Factors associated with cortisol levels and health in 5-6-year-old children.

OBJECTIVES: This study assesses the relationships between social context (family and inter-peer context), stress, and illness in 5-6-year-old children. METHODS: To this end, data were collected on spontaneous social interpeer behavior; families provided data on stress, anxiety, and parental acceptance-rejection; and the children's pediatricians provided data relative to their health. Data on stress-related hormones (cortisol) were collected using saliva samples. RESULTS: The results revealed that none of the variables examined were significantly related to illness development in the subjects in the sample group. Cortisol levels, however, were positively associated with a record of chronic or congenital illnesses, the manifestation of behaviors related to the search for leadership status in the group and the presence of stressful events in the family environment. CONCLUSIONS: Despite finding no relationship between children's level of adrenocortical activity and the contracting or contingent development of diseases, we did find that chronic/congenital diseases may constitute a source of early stress in childhood. Certain conditions of uncertainty in the social context (family and interpeer) also seem to constitute different sources of stress.

Effects of antalarmin and nadolol on the relationship between social stress and pulmonary metastasis development in male OF1 mice.

It has been found that acute social stress in male OF1 mice produced a general immunosuppression and increased B16F10 tumor development. This study examined the effects of blocking either the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic adrenomedullary (SAM) system on the impact of such stress on tumor development. Naive male OF1 mice were individually housed for 12 days before being inoculated with tumor cells or vehicle. Six days later, tumor-bearing mice were inoculated with antalarmin (a corticotropin-releasing factor receptor antagonist), nadolol (a beta-adrenergic antagonist) or vehicle. All these mice were subjected to social stress by pairing them for 24h with counterparts selected for their high and homogeneous levels of aggressiveness. The pairs were only in physical contact for three 5-min periods, being in sensory contact for the rest of this period. One hour after social stress, serum corticosterone and IFN-gamma levels were analyzed in each experimental group. Fifteen days later, lungs were removed to determine the number of metastatic foci with their areas, and blood samples were taken to assess serum titers of corticosterone and IFN-gamma. Both antalarmin and nadolol-treated mice developed significantly fewer metastatic foci with smaller areas than vehicle-treated subjects although only the group treated with antalarmin had reduced corticosterone levels. This study confirms that social stress has complex effects on immune system and tumor development that are not simply linked to corticosterone titers.

Outcomes of the Nutri-Senex project: a co-ordination action funded by the European Commission.

This project's primary aim is to contribute to the improvement of the quality of life of the elderly. The state of the art in age-related research and technology, to highlight the most promising areas for development, has been documented in an extensive literature report. A research database has been established to map current research activities within the European research area. Through several expert group meetings with representatives from universities, research institutions, organizations concerned with the care of the elderly, and industry, suitable technologies and policies that can improve the diet of the elderly have been identified. A legislation survey relating to aspects of nutrition of the elderly has been carried out. A set of guidelines and recommendations of best practice for use in the health and care industry have been developed. The project's results are disseminated through an enhanced website, technology transfer workshops and a staff training program. Good communication between the partners has been promoted and permanent research links have been forged. The main outputs will lead to better co-ordinated European research: less duplication of effort, more rapid commercialization, increased awareness of the problems faced by the elderly, improved guidelines and recommendations for health care professionals and policymakers.

Relations between different coping strategies for social stress, tumor development and neuroendocrine and immune activity in male mice.

This study analyzes the effects of acute social stress and different coping strategies employed in response to it on the development of B16F10 melanoma pulmonary metastases, the activation of the HPA axis and the NKG2D receptor expression. To this end, male OF1 mice were subjected to 24h of social stress using the sensorial contact model. This model includes three 5-min sessions of direct social interaction with resident cagemates selected for consistent levels of aggression. Subjects' behavior was videotaped and assessed. Six days after the first social interaction (1st social stress), the animals were inoculated with tumor cells or vehicle, and six days later, both tumor-bearing and non tumor-bearing mice were subjected to a second 24h sensorial contact social stress session (2nd social stress). One hour after the 2nd social interaction, corticosterone levels and NKG2D receptor expression were determined. Lung metastatic foci numbers were determined 21 days after inoculation (15 days post-stress). Social stress increased the number of pulmonary metastases and the serum corticosterone level. A combination of cluster and discriminant analyses established the existence of two types of coping strategies: (1) a passive-reactive strategy characterized by subjects dedicating a greater percentage of time to submission, flee and avoidance behaviors; and (2) an active-proactive strategy, characterized by subjects dedicating a greater percentage of time to attack and non social exploration behaviors. Subjects belonging to the passive-reactive group were found to have a higher number of tumor foci, a higher level of corticosterone and a lower NKG2D receptor expression than subjects in the active-proactive group. These data indicate the relationship between different coping strategies for social stress and tumor development.

