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)

Less pronounced intensity of extrapyramidal hyperkineses and aggravation of motor disturbances in patients with diffuse sclerosis occurring under the effect of tegretol prompted the authors to study the action of this drug on the course of experimental allergic encephalomyelitis. Daily administration of tegretol in a dose of 375 mg/kg retarded the development of the affection and produced a marked adynamia in the animals. Slowing down of the dominant rhythm and depression of its amplitude were recorded on the EEG. Shifts in the potassium and sodium content and reduced brain cholesterase activity were noted. The authors ascribe these changes to a mediated action of tegretol upon deep-seated cerebral structures.
 ...
PMID:[Study of the mechanism of action of tegretol in experimental allergic encephalomyelitis]. 122 93

A method of rapid pathomorphological diagnosis of demyelinization with a simultaneous detection of cell elements in the nervous tissue has been described. The method tested on the model of experimental allergic encephalomyelitis (EAE) is a modified method of Marchi with subsequent staining of histological sections with toluidine blue. Due to a shorter period of nervous tissue exposure to potassium bichromate and osmium acid solutions (from 6-8 weeks to 5 days) the cells preserve their ability to uptake the dye and the endurance of histological sections increases. Their thickness (2-3 microns) makes it possible to examine them in immersion magnification of the light microscope. Using the above method, we succeeded in revealing hematogenic and glial elements in demyelinating foci in the central nervous system of animals with EAE. The method described can be used for studying pathomorphology of multiple sclerosis and other demyelinating diseases in humans and their experimental models, as well as for the express diagnosis of demyelinization in pathoanatomical practice.
 ...
PMID:[A method of detecting demyelinated nerve tissue in experimental allergic encephalomyelitis]. 328 29

Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed.
 ...
PMID:The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit. 608 51

Kaliotoxin (KTX), a blocker of voltage-gated potassium channels (Kv), is highly selective for Kv1.1 and Kv1.3. First, Kv1.3 is expressed by T lymphocytes. Blockers of Kv1.3 inhibit T lymphocyte activation. Second, Kv1.1 is found in paranodal regions of axons in the central nervous system. Kv blockers improve the impaired neuronal conduction of demyelinated axons in vitro and potentiate the synaptic transmission. Therefore, we investigated the therapeutic properties of KTX via its immunosuppressive and symptomatic neurological effects, using experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The T line cells used to induce adoptive EAE were myelin basic protein (MBP)-specific, constitutively contained mRNA for Kv1.3. and expressed Kv1.3. These channels were shown to be blocked by KTX. Activation is a crucial step for MBP T cells to become encephalitogenic. The addition of KTX during Ag-T cell activation led to a great reduction in the MBP T cell proliferative response, in the production of IL-2 and TNF, and in Ca(2+) influx. Furthermore, the addition of KTX during T cell activation in vitro led a decreased encephalitogenicity of MBP T cells. Moreover, KTX injected into Lewis rats impaired T cell function such as the delayed-type hypersensitivity. Lastly, the administration of this blocker of neuronal and lymphocyte channels to Lewis rats improved the symptoms of EAE. We conclude that KTX is a potent immunosuppressive agent with beneficial effects on the neurological symptoms of EAE.
 ...
PMID:Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation. 1114 70

Uric acid (UA) is a purine metabolite that selectively inhibits peroxynitrite-mediated reactions implicated in the pathogenesis of multiple sclerosis (MS) and other neurodegenerative diseases. Serum UA levels are inversely associated with the incidence of MS in humans because MS patients have low serum UA levels and individuals with hyperuricemia (gout) rarely develop the disease. Moreover, the administration of UA is therapeutic in experimental allergic encephalomyelitis (EAE), an animal model of MS. Thus, raising serum UA levels in MS patients, by oral administration of a UA precursor such as inosine, may have therapeutic value. We have assessed the effects of inosine, as well as inosinic acid, on parameters relevant to the chemical reactivity of peroxynitrite and the pathogenesis of EAE. Both had no effect on chemical reactions associated with peroxynitrite, such as tyrosine nitration, or on the activation of inflammatory cells in vitro. Moreover, when mice treated with the urate oxidase inhibitor potassium oxonate were fed inosine or inosinic acid, serum UA levels were elevated markedly for a period of hours, whereas only a minor, transient increase in serum inosine was detected. Administration of inosinic acid suppressed the appearance of clinical signs of EAE and promoted recovery from ongoing disease. The therapeutic effect on animals with active EAE was associated with increased UA, but not inosine, levels in CNS tissue. We, therefore, conclude that the mode of action of inosine and inosinic acid in EAE is via their metabolism to UA.
 ...
PMID:Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. 1245 Nov 83

