NF-κB-dependent regulation of brain-derived neurotrophic factor in hippocampal neurons by X-linked inhibitor of apoptosis protein

X chromosome-linked inhibitor of apoptosis protein (XIAP) is an anti-apoptotic protein enhancing cell survival. Brain-derived neurotrophic factor (BDNF) also promotes neuronal viability but the links between XIAP and BDNF have remained unclear. We show here that the overexpression of XIAP increases BDNF in transgenic mice and cultured rat hippocampal neurons, whereas downregulation of XIAP by silencing RNA decreased BDNF. XIAP also stimulated BDNF signaling, as shown by increased phosphorylation of the TrkB receptor and the downstream molecule, cAMP response element-binding protein. The mechanism involved nuclear factor-κB (NF-κB) activation and blocking of NF-κB signaling inhibited the increased activities of BDNF promoters I and IV by XIAP. In neuronal cultures XIAP also upregulated interleukin (IL)-6, which is an NF-κB-responsive gene. The addition of IL-6 elevated whereas incubation with IL-6-blocking antibodies reduced BDNF in the neurons. BDNF itself activated NF-κB in the neurons at higher concentrations. The data show that XIAP has trophic effects on hippocampal neurons by increasing BDNF and TrkB activity. The results reveal a cytokine network in the brain involving BDNF, IL-6 and XIAP interconnected via the NF-κB system.     

Normative nasalance scores for Estonian children

Normative nasalance scores are essential for the treatment and assessment purposes for clinicians. Till date, no studies have been done on nasalance in Estonia. This research was conducted to develop Estonia-specific optimized speech stimuli for Nasometer II and establish the normative nasalance scores. Ninety-two randomly selected healthy and 14 cleft palate Estonian monolingual children, aged four to seven years, were included as participants. Estonian language-specific test material was developed. The Estonian test material consisted of 24 speech stimuli. Based on the phoneme content, the stimuli were divided into three groups: (1) sentences that included oral and nasal phonemes and targeted the same phoneme distribution as in spontaneous speech, (2) sentences that included only oral phonemes and (3) sentences that were loaded with nasal phonemes. Nasometer II software was used to calculate the nasalance scores for each child and each sentence. Results indicated that there were significant differences in nasalance scores for oronasal and oral stimuli scores, and no significant differences were found in nasal stimuli scores between the study and control group. The threshold for oronasal stimuli was 42.1–18.9, oral stimuli was 27.9–3.9 and nasal stimuli was 69.4–46.2. In conclusion, Estonia-specific optimized speech stimuli were developed and normative nasalance scores were established. These normative scores can be used for the diagnosis and follow-up treatment of patients with resonance disorders, especially for patients with cleft palate.     

Body composition,maximal aerobic performance and inflammatory biomarkers in endurance-trained athletes

This study was designed to examine the relationships between body composition, cardiorespiratory fitness and simultaneously measured inflammatory parameters in endurance-trained athletes. In 20 well-trained rowers (19·0 ± 2·9 years; 185·6 ± 4·8 cm; 85·7 ± 10·8 kg; 17·1 ± 5·1% body fat; maximal oxygen consumption [VO₂max]: 63·9 ± 8·5 ml min⁻¹ kg⁻¹), body composition was measured by dual-energy X-ray absorptiometry and cardiorespiratory fitness by direct VO₂max test. Twelve inflammatory factors [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma (IFN-γ), tumour necrosis factor-alpha, IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF)] were analysed from serum samples. Serum IFN-γ was related (P<0·05) to fat-free mass (FFM) (r = −0·56) and muscle mass (r = −0·50). The stepwise regression analysis showed that IFN-γ explained 27·5%, and IFN-γ and IL-6 together explained 39·8% of the variability of FFM, while IFN-γ explained 21·1%, and IFN-γ together with EGF explained 36·6% of the variability of muscle mass in male rowers. Serum IL-8 (r = −0·65) and VEGF (r = −0·48) correlated (P<0·05) with VO₂max kg⁻¹. Serum IL-8 explained 38·5% of the variability of VO₂max kg⁻¹. Significant correlations were also found among several inflammatory parameters, indicating that various inflammatory cytokines act on the body as an ensemble. In conclusion, this cross-sectional study in endurance-trained male rowers showed that FFM and muscle mass were negatively correlated with serum IFN-γ level, whereas cardiorespiratory fitness was negatively related to serum IL-8 level.     

