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Alzheimer's disease (AD) is considered the most common and prevalent form of dementia of adult-onset with characteristic progressive impairment in cognition and memory. The cure for AD has not been found yet and the treatments available until recently were only symptomatic. Regardless of multidisciplinary approaches and efforts made by pharmaceutical companies, it was only in the past two years that new drugs were approved for the treatment of the disease. Amyloid beta (Aß) immunotherapy is at the core of this therapy, which is one of the most innovative approaches looking to change the course of AD. This technology is based on synthetic peptides or monoclonal antibodies (mAb) to reduce Aß levels in the brain and slow down the advance of neurodegeneration. Hence, this article reviews the state of the art about AD neuropathogenesis, the traditional pharmacologic treatment, as well as the modern active and passive immunization describing approved drugs, and drug prototypes currently under investigation in different clinical trials. In addition, future perspectives on immunotherapeutic strategies for AD and the rise of the aptamer technology as a non-immunogenic alternative to curb the disease progression are discussed.
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Enzyme-substrate interactions play a fundamental role in elucidating synthesis pathways and synthetic biology, as they allow for the understanding of important aspects of a reaction. Establishing the interaction experimentally is a slow and costly process, which is why this problem has been addressed using computational methods such as molecular dynamics, molecular docking, and Monte Carlo simulations. Nevertheless, this type of method tends to be computationally slow when dealing with a large search space. Therefore, in recent years, methods based on artificial intelligence, such as support vector machines, neural networks, or decision trees, have been implemented, significantly reducing the computing time and covering vast search spaces. These methods significantly reduce the computation time and cover broad search spaces, rapidly reducing the number of interacting candidates, as they allow repetitive processes to be automated and patterns to be extracted, are adaptable, and have the capacity to handle large amounts of data. This article analyzes these artificial intelligence-based approaches, presenting their common structure, advantages, disadvantages, limitations, challenges, and future perspectives.
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The focus of this study was on the development, physicochemical characterisation and evaluation of the antioxidant activity of cape gooseberry calyx extract loaded into nanoliposomal systems. Various nanoliposomes were prepared and optimised using the ethanol injection method and characterised based on particle size, polydispersity and zeta potential measurements. Subsequently, the encapsulation efficiency and in vitro release profile of the natural antioxidant extract (NAE) were evaluated, and its antioxidant activity was assessed using the oxygen radical absorbance capacity assay. The results revealed that NAE-loaded nanoliposomes described desired quality features (e.g., particle size of < 200 nm, polydispersity index of < 0.3, zeta potential of > -40 mV and encapsulation efficiency of â¼70%). Furthermore, it was found that NAE release is controlled by various stages, and its antioxidant activity improves by around 30% when loaded into the nanoliposomes, suggesting that it could be a promising antioxidant functional raw material.
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Antioxidantes , Ribes , Antioxidantes/farmacologia , Lipossomos , Lecitinas , Tamanho da PartículaRESUMO
Introducción: La aspiración de contenido gástrico representa la principal causa de muerte relacionada con la anestesia. El ultrasonido gástrico parece ser útil para el estudio del contenido gástrico, en especial en situaciones donde no existen o se desconocen las condiciones de ayuno. Objetivo: Describir la utilidad del ultrasonido para la valoración del contenido gástrico preoperatorio. Metodología: Se realizó una búsqueda estructurada en las bases de datos Pubmed, Embase, SciELO y Cochrane Library con los descriptores fasting; anesthesia; anesthesia, general; ultrasonics, ultrasonography, stomach (MeSH) Resultados: Se encontraron alrededor de 29 artículos con información relevante para el desarrollo de la presente revisión. Conclusiones: Aunque el ultrasonido gástrico parece ser una técnica útil para el estudio del contenido gástrico, se desconoce su impacto en la incidencia de aspiración neumónica, por lo que se necesitan más estudios para promover su uso rutinario en la práctica clínica.
Introduction: Gastric content aspiration represents the main cause of death related to anesthesia. Gastric ultrasound seems to be useful for studying gastric content, especially in situations where fasting conditions do not exist or are unknown. Objetive: To describe the utility of ultrasound for the evaluation of gastric content. Methods: A structured search was carried out with the descriptors: fasting; anesthesia; general anesthesia; ultrasounds, ultrasonography, stomach (MeSH), in the databases: Pubmed, Embase, SciELO and Cochrane Library. Results: 29 articles were found with relevant information for the development of this review. Conclusions: Although gastric ultrasound seems to be a useful technique for the study of gastric content, the impact that this may have on the incidence of pneumonic aspiration is unknown, so more studies are needed to promote its routine use in clinical practice.
