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W R Matson

Publications and source records attributed to W R Matson.

18 recordsLinked to original sources
PubMed1992

Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex.

Huntington's disease (HD) is characterized by gradually evolving selective neuronal death. Several lines of evidence suggest that an excitotoxic mechanism may play a role. Tryptophan metabolism leads to production of quinolinic acid, an N-methyl-D-aspartate (NMDA) receptor agonist, and to kynurenic acid, an antagonist at these same receptors. We recently found increased kynurenine to kynurenic acid ratios in HD postmortem putamen and decreased kynurenic acid concentrations in cerebrospinal fluid, consistent with decreased formation of kynurenic acid in HD brain. In the present study we used HPLC with 16 sensor coulometric electrochemical detection to measure kynurenic acid and 18 other electrochemically active compounds in 6 cortical regions, caudate and cerebellum from controls, HD, Alzheimer's disease (AD), and Parkinson's disease (PD) patients. Significant reductions in kynurenic acid concentrations were found in 5 of 6 cortical regions examined. Smaller reductions of kynurenic acid in the caudate, cerebellum and frontal pole were not significant. No significant reductions were found in the AD and PD patients. Both uric acid and glutathionine were significantly reduced in several regions of HD cerebral cortex, which could signify abnormal energy metabolism in HD. Since kynurenic acid is an antagonist of excitatory amino acid receptors, a deficiency could contribute to the pathogenesis of neuronal degeneration in HD.

Aged↗
PubMed1992

Rett syndrome: stimulation of endogenous biogenic amines.

Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80% O2 and 20% CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

Brain↗
PubMed1992

Kynurenine pathway abnormalities in Parkinson's disease.

We measured metabolites of tyrosine and tryptophan (TRP) in the frontal cortex, putamen (PT), and pars compacta of the substantia nigra (SN) of control and Parkinson's disease (PD) brain tissues. Dopamine concentrations were significantly decreased in the PT and SN of PD tissue, regardless of L-dopa therapy. However, 3-O-methyldopa (3OMD) concentration showed a significant increase in each region of the PD group treated with L-dopa (PD[+]) as compared with both the control group and the PD group without L-dopa therapy (PD[-]). Therefore, 3OMD concentration appears to be a reliable marker of L-dopa therapy. Serotonin concentration was lower in each region of the PD groups than in the control group. Although the magnitude of decrease was greater in the PD(+) group, there was no statistical significance between the two PD groups. The same patterns of decrease were present in kynurenine (KYN) and kynurenic acid (KYA) concentrations, but the molar ratios of TRP to KYN and KYN to KYA were unchanged among three groups. In contrast, 3-hydroxykynurenine (3OHKY) concentration was increased in the PT PD(-) group and in three regions of the PD(+) group. Since the KYN pathway leads to formation of nicotinamide-adenine dinucleotide (NADH), the present results may be a further indication of a defect in NADH:ubiquinone oxidoreductase (complex I) in mitochondria in PD.

Aged↗
PubMed1991

Neurochemical analysis of focal ischemia in rats.

BACKGROUND AND PURPOSE: Increases in uric acid follow experimental stroke, which may be related to free radical formation by xanthine oxidase. The present study examined the time course of changes in xanthine and uric acid and their relationship to changes in the free radical scavengers glutathione, cysteine, and ascorbic acid. METHODS: Focal ischemia was induced by occluding the middle cerebral artery, followed by transient occlusion of the common carotid arteries for 60 minutes. At varying time points, animals were sacrificed, and ischemic cortex was dissected. Neurochemical measurements were made by high-performance liquid chromatography with 16-sensor electrochemical detection. RESULTS: Marked increases in uric acid were seen at all time points, with a maximal increase at 1 day and a persistent increase lasting up to 21 days. There were smaller reciprocal decreases in xanthine. Glutathione, cysteine, and ascorbic acid showed significant decreases, consistent with the generation of free radicals. Reductions in levels of cysteine and glutathione were significantly correlated with increases in uric acid levels. CONCLUSIONS: These findings confirm marked alterations in purine metabolism following focal ischemia and suggest that xanthine oxidase contributes to the generation of free radicals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Simultaneous measurements of tryptophan and its metabolites, kynurenine and serotonin, in the superficial layers of the spinal dorsal horn. A study in normal and arthritic rats.

