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Biomedical subjects

K Inanaga

Publications and source records attributed to K Inanaga.

At least 19 recordsLinked to original sources

Frontal midline theta rhythm and mental activity.

Theta rhythm at the midline of the frontal area can be observed in normal subjects, during mental task performance, rest and sleep. Frontal midline theta rhythm (Fm theta) is a train of rhythmic waves at the frequency of 6- Hz and can be induced by various mental tasks. Fm theta is induced not only during mental tasks but also during nocturnal sleep in which it was most frequent during rapid eye movement (REM) and second most frequent during stage 1 of non-REM (NREM) sleep, and the relationship of Fm theta to dream images during sleep was found. It is concluded, therefore, that the appearance of Fm theta is related to mental activity even during sleep. Fm theta shows individual differences and is related to certain personality traits. High Fm theta groups showed the lowest anxiety score in the Manifest Anxiety Scale (MAS), the highest score in the extrovertive scale of the Maudsley Personality Inventory (MPI) and the lowest score in the neurotic scale of MPI. Low Fm theta groups showed the opposite correlation. Significant negative correlation was found between the amount of Fm theta and platelet monoamine oxidase (MAO) activity. Summarizing the above-mentioned results, it may be concluded that the appearance of Fm 0 is related to mental activity, personality traits and platelet MAO activity. Furthermore, the correlation of such markers as platelet MAO activity and Fm theta with personality traits as measured by various psychological tests may prove to be of great importance in the exploration of the biological bases of personality.

Frontal Lobe↗

Analysis of sleep EEGs by the interval histogram method--validity of the baseline night as a control and the effect of ethyl loflazepate (CM6912).

The effects of an anxiolytic drug, ethyl loflazepate (CM6912) on sleep EEGs were investigated by the interval histogram method originally developed. EEGs were classified into each of the delta 2-beta 2 and sigma 1 wave-form parameters, and the individual frequencies were determined on the third baseline, second drug and the first recovery nights in each sleep stage. In comparison with the second baseline night, the sigma 1 waves in stage 2 sleep and the delta 1 waves in REM sleep were decreased and the alpha and sigma 1 waves in stage 3 sleep were increased on the third baseline night. In consideration of the 5% significance level and the remarkable influence of drug administration, described below, no major problems were encountered in the use of the night as a control in this experimental schedule. The main characteristics of administration of CM6912 manifested as decreases in the slow wave, increases in the fast wave, and an increase in the sigma 1 wave in sleep stages other than stage 1. These tendencies were remarkable on the second drug night and were still evident even on the recovery night. Increases in sigma 1 wave were related to increases in sleep spindles. The increases in the beta 2 wave were particularly remarkable in REM sleep.

Adult↗

Effectiveness of concomitant setiptiline maleate (Tecipul) on negative symptoms of schizophrenia.

1. Setiptiline maleate was administered to schizophrenic patients with the object of improving their negative symptoms. 2. Moderate improvements were observed in 58% of the treated patients, thus usefulness of this drug was demonstrated. 3. There was no aggravation of symptoms, and side effects were minor. 4. Measurements of plasma monoamine metabolites showed a tendency of MHPG to decrease and a significant decrease in 5-HIAA, but no change in the level of HVA was observed, suggesting a relationship between the negative symptoms and noradrenaline and/or serotonin systems.

Adult↗

A case of tardive Tourette-like syndrome.

We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.

Adult↗

Three cases of respiratory dyskinesia.

We present here three cases of respiratory dyskinesia (RD). RD was observed with a video recording and other recordings were made of a respiratory airflow with a thermistor, and abdominal movement with a strain gauge. Neurological findings and CT scanning indicated marked organic changes in the brain in these 3 cases. RD was complicated with tardive dyskinesia of the tongue and lips, and the symptoms were aggravated during stress and absent during sleeping, which are the characteristic features of extrapyramidal symptoms. The symptoms of the three cases have improved by decreasing the dose of butyrophenone derivatives and discontinuing anti-parkinsonian drugs, which suggested that an intracerebral imbalance of DA and ACh may be the cause of RD.

Acetylcholine↗

GM1 ganglioside reduces edema and monoaminergic neuronal changes following experimental focal ischemia in rat brain.

Seventy-two hours following a middle cerebral artery occlusion, the associated increase in water content on the ischemic side was significantly reduced by the exogenous administration of monosialoganglioside GM1 (30 mg/kg, i.p.). The levels of dopamine and serotonin on the ischemic side were approximately 50% and 80% of those on the contralateral non-ischemic side, respectively. Treatment with GM1 (5 times during the first 48 h after occlusion) produced a significant reduction in the levels of dopamine and serotonin loss. The present findings are compatible with the observed protective action of the exogenously administered GM1 following ischemic brain injury.

