A Brain Ischemia-Reperfusion Model for the Study of Tau Phosphorylation and O-GlcNAcylation.

Cerebral ischemia produces a decrease, loss, or instability of the assembly processes in the neuronal cytoskeleton, related to the alteration in the normal processes of phosphorylation of the Tau protein, triggering its hyperphosphorylation and altering the normal processes of formation of neuronal microtubules. Here we describe the methods used to study the impact of middle cerebral artery occlusion (MCAo) on neurological functions and Tau phosphorylation in Wistar rat brain.

Trastorno depresivo, trastorno de ansiedad y dolor crónico: múltiples manifestaciones de un núcleo fisiopatológico y clínico común / Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core

RESUMEN Introducción: Una alta proporción de los trastornos depresivos se acompañan de manifestaciones ansiosas, así como la depresión y la ansiedad cursan frecuentemente con dolor. En otro sentido, las manifestaciones dolorosas causan o empeoran los síntomas depresivos y ansiosos. Cada vez hay más evidencia sobre la similitud fisiopatológica, imagenológica y neurofisiológica del dolor y la depresión. Métodos: Revisión narrativa de los aspectos fisiopatológicos y clínicos de la comorbilidad depresión y dolor crónico. Se incluyen los artículos de investigación que enfatizan los elementos relevantes relacionados con la comprensión de la fisiopatología de ambas manifestaciones. Resultados: Con los más recientes avances en técnicas bioquímicas y celulares y el advenimiento de tecnologías imagenológicas de avanzada, se ha podido considerar cada vez más claramente la aproximación etiopatogénica, fisiopatológica y clínica de estos trastornos. Se sistematiza esta información en imágenes y cuadros comprensivos. Conclusiones: El reconocimiento de que el polimorfismo de los genes relacionados con la inflamación genera susceptibilidad a las manifestaciones depresivas y puede modificar la respuesta a los tratamientos antidepresivos establece que la respuesta inflamatoria no solo es un componente etiopatogénico del dolor, sino del estrés y la depresión. De igual manera, la similitud en la aproximación con imágenes corrobora la analogía no solo estructural, sino también funcional y fisiopatológica, entre la depresión y el dolor crónico. El conocimiento de la comorbilidad depresión-ansiedad-dolor crónico es importante en la búsqueda de intervenciones terapéuticas eficaces.

ABSTRACT Introduction: A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Methods: Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. Results: The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. Conclusions: The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions.

Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core. / Trastorno depresivo, trastorno de ansiedad y dolor crónico: múltiples manifestaciones de un núcleo fisiopatológico y clínico común.

INTRODUCTION: A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. METHODS: Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. RESULTS: The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. CONCLUSIONS: The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions.

Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock.

Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg-1·min-1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] (R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes (R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock.NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.

Assessment transcallosal Diaschisis in a model of focal cerebral ischemia in rats.

OBJECTIVE: To evaluate transcallosal changes after a local ischemic injury in rats by using the monoclonal marker anti-NeuN (Mouse anti-neuronal nuclei). METHODS: Twenty-eight adult, male, Wistar rats were subjected to focal injury in the right hemisphere. The technique used was the experimental model of focal ischemic injury through intraluminal suture of the middle cerebral artery. Analyses were made for the five groups: after the lesion (control), at 24 h, 96 h, 10 days and 20 days. Exofocal neuronal damage was inferred from neuronal immunoreactivity changes to NeuN. RESULTS: In the cortex contralateral to the lesion, immunoreactivity was diminished. This finding was most notable in the supra-granular sheets 24 h post ischemia. After 96 h, there was a generalized diminishment of the inmmunoreactivity in the supra and infra-granular sheets. At 10 and 20 days, the tissue recovered some immunoreactivity to NeuN, but there were some changes in the VI layer. CONCLUSION: The immunoreactive changes to NeuN support the process of inter-hemispheric diaschisis. Changes in immunoreactivity could indicate metabolic stress secondary to the disruption in connectivity to the site of lesion.

