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)

A comparison of structure-choleretic activity relationship has been made for several branched- and straight-chain carboxylic acids including valproic acid. Cumulative bile flow was 13.8, 23.8, 29.4 and 14.9 ml/4hr/kg body weight for dimethyl-, diethyl-, dipropyl- (valproic acid), and dibutyl-acetic acid, respectively, after iv administration of approximately equimolar doses (1100 mumoles/kg). Except for dibutylacetic acid, maximal bile flow increased from control rates of 50-60 to 120-140 microliters/min/kg. Administration of higher doses of 2,2-dimethylbutanoic acid and 2-ethylbutanoic acid did not increase maximal bile flow above 125-140 microliters/min/kg but did prolong the duration of choleresis. Maximal and cumulative bile flows increased with length of carboxylic acid chain for 2,2-dimethyl substituted acids (2,2-dimethylacetic acid to 2,2-dimethylbutanoic acid). If the two methyl groups were on C-3 (3-methylbutanoic acid), no change in bile flow was observed. Straight-chain acids from C-5 to C-11 and pent-4-enoic acid did not alter bile flow. Thus, the effectiveness of several branched-chain carboxylic acids as choleretics parallel their ability as anticonvulsants. In contrast, the straight-chain acids which cause central nervous system depression have no choleretic activity.
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PMID:Choleretic effect of structural analogs of valproic acid in the rat. 640 71

The pharmacological properties of a new type of anti-cancer agent, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil (U), in a molar ratio of 1:4, were investigated and compared with those of FT, 5-fluorouracil (5-FU) and uracil. UFT at doses larger than 874.8 (FT: 270.0) mg/kg p.o. produced slight central nervous depression in mice and rats, as demonstrated by prolongation of the thiopental anesthesia, analgesic activity in the acetic acid stretching test, an anticonvulsant effect on maximal electroshock convulsions and decrease in body temperature. In rabbits UFT at a dose of 291.6 (FT: 90.0) mg/kg p.o. produced an increase in the drowsy EEG pattern. UFT at high dose produced clonic convulsions in mice and rats and cardiac fibrillation in rabbits. UFT had slight cardiorespiratory effects in anesthetized rabbits and dogs and at a dose of 291.6 (FT: 90.0) mg/kg i.v. it increased the voltage of the T-wave in ECG in anesthetized dogs. At high doses UFT inhibited gastrointestinal transit in mice and it caused emesis in dogs. At doses larger than 291.6 (FT: 90.0) mg/kg p.o. it had a diuretic effect and at higher doses it slightly increased the blood glucose level in rats. FT at equal doses to UFT had the same effects as UFT and the effect of 5-FU was similar to that of UFT. The pharmacological activity of uracil was much less potent. It was concluded that the pharmacological effect of UFT was almost entirely due to FT, however, UFT had much less effect than FT in inducing clonic convulsions, increasing the voltage of the T-waves in ECG and inducing emesis, its depressant effect is probably due to its constituent uracil.
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PMID:General pharmacological properties of UFT, a new type of anti-cancer agent consisting of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil. I: Pharmacological analysis of the combined effect of FT and uracil. 679 78

A study was undertaken to further the understanding of the mechanism by which suckling inhibits the release of pituitary LH and depresses the postovariectomy rise of plasma LH in lactating mammals. To that end, the effect of suckling (10 pups/animal) for 1 or 3 weeks on the LHRH content of the hypothalamus and preoptic area (POA) in ovariectomized and intact rats was examined. Controls consisted of intact and 1 or 3 week ovariectomized, nonlactating animals. Following decapitation, the brains were rapidly removed and blocks containing the POA and the hypothalamus (with median eminence) were isolated. Tissue was extracted with acetic acid and LHRH quantitated via validated RIAs utilizing 2 antisera specific for different portions of the LHRH molecule. Ovariectomy of nonlactating, diestrous animals resulted in a significant decline in hypothalamic LHRH, reaching 50% of control levels by 3 weeks. During the same intervals, plasma LH increased dramatically to 20- and 60-fold over intact controls by 1 and 3 weeks, respectively. In contrast, LHRH levels were not decreased at 1 or 3 weeks in ovariectomized rats which were suckled, at which time plasma LH was greatly depressed. When intact animals were evaluated, the suckling stimulus failed to induce a detectable change in LHRH content of the hypothalamus of LHRH in the POA between any of the treatment or control groups. These data from ovariectomized rats suggest that suckling inhibits LHRH release from the hypothalamus and hence provides an explanation for the depression of plasma LH observed in suckled ovariectomized and intact animals.
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PMID:Inhibition of the postovariectomy depletion of hypothalamic luteinizing hormone releasing hormone (LHRH) by suckling. 704 34

Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5-hydroxyindole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17-hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated the alteration in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.
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PMID:Serotonin metabolism and depression in oral contraceptive users. 714 Feb 95

The effects of intravenous administration of 50-400 mg/kg imidazole-4-acetic acid (IMA) on the carbohydrate metabolism of the rat brain were assessed by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic--citric acid cycle metabolites. IMA (100-400 mg/kg) produced a spectrum of electroencephalographic (EEG) change ranging from desynchronization to electrical suppression which was associated with unchanged tissue contents of ATP, ADP, and AMP, increasing levels of phosphocreatine, glucose, and aspartate, and decreasing levels of pyruvate, lactate, alpha-ketoglutarate, and malate. The changes in glycolytic intermediates were present within 5 min of injecting IMA (200 mg/kg) and the pattern suggested a suppression of glycolysis. The EEG stage of electrical suppression with episodic spiking (400 mg/kg) was associated with a 30% reduction of cortical high-energy phosphate use. The lowest dose of IMA (50 mg/kg) resulted in episodic EEG desynchronization which was associated with no significant changes of the measured metabolites. The results indicate that IMA is associated with metabolite changes that are compatible with a state of cerebral depression and that the desynchronous EEG pattern is without a biochemical correlate of increased neuronal activity.
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PMID:The effects of imidazole-4-acetic acid on cerebral carbohydrate metabolism. 716 56

The metabolic effects of intravenous administration of 200 mg/kg imidazole-4-acetic acid (IMA) on normoxic, hypoxemic and hypoxemic-oligemic rat brain were assessed by measurement of the cerebral contents of energy phosphates and selected glycolytic-citric acid cycle intermediates. In normoxic brain IMA was associated with unaltered adenylates, increased glucose and aspartate, and decreased pyruvate, lactate, citrate, alpha-ketoglutarate and malate; a pattern which is compatible with cerebral metabolic depression. In hypoxemic brain IMA was associated with a lower accumulation of lactate and a higher level of tissue glucose; again conforming to patterns documented for classical cerebral depressants. In hypoxemic-oligemic brain IMA was associated with a gross deterioration of the tissue ATP content and with a massive lactacidosis which indicated a detrimental action in this hypoxic state.
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PMID:The effects of imidazole-4-acetic acid upon the energy metabolism of normoxic and hypoxic rat brain. 718 30

Aspartame (APM) or L-aspartyl-L-phenylalanine, and a 3 : 1 combination of APM with its decomposition product, 5-benzyl-3,6-dioxo-2-piperazine acetic acid (DKP), were incorporated at levels of up to 4 g/kg in the diet of male and female Wistar rats from 6 weeks to 104 weeks of age. There was a dose-dependent depression of body weight gain at 2 and 4 g/kg AMP and at 4 g/kg APM + DKP in males, and at all dose levels in females, correlated with decreased food consumption and attributed to liberation of amino acids from hydrolysis of APM. Increases in urinary specific gravity and pH, with increase of relative kidney weight, were attributed to the urinary excretion DKP and acidic metabolites of APM. A dose-related increase in urinary calcium probably reflected increased calcium absorption, as from high protein diets. A slight decrease in serum cholesterol and an increase in relative spleen weight appeared to be without adverse effect. It is concluded that the treatments were without toxic effect.
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PMID:Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks. 728 Dec 5

Caffeine injected at doses of 20, 40 and 80 mg/kg increased brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in rat brain. In view of a possible role of 5-HT in caffeine-induced depression the effects of repeated administration of high doses of caffeine on brain 5-HT metabolism are investigated in rats. Caffeine was injected at doses of 80 mg/kg daily for five days. Control animals were injected with saline daily for five days. On the 6th day caffeine (80 mg/kg) injected to 5 day saline injected rats increased brain levels of tryptophan, 5-HT and 5-HIAA. Plasma total tryptophan levels were not affected and free tryptophan increased. Brain levels of 5-HT and 5-HIAA but not tryptophan decreased in 5 day caffeine injected rats injected with saline on the 6th day. Plasma total and free tryptophan were not altered in these rats. Caffeine-induced increases of brain tryptophan but not 5-HT and 5-HIAA were greater in 5 day caffeine than 5 day saline injected rats. The findings are discussed as repeated caffeine administration producing adaptive changes in the serotonergic neurons to decrease the conversion of tryptophan to 5-HT and this may precipitate depression particularly in conditions of caffeine withdrawal.
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PMID:24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression. 747 12

