Brain mechanisms underlying emotional alterations in the peripartum period in rats

In the period before and after parturition, i.e., in pregnancy and lactation, a variety of neuroendocrine alterations occur that are accompanied by marked behavioral changes, including emotional responsiveness to external challenging situations. On the one hand, activation of neuroendocrine systems (oxytocin, prolactin) ensures reproduction-related physiological processes, but in a synergistic manner also ensures accompanying behaviors necessary for the survival of the offspring. On the other hand, there is a dramatic reduction in the responsiveness of neuroendocrine systems to stimuli not relevant for reproduction, such as the hypothalamo-pituitary-adrenal (HPA) axis responses to physical or emotional stimuli in both pregnant and lactating rats. With CRH being the main regulator of the HPA axis, downregulation of the brain CRH system may result in various behavioral, in particular emotional, adaptations of the maternal organisms, including changes in anxiety-related behavior. In support of this, the lactating rat becomes less emotionally responsive to novel situations, demonstrating reduced anxiety, and shows a higher degree of aggressive behavior in the test for agonistic behavior as well as in the maternal defense test. These changes in emotionality are independent of the innate (pre-lactation) level of anxiety and are seen in both rats bred for high as well as low levels of anxiety. Both brain oxytocin and prolactin, highly activated at this time, play a significant role in these behavioral and possibly also neuroendocrine adaptations in the peripartum period.     

Postantibiotic and sub-MIC effects of benzylpenicillin against Streptococcus pneumoniae with different susceptibilities for penicillin

BACKGROUND: The purpose of the study was to examine whether penicillin-susceptible and nonsusceptible strains of Streptococcus pneumoniae exhibited different pharmacodynamic responses to benzylpenicillin. METHODS: The postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects (PA SMEs) were investigated by optical density against strains of S. pneumoniae with different susceptibilities to benzylpenicillin. To validate the data, the PAE and PA SME of one susceptible and one resistant strain were also tested with the viable count method. The post-MIC effects (PMEs) were studied in an in vitro kinetic model, simulating human pharmacokinetics with a half-life of 1 h and a time above MIC of approximately 20% of 24 h. RESULTS: There were no differences with respect to the PAEs, PA SMEs and PMEs of benzylpenicillin for the various strains of S. pneumoniae, irrespective of their susceptibility to penicillin. For both some of the susceptible and resistant strains investigated, longer PA SMEs at 0.2 and 0.3 x MIC were noted, indicating that these parameters might be more dependent on the type of strain rather than on the susceptibility status. CONCLUSION: No differences in the pharmacodynamic response after similar drug exposure were seen for S. pneumoniae strains with different penicillin susceptibility.     

Systemic Osmotic Stimulation Increases Vasopressin and Oxytocin Release Within the Supraoptic Nucleus

Vasopressin (VP) and oxytocin (OT) are released within the hypothalamic nuclear region in response to direct microdialysis with hypertonic solutions. Experiments were performed to determine whether systemic osmotic stimulation causes changes in intranuclear peptide release within the supraoptic nucleus (SON). A hypertonic sodium chloride solution was injected intraperitoneally (ip) or intravenously (iv) and microdialysis techniques were used to simultaneously monitor central and peripheral peptide release in urethane anesthetized rats. Systemic osmotic stimuli elicited increases in intranuclear peptide release which were delayed and long-lasting, occurring over a 2.5 h period. In contrast, plasma peptide levels peaked at 30-min after the stimulus. The results demonstrate that increased plasma sodium elicits an increase in VP and OT release into the extracellular space of the hypothalamic SON. The different patterns of peptide release in plasma and brain point toward the possibility of independently regulated release into the different compartments.     

Predictive value of clinical and radiological findings in inflicted traumatic brain injury

