Nitric oxide modulates apomorphine-induced recognition memory deficits in rats

Nitric oxide (NO) is an important intracellular messenger in the brain. The implication of NO in schizophrenia is well documented although it is not yet clear whether net over or underproduction of NO is typical of this disease. In line with this, either NO donors or NO synthase (NOS) inhibitors were found to abolish psychotomimetic effects, including cognition deficits, produced by N-methyl-d-aspartate (NMDA) receptor hypofunction. In addition, there is poor experimental evidence concerning the efficacy of NO to modulate memory deficits produced by dopamine (DA) dysfunction. The present study was designed to investigate the ability of NO modulators (NO donors and NOS inhibitors to reverse recognition memory impairments produced by the DA D₁/D₂ mixed receptor agonist apomorphine in rats. For these studies, the novel object recognition test (NORT) was used as the memory test. Apomorphine (0.05, 0.1, 0.5 and 1.0 mg/kg), dose-dependently, disrupted performance in this recognition memory procedure in rats. The NO donors molsidomine (2.0 and 4.0 mg/kg) and SNP (0.3 and 1.0 mg/kg), reversed the impairing effects of apomorphine (1.0 mg/kg) in the NORT. Administration of the NOS inhibitors L-NAME (1.0 and 3.0 mg/kg) or 7-NI (1.0 and 3.0 mg/kg) produced similar results. The present findings indicate a) that apomorphine dose-dependently impaired recognition memory and b) that a cognitive deficit produced by DA dysfunction is sensitive to NO.     

Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses

Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -ΔEx3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of immunotherapeutic approaches targeting survivin in CML.     

Brief Report: “Allergic Symptoms” in Children with Autism Spectrum Disorders. More than Meets the Eye?

Many children with Autism Spectrum Disorders (ASD) have either family and/or personal history of “allergic symptomatology”, often in the absence of positive skin or RAST tests. These symptoms may suggest mast cell activation by non-allergic triggers. Moreover, children with mastocytosis or mast cell activation syndrome (MCAS), a spectrum of rare diseases characterized by increased number of activated mast cells in many organs, appear to have ASD at a rate tenfold higher (1/10 children) than that of the general population (1/100 children). Mast cell activation by allergic, infectious, environmental and stress-related triggers, especially perinatally, would release pro-inflammatory and neurotoxic molecules. We speculate these could disrupt the gut–blood–brain barriers, thus contributing to brain inflammation and ASD pathogenesis. Increased mast cell responsiveness may define at least a subgroup of ASD subjects, who could benefit from inhibition of mast cell activation.     

Associations between Lifestyle Patterns and Body Mass Index in a Sample of Greek Children and Adolescents

Background

Although eating and physical activity behaviors have been previously individually investigated with regard to overweight in children, multidimensional lifestyle patterns, based on these behaviors, have not been explored.

Objective

To assess lifestyle patterns in relation to body mass index (BMI), in a nationally representative sample of the Greek pediatric population

Design

Cross-sectional study. Data were collected from May through July 2007.

Subjects

The sample consisted of 1,305 children and adolescents (ages 3 to 18 years).

Main outcome measures

Information on participants' dietary intake, eating behaviors, physical activity habits, and BMI were collected. Adherence to the Mediterranean diet guidelines was evaluated using the KIDMED Mediterranean diet quality index; the higher the score in this index the more favorable the dietary pattern. The Goldberg cut-off limits for the ratio of energy intake/basal metabolic rate were used to evaluate dietary low energy reporting and participants were accordingly classified as low-energy reporters.

Statistical analysis

Principal component analysis was performed to identify participants' lifestyle patterns. Associations between BMI and lifestyle patterns were further evaluated using multiple linear regression analyses, after controlling for potential confounders.

Results

Principal component analysis identified seven lifestyle patterns explaining 85% of the total variance of lifestyle habits. A lifestyle pattern characterized by higher eating frequency, breakfast consumption and higher KIDMED score was negatively associated with BMI (standardized β=−.125, P<0.001), after controlling for age, sex, and parental education. The association remained significant even when low-energy reporters were excluded from the analysis.

Conclusions

Results from the study suggest a potential intercorrelation and protective action of selected eating behaviors, namely eating frequency, breakfast consumption, and adherence to the Mediterranean diet, against overweight and obesity in children and adolescents.     

Predictors of caesarean section – a cross-sectional study in Hungary

Purpose: The aim of this study was to analyse the factors associated with caesarean section (CS) at the Department of Obstetrics and Gynaecology, University of Szeged, Hungary.

Study design: Data collection was based on self-administered questionnaire and medical records related to the deliveries in the year of 2014. Maternal age, education level, marital status, pre-gestational body mass index (BMI), infertility treatment, previous CS, gestational diabetes mellitus (GDM), pre-pregnancy hypertension and pregnancy-induced hypertension (HT/PIH) were examined. The participation rate was 67.3%, multiple pregnancies and questionnaires with missing data were excluded (n?=?1493). Univariate and multivariate comparisons were performed.

