Marcela Bitran

On the mechanism of presynaptic autoreceptor-mediated inhibition of transmitter synthesis in dopaminergic nerve terminals

The effect of apomorphine (APO) upon dopamine (DA) synthesis and release from rat striatal slices was studied. The synthesis of DA was measured by incubating the slices in Krebs-Ringer phosphate (KRP) medium of variable ionic composition containing l-tyrosine[14C-U] as DA precursor. A superfusion system was used to study both spontaneous and K+-induced release of labeled DA from striatal slices. The addition of APO directly to the normal KRP medium markedly blocked the formation of [14C]DA from [14C]tyrosine with an ic50 of 1.8 × 10−7 M. Haloperidol (4 × 10−7 M), a known DA antagonist, produced a shift to the right of the concentration-response curve for APO inhibition on DA synthesis, whereas the DA antagonist (+)butaclamol (4 × 10−7 M) completely reversed the inhibition caused by APO (2 × 10−7 M). DA uptake blockers, such as benztropine (2 × −6 M) or cocaine (1 × 10−5 M), did not affect the ability of APO to inhibit DA synthesis. Furthermore, the α2-adrenergic agonist clonidine produced only a mild inhibition and the β-adrenergic agonist isoproterenol produced no inhibition of [14C]DA formation. APO was able to inhibit DA formation both in the absence of calcium in the incubation medium or in the presence of high external calcium concentrations (4, 8 and 24 mM) which depress the rate of DA synthesis. Incubation conditions that cause an increase of free intraneuronal calcium concentrations, such as Na+-free medium, the presence of ouabain (1 × 10−4 M), or K+ depolarization, dramatically abolished or impaired the ability of APO to inhibit DA synthesis in striatal slices. It was not possible to demonstrate any change in spontaneous and K+ (27 mM)-induced release of DA in the presence of APO concentrations that produced a marked inhibition of DA synthesis. The results reported in this work indicate that tissue slices can be used as a valuable experimental tool to study the inhibitory effect of APO on DA synthesis, and that this effect occurs through an interaction of APO with presynaptic DA autoreceptors located in striatal dopaminergic nerve terminals. The results obtained are not in keeping with the hypothesis that this autoreceptormediated inhibition of DA synthesis occurs through regulation of calcium influx into the DA nerve terminals. However, the possibility is raised that a sensitivity to high intraneuronal calcium concentration exists during the events that mediate APO-DA autoreceptor interaction and DA synthesis inhibition. It is further suggested that DA-synthesis-modulating autoreceptors do not participate in the modulation of DA release.

Neuropeptide Y induced inhibition of noradrenaline release in rat hypothalamus: role of receptor subtype and nitric oxide

We aimed at characterizing the receptor subtype and the signaling pathway involved in the inhibitory effect of neuropeptide Y on the release of endogenous noradrenaline from rat hypothalamus. Slices of hypothalamus were stimulated with two trains of electrical pulses, and the release of noradrenaline and nitric oxide was measured. The electrical stimulation of hypothalamic slices induced a consistent release of both endogenous noradrenaline and NO. Neuropeptide Y inhibited concentration dependently the stimulated noradrenaline release. Similarly, agonists for neuropeptide Y Y1, Y2 and Y5 receptors inhibited noradrenaline release, albeit with a potency lower than neuropeptide Y. GW1229, a selective neuropeptide Y Y1 receptor antagonist counteracted the effect of neuropeptide Y, but not that of PYY-(3-36), an agonist active at neuropeptide Y Y5 and Y2 receptors. These results indicate that the inhibitory effect of neuropeptide Y is likely mediated by several receptor subtypes, including neuropeptide Y Y1, Y5 and possibly Y2 receptors. One microM NPY significantly enhanced NO release induced by the electrical stimulation. NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, abolished NO release and blocked the inhibitory effect of neuropeptide Y on noradrenaline release. We conclude that nitric oxide participates in the signaling pathway of neuropeptide Y in the rat hypothalamus.

GW1229, a novel neuropeptide Y Y1 receptor antagonist, inhibits the vasoconstrictor effect of neuropeptide Y in the hamster microcirculation

We studied the effect of GW1229, a novel neuropeptide Y Y1 receptor antagonists, on the vasoconstriction induced by neuropeptide Y and structurally related analogs in the hamster cheek pouch microcirculation. Changes in arteriolar diameter and microvascular conductance were assessed by intravital microscopy and measurement of sodium22 clearance. GW1229 did not affect basal vascular conductance but inhibited, concentration dependently, the reduction in arteriolar diameter and vascular conductance induced by 100 nM neuropeptide Y. GW1229 also counteracted the vasoconstrictor effect of 100 nM [Leu31,Pro34]neuropeptide Y, and that of 300 nM neuropeptide Y-[(13-36). In contrast, GW1229 had no effect on the vasoconstriction induced by noradrenaline. We conclude that the vasoconstrictor effect on neuropeptide Y in the hamster cheek pouch is mediated by neuropeptide Y Y1 receptors. The maintenance of physiological tone in this vascular bed does not involve the participation of endogenous neuropeptide Y.