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This study was focused on synthesizing, characterizing, and evaluating the antimicrobial effect of polymer nanoparticles (NPs) loaded with ampicillin. For this, the NPs were produced through polymeric self-assembly in aqueous media assisted by high-intensity sonication, using anionic polymers corresponding to the sodium salts of poly(maleic acid-co-vinylpyrrolidone) and poly(maleic acid-co-vinylpyrrolidone) modified with decyl-amine, here named as PMA-VP and PMA-VP-N10, respectively. The polymeric NPs were analyzed and characterized through the formation of polymeric pseudo-phases utilizing pyrene as fluorescent probe, as well as by measurements of particle size, zeta potential, polydispersity index, and encapsulation efficiency. The antimicrobial effect was evaluated by means of the broth microdilution method employing ampicillin sensitive and resistant Staphylococcus aureus strains. The results showed that PMA-VP and PMA-VP-N10 polymers can self-assemble, forming several types of hydrophobic pseudo-phases with respect to the medium pH and polymer concentration. Likewise, the results described that zeta potential, particle size, polydispersity index, and encapsulation efficiency are extremely dependent on the medium pH, whereas the antimicrobial activity displayed an interesting recovery of antibiotic activity when ampicillin is loaded in the polymeric NPs.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Ampicilina/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Maleatos , Nanopartículas/química , Tamanho da Partícula , Polímeros/química , Staphylococcus aureusRESUMO
In the past decade, pharmaceutical nanotechnology has proven to be a promising alternative for improving the physicochemical and biopharmaceutical features for conventional pharmaceutical drug formulations. The goal of this study was to develop, characterize, and evaluate the in vitro and in vivo release of the model drug carbamazepine (CBZ) from two emulsified formulations with different droplet sizes (coarse and nanometric). Briefly, oil-in-water emulsions were developed using (i) Sacha inchi oil, ultrapure water, TweenTM 80, and SpanTM 80 as surfactants, (ii) methyl-paraben and propyl-paraben as preservatives, and (iii) CBZ as a nonpolar model drug. The coarse and nanometric emulsions were prepared by rotor-stator dispersion and ultra-high-pressure homogenization (UHPH), respectively. The in vitro drug release studies were conducted by dialysis, whereas the in vivo drug release was evaluated in New Zealand breed rabbits. The results showed that nanoemulsions were physically more stable than coarse emulsions, and that CBZ had a very low release for in vitro determination (<2%), and a release of 20% in the in vivo study. However, it was found that nanoemulsions could significantly increase drug absorption time from 12 h to 45 min.
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This study aimed to evaluate and compare, using the methodology of Franz diffusion cells, the ketoprofen (KTP) releasing profiles of two formulations: A gel and a conventional suspension. The second aim was to show that this methodology might be easily applied for the development of semi-solid prototypes and claim proof in pre-formulation stages. Drug release analysis was carried out under physiological conditions (pH: 5.6 to 7.4; ionic strength 0.15 M; at 37 °C) for 24 h. Three independent vertical Franz cells were used with a nominal volume of the acceptor compartment of 125 mL and a diffusion area of 2.5 cm². Additionally, two different membranes were evaluated: A generic type (regenerated cellulose) and a transdermal simulation type (Strat-M®). The KTP permeation profiles demonstrated that depending on the membrane type and the vehicle used, the permeation is strongly affected. High permeation efficiencies were obtained for the gel formulation, and the opposite effect was observed for the suspension formulation. Moreover, the permeation studies using Strat-M membranes represent a reproducible methodology, which is easy to implement for pre-formulation stage or performance evaluation of semi-solid pharmaceutical products for topical or transdermal administration.
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Lipids are considered important factors in the pathogenesis of Alzheimer's disease (AD). In this study, we realized a comparative analysis of the phospholipid profile and phospholipid composition of the temporal cortex from E280A-familiar AD (FAD), sporadic AD (SAD), and healthy human brains. Findings showed a significant decrease of lysophosphatidylcholine and phosphatidylethanolamine formed by low levels of polyunsaturated fatty acids (20â:â4, 22â:â6) in AD brains. However, phosphatidylethanolamine-ceramide and phosphoglycerol were significantly increased in SAD, conformed by high levels of (18â:â0/18â:â1) and (30/32/36â:â0/1/2), respectively. Together, the findings suggest a deficiency in lysophosphacholine and phosphatidylethanolamine, and alteration in the balance between poly- and unsaturated fatty acids in both types of AD, and a differential pattern of phospholipid profile and fatty acid composition between E280A FAD and SAD human brains.