OBJETIVO: Evaluar los cambios exofocales transcallosos después de lesión isquémica focal en ratas, mediante marcación inmunohistoquímica con el anticuerpo monoclonal anti-NeuN (Mouse Anti-Neuronal Nuclei). MÉTODOS: Se intervinieron 28 ratas machos Wistar adultas. Mediante el modelo experimental de isquemia cerebral focal del territorio de la arteria cerebral media por filamento intraluminal, se les ocasionó una lesión focal en el hemisferio derecho. Posteriormente se evaluó el hemisferio contralateral, marcando la población neuronal con el anticuerpo monoclonal anti-NeuN. Se definieron cinco grupos de evaluación: uno de control, 24 horas, 96 horas, 10 días y 20 días. Se evaluaron los cambios neuronales exofocales después de la lesión con base en la observación de los cambios en la inmunoreactividad de las neuronas al NeuN. RESULTADOS: Se redujo la inmunoreactividad en la corteza contralateral a la lesión. Este fenómeno fue más notable en las capas supragranulares después de 24 h post isquemia. Después de 96 h hubo una disminución generalizada de la inmmunoreactivity en las capas supra e infragranulares. A los 10 y 20 días, el tejido recobró alguna inmunoreactividad NeuN, estos cambios se dieron en la capa VI. CONCLUSIONES: Los cambios inmunorreactivos a NeuN apoyan el proceso de diasquisis interhemisférica. Los cambios en la inmunorreactividad podrían indicar estrés metabólico secundario a la interrupción en la conectividad con el sitio de la lesión.

Assessment transcallosal Diaschisis in a model of focal cerebral ischemia in rats / Evaluación de la diásquisis transcallosa en un modelo de isquemia cerebral focal en ratas

Objective: To evaluate transcallosal changes after a local ischemic injury in rats by using the monoclonal marker anti-NeuN (Mouse anti-neuronal nuclei). Methods: Twenty eight adult, male, Wistar rats were subjected to focal injury in the right hemisphere. The technique used was the experimental model of focal ischemic injury through intraluminal suture of the middle cerebral artery. Analyses were made for the five groups: and after the lesion (control), at 24 h, 96 h, 10 days and 20 days. Exofocal neuronal damage was inferred from neuronal immunoreactivity changes to NeuN. Results: In the cortex contralateral to the lesion, immunoreactivity was diminished. This was most notable in the supragranular layers 24 h post ischemia. After 96 h, there was a generalized diminishment of the inmmunoreactivity in supra and infragranular layers. At 10 and 20 days, the tissue recovered some NeuN immunoreactivity, but there were set changes in the VI layer. Conclusion: The immunoreactive changes to NeuN support the process of interhemispheric diaschisis. Changes in immunoreactivity could indicate metabolic stress secondary to the disruption in connectivity to the site of lesion.

Objetivo: Evaluar los cambios exofocales transcallosos después de lesión isquémica focal en ratas, mediante marcación inmunohistoquímica con el anticuerpo monoclonal anti-NeuN (Mouse Anti-Neuronal Nuclei). Métodos: Se intervinieron 28 ratas machos Wistar adultas. Mediante el modelo experimental de isquemia cerebral focal del territorio de la arteria cerebral media por filamento intraluminal, se les ocasionó una lesión focal en el hemisferio derecho. Posteriormente se evaluó el hemisferio contralateral, marcando la población neuronal con el anticuerpo monoclonal anti-NeuN. Se definieron cinco grupos de evaluación: uno de control, 24 h, 96 h, 10 días y 20 días. Se evaluaron los cambios neuronales exofocales después de la lesión con base en la observación de los cambios en la inmunoreactividad de las neuronas al NeuN. Resultados: Se redujo la inmunoreactividad en la corteza contralateral a la lesión. Este fenómeno fue más notable en las capas supragranulares después de 24 h post isquemia. Después de 96 h hubo una disminución generalizada de la inmmunoreactivity en las capas supra e infragranulares. A los 10 y 20 días, el tejido recobró alguna inmunoreactividad NeuN, estos cambios se dieron en la capa VI. Conclusiones: Los cambios inmunorreactivos a NeuN apoyan el proceso de diasquisis interhemisférica. Los cambios en la inmunorreactividad podrían indicar estrés metabólico secundario a la interrupción en la conectividad con el sitio de la lesión.

Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock?

PURPOSE: Septic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock. METHODS: Prospective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures. RESULTS: Progressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient -5.35, 95 % CI -6.41 to -4.29, p < 0.001; T6: coefficient, -3.49, 95 % CI -4.43 to -2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R (2) = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect. CONCLUSIONS: During early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.

Combination of arterial lactate levels and venous-arterial CO2 to arterial-venous O 2 content difference ratio as markers of resuscitation in patients with septic shock.

PURPOSE: To evaluate the prognostic value of the Cv-aCO2/Da-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock. METHODS: Prospective observational study in a 60-bed mixed ICU. One hundred and thirty-five patients with septic shock were included. The resuscitation protocol targeted mean arterial pressure, pulse pressure variations or central venous pressure, mixed venous oxygen saturation, and lactate levels. Patients were classified into four groups according to lactate levels and Cv-aCO2/Da-vO2 ratio at 6 h of resuscitation (T6): group 1, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; group 2, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0; group 3, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; and group 4, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0. RESULTS: Combination of hyperlactatemia and high Cv-aCO2/Da-vO2 ratio was associated with the worst SOFA scores and lower survival rates at day 28 [log rank (Mantel-Cox) = 31.39, p < 0.0001]. Normalization of both variables was associated with the best outcomes. Patients with a high Cv-aCO2/Da-vO2 ratio and lactate <2.0 mmol/L had similar outcomes to hyperlactatemic patients with low Cv-aCO2/Da-vO2 ratio. The multivariate analysis revealed that Cv-aCO2/Da-vO2 ratio at both T0 (RR 3.85; 95 % CI 1.60-9.27) and T6 (RR 3.97; 95 % CI 1.54-10.24) was an independent predictor for mortality at day 28, as well as lactate levels at T6 (RR 1.58; 95 % CI 1.13-2.22). CONCLUSION: Complementing lactate assessment with Cv-aCO2/Da-vO2 ratio during early stages of resuscitation of septic shock can better identify patients at high risk of adverse outcomes. The Cv-aCO2/Da-vO2 ratio may become a potential resuscitation goal in patients with septic shock.

Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock.

INTRODUCTION: Venous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters. METHODS: We conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ≥ 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2. RESULTS: Patients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ≥ 70% or mixed venous oxygen saturation (SvO2) ≥ 65% but with concomitantly high Pv-aCO2 at different developmental points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28. CONCLUSION: The persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of death in apparently resuscitated patients.

Aspectos conceptuales de la enseñanza de la psiquiatría en Colombia / Conceptual Aspects of the Teaching Psychiatry in Colombia

Introducción: La enseñanza de la psiquiatría en Colombia es el resultado de la confluencia de diferentes corrientes conceptuales que desde inicios del siglo XX empezaron a hacer parte del quehacer psiquiátrico. Este conocimiento se trasladó de generación en generación mediante métodos pedagógicos hasta cristalizarse en la noción actual de la formación. Métodos: Se reconocen los diferentes momentos fundamentales de la historia de la psiquiatría en el mundo y la introducción de estas tendencias en Colombia, especificando su impacto en la enseñanza. Resultados: La estructuración actual toma de la psiquiatría organodinámica francesa algunos reductos, especialmente de los aspectos conceptuales y clínicos; así mismo, se forma a partir de la concepción kraepeliana y las terapias biológicas introducidas desde el segundo cuarto del siglo pasado y la tendencia psicoanalítica introducida desde 1950. Conclusión: Los departamentos de psiquiatría de nuestro país forman un psiquiatra hábil y destacado en el manejo de las enfermedades mentales, con conocimientos básicos en la fisiopatología y la psicopatología, con buen entrenamiento en psicofarmacología y en mayor o menor proporción en psicoterapia, se evidencia una limitación en la formación de salud mental comunitaria.