Identificación de las necesidades de capacitación docente de los jefes de programa de especialización médica

BACKGROUND Training of postgraduate medical specialty program managers (PMSPM) is essential for the proper development of their programs. AIM To identify the main training needs of PMSPM at a medical school. MATERIAL AND METHODS A mixed-methodology approach was implemented including focus group/interviews and the administration of the Program Managers Training Needs Assessment Questionnaire (PROMANAQ) developed by an expert panel with 59 items (with two sections: relevance/performance-self-perception). Higher priority was assigned to items with high relevance and low performance. RESULTS Forty five PMSPM completed the PROMANAQ (81.8% response rate). Both sections of PROMANAQ were highly reliable (Cronbach alpha of 0.95/0.97 for relevance/performance-self-perception, respectively). The items with higher priority value were evaluation of clinical educators, evaluation of teaching programs and accreditation of programs. Ten PMSPM were included in the focus group (18.2% of the universe). The findings of the qualitative component were concordant with the areas explored in the questionnaire. CONCLUSIONS The PROMANAQ is valid and reliable to identify the training needs of PMSPM. The views of PMSPM must be taken into account for faculty development planning.BACKGROUND Training of postgraduate medical specialty program managers (PMSPM) is essential for the proper development of their programs. AIM To identify the main training needs of PMSPM at a medical school. MATERIAL AND METHODS A mixed-methodology approach was implemented including focus group/interviews and the administration of the Program Managers Training Needs Assessment Questionnaire (PROMANAQ) developed by an expert panel with 59 items (with two sections: relevance/performance-self-perception). Higher priority was assigned to items with high relevance and low performance. RESULTS Forty five PMSPM completed the PROMANAQ (81.8% response rate). Both sections of PROMANAQ were highly reliable (Cronbach alpha of 0.95/0.97 for relevance/performance-self-perception, respectively). The items with higher priority value were evaluation of clinical educators, evaluation of teaching programs and accreditation of programs. Ten PMSPM were included in the focus group (18.2% of the universe). The findings of the qualitative component were concordant with the areas explored in the questionnaire. CONCLUSIONS The PROMANAQ is valid and reliable to identify the training needs of PMSPM. The views of PMSPM must be taken into account for faculty development planning.

Evaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14

Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947.

Recursos psicosociales positivos y salud cardiovascular

Health is defined as a state of complete physical, mental and social wellbeing and not merely as the absence of disease. Thus, medical practice must not only deal with diagnosis and treatment of pathological conditions and solve physical ailments, but also promote a comprehensive wellbeing state -including the psychological domain- to achieve positive health. Therefore, it is necessary to scientifically identify the psychological and social determinants that contribute more effectively to prevent disease and achieve optimal health. This article reviews the most recent evidence showing the importance of positive psychological and social resources on cardiovascular disease, the leading cause of morbidity and mortality as well as health care costs worldwide. Evidence is summarized regarding the role of positive psychosocial factors as health promoters and protectors against cardiovascular risk, the possible mechanisms that explain this association, and the practical implications and future research arising from this perspective. The development of interdisciplinary research in this field, incorporating the area of psychological wellbeing, should help to generate and test new strategies aimed at more effective cardiovascular disease prevention and treatment.Health is defined as a state of complete physical, mental and social wellbeing and not merely as the absence of disease. Thus, medical practice must not only deal with diagnosis and treatment of pathological conditions and solve physical ailments, but also promote a comprehensive wellbeing state -including the psychological domain- to achieve positive health. Therefore, it is necessary to scientifically identify the psychological and social determinants that contribute more effectively to prevent disease and achieve optimal health. This article reviews the most recent evidence showing the importance of positive psychological and social resources on cardiovascular disease, the leading cause of morbidity and mortality as well as health care costs worldwide. Evidence is summarized regarding the role of positive psychosocial factors as health promoters and protectors against cardiovascular risk, the possible mechanisms that explain this association, and the practical implications and future research arising from this perspective. The development of interdisciplinary research in this field, incorporating the area of psychological wellbeing, should help to generate and test new strategies aimed at more effective cardiovascular disease prevention and treatment.