Review on aging, unloading and reloading: changes in skeletal muscle quantity and quality

Aging and muscle unloading are associated with a decline in muscle mass, structure, force and changes in the mechanical properties of skeletal muscle. There is a perception that reloading restores muscle architecture and function but differences in the regeneration capacity of intra- and extra-cellular compartments, age dependent susceptibility to muscle damage, particularly in the contractile machinery, make it difficult to attribute the main role of the above mentioned components. This review briefly summarizes studies that examine aging skeletal muscle during unloading and reloading. The article highlights changes in muscle mass, structure, extra-cellular matrix (ECM) components, strength, locomotion, adaptability to exercise, peculiarities of protein metabolism, susceptibility to glucocorticoids and recovery of muscle from injury.     

Association between arterial elasticity, C-reactive protein and maximal oxygen consumption in well-trained cadets during three days extreme physical load: a pilot study

Regular aerobic training has beneficial effects on inflammatory pathways and on arterial elasticity, which are both important cardiovascular risk factors. The aim of the present study was to evaluate the effect of extreme physical load on arterial elasticity and inflammatory markers in well-trained healthy men who participated in a high-ranking combat course. Seven well-trained male cadets were examined during an international military combat course of 3.5 days duration. Small (C2) and large (C1) artery elasticity was assessed using diastolic pulse wave analysis. Inflammatory markers and arterial elasticity measurement were performed before and after the competition. The extreme prolonged physical load caused individually different responses in arterial elasticity, C-reactive protein (CRP) and creatine kinase in individual cadets. Maximal oxygen consumption (VO(2) max kg(-1)) correlated significantly with the change (Delta-difference between baseline and 24 h recovery period) of creatine kinase (r= -0.78; p=0.04) and DeltaC2 (r=0.78; p=0.04) and DeltaC1 (r=0.82; p=0.02). In multivariate analysis (R(2)=0.89, p=0.01) the DeltaC2 correlated strongly with VO(2) max kg(-1) (p=0.005) and with the DeltaCRP (p=0.03), whereas the DeltaC1 correlated only with VO(2) max kg(-1) and did not correlate significantly with the DeltaCRP. Changes in small arterial elasticity induced by extreme physical load were significantly related to VO(2) max kg(-1) and DeltaCRP, whereas the change of large artery elasticity was only associated with VO(2) max kg(-1). Our preliminary results indicate that acute exercise-induced inflammation may affect small artery elasticity. However, further, more extensive studies are needed in this area.     

Plasma ghrelin responses to acute sculling exercises in elite male rowers

The regulatory effect of ghrelin on growth hormone (GH) is limited in describing ghrelin response to acute submaximal exercise intensities in elite athletes. We investigated the effects of a single sculling exercise performed above and below the individual anaerobic threshold (IAT) on total ghrelin concentration in highly trained male rowers. Nine elite male rowers (20.1 ± 3.7 years; 190.0 ± 5.2 cm; 89.6 ± 4.6 kg; %body fat: 9.9 ± 2.5%) volunteered for this study. Single scull rowing was performed below and above IAT using a mean of 5 bpm above and below the heart rate of the IAT during graded exercise test. Ghrelin, leptin, GH, insulin, and glucose were measured before, immediately after, and after 30 min of recovery. Plasma ghrelin concentration did not increase significantly in either exercise but was approaching significance after 30 min of recovery (P = 0.051) when the constant load sculling was performed at the intensity above the IAT. There were no changes in plasma leptin levels. GH increased significantly immediately after exercise and remained elevated during the 30 min of recovery in both exercise conditions, while insulin decreased significantly immediately after exercise and remained significantly lower after the 30 min of recovery in both exercise intensities. Baseline ghrelin was not correlated with the body composition, physical performance, or blood biochemical data. There was no significant relationship between plasma ghrelin and other blood variables immediately after the 30 min of recovery in both exercise tests and changes in ghrelin were not related to blood biochemical variables after the exercise tests. The acute constant load sculling exercise above or below IAT that increased GH concentrations did not significantly increase the circulating plasma ghrelin levels.     