Animals↗

Involvement of the cholinergic system in haloperidol-induced release of dopamine from slices of striatum in the rat.

The effects of cholinergic and anticholinergic drugs on spontaneous or haloperidol-induced release of dopamine (DA) were studied in vitro. The slices of striatum were placed in a chamber and continuously superfused with Krebs' solution, containing various concentrations of haloperidol, with or without atropine, d-tubocurarine (d-TC), tetrodotoxin (TTX), physostigmine or carbachol. Haloperidol, enhanced the release of endogenous DA from the slices of striatum at an EC50 value of 25.6 microM. The effect of haloperidol was significantly reduced by atropine (2.5 microM), while it was unaffected by d-TC (10 microM) and TTX (1 microM). In contrast, physostigmine (3.7 microM) significantly increased the haloperidol-induced efflux of DA from the slices of striatum. In addition, acetylcholine (ACh), in the presence of physostigmine or carbachol, enhanced the basal efflux of DA at EC50 values of 2.8 microM and 83 microM, respectively. The effect of ACh on the efflux of DA was antagonized by atropine. These data suggest that haloperidol-induced release of DA is, at least partially, mediated by the activation of muscarinic ACh receptors located in the striatum.

Acetylcholine↗

Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study.

A multi-institutional study comparing the antimanic effect of carbamazepine (CBZ) and lithium carbonate (Li) was performed using a double-blind group comparison design in a series of 105 patients with bipolar disorders. CBZ and Li were given for four weeks using a fixed-flexible method at an equipotent dose ratio of 1:1, starting from an initial dosage of 400 mg with a maximum dosage of 1200 mg. The final global improvement rate, based on the number of cases showing moderate to marked amelioration of manic symptoms, was 62% in the CBZ group and 59% in the Li group, with no significant difference being found between the two groups. Incidence of cutaneous side-effects was significantly higher in the CBZ group. The mean daily dosage and serum level of CBZ in the fourth week were 674 +/- 239 mg and 7.3 +/- 2.4 micrograms/ml respectively; these were within the therapeutic range. The daily dose and serum level of Li, however, were 710 +/- 239 mg and 0.46 +/- 0.22 mEq/l, and the Li level seemed to be too low to compare its therapeutic effect with that of CBZ. Prior to the present study, approximately 80% of the patients in both groups had been receiving antipsychotic medication, equivalent to 8.0 mg of haloperidol on average, without favorable response. This medication was maintained unchanged during treatment. While the shortcomings of the present study limit the interpretation of the data, it may be suggested that the usefulness of CBZ as a drug for the treatment of manic states is comparable to that of Li.

Adolescent↗

Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders.

The therapeutic effects of carbamazepine (CBZ) were evaluated in 103 patients with affective disorders, 54 with schizophrenic disorders, and 26 with schizoaffective disorders by a multi-institutional open study. The rate of marked and moderate improvement was 72.8% in affective disorders, 54.6% in schizophrenic disorders, and 61.5% in schizoaffective disorders. Symptom items of the Clinical Psychopharmacology Research Group rating scale for mania showed significant improvement in the patients with affective disorders as well as in those of the other two groups. In the Brief Psychiatric Rating Scale as applied to patients with schizophrenic or schizoaffective disorders, symptom items related to affect and emotion showed significant improvement. The antimanic efficacy of CBZ was also noted in many poor responders to lithium. Side-effects were observed in 82 patients (44.8%), and abnormal laboratory findings in 37 patients (44.8%), and abnormal laboratory findings in 37 patients. The present study seems to confirm the usefulness of CBZ for the treatment of affective disorders and in some cases, of schizophrenic and schizoaffective disorders.

Adult↗

Parkinsonism manifesting depression as the first sign.

We have had experience in treating two patients with parkinsonism of which the first manifestation was depression. Case 1 was a 61-year-old woman. A diagnosis of depression had been made and repeated medication consisting mainly of antidepressants was given. However, the depressive state persisted and the signs of parkinsonism gradually became evident. The initial treatment with antidepressant drugs was replaced with one based on L-DOPA (400 mg a day). Subsequently, the symptoms of parkinsonism and depression diminished relatively rapidly. Case 2 was a 66-year-old man. His parkinsonism was suspected shortly after the onset, although the symptoms of depression were predominant. Similarly, the treatment based on L-DOPA (400 mg a day) relieved the symptoms of depression and parkinsonism rapidly. The present study described above indicates that parkinsonism should be suspected in cases of persistent depression and in patients who have depressive symptoms resistant to antidepressants, since parkinsonism may first manifest itself as depression.

Aged↗

Panic anxiety after abrupt discontinuation of mianserin.

