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)

The effects of 2-nicotinamidoethyl nitrate (SG-75) on norepinephrine (NE)- and KCI-induced responses in rabbit aorta were quantitated, correlated with 45Ca studies and compared with the effects of nifedipine (NIF) on similar parameters. NE- and KCI-induced dose-response relationships were differentially depressed by SG-75 (NE much greater than KCI) and NIF (KCI much greater than NE). Responses to KCI were relatively insensitive to prior SG-75, yet moderately relaxed by subsequent SG-75. Conversely, NIF markedly inhibited and completely relaxed similar responses. Responses to NE were relaxed and inhibited with SG-75, but unaffected by NIF. Responses to NE in La or O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 (with and without KCI) solutions were phasic, reduced by SG-75 and insensitive to NIF. NE-dependent, Ca++-induced responses in a O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 solution (with and without KCI) were attenuated by SG-75. Equilibrated (60 min) La -resistant (residual), high apparent affinity Ca++ binding was increased 26% with SG-75 and decreased 34% with NIF, yet neither altered the rate of exchange (10 min). Rate of exchange at low apparent affinity, residual sites was increased 21% by SG-75 without altering equilibrated values, whereas NIF reduced equilibrated values 11%, without affecting rate. NE reduced, SG-75 + NE augmented and NIF + NE decreased, in an additive fashion, high apparent affinity, residual bound Ca++. Residual Ca++ binding at low apparent affinity sites was increased with 160 mM substituted KCI (380%). This increase was only partially inhibited with SG-75, and eliminated by NIF. Net Ca++ efflux was persistently slowed by SG-75 and unaltered by NIF. The primary effects of SG-75 appear to be depression of Ca++ release and inhibition of receptor-operated (potential-independent) Ca++ entry, with limited attenuation of voltage-dependent Ca++ entry. NIF primarily inhibits voltage-dependent Ca++ entry.
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PMID:Effects of 2-nicotinamidoethyl nitrate on agonist-sensitive Ca++ release and Ca++ entry in rabbit aorta. 258 75

The effects of lethal (2.0 mg/kg) and high sublethal (1.3 mg/kg) dosages of the organophosphate acetylcholinesterase (AChE) inhibitor paraoxon on FR10 performance rate was determined 1 and 2 days after intoxication. The lethal doses were antidoted with either centrally acting atropine sulfate (AS), or atropine methyl bromide (AMB) or atropine methyl nitrate (AMN), both quaternary salts and not expected to act centrally. AChE inhibition in the brain was about 35-60% on the second day after treatment. AS yielded a small transient depression in performance, while AMB and AMN yielded severe deficits, with incomplete recovery. Performance was depressed by 1.3 mg/kg paraoxon by 52% and 34% on days 1 and 2, respectively, while performance was more greatly depressed by the lethal dose, especially with the noncentrally acting antidotes: AS, 67 and 48%; AMB, 81 and 55%; AMN, 91 and 78%. However, a low dose of AS with 2 mg/kg paraoxon resulted in very severe, nonrecovering deficits. A lethal dose of the nonpersistent anti-AChE eserine sulfate, antidoted with a low dose of AS, yielded no deficits. Thus, a high level, acute intoxication with paraoxon yields behavioral deficits which are attenuated by high levels of a centrally acting muscarinic receptor antagonist. The paraoxon-induced performance deficits or their recovery do not correlate directly with AChE inhibition.
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PMID:Short-term effects of paraoxon and atropine on schedule-controlled behavior in rats. 259 81

A number of plants are capable of producing intoxication of sufficient severity as to cause death within 12 hours of the onset of clinical signs. Those most rapid in their lethal effects are the cyanogenic plants and yew. Nitrate-accumulating plants likewise are capable of causing sudden death with only a brief appearance of signs. Most toxic plants, however, typically either require a longer time for the intoxication to develop and become lethal or sudden death is the exception rather than the rule following ingestion. In these cases, diagnosis of the problem may be facilitated by recognition of arrays of clinical signs that appear. Seven major groups of presenting signs can be distinguished: dyspnea and polypnea, hemorrhage, prominent excessive muscular activity, depression and/or weakness, diarrhea and weakness, excessive salivation and/or regurgitation and/or colic, and weakness and incoordination and/or tremors. Based on these and accompanying signs in surviving animals, many of the causes of sudden death can be differentiated. In addition, pathological changes visible on necropsy and identification of plant fragments in the rumen and stomach may be of diagnostic value.
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PMID:Plants causing sudden death in livestock. 266 7

