Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients developed acute hepatitis after receiving Atrium, an association of phenobarbital, febarbamate and difebarbomate, for the treatment of tremor or for the prevention of alcohol withdrawal symptoms. Hepatitis occurred 1 to 3 months after treatment. Asthenia was the unique clinical manifestation. Marked increase in serum aminotransferases and gamma-glutamyltranspeptidase levels were the main biological features. Histological examination showed liver cell necrosis in two cases, prominent in the centrolobular area in one case. There was no case of hepatic failure. Atrium withdrawal was followed by complete recovery within 6 to 12 weeks. The mechanism of Atrium hepatotoxicity remains unknown.
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PMID:[Atrium-related hepatitis. Report of four cases]. 168 28

Oxidation of the catecholaminergic neurotransmitter dopamine (1) at physiological pH normally results in formation of black, insoluble melanin polymer. In this study, it is demonstrated that L-cysteine (CySH) can divert the melanin pathway by scavenging the proximate o-quinone oxidation product of 1 to give 5-S-cysteinyldopamine (8). This cysteinyl conjugate is further oxidized in the presence of free CySH to give 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H- 1,4-benzothiazine-3-carboxylic acid (11) and its 6-S-cysteinyl (12), 8-S-cysteinyl (14), and 6,8-di-S-cysteinyl (16) conjugates in addition to many other unidentified compounds. 5-S-Cysteinyldopamine (8) and dihydrobenzothiazines 11, 12, 14, and 16 are all more easily oxidized than 1. With increasing molar excesses of CySH, the formation of melanin is decreased and, ultimately, completely blocked. Preliminary experiments have revealed that when injected into the brains of laboratory mice, dihydrobenzothiazine 11 and its cysteinyl conjugates 12 and 14 are lethal and evoke profound behavioral responses including hyperactivity and tremor. On the basis of these results and other recent observations, a new hypothesis has been advanced which might help explain the selective degeneration of nigrostriatal dopaminergic neurons which occurs in idiopathic Parkinson's Disease (PD). This hypothesis proposes that in response to some form of chronic brain insult, the activity of gamma-glutamyltranspeptidase is upregulated leading to an increased rate of translocation of glutathione (GSH) into the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN) para compacta. The results of this in vitro study predict that such an elevated translocation of GSH into heavily pigmented dopaminergic neurons would cause a diversion of the neuromelanin pathway with consequent depigmentation of these cells and formation of 8, all of which occur in the Parkinsonian SN. The further very facile oxidation of 8 which must occur under intraneuronal conditions where 1 is autoxidized, i.e., in neuromelanin-pigmented cells, would lead to dihydrobenzothiazine 11 and its cysteinyl conjugates which could be the endotoxins responsible for the selective degeneration of dopaminergic SN neurons in PD. The ease of autoxidation of 8 is suggested to account for the low levels of this conjugate found in the degenerating and Parkinsonian SN.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of L-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson's disease. 790 37

A disturbance of the integrity of the intestinal epithelium with an increased risk for bacterial translocation is one of the suggested factors underlying the increased incidence of infections and septicaemia during vitamin A deficiency. In the present study the effects of vitamin A deficiency on the enzymic activity of enterocytes in response to bacterial colonization with a non-pathogenic Escherichia coli strain were studied in monocolonized and conventional Wistar rats. The monocolonized, but not the conventional, vitamin A-deficient rats had markedly reduced weight compared to their pair-fed controls and presented neurological symptoms, such as hind leg weakness, tremor and slow gait. Moreover, only in the monocolonized vitamin A-deficient rats were severe diarrhoea and bacterial translocation to extraintestinal sites-mainly kidneys-detected. Measurements of enterocyte brush-border enzyme activities revealed that lactase, sucrase, gamma-glutamyltranspeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) were significantly reduced in the monocolonized vitamin A-deficient rats compared to the pair-fed controls, indicating a severe functional disturbance of the enterocytes. In conventional vitamin A-deficient rats only sucrase activity was markedly lower than in the respective controls. Our observation, that the deficient vitamin A status led to a strong reduction of enterocyte enzymic activities, associated with diarrhoea and increased bacterial translocation, mainly in the gnotobiotic rats, suggests that the composition of the bacterial flora, i.e. the colonization state, has a strong influence on triggering the severity of the functional disturbances of the intestinal epithelium, and adds to the clinical manifestations of vitamin A deficiency.
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PMID:Vitamin A deficiency leads to severe functional disturbance of the intestinal epithelium enzymes associated with diarrhoea and increased bacterial translocation in gnotobiotic rats. 1273 96