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)

Effect of postsynaptic activity on the synaptic efficacy was studied in Xenopus nerve-muscle cultures. Repetitive postsynaptic depolarizations induced by injection of current pulses into singly innervated myocytes resulted in significant reduction in the frequency of spontaneous synaptic currents and the amplitude of nerve-evoked synaptic currents at the majority of synapses that showed immature synaptic properties. Repetitive hyperpolarizations and steady depolarizations of similar duration were without effect. The depolarization-induced synaptic depression appeared to result predominantly from a reduced ACh secretion from the presynaptic nerve terminal. Buffering the myocyte cytosolic Ca2+ at a low level with intracellular loading of a Ca2+ buffer, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), significantly reduced the effect of the depolarizations. Thus postsynaptic electrical activity can regulate the synaptic efficacy of the developing neuromuscular synapases and the regulation may be mediated by retrograde transsynaptic interactions.
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PMID:Depression of developing neuromuscular synapses induced by repetitive postsynaptic depolarizations. 804 44

Rumen-fistulated lactating cows were individually fed on hay or silage and intakes were monitored during 3 h treatment periods and for 2 h after. Each experiment used five, six or seven animals and the treatments were applied in a Latin Square design. Sodium acetate infusions of 1.8-11.0 mol in 4.5 litres water caused a dose-related depression in hay intake, the extent being 82 g dry matter (DM)/mol infused (P < 0.01). Sodium acetate infusions of 6.0-15.0 mol in 4.5 litres water caused a dose-related depression in silage intake of 118 g DM/mol infused. Rumen fluid pH for both diets was unaffected by treatment. Acetate and Na concentrations were increased and significantly negatively correlated with intake of both diets. Infusions of 2-8 mol sodium propionate caused a dose-related depression of hay intake which was significant when cow and day effects were accounted for. Sodium propionate infusions of 4-8 mol significantly depressed silage intake by 140 g DM/mol infused (P < 0.001). Rumen fluid pH was unaffected by treatment while propionate and Na concentrations were elevated and significantly negatively correlated with intake for both diets. Inflation of a rubber balloon in the rumen with 12.5-20 litres warm water resulted in a dose-dependent depression in hay intake of 66 g DM/l distension (P < 0.05). There was significant overeating during the 2 h following the 20 litre treatment. With silage, 15-25 litres of balloon distension for 3 h resulted in a dose-dependent depression in intake of 28 g DM/l distension (P < 0.001). There was no significant overeating during the 2 h following distension. When given in physiological amounts, at the lower end of the range used in these experiments, acetate, propionate and distension of the rumen did not significantly affect hay intakes. However, in each case the linear relationship between intake depression and level of treatment suggested that these factors could contribute to the control of feed intake.
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PMID:Responses in the voluntary intake of hay or silage by lactating cows to intraruminal infusions of sodium acetate or sodium propionate, the tonicity of rumen fluid or rumen distension. 832 46

Ten free monoamines and their metabolites in plasma and cerebrospinal fluid (CSF) were simultaneous measured in 6 levodopa-untreated (LU), 18 levodopa-treated (LT) and 37 levodopa-withdrawn (LW) Chinese patients with Parkinson's disease (PD) and 26 controls. We found that the levels of these substances in LW patients were not significantly different from those in LU patients. In LU- and LW-PD patients, CSF epinephrine (EPI) was higher (P < 0.05) than that of the controls. 3-methoxy-DOPA (3-OMDOPA) might not inhibit the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and dopamine metabolites in CSF. Levodopa treatment might change the dopaminergic and serotoninergic neuronal systems, but not the noradrenergic or adrenergic neuronal systems, in CNS of PD patients. Benserazide (a peripheral decarboxylase inhibitor) in Madopar might decrease the levels of serotonin (5-HT) and norepinephrine (NE), but not those of DOPA and homovanillic acid (HVA), in plasma. HVA, NE and EPI in plasma were not good indices for those in CSF. Otherwise, our results were consistent with some other studies by showing a significantly lower level (P < 0.01) of HVA in CSF of LU- and LW-PD patients than that of the controls, while no difference for NE, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindole acetic acid (5-HIAA) or 3-OMDOPA was noted. The severity of clinical disability was related to the deficiency of CSF HVA and DOPAC in LU- and LW-PD patients; however, there was no relationship between clinical symptoms of tremor, rigidity-bradykinesia, autonomic dysfunction, dementia, depression or levodopa-induced dyskinesia and CSF monoamines or their metabolites.
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PMID:Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease. 833 58

