Competencias de investigación en el Grado en Medicina en la universidad española / Research competences in Medicine Degree at Spanish universities

Objetivo: Analizar la distribución de competencias generales y específicas de investigación en los Grados en Medicina. Sujetos y métodos: Se utilizaron las memorias de verificación, las fichas de las asignaturas y la información del Registro de Universidades, Centros y Titulaciones como bases documentales para el estudio. Las competencias generales y específicas analizadas son las contenidas en la Orden ECI 332/2008. Se consideraron asignaturas de investigación las que así lo indican en su denominación, y complementarias, aquellas otras relacionadas con el proceso de investigación. Resultados: El Grado en Medicina es impartido en 40 universidades, que proponen 49 asignaturas de investigación: 22,5% básicas, 40,8% obligatorias y 36,7% optativas. Las asignaturas complementarias identificadas fueron 91: 46,1% básicas, 41,8% obligatorias y 12,1% optativas. Las competencias generales de investigación se encuentran mayoritariamente en asignaturas relacionadas con los módulos 'Medicina social, habilidades de comunicación e iniciación a la investigación' y 'Prácticas tuteladas y trabajo de fin de grado', mientras que las competencias específicas se concentran en los módulos 'Medicina social' y 'Optatividad'. Algunos grados no asignan competencias generales (n = 11) ni específicas (n = 30) de investigación al trabajo de fin de grado; de los que lo hacen, 16 le atribuyen todas las competencias generales, y cinco, todas las específicas. Conclusiones: La distribución de competencias y la presencia de asignaturas de investigación es heterogénea. En pocas universidades, el trabajo de fin de grado tiene una clara orientación a la investigación. Los grados en general no están orientados a la investigación

Aim: To analyse the distribution of general and specific research competences in Medicine Degrees. Subjects and methods: Verification reports, subject sheets and information included in the RUCT were used as documentary bases for the study. The general and specific competences analysed were those contained in the legislation ECI 332/2008. As research subjects were considered those that mentioned research in their name, and as complementary subjects those related with the research process. Results: Medicine Degree is taught at 40 universities across Spain, with 49 research subjects: 22.5% core, 40.8% mandatory and 36.7% optional. Ninety-one complementary subjects have been identified: 46.1% core, 41.8% mandatory and 12.1% optional. General research competences were found to a greater extent in subjects related to the module 'Social Medicine, Communication Skills and Initiation to Research' and the module 'Clinical Clerkships and Degree Final Project'. The specific competences were focused on modules 'Social Medicine' and 'Optional'. Several degrees analysed did not assign competences of research to the degree final project, neither general (n = 11) nor specific (n = 30) competences. However, other degrees assigned competences of research attributed to general and specific research competences with a distribution of sixteen and five, respectively. Conclusions: The distribution of competences and the presence of research subjects across Medicine Degrees in Spain was very heterogeneous. Surprisingly, only in a few universities the degree final project has a clear research orientation, suggesting a main focus on clinical medicine. Medicine Degree are not oriented to research

Utilidad potencial de las artes visuales en la enseñanza de la medicina / Potential utility of the visual arts in medical teaching

INTRODUCCIÓN Y OBJETIVO: Las habilidades de observación pueden facilitarse mediante la descripción de obras de arte. Presentamos una experiencia de observación y descripción de obras pictóricas desarrollada en la Facultad de Medicina de la Universidad de Oviedo. Sujetos y métodos: Los estudiantes (150-155/curso) realizaron 2 seminarios (4 h y 45 min) en subgrupos de 4-5. En el primer seminario, el profesor comenta los objetivos generales y particulares y realiza un ejercicio de lectura de varios cuadros incidiendo en los aspectos que debe observar el estudiante. En el segundo, cada subgrupo expone la tarea realizada sobre los cuadros asignados. Se evaluó el contenido, la organización y la expresión oral. La evaluación de la satisfacción de los estudiantes se realizó mediante una encuesta. RESULTADOS: Las obras de arte utilizadas han sido 90, con predominio de las realizadas en los siglos XVII (n = 30) y XIX (n = 32). De los 9 apartados que contiene la actividad de observación, descripción y documentación, analizada en los cursos 2015-2016 y 2016-2017, los estudiantes cumplimentaron una media de 6,9 ± 0,28 y 6,4 ± 0,25, respectivamente, e identificaron 2,7 ± 0,24 frente a 3,02 ± 0,26 elementos de interés médico. Las calificaciones de la presentación oral fueron superiores al 90% de la máxima posible. La encuesta, cumplimentada por el 95,4% de los asistentes, muestra que el 78,3% de los estudiantes está satisfecho con la actividad y el 63,4% la considera relevante para su formación médica. CONCLUSIÓN: La observación y descripción de obras de arte es aceptada por los estudiantes de medicina como una actividad educativa relevante en su formación

