Con qué medicamentos están siendo tratados los pacientes con trastorno afectivo bipolar en Colombia / Which drugs are being treated patients with bipolar affective disorder in Colombia / Com quais medicamentos os pacientes com transtorno afetivo bipolar estão sendo tratados na Colômbia?

Introducción:El trastorno bipolar (TB) es una condición psiquiátrica grave caracterizada por alteraciones progresivas en las funciones sociales y cognitivas. Objetivo:Determinar cuáles son los medicamentos con que se está tratando a un grupo de pacientes con diagnóstico de TB, afiliados al Sistema de Salud de Colombia.Materiales y métodos:Estudio de corte para identificar prescripciones de medicamentos de pacientes ambulatorios de cualquier edad y sexo con TB, a partir de una base de datos poblacional de dispensaciones. Se consideraron variables sociodemográficas, clínicas y farmacológicas buscando medicamentos en indicaciones aprobadas y no aprobadas por agencias reguladoras.Resultados:Se identificaron 1334 pacientes, con edad media de 40,2±18,5 años y 50% eran mujeres. Un total de 809 (60,6%) pacientes eran tratados en monoterapia principalmente con ácido valproico (286/615 pacientes, 46,4%), quetiapina (259/525, 49,3%) y Carbonato de Litio (98/275, 35,6%). Las combinaciones más comunes de fármacos para su tratamiento fueron ácido valproico más quetiapina (n=162, 12,1%), ácido valproico más risperidona (n=73, 5,5%) y carbonato de litio más quetiapina (n=62, 4,6%). El 57,4% (n=766) tenían prescripciones de fármacos con indicaciones no aprobadas.Conclusiones:Los pacientes con TB son tratados principalmente en monoterapia y más de la mitad estaba recibiendo fármacos en indicaciones no aprobadas.

Introduction:Bipolar disorder (BP) is a serious psychiatric condition characterized by progressive changes in social and cognitive functions. Objective: To determine which medications are being used to treat a group of patients diagnosed with BP who receive treatment from the Colombian Health System. Materials and methods: Cross-sectional study to identify medication prescriptions of outpatients (regardless of their age) using a population database. Sociodemographic, clinical, and pharmacological variables were considered, searching for medications that are both approved and not approved by regulatory agencies. Results: 1,334 patients were identified, who had a mean age of 40.2±18.5 years, 50% of which were women. A total of 809 (60.6%) patients followed monotherapy, mainly using valproic acid (286/615 patients, 46.4%), quetiapine (259/525, 49.3%), and lithium carbonate (98/275, 35.6%). The most common combination of medications to treat these patients were valproic acid combined withquetiapine (n=162, 12.1%), valproic acid combined withrisperidone (n=73, 5.5%), and lithium carbonate combined withquetiapine (n=62, 4,6%). 57.4% (n=766) of patients had prescriptions with non-approved medications. Conclusions: BPpatients are mostly treated with monotherapy and more than half of them received drugs that are not approved.

Introdução:O transtorno bipolar (TB) é uma condição psiquiátrica grave caracterizada por alterações progressivas nas funções sociais e cognitivas. Objetivo:Determinar quais medicamentos estão sendo usados para tratar um grupo de pacientes diagnosticados com TB, vinculados ao Sistema de Saúde da Colômbia. Materiais e métodos:Estudo transversal para identificação de prescrições de medicamentos para pacientes ambulatoriais de qualquer idade e sexo com TB, a partir de um banco de dados populacional de dispensações. Foram consideradas variáveis sociodemográficas, clínicas e farmacológicas, buscando medicamentos em indicações aprovadas e não aprovadas pelos órgãos reguladores. Resultados:Foram identificados 1.334 pacientes, com média de idade de 40,2 ± 18,5 anos, sendo 50% mulheres. Um total de 809 (60,6%) pacientes foram tratados em monoterapia principalmente com ácido valpróico (286/615 pacientes, 46,4%), quetiapina (259/525, 49,3%) e carbonato de lítio (98/275, 35,6%). As combinações medicamentosas mais comuns paraseu tratamento foram ácido valpróico mais quetiapina (n=162, 12,1%), ácido valpróico mais risperidona (n=73, 5,5%) e carbonato de lítio mais quetiapina (n=62, 5,5%).4,6 %). 57,4% (n=766) tinham prescrições de medicamentos com indicações não aprovadas. Conclusões:Os pacientes com TB são tratados principalmente com monoterapia e mais da metade estava recebendo medicamentos em indicações não aprovadas.

