Early-Life Stress as a Probe to Study the Opioid System in Developing Rodents.

The developmental origins of disease or fetal programming model predict that early (intrauterine and/or postnatal) exposures to external insults of sufficient length and intensity may have enduring or lifelong consequences for physical and psychological health. The method described in this chapter considers an animal model to study the pathophysiological alterations connected to an HPA axis (hypothalamic-pituitary-adrenal) hyperactivity that are induced by an early-life stressful procedure involving the opioid system.

Etiopathogenesis and Pharmacological Prevention of a Type-2 Diabetes Model in Male Mice.

We describe a stress-derived type-2 diabetes model in male mice, and formulate new hypotheses on how the model was induced, how diabetes-like alterations were prevented through specific pharmacological treatments, and how its possible neuroendocrine pathogenesis could be hypothesized. Pregnant females arrived in our laboratory on their 14th day of conceptional age. After birth, control mice never showed any apparent behavioral-metabolic-endocrine alterations. However, application of postnatal stress (brief mother deprivation, plus sham injection, daily from birth to weaning), was followed in adult male mice by two series of diabetes-like alterations. Some alterations (e.g., body overweight, immune, neurophysiologic, neurobehavioral alterations) were selectively prevented by opioid antagonist naloxone daily administered during nursing period. The aforementioned alterations plus several others (e.g., hyperglycemia, neuroendocrine alterations) were prevented by administration of specific antisense oligodeoxinucleotide, which modulated synthesis-hyperfunction of proopiomelanocortin-derived corticotropin (ACTH)-corticosterone and endorphins in the pituitary. Surprisingly, together with metabolic alterations, enduring increment of neurophysiologic/neurobehavioral brain performances were observed, accompanied by energy compensative reactions, and brain mitochondria hyperfunction. Thus, increased glycemia/lipidemia appeared to furnish fuel necessary to cope with increased request of energy. Diabetes-like alterations were accompanied by enduring hyperfunction of opioid- and ACTH-corticosterone-endogenous structures in the brain, which were apparently due to failure of negative feedback hormone mechanisms in the pituitary, for the control of the hypothalamus-pituitary-adrenal axis. In conclusion, for the first time we can hypothesize that a diabetes-like syndrome is produced by enduring hyperfunction of two proopiomelanocortin-dependent endogenous systems (brain opioid- and ACTH-corticosterone systems), following failure of pituitary feedback hormonal control, after complex stress procedures.

Antisense versus proopiomelanocortin mRNA reduces vascular risk in a murine model of type-2 diabetes following stress exposure in early post-natal life.

Mechanisms of vascular complications in type-2 diabetes patients and animal models are matter of debate. We previously demonstrated that a double-stress model applied to male mice during nursing period produces enduring hyperfunction of endogenous opioid and adrenocorticotropin (ACTH)-corticosteroid systems, accompanied by type-2 diabetes-like alterations in adult animals. Administration of the opioid receptor antagonist naloxone, or of an antisense oligodeoxynucleotide versus proopiomelanocortin mRNA, capable to block the pro-opiomelanocortin-derived peptides ß-endorphin and ACTH, selectively prevent these alterations. Here, we investigated alterations produced by our stress model on aorta endothelium-dependent relaxation and contractile responses. Mice, stressed during nursing period, showed in the adulthood hormonal and metabolic type-2 diabetes-like alterations, including hyperglycemia, increased body weight and increased plasma ACTH and corticosterone levels. Ex vivo isolated aorta rings, gathered from stressed mice, were less sensitive to noradrenaline-induced contractions versus controls. This effect was blocked by nitric-oxide synthase-inhibitor l-N(G)-nitroarginine added to bath organ solution. Aorta rings relaxation caused by acetylcholine was enhanced in stressed mice versus controls, but following treatment with the nitric-oxide donor sodium nitroprusside, concentration-relaxation curves in aorta from stressed groups were similar to controls. Therefore, vascular response alterations to physiologic-pharmacologic stimuli were apparently due to nitric-oxide hyperfunction-dependent mechanisms. Aorta functional alterations, and plasma stress hormones enhancement, were prevented in mice stressed and treated with antisense oligodeoxinucleotide, addressed to reduce ACTH- and corticosteroid-mediated hyperfunction. This study demonstrates the key role of ACTH-corticosteroid axis hyperfunction for the triggering of vascular conditions in male adult rodents following postnatal stress in a type-2 diabetes model.