Using invasive techniques we have studied various hemodynamic and gasometric parameters in the course of hemodialysis (HD) with different buffers in an animal model. HD sessions of 180 minutes at zero ultrafiltration were carried out on three groups of eight uremic dogs each, under anesthesia and constant mechanical ventilation. The three groups differed only in the buffer used: acetate (Group AC), equal proportions of DL-lactate and acetate (Group AC+LA), and bicarbonate (Group BC). No hemodynamic changes were seen in Group BC. In the AC and AC+LA groups we observed on minute 1 a decrease of the mean blood pressure (MBP) and of the systemic vascular resistances (SVR). These parameters returned to baseline values within the first 30 minutes in Group AC+LA. In Group AC the SVR also returned to baseline values after the minute 30, but the MBP remained below baseline throughout the study period, together with cardiac index and left ventricular stroke work index decreases. Only in Group AC did we see a flattening of the ventricular function curves. Only in this Group was there a decrease of the arterial oxygen pressure (PaO2) with an associated increase of the alveolo-arterial and arterio-venous O2 differences. The O2 consumption was not modified in any of the groups. Acetate as a single buffer induces hemodynamic instability through peripheral vasodilation and reduction of myocardial contractility. The myocardial depression induced by acetate, in its turn, causes a reduction in PaO2. The mixed acetate+lactate buffer is hemodynamically better tolerated than acetate as single buffer, as it induces only vasodilation.
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PMID:Hemodialysis with acetate, DL-lactate and bicarbonate: a hemodynamic and gasometric study. 786 13

Activity-dependent competition between two spinal neurons coinnervating an embryonic myocyte was studied in Xenopus cell culture. We have characterized in detail the phenomenon of heterosynaptic suppression by which tetanic stimulation of one neuron results in functional suppression of the synapse made by the untetanized neuron (Lo and Poo, 1991). Fluorescence labeling of the neurons using two different fluorophores revealed that the coinnervating nerve terminals on the spherical myocyte were in close proximity. Heterosynaptic suppression could be induced when the postsynaptic cell was held under either current-clamp or voltage-clamp conditions during the tetanic stimulation. This finding, together with the observation that repetitive postsynaptic depolarization of the myocyte by direct current injection was much less effective in inducing synaptic depression, suggests that postsynaptic ACh receptor activation plays a dominant role in the induction of heterosynaptic suppression. The heterosynaptic suppression appears to be mediated by a rise of Ca2+ levels in the postsynaptic cell, since it was not observed when the cytosolic Ca2+ concentration of the myocyte was buffered at a low level with intracellular loading of a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA). The dependence of heterosynaptic suppression on the pattern of tetanic stimulation was also studied. At a stimulation frequency of 2 Hz, detectable heterosynaptic suppression could be induced after 20 repetitive stimuli were applied to one of the presynaptic neurons and the suppression was more effective with increasing number of stimuli. Over the range of 0.5-5 Hz, the extent of suppression was independent of the frequency of tetanic stimulation and, in some cells, detectable suppression could be induced at a frequency as low as 0.05 Hz. Except for a few cases, heterosynaptic suppression was found to last for as long as the recording was made after tetanus (up to 1 hr). The fact that the mean amplitude of spontaneous synaptic currents remained the same before and after the suppression while the evoked synaptic currents exhibited higher fluctuation after suppression suggests that the observed synaptic suppression involves a reduction of evoked ACh release from the nerve terminal, although postsynaptic changes have not been excluded. Finally we found that spontaneous synaptic activity may also contribute in part to the synaptic competition between coinnervating nerve terminals. Taken together, these findings provide a quantitative basis for further understanding of activity-dependent competition between developing neuromuscular synapses.
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PMID:Heterosynaptic suppression of developing neuromuscular synapses in culture. 804 43


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