Protection with estradiol in developmental models of apoptotic neurodegeneration

Medical measures that bear no known danger for the adult brain may trigger active neuronal death in the developing brain. Pharmacological blockade of N-methyl-D-aspartate or activation of GABA(A) receptors, blockade of voltage-dependent sodium channels, and oxygen induce widespread apoptotic neurodegeneration during the period of rapid brain growth in rodents. Because such measures are often necessary in critically ill infants and toddlers, search for adjunctive neuroprotective strategies is warranted. We report that 17beta-estradiol ameliorates neurotoxicity of drugs that block N-methyl-D-aspartate receptors, activate GABA(A) receptors, or block voltage-gated sodium channels and reduces neurotoxicity of oxygen in the infant rat brain. This neuroprotective effect is reversed by tamoxifen and cannot be reproduced by 17alpha-estradiol. 17Beta-estradiol did not affect GABA(A) or N-methyl-D-aspartate currents in hippocampal neuronal cultures, indicating that direct modulation of neurotransmitter receptor/channel properties by this compound cannot explain neuroprotective effect. 17beta-Estradiol did, however, increase levels of phosphorylated extracellular signal-regulated kinase 1/2 and AKT, suggesting that activation of these prosurvival proteins may represent one mechanism for its neuroprotective action. 17Beta-estradiol and related compounds may be neuroprotective agents suitable for use in critically ill infants and toddlers. Its supplementation may particularly help to improve neurocognitive outcome in preterm infants who are prematurely deprived of maternal estrogen.     

Fluorescence in situ hybridization BCR/ABL fusion signal rate in interphase nuclei of healthy volunteer donors: a test study for establishing false positive rate

Fluorescence in situ hybridization (FISH) using chromosome-specific DNA probes is rapidly becoming a part of clinical laboratory practice. However, as a relatively new clinical test, it is not yet standardized and for practical reasons each laboratory must establish its own criteria. For this purpose we have evaluated the specificity of a dual-color BCR/ABL translocation probe by establishing the range of BCR/ABL fusion-positive scores in a healthy donor group. The false positive rate (FPR), determined by the percent of FISH BCR/ABL fusion-positive cells found in the specimens of healthy donors, was estimated at 2.3% (mean = 1%-4%). Thus the cut-off value for false positive nuclei was set at 5%.     

Saccharomyces boulardii interferes with enterohemorrhagic Escherichia coli-induced signaling pathways in T84 cells

Enterohemorrhagic Escherichia coli (EHEC) infections are associated with the modification of tight-junction permeability and synthesis of proinflammatory cytokine interleukin-8 (IL-8). In a previous study, it was demonstrated that EHEC-induced IL-8 secretion is due to the involvement of the mitogen-activated protein kinase (MAPK), AP-1, and NF-kappaB pathways. In this study, we investigated the effect of the yeast Saccharomyces boulardii on EHEC infection in T84 cells. For this purpose, cells were (i) incubated with bacteria and yeast at the same time or (ii) incubated overnight with yeast cells that were maintained during infection or eliminated by several washes before infection. Coincubation is sufficient to maintain the transmonolayer electrical resistance (TER) of EHEC-infected cells, whereas the preincubation of cells with the yeast without elimination of the yeast during infection is necessary to significantly decrease IL-8 secretion. We thus analyzed the mechanisms of S. boulardii action. We showed that S. boulardii has no effect on EHEC growth or on EHEC adhesion. Kinetics studies revealed that EHEC-induced myosin light chain (MLC) phosphorylation precedes the decrease of TER. ML-7, an MLC kinase inhibitor, abolishes the EHEC-induced MLC phosphorylation and decrease of TER. Studies show that S. boulardii also abolishes EHEC-induced MLC phosphorylation. We demonstrated that the preincubation of cells with S. boulardii without washes before EHEC infection inhibits NF-kappaB DNA binding activity, phosphorylation and degradation of IkappaB-alpha, and activation of the three members of a MAPK group (extracellular signal-regulated protein kinases 1 and 2, p38, and c-jun N-terminal kinase). These findings demonstrate that S. boulardii exerts a preventive effect on EHEC infection by (i) interfering with one of the transduction pathways implicated in the control of tight-junction structure and (ii) decreasing IL-8 proinflammatory secretion via inhibition of the NF-kappaB and MAPK signaling pathways in infected T84 cells.     

