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)

The subacute myelo-optico-neuropathy (SMON) was hazard caused by clioquinol, an antiseptic, prescribed for the treatment of diarrhea and other bowel symptoms. Its overdosing and long-term taking led to the occurrence of SMON, for which physicians should be responsible. Clioquinol, originally a disinfectant powder for external use, was diverted later to a drug for internal use to sterilize the bowel where no intestinal absorption or action after absorption was expected. An annotation on the 6th Revision of the Japan Pharmacopoeia (1954) allowed irregular increase in its dosage depending on the severity of illness. An annotation on the 7th Revision (1961) ignoring the 6 papers published in the 1930's, 1940's or 1950's claimed that its metabolism was poorly known, yet neglected significant side effect and substantial absorption from the intestine. Its characterization as a superficial disinfectant helped the annotators be less interested in its absorption and its internal actions and side effects. Attention paid by clinicians to a polyneuropathy-like syndrome that complicated an uncontrollable hemorrhagic diarrhea (1958) and an encephalomyelitis or a paralysis of the lower half of the body associated with diarrhea or other bowel symptoms (1960, 1961) started the recognition of a new disease. During the dispute induced by the mass occurrence of the disease in several instances postmortem examination with neuropathologic expertise, especially of T. Tsubaki, Y. Toyokura and H. Tsukagoshi (1964), characterized SMON as a non-inflammatory new disease of the spinal cord, optic nerve and peripheral nerve with a pseudo-systemic degeneration of posterior and lateral columns and, therefore played a decisive role in establishing the truth of SMON. The discovery of the green hairy tongue (the tongue coated with green hairs) of SMON by T. Takasu, A. Igata and Y. Toyokura (January 1970) aroused researchers' interest in the green color of SMON and thereby began solving the cause of SMON. The discovery of the green urine in SMON patients by A. Igata, M. Hasebe and T. Tsuji (May 1970) especially facilitated the identification of the green substance in SMON that was achieved by M. Yoshioka and Z. Tamura (June 1970). The green color was derived from a chelate compound of clioquinol with ferric iron. The early epidemiological analysis related clioquinol taking to the occurrence of SMON well enough for the Japanese Government to take an administrative measure for the temporary suspension of selling clioquinol containing drugs and the postponing of their use (September 1970). Extensive and intensive multidisciplinary investigations conducted for the subsequent 20 months led to the conclusion by the SMON Investigation and Research Committee (Head: R. Kono) that the neurological disorders of patients who were diagnosed as SMON for the most part were caused by taking clioquinol (March 1972). Close clinical observation of patients opened a way to recognize a new disease and elucidate its cause. Expert specialized technical knowledge and skills established the firm knowledge of the new disease. The study of SMON began as a personal research and after its achievement was exposed to the public a great many investigators in different fields concerted efforts to solve problems. Both steps were indispensable for completing the study.
 ...
PMID:[SMON--a model of the iatrogenic disease]. 1515 88

Central European tick-borne encephalitis (TBE) is caused by a flavivirus vectored by the Ixodes ricinus tick. In severe infections, TBE presents as (myelo)meningoencephalitis with considerable mortality. Characteristic neuropathologic changes feature a multinodular to patchy polioencephalomyelitis accentuated in spinal cord, brainstem, and cerebellum. Visualization of viral infection by immunohistochemistry has not yet been achieved. We analyzed immunohistochemically the distribution of viral antigens and its correlation with neuropathologic changes, serological data, and disease duration in 28 brains of cases with a clinical diagnosis of TBE and neuropathologically confirmed (meningo)encephalomyelitis. In 20 brains (including 10 seropositives), viral antigens were detectable. These cases were characterized by relatively short clinical duration ranging from 4 to 35 days. Immunoreactivity was most prominent in perikarya and processes of Purkinje cells and large neurons of dentate nucleus, inferior olives, and anterior horns. In addition, immunoreactivity was detected in neurons of other brainstem nuclei, isocortex, and basal ganglia. There was an inverse topographical association of severe inflammatory changes with presence of viral antigens. Some cytotoxic T cells were in direct contact with tick-borne encephalitis virus (TBEV)-infected neurons. We conclude that 1) TBE viral antigens are immunohistochemically detectable in brains of fatal cases with relatively short natural clinical course; 2) TBE virus neurotropism preferentially targets large neurons of anterior horns, medulla oblongata, pons, dentate nucleus, Purkinje cells, and striatum; 3) topographical correlation between inflammatory changes and distribution of viral antigens is poor; and 4) immunologic mechanisms may contribute to nerve cell destruction in human TBE.
 ...
PMID:Visualization of Central European tick-borne encephalitis infection in fatal human cases. 1597 42

Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the acid-sensing ion channel 1 which, when activated under the acidotic tissue conditions found in inflammatory lesions opens to allow influx of sodium and calcium ions, contributes to axonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, the extent and cellular distribution of acid-sensing ion channel 1 expression in neurons and glia in inflammatory lesions is unknown and, crucially, acid-sensing ion channel 1 expression has not been determined in multiple sclerosis lesions. Here we studied acute and chronic experimental autoimmune encephalomyelitis and multiple sclerosis spinal cord and optic nerve tissues to describe in detail the distribution of acid-sensing ion channel 1 and its relationship with neuronal and glial damage. We also tested the effects of amiloride treatment on tissue damage in the mouse models. We found that acid-sensing ion channel 1 was upregulated in axons and oligodendrocytes within lesions from mice with acute experimental autoimmune encephalomyelitis and from patients with active multiple sclerosis. The expression of acid-sensing ion channel 1 was associated with axonal damage as indicated by co-localization with the axonal injury marker beta amyloid precursor protein. Moreover, blocking acid-sensing ion channel 1 with amiloride protected both myelin and neurons from damage in the acute model, and when given either at disease onset or, more clinically relevant, at first relapse, ameliorated disability in mice with chronic-relapsing experimental autoimmune encephalomyelitis. Together these findings suggest that blockade of acid-sensing ion channel 1 has the potential to provide both neuro- and myelo-protective benefits in multiple sclerosis.
 ...
PMID:Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model. 2123 44