Preterm infants frequently suffer from respiratory distress syndrome (RDS), possibly due to lower expression of epithelial Na+ channels (ENaC). RDS incidence is sex-specific, affecting males almost twice as often. Despite the use of antenatal glucocorticoids (GCs), the sex difference persists. It is still controversial whether both sexes benefit equally from GCs. We previously showed that Na+ transport is higher in female compared with male fetal distal lung epithelial (FDLE) cells. Since GCs increase Na+ transport, we hypothesized that their stimulating effect might be sex-specific. We analyzed FDLE cells with Ussing chambers and RT-qPCR in the presence or absence of fetal serum. In serum-free medium, GCs increased the ENaC activity and mRNA expression, independent of sex. In contrast, GCs did not increase the Na+ transport in serum-supplemented media and abolished the otherwise observed sex difference. Inhibition of the GC receptor in the presence of serum did not equalize Na+ transport between male and female cells. The GC-induced surfactant protein mRNA expression was concentration and sex-specific. In conclusion, female and male FDLE cells exhibit no sex difference in response to GCs with regard to Na+ transport, and GR activity does not contribute to the higher Na+ transport in females.

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Stress is a widespread phenomenon in the western society of these days. It is a risky factor for health and well-being of the majority of people. Based on these facts, it is the main subject for the field of "stress physiology" research, which aims to study processes occurring during stress response and tries to elucidate mechanisms leading to stress-induced health impairment. The first aim of this thesis was to describe effects of psycho-social stress on organism. The second aim was to find out if can stress applied in juvenile age affect the stress response in adulthood. If so, how is the role of glucocorticoid-metabolism enzyme 11β-HSD1 in this influence? To answer these questions, two different animal models inducing stress response in the laboratory rat were used. The first one is the model of mild social stress based on the resident-intruder paradigm. Our results show efficancy of this model. Fisher 344 male rats treated under this model for seven consecutive days show highly elevated plasma corticosterone concentrations and elevated expression of the glucocorticoid receptor gene in the pituitary. Behavioral analysis demonstrates a decreased social behavioral profile of the intruders, suggesting submisive social position of these animals in the resident-intruder paradigm. The second model used is...

Antibiotics are routinely used in modern livestock production systems to treat and prevent disease as well as to enhance livestock production and/or outputs. This widespread use of antibiotics has led to a growing worldwide interest in antibioticfree animal production. The addition of feed supplements such as nucleotides to improve intestinal health as well as the early development of the immune system needs to be investigated as an environmentally-friendly nutritional management activity. In this study four (4) groups of newborn Holstein calves (n=24) were evaluated after being treated as follows: Group 1 (Negative control), Group 2 (Investigational Veterinary Product (IVP) 1 – Oral supplement containing nucleotides, vitamins, essential fatty acids, essential amino acids, pre-biotics and trace-minerals), Group 3 (IVP 2 – Oral supplement containing nucleotides only at concentration and dosage equal to IVP1) and Group 4 (IVP 3 - Parenteral glucocorticoids). Results of the study indicated that: Pre-colostral Serum IgG titres – After titration of the serum the anti-BVDV results showed no difference between the study groups. All calves recorded a SP ratio of zero value (0.00 ± 0.2) indicating that they had not been nursed by their mothers prior to the start of the study. This was an entrance requirement for the calves to be enrolled into the study. Apparent Efficiency of Absorption % (AEA%) – Literature shows that an AEA% result of between 20%-30% is good and 35% is excellent. The AEA% recorded for this study fell within this range although there was no statistically significant difference shown between the groups. In spite of a strictly controlled study protocol, 7 of the 24 calves (29%) still suffered from FPT in this study. The result falls within the range of 19% - 37% reported on United States of America (USA) farms by Doepel and Bartier in 2014. Serum cortisol - When compared to the control group, there were no statistical significant difference evident for group 2 and group 3. However, the difference between the Glucocorticoid – Group 4 and the control and other groups was statistically significant (P = 0.0001; table 12) at the various time intervals. It was also evident that the inclusion of parenteral glucocorticoids (group 4) may have assisted in prolonging the natural “gut closure”. Gut closure – a positive 2 point linear regression forecast line indicated an increasing trend in IgG absorption post-24 hours for group number 4 whilst groups 1, 2 and 3 each had a negative 2 point linear regression forecast line (figure 23). Weight / ADG (D42) - Group 2 showed a statistically significant increase in mean D42 weight (P = 0.0042) of 59.167 kg ± 3.545 kg when compared to the other study groups and compared to the control group (P = 0.0227). A comparison of the relative increase in mass of groups indicated that Group 2 efficiently achieved this result with a statistically significant ADG of 0.536 kg (P = 0.014) compared to the other study groups and compared to the control group (P = 0.022). In addition, weight / FCR – FCR was calculated for all groups as follows: G1 – 4.000 kg, G2 - 2.593 kg, G3 – 2.703 kg and G4 - 3.012 kg feed required for the production of 1 kg meat. The results indicated that the group 2 feed input was the most economical followed by groups 3, 4 and control respectively. In conclusion, it is evident that a nutritional supplement containing nucleotides, vitamins, trace- minerals, essential fatty acids, essential amino acids and pre-biotics may contribute significantly to important economic indicators such as weight gain, ADG and FCR on a commercial dairy farm. / Environmental Sciences / Ph. D. (Environmental Science)