Cardiovascular magnetic resonance findings in a case of Danon disease

Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies.     

Increasing recreational and leisure time physical activity in Poland–how to overcome barriers of inactivity

Title Increasing recreational and leisure time physical activity in Poland–how to overcome barriers of inactivity Aim International experts have alerted us about the burden of a sedentary lifestyle. In recent WHO reports, lack of physical activity was placed as one of the leading risk factors of chronic diseases affecting both developed and developing countries. Despite some beneficial changes in lifestyle during the last decade, the level of physical activity in Poland still differs from many other European countries and international recommendations as well. Methods The analysis was based on a review of the Medline database, the main Polish governmental documents and studies concerning physical activity levels and the most interesting recent programmes on the topic. Results In the article the physical activity level of the Polish population and the main factors influencing it are discussed. The results of the national WOBASZ Project (2003–2005) revealed that nearly 35% of Polish adults are not active during their leisure time, while only about 17% are only occasionally engaged in any exercise. Over 42% of children up to 14 years old spend above 3 h per day in front of a TV or computer monitor. Over 50% of Polish teenagers aged 15–19 years do not participate in any kind of recreational physical activity. The most successful or promising programmes promoting active lifestyles recently applied in Poland are described in the article. The Great Polish Nationwide Physical Activity Campaign “Revitalize Your Heart” as an innovative and effective complex method is discussed by the authors. Conclusions Promising results from several new innovative large-scale physical activity-promoting programmes developed and implemented in Poland in last 5 years let us hope that the battle against a sedentary lifestyle and its health consequences could result in further progressive improvement of the physical activity level of the whole society.     

Effectiveness of the Thin Prep® Imaging System in the detection of adenocarcinoma of the gynecologic system

BACKGROUND.

The ThinPrep Imaging System (TIS) has been approved by the U.S. Food and Drug Administration for use to decrease the number of false‐negative results in ThinPrep (TP) gynecologic specimens and increase cytotechnology productivity. Although the increased detection of squamous abnormalities using the TIS has been well documented, to the authors' knowledge, data regarding the impact of the TIS in the detection of glandular abnormalities is limited. The goal of the current study was to evaluate the effectiveness of the TIS in detecting glandular abnormalities in cervicovaginal specimens.

METHODS.

TIS evaluated TP tests with histologic confirmation of adenocarcinoma involving the gynecologic system were included in the current study. Two cytotechnologists independently reviewed the cases for the presence or absence of atypical glandular cells. Review results were correlated with initial cytologic and histologic diagnoses.

RESULTS.

A total of 124 cases met the criteria for inclusion in the current study. Seventy of these cases (56%) were found to contain atypical glandular cells on the TP slide. TIS was able to identify atypical cells in 97% of these cases (68 of 70 cases). Nine cases initially reported as benign were found to contain atypical glandular cells on secondary review. All but 1 of these cases contained atypical glandular cells detected by the TIS. The majority of these false‐negative cases (6 of 9 cases) derived from endometrial adenocarcinoma. No cytologic evidence of a glandular abnormality was found in the 54 remaining cases.

CONCLUSIONS.

The TIS was found to be effective in identifying atypical glandular cells in specimens containing malignant glandular cells, leading to a full review of the slide. Cancer (Cancer Cytopathol) 2008. © 2007 American Cancer Society.     

The effect of monocytes on early activation of lymphocytes T among children with idiopathic uveitis

PURPOSE: We have investigated T Lymphocytes ability for CD69 molecule induction in presence and absence of monocytes in idiopathic uveitis. MATERIAL AND METHODS: Twenty-five children with idiopathic uveitis were studied. The control group consisted of 12 healthy children. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinised venous blood, by density gradient centrifugation. CD69 expression was cytometrically assessed on freshly isolated and cultured T lymphocytes. RESULTS: CD69 expression on freshly isolated peripheral blood T lymphocytes was low in both studied groups. LPS-stimulated monocytes added to cultures of T lymphocytes induced increase in CD69 expression but significantly lower in children with idiopathic uveitis compare to healthy children.