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)

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.
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PMID:Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. 1160 39

Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders.
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PMID:Matrix metalloproteinases in neuroinflammation. 1220 94

Diagnosis depends on the clinical manifestations, blood or cerebrospinal fluid study and MRI findings. Acute and subacute intraparenchymal spinal cord disorders are due to vascular disorders or myelitis. Spinal cord infarction is associated with dissecting aortic aneurysm, surgical clipping of aortic aneurysms, aortic atherosclerosis or hypotension from any cause. Hematomyelia results from trauma, vascular malformations, vasculitis, or a coagulation disorder. Acute infectious myelopathies result from direct invasion of the spinal cord by bacteria, parasite, or virus. The cause of acute or subacute inflammatory disease include multiple sclerosis, Devic disease, acute disseminated encephalomyelitis, SLE, or sarciodosis. Sarcoidosis sometimes requires differential diagnosis with cord tumor. Chronic intraparenchymal spinal cord disorders are due to syringomyelia, familial spastic paraplegia, HTLV-1 associated myelopathy, adrenomyeloneuropathy, and vascular malformations. HTLV-1 associated myelopathy present with progressive spastic paraplegia with bladder disturbance and has antibodies to HTLV-1 in the cerebrospinal fluid and serum. Diagnosis of adrenomyeloneuropathy is made by demonstration of elevated levels of very long chain fatty acids in plasma. Vascular malformations are important lesions because they present a treatable cause of progressive myelopathy.
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PMID:[Medical approach to intraparenchymal spinal cord disorders]. 1278 77

Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is crucial for cholesterol biosynthesis, and are widely used as lipid-lowering agents. These drugs greatly reduce atherosclerosis and cardiovascular morbidity, which in the past was mainly attributed to their cholesterol-lowering properties. However, recent evidence suggests that statins are also potent immunomodulators. They exerted beneficial effects on animal models of experimental autoimmune encephalomyelitis and thus have therapeutic potential for multiple sclerosis. Their exact mechanism of action is still unclear. HMG-CoA-dependent effects and a direct effect on immune receptors are conceivable and are reviewed here.
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PMID:[Cholesterol-reducing medications-a new therapeutic option for multiple sclerosis? Statins as immunomodulators]. 1290 73

Statins, 3-hydroxy-3 methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors, are approved for cholesterol reduction and are commonly used to treat atherosclerosis and coronary disease. Statins may also be potent immunomodulatory agents and be beneficial in the treatment of autoimmune diseases. Statins have already been used to reduce the rejection of human heart transplants by the immune system, and there have been reports of a protective effect of injected statins in models of brain autoimmunity similar to experimental autoimmune encephalomyelitis. In vitro studies in multiple sclerosis(MS) revealed that statins reduced the expression of activation-induced adhesion molecules on T cells, modified Th1/Th2 cytokine balance, reduced matrix metalloproteinase(MMP)-9, and downregulated chemokine receptors on both B and T cells. Thus statins are effective immunomodulators in vitro that merit evaluation as treatment for MS. In vivo studies using three different animal models of MS revealed that oral atorvastatin prevented or reversed chronic and relapsing paralysis. Atorvastatin has been shown to have pleiotropic immunomodulatory effects involving both antigen presenting cells and T cell compartment. Thus, statins may be beneficial for MS, and clinical trials of the effects of statins on MS are now in progress, hopefully in a favorable way.
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PMID:[Effects of atorvastatin in multiple sclerosis]. 1296 38

Roentgen computed tomography (RCT) and MR-imaging (MRI) were used in investigation of vertigo etiology and affection of the cochleovestibular analyzer in 130 patients aged 28 to 74 years with recurrent systemic rotatory vertigo or its other symptoms. All the patients have undergone comprehensive otoneurological examination, RCT and MRI which showed that peripheral cochleovestibular syndromes (PCVS) caused by arterial hypertension (AH), atherosclerosis (AS), vascular dystonia (VD) are rarely characterized by focal alterations in the brain. PCVS comparison with blood flow in the vertebral arteries (VA) detected most frequently anomalies and asymmetries of the diameters. MR-angiography plays an important role in verification of pathology of intracranial VA. In central cochleovestibular syndrome (CCVS) with AH, AS, VD, principal pathological changes were registered in the brain trunk and cerebellum by MRI. Vestibulometry and otoneurological method detect not only vascular cochleovestibular peripheral and central syndromes but also to make differential diagnosis. RCT and MRI verify cochleovestibular syndromes in patients with multiple encephalomyelitis, VIII nerve neurinoma and tumors of the posterior cranial fossa.
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PMID:[The role of neurovisualization methods in diagnosis and verification of vertigo etiology]. 1648 4

