J. Uberos

Normalization of the sleep–wake pattern and melatonin and 6-sulphatoxy-melatonin levels after a therapeutic trial with melatonin in children with severe epilepsy

Abstract:  This study evaluated the sleep–wake pattern, plasma melatonin levels and the urinary excretion of its metabolite, 6‐sulphatoxy‐melatonin among children with severe epileptic disorders, before and after a therapeutic trial with melatonin. Ten paediatric patients, suffering from severe epileptic disorders, were selected and given a nightly dose of 3 mg of a placebo, for 1 wk; for the next 3 months, the placebo was replaced with a nightly dose of 3 mg of melatonin. At the end of each treatment period, the urinary excretion of 6‐sulphatoxy‐melatonin (for the intervals 09.00 – 21:00 hr or 21:00–09:00 hr) and plasma levels of melatonin (recorded at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00 hr) were recorded, over a period of 24 hr; an actigraph record was also kept. Sleep efficiency among patients who received melatonin was significantly higher than among those given the placebo, with fewer night‐time awakenings. Periodic plasma melatonin levels were regained and a better control gained of convulsive episodes, in that the number of seizures decreased. We conclude that melatonin is a good regulator of the sleep–wake cycle for paediatric patients suffering from severe epilepsy, moreover, it to a better control of convulsive episodes.

Characterization by high-performance liquid chromatography with diode-array detection coupled to time-of-flight mass spectrometry of the phenolic fraction in a cranberry syrup used to prevent urinary tract diseases, together with a study of its antibacterial activity.

The phenolic fraction of a commercial cranberry syrup, which is purported to have good properties for the prevention of urinary diseases, has been thoroughly characterized using HPLC-DAD-TOF-MS. A study of its antibacterial activity has also been carried out. For this purpose a new HPLC-DAD-TOF-MS method using negative and positive ionization modes was developed and it was thus possible to identify 34 different compounds, nine of which have been tentatively characterized for the first time in cranberry syrup. It is also important to highlight that different coumarins in this matrix were also determined, which, to our knowledge, have not been found previously in the cranberry. The phenolic fraction obtained by HPLC-DAD was found to be 5.47 mg/mL. Catechin and procyanidins belonging to flavanols were the family of compounds found at the highest concentrations (2.37 mg/mL); flavonols were at a concentration of 1.91 mg/mL and phenolic-acid derivatives were found at the lowest concentration (0.15 mg/mL). With regard to antibacterial activity, the incubation of Escherichia coli with cranberry syrup was found to reduce surface hydrophobicity as a function of the concentration of the extract.

Identification of polyphenols and their metabolites in human urine after cranberry-syrup consumption.

As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial. A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup. Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure. All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns. Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O-β-d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine. Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis(TM) software.

Melatonin Levels during the First Week of Life and Their Relation with the Antioxidant Response in the Perinatal Period

Aim: Melatonin is a potent free radical scavenger and an indirect antioxidant. Knowledge about the behavior of melatonin secretion in the early neonatal period, which may relate to its properties at a vital stage during very high antioxidant demands, is limited. Patients and Methods: We studied 35 newborns admitted to the Neonatal Unit with respiratory distress syndrome (RDS) and with no signs of sepsis, severe anemia, hemodynamic compromise or malformation. The gestational age of the newborns was 26–40 weeks (mean value 32.5 weeks) and the weight at birth was 870–4,400 g (mean value 1,800 g). They were classified into two groups: ≤1,500 g or >1,500 g birthweight. In all cases, at 09:00 h on their 1st, 3rd and 7th days of life, serum melatonin was measured by RIA. The clinical history was recorded and treatment and follow-up were performed according to established neonatology practice, and the resultant data recorded. Informed consent from the parents or guardians was obtained in accordance with the Declaration of Helsinki. Statistical analysis was carried out using ANOVA-II (factor I: day of sample; factor II: birthweight). Results: There were significant increases in melatonin levels with increasing birthweight (p = 0.017), but no changes by day of sample. Although in both study groups melatonin levels increased during the first few days this was not statistically significant. Conclusions: In newborns of low birthweight, we report high melatonin concentrations in the morning and during the first week of life. These increase with maturation, and at full-term were similar to nocturnal levels during the acrophase of pineal gland secretion in toddlers and schoolage children, when pineal gland secretion is maximal and takes place reflecting environmental variations. In the early neonatal period these high levels of melatonin seem to derive from extrapineal sources, which mature to provide antioxidant protection in accordance with other elements of the antioxidant network to compensate for the high levels of oxidative stress that are present in the perinatal period.