Intestinal sensitivity testing by transmucosal electrical nerve stimulation: stimulus parameters to induce conscious perception.

Intestinal sensitivity can be tested using transmucosal electrical nerve stimulation. The aim of this study was to establish the stimulus characteristics that determine perception. In six healthy subjects constant current electrical stimuli were applied via an intrajejunal bipolar electrode while measuring perception. Intensity-response tests with stimuli trains of various frequencies (5 and 100 Hz) and pulse durations (50 and 1000 mus) were performed. All stimuli within the broad range tested induced similar-type abdominal sensations, but the intensity of the stimuli to produce perception differed depending on both pulse duration and frequency. A 20-fold increase in pulse duration decreased the intensity of perceived stimuli by a factor of 0.34 +/- 0.04 (P < 0.05); a similar increase in pulse frequency decreased the intensity by a 0.63 +/- 0.07 factor (P < 0.05). When the frequency and duration concomitantly increased, the stimulus intensity decreased by the product of both factors (0.22 +/- 0.04). Transmucosal electrical nerve stimulation of the intestine induces perception within a broad range of stimuli. However, the intensity of the stimuli required to activate sensory pathways is primarily weighted by the duration rather than by the frequency of the pulses.

Time-dependent behavioral, neurochemical, and immune consequences of repeated experiences of social defeat stress in male mice and the ameliorative effects of fluoxetine.

This study attempted to determine whether differing numbers of days of repeated defeat experience altered behavior, immune measures, and neuroendocrine mediators in mice. OF1 male mice were socially stressed by repeated experiences of defeat in a sensorial contact model. Subjects exposed to nine defeats showed more stretch-attend postures and fewer active defense elements than counterparts exposed to 23 defeats. Submissive subjects with nine experiences of defeat also had a lower splenocyte proliferative response than unmanipulated controls. The proliferation index progressively increased but at a higher rate in manipulated controls than in socially stressed subjects, resulting in a significant immunosuppressive effect after 23 days of exposure to social stressors. Nine days of such exposure resulted in higher hypothalamic ratios of serotonin and dopamine to their major metabolites than in unmanipulated or manipulated controls and subjects socially stressed for 23 days. The data generally indicate that the acute social stressors (such as nine defeats) produce a profile of behavioral and physiological variables characteristic of a state of anxiety. The proliferation index was also lower after 52 days of social stress than in manipulated controls. Fluoxetine treatment appeared to have an anxiolytic effect, reducing immobility, and even seemed to protect subjects from the immune impairment and endocrine alteration caused by social stressors. The results generally provide clues that improve our knowledge of the consequences of social stressors and their possible treatment.

Behavioral and neurochemical responses in mice bearing tumors submitted to social stress.

Through the proinflammatory cytokines secreted in response to inflammation or injury, the immune system produces physiological and behavioral alterations. This study analyzes the effects on behavior, mononuclear proliferative response and central monoamine activity in response to the inoculation of tumor cells in mice submitted to social stress. Two groups of male OF1 mice were used, one of which was inoculated with B16 melanoma cells. Both groups were subdivided into two new groups, with one being submitted to social stress through sensory contact model with a selected aggressive subject, and the other being handled without social interaction. Subjects were exposed to social stress for a 24-h period, with three 5 min intervals of direct physical interaction, where the behavior was recorded and assessed. One hour after the stress and/or handling, they were put down and samples taken for physiological assessment. Significant behavioral changes were found in subjects with implanted tumors, mainly characterized by an increase in avoidance behavior and a decrease in immobility, defense-submission and non-social exploration behavior, coupled with an increase in the spleen mononuclear cell proliferative response. Similarly, an increase was observed in the density of dopamine(2) (D(2))-receptors in the striatum (SRT) and an increase in dopaminergic (DOPAC/DA) and serotonergic (5HIAA/5HT) turnover in the hypothalamus. The increase in the density of D(2)-receptors in the SRT coincides with the decrease in some behaviors with a predominant motor component. The results indicate significant changes in the defensive strategy used to cope with situations of intense social stress in mice bearing tumors.

