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Biomedical subjects

K F Faull

Publications and source records attributed to K F Faull.

At least 91 records · Page 5Linked to original sources
PubMed1989

1H NMR spectroscopy: an approach to evaluation of diseased skin in vivo.

1H nuclear magnetic resonance (NMR) spectroscopy was tested for its applicability in evaluating diseased skin. In order to explore potential spectral markers characteristic of diseased tissue, perchloric acid (PCA) extracts of psoriasis and malignant melanoma tissues were compared with normal skin, and changes in melanoma after heat treatment were monitored. In psoriatic plaque extract, the spectral peak intensity ratios of Glu: Ser, creatine: Gly, and taurine: Ala were approximately three-fold compared with symptom-free or normal skin, whereas Val: Leu/Ile was one-half the normal skin ratio. In melanoma extracts, the phosphorylcholine (PC)/glycerophosphorylcholine (GPC): Ala, Glu: Ser, and lactate: Ala ratios were five-, three-, and two-fold higher, respectively, than normal skin and the Val: Leu/Ile ratio was two-thirds of normal skin. With heat treatment, PC/GPC: Ala and Glu: Ser ratios decreased, whereas lactate: Ala and Val: Leu/Ile ratios increased three-fold and one-third, respectively. Results indicate that 1H NMR spectroscopy is a sufficiently sensitive technique to distinguish normal from diseased skin. The main attraction of this technique lies in the possibility of non-invasive study of various skin diseases, malignant transformation of benign tumors, and responses to treatment. Several methodologic problems remain to be resolved before a meaningful interpretation of in vivo observations becomes feasible. Correlation of in vivo and in vitro findings is an essential step toward this goal.

Adult↗
PubMed1989

Concentrations of tryptoline and methtryptoline in rat brain.

Combined gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry have been used to identify and quantify tryptoline, methtryptoline, 5-hydroxytryptoline, and 5-hydroxymethtryptoline as their heptafluorobutyryl derivatives in extracts of rat brain. Tryptoline and methtryptoline were identified on the basis of their retention times and mass spectral characteristics: they were reliably detected in brain tissue extracts without interference from artifactual formation; their whole brain concentrations ranged between 0.2 and 3 ng/g; and they had a similar neuroanatomical distribution, with the highest concentrations in the cerebellum and the cortex. Smaller quantities of 5-hydroxytryptoline and 5-hydroxymethtryptoline were also identified on the basis of their retention times and mass spectral characteristics. However, the significance of this finding is unclear, because these two compounds were accompanied by larger quantities of their tetradeuterated analogues formed from tetradeuterated-5-hydroxytryptamine added at the time of tissue homogenization; this result suggests that formation of 5-hydroxytryptoline and 5-hydroxymethtryptoline occurred during tissue homogenization, sample preparation, or both.

Animals↗
PubMed1989

Relationship between plasma and cerebrospinal fluid norepinephrine and dopamine metabolites in a nonhuman primate.

Major and minor pathways of metabolism in the mammalian CNS result in the formation of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMN) from norepinephrine (NE), and homovanillic acid (HVA) and 3-methoxytyramine (3-MT) from dopamine (DA), respectively. The correlational relationships between HVA and 3-MT and between MHPG and NMN in primate CSF and plasma have not been described. These relationships may help to elucidate the usefulness of CSF and plasma metabolites as indices of CNS NE and DA activity. In addition, because NMN is unlikely to cross the blood-brain barrier. CSF NMN concentrations would not be confounded by contributions from plasma, which is a major issue with CSF MHPG. We have obtained repeated samples of plasma and CSF from drug-naive male squirrel monkeys and have measured the concentrations of MHPG, HVA, NMN, and 3-MT to define their correlational relationships. For the NE metabolites, significant correlations were obtained for CSF MHPG and NMN (r = 0.806, p less than 0.001), plasma MHPG and CSF NMN (r = 0.753, p less than 0.001), and plasma and CSF MHPG (r = 0.776, p less than 0.001). These results suggest that CSF and plasma MHPG and CSF NMN may reflect gross changes in whole brain steady-state noradrenergic metabolism. Only a single significant relationship was demonstrated for the DA metabolites, with CSF 3-MT correlating with plasma HVA (r = 0.301, p less than 0.025). The results for the DA metabolites probably reflect regional differences in steady-state brain dopaminergic metabolism.

Animals↗
PubMed1988

Measurement of beta-carbolines by high-performance liquid chromatography with fluorescence detection.

A method using high-performance liquid chromatography with fluorescence detection was developed for the determination of beta-carboline compounds norharman, harman, norharmol, and harmol in lung. Aqueous derivatization with acetic anhydride was used to facilitate the isolation and separation of the phenolic compounds and to reduce the fluorescence background of the biological samples. Harman was identified and quantitated in rat lung (1.88 +/- 0.55 ng/g) using this method and its identity confirmed by means of gas chromatography-negative-ion chemical ionization mass spectrometry.

Animals↗
PubMed1988

Influence of freezer storage time on cerebral biogenic amine and metabolite concentrations and receptor ligand binding characteristics.

Brains from breed and age-matched canines stored at -80 degrees C for between 3 and 44 months showed a time-dependent decline in the concentration of norepinephrine in the amygdala and dopamine and norepinephrine in the caudate. No changes were seen in the density or ligand affinities of prazosin or spiperone binding sites in the same areas nor were there changes in quinuclidinyl benzylate binding sites in the frontal cortex. The changes in dopamine concentrations in the caudate were not accompanied by changes in the concentrations of dopamine metabolites. The chromatograms from which the dopamine and norepinephrine concentrations were estimated contained several unidentified, amperometrically detectable, extraneous peaks which increased in size in the older tissue samples. These results suggest that the decline in dopamine and norepinephrine concentrations was not the result of enzymatic breakdown, but probably the result of chemical decomposition. These findings have significance for the measurement of dopamine and norepinephrine concentrations in autopsied brains kept frozen in storage.

