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PubMed1980

Amine metabolism, thyroid function and response to clomipramine and maprotiline medication in depression.

The various clinical types of depression may correspond to biochemically distinct forms of the condition. If these could be characterized, antidepressant treatment might be tailored to correction of the underlying biochemical change(s) in individual patients. In particular, the selective actions of clomipramine and maprotiline on the serotonergic and noradrenergic systems respectively might be exploited therapeutically. Studies of the clinical response to these two antidepressants included tests of urinary 5-hydroxy-indoleacetic acid (5-HIAA) excretion and of serum thyroxine levels. While thyroid stimulation tests may prove of value for investigating depressed patients, urinary 5-HIAA levels are inconvenient, subject to extraneous influences and hard to interpret in terms of brain chemistry. (An alternative is proposed in the next paper.)

Adolescent↗
PubMed1983

Liquid-chromatographic determination of indole-3-acetic acid and 5-hydroxyindole-3-acetic acid in human plasma.

We describe a "high-performance" reversed-phase liquid-chromatographic method for determination of indole-3-acetic acid (I) and 5-hydroxyindole-3-acetic acid (II) in human plasma. I is eluted at 1.0 mL/min with a mixture of 1-pentanesulfonic acid (pH 3.1), methanol, and water. It is detected by fluorometry. A mixture of citric acid/sodium phosphate solution (pH 4.8) and methanol, at 1.5 mL/min, is used to elute II, which is detected with an electrochemical cell. Platelet-poor plasma samples were pretreated with HCl, perchloric acid, and trichloroacetic acid for protein precipitation. Best results were obtained with the last (protein precipitation is incomplete with HCl, while recoveries of I are concentration dependent with perchloric acid). Analytical recoveries were 58% (SD 3.1%, CV 5.3%, n = 12) and 79% (SD 3.3%, CV 5.3%, n = 9) for I and II, respectively. Concentrations of I and II in plasma ranged from 0.61 to 3.32 (mean 1.54, SD 0.59, n = 15) mumol/L and from 33.0 to 102.6 (mean 51.8, SD 20.1, n = 16) nmol/L, respectively.

Adult↗
PubMed1984

Novel flushing provoked by volatile anesthetics in Mastomys natalensis bearing a transplantable substrain of gastric carcinoid that predominantly secretes serotonin.

A tumor substrain secreting a large amount of serotonin [5-hydroxytryptamine (5-HT); CAS: 50-67-9; 3-(2-amino-ethyl)indol-5-ol] and a minute amount of histamine (CAS: 51-45-6) has been isolated from the previously established strain of transplantable gastric carcinoid of Mastomys (Praomys) natalensis secreting both histamine and 5-HT. Mastomys bearing a large growing transplant and excreting a large amount of 5-hydroxy-indoleacetic acid [(5-HIAA) CAS: 54-16-0] were associated often with reddening of the nose, lower lip, auricles, hands, and feet. Soon after the animals were anesthetized by ether or other volatile anesthetics, the tinges of red of the above-mentioned exposed parts abruptly turned bright red and rapidly spread over the neck, upper chest, and epigastric area. The reddening was transient, lasting 1.5-5 minutes, thereby fulfilling the criteria of flushing. The severity of ether-provoked flushing in tumor-bearing Mastomys paralleled the urinary excretion levels of 5-HIAA. The ether-provoked flushing was prevented completely by sc injection of either ketanserin (150 micrograms) or somatostatin (20 micrograms). The same ether-provoked flushing as found in tumor-bearing Mastomys could be reproduced in normal ones by constant infusion of 20 mg 5-HT/kg/24 hours (i.e., doses comparable to those released from a transplanted tumor) through an osmotic minipump implanted subcutaneously.

Anesthetics↗
PubMedDate not supplied

The effect of multiple imipramine administration on monoaminergic systems of the rat brain.

