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Biomedical subjects

K F Faull

Publications and source records attributed to K F Faull.

At least 109 records · Page 6Linked to original sources
PubMed1987

TRH stimulation test and depression.

A thyrotropin-releasing hormone (TRH) stimulation test was performed in 52 male inpatients with major depressive disorder. Twenty-nine percent of the 52 subjects had a delta thyroid-stimulating hormone (delta TSH) less than 5 microU/ml. The cerebrospinal fluid (CSF) amine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA), were measured in 29 subjects, and a dexamethasone suppression test (DST) was performed in 48 subjects. Of the three CSF amine metabolites, only MHPG correlated significantly with baseline TSH and none correlated with delta TSH. The baseline TSH correlated positively with the TSH response at 30 minutes. Neither baseline TSH nor delta TSH correlated with cortisol levels before or after dexamethasone. The correlation between CSF MHPG and serum TSH suggests a relationship between central norepinephrine and baseline TSH.

Adult↗
PubMed1987

CSF amine metabolites and depression.

Cerebrospinal fluid (CSF) amine metabolites were measured in 37 male subjects with major depressive disorder. Scores on the Hamilton Rating Scale for Depression (HRSD) correlated significantly with 5-hydroxyindoleacetic acid (5HIAA) and with homovanillic acid (HVA). In addition, the single suicide item of the HRSD correlated significantly with 5HIAA. Further, 5HIAA and HVA correlated significantly with each other. There was a significant positive correlation between HVA and two HRSD items, the depersonalization/derealization item and the paranoid item. Since lumbar CSF metabolite concentrations may reflect central nervous system activity of parent amines, these data suggest a relationship between depression and decreased dopaminergic and serotonergic activity.

Adult↗
PubMed1987

Plasticizers as contaminants in commercial ethanol.

A batch of 95% ethanol caused unusually strong disordering of biomembranes, which could be detected either by fluorescence anisotropy in synaptosomal membranes or by electron paramagnetic resonance spectroscopy in erythrocyte membranes. The contaminated batches of ethanol were visibly fluorescent when evaporated on filter paper. The adulterants were separated by capillary gas chromatography and the ubiquitous pollutant dioctylphthalate was identified by its low resolution electron impact mass spectrum. The remaining peaks, which were not recognized by any of the available mass spectral libraries, were identified by high resolution electron impact and chemical ionization mass spectrometry and low resolution tandem mass spectrometry using fast atom bombardment ionization; they were triethylene glycol esters and aryl phosphates. All the contaminants are industrial plasticizers. Distillation resulted in loss of the strong disordering properties of the alcohol.

Animals↗
PubMed1987

Modulation of activity of the striatal dopaminergic system during the hibernation cycle.

To evaluate how the activity of a well-established neurotransmitter pathway is modulated by a behavioral state, 3H-spiperone binding sites and dopamine (DA) and DA metabolite concentrations were measured in the striata of ground squirrels in 5 phases of the hibernation cycle. Whereas levels of striatal DA and its deaminated metabolite DOPAC did not change significantly, the concentrations of the O-methylated-deaminated metabolite, homovanillic acid (HVA), decreased in all phases of hibernation relative to euthermia. Striatal 3H-spiperone binding sites declined across the hibernation cycle in parallel with the reduction of HVA concentration; receptor binding affinity was unchanged by arousal state. In conjunction with previously reported findings, these results are consistent with the hypothesis that hibernation is associated with a down-regulation of the postsynaptic D2 receptors secondary to increased extracellular DA concentration and reduced DA degradation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Neurochemistry of dopamine in Huntington's dementia and normal aging.

We measured the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) before and after probenecid administration in normal controls and in patients with Huntington's disease. Baseline CSF HVA concentrations correlated positively with age in normal control subjects. Baseline CSF HVA concentrations were reduced in patients with Huntington's disease, and the degree of this reduction correlated with the severity of dementia and with the duration of disease. These results suggest that changes in the metabolism of dopamine by dopaminergic neurons may be associated with the dementia of Huntington's disease as well as with normal aging. These changes in dopaminergic functioning are apparently different in Huntington's disease than in normal aging and can be detected by measuring CSF HVA concentration.

Adult↗
PubMed1986

6-Hydroxymethtryptoline is naturally occurring in mammalian urine: identification by combined chiral capillary gas chromatography and high resolution mass spectrometry.

The tricyclic indole derivative 6-hydroxymethtryptoline (7-hydroxy-1-methyltetrahydro-beta-carboline) was identified as a normal constituent of human and cat urine. The identification was based on the correct retention time on a chiral capillary gas chromatographic column and on selected ion monitoring of the molecular ion with the mass spectrometer set at high resolving power (RP 10,000). The quantitation utilized a 13C-labeled analog as internal standard and demonstrated levels of 135 +/- 35 and 174 +/- 42 (pmol ml-1, mean +/- SEM) for the S(-) and R(+) enantiomers, respectively, in human urine. In cat urine, the levels were 203 +/- 55 and 108 +/- 44 (pmol ml-1, mean +/- SEM) for the S(-) and R(+) enantiomers, respectively. In human urine, the compound occurred predominantly in a conjugated form while in cat urine the free compound predominated. It was concluded that 6-hydroxymethtryptoline is naturally occurring in mammalian urine and that it most likely constitutes a metabolite of endogenous methtryptoline (1-methyltetrahydro-beta-carboline).

