UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH+4/NH3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.
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PMID:The importance of the highest normokalemia in the treatment of early hepatic encephalopathy. 816 17

Chronic hyperammonemia is known to lead to pathological forms of astrocytes. To test the influence of these changes on the neurotoxicity of ammonia, the glial metabolic poison fluoroacetate (FA) was applied locally, through microdialysis to the hippocampal dentate gyrus. The penetration of ammonia into the brain following the i.p. injection of 7.8 mmol/kg NH4 acetate was evaluated by measuring the ammonia and glutamine content of the microdialysate. Field EPSPs (fEPSPs) evoked by perforant path stimulation were recorded 1.5 mm from the microdialysis probe. When 20 mM FA was perfused, NH4 acetate injection increased the ammonia efflux by 300% and decreased fEPSPs by 40%, but glutamine concentration remained low. With no FA in the microdialysate, NH4 acetate treatment increased the efflux of ammonia by only 60%, did not affect fEPSPs but doubled glutamine efflux. Arterial ammonia content, as measured by microdialysis in the common carotid, increased 4-5 fold following i.p. administration of NH4 acetate, while arterial glutamine was not elevated. Systemically administered FA did not affect either of these changes significantly, but slightly reduced arterial pH. These observations indicate that FA applied by microdialysis acted locally on astrocytes and therefore impaired astrocytic function contributes to the development of hepatic encephalopathy by facilitating the entry of ammonia into the brain. Inhibition of excitatory synaptic transmission by elevated brain ammonia may underlay CNS depression in hepatic encephalopathy.
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PMID:Astrocytes and the entry of circulating ammonia into the brain: effect of fluoroacetate. 819 41

The authors report two cases of hepatic encephalopathy with chronic hepatic failure. Case 1 was a 78-year-old woman with liver cirrhosis, admitted because of general fatigue and loss of appetite. Her electroencephalogram showed frequent slow waves in the theta range with intermittent triphasic waves T1-weighted MR images showed increased signal intensity in the globus pallidus and the putamen. Case 2 was a 71-year-old woman with chronic hepatitis, admitted because of depression. Her electroencephalogram showed frequent slow wave activities in the theta-delta range with intermittent trisphasic waves. Her serum ammonia level was 84 micrograms/dl (normal 12-54 micrograms/dl). T1-weighted MR images showed increased signal intensity in the globus pallidus, the putamen and the hypothalamus. On the basis of these findings, both patients were diagnosed as having hepatic encephalopathy, although disturbance of consciousness was not obvious. The observed MR image abnormalities might be due to the metabolic and pathological changes of chronic hepatic failure. Such MRI findings may be useful for the diagnosis of hepatic encephalopathy.
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PMID:[Two cases of hepatic encephalopathy associated with a high-intensity area in the basal ganglia on T1-weighted MR images]. 823 Jul 86

Portacaval shunting causes liver atrophy, hyperammonemia, and hepatic encephalopathy. A fundamental question is whether the changes, especially those to brain, are permanent. To answer this, it is necessary to have a model whereby a portacaval shunt can be created for a period of time and then the normal pattern of circulation to the liver restored at will. An end-to-side shunt, the most extensively studied model of liver dysfunction, is permanent. However, a side-to-side shunt can be constructed that results in a somewhat different pattern of circulation but with the potential to be reversed. The purpose of the present study was to compare the severity of the metabolic disturbances caused by the two models. Rats with an end-to-side shunt, a side-to-side shunt, or sham operation were prepared and studied after 14-19 days. Both models of shunting caused the same degree of liver atrophy, hyperammonemia, and indistinguishable disturbances in the amino acid content of plasma and brain. Furthermore, both models produced the same degree of cerebral depression as measured by glucose consumption.
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PMID:Comparison of the metabolic disturbances caused by end-to-side and side-to-side portacaval shunts. 896 52

