RESUMO
Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of â¼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.
Assuntos
Tonsila do Cerebelo/metabolismo , Hiperglicemia/metabolismo , Hipotálamo/metabolismo , Septo do Cérebro/metabolismo , Aloxano , Tonsila do Cerebelo/patologia , Anedonia , Animais , Ansiedade , Doença Crônica , Sacarose Alimentar , Modelos Animais de Doenças , Hiperglicemia/patologia , Hiperglicemia/psicologia , Hipotálamo/patologia , Imuno-Histoquímica , Cetose/metabolismo , Cetose/patologia , Cetose/psicologia , Masculino , Atividade Motora/fisiologia , Orexinas/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Septo do Cérebro/patologiaRESUMO
Acetone is considered to be a substance that can disturb cellular oxidative status, being also associated with the production of glucose during its metabolization. The objective of the present study was to determine the effects of chronic treatment with acetone in oxidative stress and metabolic parameters in rats. Twenty male Wistar rats were divided into two groups: control (CG) and chronic acetone group (CAG). After 28 days of acetone ingestion in a 5% aqueous solution (CAG) or water (CG) the animals were euthanized and urine, plasma and liver were collected for the determination of acetone, glucose, lipemia, hepatic fat, malondialdehyde (MDA), reduced glutathione (GSH), and vitamin E. As expected, urinary and plasma acetone levels were higher in CAG. There was no difference in hepatic MDA values between groups, whereas hepatic GSH was lower in CAG than in CG and hepatic vitamin E was higher in CAG than in CG. There was also an increase in glycemia, cholesterolemia and hepatic fat in CAG compared to CG. Chronic treatment with a 5% acetone solution produced an increase in acetonemia that was able to promote changes in hepatic oxidative metabolism and in lipid content in rats similar to those observed in nonalcoholic steatohepatitis.
Assuntos
Acetona/toxicidade , Fígado Gorduroso/metabolismo , Cetose/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Estresse Oxidativo , Solventes/toxicidade , Animais , Glicemia/análise , Colesterol/sangue , Doença Crônica , Modelos Animais de Doenças , Fígado Gorduroso/induzido quimicamente , Glutationa/metabolismo , Corpos Cetônicos/sangue , Corpos Cetônicos/urina , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangue , Vitamina E/sangue , Vitamina E/metabolismoRESUMO
It is also necessary to emphasize that as well as the weight loss, ketogenic diets are healthier because they promote a non-atherogenic lipid profile, lower blood pressure and diminish resistance to insulin with an improvement in blood levels of glucose and insulin. Such diets also have antineoplastic benefits, do not alter renal or liver functions, do not produce metabolic acidosis by Ketosis, have many neurological benefits in central nervous system, do not produce osteoporosis and could increase the perfomance in aerobic sports.
Assuntos
Pressão Sanguínea/fisiologia , Dieta com Restrição de Carboidratos/normas , Dieta Cetogênica/normas , Insulina/sangue , Obesidade/dietoterapia , Redução de Peso/fisiologia , Glicemia/fisiologia , Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Carboidratos/efeitos adversos , Dieta Cetogênica/efeitos adversos , Humanos , Corpos Cetônicos/metabolismo , Cetose/metabolismo , Neoplasias/etiologiaRESUMO
Background: Ketogenic diet (KD) represents an alternative in treatment of refractory epilepsy (RE). Objective: To evaluate the efficacy of the diet and the frequency of complications in patients belonging to the KD Program from Luis Calvo Mackenna Children's Hospital (HLCM). Methods: Evaluation of all children enrolled in the program between 1999 and 2004, with analysis every 6 months of the diet efficacy, digestive tolerance, nutritional status, cholesterol levels and nephrolithiasis. Results: 21 children were admitted, 14 boys, age between 6 months - 17 years-old. 76 percent, 71 percent and 67 percent of patients followed KD at 6, 12 and 18 months, respectively, with KD efficacy of 67 percent. At 12 months, 24 percent of patients did not present seizures. At 18 months, 85 percent remained close to ideal body weight (15 percent obesity) and height/age Z score decreased (-0,7 +/- 0,4; p < 0,05). Total cholesterol significantly increased at 6 months (64 percent hypercholesterolemia; decreased to 15 percent at 18 months). 2 patients developed nephrolithiasis. Conclusions: The study shows high efficacy of the KD for treatment of refractory epilepsy, with low rate of complications. It should be considered as a therapeutic alternative for these patients.