Wistar rats received imipramine (IMI) in daily single doses of 1 or 10 mg/kg ip for up to 4 weeks. They were killed after 1,2 or 4 weeks, 24 hr after the last dose of IMI. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) were assayed in the whole brain. Whole brain dopa and 5-hydroxytryptophan (5-HTP) were assayed 30 min after administration of a central decarboxylase inhibitor, 3-hydroxybenzylhydrazine (100mg/kg). Specific binding of 3H-clonidine and 3H-WB4101 to cortical membranes was tested in rats after 1 week (only 3H-clonidine binding) and 4 weeks of IMI treatment. The levels of biogenic amines did not change during the treatment; the accumulation of dopa was transiently depressed, and that of 5-HTP - transiently elevated (only after the high dose of IMI), but after 4 weeks of treatment the accumulation of both amino acids did not differ from that in control rats. After 4 weeks of treatment with the high dose of IMI the binding of both 3H-clonidine and 3H-WB4101 to specific receptors was significantly depressed. The results suggest that under the influence of chronically administered IMI transient disturbances of the synthesis of biogenic amines occur, but they disappear after a more prolonged treatment. In the course of prolonged treatment, however, the capability of binding of radioligands by kappa-adrenergic receptors diminishes, and this suggests the development of hyposensitivity of the kappa-adrenergic system.

Animals↗
PubMed1983

The effect of positive and negative air ions on bronchial asthma.

The effect of prolonged exposure to either positive or negative small air ions was studied in nine patients with bronchial asthma, of whom seven had reported increased respiratory symptoms in association with weather changes. On consecutive days, while grounded, patients were exposed for six hours to approximately 10,000/cc of either positive or negative ions. Pulmonary function, pulse and blood pressure were measured throughout the exposure. Questionnaires to assess emotional state and physical symptoms were completed after 15 minutes and five hours each day. Urinary 5-hydroxy indoleacetic acid (5HIAA) excretion was measured. Patients were continued on theophylline but adrenergics and corticosteroids were withheld. No patient experienced an exacerbation of asthma. Symptoms, pulmonary function, pulse and blood pressure, urinary 5HIAA excretion and the response to the questionnaires did not differ significantly between the two ion exposures. Thus moderately long exposure to positive or negative small air ions did not influence the clinical condition of these patients, many of whom reported exacerbations with weather changes. The findings do not support a significant role of small air ions in exacerbations or treatment of bronchial asthma.

Adult↗
PubMed1978

Effect of prazosin on norepinephrine concentration and turnover in rat brain and heart.

Prazosin hydrochloride injected i.p. into rats markedly increased MOPEG sulfate (3-methoxy-4-hydroxy-phenylethylene glycol sulfate) concentration in brain and the rate of MOPEG sulfate accumulation after probenecid. The increase in MOPEG sulfate was dose-related over a 5-40 mg/kg dose range. After a 20 mg/kg dose of prazosin, the increase in MOPEG sulfate was greater than after the same dose of phenoxybenzamine and persisted for up to 24 hr. The rate of metaraminol disappearance from rat brain after alpha-methyl-m-tyrosine injection and the decline in brain norepinephrine after inhibition of its synthesis by alpha-methyltyrosine injection were increased in rats pretreated with prazosin. These findings indicate that prazosin increased brain norepinephrine turnover, probably via compensation to central alpha adrenoceptor blockade. Prazosin increased sertonin and 5-hydroxy-indoleacetic acid concentration and slightly decreased 3,4-dihydroxy-phenylacetic acid in rat brain. Although prazosin had little effect on brain norepinephrine concentration, heart norepinephrine was depleted for up to 16 hr after a 20 mg/kg dose of prazosin, and the depletion at 4 hr was dose-related down to 2 mg/kg of prazosin. These biochemical changes may all result from prazosin's block of alpha adrenergic receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

[Model for auxin receptor].

Literary data on correlation between the structure and auxin activity of aryl-, arylalkan- and aryloxyalkancarboxylic acids and those of 3-indolylacetic acid are reviewed. The structure of auxins is compared to that of their inactive structural analogs in terms of a literary hypothesis on the bifunctional binding of auxins to the receptor, which allowed to construct a model for the structure of the auxin receptor (site responsible for intrinsic binding of auxins). The geometric parameters of this receptor site and specific arrangement of specific auxin binding sites have been proposed. It is demonstrated that during auxin absorption on the receptor the conformation of the latter is changed, which may be accounted for as a primary functional effect of auxins on the receptor.

Carboxylic Acids↗
PubMed1981

[Effects of peripheral electric stimulation on the central 5-hydroxytryptamine in mice: relation to the peripheral stimulation-produced analgesia (author's transl)].