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily that is expressed in many tissues, including immune cells. UCP2 prevents oxidative stress by reducing reactive oxygen species. Using UCP2-deficient mice, it was shown that UCP2 is involved in the regulation of insulin secretion, in the resistance to infection, and in atherosclerosis. Here, we investigated the role of UCP2 in experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis. Immunized C57BL/6J UCP2-deficient mice showed a slightly delayed onset during experimental autoimmune encephalomyelitis (13.0 +/- 0.6 versus 11.5 +/- 0.8 in wild-type controls) and developed significantly higher disease scores than littermate controls (maximum disease score of 2.9 +/- 0.2 versus 1.7 +/- 0.2, P = 0.001). Higher levels of infiltrating T cells into the spinal cord meninges and parenchyma were observed. The T-cell proliferative response to the specific antigen was increased in UCP2-deficient mice compared with littermate controls, and CD4 cells of UCP2 knockout mice produced significantly higher levels of pro-inflammatory cytokines, eg, tumor necrosis factor-alpha and interleukin-2, resulting from a Th1 response. Mice lacking UCP2 also developed a higher B-cell response. Concomitantly, CD4 and CD8 cells of the UCP2-deficient mice showed increased production of reactive oxygen species. These results suggest a protective function of UCP2 in chronic inflammatory diseases such as multiple sclerosis.
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PMID:Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis. 1665 23

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.
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PMID:Oral tolerance: therapeutic implications for autoimmune diseases. 1716 57

Multiple sclerosis (MS) is a common autoimmune neurodegenerative disease of unknown cause, which results in inflammation and plaques of demyelination in brain and eventual axonal degeneration. We report the novel presence of oxidized phosphatidylcholine [1-palmitoyl-2-(5'-oxo)valeryl-sn-glycero-3-phosphorylcholine (POVPC)], a lipid associated with inflammatory diseases such as atherosclerosis and lung disease, in the brain of MS patients. The OxPC epitope was detected by Western blotting with the E06 monoclonal antibody. E06-positive lipid was present in the highest amounts in MS plaques, which also showed evidence of low-molecular-weight (15-kDa) OxPC-modified protein. E06 reactivity did not change with post-mortem interval, and E06-positive lipids were largely absent from control tissue. We then used a second monoclonal antibody (AB1-2, which recognizes the E06/T15 idiotype and therefore detects the presence of antibody to OxPC) to show that MS brain samples were strongly positive for the 50-kDa antibody heavy chain. We also showed that isoelectric focussing of the oligoclonal IgG characteristic of MS revealed some immunoglobulin bands that Western blotted with the AB1-2 antibody. Spinal cords from mice induced to undergo experimental allergic encephalomyelitis (EAE) also showed strong AB1-2 reactivity by both immunocytochemistry and Western blot analysis. We therefore conclude that we can detect both OxPC and 15-kDa protein modified by OxPC and the antibody to the antibody to OxPC (antiidiotype) in pathological tissue and suggest that this could play a role in the progression of MS.
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PMID:Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. 1730 73

Since its discovery in 1910, histamine has been regarded as one of the most important biogenic amines in the medical and biological fields. This article summarizes the information about the role of histamine in allergic situations, atherosclerosis, and autoimmune encephalomyelitis, especially focusing on our study with histidine decarboxylase gene knockout mouse. In the allergic bronchial asthma model, histamine positively controls eosinophilia but not bronchial hypersensitivity. Histamine is proved to be an important substance that controls body temperature and respiration in systemic anaphylaxis but its role in controlling blood pressure is minor. Histamine also plays a role in inducing atherosclerosis in the mouse model. We showed that experimental autoimmune encephalomyelitis (EAE) is significantly more severe in histamine-deficient mice with diffuse inflammatory infiltrates in the brain and cerebellum, including a prevalent granulocytic component. Histamine is mainly produced in mast cells and basophils in hematopoietic cells. We've shown that mast cells not only produce histamine, but also uptake it from the environmental medium and release it by allergic stimulants. The protein used for the plasma transport of histamine in basophils was identified as organic cation transporter (OCT3).
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PMID:Progress in allergy signal research on mast cells: the role of histamine in immunological and cardiovascular disease and the transporting system of histamine in the cell. 1836 91


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