It has been demonstrated that 5-hydroxytryptamine (5-HT) is not the only neuroactive metabolite of tryptophan (TRP) in the CNS. The presence of kynurenine (KYN) and its metabolites has been reported in the brain of several mammalian species and the neuroactive properties of these compounds are now well established. In the present study, we report the identification of KYN in the superficial layers of the rat spinal dorsal horn. KYN was measured simultaneously with TRP. 5-hydroxytryptophan, 5-HT, 5-hydroxyindoleacetic acid and 5-HT-O-sulfate by means of liquid chromatography with coulometric electrode array detection. The results observed in the normal rat and in an animal model of persistent pain, the arthritic rat, are discussed in view of the hypothesis relating to the involvement of the bulbospinal serotonergic system in pain mechanisms and of the possible participation of KYN and its metabolites in these mechanisms.

Animals↗
PubMed1990

Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode array detection.

Kynurenic acid is a broad-spectrum excitatory amino acid (EAA) receptor antagonist which is present in the mammalian central nervous system. We describe a method for the measurement of kynurenic acid using isocratic reverse-phase high-performance liquid chromatography (HPLC) with fluorometric detection enhanced by Zn2+ as a postcolumn reagent. The method requires no prior sample preparation procedures other than extraction with 0.1 M HClO4. The reliability of the primary fluorometric method was verified by comparing measurements of tissue concentrations of kynurenic acid in human cerebral cortex and putamen using three different methods of separation with fluorometric detection, as well as four methods utilizing HPLC with coulometric electrode array system (CEAS) detection. All seven methods produced comparable results. The concentration of kynurenic acid in human cerebral cortex was 2.07 +/- 0.61 pmol/mg protein, and in human putamen, 3.38 +/- 0.81 pmol/mg protein. Kynurenic acid was also found to be present in human cerebrospinal fluid (CSF) at a concentration of 5.09 +/- 1.04 nM. The regional distribution of kynurenic acid in the rat brain was examined. Kynurenic acid concentrations were highest in brainstem (149.6 fmol/mg protein) and olfactory bulb (103.9 fmol/mg protein) and lowest in thalamus (26.0 fmol/mg protein). There were no significant postmortem changes in kynurenic acid concentrations in cerebral cortex, hippocampus, and striatum at intervals ranging from 0 to 24 h. Perfusion of the cerebral vasculature with normal saline prior to sacrifice did not significantly alter kynurenic acid content in rat hippocampus, cerebral cortex, or striatum. The analytical methods described are the most sensitive (10-30 fmol injection-1) and specific (utilizing both excitation and emissions properties and electrochemical reaction potentials, respectively) methods for determining kynurenic acid in brain tissue extracts and CSF. These methods should prove useful in examining whether kynurenic acid modulates EAA-mediated neurotransmission under physiologic conditions, as well as in determining the role of kynurenic acid in excitotoxic neuronal death.

Animals↗
PubMed1990

Kynurenine pathway measurements in Huntington's disease striatum: evidence for reduced formation of kynurenic acid.

Recent evidence suggests that there may be overactivation of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors in Huntington's disease (HD). Tryptophan metabolism by the kynurenine pathway produces both quinolinic acid, an NMDA receptor agonist, and kynurenic acid, an NMDA receptor antagonist. In the present study, multiple components of the tyrosine and tryptophan metabolic pathways were quantified in postmortem putamen of 35 control and 30 HD patients, using HPLC with 16-sensor electrochemical detection. Consistent with previous reports in HD putamen, there were significant increases in 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, and serotonin concentrations. Within the kynurenine pathway, the ratio of kynurenine to kynurenic acid was significantly (p less than 0.01) increased twofold in HD patients as compared with controls, consistent with reduced formation of kynurenic acid in HD. CSF concentrations of kynurenic acid were significantly reduced in HD patients as compared with controls and patients with other neurologic diseases. Because kynurenic acid is an endogenous inhibitor of excitatory neurotransmission and can block excitotoxic degeneration in vivo, a relative deficiency of this compound could directly contribute to neuronal degeneration in HD.

Aged↗
PubMed1989

Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness.

Six female cats, varying in susceptibility to motion sickness, were implanted with chronic cannulae in the rostral portion of the fourth ventricle. The cats were then challenged with a motion sickness-inducing stimulus. Samples of cerebrospinal fluid were withdrawn before and after emesis or 30 min of motion if emesis did not occur and again on control (no motion) days. The samples were analyzed by HPLC with an array of 16 coulometric detectors. Thirty-six compounds were identified in the samples. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not become motion sick. None of the identified compounds varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

Animals↗
PubMed1987

EC array sensor concepts and data.

The use of multiple parameter assays of entire metabolic pathways is potentially a powerful tool for unraveling mechanisms of disorders or drug action and classification of neurological diseases. Coulometric electrode series array sensors, coupled with liquid chromatography (n-ELC), provide a route to multiplying the resolving power of conventional LC by factors of 10 to 50. Since the original description of the n-ELC concept by Matson et al. (1), fundamental issues of optimizing sensor design and integration with computer controlled LC systems have been addressed. Femtogram level potential time (ET) separations can now be performed for multiple components in both isocratic and gradient modes. A 56-component isocratic method for the study of the kynurenine system in Huntington's Disease (HD) is presented as an indication of the analytical definitions and nomenclature used to qualify an n-ELC procedure, and an indication of the implications of multiparameter data bases on data handling and experimental design.

