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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium (DS) was investigated for its effects on cat soleus muscle contractile properties and motor nerve terminal activity in particular. DS, 0.1-1.5 mg/kg i.v., caused a dose-dependent depression of indirectly elicited contractile strength which was more pronounced at lower frequencies of stimulation. Maximum tetanic strength at frequencies of 10-400 Hz was depressed to a lesser degree than contractile responses evoked by lower frequencies of stimulation; the twitch/tetanus contraction ratios were reduced with increasing dose, primarily because of diminished twitch. DS was without effect on motor nerve terminals as evidenced by normal post-tetanic repetition in the nerves following DS administration. Post-tetanic potentiation became relatively larger in amplitude as contractile strength was diminished. These data suggest that DS depresses neuromuscular function at a site other than the neural apparatus at the neuromuscular junction.
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PMID:Dantrolene effects on neuromuscular function in cat soleus muscle. 114 11

The changes in certain reflex responses of the rat spinal cord after local depression of inhibitory processes by tetanus toxin (the so-called phenomenon of "determinative dispatch station") were studied. It is shown that the tonic and rhythmic activity generated by this locus in the lumbar part of the spinal cord evokes generalized activity of all spinal motoneurons with similar time characteristics. The depression of its neurons by glycine removes this phenomenon. The excitation of "determinative dispatch station" neurons in cervical segments causes a pathologically enhanced scratch reflex in the ipsilateral hind limb. The enhancing of the scratch reflex is not connected with the depression of inhibitory processes of lumbar motoneurons. The formation of the "determinative dispatch station" in cervical segments produces both excitatory and inhibitory influences on monosynaptic reflexes of the lumbar flexor motoneurons. The role of local inhibitory processes depression in the functioning of the nervous system is discussed.
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PMID:[Intercentral relations in rat spinal cord with local depression of the inhibitory processes]. 116 Nov 6

The isometric responses of the medial gastrocnemium (MG), soleus (SOL) and anterior tibial (TA) muscles to single shocks and different modes of repetitive stimulation were studied in kittens of varying postnatal ages and in adult cats. The postnatal decrease in time-to-peak and half-relaxation time of the twitch contractions were similar for the MG and TA muscles and adult values were attained at around 6-7 weeks of age. The SOL muslce displayed a transient decrease in contraction time during the first postnatal weeks, followed later by a slowing towards adult values. The susceptibility to fatigue during iterative stimulation was smallest in the SOL at all ages studied, and usually largest in TA. It changed only little for the MG and SOL postnatally while increasing markedly for the TA up until 6-7 weeks of age. Tetanic contraction resulted in similar depressions in contractile tension of all three muscles in the youngest kittens, but the SOL displayed a greater ability to recover from this depression than the MG and, in particular, the TA muscles. Tetanus resistance increased postnatally and adult responses were attained at 6-7 weeks of age.
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PMID:The postnatal development of some twitch and fatigue properties of the ankle flexor and extensor muscles of the cat. 118 26

Cord dorsum potentials, dorsal root potentials and field potentials were studied in rats with local depression of inhibitory processes in lumbar spinal segments produced by tetanus toxin. The study was carried out at a stage when excitation of a neuronal population with depressed inhibitory processes (the so-called "determinative dispatch station") evoked generalized excitation of spinal and bulbar motoneurons. In experiments with spinal animals it was shown that the stimulation of a cutaneous nerve on the affected side evokes DRP's P-waves and field potentials of greater amplitude and longer duration than those evoked on the opposite side or in healthy rats. The prolonged P-wave revealed several components which coinsided with prolonged ventral root discharges. This wave could be recorded from an enlarged spinal cord region. The maximal increased and prolonged negative field potentials corresponding in time to the enlarged P-wave were found in the ventral quadrant of the affected side. In this region "spontaneous" rhythmical negative slow waves were recorded. The mechanisms of spreading excitation from the site with depressed inhibitory processes and the localization of this site are discussed.
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PMID:[Spinal cord electrical activity during focal depression of inhibitory processes]. 120 33