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Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Mutação/genética , Fosfolipídeos/metabolismo , Presenilina-1/genética , Lobo Temporal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/genética , Análise de Variância , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Ácido Glutâmico/genética , Humanos , Lisofosfatidilcolinas/metabolismo , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Fosfatidiletanolaminas/metabolismoRESUMO
Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.
Resumen La enfermedad de Alzheimer (EA) es la forma más frecuente de demencia de inicio en el adulto, caracterizada por un deterioro progresivo en la cognición y la memoria. No hay cura para la enfermedad y los tratamientos actuales son sólo sintomáticos. El descubrimiento de fármacos es un proceso costoso y que consume mucho tiempo; en la última década no se han encontrado nuevos fármacos para la EA a pesar de los esfuerzos de la comunidad científica y las compañías farmacéuticas. La inmunoterapia contra Aβ es uno de los enfoques más prometedores para modificar el curso de la EA. Esta estrategia terapéutica utiliza péptidos sintéticos o anticuerpos monoclonales (mAb) para disminuir la carga de Aβ en el cerebro y retardar la progresión de la enfermedad. Por lo tanto, este artículo discutirá los principales aspectos de la neuropatogénesis de la EA, el tratamiento farmacológico clásico, así como la inmunización activa y pasiva describiendo los prototipos de fármacos evaluados en diferentes ensayos clínicos.
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Humanos , Peptídeos beta-Amiloides/imunologia , Doença de Alzheimer/terapia , Imunoterapia/métodos , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Progressão da Doença , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologiaRESUMO
ß-amyloid (Aß) is produced by the ß-secretase 1 (BACE1)-mediated enzymatic cleavage of the amyloid precursor protein through the amyloidogenic pathway, making BACE1 a therapeutic target against Alzheimer's disease (AD). Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism. The objective of this study was to determine the effect of RNA interference against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice. The shBACEmiR treatment induced cognitive function recovery and restored mainly the fatty acid composition of lysophosphatidylethanolamine and etherphosphatidylethanolamine, reduced the cPLA2's phosphorylation, down-regulated the levels of arachidonic acid and COX2 in the hippocampi of 3xTg-AD mice. Together, our findings suggest, for the first time, that BACE1 silencing restores phospholipids composition which could favor the recovery of cellular homeostasis and cognitive function in the hippocampus of triple transgenic AD mice.
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El síndrome de Diógenes, tema de revisión de este artículo, constituye el trastorno deacumulación más conocido y con mayor impacto socio-ambiental. La importancia,extensión y complejidad de dicho trastorno ha determinado una considerable suma debibliografía científica, especialmente en los últimos años. La revisión bibliográficaefectuada, fue de modalidad integrativa, con el fin de obtener material científico para latesis de Doctorado en Ciencias de la Salud. De ella se desprende este artículo con elobjetivo: Identificar la producción bibliográfica acerca del Síndrome de Diógenes endiversos abordajes y área de conocimiento. El relevamiento de los datos, fue entre elperiodo 2006-2014. En dicha revisión de diferentes artículos, se destaca que el Síndromede Diógenes se asocia mayoritariamente a los adultos mayores, que viven solos, conescaso o nulo apoyo familiar y social. Otra característica de estas personas es quegeneralmente presentan trastornos psiquiátricos, sin conciencia de enfermedad yacompañados de apragmatismos. Mayoritariamente fueron captados a través de consultasmédicas realizadas por presencia de patologías orgánicas, siendo necesario en algunoscasos internaciones psiquiátricas o médicas, sin presentar antecedentes. Estas personastienen en común que en sus hogares practican la acumulación de los objetos más diversos,de los cuales no pueden desprenderse. La mayoría de las publicaciones comprueban lacomplejidad de aspectos referentes en este síndrome, que van desde lo psicológico, loambiental y social, entre otros. Surge consecuentemente, el abordaje interdisciplinar, quetrasvasa las áreas tradicionales de la salud...
