Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Eleven cows in late lactation were exposed to butyric acid for three weeks and were compared to five controls. Two intraruminal doses were daily applied, that is 1.0 g/kg B.W. of butyric acid to six animals and 1.0 g/kg B.W. of sodium butyrate to another five. Decline in milk yield was clinically recorded in response to butyric acid, while muscle tremor and diarrhoea resulted additionally from sodium butyrate. Behaviours of the clinico-chemical parameters of beta-OH-butyrate, glucose, free fatty acids, bilirubin, ASAT, gamma-GT, AP, and cholesterol were comparable to those in fattening bulls. Liver damage was not safely established. Some of the clinico-chemical alterations were more strongly pronounced after administration of sodium butyrate. One cow fell ill with ketosis under butyric acid load.
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PMID:[Subacute butyric acid exposure in cattle. 4. Clinical influence and effect on the carbohydrate-fat metabolism and liver function of cows]. 210 47

Metadoxine is an active drug for treatment of acute and chronic alcohol intoxication, affecting both liver and brain function. The authors reviewed the international pharmacological and clinical literature on the drug which shows the potential usefulness of metadoxine in the treatment of alcohol-induced diseases. The case report concerns the results in 20 chronic alcoholics, admitted to the hospital for acute alcohol intake treated with metadoxine (one 500 mg tablet twice daily). Biohumoral hepatopathy parameters and clinical parameters of neuropsychic behaviour were examined simultaneously. Compared with a control group of patients undergoing traditional therapy (sedative and multi-vitamin drugs), metadoxine showed a significant improvement of the values of gamma-GT, GPT, blood ammonia, blood alcohol and of neuropsychic and behavioural parameters such as agitation, tremor, asterixis, sopor and depression. No side-effects or unfavourable reactions occurred during metadoxine treatment, which confirms the safety of this molecule.
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PMID:[Metadoxine in alcohol-related pathology]. 252 84

A study was made of opportunities for the use of some signs of alcoholic intoxication in the verification of alcoholic etiology of heart lesion. Clinical signs like hyperemia of the face with telangiectasia, venous plethora of the eyeballs, tremor of the lips, tongue, limbs, Dupuytren's contracture, enlarged liver size combined with a positive macrocytosis test and, to a lesser degree, with a higher activity of gamma-glutamyl transpeptidase, and the detection of fatty hepatosis in liver puncture biopsy were shown to suggest alcoholic intoxication, and excluding other cases of heart lesion they can be of great help in the verification of diagnosis of alcoholic heart lesion.
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PMID:[Importance of alcoholism markers in the diagnosis of alcoholic heart lesions]. 289 79

The purpose of this pilot study was to determine whether daily administration of cyclosporin A to symptomatic patients with primary biliary cirrhosis for 1 yr would lead to a significant and sustained improvement in liver enzyme abnormalities. Twelve adult patients (11 female, 1 male; aged 52.6 +/- 8.9 yr, mean +/- SD) with serologic and histologically defined primary biliary cirrhosis were randomized to receive either oral cyclosporin A or vehicle placebo. Cyclosporin A was administered at sufficient dosages to maintain serum radioimmunoassay trough levels between 100 and 200 ng/ml (starting dosage, 2.5 mg/kg.day). After 1 yr of therapy, significant changes from pretreatment values were seen only in recipients of cyclosporin A. These included a 37% decrease in mean serum alkaline phosphatase and a 43% decrease in gamma-glutamyltransferase (controls +3% and -14%, respectively). Mean serum bilirubin and albumin levels and prothrombin times remained unaltered in the two groups, as did the extent of inflammation and fibrosis and the histologic staging of liver biopsy specimens. Although mean serum creatinine levels increased by 51% in recipients of cyclosporin A (+2% in controls), there were no associated changes in diastolic blood pressure or creatinine clearance values. Other side effects including thrombocytopenia, hirsutism, headaches, tremor, and parasthesiae were common in the treated group but not of sufficient severity to warrant adjustment in the dosage or discontinuation of therapy. The observed changes in hepatic, renal, and hematologic tests tended to return to baseline after discontinuation of therapy. Two patients, both placebo recipients, died of liver failure during the study period. The results of this study indicate that in symptomatic primary biliary cirrhosis, cyclosporin A administration is associated with a significant improvement in cholestatic liver enzyme abnormalities that persists for the duration of therapy. A progressive rise in serum creatinine levels and a high incidence of side effects raise concerns regarding the long-term safety of this agent in primary biliary cirrhosis.
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PMID:Pilot study of cyclosporin A in patients with symptomatic primary biliary cirrhosis. 316 99