Depression of one or more parameters of cellular and/or humoral immune responses was found in 60% of general hospital patients treated with phenytoin and 47% of patients treated with carbamazepine. Phenytoin-treated patients failed to manifest delayed hypersensitivity (DHS) reactions to common antigens, and to make antibody to Salmonella typhi and tetanus toxoid. Serum levels of IgA and IgM, DNA synthesis in circulating leucocytes, and phytohaemagglutinin (PHA) induced deoxyribonucleic acid synthesis were also low. Depression of IgA, DHS reactivity and antibody responsiveness to S. typhi were shown to develop after the commencement of phenytoin therapy in a study of eleven patients. The presence of immunological defects was independent of the dosage of drug, its serum concentration, the duration of therapy and the sex of the subject. Studies in vitro provided evidence that immunosuppression was the result of a direct effect of phenytoin on the metabolism of lymphoid cells. Carbamazepine was shown to have a similar but less potent direct effect. Pharmacological concentrations of phenytoin caused a significant depression of DNA synthesis in PHA-stimulated and non-stimulated blood cell cultures in vitro. High concentrations in addition caused depression of cell counts, lymphocyte blastogenesis, ribonucleic acid and protein synthesis. Phenytoin was not cytocidal at concentrations of up to 125 mug/ml. Depression of DNA synthesis by phenytoin was maximal when phenytoin was added within 4-8 hr of the addition of PHA. PHA-induced DNA synthesis was not significantly affected by pre-incubation with phenytoin. In vivo, the presence of immunological defects was not related to phenytoin-induced folic acid deficiency. High concentrations of carbamazepine, but not phenobarbitone or diazepam caused a significant depression of PHA-stimulated DNA synthesis in blood cell cultures. The data show that immunosuppression is a common side-effect of phenytoin therapy, and that lymphoma is rare. They suggest that in the presence of phenytoin-induced immunosuppression another factor, or factors are required to induce the formation of lymphoma.
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PMID:Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro. 121 10

1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature, 2-5 degrees C; sarcomere length, 2.10 microns) were fatigued using two separate protocols that led to different degrees of depression of tetanic force. Under control conditions the fibre was stimulated to produce a 1 s fused isometric tetanus at 300 s intervals. A moderate degree of fatigue (tetanic force reduced to 70-80% of the control value) was produced by decreasing the intervals between tetani to 15 s ('fatiguing protocol 1'). A more pronounced depression of tetanic force (to 40-50% of the control value) was produced by evoking a single twitch at 1-2 s intervals ('fatiguing protocol 2'). 2. Fatiguing protocol 1 reduced the contracture response to submaximal and supramaximal concentrations of caffeine (3-15 mM) in proportion to the decrease in tetanic force. These results support the view that fatiguing stimulation according to protocol 1 leads to a true 'myofibrillar fatigue' with no failure of activation of the muscle fibre. 3. Fatiguing protocol 2 reduced the amplitudes of isometric twitch and tetanus to below 10 and 50% of the control values, respectively. By contrast, the maximal contracture response to caffeine (15 mM) was depressed by merely 2-3% of its prefatigue value. 4. Force and instantaneous fibre stiffness were recorded simultaneously during twitch and tetanus as fatigue was induced by protocol 2. During the initial part of fatigue (tetanic force reduced by 25% of control) stiffness was reduced by merely 9% in accordance with previous measurements during fatigue induced by protocol 1. However, with further depression of twitch and tetanus by protocol 2 there was a marked reduction of fibre stiffness. These results, together with the findings reported under point 3, strongly suggest that at an advanced state of fatigue induced by protocol 2 the decrease in active force is largely due to failure of activation of the contractile system. 5. Muscle fibres were quickly frozen for electron microscopical examination after shortening below slack length (to approximately 1.6 microns sarcomere spacing) during tetanic stimulation. In non-fatigued fibres, and in fibres fatigued according to protocol 1, the myofibrils exhibited a straight appearance throughout the preparation suggesting that the entire volume of the fibre was properly activated. In fibres fatigued by protocol 2, on the other hand, only the most peripheral layers of myofibrils remained straight after shortening, whereas the centre of the fibre showed marked waviness indicating failure of the inward spread of activation in this case.
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PMID:Myofibrillar fatigue versus failure of activation during repetitive stimulation of frog muscle fibres. 129 47