In this randomised, double-blind placebo-controlled crossover study we investigated the efficacy of 120 mg isosorbide dinitrate s.r. 12 h after application in comparison to 2 and 6 h in 18 patients with angiographically proven coronary artery disease, stable exercise-induced angina and reproducible ST-segment depression. Bicycle ergometry was performed before, 2, 6 and 12 h after medication and nitrate plasma levels were drawn before each exercise test. After 2 h, the exercise-induced ST-segment depression in comparison to placebo was reduced from 2.3 mm +/- 0.8 to 0.7 +/- 0.5, after 6 h to 1.0 mm +/- 0.8) and after 12 h to 1.9 mm +/- 0.8 (p less than 0.01). 82% of the patients suffering from angina on the control exercise test before medication were free of symptoms 2 and 6 h after ISDN 120 mg s. r., but showed angina again after 12 h. In comparison to the plasma levels 2 h after ingestion, the concentrations in plasma after 12 h were much lower for ISDN, equal for IS-2-MN, and more than double for IS-5-MN. Thus, 12 h after ingestion of 120 mg ISDN s.r. there is still a significant reduction of ST-segment depression. This 12-h benefit is 40% od the maximum effect.
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PMID:[Extent of therapeutic effect and duration of 1 capsule of 120 mg isosorbide dinitrate in a slow release form]. 267 52

With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells.
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PMID:The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate. 273 90

1. The inhibitory effects of inorganic and organic sulphur-containing compounds, copper and tungsten on nitrate reduction by mixed rumen micro-organisms were investigated in two in vitro studies. 2. Coarsely strained rumen fluid from nitrate-adapted (Expt 1) or non-adapted (Expt 2) Suffolk Down wethers maintained on lucerne (Medicago sativa) cubes was used as an inoculum. In Expt 1, anaerobic incubation was carried out for 24 h for each medium supplemented with 10 mM-sodium nitrate and the following chemicals: 0, 1, 2, 3, 5, 8 and 10 mM-sodium sulphide, 1 and 10 mM-sodium sulphite, 1 and 10 mM-sodium sulphate, 1 and 10 mM-L-cysteine, 1 and 10 mM-DL-methionine, 1 mM-sodium tungstate and 1 mM-copper sulphate. In Expt 2, 1 and 10 mM-Na2S, 1 and 10 mM-L-cysteine, 1 mM-Na2WO4, and 1 mM-CuSO4 were added to incubation media to test for chemical inhibition of microbial reduction of nitrate. 3. In Expt 1, the amount of nitrite formed decreased with increasing concentration of sulphide-S added. The additions of L-cysteine, W and Cu suppressed nitrite formation in media from both nitrate-adapted and non-adapted sheep. 4. In contrast to the effects of sulphide, L-cysteine and W counteracted, to some degree, nitrate-induced reduction of volatile fatty acid (VFA) production. Addition of Cu to the media resulted in a further depression of VFA production.
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PMID:Inhibitory effects of sulphur compounds, copper and tungsten on nitrate reduction by mixed rumen micro-organisms. 275 22

Combined nitrate/beta-blocker/nifedipine therapy is commonly used to treat refractory angina pectoris. We have observed "paradoxical" myocardial ischemia in ten patients with refractory angina (seven receiving combined beta-blocker and nitrate therapy, and three receiving nitrate treatment alone) in whom nifedipine (mean dosage, 92 mg/day; range, 60 to 120 mg/day) induced a decrease in blood pressure, angina pectoris (10/10 patients), and ischemic ECG changes (7/10 patients). These ten patients, all of whom regularly reported angina within 20 to 30 minutes of nifedipine ingestion, were prospectively studied before and after usual nifedipine dose administration, while blood pressures, heart rate, and ECGs were recorded. Mean systolic BP fell from 109 to 94 mm Hg after nifedipine (P less than .001, paired t test); mean heart rate increased from 64 to 68 beats per minute (P less than .05); seven patients developed transient ECG changes (five with ST-T wave depression and two with ST-T wave elevation) during the hypotensive period. Nifedipine may provoke angina and myocardial ischemia in certain patients with refractory angina pectoris receiving concomitant beta-blocker and nitrate therapy.
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PMID:Nifedipine-induced hypotension and myocardial ischemia in refractory angina pectoris. 285 6