Introduction: The teaching of Psychiatry in Colombia is the result of the accumulation of different conceptual streams dating back to early twentieth century and the beginning of Psychiatric study. By a way of different teaching methods, this knowledge was transferred from generation to generation to materialize into its current formation. Methods: Different key moments are recognized in the history of Psychiatry throughout the world and the introduction of these trends in Colombia, and specifically its impact on teaching. Results: The current structure derives from French elements of organdynamic Psychiatry, both conceptual and clinical, likewise, it is formed from conception kraepeliana and biologic therapies introduced from the second quarter of the last century and the psychoanalytic trend introduced since 1950. Conclusion: The Psychiatric Departments of Colombia form prominently in Psychiatry and are skillful in managing mental illness, with basic knowledge of pathophysiology and psychopathology, as well as good training in psychopharmacology and psychotherapy. A limitation is evident in the formation of community mental health.

[Conceptual Aspects of the Teaching Psychiatry in Colombia]. / Aspectos conceptuales de la enseñanza de la psiquiatría en Colombia.

INTRODUCTION: The teaching of Psychiatry in Colombia is the result of the accumulation of different conceptual streams dating back to early twentieth century and the beginning of Psychiatric study. By a way of different teaching methods, this knowledge was transferred from generation to generation to materialize into its current formation. METHODS: Different key moments are recognied in the history of Psychiatry throughout the world and the introduction of these trends in Colombia, and specifically its impact on teaching. RESULTS: The current structure derives from French elemens of organ-dynamic Psychiatry, both conceptual and clinical, likewise, it is formed from conception kraepeliana and biologic therapies introduced from the second quarter of the last century and the psychoanalytic trend introduced since 1950. CONCLUSION: The Psychiatric Departments of Colombia form prominently in Pychiatry and are skillful in managing mental illness, with basic knowledge of pathophysiology and psychopathology, as well as good training in psychopharmacology and psychotherapy. A limitation is evident in the formation of community mental health.

[Study of Flexible Doses of Paliperidone ER in Pacients with Schizophrenia who Have Undergone Inefficient Treatment with other Antipsychotics]. / Estudio de dosis flexibles de paliperidona ER en pacientes con esquizofrenia previamente tratados sin efectividad con otros antipsicóticos.

BACKGROUND: Extended-release (ER) paliperidone is an innovative atypical antipsychotic that allows minimal peak-to-through fluctuations with once-daily dosing. OBJECTIVE: To evaluate effectiveness, safety and tolerability of flexible, once-daily doses of paliperidone ER (3-12 mg/day) in patients with schizophrenia from Argentina and Colombia who had previously failed treatment with other antipsychotic agents. METHODS: The authors conducted a 6-month, open-label, prospective and multicentric study. Effectiveness was assessed with Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Other measures of effectiveness, safety and tolerability, were also conducted. RESULTS: Paliperidone ER 3-12 mg/day improved Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint) from baseline to study end (p < 0,001). In the PANSS total score, the mean change from baseline (83, 9 units) to end point (53,7 units) was significant (p < 0,001). Flexible doses of paliperidone ER demonstrated a ≥20% reduction in the PANSS total score (p<0.001) in almost two-thirds of patients. PSP mean change from baseline (52 units) to end point (85 units) was significant (p < 0,001). Secondary effectiveness assessments, as well as safety and tolerability measures, demonstrated favourable results throughout the study. CONCLUSIONS: Flexible doses of paliperidone ER over 6 months were effective, safe and well tolerated in patients with schizophrenia from Argentina and Colombia.

Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational study.