We observed a case of withdrawal after abrupt discontinuation of mianserin. A 41-year-old woman was treated according to a diagnosis of depression, which was her 6th episode. Mianserin 30 mg/day, etizolam 1 mg/day and flunitrazepam 1 mg/day were administered. When the patient discontinued taking the drugs by herself because of subsiding of these symptoms, severe panic anxiety appeared. This panic anxiety was not relieved by taking etizolam and flunitrazepam again, but subsided rapidly by the re-administration of mianserin 30 mg/day, and because of that the depressive symptom also disappeared. From these experiences panic anxiety seemed to be a withdrawal symptom, and involvement of the noradrenergic system in panic anxiety as well as serotonergic system was suggested.

Adult↗

A double-blind study of adjunctive carbamazepine versus placebo on excited states of schizophrenic and schizoaffective disorders.

A multi-institutional double-blind study comparing the therapeutic effect of adjunctive carbamazepine and placebo with standard neuroleptic treatment was performed on 162 patients with DSM-III diagnosis of schizophrenic (n = 127) or schizoaffective disorders (n = 35) who had excited states or aggressive/violent behavior that responded unsatisfactorily to neuroleptic treatment. The patients participated in a 4-week trial of carbamazepine plus neuroleptics (n = 82) or placebo plus neuroleptics (n = 80). The sum of patients with marked and moderate improvement was modestly larger in the carbamazepine group (48 vs. 30%, P less than 0.05). There was no significant difference between the carbamazepine and placebo groups in the changes of total BPRS scores, although the carbamazepine group showed more improvement on the items suspiciousness, uncooperativeness and excitement. The results suggest that carbamazepine, when used in combination with neuroleptics, is a useful drug for the treatment of excited states of patients with schizophrenic and schizoaffective disorders.

Adolescent↗

Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment.

1. Intracellular recordings were made from the nucleus accumbens neurons in brain slices from rats previously treated with saline or methamphetamine. 2. In neurones from both methamphetamine- and saline (control)-treated rats, dopamine (0.1 mM) produced three types of responses: a biphasic response consisting of an initial hyperpolarization followed by a depolarization, a monophasic hyperpolarization and a simple depolarization. 3. Haloperidol (1 microM) reversibly suppressed both responses to dopamine; (-)-sulpiride (1 microM) selectively abolished the depolarization and prolonged the hyperpolarization. Forskolin (10 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) mimicked the hyperpolarization. Both of the latter two substances were more effective in neurones from methamphetamine-treated rats than in neurones from control rats. 4. In slices from methamphetamine-treated rats, the dose-response curve for the dopamine hyperpolarization was shifted to the left of that seen in neurones from control rats by a factor of approximately 100. The dose-response curve for the dopamine depolarization was shifted to the right about 10-fold in neurones from rats treated with methamphetamine. 5. In slices from control rats, dopamine (less than or equal to 0.1 mM) and methamphetamine (less than or equal to 1 microM) had no effect on the EPSPs evoked by focal electrical stimulation of the periaccumbens regions: dopamine (greater than or equal to 10 nM) and methamphetamine (1 microM) markedly depressed the EPSPs in slices from methamphetamine-treated rats. Depolarizations evoked by application of exogenous glutamate were unaffected by dopamine (less than 5 microM). 6. In slices from methamphetamine-treated rats, dopamine (greater than or equal to 10 nM), forskolin (greater than or equal to 1 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) depressed Ca2+-dependent spikes as well as the EPSPs. Haloperidol (1 microM) completely reversed the depressions of the EPSPs and Ca2+-dependent spikes by dopamine, while (-)-sulpiride (1 microM) was only partially effective. 7. These results indicate that chronic methamphetamine administration leads to enhancement of the actions of dopamine at D1 receptors located on glutamate and/or aspartate nerve terminals and of the dopamine hyperpolarization of principal neurones, which is also mediated by D1 receptors.

Action Potentials↗

Frontal midline theta activity and platelet MAO in human subjects.

The distinctive theta rhythm that appears at the frontal midline during the performance of mental tasks has been designated as frontal midline theta (Fm theta). Fm theta shows individual differences and seems to be related to certain personality traits. In several studies, it has been indicated that low platelet monoamine oxidase (MAO) activity is also associated with certain personality traits. In the present study, we found a negative correlation between the appearance of Fm theta and platelet MAO activity. Subjects with marked extroversion show a high amount of Fm theta and low MAO activity. It is therefore suggested that Fm theta, an electrophysiological marker, may be useful in the investigation of monoamine functions in the central nervous system (CNS) by way of platelet MAO activity, a biochemical marker.

Adult↗

Enhancement of dopamine release from striatal slices of rats that were subchronically treated with methamphetamine.