Effects of peripheral electric stimulation (PES) on the functional state of central 5-hydroxytryptamine (5-HT) and on the analgesic effect were investigated in mice. The PES was administered by a passing rectangular wave (0.45 mA, 5 msec, 5-100 Hz) for 2 hr through bipolar electrodes implanted subcutaneously at the base of the tail. Whole brain 5-HT concentration remained unchanged with the PES at 20 Hz, whereas 5-hydroxy-indoleacetic acid concentrations were significantly increased in the whole brain. A significant increase in the whole brain compared with that in control was already attained at 30 min after initiation of the PES. Number of head-twitches induced by 5-methoxy-N,N-dimethyltryptamine after the PES was clearly potentiated. Increase in the number of head-twitches after the PES was abolished by administration of p-chlorophenylalanine, a 5-HT depletor, and 5,6-dihydroxytryptamine, a 5-HT neurotoxin. The PES for 1 hr produced an antinociceptive effect. Administration of L-5-hydroxytryptophan enhanced the antinociceptive effect induced by PES, while methysergide and naloxone completely abolished this antinociception. Thus, 5-HT neurons are probably excited functionally by the PES, and the mechanisms of analgesia produced by the PES involve both endogenous opiate systems and central serotonergic mechanisms.

5-Hydroxytryptophan↗
PubMed1994

[Neuro-acanthocytosis with associated myopathy. A case report].

Abnormalities of striated muscle histology in patients with neuroacanthocytosis have been previously attributed to chronic denervation. This hypothesis is based in the presence of axonal peripheral neuropathy. In this 37-year-old patient clinical, biochemical and histologic data revealed a non specific primary myopathy. Other important findings were decreased levels of 5-hydroxy-indoleacetic acid (5-HILA) and homovanillic acid (HVA) in the CSF, cerebellar and basal ganglia atrophy seen in MRI and infertility of probable gonadal origin.

Acanthocytes↗
PubMed1994

Tolerance to diacetyl morphine antinociception: effects on brain serotonin.

The effects of 5 mg kg-1 diacetyl morphine (DAM) on brain serotonin metabolism of rats were investigated following tolerance to the antinociceptive effects of 2.5 mg kg-1 DAM. Brain levels of tryptophan and 5-hydroxy indoleacetic acid (5-HIAA) were higher in the DAM-tolerant rats killed 24 h after last daily administration of 2.5 mg kg-1 DAM. Administration of 5 mg kg-1 DAM produced less antinociception in DAM-tolerant than DAM-naive rats and increased brain tryptophan concentration in both tolerant and naive rats. 5-HIAA concentrations increased only in naive rats. Combined use of drugs interfering with brain 5-HT turnover along with opiates may be of future benefit for the treatment of chronic pain.

Analysis of Variance↗
PubMed1995

[Pharmacokinetic investigation of 5-day multiple dose of tropisetron capsule in patients who had received cisplatin and the usefulness of tropisetron capsule in the treatment of nausea and vomiting].

We have investigated the pharmacokinetics of a 5-day multiple oral dose of 5 mg tropisetron capsule in patients with malignant tumour who had received cisplatin single administration. Its anti-emetic effects on acute and delayed emesis and vomiting were also investigated. During the 5 days after this administration, changes in the release and metabolism of serotonin were investigated. The results may be summarized as follows: 1) The pharmacokinetic parameters of tropisetron revealed no significant change in the data between day 1 and day 5. Also, the parameters were almost similar to those observed in healthy adult males (clinical phase I study); Cmax. T1/2 and AUC 0-24 hrs on day 1 were 9.1 +/- 2.1 ng/ml, 12.5 +/- 4.2 hrs, 85.5 +/- 22.7 ng.hr/ml, respectively. The urinary excretion of the parent drug up until 24 hours after administration on day 1 was 3.8% of the dose administered and 2.9% of the total dose after the last administration; no difference in the urinary excretion rate was observed in healthy subjects. It was thus suggested that hydration accompanied by cisplatin administration did not affect the pharmacokinetics of tropisetron. 2) The changes in the amount of urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) during 5 days after cisplatin administration were observed; urinary excretion of 5-HIAA increased 2.3 times (1.3-5.4 times) the baseline on the average during 6 to 12 hours on day 1. In 6 out of 10 patients, the increases in urinary excretion of 5-HIAA showed double or more the baseline during 2 to 5 days after cisplatin administration. Serotonin was thus deemed to be related to the development of delayed emesis. 3) The anti-emetic effects of tropisetron on acute and delayed emesis and vomiting were rated as "markedly effective" in 6 out of 11 patients (54.6%) and "effective" in 1 out of 11 patients (9.1%) on day 1; vomiting did not occur in any of these 7 patients. Tropisetron also controlled emesis and vomiting during days 2-5, and was rated as "almost favorable" in 6 out of 11 patients (54.5%). Further, in 4 out of 6 patients, in whom the urinary excretion of 5-HIAA was increased on day 2 onwards, vomiting did not occur during the time when the urinary excretion of 5-HIAA was increasing. On the basis of the above results, tropisetron is deemed to have certain antiemetic effects on delayed vomiting as well. Its 5-HT3 receptor mediated mechanism was similarly seen to inhibit acute nausea and vomiting.

