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)

An age-related canine distemper virus-associated cardiomyopathy characterized by multifocal myocardial degeneration necrosis and mineralization with minimal inflammatory cell response was found in gnotobiotic Beagle pups. Of the 30 dogs infected experimentally at 5 to 7 days of age with virulent R252 strain of canine distemper virus, 11 had gross or microscopic cardiac involvement as early as 16 days post-infection. The 25 dogs similarly infected at 10 to 21 days of age, the uninfected age-matched controls, and pups infected at 5 to 7 days of age with avirulent R252 canine distemper virus had no cardiac lesions. Although the lesions are attributed to a direct viral effect, they occur against a background of other canine distemper virus-related changes including immunosuppression, anemia and encephalomyelitis. All these factors may have a modifying role in the development of this age dependent susceptibility to virus-associated myocardial necrosis.
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PMID:Canine distemper virus-associated cardiac necrosis in the dog. 725 89

A 25-year-old man was hospitalized because of dyspnoea and retrosternal pain. There were clinical and radiological signs of severe left ventricular failure which within a few hours necessitated artificial ventilation. A year before he had been diagnosed as having pseudohyperparathyroidism and disseminated encephalomyelitis. Administration of calcium and vitamin D was only partially efficacious. On admission the calcium concentration was 1.5 mmol/l. The severe left ventricular failure did not respond adequately to the usual therapeutic measures including artificial ventilation and catecholamines. A cumulative dose of about 50 mmol calcium was administered intravenously over 10 days, but marked improvement in myocardial function already became apparent at a calcium concentration of about 1.8 mmol/l. Lasting correction of the hypocalcaemia was achieved with 0.5 g calcium three times daily by mouth and 0.5 mg/d dihydrotachysterol. After transfer to a special neurological department because of an acute attack of multiple sclerosis there was no detectable impairment of cardiac function. This case demonstrates that hypocalcaemic cardiomyopathy should be considered in the differential diagnosis of heart failure in previously well young persons who do not respond adequately to the usual treatment. Myocardial impairment is fully reversible after administration of calcium.
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PMID:[Hypocalcemic cardiomyopathy as the cause of severe left heart failure]. 792 18

Multiple sclerosis (MS) is an important cause of progressive neurological disability, typically commencing in early adulthood. There is a need for safe and effective therapy to prevent the progressive central nervous system (CNS) damage and resultant disability that characterize the disease course. Increasing evidence supports a chronic autoimmune basis for CNS damage in MS. In the present study, we review current concepts of autoimmune pathogenesis in MS, assess current therapies aimed at countering autoimmune attack and discuss potential therapeutic strategies. Among currently available therapies, beta-interferon and glatiramer acetate have a modest effect on reducing relapses and slowing the accumulation of disability in relapsing-remitting MS. Beta-interferon is of doubtful efficacy in secondary progressive MS and appears to aggravate primary progressive MS, possibly by increasing antibody-mediated CNS damage through inhibition of B-cell apoptosis. Mitoxantrone may reduce relapses and slow disability progression in relapsing-remitting and secondary progressive MS, but its use is limited by the risk of cardiomyopathy. There are currently no effective treatments for primary progressive MS. Many therapies that are effective in the animal model, experimental autoimmune encephalomyelitis (EAE), are either ineffective in MS or--in the case of gamma-interferon, lenercept and altered peptide ligands--actually make MS worse. This discrepancy may be explained by the occurrence in MS of defects in immunoregulatory mechanisms, the integrity of which is essential for the efficacy of these treatments in EAE. It is likely that the development of safe, effective therapy for MS will depend on a better understanding of immunoregulatory defects in MS.
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PMID:Prevention of autoimmune attack and disease progression in multiple sclerosis: current therapies and future prospects. 1241 39

Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677G>T, 3435C>T and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2% of patients) was 37.7% lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P < 0.05, 14.8% of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(-/-) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(-/-) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n = 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1%)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5%) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6%), ABCB1/ABCG2-L 28/33 (84.8%), exact Cochran-Armitage test P = 0.039]. The odds ratio for response was 1.9 (95% CI 1.0-3.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to -I-, and -I to -L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m2 MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation.
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PMID:ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis. 1960 31

Brainstem lesions are rarely associated with neurogenic pulmonary oedema (NPO) in multiple sclerosis and other disorders. The exact mechanism for this is unknown. We describe a case of a 15-year-old boy who presented with transient cardiomyopathy and severe acute pulmonary oedema. Several days after his initial presentation he developed an ataxic syndrome with limb, truncal and gait ataxia and nystagmus on primary gaze. Investigations confirmed acute disseminated encephalomyelitis (ADEM). For the first time, we describe a case of transient cardiomyopathy and NPO as the initial manifestation of ADEM.
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PMID:Transient cardiomyopathy as the presenting feature of acute disseminated encephalomyelitis. 2001 97

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.
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PMID:PACAP is an endogenous protective factor-insights from PACAP-deficient mice. 2252 55

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.
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PMID:Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla. 2701 35

Epigenetic regulators are increasingly recognized as relevant modulators in the immune and nervous system. The class of sirtuins consists of NAD+-dependent histone deacetylases that regulate transcription. Sirtuin family member Sirt1 has already been shown to influence the disease course in an animal model of autoimmune neuroinflammation (experimental autoimmune encephalomyelitis (EAE). A role of Sirt7, a related epigenetic regulator, on immune system regulation has been proposed before, as these mice are more susceptible to develop inflammatory cardiomyopathy. Sirt7-/- animals showed no differences in clinical score compared to wild-type littermates after EAE induction with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, although we found subtle immune alterations at different phases of EAE and decreased survival of newly generated neurons in the hippocampus. Our data indicate that Sirt7 has a slight protective impact on both the adaptive immune system and neurogenesis. However, overall this epigenetic factor is not capable of impacting the acute or chronic phase of neuroinflammation.
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PMID:Role of the epigenetic factor Sirt7 in neuroinflammation and neurogenesis. 2893 14