Chronic relapsing/remitting experimental autoimmune encephalomyelitis (EAE) can be induced in 8-week-old female SJL/J(H-2) mice via inoculation with the p139-151 peptide of myelin proteolipid protein (PLP), Mycobacterium tuberculosis (MT), complete Freund's adjuvant (CFA), and Bordatella pertussis. EAE is a relevant preclinical model of MS that incorporates several aspects of the clinical disease. Chief among these are the inflammatory mediated neurological deficits. While the impact of localized spinal cord demyelination on neurotransmission has been modeled successfully, relatively little work has been done with spinal cord from animals with EAE. The goal of this study was to assess the utility of a grease-gap tissue bath methodology in the detection of transmission deficits in EAE spinal cord tissue. Spinal cords removed from EAE mice at different phases of the neurological deficit were assessed for their response to both lumbar and sacral application of one of several depolarizing agents (veratridine, potassium chloride [KCl], (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA]). The main finding of this study is that transmission deficits were detected in EAE mice at the onset of the neurological deficits. They were sustained for a period of approximately 2 to 3 weeks post disease onset followed by a gradual recovery of group function. The other finding is that there is a decrease in the latency to achieve AMPA-mediated depolarization in sacral spinal cord that is independent of the magnitude of the depolarization response. These results suggest that this methodology can be utilized to assess sensory and motor deficits in spinal cord from EAE animals.
 ...
PMID:An electrophysiological model of spinal transmission deficits in mouse experimental autoimmune encephalomyelitis. 1456 7

Voltage-gated potassium channels (Kv channels) are ion channels, openings of which provide an outward flow of potassium ions repolarising the cell. In neurons, Kv channels play a crucial role in action potential repolarisation and in shaping neuronal excitability. In non-excitable cells, such as T lymphocytes, Kv channels and calcium-activated K+ channels (KCa channels) determine the driving force for Ca2+ entry. During T cell activation the calcium entry depolarises the cell and increases the cytosolic calcium concentration, which in return activates Kv and KCa channels. K+ channel opening repolarises the cell and drives the membrane potential to a negative voltage. The roles of Kv channels in nervous and immune systems have been investigated here by means of a rat experimental autoimmune disease of the central nervous system, the experimental autoimmune encephalomyelitis (EAE). EAE is characterised clinically by paralysis, and pathologically by inflammatory cell infiltrations into the brain and the spinal cord. Among the inflammatory cells, T lymphocytes play a major role. Hence, EAE can be adoptively transferred into syngenic animals by the injection of T cells reactive to myelin antigens. During adoptive-EAE, somato-sensory evoked potentials recorded along the spinal tracts decrease in amplitude and axonal propagation is disrupted. We have analysed the consequences of Kv channels blockade by peptidyl toxins on central nerve conduction, on T cell activation and on the time course of EAE. In rat optic nerves, Kv channels have been identified up from postnatal day 1. Their blockade by kaliotoxin (a scorpion toxin) or by dendrotoxin-I (a snake toxin) enlarges the compound action potentials, demonstrating the participation of Kv channels to spike repolarisation. This effect disappears at adult age due to the sequestration of Kv channels under the myelin, in the paranodal regions. During acute demyelination by lysophosphatidyl-choline, the surface area of compound action potential decreased probably because conduction block occurred. Demyelination unmasked Kv channels, which are again accessible to toxins. Their blockade by dendrotoxin-I or kaliotoxin favoured a slow delayed conduction suggesting that those Kv channel blockers exert a neurological benefit during demyelinating diseases. In a T-cell line reactive to myelin basic protein antigen, which is used to adoptively transfer experimental autoimmune encephalomyelitis, Kv1.3 channels are constitutively expressed. Their blockade leads to a pronounced reduction of the T cell proliferative response, cytokine production and Ca2+ influx. In the rat, blockade of Kv1.3 inhibits the delayed type hypersensitivity response to myelin basic protein prevents and treats adoptive experimental autoimmune encephalomyelitis. Blockade of Kv channels alone or in combination with KCa channels improves the symptoms of the disease. These results demonstrate that K+ channel blockers displaying high selectivity are potent immunosuppressive agents with beneficial symptomatic effects in experimental autoimmune encephalomyelitis.
 ...
PMID:[Ion channels and demyelination: basis of a treatment of experimental autoimmune encephalomyelitis (EAE) by potassium channel blockers]. 1526 56

