Probiotics to prevent necrotising enterocolitis and nosocomial infection in very low birth weight preterm infants.

The aim of the study was to determine whether routine probiotic supplementation (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus +Lactobacillus bifidum is associated with reduced risk of necrotising enterocolitis (NEC)≥Stage II in preterm neonates born at ≤32 weeks' gestation. We conducted a retrospective cohort study on the effect of probiotic supplementation in very low birth weight infants in our neonatal unit by comparing two periods: before and after supplementation. The incidence of NEC≥Stage II, late-onset sepsis and all-cause mortality was compared for an equal period 'before' (Period I) and 'after' (Period II) RPS with LGG or L. acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. The study population was composed of 261 neonates (Period I v. II: 134 v. 127) with comparable gestation duration and birth weights. In <32 weeks, we observed a significant reduction in NEC≥Stage II (11·3 v. 4·8 %), late-onset sepsis (16 v. 10·5 %) and mortality (19·4 v. 2·3 %). The benefits in neonates aged ≤27 weeks did not reach statistical significance. RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of NEC≥Stage II, late-onset sepsis and mortality in preterm neonates born at ≤32 weeks' gestation.

Sexual health in Spanish postmenopausal women presenting at outpatient clinics.

OBJECTIVE: One of the most common complaints among postmenopausal women is a change in sexual drive. The aim of this study was to assess the current state of sexual health in Spanish postmenopausal women who present at outpatient gynecology clinics. METHOD: In this multicenter, observational, cross-sectional, questionnaire-based study, a survey was conducted that included 3026 Spanish postmenopausal women in a routine clinical setting in outpatient gynecology clinics at public and private institutions throughout Spain. We used the Women's Sexual Function questionnaire, which has been validated in Spain. RESULTS: In the multivariate analysis, we found that the best indicators of sexual health in postmenopausal women were a higher education (p < 0.001), working or previously worked (p < 0.001), a stable partner (p < 0.001), living in an urban area (p < 0.01), healthy habits and received information about menopause (p < 0.001). CONCLUSION: These results indicate that it is important to provide health education and information about menopause and the complaints associated with this period in a woman's life.

Factors determining the use of hormonal therapy and phytotherapy in Spanish postmenopausal women.

OBJECTIVE: To identify women's sociodemographic and variables related to health care with the prescription of hormonal therapy (HT) and phytotherapy (PT) in Spanish postmenopausal women. METHOD: The survey consisted of a multicenter, observational, cross-sectional, questionnaire-based investigation and was conducted among 3022 postmenopausal women. RESULTS: Of all the women, 31.8% reported the use of systemic HT or PT sometime in their lives. Hot flushes and information received about menopause were the most important variables that influence HT and PT use, although far more intense symptoms were observed in those who were inclined to use HT. The use of HT or PT was more frequently reported among women with high levels of education, who came from private clinics and lived in urban areas. Women who had primary ovarian insufficiency or surgical menopause were inclined to use HT. CONCLUSION: Hot flushes and information received about menopause are the most important variables that influence HT and PT use.

Epoxide of diosgenin acetate synthesis: DoE for diastereoselective yield optimization, antimicroibial, antioxidant and antiproliferative effects.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (nk), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3:1 of α and ß-epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1ß better to 1α. The antiproliferative capacity was higher for diastereoisomer ß, agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity.

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

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.

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.

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 Down's 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.

Effects on the glutathione pool of the insulin-induced hypoglycaemia test.

The growth hormone (GH) stimulation test shows that hypoglycaemia can cause the generation of free radicals, or reactive oxygen species (ROS), together with the migration of amino acids, glutathione and various ions to the interior of fat or muscle cells. The aim of the present study is to evaluate the splitting of plasma glutathione into its two fractions, oxidized (GSSG) and reduced (GSH), after the induction of hypoglycaemia with insulin in the course of the GH stimulation test. We studied 41 short children (47% boys and 53% girls) at the Paediatric Department of the San Cecilio Hospital (Granada, Spain) to evaluate their size and growth. A GH stimulation test using insulin-induced hypoglycaemia was carried out, and GSSG and GSH values in plasma were determined. The glutathione level is associated with the level of glucose reached at 30 min after initiating the test. This provoked an initial reduction in the GSH/GSSG ratio, which fell to a minimum at 30 min after starting the test, although the values rose again at 60 min. The results obtained show that the insulin-induced GH stimulation test produces a decrease in plasma levels of the glutathione pool, that persists at least for 2 hours following the beginning of the test.

Serum melatonin concentration in the child with non-organic failure to thrive: comparison with other types of stress.

