Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hymenoptera are the large group of insects which includes honey-bees, bumble-bees, paper wasps, hornets, ants. Female hymenoptera possess specialized stinging apparatus with which they inject their venom into prey's or intruder's body. It could be life-threatening for people sensitive to the venom. The hymenoptera venom consists of mixture of biologically active substances, eg. enzymes (phospholipases, hialuronidase), peptides (melittin, apamin, mastoparans, bombolitins) and low-molecular-weight compounds (biogenic amines, acetylcholine, carbohydrates, lipids, free amino acids). Several types of reactions are possible to develop after stinging by hymenopteran insects: (1) non-allergic local reaction (pain, small oedema, redness at the site of the sting); allergic reactions: (2) large local reaction (extensive local swelling, exceeding 10 cm, persisting longer than 24 hours) and (3) anaphylaxis (generalized urticaria, bronchospasm, hypotension, cardiovascular collapse, loss of consciousness); (4) systemic toxic reaction (oedema, vomits, diarrhoea, headache, hypotension, seizures, altered mental status); (5) unusual reactions (cardiac ischaemia, encephalomyelitis et al.). Therapeutic management after stings includes removing of the stinger (bee stings), local remedies (ice-packs, topical steroids) and prevention and treatment of an anaphylactic shock (epinephrine, general steroids, beta-mimetics, fluid resuscitation, oxygen therapy). In the present review types of reaction after hymenoptera stings were described with special interest of anaphylactic and toxic reactions as well as therapeutic management after stings.
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PMID:[Hymenoptera stings]. 1772 87

This review examines the efficacy of photodynamic therapy in the treatment of immunological disorders. Photodynamic therapy (PDT) is a 2-step procedure. Firstly, a photosensitiser is introduced into the body, where it accumulates selectively in cells with elevated metabolism, such as cancer cells or activated cells of the immune system. Second, light is applied at a wavelength that excites the photosensitiser, producing a variety of short-lived oxygen-derived species. The effect is dependent on the doses of both photosensitiser and activating light. The mechanisms of action of PDT are multifactorial. Induction of high levels of oxidative stress results in necrotic cell death, while lower intensity oxidative stress initiates apoptosis. Sublethal doses may result in the modification of cell surface receptor expression levels and cytokine release and consequently influence cell behaviour. Immunomodulatory PDT (IPDT) utilises mainly apoptotic and sublethal doses. The studies reported here utilise verteporfin, a benzoporphyrin-derived chlorin-like photosensitiser. Veteporfin is a second generation photosensitiser, displaying rapid clearance and consequently a reduced period of skin photosensitivity compared with the first generation photosensitiser, porfimer sodium. In vivo studies showed that IPDT was effective in alleviating immunopathology in murine models of arthritis, contact hypersensitivity, experimental allergic encephalomyelitis and retention of allogeneic skin grafts. Based on these findings, early stage clinical trials with IPDT were initiated recently for the treatment of psoriasis, psoriatic arthritis and rheumatoid arthritis. While verteporfin has been the photosensitiser which pioneered IPDT, a new benzoporphyrin derivative photosensitiser, QLT0074, is under development. This has demonstrated an enhanced avidity for target cells as well as improved clearance characteristics.
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PMID:Photodynamic therapy in immune (non-oncological) disorders: focus on benzoporphyrin derivatives. 1803 64

Reactive oxygen species (ROS) play a pivotal role in the development of neuroinflammatory disorders, such as multiple sclerosis (MS). Here, we studied the effect of ROS on protein expression in brain endothelial cells (BECs) using proteomic techniques and show that long-term exposure to ROS induces adaptive responses in BECs to counteract an oxidative attack. ROS induce differential protein expression in BECs, among which is peroxiredoxin-1 (Prx1). To further study the role of Prx1 we established a BEC line overexpressing Prx1. Our data indicate that Prx-1 overexpression protects BECs from ROS-induced cell death, reduces adhesion and subsequent transendothelial migration of monocytes by decreasing intercellular adhesion molecule-1 expression, and enhances the integrity of the BEC layer. Interestingly, vascular Prx1 immunoreactivity was markedly upregulated in inflammatory lesions of experimental autoimmune encephalomyelitis (EAE) animals and active demyelinating MS lesions. These findings indicate that enhanced vascular Prx1 expression may reflect the occurrence of vascular oxidative stress in EAE and MS. On the other hand, it may function as an endogenous defense mechanism to inhibit leukocyte infiltration and counteract ROS-induced cellular injury.
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PMID:Protective effects of peroxiredoxin-1 at the injured blood-brain barrier. 1845 19

