Clima ético egoísta y el teletrabajo en el sector eléctrico colombiano. El papel moderador del liderazgo ético

El sector eléctrico colombiano ha impulsado políticas organizacionales fundamentadas en la inclusión y el bienestar de la sociedad en general, que pretenden trasladarse al teletrabajo a través de un estilo de liderazgo ético. Sin embargo, el egoísmo -que se caracteriza por maximizar el interés propio como base de razonamiento moral-, es un factor subyacente que puede deteriorar cualquier iniciativa que busque un equilibrio institucional justo e íntegro, mediante un clima ético donde las decisiones descuiden las necesidades colectivas. Por consiguiente, el objetivo de esta investigación es determinar la relación entre un clima laboral egoísta y el teletrabajo, a través del rol moderador de liderazgo ético. El estudio aplicó un diseño cuantitativo, transversal y correlacional explicativo. La muestra fue de 448 empleados evaluados por una encuesta en línea. Se encontró que el clima ético egoísta (X) y el liderazgo ético (W) se asocian significativamente con el teletrabajo (Y). Sin embargo, cuando el liderazgo ético regula la relación entre las variables independiente y dependiente (6X - Y/W), se hace visible que a mayor percepción de una dirección ética más débil se torna el efecto del clima egoísta sobre el teletrabajo hasta desaparecer. En conclusión, el sector eléctrico colombiano, por su enfoque en la responsabilidad social y erradicación de conductas deshonestas mediante un liderazgo ético, no es compatible con un clima laboral egoísta. De hecho, el impulsar una cultura de trabajo, a través del interés propio, neutraliza todo el esfuerzo ético propuesto por el sector eléctrico colombiano en los últimos siete años, puesto que su finalidad ha sido propender por iniciativas sociales e inclusivas.

The Colombian electricity sector promotes organizational policies based on the inclusion and well-being of society in general, which also intend to transfer to teleworking through an ethical leadership style. However, the selfishness that is characterized by maximizing self-interest as the basis of moral reasoning is an underlying factor that can deteriorate any initiative that seeks a fair and comprehensive institutional balance through an ethical climate where decisions neglect collective needs. Therefore, the objective of this research is to determine the relationship between a selfish climate and teleworking through the moderating role of ethical leadership. The study applies a quantitative, cross-sectional, explanatory correlational design. The sample is 448 employees who are evaluated with an online survey. The selfish ethical climate (X) and ethical leadership (W) are significantly associated with telecommuting (Y). However, when ethical leadership regulates the relationship between the independent and dependent variables (6X - Y/W) it becomes visible that the greater the perception of a weaker ethical leadership, the effect of the selfish climate on telework becomes until it disappears. The Colombian electricity sector, due to its focus on social responsibility and on eradicating dishonest conduct through ethical leadership, is not compatible with a selfish climate. In fact, promoting only individual interests in virtual work environments would nullify all the ethical effort proposed by the sector in question in the last seven years. Since its purpose has been to promote social and inclusive initiatives.

Clozapine and desmethylclozapine: correlation with neutrophils and leucocytes counting in Mexican patients with schizophrenia.

PURPOSE: The aim of present study is to measure plasma clozapine (CLZ) and N-desmethyl clozapine (DMC) as biomarkers to correlate drug concentrations with the appearance of preclinical adverse hematic effects. METHODS: A high-performance liquid chromatographic method, using a diode-array (ultraviolet) detector, was validated to obtain reliable concentrations of CLZ and DMC, its main metabolite, in plasma of 41 schizophrenic patients taking CLZ. Blood neutrophils and leucocytes counting were concurrently assessed as a proxy to subclinical adverse reactions. RESULTS: The analytical method employed was linear, reproducible, and stable to measure concentrations of CLZ between 30 and 1000 ng/mL, while 12.5-560 ng/mL of the metabolite. The method allowed us to correlate CLZ plasma concentrations, the time taking CLZ and CLZ dose as determinants of neutrophils' counting with a R2 = 0.447, using a multiple regression analysis model. Likewise, the correlation of leucocyte counting vs CLZ plasma levels and CLZ time, showed a R2 = 0.461. DMC correlated significantly with both neutrophils and leucocytes counting, but was excluded from the regression when CLZ concentration was included in the model. Finally, no other hematological adverse reactions were recorded. One patient presented a cardiovascular complication. The negative correlation between clozapine and neutrophil count observed in patients, suggest that CLZ itself, but not DMC, could be related to hematologic side-effects. CONCLUSION: The findings of this study, demonstrate for the first time, that plasma levels of CLZ and time taking the drug are independent determinants of blood neutrophils and leucocytes, so the monitoring of plasma CLZ may be useful in the clinic practice to determine safe dosing of the drug.

Características metodológicas de las investigaciones realizadas por los estudiantes de la licenciatura en medicina de la Universidad Autónoma Metropolitana de México / Methodological characteristics of the research carried out by undergraduate medical students at the Metropolitan Autonomous University of México

Objetivo: Analizar las características metodológicas de las investigaciones presentadas por los alumnos de pregrado en medicina, en los congresos de investigación médica de una universidad pública en México. Sujetos y métodos: Se realizó una investigación observacional, transversal y retrospectiva; la información se obtuvo de las listas de cotejo que se emplearon para determinar las mejores investigaciones que presentaron los alumnos, en los congresos de fin de clases. En las listas de cotejo, los indicadores tenían una elección dicotómica (sí/no), dependiendo de si estaba bien trabajado el aspecto de la investigación a evaluar. Para analizar los datos se calculó el porcentaje de respuestas afirmativas de cada indicador de las listas de cotejo y se promedió por cada congreso. Resultados: Se evaluaron 432 investigaciones estudiantiles provenientes de nueve congresos. Los datos muestran que el planteamiento lógico para hacer las investigaciones se trabajó adecuadamente en la mayoría de los congresos, mientras que en los aspectos metodológicos, los alumnos tuvieron dificultades para diseñar y ejecutar de forma adecuada sus investigaciones. La dificultad mayor para los alumnos estuvo en el análisis de los resultados y en la discusión del significado, la aplicabilidad y el alcance de su investigación. Conclusión: Es necesario evaluar constantemente el método de enseñanza de investigación en la carrera de medicina y trabajar más en la tutoría de las actividades de los alumnos

