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)

In vivo electrochemistry has been a valuable tool in detecting real time neurochemical changes in extracellular fluid. Absolute selectivity has been difficult to achieve previously, but we report here a carbon fiber electrode and measurement technique which is specific for one oxidizable species: ascorbic acid. Ascorbic acid is highly concentrated in extra- as well as intracellular brain spaces, and appears to undergo dynamic changes in response to a variety of physiological and pathophysiological circumstances. Recent studies have implicated glutamatergic mechanisms which give rise to extracellular changes in brain ascorbate, and we confirm and extend these observations. Preliminary studies, directed towards examining ascorbic acid as an index and/or result of hypoxia, spreading depression, and seizure activity, have been undertaken and the results are reported herein.
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PMID:Electrochemical monitoring of brain ascorbic acid changes associated with hypoxia, spreading depression, and seizure activity. 134 61

The clinical features and management of nine cases of mushroom poisoning due to Amanita pantherina (eight cases) and Amanita muscaria (one case) admitted to a children's hospital are described. Most ingestions were in the toddler age group with males being more frequently involved. Symptoms occurred between 30-180 min with the onset of central nervous system depression, ataxia, waxing and waning obtundation, hallucinations, intermittent hysteria or hyperkinetic behavior. Vomiting was rare. Seizures or myoclonic twitching occurred in 4/9 patients, but was controlled with standard anticonvulsant therapy. No other anticholinergic or cholinergic signs were prominent. Recovery was rapid and complete in all patients.
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PMID:Mushroom poisoning in infants and children: the Amanita pantherina/muscaria group. 134 20

The abundant CNS cholesterol and its sulfate derivative serve as precursors of different neurosteroids, which bidirectionally modulate neuronal excitability, by potentiating or inhibiting function of the GABAA receptors. The regulation of GABAA receptors in the CNS by the steroids of central or peripheral origin may constitute a vital means of brain-body communication, essential for integrated whole organism responses to external stimuli or internal signals. Modulation of the brain GABA receptors by neurosteroids may form the basis of a myriad of psychophysiological phenomena, such as memory, stress, anxiety, sleep, depression, seizures and others. Therefore, the aberrant synthesis of centrally-active steroids may contribute to defects in neurotransmission, resulting in a variety of neural and affective disorders. The biosynthesis of neurosteroids may also be altered by diet and certain psychotropic drugs, thereby affecting excitation of neurons. Hereditary differences in the level of synthesis and catabolism of different neurosteroids may underlie individual variations in CNS excitability, contributing to differences in personality traits, including the inherited susceptibility to drug addition.
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PMID:Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. 134 41

1. We studied the effect of pentylenetetrazol (PTZ)-induced myoclonic jerks and generalized clonic-tonic convulsions (GC) on the levels of neurotransmitter amino acids in the cisternal CSF of rats. 2. The levels of aspartate, glutamate, glycine, and taurine were elevated in the CSF during myoclonic jerks and more distinctly immediately after GC. 3. During the recovery period of postictal depression seen in EEG (5 min after GC), the CSF levels of transmitter amino acids were lower than in the control group. 4. PTZ-induced irritative activity in the EEG disappeared in 24 hr but the levels of amino acids remained abnormal. 5. Amino acid changes in the CSF following PTZ-induced convulsions might indicate that the release of amino acids into the extracellular space is increased before and during the propagation of PTZ-induced seizure and decreased during postictal depression.
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PMID:Amino acid levels in cerebrospinal fluid of rats after administration of pentylenetetrazol. 135 Sep 65

The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis and treatment of intoxications in which benzodiazepines are involved. In case of a positive response, patients will regain consciousness immediately, thus verifying the diagnosis and making a brief history possible to identify other drugs that might be involved. Moreover, invasive diagnostic and therapeutic procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc., may then be unnecessary. In cases of pure benzodiazepine overdose a single injection of flumazenil 0.2mg should be given, followed by individually titrated increments of 0.1 mg/min until the patient is awake and responsive. In these cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may be necessary in cases of combined drug overdose. Because of its high therapeutic index, the administration of flumazenil is usually not accompanied by serious adverse effects. Benzodiazepine withdrawal syndromes characterised by transient anxiety and depression can occur, but the incidence is low. Increases of blood pressure and heart rate due to a release of catecholamines are possible, which might endanger patients with cardiovascular diseases. In severe cases, seizures have been observed which usually respond well to small doses of benzodiazepine agonists. In all cases of successful treatment it should be remembered that the effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to resedation. In these patients additional bolus injections or a continuous infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in cases of alcohol (ethanol) poisoning is questionable and should be further investigated.
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PMID:Benzodiazepine antagonists. An update of their role in the emergency care of overdose patients. 135 15

