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)

Crude brain homogenates and cerebral tissue slices from rats with cobalt metal implanted in right and left cerebral cortices were used to examine high- and low-affinity GABA transport. High-affinity GABA transport was maximally reduced to 34% of controls 7 days after cobalt implantation, a time that coincides with peak seizure activity in this model. Kinetic analysis of high-affinity GABA transport, using brain homogenates, revealed a significant change in Vmax 7 days after cobalt implantation. (Vmax = 446.4 +/- 26.2 pmol/mg prot./min, cobalt, versus 787.8 +/- 67.3, control). An analysis of the low-affinity system revealed no depression of Km or Vmax parameters. Administration of valproic acid at a concentration as high as 1 mM in vitro or a dose of 300 mg/kg in vivo had no effect on high- or low-affinity GABA transport. The results obtained from cobalt-treated rats provide additional evidence for an involvement of GABA in experimental epilepsy.
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PMID:Studies on gamma-aminobutyric acid transport in cobalt experimental epilepsy in the rat. 678 93

Pregnant ewes were fed a depletion diet low in cobalt (0.06 ppm) for 3 1/2 months. Chronic catheters were implanted 8 weeks postpartum and 7 experiments were performed on these nonlactating vitamin B-12-depleted sheep (de-B12: 340 +/- 30 ng vitamin B-12 per gram wet liver) prior to repletion by intramuscular injection of hydroxocobalamin. Six experiments were then repeated after vitamin B-12 repletion (re-B12: 2220 +/- 50 ng vitamin B-12 per gram wet liver). The hepatic extraction ratios (HER) in continuously fed sheep were 0.81 and 0.77 for de-B12 and re-B12 corresponding to net hepatic uptakes of 460 +/- 50 and 440 +/- 40 mumol propionate per minute, respectively. Continuous infusion of unlabeled propionate into a mesenteric vein at 1 mmol/minute reduced the HER, yet this depression was greatest for re-B12 (0.74 vs. 0.63 for de-B12 and re-B12, respectively). Net hepatic uptake of propionate was increased (1145 +/- 100 vs. 985 +/- 95 mumol/minute, respectively), although vitamin B-12 status was without effect. It is concluded that the ability of liver to extract propionate is not affected at vitamin B-12 concentrations greater than 250 ng/g wet liver. However, when propionate entry rate was enhanced by intramesenteric infusion, the livers of de-B12 sheep had a greater capacity to remove propionate suggesting that alternate routes of metabolism may occur.
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PMID:Influence of vitamin B-12 status on hepatic propionic acid uptake in sheep. 685 14

An experiment was conducted with young, male, crossbred chicks to investigate the interaction between dietary cobalt, methionine and experimental Eimeria acervulina infection (duodenal coccidiosis). Coccidiosis and dietary cobalt (250 mg/kg) depressed weight gain and efficiency of feed utilization; cobalt toxicity, however, was exacerbated by the coccidial infection, resulting in a depression in performance greater than could be accounted for by the independent additive effect of each entity. Dietary cobalt increased the cobalt concentration of the liver, kidney and gallbladder (with bile); experimental coccidiosis in the absence of excess dietary methionine resulted in a twofold increase in cobalt deposition in the liver and gallbladder. Excess supplemental methionine partially alleviated the decrease in chick performance and the increase in tissue cobalt content caused by dietary cobalt in both healthy and infected chicks, but with a slightly greater efficacy in the coccidiosis-infected chicks.
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PMID:Eimeria acervulina infection in chicks fed cobalt in the presence or absence of excess dietary methionine. 708 48

Three experiments were conducted to investigate the interaction of cobalt with sulfur-containing amino acids in the chick. Fortified corn-soybean meal diets were fed and tissue concentrations of cobalt were assessed. In Experiment 1, three levels of cobalt (0, 250, and 500 microgram/g) were fed in the presence and absence of .50% supplemental DL-methionine. Dietary additions of cobalt depressed growth rate and caused cobalt accumulation in the liver and kidney. Supplemental methionine in excess of the requirement for maximal chick weight gains partially alleviated the depression in performance and decreased cobalt accumulation in the liver and kidney. Two levels of cobalt (0 and 500 microgram/g) were fed in the presence and absence of .59% supplemental L-cysteine.HCl.H2O (isosulfurous to .50% DL-methionine) in Experiment 2. Again, cobalt depressed performance and accumulated in the liver and kidney. The surfeit of cysteine increased weight gain and decreased cobalt accumulation in the liver but not in the kidney. In Experiment 3, two levels of cobalt (0 and 250 microgram/g) were fed in the presence and absence of two levels of excess DL-methionine (.50 and 1.0%) or two levels of excess cysteine.HCl.H2O (.59 and 1.18%). Multiple linear regression analysis of gain on sulfur consumed from methionine or cysteine indicated that cysteine was almost 6 times more efficacious than methionine in alleviating cobalt toxicity. In fact, cysteine supplemented at a level of 1.18% completely alleviated the growth depression caused by 250 microgram/g cobalt. Both methionine and cysteine reduced cobalt accumulation in the liver and kidney, but the liver was affected to a greater extent than the kidney.
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PMID:The effect of methionine or cysteine on cobalt toxicity in the chick. 726 58