Enhanced brain performance in mice following postnatal stress.

The double postnatal stress model (brief maternal separation plus sham injection daily applied from birth to weaning) induces metabolic alterations similar to type 2 diabetes in young-adult male mice. We verify whether 1) the stress also induces brain metabolic-functional alterations connected to diabetes and 2) different alterations are modulated selectively by two stress-damaged endogenous systems (opioid- and/or ACTH-corticosteroid-linked). Here, diabetes-like metabolic plus neurophysiologic-neurometabolic parameters are studied in adult mice following postnatal stress and drug treatment. Surprisingly, together with 'classic' diabetes-like alterations, the stress model induces in young-adult mice significantly enhanced brain neurometabolic-neurophysiologic performances, consisting of decreased latency to flash-visual evoked potentials (- ~8%); increased level (+ ~40%) and reduced latency (- ~30%) of NAD(P)H autofluorescence postsynaptic signals following electric stimuli; enhanced passive avoidance learning (+ ~135% latency); and enhanced brain-derived neurotrophic factor level (+ ~70%). Postnatal treatment with the opioid receptor antagonist naloxone prevents some alterations, moreover the treatment with antisense (AS; AS vs proopiomelanocortin mRNA) draws all parameters to control levels, thus showing that some alterations are bound to endogenous opioid-system hyper-functioning, while others depend on ACTH-corticosterone system hyper-functioning. Our stress model induces diabetes-like metabolic alterations coupled to enhanced brain neurometabolic-neurophysiologic performances. Taken all together, these findings are compatible with an 'enduring acute-stress' reaction, which puts mice in favorable survival situations vs controls. However, prolonged hormonal-metabolic imbalances are expected to also produce diabetes-like complications at later ages in stressed mice.

Potential therapeutic effects of vitamin e and C on placental oxidative stress induced by nicotine: an in vitro evidence.

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.

Post-natal stress-induced endocrine and metabolic alterations in mice at adulthood involve different pro-opiomelanocortin-derived peptides.

In previous investigations we added a physical stress (mild pain) to the "classical" post-natal psychological stress in male mice, and we found that this combination produced a series of dysmetabolic signs very similar to mild human type-2 diabetes. Here, for the first time we demonstrate that within this diabetes model at least two groups of signs depend on the unbalance of two different endogenous systems. Newborn male mice were daily exposed to stressful procedures for 21 days (brief mother separation plus sham injection). Other groups underwent the same procedure, and also received naloxone (Na) to block µ-δ endogenous receptors, or a phosphorothioate antisense oligonucleotide (AS) directed against pro-opiomelanocortin (POMC)-mRNA [to block adrenocorticotropin (ACTH)- and POMC-derived opioid peptides]. Adult mice which received only post-natal stress increased body weight (+7.5%), abdominal overweight (+74%), fasting glycemia (+43%), plasma corticosterone (+110%), plasma (+169%) and pituitary (+153%) ACTH levels. Conversely, hypothalamic ACTH and corticotropin-releasing hormone (CRH) were reduced (-70% and -75%, respectively). Neonatal AS administration reverted all parameters to control values. Neonatal naloxone had little or no influence on glucose, corticosterone, ACTH, CRH levels, whereas it prevented body overweight and abdominal overweight. We conclude that, within this type-2 diabetes model in male mice at least two endocrino-neurohumoral systems are damaged, one concerning the opioid system, and the other concerning HPA hormones. The use of the two drugs was of primary importance to demonstrate this statement, and to demonstrate that these two groups of signs could be defined as "separate entities" following our complex post-natal stress model.

Sexual dimorphic evolution of metabolic programming in non-genetic non-alimentary mild metabolic syndrome model in mice depends on feed-back mechanisms integrity for pro-opiomelanocortin-derived endogenous substances.

Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (POMC) endogenous systems alterations in male mice at weaning. These alterations last up to adult age, and are at the basis of adult hormonal and metabolic conditions similar to mild metabolic syndrome/type-2 diabetes. Here, we evaluate how sex influences post-natal programming in these metabolic conditions. Subjects are adult control (non-handled) female (NHF) and male (NHM) CD-1 mice; adult post-natal handled female (HF) and male (HM) mice. Handling consists of daily maternal separation (10 min) plus sham injection, from birth to weaning (21 days). In adult handled males (90-days old) we find not only POMC-derived hormones alterations (enhanced basal plasma corticosterone (+91%) and ACTH (+109%)) but also overweight (+5.4%), fasting hyperglycemia (+40%), hypertriglyceridemia (+21%), enhanced brain mRNA expression of hydroxysteroid(11-beta)dehydrogenase type-1 (HSD11B1) (+49%), and decreased mRNA-HSD11B2 (-39%). Conversely, uric acid, creatinine, HDL(C), total cholesterol, glucose and insulin incremental area under-the-curve are not affected. In females, post-natal handling does not produce both hormonal and dysmetabolic diabetes-like changes; but handling enhances n3- and n6-poly-unsaturated, and decreases saturated fatty acids content in erythrocyte membrane composition in HF versus NHF. In conclusion, for the first time we show that female sex in mice exerts effective protection against the hypothalamus-pituitary-adrenal homeostasis disruption induced by our post-natal handling model on POMC cleavage products; endocrine disruption is in turn responsible for altered metabolic programming in male mice. The role of sex hormones is still to be elucidated.

EEG responses to visual landmarks in flying pigeons.

BACKGROUND: GPS analysis of flight trajectories of pigeons can reveal that topographic features influence their flight paths. Recording electrical brain activity that reflects attentional processing could indicate objects of interest that do not cause changes in the flight path. Therefore, we investigated whether crossing particular visual landmarks when homing from a familiar release site is associated with changes in EEG. RESULTS: Birds carried both data-loggers for recording GPS position and EEG during flight. First, we classified characteristic EEG frequencies of caged birds and found five main bands: A: 0-3, B: 3-12, C: 12-60, D: 60-130, and E: 130-200 Hz. We analyzed changes in these activity bands when pigeons were released over sea (a featureless environment) and over land. Passing over the coastline and other prominent landmarks produced a pattern of EEG alterations consisting of two phases: activation of EEG in the high-frequency bands (D and/or E), followed by activation of C. Overlaying the EEG activity with GPS tracks allowed us to identify topographical features of interest for the pigeons that were not recognizable by distinct changes of their flight path. CONCLUSIONS: We provide evidence that EEG analysis can identify landmarks and objects of interest during homing. Middle-frequency activity (C) reflects visual perception of prominent landmarks, whereas activation of higher frequencies (D and E) is linked with information processing at a higher level. Activation of E bands is likely to reflect an initial process of orientation and is not necessarily linked with processing of visual information.

Neurobiology of pain in children: an overview.

The evaluation of pain in the newborn and the infant is difficult because pain is mainly a subjective phenomenon. Until a few years ago, several myths persisted. First, the myth that children, especially infants, do not feel pain the way adults do, therefore there is no untoward consequences for them. Second, lack of assessment and reassessment for the presence of pain. Third, misunderstanding of how to conceptualise and quantify a subjective experience. Fourth, lack of knowledge of pain treatment. Fifth, the notion that addressing pain in children takes too much time and effort, in ultimate analysis resulting in wasting time. Sixth, fears of hidden -and not easy to diagnose or prevent- adverse effects of analgesic medications, including respiratory depression and addiction. Finally, from a conceptual point of view, high thresholds of pain in neonates and infants were considered to be present by natural character, and useful in protecting infant from pain during birth and transit through the narrow vaginal channel.The present review is focused on the description of different theories on the pain pathogenesis in children.

Estrogen exposure in a child from hair lotion used by her mother: clinical and hair analysis data.