Tetanus-induced (400 Hz, 200 pulses) long-lasting potentiation of the stratum radiatum-evoked CA1 population spike in hippocampal slices is not accompanied by any change in Na+-independent [3H]glutamate binding sites. Homosynaptic depression that occurs subsequent to either a low frequency tetanus (20 Hz, 600 pulses) or a transient exposure to Cl(-)-free (containing NO3-) medium is associated with an elevation in the amino acid binding. [3H]Glutamate uptake into slices was decreased following a high frequency (400 Hz, 200 pulses) tetanus but in the majority of cases was increased following a low frequency (20 Hz, 600 pulses) tetanus to stratum radiatum. When the high frequency tetanus was given in the absence of extracellular Ca2+, there was a further reduction in [3H]glutamate uptake.
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PMID:Tetanic stimulation-induced changes in [3H]glutamate binding and uptake in rat hippocampus. 287 13

Effects of nicorandil, a recently introduced 2-nicotinamidethyl nitrate, on exercise performance were studied in 11 patients with stable effort angina. The duration of exercise before the onset of angina and time to the onset of ischemic ST depression 30 minutes after 20 mg of oral nicorandil were compared with events 30 minutes after oral placebo and 5 minutes after 0.3 mg of sublingual nitroglycerin. Nicorandil and placebo were given according to the randomized double-blind method. Nicorandil prolonged the duration of exercise in all 11 patients by 2.3 +/- 2.2 minutes (mean +/- SD, p less than 0.01) and delayed the onset of ischemic ST depression by 2.3 +/- 1.7 minutes compared to placebo (p less than 0.01). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 20 mg of oral nicorandil were almost equivalent to findings after sublingual nitroglycerin (by 2.0 +/- 1.8 and 2.5 +/- 1.7 minutes, respectively). Nicorandil also increased the pressure-rate product at the time of angina compared with placebo (20,420 +/- 480 vs 17,480 +/- 370, p less than 0.05). These results indicate that oral administration of nicorandil should be considered for the clinical treatment of effort angina.
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PMID:Effects of nicorandil on exercise tolerance in patients with stable effort angina: a double-blind study. 294 47

The efficacy of nicorandil, a new anti-anginal agent, was evaluated in 11 patients with rest and effort angina not inhibited by combination therapy with a calcium antagonist and an oral nitrate. Electrocardiographic findings during an attack demonstrated ST depression in seven patients, ST elevation in three, and either elevation or depression in two. Coronary angiography in nine patients revealed significant stenosis (greater than or equal to 75%) in eight. Angina persisted in all 11 patients in spite of treatment with 120 to 360 mg/day of diltiazem or 80 mg/day of nifedipine plus 20 to 160 mg/day of isosorbide dinitrate. Three patients were receiving beta-blocker as well; seven were receiving antiplatelet therapy. During combination therapy, patients had between 3.7 and 25 anginal attacks per week (mean +/- SD, 12.2 +/- 6.9). When nicorandil in a dosage of 20 to 40 mg/day was added to the regimen, the mean number of attacks dropped significantly (P less than 0.01) to 1.4 +/- 1.8 times/week. Two patients did not respond to nicorandil. When placebo was substituted for nicorandil in eight of nine responders, the frequency of attacks increased significantly (P less than 0.05) from 0.6 +/- 0.7 to 6.7 +/- 4.8 times/week. Nicorandil did not affect heart rate or blood pressure. These results suggest that nicorandil inhibits rest and effort angina unresponsive to usual doses of calcium antagonist and oral nitrate.
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PMID:Effects of nicorandil on rest and effort angina unresponsive to combination therapy with a calcium antagonist and oral nitrate. 295 76


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