作者: Anton Terasmaa ; Vallo Matto ; Kersti Ehrlich ; Julia Oflijan ; Anne Must ; Eero Vasar ; Marite Punapart ; Ursel Soomets ; Mats Hansen ; Sulev Kõks

Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice.

2001-05-01·Annals of Neurology1区 · 医学

Cellular and humoral immune response in progressive multifocal leukoencephalopathy

1区 · 医学

Article

作者: Wolfgang Lüke ; Harald Petry ; Marcus Pickhardt ; Frank Weber ; Marcus Krämer ; Thomas Weber ; Franz Josef Kaup ; Peter Young ; Claudia Goldmann

AbstractProgressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV‐specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus‐1 (HIV‐1)‐infected patients without PML (HIV), 4 HIV‐1‐negative patients with PML (PML), and 8 HIV‐1‐positive patients with PML (HIV/PML). As antigens, recombinant virus‐like particles of the major structural protein VP1 (VP1‐VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1‐VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon‐γ (IFN‐γ) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin‐10 (IL‐10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1‐VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1‐type T‐helper cell function of cell‐mediated immunity.

100 项与登革热病毒疫苗 (VLP Therapeutics) 相关的药物交易

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