Soy isoflavones administered pre- and postnatally may affect the ERα and ERβ expression and elements' content in bones of mature male rats

The aim of this study was to assess the influence of soy isoflavones, administered pre- and later postnatally, on the estrogen receptor α (ERα) and β (ERβ) expression in bones and to examine the mineral metabolism of the skeletal system in male rats. In bones, ERs were examined with an immunohistochemical method; in blood, estradiol with chemiluminescence immunoassay and in blood and bones, calcium and magnesium with atomic absorption spectrometry and fluorides with a potentiometric method were examined. Decreased immunoexpression of ERα and the increased intensity of immunofluorescence of ERβ in osteocytes in the femur of experimental rats were observed. In the serum of treated rats, a significantly higher concentration of estradiol and lower calcium were observed. The content of magnesium and fluoride were significantly higher in the bones of the examined animals. The data presented show that pre- and postnatal supplementation of male rats with soy isoflavones may considerably increase the concentration of estrogens in serum, with a concurrent effect on the mineral composition of bones.     

Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome

Triplication of chromosome 21 in Down syndrome (DS) results in overexpression of the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A gene (DYRK1A). DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs). We have previously shown significantly more DYRK1A-positive NFTs in DS brains than in sporadic Alzheimer disease (AD) brains. This study demonstrates a gene dosage-proportional increase in the level of DYRK1A in DS in the cytoplasm and the cell nucleus, and enhanced cytoplasmic and nuclear immunoreactivity of DYRK1A in DS. The results suggest that overexpressed DYRK1A may alter both phosphorylation of tau and alternative splicing factor (ASF). Two-dimensional electrophoresis revealed modification of ASF phosphorylation in DS/AD and AD in comparison to controls. Altered phosphorylation of ASF by overexpressed nuclear DYRK1A may contribute to the alternative splicing of the tau gene and an increase by 2.68 × of the 3R/4R ratio in DS/AD, and a several-fold increase in the number of 3R tau-positive NFTs in DS/AD subjects compared with that in sporadic AD subjects. These data support the hypothesis that phosphorylation of ASF by overexpressed DYRK1A may contribute to alternative splicing of exon 10, increased expression of 3R tau, and early onset of neurofibrillary degeneration in DS.     

Iatrogenic influence of testosterone therapy among persons with Klinefelter Syndrome

The purpose of this work is a presentation of cases of persons with Klinefelter Syndrome where, most probably--as a result of testosterone supplementation therapy, some aggressive behaviours occurred requiring implementation of pharmacotherapy and psychiatric hospitalisation. The authors contemplate adequacy of standard hormone treatment where the main purpose is to improve the quality of life of the karyotype 47, XXY patients described. The article has been enhanced by a theoretical introduction into the basic subject which is the Klinefelter Syndrome.     

Temporal pattern of suicide risk in young individuals with early psychosis

Individuals with a first episode of psychotic illness are known to be at high risk of suicide, yet little is understood about the timing of risk in this critical period. The present study aimed to examine the temporal pattern of suicide risk in patients with early psychosis (EP) and to determine whether discrete periods of significantly elevated risk can be identified up to 24 months after commencing treatment. Suicidality ratings collected each month as part of patient routine assessment at the Early Psychosis Prevention and Intervention Centre (EPPIC) were retrieved from the service database for patients treated between December 2002 and December 2005 (N = 696). Time-series analysis was performed on suicide risk estimated from the aggregated data of 94 individuals who met the study inclusion criteria. Suicide risk was highest in the first month of treatment, decreasing rapidly over the next 6 months and declining slightly thereafter. A power function adequately described this curvilinear trend. Fluctuations around the trend were unpredictable, except for a mild tendency to reverse from month to month, and did not reach statistical significance. The findings suggest limited scope for preventative interventions driven by chronology alone. Intensive routine suicide screening across the course of treatment may facilitate identification and early management of EP patients at suicide risk.     

A genistein derivative, ITB-301, induces microtubule depolymerization and mitotic arrest in multidrug-resistant ovarian cancer

Purpose  

To investigate the mechanistic basis of the anti-tumor effect of the compound ITB-301.     

Are low and high number magnitudes processed differently while resolving the conflict evoked by the SNARC effect?

In the brain, numbers are thought to be represented in a spatially organised fashion on what is known as the Mental Number Line (MNL). The SNARC (Spatial-Numerical Association of Response Codes) effect refers to the faster responses to digits when the reaction side is congruent with the digit position on the MNL (e.g. a left-handed response to a small magnitude) and the slowing down of responses (inhibition) in the case of incongruity. We examined the electrophysiological correlates of conflict, which are linked to that of inhibition, to shed light on the relationship between the SNARC effect and executive attention. Event-related potentials (ERPs) were recorded from twenty-nine participants during a parity-judgment task. The participants responded more quickly on congruent than on incongruent trials. The congruency effect was reflected in early sensory (N1, N2) components above parieto-occipital and frontal regions, as well as in the later P3 component above centro-parietal areas. Moreover, both the N1 amplitude and N2 latency were greater with high than low magnitude digit targets. P3 amplitude modulation implies that the SNARC effect is the result of first evoking the parallel processing of digit magnitude categorisation (in the occipital and central areas) and numeric conflict detection (in the parieto-occipital and frontal areas) and secondly conflict monitoring and resolution localised in the centro-parietal and frontal sites. These results also suggest that the left hemisphere specialises in conflict processing of high magnitude digit targets, while the right hemisphere of low digit magnitudes.     

Peripheral blood T lymphocyte subsets in children with congenital asplenia

The aim of the current study was to examine whether a congenital lack of the spleen changes distribution, state of activation and function of peripheral lymphocyte T subsets. Seven children with congenital asplenia (CA) aged 1.5–17 years and seven age-matched controls were tested. By triple-color flow cytometry we examined: (1) the expression of CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD56⁺ on lymphocytes; (2) the distribution of CD45RA⁺ and CD45RO⁺ in CD4⁺ and CD8⁺; (3) the expression of CD27⁺ in the CD4⁺ and CD8⁺ T-cell-bearing CD45RA⁺, CD45RO⁺, or CD45RB⁺. Lymphocyte proliferative responses and cytokines production (IFN-gamma, IL-6, TNF-alfa, and IL-10) in anti-CD3-induced peripheral blood mononuclear cells were tested. The results indicate (1) a normal distribution of the basic lymphocyte subsets, (2) low CD3⁺/CD8⁺ percentage but expressing CD8^+high and non-significantly elevated CD4⁺/CD8⁺ ratio, (3) CD45RA^+high and CD27^+high in the CD4⁺ and CD8⁺ T cell, and (4) CD45RB^+high in the CD4⁺ and CD45RO^+high in the CD8⁺. The distribution of CD27⁺ in the CD45RA⁺ and CD45RO⁺ CD4⁺ T cells remained unchanged. However, the percentage of CD8⁺/CD45RO⁺/CD27⁺ T cells tended to be elevated. Altogether, these data indicate that CA is connected with (1) the presence CD4⁺ T cells expressing the “naive” phenotype (CD45RA^+high RB^+high and CD27^+high), (2) high numbers of activated CD8⁺ T cells shifted toward the memory phenotype (CD45RO^+high) but still showing high CD27⁺ expression, which may indicate failure in T CD8⁺ cytotoxic effectors differentiation, and (3) a tendency to the rather pro-inflammatory status of cells, low IL-10 expression, and suboptimal lymphocytes responses to mitogenic stimulation.