Results: There were 1125 (45.4%) CSs out of 2479 deliveries. CS rate: 40.0%. Underweight 109 (7.1%), normal 921 (60.2%), overweight 320 (20.9%) obese 181 (11.8%). HT/PIH: 7.6% (n?=?117), GDM: 10.1% (n?=?155). The odds of CS were significantly higher among obese mothers (OR: 1.81) compared with the normal weight group. Increasing maternal age (OR: 0.97) and being underweight (OR: 0.59) significantly decreased, previous CS (OR: 12.19), infertility treatment (OR: 1.91) and HT/PIH (OR: 1.87) significantly increased the probability of CS.

Conclusions: Pre-gestational obesity, infertility treatment, previous CS and HT/PIH had significant effect on the mode of delivery.     

Substance P (SP) induces expression of functional corticotropin-releasing hormone receptor-1 (CRHR-1) in human mast cells

Corticotropin-releasing hormone (CRH) is secreted under stress and regulates the hypothalamic-pituitary-adrenal axis. However, CRH is also secreted outside the brain where it exerts proinflammatory effects through activation of mast cells, which are increasingly implicated in immunity and inflammation. Substance P (SP) is also involved in inflammatory diseases. Human LAD2 leukemic mast cells express only CRHR-1 mRNA weakly. Treatment of LAD2 cells with SP (0.5-2?μM) for 6?hours significantly increases corticotropin-releasing hormone receptor-1 (CRHR-1) mRNA and protein expression. Addition of CRH (1?μM) to LAD2 cells, which are "primed" with SP for 48?hours and then washed, induces synthesis and release of IL-8, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) 24?hours later. These effects are blocked by pretreatment with an NK-1 receptor antagonist. Treatment of LAD2 cells with CRH (1?μM) for 6?hours induces gene expression of NK-1 as compared with controls. However, repeated stimulation of mast cells with CRH (1?μM) leads to downregulation of CRHR-1 and upregulation in NK-1 gene expression. These results indicate that SP can stimulate mast cells and also increase expression of functional CRHR-1, whereas CRH induces NK-1 gene expression. These results may explain CRHR-1 and NK-1 expression in lesional skin of psoriatic patients.     

MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis

MicroRNAs are short non-coding RNAs that regulate gene expression. Previously, in a genome-wide screen, we found deregulation of microRNA expression in psoriasis skin. MicroRNA-21 (miR-21) is one of the microRNAs significantly up-regulated in psoriasis skin lesions. To identify the cell type responsible for the increased miR-21 level, we compared expression of miR-21 in epidermal cells and dermal T cells between psoriasis and healthy skin and found elevated levels of miR-21 in psoriasis in both cell types. In cultured T cells, expression of miR-21 increased markedly upon activation. To explore the function of miR-21 in primary human T helper cells, we inhibited miR-21 using a tiny seed-targeting LNA-anti-miR. Specific inhibition of miR-21 increased the apoptosis rate of activated T cells. Our results suggest that miR-21 suppresses apoptosis in activated T cells, and thus, overexpression of miR-21 may contribute to T cell-derived psoriatic skin inflammation.     

The expression of keratinocyte growth factor receptor (FGFR2-IIIb) correlates with the high proliferative rate of HaCaT keratinocytes

Keratinocyte growth factor receptor (KGFR = FGFR2-IIIb) is a tyrosine kinase receptor expressed by keratinocytes, which mediates the effects of fibroblast growth factors (FGF). There are contradictory data in the literature regarding the role of FGFR2-IIIb during the proliferation/differentiation programme of keratinocytes. In this study, we aimed to investigate whether overexpression of FGFR2-IIIb may have a role in the regulation of keratinocyte proliferation. We analysed the expression of FGFR2-IIIb in an in vitro HaCaT model system representing different stages of proliferation and differentiation of keratinocytes. Real-time RT-PCR and Western blot analyses demonstrated a correlation between FGFR2-IIIb mRNA and protein expression and the proportion of cells in S/G2/M phase in synchronized HaCaT keratinocytes and thus with proliferation activity (r = 0.96). After treatment with the antipsoriatic drug, dithranol, FGFR2-IIIb is downregulated dose dependently both at mRNA and protein levels. Moreover, when the rate of proliferation is decreased by the lack of cell attachment to the culturing surface, FGFR2-IIIb mRNA (P = 0.0315) and protein expressions were also reduced (P = 0.0242), while a differentiation marker, keratin 10, mRNA (P = 0.0003) and protein levels (P = 0.001) were increased (r = -0.92). Based on our results we conclude that FGFR2-IIIb expression in HaCaT keratinocytes corresponds with the proliferative activation of the cells and is not related to the differentiation programme.