We tested a theoretical prediction that patterns of excitatory input activity that consistently fail to activate target neurons sufficiently to induce synaptic potentiation will instead cause a specific synaptic depression. To realize this situation experimentally, the Schaffer collateral projection to area CA1 in rat hippocampal slices was stimulated electrically at frequencies ranging from 0.5 to 50 Hz. Nine hundred pulses at 1-3 Hz consistently yielded a depression of the CA1 population excitatory postsynaptic potential that persisted without signs of recovery for greater than 1 hr after cessation of the conditioning stimulation. This long-term depression was specific to the conditioned input, ruling out generalized changes in postsynaptic responsiveness or excitability. Three lines of evidence suggest that this effect is accounted for by a modification of synaptic effectiveness rather than damage to or fatigue of the stimulated inputs. First, the effect was dependent on the stimulation frequency; 900 pulses at 10 Hz caused no lasting change, and at 50 Hz a synaptic potentiation was usually observed. Second, the depressed synapses continued to support long-term potentiation in response to a high-frequency tetanus. Third, the effects of conditioning stimulation could be prevented by application of NMDA receptor antagonists. Thus, our data suggest that synaptic depression can be triggered by prolonged NMDA receptor activation that is below the threshold for inducing synaptic potentiation. We propose that this mechanism is important for the modifications of hippocampal response properties that underlie some forms of learning and memory.
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PMID:Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. 135 90

The effect of tetanic activation of corticostriatal glutamatergic fibers was studied in striatal slices by utilizing extracellular and intracellular recording techniques. Tetanic stimulation produced a long-term synaptic depression (LTD) (> 2 h) of both extracellularly recorded field potentials and intracellularly recorded EPSPs. LTD was not coupled with changes of intrinsic membrane properties of the recorded neurons. In some neurons, repetitive cortical activation produced a short-term posttetanic potentiation (1-3 min). Subthreshold tetanic stimulation, which under control condition did not cause LTD, induced LTD when associated with membrane depolarization. Moreover, LTD was not expressed in cells in which the conditioning tetanus was coupled with hyperpolarization of the membrane. Bath application of aminophosphonovalerate (30-50 microM), an antagonist of NMDA receptors, did not affect the amplitude of the synaptic potentials and the expression of LTD. Striatal LTD was significantly reduced by the pretreatment of the slices with 30 microM 2-amino-3-phosphonopropionic acid, an antagonist of glutamate metabotropic receptors. LTD was not blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. Scopolamine (3 microM), an antagonist of muscarinic receptors, induced a slight, but significant, increase of the amplitude of LTD. Both SCH 23390 (3 microM), an antagonist of D1 dopamine (DA) receptors, and I-sulpiride (1 microM), an antagonist of D2 DA receptors, blocked LTD. LTD was also absent in slices obtained from rats in which the nigrostriatal DA system was lesioned by unilateral nigral injection of 6-hydroxydopamine. In DA-depleted slices, LTD could be restored by applying exogenous DA (30 microM) before the conditioning tetanus. In DA-depleted slices, LTD could also be restored by coadministration of SKF 38393 (3-10 microM), a D1 receptor agonist, and of LY 171555 (1-3 microM), a D2 receptor agonist. Application of a single class of DA receptor agonists failed to restore LTD. These data show that striatal LTD requires three main physiological and pharmacological conditions: (1) membrane depolarization and action potential discharge of the postsynaptic cell during the conditioning tetanus, (2) activation of glutamate metabotropic receptors, and (3) coactivation of D1 and D2 DA receptors. Striatal LTD may alter the output signals from the striatum to the other structures of the basal ganglia. This form of synaptic plasticity can influence the striatal control of motor activity.
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PMID:Long-term synaptic depression in the striatum: physiological and pharmacological characterization. 135 31

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

A study was conducted to evaluate repeated intrathecal injections of baclofen, without artificial ventilation, in the treatment of severe tetanus. Ten patients, 5 men and 5 women, with a mean age of 34 +/- 7 years, were included in the study. The dose of baclofen injected was 1000 micrograms between the ages of 16 and 55 years, 800 micrograms over the age of 55 years and 500 micrograms under the age of 16 years. The efficacy was assessed on the basis of the resolution of contractures and paroxysms and the initial dose was reinjected prior to the reappearance of these symptoms. Treatment was discontinued in the case of central nervous system depression or inefficacy. The first injection was effective in 9 cases for 24-48 h. The haemodynamic safety was always good. Five patients developed central depression with coma and respiratory depression, requiring artificial ventilation in 3 cases and reversed by flumazenil in 2 cases. Five patients were treated exclusively with baclofen with 4 cures. Five patients had to be ventilated with only one cure. This study confirms earlier studies concerning the efficacy of intrathecal baclofen in tetanus. However, the frequency of episodes of respiratory depression prevents the recommendation of repeated injections when respiratory intensive care facilities are not available.
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PMID:Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. 143 May 90


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