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)

Previous studies, which have demonstrated that carbamazepine (CBZ) possesses direct muscle spindle suppressant activity, suggest that CBZ may have therapeutic value in the treatment of hypertonic disorders characterized by high fusimotor drive. The effects of CBZ on motor tone in the midcollicular decerebrate cat were therefore examined. CBZ, in a concentration-dependent manner, reduced muscle tone, as measured by the force necessary to overcome hyperextension. Significant depression was first observed at a serum concentration of about 25 micrograms/ml, whereas 50% depression occurred at about 40 micrograms/ml. These effects could not be attributed to the hypotensive effect of the drug. CBZ produced little or no effect on spontaneous gamma motoneuron activity recorded in teased ventral roots of segmentally deafferented spinal cords of decerebrate animals; chlorpromazine, however, was effective in suppressing such activity. In the same preparations, CBZ reduced polysynaptic but had little effect on monosynaptic spinal reflexes evoked by dorsal root stimulation. The drug also shortened the duration of the pause in spontaneous gamma motoneuron activity after dorsal root stimulation. Serum concentrations which diminished extensor rigidity in decerebrate cats induced mild to moderate intoxication in intact unanesthetized cats. This was characterized by ataxic gait, sedation and hypotonia. These experiments indicate that CBZ may be of value alone or adjunctively in the reduction of some forms of muscle hypertonicity.
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PMID:Effects of carbamazepine on muscle tone in the decerebrate cat. 682 68

Reported is a case of baclofen overdose in a 23-year-old woman. The patient manifested typical symptoms of baclofen overdose, including hypotonia, respiratory depression, and seizures. She was treated successfully with positive pressure ventilation, sedation, and intravenous antibiotics, and was discharged from the hospital on the 14th day following admission with no residual neurological signs, to be followed up in medical and psychiatric outpatient clinics. As baclofen becomes increasingly popular in the treatment of muscle spasm in certain neurological disorders, its availability for misuse increases.
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PMID:Baclofen overdose. 682 97

We studied the effect of alcohol ingestion on sleep-induced breathing abnormalities and arterial oxyhaemoglobin saturation in seven patients with a range of sleep-induced upper airway occlusion. The characteristics of each patient's sleep-induced breathing abnormality was established on one or more control all-night studies, and then a further all-night study was done immediately following alcohol ingestion. Alcohol increased the duration and frequency of the occlusive episodes in five patients with obstructive sleep apnoea, and resulted in a marked increase in the degree of hypoxaemia in the first hour of sleep. In two patients with benign chronic snoring, alcohol induced frank obstructive sleep apnoea during the first hour of sleep. We suggest that the increased tendency to develop obstructive apnoea after alcohol is the result of alcohol-induced oropharyngeal muscle hypotonia, while the increased duration of obstructive apnea is the result of alcohol-induced depression of arousal mechanisms.
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PMID:Alcohol, snoring and sleep apnea. 707 45

To investigate whether prolonged severe swelling would cause irreversible injury to neurons, we exposed hippocampal tissue slices to hypotonic solutions (142 mosmol/kg) and followed the recovery of evoked responses for 5 h. Orthodromically evoked responses increased during hypotonia, except during recurrent waves of spreading depression (SD). After restoring normal osmotic pressure (pi o), evoked potentials became profoundly depressed. Following 30 min exposure, nearly maximal orthodromic responses recovered completely but responses to submaximal stimuli remained depressed, indicating elevated threshold. Following 60 min exposure, orthodromic transmission remained depressed. In slices from young animals, antidromic population spikes recovered completely, but in slices from older rats they remained partly depressed. Withdrawing calcium and raising magnesium concentration before and during hypotonic exposure resulted in modest but significant improvement of the recovery of synaptically transmitted responses, but made no difference for antidromic responses. With [Ca2+]o reduced and [Mg2+]o elevated, electrographic seizures replaced the episodes of SD during low pi o treatment. We conclude that even 60 min of severe hypotonic swelling did not kill CA1 pyramidal cells in tissue from young rats, but in its aftermath synaptic transmission was disrupted. Uptake of calcium may have played a minor role in the impairment of synaptic transmission. We propose hypothetically that post-hypotonic shrinkage of dendrites disrupted the integrity of excitatory synapses.
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PMID:The extent and mechanism of the loss of function caused by strongly hypotonic solutions in rat hippocampal slices. 855 31

