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)

1. The effects of single doses of ethionine or sodium salicylate on the nicotinamide-adenine dinucleotide content of rat liver have been studied. 2. There was no significant change in the sum of NAD+NADH(2) during the early period (0-2hr.) of the liver injury induced by ethionine but there was a decrease in this value of approx. 30% by 4hr. after administration. 3. Ethionine had no significant effect on the NADP+NADPH(2) during the first 2hr. period after administration. The sum then decreased to a value approx. 70% of the control by 3hr. after dosing but showed a partial recovery at the 4hr. period before decreasing again in later stages of the poisoning. 4. Salicylate produced a very rapid decrease in the NADP+NADPH(2) in the liver after intraperitoneal injection. After 1hr. the decrease was approx. 30% of the initial value; the sum slowly returned towards the normal range during the following 4hr. 5. A high parenteral dose of salicylate was found to cause only a small depression in the concentration of ATP in rat liver in contrast with the rapid depletion produced by ethionine. 6. These results are discussed in terms of the liver disturbances produced by ethionine and salicylate.
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PMID:Nicotinamide-adenine dinucleotides in acute liver injury induced by ethionine, and a comparison with the effects of salicylate. 438 11

1. Assessment of the overall metabolic changes in lactating mammary gland after thyroidectomy has been made by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into (14)CO(2) and (14)C-labelled lipid in the experimental rats and in sham-operated control animals. 2. Thyroidectomy depressed the oxidation of (14)C-labelled substrates, an effect still apparent when the control rats were pair-fed with thyroidectomized rats; however, the ratio of oxidation of [1-(14)C]glucose/oxidation of [6-(14)C]glucose was unaltered. In parallel with these studies it was revealed that the activities of hexokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-linked isocitrate dehydrogenase were all lower in the thyroidectomized group than in the pair-fed control group. 3. Thyroidectomy also lowered the incorporation of (14)C-labelled substrates into (14)C-labelled lipid, an effect further studied by measurement of the activities of citrate-cleavage enzyme and acetate thiokinase. Restricting the food intake of the control rats to that of the thyroidectomized group lowered the activity of citrate-cleavage enzyme, but no further depression was observed on thyroidectomy. The oxidized and reduced nicotinamide nucleotide content of mammary tissue was shown to be decreased in the thyroidectomized rats compared with the control rats.
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PMID:Effect of thyroidectomy on pathways of glucose metabolism in lactating rat mammary gland. 438 95

1. The effect of dinitrophenol on the metabolism of glucose labelled with (14)C and tritium by epididymal fat-pad segments from fed rats was studied. Dinitrophenol at concentrations of 0.1-0.3mm: (a) had little effect on glucose utilization; (b) depressed synthesis of fatty acids and greatly increased that of lactate; (c) increased the T/(14)C ratio in fatty acids synthesized from [U-(14)C,3-T]glucose and decreased that in fatty acids synthesized from [U-(14)C,4-T]glucose; (d) abolished randomization of (14)C from [6-(14)C]glucose in lactate. 2. Dinitrophenol stimulated oxidation of pyruvate and greatly inhibited the oxidation of lactate. It inhibited lipogenesis from pyruvate and lactate. 3. From the isotope data it was calculated that: (a) dinitrophenol stimulates oxidation via the tricarboxylic acid cycle three- to six-fold; (b) dinitrophenol depresses markedly the operation of the pentose cycle; (c) in the presence of dinitrophenol, NADPH formed in the pentose cycle provides all the hydrogen equivalents for fatty acid reduction, whereas, in its absence, NADPH provides 50-70% of the hydrogen equivalents; (d) in the presence of dinitrophenol, there is an excess of ATP produced in the cytoplasm, which flows into the mitochondria. A reverse flow operates in the absence of dinitrophenol. 4. A balance of formation and utilization of reduced nicotinamide nucleotides in the cytoplasm was established. With dinitrophenol there is some excess of NADH. There are indications that this excess may be transferred into mitochondria in the form of malate. 5. Our results are interpreted to indicate the absence from adipose tissue of the alpha-glycerophosphate shuttle for transferring reducing equivalents from the cytoplasm to mitochondria. 6. The effects of dinitrophenol are accounted for in terms of decreased ATP concentrations in the cells, leading to marked decrease in pyruvate carboxylation in the mitochondria and depression of fatty acid synthesis in the cytoplasm.
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PMID:The effect of 2,4-dinitrophenol on adipose-tissue metabolism. 438 39

During 26-51 months of valproic acid amide treatment of 15 patients with affective and schizoaffective disorders, the authors observed reduction in the number, length and severity of affective episodes, especially mania. In a few patients, "fragmentation" of long and severe relapses into short and mild mania or depression occurred. The number and length of hospital admissions dropped in all patients.
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PMID:Valproic acid amide in the treatment of affective and schizoaffective disorders. 614 11