INTRODUCTION AND OBJECTIVE: Art-based teaching is a strategy for increasing the observational skills of medical students. We present our experience using artworks with first-year students in the Faculty of Medicine, University of Oviedo. Subjects and methods: The activity was performed in the form of 2 seminars (4 h and 45 min). Students (150-155 per year) perform this activity in subgroups of 4 or 5. In the first seminar, the lecturer explains the general and specific aims, and presents several pictures with the relevant aspects that the students should observe. During the second of the seminars, each group presents the work they have carried out on the assigned artistic image. The contents, structure and oral expression of the presentations were evaluated. Student satisfaction was measured using a questionnaire. RESULTS: The number of paintings used was 90, distributed from XVII (n = 30), XIX (n = 32) and others centuries (n = 28). An evaluation of the observation, description and documentation of the artworks was performed through 9 questions. The students of the 2015-2016 and 2016-2017 academic course completed 6.9 ± 0.28 and 6.4 ± 0.25 of these items. Likewise, these students identified 2.7 ± 0.24 vs. 3.02 ± 0.26 elements of medical interest. Oral presentations scores were over 90% of the maximum possible. A survey, completed by 95.4% of participant's suggested that 78.3% were satisfied with the activity, and that 63.4% considered it relevant for their medical training. CONCLUSION: The observation and description of artworks is accepted by students as a relevant educational activity for their medical education

Modulatory effect of intestinal polyamines and trace amines on the spontaneous phasic contractions of the isolated ileum and colon rings of mice.

Background: Gastrointestinal motility modulatory factors include substances of the intestinal content, such as polyamines and trace amines (TAs), the focus of this study. Methods: The amines of food, intestinal content and from faecal bacteria of Swiss mice were determined by HPLC and functionally characterised in isolated distal ileum and medial colon rings. Results: Mouse food and intestinal content contain polyamines (spermidine>putrescine>spermine) and TAs (isoamylamine>cadaverine). Intestinal bacteria mainly produce putrescine and cadaverine. The amines inhibited the spontaneous motility of the ileum (0.1-3 mM) and colon rings (0.01-3 mM, with lower IC50), with: spermine~isoamylamine~spermidine. Spermine inhibition was tetrodotoxin (TTX)-insensitive, while isoamylamine was TTX-sensitive, suggesting neural control. Mainly in the ileum, isoamylamine (3 mM) elicited acute effects modified by TTX, atropine and propranolol, and suppressed by spermine (3 mM), not being localized at the smooth muscle level. The amines assayed (3 mM), except putrescine and cadaverine in the ileum and isoamylamine in the colon, antagonised acetylcholine (ACh, 0.1 mM)-elicited phasic contractions. Isoamylamine and spermine in colon relaxed KCl (100 mM)-elicited tonic contractions, suggesting an effect on smooth muscle, but did not justify the suppression of motility caused by spermine and isoamylamine. Conclusions: Polyamines and TAs of the intestinal content might act on chemosensors and modulate intestinal peristalsis.

Estradiol-modified prolactin secretion independently of action potentials and Ca2+ and blockade of outward potassium currents in GH3 cells.

Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca2+ and noninactivating K+ currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH3. Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 µM), without a latency period, blocked Ca2+ channels and noninactivating K+ currents, including the large-conductance voltage- and Ca2+-activated K+ channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH3 and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory ß1-subunits of the BK, which GH3 cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH3 cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca2+ influx.

Papel de la literatura en la formación del médico. Una experiencia en el segundo curso del grado en Medicina en la Universidad de Oviedo / Role of literature in medical formation. An experience in the second year of Medicine Degree in the University of Oviedo