Diogenes syndrome, or hoarding disorder, is named in honour to Diogenes of Sinope,representative of the Greek philosophy cynicism. "Cynicism is a philosophicalmovement that preaches non-attachment to material goods, believing that happiness doesnot depend on anything external to oneself. This article systematically reviews theliterature, analysing a period from 2006 to 2014, including 18 clinical case studies, somealso reviewing the scientific literature on Diogenes syndrome, with conceptual definitionsand dimensions that cover the subject. The main signs of the disorder described by thestudies are that it mainly affects elderly people that live alone, with little or no family andpoor social support. They mostly have psychiatric disorders, unaware of the disease, andthe presence of apragmatisms. Mainly, the disorders were found when conductingmedical consultations for organic pathologies that required health services. In some casespsychiatric or medical hospitalization was needed and most patients didn`t havepsychiatric treatment before. At their houses, patients hoard different objects, books,newspaper clippings, paper, clothing, faeces, bottles and useless objects, from which theycannot detached. As it will be develop in this article, people with this disorder suffercomplex and diverse problems, and this obliges institutions and disciplines to have analso complex approach to each situation...
Síndrome de Diógenes, ou acumulação desordem, tem esse nome em homenagem aDiógenes de Sinope, representante do cinismo filósofo grego. "O cinismo é ummovimento filosófico que prega o desapego aos bens materiais, acreditando que afelicidade não depende de qualquer coisa externa a si mesmo. A revisão sistemática daliteratura período, revisão de análise 2006-2014 set, sendo 18 estudos de casos clínicos,alguns com revisão da literatura científica sobre a síndrome de Diógenes, a definiçãoconceitual e dimensões cobrindo o assunto. Os principais sinais, realizando os estudos éque eles são idosos, que vivem sozinhos, com pouco ou nenhum apoio familiar e social.É, sobretudo, as pessoas com transtornos psiquiátricos, sem saber da doença, bem comoa presença de apragmatismos. A descoberta desses usuários foi a realização de consultamédica para patologias orgânicas por isso foi necessário para ser levado para os serviçosde saúde, em alguns casos com internações psiquiátricas ou médicas, que não estavamem tratamento psiquiátrico...
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Humanos , Isolamento Social , Pessoas Mentalmente Doentes , Saúde Mental , Transtornos Mentais , Enfermagem PsiquiátricaRESUMO
Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aß immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aß load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.
La enfermedad de Alzheimer (EA) es la forma más frecuente de demencia de inicio en el adulto, caracterizada por un deterioro progresivo en la cognición y la memoria. No hay cura para la enfermedad y los tratamientos actuales son sólo sintomáticos. El descubrimiento de fármacos es un proceso costoso y que consume mucho tiempo; en la última década no se han encontrado nuevos fármacos para la EA a pesar de los esfuerzos de la comunidad científica y las compañías farmacéuticas. La inmunoterapia contra Aß es uno de los enfoques más prometedores para modificar el curso de la EA. Esta estrategia terapéutica utiliza péptidos sintéticos o anticuerpos monoclonales (mAb) para disminuir la carga de Aß en el cerebro y retardar la progresión de la enfermedad. Por lo tanto, este artículo discutirá los principales aspectos de la neuropatogénesis de la EA, el tratamiento farmacológico clásico, así como la inmunización activa y pasiva describiendo los prototipos de fármacos evaluados en diferentes ensayos clínicos.
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Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/imunologia , Imunoterapia/métodos , Doença de Alzheimer/imunologia , Doença de Alzheimer/fisiopatologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Progressão da Doença , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêuticoRESUMO
During the estrous cycle, a remodeling of synapses on somas and dendritic spines occurs in the rat hypothalamic arcuate nucleus. The synaptic remodeling is known to be induced by estradiol, but the molecular mechanisms involved still have not been fully clarified. ß-catenin is known to regulate synaptic plasticity, so we have assessed possible modifications of ß-catenin in the rat mediobasal hypothalamus during the estrous cycle. Our findings indicate that ß-catenin expression is increased during proestrus and estrus in comparison with diestrus day. This increase was accompanied by an enhanced phosphorylation of Akt in Ser473 and of glycogen synthase kinase-3ß (GSK3ß) in Ser9. Also, the association of ß-catenin with the synaptic protein PSD95 was increased during these same stages of the estrous cycle, whereas the levels of synapsin I were significantly decreased in proestrus. These findings suggest that Akt/GSK3ß/ß-catenin signaling is involved in the synaptic modifications that occur in the basal hypothalamus during the estrous cycle.