Human beings must adapt both to novel, unfavourable conditions and to circumstances of physical or psychological isolation. The initial response to stress depends fundamentally on the activation of the HPA axis. In regaining homeostatic equilibrium, melatonin plays a role due to its synchronising and anti-stress properties. To study the role of melatonin and the pineal gland in the organic and/or behavioural response to acute or chronic stress, 311 children were divided into two large groups: 1) Control Group - 121 healthy children classified, in turn, into 4 control subgroups, one for each pathology being studied; 2) Problem Groups, classified as traumatic stress (n=58), surgical stress (n=38), psychic stress (n=64) and febrile stress (n=30), according to pre-established clinical criteria. These groups were sub-classified according to the degree (low or high) and duration (acute or chronic) of the stress. This study used a case controlled, cross sectional design. Serum melatonin was measured by radioimmunoassay (RIA). In all the situations of acute stress, melatonin increased at a rate directly proportional to the severity and/or duration of the stress-causing stimulus. In contrast, in chronic stress, i.e. the Affective Deprivation Syndrome (or Psychological Dwarfism) with or without non-organic failure to thrive, resulted in the opposite response with a significant reduction of melatonin. In conclusion, in acute stress an increase in the bioavailability of melatonin could contribute to maintaining homeostatic balance. The lack of an appropriate response to acute stress could make some groups of patients (Affective deprivation syndrome with or without growth failure) predisposed to suffer depressive symptoms associated with a wide range of neurological, endocrinological or immunological consequences.

Deep Seated Density Anomalies Across the Iberia-Africa Plate Boundary and Its Topographic Response.

The modes in which the lithosphere deforms during continental collision and the mechanisms involved are not well understood. While continental subduction and mantle delamination are often invoked in tectonophysical studies, these processes are difficult to be confirmed in more complex tectonic regions such as the Gibraltar Arc. We study the present-day density and compositional structure of the lithosphere along a transect running from South Iberia to North Africa crossing the western Gibraltar Arc. This region is located in the westernmost continental segment of the African-Eurasian plates, characterized by a diffuse transpressive plate boundary. An integrated and self-consistent geophysical-petrological methodology is used to model the lithosphere structure variations and the thermophysical properties of the upper mantle. The crustal structure is mainly constrained by seismic experiments and geological data, whereas the composition of the lithospheric mantle is constrained by xenolith data. The results show large lateral variations in the topography of the lithosphere-asthenosphere boundary. We distinguish different chemical lithospheric mantle domains that reproduce the main trends of the geophysical observables and the modeled P and S wave seismic velocities. A sublithospheric body colder than the surrounding mantle is needed beneath the Betics-Rif to adjust the measured potential fields. We link this body to the Iberian slab localized just to the east of the profile and having some effect on the geoid and Bouguer anomalies. Local isostasy allows explaining most of the topography, but an elastic thickness higher than 10 km is needed to explain local misfits between the Atlas and the Rif Mountains.

Longitudinal study of the simultaneous secretion of melatonin and leptin during normal puberty.

BACKGROUND/AIMS: Pubertal changes are a consequence of the activation of the hypothalamic-pituitary-gonadal axis due to an increase in the frequency and magnitude of pulses of gonadotropin-releasing hormone (GnRH), which may depend on the intrinsic properties of the neurons of the hypothalamic arcuatus nucleus, or on the influence of neurotransmitters and/or neuromodulators. We evaluated the serum concentrations of melatonin and leptin in healthy prepubertal and adolescent subjects of both sexes, to define their participation at the initial stages and during the progression of pubertal development. METHODS: 80 pediatric subjects (47 females and 33 males), aged 6-18 years, were divided into 2 groups, prepubertal (n = 25) and adolescent (n = 55), according to the absence or presence, respectively, of physical signs of pubertal development. The subjects were assessed on two occasions: at the time of their inclusion in the study, and 12-18 months later when the subject had advanced one pubertal stage according to the Tanner classification. Blood was obtained in fasting for clinical purposes and for the hormonal study. Melatonin and leptin were measured by radioimmunoanalysis. RESULTS: As described previously, melatonin decreases at the onset of puberty and during pubertal development. Both the absolute melatonin value and the decrease between evaluations tended to be greater in females; the variations were correlated with neither an increase in body weight nor with the degree of pubertal development. The concentration of leptin increased in both sexes with the progression of puberty, this value being 40% greater in women, and correlated with the indicators of an increase in body volume and fat accumulation. Although its concentration remained stable between evaluations for both sexes, among the males the association between leptin and pubertal development took place at the start of the process, while for the females we observed a significant overall association between pubertal stage and leptin concentration, this association being stronger at more advanced Tanner stages. Neither at the onset of puberty nor during its course did we observe any significant relation between melatonin concentration and any of the Tanner stages, whether for males or for females. Neither was there any correlation between the absolute values or rates of modification of melatonin and leptin. CONCLUSION: According to the evolutionary dynamics of their respective concentrations, both initially and during pubertal progress, melatonin and leptin do not interact in the initiation or progression of human pubertal development, and do not seem to play a key role in this process.