Premature estrogenic effects may result from exogenous exposure to estrogenic substances. We report the case of a 36-month-old girl who presented with vaginal bleeding, uterus enlargement, and thelarche. Questioning of the parents revealed that the child's mother had used hormone-based hair lotions on her own scalp and that the child was in the habit of playing with her mother's hair while falling asleep, and that the girl played with her mother's combs and the empty lotion vials. The onset of hyperestrogenic syndrome was temporally related to the handling of lotions containing ethynylestradiol 0.5%. Analysis of long scalp hairs from the girl and her mother identified ethynylestradiol in concentrations of 10.6 and 46.6 microg/g, respectively. Six months after the mother discontinued use of the estrogen-containing hair lotion, the girl's hyperestrogenic signs resolved. This case highlights the importance of obtaining histories of possible food and non-food environmental sources of contamination, the suitability of hair sampling to identify the origin of the contamination, and the opportunity to warn parents about hazards related not only to oral contraceptives, but also custom-compounded topical hormone preparations.

Functional interference of dexamethasone on some morphine effects: hypothesis for the steroid-opioid interaction.

The effect of dexamethasone (DEX) and its interaction with morphine has been studied on transmurally-stimulated guinea-pig ileum preparation, gastrointestinal transit and analgesia. TRANSMURALLY-STIMULATED GUINEA-PIG ILEUM PREPARATION: DEX dose-dependently reduced the contractions of the ileum. Proteic synthesis inhibitors did not modify the inhibition induced by DEX whereas RU-38486, a glucocorticoid antagonist receptor, antagonized completely the inhibitory effect of DEX. GASTROINTESTINAL TRANSIT: DEX was found to antagonize morphine-, atropine- and verapamil-induced constipation. Cycloheximide does not modify the DEX effects. RU-38486 reverses both the inhibitory action of DEX on gastrointestinal transit and its reducing effect on morphine-induced constipation. ANALGESIA: DEX reduced the antinociception induced by mu agonists, morphine, DAMGO and beta endorphin whereas the steroid exerted little or no influence on the antinociception induced by a delta1 agonist, DPDPE and delta2 agonist deltorphin II. DEX potentiated the antinociception induced by the K agonist, U50,488. Cycloheximide, a protein synthesis inhibitor, prevented the antagonism by DEX of responses to the mu opioid agonists. Finally, i.c.v. injection of DEX significantly reduced morphine analgesia in Swiss mice whereas no effects were observed in DBA/2J and C57BL/6 mice. In addition, i.p. injection of DEX significantly reduced morphine analgesia in all three strains. Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the mu. receptor level, while delta and K receptors are modulated in different ways. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for DEX and RU 38486 action as well as the use of different genetic strains may provide a useful approach for studying DEX-morphine analgesia interaction.

Neonatal taurine administration modifies metabolic programming in male mice.

The semi-essential amino-acid taurine is involved in glucose homeostasis either in adults or in parental life. Taurine is currently used in neonatal life because it is added to milk formula for babies, and to parental solution for prematures. Here, it has been examined whether taurine administration in lactation modifies adult glucose metabolism. Neonatally taurine-treated mice (50 mg/kg body weight/day, for the first 21 days of life) as adults have lower basal glucose and iAUC after glucose loading curves in comparison with vehicle-treated mice, whereas iAUC following insulin loading curves, plasma lipids and malondialdehyde (MDA), an index of lipid peroxidation were not significantly changed. Thus, in rodents, neonatally administered taurine produces enduring effects in a way that could be advantageous for the control of glucose homoeostasis.

A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model.

