Diacylated anthocyanins from purple sweet potato (Ipomoeabatatas L.) attenuate hyperglycemia and hyperuricemia in mice induced by a high-fructose/high-fat diet / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.

Fructose and metabolic diseases: too much to be good / 中华医学杂志(英文版)

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.

Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity

Background Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Efectos metabólicos del consumo excesivo de fructosa añadida / Metabolic effects of excessive fructose consumption added

El consumo de fructosa ha aumentado en los últimos 50 años por la incorporación a la dieta de jarabe de maíz alto en fructosa (JMAF), presente en productos industrializados, como las bebidas azucaradas. Se puede asociar la ingesta de fructosa en altas concentraciones con el aumento de la obesidad y trastornos metabólicos. La fructosa, un azúcar natural que se encuentra en muchas frutas, se consume en cantidades significativas en las dietas occidentales. En cantidades iguales, es más dulce que la glucosa o la sacarosa y, por lo tanto, se usa comúnmente como edulcorante. Debido al incremento de obesidad entre la población joven y general y a los efectos negativos que puede tener a corto y largo plazo es importante considerar de donde provienen las calorías que se ingieren diariamente. Esta revisión describirá la relación entre el consumo de fructosa en altas concentraciones y el riesgo de desarrollar obesidad, resistencia a la insulina, lipogenesis de novo e inflamación.

The consumption of fructose has increased in the last 50 years due to the incorporation into the diet of high fructose corn syrup (HFCS), present in industrialized products, such as sugary drinks. The intake of fructose in high concentrations can be associated with the increase of obesity and metabolic disorders. Fructose, a natural sugar found in many fruits, is consumed in significant quantities in Western diets. In equal amounts, it is sweeter than glucose or sucrose and, therefore, is commonly used as a sweetener. Due to the increase of obesity among the young and general population and the negative effects that can have in the short and long term it is important to consider where the calories that are ingested daily come from. This review will describe the relationship between fructose consumption in high concentrations and the risk of developing obesity, insulin resistance, de novo lipogenesis, nonalcoholic fatty liver, inflammation and metabolic syndrome.

Experimental model of hepatic steatosis by fructose in adult zebrafish: a pilot study

Introduction: The consumption of fructose has been questioned, since its increase has led to an associated increase in steatosis caused by nonalcoholic fatty liver disease. Despite the advantages presented by the zebrafish as an animal model, at present there are no models of steatosis by fructose in adult zebrafish. The aim of this study is to establish a model of hepatic steatosis by fructose in adult zebrafish. Methods: Firstly, adult zebrafish were daily exposed to 4% or 6% fructose. Then, animals were exposed to 6% fructose every 2 days. The hepatic lipid accumulation was analyzed by Nile Red and Oil Red O staining. Results: The daily exposure to 6% fructose showed increased accumulation of hepatic lipids when compared to 4% and control groups, but the same concentration showed no difference when the exposure happened every 2 days. Conclusion: We can suggest the daily exposure to a concentration of 6% fructose can be considered as a new experimental model of adult zebrafish. (AU)

NAFLD e ingesta de fructosa en altas concentraciones: una revisión de la literatura / NAFLD and high fructose intake: a review of literature

Uno de los endulzantes más comúnmente utilizado es la fructosa. La fructosa es directamente metabolizada en el hígado y se puede transformar en glucosa, posteriormente es almacenada como glicógeno constituyéndose en una fuente de energía para los hepatocitos. Todo el exceso de fructosa se convierte en lípidos ejerciendo un efecto tóxico sobre el hígado, similar al producido por el exceso de alcohol, pudiendo provocar hígado graso no alcohólico (NAFLD). El objetivo de esta revisión es reunir hallazgos recientes en relación al efecto de la ingesta de fructosa en altas concentraciones y su relación con el NAFLD.