OBJECTIVE: To explore the relative association of adverse events with health-related quality of life (HRQL) in patients (N = 16 091) with schizophrenia, treated with antipsychotic medication. METHODS: In this post hoc analysis of data from two 3-year observational studies, a mixed effects model with repeated measures was used to evaluate the association between HRQL (EuroQoL visual analogue scale (EQ-VAS)) and pre-specified covariates including: severity of illness, extrapyramidal symptoms, tardive dyskinesia, sexual dysfunction, and clinically significant weight gain (> 7% increase from baseline after > or = 3 months of treatment). RESULTS: Mean EQ-VAS increased from 47.8 +/- 21.7 at baseline to 72.4 +/- 18.4 after 36 months. The rank order of the negative association of adverse events with HRQL was: sexual dysfunction (effect estimate -4.04; 95% CI -4.30 to -3.79), extrapyramidal symptoms (effect estimate -2.09; 95% CI -2.43 to -1.75), and tardive dyskinesia (effect estimate -0.89; 95% CI -1.46 to -0.32). CONCLUSIONS: Differences were observed in the direction and magnitude of the association between each adverse event and HRQL. Recognition of the relative association of adverse events with HRQL may contribute to improved adherence of patients with schizophrenia to antipsychotic therapy.

Análisis de los aspectos asociados a la enfermedad mental en Colombia y la formación en psiquiatría / Analysis of Aspects Related to Mental Illness in Colombia and Training in Psychiatry

Introducción: La salud y la enfermedad mental son fenómenos de gran complejidad en los cuales intervienen aspectos ecológicos y biopsicosociales. La historia natural de la salud y la enfermedad mental podrían ser modificadas por la ejecución de programas de salud general y salud pública. Método: En primer lugar, se construye un panorama epidemiológico y social mediante un análisis multifactorial de aspectos relacionados con la enfermedad mental, como la pobreza, la violencia, la farmacodependencia y los desastres naturales. En segundo lugar, se examinan las necesidades en psiquiatría y salud mental con el fin de confrontarlas con el primer punto. Y, en tercer lugar, se evalúa mediante diferentes estrategias el estado de la especialidad y las posibilidades de atención. Resultados: La formación del profesional en psiquiatría en Colombia carece de los conceptos de psiquiatría comunitaria y de salud mental comunitaria, pues su formación tiene un énfasis médico y asistencial. La literatura colombiana en el contexto nacional e internacional prácticamente no contiene temas relacionados con experiencias en salud mental comunitaria o aspectos sociológicos de la psiquiatría. Conclusión: Se observa una incongruencia entre la realidad en salud mental y la formación en psiquiatría en Colombia, lo que podría tener repercusiones en el momento de plantear políticas de intervención en salud mental para las comunidades. Es necesario que, desde el punto de vista de la salud mental y la psiquiatría, se aborden temas cruciales como son la violencia, la pobreza, la farmacodependencia y las consecuencias de los desastres naturales.

Introduction: Mental health and mental illness are phenomena of great complexity in which ecological and biopsychosocial aspects intervene. The natural history of mental health and mental illness could be modified by carrying out programs of general and public health. Method: First, the reality of mental health in Colombia is assessed by depicting epidemiological and social aspects and analyzing the circumstances related with mental illness such as poverty, violence, drug dependence and natural disasters. Second, the needs of psychiatry and mental health are assessed with the purpose of confronting them with the first point. Third, by means of different strategies the state of the specialty and the possibilities of care are examined. Results: Training of the psychiatrist in Colombia does not include concepts of community psychiatry and community mental health, as its main emphasis is on medical training and assistance. Colombian literature in the national and international context does not include topics related with experiences in community mental health. Conclusion: Great incongruity is observed between reality in mental health and training in psychiatry that could have grave repercussions when the time comes to outline intervention policies regarding mental health for communities.

