkucaj regulacije krvnog pritiska. Farmakolo&scaron;ka validacija je izvedena administracijom lekova koji inhibiraju autonomni nervni sistem, pri čemu su dobijeni rezultati imali jasan fiziolo&scaron;ki odziv.</p> / <p>The thesis investigates a possibility to apply a copula method for a more refined analysis of mutual dependency of cardiovascular signals. Different GoF (Goodness of Fit) techniques and mathematical tools based on copula are applied to prove this possibility. Proposed method determines the level of dependency of the pulse interval response in respect to the systolic blood pressure for different time lags and provides further insight into the beat-to-beat regulation of blood pressure. Pharmacological validation of the method was performed by administration of autonomic blockers drugs, as the obtained copula response was in accordance with the physiological interpretation.</p>

Résumé en français Objectifs : Ce mémoire propose d’explorer l’assiduité aux interventions psychosociales chez les personnes atteintes de troubles psychotiques en répondant à trois questions : 1- Quels sont les facteurs influençant l’assiduité aux interventions psychosociales pour une clientèle atteinte de troubles psychotiques? 2- Sont-ils comparables aux facteurs influençant l’observance à la médication? 3- Quel est le taux d’abandon des interventions psychosociales et quels sont les facteurs qui font varier ce taux? Méthodes : Cette étude a permis de faire la synthèse des facteurs influençant l’observance à la médication à partir des revues systématiques publiées sur le sujet, et d’établir les facteurs influençant l’assiduité aux interventions psychosociales à partir des raisons d’abandon citées dans les essais cliniques randomisés publiés. Une méta-analyse a permis de combiner les essais cliniques rapportant les abandons et ainsi d’en établir un taux. Résultats : Nous avons répertorié 92 essais cliniques randomisés sur les interventions psychosociales avec les personnes atteintes de troubles psychotiques. De ce nombre, 43 ont permis de répertorier les raisons d’abandon. Les raisons d’abandon s’avèrent principalement liées à la maladie et liées à l’accessibilité, la continuité et la qualité des soins et services. Un taux d’abandon de 13% a été obtenu à partir de l’agrégation de 74 études dans la méta-analyse. Des facteurs faisant varier ce taux ont été identifiés. Conclusion : Plusieurs facteurs (personnels, lié aux traitements, sociaux) influençant l’assiduité aux interventions psychosociales chez les personnes atteintes de troubles psychotiques ont été identifiés. De plus, le faible taux d’abandon obtenu démontre bien la faisabilité clinique de ce type d’intervention. S’ajoutant à l’efficacité déjà bien démontrée de certaines modalités d’intervention psychosociales, le taux d’assiduité à ces mêmes modalités constitue un argument supplémentaire pour en assurer la disponibilité aux personnes atteintes d’un trouble psychotique. / Abstract Aims : This report suggest investigating the compliance in the psychosocial treatment among persons with schizophrenia spectrum disorder by answering three questions : 1- What are factors influencing compliance in the psychosocial treatment among persons with schizophrenia spectrum disorder? 2- Are they comparable to factors influencing compliance with pharmacological treatment? 3- What is the dropout rate of the psychosocial treatment and which are the factors which make vary this rate? Methods : A systematic review allowed to make the synthesis of factors influencing the compliance in the medication from the systematic reviews published on the subject and to establish factors influencing the compliance in the psychosocial treatment from the reasons of drop-out specified in the published randomized clinical trials. A meta-analysis allowed to combine clinical trials reporting drop-out and so to establish a rate. Results : We listed 92 clinical trials randomized on the psychosocial treatment among persons suffering from schizophrenia spectrum disorder , of this number 43 allowed to list the reasons of drop-out. The reasons of drop-out turn out mainly related to the disease and related to the accessibility, the continuity and the quality of the care and the services. A 13 % dropout rate was obtained from the aggregation of 74 studies in the meta-analysis. Factors making vary this rate were identified. Conclusions: Several factors which influence the compliance in the psychosocial treatment among persons suffering from schizophrenia spectrum disorders are identified. Furthermore, the low drop-out rate calculated demonstrates well the clinical feasibility of this type of treatment. Being added to the efficiency already well demonstrated by certain psychosocial modalities of treatnebt, the compliance rate in these same modalities establishes an additional argument to assure the availability among persons suffering from schizophrenia spectrum disorders.

