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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthesis of glucose from lactate and generation of urea from ammonia were inhibited when sodium benzoate was added to suspensions of rat hepatocytes. Assays with isolated mitochondria suggested pyruvate carboxylase and the N-acetyl-L-glutamate (NAG)-dependent carbamoylphosphate synthetase (CPS-I) as potential sites of inhibition for both pathways, owing to a shared dependency on aspartate efflux from the mitochondria and its subsequent conversion to oxaloacetate in the cytosol. Assays with isolated hepatocytes indicated inhibition to be initiated by accumulation of benzoyl CoA with a resultant depletion of free CoA and acetyl CoA. Measurements of adenine nucleotides showed that benzoate metabolism did not sufficiently alter energy status to account for the observed inhibition. Consistent with these interpretations, acceleration of the conversion of benzoyl CoA to hippurate by the addition of glycine restored the levels of free CoA and acetyl CoA and the rates of gluconeogenesis and ureagenesis. Reduction of the levels of aspartate and glutamate, presumably by interference with the anapleurotic function of pyruvate carboxylase, most likely accounted for inhibition of gluconeogenesis by benzoate. Whether reduced flux through the urea cycle also contributed to inhibition of gluconeogenesis (by diminishing cytosolic conversion of aspartate to oxaloacetate) requires further study. Depression of glutamate and acetyl CoA to levels at or below the Km for NAG synthetase probably accounted for the observed inhibition of ureagenesis. Rates of urea production were observed to vary with changes in the levels of NAG, suggesting NAG-dependent CPS-I to be the primary site of inhibition of ureagenesis by benzoate.
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PMID:On the mechanism of inhibition of gluconeogenesis and ureagenesis by sodium benzoate. 167 73

This study was designed to investigate the effect of short-term, submaximal training on changes in blood substrates, metabolites, and hormonal concentrations during prolonged exercise at the same power output. Cycle training was performed daily by eight male subjects (VO2max = 53.0 +/- 2.0 mL.kg-1.min-1, mean +/- SE) for 10-12 days with each exercise session lasting for 2 h at an average intensity of 59% of VO2max. This training protocol resulted in reductions (p less than 0.05) in blood lactate concentration (mM) at 15 min (2.96 +/- 0.46 vs. 1.73 +/- 0.23), 30 min (2.92 +/- 0.46 vs. 1.70 +/- 0.22), 60 min (2.96 +/- 0.53 vs. 1.72 +/- 0.29), and 90 min (2.58 +/- 1.3 vs. 1.62 +/- 0.23) of exercise. The reduction in blood lactate was also accompanied by lower (p less than 0.05) concentrations of both ammonia and uric acid. Similarly, following training lower concentrations (p less than 0.05) were observed for blood beta-hydroxybutyrate (60 and 90 min) and serum free fatty acids (90 min). Blood glucose (15 and 30 min) and blood glycerol (30 and 60 min) were higher (p less than 0.05) following training, whereas blood alanine and pyruvate were unaffected. For the hormones insulin, glucagon, epinephrine, and norepinephrine, only epinephrine and norepinephrine were altered with training. For both of the catecholamines, the exercise-induced increase was blunted (p less than 0.05) at both 60 and 90 min. As indicated by the changes in blood lactate, ammonia, and uric acid, a depression in glycolysis and IMP formation is suggested as an early adaptive response to prolonged submaximal exercise training.
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PMID:Early adaptations in blood substrates, metabolites, and hormones to prolonged exercise training in man. 178 5

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

1. It has been established that chronic hyperammonaemia, whether caused by portacaval shunting or other means, leads to a variety of metabolic changes, including a depression in the cerebral metabolic rate of glucose (CMRGlc) increased permeability of the blood-brain barrier to neutral amino acids, and an increase in the brain content of aromatic amino acids. The preceding paper [Jessy, DeJoseph & Hawkins (1991) Biochem. J. 277, 693-696] showed that the depression in CMRGlc caused by hyperammonaemia correlated more closely with glutamine, a metabolite of ammonia, than with ammonia itself. This suggested that ammonia (NH3 and NH4+) was without effect. The present experiments address the question whether ammonia, in the absence of net glutamine synthesis, induces any of the metabolic symptoms of cerebral dysfunction associated with hyperammonaemia. 2. Small doses of methionine sulphoximine, an inhibitor of glutamine synthetase, were used to raise the plasma ammonia levels of normal rats without increasing the brain glutamine content. These hyperammonaemic rats, with plasma and brain ammonia levels equivalent to those known to depress brain function, behaved normally over 48 h. There was no depression of cerebral energy metabolism (i.e. the rate of glucose consumption). Contents of key intermediary metabolites and high-energy phosphates were normal. Neutral amino acid transport (tryptophan and leucine) and the brain contents of aromatic amino acids were unchanged. 3. The data suggest that ammonia is without effect at concentrations less than 1 mumol/ml if it is not converted into glutamine. The deleterious effect of chronic hyperammonaemia seems to begin with the synthesis of glutamine.
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PMID:Hyperammonaemia does not impair brain function in the absence of net glutamine synthesis. 187 6

