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Biomedical subjects

G Sedvall

Publications and source records attributed to G Sedvall.

At least 163 records · Page 9Linked to original sources

Tryptophan levels in human cerebrospinal fluid after acute and chronic ethanol consumption.

The essential amino acid tryptophan was measured in human cerebrospinal fluid by a fluorometric high-performance liquid chromatographic method. Acute ethanol consumption (80 g) by healthy volunteers lead to a decrease in tryptophan levels during intoxication. After intoxication no difference from base levels was evident. Following ingestion of a higher dose (120 g) the mean levels of tryptophan remained unchanged. Alcoholics were found to have elevated tryptophan levels in the cerebrospinal fluid as compared to healthy subjects even after abstention from ethanol for several weeks.

Adolescent↗

Improvement in central monoamine metabolism in adult coeliac patients starting a gluten-free diet.

Adult coeliac patients taking a gluten-free diet for one year showed an increase of 33% in the concentrations in CSF of major monoamine metabolites (5-HIAA, HVA and MOPEG). Tryptophan in CSF rose by 10%. There was concomitant morphological improvement in the jejunal mucosa, and the results would seem to indicate that the reduced central monoamine metabolism in untreated adult coeliacs is not primarily genetically determined but is probably related to the poor intestinal absorption.

Adult↗

Identification and determination of 1-methylimidazole-4-acetic acid in human cerebrospinal fluid by gas chromatography-mass spectrometry.

A method for the quantification of 1-methylimidazole-4-acetic acid in human CSF was developed. Methylimidazole-acetic acid was identified and quantitated in CSF. The method involves concentration of the compound on a cation exchanger, extraction of the methyl ester with ethyl acetate, and preparation of a heptafluorobutyryl derivate of the methyl ester, which is finally purified by chromatography on silica gel and quantitated by gas chromatography-mass spectrometry with the deuterated analogue as internal standard. The coefficient of variation at 1 ng/ml was 13%. The limit of sensitivity was about 0.2 ng/ml. The concentration of methylimidazole-acetic acid in lumbar CSF from healthy volunteers was below 1 ng/ml. Ventricular CSF contained higher concentrations than lumbar fluid. The existence of a rostrocaudal concentration gradient was established. There was a correlation between the concentration of methylimidazole-acetic acid and tele-methylhistamine in CSF. The concentration of methylimidazole-acetic acid in lumbar CSF from schizophrenic patients, patients with subarachnoidal haemorrhage, or patients with rheumatic disease was in the range of that in healthy volunteers.

Gas Chromatography-Mass Spectrometry↗

Clinical conditions and concentrations of MOPEG in the cerebrospinal fluid and urine of male alcoholic patients during withdrawal.

The levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG), the major noradrenaline metabolite in the central nervous system, were analyzed in lumbar cerebrospinal fluid (CSF) and urine from 74 male alcohol addicts during acute withdrawal and after 1 week of abstinence. The values obtained were compared to those of 21 healthy male volunteers. Clinical conditions were rated on the sampling days. Concentrations of MOPEG were elevated during early withdrawal and the levels decreased during detoxication. This pattern was found in both the CSF and urine, irrespective of type of drug treatment during withdrawal. The clinical symptoms improved during withdrawal and, in the beginning, there were significant positive correlations between MOPEG levels in the CSF and sleeping problems, tremors, restlessness, visual hallucinations, and elevated muscle tension. Changes in MOPEG levels correlated to changes of mood. A significant correlation was also found between low MOPEG level and craving for alcohol. Few correlations were found between MOPEG levels in the urine and clinical symptoms. The results indicate an elevated noradrenergic transmitter turnover rate in the early phase of alcohol withdrawal and a connection between noradrenaline metabolism and several clinical conditions during alcohol withdrawal.

Adult↗

Smooth pursuit eye movements, clinical symptoms, CSF metabolites, and skin conductance habituation in schizophrenic patients.

