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)

Experiments were conducted on rats; in depression of blood cholinesterase activity by 68.6 percent phthalafos proved to decrease the myocardial nicotinamide coenzymes content on account of reduction in the amount of the oxidized forms. In the liver phthalafos diminished the content of oxidized and reduced forms of nicotinamide coenzymes, decreased the level of adenylic nucleotides chiefly at the expense of ATP. Diproxim prevented the changes caused by phthalafos in blood cholinesterase reactivation to 47.5 percent. It is supposed that the capacity of diproxim to normalize the oxidative processes in the cell by acting upon the nicotinamide coenzymes and adenylic nucleotides underlies its antidote action.
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PMID:[Effect of dipyroxime on the concentration of nicotinamide coenzymes and adenylate nucleotides in the myocardium and liver of rats poisoned with phthalophos]. 2 70

This study investigations whether the synthesis of nicotinamide out of L-tryptophan is disordered in depression or in anxiety. To this end the excretion of xanthurenic acid (XA) in 24 hours urine was measured after administration of an oral loading dose of 5 grams L-tryptophan. The subjects were depressive, anxious, and alcoholic patients, while other psychiatric patients, served as control group. Anxiety and not depression is the clinical correlate of an elevated excretion of XA. Liver disorder and vitamin B-6 deficiency have to be excluded. A psychiatric control group is necessary.
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PMID:The clinical significance of an elevated excretion of xanthurenic acid in psychiatric patients. 16 16

Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg.
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PMID:Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity. 16 47

Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA. DNase treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU.
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PMID:A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea. 19 15

Endotoxin was shown to depress neutrophil bactericidal activity while enhancing Nitro Blue Tetrazolium reduction and hexose monophosphate shunt activity. Separation of bactericidal action from oxidative metabolism suggests that the effect of endotoxin might involve the formation of reactive oxygen radicals such as superoxide. Chemiluminescence often accompanies metabolic activation of polymorphonuclear neutrophils (PMNs). However, human PMNs did not show chemiluminescence when challenged with endotoxin (lipopolysaccharide; LPS) or lipid A. Superoxide formation was also unaffected by endotoxin. In contrast, preincubation of PMNs with LPS for 30 min produced significant depression of chemiluminescence, oxygen consumption, and superoxide formation. Decreased chemiluminescence was not the result of complement consumption. In a cell-free system, superoxide was not scavenged by LPS, nor did LPS stimulate superoxide dismutase. Oxidase enzymes for reduced nicotinamide adenine dinucleotide or reduced nicotinamide adenine dinucleotide phosphate harvested from broken cells were not affected by LPS. The toxicity of LPS may reside in its ability to activate the PMNs while simultaneously blocking bactericidal capacity.
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PMID:Endotoxin in vitro interactions with human neutrophils: depression of chemiluminescence, oxygen consumption, superoxide production, and killing. 22 88

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.
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PMID:Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate. 49 44

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 microns in depth by superfusion with the membrane-permeant indo-1 acetoxy-methyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 microM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18-22 Hz polyspikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.
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PMID:Mechanism underlying protective effect of MK-801 against NMDA-induced neuronal injury in vivo. 171 15

The steady-state flux (SSF) of nicotinamide from an aqueous donor phase across a model Silastic membrane did not increase proportionally with increasing donor phase concentration. The suspected self-association of the drug in aqueous solution was evaluated by studying the concentration-dependent changes in (i) the molal osmotic coefficient of nicotinamide (freezing-point depression studies) and (ii) the partition coefficient between water and n-octanol. The freezing points of aqueous solutions of nicotinamide were measured and a plot of osmolality vs molality was nonlinear. The partition coefficient of nicotinamide, studied at 15, 25, and 32 degrees C, also decreased with increasing concentration of drug. Mathematical models describing dimerization and higher orders of association were applied to the data. The results indicated the involvement of higher orders of association and it was found that an isodesmic (step-association) model was an adequate description of the freezing-point depression and partition coefficient data. The association constant, K, ranged between 1.59 +/- 0.02 M-1 at the freezing point and 0.48 +/- 0.01 M-1 as estimated from the partition coefficient data at 32 degrees C. These models for the self-association of nicotinamide allowed estimation of the apparent concentration of "monomeric" nicotinamide in the donor phase solutions studied in the SSF experiments. When the SSF data were analyzed with regard to the concentration of monomeric nicotinamide in the donor phase, a relationship close to linearity was observed.
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PMID:Self-association of nicotinamide in aqueous solution: mass transport, freezing-point depression, and partition coefficient studies. 183 97

The relation between isometric force and phosphate concentration in skinned skeletal muscle fibers of the frog is found to depend on fiber size. Force decreased with increasing phosphate concentration, but depression of force in thick fibers was smaller than in thin segments. When the external phosphate concentration was abruptly altered during a sustained contracture, force changed. The half-time of the force change was proportional to the cross-sectional area of the preparation. From this relation, a value for the diffusion constant of phosphate in skinned fibers of 0.9 x 10(-10) m2/s was derived. The rate of phosphate production was determined photometrically via the enzymatic coupling of the resynthesis of ATP to the oxidation of nicotinamide adenine dinucleotide. The average value (+/- SE) of the rate of ATP hydrolysis (at 4 degrees C) was 2.7 +/- 0.3 mumol.s-1.g dry wt-1, which corresponds to 0.34 mmol.l-1.s-1. From a calculation based on the diffusion constant and the rate of phosphate production determined, it follows that the dependency of the force-phosphate relation on fiber diameter is due to phosphate accumulation inside the fiber.
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PMID:Depression of force by phosphate in skinned skeletal muscle fibers of the frog. 214 56

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.
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PMID:Pharmacology and therapeutic effects of nicorandil. 215 May 92


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