The fragile X mental retardation protein (FMRP) is an important regulator of protein translation, and a lack of FMRP expression leads to a cognitive disorder known as fragile X syndrome (FXS). Clinical symptoms characterizing FXS include learning impairments and heightened anxiety in response to stressful situations. The Fmr1-/y mouse has previously been shown to have deficits in context discrimination and novel object recognition tasks, which primarily rely on the dentate gyrus (DG) region of the hippocampal formation, but not in the Morris water maze (MWM) or the elevated plus-maze tasks, which primarily depend on the Cornu Ammonis (CA1) region. Furthermore, previous research has demonstrated N-methyl-D-aspartate receptor (NMDAR)-associated synaptic plasticity impairments in the DG but not in the CA1. However, the impact of acute stress on synaptic plasticity in the Fmr1-/y hippocampus has not been examined. The current study sought to extend previous behavioural investigations in the Fmr1-/y mouse, as well as examine the impact of stress on activation of the hypothalamic-pituitary-adrenal (HPA)-axis and on hippocampal synaptic plasticity. To further characterize hippocampus-dependent behaviour in this mouse model, the DG-dependent metric change spatial processing and CA1-dependent temporal order discrimination tasks were evaluated. The results reported here support previous findings and demonstrate that Fmr1-/y mice have performance deficits in the DG-dependent task but not in the CA1-dependent task, suggesting that previously reported subregional differences in NMDAR-associated synaptic plasticity deficits in the hippocampus of the Fmr1-/y mouse model may also manifest as selective behavioural deficits in hippocampus-dependent tasks. In addition, following acute stress, mice lacking FMRP showed a faster elevation of the glucocorticoid corticosterone and a more immediate impairment in long-term potentiation (LTP) in the DG. Stress-induced LTP impairments were rescued by administering the glucocorticoid receptor (GR) antagonist RU38486. Administration of RU38486 also enhanced LTP in Fmr1-/y mice in the absence of acute stress to wild-type levels, and this enhancement was blocked by application of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid. These results suggest that a loss of FMRP results in enhanced GR signalling that may adversely affect NMDAR-dependent synaptic plasticity in the DG. Finally, synaptic plasticity alterations reported in this work were found to be specific to the DG and were unidirectional, i.e., restricted to LTP, as NMDAR- and metabotropic glutamate receptor (mGluR)-LTD were both unaffected by acute stress in the DG or the CA1 regions. This study offers new insights into synaptic plasticity impairments in the Fmr1-/y mouse model, and suggests stress and GRs as important contributors to learning and memory deficits in FXS. / Graduate