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BACKGROUND: Diabetic vascular complications are associated with elevated concentrations of advanced glycation end-products (AGEs). These substances can be originated endogenously by hyperglycaemia and oxidative stress, but also by dietary intake. There is indirect evidence suggesting that these complications can be prevented by lowering AGEs levels by dietary or pharmacological interventions, however its clinical benefits are still not clear enough because this would require long periods of treatment. Specific neuro-ophthalmologic tests like Multifocal Electroretinogram (MFERG) and visual evoked potentials (VEP) can detect retinal and myelinic nerve early changes, and thus could represent good methods to study the results of certain interventions in shorter lapses. The aim of this preliminary study was to evaluate the effects of a pharmacological intervention designed to lower AGEs levels, on these variables. PATIENTS AND METHODS: We included 7 patients with type 2 diabetes (DM2), with more than 5 and less than 10 years of disease, without clinically evident micro and macrovascular disease, without renal failure, hypothyroidism nor vitamin B12 deficiency, whose AGEs dietary intake was moderately elevated or high (according to dietary recalls). Upon admission, a clinical evaluation, urine and blood samples were obtained for routine labs, plus ultrasensitive C Reactive Protein (usCRP) as an inflammatory marker, and carboxymethyl-lysine (CML) as representative of AGEs. Then a complete ophthalmologic evaluation was performed, including fundus, MFERG and VEP. After the initial evaluation, placebo capsules were prescribed (12 daily capsules, 4 with each main meal) during 3 months, repeating the same initial evaluation at completion of this period. Then the active treatment followed, with capsules containing cholestyramine (4 capsules containing 500 mg each, totaling 6 g per day). Patients were cited each month, to register adverse events and repeating the same evaluation after this second 3 months period. RESULTS: The sample was composed of 2 male patients, mean age was 55.1 ± 3.8 years, and diabetes was managed with metformin plus other oral agents or o insulin (4 cases). In addition, 4 patients received lipid lowering and 4 antihypertensive drugs. Metabolic control and lipid levels were variable (ranges of HbA1c 6.2-8.4%, LDL cholesterol 45-141 mg/dL, triglycerides 70-220 mg/dL). AGEs levels represented by CML were highly variable (median 31.7, range min-max 3.4-58.9 ug/uL). Basal usCRP was also variable (median 405.9, range min-max 265.6-490.7 mg/L). The treatment was well tolerated, except for mild constipation associated with cholestiramine intake. No significant changes in electroretinography or evoked potentials were observed when comparing the initial placebo period with cholestyramine treatment. A significant increase in triglyceride levels and decrease of vitamin D levels after cholestyramine treatment was observed. No changes were detected in serum concentrations of CML, usCRP or glycemic control, after treatment. The latter variables were not correlated with neurophthalmologic studies. DISCUSSION: In this preliminary study we did not observe changes in MFERG nor VEP after 6 g/day cholestyramine treatment, which did not induce lowering of CML levels. This could be attributed to the many limitations of a pilot study, such as a small sample size, short duration of treatment, reduced doses. However this design allowed to evaluate the patients´ tolerance to the drug and rule out adverse effects, in order to plan further studies using the necessary doses to obtain lowering of AGEs

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BACKGROUND: Preventing obesity is a worldwide public health priority. In vulnerable children living in obesogenic environments, with easy access to high-caloric food, alterations in inhibitory control functions might favor excessive food intake and affect energy regulation. We hypothesized that overweight/obese children would present lower inhibitory control in comparison to normal weight children. METHODS: We measured inhibitory control functions in 93 otherwise healthy overweight/obese and 92 normal weight 10-year-old children using the Stroop test and the Go/No-Go task. Event-related potentials were recorded during the Go/No-Go task. RESULTS: Overweight/obese children showed slower reaction times (1248.6 ms (95% confidence interval (CI): 1182.9-1314.3) vs 1149.0 ms (95% CI: 1083.0-1215.1)) on the Stroop test, higher reaction time variability (0.25 (95% CI: 0.22-0.27) vs 0.21 (95% CI: 0.19-0.24)) on the Go/No-Go task and decreased P300 amplitude (4.1 µV (95% CI: 3.0-5.2) vs 6.4 µV (95% CI: 5.2-7.6)) on event-related potentials compared with normal weight children. CONCLUSIONS: Our results indicate altered inhibitory control functions in otherwise healthy overweight/obese children, which might contribute to their excessive food consumption.