1 Repetitive application of acetylcholine (ACh) revealed two types of ACh depolarization in two types of snail neurone, depending on their desensitization properties. 2 Further experiments were carried out on neurones which displayed a rapidly desensitizing response. 3 The amplitude of the response depended on the external sodium and calcium levels. 4 Procaine antagonized ACh effects with the same efficiency as atropine or hexamethonium, half maximal depression being obtained at a concentration of 10(-4) M. The blocking effect was independent of the dose of ACh. 5 The depression of the ACh-induced depolarization by cobalt ions and D600 suggests that calcium may participate in this response.
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PMID:A calcium-dependent acetylcholine depolarization blocked by methoxyverapamil (D600) and procaine in snail neurones. 735 7

Single microelectrode voltage-clamp recordings were made from submucous neurons of the guinea-pig caecum. The slow excitatory postsynaptic current was compared with the currents induced by neurokinin A and substance P. The current induced by neurokinin A (100-300 nM) was associated with a decreased membrane conductance and reversed in polarity between -90 and -100 mV. The neurokinin A current was reduced by Co2+ (1-2 mM), but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In about 80% of the neurons, the current induced by substance P (100-300 nM) was associated with a decreased membrane conductance and did not reverse with hyperpolarization of the membrane potential up to -130 mV. The current was reduced by Co2+ (1-2 mM) and augmented by low Cl- (20-40 mM) solutions, but was not affected by Cs+ (1-2 mM) or Ba2+ (10-100 microM)-containing solutions. In about 20% of the neurons, the substance P current reversed in polarity between -100 and -120 mV. The slow excitatory postsynaptic current elicited by repetitive nerve stimulation (10-40 Hz, three to five pulses) was accompanied by a decreased membrane conductance, and reversed in polarity between -90 and -100 mV. The slow excitatory postsynaptic current was abolished by Co2+ (1-2 mM) or low Na+ (12 mM) solutions, but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In such neurons, the neurokinin A current was reversed at approximately the same potential at which the slow excitatory postsynaptic current was reversed, while the substance P current was not reversed even by much stronger hyperpolarizations. It was concluded that the neurokinin A current was mainly due to depression of potassium conductances, while the substance P current resulted from both increased anion conductance and decreased potassium conductances. The conductance change underlying the slow excitatory postsynaptic current is similar to that caused by neurokinin A.
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PMID:Neurokinin A mimics the slow excitatory postsynaptic current in submucous plexus neurons of the guinea-pig caecum. 753 3

1. The ionic mechanism responsible for hyperpolarization of the rat superior cervical ganglion (SCG) and depression of the depolarizing response to muscarine by adenosine was studied using an extracellular grease-gap recording technique. 2. Both the hyperpolarizations to adenosine and 2-chloroadenosine and the depression of the response to muscarine by adenosine were potentiated in reduced external calcium (Ca2+). Hyperpolarizations to adenosine were either unaltered or potentiated in the presence of the dihydropyridine Ca2+ channel antagonists, nitrendipine or (+)PN200 110 respectively. Hyperpolarizations to adenosine were unaltered by inorganic Ca2+ channel antagonists except for cobalt, which also antagonized hyperpolarizations to carbachol and depolarizations to muscarine. 3. Hyperpolarizations to adenosine were unaltered in nominally magnesium (Mg2+)-free or in reduced external chloride (Cl-) media. When sodium ions (Na+) were replaced by lithium ions (Li+) maximal responses to adenosine were initially enhanced, returning to pretreatment levels and subsequently reduced in their duration. In contrast, responses to adenosine were significantly enhanced in nominally potassium (K+)-free medium and reduced upon doubling the extracellular K+. 4. Hyperpolarizations were enhanced in the presence of the K+ channel antagonists, 4-aminopyridine and 3,4-diaminopyridine, and reduced by a low concentration (2 mM) of tetraethylammonium (TEA), but not in 10 mM TEA. 5. The results support the hypothesis that adenosine-mediated hyperpolarization of postganglionic neurones of the rat SCG is by a Ca(2+)-independent mechanism and is probably mediated via an increase of a K+ current. The results also indicate that adenosine-induced hyperpolarizations of the rat SCG are independent of the presence of extracellular magnesium.
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PMID:Ionic mechanism of action of adenosine on the rat superior cervical ganglion. 769 24

