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)

In the unicellular green alga Chlamydomonas reinhardi (strain y-1), synthesis of the enzymes required for urea hydrolysis is under substrate induction control by urea and under end product repression control by ammonia. Hydrolysis of urea if effected by the sequential action of the discrete enzymes urea carboxylase and allophanate lyase, collectively called urea amidolyase. The carboxylase converts urea to allophanate in a reaction requiring biotin, adenosine 5'-triphosphate, and Mg2+. The lyase hydrolzyes allophanate to ammonium ions and bicarbonate. Neither activity is present in more than trace amounts when cultures are grown with ammonia or urea plus ammonia, or when they are starved for nitrogen for 8 h. Urea in the absence of ammonia induces both activities 10 to 100 times the basal levels. Addition of ammonia to an induced culture causes complete cessation of carboxylase accumulation and an 80% depression of lyase accumulation. Ammonia does not reduce urea uptake by repressed cells, so it does not prevent induction by the mechanism of inducer exclusion. The unicellular green alga Chlorella pyrenoidosa (strain 3 Emerson) also has discrete carboxylase and lyase enzymes, but only the carboxylase exhibits metabolic control.
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PMID:Metabolic control of urea catabolism in Chlamydomonas reinhardi and Chlorella pyrenoidosa. 111 94

Recent studies showed that hyperammonaemia caused many of the metabolic changes in portacaval-shunted rats, a model of hepatic encephalopathy. These changes included a depression in the cerebral metabolic rate of glucose (CMRGlc), an indication of decreased brain function. 2. The purpose of the present experiments was to determine whether the depression of CMRGlc caused by ammonia is confined to certain brain structures, or whether the depression is an overall decrease in all structures, such as occurs in portacaval-shunted rats. To accomplish this objective, rats were made hyperammonaemic by giving them intraperitoneal injections of 40 units of urease/kg body wt. every 12 h; control rats received 0.154 m-NaCl. CMRGlc was measured 48 h after the first injection, by using quantitative autoradiography with [6-14C]glucose as a tracer. 3. The experimental rats had high plasma ammonia concentrations (control 70 nmol/ml, experimental 610 nmol/ml) and brain glutamine levels (control 5.4 mumol/ml). Hyperammonaemia decreased CMRGlc throughout the brain by an average of 19%. CMRGlc showed an inverse correlation with plasma ammonia, but a stronger correlation with the brain glutamine content. 4. Hyperammonaemia led to a decrease in CMRGlc throughout the brain that was indistinguishable from the pattern seen in portacaval-shunted rats. This is taken as further evidence that the cerebral depression found in portacaval-shunted rats is a consequence of hyperammonaemia. The observation that depression of CMRGlc correlated more closely with brain glutamine content than with plasma ammonia suggests that metabolism of ammonia is an important step in the pathological sequence.
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PMID:Hyperammonaemia depresses glucose consumption throughout the brain. 187 5

The toxicity of Cu, Ni and Fe individually, as well as in combination (Cu + Ni, Cu + Fe, Ni + Fe), on growth-rate depression, uptake of NO3- and NH4+, photosynthesis, nitrate reductase and urease activity of Chlorella vulgaris has been studied. All the test metals when used individually showed pronounced toxicity on all the parameters studied. However, their interactive effect was mostly antagonistic except for Cu + Ni (synergism). Pre-addition of Fe offered more protection to the cells against copper and nickel toxicity. The data of statistical analysis reconfirmed that 14CO2 uptake is the most sensitive parameter (significant at P less than 0.005, both for time and treatment) than others in metal toxicity assessment. However, these results suggest further that exposure time and sequence of metal addition are very important in biomonitoring of heavy metal toxicity.
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PMID:Impact of bimetallic combinations of Cu, Ni and Fe on growth rate, uptake of nitrate and ammonium, 14CO2 fixation, nitrate reductase and urease activity of Chlorella vulgaris. 216 14