Altered biogenic amine metabolism and function are believed to underlie certain of the neuropsychiatric symptoms, e.g., depression, mania, and anxiety, encountered in clinical hepatic encephalopathy (HE). We therefore investigated the activity of the degradative enzyme monoamine oxidase (MAO) and its binding parameters using [3H]Ro 41-1049 (defining MAO-A) and [3H]Ro 19-6327 (Lazabemide; defining MAO-B) in autopsied brain tissue from male cirrhotic patients with HE. The MAO-B parameters in HE patient tissue were not significantly different from those determined for control tissue. In contrast, increases in MAO-A activities in HE patient frontocortical (by approximately 50%) and cerebellar (by approximately 145%) tissues were observed, confirming our previous findings using comparable tissues. Increases in the abundance of the active MAO-A protein were of the same order of magnitude, e.g., in frontal cortex by approximately 85% and in cerebellum by approximately 225%. Reverse transcriptase-polymerase chain reaction indicated an increase in the level of gene expression (by approximately 155%) and thus offers some of the first evidence of a transcriptional event potentially mediating MAO-A function in human brain tissue. The levels of biogenic amine acid metabolites were increased as expected. As HE patients are most often treated for their hepatic symptoms rather than their neuropsychiatric manifestations, they represent an important "untreated" psychiatric population. The present findings are therefore not only important for our understanding of the pathophysiology of HE but also extremely relevant to our understanding of the pharmacotherapy of other neuropsychiatric disorders in which biogenic amine and MAO-A dysfunction is indicated.
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PMID:Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy. 904 67

In cattle with hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi or fasciolosis, the progression of the disease was studied by serial measurements of serum total bile acid concentrations, plasma glutamate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase and leucine aminopeptidase activities Terminalia avicennioides and by liver biopsy. Regardless of the cause of the hepatic disease, weight loss, anorexia, dullness and depression were consistent features. Signs of hepatic encephalopathy, such as blindness, head pressing, excitability, ataxia and weakness were less common and, together with pyrexia and jaundice, were grave prognostic signs. Plasma ammonia concentrations were significantly elevated compared to clinically normal cattle, but such changes were not always accompanied by a decline in plasma urea concentrations. In normal, healthy cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration is 11:1. In hepatic disease, a plasma ammonia:glucose ratio > 40:1 or plasma ammonia:urea ratio > 30:1, particularly with a rising total ketone body concentration and a declining glucose concentration, carried a guarded prognosis. The study suggested that other factors, such as hypokalaemia, alkalosis, short-chain volatile fatty acids, and false and true neuro-transmitters, may be important in the pathogenesis of hepatic coma in cattle.
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PMID:Clinical and pathological studies in cattle with hepatic disease. 909 45

Sleep disturbance is a classic sign of hepatic encephalopathy. However, there are limited data regarding its prevalence in cirrhotic patients without overt hepatic encephalopathy. We assessed the characteristics of sleep in cirrhosis using a sleep questionnaire (n = 44) and actigraphy (n = 20). The results were compared with those of subjects with chronic renal failure and those of healthy controls. Presence of subclinical hepatic encephalopathy, chronotypology profile, and individual's affective state were also analyzed. The questionnaire indicated an elevated number of cirrhotic patients (47.7%) and patients with chronic renal failure (38.6%) who complained of unsatisfactory sleep compared with healthy controls (4.5%, P < .01). Actigraphy corroborated the deterioration of sleep parameters in cirrhotic patients with unsatisfactory sleep. The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Cirrhotic subjects and patients with chronic renal failure with unsatisfactory sleep showed higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. However, in contrast to chronic renal failure, unsatisfactory sleep in cirrhosis was associated with delayed bedtime, delayed wake-up time, and evening chronotypology. In conclusion, a sleep disturbance is frequent in cirrhotic patients without hepatic encephalopathy and may be related to abnormalities of the circadian timekeeping system.
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PMID:High prevalence of sleep disturbance in cirrhosis. 946 28

Numerous studies suggest that modifications in concentrations of both excitatory and inhibitory amino acids are implicated in the pathophysiology of portal-systemic encephalopathy (PSE), a neuropsychiatric disorder associated with chronic liver disease in humans. In this study, amino acid levels were measured by High Performance Liquid Chromatography (HPLC) in Cerebrospinal Fluid (CSF) of 10 dogs (age range: 3 mo.- 3 yr 4 mo.) exhibiting a congenital portal-systemic shunt, either intra or extra-hepatic, and 8 age-matched control dogs who showed no signs of hepatic or neurologic disorders. Dogs with congenital shunts manifested signs of encephalopathy such as disorientation, head pressing, vocalization, depression, seizures and coma. CSF from dogs with congenital shunts contained significantly increased amounts of glutamate (2 to 3-fold increase, p<0.01), glutamine (6-fold increase, p<0.05) and aromatic amino acids (phenylalanine, tyrosine and tryptophan) compared to CSF of control dogs. Concentrations of GABA and branched chain amino acids (valine, leucine, isoleucine) were within normal limits. Modifications of brain glutamate (an excitatory amino acid) as well as tryptophan (the precursor of serotonin) could contribute to the neurological syndrome characteristic of congenital PSE in dogs.
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PMID:Selective alterations of cerebrospinal fluid amino acids in dogs with congenital portosystemic shunts. 947 3