Aim: To analyze the methodological characteristics of the research works presented by the undergraduate medical students, at the medical research congresses of a public university in Mexico. Subjects and methods: An observational, transversal and retrospective research was carried out; the information was obtained from the checklists that were used to determine the best research works presented by the students at the end-ofcourse congresses. In the checklists the indicators had a dichotomous choice (yes/no), depending on whether the aspects to be evaluated in each research work was well worked out. To analyze the data, the percentage of affirmative responses of each item in the checklists was calculated, and averaged for each congress. Results: We evaluated the research presented by 432 students at nine congresses. The data show that the logical approach to the research was adequately worked in most of the congresses, while in methodological aspects the students had difficulties to design and adequately execute their research work. The greatest difficulty for the students was in the results' analysis, as well as in the discussion of the meaning, applicability and scope of their research. Conclusion: It is necessary to constantly evaluate the teaching method of the research skills in the medical career, and work more in the tutoring of the students' activities

Efecto de la exposición al pesticida rotenona sobre el desarrollo del sistema dopaminérgico nigro-estriatal en ratas / Developmental effects of rotenone exposure on the rat nigro-striatal dopaminergic system

Rotenone is a pesticide used in Mexico, despite the experimental evidence showing dopaminergic neurons degeneration induced by this compound, which may lead to a psychomotor impairment. However, the possible effects of rotenone on the offspring when they are indirectly exposed through their mothers are still unknown. In this study rotenone was administered to female rats during pregnancy and nursing, in order to assess its effects on the offspring's dopaminergic neurons in the substantia nigra, as well as on motor coordination at 30 or 60 postnatal days. Six groups of pregnant Wistar rats were used: an intact control group, a vehicle group injected with the rotenone solvent, and four groups injected subcutaneously with the following doses of rotenone: 0.2, 0.4, 0.6, and 1 mg/kg/day. In a parallel experiment, the offspring of other groups of dams treated with rotenone 1 mg/kg/day, or controls vehicle-treated, were used to evaluate motor coordination at 30 and 60 postnatal days. Rotenone treated dams showed a significant lower amount of dopaminergic neurons in the substantia nigra, but only with the 1 mg/kg dose. This effect was also observed in the offspring but at all doses of rotenone tested, either at 30 or 60 postnatal days. Furthermore, the offspring of rotenone exposed dams significantly increased the time in which they accomplished the motor coordination test, compared to the offspring of control dams. These data indicate that rotenone is able to damage the dopaminergic neurons of the offspring though their mothers. This effect requires lower rotenone doses than in adult rats. The reduced number of dopaminergic neurons at early stages of life enhances the risk of developing disorders related to the brains' dopaminergic system.

La rotenona es un pesticida utilizado en México a pesar de que se ha demostrado experimentalmente que produce una degeneración de las neuronas dopaminérgicas, y puede derivar en deterioro psicomotor. Sin embargo, no existen estudios de la exposición indirecta a rotenona a través de las madres en el efecto que produzca sobre su descendencia. Nosotros administramos rotenona a ratas durante la gestación y la lactancia para evaluar las alteraciones producidas sobre las neuronas dopaminérgicas y la coordinación motora de sus crías, a los 30 o 60 días posnatales. Para cuantificar las neuronas inmunorreactivas a tirosina hidroxilasa de la sustancia nigra, se inyectaron subcutáneamente seis grupos de hembras Wistar: intactas (control), con solvente de rotenona (vehículo) y cuatro grupos con rotenona en dosis: 0.2, 0.4, 0.6 y 1.0 mg/kg/día. En un experimento paralelo, las crías de otros grupos de hembras tratadas con rotenona 1 mg/kg/día o controles fueron evaluados en la prueba de coordinación motora a los 30 y 60 días posnatales. Las madres tratadas con 1 mg/kg de rotenona tuvieron menos neuronas dopaminérgicas en la sustancia nigra. Dicho efecto se observó también en las crías, pero con todas las dosis de rotenona utilizadas, tanto a los 30 como a los 60 días posnatales. Además, la exposición indirecta a rotenona aumentó significativamente el tiempo que requirieron las crías para ejecutar la prueba de coordinación motora. Estos datos indican que la rotenona es capaz de inducir daño en las neuronas dopaminérgicas de las crías cuando son expuestas a través de sus madres. Este efecto en las crías se observa con dosis menores de rotenona que en ratas adultas. Por lo tanto, los individuos indirectamente expuestos a rotenona podrían tener menos neuronas dopaminérgicas desde etapas tempranas de la vida, lo que aumenta el riesgo de desarrollar trastornos relacionados con el sistema dopaminérgico.

Ultrastructural changes and immunolocalization of P-selectin in platelets from patients with major depression.

Depression is considered an important risk factor in patients with cardiovascular disease (CVD). Although the biological mechanism is unknown, it has been suggested that hyperactivity of platelets may have an important role in the onset and evolution of cardiovascular damage. The goals of this study were to evaluate by transmission electron microscopy and immunohistochemistry the presence of ultra-structural variations in platelets from individuals with recent diagnosis of major depression disease (MDD, patients without previous anti-depressant treatment and from healthy control subjects.). Platelets from depressed patients had a greater proportion of dendritic forms compared with those obtained from control subjects. Morphological changes, such as dilation of open canalicular and dense tubular systems, platelet vacuolization, electrodense pattern of membranes, and a different immunolocalization of P-selectin were observed in the platelets from depressed patients compared with those isolated from healthy subjects. Our results revealed ultra-structural changes in platelets isolated from patients with MDD suggestive of enhanced platelet activation.