In a recent study, utilizing single cell recording techniques, we have shown that administration of 5-HT1A receptor antagonists, e.g. (S)-UH-301, to rats concomitantly treated, acute or chronically, with the selective serotonin reuptake inhibitor (SSRI) citalopram significantly increases the activity of 5-hydroxytryptamine (5-HT) containing neurons in the dorsal raphe nucleus (DRN). Here we report correlative experiments using microdialysis in freely moving animals to measure extracellular levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in the frontal cortex, a major projection area for DRN-5-HT neurons. Acute administration of (S)-UH-301 (2.5 mg/kg s.c.) or citalopram (2.0 mg/kg s.c.) increased 5-HT concentrations with a maximum of about 70% and 185%, respectively, above baseline. However, when (S)-UH-301 was administered 30 min before citalopram the maximal increase in 5-HT levels was approximately 400%. In rats chronically treated with citalopram (20 mg/kg/day i.p. for 14 days) basal 5-HT concentrations in the frontal cortex were significantly increased and 5-HIAA concentrations were decreased when measured 10-12 h, but not 18-20 h, after the last injection of citalopram, as compared to basal 5-HT and 5-HIAA concentrations in chronic saline-treated rats. When (S)-UH-301 (2.5 mg/kg s.c.) was administered 12 h, but not 20 h, after the last dose of citalopram it produced a significantly larger increase in extracellular concentrations of 5-HT than in control rats. However, in rats pretreated with a single, very high dose of citalopram, 20 mg/kg i.p., administration of (S)-UH-301 at 12 h after citalopram did not increase 5-HT levels. The augmentation by (S)-UH-301 of the increase in brain 5-HT output produced by acute administration of citalopram is probably due to antagonism of the citalopram induced feedback inhibition of 5-HT cells in the DRN, as previously suggested. However, the capacity of (S)-UH-301 to further increase the already elevated extracellular concentrations of 5-HT in brain in animals maintained on a chronic citalopram regimen, in which significant tolerance to the initial feedback inhibition of DRN-5-HT cells and developed, represents a novel finding. Generally, the reduced feedback inhibition of 5-HT neurons obtained with chronic citalopram treatment, and the associated elevation of brain 5-HT concentrations, may be related to functional desensitization of somatodendritic 5-HT1A autoreceptors in the DRN. This phenomenon may also largely explain the larger increase in 5-HT output produced by (S)-UH-301 in chronic citalopram treated animals as compared to its effect in control animals. Yet, a contributory factor may be a slight, remaining feedback inhibition of the 5-HT cells caused by residual citalopram at 12, but not 20 h after its last administration. Previous clinical studies suggest that addition of a 5-HT1A receptor antagonist to an SSRI in the treatment of depression may accelerate the onset of clinical effects. Moreover, in therapy-resistant cases maintained on SSRI treatment, addition of a 5-HT1A receptor antagonist may improve clinical efficacy. Since the therapeutic effect of SSRIs in depression has been found to be critically linked to the availability of 5-HT in brain, our experiments results support, in principle, both of the above clinically based notions.
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PMID:The 5-HT1A receptor antagonist (S)-UH-301 augments the increase in extracellular concentrations of 5-HT in the frontal cortex produced by both acute and chronic treatment with citalopram. 873 96

Cholinergic stimulation of the hippocampal formation results in excitation and/or seizure. We report here, using whole-cell patch-clamp techniques in the hippocampal slice (34-35 degrees C), a cholinergic-dependent slow afterdepolarization (sADP) and long-lasting plateau potential (PP). In the presence of 20 microM carbachol, action potential firing evoked by weak intracellular current injection elicited an sADP that lasted several seconds. Increased spike firing evoked by stronger depolarizing stimuli resulted in long-duration PPs maintained close to -20 mV. Removal of either Na+ or Ca2+ from the external media, intracellular Ca2+ ([Ca2+]i) chelation with 10 mM bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid, or the addition of 100 microM Cd2+ to the perfusate abolished both the sADP and PP. The sADP was depressed and the PP was abolished by either 10 microM nimodipine or 1 microM omega-conotoxin, whereas 1.2 microM tetrodotoxin was ineffective. The involvement of a Na+/Ca2+ exchanger was minimal because both the sADP and PP persisted after equimolar substitution of 50 mM Li+ for Na+ in the external media or reduction of the bath temperature to 25 degrees C. Finally in the absence of carbachol the sADP and PP could not be evoked when K+ channels were suppressed, suggesting that depression of K+ conductances alone was not sufficient to unmask the conductance. Based on these data, we propose that a Ca2+-activated nonselective cation conductance was directly enhanced by muscarinic stimulation. The sADP, therefore, represents activation of this conductance by residual [Ca2+]i, whereas the PP represents a novel regenerative event involving the interplay between high-voltage-activated Ca2+ channels and the Ca2+-activated nonselective cation conductance. This latter mechanism may contribute significantly to ictal depolarizations observed during cholinergic-induced seizures.
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PMID:Cholinergic-dependent plateau potential in hippocampal CA1 pyramidal neurons. 875 73