First Report of Pantoea agglomerans Causing Leaf Blight and Vascular Wilt in Maize and Sorghum in Mexico.

Zea mays and Sorghum bicolor are important crops for animal and human nutrition worldwide. In the Central Highland Valley of Mexico, both crops are extremely important, and research is aimed toward increasing yield, disease resistance, and crop adaptation from 1,900- to 2,700-m elevation. In a 3-year field breeding experiment (2004 to 2006), leaf blight and vascular wilt symptoms were frequently observed in contiguous plots of maize and sorghum crops in Montecillo, Mexico and maize plots in Tecamac, Mexico. To identify and characterize the causal agent of these symptoms, isolations were conducted on leaves from areas where healthy and diseased tissues converged. Leaf sections of 1 cm2 from both crops were disinfested, placed on casamino acid-peptone-glucose (CPG) medium, and incubated at 28°C. After 48 h, only yellow colonies were observed and 12 isolates were selected for further characterization. Physiological and biochemical tests indicated that the isolates were nonfluorescent on King's B medium, and API 50 CHE (bioMérieux, Marcy l'Etoile, France) revealed that they were negative for gelatin hydrolysis, indole production, acid production from raffinose and positive for utilization of glycerol, D-glucose, mannitol, arbutine, esculine, salicine, cellobiose, maltose, melibiose, D-fucose, and D-arabitol; all characteristics of Pantoea agglomerans. Further identification of these isolates was accomplished by DNA analysis. For DNA analysis, 1.4-kbp fragments of the 16S rRNA gene were amplified with primer set 8F/1492R (3) and sequenced with U514F/800R universal primers (2). Five sequences were obtained and deposited in GenBank (Accession Nos. EF050806 to EF050810). A phylogenetic tree was constructed using the UPGMA method (mega version 3.1). Results of the phylogenetic analysis grouped the species P. ananatis, P. stewartti, and P. agglomerans into three clusters. The five unknown sequences were grouped into the P. agglomerans cluster. There was a 98 to 99% similarity of the five 16S rRNA gene sequences with P. agglomerans strain type ATCC 27155. Pathogenicity of the 12 isolates was confirmed by injecting 108 CFU mL-1 of inoculum into stems of 3-week-old maize cv. Triunfo and sorghum cold tolerant hybrid (A1×B5)×R1 seedlings in the greenhouse at 28°C and 80% relative humidity. Also, seedlings were inoculated with water, nonpathogenic isolates of P. agglomerans from maize (GM13, and HLA1), and not inoculated as negative controls. Three replications were included for each isolate and control. All test strains developed water-soaked lesions on juvenile leaves at 8 days postinoculation and were followed by chlorotic to straw-colored leaf streaks and then leaf blight symptoms at 3 weeks postinoculation. All negative control seedlings did not develop symptoms. In addition, the 12 isolates were infiltrated at 107 CFU mL-1 into tobacco leaves that displayed a hypersensitive response at 4 days, indicating the presence of the type III secretion system (1). Isolates were reisolated, and the 16S rRNA gene fragments were 100% similar to their original isolate sequences. P. agglomerans has been reported to affect other crops, including chinese taro in Brazil (2007), onion in the United States (2006) and South Africa (1981), and pearl millet in Zimbabwe (1997); however, to our knowledge, this is the first report of P. agglomerans associated with leaf blight and vascular wilt symptoms in maize and sorghum in the Central Highland Valley of Mexico. References: (1) J. Alfano and A. Collmer. Annu. Rev. Phytopathol 42:385, 2004. (2) Y. Anzai et al. Int. J. Syst. Evol. Microbiol. 50:1563, 2000. (3) M. Sasoh et al. Appl. Environ. Microbiol. 72:1825, 2006.

Comparison of plasma membrane H+-ATPase activity in vesicles obtained from dry and hydrated maize embryos.

