Suicidality and corticosteroid-induced psychosis.
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Adrenal Cortex Hormones↗
Biomedical subjects
M L Rao
Publications and source records attributed to M L Rao.
Thyroid function in anxious and depressed patients.
We measured serum thyroid hormone levels, and pre- and post-TRH administration serum thyrotropin (TSH) in 46 psychiatric inpatients with major depression (n = 20), anxiety disorder (n = 9), and anxious depression (n = 17), and in 56 healthy subjects. Basal serum triiodothyronine was lower in female patients with major depression and anxious depression than in healthy women (P less than 0.05). Basal serum thyroxine was lower in female patients with anxious depression than in controls; all patients showed lower basal serum TSH than controls. In healthy subjects, basal triiodothyronine and thyroxine, basal TSH, and delta TSH (the increment of TSH after TRH administration) correlated, whereas no correlation was found between triiodothyronine and thyroxine in male patients with major depression, or between TSH and delta TSH in female patients with major depression or anxious depression. In female patients, 45% with major depression, 25% with anxiety disorder, and 35% with anxious depression showed a blunted TSH response. We also investigated pre- and post-dexamethasone administration cortisol levels in these patients. The sensitivity obtained by the combination of the results of the TRH and dexamethasone suppression tests for major depression, anxiety disorder, and anxious depression was 45%, 55%, and 65%, respectively.
Adult↗
Monitoring of serum bioactivity levels of perazine and its metabolites by radioreceptor assay.
The bioactivity of perazine and its metabolites in human serum was analysed by radioreceptor assay. The IC50 value (the concentration eliciting a 50% blockade of 3H-spiroperidol binding to the dopamine receptor in a membrane suspension of porcine striatum) was for perazine 175 nmol/l, and for its metabolites perazine sulfoxide 1050 nmol/l, desmethylperazine 330 nmol/l, N-(3-phenothiazin-10-yl-propyl)-ethylenediamine 2800 nmol/l, and N-(3-phenothiazin-10-yl-propyl)-N'-methylethylenediamin 2850 nmol/l. Thus, perazine metabolites possess low affinity to the dopamine receptor. In a pilot study we measured the bioactivity of perazine and its metabolites in sera of perazine-treated psychiatric patients by radioreceptor assay and compared the results to levels obtained by high-performance thin-layer chromatography; the correlation coefficient r was 0.85 and the slope 0.95 (n = 11). Thus serum perazine can be adequately monitored by radioreceptor assay, as evidenced by the results from high-performance thin-layer chromatography.
Adolescent↗
Blood serotonin levels in suicidal schizophrenic patients.
A decrease in central serotonin metabolism has been found in suicidal patients. In schizophrenic patients suicidality is predominantly observed as a transient phenomenon being most pronounced during an acute psychotic episode. We investigated blood serotonin levels as a paradigm for serotonin metabolism in suicidal schizophrenic women who were psychotic and compared their data with those of nonsuicidal psychotic schizophrenic women and healthy controls. Blood serotonin was lower in suicidal female schizophrenic patients (0.44 +/- 0.05 mumol/l, n = 17) than in nonsuicidal female schizophrenic patients (0.94 +/- 0.07 mumol/l, n = 17; P less than 0.001) or in healthy women (0.90 +/- 0.02 mumol/l, n = 26; P less than 0.001). These findings support the hypothesis that decreased serotonin metabolism may be associated with suicidal behavior in schizophrenic women.
Adult↗
Epileptic but not psychogenic seizures are accompanied by simultaneous elevation of serum pituitary hormones and cortisol levels.