Low extracellular osmotic pressure (pi o) is known to enhance CNS responsiveness and the chance of seizures, but the mechanism of the hyperexcitability is not clear. We recorded evoked potentials in st. radiatum and st. pyramidale of CA1. Tissue electrical resistance (Ro) was determined from the voltage drop (VRo) evoked by constant current pulses. Lowering of pi o by reducing [NaCl] caused a concentration-dependent increase of amplitude and duration of extracellular excitatory postsynaptic potentials (fEPSPs). fEPSPs increased much more than did VRo, but antidromic population spikes increased in proportion to VRo. fEPSP increased also in isosmotic low NaCl (fructose or mannitol substituted) solutions, but not as much as in low pi o. In moderately hypotonic solutions orthodromic population spikes increased as expected from the augmented fEPSP, but in strong hypotonia input-output curves shifted to the left and single stimuli evoked multiple population spikes, indicating lowering of threshold of postsynaptic neurons. Blocking N-methyl-D-aspartate (NMDA) receptors did not diminish the enhancement of fEPSP amplitude. Spreading depression (SD) erupted in most slices in very low pi o, but not in isoosmotic low [NaCl] solutions. We conclude that the hypotonic enhancement of EPSPs depends, in part, on the lowering of [Na+]o and/or of [Cl-]o, and it may be augmented by dendritic swelling favoring electrotonic spread of EPSPs from dendrites to somata, and buildup of transmitter concentration due to swelling of perisynaptic glia. SD can be initiated by cell swelling, but the depolarization associated with SD is probably not caused by the opening of stretch-gated ion channels.
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PMID:Hypotonic exposure enhances synaptic transmission and triggers spreading depression in rat hippocampal tissue slices. 855 32

The origin of both sleep and memory appears to be closely associated with the evolution of mechanisms of enhancement and maintenance of synaptic efficacy. After the origin of activity-dependent synaptic plasticity, whereby single activations of synapses led to short-term efficacy enhancements, lengthy maintenance of the enhancements probably was achieved by repetitive activations ("dynamic stabilization"). These are thought to have occurred either in the course of frequent functional use, or to have been induced spontaneously within the brain to maintain synaptic efficacies in circuits that were in infrequent use. The latter repetitive activations are referred to as 'non-utilitarian' dynamic stabilization. With the evolution of increasing repertories and complexities of behavioral and sensory capabilities-with vision usually being the vastly preeminent sense-brain complexity increased markedly. Accompanying the greater complexity, needs for storage and maintenance of hereditary and experimental information (memories) also increased greatly. It is suggested that these increases led to conflicts between sensory input processing during restful waking and concomitant 'non-utilitarian' dynamic stabilization of infrequently used memory circuits. The selective pressure for the origin of primitive sleep may have been a need to achieve greater depression of central processing of sensory inputs-largely complex visual information-than occurs during restful waking. The electrical activities of the brain during sleep (aside from those that subserve autonomic activities) may function largely to maintain sleep and to dynamically stabilize infrequently used circuitry encoding memories. Sleep may not have been the only evolutionary adaptation to conflicts between dynamic stabilization and sensory input processing. In some ectothermic vertebrates, sleep may have been postponed or rendered unnecessary by a more readily effected means of resolution of the conflicts, namely, extensive retinal processing of visual information during restful waking. By this means, processing of visual information in central regions of the brain may have been maintained at a sufficiently low level to allow adequate concomitant dynamic stabilization. As endothermy evolved, the skeletal muscle hypotonia of primitive sleep may have become insufficient to prevent sleep-disrupting skeletal muscle contractions during 'non-utilitarian' dynamic stabilization of motor circuitry at the accompanying higher body temperatures and metabolic rates. Selection against such disruption during dynamic stabilization of motor circuitry may have led to the inhibition of skeletal muscle tone during a portion of primitive sleep, the portion designated as "rapid-eye-movement sleep." Many marine mammals that are active almost continuously engage only in unihemispheric non-rapid-eye-movement sleep. They apparently do not require rapid-eye-movement sleep and accompanying 'non-utilitarian' dynamic stabilization of motor circuitry because this circuitry is in virtually continuous use. Studies of hibernation by arctic ground squirrels suggest that each hour of sleep stabilizes brain synapses for as long as four hours.
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PMID:Origin and evolution of sleep: roles of vision and endothermy. 904 11