Beta(2)-receptor adrenergic agonists as clenbuterol and analogues are illegally used as growth promoters in cattle, in Europe, as well as in other countries. Following consumption of meat or liver, intoxication cases were described, and cardiovascular toxic effects (tachycardia, hypertension) were of clinical relevance. Therefore, we investigated whether heart rate increase induced by clenbuterol could depend upon stimulation of beta(1)- and/or beta(2)-adrenergic receptors, and in which ratio. We used in vitro guinea-pig atria, a model in which beta(1)-/beta(2)-receptors ratio is similar to that found in men. In our experiments both beta(1)- and beta(2)-receptors contributed to clenbuterol-induced heart rate increase, but with a different potency. The selective beta(2)-antagonist ICI-118,551 competitively antagonized responses to clenbuterol with high affinity (pA(2) 9.47+/-0.28, SchildSlope 0.98+/-0.20 not significantly different from unity, K(B) 0.34 nM). The selective beta(1)-antagonist atenolol antagonized clenbuterol with a relatively lower affinity (pA(2)=7.59+/-0.14), the SchildSlope=1.97+/-0.33 was significantly different from unity (P<0.05). Results show that clenbuterol stimulates guinea-pig heart rate by acting chiefly on beta(2)-adrenoceptor, although responses to clenbuterol apparently are mediated by an inter-play between both beta-adrenoceptors. Further experiments are necessary to understand which beta-adrenergic antagonists are of effectiveness to counteract cardiovascular effects in case of intoxication following clenbuterol, or other beta-adrenergic stimulants.

Ex vivo formation of gastric metabolites of clenbuterol: preliminary characterisation of their chemical structure.

The epidemiology of clenbuterol food-borne intoxication outbreaks indicates a possible discrepancy between the severity and long duration of clinical symptoms, and the presumed dose ingested as parent compound residue. In this work, we explore the possibility that clenbuterol could undergo to a biological transformation, in presence of salivary nitrites, at gastric pH (< 3). Human salivary specimens were drawn before and after meal, accounting for the different physiological nitrite content (40 and 400 micromol L(-1), respectively, as average). Clenbuterol (10 micromol L(-1)) was then incubated within the pH range 2-6 and possible products monitored by liquid chromatography-mass spectrometry (LC-MS), drawing at regular intervals serial aliquots of the incubation mixture. With respect to controls, two differential peaks were noted along with a quantitative bio-transformation of the parent compound, at pH values < or = 3. Under pre-meal conditions, a 4 mono-nitro compound was identified as main metabolite, whereas under post-meal condition a second metabolite, showing a complete de-chlorination, along with the probable presence of three nitro groups on the aromatic ring, was revealed. The reaction was highly reproducible and the kinetics suggested the involvement of nitrogen-related free radicals. The results are discussed in the light of the possible formation of pharmacological active tissue-bound residues as cause of symptoms severity.

Taurine in women with a history of gestational diabetes.

Taurine is the most abundant amino acid in the human body and seems to play an important role in increasing glucose-mediated insulin secretion, as well as in programming beta-cell maturation during the prenatal life in utero. To test the hypothesis that plasma taurine is related to glucose tolerance, insulin sensitivity and insulin secretion in subjects with history of beta-cell dysfunction such as women with history of gestational diabetes (GDM), we studied 72 non-diabetic women with history of GDM (n=43), impaired glucose tolerance (IGT; n=7), and normal glucose tolerance (NGT; n=22) as previously classified by a 100g-3h-OGTT performed between the 24th and the 28th gestational week. Insulin sensitivity (ISIogtt, calculated through Matsuda-DeFronzo index) and a proxy for insulin secretion (basal plasma C-peptide/fasting plasma glucose; CP/glucose) were measured during and after pregnancy. Plasma taurine was measured after a median period of 6 years (2-11 years) from index pregnancy, when glucose tolerance was retested by a 75 g-2h-OGTT. Plasma taurine was significantly lower in women who had experienced GDM and was unrelated to ISIogtt. Moreover, plasma taurine was inversely related to previous gestational area-under-curve of glucose and directly related to post-gestational CP/glucose, as well to CP/glucose measured during pregnancy (p<0.05 for both). The relative risk of altered glucose metabolism during previous pregnancies (IGT+GDM) was higher as plasma taurine decreased, even after adjusting for age, time-lag from pregnancy, body mass index and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003). In conclusion plasma taurine seems to be a fair marker of altered glucose metabolism during past pregnancies in women with antecedent GDM and appears to be inversely related to the previous as well as to the actual insulin secretion in these subjects.

Administration of antisense oligonucleotide against pro-opiomelanocortin prevents enduring hormonal alterations induced by neonatal handling in male mice.