Auditory brainstem responses as a clinical evaluation tool in children after perinatal encephalopathy.

UNLABELLED: Auditory brainstem responses (ABR) reveals the neurophysiological status of the neural axis. In this study we compared the ABR of healthy children, under 1-year-old, with children who suffered from perinatal encephalopathy (PE). OBJECTIVE: The purpose of this study was to characterize the ABR differences between children with PE and healthy children in order to identify groups with specific neurophysiological profiles, associated with their neurological condition. METHODS: Thirty-six children with perinatal encephalopathy (PE) and 36 healthy children, ages 1-12 months, were studied. The variables considered were: latencies of waves I, II, N1, III, V, and N2; interpeak latency interval (IPL) of waves I-III, III-V, and I-V; as well as amplitudes of waves I, III, and V. The results were analyzed using ANOVA, as well as Ji(2), and Ward's cluster analysis. RESULTS: The absolute latencies of the ABR showed an inverse correlation with the children's age. Latencies of waves I, II, N1, V, and N2, IPL III-V, and amplitude of waves III and V show significant differences (p<0.05) between healthy and PE children. Children with PE showed greater absolute latencies and larger wave amplitudes than the control group. Ward's cluster analysis, used to define the groups with similar functional characteristics, revealed three groups: fast, intermediate, and slow-responders, depending on their wave latencies and IPL wave amplitudes. These groups were gender- (p<0.03), age- (p<0.0001), and neurological damage- (p<0.01) related. CONCLUSIONS: Our data clearly show that the ABR obtained from PE children differ from ABR obtained from healthy children. PE infants showed larger wave latencies, intervals amplitudes than the control group. Three functional profiles resulted from the groups established using the Ward's method, and these indicate their neurological functional condition.

Tryptophan and serotonin in blood and platelets of depressed patients: Effect of an antidepressant treatment

Abstract: Platelets llave serotonin (5-HT) uptake and storage mechanisms similar to those from neurons. In addition, they represent nearly 99% of blood 5-HT concentration. For these characteristics, platelets are considered useful biomarkers of the serotonergic synaptic neurotransmission, particularly in psychiatric disturbances such as depression. However, most studies which have evaluated platelet 5-HT concentrations in depression have not shown similar findings. It has been suggested that changes in plasma tryptophan (TRP) concentrations might modify 5-HT concentration in the brain, as well as in platelets. Likewise, decreased plasma concentrations of TRP have been found in depressed patients, and the selective 5-HT reuptake inhibitors (SSRIs) induce changes in platelet 5-HT concentration. Considering the controversy surrounding platelet 5-HT concentrations in depressed patients, and the fact that blood 5-HT and TRP have not been studied in the Mexican population, we decided to study 5-HT and tryptophan concentrations in blood and platelets from depressed and control Mexican subjects to evaluate a possible correlation with the severity of depression. The effect of fluoxetine and citalopram treatment on blood and platelet 5-HT and TRP concentrations in depressed patients was also studied. Material and methods Depressed patients The patients of this study were carefully selected and evaluated. Scales based on semi-structured interviews were applied (MINI and SCID-II) by clinical investigators to reduce any possible bias in patient selection. The influence of the seasonal variability on the 5-HT or TRP blood concentrations was controlled by pairing depressed patients and healthy subjects according to age, gender and, in the case of women, menstrual cycle phase. Patients with a complete remission of depression symptoms (defined as a score not higher than 5 points in the Hamilton's scale, and lower than 7 points in Beck's scale) were asked for a blood sample to measure platelet and blood concentrations of 5-HT and TRP. The patients were weighted before the treatment and after their improvement. Control subjects The control group was integrated by 30 healthy subjects, 24 women and 6 men, with an average age of 32.3 ± 10.8 years. Participants were recruited from the overall Mexican population, interviewed by a psychiatrist, and evaluated with the structured interview MINI and the SCID-II, all these to discard any psychiatric diagnose. None of them had received any pharmacological treatment during the three weeks prior to the study. Control and depressed women were paired according to their menstrual cycle phase. All participants received a detailed explanation of the study, and those who voluntarily accepted the stipulations signed an informed consent document. Control and patient subjects were clinically examined and studied with routine laboratory tests (blood count, blood chemistry, urinalysis, and thyroid function test). Blood sample procedures 5-HT and TRP measurements in total blood preparation were carried out according to the method described by Anderson, and were quantified by high performance liquid chromatography (HPLC). Statistical analysis The differences were statistically determined through an analysis of variance (ANOVA), with the assistance of the SPSS 12.00 (Statistical Software by SPPS Inc.). Results Results from laboratory tests, such as blood count, blood chemistry, thyroid function (T3, T4 and TSH) and urinalysis were normal in depressed subjects, as well as in healthy volunteers. Platelet number, blood 5-HT concentration, platelet content of 5-HT, and blood tryptophan concentration showed no significant differences in depressed patients in comparison to control subjects. 5-HT values in blood and platelet were significantly lower than the initial concentrations in patients after antidepressant treatment. Discussion and conclusions Discrepancies between our study and those found in the literature can be explained with three different approaches: ethnical, physiological, and methodological, as is further discussed. The significant decrease produced by the antidepressant treatment in blood and platelet serotonin concentration may be a consequence of the action of SSRIs, due to a 5-HT diminished uptake by the platelet. Considering our results, we conclude that: Blood and platelet 5-HT concentrations were not different between depressed patients and healthy volunteers. Blood TRP concentrations were not different between depressed patients and healthy volunteers. SSRIs (fluoxetine or citalopram) used in the treatment of depressed patients induced a significant decrease in blood and platelet content of 5-HT, and had no effect in TRP concentrations. Based on these results, neither blood/platelet 5-HT nor blood tryptophan concentrations seem to be good biological markers of depressive patients status. However, 5-HT, but not tryp-tophan, might be a reference point for pharmacological treatment effect.