Análisis de estudios sobre psicofármacos en una IPS del departamento de Córdoba 2012-2020 / Analysis of studies of psychopharmacers in a IPS of the department of Córdoba 2012-2020

Resumen Introducción. Los psicofármacos son medicamentos utilizados en la práctica médica para tratar enfermedades mentales. Objetivo. Realizar un análisis comparando indicadores de consumo en la utilización de psicofármacos en una Institución de Salud mental en el Departamento de Córdoba- Colombia. Metodología. Estudio longitudinal, retrospectivo-transversal, estudio de utilización de medicamentos (EUM) para comparar indicadores de consumo como dosis diaria definida (DDD), número de envases, considerando el diagnóstico y variables sociodemográficas. Resultados. población de 3.089 pacientes, donde el 48% presento diagnóstico de trastorno mental y del comportamiento por consumo de sustancias psicoactivas, el 17% presentó trastorno afectivo bipolar y el 15% esquizofrenia paranoide, el 70% de sexo masculino y un 30% sexo femenino. Los medicamentos más consumidos fueron ácido valproico en cápsulas de 250mg, carbonato de litio en tabletas de 300mg y sertralina en tabletas de 50mg; mayor consumo lo obtuvieron los antidepresivos con 45,77%, seguido por antipsicóticos con 23,19% y por último los anticonvulsivantes con 22,39%. Conclusión.Se observó diferencias en la tendencia del aumento en el consumo de psicofármacos utilizando como indicadores de consumo la dosis diaria definida (DDD) 54versus número de envases en los años de estudio. Esta investigación difiere con los resultados a nivel nacional y departamental en el sentido de que la depresión y demás problemas de salud mental se encuentran en mayor incidencia en los hombres

Results.Population of 3,089 patients, where 48% presented a diagnosis of mental and behavioral disorder due to the use of psychoactive substances, 17% presented bipolar affective disorder and 15% paranoid schizophrenia, 70% male and 30% sex feminine. The most used medications were valproic acid in 250mg capsules, lithium carbonate in 300mg tablets and sertraline in 50mg tablets; The highest consumption was obtained by antidepressants with 45.77%, followed by antipsychotics with 23.19% and finally anticonvulsants with 22.39%. Conclusion.Differences were observed in the trend of the increase in the consumption of psychotropic drugs using as consumption indicators the defined daily dose (DDD) versus the number of containers in the years of study. This research differs from the results at the national and departmental levels in the sense that depression and other mental health problems are found to be more prevalent in men

A influência dos aspectos subjetivos na adesão ao tratamento do transtorno bipolar: uma revisão sistemática / The influence of subjective aspects on adherence to the treatment of bipolar disorder: a systematic review

OBJETIVO: Evidenciar a influência dos aspectos subjetivos na adesão ao tratamento do transtorno bipolar. MÉTODOS: Foi realizada revisão sistemática com base nas diretrizes PRISMA. A identificação dos estudos foi realizada por meio da busca nos bancos de dados PubMed, Scopus e SciELO, com base nos descritores "Bipolar Disorder" AND "Treatment Adherence and Compliance" AND "Mental Health". A busca contemplou todos os artigos publicados até o ano 2020, sem restrição de idioma. RESULTADOS: Foram localizados 743 artigos, 714 foram excluídos no processo de seleção, 29 foram lidos na íntegra e 11 foram elegíveis para a composição da amostra. A influência dos aspectos subjetivos na adesão ao tratamento foi associada (1) às atitudes resultantes das percepções do sujeito sobre o transtorno e o tratamento e (2) as atitudes por influência de pessoas próximas. Os estudos apontam para a ocorrência de atitudes negativas em ambas as esferas, tendo a má adesão ao tratamento como desfecho. Na esfera da percepção do sujeito, evidenciam-se: presença de comportamentos intencionais e não intencionais; percepção de consequências; medo dos efeitos colaterais; sentimentos negativos; falta de compreensão sobre o transtorno e negação do diagnóstico. Na esfera da influência das pessoas próximas, destacam-se a baixa qualidade da aliança terapêutica e o suporte ineficaz oferecido pela família. CONCLUSÕES: Para melhorar a adesão ao tratamento do transtorno bipolar, é salutar que os esforços terapêuticos estejam centrados na experiência particular do sujeito, na sua satisfação e na colaboração pactuada com o tratamento.

OBJECTIVE: Evidence the influence of subjective aspects on adherence to the treatment of bipolar disorder. METHODS: A systematic review was performed based on the PRISMA guidelines. The identification of studies was performed by searching the PubMed, Scopus and Scielo databases based on the descriptors "Bipolar Disorder" AND "Treatment Adherence and Compliance" AND "Mental Health". The selection included all articles published up to the year 2020 and without language restrictions. RESULTS: A total of 743 articles were found, 714 were excluded from the selection process, 29 articles were read in full and 11 were eligible for sample composition. The influence of subjective aspects on treatment adherence was associated (1) with attitudes resulting from the subject's perceptions about the disorder and treatment and (2) attitudes influenced by people close to them. Studies point to the occurrence of negative attitudes in both spheres, with poor adherence to treatment as an outcome. In the sphere of the subject's perception, they show the presence of intentional and unintentional behaviors; perception of consequences; fear of side effects; negative feelings; lack of understanding about the disorder and denial of diagnosis. In the sphere of influence of those close to them, they highlight the low quality of the therapeutic alliance and the ineffective support offered by the family. CONCLUSIONS: To improve adherence to treatment for bipolar disorder, it is beneficial that therapeutic efforts are centered on the individual's particular experience, on their satisfaction and on the agreed collaboration with the treatment.