Early life events have been implicated in the programming of adult chronic diseases. Several investigations suggest that the role of early environment in influencing development mainly involves the hypothalamic-pituitary-adrenal axis. Therefore, we examined whether 1) daily neonatal handling, applied from birth to weaning induces HPA hormones alterations in mice lasting up to the adult age; and 2) if the administration of an antisense oligodeoxynucleotide versus pro-opiomelanocortin (As-POMC) prevents hormonal alterations observed in previously handled mice (Handled). In the adult phase (90 days), Handled are overweight and have higher basal plasma immuno-reactive (ir)-corticosterone and adrenocorticotropin (ir-ACTH), and higher pituitary ir-ACTH; while they have lower hypothalamic ir-ACTH and corticotropin-releasing hormone (ir-CRH) in comparison with the non-handled mice. As-POMC (0.05-0.1 nmol/g body weight per day) administered during the same period dose-dependently prevents the increase in body weight, in plasma ir-corticosterone, ir-ACTH, and pituitary ir-ACTH, also preventing the decrease in hypothalamic ir-CRH and ir-ACTH; while the mismatch oligonucleotide is nearly inactive. This data indicates that pharmacological treatment in neonatal life may have enduring effects, reducing the alterations in hormonal homeostatic programming mechanisms induced by early repeated handling.

Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study.

The methanol extract from Hypericum hircinum leaves exhibited in vitro inhibition of monoamine oxidases (MAO). Bioassay-guided fractionation led to the isolation of quercetin and five compounds identified for the first time from H. hircinum. Quercetin was the only compound with a selective inhibitory activity against MAO-A, with an IC50 value of 0.010 microM. To explain MAO selective inhibition at the molecular level, a computational study was carried out by conformational search and docking techniques using recently determined crystallographic models of both enzymatic isoforms. An in vivo study in mice was carried out using the forced swimming test in order to elucidate the behavioral effects of quercetin.

Overweight and metabolic and hormonal parameter disruption are induced in adult male mice by manipulations during lactation period.

Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features.

Adolescence as possible critical temporal window for blood pressure short term monitoring in boys and girls.

Adolescence is a critical temporal window for the development of obesity in adult age. We studied this period for short-term monitoring of blood pressure in both genders. Weight, height, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP) were recorded in 937 adolescents, 474 boys and 463 girls aged 12 years, and again 2 years later in the same subjects. Boys with BP values > or = 95th percentile at both ages (no. = 8) showed at 12 years weight (kg 61.4) height (cm 159.5) and BMI (23.5), and also at 14 years (77.0, 172.4, 25.6) values consistently higher than boys with high BP values at either ages taken singularly (no. = 32 + 32) (mean 49.2, 154.4, 21.5, respectively, at 12 years, and 62.1, 167.0, 22.2 at 14 years). These 64 boys, had values higher than boys with BP always below the 95th percentile (no. = 402) (45.5, 151.4, 19.7 at 12 years, and 56.9, 164.6, 20.9 at 14 years). This was confirmed for weight and BMI in girls. Stepwise logistic regression revealed that weight at 12 years and high BP values at 12 years were predictive independent risk factors for hypertension at 14 years. Odds ratio indicated that increment of body weight unit (1 kg) at 12 years predicted an average increase of 4% of risk for high BP values at 14 years, while high BP values at 12 years was predictive for a 2.19 times risk for high BP values at 14 years. Body weight, BMI and BP at 12 years of age may give useful indications for the prevision (and possible prevention) of hypertension and overweight at 14 years of age.

Neurophysiological studies of Heteropteris glabra Hok. & Arn. (Malpighiaceae) in DBA/2J mice.

Fruits of Heteropterys glabra (Malpighiaceae) are used in South-American folk medicine as a sedative and anxiolytic agent. In present research, we studied neurophysiological effects of the plant. Ethanolic extract was assayed in DBA/2J mice in order to evaluate the sleep wakefulness cycle, electroencephalogram (EEG) and visual evoked potentials (VEP). The results of our experiments indicated that the EtOH extract of the plant induced a reduction of motor activity and alterations of EEG and VEP parameters, supporting the possibility that the plant acts as an anxiolytic/sedative agent, thus, confirming its usual assumption and the traditional use.