La dieta cetogénica (DK) es una opción de tratamiento en epilepsia refractaria (ER). En Chile no hay estudios publicados al respecto. Objetivo: Evaluar la eficacia de la dieta en el control de las convulsiones y la frecuencia de complicaciones en los pacientes del programa de DK, para el tratamiento de ER, del Hospital Luis Calvo Mackena (HLCM). Pacientes y Método: Evaluamos todos los niños ingresados al programa entre 1999-2004. Para efectos de este trabajo se consideró el control al ingreso y cada 6 meses, evaluándose: eficacia de la dieta, tolerancia digestiva, evolución nutricional, niveles de colesterol plasmático y litiasis renal. Resultados: Ingresaron 21 niños de 6,2 años (6 meses a 17 años), 14 de sexo masculino. A los 6, 12 y 18 meses, 76 por ciento, 71 por ciento y 67 por ciento de los pacientes, respectivamente, se mantenía en dieta. La eficacia del tratamiento fue 67 por ciento. A los 12 meses, 24 por ciento de los pacientes estaba sin crisis. A los 18 meses 85 por ciento de los pacientes estaba eutrófico y 15 por ciento obeso. Se observó deterioro en la talla (delta zT/E -0,7 +/- 0,4; p < 0,05). El colesterol total aumentó significativamente a los 6 meses, encontrándose el 64 por ciento hipercolesterolémico; a los 18 meses este porcentaje se redujo a 15 por ciento. Dos pacientes presentaron litiasis renal (9 por ciento). Conclusiones: Este estudio muestra una muy buena eficacia de la dieta cetogénica para el tratamiento de la epilepsia refractaria, y una baja frecuencia de complicaciones, por lo que debería ser considerada como alternativa terapéutica en estos pacientes.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Epilepsia/dietoterapia , Gorduras na Dieta/uso terapêutico , Anticonvulsivantes/uso terapêutico , Cálculos Renais/etiologia , Cetose/metabolismo , Colesterol/sangue , Convulsões/dietoterapia , Corpos Cetônicos/biossíntese , Epilepsia/metabolismo , Epilepsia/sangue , Seguimentos , Gorduras na Dieta/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
The ketogenic diet is traditionally introduced with an initial period of fasting. This study compares the efficacy and tolerability of the introduction of a prediet (2:1 ratio of fat:protein + carbohydrates) before hospitalization with the aim at reducing the time of same and the period of fasting necessary to reach ketosis. For a minimum period of 1 year, adverse effects, metabolic profile, and linear growth were prospectively evaluated in 46 children. Twenty-three children received a prediet for a period of 10 days, and in the other 23 children, the ketogenic diet was introduced by hospitalization regimen after a fasting period. The use of the prediet led to a shorter fasting period of a mean 18.3 hours compared with the group without prediet, in which the fasting period was 41.3 hours (P = .001). At the end, there was no difference in the adverse effects between the groups. In those submitted to the prediet, a better adaptation to the diet and acceptance to the proposal of introducing the ketogenic diet were observed.
Assuntos
Epilepsia/dietoterapia , Hospitalização , Adolescente , Criança , Pré-Escolar , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Eletroencefalografia/métodos , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Jejum/metabolismo , Feminino , Humanos , Lactente , Cetose/metabolismo , Masculino , Estudos ProspectivosRESUMO
The in vitro effect of different concentrations of beta-hydroxybutyric acid (betaHBA) on bovine milk leukocytes was examined. betaHBA level similar to those found in cows with clinical ketosis induced a significant inhibitory effect on the nitroblue tetrazolium reduction as a mean of assaying the metabolic integrity of macrophages after the phorbol-mirystate- acetate and opsonized zymosan stimulation. In the same way, the H2O2 production after stimulation with both soluble and particulate agents decreased significantly in 33 and 26%, respectively, compared with cells incubated without ketone bodies. This result suggests a possible fault in the microbicidal oxidative activity. The macrophage phagocytosis also decreased in cells treated with different betaHBA concentrations, in relation to that obtained from control cells. Neutrophils migration in agarose was determined, and the mean chemotactic response was higher when the cells were incubated with lower level or absence of ketone bodies. Considering the determined differences, we hypothesize that abnormally high levels of ketone bodies could produce a direct effect on leukocyte membranes. The induction of some modification on the receptor structure impairment the interaction ligand-receptor and this may be, in part, responsible for the higher susceptibility to local infections in mammary gland during subclinical and clinical ketosis.
Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Leucócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Leite/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Animais , Bovinos , Feminino , Peróxido de Hidrogênio/metabolismo , Corpos Cetônicos/metabolismo , Cetose/metabolismo , Cetose/veterinária , Leucócitos/metabolismo , Macrófagos/metabolismo , Leite/metabolismo , Neutrófilos/metabolismo , Nitroazul de Tetrazólio/metabolismo , Fagocitose/fisiologia , Acetato de Tetradecanoilforbol/farmacologia , Zimosan/farmacologiaRESUMO
For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment. Objective. In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic-astatic epilepsy. Material and methods. Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic-astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months. Results. The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure-free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting). Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic-astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic-astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.
