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)

Isometric tetani of single muscle fibers of Rana temporaria were studied as a function of stimulation rate, sarcomere length (1.7-2.3 micron), twitch-to-tetanus ratio, and exposure to twitch potentiators (Zn2+ and NO3-) at 20 degrees C. As the stimulation rate was decreased below a maximal level, tension generation decreased. This depression in tension generation was more pronounced at shorter sarcomere lengths. Therefore the magnitude and shape of the sarcomere length curve was dependent on stimulation rate. Although the depression in tension generation was always accompanied by a noticeable ripple in the tension record in fibers with large twitch-to-tetanus ratios, it could be observed even during well-fused tetani in fibers with low twitch-to-tetanus ratios. In all fibers, however, high stimulation rates or exposure to potentiators resulted in maximum tension generation at each length, and the sarcomere length-tension curve followed that found by Gordon, Huxley, and Julian. This indicates that the fall in tension between sarcomere lengths of 2.0 and 1.7 micron is not due to length-dependent activation but is more likely to be the result of mechanical interference in the force-generating interaction between cross bridges and thin filament sites.
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PMID:Stimulation rate, potentiators, and sarcomere length-tension relationship of muscle. 387 67

When sperm of Strongylocentrotus purpuratus or Lytechinus pictus are diluted into seawater, motility is initiated; and when exposed to egg jelly, an acrosome reaction is induced. In the presence of a variety of structurally different metal chelators (0.1-1 mM EDTA, EGTA, phenanthroline, dipyridyl, cysteine, or dithiothreitol), motility initiation is delayed and the acrosome reaction is inhibited. Of the metals detected in the sperm of these two species, very low levels of Zn+2 (0.1 microM free Zn+2) uniquely prevent this chelator inhibition. L. pictus sperm concentrate 65Zn+2 from seawater, and EDTA removes 50% of the accumulated 65Zn+2 by 5 min. Since both sperm motility and acrosome reactions are in part regulated by intracellular pH (pHi), the effect of chelators on the sperm pHi was examined by using the fluorescent pH sensitive probe, 9-aminoacridine, EDTA depresses sperm pHi in both species, and 0.1 microM free Zn+2 reverses this pHi depression. When sperm are diluted into media that contain chelators, both NH4Cl and monensin (a Na+/H+ ionophore) increase the sperm pHi and reverse the chelator inhibition of sperm motility and acrosome reactions. The results of this study are consistent with the involvement of a trace metal (probably zinc) in the pHi regulation of sea urchin sperm and indicate a likely mechanism for the previously observed effects of chelators on sperm motility and acrosome reactions.
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PMID:Involvement of zinc in the regulation of pHi, motility, and acrosome reactions in sea urchin sperm. 392 92

Zinc deficiency is associated with depression of a number of immune responses. To assess the relationship of zinc and natural killer activity, we studied natural killer activity in adults with sickle cell disease and in two normal volunteers rendered zinc deficient by dietary restriction. Natural killer activity was significantly lower in patients with sickle cell disease and zinc deficiency (5.1 +/- 2.9 lytic units per 10(6) cells) than in controls (11.7 +/- 5.0 lytic units per 10(6) cells). In the two volunteers, natural killer activity declined during zinc restriction and returned to near initial levels with zinc repletion. These results suggest that zinc deficiency is associated with a lowering of natural killer activity.
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PMID:Decreased natural killer cell activity in patients with zinc deficiency with sickle cell disease. 396 62