Introducción: La literatura es una disciplina humanística con un papel formativo en los estudiantes de medicina. Sujetos y métodos: La actividad presentada se ha realizado en tres cursos académicos en una asignatura optativa del segundo curso del grado en Medicina. Los objetivos y ejemplos de la relación entre literatura y profesión médica se presentan en una sesión (dos horas). Posteriormente, los estudiantes eligen un libro y realizan un trabajo sobre él. Se ha evaluado la capacidad argumental, de síntesis, de redacción, de profundidad y de organización de los trabajos. La satisfacción del alumno con la actividad se midió mediante una encuesta. Resultados: Un número creciente de estudiantes (54 a 127) han participado en la asignatura; se han utilizado un total de 90 libros (el 45,5% posterior al año 2000), y El árbol de la ciencia ha sido el más comentado. Las enfermedades infecciosas (15,5%), psiquiátricas (15,5%), neurológicas (13,8%) y oncológicas (10,3%) fueron las tratadas con más frecuencia, y los temas relacionados con el médico (33,1%), el paciente (22,3%), y la relación médico-paciente (12,7%), los referidos con más frecuencia. Las puntuaciones medias obtenidas por los estudiantes en la actividad han oscilado entre 8,3 y 9 (sobre 10). La opinión sobre la actividad ha sido favorable y considerada útil para diferentes aspectos de la medicina: formación humanística (4,5 sobre 5), relación médico-paciente (4,5), actitud del paciente ante la enfermedad (4,4) o dimensión social de la enfermedad (4,4). Conclusión: La actividad ha sido valorada favorablemente por los estudiantes, que la consideran útil para contribuir a diferentes aspectos formativos de los estudiantes de medicina

Introduction: Literature is one of the humanistic disciplines playing a role in the training of medical students. Subjects and methods: The activity has been performed over three academic years included in an optional subject of the second year of the Medicine Degree. Professor introduced the activity and showed examples of the relationship between literature and aspects of the medical profession in a two-hour class. Then, students chosen a book and prepared a written assignment on such book. Results: An increasing number of students (from 54 to 127) have taken the course; a total of 90 books were used (45.5% published after 2000) being El árbol de la ciencia (The Tree of Knowledge), the most commented one. Infectious (15.5%), psychiatric (15.5%), neurologic (13.8%) and oncologic diseases (10.3%) were the most frequently discussed and issues related to doctors (33.1%), patients (22.1%) and the doctor-patient relationship were the most frequently cited. Students’ scores on the activity ranged from 8.3 and 9 (out of 10) in the three years. Opinions regarding the activity have been positive and it has been considered useful for different aspects of Medicine: the humanistic formation (4.5 out of 5), the doctor-patient relationship (4.5), the patient’s attitude towards disease (4.4) or the social dimension of disease (4.4). Conclusion: The activity has been favorably evaluated by students who consider it useful in the training of medical students

Utilización de relatos literarios como actividad formativa para la enseñanza de la medicina en la Universidad de Oviedo / Use of literary stories as training activity for the teaching of medicine in the University of Oviedo

Introducción: La lectura y el análisis de textos narrativos pueden contribuir a la adquisición de las competencias humanísticas que deben adquirir los estudiantes de medicina. Este trabajo presenta una actividad realizada con este fin. Sujetos y métodos: La actividad se ha realizado durante cinco años dentro de una asignatura obligatoria del primer curso del grado de Medicina en la Universidad de Oviedo, en dos seminarios (cuatro horas). Los estudiantes (150-155/año) realizan la actividad en subgrupos de cuatro-cinco. En el primer seminario, el profesor comenta dos poemas para iniciar a los estudiantes en la identificación de términos relacionados con la medicina. En el segundo, cada subgrupo expone el análisis realizado sobre un relato asignado por el profesor. Se evaluó el contenido y la organización del trabajo, así como la exposición oral. La evaluación de la satisfacción de los estudiantes se realizó mediante una encuesta. Resultados: Se han utilizado 79 relatos, de los que 33 han sido comentados en dos-tres cursos académicos. Las puntuaciones obtenidas por los estudiantes en la actividad han variado entre 3,59 ± 0,11 y 3,85 ± 0,05 sobre cuatro en los diferentes cursos. Los estudiantes han mostrado su satisfacción con la actividad y resaltan (sobre 5) que la formación humanista (3,9), la descripción de enfermedades (4), la relación médico-paciente (3,7), la dimensión social (3,8) y la actitud del paciente ante la enfermedad (3,8) pueden adquirirse mediante el análisis de textos literarios. Conclusión: La lectura y el análisis de textos literarios permiten aproximar a los estudiantes a aspectos relevantes de la práctica profesional ausente durante el grado