Bifemelane hydrochloride (BH) is widely employed in Japan in the treatment of cerebral infarction patients with depressive symptoms and its antidepressant action is considered to be caused by the normalizing effects of neurotransmitters. The relationship between the normalizing effects of neurotransmitters of BH and the depressive state of patients with cerebral infarction was examined. BH 150 mg/day was administered for three months to 13 cerebral infarction patients with depressive state. We measured the plasma neuropeptide Y (NPY), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 5-hydroxy-indole acetic acid (5-HIAA), and assessed the depressive symptoms using the 21-item Hamilton's Rating Scale for Depression (HRSD) before and after administration of BH. After treatment, the plasma NPY concentration was significantly increased, the plasma MHPG concentration and total score of HRSD were significantly decreased, and the plasma 5-HIAA concentration showed no changes. These findings suggest that the antidepressant effect of BH is caused by the normalizing effects of NPY and noradrenalinergic neurons.
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PMID:Effects of bifemelane hydrochloride on plasma neuropeptide Y, 3-methoxy-4-hydroxyphenylethylene glycol and 5-hydroxy-indole acetic acid concentrations in patients with cerebral infarction. 884 47

The effects of chronic administration of the antidepressant drugs desipramine, nortryptiline and paroxetine (PAR) (10 mg/kg/day, 21 days) on changes in turning (circling) behavior and on norepinephrine (NE), dopamine (DA) and serotonin and their metabolites 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex (PFC), nucleus accumbens and striatum were evaluated in rats. All three drugs eliminated turning biases in right turning rats. All drugs increased DA concentrations in the PFC while PAR increased NE in the PFC and reduced 5-HIAA in all three structures. The results are discussed with reference to previous findings involving brain asymmetry in depression.
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PMID:Chronic antidepressant drug treatment reduces turning behavior and increases dopamine levels in the medial prefrontal cortex. 886 21

Cardiac function improvement seen with hemofiltration may be attributable to "cardiac depressant factor(s)" removal. The authors have attempted "factor" isolation. Initial 12 hr hemofiltrate was obtained from: 4 patients with acute congestive heart failure (cardiac index: 2.02 +/- 0.48) and acute renal failure (blood urea nitrogen [BUN] 97.7 +/- 32.7; serum creatinine [SCr] 6.2 +/- 3.4 mg%) (Group I); 8 patients with chronic congestive heart failure (CI: 2.69 +/- 1.3) and mild renal failure (BUN 48.8 +/- 31.4; SCr 3.5 +/- 2.4 mg%) (Group II); and 8 patients with end-stage renal disease and no congestive heart failure (Group III). Crude samples were passed through C18Sep-Pak, and eluted with methanol/water mixtures, and 50% methanol samples were fractionated by high pressure liquid chromatography. Inotropic response was studied by injecting samples (in Krebs-Hensleit buffer) into a Langendorff rat heart preparation. The effect of pH, acetate, salts, and adding propranolol on the inotropic response also was tested. Myocardial depression followed all vehicle and preparatory elements: 0.1 M HCl (-47%); 0.08 M acetic acid (-75%); Na acetate (-25%); 0.1 M NaHCO3 (-11%); Na citrate (-84%); and Na glutarate (-14%). Group I had biphasic responses, the positive inotropism accorded to catecholamines, whereas negative inotropism was equal in each patient (-40.3%). Group II had a biphasic response with negative (-15%) inotropism noted. Group III was weakly biphasic. The data indicate there was myocardial depressive activity, most pronounced in Groups I and II, after method interference was corrected.
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PMID:Isolation of "myocardial depressant factor(s)" from the ultrafiltrate of heart failure patients with acute renal failure. 894 20

The cerebral cortex of anaesthetised 2- to 12-day-old rats was superfused with artificial cerebrospinal fluid containing 100 mM acetate substituted for chloride to condition the brain for spreading depression (SD). After such superfusion, the earliest SD-like events were found at day 9 and full blown SD at day 10, whereas in the unconditioned brain the first SD occurred between days 12 and 15. Acetate conditioning of the cerebral cortex may be used to unmask neuronal and glial properties that are hidden in early stages of development.
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PMID:Postnatal conditioning for spreading cortical depression in the rat brain. 955 23

Six patients with documented systemic mast cell disease were enrolled in a 1-year, phase I study to determine the possible benefits of interferon alpha-2b (IFN-alpha). IFN-alpha therapy was begun at a dosage of 0.5 million units/day (MU/day) by subcutaneous injection and increased, as tolerated, to 3.0 MU/day. Subsequent dose modifications were made based on clinical tolerance and response. No immediate, adverse reactions to IFN-alpha occurred. Several patients showed symptomatic improvement. In two patients ascites resolved and did not recur. Two other patients reported improved energy levels and had decreased size of retroperitoneal, measenteric and retrocrural nodes. One patient failed to benefit and died shortly after completing 12 months of therapy. Bone marrow mastocytosis decreased by 5% to 10% after 12 months of therapy with IFN-alpha. Although five of the six patients had a decrease in the urinary excretion of 1-methyl-4-imidazole acetic acid, serum tryptase values did not appreciably change in any patient. Side-effects from IFN-alpha included hypothyroidism, thrombocytopenia and depression. It is concluded that although treatment with IFN-alpha was associated with a decline in bone marrow mastocytosis and reduced excretion of histamine metabolites, prolonged therapy may be needed and dose-limiting side-effects are frequent.
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PMID:Response of severe systemic mastocytosis to interferon alpha. 958 Aug 6


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