Adult↗
PubMed1993

Ondansetron, an antagonist of 5-HT3 receptors, in the treatment of antineoplastic drug-induced nausea and vomiting in children.

The aim of this study was to evaluate the efficacy and safety of ondansetron, an antagonist of 5-hydroxytryptamine type 3 (serotonin 3) (5-HT3) receptors, in controlling nausea and vomiting induced by antineoplastic therapy in children affected by cancer. Six patients affected by nausea and vomiting due to antineoplastic drugs were treated with ondansetron (4 mg/m2). Urinary samples for the assay of serotonin and 5-hydroxy-indoleacetic acid (5-HIAA) were collected 24 hr before antineoplastic drug treatment, 24 hours after the start of antineoplastic therapy and, 24 hr after the start of ondansetron therapy. All patients were affected by nausea and vomiting within two to four hr after the antineoplastic treatment. Urinary concentrations of serotonin and 5-HIAA were higher and statistically significant (P < 0.01) with respect to basal values. Treatment with ondansetron significantly reduced the number of episodes of nausea and vomiting, as well as the urinary values for serotonin and 5-HIAA.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Biogenic amines derived from tryptophan in systemic and cutaneous scleroderma.

Blood levels of serotonin (5-HT) and urinary excretion of 5-hydroxyindole-acetic acid (5-HIAA), tryptamine (T), and indole-acetic acid (IAA) were determined in 39 cases of systemic scleroderma and in 7 cases of very severe cutaneous scleroderma. The T/IAA ratio was normal and serotonin elevated in mild and rather severe acrosclerosis alike, i.e. in systemic scleroderma with pronounced vascular involvement. The T/IAA ratio was increased and serotonin normal in severe acroscleroderma, representing an intermediate form or transition to diffuse scleroderma, in severe diffuse scleroderma, and in severe cutaneous scleroderma. The T/IAA ratio and serotonin level were both elevated in a few cases of systemic scleroderma and in severe generalized morphea with concomitant vascular changes. The findings suggest impaired monoamine oxidase (MAO) activity in scleroderma with consequent accumulation in the organism of biogenic amines derived from tryptophan. An increased T/IAA ratio seems to be of prognostic significance in scleroderma, suggesting an adverse course of the disease.

Colorimetry↗
PubMed1993

Urinary excretion of indolylacryloylglycine, indolylacetic acid and 5-hydroxyindolylacetic acid in burn patients.

Indolylacryloylglycine (IAcrGly) is a regular constituent of human urine. Changes in its excretion have been observed, among other conditions, in some skin diseases. Skin lesions in burns are dealt with in the present paper. IAcrGly excretion has been followed during several weeks of hospital treatment and compared with that of two other tryptophan metabolites, namely indolylacetic acid (IAA) and 5-hydroxyindolylacetic acid (5-HIAA). The average excretion of IAcrGly was significantly lower especially between day 3 and 15 post injury. Some alternative explanations of these results are put forward.

Adolescent↗
PubMed1977

Comparison of the Hoesch and the Watson-Schwartz tests for urinary porphobilinogen.

A comparison of the Hoesch and the Watson-Schwartz tests shows that the latter, although slightly more complicated, generally yields more concise results and is superior in sensitivity and specificity for porphobilinogen. The recommendation of the Hoesch test for use as a "bedside screening" method seems unrealistic. Before the diagnosis of an "inducible" porphyria is made, a positive Hoesch test requires that indoles, indoleacetic acid, methyldopa, end-stage alcoholic malnutrition, and phenazopyridine HCl be excluded, to avoid misinterpretation.

Chromatography, Thin Layer↗
PubMed1997

Urinary 5-hydroxytryptophol following acute ethanol consumption: clinical evaluation and potential aviation applications.