Phosphodiesterase Type 5 (PDE5) inhibitors are cardioprotective against ischemia/reperfusion (I/R) injury. However, it remains uncertain if I/R affects PDE5. We hypothesized that generation of reactive oxygen species (ROS) during I/R leads to upregulation of PDE5, which contributes to pathological changes following acute myocardial infarction (AMI). Adult male ICR mice were subjected to 30 minutes of in vivo or ex vivo I/R. To examine the role of ROS, a subset of hearts were perfused with 100 µM hydrogen peroxide (H2O2). Expression and activity of PDE5, pPDE5, and cGMP-dependent protein kinase (PKG) were measured by Western blots and spectrophotometric assay. The results show that ischemia and I/R significantly increased expression of PDE5. H2O2 had no effect on PDE5 expression and activity but significantly increased PKG activity. We conclude that acute cardiac ischemia or I/R upregulate PDE5 independent of oxidant stress in the heart.

L’infarctus du myocarde (IC) représente plus de 15 % de la mortalité mondiale liés aux maladies cardiovasculaires (MC). En absence d’une rapide reperfusion des coronaires occluses, aucune intervention thérapeutique n’est capable de limiter les effets délétères de l’IC. Un des moyens les plus efficaces de la cardioprotection, étudié en recherche, est le préconditionnement cardiaque ischémique (PCI). L’adénosine libérée au cours du PCI active via ces récepteurs P1 les voies de cardioprotection. Des études mettent en évidence également l’implication des purinorécepteurs P2Y dans la cardioprotection. Les récepteurs P2Y2, 4 et 6 sont les plus étudiés dans la cardioprotection. Les récepteurs P2Y sont sensibles aux nucléotides comme l’ATP et l’UTP libérés au cours de l’ischémie. Parmi les récepteurs P2Y seul le récepteur P2Y11 est doublement couplé à l’adénylate cyclase et à la phospholipase C (PLC). Il est également le seul récepteur dont le polymorphisme génétique, induisant une perte du signal métabotropique, prédispose à plus de risques d’IC et d’inflammation dans toutes les catégories d’âge indépendamment des facteurs de risques variables de l’IC (Amisten et al., 2007). Ceci suggère un important rôle du récepteur P2Y11 dans la prévention primaire et comme cible thérapeutique de l’infarctus du myocarde. Le β-NAD, nucléotide à base de pyridine, est libéré au cours de l’ischémie comme les médiateurs de cardioprotection notamment l’adénosine, l’ATP et l’UTP. Cependant, aucune étude ne s’est intéressée spécifiquement aux rôles du P2Y11 et des nucléotides pyridiniques, comme médiateurs, dans la cardioportection alors que le NAADP, un métabolite du β-NAD, est rapporté comme agoniste (Moreschi et al., 2008) du récepteur P2Y11. Dans ce travail, nous avons mis en évidence pour la première fois l’augmentation des concentrations interstitielles des métabolites du β-NAD comme le NAADP au cours de l’ischémie. L’augmentation des concentrations du NAADP décrit une cinétique comparable à celle de l’adénosine. Le NAADP extracellulaire ([NAADP]e), appliqué avant un cycle d’ischémie/reperfusion (I/R), déclenche une cardioprotection envers les effets délétères de l’I/R. En effet, le [NAADP]e améliore les fonctions contractiles, réduit les contractures, les arythmies de reperfusion et la taille de l’infarctus, dans un modèle d’I/R cardiaque chez le rat. Ce préconditionnement pharmacologique induit par le [NAADP]e implique les récepteurs P2Y11-like. Dans un modèle de cardiomyocytes, nous mettons en évidence l’activité métabotropique spécifique du récepteur P2Y11-like déclenché par le [NAADP]e. Le [NAADP]e déclenche via le récepteur P2Y11-like l’activation de la PKCε, ERK1/2, AKT et GSK-3β, des protéines kinases de prosurvie cellulaire, ce qui explique ses effets cardioprotecteurs. La phosphorylation des protéines de prosurvie cellulaire nécessite la médiation de la PKA, de la PLC et de la src. Le NF546, un nouvel agoniste sélectif du récepteur P2Y11, déclenche une activité métabotropique semblable à celle du [NAADP]e, confirmant ainsi l’existence