Cambios exofocales en la isquemia cerebral focal experimental: una visión experimental y su correlato clínico / Exofocal changes in experimental focal cerebral ischemia: an experimental approach and its clinical correlation

Introducción: El cerebro es un órgano extraordinariamente dinßmico, su fisiología es sorprendente especialmente por la respuesta concertada del tejido nervioso en su conjunto ante situaciones patológicas. Estas respuestas incluyen no solo aquellas desencadenadas por la estimulación de receptores o cambios en el metabolismo celular sino los complejos cambios genéticos y las modificaciones continuas de los fenotipos celulares y la conectividad que se reflejan en el conjunto del cerebro incluyendo los procesos de neurogénesis, neuritogénesis y en general de plasticidad neuronal. Los aspectos relacionados con la neuroplasticidad han sido planteados como el fundamento de la fisiopatología de la isquemia cerebral y los fenómenos exofocales relacionados. El progreso en el entendimiento de la fisiopatología de la lesión cerebral ha requerido de la implementación de modelos experimentales contrastables que permiten evaluar los fenómenos celulares inmediatos y a largo plazo, asociar los hallazgos a la clínica y plantear posibles intervenciones farmacológicas. Objetivo: Revisar los avances en los fenómenos de plasticidad después de lesión desde el punto de vista experimental haciendo énfasis en los sectores alejados del foco de injuria.Discusión y conclusiones: En el presente trabajo se exponen los avances recientes en el entendimiento de los fenómenos de neuroplasticidad desde la óptica de un modelo experimental, así como también se exponen los hallazgos preclínicos relacionados con los fenómenos exofocales isquémicos: las alteraciones en ßreas en las cuales la isquemia no es completa, las alteraciones en areas no isquémicas ocasionadas por señales químicas o eléctricas emanadas del foco isquémico, las alteraciones de los patrones de conectividad y los cambios adaptativos en estructuras cerebrales remotas al foco. Se finaliza con un recuento de los aspectos clínicos asociados con estos cambios y las estrategias experimentales y clínicas de intervención farmacológica.

Introduction: The brain is an extraordinarily dynamic structure specially its physiology in response to pathological events. This response include several mechanisms such as changes in cell metabolism, genes expression and possible modifications in cell phenotype and in connectivity that reflect activation of processes like neurogenesis, neuritogenesis and synaptogenesis. Several aspects related with neuroplasticity has been proposed as part of the pathophysiological bases to understand brain ischemia and its exofocal phenomena. Progress in understanding of the pathophysiology of brain lesion has required the use of experimental models to evaluate cellular events that occur immediately after the lesion or later, to associate this changes with clinical observations and to propose pharmacological neuroprotection therapies.Objective: The purpose of the present work is to compile the advances in understanding of plasticity after brain lesion, mainly related with exofocal areas to a core lesion. Discussion and conclusions: The present work shows recent advances in neuroplasticity based on experimental approaches, and preclinical findings related with the exofocal ischemic phenomena: changes in areas not completely ischemic, changes in no ischemic areas affected by chemical or electrical signals, changes in the pattern of connectivity and adaptative changes in remote areas to the ischemic core. Finally, we discuss clinical aspects associated with this changes, experimental strategies and clinical pharmacological interventions.

Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.

During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.

Response and relapse in patients with schizophrenia treated with olanzapine, risperidone, quetiapine, or haloperidol: 12-month follow-up of the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study.

OBJECTIVE: The primary aim of this study was to compare the effectiveness of 12 months' treatment with olanzapine, risperidone, quetiapine, or haloperidol in preventing relapse of schizophrenia. The study also examined other measures of clinical effectiveness and tolerability. METHOD: Outpatients with schizophrenia (ICD-10 or DSM-IV), who initiated or changed antipsychotic treatment, entered this 3-year, naturalistic, prospective, observational study between November 2000 and December 2001. At baseline, subsets of patients were prescribed monotherapy with olanzapine (N = 3222), risperidone (N = 1116), quetiapine (N = 189), or haloperidol (N = 256). Patients remaining on monotherapy were assessed using the Clinical Global Impression-Schizophrenia scale. Relapse rate was determined from the responder subset. Treatment patterns, patient perception of treatment compliance, substance and alcohol intake patterns, and treatment tolerability were recorded. Results are based on 12-month treatment data. RESULTS: Compared to haloperidol-treated patients, olanzapine- and risperidone-treated patients had approximately 3 to 4 times higher odds of response at 12 months (p