Assuntos
Gorduras na Dieta/administração & dosagem , Epilepsias Mioclônicas/dietoterapia , Cetonas/metabolismo , Cetose/metabolismo , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Epilepsias Mioclônicas/tratamento farmacológico , Humanos , Cetose/etiologia , Estudos Prospectivos , Falha de Tratamento , Resultado do TratamentoRESUMO
PURPOSE: The ketogenic diet (KD) has been used as a therapeutic alternative to antiepileptic drugs (AEDs) for refractory epilepsy. Severe myoclonic epilepsy in infants or Dravet syndrome (DS) is one of the most malignant epileptic syndromes. In this retrospective study, we evaluated the efficacy and tolerability of the KD in patients with diagnostic criteria of DS. METHODS: Between March 1, 1990, and August 31, 2004, 52 patients who met diagnostic criteria for DS were enrolled in a study at our department. Twenty of them were placed on the KD with the Hopkins protocol and followed up for a minimum of 1 year. RESULTS: Three of the 20 original children stayed on the diet for 12 months, four children for 2 years, four children for 3 years, and two children for 4 years. One year after initiating the diet, 13 (65%) of the initial patients remained on the diet. Two (15%) patients were seizure free, eight (61.7%) children had a 75-99% decrease in seizures, and the remaining three (23%) children had a 50-74% decrease in seizures. Thus 1 year after starting the diet, 10 (77%) children had achieved a >75% decrease in their seizures. Four patients have been off the diet for >2 years; one of them is seizure free, two have sporadic seizures, and one, who abandoned the diet after 2 years of adhering to it, relapsed. No differences in seizure control when compared with age, sex, or seizure type were found. CONCLUSIONS: Considering the severity and intractability of seizures in patients with DS, the fact that 10 of the 13 children who remained on the diet had a significant reduction in number of seizures shows that the KD is at present an interesting therapeutic alternative. Even in patients in whom seizure reduction was not dramatic, quality of life improved, and in all of them, the number of AEDs was reduced to one or two. We consider that children with DS should be offered the KD immediately after three adequate trials of AEDs have failed.
Assuntos
Gorduras na Dieta/metabolismo , Epilepsias Mioclônicas/dietoterapia , Cetose/metabolismo , Idade de Início , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/metabolismo , Feminino , Humanos , Corpos Cetônicos/biossíntese , Cetonas/metabolismo , Cetose/etiologia , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJETIVO: Descrever a introdução e o manejo da dieta cetogênica em um grupo de seis crianças e adolescentes com epilepsia refratária. MÉTODOS: Os autores reviram o prontuário médico de cada paciente menor de 15 anos submetido à dieta cetogênica entre abril de 1999 e julho de 2003 e compararam os resultados terapêuticos e efeitos adversos e benéficos com a literatura pertinente. RESULTADOS: A dieta cetogênica foi introduzida para seis pacientes, com idade mediana de sete anos (faixa: 1,8-12,2). A duração média da aplicação da dieta foi 9,7 meses (faixa: 7 dias-4 anos). Observou-se uma redução igual ou maior que 50 por cento da freqüência das crises epilépticas em metade dos casos. As complicações observadas foram leucopenia, constipação, desidratação, priapismo e recorrência das crises epilépticas. CONCLUSÕES: A dieta cetogênica foi eficaz e segura em três pacientes de uma série de seis casos com epilepsia intratável. A complicação mais comum foi leucopenia.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Nutrição da Criança , Epilepsia/dietoterapia , Cetose/metabolismo , Idade de Início , Anticonvulsivantes/uso terapêutico , Ingestão de Energia , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Corpos Cetônicos/efeitos adversos , Corpos Cetônicos/metabolismo , Cetose/complicações , Cetose/fisiopatologia , Estudos RetrospectivosRESUMO
Se revisan las enfermedades metabólicas que pueden manifestarse en el período neonatal, destacando los elementos clínicos y de laboratorio que el pediatra general debe considerar para aproximarse al diagnóstico y ofrecer el manejo inicial apropiado de estos pacientes. La evaluación de los gases en sangre, el hiato aniónico, el ácido láctico en el suero, la amenomia y la glicemia debe hacerse cuidadosamente para un diagnóstico diferencial apropiado. El tratamiento incial incluye, además del manejo general correspondiente a cualquier recién nacido enfermo, el control de la hipoglicemia, la acidosis y los trastornos del metabolismo del agua y los electrolitos, la restricción de las proteínas, el aporte energético necesario, la suplementación de cofactores metabólicos considerados específicos y la solicitud oportuna de apoyo especializado