Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs).Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0–10 mg/kg/d), duration of exposure, and cumulative dose.Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p < 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate.Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants

Effect of blood type on anti-a-Gal immunity and the incidence of infectious diseases

The identification of factors affecting the susceptibility to infectious diseases is essential toward reducing their burden on the human population. The ABO blood type correlates with susceptibility to malaria and other infectious diseases. Due to the structural similarity between blood antigen B and Gala1-3GalB1-(3)4GlcNAc-R (a-Gal), we hypothesized that self-tolerance to antigen B affects the immune response to a-Gal, which in turn affects the susceptibility to infectious diseases caused by pathogens carrying a-Gal on their surface. Here we found that the incidence of malaria and tuberculosis, caused by pathogens with a-Gal on their surface, positively correlates with the frequency of blood type B in endemic regions. However, the incidence of dengue fever, caused by a pathogen without a-Gal, was not related to the frequency of blood type B in these populations. Furthermore, the incidence of malaria and tuberculosis was negatively correlated with the anti-a-Gal antibody protective response. These results have implications for disease control and prevention.Peer reviewedVeterinary Pathobiolog

Emergence of an egocentric cue guiding and allocentric inferring strategy that mirrors hippocampal brain-derived neurotrophic factor (BDNF) expression in the Morris water maze

From insects to humans, successful navigation relies on retained representations of spatial relations. These representations are thought to depend on the hippocampal formation, particularly those that are independent of the navigator (allocentric representations). The Morris water maze is a simple and popular task often used to assess spatial navigation. But how animals navigate toward and retain information regarding the location of the goal in this task remains unclear. We provide a comprehensive account of how the water maze is accomplished behaviourally. Our findings suggest that animals solve the task using distal cues via an initial view-matching strategy that is supported by egocentric guidance. Through increased training, however, an emergence of an egocentric-guiding strategy combined with the animal’s greater ability to infer the hidden platform’s location (via allocentric extrapolation) emerges. We also demonstrate that behavioural changes, towards a more allocentric strategy, are reflected in increases in hippocampal brain-derived neurotrophic factor

Vestibular influence on water maze retention: transient whole body rotations improve the accuracy of the cue-based retention strategy

Spatial learning in the water maze is thought to rely both on distal cues and vestibular information [Aggleton JP, Vann SD, Oswald CJP, Good M. Identifying cortical inputs to the rat hippocampus that subserves allocentric spatial processes: a simple problem with a complex answer. Hippocampus 2000;10:466–74; Pearce JM. Animal learning and cognition: an introduction. UK: Psychology Press; 1997]. Experiment 1 demonstrates that while water maze retention relies primarily on cue-platform based associations, this strategy is not precise, as animals tend to focus at the side of the pool. In experiment 2, we demonstrate that vestibular rotation eliminates this inaccuracy. These experiments highlight the importance of both cue and vestibular information for accurate retention of the water maze

Retention of cue-based associations in the water maze is time-dependent and sensitive to disruption by rotating the starting position

Research has focused mainly on the acquisition phase of spatial tasks, while retention has been relatively ignored. In three experiments, we determine the type of information that is retained in spatial memory using the water maze task. In experiment 1, we demonstrate that by rotating the distal cues 180° post-acquisition Wistar rats search in the opposite area to where the platform should be. This search continues for a maximum of 30 s. We then demonstrate (experiment 2) that by rotating the starting position (180° post-acquisition) animals remain at the starting-point for 10 s. They then commence searching in the platform area. In experiment 3, we demonstrate that rotations of distal cues and starting position post-acquisition impair retention of the platform’s location. We suggest that the association between the configuration of distal cues and platform location is retained in memory but the association is fragile and sensitive to disruption

A Possible Role for Protein Synthesis, Extracellular Signal-Regulated Kinase, and Brain-Derived Neurotrophic Factor in Long-Term Spatial Memory Retention in the Water Maze

Hippocampal protein synthesis is dependent upon a number of different molecular and cellular mechanisms that act together to make previously labile memories more stable and resistant to disruption. Both brain-derived neurotrophic factor (BDNF) and extracellular signal-Regulated kinase (ERK) are known to play an important role in protein synthesis-dependent memory consolidation, via the mitogen-activated protein-kinase (MAP-K) signaling pathway during the transcription phase of protein synthesis. The current study investigates the influence of protein synthesis inhibition (PSI) by cycloheximide on spatial learning and memory. In an initial experiment, the authors utilized two doses of cycloheximide (0.5 mg/kg and 1.0 mg/kg, intraperitoneally) to determine the dose at which long-term (>24 hours) memories are impaired. A second experiment was designed to investigate the effect of PSI on the formation of cue-platform associations in the watermaze, and on BDNF and ERK expression in the hippocampus. At the higher dose (1.0 mg/kg) cycloheximide resulted in impaired retention of the water maze. BDNF and ERK expression was also down-regulated in animals injected with this dose of cycloheximide. Our results demonstrate a role of protein synthesis in spatial memory retention, along with a possible relationship between protein synthesis and hippocampal BDNF/ERK expression