Effects of lead exposure on hippocampal metabotropic glutamate receptor subtype 3 and 7 in developmental rats

Background A complete explanation of the mechanisms by which Pb2+ exerts toxic effects on developmental central nervous system remains unknown. Glutamate is critical to the developing brain through various subtypes of ionotropic or metabotropic glutamate receptors (mGluRs). Ionotropic N-methyl-D-aspartate receptors have been considered as a principal target in lead-induced neurotoxicity. The relationship between mGluR3/mGluR7 and synaptic plasticity had been verified by many recent studies. The present study aimed to examine the role of mGluR3/mGluR7 in lead-induced neurotoxicity. Methods Twenty-four adult and female rats were randomly selected and placed on control or 0.2% lead acetate during gestation and lactation. Blood lead and hippocampal lead levels of pups were analyzed at weaning to evaluate the actual lead content at the end of the exposure. Impairments of short -term memory and long-term memory of pups were assessed by tests using Morris water maze and by detection of hippocampal ultrastructural alterations on electron microscopy. The impact of lead exposure on mGluR3 and mGluR7 mRNA expression in hippocampal tissue of pups were investigated by quantitative real-time polymerase chain reaction and its potential role in lead neurotoxicity were discussed. Results Lead levels of blood and hippocampi in the lead-exposed rats were significantly higher than those in the controls (P < 0.001). In tests using Morris Water Maze, the overall decrease in goal latency and swimming distance was taken to indicate that controls had shorter latencies and distance than lead-exposed rats (P = 0.001 and P < 0.001 by repeated-measures analysis of variance). On transmission electron microscopy neuronal ultrastructural alterations were observed and the results of real-time polymerase chain reaction showed that exposure to 0.2% lead acetate did not substantially change gene expression of mGluR3 and mGluR7 mRNA compared with controls. Conclusion Exposure to lead before and after birth can damage short-term and long-term memory ability of young rats and hippocampal ultrastructure. However, the current study does not provide evidence that the expression of rat hippocampal mGluR3 and mGluR7 can be altered by systemic administration of lead during gestation and lactation, which are informative for the field of lead-induced developmental neurotoxicity noting that it seems not to be worthwhile to include mGluR3 and mGluR7 in future studies. Background

Introducing solids and water to Australian infants

Background: Recommendations for the introduction of solids and fluids to an infant’s diet have changed over the past decade. Since these changes, there has been minimal research to determine patterns in the introduction of foods and fluids to infants. Methods: This retrospective cohort study surveyed mothers who birthed in Queensland, Australia, from February 1 to May 31, 2010, around 4 months postpartum. Frequencies of foods and fluids given to infants at 4, 8, 13, and 17 weeks were described. Logistic regression determined associations between infant feeding practices, the introduction of other foods and fluids at 17 weeks, and sociodemographic characteristics. Results: Response rate was 35.8%. At 17 weeks, 68% of infants were breastfed and 33% exclusively breastfed. Solids and water had been introduced in 8.6% and 35.0% of infants, respectively. The introduction of solids by 17 weeks was associated with younger maternal age and the infant being given water and infant formula at 4 weeks. The infant being given water at 17 weeks was associated with younger maternal age, the infant being given infant formula at 4 weeks, level of education, relative socioeconomic disadvantage, parity, and birth facility. Conclusion: Over the past decade, there has been a significant reduction in the proportion of infants in Australia who have been given solids by 17 weeks. Sociodemographic characteristics and formula feeding practices at 4 weeks were associated with the introduction of solids and water by 17 weeks. Further research should examine these barriers to improve compliance with current infant feeding recommendations.

Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine

Introduction: Domperidone is a dopamine D2-receptor antagonist developed as an antiemetic and prokinetic agents. Oral domperidone is not approved in the US, but is used in many countries to treat nausea and vomiting, gastroparesis, and as a galactogogue (to promote lactation). The US Food and Drug Administration (FDA) have issued a warning about the cardiac safety of domperidone. Areas covered: The authors undertook a review of the cardiac safety of oral domperidone. Expert opinion: The data from preclinical studies are unambiguous in identifying domperidone as able to produce marked hERG channel inhibition and action potential prolongation at clinically relevant concentrations. The compound’s propensity to augment instability of action potential duration and action potential triangulation are also indicative of proarrhythmic potential. Domperidone should not be administered to subjects with pre-existing QT prolongation/LQTS, subjects receiving drugs that inhibit CYP3A4, subjects with electrolyte abnormalities or with other risk factors for QT-prolongation. With these provisos, it is possible that domperidone may be used as a galactogogue without direct risk to healthy breast feeding women but more safety information should be sought in this situation. Also, more safety information is required regarding risk to breast feeding infants or before domperidone is routinely used in gastroparesis or gastroesphageal reflux in children.

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk. © 2013 Springer Science+Business Media New York.