Lithium ameliorates tubule-interstitial injury through activation of the mTORC2/protein kinase B pathway.

Tubule-interstitial injury (TII) is a critical step in the progression of renal disease. It has been proposed that changes in proximal tubule (PT) albumin endocytosis plays an important role in the development of TII. Some reports have shown protective effects of lithium on kidney injury animal models that was correlated to proteinuria. We tested the hypothesis that lithium treatment ameliorates the development of TII due to changes in albumin endocytosis. Two experimental models were used: (1) TII induced by albumin overload in an animal model; (2) LLC-PK1 cells, a PT cell line. Lithium treatment ameliorates TII induced by albumin overload measured by (1) proteinuria; (2) collagen deposition; (3) area of tubule-interstitial space, and (4) macrophage infiltration. Lithium treatment increased mTORC2 activity leading to the phosphorylation of protein kinase B (PKB) at Ser473 and its activation. This mechanism enhanced albumin endocytosis in PT cells, which decreased the proteinuria observed in TII induced by albumin overload. This effect did not involve changes in the expression of megalin, a PT albumin receptor. In addition, activation of this pathway decreased apoptosis in LLC-PK1 cells, a PT cell line, induced by higher albumin concentration, similar to that found in pathophysiologic conditions. Our results indicate that the protective role of lithium treatment on TII induced by albumin overload involves an increase in PT albumin endocytosis due to activation of the mTORC2/PKB pathway. These results open new possibilities in understanding the effects of lithium on the progression of renal disease.

Microbialite-like structures in Cladophora sp. (Ulvophyceae) mats from a subtropical Andean basin: ecological implications / Estructuras de tipo microbialito en Cladophora sp. (Ulvophyceae) de una cuenca andina subtropical: implicaciones ecológicas

Abstract The solubility equilibrium of calcite is influenced by physicochemical, climatic and biological factors. Annual cycles of exceptionally prolonged drought, in conjunction with naturally occurring diffuse organic pollution, generate the unique conditions for the precipitation of lithified carbonate structures (microbialites). The aim of this article is to analyze the possible implications of calcite precipitation produced in mats of Cladophora sp. in an Andean subtropical basin, considering it is the first time this phenomenon is described for the region. We collected samples from selected sites at the Lules River Basin, in four sampling dates between the years 2003 and 2004, within a monitoring work of 15 years. Samples were analyzed using an electron microscope and X-ray diffraction analysis. We found that Gomphonema sp. attached to Cladophora sp. contributes to precipitation of calcite and formation of microbialite like structures, in the studied area. This work presents an initial discussion of the discovery of microbialites-like structures attached to Cladophora sp. mats in a subtropical Andean stream and the environmental conditions that lead to their production, as well as the possible ecological implications of these microbialites.(AU)

Resumen La fase sólida de las sales de los cuerpos de agua juega un papel importante en la concentración de los elementos mayoritarios. El equilibrio de solubilidad de la calcita está influenciado por factores fisicoquímicos, climáticos y biológicos. Los ciclos anuales de sequía excepcionalmente prolongada, junto con la contaminación orgánica difusa de origen natural, generan condiciones únicas para la precipitación de estructuras de carbonato litificado (microbialitos). El objetivo de este artículo es analizar las posibles implicaciones de la precipitación de calcita producida en Cladophora sp. en una cuenca subtropical andina, considerando que es la primera vez que se describe este fenómeno para la región. Recolectamos muestras en sitios seleccionados en la Cuenca del Río Lules, en cuatro fechas de muestreo entre 2003 y 2004, en el marco de un trabajo de monitoreo de quince años. Usamos red Surber para realizar los muestreos. Las muestras de algas, una vez libres de macroinvertebrados, se secaron y pesaron. Analizamos utilizando microscopía electrónica y difracción de rayos X. Encontramos que Gomphonema sp. unido a Cladophora contribuye a la precipitación de calcita y la formación de estructuras similares a microbialitos, en el área estudiada. Este trabajo presenta una discusión inicial sobre el descubrimiento de estructuras similares a microbialitos unidas a filamentos de Cladophora sp. en una cuenca andina subtropical y las condiciones ambientales que conducen a su producción, así como las posibles implicaciones ecológicas de lo mencionado anteriormente.(AU)

Alteraciones endocrinas vinculadas a la prescripción médica de carbonato de litio. Una revisión narrativa / Endocrinological Disorders Related to the Medical Use of Lithium. A Narrative Review