To investigate the mechanism of the anti-urease action of ecabet sodium (ecabet) observed in Helicobacter pylori in vitro, the effects of ecabet on purified urease from jack bean were studied in comparison with the effects of the specific urease inhibitor benzohydroxamic acid (BHA). After incubation of the enzyme with the test drug for a period of time, urease activity was measured. Ecabet depressed the activity below pH 5, and the lower the pH, the greater the degree of depression. The degree of depression by ecabet increased gradually during incubation and reached a plateau in 20 min, whereas that by BHA attained a maximum rapidly. The IC50 values of ecabet and BHA were 2.1 mg/ml and 0.5 microgram/ml, respectively. When the incubation mixture of urease with an inhibitor was diluted and further incubated, the depressed activity by BHA reverted gradually, but that by ecabet did not. When the incubation mixture of urease with ecabet was centrifuged, the urease activity of the mixture decreased in parallel with the reduction in protein concentration of the supernatant. When the incubation mixture of urease and 14C-ecabet was ultrafiltered to remove the drug, the radioactivity in the retentate remained in parallel with the degree of reduction of urease activity in the retentate. These results indicate that ecabet irreversibly depresses the urease activity of jack bean, and suggest that the depression is caused by irreversible binding of ecabet to urease followed by denaturation of the enzyme protein.
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PMID:Mechanism of anti-urease action by the anti-ulcer drug ecabet sodium. 755 Jan 19

Colonisation with Helicobacter pylori may influence susceptibility to gastroduodenal injury and ulceration in patients taking non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to determine if Helicobacter pylori colonisation altered eicosanoid synthesis by gastric mucosa in these patients. Sixty five patients with long-standing NSAID intake and 23 control subjects underwent endoscopy. In vitro gastric antral biopsies were stimulated by vortex mixing and eicosanoid measurements determined by radioimmunoassay. Helicobacter pylori colonisation was determined by a CLO test (a gel based rapid urease test) and histological assessment. Median prostaglandin E2 synthesis by gastric mucosa was 61.0 (interquartile range: 19.2-73.1) pg/mg in control subjects colonised with Helicobacter pylori compared with 46.5 (23.3-65.5) pg/mg in Helicobacter pylori negative subjects. This was not significantly different. Treatment with NSAIDs was associated with a significant difference (p < 0.001) in prostaglandin E2 (PGE2) synthesis between those colonised with Helicobacter pylori (37.5(22.0-77.3) pg/mg) compared with patients not infected (12.6(7.0-19.3) pg/mg). Values in patients taking NSAIDs who were colonised were not different from control subjects. Synthesis of PGE2 was strongly associated with type B (chronic active), but not type C (chemical) gastritis. Dyspeptic symptoms were more common in subject colonised with Helicobacter pylori (p < 0.002) and were associated with higher PGE2 synthesis. In patients taking NSAIDs Helicobacter pylori colonisation removes rather then enhances depression of PGE2 synthesis associated with NSAIDs and may promote dyspepsia associated with ulcers and prevent superficial mucosal injury.
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PMID:Effect of Helicobacter pylori colonisation on gastric mucosal eicosanoid synthesis in patients taking non-steroidal anti-inflammatory drugs. 831 5

The authors describe a simple and rapid method for measuring urease and glycolytic activity of mixed saliva. It is based on alteration of the color of some acid-alkaline indicators during incubation of the saliva with appropriate substrata (carbohydrates and urea). Examinations of 32 normal subjects revealed that with the developed procedure, the reactions of carbohydrate fermentation and urea hydrolysis are rapidly detected in mixed saliva samples, the test taking approximately 20 min. Urea hydrolysis was accelerated in 62 patients with inflammatory processes in the periodontium, whereas the glycolytic processes were inhibited, this indicating an increase in the share of urease-positive microorganisms and depression of glycolytic flora. Hence, the described method for measuring urease and glycolytic activities of the oral fluid is recommended for clinical dentistry to be used for rapid diagnosis of oral diseases and for screening examination, as a simple, economic, easily reproducible, and noninvasive technique.
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PMID:[The determination of the ureolytic and glycolytic activities of human oral fluid]. 903 93