The circadian rhythm of serum prolactin was determined in 12 patients with seizures, and 28 age- and sex-matched healthy subjects (14 men and 14 women). Blood was also collected every 15 min for 2 h immediately after a simultaneously video/EEG-documented epileptic (6 patients) and psychogenic seizure (5 patients) for the determination of prolactin, thyrotropin, growth hormone, cortisol, melatonin, catecholamines and serotonin. During the seizure-free interval, the circadian profile of serum prolactin was lower in female patients than in healthy women. Serum prolactin, thyrotropin, growth hormone, and cortisol were increased postictally, followed by a decrease, after a grand mal or complex partial seizure, but not after a psychogenic seizure in comparison to baseline serum hormone levels obtained during the same time on a seizure-free day. During the seizure and for 2 h afterwards, blood serotonin, serum melatonin, dopamine, and epinephrine did not alter and were within the reference limits of healthy subjects. Serum norepinephrine was lower in patients compared to healthy subjects (p less than 0.05). The simultaneous elevation of serum prolactin, thyrotropin, growth hormone, and cortisol points to a central stimulation of the hypothalamic-pituitary axis during an epileptic seizure, but not during seizures of psychogenic origin.
Catecholamines↗
Gabapentin augments whole blood serotonin in healthy young men.
It has been previously demonstrated that gabapentin, a gamma-amino butyric acid analogue, inhibits monoaminergic neurotransmitter release from rabbit caudate nucleus slices and from rat cortex. In humans this drug has been shown to have anti-epileptogenic activity. Serotonin may act as an inhibitory neurotransmitter and its interaction with blood platelets is thought to reflect its central actions. We investigated sleep stages, whole blood serotonin levels, and serum melatonin in healthy men after the administration of gabapentin. With increasing serum gabapentin levels six healthy subjects showed an increase in sleep stages 3 and 4 and in whole blood serotonin (P less than 0.05) Serum melatonin levels were not influenced. On account of these results we speculate that gabapentin modulates the release of serotonin from blood platelets. The increase in peripheral serotonin points paradigmatically to an increase in the bioavailability of serotonin which may account for the increase in sleep stages 3 and 4.
Acetates↗
Increased serotonin after a suicide attempt: coincidence or catharsis?
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Abreaction↗
Nuclear triiodothyronine receptor of human adipose tissue.
L-Triiodothyronine induces malic enzyme in explants from human adipose tissue. Consequently, we looked for the presence of receptors for L-triiodothyronine in nuclei isolated from human adipose tissue. The binding of 125I-triiodothyronine by the nuclei was time- and temperature-dependent. At 37 degrees C binding reached a steady state after 60 minutes. Dithiothreitol enhanced total binding and suppressed nonspecific binding. Scatchard analysis showed the presence of a single class of binding sites. The apparent association constant, Ka, was 0.13 +/- 0.03 X 10(10) M-1, the maximal binding capacity 2.20 +/- 0.81 pmol/mg DNA (mean +/- SD, n = 7) and the number of binding sites 8,000/nucleus. L-Triiodothyronine and D-triiodothyronine had equal affinity to the nuclear receptor; triiodothyroacetic acid had three times higher affinity. L- and D-thyroxine had 8% and 12%, respectively, and tetraiodothyroacetic acid had 19% affinity compared to that of L-triiodothyronine. Reverse triiodothyronine was a weak competitor. Digestion of nuclei with micrococcal nuclease abolished specific binding. These results show that nuclei from human white adipose tissue possess high affinity receptors for L-triiodothyronine, which are associated with nuclear chromatin. It is likely that induction of malic enzyme in human adipose tissue by L-triiodothyronine is mediated by the nuclear receptors.
Adipose Tissue↗
Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.
The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.
Adolescent↗
Radioreceptor assay and high-performance liquid chromatography yield similar results for serum thioridazine and its major metabolites.
Thioridazine and its major metabolites were quantified in serum of thioridazine-treated psychiatric patients by radioreceptor assay and high performance liquid chromatography (HPLC) every second day during 3 weeks of drug administration. Serum neuroleptic levels measured by radioreceptor assay and serum concentrations of thioridazine and its active metabolites estimated by HPLC correlated (r = 0.82, n = 60); the intra- and interassay coefficients of variation of both assays were low (less than 7%). Thus, serum thioridazine can be adequately monitored by radioreceptor assay as well as by HPLC.
