No Evidence of Persisting Unrepaired Nuclear DNA Single Strand Breaks in Distinct Types of Cells in the Brain, Kidney, and Liver of Adult Mice after Continuous Eight-Week 50 Hz Magnetic Field Exposure with Flux Density of 0.1 mT or 1.0 mT

BACKGROUND: It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. METHODS: In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. RESULTS: Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. CONCLUSION: No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT

A lurking threat: transfer of peanut allergy through peripheral blood stem cell transplantation

Background There exist several reports of atopy and allergen-specific IgE-mediated hypersensitivity transferred by bone marrow transplantation, and it has been concluded that the transfer of allergic reactivity results from adoptive transfer of IgE-producing donor-derived B- and/or plasma cells. To the best of our knowledge we report the first case of peanut allergy after PBSCT.Case presentation A 55-year-old anciently non allergic man with secondary acute myeloid leukemia (AML) received an allogeneic peripheral blood stem cell transplantation from a matched unrelated donor following reduced-intensity conditioning. On day 32 after PBSCT, while still on prophylactic systemic immunosuppression, the patient noticed a first episode of angioedema with swelling of the nasal and oral mucosa 30 min after consuming peanut puffs. In a second episode, eight months after PBSCT, he again developed angioedema, generalized pruritus and nausea within minutes after eating biscuits containing hazelnut and peanut. Moreover, after topical application of a peanut oil-containing ointment, the patient experienced facial erythema and angioedema. Nine months after PBSCT an evaluation for peanut allergy revealed a highly increased specific IgE to peanut of 75.9 kU/l. Accordingly, skin prick tests for peanut extract were also positive. In consequence, the patient was counseled to strictly avoid peanut-related products, and provided with an emergency set. No adverse allergic events have occurred since for an observation time of 15 months after PBSCT. The stem cell donor was contacted and confirmed intolerance to peanuts. His specific serum IgE pattern nine month after PBSCT harvest was analysed and showed similar sensitization profiles compared to those of the transplant recipient.Conclusions Because of the close temporal association between the onset of allergic symptoms in the PBSC recipient it is reasonable to assume that the acquired peanut allergy had been transferred from the donor to the recipient by the PBSC graft. Keywords: Peanut allergy, Stem cell transplantation, Allergy transfer, IgE-mediated hypersensitivit

Infliximab-Associated Chronic Inflammatory Central Nervous System Disease and Peroneal Nerve Injury in a Psoriatic Patient Refractory to Treatment: Case Report with 10-Year Follow-Up

The tumor necrosis factor-α (TNF-α) antagonists infliximab, adalimumab, and etanercept have been approved for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, and psoriatic arthritis. Manifestations of demyelinating disease have been reported for patients receiving TNF-α antagonists. We describe a rare manifestation of a chronic inflammatory process affecting both the central and peripheral nervous system in a patient who received infliximab for the treatment of psoriasis and psoriatic arthritis. Infliximab therapy was discontinued and symptoms improved under high-dose intravenous glucocorticoid pulse therapy

Transient epidermal barrier deficiency and lowered allergic threshold in filaggrin-hornerin (FlgHrnr −/− ) double-deficient mice

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr −/− ) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr −/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr −/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady-state conditions, FlgHrnr −/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr −/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions

Experimental set-up of the 50 Hz MF exposure of the present study.

<p>Details are provided in the main text.</p

Representative autoradiographs of Feulgen-prestained and Light Green SF Yellowish post stained paraffin sections analyzed in the present study.

<p>The photomicrographs show details of the mouse liver after an 8-week 50 Hz MF exposure with 1.0 mT with (A, B) or without (C) injection of ³H-TdR 5 min after the end of the MF exposure. Both autoradiographs were exposed in the same box for 125 days, i.e. under completely identical conditions. In A, a few (out of many) individual silver grains found over the nucleus (arrows) and cytoplasm (arrowheads) of two hepatocytes are marked; the cell bounds are indicated. In B, the arrow points to a cell that was in S phase after injection of ³H-TdR (i.e., during the last two hours of life). In C, single silver grains found over the nucleus (arrow) or cytoplasm (arrowhead) of hepatocytes are marked, representing autoradiographic background. In all panels A to C, black dots and asterisks indicate small and larger sections of liver sinusoids, respectively. The scale bar represents 25 µm.</p

Results of the autoradiographic analyses.

<p>The graphs show mean and standard error of the mean (SEM) of grain numbers representing UDS (<b>A</b>, <b>D</b>, <b>G</b>, <b>J</b>), unrepaired nDNA SSB/ISNT (<b>B</b>, <b>E</b>, <b>H</b>, <b>K</b>) and mtDNA synthesis (<b>C</b>, <b>F</b>, <b>I</b>, <b>L</b>) of neurons in the caudate nucleus in the brain (<b>A–C</b>), epithelial cells in the choroid plexus of the fourth ventricle in the brain (<b>D–F</b>), epithelial cells of the cortical collecting duct in the kidney (<b>G–I</b>), and pericentral hepatocytes in the liver (<b>J–L</b>) after sham-exposure (open bars), MF exposure with 0.1 mT for eight weeks (gray bars), or MF exposure with 1.0 mT for eight weeks (closed bars). For a detailed description of the generation of these grain numbers and grain densities see Section “Evaluation of Autoradiographs” in the main text. Statistically significant differences between groups are indicated.</p