Introduction: Reading and analysis of narrative texts may contribute to the acquisition of humanistic skills required for medical students. This article presents an activity performed to this aim. Subjects and methods: The activity has been performed over five academic years, in the form of two seminars (four hours) as a part of an obligatory subject in the first year of the Medicine degree of the University of Oviedo. Students (150-155 per year) perform this activity in subgroups of four-five. At the first seminar, the teacher comments two poems in order to initiate the students in the identification of medical terms. During the second of the seminars, every group presented an analysis of a short story assigned by the teacher. Contents, structure and oral presentations were evaluated. Student satisfaction was measured in a survey. Results: We used 79 stories whose 33 were commented in two-three academic courses. Students' mean scores on this activity ranged from 3.59 ± 0.11 to 3.85 ± 0.05 out of 4 in the different courses. Students expressed satisfaction with the activity and stressed (out of 5 points) that the humanistic formation (3.9), the description of diseases (4), the doctor-patient relationship (3.7), the social dimension (3.7) and the patient's attitude towards disease (3.8) may be acquired through the analysis of literary texts. Conclusion: Reading and analysis of literary texts allow students to approach relevant aspects of the professional practice absent in the curriculum of the degree

Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of polyamines in different stages of heart failure.

Androgens block outward potassium currents and decrease spontaneous action potentials in GH3 cells.

Androgens produce nongenomic effects in several cells by different mechanisms, including ion channel modulation. Adenohypophyseal cells express several K(+) channels, including voltage and Ca(2+)-dependent K(+) (BK) channels, which might be the target of androgens to modulate cellular action potentials and hormonal secretion. Androgen effects were studied in GH3 cells (from anterior pituitary rat tumor) by means of the patch-clamp technique. Cells were continuously perfused with saline solution, in the absence or presence of the androgens studied, while applying 40 mV pulses of 400 ms from a holding potential of -60 mV in whole-cell configuration with nystatin-perforated patches. Androgens reversibly blocked noninactivating K(+) currents in a concentration-dependent manner without a latency period and with an order of efficacy of: 5ß-dihydrotestosterone (DHT)>testosterone>5α-DHT. RT-PCR showed two isoforms of the α-pore forming subunits of BK channels. These channels are responsible for one third of the noninactivating current, according to the blockade of paxilline, a selective BK antagonist. Androgens seem to directly interact with BK channels since they were blocked in excised inside-out patches and independent of the whole-cell configuration and the NO-cGMP-dependent pathway. Testosterone, but not 5α- or 5ß-DHT, increased BK currents in HEK-293 cells overexpressing the short isoform, suggesting a cellular selectivity based on the α-subunits. The effect on noninactivating currents may be responsible for the decrease of spontaneous action potential frequency. Long-term cellular incubation with testosterone did not modify noninactivating currents density in GH3 cells. It is remarkable that 5ß-DHT, a reductase metabolite with weak androgenic activity, was the most efficient blocker.

Apropiación de terminología médica por estudiantes de primer curso del grado en medicina a través de prensa diaria / Use of newspaper for the terminology appropriation by first year medical students

Objetivo. Presentar y analizar una tarea formativa de apropiación de terminología médica y científica por los estudiantes de primer curso de medicina. Sujetos y métodos. Participaron los 161 alumnos matriculados en primer curso que fueron distribuidos en grupos de cinco o seis para realizar el trabajo propuesto en forma de seminario. Los alumnos seleccionaron noticias relacionadas con ciencia y medicina publicadas en diarios de ámbito nacional o regional para estudiar diferentes características. Las instrucciones para la realización de la tarea, así como algunos ejemplos, estuvieron disponibles en el campus virtual de la universidad al comienzo de curso. Resultados. Los alumnos seleccionaron 103 artículos, de los que sólo seis trataban de ciencias naturales no relacionadas con la medicina, predominando en estos últimos los dedicados a neurología. En esos 103 artículos se identificaron 316 términos médicos; otros 219 términos fueron seleccionados en artículos generales. El 88,3% de los términos fueron documentados mediante distintos diccionarios. El 51,5% de los alumnos contestaron una encuesta sobre la actividad formativa en la que otorgaron una calificación de 3,2 puntos sobre 5. Conclusiones. El estudio demuestra que las noticias sobre medicina y salud son habituales en la prensa nacional y regional. Los alumnos consideraron que la actividad favorece la adquisición de vocabulario médico y científico, a la vez que facilita la aproximación a los aspectos sociales de la medicina (AU)

