RESUMO
Objectives: The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast.Methods: Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50â g/300â ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity.Results: Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex.Discussion: Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward.Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Glucose/administração & dosagem , Adolescente , Adulto , Glicemia/análise , Estudos Cross-Over , Ingestão de Energia , Metabolismo Energético , Jejum , Glucose/metabolismo , Humanos , Insulina/sangue , Imageamento por Ressonância Magnética , Masculino , Saciação/efeitos dos fármacos , Saciação/fisiologia , Método Simples-Cego , Água/administração & dosagem , Adulto JovemRESUMO
In untreated phenylketonuria (PKU), deficiency of phenylalanine hydroxylase (PAH) results in elevated blood phenylalanine (Phe) concentrations and severe mental retardation. Current dietary treatment prevents mental retardation, but cognitive outcome remains suboptimal. The mechanisms by which elevated blood Phe concentrations disturb cerebral metabolism and cognitive function have not been fully elucidated. In this review, we discuss different hypotheses on the pathogenesis of PKU, focusing on the effects of disturbed large neutral amino acid (LNAA) transport from blood to brain on cerebral neurotransmitter and protein synthesis. Although the definitive roles of these processes in PKU pathogenesis are not fully understood yet, both substantially influence clinical outcome.
Assuntos
Transtornos Cognitivos/complicações , Fenilcetonúrias/complicações , Aminoácidos Neutros/metabolismo , Barreira Hematoencefálica , Humanos , Fenilcetonúrias/dietoterapiaRESUMO
BACKGROUND: The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. AIM: This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. METHOD: Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. RESULTS: Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. CONCLUSION: Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.
Assuntos
Tolerância a Medicamentos , Fenilalanina/farmacologia , Fenilcetonúrias/diagnóstico , Fatores Etários , Criança , Pré-Escolar , Tolerância a Medicamentos/fisiologia , Seguimentos , Humanos , Recém-Nascido , Triagem Neonatal , Fenilalanina/sangue , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/sangue , Fenilcetonúrias/genética , PrognósticoRESUMO
Although it is well known that food intake is affected by the palatability of food, the actual effect of flavoring on regulation of energy-homeostasis and reward perception by the brain, remains unclear. We investigated the effect of ethyl-butyrate (EB), a common non-caloric food flavoring, on the blood oxygen level dependent (BOLD) response in the hypothalamus (important in regulating energy homeostasis) and ventral tegmental area (VTA; important in reward processes). The 16 study participants (18-25 years, BMI 20-23 kg/m2) drank four study stimuli on separate visits using a crossover design during an fMRI setup in a randomized order. The stimuli were; plain water, water with EB, glucose solution (50gram/300 ml) and glucose solution with EB. BOLD responses to ingestion of the stimuli were determined in the hypothalamus and VTA as a measure of changes in neuronal activity after ingestion. In the hypothalamus and VTA, glucose had a significant effect on the BOLD response but EB flavoring did not. Glucose with and without EB led to similar decrease in hypothalamic BOLD response and glucose with EB resulted in a decrease in VTA BOLD response. Our results suggest that the changes in neuronal activity in the hypothalamus are mainly driven by energy ingestion and EB does not influence the hypothalamic response. Significant changes in VTA neuronal activity are elicited by energy combined with flavor.