Sodium diethyldithiocarbamate (DDTC) administered following cis-diamminedichloroplatinum(II) (DDP) has been reported to attenuate structural renal damage and elevation of blood urea nitrogen in rats. Since DDP damages primarily proximal tubular epithelium in this species, we compared proximal tubular function, glomerular function, and histology in male Sprague-Dawley rats treated with DDP followed by either DDTC or 0.9% NaCl solution (NS) rescue. Male Sprague-Dawley rats received a single i.p. injection of DDP (7.5 mg/kg)-mannitol (75 mg/kg)-NaCl (67.5 mg/kg). Forty-five min later, rats were given i.p. injections of either DDTC (750 mg/kg) dissolved in 0.5 ml of NS (DDP + DDTC group; ten rats) or 0.5 ml NS (DDP + NS group; nine rats); additional rats received either DDTC only (DDTC group; six rats) or no treatment (untreated control group; six rats). All groups were sacrificed 5 days later by ether anesthesia and exsanguination. Compared to the untreated control group, the DDTC group had slightly lower mean blood urea nitrogen at sacrifice [12.5 +/- 0.5 (S.E.) versus 15.4 +/- 0.8 mg/dl; p less than 0.025 by unpaired Student's t test]; there was no difference in serum creatinine. The DDP + DDTC group had no diarrhea and no presacrifice deaths in contrast to diarrhea and three presacrifice deaths in the DDP + NS group. Blood urea nitrogen was also lower in the DDP + DDTC group at sacrifice (187 +/- 30 versus 383 +/- 39 mg/dl; p less than 0.005). However, weight loss and serum creatinine were not different. Structural acute tubular necrosis was marked in both DDP groups but was less severe in the DDP + DDTC group than in the DDP + NS group. Proximal tubular function was indexed by the uptake of the organic base N-[14C]methyl nicotinamide (NMN) and the organic acid p-aminohippurate in renal cortical slices incubated 90 min in Cross and Taggart medium. NMN uptake (expressed as slice to medium ratio) was slightly lower in the DDTC group than in untreated controls (4.1 +/- 0.2 versus 5.0 +/- 0.2; p less than 0.025). Marked depression of p-aminohippurate and NMN uptake occurred in both DDP + DDTC and DDP + NS groups. There was no difference in NMN uptake, but depression of p-aminohippurate uptake was slightly less severe in the DDP + DDTC group (5.3 +/- 0.7 versus 3.1 +/- 0.3; p less than 0.005). We conclude that DDTC rescue attenuates structural DDP injury in this animal model. DDP-mediated proximal tubular dysfunction was only marginally attenuated by DDTC; glomerular filtration rate, as indexed by serum creatinine, was not protected. DDTC attenuation of DDP toxicity may be mediated in part via reducing volume depletion due to DDP-associated diarrhea.
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PMID:cis-diamminedichloroplatinum(II) nephrotoxicity: tubular function after rescue with sodium diethyldithiocarbamate in rats. 630 93

The electrical activity of transverse slices of hippocampus was used as a bioassay in which extracts of fresh brain tissue were screened for biological activity. A factor that depressed synaptic transmission was identified as nicotinamide adenine dinucleotide (NAD). This depressant action of NAD could be observed at concentrations in the range 1-10 microM and the degree of depression was monotonically related to the concentration of NAD in the bathing medium. NAD did not affect the antidromic invasion of the granule cells nor did it alter the relationship between the electrically evoked excitatory postsynaptic field potential (e.p.s.p.) and the population discharge of the granule cells (population spike). These results suggest that NAD did not affect the electrical excitability of the neuronal membranes. NAD had little effect on the sensitivity of granule cells to iontophoretically applied L-glutamate, the putative excitatory transmitter for the perforant path-granule cell pathway. Pure synaptosomal membranes, free of mitochondria, had two binding sites for NAD: a high affinity site with a Kd of 1 microM and a low affinity site with a Kd of 17 microM. These sites were similar in affinity to those of mitochondria, although the density of the high affinity sites was 5 X greater in the synaptosomal membranes. Adenosine had a relatively weak affinity for the NAD binding sites. It was concluded that NAD probably depressed synaptic transmission in the dentate gyrus by binding to sites on the presynaptic nerve terminal and reducing the amount of transmitter released by a nerve impulse. The physiological significance of this view is discussed.
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PMID:Nicotinamide adenine dinucleotide depresses synaptic transmission in the hippocampus and has specific binding sites on the synaptic membranes. 631 13

