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)

Effects of insulin on contractile and energy metabolic dysfunctions during hypoperfusion (2 ml/min/g heart wt., 60 min) with 10(-6) M norepinephrine were studied in paced hearts isolated from streptozotocin-diabetic rats. Insulin (2 mU/min/g heart wt.) was infused 20 min before and during hypoperfusion (pre-treated group) or 30 min after the onset of hypoperfusion (post-treated group). Hearts in the non-treated group were hypoperfused without insulin and other hearts in the control group were not hypoperfused. In the non-treated group, resting contractile force (CF) and resting left ventricular pressure (LVP) were significantly elevated to maximum levels within 30 min after hypoperfusion and these elevations were restored in the pre-treated group but not in the post-treated group. Developed CF was depressed in the non-treated group and improved significantly in the pretreated group but not in the post-treated group. Developed LVP was depressed in the non-treated group, and depression was slightly larger in the pre-treated group. In the non-treated group, ATP and creatine phosphate contents in the left ventricle significantly decreased. Decreases in ATP and creatine phosphate contents in the inner layer were partially restored in the pre-treated group but not in the post-treated group. Lactate significantly increased in the non-treated group and increased even further in the insulin treated groups. These results indicate that contractile dysfunction during hypoperfusion with norepinephrine is improved by pre-treated insulin, as is partial recovery of energy metabolism.
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PMID:Improvement of hypoperfusion with norepinephrine injury by ex vivo insulin in isolated diabetic rat hearts. 209 Aug 38

Total serum testosterone, serum testosterone binding globulin and free androgen index were determined before and during treatment in 14 patients with previously untreated disseminated prostatic cancer. Six patients received estramustine phosphate and six other patients underwent orchiectomy. Two further patients received estramustine phosphate because of tumor progression one and two years after orchiectomy. The result of the study indicates that estramustine phosphate is significantly more effective than orchiectomy in eliciting low levels of free androgens. This complete androgen ablation is produced by a depression of total testosterone and a concomitant increase of total serum testosterone binding globulin which yields a free androgen index an average 4.6 times lower in estramustine phosphate treated patients than in patients who underwent orchiectomy.
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PMID:Effect of estramustine phosphate on free androgens. A comparative study of the effect of orchiectomy and estramustine phosphate on free androgens in patients with prostatic cancer. 209 2

The pathogenesis of post-ischaemic depression of contractility in myocardium was examined in isovolumic rat heart. 31P-NMR was used to monitor changes in ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and [H+] during brief periods of ischaemia and reperfusion with and without allopurinol treatment. During 5, 10, or 15 min of total global ischaemia, the decline in function (rate-pressure product) correlated inversely with [Pi] (r = 0.92, P less than 0.01). Cardiac function exhibited a slow progressive recovery during 20 min of reperfusion, ultimately reaching only 85%, 78%, and 69% of its pre-ischaemic value following 5, 10, and 15 min of global ischaemia respectively. Following each ischaemic period [ATP], [CrP], [Pi], and [H+] all recovered to control levels within 5-10 min of initiating reperfusion. Allopurinol (2 mM) treatment of hearts made ischaemic for 15 min significantly improved contractile recovery to 89 +/- 7%. Allopurinol also exhibited significant anti-arrhythmic activity during the reperfusion period, decreasing the incidence of premature contractions and the duration of tachy-arrhythmias. Allopurinol had no effect on the final repletion of [ATP] and [CrP], or the recovery of [Pi] and [H+], although the rate of ATP repletion was elevated in the initial 5 min of reperfusion. These results show that neither depletion of the cytosolic high-energy phosphate pool, nor sustained elevations in [Pi] or [H+] are important in the production of post-ischaemic contractile impairment. The beneficial action of allopurinol suggests that xanthine oxidase derived oxygen free-radicals may be involved in the sustained contractile dysfunction following brief ischaemic episodes.
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PMID:Behaviour of energy metabolites and effect of allopurinol in the "stunned" isovolumic rat heart. 209 34