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El sistema serotoninérgico en el paciente deprimido. Segunda parte

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Abstract: Nowadays there are increasing number of studies to support the crucial role of monoamines in depressive disorders. Among them are studies such as long-term treatment of antidepressants whose mechanism of action regulates monoamine metabolism, monoamine receptor density and post-mortem studies. An acute increase in monoamine concentration at the synaptic cleft might induce desensitization of brain auto- and hetero-receptors which explains the therapeutic antidepressive response. This has been proved by monoamine depletion studies in which an antidepressant effect or a patient relapse has been observed. Likewise, the antidepressive therapeutic response occurs earlier when auto-receptors are pharmacologically blocked at nervous and somatodendritic terminals. In the first part of this review, post-mortem studies related with the serotoninergic system were analyzed, as well as the usefulness of measuring serotonin, triptophan, and serotonin metabolite levels in different biological fluids of depressed patients. In this second part, alterations in platelet transporter and serotonin receptors are discussed as platelet is considered a neural serotoninergic model. Platelets are capable of storing and releasing serotonin in a similar manner as serotoninergic synaptosomes. Thus, platelets and serotoninergic synaptic terminals share biochemical and morphological properties. Serotonin transporter in platelets of depressed patients Due to the difficulty to obtain human brain samples and disagreements in the post-mortem studies, platelets have been suggested as a peripheral model to study neural serotonin uptake. The model is supported by the fact that platelet properties are similar to those of neuronal serotoninergic synaptic terminals. Serotonin studies in platelets have been useful in clinical aspects such as depressive disturbances. Radioligand studies in platelets from untreated depressed patients have shown a decrease in [H]-imipramine binding sites, compared to the binding in platelets from control subjects. Since that decrease has been consistently confirmed in studies on affective subjects, it has been proposed as a specific biomarker of depressed patients. Nevertheless, some researchers have not found similar results, and no explanation of the variability in the density of [H]-imipramine binding sites has been proposed. Serotonin receptor changes in depressed patients The hypothesis on receptor adaptative changes proposes that there is a depletion of monoaminergic neurotransmitters in depressed subjects which induces a compensatory regulation in the number and/or function of receptors. To explore this different techniques as the following have been developed: • Techniques to evaluate receptor density and affinity, including post-mortem radioligand binding to serotonin receptors in brain tissue and in platelets from depressed patients. • Techniques to evaluate receptor regulation and sensitivity by using neuroendocrine tests described below. Somatodendritic 5HT 1A autoreceptor dysfunction in depressive disorders Dysfunction of presynaptic somatodendritic 5HTja autoreceptors has been found in behavioral changes related to anxiety, depression and alcoholism. Neuroendocrine tests after the administration of 5-HT1a agonists have been used as an index of 5-HTta receptor function. It seems that azapirodecanediones increase plasmatic concentrations of prolactin, somatotropin, and adrenocortico-tropin; they also seem to decrease body temperature. In depressed patients, the hypothermia response, following presynaptic 5-HTta receptor stimulation, and the neuroendocrine response, following hypothalamus postsynaptic 5-HTta receptor stimulation, were both diminished. These findings suggest a desensitization or down-regulation of pre- and post-synaptic 5-HTja receptors in depressed patients. Platelet 5-HT 2A receptors in depressed patients Density and affinity Most radioligand studies have found an increase of platelet 5-HT2a receptors either in major depression patients or in attempted suicide patients. However, Rosel et al. studied platelets from depressed patients, finding an increment in the 5-HT2a platelet receptors affinity for [H]-ketanserin, but not in the receptors density. Functional capacity The evaluation of receptor function and sensitivity in platelets is performed after serotonin stimulation by using neuroendocrine tests and some other functional tests, such as platelet aggregation, morphological changes, quantification of intracellular calcium, and second messengers quantification. Despite being widely used, neuroendocrine tests are not completely reliable because they could be influenced by factors such as: stress on the hypothalamus-hypophysis axis, the lack of stereo-selective agonists and antagonists for different subtype serotonin receptors, and the effect of the drugs on other neurotransmitter systems. Other methodological aspects, such as: population heterogeneity, small samples, lack of variable control (i.e. age, sex, doses, diet, menstrual cycle), and placebo effects, are limitations to the neuroendocrine tests related to a single neurotransmitter system (serotonin). Results from platelet functional studies are contradictory as well. Platelet aggregation assays in depressed patients suggested a down-regulation of 5-HT2A receptors, compared to platelets from healthy subjects. However, some other studies have found no differences. Other platelet function responses mediated by 5-HT2A receptors, such as morphology changes, intracellular calcium, and phosphatidyl inositol hydrolysis, suggest a receptor up-regulation or hypersensitivity in depressed patients. Despite some disagreement among the results of platelet 5-HT2A receptor studies in depressed patients, most of them have reported an increase in 5-HT2A receptors density in these patients. However, suicidal behavior is clearly correlated to such an increase. Similar results have been observed in most post-mortem studies reporting an increase of 5-HT2A receptors in the prefrontal cortex. Protein synthesis and mRNA for 5-HT2A receptors are increased in prefrontal cortex and hippocampus in adolescent and adult suicide victims. These findings suggest that changes in the brain serotonergic system are related to depressive states and suicidal behavior. Human brain imaging techniques as well as molecular genetics studies may be additional tools to support the understanding of the neurobiology of depressive states, and their treatment.