Reactive oxygen species (ROS) are implicated in the pathogenesis of multiple sclerosis (MS) and its murine model experimental autoimmune encephalomyelitis (EAE). The effect of edaravone, a free radical scavenger, on EAE was investigated in this study. Treatment with edaravone significantly ameliorated the clinical severity of EAE, and a reduced infiltration of lymphocytes was observed based on a histological analysis. The expression of inducible NO synthase (iNOS) in the spinal cords appeared to be reduced by the treatment with edaravone and this effect was confirmed in vitro. A reduction of both the cellular infiltration and the expression of iNOS may therefore underlie the mechanisms of the beneficial effect of edaravone on EAE.
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PMID:Edaravone, a free radical scavenger, ameliorates experimental autoimmune encephalomyelitis. 1857

Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.
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PMID:Altered lipid metabolism in brain injury and disorders. 1875 14

The importance of lipids in cell signaling and tissue physiology is demonstrated by the many CNS pathologies involving deregulated lipid metabolism. One such critical metabolic event is the activation of phospholipase A(2) (PLA(2)), which results in the hydrolysis of membrane phospholipids and the release of free fatty acids, including arachidonic acid, a precursor for essential cell-signaling eicosanoids. Reactive oxygen species (ROS, a product of arachidonic acid metabolism) react with cellular lipids to generate lipid peroxides, which are degraded to reactive aldehydes (oxidized phospholipid, 4-hydroxynonenal, and acrolein) that bind covalently to proteins, thereby altering their function and inducing cellular damage. Dissecting the contribution of PLA(2) to lipid peroxidation in CNS injury and disorders is a challenging proposition due to the multiple forms of PLA(2), the diverse sources of ROS, and the lack of specific PLA(2) inhibitors. In this review, we summarize the role of PLA(2) in CNS pathologies, including stroke, spinal cord injury, Alzheimer's, Parkinson's, Multiple sclerosis-Experimental autoimmune encephalomyelitis and Wallerian degeneration.
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PMID:Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. 1875 70

Reactive oxygen species are involved in the pathogenesis of multiple sclerosis (MS), Parkinson's disease and neurodegenerative diseases. Here we report that Tempamine (TMN), a stable radical with antioxidant and proapoptotic activities, when encapsulated in the intraliposome aqueous phase of pegylated (<100 nm) nanoliposomes (nSSL), is efficient in inhibiting experimental autoimmune encephalomyelitis (EAE) in mice. The TMN is remote-loaded into nSSL by an intraliposome high/extraliposome low transmembrane ammonium sulfate gradient. Biodistribution studies of nSSL-TMN labeled with the liposome non transferable non metabolizable (3)H-cholesteryl hexadecyl ether show that almost 3% of the injected dose of liposomes reached the brain of the EAE mice, compared with less than 1% in the control healthy mice. This accumulation in the brain, combined with the fact that TMN demonstrates a controlled slow release out of the nSSL, may explain the superior therapeutic activity of nSSL-TMN over free TMN. Our results suggest that the study of nSSL-TMN for therapy of MS, and other neurodegenerative diseases involving oxidative damage, is worth pursuing.
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PMID:Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis. 1956 52