HYPOTHESIS: The unknown prevalence of alcohol use and misuse among aviation pilots, crewmembers and associated support personnel call for continuous improvement of methods for detecting recent alcohol use. Early detection is essential to proper treatment and prevention of potentially catastrophic mishaps. Urinary 5-hydroxytryptophol (5HTOL), a serotonin (5HT) metabolite, has shown promise in the clinical setting as a noninvasive marker of recent alcohol consumption. METHODS: The urinary 5HTOL concentrations of 11 male and female subjects were followed for approximately 24 h following dosing with ethanol 0.6 g.kg-1. Concentrations were reported as a ratio of 5HTOL to 5-hydroxy-indoleacetic acid (5HIAA), 5HTOL/5HIAA (pmol/nmol), to compensate for urinary dilution and elevated 5HTOL levels due to dietary intake. Data from one male subject was excluded after he admitted to continued alcohol consumption subsequent to dosing and missing several urine samples. RESULTS: 5HTOL/5HIAA ratios remained above the 15 pmol/nmol cutoff for recent alcohol use for approximately 11-16 h in all except one subject. Calculations based on body weight and administered alcohol dose suggest that measurable blood alcohol levels would exist for only 5-7 h post ingestion. CONCLUSION: This study confirmed the extended elevation of 5HTOL/5HIAA ratios observed in earlier studies, even at the relatively low alcohol dose used herein. 5HTOL appears to be a marker for acute alcohol consumption worthy of further investigation by military and civilian authorities. Potential aviation applications of 5HTOL include validation of measurable blood alcohol concentrations, investigation of poor performance due to hangover effects, and as a forensic toxicology tool in aircraft accident investigations to distinguish between actual alcohol ingestion and post-mortem alcohol synthesis.

Acute Disease↗
PubMed1997

Effects of exogenous phytohormones on plastid tRNA modifications in ragi coleoptiles.

The effects of phytohormones on plastid tRNA modifications were investigated in ragi (Eleucine coracana) coleoptiles. Intact 7-day old dark-grown ragi seedlings were given phytohormone, indoleacetic acid (IAA) or isopentenyladenine (i6A) treatment and grown in the dark or under white fluorescent light; coleoptiles were harvested 24 hr following treatment, and plastid total tRNAs were isolated and analyzed for their content of modified nucleotides. A total of 14 modified nucleotides were identified in the total digests of ragi plastid total tRNA preparations; significant increases in the content of some modified nucleotides were observed following treatment of phytohormones in the dark and light. The relative amounts of pT, pm1G, pm7G and pm1A in IAA-treated dark-grown, pi6A, pm2G and pCm in IAA-treated light-grown, and pT and pm2G in i6A-treated light-grown ragi coleoptiles were 2 to 10 times higher than the untreated control coleoptile plastid total tRNA. In order to gain a better understanding of the effects of phytohormones on ragi plastid tRNA modifications, we purified plastid tRNA(Ile)(GAU) from coleoptiles of the aforementioned ragi seedlings and analyzed its modifed nucleotide content. We find that the content of pGm was 4 to 5 times higher in the tRNA(Ile)(GAU) purified from i6A- or IAA-treated dark-grown coleoptiles, and pm7G was 5 to 6 times higher in the tRNA(Ile)(GAU) of i6A-treated light-grown ragi coleoptiles. These results suggest that the synthesis or activity of some plastid-specific tRNA-modifying enzymes may be enhanced by i6A and IAA with two different modes of regulation, one operating in the light and the other operating in the dark.

Darkness↗
PubMed1979

Urinary neurotransmitter metabolites in drug-free chronic schizophrenic patients measured by gas chromatography selected positive ion monitoring.

The free urinary metabolites, homovanillic, indoleacetic and 5-hydroxyindoleacetic acid were measured in 24 h urines obtained from seven highly selected drug-free chronic schizophrenic patients and seven mentally normal control subjects on a low amine diet. Gas chromatography selected ion monitoring of silylated extracts was used to assay each metabolite using its own deuterated form as an internal standard. In the electron impact mode the positive ion fragments used to quantitate the amount of each metabolite in the urine were, respectively, m/z 209/211 for homovanillic acid, 319/321 for indoleacetic acid and 290/292 for 5-hydroxyindoleacetic acid. It was found essential that each compound be assayed using its own deuterated derivative as the internal standard. When expressed per mg creatinine, the homovanillic and 5-hydroxyindoleacetic acid levels of the chronic schizophrenic patients were in the normal range, but indoleacetic acid was slightly and statistically significantly higher, p = 0.01.

Acids↗