The ammonia and GABAergic neurotransmission hypotheses of the pathogenesis of hepatic encephalopathy (HE) have appeared to be unrelated and perhaps mutually exclusive. Observations in animal models of fulminant hepatic failure, that are consistent with increased GABAergic inhibitory neurotransmission contributing to the manifestations of HE, include: (i) abnormal visual evoked potential waveforms that resemble those induced by GABA(A)/benzodiazepine (BZ) receptor complex agonists; (ii) GABA(A)/BZ receptor complex antagonist-induced ameliorations of encephalopathy; (iii) increased resistance to drugs which decrease GABAergic tone; and (iv) hypersensitivity of CNS neurons to depression by GABA(A)/BZ receptor complex agonists. Mechanisms of increased GABAergic tone in HE may include the following: (i) increased brain concentrations of natural BZs; and (ii) increased GABA concentrations in synaptic clefts, possibly due to increased blood-brain-barrier permeability to GABA and a decrease in GABA(B) receptor density. Both neuroelectrophysiological and behavioral data indicate that ammonia concentrations in the range 0.75-2 mM induce increased excitatory neurotransmission. In contrast, recently, ammonia concentrations in the range 0.15-0.75 mM, i.e. concentrations that commonly occur in plasma in precoma HE, have been shown: (i) to increase GABA-induced chloride current in cultured neurons; and (ii) to enhance synergistically the binding of GABA(A)/BZ receptor agonists. In addition, increased ammonia concentrations enhance synthesis of neurosteroids in astrocytes, and some neurosteroids potently augment GABAergic neurotransmission. Thus, the modestly elevated concentrations of ammonia, that commonly occur in liver failure, may contribute to the manifestations of HE by enhancing GABAergic inhibitory neurotransmission. This concept appears to unify the ammonia and GABAergic neurotransmission hypotheses.
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PMID:Does ammonia contribute to increased GABA-ergic neurotransmission in liver failure? 1020 26

Hepatic encephalopathy is suspected in non-cirrhotic cases of encephalopathy because the symptoms are accompanied by hyperammonaemia. However, the cause of the large portal-systemic shunt formation observed in these cases is not clear, as cirrhosis and portal hypertension are absent. The frequency of such cases reported in the literature is increasing with progress and spread of abdominal imaging diagnostic techniques. Some cases have been misdiagnosed as psychiatric diseases (dementia, depression and others) and consequently patients have been hospitalized in psychiatric institutions or geriatric facilities. Some paediatric cases have also been misdiagnosed. Therefore, the importance of accurate diagnosis of this disease should be strongly emphasized. Some paediatric cases have also been misdiagnosed. When psychoneurological symptoms are suggestive of hepatic encephalopathy but objective and subjective symptoms or abnormal values of liver function tests are not sufficiently indicative of liver cirrhosis, portal-systemic encephalopathy should be suspected. Abnormal angiograms of the portal vein, superior mesenteric vein or splenic vein are conclusive evidence of portal-systemic encephalopathy. Transrectal portal scintigraphy also provides information useful for detection of shunts and a quantitative estimation of shunt index. We classified the disease into five types based on whether the shunt is formed inside or outside the liver. Type I (intrahepatic type) designates cases in which shunts are located between the portal and systemic veins. Type II designates a type of intra/extrahepatic shunt that originates from the umbilical part of the portal vein and serpentines in the liver, then leaves the liver. Type III (extrahepatic type) occurs most frequently. Type IV (extrahepatic) is accompanied by shunts similar to those in type III, but hepatic pathology presents as idiopathic portal hypertension. Type V (extrahepatic) represents the congenital absence of the portal vein, where the superior mesenteric vein joins the intrahepatic inferior vena cava or the left renal vein. The prevalence of each type in our country was examined by a nationwide investigation. In addition to the conventional diet or drug treatments, obliteration by less invasive interventional radiology using a metallic coil and ethanol has recently been used more frequently than surgical occlusion of shunts. Shunt-preserving disconnection of portal and systemic circulation and partial splenic artery embolization are also performed. International investigation of the disease status and establishment of diagnostic and therapeutic methods for the disease are awaited and investigation of long-term prognosis after therapy is also necessary.
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PMID:Portal-systemic encephalopathy in non-cirrhotic patients: classification of clinical types, diagnosis and treatment. 1105 25

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