One of the most commonly used sweeteners is fructose. Fructose is directly metabolized in the liver and can be converted into glucose, later stored as glycogen constituting a source of energy for the hepatocytes. All excess fructose is converted into lipids by exerting a toxic effect on the liver, similar to that produced by excess of alcohol, and can cause nonalcoholic fatty liver (NAFLD). The aim of this review is to gather recent findings regarding the effect of fructose intake at high concentrations and its relationship with NAFLD.

Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model.

This study investigates if glycyrrhizin, a constituent of licorice (Glycyrrhiza glabra) root, is able to treat the complications (insulin resistance, hyperglycemia, dyslipidemia and oxidative stress) of metabolic syndrome. Metabolic syndrome was induced in rats by feeding a fructose-enriched (60%) diet for six weeks, after which single dose of glycyrrhizin (50 mg/kg body weight) was administered intraperitoneally. Different biochemical parameters from blood were estimated during three weeks after treatment. Then the rats were sacrificed to collect skeletal muscle tissue. Glycyrrhizin reduced the enhanced levels of blood glucose, insulin and lipids in metabolic syndrome group. Increased advanced glycation end products of hemoglobin, glycohemoglobin, hemoglobin-mediated iron release and iron-mediated free radical reactions (arachidonic acid and deoxyribose degradation) in metabolic syndrome were inhibited by glycyrrhizin treatment. Reduced activities of enzymatic antioxidants (superoxide dismutase and catalase) and elevated oxidative stress markers (malonaldehyde, fructosamine, hemoglobin carbonyl content and DNA damage) in metabolic syndrome were reversed to almost normal levels by glycyrrhizin. The decreased levels of peroxisome proliferator activated receptor (PPAR) and glucose transporter 4 (GLUT4) proteins in skeletal muscle of metabolic syndrome group were elevated by glycyrrhizin, indicating improved fatty acid oxidation and glucose homeostasis.

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report / Glaucoma agudo de ângulo fechado, bilateral, desencadeado pelo topiramato: relato de caso

This paper describes a topiramate induced acute bilateral angle-closure glaucoma. This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion and lens forward displacement, leading to increased intraocular pressure and vision loss. We describe a 55 year-old white woman with migraine, spasmodic torticollis and essential tremor, who developed bilateral acute angle-closure glaucoma, one week after starting topiramate 25 mg/day. She was seen at the Ophthalmology Emergency Department of the Fundação João Penido Burnier (Campinas, SP, Brazil) with a 4 hours history of blurry vision, ocular pain and bright flashes vision. Slit lamp examination revealed moderate conjunctival injection and corneal edema, and shallow anterior chambers. Intraocular pressure was 48 mmHg in both eyes. Fundoscopic examination findings were normal. She was treated with timolol, brimonidine, dorzolamide, pilocarpine, prednisone acetate eye drops and acetazolamide. One hour after those measures, as the intraocular pressure was 30 mmHg, she received a manitol intravenous injection and the intraocular pressure normalized. After 24 hours an iridotomy with Yag laser was performed. Topiramate was discontinued and she was totally recovered after one week.

Relato de um caso de glaucoma bilateral de ângulo fechado induzido pelo topiramato. Este raro efeito colateral é uma idiosincrasia causada por efusão uveal e deslocamento do cristalino para frente, causando aumento da pressão intraocular e perda visual. Descrevemos o caso de uma paciente de 55 anos com migrânea, torcicolo espasmódico e tremor essencial, que desenvolveu glaucoma bilateral de ângulo fechado uma semana após iniciar o uso de topiramato, 25 mg/dia. A paciente foi atendida no setor de Emergências Oftalmológicas da Fundação Penido Burnier (Campinas, SP, Brasil), com história de 4 horas de embaçamento visual, dor ocular e visão de flashes brilhantes. O exame com lâmpada de fenda revelou injeção conjuntival moderada, edema corneano e câmara anterior rasa em ambos os olhos. A pressão intraocular era de 48 mmHg bilateralmente e a fundoscopia era normal. Foi tratada com colírios de timolol, brimonidina, dorzolamida, pilocarpina e acetato de prednisona e acetazolamida via oral. Uma hora após essas medidas, a pressão intraocular era 30 mmHg, e a paciente recebeu uma injeção intravenosa de manitol, ocorrendo normalização da pressão intraocular após essa medida. Após 24 horas foi realizada iridectomia com Yag laser. O topiramato foi interrompido e ela se recuperou totalmente após uma semana.