The effect of dopamine (DA) uptake inhibitors (methamphetamine, nomifensine, and phenylethylamine) on the release of endogenous DA from striatal slices of rats pretreated with methamphetamine (6 mg/kg/day for 9 days) was investigated. The exposure of methamphetamine-pretreated rat striatal slices to a low concentration (10(-7) M, 5 X 10(-7) M) of methamphetamine caused a greater increase in DA efflux than that of saline-treated rat striatal slices. The drug-treated rats displayed an enhanced stereotyped behavioral response to a small dose of methamphetamine (1 mg/kg). Removal of Ca2+ from the superfusion medium did not affect the difference in the rates of methamphetamine (10(-7) M) induced DA release between methamphetamine-treated and saline-treated rat striatal slices. Nomifensine- and phenylethylamine-induced DA release from striatal slices was also enhanced by repeated administration of methamphetamine. On the other hand, there was no difference in K+-induced DA release between the two groups. Moreover, repeated administration of methamphetamine caused a significant increase in 3H-dopamine uptake in rat striatal synaptosomes. These results suggest that the behavioral sensitization produced by the repeated administration of methamphetamine is accompanied by an enhancement in the release of DA induced by methamphetamine, nomifensine, and phenylethylamine in vitro and is also accompanied by increased DA uptake into striatal synaptosomes.

Animals↗

Automatic real-time analysis of human sleep stages by an interval histogram method.

A new interval histogram method for automatic, all-night sleep stage scoring, simulated on a digital computer, is described. The system consists of a 2-step analysis. The first step is recognition of elementary patterns in EEG, EOG and EMG, and the second step is the determination of sleep stages based on these parameters. Correlation of this method with power spectral analysis of the dominant EEG patterns during each sleep stage supported the reliability of the first step analysis. Overall agreement (89.1%) between the computer and human judges was only 3% less than the agreement (92.1%) among the scorers, indicating considerable reliability of the second step. The primary areas of disagreement that arose in the identification of sleep stages occurred with stages 1, 2 and REM. To improve scoring accuracy, the system may require epoch sequence information. The profile of the elementary parameters of the EEG signals clearly illustrated the cyclic nature of these activities throughout the night. The alpha and delta 2 waves clearly separated the awake state from sleep stages. Beta 2 can discriminate stages 1 and REM from stage 2, and the best indicator for distincting stage 1 from REM was muscle activity. Sigma and spindles were prominent during stage 2 sleep. Both delta 2 and high voltage delta waves distinguished stage 3 from stage 4. On the other hand, delta 1 was evenly distributed and seemed to be common to all sleep stages.

Adolescent↗

Effect of acute ethanol administration on noradrenaline metabolism in brain regions of stressed and nonstressed rats.

The effects of ethanol on noradrenaline (NA) metabolism of brain regions in stressed and nonstressed rats were investigated. Male Wistar rats were injected IP with either saline, or ethanol at 0.5 g/kg or 2 g/kg, 5 min before exposure to 1-hr immobilization stress. Levels of NA and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in various brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases in MHPG-SO4 levels in all brain regions examined, i.e., the hypothalamus, amygdala, hippocampus, cerebral cortex and locus coeruleus (LC) region. In nonstressed rats, ethanol significantly increased MHPG-SO4 levels in the hypothalamus, hippocampus and cerebral cortex, but not in the amygdala or in the LC region. In stressed rats, ethanol attenuated stress-induced increases in MHPG-SO4 levels preferentially in the amygdala and LC region, but not in the remaining three regions. Although ethanol per se dose-dependently elevated plasma corticosterone levels in nonstressed rats, ethanol at 2 g/kg attenuated the stress-induced elevation of corticosterone. These results suggest that the attenuating effect of ethanol on stress-induced increases in NA turnover in the amygdala and LC region might be related to the stress-relieving properties of this drug.

Animals↗

Biorhythm of core temperature in depressive and non-depressive alcoholics.

Core temperature was longitudinally evaluated during the day- and nighttime in six non-depressive and in four depressive alcoholics who had been abstaining from alcoholic beverages. The least squares spectrum method was employed for detecting the periods and acrophase of the circadian rhythm of core temperature. Although normal periods were observed in all the patients throughout the study, an abnormal acrophase was found in many patients, especially in depressive alcoholics. On the 3rd and 4th days after alcohol withdrawal, all of the four depressive alcoholics showed a phase advance of the circadian rhythm, and three patients of the six non-depressive alcoholics exhibited an abnormal acrophase. On the 21st and 22nd days after alcohol withdrawal, a normal acrophase was observed in two patients of the four depressives and in four of the six non-depressives. The mean core temperature was higher in the depressives than in the non-depressives on the third and fourth days after alcohol withdrawal.

Adult↗