Experiments were conducted to examine the role of zinc in the prevention of bromobenzene hepatoxicity in male rats. Bromobenzene (BB) (7.5 mmol/kg, ip) produced a marked hepatotoxicity as evidenced by increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and a marked depression in hepatic glutathione (GSH) content 24 hr after administration. The administration of zinc (92 mumol Zn/kg, ip, at 48 and 24 hr prior to the bromobenzene) ameliorated the bromobenzene elevations in plasma AST (25%) and plasma ALT (50%) but did not alter the decreases in hepatic GSH. Following administration of [14C]BB, the radioactive label was distributed primarily in the cytosolic and lipid fractions derived from liver homogenates. Furthermore, the subcellular distribution of [14C]BB was not altered by zinc pretreatment. The extent of covalent binding of [14C]BB metabolites to hepatic tissue was significantly depressed in zinc-treated rats. Zinc induced the hepatic levels of metallothionein but [14C]BB did not bind to this sulfhydryl rich protein. Further experiments showed that zinc treatment depressed cytochrome P-450 content, the activity of NADPH cytochrome c reductase, and the metabolism of aniline, but not that of ethylmorphine. These studies suggest that the hepatoprotective effect of zinc against bromobenzene toxicity does not involve altered binding of the reactive toxic metabolite to glutathione or metallothionein, but it may be mediated by the inhibitory effect of zinc on the microsomal cytochrome P-450-dependent drug metabolizing system.
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PMID:Amelioration of bromobenzene hepatotoxicity in the male rat by zinc. 398

To evaluate critical exposure levels and the reversibility of lead neurotoxicity a group of lead exposed foundry workers and an unexposed reference population were followed up for three years. During this period, tests designed to monitor neurobehavioural function and lead dose were administered. Evaluations of 160 workers during the first year showed dose dependent decrements in mood, visual/motor performance, memory, and verbal concept formation. Subsequently, an improvement in the hygienic conditions at the plant resulted in striking reductions in blood lead concentrations over the following two years. Attendant improvement in indices of tension (20% reduction), anger (18%), depression (26%), fatigue (27%), and confusion (13%) was observed. Performance on neurobehavioural testing generally correlated best with integrated dose estimates derived from blood lead concentrations measured periodically over the study period; zinc protoporphyrin levels were less well correlated with function. This investigation confirms the importance of compliance with workplace standards designed to lower exposures to ensure that individual blood lead concentrations remain below 50 micrograms/dl.
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PMID:Occupational lead neurotoxicity: improvement in behavioural effects after reduction of exposure. 401 2

Serum zinc levels were measured in three groups of children aged 6 months to 6 years. In group I, there were 25 children with diarrhoea, who had a history of measles within the 2 weeks preceding the zinc level tests (post-measles diarrhoea); in group II there were 17 children who had diarrhoea only; and in group III there were 20 children who were apparently healthy and had neither diarrhoea nor measles (controls). Serum zinc concentrations of less than 5 mumol/l were observed in 5 out of 16 children in group I, but none of the children in group II had such low levels. The serum zinc level in group II rose significantly during the recovery stage compared to the acute stage (P less than 0.01). Children with post-measles diarrhoea showed a continued and prolonged depression of serum zinc levels.
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PMID:Prolonged depression of serum zinc concentrations in children following post-measles diarrhoea. 407 77

Two groups of five female store pigs, weighing an average of 60 kg at the start of the experiment, were given either 1 or 10 mg metallibure zinc complex (SUISYNCHRON) per kg body weight once daily for six months, in the form of a 2% talcum premix added to concentrates. Clinical inspection, weight gain, haematological findings, blood sugar, serum transaminases, properties of urine and faeces, carcass examination and histological study (internal organs, endocrine glands, skeletal muscle) showed that the 1 mg/kg dosage had no toxic effect. The 10 mg/kg dosage resulted in considerable depression in appetite and some apathy in the pigs, but there was no evidence of a toxic effect.
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PMID:[Effect of long-term application of SUISYNCHRON-premix on swine]. 421 72