The use of metal-backed tibial plates in total knee replacement prostheses can result in the flow of ultra-high molecular weight polyethylene (UHMWPE) from the tibial insert into a cavity on the metal tray surface. A study of the relationship between the thickness of UHMWPE inserts and the amount of cold extrusion is reported here. An attempt was made to correlate the occurrence of cold extrusion with computer-aided analysis. UHMWPE samples of varying thickness, from 3 mm to 10 mm, were placed over cobalt-chrome (Co-Cr) discs. The Co-Cr discs had a 5 mm diameter hole placed centrally to simulate a tibial tray cavity. A cyclic load was applied at 20 Hz through a Co-Cr spherical indentor for a million cycles. The application of cyclic loading on UHMWPE samples resulted in cold-extrusion values comparable to those reported for retrieval analysis studies. Results after fatigue loading show that the samples do not suffer any gross surface damage. A shiny depression was visible at the load application site and the surface roughness value was decreased. The amount of cold extrusion increased with decreasing UHMWPE sample thickness. From the results, a minimum UHMWPE thickness of 12 mm is required if cold extrusion of UHMWPE is to be eliminated.
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PMID:Cold extrusion deformation of UHMWPE in total knee replacement prostheses. 774 98

The whole cell patch clamp technique was used to examine the electrophysiological properties of embryonic hippocampal neurons maintained in a very low density (VLD) culture preparation. The goal of these experiments was to establish the viability of the VLD culture as a model system in which to study regulation of neurotransmission at single monosynaptic connections, in the absence of polysynaptic innervation. Depolarization of neurons in the VLD culture revealed voltage-dependent sodium, calcium, and potassium currents which were blocked with, respectively, tetrodotoxin (TTX), cobalt, and tetraethylammonium and 4-aminopyridine. When pairs of neurons were simultaneously recorded, action potentials evoked in presynaptic neurons elicited either excitatory or inhibitory postsynaptic currents (EPSCs or IPSCs, respectively). The dual component EPSCs were due to the activation of both types of postsynaptic, ionotropic glutamate receptors: N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Evoked IPSCs were due to the activation of postsynaptic gamma-aminobutyric acid (GABA) receptors. Both excitatory and inhibitory synapses exhibited short term depression in response to high frequency stimulation, although IPSCs were routinely decreased to a much greater degree than EPSCs. Spontaneous miniature EPSCs and IPSCs were found to persist in TTX, were blocked by the same pharmacological antagonists which blocked evoked responses, increased in frequency in response to hypersomotic solution, and were unaffected by changes in extracellular calcium concentration. mIPSCS were found to occur at a significantly lower frequency than mEPSCs. These experiments indicated that neurotransmission in the VLD cultures occurs in a manner consistent with the quantal hypothesis and, therefore, the VLD culture is a good model for studying excitatory and inhibitory neurotransmission between isolated pairs of neurons. In addition, these experiments, performed under comparable physiological conditions, demonstrated that there are fundamental differences underlying neurotransmitter release between excitatory and inhibitory neurons.
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PMID:Properties of inhibitory and excitatory synapses between hippocampal neurons in very low density cultures. 783 12

IKx is a voltage-dependent K+ current in the inner segment of rod photoreceptors that shows many similarities to M-current. The depression of IKx by external Ba2+ was studied with whole-cell voltage clamp. Ba2+ reduced the conductance and voltage sensitivity of IKx tail currents and shifted the voltage range over which they appeared to more positive potentials. These effects showed different sensitivities to Ba2+: conductance was the least sensitive (K0.5 = 7.6 mM), voltage dependence intermediate (K0.5 = 2.4 mM) and voltage sensitivity the most sensitive (K0.5 = 0.2 mM). Ca2+, Co2+, Mn2+, Sr2+, and Zn2+ did not have actions comparable to Ba2+ on the voltage dependence or the voltage sensitivity of IKx tail currents. In high K+ (100 mM), the voltage range of activation of IKx was shifted 20 mV negative, as was the tau-voltage relation. High K+ did not prevent the effect of Ba2+ on conductance, but abolished its ability to affect voltage dependence and voltage sensitivity. Ba2+ also altered the apparent time-course of activation and deactivation of IKx. Low Ba2+ (0.2 mM) slowed both deactivation and activation, with most effect on deactivation; at higher concentrations (1-25 mM), deactivation and activation time courses were equally affected, and at the highest concentrations, 5 and 25 mM Ba2+, the time course became faster than control. Rapid application of 5 mM Ba2+ suggested that the time dependent currents in Ba2+ reflect in part the slow voltage-dependent block and unblock of IKx channels by Ba2+. This blocking action of Ba2+ was steeply voltage-dependent with an apparent electrical distance of 1.07. Ba2+ appears to interact with IKx channels at multiple sites. A model which assumes that Ba2+ has a voltage-independent and a voltage-dependent blocking action on open or closed IKx channels reproduced many aspects of the data; the voltage-dependent component could account for both the Ba(2+)-induced shift in voltage dependence and reduction in voltage sensitivity of IKx tail currents.
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PMID:Mechanism of Ba2+ block of M-like K channels of rod photoreceptors of tiger salamanders. 816 97


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