Aim. To describe and analyze a formative task of appropriation of medical and scientific terminology by students of first year at medical school. Subjects and methods. Participants were 161 students distributed in groups of five or six to perform the proposed assignments in form of seminars. The students selected science and medicine news, published in national and regional newspapers, to analyze different characteristics of these articles. The instructions for the task as well as some examples were available in the university's virtual campus at the beginning of the course. Results. Students chose 103 news; only six of natural sciences and the rest related to Medicine, being predominant those related to neurology. Medical terms identified in those articles were 316. Moreover 219 items in general news were chosen. The 88.3% of the terms were documented via consulting dictionaries. The 51.5% of the students answered a survey in which, the task got an average score of 3.2 out of 5 possible points. Conclusions. The study shows that medicine and health information is common in national and regional press. The students think that this activity promotes medical and scientific vocabulary acquisition while it favors the approach to the social aspects of medicine (AU)

Protagonismo de los alumnos en el aprendizaje. Una experiencia en el primer curso de medicina / Role of students in learning. An experience in the first year of Medicine Degree

Objetivo. Presentar y analizar la experiencia realizada en una asignatura del primer curso del Grado de Medicina para abordar competencias formativas en documentación, método científico y humanismo médico. Sujetos y métodos. Participaron 151 alumnos distribuidos en grupos de 5-6 estudiantes para realizar los trabajos propuestos en forma de seminarios y aprendizaje basado en problemas (ABP), utilizando, entre otros materiales, narraciones literarias e imágenes de cuadros pictóricos cuyo análisis y discusión se presentaron oralmente. En las prácticas se inició a los estudiantes en la búsqueda y evaluación de la información. Un ensayo y las clases teóricas completan los métodos utilizados. Todos los materiales a utilizar estuvieron disponibles en el campus virtual. Resultados. La asistencia a prácticas, seminarios y ABP fue próxima al 100%, y a clases teóricas, del 67%. Los alumnos mostraron inquietud intelectual en las tareas. El método ha demostrado una elevada implicación en el proceso de autoaprendizaje, capacidad de autorregulación en el trabajo, trabajo en grupo, grado de adquisición de conceptos y capacidad de redactar documentos. La adecuación de los contenidos a los objetivos ha sido considerada favorable por más del 70% de los alumnos. El grado de adquisición de las competencias fue favorable en un 80% de los casos. Conclusiones. Las características de la asignatura pueden fomentar la inquietud científica y el humanismo médico entre los alumnos. La literatura y la lectura de cuadros pueden contribuir a identificar los aspectos del acto médico y a desarrollar la observación de las características físicas y conductuales en los pacientes (AU)

Aim. To present and analyze the experience carried out in a subject of the first year of Medicine Degree to address training skills in documentation, scientific method and medical humanism. Subjects and methods. The participants were 151 students distributed in groups of 5-6 to perform the proposed assignments in form of seminars and problem based learning (PBL), using, among other materials, short literary texts and images of paintings whose analysis and discussion were presented orally. Practical lessons introduced the students to the search and evaluation of information. An essay and lectures complete the methods used. All materials used were available in the virtual campus. Results. Attendance at workshops, seminars and PBL sessions was close to 100% and 67% for lecture sessions. The students expressed intellectual interest on the tasks performed. The method showed high student involvement in the process of self-learning, ability of self-regulation at work, degree of concept acquisition and ability to draw up documents. The adequacy of the contents to the objectives has been considered suitable by more than 70% of the students. The acquisition of competences was favorable in 80% of cases. Conclusions. The characteristics of the subject might be useful to promote scientific inquiry and medical humanism among students. Literature and description of paintings might help to identify aspects of medical act, as well as to develop the observation of physical and behavioral characteristics in patients (AU)

Sex hormones modulate salbutamol-elicited long-term relaxation in isolated bovine tracheal strips.

Sex hormones are of interest regarding gender differences in the clinical manifestations of airway diseases. No conclusive data are available on the sex hormone modulation of ß-adrenoceptor-mediated responses on airways. To this aim, isolated preparations of bovine trachea were used to establish the sex hormone influence on salbutamol-elicited relaxation. This had 2 components, a full acute relaxation followed by a loss of efficacy, close to half of the effect. The remaining half was reverted by the ß-blocker, propranolol. The loss of salbutamol-elicited relaxation might reflect the receptor desensitization, as shown by the lack of effect by subsequent administration of salbutamol, and the decrease in the immunostaining of ß(2)-adrenoceptors. Sex hormones differently modified the salbutamol-elicited response. Testosterone, but not other androgens or estradiol, had a synergic effect, facilitating the acute relaxation and decreasing the loss of spasmolytic effect, associated with an increase in the latency of desensitization and a decrease in the time taken to reach long-term steady-state tone. These effects, not modified by the antiandrogen flutamide or epithelium removal, seem to be independent of a modulation of ß(2)-adrenoceptor desensitization. Testosterone also relaxed preparations with desensitized ß-adrenoceptor. Therefore, testosterone modulates tracheal smooth muscle tone, facilitating bronchodilation caused by ß(2)-adrenoceptor agonists which might be of pharmacological interest.