The present study aimed to study the relation between the release of arachidonic acid (AA) and the energy state in cerebral cortices of rats during single episodes of cortical spreading depression (CSD). The changes in concentrations of AA, labile phosphate compounds [ATP, ADP, AMP, and phosphocreatine (PCr)], and glycolytic metabolites (lactate, pyruvate, glucose, and glycogen) were studied during and following the large change of the local direct current (DC) potential. Free AA increased markedly during the DC shift, continued to increase during the subsequent 3 min, and returned to control levels at 4-5 min after CSD. PCr decreased by 38% in the first minutes following the DC shift, while ADP increased by 38%. Both returned to normal within a few minutes. ATP, AMP, and energy charge remained constant throughout the experimental period. Glucose decreased by 47% and glycogen by 34% for a few minutes following CSD, while lactate increased by 105% at 2-3 min and by 77% at 4-5 min after CSD. The metabolites returned to control levels at 10 min after CSD. Considering the constant energy charge at all time points during CSD, it is suggested that the AA rise reflects augmented phospholipase activity due to either increased intracellular [Ca2+] or receptor stimulation or both. The possibility that N-methyl-D-aspartate receptors play a role in the release of AA, and that free AA in turn could be part of the mechanism of CSD, is discussed.
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PMID:Cortical spreading depression is associated with arachidonic acid accumulation and preservation of energy charge. 210 27

The effects of chronic administration of desimipramine (DMI, 10 mg/kg i.p. daily for 4 or 5 weeks), short-term administration of lithium (Li, 0.2% in food for 10 days) and a combination of these treatments on serotonergic receptors and second messengers were studied in the rat brain. DMI alone had no effect on [3H]5-HT binding but reduced [3H]ketanserin binding in cortical membranes, 5-HT-stimulated inositol phosphate (IP) formation in cortical slices and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes. Li alone reduced [3H]5-HT binding and the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes, and also reduced [3H]ketanserin binding and 5-HT-stimulated IP formation in the cortex. The two treatments combined in general produced effects similar to those of Li alone, but the decrease in [3H]ketanserin binding in cortical membranes was significantly greater than that given by Li alone, whereas the reduction in the degree of inhibition of forskolin-stimulated adenylate cyclase by 5-HT in hippocampal membranes was significantly greater than that produced by DMI alone. It is concluded that the therapeutic action of Li when added to tricyclic antidepressants in the treatment of refractory depression may partly have its basis in potentiation of effects on the serotonergic system in the brain.
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PMID:Single and combined effects of desimipramine and lithium on serotonergic receptor number and second messenger function in rat brain. 213 25

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

The structure of Mengo virus had been determined from crystals grown in the presence of 100 mM phosphate buffer at pH 7.4. It is shown that Mengo virus is poorly infectious at the phosphate concentration similar to that in which it was crystallized. Maximal infectivity is achieved at 10 mM phosphate or less in physiological saline. The phosphate effect is ameliorated when the pH is lowered to 4.6. Although it has not been possible to study the crystal structure of the virus at low phosphate concentrations, it is shown that increasing the Cl- concentration at pH 6.2 or decreasing the pH to 4.6 causes substantial conformational changes confined to the "pit," a deep surface depression. These structural changes involve a movement of the "FMDV loop" (GH loop) in VP1, an ordering of the "VP3 loop" (GH loop in VP3) between 3176 and 3182, the displacement of a bound phosphate near the "FMDV loop" (GH loop in VP1), and movement of the carboxy terminus of VP2. The changes in conformation are correlated with the dissociation of the virion into pentamers at pH 6.2 and 150 mM Cl-. The localization of the conformational changes and the correlated role of the phosphate in controlling infectivity support the hypothesis that the "pit" is the receptor attachment site.
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PMID:Conformational variability of a picornavirus capsid: pH-dependent structural changes of Mengo virus related to its host receptor attachment site and disassembly. 215 8

The clinical use of citrate-phosphate-dextrose during blood-product transfusion is known to affect ionized calcium levels and can result in depression of myocardial contractility. The immature heart appears to have an intrinsic reduction in contractile state compared with the adult heart and may be more dependent on transsarcolemmal calcium flux for regulation of contraction. The myocardial contractile response to citrate infusion was compared in neonatal and adult rabbit hearts using clinically comparable citrate-phosphate-dextrose concentrations. Isovolumic left ventricular pressures were monitored in an isolated, crystalloid-perfused heart model before, during, and after 15 minutes of citrate-phosphate-dextrose infusion. Developed pressure decreased 42.1 +/- 4.9% from control within 1 minute in the neonatal group versus 24.3 +/- 4.3% in the adult group (p less than 0.02). The effect on diastolic function was paradoxical in the neonate with a 43.1 +/- 11.9% increase in end-diastolic pressure compared with a 9.7 +/- 7.8% decrease in the adult (p less than 0.01). These results indicate that the neonatal heart appears more sensitive to the myocardial effects of citrate infusion with impairment of both systolic and diastolic function. The decreased ventricular compliance in the neonate with citrate-phosphate-dextrose suggests that the myocardial effects may not be simply due to changes in ionized calcium concentration.
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PMID:Altered contractile response in neonatal myocardium to citrate-phosphate-dextrose infusion. 217 10