Assuntos
Hipotálamo/fisiologia , Recompensa , Paladar/fisiologia , Área Tegmentar Ventral/fisiologia , Administração Oral , Adolescente , Adulto , Animais , Butiratos/administração & dosagem , Butiratos/metabolismo , Estudos Cross-Over , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Aromatizantes/administração & dosagem , Aromatizantes/metabolismo , Glucose/administração & dosagem , Glucose/metabolismo , Voluntários Saudáveis , Humanos , Hipotálamo/citologia , Hipotálamo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Neurônios/fisiologia , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: The brain is essential in regulating intake of food and beverages by balancing energy homeostasis, which is regulated by the hypothalamus, with reward perception, which is regulated by the ventral tegmental area (VTA). The aim of this study was to investigate the effects of ingestion of glucose, fructose, sucrose, and sucralose (a non-caloric artificial sweetener) on the magnitude and trajectory of the hypothalamic and the VTA blood oxygen level-dependent (BOLD) responses. METHOD: In five visits, 16 healthy men between 18 to 25 y of age with a body mass index between 20 and 23 kg/m2 drank five interventions in a randomized order while a functional magnetic resonance imaging scan was taken. The interventions consisted of 50 g of glucose, fructose, or sucrose, or 0.33 g of sucralose dissolved in 300 mL tap water. The control condition consisted of 300 mL of plain tap water. BOLD signals were determined in the hypothalamus and the VTA within a manually drawn region of interest. Differences in changes in BOLD signal between stimuli were analyzed using mixed models. RESULTS: Compared with the control condition, a decrease in BOLD signal in the hypothalamus was found after ingestion of glucose (Pâ¯=â¯0.0003), and a lesser but delayed BOLD response was found after ingestion of sucrose (Pâ¯=â¯0.006) and fructose (Pâ¯=â¯0.003). Sucralose led to a smaller and transient response from the hypothalamus (Pâ¯=â¯0.026). In the VTA, sucralose led to a very similar response to the water control condition, leading to an increase in VTA BOLD activity that continued over the measured time period. The natural sugars appeared to only lead to a transient increase in VTA activity. CONCLUSIONS: Glucose induces a deactivation in the hypothalamus immediately after ingestion and continued over the next 12 min, which is correlated with satiety signaling by the brain. Fructose and sucrose are both associated with a delayed and lesser response from the hypothalamus, likely because the sugars first have to be metabolized by the body. Sucralose leads to the smallest and most transient decrease in BOLD in the hypothalamus and leads to a similar response as plain water in the VTA, which indicates that sucralose might not have a similar satiating effect on the brain as the natural sugars.
Assuntos
Encéfalo/efeitos dos fármacos , Açúcares da Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Edulcorantes/farmacologia , Adolescente , Adulto , Anedonia/efeitos dos fármacos , Gasometria , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Feminino , Frutose/farmacologia , Glucose/farmacologia , Voluntários Saudáveis , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Oxigênio/análise , Sacarose/análogos & derivados , Sacarose/farmacologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/efeitos dos fármacos , Adulto JovemRESUMO
A 16-year-old girl presented at the emergency unit with myalgia following a flu-like episode. Laboratory tests indicated severe rhabdomyolysis and nephritis. Autoimmune-induced myositis was excluded on the basis of negative tests for antinuclear antibodies; prednisolone treatment was discontinued 1 week later. The patient recovered gradually and was discharged with physiotherapy 2 weeks later. High positive titres of complement-binding antibody against influenza B virus were found, i.e. 1:125 and 1:250 on days to and 25 of illness, respectively. Viral myositis is an uncommon disease entity that occurs following a viral infection, especially with influenza virus, that has been experienced for the first time. It usually runs a benign course: children often present with calf tenderness that resolves within a few days. There are cases, however, with a more serious course involving severe rhabdomyolysis and acute renal failure that can be sometimes fatal.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza B/imunologia , Influenza Humana/complicações , Miosite/virologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Miosite/diagnóstico , Miosite/etiologia , Nefrite/diagnóstico , Nefrite/etiologia , Nefrite/virologia , Rabdomiólise/diagnóstico , Rabdomiólise/etiologia , Rabdomiólise/virologiaRESUMO
Histopathological findings of muscle biopsies from five patients with two different muscular glycogen storage diseases (mGSD) were presented. From these investigations it emerged that the yield of histopathology in mGSD is low. In only one of five patients histopathological findings gave a clue towards diagnosis. It can be concluded that non-specific findings or even normal appearance of a muscle biopsy does not exclude mGSD.
Assuntos
Doença de Depósito de Glicogênio/patologia , Glicogênio/metabolismo , Músculo Esquelético/patologia , Criança , Pré-Escolar , Doença de Depósito de Glicogênio/metabolismo , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/ultraestruturaRESUMO
In a previous study, Dutch children with phenylketonuria (PKU) were found to be slightly shorter than their healthy counterparts. In the literature, it has been hypothesized that a higher protein intake is necessary to optimize growth in PKU patients. The study aimed to investigate whether protein intake (total, natural and protein substitute) in this group might be an explanatory factor for the observed growth. Growth of height and head circumference and dietary data on protein intake (total, natural and protein substitute) from 174 Dutch PKU patients born between 1974 and 1996 were analysed retrospectively for the patients' first 3 years of life. Analyses were corrected for energy intake during the first year of life and for the clinical severity of the deficiency of phenylalanine hydroxylase by means of plasma phenylalanine concentration at birth. Neither protein nor energy intake correlated with height growth. A positive, statistically significant relation between head circumference growth and natural protein and total protein intake was found, but not with the intake of the protein substitute or energy. Therefore, this study suggests that improvement of the protein substitute rather than an increase of total protein intake may be important in optimizing head circumference growth in PKU patients.