1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum.2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA-966 caused periodical sleeping episodes.3. The exploratory behaviour and the amphetamine-induced motor activity in mice were blocked by HA-966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA-966 differs from neuroleptics.4. Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA-966. The muscarinic effects of tremorine were not reduced by HA-966, indicating a selective central antitremor effect.5. HA-966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA-966 depresses central internuncial neurones.6. In rats and rabbits HA-966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ;sleep-EEG' and behaviour.7. In rat brain, HA-966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5-hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with alpha-methyl-p-tyrosine.8. Several effects of intravenously administered HA-966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA-966 is converted to a pharmacologically active metabolite.9. The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA-related hypothesis as to the mode of action of HA-966 is presented.
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PMID:1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases. 515 20

The metallic ions, copper and zinc, are extensively associated with biological processes. An imbalance in the normal concentration of these metals can alter the reproductive function. The experiments reported here were done to determine whether the insertion of a metallic device into the uterus of rats is associated with metabolic changes in the endometrium. For this purpose the effect of IUDs on the incorporation of 2Na 35S40 into the mucoproteins and of thymidine 2-carbon-14 into the DNA of the endometrium of normal rats was studied. Estradiol benzoate, 20 mcg, was injected im the day before instillation with radioisotopes in order to have all the rats under similar estrogenic stimulation. In Experiment 1 either .2 mc of 2Na35S40 or 2.5 mcc of thymidine 2-carbon-14 in .1 ml of distilled water was instilled into each uterus. To avoid expulsion of the isotope a ligature was placed in the lower portion of each horn. The opposite horn served as a control. The horns were excised at different intervals from 1 to 88 hours later. The results showed that the accumulation of radioactivity in the endometrium reaches its maximum concentration in about 22 hours and then gradually declines. In Experiment 2 copper wire, zinc wire, or nylon thread was used as an IUD. The opposite horn was used as a control. About 14 days later the isotope was instilled as in Experiment 1 and left for 24 hours. In the presence of an inert foreign body, such as nylon thread, a significant decrease in the accumulation of sulfur-35 in the endometrium (18.5%; p less than .05) was noted. With zinc wire the assimulation decrese was 44.2% (p less than .001), and with copper wire, it was 69.6% (p less than .001). Absorption of thymidine 2-carbon-14 was the same in both horns in the control group. Nylon thread produced no significant difference. Copper and zinc produced statistically significant depressions of absorption (p less than .001). Copper depression was greater than zinc depression (p less than .01). The nylon thread is considered to be an inert foreign body while the copper and zinc wires are active.
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PMID:Effect of various types of intrauterine foreign bodies on the incorporation of 35S into mucoprotein and of thymidine 2-14C into DNA of rat's endometrium. 536 69

This review examines the interaction of pyridoxal phosphate with select neuroendocrine and neuropharmacological systems and their health related therapeutic implications. Vitamin B6 and its vitamers can be involved in many interactions with a number of drugs as well as the actions of various endocrines and neurotransmitters. Nutritional deficiencies, particularly of vitamins and proteins, can affect the manner in which drugs undergo biotransformation and thus may modify the therapeutic efficacy of certain drugs. In addition to pyridoxine deficiency adversely affecting drug actions, improper supplementation with viatmin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridocxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions amony pyridoxine vitamers, both phosphorylated and nonphosphorylated, are briefly discussed, particularly concerning their pharmacokinetic properties. The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pryidoxine hydrochloride prevents or stops these seizures. The acute ingestion of excessive monosodium glutamate will, in some persons, cause a group of symptoms, including headache, weakness, stiffness, and heartburn, collectively known as the "Chinese Restaurant Syndrome." These symptoms can be prevented by prior supplementation with vitamin B6. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate. Therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phospate appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase. Treatment with daily pyridoxine can reverse a state of depression induced in women who take oral contraceptives (OCs). 1 hypothesis to explain this effect is that the OC is somehow causing a deficiency of seroton serotonin in the brain and that the vitamin B6 helps to overcome this deficiency through the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, pyridoxal phosphate in physiological concentrations seems to function as an endogenous "down regulator" of several receptor sites, including estrogen, progesterone, and androgen.
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PMID:Drug-pyridoxal phosphate interactions. 608 25


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