The release of norepinephrine (NE) from the right atrium of the rabbit heart was used as a model to investigate biphasic effects due to tricyclic antidepressants, similar to those clinically observed in the treatment of depression and known as "therapeutic window". Strips of the atrium were loaded with 3H-NE, and then superfused by Krebs solution. The basal release and the electrical stimulation evoked release of 3H-NE were measured in the presence and absence of four clinically used tricyclic antidepressants: imipramine, amitriptyline, desipramine and nortriptyline. In addition, guanethidine, an adrenergic neuron blocker, was also studied. At lower concentrations (0.5-10 microM) tricyclic antidepressants increased, whereas higher concentrations (50-100 microM), inhibited the evoked release of NE. This inhibition was not prevented by the alpha2 adrenoceptor antagonist yohimbine, excluding the possibility of alpha 2 adrenoceptor-mediated inhibition of NE release. In higher concentrations the tricyclic antidepressants increased the basal release of NE in a Ca-independent way. Secondary amine derivatives were more potent inhibitors of the evoked release, and enhance the resting basal release of NE to a greater extent than the tertiary ones. Similarly, guanethidine (1-50 microM) also decreased the evoked release and increased the basal release of NE in a concentration dependent manner. Yohimbine failed to counteract the inhibition caused by guanethidine and the increment of the basal release was Ca-independent. It is concluded that the effect of tricyclic antidepressants in potentiating the release of NE is masked by their adrenergic neuron blocking properties, i.e. they inhibit the release of NE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biphasic effect of tricyclic antidepressants on the release of norepinephrine from the adrenergic nerves of the rabbit heart. 187 68

Four diets containing 15% CP were formulated to study the effects of dietary carbohydrate and protein sources on N metabolism and carbohydrate fermentation by ruminal bacteria. Diets were supplied to eight dual-flow continuous culture fermenters during three experimental periods in a randomized complete block design. Six replications were obtained for each diet. Treatments were arranged as a 2 X 2 factorial with two carbohydrate and two protein sources. Carbohydrate sources were corn and barley and protein sources were soybean meal (SBM) and fish meal (FM). Approximately 40% of the dietary CP was derived from SBM or FM and corn or barley provided 39% of dietary DM. All diets contained 15% grass hay, 20% wheat straw, and 10.1 to 15.3% solka floc (DM basis). Interactions (P less than .05) were observed between dietary carbohydrate and protein sources, resulting in a depression of VFA production (moles/day) and digestion (percentage) of ADF and cellulose when the corn-FM diet was fed. True OM digestion (percentage) was higher (P less than .05) for SBM than for FM diets and for corn than for barley diets. Although dietary CP degradation (percentage) was higher (P less than .05) for SBM than for FM diets, non-NH3 N in the effluent (grams/day) was not different among diets due to a greater (P less than .05) bacterial N flow for SBM than for FM diets. Despite the lower amino acid (AA) intake (P less than .05) for corn than for barley diets and also for FM than for SBM diets, flows (grams/day) of total AA, essential AA (EAA), and nonessential AA (NEAA) were similar (P greater than .05) among diets. However, greater (P less than .05) total AA, EAA, and NEAA flows (percentage of AA intake) were found for corn than for barley diets and for FM than for SBM diets. It is concluded, therefore, that ruminal escape protein derived from corn or FM has a significant effect on manipulating AA leaving the ruminal fermentation.
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PMID:Influence of dietary protein and carbohydrate sources on nitrogen metabolism and carbohydrate fermentation by ruminal microbes in continuous culture. 206 23

Responses of dairy cows given silage diets to the intraruminal infusion of urea in progressively increasing doses were studied in four experiments, two with non-lactating cows and two with lactating cows. No clinical symptoms of NH3 toxicity were observed in any of the experiments. When urea was infused continuously, silage intake was depressed (P less than 0.05) when the total supply of N exceeded the equivalent of 250 g crude protein (CP)/kg DM in the total diet. However, when the urea load was administered twice daily, as opposed to continuously, intake depression (P less than 0.05) occurred at the equivalent of 170 g CP/kg DM. At the higher doses of urea, concentrations of NH3 in peripheral blood increased and were accompanied by increased concentrations of glucose and reduced levels of insulin in plasma. In general, responses of milk production followed those of silage intake but there was evidence of greater proportional reductions in the yield of lactose relative to that of fat and protein. It is concluded that the voluntary intake of high-protein silages may be depressed by factors associated with high rates of absorption of NH3 from the rumen.
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PMID:The effects of intraruminal infusions of urea on the voluntary intake and milk production of cows receiving grass silage diets. 226 98

An 8-year-old mare was presented to the New York State College of Veterinary Medicine Large Animal Clinic for evaluation of anorexia, fever and icterus. The mare had a 5-day history of anorexia, depression and tongue protrusion. Diagnostic procedures included serum hepatic enzyme activities, serum bile acid concentrations, blood ammonia evaluations and hepatic ultrasound and ultrasound guided biopsy. The history, clinical pathology and histopathology in this case supported a probable diagnosis of primary septic cholangiohepatitis.
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PMID:Primary cholangiohepatitis in a horse. 229 63

Scope for growth (SfG), a measure of energy balance (between food intake and metabolic output) within animals, has been used as an indicator of pollution stress in marine systems. However, it has not been used commonly in freshwater systems and here we investigate the sensitivity of SfG in Gammarus pulex, a benthic freshwater crustacean, under conditions often associated with pollution. The effects of four specific substances were investigated; a metal (zinc), an organic (3,4-dichloroaniline), and two dissolved gases (oxygen and ammonia). In all cases SfG was reduced by the stress, primarily due to a depression in energy intake. Only with ammonia was energy output (respiration) significantly affected.
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PMID:Effect of stress on a freshwater benthic detritivore: scope for growth in Gammarus pulex. 236 11

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.
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PMID:Depressed metabolism and low protein catabolism in fasting grey seal pups. 236 22


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