ATP hydrolysis from H+-ATPase of plasma membrane was measured in vesicles from maize embryos imbibed at times between 0 and 5 h. The activity had a maximum at 2 h of imbibition. In order to detect whether the enzyme had the same characteristics through the first 5 h of imbibition, vanadate and lysophophatydilcholine sensitivities, as well as trypsin, pH and temperature effects on the activity of the H+-ATPase from plasma membrane vesicles isolated from embryos imbibed at 0 or 5 h were studied. The results indicate that the activity expressed at 0 h is very different from the activity at 5 h. The activity from embryos imbibed for 5 h was less sensitive to vanadate, trypsin and lysophosphatidylcholine, more sensitive to denaturing temperatures and with a broader pH dependence, as compared to the activity from embryos that were not imbibed. When vanadate-sensitive ATPase activity was purified by anion exchange chromatography, the peaks obtained from the 0 and 5 h imbibed embryos were different and non-overlapping. These data could be interpreted in terms of different enzyme structures from dry and imbibed embryos due to either different primary structures or covalent modifications, or differences in membrane vicinities.

Effects of water deficit on radicle apex elongation and solute accumulation in Zea mays L.

In this study, we examined the effects of water deficit on the elongation of radicles of maize seedlings and on the accumulation of solutes in the radicle apices of two maize varieties: VS-22 (tolerant) and AMCCG-2 (susceptible). Sections of radicle corresponding to the first 2 mm of the primary roots were marked with black ink, and the seedlings were allowed to grow for 24, 48, and 72 h in polyvinyl chloride (PVC) tubes filled with vermiculite at three different water potentials (Ψ(w), -0.03, -1.0, and -1.5 MPa). The radicle elongation, sugar accumulation, and proline accumulation were determined after each of the growth periods specified above. The Ψ(w) of the substrate affected the dynamics of primary root elongation in both varieties. In particular, the lowest Ψ(w) (-1.5 MPa) inhibited root development by 72% and 90% for the VS-22 and AMCCG-2 varieties, respectively. The osmotic potential (Ψ(o)) was reduced substantially in both varieties to maintain root turgor; however, VS-22 had a higher root turgor (0.67 MPa) than AMCCG-2 (0.2 MPa). These results suggest that both varieties possess a capacity for osmotic adjustment. Sugar began to accumulate within the first 24 h of radicle apex growth. The sugar concentration was higher in VS-22 root apices compared to AMCCG-2, and the amount of sugar accumulation increased with a decrease in Ψ(w). Significant amounts of trehalose accumulated in VS-22 and AMCCG-2 (29.8 µmol/g fresh weight [FW] and 5.24 µmol/g FW, respectively). Starch accumulation in the root apices of these two maize varieties also differed significantly, with a lower level in VS-22. In both varieties, the proline concentration also increased as a consequence of the water deficit. At 72 h, the proline concentration in VS-22 (16.2 µmol/g FW) was almost 3 times greater than that in AMCCG-2 (5.19 µmol/g FW). Trehalose also showed a 3-fold increase in the tolerant variety. Accumulation of these solutes in the root growth zone may indicate an osmotic adjustment (OA) to maintain turgor pressure.

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

Absence of plasma melatonin circadian rhythm during the first 72 hours of life in human infants.

To assess whether the circadian rhythm of melatonin (MT) described in umbilical cord blood of term babies is due to an active pineal in the newborn, we analyzed 119 normal neonates during the first 72 h of life. Plasma MT was measured by RIA in different neonates at different hours of the day. Statistical analysis consisted of comparison of the means of MT values grouped in two time periods of 12 h each [day period, 0900-2100 h (77 neonates); night period, 2100-0900 h (42 neonates)] and cosinor analyses to determine the existence of a circadian rhythm of MT. Mean MT levels did not vary greatly during the first 72 h of life, and no differences were found between day and night periods. These results suggest that the pineal gland in the neonate actively secretes MT, but not in a rhythmic manner, implying that the circadian rhythm of MT described previously in cord blood is a reflection of the maternal rhythm.

Characterization of nocturnal ultradian rhythms of melatonin in children with growth hormone-dependent and independent growth delay.

To assess the existence of a possible nocturnal ultradian rhythm of melatonin in children, we analyzed 28 pediatric patients (mean age, 9.08 +/- 2.2 yr) with GH-dependent and GH-independent growth delay. Plasma melatonin was measured by RIA in children sampled every 30 min between 2100-0900 h. Statistical analysis consisted of cluster analysis to examine the presence of peaks and troughs. The pattern of melatonin levels was related to the cause of growth delay, although the means of the nocturnal concentrations of melatonin were similar in all children. Interestingly, children with a GH deficit showed a nearly normal melatonin profile, whereas children with normal GH values but abnormal growth displayed atypical profiles of melatonin. The results also prove the existence of an ultradian rhythm of melatonin in most of the patients studied. The ultradian rhythm of melatonin in children was characterized by irregular interburst intervals, thus differing from the rhythm previously described in adults that had an almost constant pulse frequency. Moreover, the existence of low and high melatonin producers was revealed in the study, a feature unrelated to the cause of growth delay. The group of children with a GH deficit showed the lowest values of integrated melatonin production and of the area of peaks and troughs. These results prove that children exhibit an ultradian rhythm of melatonin like that in adults. Whereas it is not clear whether the episodic production of melatonin is required for its biological actions, the existence of irregular pulses may reflect endocrine influences at this age and/or the immaturity of the intrinsic pulse generator.