RESUMEN La prescripción de carbonato de litio es común en la actividad psiquiátrica cotidiana. El objetivo es identificar las alteraciones endocrinas secundarias y sus bases fisiopatológicas. La revisión de la literatura se realizó en Psycinfo, EMBASE, PubMed y Scopus. Se efectuó una búsqueda computarizada de información utilizando la estrategia PICO. Las alteraciones más comunes están en riñones, tiroides, paratiroides, páncreas y vías neuroendocrinas. Los mecanismos fisiopatológicos subyacentes son diversos, y destacan la inhibición de la adenilato ciclasa tiroidea sensible a tirotropina como causa de hipotiroidismo, la expresión reducida de acuaporina 2 como causa de diabetes insípida nefrogénica, la pérdida del equilibrio iónico del calcio y la presencia de hiperparatiroidismo e hipercalcemia. En el eje hipotálamo-hipófiso-adrenal, se documenta una disminución en la producción de catecolaminas. Finalmente, se documenta la desregulación en el control de la glucemia al aumentar la resistencia a la insulina. Es necesario conocer estas eventualidades e identificarlas tempranamente a través de evaluaciones periódicas. Se propone un esquema de evaluación integral, sin que implique un algoritmo de tratamiento.

ABSTRACT The prescribing of Lithium is common in psychiatric clinical practice. The aim of this study was to identify the most common endocrine side effects associated with this drug and to clarify the pathophysiological basis. A systematic review was conducted in Psycinfo, Embase, PubMed, and Scopus. A computerised search for information was performed using a PICO (patient, intervention, comparative, outcomes) strategy. The main neuroendocrine alterations were reported in kidneys, thyroid and parathyroid glands, pancreas, and the communication pathways between the pituitary and adrenal glands. The pathophysiological mechanisms are diverse, and include the inhibition of the thyroid adenylate cyclase sensitive to the thyroid stimulant hormone (TSH) sensitive adenylate cyclase, which causes hypothyroidism. It also reduces the expression of aquaporin type 2, which is associated with nephrogenic diabetes insipidus, and the loss of the ionic balance of calcium that induces hyperparathyroidism and hypercalcaemia. Other considerations are related to alterations in the hypothalamic-pituitary-adrenal axis and a decrease in the production of catecholamines. Finally, another side-effect is the glycaemic dysregulation caused by the insulin resistance. Periodical clinical and para-clinical evaluations are necessary. The author proposes an evaluation scheme.

Mania-like elevated mood in rats: Enhanced 50-kHz ultrasonic vocalizations after sleep deprivation.

Mania is characterized by elevated drive and mood but animal models of mania have often neglected elevated mood. Ultrasonic vocalizations (USV) of 50-kHz emitted by rats are thought to index the subject's positive affective state. Fifty-kHz USV emission is increased by amphetamine, an effect blocked by lithium administration. Sleep deprivation (SD) is an environmental model of mania and the present study evaluated SD effects on behavioral activity and USV emission, together with the impact of lithium treatment. Adult rats were submitted to 24h or 72h SD, and locomotor activity and USV emission were assessed. To test their sensitivity to a standard antimanic drug, these behavioral parameters were also evaluated after acute administration of lithium carbonate (25, 50 or 100 mg/kg, i.p.). Striatal monoamine content was measured post-mortem. SD (24h and 72h) led to increased locomotor activity, rearing behavior and 50-kHz USV emission, together with a change in the call profile characterized by an increase in the percentage of frequency-modulated 50-kHz USV, which may indicate the mania-like consequences of SD. Importantly, all SD effects were reverted by lithium administration. SD also led to a decrease in dopamine content in the ventral striatum, while increasing dopamine turnover. In conclusion, SD increased 50-kHz USV emission, an effect prevented by acute lithium administration. This suggests 50-kHz USV as a new marker for mania-like elevated mood, which shows construct validity (associated with increased dopaminergic tone), face validity (reflecting increased positive affect) and predictive validity (high sensitivity to lithium treatment).

Bioaccumulation of Lithium (Li2CO3) in Mycelia of the Culinary-Medicinal Oyster Mushroom, Pleurotus ostreatus (Agaricomycetes).

Pleurotus ostreatus is a white-rot mushroom that bioaccumulates metals in basidiocarps and vegetative mycelia. This fungus has been used in soil and water bioremediation of several heavy metals; however, there are few studies of lithium mycelial bioaccumulation for pharmacological use. The aim of this study was to evaluate lithium bioaccumulation in P. ostreatus mycelia grown in a liquid malt extract cultivation medium with Li2CO3 or LiCl. Each lithium source was added to the medium to obtain a concentration of 0, 5, 10, 15, 20, 25, 30, 40, 50, 100, or 200 mg · L-1 lithium. The highest bioaccumulation of lithium in mycelia was 1575.29 µg · g-1 upon treatment with 40 mg · L-1 Li2CO3. P. ostreatus mycelia produce biomass and bioaccumulate both lithium sources, but more lithium bioaccumulates when in the form of Li2CO3. This study provides a prospective for the development of biotechnological products with high aggregate values and alternative ways to deliver lithium and eventually other salts for pharmacological use.