Testosterone inhibits cAMP-phosphodiesterases in heart extracts from rats and increases cAMP levels in isolated left atria.

Several mechanisms have been proposed to explain the acute cardiovascular effects elicited by androgens, such as vasodilation and positive inotropism. Phosphodiesterases (PDEs) are important modulators of cardiac contractility. However, an effect on PDEs by androgens in cardiac tissues has not previously been reported. In this study, extracts from rat ventricles and isolated left atria were assayed for cAMP-dependent PDE activity. To study the tissue selectivity, the enzymatic activity was also assayed in extracts from bovine tracheal smooth muscle and Chinese hamster ovary (CHO) cells. Functional assays were also performed with isolated atria. Testosterone, but not 5α- and 5ß-dihydrotestosterone, inhibited cAMP-PDE activity in extracts from left ventricles and atria. In atria, the inhibition of cAMP-PDE activity was associated with an increase in intracellular levels of cAMP and a cardiotonic response. This effect was not elicited in tracheal muscle strips or CHO cell extracts, suggesting the possibility of tissue and cAMP-PDE selectivity. The results of these studies suggest a new mechanism of action of testosterone in the rat heart, which might contribute to the reported cardiotonic effect.

Functional effects of polyamines via activation of human ß1- and ß2-adrenoceptors stably expressed in CHO cells.

Polyamines mediate acute metabolic effects and cardiac hypertrophy associated with ß-adrenoceptor stimulation. They may also modulate ß-adrenoceptors, causing functional responses in rat atria and tracheal smooth muscle. The aim of this study was to determine whether polyamines interact with human ß(1)- and ß(2)-adrenoceptors and the functional consequences of such an interaction. Chinese hamster ovary (CHO) cells stably transfected with human ß(1)- and ß(2)-adrenoceptors were used to evaluate the effect of polyamines binding to ß-adrenoceptors, cAMP production and morphological changes, which were pharmacologically validated by investigating the effects of the ß-adrenoceptor agonists, isoproterenol and salbutamol. Polyamines interacted with human ß(1)- and ß(2)-adrenoceptors, as shown by the displacement of [(125)I]iodocyanopindolol in the binding assay. Putrescine showed higher affinity to ß(1)- than ß(2)-adrenoceptors. Spermidine and spermine produced partial displacement (approximately 50%) and, at the highest concentration, the effect was reversed. Putrescine and spermine acutely increased cAMP and, in a serum-free medium, induced a stellate-like form in cells, which was inhibited by propranolol, a ß-blocker. A 10 to 15 h incubation with putrescine produced a spindle-like form and spatial organization via ß-adrenoceptor activation, evidenced by the antagonizing effect by propranolol and lack of effect in wild-type CHO cells. Additionally, it decreased cell proliferation independently of ß-adrenoceptor activation. Spermine caused cell death via fetal bovine serum-dependent and -independent mechanisms. The results suggest that putrescine may act as a non-selective and low affinity agonist of human ß(1)- and ß(2)-adrenoceptors, eliciting morphological changes. These findings may be of importance in physiology and in diseases involving ß-adrenoceptor functionality.

Role of ß-adrenoceptors, cAMP phosphodiesterase and external Ca2+ on polyamine-induced relaxation in isolated bovine tracheal strips.

Polyamines relax several smooth muscles and elicit cardiotonic effects in the rat heart via interactions with ß-adrenoceptors. The aim of this work was to establish whether ß(2)-adrenoceptors were involved in polyamine-relaxation of bovine tracheal strips. Endogenous polyamines displaced the specific radioligand, [(3)H]dihydroalprenolol, but spermine was the most potent. The polyamines elicited an acute transient relaxation, which was independent of ß-adrenoceptor activation, followed by a maintained component, which was shown to be dependent on ß-adrenoceptor activation because it was antagonized and reversed by propranolol. Polyamines did not alter salbutamol-induced acute relaxation. Polyamines modified the salbutamol-induced long-term effect on airway tone, which was shown by a partial reversal of ß-adrenoceptor desensitization. This process was delayed by α-difluoromethylornithine, but spermine increased the latency and time of reversal and decreased receptor desensitization. Putrescine prolonged the time-constant without changes in the desensitization. Spermine, but not putrescine, might block Ca(2+) channels, because it relaxed KCl- or electrical stimulated-contractions, which are related to Ca(2+) influx, and the inhibition of cAMP phosphodiesterase activity. These differences might explain the functional differences observed between putrescine and spermine. Therefore, polyamines may modulate airway smooth muscle tone and interfere with the mechanism of receptor desensitization via several mechanisms involving ß(2)-adrenoceptors, Ca(2+) influx and cAMP phosphodiesterase.