Metallothionein (MT)-I+II synthesis is induced in the central nervous system (CNS) in response to practically any pathogen or disorder, where it is increased mainly in reactive glia. MT-I+II are involved in host defence reactions and neuroprotection during neuropathological conditions, in which MT-I+II decrease inflammation and secondary tissue damage (oxidative stress, neurodegeneration, and apoptosis) and promote post-injury repair and regeneration (angiogenesis, neurogenesis, neuronal sprouting and tissue remodelling). Intracellularly the molecular MT-I+II actions involve metal ion control and scavenging of reactive oxygen species (ROS) leading to cellular redox control. By regulating metal ions, MT-I+II can control metal-containing transcription factors, zinc-finger proteins and p53. However, the neuroprotective functions of MT-I+II also involve an extracellular component. MT-I+II protects the neurons by signal transduction through the low-density lipoprotein family of receptors on the cell surface involving lipoprotein receptor-1 (LRP1) and megalin (LRP2). In this review we discuss the newest data on cerebral MT-I+II functions following brain injury and experimental autoimmune encephalomyelitis.
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PMID:Metallothionein-I+II in neuroprotection. 1965 89

Multiple sclerosis (MS) is an autoimmune disease characterized by peripheral activation of CD4(+) T cells that migrate into the central nervous system (CNS) and mount an autoimmune neuroinflammatory attack on myelin and oligodendrocytes. Secondary to these events, however equally destructive, is the generation of inflammatory-mediated reactive oxygen and nitrogen species generated by persistently activated microglia and astrocytes. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that regulates genetic expression of many protective antioxidant and detoxication enzymes. Here we describe the Nrf2 modulation of innate and adaptive immune responses in an acute autoimmune model of MS, experimental autoimmune encephalomyelitis (EAE). Wild-type (WT) mice and Nrf2 knockout mice were immunized with myelin oligodendrocyte glycoprotein (MOG 35-55) and monitored daily for clinical scores of disease. Disruption of Nrf2 resulted in a more severe clinical course, a more rapid onset, and a greater percentage of mice with the disease. Furthermore, increased immune cell infiltration and glial cell activation in spine was observed. In conjunction, we observed increased inflammatory enzyme (iNOS, phox-47, gp91-phox, and phox-67), cytokine (IFN-gamma, IL1-b, TNF-alpha, and IL-12), and chemokine (BLC and MIG) gene expression levels in the Nrf2-deficient mice compared to the WT mice, supporting the notion that Nrf2 can modulate an autoimmune neuroinflammatory response. Our results show that the absence of Nrf2 exacerbates the development of EAE and thus suggests that activation of Nrf2 may then attenuate pathogenesis of autoimmune diseases such as MS as well as other neurodegenerative diseases that present with neuroinflammation.
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PMID:The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. 2023 54

Recently T-helper 17 (Th17) cells were demonstrated to disrupt the blood-brain barrier (BBB) by the action of IL-17A. The aim of the present study was to examine the mechanisms that underlie IL-17A-induced BBB breakdown. Barrier integrity was analyzed in the murine brain endothelial cell line bEnd.3 by measuring the electrical resistance values using electrical call impedance sensing technology. Furthermore, in-cell Western blots, fluorescence imaging, and monocyte adhesion and transendothelial migration assays were performed. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. IL-17A induced NADPH oxidase- or xanthine oxidase-dependent reactive oxygen species (ROS) production. The resulting oxidative stress activated the endothelial contractile machinery, which was accompanied by a down-regulation of the tight junction molecule occludin. Blocking either ROS formation or myosin light chain phosphorylation or applying IL-17A-neutralizing antibodies prevented IL-17A-induced BBB disruption. Treatment of mice with EAE using ML-7, an inhibitor of the myosin light chain kinase, resulted in less BBB disruption at the spinal cord and less infiltration of lymphocytes via the BBB and subsequently reduced the clinical characteristics of EAE. These observations indicate that IL-17A accounts for a crucial step in the development of EAE by impairing the integrity of the BBB, involving augmented production of ROS.-Huppert, J., Closhen, D., Croxford, A., White, R., Kulig, P., Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A., Kuhlmann, C. R. W. Cellular mechanisms of IL-17-induced blood-brain barrier disruption.
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PMID:Cellular mechanisms of IL-17-induced blood-brain barrier disruption. 1994 Feb 58


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