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress.

OBJECTIVE: To analyze the kynurenine and methoxyindole metabolic pathways of tryptophan in order to identify changes in premature neonates and in neonates suffering from fetal distress. METHODS: One hundred and twelve neonates were assigned to three groups: normal neonates (control group), preterm neonates (neonates born before the 37th gestational week) and neonates suffering from fetal distress. Each of these groups was then divided in two subgroups according to the time of birth corresponding with the time of blood sampling: a diurnal subgroup, comprising neonates whose blood was sampled between 0900 and 2100 h, and a nocturnal subgroup, comprising neonates whose blood was sampled between 2100 and 0900 h. Blood samples from the umbilical artery and vein were taken in the delivery room at birth from each neonate for measurement of melatonin, the main methoxyindole pathway metabolite. Urine samples were collected from 0900 to 2100 h (diurnal groups) and from 2100 to 0900 h (nocturnal groups), and the presence of kynurenic acid, xanturenic acid, 3-hydroxyantranilic acid, L-kynurenine and 3-hydroxykynurenine determined. RESULTS: The results show the existence of diurnal/nocturnal differences in the concentration of melatonin in cord blood and in the urinary excretion of kynurenines. In normal neonates, the production of methoxyindoles (determined as melatonin) is decreased during the day and increases at night, whereas production of kynurenines is high during the day, decreasing at night. In the fetal distress group, a significant increase in the umbilical artery concentration of melatonin was found. This group also showed a reduction in L-kynurenine concentrations in the diurnal and nocturnal groups, and an increase in xanturenic acid and 3-hydroxyantranilic acid during the day. Correlation and regression studies confirmed that the differences in the day/night pattern of the tryptophan metabolic pathways were greater in normal neonates than in the preterm and fetal distress groups. CONCLUSIONS: The results indicate the existence of an imbalance in tryptophan metabolites in preterm infants and those with fetal distress, blunting the normal diurnal/nocturnal rhythm of both melatonin and kynurenines.

Lipoproteins in pregnant women before and during delivery: influence on neonatal haemorheology.

AIMS: To investigate whether the lipid profile of pregnant women during parturition differs from the profile at previous stages of pregnancy and to determine the effects of maternal lipid changes on fetal or neonatal haemorheology. METHODS: Sixty pregnant women were studied, divided into two groups. Group 1 contained 30 women of mean age of 27 (SD 3) years and gestational age > 38 weeks in whom delivery had not yet begun; all these pregnancies followed an uncomplicated course and there was no evidence of any fetal pathology from previous obstetric examinations. All the women reached term and birth weight was 3340 (350) g. Group 2 contained women of mean age 26 (4) years, in whom delivery was ongoing, all of whose pregnancies reached term. The following variables were determined in all cases: total cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL), free fatty acids and phospholipids, and apoprotein A (apo-A) and apoprotein B (apo-B). Serum and plasma viscosity was measured with a capillary viscosimeter. RESULTS: The apo-B/apo-A and HDL/apo-A ratios increased during delivery, indicating that in pregnant women these atherogenic indices are raised during delivery compared with previous gestational stages. Significant correlation coefficients were obtained between maternal lipids (triglycerides, total cholesterol, LDL, total cholesterol/HDL, and LDL/HDL) and plasma viscosity in the neonate. CONCLUSIONS: Plasma atherogenic indices increase progressively until birth. These changes have implications for neonatal haemorheology because they cause an increase in plasma viscosity.

Day-night variations in melatonin secretion by the pineal gland during febrile and epileptic convulsions in children.

The pineal gland is a complex neuroendocrine organ with pronounced effects on central nervous system activity. Because previous studies in animals and humans have suggested an anticonvulsant role for the pineal hormone melatonin, we studied the day-night variations in plasma melatonin in normal children and children with febrile or epileptic convulsions. We found significant changes in day-night melatonin levels during convulsions, consistent with the hypothesis that melatonin has an inhibitory function on central nervous system activity.