El sistema serotoninérgico en el paciente deprimido. Primera parte

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Summary According to Spitzer et al., depression is a mood disorder characterized by sadness and accompanied by other symptoms such as irritability, anxiety, significant weight/appetite loss or gain, and feelings of guilt, worthlessness and hopelessness. Depressed patients are unable to accomplish everyday activities and may develop thoughts of death or suicide. Different neurotransmitters have been involved in the pathogenesis of depression; among them are noradrenaline, dopamine, gamma-aminobutyric acid, neuropeptides such as vasopressin and somatostatin, and endogenous opioids. However, serotonin (5-HT) has been the most studied and is suggested to play a central, but not exclusive, role in depression. This review analyzes studies which have involved serotonin as the vulnerable biochemical factor in depression. Postmortem studies Postmortem studies and 5-HT and 5-hydroxy-indolacetic acid quantification Many researchers have reported a decrease in 5-HT or its metabolite 5-hydroxy-indolacetic acid (5-HIAA) concentration in the brain stem of suicidal people. However, results are inconsistent since in other cerebral regions, such as the hypothalamus, cingulate and frontal cortex, no 5-HT or 5-HIAA concentrations have been found. Validity of postmortem results is limited by methodological issues as postmortem interval length, age of subjects, lack of assessment of nutritional status of suicide victims, drug abuse, medication, and differences in psychiatric diagnosis. Serotonin transporter and post-mortem studies Serotonin transporters are localized in cell presynaptic membranes in raphe and serotoninergic terminals projected to brain cortex. Radioligand studies have shown the occurrence of high affinity binding sites for [3H]-imipramine in human brain. Because of their localization in serotoninergic terminals and their likely participation in depression pathology, these binding sites have been suggested to be depression biomarkers. Early studies reported a decrease in [3H]-imipramine binding to prefrontal cortex in suicide victims with previous depression, as well as in occipital cortex and hippocampus in depressed patients who died of natural causes. These findings have been confirmed by other compound studies including [3H]-citalopram which has been identified as a more selective ligand for the serotonin transporter. A review by Purselle and Nemeroff of studies correlating depression, serotonin and suicide behavior found ambiguous data. These were likely due to methodological deficiencies such as a small sample size, deficient pairing criteria for control and treated groups, differences in radioligands, as well as disregarding comorbidity. These differences limit validation, comparison and interpretation of study results. Serotonin receptors and postmortem studies 5-HT 1A receptors. A decrease in 5-HT1A receptor density has been reported in suicidal depressed victims in the hippocampus, an important brain area for cognitive function. However, this receptor is highly sensitive to antidepressant treatment, which makes its determination rather ambiguous. On the other hand, no significant difference in brain cortex 5-HT1A receptors has been found between non-suicidal and suicidal subjects. 5-HT 1D receptors affinity has been reported to be decreased in depressed patients. 5-HT 2 receptors. Several researchers have observed an increase in postsynaptic 5-HT2 receptors in the frontal cortex and amygdala in suicidal depressed victims and depressed patients with no pharmacological treatment. An increase in 5-HT2A receptors has been reported in prefrontal cortex of suicidal adolescents, as well as higher levels of mRNA codifying for these receptors in prefrontal cortex and hippocampus. Tryptophan, serotonin, melatonin and 5-hydroxy-indolacetic acid in biological fluids Tryptophan in cerebrospinal fluid Findings on tryptophan levels in cerebrospinal fluid are controversial, for both normal and low levels have been found in depressed patients. Tryptophan in plasma Using the hypothesis of a decreased tryptophan availability to explain a low serotoninergic central activity in depressed patients does not stand due to different findings in levels of plasma-free tryptophan. Lower, normal and even higher levels of free tryptophan have been reported. Tryptophan availability might be influenced by neutral amino acids competing to cross the blood-brain barrier. Brain tryptophan levels might be modified if the free tryptophan/neutral amino acids ratio is reduced. It has been observed that depressed patients receiving antidepressants experienced a depressive relapse after receiving a low-tryptophan diet and returned to the remission state on returning to a regular food intake. Pharmacokinetic and pharmacodynamic factors might play a role in tryptophan availability in some depressed patients. Serotonin in cerebrospinal fluid Serotonin levels in cerebrospinal fluid are very low; this difficult carrying out studies in depressed patients. Serotonin in platelets Methodological and clinical criteria may explain the controversial results on platelet serotonin levels, which have found to be increased, decreased or unchanged. Serotonin in blood As platelet serotonin content includes 99% blood serotonin, serotonin blood levels might reflect brain serotonin content. After using fluvoxamine, a specific serotonin-reuptake inhibitor, the serotonin concentration in whole-blood preparation of patients was strongly reduced. After treatment with an unspecific mono-amine oxidase inhibitor, serotonin content was increased. Determination of 5-HT in whole blood preparation of patients treated with fluvoxamine might indicate a measure of drug compliance. Serotonin in plasma A significant decrease in plasma serotonin levels has been reported in depressed patients. Melatonin in plasma The melatonin synthesis use serotonine as building blocka. Melatonin have an important role in depression. It has been proposed that depressive states are a consequence of an inappropriate melatonin secretion. Therefore low plasmatic melatonin levels may be used as a biological marker for some types of depression. 5-HIAA in cerebrospinal fluid and plasma 5-HIAA, the major metabolite of 5-HT in plasma, has been suggested as a depression biomarker since cerebrospinal fluid 5-HIAA levels have found to be decreased in depressed patients. On the other hand, plasma 5-HIAA levels from untreated depressed patients were found to be significantly negatively correlated with severity of depression, despite the fact that the origin of plasma 5-HIAA is largely peripheral. 5-HIAA in urine Studies concerning urine 5-HIAA levels have been inconclusive in depression, likely due to the 5-HIAA urinary level variations from one day to another. Furthermore, the major fraction of 5-HIAA in blood as an intestinal precedence, therefore, blood 5-HIAA levels may not correlate with cerebral levels. Conclusion The serotoninergic system seems to be the neurotransmission system whose variations may explain every clinical manifestation in depressed patients. However, interpretation of measurements of tryptophan, serotonin, and its metabolites in biological fluids as an index of brain serotonin availability and function is difficult to achieve, mainly due to methodological discrepancies.