Endocrine and lymphoproliferative response changes produced by social stress in mice.

Daily dyadic resident-intruder encounters and uninterrupted cohabitation in pairs were used to assess the impact of different durations (5 and 15 days) of dominance and subordination experiences on splenic lymphoproliferative responses in male OF1 strain mice. HPA axis activity was assessed by measuring serum corticosterone levels, whereas splenic norepinephrine (NE) content provided a sympathetic activity index. Corticosterone levels in subordinate subjects were generally higher than in their control or dominant counterparts in both treatment paradigms. Corticosterone levels in dominant subjects were lower than in their control counterparts in both. Increasing the duration of treatments generally decreased such titers, especially so in subordinate subjects. No differences were detected in splenic NE content. Animals subjected to social interaction generally showed greater proliferation than their control counterparts. This effect was more pronounced in subordinates than dominants and after longer- rather than short-duration treatments. There was no inverse relation between proliferative responses and the subject's corticosterone levels. While corticosterone may have a general immunomodulating effect, other mediators apparently account for the effects produced by these social stress paradigms on splenic proliferative response.

Social stress paradigms in male mice: Variations in behavior, stress and immunology.

Male OF1 strain mice were allocated, after 2 weeks of individual housing, to cohabitating (6 or 16 days), fixed dyadic interaction pairs (6 or 16 daily encounters) or control groups (6 or 16 days). These different social stress situations were assessed for their effects on splenic contents of NE, IL-1 and IL-2 and serum levels of corticosterone. Spleen NE contents showed no significant variations, but serum corticosterone titers were generally higher in interacting pairs and subordinates. Splenic IL-2 did not respond in the same way to the treatments as IL-1. The differences in splenic interleukin contents could not be simply related to observed changes in serum corticosterone levels. Different mechanisms appear to regulate changes in glucocorticoids and the measured cytokines. These physiological phenomena do not simply reflect in the animal's social status (dominant or submissive). The intensity and duration of the agonistic behavior displayed as well as the interaction experience accumulated may account for the observed differences between the paradigms.

Social behavior, cortisol, and sIgA levels in preschool children.

OBJECTIVE: This study aims to explore the possible existence of behavioral states in early stages of development, which are associated with specific cortisol production profiles and consequently with changes in the immune response [secreted immunoglobulin A (sIgA)]. METHODS: The subjects were 27 boys and 21 girls of preschool age whose behavior was videotaped in free play interactions. Their behavior was then evaluated using an ethogram of the social behavior of the child. Cortisol levels were measured using a radioimmunoassay in saliva samples, and sIgA levels were measured by means of an ELISA, also in saliva samples. RESULTS: No correlation between cortisol and sIgA levels was found. Variance analysis revealed that the only behavioral pattern, which showed significant differences with regard to cortisol levels, was isolation. CONCLUSIONS: There seems to be a connection between cortisol levels and isolation behavior; we found no relation between high cortisol levels and a lower sIgA secretion.

Relating testosterone levels and free play social behavior in male and female preschool children.

This study assessed potential relationships between a series of behavioral measures seen in the interactions of preschool children with their peers (particularly aggressive behavior) and testosterone levels. 28 boys and 20 girls of preschool age were videotaped in free play interactions. Their behavior was then evaluated with particular emphasis on aggression and affiliation in play and social interactions. Testosterone levels were measured using radioimmunoassay in saliva samples. Correlation analysis revealed a positive relationship in boys between testosterone and giving and receiving aggression in the context of 'social interactions' (serious aggression), but not in the context of play (playful aggresstion). Testosterone can be a useful biological marker for serious aggression (and behavioral patterns reflecting different levels of sociability) in preschool boys.

Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice.

There is increasing evidence that stress and emotional reactions produce changes in various immune processes. These changes may be due to alterations of the stress responses endocrine and for autonomic mediating mechanisms. In order to study such effects, the impact of chronic mild stress (CMS) application, and of subsequent imipramine administration were studied on the spleen mononuclear cell proliferative response period. OFI strain male mice were subjected to 4 or 7 weeks of CMS. The effects of these treatments on serum corticosterone levels and hypothalamic and hippocampal norepinephrine (NE) contents were also assessed. Subjects submitted to CMS had a higher spleen mononuclear cell proliferative response after either treatment duration. Imipramine treatment diminished this response enhancement in CMS exposed animals, but did not alter the proliferative responses of control subjects. Serum corticosterone levels, as well as hypothalamic and hippocampal nonrepinephrine contents did not significantly vary between groups. Taken together, these results suggest that CMSs effects on immune reactivity are not related to serum glucocorticoids or NE changes in these locations associated with the hypothalamic-pituitary- adrenocortical (HPA) axis.