The effect of the teratogen 2-amino-1,3,4-thiadiazole on glycogenesis and glycogenolysis was investigated in the fetal and neonatal rat liver. At day 15, 16, or 17 of gestation (sperm day = day 0) pregnant Sprague-Dawley rats received a single IP injection of an aqueous solution of aminothiadiazole. Dosages used were teratogenic (100 mg/kg maternal body weight) and nonteratogenic (10 mg/kg). At day 16 some rats received nicotinamide (100 mg/rat) in addition to a teratogenic dose of aminothiadiazole. Livers were recovered for assay at fetal day 20 and postnatal day 1. Only at day 16 did a teratogenic dose induce a significant depression in the fetal activity of glycogen synthetase (to 49.6% of control activity) and glucose-6-phosphatase (to 72.2% of control activity), and in glycogen accumulation (to 72.6% of control accumulation). At day 15, a teratogenic dose significantly depressed glucose-6-phosphatase activity but not glycogen synthetase activity or glycogen accumulation. Nicotinamide, given immediately after aminothiadiazole, was effective in blocking the inhibition. Teratogenic treatment had no effect on the postnatal activity of glucose-6-phosphatase. Apparently some event associated with birth releases the enzyme from its prenatal inhibition. These results demonstrate a parallelism between the perturbing effect of aminothiadiazole on biochemical development and morphological development with respect to time of insult, dose response, and protection with its antiteratogen. The mechanism of action whereby aminothiadiazole depresses the activity of glycogen synthetase and glucose-6-phosphatase remains to be determined.
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PMID:The effect of aminothiadiazole on glycogenesis and glycogenolysis in fetal and neonatal rat liver. 632 Apr 84

In order to elucidate that which are the factors that may influence the direction of brain activation-induced changes in the redox state of oxidized/reduced nicotinamide adenine dinucleotide (NAD/NADH), the brain cortex was electrically stimulated during arterial hypotension and following reinfusion of the shed blood, during arterial hyper- and hypoxia, and during the second phase of spreading cortical depression (SD). Cerebrocortical NADH fluorescence and vascular volume ( CVV ) of cats, anaesthetized by chloralose, were measured with a microscope fluororeflectometer . Under physiologically normal conditions electrical stimulation resulted in pronounced cortical NAD reduction and increase in CVV . These reactions were not altered by arterial hyperoxia and continuous superfusion of the brain cortex with oxygenated artificial cerebrospinal fluid (mock CSF). Arterial hypotension and SD (in phase II) increased NAD reduction and CVV markedly, and the superimposed electrical stimulation brought about NADH oxidation and greatly depressed CVV responses. Reinfusion of the shed blood did not restore NAD/NADH redox state and CVV to their reference levels, and electrical stimulation under this condition led to NADH oxidation and negligible vascular reactions. Since under physiologically normal conditions electrical activation of the brain cortex resulted in NAD reduction and marked increase in CVV and the magnitude of these reactions were not altered by arterial hyperoxia or by superfusion of the brain cortex with oxygenated CSF, it is very unlikely that the brain cortex became hypoxic during stimulation. Because when the steady NAD/NADH redox state of the brain cortex was shifted toward reduction by arterial hypotension and reinfusion and SD, electrical stimulation led to NADH oxidation, it is suggested that the prestimulatory steady redox state has great importance in determining the direction of NAD/NADH redox reactions evoked by activation of the brain cortex.
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PMID:Determinants of brain activation-induced cortical NAD/NADH responses in vivo. 632 66

In experiments on cats it was shown that nicotinamide injected intravenously in a dose of 300 to 500 mg per kg body weight depressed singular epileptic foci and groups of foci with synchronized activity induced in the animals' brain cortex by application of strychnine (0.1 ml of 3% solution). The vitamin was also effective, though to a lesser degree, in depressing foci induced by application of penicillin (2% solution). Pyridoxal-5-phosphate (Pyr-5-Ph) injected intravenously in a dose of 10 mg/kg depressed singular foci and groups of foci with synchronized activity induced by application of 2% solution of penicillin, but was less effective in depressing strychnine-induced foci. Combined application of both drugs even in lower doses (nicotinamide, 200 mg/kg; Pyr-5-Ph, 5 mg/kg) resulted in depression of groups of epileptic foci induced by combined application of strychnine and penicillin. Mechanisms of the effects discovered are discussed. A question on possible use of combined nicotinamide and pyridoxal-5-phosphate in the treatment of epilepsy is raised.
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PMID:[Use of nicotinamide and pyridoxal-5-phosphate to treat experimental epilepsy]. 645 75

This work is centered on the involvement of glutamate in spreading depression. Chick eye cup preparations bathed with Ringer solution at 28 degrees C were used. For chemical stimulation KCl was increased and glutamate was added to the Ringer solution. The occurrence of spreading depression was detected by visual observation of the optical changes accompanying the phenomenon. Enzymatic method based on the fluorescence of the reduced form of nicotinamide adenine dinucleotide was used for glutamate dosage in the Ringer's samples. The investigations proceeded under six different experimental conditions, and the results were analysed by nonparametric statistical methods. No correlation was found between spreading depression and glutamate outflux. The glutamate hypothesis to account for spreading depression was discussed, and experimental situations involving glutamate, K+ and Cl- were indicated that proved unfavorable to the incidence of the reaction.
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PMID:Glutamate and spreading depression in chick retina. 667 91


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