La plaqueta como marcador biológico periférico de la función serotoninérgica neuronal

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Abstract: Among all neurotransmitters, serotonin or 5-hydroxi-triptamine (5-HT) is probably the most studied in neuropsychopharmacology. Interest in this neurotransmitter is due to cumulative evidences showing that neuronal serotonergic systems are altered in depressed patients, as well as in several behavior dysfunctions like aggressiveness, impulsiveness, and suicide attempts, among others. Also, specific agonists and antagonists have been synthesized, which has enabled the characterization of the serotonergic receptor subtypes. Furthermore, highly selective inhibitors ofserotonin uptake have been developed, and these are capable of working in the synaptic terminals, as well as in other cell systems, such as platelets. This has allowed for the understanding and characterization of the action mechanisms of diverse psychoactive drugs interacting with the serotonergic system. Platelets have been proposed as an outlying model resembling that of serotonergic neurons due to the similarities they present in the uptake, storage, and serotonin release mechanisms, as well as the presence in platelet membranes of serotonin 5-HT2A receptors. The platelets have a serotonergic system consisting of four main components: 1. an uptake mechanism, 2. intracellular storage organelles, 3. serotonergic receptors in the plasmatic membrane, and 4. a mitochondrial enzyme, the monoamine oxidase (MAO), which metabolizes serotonin. All these elements show physiologic similarities with the neuronal serotonergic system. Serotonergic similarities in neurons and platelets In the Central Nervous System (SNC) serotonin acts mainly as an inhibitory neurotransmitter. The precursor for its synthesis is the aminoacid tryptophan. This is taken from the blood to the cerebral interstice, where it is taken up by the nervous terminals and converted into 5-hidroxytryptophan (5-HTP) by the enzyme tryptophan hydroxilase. The conversion to 5-HTP is a key regulatory step in serotonin synthesis, and is converted quickly in 5-HT by the action of the aromatic L-acid descarboxilase. However, platelets do not synthesize 5-HT, since they do not possess tryptophan hydroxilase. Thus they only display uptake, storage, and serotonin release functions. Serotonin actions The neurotransmitter functions of neuronal serotonin, generally inhibitory, depend on the serotonergic receptor characteristics it interacts with. Its action mechanism can be mediated through second messengers (metabotrophic receptors) or through a direct action over ionic channels (ionotrophic receptors). In the platelets, serotonin is stored in a slow replacement depot, where it can be released from by exocythotic mechanisms. Serotonin participates in the platelet activation that allows for their aggregation to each other for blood clotting process. Serotonin uptake To stop the serotonin neurotransmitter function, neuronal serotonin is taken up from the synaptic cleft by transporter proteins. The serotonin neuronal uptake is impelled by a proton gradient that requires ATP. The 5-HT uptake can follow two paths: the 5-HT can be metabolized by the MAO into 5-hydroxy-indolacetic acid, or it can be reintroduced into release vesicles in order to be reutilized as a neurotransmitter. The serotonin uptake by platelets occurs either by passive diffusion or by active transport mechanisms. Under physiological conditions, the active uptake mechanism is the most effective. This uptake is mediated by proteins similar to the ones required for the neuronal serotonin uptake in the brain. It requires energy and the presence of Na+ and Cl-. The platelet uptake system has a relatively high affinity (Kd) for 5-HT, being similar in magnitude from platelets to neurons. The platelet storage of 5-HT is located mainly in the dense bodies and in the storage granules. Serotonin transporters in platelets and synaptic terminals The main form of ending a serotonergic transmission pulse is by taking up 5-HT molecules from the synaptic cleft directed to reduce the serotonin concentration, which then stops the serotonergic neurotransmission. The uptake process involves a molecular recognition of 5-HT by the transporter, its binding, and passing through the membrane to be released within the cellular. Serotonin molecules bound to its transporter protein cross through the membrane using Na+ as a driving force. The return ofthe transporter to its original position requires K+ as the driving force to step this protein toward its original position. When a selective serotonin reuptake inhibitor is administered, the 5-HT concentration increases in the synaptic cleft, which enhances serotonin neurotransmission. This increase induces a down regulation cascade of both: serotonin autoreceptors (presynaptic) and postsynaptic receptors, that may finally reestablish the resting state of the neuron. It has been confirmed that the protein for neuronal as well as platelet serotonin uptake transport are synthesized by the same gene. Experimental evidence has shown that the platelet transporter presents the same functional and pharmacological characteristics than the neuronal transporter. Serotonergicreceptors Seven types of pre and post synaptic serotonin receptors, which have also several subtypes, have been characterized. Pre and post synaptic 5-HT 1 receptors . The 5-HT1 receptors are involved in both pre and post synaptic serotonergic neurotransmission. The presynaptic 5-HT1A receptors are autoreceptors. Due to their localization in the cellular body and in the dendrites, they have been named somatodendritic autoreceptors, which control the serotonin release. The postsynaptic receptors may play a role in hypothalamic thermoregulation. The presynaptic 5-HT1D receptors are autoreceptors that perform a regulation by blocking the 5-HT release. These receptors are not synthesized in platelets. Postsynaptic 5-HT 2 receptors . The 5-HT2 receptor subtypes are 5-HT2A,BandC. When postsynaptic 5-HT2Areceptors are bound to serotonin, they drive the transduction of neuronal impulses through the production of second messengers within the postsynaptic neuron. These second messengers induce the synthesis of intracellular proteins denominated transcription factors, which may regulate the expression of several neuronal genes. Platelet 5-HT2A receptors correspond to the neuronal 5-HT2A metabothropic receptors and induce alterations in platelet density and affinity. 5-HT 3 receptors . These receptors were originally described in the periphery, specifically as part of the enteric nervous system. In the CNS 5-HT3 receptors are densely present in the solitary tract nucleus and in the area postrema. These receptors are the onlymonoaminergic receptors consistingofionic channels operated by aminergic neurotransmitters. The stimulation of 5-HT3 receptors is responsible of several secondary effects of the selective inhibitors of serotonin reuptake (SISR). These effects are not mediated only in the CNS, but also in sites outside the brain, such as the intestine, which possess this type of receptors also. These receptors are not located in the platelets. 5HT 4-7 serotonergic receptors . These receptors are distributed throughout the body, where they stimulate the alimentary tract secretions and facilitate peristaltic reflexes. Their localization in serotonergic areas in the brain and platelets has not been established. Notwhithstanding their limitations, the characteristics reviewed support the conclusion that platelets can be used as partial models to study the neuronal serotonin 5-HT2 binding and uptake functions. As Alfred Pletscher stated: "although the incomplete of the pattern demands care in its application, they could have the advantage of the relative simplicity".