Lactancia materna y tratamiento con litio: Caso clínico / Lithium while breastfeeding: Case report

El tratamiento con litio forma parte de la terapia habitual en las personas que sufren el trastorno bipolar. Habitualmente, aquellas madres que desean dar el pecho a sus hijos son sometidas a la disyuntiva entre modificar el tratamiento o bien administrar lactancia artificial. La administración de litio durante la lactancia materna se ha asociado con diversos efectos adversos en el lactante, tales como alteraciones tiroideas, hipotermia o hipotonía, entre otros. Son pocas las publicaciones en las que no se observan dichas anomalías en los lactantes. A continuación, se presenta el caso de un lactante amamantado por su madre en tratamiento con litio que no presentó alteraciones renales ni tiroideas.

Lithium therapy is currently a cornerstone of treatment for mothers who suffer bipolar disorders. Those who wish to breastfeed their children are often told they have to decide whether modifying the treatment for their disorder or even avoiding lactation. Lithium administration during breastfeeding has been described to produce certain side effects such as thyroid disorders, hypothermia and hypotonia. To our knowledge, there are few publications where infants have no laboratory abnormalities. Here we present the case of an infant without renal or thyroid alteration while he was breastfed.

[Lithium while breastfeeding: Case report]. / Lactancia materna y tratamiento con litio: Caso clínico.

Lithium therapy is currently a cornerstone of treatment for mothers who suffer bipolar disorders. Those who wish to breastfeed their children are often told they have to decide whether modifying the treatment for their disorder or even avoiding lactation. Lithium administration during breastfeeding has been described to produce certain side effects such as thyroid disorders, hypothermia and hypotonia. To our knowledge, there are few publications where infants have no laboratory abnormalities. Here we present the case of an infant without renal or thyroid alteration while he was breastfed.

El tratamiento con litio forma parte de la terapia habitual en las personas que sufren el trastorno bipolar. Habitualmente, aquellas madres que desean dar el pecho a sus hijos son sometidas a la disyuntiva entre modificar el tratamiento o bien administrar lactancia artificial. La administración de litio durante la lactancia materna se ha asociado con diversos efectos adversos en el lactante, tales como alteraciones tiroideas, hipotermia o hipotonía, entre otros. Son pocas las publicaciones en las que no se observan dichas anomalías en los lactantes. A continuación, se presenta el caso de un lactante amamantado por su madre en tratamiento con litio que no presentó alteraciones renales ni tiroideas.

Lithium prevents scopolamine-induced memory impairment in zebrafish.

We examined whether lithium carbonate (Li2CO3, 100mg/L) is able to prevent memory impairment induced by scopolamine. Moreover, we evaluated the effects of lithium on anxiety-like behavior and acetylcholinesterase activity in adult zebrafish. We demonstrated that lithium prevents the memory impairment induced by scopolamine, decreases exploration and increases the activity of acetylcholinesterase in zebrafish. Collectively, this contributes to a better understanding of the pharmacology of lithium, its interaction with cholinergic neurotransmission, and its possible application to therapeutic treatments aimed at improving cognition.

Salud mental y uso racional de litio en el Ecuador, un tema controversial / Mental health and rational use of lithium in Ecuador, a controversial topic

El uso de litio es tan antiguo como su historia generándose en el tiempo voces detractoras e como importantes defensores. En Ecuador, no está exenta esta controversia soslayándose el uso de litio para tratar cuadros el trastorno bipolar, eventos suicidas y como coadyuvante en casos de depresión resistente al tratamiento, pese a ser un medicamento básico de comprobada eficacia en estas patologías. Un manejo y monitoreo adecuados, evitaría su sustitución por medicamentos de mayor costo sobre todo para el Sistema Nacional de Salud Pública, que asiste a un importante segmento poblacional de bajos recursos económicos.(AU)

The use of lithium is as old as its history, generating in time detractor voices and as important defenders. In Ecuador, this controversy is not exempt from the use of lithium to treat bipolar disorder, suicidal events and as an adjuvant in cases of treatment-resistant depression, despite being a basic drug with proven efficacy in these pathologies. Adequate management and monitoring would avoid its substitution by drugs of greater cost, especially for the National Public Health System, which assists an important segment of the population with low economic resources. (AU)

[Profile of lithium carbonate use in patients with bipolar disorder in Colombia].