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 ± 0.2 vs. C: 4.5 ± 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 ± 3 vs. C: 104 ± 4 mmHg) and obesity (F: 0.31±0.001 vs. C: 0.29 ± 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Fructose and NAFLD: metabolic implications and models of induction in rats / Frutose e NAFLD: implicações metabólicas e modelos de indução em ratos

PURPOSE: The increase in fructose consumption is paralleled by a higher incidence of obesity worldwide. This monosaccharide is linked to metabolic syndrome, being associated with hypertriglyceridemia, hypertension, insulin resistance and diabetes mellitus. It is metabolized principally in the liver, where it can be converted into fatty acids, which are stored in the form of triglycerides leading to NAFLD. Several models of NAFLD use diets high in simple carbohydrates. Thus, this study aimed to describe the major metabolic changes caused by excessive consumption of fructose in humans and animals and to present liver abnormalities resulting from high intakes of fructose in different periods of consumption and experimental designs in Wistar rats. METHODS: Two groups of rats were fasted for 48 hours and reefed for 24 or 48 hours with a diet containing 63 percent fructose. Another group of rats was fed an diet with 63 percent fructose for 90 days. RESULTS: Refeeding for 24 hours caused accumulation of large amounts of fat, compromising 100 percent of the hepatocytes. The amount of liver fat in animals refed for 48 hours decreased, remaining mostly in zone 2 (medium-zonal). In liver plates of Wistar rats fed 63 percent fructose for 45, 60 and 90 days it's possible to see that there is an increase in hepatocytes with fat accumulation according to the increased time; hepatic steatosis, however, is mild, compromising about 20 percent of the hepatocytes. CONCLUSIONS: Fructose is highly lipogenic, however the induction of chronic models in NAFLD requires long periods of treatment. The acute supply for 24 or 48 hours, fasted rats can cause big changes, liver steatosis with macrovesicular in all lobular zones.

OBJETIVO: O aumento do consumo de frutose é concomitante a maior incidência mundial de obesidade. Este monossacarídeo está relacionado à Síndrome Metabólica, sendo vinculado à hipertrigliceridemia, hipertensão arterial, resistência à insulina e diabetes mellitus. É metabolizada principalmente no fígado, onde pode ser convertida em ácidos graxos, os quais serão estocados na forma de trigligérides ocasionando a esteatose hepática não alcoólica (NAFLD). Vários modelos de NAFLD utilizam dietas ricas em carboidratos simples. Desta forma, este trabalho teve como objetivos descrever as principais alterações metabólicas causadas pelo consumo excessivo de frutose em humanos e em animais e apresentar as alterações hepáticas decorrentes da alta ingestão de frutose em diferentes períodos de consumo e desenhos experimentais em ratos Wistar. MÉTODOS: Dois grupos de ratos Wistar foram mantidos em jejum durante 48 horas e realimentados por 24 ou 48 horas com dieta contendo 63 por cento de frutose. Outro grupo de ratos Wistar foi alimentado com 63 por cento de frutose durante 90 dias. RESULTADOS: A realimentação por 24 horas provocou acúmulo de grande quantidade de gordura. A quantidade de gordura hepática nos animais realimentados por 48 horas diminuiu, mantendo-se principalmente nas zona 2 (medio-zonal). Em fígados de ratos Wistar alimentados com 63 por cento de frutose até 90 dias foi possível observar que há aumento de hepatócitos com acúmulo de gordura consequente ao aumento do tempo, no entanto a esteatose hepática é leve (20 por cento). CONCLUSÕES: A frutose é altamente lipogênica, no entanto a indução de NAFLD em modelos crônicos necessita de longos períodos de tratamento. A oferta aguda, por 24 ou 48 horas, a ratos mantidos em jejum é capaz de ocasionar grandes mudanças hepáticas, com presença de esteatose macrovesicular em todas as zonas lobulares.