Methodologic pitfalls in measurement of 5-hydroxytriptamine uptake transporters in human platelets by [3H]-paroxetine binding assay.

BACKGROUND: Studies in platelet of 5-HT uptake transporters have been performed using binding assay methodology designed for ligand-receptor interactions; however, uptake transporters present requirements that may question the validity of these particular binding assays. METHODS: To explore methodologic aspects that may be crucial to the validity of these assays, we studied the binding of [3H]-paroxetine to platelet membranes of healthy subjects under different conditions of time, temperature, and protein concentrations. RESULTS: A correlation between protein concentration in incubation media and percentage of specific binding of [3H]-paroxetine was found: the lower the protein concentrations (10 and 20 microg/mL) in incubation media, the lower the percentage of specific [3H]-paroxetine binding. Moreover, low specificity in [3H]-paroxetine binding affected Bmax values obtained in saturation binding experiments. CONCLUSIONS: The use of low protein concentrations could affect Bmax values in binding assays of 5-HT uptake transporters. This may induce confusing interpretation of data in clinical experiments that use human platelets to explore the participation of serotonin in depressed patients.

Diurnal variations of extrapyramidal symptoms induced by haloperidol in schizophrenic subjects.

Despite the fact that the circadian variations in the density of striatal dopaminergic D2 receptors are well documented, there are few reports concerning whether these variations may regulate the extrapyramidal symptoms produced by antipsychotic drugs. To test this hypothesis, we selected 18 male hospitalized schizophrenic subjects, who had been treated for 2 wk with 10 mg haloperidol three times a day. The extrapyramidal symptoms were evaluated 1 h after each haloperidol administration (e.g. 09:00, 14:00 and 19:00 hours). The diurnal profiles of haloperidol-induced extrapyramidal symptoms showed that akathisia and dystonia were milder in the morning and increased in severity during the night. However, Parkinsonian symptoms were more severe during the morning evaluations than during the evening tests. The difference in the diurnal pattern of the haloperidol-induced side-effects, suggests that receptor-related mechanisms with a different circadian profile contribute to the induction of the extrapyramidal symptoms.

The different effects produced by a evening dose versus daily distributed doses of haloperidol

Comparaçä0 dos efeitos terapeuticos e secundarios do haloperidol administrado em doses repartidas no dia contra os efeitos da dose noturna. Em observaçöes clínicas preliminares se encontrou que a hora do dia em que os medicamentos antipsicóticos säo administrados parece que atua na severidade dos efeitos secundários, o que sugere a participaçäo de algum mecanismo circadiano. Para determinar se a hora da administraçäo dos medicamentos aantipsicóticos determina a produçäo dos efeitos tanto terapêuticos com colaterais, comparam-se os efeitos produzidos pela administraçäo do haloperidol em doses distribuidas no dia, contra os efeitos produzidos pela administraçäo em doses noturnas. A avaliaçäo de evoluçäo antipsicotica dos pacientes esquizofrenicos hospitalizados, se realizou mediante a escala dos sintomas positivos e negativos(PANSS). Näo se encontraram diferenças no efeito terapeutico do haloperidol administrado em doses repartidas ou noturnas, em quanto à sub-escala dos sintomas negativos (F(4,87) = 1.709, p = 0,1731) nem dos sintomas gerais (F(4,870 = 2.01, p=0.1187)

Psiquiatría biológica mexicana / Mexican biological physchiatry

Compilación de trabajos que forman parte del archivo de la Sociedad Mexicana de Psiquiatría Biológica y que han sido reunidos en el presente libro para mostrar los avances de dicho Instituto en cuestión de salud mental. El documento se divide en: 1. Presentación 2. Veinticinco años de la Sociedad Médica de Psiquiatría Biológica 3. Epistemología de la psiquiatría 4. Psicoterapia y psicofármacos 5. Jaqueca: su perfil psicológico 6. Diagnóstico de la depresión 7. La rehabilitación del enfermo mental 8. Regulación neuroendócrina y alteraciones del sueño en la depresión 9. Litio en esquizofrenia 10. Tratamiento de la depresión en el anciano 11. Fiebre reumática y enfermedad mental 12. Demencia senil

