Cell-line specific protection by berry polyphenols against hydrogen peroxide challenge and lack of effect on metabolism of amyloid precursor protein

Amyloid precursor protein (APP) altered metabolism, Aβ‐overproduction/aggregation and oxidative stress are implicated in the development of Alzheimer's disease pathology. Based on our previous data indicating that administration of a polyphenol‐rich (PrB) blueberry extract (from wild Vaccinium angustifolium) is memory enhancing in healthy mice and in order to delineate the neuroprotective mechanisms, this study investigated the antioxidant effects of PrB in H₂O₂‐induced oxidative damage, Aβ peptide fibrillogenesis and APP metabolism. PrB suppressed H₂O₂‐initiated oxidation (DCF assay) and cell death (MTT assay) in SH‐SY5Y cells. Protective effects were observed on Chinese hamster ovary (CHO) cells overexpressing APP770 carrying the mutation Val717Phe only at high concentrations, while further damage on HEK293 cells was induced after co‐treatment with 250 µ m H₂O₂ and PrB in comparison with H₂O₂ alone. Using the thioflavine T assay, blueberry polyphenols inhibited Aβ‐aggregation (~70%, 15 µg/mL) in a time‐dependent manner, while in the CHO^APP770 cells it had no effect on APP metabolism as assessed by western blot. The results suggest that blueberry polyphenols exhibit antioxidant and/or pro‐oxidant properties according to the cellular environment and have no effect on APP metabolism. Copyright © 2011 John Wiley & Sons, Ltd.     

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: a systems biology approach

A part of current research has intensively been focused on the proliferation and metabolic processes governing biological systems. Since the advent of high throughput methodologies such as microarrays, the load of genomic data has increased geometrically and along with that the need for computational methods to interpret these data. In the present study, we investigated in?vitro the common proliferation and metabolic processes, associated with common oncogenic pathways, as far as gene expression is concerned, between the T-cell acute lymphoblastic leukemia (CCRF-CEM) and the rhabdomyosarcoma (TE-671) cell lines. We present a computational approach, using cDNA microarrays, in order to identify commonalities between diverse biological systems. Our analysis predicted that JAK1, STAT1, PIAS2 and CDK4 are the driving forces in the two cell lines. This type of analysis may lead to the understanding of the common mechanisms that transform physiological cells to malignant, and may reveal a new holistic approach to understanding the dynamics of tumor onset as well as the mechanistics behind oncogenic drivers.     

Evaluation of the potential excess of statistically significant findings in published genetic association studies: application to Alzheimer's disease

The authors evaluated whether there is an excess of statistically significant results in studies of genetic associations with Alzheimer's disease reflecting either between-study heterogeneity or bias. Among published articles on genetic associations entered into the comprehensive AlzGene database (www.alzgene.org) through January 31, 2007, 1,348 studies included in 175 meta-analyses with 3 or more studies each were analyzed. The number of observed studies (O) with statistically significant results (P = 0.05 threshold) was compared with the expected number (E) under different assumptions for the magnitude of the effect size. In the main analysis, the plausible effect size of each association was the summary effect presented in the respective meta-analysis. Overall, 19 meta-analyses (all with eventually nonsignificant summary effects) had a documented excess of O over E: Typically single studies had significant effects pointing in opposite directions and early summary effects were dissipated over time. Across the whole domain, O was 235 (17.4%), while E was 164.8 (12.2%) (P < 10(-6)). The excess showed a predilection for meta-analyses with nonsignificant summary effects and between-study heterogeneity. The excess was seen for all levels of statistical significance and also for studies with borderline P values (P = 0.05-0.10). The excess of significant findings may represent significance-chasing biases in a setting of massive testing.     