Influence of the antioxidant content of saliva on dental caries in an at-risk community

Objective This study aims to evaluate the relationship between the total antioxidant capacity of saliva and the presence of dental caries in deciduous and permanent teeth, in a group of Saharan children.Methods The dental examination was carried out in accordance with the recommendations of the World Health Organization (WHO). The total antioxidant capacity of the saliva was determined by colorimetry.Results The total antioxidant capacity (TAC) of the saliva of patients with caries in deciduous teeth was 2.89 1/IC50 greater than among those without. We observed a statistically significant linear regression between the number of deciduous teeth affected by caries and the total antioxidant capacity of the saliva: y = 0.24 + 0.53 × TAC saliva (t = 2.93; p = 0.004) (95% CI of b: 0.018-0.088).Conclusions Our results show that the amount of caries in deciduous teeth is in direct proportion to the observed TAC of saliva, and that the presence of caries in deciduous teeth is associated with caries in permanent teeth.

Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD

UNLABELLED The neuroendocrine mediators that may contribute to ADHD (Attention deficit and hyperactivity disorder), serotonin and melatonin, are both thought to regulate circadian rhythms, neurological function and stress response. The objective of this study was to determine the effect of the chronic administration of prolonged release methylphenidate (PRMPH) on daily variations in blood serotonin and melatonin and on the excretion of 6-sulphatoxy-melatonin. A total of 179 children (136 males, 42 females) between the ages of 5 and 14 (9.70 ± 2.55) years were enrolled in a controlled quasi-experimental open clinical study. Of the sample, there were 136 Children with ADHD (based on DSM-IV-TR criteria), who were further grouped into subtypes, and the 42 siblings of the participants who did not ADHD patients. Blood samples were taken at 20:00 and 09:00; urine was collected between 21:00 and 09:00. In the ADHD group, the study protocol was repeated after 4.61 ± 2.3 months of treatment. Measurements included melatonin and serotonin by RIA and urine 6-S-aMT by ELISA. Factorial analyses were conducted by STATA 12.0. RESULTS ADHD patients showed reduced morning serotonin with a daily profile that was different than the control group due to the predominance of nocturnal concentrations. PRMPH did not result in any significant changes. Melatonin and its daily profile did not differ between controls and the ADHD group with a diurnal rhythm showing higher morning levels that disappear after PRMPH administration. Melatonin was higher in children with predominantly hyperactive-impulsive/conduct disorder subtype. PRMPH resulted in a decrease in 6-S-aMT excretion for both ADHD subtypes. CONCLUSION Chronic treatment with prolonged release methylphenidate induces subtle changes in the daily fluctuations and concentrations of both serotonin and melatonin. Improvement in Childrens Depression Inventory (CDI) scores was not related to a morning increase in serotonin.

Psychosocial dwarfism: psychopathological aspects and putative neuroendocrine markers.

There exists an extensive terminology for defining the situation of children who, in varying circumstances, suffer from affective deprivation (AD), within an unsatisfactory family situation or in institutions. Nevertheless, the neuroendocrine mechanisms (if they exist) determining it have yet to be identified. Our objective was to determine if specific neuroendocrine markers, all of them previously implicated in affective disorders, could be modified, and in which sense, in affective deprivation syndrome of the child. For this purpose, we studied three separate groups of children: (1) control group (CG); (2) children suffering from AD; and (3) children with non-organic failure to thrive (NOFT). In every case, we studied the serum levels of melatonin, serotonin, β-endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway tryptophan metabolites (both during the day and at night). Significantly, there was a conspicuous reduction in the levels of each of the neuroendocrine markers (melatonin, serotonin, β-endorphins and ACTH) in the group suffering from affective deficiency, a diminution which was even more noticeable in the group of patients presenting delayed growth. Furthermore, as also occurs in other affective disorders, there were corresponding modifications in the metabolisation of tryptophan. We report the existence of neuroendocrine mechanisms that are associated with the above-mentioned clinical manifestations in these patients, mechanisms that may underlie the close connection existing between AD syndrome and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise a single process, but one with a different evolutionary continuum of psychosocial dwarfism.