Current management of transitional feeding issues in preterm neonates born in Queensland, Australia

Background: Many preterm neonates display difficulty establishing suck-feeding competence in the weeks following birth. Ineffective management of transitional feeding issues may cause patient complications, and can contribute to increased length of stay. Aims: Given that many neonatal nurseries appear to vary in their neonatal feeding management practices, the aim of this study was to investigate and document the routine level of support and intervention currently provided for preterm neonates with transitional feeding issues across the various level II (special care) nurseries (SCNs) in Queensland, Australia. Methods: A questionnaire was mailed to all Queensland SCNs in 2005 (n = 36). The questionnaire contained a series of closed-choice and short-answer questions designed to obtain information from each SCN regarding their current practices for managing transitional feeding issues in preterm neonates. Results were confirmed during a follow-up phone call. Results: Responses were obtained from 29 SCNs (80.6%). None of these nurseries reported having any formal, written policies regarding the management of transitional feeding issues in preterm neonates. Wide variations were reported in relation to the suck-feeding assessments and interventions used by staff within the various SCNs. Of the 29 nurseries, 4 (13.8%) reported using checklists or assessments to judge readiness for suck-feeds, and 5 (17.2%) reported using pulse oximetry to judge tolerance of suck-feeding attempts. Eighteen SCNs (62.1%) reported offering some form of active intervention to assist neonates with transitional feeding issues, with the most common intervention techniques reported being non-nutritive sucking during tube feeds, pre-feeding oral stimulation, and actively pacing suck-feeds. Twenty-two SCNs (75.4%) reported having access to a lactation consultant to assist mothers with breastfeeding issues. Conclusions: Differences were reported in the routine management of transitional feeding issues in preterm neonates across the various SCNs in Queensland. It is suggested that evidence based guidelines need to be developed, and that, in order to do this, further research studies are required to determine current best practice, as well as to answer remaining questions. © 2008 Elsevier Ireland Ltd. All rights reserved.

Breastfeeding duration and authoritative feeding practices in first-time mothers

Background Longer breastfeeding duration appears to have a protective effect against childhood obesity. This effect may be partially mediated by maternal feeding practices during the first years of life. However, the few studies that have examined links between breastfeeding duration and subsequent feeding practices have yielded conflicting results. Objective Using a large sample of first-time mothers and a newly validated, comprehensive measure of maternal feeding (the Feeding Practices and Structure Questionnaire1), this study examined associations between breastfeeding duration and maternal feeding practices at child age 24 months. Methods Mothers (n = 458) enrolled in the NOURISH trial2 provided data on breastfeeding at child age 4, 14 and 24 months, and on feeding practices at 24 months. Structural Equation Modelling was used to examine associations between breastfeeding duration and five non-responsive and four structure-related ‘authoritative’ feeding practices, adjusting for a range of maternal and child characteristics. Results The model showed acceptable fit (χ2/df = 1.68; RMSEA = .04, CFI = .91 and TLI = .89) and longer breastfeeding duration was negatively associated with four out of five non-responsive feeding practices and positively associated with three out of four structure-related feeding practices. Overall, these results suggest that mothers who breastfeed longer reported using more appropriate feeding practices. Conclusion These data demonstrate an association between longer breastfeeding duration and authoritative feeding practices characterised by responsiveness and structure, which may partly account for the apparent protective effect of breastfeeding on childhood obesity.

Feeding mode of Australian infants in the first 12 months of life: An assessment against national breastfeeding indicators

Background: In 2011, Australia published a set of 6 population-level indicators assessing breastfeeding, formula use, and the introduction of soft/semisolid/solid foods. Objectives: This study aimed to report the feeding practices of Australian infants against these indicators and determine the predictors of early breastfeeding cessation and introduction of solids. Methods: Mother–infant dyads (N = 1470) were recruited postnatally in 2 Australian capital cities and regional areas of 1 state between February 2008 and March 2009. Demographic and feeding intention data were collected by self-completed questionnaire at infant birth, with feeding practices (current feeding mode, age of breastfeeding cessation, age of formula and/or solids introduction) reported when the infant was between 4 and 7 months of age, and around 13 months of age. Multiple logistic regression was used to determine the predictors of breastfeeding cessation and solids introduction. Results: Although initiation of breastfeeding was almost universal (93.3%), less than half of the infants were breastfed to 6 months (41.7%) and 33.3% were receiving solids by 4 months. Women who were socially disadvantaged, younger, less educated, unpartnered, primiparous, and/or overweight were most likely to have ceased breastfeeding before 6 months of age, and younger and/or less educated women were most likely to have introduced solid food by 4 months of age. Not producing adequate milk was the most common reason provided for cessation of breastfeeding. Conclusion: The feeding behaviors of Australian infants in the first 12 months fall well short of recommendations. Women need anticipatory guidance as to the indicators of breastfeeding success and the tendency of women to doubt the adequacy of their breast milk supply warrants further investigation.