Smooth pursuit eye movements (SPEM) for two stimulus velocities (sinusoidal and triangular) were studied by visual inspection in 12 unmedicated RDC-diagnosed schizophrenic patients and in 13 matched controls. SPEM was worse in the patient group and their performance deteriorated with repeated presentations of the task. Patients with previous antipsychotic medication, previous hospitalization, higher age, late onset of manifest psychotic symptoms, and few positive psychotic symptoms had worse SPEM according to the Comprehensive Psychopathological Rating Scale. Subjects with poor SPEM showed slower habituation of skin conductance responses. There were no correlations between SPEM ratings and levels of CSF monoamine metabolites HVA, 5-HIAA, and MHPG.

Adult↗

Prolactin response following intravenous and oral sulpiride in healthy human subjects in relation to sulpiride concentrations.

Sulpiride (100 mg) was administered intravenously and orally to healthy human subjects. Serum concentrations of sulpiride and prolactin were followed for 36 h. Both routes of drug administration resulted in a pronounced and sustained increase in serum prolactin concentration. The prolactin response was positively correlated to the prolactin baseline value. The concentrations of prolactin remained at an elevated plateau for 9--36 h after drug treatment despite low drug concentrations. The level of this plateau was directly related to the normal circadian secretion of prolactin. The sustained prolactin elevation may be due to high affinity and strong binding of the compound to the regulating receptors or the formation of an active sulpiride metabolite. Prolactin and sulpiride concentrations were significantly correlated during the initial phase after intravenous sulpiride. Following intravenous and oral sulpiride the area under the concentration-time curve (AUC) for prolactin was similar despite a considerable difference in the sulpiride concentration.

Administration, Oral↗

The presence of 7-hydroxychlorpromazine in CSF of chloropromazine-treated patients.

7-Hydroxychlorpromazine (7-OHCPZ) has been identified and quantified in CSF from chlorpromazine (CPZ)-treated schizophrenic patients. The level of the metabolite in CSF was similar to that of CPZ. In serum the amount of 7-OHCPZ was about 30% of CPZ. The concentration of 7-OHCPZ in csf was positively and significantly correlated to the serum level.

Adult↗

High level of pyridoxal 5'-phosphate in the cerebrospinal fluid of adult celiac patients.

Adults with intestinal malabsorption due to celiac disease show reduced central serotonin metabolism, probably induced by a lack of essential dietary factors. Investigating a role proposed for vitamin B6 deficiency, a regular finding in untreated celiacs, the present study yields no support for the hypothesis that direct inhibition at the decarboxylation step by vitamin B6 deficiency accounts for low central serotonin turnover in adult celiacs: 11 untreated patients showing reduced 5-HIAA in the cerebrospinal fluid (71+/- 26.8 pmol/ml) had a significantly higher concentration of the metabolically active B6 vitamer pyridoxal 5'-phosphate in lumbar cerebrospinal fluid (0.06 +/- 0.34 ng/ml) than controls (0.24 +/- 0.07 ng/ml) (p less than 0.01). Cerebrospinal fluid tryptophan, precursor of serotonin, was normal (2035 %/- 649 pmol/ml). Raised pyridoxal 5'-phosphate in the cerebrospinal fluid in untreated celiac disease is an unexpected finding. Possibly it is secondary to the diminished central monamine metabolism in these patients, but further studies are needed bearing in mind that mental depression is a major cause for disability in adult celiac disease.

Adult↗

Psychic disturbances in adult coeliac disease. III. Reduced central monoamine metabolism and signs of depression.

Untreated adult coeliac patients have previously been shown to have a high frequency of depressive symptoms as reported in a personality inventory (the MMPI). In the present study we determined the concentrations of three major monoamine metabolites in samples of lumbar cerebrospinal fluid of ten consecutive adults with newly detected coeliac disease. They showed significant reduction in levels of 5-HIAA (70.3 +/- 25.4 pmol/ml). HVA (128.2 +/- 58.3 pmol/ml), and MOPEG (27.7 +/- 7.4 pmol/ml), indicating reduced central metabolism in all three monoamine pathways. The concentrations, in particular that of MOPEG, were inversely correlated with depressive symptoms reported on the MMPI scale 2 ('depression'), which conforms with current concepts on the pathogenesis of depression.