El Cerebro: De la Estructura y la Función a la Psicopatología. Primera Parte: Bloques Funcionales / The Brain: From Structure and Function to Psychopathology, First Part: Functional Blocks

Las últimas dos décadas han sido de fundamental importancia para el estudio y para el entendimiento del sistema nervioso. Este progreso no sólo ha incluido el abordaje de fenómenos subyacentes a la masa cerebral de tipo neuroquímico, neurofisiológico, neuroanatómico, citoarquitectónico, imagenológico, etc., sino también la relación de estos conocimientos con aspectos complejos de la conducta y el psiquismo. La intención de recalcar con una visión moderna el alcance de las neurociencias necesariamente ha de reflejarse en una comprensión más amplia de la realidad de la enfermedad mental, lo que permite una confluencia entre nuestra condición biológica, conductual, psíquica y social. Con este artículo se pretende revisar las bases biológicas para el entendimiento de los trastornos mentales y del comportamiento. Para tal fin, y basados en las investigaciones neurobiológicas recientes, se describen los elementos constitutivos de las funciones mentales superiores en cinco bloques funcionales, los cuales dan cuenta de la organización global como punto de partida para la interpretación del procesamiento de información y el origen de las diferentes manifestaciones psicopatológicas que se explicarán en la segunda parte, en esta misma revista, en el artículo denominado "La microestructura y el procesamiento de la información"...

El Cerebro: De la Estructura y la Función a la Psicopatología. Segunda Parte: La microestructura y el procesamiento de la información / The Brain: From Structure and Function to Psychopathology. Second Part: Microestructure and the Processing of Information

Las últimas dos décadas han sido de fundamental importancia para el estudio y entendimiento del sistema nervioso. Este progreso no sólo ha incluido el abordaje de fenómenos subyacentes a la masa cerebral de tipo neuroquímico, neurofisiológico, neuroanatómico, citoarquitectónico, imagenológico, etc., sino la relación de estos conocimientos con aspectos complejos de la conducta y el psiquismo. La intención de recalcar con una visión moderna el alcance de las neurociencias en la comprensión del psiquismo humano ha de reflejarse necesariamente en una comprensión más amplia de la enfermedad mental, lo que permite una confluencia entre nuestra condición biológica, conductual, psíquica y social. En este artículo, basados en la organización macro y microestructural del sistema nervioso, se explican con detalle los fenómenos de procesamiento de la información en el cerebro y el resultado de las alteraciones de los sistemas de neurotransmisores en la génesis de las ideas delirantes, las experiencias de desrealización y despersonalización, las alucinaciones, las ilusiones, los trastornos del afecto y los trastornos de ansiedad...

Fundamentos moleculares y celulares de la depresión y de los mecanismos antidepresivos / Molecular and cellular basis of depression and antidepressants mechanism

Durante la segunda mitad del siglo pasado los progresos en biología molecular permitieron desarrollar métodos para estudiar las sustancias neurotransmisoras del cerebro y su relación con las neuronas a través de los receptores. En los últimos treinta años se ha generado un cuerpo de conocimientos que se aproxima a explicar cómo los receptores neuronales generan cambios en el interior de las células. Además, desde hace veinte años se han desarrollado estrategias para evaluar las modificaciones en la transcripción genética y el vínculo entre la estimulación de los receptores y la expresión genética de las neuronas. La sistematización de la información proveniente de estas investigaciones ha permitido perfilar una secuencia de sucesos en la que se observa que la transmisión intracelular de la información se hace paso a paso. Cada uno de estos pasos presenta determinada peculiaridad bioquímica o fisiológica que repercute en el paso siguiente. Por tratarse de la traducción secuencial de la información desde la superficie celular hasta el núcleo celular y hasta desencadenar la respuesta celular definitiva, a las sustancias implicadas en estos procesos se les ha denominado mensajeros. El presente artículo es una aproximación a los procesos celulares y moleculares que subyacen debajo de los mecanismos antidepresivos y al posible papel de estos mecanismos en la fisiopatología de la depresión...