The origin of both sleep and memory appears to be closely associated with the evolution of mechanisms of enhancement and maintenance of synaptic efficacy. The development of activity-dependent synaptic plasticity apparently was the first evolutionary adaptation of nervous systems beyond a capacity to respond to environmental stimuli by mere reflexive actions. After the origin of activity-dependent synaptic plasticity, whereby single activations of synapses led to short-term efficacy enhancement, lengthy maintenance of enhancements probably was achieved by repetitive activations ("dynamic stabilization"). One source of selective pressure for the evolutionary origin of neurons and neural circuits with oscillatory firing capacities may have been a need for repetitive spontaneous activations to maintain synaptic efficacy in circuits that were in infrequent use. This process is referred to as "non-utilitarian" dynamic stabilization. Dynamic stabilization of synapses in "simple" invertebrates occurs primarily through frequent use. In complex, locomoting forms, it probably occurs through both frequent use and non-utilitarian activations during restful waking. With the evolution of increasing repertories and complexities of behavioral and sensory capabilities--with vision usually being the vastly pre-eminent sense brain complexity increased markedly. Accompanying the greater complexity, needs for storage and maintenance of hereditary and experiential information (memories) increased greatly. It is suggested that these increases led to conflicts between sensory input processing during restful waking and concomitant non-utilitarian dynamic stabilization of infrequently used memory circuits. The selective pressure for the origin of primitive sleep may have been a resulting need to achieve greater depression of central processing of sensory inputs largely complex visual information than occurs during restful waking. The electrical activities of the brain during sleep (aside from those that subserve autonomic activities) may function largely to maintain sleep and to dynamically stabilize infrequently used circuitry encoding memories. Sleep may not have been the only evolutionary adaptation to conflicts between dynamic stabilization and sensory input processing. In some ectothermic vertebrates, sleep may have been postponed or rendered unnecessary by a more readily effected means of resolution of the conflicts, namely, extensive retinal processing of visual information during restful waking. By this means, processing of visual information in central regions of the brain may have been maintained at a sufficiently low level to allow adequate concomitant dynamic stabilization. As endothermy evolved, the skeletal muscle hypotonia of primitive sleep may have become insufficient to prevent sleep-disrupting skeletal muscle contractions during non-utilitarian dynamic stabilization of motor circuitry at the accompanying higher body temperatures and metabolic rates. Selection against such disruption during dynamic stabilization of motor circuitry may have led to the inhibition of skeletal muscle tone during a portion of primitive sleep, the portion designated as rapid-eye-movement sleep. Many marine mammals that are active almost continuously engage only in unihemispheric non-rapid-eye-movement sleep. They apparently do not require rapid-eye-movement sleep and accompanying non-utilitarian dynamic stabilization of motor circuitry, because this circuitry is in virtually continuous use. Studies of hibernation by arctic ground squirrels suggest that each hour of sleep may stabilize brain synapses for as long as 4 h. Phasic irregularities in heart and respiratory rates during rapid-eye-movement sleep may be a consequence of superposition of dynamic stabilization of motor circuitry on the rhythmic autonomic control mechanisms. Some information encoded in circuitry being dynamically stabilized during sleep achieves unconscious awareness in authentic and var
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PMID:Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance. 917 63