Adult↗

Relationships in healthy volunteers between secretion of monoamine metabolites in urine, and family history of psychiatric morbidity.

In 66 physically and mentally healthy human subjects the total concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), 5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and dihydroxyphenyl acetic acid (DOPAC) in urine collected between midnight and 8 AM were analyzed by mass fragmentography. In the volunteers reporting the occurrence of psychiatric morbidity among relatives an increased variance in their MOPEG levels was found as compared to the volunteers without such a family history. In the male subjects with no family history of psychiatric disease there was a positive correlation between urine and cerebrospinal fluid levels of MOPEG. The urine levels of 5-HIAA, HVA, and DOPAC did not demonstrate any changes that could be related to psychopathology within the family. Changes in urine secretion of MOPEG indicate an altered metabolism of norepinephrine/MOPEG in some subjects with the occurrence of severe psychiatric disease within the family. MOPEG levels in urine may be a predictor of a family vulnerability for psychiatric morbidity in healthy subjects.

3,4-Dihydroxyphenylacetic Acid↗

Central norepinephrine metabolism during alcohol intoxication in addicts and healthy volunteers.

The concentrations of the major norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), in lumbar cerebrospinal fluid of alcoholic patients were markedly elevated during intoxication and successively declined during 1 and 3 weeks of abstinence. During intoxication the MOPEG concentration in cerebrospinal fluid showed a statistically significant correlation with the blood alcohol concentration. In healthy volunteers who received 80 grams of ethanol, the MOPEG concentration in cerebrospinal fluid increased significantly. Healthy subjects sampled during intoxication had significantly higher concentrations of MOPEG in the cerebrospinal fluid than did subjects sampled after the end of intoxication. The results indicate that alcohol administration markedly stimulates norepinephrine metabolism in the central nervous system in human subjects possibly by increasing unit impulse activity of central noradrenergic neurons.

Adrenergic Fibers↗

Identification and determination of tele-methylhistamine in cerebrospinal fluid by gas chromatography-mass spectrometry.

The presence of tele-methylhistamine in human cerebrospinal fluid has been established. The concentration was determined with the use of deuterated tele-methylhistamine. The preparation of the deuterated standard is described. The concentration range in samples from neuropsychiatric patients was 0.1--2.5 ng/ml. The structure of the pentafluoropropionyl derivative used for gas chromatography was studied with the aid of proton nuclear magnetic resonance spectroscopy.

Child↗

Increased content of immunoreactive prostaglandin E in cerebrospinal fluid of patients with schizophrenia.

Immunoreactive prostaglandin E (I-PGE) and thromboxane B2 (I-TxB2) were measured in cerebrospinal fluid from patients with schizophrenia and from control subjects. Schizophrenics had higher I-PGE concentrations than healthy controls, patients classified as neurotics, and patients admitted for neurological investigation. I-TxB2 concentrations were similar in all four groups. These preliminary results are consistent with the hypothesis that at least in some forms of schizophrenia there may be an alteration of PG synthesis or metabolism.

Adult↗

The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects.

The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72 +/- 0.66 l/kg and total systemic clearance was 415 +/- 84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7--7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determinations of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70 +/- 9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310 +/- 91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15 +/- 5% of the dose, with a mean renal clearance of 223 +/- 47 ml/min. The bioavailability determined from combined plasma and urine data was only 27 +/- 9%. The low bioavailability was probably due to incomplete absorption.

Administration, Oral↗

Changes in endorphins and 5-hydroxyindoleacetic acid in cerebrospinal fluid as a result of treatment with a serotonin reuptake inhibitor (zimelidine) in chronic pain patients.

Both the endorphin and the serotonin systems seem to be involved in pain perception, and a significant positive correlation between the levels of endorphins and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) has been established. In the present study, 20 chronic pain patients were treated with zimelidine, a rather selective inhibitor of serotonin reuptake, or placebo. Zimelidine produced a significant pain relief and a significant reduction of the levels of endorphins and 5-HIAA in CSF, while no significant changes occurred during placebo treatment. The results indicate that both the endorphin and the serotonin systems are involved in pain perception and that the systems are functionally related.

Adult↗