Melatonin and elimination of kynurenines in children with Down's syndrome.

BACKGROUND Heightened activity of superoxide dimutase is an effect derived from the gene dose in the trisomy of Downs syndrome (DS), and has been related to the increased production of hydrogen peroxide and with greater lipid peroxidation. Many of the degenerative changes observed in patients with DS have been associated with the pathological effects of free radicals, and for this reason it is of interest to determine the levels present in these patients of powerful antioxidant molecules such as melatonin, and of metabolites with important neuroprotector and neurotoxic consequences such as those derived from the kynurenine pathway. PATIENTS AND METHODS A study was made of 15 children with DS, together with a control group of 15 non-DS children, matched for age and sex, examined at the Hospital Costa del Sol, Marbella, Spain. Serum melatonin and serotonin were analyzed by RIA; urinary tryptophan metabolites (kynurenine pathway) were determined during periods of light and darkness (09.00-21.00 h and 21.00-9.00 h) by thin-layer chromatography. RESULTS The mean values of serotonin and melatonin were found to be lower in the patients with DS, although the level of nocturnal secretion of melatonin was higher. Urinary excretion of kynurenine was lower in the patients with DS, although greater quantities of kynurenic acid and anthranilic acid were excreted. CONCLUSIONS Patients with DS present levels of plasma melatonin and urinary kynurenine that are lower than the corresponding levels in the control population, together with higher values of kynurenic acid and anthranilic acid. These circumstances constitute an added risk to these patients of damage by free radicals.

Assessment of the stability of proanthocyanidins and other phenolic compounds in cranberry syrup after gamma-irradiation treatment and during storage.

Shelf life of commercial cranberry syrup irradiated with gamma radiation at a rate of 5 kGy and stored for 6 months at 25 °C and 60% relative humidity (RH) and under accelerated stability conditions was investigated. High-performance liquid chromatography coupled to electrospray ionisation quadrupole-time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) was used to characterise cranberry syrup. Afterwards, these compounds were quantified by HPLC-ESI-QTOF-MS and 4-dimethylaminocinnamaldehyde (DMAC) assay. A significant increase in the content of procyanidin B isomer 1 (from 4.4 to 7.0 μg/ml) and procyanidin A2 (from 83 to 93 μg/ml) was observed after irradiation and compared with the non-irradiated syrup. Procyanidin B isomers and prodelphinidin were stable at 25 °C during the first month of storage, whereas quercetin and some derivatives remained constant for 3 months of storage at this temperature. In short, after gamma-irradiation in dose of 5 kGy, most compounds were highly stable for a month at 25 °C.

Overweight and obesity as risk factors for the asymptomatic carrier state of Neisseria meningitidis among a paediatric population

We analysed the asymptomatic carrier state of Neisseria meningitidis in a sample of 339 children. We obtained data for the children’s weight and height, in order to calculate the body mass index (BMI). The cutoff points defined by Cole were employed in determining the BMI, and the population was divided into three groups: normal, overweight and obese. Twenty carriers of N. meningitidis were identified. There was found to be a statistically significant trend to increased risk of being a carrier with increased BMI (z = 2.03; P = 0.04); after adjusting for age using the Mantel–Haenszel weighting method, this relationship was strengthened (z = 2.38; P = 0.01). Paediatric patients with increased BMI in the range of obesity present a three times greater risk of being carriers of N. meningitidis than non-obese patients, with a trend for this risk to increase with higher BMI.