Mejoría en las habilidades de comunicación escrita de estudiantes de medicina: Impacto de un taller de escritura

Antecedentes. Los jovenes que ingresan a la carrera de medicina se encuentran entre los estudiantes mas destacados de nuestro pais; sin embargo, muchos de ellos tienen dificultades para comunicarse por escrito. Para favorecer el desarrollo de las habilidades de comunicacion escrita, la escuela de medicina de la Pontificia Universidad Catolica de Chile introdujo en 2005 un taller de escritura en la malla curricular de tercer ano. Objetivos. Describir el taller de escritura y su impacto sobre las habilidades de comunicacion escrita de 3 cohortes de estudiantes. Metodos. El taller funciono con una metodologia participativa que privilegio la practica de la escritura y el ‘feedback’. Los estudiantes trabajaron en grupos pequenos con docentes de la escuela especialmente capacitados en redaccion. Para evaluar el impacto del taller, se comparo la calidad de los ensayos escritos por los estudiantes antes y despues del taller. La correccion estuvo a cargo de un equipo profesional que evaluo aspectos formales de redaccion y procesamiento de las ideas mediante una rubrica analitica. Resultados. La calidad de la escritura mejoro significativamente luego del taller, particularmente en argumentacion, estructura textual y estructura de parrafo. Esta mejoria fue inversamente proporcional al nivel inicial de desempeno del estudiante, e independiente del genero. Conclusiones. Es posible corregir falencias de redaccion escrita de estudiantes universitarios de alto nivel academico, con un taller basado en la practica deliberada y el ‘feedback’ oportuno. Por su diseno, pensamos que el taller aqui descrito podria ser de utilidad para estudiantes de otras escuelas y universidades.

Evaluación de aproximaciones al aprendizaje clínico a través del CEACLIN: Resultados en estudiantes de medicina en una universidad chilena

BACKGROUND Throughout medical education, students are gradually incorporated into authentic clinical practice scenarios. AIM To describe the use of clinical learning strategies by Chilean students and compare them according to sex and year of training. MATERIAL AND METHODS The Clinical Learning Strategies Questionnaire (CEACLIN) was applied to 336 students from the 4th to 6th year of medicine at a Chilean university. RESULTS The most frequently reported strategies were related to the search for autonomy, reliable environments for learning, observation of others and attention to emotions. The less frequent was the handling of academic burden. Gender accounted for significant differences in eight of the 11 strategies identified by CEACLIN, while years of training accounted for five of the 11. The cluster analysis identified two groups: the first group comprised nine CEACLIN strategies, with a slightly higher proportion of women and 5th and 6th year students. The second group consisted mainly of men in the 4th year. CONCLUSIONS Reported strategies include a set of actions oriented to the development of autonomy and confidence through the search for valid information and learning from and with others. These findings are associated with sex and year of training.

Estrategias del aprendizaje inicial de la clínica: más allá de los hábitos de estudio. Percepciones de estudiantes y docentes clínicos

Background: Teaching methods of the undergraduate medical curriculum change considerably from the first years to clinical training. Clinical learning occurs in complex and varied scenarios while caring for patients. Students have to adapt their learning approaches and strategies to be able to integrate theory and clinical practice and become experiential learners. Aim: To identify the strategies used by medical students to learn during the initial clinical years, as reported by students themselves and by their clinical tutors. Material and methods: We performed eight focus group discussions with 54 students enrolled in years three to six and we interviewed eight clinical tutors. Both focus group discussions and interviews were audio recorded, transcribed and analyzed according to Grounded Theory. Results: Four main themes were identified in the discourse of both students and tutors: Strategies oriented to theoretical learning, strategies oriented to experiential learning, strategies for integrating theory and practice and strategies oriented to evaluation. The mentioning of individual differences was present across the reports of both students and tutors. Conclusions: Students use a rich variety of strategies to face the challenges of clinical learning. Both students and tutors recognize that the learning approaches and strategies vary according the nature of the task and individual differences. The responses of students bring particular knowledge of the approaches used for the theoretical and practical integration and delve into the social dimension of learning.BACKGROUND Teaching methods of the undergraduate medical curriculum change considerably from the first years to clinical training. Clinical learning occurs in complex and varied scenarios while caring for patients. Students have to adapt their learning approaches and strategies to be able to integrate theory and clinical practice and become experiential learners. AIM To identify the strategies used by medical students to learn during the initial clinical years, as reported by students themselves and by their clinical tutors. MATERIAL AND METHODS We performed eight focus group discussions with 54 students enrolled in years three to six and we interviewed eight clinical tutors. Both focus group discussions and interviews were audio recorded, transcribed and analyzed according to Grounded Theory. RESULTS Four main themes were identified in the discourse of both students and tutors: Strategies oriented to theoretical learning, strategies oriented to experiential learning, strategies for integrating theory and practice and strategies oriented to evaluation. The mentioning of individual differences was present across the reports of both students and tutors. CONCLUSIONS Students use a rich variety of strategies to face the challenges of clinical learning. Both students and tutors recognize that the learning approaches and strategies vary according the nature of the task and individual differences. The responses of students bring particular knowledge of the approaches used for the theoretical and practical integration and delve into the social dimension of learning.

Reading Strategies used by Undergraduate Medical Students to Comprehend Scientific Publications

This study identifies strategies used by non-English speaking medical students to comprehend scientific biomedical publications. It also describes the relationship among self-reported proficiency (both in English and in topic matter), perceived difficulty of the publication, reading time and subjective perceptions of learning and satisfaction.