Hypoxia-ischemia damages selected regions of the immature at different ages. Prior to 32 weeks gestation the periventricular white matter is selectively vulnerable but in the last trimester the basal ganglia become especially vulnerable to injury. Hypoxia-ischemia causes injury by activating a series of biochemical events that unfolds over a period of hours to days following the initial insult and we are investigating the ways in which age modifies these events. The cascade includes release of glutamate, overstimulation of excitatory amino acid receptors and raised intracellular levels of calcium. Clinically this series is manifested by hypoxic-ischemic encephalopathy (HIE), a syndrome that includes coma, seizures, a burst suppression EEG, respiratory depression and severe hypotonia. Clinical studies have established a relationship between the severity of neonatal encephalopathy and later manifestations of brain damage or cerebral palsy. Potential neuroprotective therapies need to be effective when given after the insult but the 'therapeutic time window' for most N-methyl-D-aspartate (NMDA) glutamate antagonists is limited after injury. Using a model of hypoxic-ischemic injury and neonatal rats and hypothermic-circulatory arrest in dogs, we found that immunohistochemical staining for neuronal nitric oxide synthase (nNOS) is markedly increased from 6 to 24 h after the insult in the basal ganglia and cortex. The induction of nNOS preceded the time of maximal neuronal necrosis and during the time when many apoptotic nuclei were appearing. We have also found that a brief period of 2 h of mild hypothermia (32 degrees C) following hypoxia-ischemia in neonatal rats delayed neuronal necrosis by more than a week. We are determining whether this delay is related to a change in nNOS activation. Induction of nNOS in the post-insult period may contribute to expression of injury and signs of encephalopathy following a hypoxic-ischemic insult.
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PMID:Hypoxic and ischemic disorders of infants and children. Lecture for 38th meeting of Japanese Society of Child Neurology, Tokyo, Japan, July 1996. 918 71

Prader-Willi syndrome (PWS) is a neurobehavioural disorder characterized by neonatal respiratory depression, hypotonia and failure to thrive in infancy, followed by hyperphagia and obesity among other symptoms. PWS is caused by the loss of one or more paternally expressed genes on chromosome 15q11-q13, which can be due to gene deletions, maternal uniparental disomy or mutations disrupting the imprinting mechanism. Imprinted genes mapped to this region include SNRPN (refs 3,4), ZNF127 (ref. 5), IPW (ref. 6) and NDN (which encodes the DNA-binding protein necdin; refs 7,8,9,10). The mouse homologues of these genes map to mouse chromosome 7 in a region syntenic with human chromosome 15q11-q13 (refs 7,11). Imprinting of the human genes is under the control of an imprinting center (IC), a long-range, cis-acting element located in the 5' region of SNRPN (ref. 12). A related control element was isolated in the mouse Snrpn genomic region which, when deleted on the paternally inherited chromosome, resulted in the loss of expression of all four genes and early post-natal lethality. To determine the possible contribution of Ndn to the PWS phenotype, we generated Ndn mutant mice. Heterozygous mice inheriting the mutated maternal allele were indistinguishable from their wild-type littermates. Mice carrying a paternally inherited Ndn deletion allele demonstrated early post-natal lethality. This is the first example of a single gene being responsible for phenotypes associated with PWS.
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PMID:Disruption of the mouse necdin gene results in early post-natal lethality. 1050 1

A total of 8000 anesthesias with ketamine or ketamine + halothane in children with infantile cerebral paralysis, operated in a one-day hospital, are analyzed. The complications were as follows: tachycardias in 12%, hypotonia in 8%, repeated vomiting in 5%, postnarcosis depression in 10%, psychomotor excitation in 9%, and painful syndrome in 7%. The most incident combination of complications was hypotonia, tachycardia, repeated vomiting, and postnarcosis depression. Complications occurred in 14.2% cases in ketamine anesthesia and in 4.3% cases in halothane + ketamine anesthesia.
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PMID:[Complications of anesthesia and their prevention in children with spastic cerebral palsy during ambulatory surgery]. 1058 65


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