Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diseases of the central nervous system (CNS) occurring during treatment of acute lymphoblastic leukemia (ALL) may be of leukemic or nonleukemic origin. Well known examples for CNS disease of nonleukemic origin are somnolence following prophylactic CNS irradiation, methotrexate-induced encephalopathy and acute infections caused by bacteria, viruses and toxoplasma gondii. Less known is the fact that also subacute CNS infections may occur in patients undergoing cytostatic therapy. Progressive multifocal leukoencephalopathy and subacute sclerosing panencephalitis (SSPE) are examples of this category of disease. Up to now 11 well documented cases of SSPE were reported occurring during treatment of ALL. Main clinical features were disorders of behaviour, consciousness and speach, seizures, paresis and inappropriate secretion of ADH. Several authors were able to demonstrate a deficiency of cellular immunity in patients with SSPE. In some cases this deficiency was consistent with reduced reactivity of T-lymphocytes against measles antigen only. The presence of inhibiting factors may be responsible for this phenomenon. Other authors found a normal or increased function of cellular immunity in SSPE; In hamsters occurrence of SSPE is induced by the simultaneous injection of hamster-adapted SSPE virus and antihamster lymphocyte serum. We, therefore, conclude that also in humans SSPE appearing during treatment of ALL is due to immunosuppression.
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PMID:[Non-leukemic disease of the central nervous system in children with acute lymphoblastic leukemia. III. Subacute sclerosing panencephalitis (author's transl)]. 36 90

Six new cases of psychogenic water intoxication are discussed in the light of 150 observations published in the literature since 1935. 87% of all patients were schizophrenic, and 13% had other psychoses and a variety of functional and organic psychopathies. Psychogenic polydipsia is a prerequisite of psychogenic water intoxication. Water intake either overrides an intact osmoregulation (46% of all cases) or, allied to an inadequate urinary dilutional capacity (54%), leads to a transitory, sometimes repeated, and (in 8% of all cases) lethal water intoxication and hypoosmolality. - The consequence of hypoosmolality is metabolic encephalopathy, with agitation, convulsions and coma as its most common symptoms. Profuse diuresis, enuresis and urinary retention, gastric dilatation, watery vomiting and watery diarrhea are diagnostically helpful symptoms of polydipsia typically denied by the patients. Hypoosmolality/hyponatremia are the hallmarks of water intoxication. However, fewer than 50% of all patients present with the expected maximal urinary dilution. Inadequate ADH activity and increased sensitivity of the renal tubule to antidiuretic hormone are the pathogenetic factors in this inappropriate urinary dilution, while psychosis, psychotropic drugs, diuretics, nicotine and alcohol withdrawal are possible causes and cofactors of polydipsia and inadequate urinary dilution. New aspects of treatment are discussed.
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PMID:[Psychogenic water intoxication]. 264 58

We report a case of limbic encephalopathy clinically characterized by a progressive amnestic syndrome and many EEG seizures mainly localized on the left temporal area. Biological investigations revealed diabetes mellitus and a syndrome of inappropriate antidiuretic hormone secretion (IADH). Haemodynamic and metabolic studies by positron-emission tomography showed an important increase in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen on the left anterior temporal region precisely where the electrical seizures were recorded. Nine months later, severe disorders of memory and a dramatic decrease in CBF and CMRO2 on the same area region were present. At autopsy, a small size oat cell bronchial carcinoma was found with metastases in two small adjacent lymph nodes. Neuropathological examination showed atrophy (neuronal loss, protoplasmic gliosis) in the amygdala; where there was in addition an area of nodular gliosis. The hippocampus and parahippocampal gyrus lesions were severe on the left and moderate on the right side. The authors discuss the nosology of their case in the paraneoplastic syndromes and, with a review of the literature, the role of ADH and cellular hyperactivity in the pathogenesis of specifically localized neuronal alterations.
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PMID:[Paraneoplastic limbic encephalopathy, inappropriate ADH secretion and recurrent subclinical epileptic seizures. Clinical, anatomo-pathological and metabolic correlations by positron emission tomography]. 282 90

The distributions of class III alcohol dehydrogenase (ADH), a glutathione-dependent formaldehyde dehydrogenase, and class I ADH in the human brain were examined immunohistochemically. The most intense immunostaining of class III ADH was observed in the dendrites and cytoplasm of cerebellar Purkinje cells. Scattered cerebral cortical neurons in layers IV and V, and some hippocampal pyramidal neurons were also immunopositive. The neuronal distribution of class III ADH resembled that of the vulnerable neurons in patients with hypoxic encephalopathy, which in view of the intense staining in the Purkinje cells, raises the possibility that this enzyme contributes to the hypoxia and cerebellar degeneration suffered by chronic alcoholics. Perivascular and subependymal astrocytes, which contribute to the maintenance of the cerebral cellular milieu and isolate the brain from the systemic circulation and cerebrospinal fluid, were also class III ADH positive. As the substrates of this enzyme include intrinsic toxic formaldehyde, inflammatory intermediate of 20-hydroxy-leukoteiene B4, and possibly ethanol, the distribution of class III ADH immunostaining indicates this enzyme contributes to the defence of the brain against degenerative processes. The finding that, unlike ependymal cells, subependymal astrocytes were class III ADH positive, suggests this enzyme may be useful for differentiating astrocytes and ependymal cells.
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PMID:Histological distribution of class III alcohol dehydrogenase in human brain. 1066 11

Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. The aim of our study was to investigate the relationship between the pharmacological and neurotoxicological properties of disulfiram with respect to the doses applied. Increasing doses of disulfiram (25, 50, 75, 100 and 150 mg/kg) were administered intraperitoneally to Wistar rats and the hepatic enzyme activities of alcohol and aldehyde dehydrogenases were measured. Also, in two brain subregions (midbrain and hypothalamus) the levels of noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were determined. The higher dose of disulfiram (150 mg/kg) produced lethal effects in all treated animals. Aldehyde dehydrogenase activities were inhibited by disulfiram in a dose-dependent way, while alcohol dehydrogenase was not affected at all. Concerning the levels of brain biogenic amines, disulfiram produced a significant reduction in noradrenaline and an increase in dopamine levels in both structures of the brain, in a dose-dependent way. However, the lowest dose applied (25 mg/kg) had no effects on brain catecholamines. It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-beta-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice 'disulfiram reaction' could still be achieved with a low dosage regimen not producing neurotoxicity
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PMID:Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism. 1116 69

To identify the target of IgG autoimmune response in Hashimoto's encephalopathy (HE), we studied the binding of IgG present in serum and cerebro-spinal fluid (CSF) from six patients with HE and 15 controls to human central nervous system (CNS) white matter antigens by 2D-PAGE and immunoblotting and by immunohistochemistry. We found that CSF IgG from HE patients specifically recognized 3 spots, which were identified as dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). DDAHI was present in two isoforms recognized respectively by five and four HE patients; immunohistochemistry with anti-DDAHI antiserum depicted endothelial cells in normal human CNS. AKRIAI was recognized by three HE CSF and this enzyme was widely distributed on neurons and endothelia by immunohistochemistry. IgG from HE CSF immunostained both neuronal and endothelial cells in mouse CNS. The presence of these autoantibodies selectively in the CSF of HE patients may have important diagnostic and pathogenetic implications, since the autoimmune response to these enzymes may lead to vascular and/or neuronal damage, two major mechanisms involved in the pathogenesis of HE.
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PMID:Novel autoantigens recognized by CSF IgG from Hashimoto's encephalitis revealed by a proteomic approach. 1840 58

We report two patients with acute hyponatremic encephalopathy which developed after massive water ingestion for pelvic ultrasound and emphasize the findings of magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI). Both subjects had completely recovered within 24 hours following fluid restriction and salt replacement. MR imaging revealed cortical sulcal narrowing, restricted diffusion and sulcal T2 hyperintensity along with diffuse pial enhancement suggesting diffuse cerebral cortical cytotoxic edema and blood-brain barrier breakdown. In addition to the first illustration of multimodality MR imaging features of water-intoxication, these two cases also highlight the need for standardized practice on the quantity of water intake recommended to distend the bladder for pelvic ultrasound, especially in patients at risk for serum inappropriate ADH syndrome-related hyponatremia.
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PMID:Hyponatremic encephalopathy after excessive water ingestion prior to pelvic ultrasound: neuroimaging findings. 2072 Mar 64

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH)/syndrome of inappropriate antidiuresis is characterized by a hypotonic hyponatremia, with an insufficiently diluted urine given the plasmatic hypoosmolality, in the absence of hypovolemia (with or without a third space), hypotension, renal or heart failure, cirrhosis of the liver, hypothyroidism, adrenal insufficiency, vomiting, or other non-osmotic stimuli of ADH secretion. The response of ADH to the infusion of hypertonic saline divides SIADH into 4 different types. In type D, there is no alteration in ADH secretion. Rather, the defect is the maintained permeability of kidney aquaporin-2 channels to water. Activating mutations of the V2 receptor have been identified. The most frequent cause of SIADH is the use of drugs that induce secretion of the hormone. Old age is per se a risk factor for its development. SIADH is underdiagnosed, and hospitalization often worsens the clinical situation, due to an iatrogenic excess in the use of oral and i.v. liquids, often hypotonic, together with a reduction in salt intake. Treatment is directed towards normalization of natremia when possible, together with the avoidance of both hyponatremic encephalopathy as well as the osmotic demyelinization syndrome. Cases of "appropriate" secretion of ADH with normovolemic hyponatremia and high mortality rates should be treated with the same urgency as SIADH--such is the case of post-surgical hyponatremia.
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PMID:[Current considerations in syndrome of inappropriate secretion of antidiuretic hormone/syndrome of inappropriate antidiuresis]. 2113 Sep 59

Hashimoto's encephalopathy (HE) is a syndrome occurring in some patients with Hashimoto's thyroiditis or, less frequently, Graves' disease. Three known autoantigens are involved in HE: alpha-enolase, dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). We searched for amino acid sequence homologies between these proteins and the three classical thyroid autoantigens (thyroperoxidase (TPO), thyroglobulin (Tg), TSH-receptor (TSH-R)), which are also expressed in the central nervous system (CNS). TSH-R shows homologies with alpha-enolase (n=4), DDAHI (n=2) and AKRIAI (n=5); of these segments, two, two and four, respectively, overlap totally or partially with epitope-containing TSH-R segments. Tg has 10 homologies with alpha-enolase, five with DDAHI, and eight with AKRIAI; epitope-containing segments of Tg overlap four, three and four segments, respectively. TPO has six segments homologous to alpha-enolase, three to DDAHI and seven to AKRIAI; of these segments, five, one and four, respectively, are located in epitope-containing parts. These data suggest that cross-reactivity between CNS autoantigens and thyroid autoantigens might contribute to the HE pathogenesis, together with other proposed mechanisms, including autoimmunity involving autoantigens common to CNS and thyroid.
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PMID:Homology between TSH-R/Tg/TPO and Hashimoto's encephalopathy autoantigens. 3158 87