Fructose and cardiometabolic disorders: the controversy will, and must, continue: [review]

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit. Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.

Miopia aguda e glaucoma de ângulo fechado associados ao uso de topiramato em paciente jovem: relato de caso / Acute myopia and angle closure glaucoma associated with topiramate use in a young patient: case report

O glaucoma agudo de ângulo fechado pode ser secundário, dentre outras causas, ao uso de medicações sistêmicas, como o anticonvulsivante topiramato. Esse trabalho descreve o caso de uma paciente jovem com quadro agudo bilateral de miopia e glaucoma de ângulo fechado induzidos por terapia com topiramato para prevenção de crises de enxaqueca, fazendo relação com casos semelhantes descritos na literatura e revisão bibliográfica referentes à entidade.

Acute angle-closure glaucoma may be induced, among other causes, by therapy with systemic drugs, such as the anticonvulsant topiramate. This paper reports the case of an young patient with acute myopia and angle-closure glaucoma associated with migraine prevention with topiramate. We make a link with similar cases described in medical journals and in a bibliographic review related to this entity.

Long-term Effectiveness and Tolerability of Topiramate in Children with Epilepsy under the Age of 2 Years: 4-Year Follow-up

This is a long-term, open label, observational study aimed to broaden our clinical experiences in managing infants and toddlers with epilepsy. The long-term retention rate and side effects of topiramate (TPM) in them were evaluated and compared with carbamazepine (CBZ). A total of 146 children were involved in the study (TPM=41, CBZ=105). The retention rates at 24 , 36, and 48 months were 46.3%, 34.1%, 26.8% for TPM and 36.2%, 23.8%, 13.3% for CBZ, respectively. At 6 months after starting antiepileptic drugs (AED), the seizure freedom or clinical efficacy (seizure reduction rate more than 50 percent) were 73.2% for TPM and 62.9% for CBZ. The major side effects led to discontinuation included psychomotor slowing, poor oral intake from TPM and sleepiness and skin rash from CBZ. TPM was discontinued due to side effects in one case (2.4%) and lack of efficacy in five cases (12.2%), whereas CBZ was discontinued due to lack of efficacy (22.9%) and side effects (6.7%). As compared with CBZ, TPM showed the same long-term retention rate in children under the age of 2 yr, and no serious side effects. It is therefore concluded that TPM can be considered as a major AED for treating children with epilepsy under the age of 2 yr.

Influência da sacarose, lactose e glicose + frutose no potencial cariogênico de S. mutans: estudo in situ e in vitro / Influence of sucrose, lactose and glucose + fructose on the cariogenic potential of S. mutans: an in situ and in vitro study

Objetivo: Este estudo determinou o efeito in situ de sacarose, lactose e glicose+frutose na colonização do esmalte por S. mutans e seu potencial cariogênico in vitro. Metodologia: Doze voluntários participaram da etapa in situ, tipo duplo-cego, cruzada, em quatro etapas de 48 horas. Dispositivos palatinos contendo três blocos de esmalte bovino receberam uma gota de substrato 4 vezes/dia. O biofilme formado foi inoculado em meio de cultura Mitis-Salivarius-Bacitracina (MSB) para determinação do número de colônias (UFC). No experimento in vitro, os açúcares e S. mutans foram adicionados ao meio Brain-Heart-Infusion; o pH foi aferido após 6, 12, 24, 48 horas; o peso úmido do biofilme foi determinado e inoculado em MSB. Resultados: Não houve diferença estatisticamente significante na colonização pelos microorganismos no modelo in situ. No estudo in vitro, os meios contendo sacarose e lactose apresentaram maior número de colônias e de peso úmido de biofilme que glicose+frutose (P<0,05). O pH reduzido do meio foi mantido por maior período de tempo na presença de sacarose (48h/pH=4,4). Conclusão: Embora não tenha havido diferença de colonização por S. mutans frente à sacarose e lactose neste delineamento in situ, o estudo in vitro mostrou potencial cariogênico distinto das soluções testadas.