INTRODUCTION: Lithium is the drug of choice for the treatment of bipolar affective disorder. OBJECTIVE: To define lithium therapeutic profile and adverse reactions to its use in patients with bipolar affective disorder in Colombia. MATERIALS AND METHODS: We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions. A multivariate analysis was done using SPSS 22.0. RESULTS: The 331 patients had an average age of 44.5 ± 13.9 years; 59.2% were women. The mean dose of lithium was 898 ± 294 mg/day; 22% received doses lower than recommended, and patients had received lithium for 38.0 ± 39.5 months (range: 12-159 months). Lithium levels in blood had been measured only in 13.5% of patients; 71.3% of them had received adjuvant therapy for bipolar disorder with other drugs, especially clozapine (16.6%) and valproic acid (16.6%). The main comorbidities were hypothyroidism (18.1%) and hypertension (12.7%); 390 potentially toxic drug interactions were found, and adverse reactions were reported in 1.2% of patients. A statistically significant association was found between a lower risk of combination therapy and receiving treatment in the cities of Bogotá (OR=0.4, p=0.025), Cartagena (OR=0.3, p=0.015) and Ibagué (OR=0.3, p=0.025). CONCLUSION: Lithium was generally used at recommended doses and intervals, but a significant percentage of patients received lower doses than those recommended, and it was not possible to compare with lithium levels in blood. Adverse reactions and blood lithium levels reporting should be improved in patients with bipolar disorder in Colombia.

Perfil de utilización del carbonato de litio en pacientes con trastorno afectivo bipolar en 25 ciudades de Colombia / Profile of lithium carbonate use in patients with bipolar disorder in Colombia

Resumen Introducción. El litio es el medicamento de elección para el tratamiento del trastorno afectivo bipolar. Objetivo. Determinar el perfil de uso y las reacciones secundarias del litio en pacientes con trastorno afectivo bipolar en Colombia. Materiales y métodos. Se hizo un estudio observacional de cohorte retrospectiva entre el 1° de enero y el 31 de diciembre de 2013, en pacientes con diagnóstico de trastorno afectivo bipolar tratados con carbonato de litio en 25 ciudades colombianas. Se evaluaron las variables sociodemográficas, las dosis del litio, la medicación simultánea con otros fármacos, las interacciones medicamentosas y las reacciones adversas. Se hizo un análisis multivariado utilizando el programa SPSS 22.0®. Resultados. La edad promedio de los 331 pacientes fue de 44,5 ± 13,9 años, 59,2 % de ellos eran mujeres, la dosis promedio de litio fue de 898 ± 294 mg/día, y 22 % recibía dosis inferiores a las recomendadas; los participantes habían recibido el medicamento durante 38,0 ± 39,5 meses en promedio (rango: 12-159 meses), y solo a 13,5 % de ellos se les había hecho el análisis de litio en sangre. El 71,3 % recibía otros medicamentos como tratamiento coadyuvante para el trastorno afectivo bipolar, especialmente clozapina (16,6 %) y ácido valproico (16,6 %). Las principales enfermedades concomitantes fueron el hipotiroidismo (18,1 %) y la hipertensión arterial (12,7 %). Se encontraron 390 interacciones medicamentosas potencialmente tóxicas y se reportaron reacciones secundarias en 1,2 % de los casos. Se encontró una asociación estadísticamente significativa con un menor riesgo de recibir tratamiento combinado en pacientes tratados en las ciudades de Bogotá (odds ratio, OR=0,4; p=0,025), Cartagena (OR=0,3; p=0,015) e Ibagué (OR=0,3; p=0,025). Conclusiones. El litio se administraba en las dosis e intervalos recomendados, pero un porcentaje significativo recibía dosis inferiores a las recomendadas y no fue posible contrastar el efecto con los niveles de litio en suero. Se debe mejorar el reporte de reacciones adversas y la medición de los niveles de litio en suero en los pacientes con trastorno afectivo bipolar en Colombia.

Abstract Introduction: Lithium is the drug of choice for the treatment of bipolar affective disorder. Objective: To define lithium therapeutic profile and adverse reactions to its use in patients with bipolar affective disorder in Colombia. Materials and methods: We conducted an observational retrospective cohort study between January 1 and December 31, 2013, which included patients with a diagnosis of bipolar disorder treated with lithium carbonate in 25 Colombian cities; we evaluated socio-demographic variables, lithium dose, co-medication, drug interactions and adverse reactions. A multivariate analysis was done using SPSS 22.0. Results: The 331 patients had an average age of 44.5 ± 13.9 years; 59.2% were women. The mean dose of lithium was 898 ± 294 mg/day; 22% received doses lower than recommended, and patients had received lithium for 38.0 ± 39.5 months (range: 12-159 months). Lithium levels in blood had been measured only in 13.5% of patients; 71.3% of them had received adjuvant therapy for bipolar disorder with other drugs, especially clozapine (16.6%) and valproic acid (16.6%). The main comorbidities were hypothyroidism (18.1%) and hypertension (12.7%); 390 potentially toxic drug interactions were found, and adverse reactions were reported in 1.2% of patients. A statistically significant association was found between a lower risk of combination therapy and receiving treatment in the cities of Bogotá (OR=0.4, p=0.025), Cartagena (OR=0.3, p=0.015) and Ibagué (OR=0.3, p=0.025). Conclusion: Lithium was generally used at recommended doses and intervals, but a significant percentage of patients received lower doses than those recommended, and it was not possible to compare with lithium levels in blood. Adverse reactions and blood lithium levels reporting should be improved in patients with bipolar disorder in Colombia.

Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

Studies have shown that oxidative stress is involved in the pathophysiology of bipolar disorder (BD). It is suggested that omega-3 (ω3) fatty acids are fundamental to maintaining the functional integrity of the central nervous system. The animal model used in this study displayed fenproporex-induced hyperactivity, a symptom similar to manic BD. Our results showed that the administration of fenproporex, in the prevent treatment protocol, increased lipid peroxidation in the prefrontal cortex (143%), hippocampus (58%) and striatum (181%), and ω3 fatty acids alone prevented this change in the prefrontal cortex and hippocampus, whereas the co-administration of ω3 fatty acids with VPA prevented the lipoperoxidation in all analyzed brain areas, and the co-administration of ω3 fatty acids with Li prevented this increase only in the prefrontal cortex and striatum. Moreover, superoxide dismutase (SOD) activity was decreased in the striatum (54%) in the prevention treatment, and the administration of ω3 fatty acids alone or in combination with Li and VPA partially prevented this inhibition. On the other hand, in the reversal treatment protocol, the administration of fenproporex increased carbonyl content in the prefrontal cortex (25%), hippocampus (114%) and striatum (91%), and in prefrontal coxter the administration of ω3 fatty acids alone or in combination with Li and VPA reversed this change, whereas in the hippocampus and striatum only ω3 fatty acids alone or in combination with VPA reversed this effect. Additionally, the administration of fenproporex resulted in a marked increase of TBARS in the hippocampus and striatum, and ω3 fatty acids alone or in combination with Li and VPA reversed this change. Finally, fenproporex administration decreased SOD activity in the prefrontal cortex (85%), hippocampus (52%) and striatum (76%), and the ω3 fatty acids in combination with VPA reversed this change in the prefrontal cortex and striatum, while the co-administration of ω3 fatty acids with Li reversed this inhibition in the hippocampus and striatum. In conclusion, our results support other studies showing the importance of ω3 fatty acids in the brain and the potential for these fatty acids to aid in the treatment of BD.

Desenvolvimento, caracterização e desempenho biológico de um novo biomaterial de liberação controlada à base de carbonato de lítio aplicado ao reparo ósseo / Development, characterization and biological performance of a new biomaterial of controlled release based on lithium carbonate applied to bone repair

Neste trabalho desenhou-se bases de desenvolvimento, caracterização e avaliação dos aspectos biológicos relacionados ao Sistema BoneLithium, idealizado a partir da associação de partículas de carbonato de lítio dispersas em matriz gel de carbopol®, com capacidade de atuar como um sistema liberador de fármacos. Metodologicamente este estudo se dividiu em quatro partes: Na primeira delas, o objetivo central foi o desenvolvimento e a caracterização do biomaterial através da manipulação farmacológica. Na segunda etapa, avaliou-se a reação tecidual em subcutâneo de ratos, na terceira a influência das partículas de lítio liberadas pelo Sistema BoneLithium no reparo ósseo através de modelos experimentais utilizando coelhos, e por ultimo, a capacidade de cicatrização de defeitos ósseos criados cirurgicamente em calvária de ratos, tratados com o biomaterial e diferentes opções de enxertos ósseos com o objetivo de comparar a eficiência do Sistema BoneLithium aos protocolos pré-existentes. Experimentalmente, avaliou-se a reação tecidual onde se utilizou 15 ratos machos divididos aleatatoriamente em 5 grupos onde implantouse no subcutâneo tubos de butterfly contendo o biomaterial por períodos de preservação recomendados pela norma ADA 10993 para teste de reação tecidual. Os resultados demonstram que o Sistema BoneLithium apresenta reação tecidual normal. Para a avaliação do comportamento biológico do Sistema BoneLithium foram utilizados coelhos brancos adultos da raça New Zealand nos quais defeitos ósseos bilaterais de 1 cm de diâmetro foram confeccionados cirurgicamente na calvária e foram Tratados com o Sistema Bone Lithium do (lado Direito) e somente o Gel de Carbopol (lado esquerdo)/Coágulo sanguíneo (controle). A Histomorfometria demonstrou comportamento favorável ao reparo ósseo e adicionalmente através de Microtomografia Computadorizada (CT SKYSCAN), foi possível constatar diferenças significativas considerando p> 0.05 (ANOVA, Tukey) para o processo de reparo ósseo. A avaliação da performance do Sistema BoneLithium utilizando ratos Wistar nos quais foram criados defeitos críticos no centro da calvária e tratados com diferentes modalidades de enxertos ósseos (controle, autógeno, osso de banco (Unioss®, Marília Brasil), Bio-Oss® e associações com o Sistema BoneLithium. A histomorfometria mostrou diferenças significativas considerando p> 0.05 (ANOVA, Tukey) para avaliação de tecido conjuntivo pré-osteogênico e tecido ósseo neoformado, e quando avaliado qualitativamente por tomografia computadorizada de feixe cônico (I cat Cone Beam FOV 0.05 Xoran Tecnology, LLC, EUA e E-vol, CDT, Brasil), observaram-se áreas de neoformação óssea compatíveis com hiperdensidade óssea em toda a extensão do defeito quando apuradas em analises de paridade em escala Hounsfield. Dessa forma, conclui-se que no contexto deste estudo é possível concluir que Sistema BoneLithium representa uma alternativa com potencial viabilidade clínica e necessita seguimento de aplicação em novas metodologias.(AU)