Expression of the two lymphocyte potassium channels, the voltage-gated channel Kv1.3 and the calcium activated channel IKCa1, changes during differentiation of human T cells. While IKCa1 is the functionally dominant channel in naive and "early" memory T cells, Kv1.3 is crucial for the activation of terminally differentiated effector memory (TEM) T cells. Because of the involvement of TEM cells in autoimmune processes, Kv1.3 is regarded as a promising target for the treatment of T-cell mediated autoimmune diseases such as multiple sclerosis and the prevention of chronic transplant rejection. ShK, a 35-residue polypeptide toxin from the sea anemone, Stichodactyla helianthus, blocks Kv1.3 at low picomolar concentrations. ShK adopts a central helix-kink-helix fold, and alanine-scanning and other mutagenesis studies have defined its channel-binding surface. Models have been developed of how this toxin effects K+-channel blockade and how its docking configuration might differ in ShK-Dap22, which contains a single side chain substitution that confers specificity for Kv1.3 blockade. ShK, ShK-Dap22 and the Kv1.3 blocking scorpion toxin kaliotoxin have been shown to prevent and treat experimental autoimmune encephalomyelitis in rats, a model for multiple sclerosis. A fluoresceinated analog of ShK, ShK-F6CA, has been developed, which allows the detection of activated TEM cells in human and animal blood samples by flow cytometry and the visualization of Kv1.3 channel distribution in living cells. ShK and its analogs are currently undergoing further evaluation as leads in the development of new biopharmaceuticals for the treatment of multiple sclerosis and other T-cell mediated autoimmune disorders.
 ...
PMID:Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases. 1557 98

The KCNN4 potassium-ion channel has been reported to play an important role in regulating antigen-induced T cell effector functions in vitro. This study presents the first evidence that a selective KCNN4 blocker, TRAM-34, confers protection against experimental autoimmune encephalomyelitis (EAE) in the mouse model. Treatment with the KCNN4 blocker did not prevent infiltration of T cells in the spinal cord, but resulted in the reduction of both the protein and the message levels of TNF-alpha and IFN-gamma as well as the message levels of several other pro-inflammatory molecules in the spinal cord. Plasma concentrations of TRAM-34 within a 24-h period were between the in vitro IC(50) and IC(90) values for the KCNN4 channel. The effect of TRAM-34 was reversible, as indicated by the development of clinical EAE symptoms within 48 h after withdrawal of treatment. In summary, our data support the idea that KCNN4 channels play a critical role in the immune response during the development of MOG-induced EAE in C57BL/6 mice.
 ...
PMID:Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice. 1577 Jun 97

Mammalian tissues express beta-isoforms of glycosphingolipids and, among these, sulfatide (sulphated galactosylceramide) is present in the beta cells, and it is here that the short fatty acid chain (C16) isoform is predominately found. In vitro studies have shown that sulfatide preserves insulin crystals and facilitates insulin monomerisation under certain biochemical conditions. It also activates beta cell potassium channels and moderates insulin secretion. Anti-sulfatide antibodies are seen in type 1 diabetes, and immunological presentation of glycosphingolipids by the non-classical CD1 molecules has recently been reported. It is via this mechanism that alpha-galactosylceramide and sulfatide are able to influence the innate immune system and inhibit autoimmunity, possibly through regulatory natural killer T cells. Administration of sulfatide substantially reduces the incidence of diabetes in non-obese diabetic mice and prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type mice. Sulfatide has specific anti-inflammatory properties, increasing the number of CD3+CD25+ regulatory T cells and reducing production of several cytokines, including TNF-alpha. Patients with type 2 diabetes have low serum concentrations of sulfatide, and some animal models of type 2 diabetes have low pancreatic expression of C16:0 sulfatide; administration of this increases insulin secretion and improves first-phase insulin response in Zucker fatty rats. Glycosphingolipids in general, and sulfatide in particular, appear relevant to both type 1 and type 2 diabetes.
 ...
PMID:Involvement of sulfatide in beta cells and type 1 and type 2 diabetes. 1614 63


1 2 3 4 Next >>