Propuesta de un modelo de aparato mental basado sobre las funciones mentales / Proposal of a model of mental apparatus based on mental functions

Si se utilizan las funciones mentales que se revisan en el examen del estado mental de los pacientes psiquiátricos y sí se los agrupa en áreas, de acuerdo con criterios fisiológicos clásicos, se obtiene un sistema de manejo de información de valor heurístico en la clínica psiquiátrica. Este sistema considera las funciones mentales del área sensoperceptual como la parte receptora de la inofrmación por el sistema. Tal información continúa su análisis en las áreas cognitiva y afectiva; la salida principal de la información resultante del análisis ocurre a través del área psicomotriz. Este sistema permite elaborar una estructura teórica que correlaciona elementos de las neurociencias con aspectos clínicos psiquiátricos. Por otra parte, permite entender los trastornos mentales como trastornos del manejo de información en el tejido nervioso

Propuesta de un modelo de aparato mental basado sobre las funciones mentales / Proposal of a model of mental apparatus based on mental functions

Si se utilizan las funciones mentales que se revisan en el examen del estado mental de los pacientes psiquiátricos y sí se los agrupa en áreas, de acuerdo con criterios fisiológicos clásicos, se obtiene un sistema de manejo de información de valor heurístico en la clínica psiquiátrica. Este sistema considera las funciones mentales del área sensoperceptual como la parte receptora de la inofrmación por el sistema. Tal información continúa su análisis en las áreas cognitiva y afectiva; la salida principal de la información resultante del análisis ocurre a través del área psicomotriz. Este sistema permite elaborar una estructura teórica que correlaciona elementos de las neurociencias con aspectos clínicos psiquiátricos. Por otra parte, permite entender los trastornos mentales como trastornos del manejo de información en el tejido nervioso (AU)

Trabajos de investigación 1990 / Research works 1990

El estudio surgío con la necesidad de revisar la confiabilidad diagnóstica de los pacientes (82 expedientes primer trimestre 1988) el tratamiento y la evolución hospitalaria que se ha brindado a pacientes con diagnóstico de esquizofrenia, siendo que este diagnóstico es uno de los más frecuentes en el Hospital Psiquiátrico "Fray Bernardino Alvares". Se encuestaron 44 pacientes masculinos y 38 del sexo femenino, 30-36 promedio de edad, escolaridad 15.9% primaria completa, 13.4% con secundaria, 7.3% con preparatoria, 2.4% educación profesional y 2.4% analfabeta; 56.1% no tenian ocupación, la mayoria provenian del D.F. o Valle de México; 74.4% su estado civil eran solteros, 23 pacientes se hospitalizaron por primera vez; 32 pacientes provenian de familias desintegradas, 25 de familias integradas y 2 no se corroboró. El promedio de estancia en el hospital es de 68-93 días. El uso de fármacos demostró que la perfenazina tuvo un 92% de resultados satisfactorios,los medicamentos más usados fueron los neviolepticos (125 ocasiones). A su egreso se ha controlado el brote agudo de enfermedad y diagnóstico emitido es concordante en un 71% con el

Trabajos de investigación. Volumen I / Research work Vol.I. 1990

En este estudio se intentó correlacionar los síntomas y signos que caracterizan al trastorno por déficit de atención con hiperactividad, con las alteraciones electroencefalográficas, y además con las pruebas psicológicas como el test guestáltico psicosomotor de Bender, el test de matices progresivas de Ranven y el test de la figura humana de Goodenough. Estudiando a 20 niños de 5 a 14 años en el período enero-noviembre de 1989. En 19 casos el profesor solicitó el tratamiento; hubo 16 niños y 4 niñas, 14 pacientes no mostraron trastornos prenatales. El desarrollo psicomotor fue normal en 18 casos. La población estudiada presenta una alta incidencia en trastornos del sueño, 15 resultados de encefalograma fueron normales. Se presenta agresividad en 8 casos y anota que para llegar al diagnóstico de trastorno por déficit de atención con hiperactividad se debe realizar un diagnóstico de exclusión pues hay que eliminar multiples posibilidades

Aspectos clínico-epidemiológicos en pacientes con trastornos mentales relacionados con el uso y abuso de substancias tóxicas / Clinical-epidemiological aspects in patients with mental disturbances related with use and abuse of toxic subsances

Estudio para conocer la frecuencia de presentación de los problemas relacionados al uso y abuso de drogas en la casuistica del hospital psiquiátrico. analizando 711 casos de pacientes egresados del hospital en el periodo enero-abril 1987; de éstos, 127 (17.86) eran dependientes a alguna droga que representa el 100 (total de pacientes farmacodependientes), hay una relación que cada 100 pacientes 5 tuvieron algún tipo de adicción, acudiendo al centro en un promedio de edad de 24.7 fueron reingresos, las sustancias más utilizadas: inhalantes 5.52, mariguana 3.92 la mayoría residía en la zona metropolitana, 18.22 contaban con empleo fijo en los farmacodependientes múltiples se encontró el mayor número de desempleo 72.44. El diagnóstico 63 psicosis por droga

Trabajos de investigaciones

Cuestionario de 21 preguntas realizado a 56 familiares de 11 pacientes internados que asistieron a grupos de orientación familiar. Predominan las visitas a hermanos 31 y madre 22; 28 de los encuestados su ocupación es el hogar; y la residencia es 53 del D.F. y 30 del Estado de México. En cuadros está la información y expectativas de los familiares en cuanto a enfermedad y causa; la participación del familiar en el tratamiento y como se lleva con su paciente. La opinión acerca de la atención médica y sugerencias y quejas