Aims: The aim of this study is to evaluate the value of early radiological investigations in predicting the long‐term neurodevelopmental outcome of infants with inflicted traumatic brain injury (ITBI). Methods: Clinical and radiological investigations of 24 infants with ITBI were performed during the acute phase of injury (1–3 days), and during the early (4 days up to 3 months) and late (>9 months) postinjury phases. The clinical outcome in survivors (n = 22) was based on the Rankin Disability Scale and the Glasgow Outcome Score. Results: Five out of 24 infants (21%) had a poor neurodevelopmental outcome (death and severe disability), 17 infants (71%) had different developmental problems and 2 infants were normal at the mean age of 62 (54–70) (95% CI) months. A low initial Glasgow Coma Scale score of 8 or below [p < 0.05, OR 13.0 (1.3–133.3)], the development of brain oedema [p < 0.005, OR 13.0 (1.6–773)], focal changes in the basal ganglia during the acute phase [p < 0.01, OR 45 (2.1–937.3)], the development of new intracerebral focal changes early postinjury [p < 0.05, OR 24.1(1.0–559.1)], a decrease in white matter [p < 0.01, OR 33 (1.37–793.4)] and the development of severe atrophy before 3 months postinjury [p < 0.05, OR 24 (11.0–559.1)] were significantly correlated with a poor neurodevelopmental outcome. Conclusions: Early clinical and radiological findings in ITBI are of prognostic value for neurodevelopmental outcome.     

Promoting and sustaining health through increased vegetable and fruit consumption among European schoolchildren: The Pro Children Project

Aim The Pro Children consortium consists of the following partners: Knut-Inge Klepp (Coordinator), Department of Nutrition, University of Oslo, Norway; Carmen Perez Rodrigo, Unidad de Nutricion Comunitaria, Bilbao, Spain; Inga Thorsdottir, Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland; Pernille Due, Department of Social Medicine, University of Copenhagen, Denmark; Maria Daniel Vaz de Almeida, Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto, Portugal; Ibrahim Elmadfa and Alexandra Wolf, Institute of Nutrition, University of Vienna, Austria; Jóhanna Haraldsdóttir, Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark; Johannes Brug, Erasmus Medical Center Rotterdam, Department of Public Health, The Netherlands; Michael Sjöström and Agneta Yngve, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden; Ilse De Bourdeaudhuij, Department of Movement and Sport Sciences, Ghent University, Belgium.The Pro Children study is designed to assess vegetable and fruit consumption and determinants of the consumption patterns among European school children and their parents. A second objective is to develop and test strategies for promoting increased consumption of vegetables and fruits among school children and their parents.Subjects and methods Surveys of national, representative samples of 11-year-old school children and their parents were conducted in nine countries during October–November 2003, i.e. in Austria, Belgium, Denmark, Iceland, The Netherlands, Norway, Portugal, Spain and Sweden. Comprehensive school-based educational programmes were developed and tested in three settings, i.e. in the Bilbao region, Spain, in Rotterdam, The Netherlands, and in Buskerud county of Norway. A 24-h recall format and frequency items assessing regular intake were used to assess vegetable and fruit consumption. Determinants were assessed employing the theoretical framework of the ASE model (Attitudes, Social Influences and Self-Efficacy), including cognitive factors, normative influences, skills and environmental barriers related to vegetable and fruit consumption. The intervention programmes were tested employing a group-randomized trial design where schools were randomly allocated to an intervention arm and a delayed intervention arm. Surveys among all participating children and their parents were conducted prior to the initiation of the intervention (September 2003; month 0), immediately after the end of the intervention (at month 8) and at the end of the subsequent school year (month 20).Results Preliminary data from the project indicate that girls eat vegetables and fruit significantly more often than do boys across all participating countries. There are no sex differences, however, with respect to perceived availability of vegetables and fruit at home and outside the home setting. In all countries, perceived availability appears to be significantly associated with reported frequency of both vegetable and fruit consumption.Conclusion Experience so far indicates that the Pro Children Project will succeed in producing valid and reliable research instruments for assessing vegetable and fruit consumption among school children and their parents and that comparable, comprehensive intervention programmes can be implemented across geographic and cultural settings within Europe.     

Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential

Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g. amygdala, hippocampus, hypothalamus and frontal cortex). Second, the SP content in these areas changes upon application of stressful stimuli. Third, the central administration of SP produces a range of fear-related behaviours. In addition, the SP/NK1R system shows significant spatial overlap with neurotransmitters such as serotonin and noradrenaline (norepinephrine), which are known to be involved in the regulation of stress, mood and anxiety. Therefore, it was hypothesised that blockade of the NK1R might have anxiolytic as well as antidepressant effects.Preclinical studies investigating the effects of genetic or pharmacological NK1R inactivation on animal behaviour in assays relevant to depression and anxiety revealed that the behavioural changes resemble those seen with reference antidepressant or anxiolytic drugs. Furthermore, antagonism or genetic inactivation of the NK1R causes alterations in serotonin and norepinephrine neuronal transmission that are likely to contribute to the antidepressant/anxiolytic activity of NK1R antagonists but that are--at least partially--distinct from those produced by established antidepressant drugs. This underlines the conceivable unique mechanism of action of this new class of compounds. In three independent clinical trials with three different compounds (aprepitant [MK-869], L-759274 and CP-122721), an antidepressant effect of NK1R antagonists could be demonstrated. These results, however, have been challenged by recent failed studies with aprepitant.There are numerous indications from preclinical studies that, in addition to SP and NK1R, other neurokinins and/or neurokinin receptors might also be involved in the modulation of stress-related behaviour and that exclusive blockade of the NK1R might not be sufficient to produce consistent anxiolytic and antidepressant effects. One such candidate is the neurokinin-2 receptor (NK2R), and clinical trials to assess the antidepressant effects of NK2R antagonists are currently underway. Of special interest might also be substances that block more than one receptor type such as NK1/2R antagonists or NK1/2/3R antagonists. These compounds may be more efficacious in antagonising the effects of SP than compounds that only block the NK1R.     

Birth weight, growth and feeding in infancy: relation to serum lipid concentration in 12-month-old infants

OBJECTIVE: To assess the effects of birth size, growth and feeding in infancy on serum lipids in 12-month-old infants. DESIGN: A longitudinal observation study on infants' consumption and growth. Food and growth records were made every month. At 6, 9 and 12 months, food records were weighed to calculate intake. Serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL), low-density lipoprotein (LDL) -cholesterol and triglyceride concentrations were analysed at 12 months. SETTINGS: Birth and growth information was gathered from maternity wards and healthcare centres in Iceland and food consumption data at home. SUBJECTS: Randomly selected newborns (n=180) according to the mother's domicile and 77% (n=138) participated, of them 75% (n=103), came in for blood sampling. RESULTS: Among boys, a 1 kg higher birth weight resulted in a 0.79 mmol/l higher TC (P=0.005), but nonsignificant after adjustment for growth. Duration of breastfeeding was related to LDL-cholesterol (B=0.06 +/-0.02, P=0.020, adj. R(2)=0.039), adjusting for gender. Independent of size at birth and breastfeeding, increase in length from 6 to 12 months and in weight from birth to 12 months were negatively related to TC (B=-0.455+/-0.156, P=0.008 and B=-1.086+/-0.474, P=0.032, respecitvely) in boys. PUFA was the strongest nutrient variable predicting TC (B=0.332, adj. R(2)=0.24, P>0.001). Cod liver oil consumption increased both TC and LDL-cholesterol in girls (B=0.141+/-0.051, P=0.008 and B=0.112+/-0.047, P=0.021, respectively). CONCLUSION: Slower growth of high birth weight infants and breastfeeding contributes to higher TC concentration at the age of 12 months. Nutrient intake in infancy also affects lipid profile. The effect of birth weight, growth and nutrient intake in infancy on lipid profile is different for boys and girls.     

Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.     

Is high consumption of fatty fish during pregnancy a risk factor for fetal growth retardation? A study of 44,824 Danish pregnant women

The authors examined the relation between fish consumption during pregnancy and fetal growth among 44,824 women from the Danish National Birth Cohort (1996-2002). They evaluated the associations between consumption of total fish, fatty fish, and lean fish in midpregnancy and birth weight, birth length, and head circumference among singleton full-term infants. Fish consumption was ascertained by food frequency questionnaire. The birth of infants classified below the 10th percentile for gestational age and gender was significantly increased among women who consumed more than 60 g of fish per day, as compared with women who consumed 5 g or less per day. Adjusted odds ratios were 1.24 (95% confidence interval (CI): 1.03, 1.49) for birth weight and 1.21 (95% CI: 1.01, 1.43) for head circumference. The adjusted odds ratio was borderline significant for birth length (odds ratio = 1.20, 95% CI: 1.00, 1.45). These increases in risk were followed by small decreases in average values for these growth measures. Furthermore, the inverse association for total fish consumption could be explained by consumption of fatty fish, while no association was found for lean fish. These results indicate that consumption of fatty fish, a known route of exposure to persistent organic pollutants, could be associated with reduced fetal growth.