ETIOLOGICAL AND EPIDEMIOLOGICAL INVESTIGATIONS OF INFLUENZA IN VARNA AND VARNA DISTRICT DURING THE EPIDEMIC WAVE IN 1974—1975

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IGF-1 Induction by Acylated Steryl β-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

BACKGROUND: The pathology of diabetic neuropathy involves oxidative stress on pancreatic β-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl β-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic β-cells remains unknown. Here we examined the effects of PR-ASG on IGF-1 and glucose metabolism in β-cells exposed to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a pre-germinated brown rice (PR)-diet was tested in streptozotocin (STZ)-induced diabetic rats. Compared with diabetic rats fed control diets, the PR-diet fed rats showed an improvement of serum metabolic and neurophysiological parameters. In addition, IGF-1 levels were found to be increased in the serum, liver, and pancreas of diabetic rats fed the PR-diet. The increased IGF-1 level in the pancreas led us to hypothesize that PR-ASG is protective for islet β-cells against the extensive injury of advanced or severe diabetes. Thus we examined PR-ASG to determine whether it showed anti-apoptotic, pro-proliferative effects on the insulin-secreting β-cells line, INS-1; and additionally, whether PR-ASG stimulated IGF-1 autocrine secretion/IGF-1-dependent glucose metabolism. We have demonstrated for the first time that PR-ASG increases IGF-1 production and secretion from pancreatic β-cells. CONCLUSION/SIGNIFICANCE: These findings suggest that PR-ASG may affect pancreatic β-cells through the activation of an IGF-1-dependent mechanism in the diabetic condition. Thus, intake of pre-germinated brown rice may have a beneficial effect in the treatment of diabetes, in particular diabetic neuropathy

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227

Gastroesphageal Reflux Disease and Otorhinolaryngologic Diseases in Children and Adolescents

Gastroesophageal reflux (GER) is a retrograde flow of gastric contents into the esophagus with or without regurgitation and vomiting. This physiologic phenomenon is most frequently after meals and could happen several times a day for a short period (no more than 3 minutes). It covers 1-5% of the day in healthy infants, children and adolescents. GER accompanied by bothersome symptoms is considered gastroesophageal reflux disease (GERD). Given the lack of specific symptoms, GERD diagnosis must be made on the basis of clinical symptoms and standardized questionnaires together with esophageal 24 hour multichannel intraluminal impedance monitoring, which provides more precise information than esophageal pH monitoring because it allows identification of both acidic and nonacidic reflux and determines the relationship between symptoms and episodes of reflux. Close cooperation between general practitioners, ENT specialists, paediatricians and pediatric gastroenterologists enables refinement of diagnosis and helps correct therapeutic approach in the treatment of GERD in children

Live cell microscopy analysis of radiation-induced DNA double-strand break motion

We studied the spatiotemporal organization of DNA damage processing by live cell microscopy analysis in human cells. In unirradiated U2OS osteosarcoma and HeLa cancer cells, a fast confined and Brownian-like motion of DNA repair protein foci was observed, which was not altered by radiation. By analyzing the motional activity of GFP-53BP1 foci in live cells up to 12-h after irradiation, we detected an additional slower mobility of damaged chromatin sites showing a mean square displacement of ≈0.6 μm2/h after exposure to densely- or sparsely-ionizing radiation, most likely driven by normal diffusion of chromatin. Only occasionally, larger translational motion connected to morphological changes of the whole nucleus could be observed. In addition, there was no general tendency to form repair clusters in the irradiated cells. We conclude that long-range displacements of damaged chromatin domains do not generally occur during DNA double-strand break repair after introduction of multiple damaged sites by charged particles. The occasional and in part transient appearance of cluster formation of radiation-induced foci may represent a higher mobility of chromatin along the ion trajectory. These observations support the hypothesis that spatial proximity of DNA breaks is required for the formation of radiation-induced chromosomal exchanges

Hypoxia Differentially Regulates Arterial and Venous Smooth Muscle Cell Migration

Intimal hyperplasia (IH) is a clinical concern leading to failure of up to 50% of vein grafts and 10% of arterial grafts after 10 years with no known current treatment. Recent studies have shown that hypoxia differentially regulates proliferation of vein derived smooth muscle cells (V-SMC) compared to artery derived smooth muscle cells (A-SMC). The objective of this study is to evaluate the effect of hypoxia on cellular migration and the mechanisms underlying the differential effects of hypoxia on A-SMC and V-SMC migration.Hypoxic treatment (3-5% O2) of Smooth Muscle Cells (SMC) resulted in differential migration in scratch wound and electric cell substrate impedance sensing (ECIS) assays. Hypoxia led to greater migration compared to normoxia with venous derived wound closure (V-SMC 30.8% Normoxia to 67% Hypoxia) greater than arterial wound closure (A-SMC 6.2% Normoxia to 24.7% Hypoxia). Paracrine factors secreted by hypoxic endothelial cells induced more migration in SMC compared to factors secreted by normoxic endothelial cells. Migration of V-SMC was greater than A-SMC in the presence of paracrine factors. Neutralizing antibody to Vascular Endothelial Growth Factor Receptor -1 (VEGFR-1) completely inhibited V-SMC migration while there was only partial inhibition of A-SMC migration. A-SMC migration was completely inhibited by Platelet Derived Growth Factor BB (PDGF-BB) neutralizing antibody. p38 Mitogen Activated Protein kinase (p38 MAPK) inhibitor pre-incubation completely inhibited migration induced by paracrine factors in both A-SMC and V-SMC.Our study determines that SMC migration under hypoxia occurs via both an autocrine and paracrine mechanism and is dependent on Vascular Endothelial Growth Factor-A (VEGF-A) in V-SMC and PDGF-BB in A-SMC. Migration of both A-SMC and V-SMC is inhibited by p38 MAPK inhibitor. These studies suggest that pharmacotherapeutic strategies directed at modulating p38 MAPK activity can be exploited to prevent IH in vascular grafts