In this work, bases for the development, characterization and evaluation of the biological aspects related to the BoneLithium System were designed, based on the association of lithium carbonate particles dispersed in carbopol® gel matrix, capable of acting as a drug-releasing system. Methodologically this study was divided in four parts: In the first one, the central objective was the development and characterization of the biomaterial through the pharmacological manipulation. In the second step, the tissue reaction was evaluated in subcutaneous of rats, in the third the influence of the lithium particles released by BoneLithium System in the bone repair through experimental models using rabbits, and finally, the capacity of healing of bone defects created surgically in Calvaria of rats, treated with the biomaterial and different options of bone grafts with the objective to compare the efficiency of the BoneLithium System to the preexisting protocols. Experimentally, the tissue reaction was evaluated in which 15 male rats were randomly divided into 5 groups, where butterfly tubes containing the biomaterial were implanted in the subcutaneous tubes for preservation periods recommended by the ADA 10993 standard for biocompatibility test. The results demonstrate that the BoneLithium System is tissue reaction positive. To evaluate the biological behavior of the BoneLithium System, adult New Zealand white rabbits were used in which bilateral bone defects of 1 cm in diameter were surgically made on calvaria and treated with the Bone Lithium System (right side) and only Gel Of Carbopol (left side) / blood clot (control). Histomorphometry showed a favorable behavior to bone repair and, in addition, through Computerized Microtomography (CT SKYSCAN), it was possible to verify significant differences considering p> 0.05 (ANOVA, Tukey) for the bone repair process. The evaluation of the performance of the BoneLithium System using Wistar rats in which critical defects were created at the calvarial center and treated with different bone graft modalities (control, autogenous, bone bank (Unioss®, Marília Brazil), Bio-Oss® and associations (ANOVA, Tukey) for evaluation of pre osteogenic connective tissue and neoformed bone tissue, and when assessed qualitatively by cone beam computed tomography (I cat - Cone Beam - FOV 0.05 - Xoran Tecnology, LLC, USA and E-vol, CDT, Brazil), areas of bone neoformation compatible with bone hyperdensity throughout the extent of the defect were ascertained in Hounsfield scale parity analyzes, It is concluded that in the context of this study it is possible to conclude that the BoneLithium System represents an alternative with potential clinical feasibility And requires follow-up of application in new methodologies.(AU)

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

Evaluation of 50-kHz ultrasonic vocalizations in animal models of mania: Ketamine and lisdexamfetamine-induced hyperlocomotion in rats.

Drug-induced hyperlocomotion in rodents is frequently used as a behavioral model for mania. However, the use of locomotor activity as the single parameter in these animal models of mania may pose some limitations for developing new pharmacological treatments. Thus, alternative behavioral markers are required. Fifty-kHz ultrasonic vocalizations (USV), which are thought to represent positive affect, are increased by the administration of the psychostimulant d-amphetamine, an effect that can be prevented by lithium treatment, the gold standard antimanic drug for treating bipolar disorder. The aim of this study was to evaluate 50-kHz USV in two other pharmacological-induced animal models of mania: ketamine (KET)- and lisdexamfetamine (LDX)-induced hyperlocomotion. After systemic injection of LDX (10mg/kg, ip), racemic-ketamine (25mg/kg, ip) or S-ketamine (25mg/kg, ip), locomotor activity and 50-kHz USV emission were evaluated in rats. Furthermore, the effects of an antimanic treatment, namely lithium carbonate (100mg/kg, ip), on LDX-induced 50-kHz USV and hyperlocomotion were tested. Rats treated with racemic KET and S-KET showed increased locomotor activity, but these drug treatments did not significantly affect 50-kHz USV emission rates. On the other hand, LDX administration increased both locomotor activity and 50-kHz USV with both effects being reversed by lithium administration. The present findings suggest that 50-kHz USV can differentiate between drug-induced models of mania, which may represent different types of manic episodes. Thus, measuring 50-kHz USV might serve as an additional valuable behavioral variable to assess mania-like phenotypes in rat models.