Adult↗
Stability of serum neuroleptic and prolactin concentrations during short- and long-term treatment of schizophrenic patients.
The potential importance of neuroleptic activity measures in the management of schizophrenia warrants attention to the methods for assessing neuroleptic bioactivity and stability of neuroleptic bioactivity over time. We have carried out measurements of serum neuroleptic and prolactin concentrations in 18 schizophrenic patients treated with haloperidol or thioridazine for up to 1 year. Serum neuroleptic levels were measured by a radioreceptor assay using porcine striatum. The lower limit of sensitivity of the assay was 0.6 ng haloperidol/ml, the intra- and interassay coefficients of variation 3 and 9%, respectively. A linear correlation was observed between haloperidol dose (5-30 mg/d) and serum neuroleptic activity (r = 0.706, P less than 0.001) and a curvilinear relationship between thioridazine dose (50-600 mg/d) and serum neuroleptic activity in schizophrenic outpatients. There was a positive correlation between serum neuroleptic and prolactin concentrations for the patients taking haloperidol (r = 0.620, P less than 0.001) or thioridazine (r = 0.542, P less than 0.001). In patients taking a constant dose of haloperidol or thioridazine for up to 1 year serum neuroleptic activity remained stable, suggesting the absence of metabolic tolerance; the observation of a decrease of 38 +/- 16% (mean +/- SD) in serum prolactin concentrations in patients treated with haloperidol but no prolactin decrease with thioridazine suggests that under certain neuroleptic treatment conditions a functional tolerance develops in the tuberoinfundibular dopamine system.
Adult↗
Influence of the pineal gland on pituitary function in humans.
In 14 men and 14 women we examined the relationship between melatonin and the secretion of pituitary hormones. Blood pressure, and the serum concentrations of melatonin, catecholamines, prolactin, thyrotropin, growth hormone, and cortisol were determined every 3-4 hr for 24 hr. In the normal, basal (unstimulated) condition there were no significant correlations (p greater than 0.05) between the systolic blood pressure and dopamine (r = 0.09), norepinephrine (r = 0.26), or epinephrine (r = 0.27), nor were there significant correlations between melatonin and dopamine (r = -0.01), norepinephrine (r = -0.26), or growth hormone (r = 0.17). The concentrations of melatonin correlated positively with those of prolactin (r = 0.56, p less than 0.05 for men and r = 0.58, p less than 0.001 for women) and thyrotropin (r = 0.62, p less than 0.001 for all subjects), but not with those of cortisol (r = 0.004, p greater than 0.05). We speculate that the increase in melatonin at night leads to a decrease in dopaminergic activity; the diminished release of dopamine may lead to a simultaneous increase in thyrotropin and prolactin.
Adult↗
Influence of anticonvulsants and flunarizine on the metabolism of thyroid hormones: speculation about the possible role of calmodulin.
Interference of anticonvulsants with the metabolism of hormones may lead to side effects. Anticonvulsants influence the hypothalamic-pituitary-thyroid axis, in that lowering of thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine levels is observed. In the present study, flunarizine, a calcium ion blocker, administered as add-on medication, further lowered serum thyroxine but not TSH. The underlying biochemical principle may be an interference with the mediation of signals by calcium-calmodulin at the level of the thyroid follicle.
Adult↗
Cerebrospinal fluid and serum levels of albumin, IgG, IgA and IgM in patients with intracranial tumors and lumbar disc herniation.
CSF and serum albumin, immunoglobulin (Ig) G, IgA and IgM were measured in 100 patients with intracranial tumors, 79 with lumbar disc herniation and 68 free of neurologic diseases. Increases in one or more of the CSF Igs were observed in 46% of the patients with lumbar disc herniation and in 77% of those with intracranial tumors. The CSF-serum protein distribution suggested that impairment of the blood-brain barrier and CNS synthesis of IgG occurred in 15 and 8% of the patients with lumbar disc herniation, respectively; the proportions of tumor patients were 12 and 22%.