Amygdala↗
PubMed1988

Measurement of phenylacetic acid in cerebrospinal fluid and plasma using combined gas chromatography/electron capture chemical ionization mass spectrometry.

Details are presented of an ultra-sensitive gas chromatographic/mass spectrometric assay for phenylacetic acid in plasma and cerebrospinal fluid based on measurements of the relative intensities of the carboxylate anions, derived from the penta- and tetrafluorobenzyl esters under electron capture chemical ionization conditions, of unlabeled and a (13C2)-labeled internal standard. The limits of detection for the penta- and tetrafluorobenzyl esters are 0.85 and 4.0 pg respectively, and the assay is capable of measuring phenylacetic acid concentrations in samples as small as 20 microliter of CSF and plasma. The penta- and tetrafluorobenzyl esters are chromatographically separated on the gas chromatograph column, which allows for their co-injection and independent measurement from the same chromatogram.

Animals↗
PubMed1988

19F magnetic resonance imaging and spectroscopy of a fluorinated neuroleptic ligand: in vivo and in vitro studies.

The bulk biodistribution of a trifluorinated neuroleptic (fluphenazine) was studied using 19F magnetic resonance imaging (MRI). Fifteen male Sprague-Dawley rats were injected with fluphenazine (120 mg/kg) and scanned in a G.E. CSI 2.0 tesla MRI system. The rats were killed following scanning and the brains were removed. The excised brains were then scanned using 1H and 19F MR techniques. The fluorinated neuroleptic was imaged at the injection site, spectroscopically detected in vivo in the head, and spectroscopically localized in the whole brain. These data suggest that in vivo 19F MRI of fluorinated agents is possible and could have clinical and research applications to the neurosciences.

Animals↗
PubMed1988

Determination of tryptamine in rat brain by gas chromatography-mass spectrometry.

Tryptamine (TA) occurs in trace levels in the brain, but its role in the central nervous system is not clear. However, there is evidence that TA may be a neuromodulator since it binds to specific binding sites in the brain. TA was measured as a diheptafluorobutyryl derivative in rat whole brain by capillary gas chromatography-mass spectrometry using negative chemical ionization (NCI) and single ion monitoring (SIM). d(4)-TA was used as the internal standard. The ions m/z 532 and m/z 536 were monitored to identify TA and d(4)-TA, respectively and to calculate the concentration of TA in rat whole brain which was found to be 0.19 +/- 0.08 ng g(-1) (n = 8). The results confirm the earlier TA concentrations measured by GC-MS using positive electron impact ionization. However, NCI improved the signal/noise ratio of the method increasing its sensitivity for TA.

Journal Article↗
PubMed1988

6-Acetylmorphine: a natural product present in mammalian brain.

Recently, we described three substances in bovine hypothalamus, adrenal, and rat brain recognized by antisera raised against morphine, and we identified one as morphine and another as codeine by GC/MS. We now report the identification of the third immunoreactive (ir) morphinan from bovine brain as 6-acetylmorphine by chemical conversion to morphine, GC/MS, and high-resolution mass measurement. 6-Acetylmorphine has not previously been described as a natural product in plants or animals, but it has long been known as the metabolite in part responsible for the biological properties of heroin. However, we have excluded slaughter-house or laboratory contamination by any morphinan as well as derivation from the morphine in tissues during our procedures. 6-Acetylmorphine is known to be more potent than morphine in vivo chiefly by virtue of its greater penetration into the central nervous system. Should morphinans prove to have physiological functions in animals, the properties of 6-acetylmorphine make it ideal for fulfilling the role of a peripheral-to-central hormone.

Animals↗
PubMed1988

Harman in alcoholic beverages: pharmacological and toxicological implications.

Harman, a beta-carboline compound, was identified and quantitated in beer and wine samples using a combination of high performance liquid chromatography with fluorescence detection and gas chromatography-negative chemical ionization mass spectrometry. The concentration of harman in beer (7.3-140.0 ng/ml) was greater than in wine (0.8-10.5 ng/ml) and was not related to alcohol content. The pharmacological and toxicological implications of harman in alcoholic beverages are discussed.

Alcoholic Beverages↗
PubMed1987

Application of combined gas chromatography/mass spectrometry to neurotransmitter research.

The features of flexibility, sensitivity and specificity continue to make GC/MS a valuable technique for identification and quantification of neuro-transmitters and related compounds. In this report four recent examples are presented which highlight the potentials of this technique. The traditional concept that GC/MS equipment is expensive and complex to operate warrants reconsideration in light of recent manufacturing trends in automation, computerization and the introduction of cheaper bench-top models.

Animals↗
PubMed1987

Brain dopamine receptor levels elevated in canine narcolepsy.

Concentrations of dopamine D2 receptors in discrete brain areas differed significantly between dogs with the genetically transmitted form of narcolepsy, and age- and breed-matched controls. D2 receptors were assayed and quantified with Scatchard analysis using [3H]spiperone. Receptor densities in the nucleus accumbens, rostral caudate, and amygdala were consistently higher in narcoleptic animals. In amygdala, dopamine receptor abnormalities were associated with elevated dopamine and 3,4-dihydroxyphenylacetic acid concentrations, but no change in 3-methoxytyramine or homovanillic acid concentrations. These data indicate mesolimbic system involvement in canine narcolepsy and point to impaired dopamine release as a possible etiologic factor.

3,4-Dihydroxyphenylacetic Acid↗