Effects of two selective dopaminergic antagonists on ethologically-assessed encounters in male mice.

1. Although it is accepted that dopaminergic antagonists suppress aggressive behaviour, the drugs used have been relatively non-selective or specific to the D2 receptor. 2. The selective D1 antagonist, SCH 23390, makes it possible to evaluate the impact of this receptor on aggressive behaviour. 3. The effects of SCH 23390 and Spiperone (a D2 antagonist) on the aggressive behaviour of mice were assessed employing a "standard opponent" test. 4. Both drugs markedly decreased aggressive behaviour whilst increasing immobility. However, whilst SCH 23390 increased immobility to a small extent, Spiperone, produced a general decline in active behaviours. 5. It appears that the D1 receptor inhibition of aggression is the more specific.

Clozapine: strong antiaggressive effects with minimal motor impairment.

Clinical studies have shown clozapine to be effective in the treatment of schizophrenia and associated with an extremely low incidence of extrapiramidal side effects. Diverse studies indicate that clozapine is an atypical neuroleptic with a preferential activity on the mesolimbic structures and a lower affinity for striatal D2 receptors than the classical antipsychotics. The purpose of this study was to assess the behavioral properties of clozapine, especially its effects on aggressive and motor behaviors. Individually housed male mice of the OF1 strain were exposed to anosmic "standard opponents" 30 minutes after the last drug administration. One category of animals received a single IP dose of the compound (0.2, 0.5, 1 or 1.5 mg/kg). Another category received daily doses (0.5, 1 or 1.5 mg/kg) for 21 days. Encounters were videotaped and behavior evaluated using an ethologically based analysis. Clozapine, in the acute treatment condition, produced a significant decrease in "attack" and "threat" behaviors without "immobility" being significantly increased. These results suggest a rather specific antiaggressive action of the compound with little motor impairment. In the chronic administration, no significant change in aggressive behavior was observed which may be attributed to the development of some degree of tolerance.

[Prune belly syndrome. Etiopathogenic considerations in 4 cases]. / Síndrome de la tríada prune belly. Consideraciones etiopatogénicas sobre cuatro casos.

Four cases of prune belly syndrome of 19, 24, and 32 weeks of gestational age, and 14 days of postnatal life are described. All of them show urethral atresia, muscle defects of abdominal wall and undescended testes. Analysis of these four cases at different developmental stages brings authors to approach etiopathogenic basis of this syndrome.

Evaluación del uso de los antibióticos en el Hospital de Clínicas "José de San Martín" / Evaluation of antibiotics use at the Hospital of Clinical José de San Martín

El 18 de junio de 1986 se efectuó en el Hospital de Clínicas José de San Martín un estudio para evaluar el uso de los antibióticos en pacientes internados y los gastos que surgen de su empleo inadecuado. El 28% de los internados recibían antibióticos, el 69% de las indicaciones con finalidad terapéutica y el 35% de las profilaxisis fueron correctas. El error más frecuente en el tratamiento fue el uso del antibiótico no electivo y en la profilaxis, la utilización innecesaria. El gasto por uso inadecuado fue de u$s 494.17 en un día, u$s 14.825 en un mes y u$s 180.372 por año

Evaluación del uso de los antibióticos en el Hospital de Clínicas "José de San Martín" / Evaluation of antibiotics use at the Hospital of Clinical José de San Martín

El 18 de junio de 1986 se efectuó en el Hospital de Clínicas José de San Martín un estudio para evaluar el uso de los antibióticos en pacientes internados y los gastos que surgen de su empleo inadecuado. El 28% de los internados recibían antibióticos, el 69% de las indicaciones con finalidad terapéutica y el 35% de las profilaxisis fueron correctas. El error más frecuente en el tratamiento fue el uso del antibiótico no electivo y en la profilaxis, la utilización innecesaria. El gasto por uso inadecuado fue de u$s 494.17 en un día, u$s 14.825 en un mes y u$s 180.372 por año (AU)