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

Myelin basic protein (MBP) was isolated from guinea-pig spinal cord in a form retaining the binding to all the myelin lipids. This new, lipid-bound and native-like preparation was used to immunize Lewis rats in complete Freund's adjuvant (CFA) in order to produce experimental allergic encephalomyelitis (EAE). The clinical features were compared with those of Lewis rats immunized with lipid-free MBP (LF-MBP), myelin, LF-MBP + octyl-POE (the non-ionic detergent used for the purification of LB-MBP) and octyl-POE alone. The clinical observation indicate that LB-MBP exerts an encephalitogenic activity on Lewis rats which is more intense than LF-MBP and includes demyelinating lesions in the central nervous system (CNS). The data suggest that LB-MBP is a new encephalitogenic antigen, which may induce more intensive immunization in rats and may be relevant in humans for autoimmune demyelinating diseases of the CNS.
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PMID:Myelin basic protein in lipid-bound form induces experimental allergic encephalomyelitis and demyelination in Lewis rat. 171 98

The effects of some known ionic and nonionic detergents as well as that of a novel nonionic detergent MESK on various enveloped viruses were investigated. It was found that nonionic detergens (MESK, Triton X-100, octyl-beta-D-glucopyranoside) selectively solubilize glycoproteins of enveloped viruses. The most mild selective action is exerted by the nonionic detergent MESK. Using this detergent, pure preparations of glycoproteins of influenza, parainfluenza, equine Venezuela encephalomyelitis, rabies, vesicular stomatitis and herpes viruses were obtained. The procedure of isolation of purified glycoproteins includes incubation of viral suspensions with MESK, removal of subviral structures by centrifugation and purification of glycoproteins from detergent admixtures by dialysis. Purified glycoproteins retain their native structure and a high biological activity and immunogenicity. MESK seems to be due a perspective tool in the production of subunit vaccines.
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PMID:[Solubilization of glycoproteins from enveloped viruses by detergents]. 370 22

The post-translational modifications of myelin basic protein (MBP) in the form of citrullination and varying length of amino-terminus acylation may modify the biological functions and immunological features of MBP. Both modifications influence the reaction of antibodies and specific T cells recognizing MBP. The present study was undertaken to compare the encephalitogenicity of the citrullinated isomer of MBP (MBP-C8) with the unmodified isomer of MBP (MBP-C1) and to determine if the length of amino-terminal acylation of MBP peptide 1-21 altered an encephalitogenic epitope. MBP-C8, whether from patients with or without multiple sclerosis (MS), and MBP-C1 could induce active experimental allergic encephalomyelitis (EAE) in PL/J mice. A trend of reduced severity of EAE was observed in MBP-C8-injected animals. An increase in the length of amino-terminus fatty acid decreased the encephalitogenicity of MBP peptide 1-21 for both active and adoptive EAE in PL/J mice. Only lymph node cells sensitive to MBP peptide acetyl 1-21 and butyl 1-21 could transfer clinical EAE. In adoptive EAE, MBP peptides hexyl and octyl 1-21 induced moderate histopathological but no clinical change, whereas MBP peptide decyl 1-21 caused neither. A broadening in the antibody response could be detected in the sera of mice with active EAE induced by MBP-acylated peptides 1-21. Our findings demonstrate that encephalitogenicity is retained in the presence of citrullination but that the length of amino-terminus acylation diminishes the encephalitogenicity of MBP in the PL/J mouse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of citrullination or variable amino-terminus acylation on the encephalitogenicity of human myelin basic protein in the PL/J mouse. 749 2

We tested two novel bifunctional compounds: ibuprofen-N-octyl-pyridostigmine bromide (IBU-PO) and ibuprofen-N-decyl-pyridostigmine bromide (IBU-PD). They both contain a non-steroidal anti-inflammatory drug (NSAID), ibuprofen (IBU) and pyridostigmine (PO), a cholinesterase inhibitor that acts as a cholinergic up-regulator (CURE). The two moieties are conjugated by a hydrocarbon spacer consisting of 8 (octyl) and 10 (decyl) carbons, respectively. The compounds were tested for their efficiency in reducing the neurological symptoms observed in experimental autoimmune encephalomyelitis induced in mice by myelin oligodendrocyte glycoprotein (MOG). IBU-PO and IBU-PD significantly ameliorated the clinical score (a 40-50% reduction in disease severity) over a period of 30 days, following daily administration of 1 and 0.1mg/kg, i.p., respectively. Clinical improvement was accompanied by reduced responsiveness of MOG-specific T-cells. In addition, IBU-PO and IBU-PD down-regulated the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in cultured astrocytes. To determine which moiety was responsible for these effects, we tested each of the two components, IBU and PO. Our findings indicate that combining NSAID with cholinergic intervention contributes an added therapeutic value for each distinct entity and that these bifunctional compounds act both on the peripheral immunological system and on the central nervous system (CNS) inflammatory pathways.
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PMID:Bifunctional compounds eliciting both anti-inflammatory and cholinergic activity as potential drugs for neuroinflammatory impairments. 1569 72

Experimental autoimmune encephalomyelitis (EAE) is a central nervous system (CNS) inflammatory model in which MOG-specific T-cells initiate an autoimmune attack leading to demyelinization and consequently, neurological damage and morbidity. As EAE pathogenesis results from the involvement of immune cells, CNS resident-cells and inflammatory mediators, our treatment strategy was to use a bifunctional compound with dual anti-inflammatory properties: a non-steroidal anti-inflammatory moiety and a nicotinic agonist moiety, intended to interact with the alpha7 nicotinic receptor present on immune cells. We used IBU-Octyl-Cytisine, with an ibuprofen (IBU) moiety and Cytisine, as the nicotinic agonist. The two moieties are attached by an eight carbon (octyl) spacer. Treatment of EAE with IBU-Octyl-Cytisine (2.5 mg/kg/day, i.p.) reduced significantly (by 70%) disease severity and inflammatory infiltrates in the spinal cord. An equivalent dose of IBU was ineffective, whereas Cytisine was significantly toxic. Treatment with IBU-Octyl-Cytisine inhibited the T-cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). In addition, expression of CCR5 by CD4(+)T-cells was lower, indicating a reduced migratory capacity following treatment. IBU-Octyl-Cytisine reduced Th(1) but not Th(2) cytokine production. This reduction was accompanied by a drop in the level of T-bet mRNA, a transcription factor pivotal to Th(1) lineage differentiation. Thus, IBU-Octyl-Cytisine is an effective treatment for EAE, influencing T-cell responses in several stages of disease pathogenesis. This bifunctional compound was more efficient than IBU or Cytisine separately, as well as than both moieties unconjugated. Thus, it seems that this strategy may be applicable in wider context.
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PMID:IBU-octyl-cytisine, a novel bifunctional compound eliciting anti-inflammatory and cholinergic activity, ameliorates CNS inflammation by inhibition of T-cell activity. 1763 Jan 91