Evaluation of transportan 10 in PEI mediated plasmid delivery assay.

Cell-penetrating peptides (CPPs) are novel high-capacity delivery vectors for different bioactive cargoes. We have evaluated the CPP transportan 10 (TP10) as a delivery vector in different in vitro plasmid delivery assays. Tested methods include: TP10 crosslinked to a plasmid via a peptide nucleic acid (PNA) oligomer, TP10 conjugation with polyethyleneimine (PEI), and addition of unconjugated TP10 to standard PEI transfection assay. We found that without additional DNA condensing agents, TP10 has poor transfection abilities. However, the presence of TP10 increases the transfection efficiency several folds compared to PEI alone. At as low concentrations as 0.6 nM, TP10-PNA constructs were found to enhance plasmid delivery up to 3.7-fold in Neuro-2a cells. Interestingly, the transfection efficiency was most significant at low PEI concentrations, allowing reduced PEI concentration without loss of gene delivery. No increase in cytotoxicity due to TP10 was observed and the uptake mechanism was determined to be endocytosis, as previously reported for PEI mediated transfection. In conclusion, TP10 can enhance PEI mediated transfection at relatively low concentrations and may help to develop future gene delivery systems with reduced toxicity.     

Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension

OBJECTIVE: To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients. METHODS: Forty-nine middle-aged patients with untreated stage I-II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 micromol/l was considered significant. RESULTS: Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 micromol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied. CONCLUSION: Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.     

Physiological,Biomechanical and Anthropometrical Predictors of Sprint Swimming Performance in Adolescent Swimmers

The purpose of this study was to analyze the relationships between 100-m front crawl swimming performance and relevant biomechanical, anthropometrical and physiological parameters in male adolescent swimmers. Twenty five male swimmers (mean ± SD: age 15. 2 ± 1.9 years; height 1.76 ± 0.09 m; body mass 63.3 ± 10.9 kg) performed an all-out 100-m front crawl swimming test in a 25-m pool. A respiratory snorkel and valve system with low hydrodynamic resistance was used to collect expired air. Oxygen uptake was measured breath-by-breath by a portable metabolic cart. Swimming velocity, stroke rate (SR), stroke length and stroke index (SI) were assessed during the test by time video analysis. Blood samples for lactate measurement were taken from the fingertip pre exercise and at the third and fifth minute of recovery to estimate net blood lactate accumulation (ΔLa). The energy cost of swimming was estimated from oxygen uptake and blood lactate energy equivalent values. Basic anthropometry included body height, body mass and arm span. Body composition parameters were measured using dual-energy X-ray absorptiometry (DXA). Results indicate that biomechanical factors (90.3%) explained most of 100-m front crawl swimming performance variability in these adolescent male swimmers, followed by anthropometrical (45.8%) and physiological (45.2%) parameters. SI was the best single predictor of performance, while arm span and ∆La were the best anthropometrical and physiological indicators, respectively. SI and SR alone explained 92.6% of the variance in competitive performance. These results confirm the importance of considering specific stroke technical parameters when predicting success in young swimmers.

Key points

• This study investigated the influence of different anthropometrical, physiological and biomechanical parameters on 100-m swimming performance in adolescent boys.
• Biomechanical factors contributed most to sprint swimming performance in these young male swimmers (90.3% of variability in performance), followed by anthropometrical (45.8%) and physiological (45.2%) parameters.
• Two selected variables (stroke index and stroke rate) explained 92.6% of the variance in competitive performance in these adolescent swimmers.

Key words: oxygen uptake, stroke index, energy cost, front crawl