Role of polyamines and cAMP-dependent mechanisms on 5alpha-dihydrotestosterone-elicited functional effects in isolated right atria of rat.

Androgens produce acute vasodilation of systemic, pulmonary, and coronary arteries in several mammal preparations and increase cardiomyocyte contractility. A decrease of the spontaneous beating of sinoatrial cells has also been described. The aim of this study was to characterize the direct effect of 5alpha-dihydrotestosterone on the spontaneous chronotropism and inotropism in the same preparation as an approach to establish the effect on cardiac output and their mechanism of action. The effects were studied on isolated right atria of Wistar rats placed in an organ bath in Tyrode solution at 37 degrees C and bubbled with carbogen. In male rats, the acute administration of 5alpha-dihydrotestosterone, a nonaromatizable derivate of testosterone, elicited a positive inotropism, which was associated with a negative chronotropism. As reported in the left atria, polyamines and beta-adrenoceptors played a role in 5alpha-dihydrotestosterone-elicited positive inotropism because the effect was antagonized by alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, and atenolol, a beta1-adrenoceptor blocker, but not on the negative effect on chronotropism. The androgen increased the sinoatrial node recovery time, suggesting an effect on the mechanisms of spontaneous diastolic depolarization involved in atria pacemaking. These effects of 5alpha-dihydrotestosterone are not hormonally regulated because they are similarly produced in estrogenized females and gonadectomized male and female rats. These results suggest that the androgen could acutely improve cardiac performance.

Influence of gender and sex hormones on 5alpha-dihydrotestosterone elicited effect in isolated left atria of rats: Role of beta-adrenoceptors and ornithine decarboxylase activity.

Androgens elicit an acute cardiotonic effect in cardiac preparations of rats. This effect is produced via an extracellular interaction that may be coupled to pertussis-sensitive G-proteins and is associated with an increase in cAMP, polyamine synthesis and intracellular calcium. The nature of the targets and the existence of a dimorphic effect in this nongenomic effect of androgens are unknown. The purpose of this study was to characterize a possible gender and sex hormone influence on the 5alpha-dihydrotestosterone-elicited cardiotonic effect, taking into account the possible role of the beta-adrenoceptors and ornithine decarboxylase activity on this response. [Float1]Regarding this, the effect of 5alpha-dihydrotestosterone on isolated left atria from male, estrogenized female and gonadectomized male and female rats was studied. The results showed that 5alpha-dihydrotestosterone-elicited cardiotonic effect was preserved independent of gender and sex hormones, being higher in control males than in the rest of the groups. This correlated with the testosterone plasma levels, except in estrogenized females, suggesting that the androgens positively and the estrogens negatively regulated the response. In all groups, 5alpha-dihydrotestosterone produced an increase in cAMP levels, but only in control males did it produce an increase in ornithine decarboxylase activity. In the other groups, the absence of an effect on ornithine decarboxylase might limit the capability of the response to the androgen. Altogether, androgens may help to control cardiac performance by a direct interaction on the heart in both sexes. Gender and sex differences in the magnitude of inotropism being due mainly to changes in beta-adrenoceptors and cAMP production and in intracellular polyamine synthesis.

Modulatory role of endogenous androgens on airway smooth muscle tone in isolated guinea-pig and bovine trachea; involvement of beta2-adrenoceptors, the polyamine system and external calcium.