Adult↗
Modification of the radioreceptor assay technique for estimation of serum neuroleptic drug levels leads to improved precision and sensitivity.
This report describes a series of modifications in the radioreceptor assay procedure for monitoring of serum neuroleptic levels which resulted in a substantial increase in precision and in a higher sensitivity than is the case with existing assays. The use of a dopamine receptor preparation from pig striatum yielded a lower limit of sensitivity for haloperidol of 0.08 ng/ml, when 0.5 ml serum was used in the assay; the intra- and inter-assay coefficients of variation were 3 and 9%, respectively. The relative antipsychotic potency of various neuroleptics correlated with their optimal daily dosage. Anticonvulsants (carbamazepine, phenytoin, barbiturates), anxiolytics (diazepam, bromazepam), as well as other drugs or hormones such as lithium, chloral hydrate, L-tryptophan or L-thyroxine did not interfere with the assay. Simultaneous determination of haloperidol by the radioreceptor assay and radioimmunoassay in serum showed good correlation (r = 0.994). Good correlation was also noted between the average optimal clinical daily dose of the neuroleptics and their affinity to the dopamine receptor of the porcine striatum (r = 0.891). Cross-laboratory assessment indicated good correlation between the estimation of haloperidol by a dopamine receptor preparation from bovine caudata and porcine striata (r = 0.830). The sensitivity of the present assay was improved about 30-fold compared to those previously reported.
Animals↗
Acquired B character in a "A" group subject (a case report).
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ABO Blood-Group System↗
Further evidence for the presence of thyroxine binding globulin-like protein in human breast adipose tissue. Deiodination of thyroxine and triiodothyronine by the microsomal fraction.
The object of the study was to obtain information on how adipose tissue of normal subjects processes thyroid hormones. L-125I-thyroxine(125I-T4) is bound by the cytosol fraction of normal human female breast adipose tissue with high affinity. Computer analysis of the binding data revealed the presence of two saturable systems with Kd values of 3.9 and 29.1 nM and binding capacities of 1.7 and 8.7 pmol/mg of cytosol protein, respectively; a third binding system was non-saturable. The binding of the iodothyronines to the cytosol fraction indicated that L-triiodothyronine (T3) possessed two-fold higher affinity as compared to L-thyroxine (T4) whereas other iodothyronines had relative affinities of less than 3%. Binding of 125I-T4 was optimal at pH 7.0 and was sensitive to the action of pronase and neuraminidase. Affinity chromatography of the cytosol fraction using T3-epoxy-sepharose 6B and con A-sepharose 4B, yielded a 125I-T4 binding component that was purified 150-fold. Isoelectric focusing of the purified fraction yielded six major brands of protein which had pI values comparable to those of human serum thyroxine-binding-globulin (TBG); however, the pattern of separation was different. Incubation of the fraction with 125I-T4 followed by isoelectric focusing and autoradiography revealed that the protein bands bound radioactivity. The microsomal fraction of the adipose tissue deiodinated 125I-T4 to L-125I-triiodothyronine (125I-T3) to an extent of 0-0.8 fmol/(mg of protein X min) which corresponded to about 0.2%; T4 was not deiodinated to L-3,3',5'-triiodothyronine (r-T3).(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
A computerized approach towards the estimation of binding parameters to characterize cooperative and non-cooperative multicomponent ligand-receptor interactions.
A mathematical model has been developed to analyse multicomponent ligand-receptor interaction data directly from binding experiments without resorting to approximations such as linearization. This approach may be applied to analyze binding data for radioreceptor systems involving thyroid and steroid hormones, and drugs on neurotransmitters. Affinity constants, maximal binding capacity, cooperativity and nonspecific binding may be calculated for multiple binding systems.
Adipose Tissue↗