One hundred fifteen consecutive patients in the Austin Hospital Comprehensive Epilepsy Program (Melbourne, Australia) were surveyed to document the psychosocial and rehabilitation difficulties after temporal lobectomy. During the follow-up period (mean 4 years) 3 patients died, 5 patients were lost to follow-up, and 107 patients with family and friends were interviewed. Eighty-four patients (78%) had been seizure-free for the year preceding the interview; 13 others had seizure reduction greater than 75%. Success in ablation or reduction in seizures correlated with the amount of postoperative gain, but in this series, analysis of work and dependency outcome did not emphasize areas of success. Although improvement in work and financial status, interpersonal relations and sexuality were all recorded, successful patients deemed that most advance had been made in the areas of newly acquired independence, enhanced career potential, and social freedom. Significant postoperative anxiety, especially after left temporal lobectomy, was noted, possibly explained by benzodiazepine antiepileptic drug (AED) discontinuation. Although 1 patient committed suicide, neither depression nor psychosis was common in the rehabilitation period, in contrast to results in previous series. Significant sociodomestic problems emerged from this survey, however: 35% of patients considered successes reported postoperative problems stemming from the necessity to restructure family dynamics; in 6%, this resulted in divorce. Moreover, 20% of patients and relatives reported significant behavioral problems in coping with the seizure-free lifestyle. Finally, the problems of the worsened situation after surgical failure indicated the counterproductive potential of ineffective lobectomy. These results indicate the necessity for a preoperative counseling program to prevent these problems.
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PMID:Psychosocial difficulties and outcome after temporal lobectomy. 139 33

A few mouse minimum lethal doses (MLD) of tetanus toxin injected into rat hippocampus triggers prolonged changes in neuronal function. Spontaneously recurring epileptic discharges arise in both the injected and the contralateral, uninjected hippocampus. The seizures remit after about 6 weeks, to be succeeded by a permanent depression of hippocampal neuronal responses. There is no evidence of any loss of pyramidal cells at this low dose of toxin. Here we studied presumptive inhibitory, GABAergic neurons, using in situ hybridization (ISH) with a probe directed against the mRNA encoding glutamic acid decarboxylase (GAD), at each of 1, 2, 4 and 8 weeks after injection of tetanus toxin. Epileptic activity was recorded from hippocampal slices prepared from both injected and contralateral hippocampi of rats at each time point, unexpectedly persisting until 8 weeks. There were no significant differences in the numbers of neurons containing GAD mRNA between toxin- and vehicle-injected and control rats in any hippocampal subfield, at any survival time, except for an apparently transient loss of hilar signal in vehicle-injected rats at 1 and 2 weeks which we attribute to a significant, transient loss of neuronal GAD mRNA to below the threshold for detection by ISH using this probe. In contrast there was a marked increase in GAD mRNA in the toxin-injected group, which reached a peak at 4 weeks, and returned to control levels by 8 weeks. The changes were bilateral and were most marked in the hilus of the dentate area, but were also significant in CA3 and CA1. Upregulation of GAD mRNA was preceded by an increase in the levels of the mRNA for the alpha subunit of the GTP binding protein, Gs (Gs alpha), at 2 weeks which affected the GABAergic neurons selectively, and not the pyramidal or granule cells. These marked changes in GAD mRNA may contribute to putative adaptive responses within GABAergic neurons, which would help contain epileptic activity in these chronic foci. The changes in GAD expression may be due to mechanisms acting through an increase in mRNA encoding Gs alpha.
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PMID:Increased expression of GAD mRNA during the chronic epileptic syndrome due to intrahippocampal tetanus toxin. 139 47

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
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PMID:Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. 142 88

Clinical experience with gamma-vinyl GABA (GVG, vigabatrin) has accumulated mainly in Europe, where the drug has been licensed in several countries since 1989. Short-term efficacy studies in adolescent and adult patients with intractable drug-resistant epilepsy have shown that approximately 50% exhibit a reduction in seizure frequency of one-half or more but rarely complete seizure control. The best results are in patients with partial seizures with or without secondarily generalization. GVG responders have been followed for periods of up to 5 years, and overall 10-20% may exhibit subsequent seizure breakthrough, as probably occurs with any drug in such chronic patients. The most common side effect is drowsiness. Reversible behavior disorders, psychoses, and depression rarely occur in predisposed individuals. No new long-term side effects have been reported but vigilance is necessary. Studies of GVG as a first-line drug in newly diagnosed epileptic patients are proceeding.
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PMID:Gamma-vinyl GABA (vigabatrin): clinical experience in adult and adolescent patients with intractable epilepsy. 142 98

The actions of the highly selective A2 adenosine agonist, CGS 21680, in modulating kindled seizures and locomotor activity were examined. I.c.v. injections of CGS 21680 into the lateral cerebral ventricle in fully kindled rats were found to prolong the period of postictal EEG depression and reduce postictal spiking in a dose-dependent manner, while not affecting the behavioral seizure stage or afterdischarge duration. CGS 21680 injections also lead to a dose-related inhibition of locomotor activity in rats exposed to an open field apparatus compared to rats receiving control injections of saline. These observations implicate the involvement of the A2 adenosine receptor in postictal phenomena and the locomotor depressant actions of adenosine, but do not indicate a direct anticonvulsant activity following A2 activation.
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PMID:The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. 143 42


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