Androgens relax several smooth muscles, including the airways. They also contract ileum and myocardium via nongenomic mechanisms. To find out whether androgens modulate airway smooth muscles in different species and further assess their mechanism of action, regarding the role of beta-adrenoceptors, polyamines and extracellular Ca(2+), and the modulation of contraction, 5 alpha-dihydrotestosterone, testosterone and 5 beta-dihydrotestosterone were used. A preliminary study was performed to evaluate the effect of 5 alpha-dihydrotestosterone, a non-aromatisable derivate of testosterone, in isolated guinea-pig trachea and a more exhaustive characterisation was followed in bovine trachea, to also characterise the effect of testosterone and 5 beta-dihydrotestosterone. The androgens elicited a nongenomic epithelium-independent relaxation of the trachea which had been precontracted. In the bovine trachea, the order of potency was: testosterone>5 alpha-dihydrotestosterone=5 beta-dihydrotestosterone. This effect was inversely proportional to the magnitude of carbachol-raised tone and was independent of beta(2)-adrenoceptors, since the beta-blockers, propranolol and ICI-118,551, and beta(2)-adrenoceptor desensitisation did not modify 5 alpha-dihydrotestosterone-elicited relaxation. 5 alpha-Dihydrotestosterone was unable to displace the radiolabel, [(3)H]dihydroalprenolol, from these receptors in the binding assay. Polyamine synthesis was not involved in this androgen effect, since an ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, was ineffective. The androgens were more effective relaxing bovine trachea precontracted by KCl (80 mM), suggesting a calcium entry blockade, as reported for several smooth muscles. This mechanism might be involved in the observed 5 alpha-dihydrotestosterone facilitation of salbutamol-relaxation. Androgens facilitated carbachol-elicited contraction independently of polyamine synthesis, contrary to what has been reported in the ileum. Therefore, androgens modulate tracheal smooth muscle tone which might be of importance in the regulation of airway reactivity.

Role of putrescine on androgen-elicited positive inotropism in the left atrium of rats.

Functional and biochemical studies were performed in isolated left atria of male Wistar rats to study whether endogenous polyamines may mediate androgen-elicited positive inotropism and their relationship with a rise in cAMP during the cardiotonic effect. 5 alpha-Dihydrotestosterone (100 microM) exposure increased intracellular putrescine as determined by HPLC, but it did not increase spermidine and spermine. This effect was antagonized by an inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (10 mM), suggesting enzyme activation. alpha-Difluoromethylornithine also antagonized androgens-elicited inotropism and the increase in intracellular cAMP. Putrescine (1 to 10 mM) elicited a concentration-dependent positive inotropism associated with the cAMP increase. The prior incubation with putrescine antagonized 5 alpha-dihydrotestosterone-elicited inotropism and did not produce sinergism on intracellular cAMP. Short-term incubation with 5 alpha-dihydrotestosterone or forskolin shifted to the left the cardiotonic effect of isoproterenol, an agonist of beta-adrenoceptors, without any increase in Emax, suggesting that a common mechanism was involved. Therefore, polyamines might modulate the cAMP production associated with the cardiotonic effect of androgens.

Putrescine modulation of acute activation of the beta-adrenergic system in the left atrium of rat.

Endogenous polyamines mediate acute metabolic effects and cardiac hypertrophy associated to beta-adrenoceptor stimulation. The aim of this study is to characterize the role of polyamines on beta-adrenoceptor system mediated responses. To this end, the functional interaction of polyamine modifying drugs on isoproterenol-elicited cardiotonic effect, in isolated left atria of male Wistar rats, and their effects on [(3)H]dihydroalprenolol (DHA) binding on beta-adrenoceptors and on adenylyl cyclase activity of membrane heart were studied. Polyamines interact with beta-adrenoceptors in rat heart, as shown by the displacement of [(3)H]DHA binding. Furthermore, putrescine (but not spermidine or spermine) increased adenylyl cyclase activity, elicited a positive inotropism and increased intracellular cAMP. The putrescine effect on adenylyl cyclase was not antagonized by the beta-adrenoceptors blockers, alprenolol and ICI-118,551, and facilitated the isoproterenol effect. Neither alprenolol, atenolol nor ICI-118,551 antagonized putrescine-elicited positive inotropism. However, the effect was abolished in preparations with desensitized beta-adrenoceptors. alpha-Difluoromethylornithine, an inhibitor of ornithine decarboxylase, antagonized the effect of isoproterenol on inotropism and cAMP increase. In addition, putrescine might elicit effects by mechanisms independent of beta-adrenoceptor system, since in left atria with functional desensitized receptors an interaction with ouabain-elicited cardiotonic effect was observed. These results suggest that putrescine may act as a low affinity agonist on beta-adrenoceptors and modulate acute responses mediated by beta-adrenoceptors. These findings may be of importance in the physiology and in diseases involving cardiac beta-adrenoceptors.