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

The initial step in the genesis of neuromelanin, a black polymeric pigment normally found in the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN), is the autoxidation of dopamine (DA) to DA-o-quinone (1). In this investigation, it is demonstrated that in the presence of L-cysteine (CySH) o-quinone 1 is scavenged to give 5-S-cysteinyldopamine (5-S-Cys-DA, major product) and 2-S-cysteinyldopamine (2-S-CyS-DA, minor product). These cysteinyl conjugates are more easily oxidized than DA. The relative yields of the resulting products are dependent on the concentration of free CySH. These products include 2,5-bi-S-cysteinyldopamine (2,5-bi-S-CyS-DA) and 2,5,6-tri-S-cysteinyldopamine (2,5,6-tri-S-CyS-DA), 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1), 8-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-5), and a number of cysteinyl conjugates of these dihydrobenzothiazines (DHBTs). 2,5-Bi-S-CyS-DA, DHBT-1, the 6-S-cysteinyl conjugate of DHBT-1, DHBT-5, and the 6-S-cysteinyl conjugate of DHBT-5 were lethal when administered into the brains of laboratory mice and evoke a very characteristic hyperactivity syndrome and episodes of severe tremor. These and related results provide support for the hypothesis that the massive, irreversible loss of glutathione (GSH), increased 5-S-CyS-DA/DA concentration ratio, and depigmentation of dopaminergic neurons in the SN that all occur in Parkinson's disease (PD) might be caused by the gamma-glutamyl transpeptidase-mediated translocation of CySH (and/or GSH) into these cells. Furthermore, the resulting cysteinyldopamines and DHBTs might include endotoxic metabolites responsible for the selective degeneration of nigrostriatal dopaminergic neurons and PD.
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PMID:Further insights into the influence of L-cysteine on the oxidation chemistry of dopamine: reaction pathways of potential relevance to Parkinson's disease. 883 20

Four hundred and ninety-two (232 males and 260 females) randomly selected inhabitants older than 15 years of La Esperanza, a rural village of Tenerife, have been inquired about their daily alcohol intake, analyzing the relationship between this parameter and sex, age, marital status, educational level, job and smoking habit, physical signs, and biological markers of excessive ethanol consumption. One hundred and seventy-four out of them (35.4%) were teetotalers, while 318 (64.6%) consumed alcoholic beverages; 18.2% (34.1% of the males and 4.2% of the females) referred excessive ethanol consumption (more than 80 g/day and 40 g/day, respectively). Men consumed 62.3 +/- 4 g/day ethanol and women, 8 +/- 1 g/day. The distribution of the population according to the amount of ethanol consumed fits into Lederman's curve, most of the individuals being consumers of small amounts of ethanol. Male sex, middle age, married or separated status, unskilled job, sometimes unemployed, low educational level, daily drinking (mainly wine), and smoking, were all related to a higher ethanol consumption. When assessed by logistic regression, only liver enlargement, parotid swelling, retches and tremor in the morning, and hoarseness, out of the physical signs, showed independent predictive value as indicators of excessive consumption as well as serum GGT, ASAT, MCV, and urate levels out the biological markers. When all those physical and analytical signs that had previously shown predictive independent value are analyzed together, all the five physical signs (liver enlargement, parotid swelling, retches and tremor in the morning, and hoarseness) but only urate, out of the biochemical markers, showed independent predictive value.
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PMID:Alcohol intake in a rural village: physical signs and biological markers predicting excessive consumption in apparently healthy people. 901 18

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

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


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