Stomach infection with pathogenic strains of Helicobacter pylori causes in some patients severe gastroduodenal diseases. These bacteria produce various virulence factors and, here, we review the recent acquisition on the biochemical mode of action of three major factors. We discuss the role of urease both as buffer of the stomach pH and as source of ammonia. The vacuolating toxin alters the endocytic pathway of non-polarized cells, inducing the release of acid hydrolases, the depression of extracellular ligand degradation and of antigen processing and, in the presence of ammonia, swelling of late-prelysosomal compartments. In polarized epithelial monolayers, vacuolating toxin induces an increase of the paracellular permeability, independent of vacuolation. The neutrophil activating protein induces the production of oxygen radicals in human neutrophils and could contribute to the damage of the stomach mucosa. The activities of these factors are discussed in terms of the need of the bacterium of increasing the supply of nutrients from the stomach lumen and from the mucosa.
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PMID:Molecular and cellular activities of Helicobacter pylori pathogenic factors. 1037 70

Three lamb metabolism experiments were conducted to investigate the effects of chronic administration of the novel urease inhibitor N (n-butyl) thiophosphoric triamide (NBPT) on ruminal N metabolism, fermentation, and N balance. In Exp. 1, ruminally cannulated wethers (n = 28; 45.0 +/- .9 kg) were administered one of seven doses of NBPT (0 [control], .125, .25, .5, 1, 2, or 4 g of NBPT daily) and fed a common cracked corn/cottonseed hull-based diet twice daily containing 2% urea at 2.5% of initial BW for the duration of the 15-d experiment. Overall, NBPT decreased (linear P < .0001; quadratic P < .001) ruminal urease activity, resulting in linear increases (P < .0001) in ruminal urea and decreases in ruminal NH3 N concentrations. However, the detection of an NBPT x day interaction (d 2 vs 15; P < .01) indicated that this depression in urea degradation diminished as the experiment progressed. Increasing NBPT linearly decreased (P < .01) total VFA concentrations on d 2 of the experiment, but it had no effect (P > .10) on d 15. Increasing NBPT had no effect (P > .10) on DM or ADF digestibilities, but it linearly decreased (P < .01) N digestibility. Supplementing NBPT produced a linear increase (P < .05) in urinary N excretion and a linear decrease (P < .01) in N retention. In Exp. 2, ruminally cannulated wethers (n = 30; 46.8 +/- .6 kg) were fed one of two basal diets (2.0 vs 1.1% dietary urea) at 2.5% of initial BW and dosed with either 0 (control), .25, or 2 g of NBPT daily for the duration of the 15-d experiment. There were no NBPT x dietary urea interactions (P > .10) for Exp. 2. Increasing NBPT depressed (linear and quadratic P < .0001) ruminal urease activity, producing linear (P < .0001) increases in urea N and linear decreases in NH3 N in the rumen. As in Exp. 1, an NBPT x day interaction (P < .05) was noted for urea, NH3 N, and total VFA concentrations; the maximum response to NBPT occurred on d 2 but diminished by d 15 of the experiment. Administration of NBPT did not influence (P > .10) DM, ADF, or N digestibilities in Exp. 2. In Exp. 3, wether lambs (n = 30; 26.4 +/- .7 kg) were subjected to the same treatment regimen as in Exp. 2 for a 14-d N balance experiment. Although several NBPT x dietary urea interactions (P < .05) were noted, increasing NBPT did not affect (P > .10) N digestibility. Administration of NBPT quadratically increased (P < .10) urinary N excretion, producing a linear decrease (P < .05) in N retention. These results suggest that although NBPT is capable of inhibiting ruminal urease short-term, the ruminal microflora may be capable of adapting to chronic NBPT administration, thereby limiting its practical use in improving the utilization of dietary urea.
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PMID:Influence of the novel urease inhibitor N-(n-butyl) thiophosphoric triamide on ruminant nitrogen metabolism: II. Ruminal nitrogen metabolism, diet digestibility, and nitrogen balance in lambs. 1068 21