fonctionnelle du récepteur P2Y11-like au niveau des cardiomyocytes de rat. L’activation du récepteur P2Y11-like, que ce soit par le [NAADP]e ou le NF546, induit une augmentation des concentrations intracellulaires du β-NAD et de ses métabolites, le NADP, le NAADP, le NAAD et l’ADP ribose cyclique. Le β-NAD, le NAADP comme le NAAD, ont été impliqués dans le déclenchement au niveau intracellulaire des voies de cardioprotection comme la voie des sirtuines et de l’autophagie. Ces mécanismes peuvent être complementaires de l’effet cardioprotecteur du [NAADP]e. L’ensemble de nos données conforte le rôle cardioprotecteur du récépteur P2Y11 et suggère que le NAADP interstitiel accumulé au cours de l’ischémie pourrait avoir un rôle de facteur paracrine de survie cellulaire améliorant la survie des cardiomyocytes au cours des évènements ischémiques. / Myocardial infarction (MI) accounts for more than 15 % of global deaths related to cardiovascular diseases (CD). In the absence of a prompt reperfusion of occluded coronary arteries, none of therapeutic interventions is able to limit the deleterious effects of MI. One of the most effective means of cardioprotection, studied in research, is the ischemic cardiac preconditioning (ICP). Adenosine released during ICP triggers, via P1 receptors, cardioprotective effects. Involvement of the purinoceptors (P2Y) in cardioprotective effects has been also reported. P2Y2,4,6 receptors, the most studied P2Y receptors in cardioprotection, are activated by the nucleotides released during ischemia such as ATP and UTP. Among the P2Y receptors, P2Y11 is dually coupled to Gs and Gq proteins and is the single P2Y receptor which has been linked, via a genetic polymorphism, to an increased risk of acute myocardial infarction and elevated levels of C-reactive protein in humans in all age groups (Amisten et al., 2007). This suggests for the P2Y11 receptor an important role in primary prevention and as a therapeutic target of the P2Y11 receptor for myocardial infarction. β-NAD, a pyridine nucleotide, is released during ischemia like adenosine, ATP and UTP. However, no study has focused on the roles of P2Y11 receptor and pyridine nucleotide in mediating cardioprotective effects while NAADP, a β-NAD metabolite, has been reported as an agonist (Moreschi et al., 2008) of the P2Y11 receptor. In this work, we show, for the first time, increased interstitial concentrations of NAADP during ischemia. Interstitial kinetics of NAADP is similar to adenosine. Using a pharmacological preconditioning protocol, triggered by extracellular NAADP ([NAADP]e) before a prolonged ischemia/reperfusion (I/R), rat hearts rapidly recovered post-ischemic contractile function and displayed attenuated contracture, infarct size and arrhythmogenesis. This pharmacological preconditioning involves the P2Y11-like receptor. In cardiomyocytes culture, [NAADP]e induces specific metabotropic response of the P2Y11-like receptor. [NAADP]e triggers via the P2Y11-like receptor prosurvival protein kinases activation such as PKCε, ERK1/2, AKT and GSK-3β which explains its protective effects. Phosphorylation of prosurvival protein kinases requires the mediation of PKA, PLC and src. As with [NAADP]e, the NF546, a new selective agonist of P2Y11 receptor, triggers a metabotropic activity, thus confirming the functional existence of P2Y11-like receptor in rat cardiomyocytes. Activation of the P2Y11-like receptor, either by [NAADP]e or NF546 induced an increase in intracellular concentrations of β-NAD and its metabolites, NADP, NAADP, NAAD and cyclic ADP ribose. More, β-NAD, NAADP as well as NAAD have been involved in activation of cardioprotective pathways such as sirtuine pathways and autophagy. Taken together, our data demonstrate for the first time that the P2Y11 receptor mediates cardioprotective effects induced by [NAADP]e. NAADP is released during ischemia suggesting that [NAADP]e may act as a paracrine survival factor, prolonging cardiomyocytes lifespan during ischemic events.