In the presence of 1 microM ryanodine, muscles loaded with the calcium indicator aequorin were stimulated at 15-20 Hz to produce steady levels of force and intracellular Ca2+ concentrations [( Ca2+]i) at various extracellular Ca2+ concentration ([Ca2+]o). After 5, 10, and 15 min of hypoxia and 3 min of reoxygenation, tetani were initiated. Force vs. [Ca2+]i relation was shifted to the right 0.11, 0.18, and 0.24 pCa units, and maximal force was down 66, 48, and 37% after start of hypoxia. During reoxygenation, the relationship was shifted up by 26%. In skinned fiber preparations, an increase in inorganic phosphate ion concentration from 0 to 10 mM and 15 mM decreased maximal force development by 32 and 53%, respectively, and shifted the pCa-force curve to the right by 0.08 and 0.14 pCa. A decrease in pH from 7.1 to 6.8 shifted the pCa-force curve to the right by 0.20 pCa units without affecting maximal force. These changes indicate that during hypoxia, a decrease in the sensitivity of the myofilaments to Ca2+ and a depression of maximal Ca2(+)-activated force occur, whereas during reoxygenation, there is an increase in maximal Ca2(+)-activated force.
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PMID:Direct evidence of changes in myofilament responsiveness to Ca2+ during hypoxia and reoxygenation in myocardium. 220 78

1. The pH dependence of the Ca2+ sensitivities of isometric tension and stiffness was investigated at 10 and 15 degrees C in skinned single fibres from rat and rabbit fast- and slow-twitch skeletal muscles. Stiffness was determined by recording the tension responses to sinusoidal length changes (3.3 kHz); peak-to-peak amplitude of the length change was monitored by laser diffraction and averaged approximately 1.3 nm (half-sarcomere)-1. We have assumed that stiffness provides a measure of the number of cross-bridge attachments to actin. 2. At maximal Ca2+ activation, stiffness was depressed by 22 +/- 2% (mean +/- S.E.M.) in fast-twitch fibres but was unchanged in slow-twitch fibres when pH was lowered from 7.00 to 6.20. As reported previously, maximum tension was depressed by 20-45% at low pH, with the effect being greater in fast-twitch compared to slow-twitch fibres. 3. In fast-twitch fibres at 10 and 15 degrees C the Ca2+ concentrations for half-maximal activation of tension and stiffness were increased at low pH. In slow-twitch fibres, similar effects were observed at 15 degrees C, but at 10 degrees C there were no changes in the Ca2+ sensitivities of tension and stiffness when pH was lowered. 4. Linear relationships between relative tension and relative stiffness were obtained at all temperatures, with slopes of 1.04 +/- 0.01 at pH 7.00 and 0.76 +/- 0.01 at pH 6.20 in fast- and slow-twitch fibres, indicating that force per cross-bridge attachment is similarly reduced at low pH in both types of fibres. 5. In both fast- and slow-twitch fibres, rigor tension (no added ATP or creatine phosphate; pCa 9.0) was depressed by 35 +/- 7% and stiffness by 12 +/- 4% when pH was reduced from 7.00 to 6.20. Since cross-bridge cycling is inhibited in rigor the effect of low pH to depress rigor tension suggests that pH directly modulates the strength of the bond formed between actin and myosin. 6. The effect of low pH to reduce the apparent number of cross-bridge attachments during maximal Ca2+ activation in fast- but not slow-twitch fibres could account for the greater H(+)-induced depression of maximum force in fast-twitch fibres. In both fibre types, the decrease in the number of cross-bridge attachments at submaximal concentrations of Ca2+ may in part account for the loss in Ca2+ sensitivity of tension at low pH, due perhaps to a reduction in co-operative activation of the thin filament by bound cross-bridges.
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PMID:Effects of tension and stiffness due to reduced pH in mammalian fast- and slow-twitch skinned skeletal muscle fibres. 223 31


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