Purpose: This study evaluated the in situ effect of sucrose, lactose, and glucose+fructose on dental enamel colonization by S. mutans and its in vitro cariogenic potential. Methods: Twelve volunteers participated in a crossover double-blind in situ study, comprising four 48-hour stages. Acrylic resin appliances with three bovine enamel blocks received a drop of experimental solution 4 times/day. The biofilm formed was inoculated in Mitis-Salivarius-Bacitracin (MSB) culture to determine the number of colonies (CFU). In the in vitro experiment, the solutions and S. mutans were added to the Brain-Heart-Infusion medium; the pH was measured after 6, 12, 24, and 48 hours; the biofilm-wet weight was determined and inoculated in MSB. Results: There was no in situ effect of any solution on S. mutans colonization. The in vitro results showed that sucrose and lactose yielded larger number of colonies and biofilm wet-weight than glucose+fructose solution (P<0.05); sucrose samples sustained reduced pH values for a longer period of time (48 hours/pH=4.4). Conclusion: Although there was no difference of S. mutans colonization under sucrose and lactose challenge in situ, the study vitro showed different cariogenic potential of the tested solutions.

Capacidade aeróbia de ratos alimentados com dieta rica em frutose / Aerobic capacity of rats fed with fructose rich diet

INTRODUÇÃO: Evidências apontam que a ingestão exacerbada de frutose pode desencadear distúrbios característicos da síndrome metabólica. OBJETIVOS: Analisar os efeitos da ingestão de dieta rica em frutose sobre aspectos metabólicos de ratos da linhagem Wistar. Adicionalmente, verificar a capacidade aeróbia através da identificação da máxima fase estável de lactato (MFEL). MÉTODOS: Dezesseis ratos foram separados em dois grupos de oito animais: a) controle, alimentados com dieta balanceada, e b) frutose, alimentados com dieta rica em frutose. Foram analisadas a tolerância à glicose (área sob a curva de glicose durante teste de tolerância à glicose), sensibilidade à insulina (taxa de remoção da glicose sérica após sobrecarga exógena de insulina), perfil lipídico sérico e concentração de lactato sanguíneo [lac]s durante exercício na intensidade da MFEL. RESULTADOS: Teste t não pareado (p < 0,05) revelou diferença para a tolerância à glicose e triglicérides, porém não houve diferença na sensibilidade à insulina e na [lac]s. Anova one way com post hoc de Newman-Keuls (p < 0,05) revelou diferença para a cinética da glicose durante o teste de tolerância, mas não para a cinética do lactato durante exercício na MSSL. CONCLUSÃO: As Alterações fisiológicas provocadas pela dieta rica em frutose e inerentes à síndrome metabólica não prejudicam a capacidade aeróbia de ratos.

INTRODUCTION: Evidence points that exacerbated ingestion of fructose may trigger disturbs characteristic of the metabolic syndrome. OBJECTIVES: To analyze the effects of a fructose rich diet on metabolic aspects of Wistar lineage rats. Additionally, to verify the aerobic capacity, through the identification of the maximal lactate steady state (MSSL). PROCEDURES: Sixteen rats were separated in two groups of eight animals: a) Control, fed a balanced diet, and b) fructose, fed a fructose-rich diet. The glucose tolerance, (area under serum glucose during a glucose tolerance test), insulin sensibility (glucose disappearance rate after exogenous insulin administration), serum lipid profile and blood lactate concentration [lac]b during exercise at MSSL intensity, have been analyzed. RESULTS: Non-paired t test (p<0.05) revealed difference between groups in the area under the curve of glucose and serum triglycerides, no difference in insulin sensibility or in [lac]b was detected, though. One-way ANOVA with Newman Keuls post hoc revealed difference in the glucose kinetics during tolerance test, but not in the lactate kinetics during the MSSL. CONCLUSION: The physiological alterations promoted by fructose-rich diet and intrinsic to the metabolic syndrome do not harm the aerobic capacity of rats.

Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial / Diminuição da fissura com topiramato no tratamento ambulatorial para dependência de cocaína: um ensaio clínico aberto

OBJECTIVE: To evaluate anticraving action and tolerability of topiramate in cocaine user treatment. METHOD: Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects and impulsivity measure through Barratt Impulsivity Scale. Patients received assertive strategic counseling for abstinence assistance and medication monitoring evaluation every two weeks. Comparative analysis was made with intention to treat, missing values were replaced (last observation carried forward), and significance level was 5 percent. RESULTS: Adherence to treatment was 57 percent (at least three evaluations), 32 percent dropped out (one evaluation). There were no severe side effects. Negative test average was 25.4 percent (31.2). Significant reduction in craving intensity and duration was observed in 25 percent of the sample. No statistical significant reduction in craving frequency was observed in 7.1 percent. Increase in frequency was observed in 10.7 percent and 82.1 percent did not present any variation. No significant statistical variations in Barratt Impulsivity Scale or in the total score were found in the final evaluation when compared to baseline. CONCLUSION: More randomized placebo-controlled trials with topiramate for cocaine dependants should be performed to evaluate preliminary evidence.

OBJETIVO: Avaliar a ação anticraving e tolerabilidade do topiramato em usuários de cocaína. MÉTODO: Homens usuários de cocaína inalada que preenchiam critérios para dependência de cocaína (Manual Diagnóstico e Estatístico de Desordens Mentais, quarta edição) foram selecionados para 12 semanas de tratamento ambulatorial, em ensaio clínico aberto com topiramato; dosagens escalonadas entre 25-300 mg/dia. As principais variáveis clínicas foram taxa de abstinência, intensidade, freqüência e duração do craving, aderência, perdas, efeitos colaterais e impulsividade medida por meio da Escala de Impulsividade Barratt. Os pacientes receberam estratégias assertivas de aconselhamento para manutenção da abstinência e monitoramento da medicação avaliada a cada duas semanas. Análises comparativas foram feitas com intenção de tratar, valores perdidos foram substituídos (última observação carregada ao final) e o nível de significância de 5 por cento. RESULTADOS: A aderência ao tratamento foi de 57 por cento (pelo menos três avaliações), 32 por cento de perdas (uma avaliação). Não houve efeitos colaterais graves. A média de testes negativos foi 25,4 por cento (31,2). Significante redução na intensidade e duração do craving foi observada em 25 por cento da amostra. Nenhuma redução significativa na freqüência do craving foi observada em 7,1 por cento. Aumento na freqüência foi observado em 10,7 por cento e 82,1 por cento não apresentaram nenhuma variação. Nenhuma variação estatisticamente significativa na Escala de Impulsividade Barratt ou na pontuação total foi encontrada no final da avaliação quando comparado à inicial. CONCLUSÃO: Mais ensaios clínicos placebo-controlados com o topiramato para dependentes de cocaína deveriam ser conduzidos a fim de avaliar a evidência preliminar.

Topiramate associated hypohidrosis and hyperthermia.

Topiramate is a new antiepileptic drug, used for treatment of partial onset seizure and refractory seizures. Although it is well tolerated in children, some adverse effects including hypohidrosis and hyperthermia are reported. We present two children with epilepsy who were treated with topiramate and developed hypohidrosis and hyperthermia.