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Ciclo Estral/fisiologia , Quinase 3 da Glicogênio Sintase/metabolismo , Hipotálamo/metabolismo , Transdução de Sinais/fisiologia , beta Catenina/metabolismo , Análise de Variância , Animais , Proteína 4 Homóloga a Disks-Large , Feminino , Glicogênio Sintase Quinase 3 beta , Imunoprecipitação , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Fosforilação , Ratos , Ratos Wistar , Sinapsinas/metabolismoRESUMO
El DHEAS es un neuroesteroide con efecto neuromodulador de la transmisión sináptica y en la neuroprotección, sin embargo las vías moleculares a través de las cuales se inducen estos cambiosno están completamente claras. Como varios de los neuroesteroides actúan a través de los recetores ionotrópicos de glutamato, se evaluó el efecto del DHEAS en las subunidades GluR2 y GluR3 del receptor AMPA para esclarecer sus efectos. Con este fin se administró DHEAS o una sustancia control durante 7 días a ratones C57/BL6. La expresión de las subunidades se evaluó por Westernblotting.Los resultados presentados muestran que la administración prolongada de 40mg/kg/día de DHEAS a ratones C57/BL6 produce un incremento en los niveles de proteína de las subunidades GluR2/3 yGluR2 del receptor AMPA en el hipocampo. Dado el papel específico que juega la subunidad GluR2 del receptor AMPA en el control de la entrada de calcio durante los procesos de muerte celular y de plasticidad sináptica, este hallazgo contribuye al estudio de los neuroesteroides como una estrategia terapéutica relevante en enfermedades neurodegenerativas y eventos cerebrovasculares.
Dehydroepiandrosterone sulfate (DHEA-S) is a neurosteroid that has effects such as neuromodulator of synaptic transmission and neuroprotection. The specific signaling pathways for these effects are not elucidated yet. Given that, some neurosteroids act through the activation of ionotropic glutamate receptors, therefore the effect of DHEA-S on the subunits GluR2 and GluR3of the AMPA receptor was evaluated. Either DHEA-S or a control substance was administered to C57/BL6 mice. Subunit expression of the AMPA receptor was analyzed by Western blotting. Results show that long-term DHEA-S administration toC57/BL6 mice, increases the protein levels of the subunits GluR2 and GluR2/3 of the AMPA receptors located in the hippocampus. Due to the role of AMPA receptor, specifically GluR2subunit in the regulation of intracellular calcium levels, cellular apoptosis, and synaptic plasticity, the study of neurosteroids as a therapeutic strategy in neurodegenerative diseases and cerebrovascular events is very relevant.
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Camundongos , Hipocampo , Camundongos , Receptores de AMPA , Transmissão SinápticaRESUMO
During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.
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Isquemia Encefálica/patologia , Estradiol/administração & dosagem , Hipocampo/efeitos dos fármacos , Receptores de AMPA/metabolismo , Proteínas tau/metabolismo , Animais , Western Blotting , Isquemia Encefálica/tratamento farmacológico , Feminino , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/metabolismo , Imunoprecipitação/métodos , Subunidades Proteicas/metabolismo , Ratos , Ratos WistarRESUMO
OBJECTIVE: To obtain information on the level of total fluoride intake from food, beverages and toothpaste by children at the age of 22-25 months of low and high socioeconomic status (SES) in major Colombian cities. METHODS: Daily fluoride intake was assessed by the duplicate plate method and by recovered toothpaste solution during a 3-day period and afterwards analysed by the microdiffusion method. RESULTS: Mean daily fluoride intake was 0.11 (+/-0.10), 0.14 (+/-0.12), 0.10 (+/-0.07) and 0.07 (+/-0.06) mg/kg body weight (bw)/day in Bogota, Medellin, Manizales and Cartagena, respectively. The total fluoride intake was higher in low-SES subjects in the cities of Medellin and Bogota. In the high-SES children of the four cities, the average intakes ranged from 0.06 to 0.09 mg F/kg bw, whereas, the low-SES children in three cities had intakes between 0.11 and 0.21 mg F/kg bw (Cartagena, 0.07). Toothpaste (containing 1000-1500 ppm F, with 1500 ppm F being more common) accounted for approximately 70% of total fluoride intake, followed by food (24%) and beverages (<6%). More than half the children had their teeth brushed by an adult, on average twice a day, using 0.22-0.65 g of toothpaste. CONCLUSION: Children from three Colombian cities have a mean total daily fluoride intake above the 'optimal range'. Health authorities should promote an appropriate use of fluoridated dentifrices discouraging the use of dentifrices containing 1500 ppm F in children younger than 6 years of age and promoting a campaign of education of parents and oral health professionals on adequate toothbrushing practices.