Browsing by Author "Reyes, Edison"
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Item Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2a: Role in modulating secretion(2011) Brown, Stephen T.; Reyes, Edison; Nurse, Colin A.Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O2 environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O2, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O2, 24 h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic 12 upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2a which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K+ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca2+ in control, but not HIF-2a-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2a are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia.Publication Comparison of achievement in anamnesis skills in on-site and online formative Objective Structured Clinical Exam(2023) Jadue, Mariana; Munitiz, Pilar; Torres, Luz; Blacutt, Marcelo; Armijo, Soledad; Reyes, EdisonIntroduction: anamnesis is an initial step of the clinical reasoning process, which is taught throughout interviews to real or simulated patients. Its evaluation through OSCEs is widely disseminated, and in the context of a pandemic, the OSCE was adapted to be administered online. Objective: to compare the levels of achievement in anamnesis skills of two cohorts of medical students in formative OSCEs of semiology in on-site and online modality. Methods: using a blueprint established in 2017 and implemented for three years, competencies were identified that could be trained and evaluated online in third-year medical students. Telesimulations were performed with role play for anamnesis ability. Guided by a tutor, each student participated in 10 telesimulated anamnesis with peer roleplay and one anamnesis with a simulated pacientent. All of it in groups of 6 students. A formative TeleOSCE was implemented, evaluating the same skills of the year 2019 in a face-to-face training instance. In 2019 and 2020, 92 and 91 students participated respectively. The students' performance was compared in three identical scenarios. Results: at the cough, acute diarrhea, and knee pain screening scenarios, students in the 2020 cohort performed better than those in the 2019 cohort (p<0,001). Conclusions: for the development of anamnesis skill in third-year medical students, telesimulationbased teaching allows students to demonstrate adequate performance on a practical assessment administered online via TeleOSCE. Introducción: la anamnesis es parte inicial del proceso de razonamiento clínico y se enseña mediante entrevistas a pacientes reales o simulados. Su evaluación mediante OSCEs está ampliamente difundida y en contexto de pandemia, la enseñanza práctica y el OSCE se adaptaron para ser administrados en línea. Objetivo: comparar los niveles de logro en habilidades de anamnesis de dos cohortes de estudiantes de Medicina en OSCEs formativos de semiología en modalidad presencial y en línea. Métodos: utilizando un blueprint establecido el año 2017 e implementado por tres años, se identificaron las competencias susceptibles de ser entrenadas y evaluadas en línea en alumnos de tercer año de medicina. En el proceso de aprendizaje, se realizaron telesimulaciones para la habilidad de anamnesis. Guiados por un tutor, cada estudiante, en grupos de seis alumnos, participó en 10 anamnesis telesimuladas con role play entre pares o anamnesis con paciente entrenado. Se implementó un TeleOSCE formativo, evaluando las mismas competencias que el año 2019 en una instancia formativa presencial. El año 2019 y 2020 participaron 92 y 91 estudiantes respectivamente. Se comparó el desempeño de los estudiantes en tres estaciones idénticas. Resultados: en las estaciones de anamnesis de tos, diarrea aguda y gonalgia, los estudiantes de la cohorte 2020 se desempeñaron mejor que los de la cohorte 2019 (p<0,001). Conclusiones: para el desarrollo de la habilidad de anamnesis en estudiantes de Medicina de tercer año, la enseñanza basada en telesimulación permite que demuestren un desempeño adecuado en una evaluación práctica administrada en línea mediante TeleOSCE.Item Cxs and Panx- hemichannels in peripheral and central chemosensing in mammals.(Frontiers Research Foundation, 2014) Reyes, Edison; Cerpa, Verónica; Corvalán, Liliana; Retamal, MauricioConnexins (Cxs) and Pannexins (Panx) form hemichannels at the plasma membrane of animals. Despite their low open probability under physiological conditions, these hemichannels release signaling molecules (i.e., ATP, Glutamate, PGE2) to the extracellular space, thus subserving several important physiological processes. Oxygen and CO2 sensing are fundamental to the normal functioning of vertebrate organisms. Fluctuations in blood PO2, PCO2 and pH are sensed at the carotid bifurcations of adult mammals by glomus cells of the carotid bodies. Likewise, changes in pH and/or PCO2 of cerebrospinal fluid are sensed by central chemoreceptors, a group of specialized neurones distributed in the ventrolateral medulla (VLM), raphe nuclei, and some other brainstem areas. After many years of research, the molecular mechanisms involved in chemosensing process are not completely understood. This manuscript will review data regarding relationships between chemosensitive cells and the expression of channels formed by Cxs and Panx, with special emphasis on hemichannels.Item Diseases associated with leaky hemichannels(Frontiers Research Foundation, 2015) Retamal, Mauricio; Reyes, Edison; Garcia, Isaac; Pinto, Bernardo; Martinez, Agustin; Gonzalez, CarlosHemichannels (HCs) and gap junction channels (GJCs) formed by protein subunits called connexins (Cxs) are major pathways for intercellular communication. While HCs connect the intracellular compartment with the extracellular milieu, GJCs allow the interchange of molecules between cytoplasm of two contacting cells. Under physiological conditions, HCs are mostly closed, but they can open under certain stimuli allowing the release of autocrine and paracrine molecules. Moreover, some pathological conditions, like ischemia or other inflammation conditions, significantly increase HCs activity. In addition, some mutations in Cx genes associated with human diseases, such as deafness or cataracts, lead to the formation of more active HCs or "leaky HCs." In this article we will revise cellular and molecular mechanisms underlying the appearance of leaky HCs, and the consequences of their expression in different cellular systems and animal models, in seeking a common pattern or pathological mechanism of disease.Item Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats.(Springer International Publishing AG, 2015) Fernández, Ricardo; Cortés, Paula; Del Río, Rodrigo; Acuña-Castillo, Claudio; Reyes, EdisonThe acute kidney injury (AKI) observed during sepsis is due to an uncontrolled release of inflammatory mediators. Septic patients develop electrolytic disturbances and one of the most important is ionized hypocalcemia. AKI adversely affects the function of other organs and hypocalcemia is associated with cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors modulate the systemic inflammatory response during sepsis syndromes, we used pentobarbitone-anesthetized male Sprague-Dawley rats in control condition (SHAM surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated, BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL, decreased iCa, and enhanced the increase of cTnI. Our results suggest that carotid chemo/baro-receptors might contribute to the regulation of both renal function and calcemia during sepsis. In addition, results imply that the carotid chemo-baroreceptors serve as an immunosensory organ.Item Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy(Frontiers Research Foundation, 2014) Fernández, Ricardo; Nardocci, Gino; Navarro, Cristina; Reyes, Edison; Acuña-Castillo, Claudio; Cortes, PaulaSepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic–pituitary–adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.Item Petrosal ganglion: a more complex role than originally imagined(Frontiers Research Foundation, 2014) Retamal, Mauricio; Reyes, Edison; Alcayaga, JulioThe petrosal ganglion (PG) is a peripheral sensory ganglion, composed of pseudomonopolar sensory neurons that innervate the posterior third of the tongue and the carotid sinus and body. According to their electrical properties PG neurons can be ascribed to one of two categories: (i) neurons with action potentials presenting an inflection (hump) on its repolarizing phase and (ii) neurons with fast and brisk action potentials. Although there is some correlation between the electrophysiological properties and the sensory modality of the neurons in some species, no general pattern can be easily recognized. On the other hand, petrosal neurons projecting to the carotid body are activated by several transmitters, with acetylcholine and ATP being the most conspicuous in most species. Petrosal neurons are completely surrounded by a multi-cellular sheet of glial (satellite) cells that prevents the formation of chemical or electrical synapses between neurons. Thus, PG neurons are regarded as mere wires that communicate the periphery (i.e., carotid body) and the central nervous system. However, it has been shown that in other sensory ganglia satellite glial cells and their neighboring neurons can interact, partly by the release of chemical neuro-glio transmitters. This intercellular communication can potentially modulate the excitatory status of sensory neurons and thus the afferent discharge. In this mini review, we will briefly summarize the general properties of PG neurons and the current knowledge about the glial-neuron communication in sensory neurons and how this phenomenon could be important in the chemical sensory processing generated in the carotid body.Item Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated rats treated with lipopolysaccharide(Elsevier B.V., 2015) Nardocci, Gino; Martín, Aldo; Abarzúa, Sebastián; Rodríguez, Jorge; Simon, Felipe; Reyes, Edison; Acuña-Castillo, Claudio; Navarro, Cristina; Cortés, Paula; Fernández, RicardoSepsis progresses to multiple organ dysfunction (MOD) due to the uncontrolled release of inflammatory mediators. Carotid chemo/baro-receptors could play a protective role during sepsis. In anesthetized male rats, we measured cardiorespiratory variables and plasma TNF-α, glucocorticoids, epinephrine, and MOD marker levels 90min after lipopolysaccharide (LPS) administration in control (SHAM surgery) and bilateral carotid chemo/baro-denervated (BCN) rats. BCN prior to LPS blunted the tachypneic response and enhanced tachycardia and hypotension. BCN-LPS rats also showed blunted plasma glucocorticoid responses, boosted epinephrine and TNF-α responses, and earlier MOD onset with a lower survival time compared with SHAM-LPS rats. Consequently, the complete absence of carotid chemo/baro-sensory function modified the neural, endocrine and inflammatory responses to sepsis. Thus, carotid chemo/baro-receptors play a protective role in sepsis.