Identifying nutritionally vulnerable groups in case of emergencies: experience from the Athens 1999 earthquake

During emergency situations in developing countries, young children have been identified as the most nutritionally vulnerable group. Comparatively less is known regarding nutritional risk of individuals in well-nourished societies hit by a major disaster. The aim of the present study, therefore, was to assess the nutritional status of Greek people who were left homeless after the Athens 1999 earthquake. A total of 225 volunteers from two camps were surveyed for dietary intake information and surrogate measures of nutritional status. Energy consumption and anthropometric indices of the children and adolescents revealed no sign of undernourishment. On the other hand, adults and the elderly consumed considerably less energy than that required for long-term preservation of health. Short-term energy and protein deficits, however, did not jeopardise their nutritional status as it might have expected, on the basis of high body mass indexes and normal haematological and biochemical profiles that were documented. In conclusion, the results of the present study indicate that nutritional risk in the acute phase after a major emergency in a previously well-nourished population is rather low. This is especially true for younger individuals, probably due to increased provision from the family and the community. Nevertheless, older persons may face increased risk as the situation is prolonged.     

Quality of life psychosocial characteristics in Greek patients with leg ulcers: a case control study

Chronic leg ulcers are a public health problem that can have a significant impact on the patient's physical, socioeconomic and psychological status. The aim of this study is to evaluate the quality of life, anxiety and depression, self‐esteem and loneliness in patients suffering from leg ulcers. A total of 102 patients were enrolled in the study. The quality of life, anxiety and depression, self‐esteem and loneliness of the patient were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Rosenberg's Self‐esteem Scale (RSES) and the UCLA Loneliness Scale (UCLA‐Version 3), respectively. The mean DLQI score was 13·38 ± 2·59, suggesting a serious effect on the quality of life of patients. Those with leg ulcers had statistically significant higher scores according to the HADS‐total scale (P = 0·031) and HADS‐anxiety subscale (P = 0·015) compared with healthy volunteers. Moreover, a statistically significant difference was found between the two groups concerning the UCLA‐scale (P = 0·029). Female patients presented with a higher score of anxiety (P = 0·027) and social isolation (P = 0·048), and worse quality of life (P = 0·018) than male patients. A severe quality of life impairment was documented, reflecting a significant psychosocial impact on patients with leg ulcers.     

Hippocampal subfield volumetry in corticobasal syndrome of diverse underlying pathologies

Journal of Neurology - Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer’s disease (AD). Typical amnestic AD is characterized by early selective hippocampal...     

Mullerian inhibiting substance inhibits invasion and migration of epithelial cancer cell lines

Objective

Given the fact that Mullerian Inhibiting Substance (MIS) causes complex remodeling of the urogenital ridge and regression of the Mullerian ducts during male embryonic development, we examined whether MIS could affect similar cell properties such as migration and invasion that could contribute ultimately to micro-metastasis of cancers arising from Mullerian tissues. MIS receptor expressing cell lines found to be invasive and migratory in vivo are examined in an in vivo assay that is cost-effective.

Methods

We designed in vitro and in vivo experiments to determine if MIS inhibited the movement of cancer lines IGROV-1, HEp3, MDA-MB-231, and HT1080 in cell culture invasion/migration chamber assays and in chick embryo metastasis assays.

Results

MIS, at concentrations below those that inhibit cell proliferation, blocked in vitro invasion and in vivo migration of epithelial cancer cells that express the MIS receptor.

Conclusions

While our laboratory has previously established MIS as an inhibitor of cancer cell proliferation using in vitro assays and in vivo xenografts, we now show that MIS can also inhibit in vivo tumor migration.     

Transient acantholytic dermatosis (Grover's disease) in a renal transplant patient

Grover's disease ("transient acantholytic dermatosis") is a transient dermatosis of unknown cause manifesting clinically as a papular skin eruption located usually on the anterior chest and abdomen and histologically with dyskeratosis and acantholysis. Grover's disease has occasionally been reported in patients with chronic renal failure, HIV infection, hematological malignancies and bone-marrow allotransplantation. We report herein a new case of Grover's disease that developed in a renal transplant patient. To the best of our knowledge, this is the first observation of Grover's disease developing in the setting of solid organ transplantation.