Os avanços tecnológicos vêm contribuindo cada vez mais nas áreas biológicas e científicas oferecendo ferramentas computacionais e sistemas específicos que em análise de dados in silico fornecem resultados rápidos e confiáveis. O presente projeto propõe o desenvolvimento de um portal na Internet para instalação e utilização de um banco de dados laboratoriais das principais serpentes brasileiras com seus respectivos venenos e antivenenos naturais, e a análise dos dados obtidos em ensaios farmacológicos, e bioquímicos. Utilizando a via de comunicação e interação mais simples atualmente, a Internet permite o compartilhamento de dados entre comunidades de pesquisadores, viabilizando recursos e tempo, além de permitir uma significante interação entre pesquisadores de todo o mundo, principalmente brasileira, na troca de informações e compartilhamento de dados. Dados elementares relacionados às serpentes foram armazenados no banco de dados, bem como as atividades tóxicas, farmacológicas e enzimáticas dos componentes dos venenos, e ainda, as aplicações biotecnológicas dos produtos que podem ser obtidos destes venenos, abrangendo ainda dados clínicos e valores estatísticos dos acidentes ofídicos. Aspectos bioquímicos dos ensaios realizados em laboratório permitiram a construção de uma ferramenta para análise comparativa de estruturas primárias de PLA2s, depositadas em bancos de dados internacionais. Além da interatividade entre pesquisadores, em Fóruns de Discussões, o sistema conta com listas dos principais artigos publicados em periódicos indexados, e devidamente atualizados periodicamente, com revisões bibliográficas. / Technological advances have been contributing, more and more, with biological and scientific areas, offering computational tools and specific systems which in silico data analysis supply reliable and fast results. The present project considers the development of an Internet portal for installation and use of laboratory data base for the main Brazilian serpents, with its respective venom and natural anti-venom, and the analysis of obtained data in pharmacological assays and biochemists. Using the easiest way of communication and interaction, the Internet allows sharing of data and information between communities of researchers around the world, especially for Brazilian researchers, making resources and time possible. Elementary data about serpents have been stored in the data base, as well as toxic, pharmacological and enzymatic activities of venom components, besides biotechnological applications of the products that can be obtained from these venom, enclosing clinical data and statistical values of ophidian accidents. Biochemists aspects of the assays carried through in laboratory allowed the construction of a comparative analysis tool for primary structures of PLA2s, deposited in international data bases. Beyond interactivity between researchers, in discussion forums, the system counts with lists of main articles published in indexed periodic, duly and constantly updated with bibliographical revisions.

Na região nordeste é registrado o maior índice de letalidade por acidentes ofídicos do Brasil. As serpentes Bothrops erythromelas (Be) são as responsáveis pela maioria dos acidentes na região, e o veneno dessa serpente não integra o pool de antígenos utilizado pata a obtenção do soro antibotrópico (SAB). Nesse estudo avaliou-se a potência do SAB na neutralização de algumas atividades do veneno (V) de Be. Os resultados mostraram que o SAB neutraliza as atividades do VBe, mas, exceto para a atividade coagulante e letalidade, a potência do SAB foi significativamente menor, quando comparado à neutralização das mesmas atividades do veneno de B. jararaca. A utilização de um soro obtido após a inclusão do VBe ao pool de antígenos não melhorou significativamente a potência do SAB. O SAB neutralizou também o edema inflamatório induzido pelo VBe, mas a associação do SAB à dexametasona inibiu o edema quando aplicado até 45 min após o envenenamento. Nesse tempo, SAB ou dexametasona aplicados isoladamente não foram efetivos em diminuir esse edema. / In the northeast region is registered the higher lethality index by snakebites in Brazil. Bothrops erythromelas (Be) snakes are responsible for the larger number of snakebites in that region, and the venom of these snakes do not integrate the pool of antigens used to obtaining the Bothrops antivenom (BAV). In the present study, the potency of this serum in neutralizing some activities of Be venom (V) was evaluated. Results showed that BAV neutralizes BeV activities, but, except for coagulant activity and for lethality, the potency of the BAV was significantly lower, when compared to the neutralization of the same parameters of the Bothrops jararaca venom. The use of antivenom obtained after inclusion of BeV to the pool of antigens did not ameliorate the BAV potency. The BAV also neutralizes the inflammatory edema induced by BeV, but the association of BAV and dexamethasone decreased the edema when applied up to 45 min after the venom. At this time, antivenom or dexamethasone administered alone were ineffective in inhibiting this edema.