The aim of this work is to investigate sunflower plants response on stressinduced by silver(I) ions. The sunflower plants were exposed to silver(I) ions (0, 0.1, 0.5,and 1 mM) for 96 h. Primarily we aimed our attention to observation of basic physiologicalparameters. We found that the treated plants embodied growth depression, coloured changes and lack root hairs. Using of autofluorescence of anatomical structures, such aslignified cell walls, it was possible to determine the changes of important shoot and rootstructures, mainly vascular bungles and development of secondary thickening. Thedifferences in vascular bundles organisation, parenchymatic pith development in the rootcentre and the reduction of phloem part of vascular bundles were well observable.Moreover with increasing silver(I) ions concentration the vitality of rhizodermal cellsdeclined; rhizodermal cells early necrosed and were replaced by the cells of exodermis.Further we employed laser induced breakdown spectroscopy for determination of spatialdistribution of silver(I) ions in tissues of the treated plants. The Ag is accumulated mainlyin near-root part of the sample. Moreover basic biochemical indicators of environmentalstress were investigated. The total content of proteins expressively decreased withincreasing silver(I) ions dose and the time of the treatment. As we compare the resultsobtained by protein analysis - the total protein contents in shoot as well as root parts - wecan assume on the transport of the proteins from the roots to shoots. This phenomenon canbe related with the cascade of processes connecting with photosynthesis. The secondbiochemical parameter, which we investigated, was urease activity. If we compared theactivity in treated plants with control, we found out that presence of silver(I) ions markedlyenhanced the activity of urease at all applied doses of this toxic metal. Finally we studiedthe effect of silver(I) ions on activity of urease in in vitro conditions.
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PMID:Multi-instrumental Analysis of Tissues of Sunflower Plants Treated with Silver(I) Ions - Plants as Bioindicators of Environmental Pollution. 2787 16

Previously we reported that gene expression of astrocytic 5-HT2B receptors was decreased in brains of depressed animals exposed to chronic mild stress (CMS) (Li et al., 2012) and of Parkinson's disease (Song et al., 2018). Depression is also one of the psychiatric symptoms in hyperammonemia, and astrocyte is a primary target of ammonium in brain in vivo. In the present study, we have used preparations of the brains of urease-treated mice and ammonium-treated astrocytes in culture to study gene expression and function of 5-HT2B receptors. The urease-treated mice showed depressive behaviour. Both mRNA and protein of 5-HT2B receptors were increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. Further study revealed that mRNA and protein expression of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme catalyze RNA deamination of adenosine to inosine was increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. This increase in ADAR2 induced RNA editing of 5-HT2B receptors. Cultured astrocytes treated with ammonium lost 5-HT induced Ca2+ signalling and ERK1/2 phosphorylation, indicating dysfunction of 5-HT2B receptors. This is in agreement with our previous observation that edited 5-HT2B receptors no longer respond to 5-HT (Hertz et al., 2014). Ammonium effects are inhibited by ADAR2 siRNA in cultured astrocytes, suggesting that increased gene expression and editing and loss of function of 5-HT2B receptors are results of increased activity of ADAR2. In summary, we have demonstrated that functional malfunction of astrocytic 5-HT2B receptors occurs in animal models of major depression, Parkinson depression and hepatic encephalopathy albeit via different mechanisms. Understanding the role of astrocytic 5-HT2B receptors in different pathological contexts may instigate development of novel therapeutic strategies for treating disease-specific depressive behaviour.
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PMID:Ammonium induced dysfunction of 5-HT2B receptor in astrocytes. 3114 70


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