85 research outputs found

    Minocycline but not valproic acid influence the density of NogoA-immunoreactive neurons in the hilus of the dentate gyrus of the rats subjected to intracerebral haematoma

    Get PDF
    Intracerebral haemorrhage is a devastating neurological disease with high mortality rate and poor prognosis. The most prominent manifestation of the disease arethe movement disorders, but many patients also suffer from cognitive impairment. Taking into account vulnerability of the neurons located within the hilus of the dentate gyrus (HDG) to many brain insults we decided to study the effectof experimentally induced intracerebral haematoma on density of neurons expressing NogoA protein in HDG. In addition, we studied how administration of valproic acid and minocycline, the two drugs generally believed to be neuroprotective agents, influences the density of these neurons. Our study revealed that 4 weeks after intracerebral haematoma induction, minocycline and valproic acid treatment increased the densities of NogoA-ir neurons in the hilus of contralateral dentate gyrus once the data were compared to ipsilateral hemispheres within the same group. The analysis of contralateral hemisphere data, however, revealed increased densities of NogoA-positive neurons in haematoma and valproic acidtreated animals when compared to contralateral hemispheres of control animals.The administration of minocycline was, however, able to alleviate this increase.These changes may influence the haematoma-induced reorganisation of neuronal circuitries in the dentate gyrus

    Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo

    Get PDF
    Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naı¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5% vs 3.461.5%*; AITR+: 0.660.4 vs 0.560.3%, CD127low: 4.061.3 vs 5.063.0%* and CTLA4+: 13.8611.5 vs 15.6612.5%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers

    Vitamin D as an Adjunctive Therapy in Asthma. Part 1: A Review of Potential Mechanisms

    Get PDF
    Vitamin D deficiency (VDD) is highly prevalent worldwide. The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health. Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D, for example in asthmatic disease. Further, VDD and asthma share several common risk factors including high latitude, winter season, industrialization, poor diet, obesity, and dark skin pigmentation. Vitamin D has been demonstrated to possess potent immunomodulatory effects, including effects on T cells and B cells as well as increasing production of antimicrobial peptides (e.g. cathelicidin). This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections, altered airway smooth muscle-remodeling and efunction as well as modulation of response to standard anti-asthma therapy (e.g. glucocorticoids and immunotherapy). Thus, vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma. The purpose of this first of a two-part review is to review potential mechanisms whereby altering vitamin D status may influence asthmatic disease
    • …
    corecore