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OBJECTIVE: Epidemiological evidence shows an inverse relationship between sleep duration and overweight/obesity risk. However, there are few polysomnographic studies that relate the organization of sleep stages to pediatric overweight (OW). We compared sleep organization in otherwise healthy OW and normal-weight (NW) 10-year-old children. SUBJECTS: Polysomnographic assessments were performed in 37 NW and 59 OW children drawn from a longitudinal study beginning in infancy. Weight and height were used to evaluate body mass index (BMI) according to international criteria. Non-rapid eye movement (NREM) sleep (stages N1, N2 and N3), rapid eye movement (REM) sleep (stage R) and wakefulness (stage W) were visually scored. Sleep parameters were compared in NW and OW groups for the whole sleep period time (SPT) and for each successive third of it using independent Student's t-tests or nonparametric tests. The relationship between BMI and sleep variables was evaluated by correlation analyses controlling for relevant covariates. RESULTS: The groups were similar in timing of sleep onset and offset, and sleep period time. BMI was inversely related to total sleep time (TST) and sleep efficiency. OW children showed reduced TST, sleep efficiency and stage R amount, but higher stage W amount. In analysis by thirds of the SPT, the duration of stage N3 episodes was shorter in the first third and longer in the second third in OW children as compared with NW children. CONCLUSIONS: Our results show reduced sleep amount and quality in otherwise healthy OW children. The lower stage R amount and changes involving stage N3 throughout the night suggest that OW in childhood is associated with modifications not only in sleep duration, but also in the ongoing night time patterns of NREM sleep and REM sleep stages.

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BACKGROUND: A chronic or acute insult may affect the regulatory processes that guide motor and behavioral performance, leading to increased intra-individual variability (IIV). Increased variability is often interpreted as an indication of regulatory dysfunction. Iron plays an important role in the regulatory processes of the nervous system and affects motor activity. To our knowledge, no study has examined the long-lasting patterns and IIV of motor activity following iron-deficiency anemia in human infants. AIMS: This study compared 48-h motor activity and variability in preschool-aged children with or without iron-deficiency anemia (IDA) in infancy. METHODS: Motor activity was recorded through actigraphs during two week-days in 47 4-year-old Chilean children (23 former IDA and 24 non-anemic in infancy). All were given oral iron as infants. Sleep-wake states were identified by means of automated software. The frequency of movement units per minute was determined for each waking/sleep state during the individual day and night periods; data were examined in blocks of 15 min. Analyses of mean frequency and duration and intra-individual variability were conducted using multivariate mixed models. RESULTS: For daytime sleep, former IDA children were more active without a difference in the total duration. They also spent less time awake throughout the individual day period. Motor activity intra-individual variability was higher in former IDA children. CONCLUSIONS: The findings suggest that IDA in infancy sets the stage for long lasting dysfunction in the neural processes regulating sleep-wake states and spontaneous motor activity patterns.

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Iron deficiency anemia (IDA) is a very common nutritional problem that alters motor activity. The aim of this study was to compare 24-h motor activity in the home in healthy 6-month-old infants with and without IDA. Activity was assessed via actigraphs on the leg during 24 continuous hours in 17 Chilean infants with IDA and 18 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. The frequency of movement units per minute was determined for each waking/sleep state during the day and night, and the duration of each state was computed. At 6 months of age, there were no differences between anemic and nonanemic infants in time per state. However, infants with IDA showed an overall increase in motor activity compared to controls. These differences were no longer observed at 12 and 18 months of age. Increased activity during the period of IDA raises the issue of a shared underlying mechanism with restless legs syndrome, a sensorimotor dysfunction where iron deficiency increases the severity of the symptoms and iron supplementation ameliorates them. Due to previous findings of decreased motor activity in the laboratory at 12 months during the waking time surrounding an afternoon nap, we also compared those data to a nap in the home. Infants with IDA were less active in the laboratory than in the home. The home versus laboratory results suggest that contextual factors affect the motor activity of IDA infants to a larger extent than controls.

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La relación entre el hombre y su ambiente requiere, necesariamente, ajustes fisiológicos y comportamentales indispensables para el mantenimiento de la homeostasia. Para ejercer estas adecuaciones, el ser humano está dotado de dos tipos de adaptaciones funcionales: a) las reactivas, que son modificaciones del organismo en respuesta a un cambio que ya ocurrió, y b) las anticipatorias o predictivas, que suceden antes de que intervengan los predecibles cambios en las claves ambientales (homeostasia anticipatoria). Enfatizamos, entonces, el marco temporal de 24 horas en que fluctúan las diversas variables fisiológicas producto de los relojes biológicos, y, en particular, el ciclo sueño/vigilia (CSV). La relación de fase de las diversas variables del organismo, constituye el orden temporal interno (OTI). La preservación de este OTI es parte fundamental de nuestra fisiología, pues asegura el establecimiento de una adecuada eficiencia funcional y promueve una armoniosa interacción con nuestro entorno. La ruptura incluso transitoria de este OTI, determina una desincronización interna. Postulamos que la transgresión del OTI gatilla y/o magnifica las disfunciones conducentes a enfermedades crónicas, incluyendo la obesidad y sus complicaciones clínicas

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