Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development

Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ.

Cortisol, family coping and burden in informal caregivers of addicts

This study focuses on the prospective mediation role of family coping between burden and cortisol levels in informal caregivers of addicts as well as on the feasible use of two different ways to analyse the salivary cortisol levels. Participants were 120 Portuguese informal caregivers of addicts. The cortisol samples were collected at awakening, 45 minutes later and after a 30 minute presentation of images taken from the International Affective Picture System. Family coping and caregiver burden were measured using the Portuguese versions of the Caregiver Reaction Assessment, and the Family Crisis Oriented Personal Evaluation Scale. Cortisol samples were collected in salivettes and the results were computed in order to determine the Area Under the Curve scores (AUCg, AUCi). Results found family coping to be negatively correlated with burden and AUCg levels (i.e. overall intensity) and positively correlated with either AUCg and AUCi (i.e. change over time). The mediation model revealed that family coping was a partial mediator in the relationship between the burden and AUCg levels. Therefore, Family Coping appears to be an essential variable in understanding the stress response and should be considered in further studies and interventions. In addition, the use of two different formulas for calculating cortisol levels provided important new information concerning the relationship between cortisol, burden and family coping. It seems that burden has a more profound effect on the overall intensity of the neuroendocrine response to caregiver stress and not so much on the sensitivity of the system.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Infant’s psychophysiological profile and temperament at 3 and 12 months

This study is intended to analyze (1) differences in infant temperament at 3 and 12 months according to infants' psychophysiological profiles: "withdrawn" "extroverted", and "underaroused" and (2) changes in infant temperament from 3 to 12 months, namely according to the infant psychophysiological profile and the quality of mother-infant interaction. Ninety-four 8-week-old infants were assessed using the Neonatal Behavioral Assessment Scale (NBAS, Brazelton & Nugent, 1995) and the Alarm Distress Baby Scale (ADBB, Guedeney & Fermanian, 2001). Saliva samples were collected at 8-12 weeks old, both before and after a routine inoculation for cortisol reactivity measurement. Mother-infant interaction was evaluated at 12-16 weeks, using the Global Rating Scales (GRS, Murray, Fiori-Cowley, Hooper, & Cooper, 1996). Mothers' reports on infant temperament at 3 and 12 months were collected using the Infant Behavior Questionnaire (IBQ, Rothbart, 1981). Significant differences in mothers' perception of infant temperament were found at both 3 and 12 months in infants with distinct psychophysiological profiles. Stability was observed in most of the temperament's dimensions from 3 to 12 months old; still, there were changes in mothers' perception of infant temperament in terms of level of distress, cuddliness, sadness and approach. Infant psychophysiological profile and mother-infant interaction both influence with the pattern of those changes. The results corroborate that infant's characteristics early in life as well as contextual factors influence with mothers' perception of infant temperament and with changes across the 1st year of life.