Adult↗
PubMed1986

Rapid hydroxylation of methtryptoline (1-methyltetrahydro-beta-carboline) in rat: identification of metabolites by chiral gas chromatography-mass spectrometry.

Racemic methtryptoline (1-methyltetrahydro-beta-carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro-beta-carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(-) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(-)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.

Animals↗
PubMed1986

Morphine and codeine from mammalian brain.

Recently, we described the presence of six immunoreactive (ir) morphinans in bovine adrenal and hypothalamus and identified one as morphine [Goldstein, A., Barrett, R. W., James, I. F., Lowney, L. I., Weitz, C. J., Knipmeyer, L. L. & Rapaport, H. (1985) Proc. Natl. Acad. Sci. USA 82, 5203-5207]. We now report that ir morphinans corresponding to the previously reported peak 1 (morphine), peak 4, and peak 5 are consistently present in extracts of bovine hypothalamus and variably present in extracts of bovine adrenal and rat brain. We no longer detect the previously reported peaks 2, 3, or 6, and we have established that they were contamination artifacts. Peak 1 is coeluted with morphine in two distinct reversed-phase HPLC systems, as is peak 4 with codeine. We have purified peak 1 and peak 4 compounds from bovine hypothalamus and determined their identities by gas chromatography/mass spectrometry (GC/MS): peak 1 is confirmed to be morphine and peak 4 is codeine.

Adrenal Glands↗
PubMed1986

Monoamine interactions in narcolepsy and hypersomnia: a preliminary report.

Principal component analysis was performed on data obtained for the concentrations of 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, homovanillic acid, and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid from a group of normal volunteers (n = 40), hypersomniac patients (n = 13), and narcoleptic patients (n = 8). All four compounds were shown to be highly intercorrelated in the normal volunteers. In the hypersomniac patients, 3-methoxy-4-hydroxyphenylethylene glycol did not appear to be correlated with the other three compounds. In the narcoleptic patients, homovanillic acid and 3,4-dihydroxyphenylacetic acid appeared not to be correlated with the other two metabolites. The results provide tentative support for a neurochemical distinction between narcolepsy and hypersomnia and suggest that attention should be given to a possible malfunction of the dopamine system in narcolepsy and norepinephrine in hypersomnia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

CSF monamine metabolites in movement disorders and normal aging.

We measured four monoamine metabolite levels in CSF before and after probenecid administration to normal controls and to patients with Huntington's disease (HD), dystonia, and tardive dyskinesia. We identified differences only for the dopamine metabolite homovanillic acid (HVA), which showed increased baseline values and decreased turnover in normal aging, but decreased baseline values and normal turnover in HD. These results suggest that dopamine neurons are linked both to normal aging and to HD and that CSF HVA studies can distinguish differences in the functioning of dopamine neurons in normal aging and HD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Extractive acylation and mass spectrometric assay of 3-methoxytyramine, normetanephrine, and metanephrine in cerebrospinal fluid.

The chemical analysis of 3-methoxytyramine, normetanephrine, and metanephrine in tissues, blood, and cerebrospinal fluid is complicated by the low levels in which they occur and the amphoteric nature of the functional groups, which hampers their isolation from aqueous media. In the present report, we describe a practical and simple method for the routine isolation and derivatization of 3-methoxytyramine, normetanephrine, and metanephrine in high yield from aqueous samples like cerebrospinal fluid. The metabolites are simultaneously derivatized with pentafluoropropionic anhydride and extracted into an organic solvent. After further treatment with pentafluoropropionic anhydride under anhydrous conditions, the samples are ready for GC/MS analysis. The method is able to exploit the theoretical maximal sensitivity available in the electron capture negative-ion chemical ionization mode without any apparent losses during extraction and derivatization, giving limits of detection in the low picogram range. Mean levels of free 3-methoxytyramine, normetanephrine, and metanephrine in human cerebrospinal fluid were 3.77, 5.20, and 0.40 pmol/ml. Assay of pools of squirrel monkey, human, and canine cerebrospinal fluid with and without previous enzymatic hydrolysis demonstrated that the three metabolites occur predominantly in a conjugated form.

Acylation↗
PubMed1985

Serotonin and schizophrenia: correlations between serotonergic activity and schizophrenic motor behavior.

Increased serotonergic activity in animals has been associated with a variety of stereotyped motor behaviors. In addition, serotonin facilitates brainstem, reticular, and spinal motor neuronal activity implicated in the expression of these behaviors. This report presents positive correlations between both peripheral (platelet serotonin levels) and central (cerebrospinal concentrations of 5-hydroxy-indoleacetic acid) measures of serotonin metabolism and the symptom of peculiar or unusual mannerisms and posturing in schizophrenic patients. The findings are discussed in light of the animal behavioral correlates of increased serotonergic activity and the stereotyped affectomotor behavior seen in some schizophrenic patients.

Adult↗