Amino Acids↗
PubMed1985

Serotoninergic system in dementia of the Alzheimer type. Abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid.

Serotonin (5-HT), its precursor 5-hydroxytryptophan (5-HTP), and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in the cerebrospinal fluid (CSF) of 14 patients with dementia of the Alzheimer type (DAT) and in nine controls by high-performance liquid chromatography with a novel multisensor coulometric detection system. Concentrations of both 5-HT and 5-HIAA detected by this system were lower than the concentrations obtained using conventional amperometric detection. This difference was caused by coelution of compounds that could be resolved from 5-HT and 5-HIAA by the multisensor coulometric system. One of the coelution compounds, observed in DAT but not in control CSF, behaved like a partially oxidized 5-HT. A compound behaving like partially oxidized 5-HTP was also observed in DAT CSF. Concentrations of 5-HTP, 5-HT, and 5-HIAA were lower in DAT CSF than in a corresponding fraction of control CSF. These results indicate involvement of the serotoninergic system in DAT and might lead to development of a diagnostic test for DAT.

5-Hydroxytryptophan↗
PubMed1984

n-Electrode three-dimensional liquid chromatography with electrochemical detection for determination of neurotransmitters.

Coulometric electrodes in series have been used with liquid chromatography with electrochemical detection to increase selectivity and resolution for the direct analysis of tissue neurotransmitters. Use of three coulometric sensors for electrochemical modification, selectivity, and peak identification has been expanded into "gate" cells of three or four coulometric electrodes that allow elimination of all electrochemically irreversible substances, and "array" cells of up to 15 coulometric electrodes for separation of co-eluting compounds by their current/voltage characteristics. On-column sensitivity of the sensor arrays is 0.4 to 4 pg. Gate cell selectivity favors electrochemically reversible compounds over irreversible ones, e.g., 3-methoxy-4-hydroxyphenylglycol vs ascorbate, by a factor of up to 10(4). Resolution across the multi-electrode array cells allows separation of co-eluting compounds with half-wave potentials differing by as little as 30 to 40 mV. Cells with three to 15 electrodes have been used to measure monoamines and metabolites in brain; monoamines directly in serum filtrate; and the state of oxidation of 5-hydroxytryptamine and 5-hydroxytryptophan in cerebrospinal fluid of patients with Alzheimer's disease.

5-Hydroxytryptophan↗
PubMed1983

Rapid direct determination of lead in evaporated milk by anodic stripping voltammetry without sample pretreatment.

The method presented describes the direct determination of lead in evaporated milk in which the milk ashing step prior to analysis is eliminated. Digital instrument readout units are microgram Pb/mL milk. Total analysis time after instrument calibration is less than 3 min per sample. Range of the method is 0.05-1.0 ppm lead in milk, and precision of the method expressed by relative standard deviation of duplicate pairs ranged from 30% at 0.1 micrograms/mL to 3% at 1.0 micrograms/mL of lead in milk. The method compares favorably with the AOAC official first action anodic stripping voltammetric method (25.074). In addition, the method appears to work equally well for skim evaporated milk, sweetened condensed milk, and nonfat powdered dry milk when the latter two are reconstituted with water according to product label instructions. Recovery and interference studies are presented.

Animals↗
PubMed1983

Direct determination of lead in evaporated milk and apple juice by anodic stripping voltammetry: collaborative study.

A method for the direct determination of lead in evaporated milk and in fruit juice with no prior sample digestion was successfully collaborated by 13 laboratories. The anodic stripping voltammetric (ASV) method studied consisted of adding 0.2 mL aliquots of evaporated milk or 0.3 mL aliquots of fruit juice to 2.9 mL of a dechelating reagent, Metexchange. The reagent-sample mixture is then analyzed for lead by ASV with no further sample preparation. Each collaborator received 24 samples, 2 each at 5 different levels (0.07-0.70 ppm for spiked evaporated milk and 0.09-0.87 ppm for spiked apple juice) along with duplicate practice samples of labeled lead content at each of 2 levels for each sample type. All unknowns were coded with random numbers. Approximately 69% of the reporting laboratories had never analyzed either evaporated milk or fruit juice for lead. Average time between receipt of samples and reporting of results was 1.6 days for all laboratories. The pooled variations between duplicate determinations for apple juice and evaporated milk were 0.00059 and 0.00043, respectively. The method was adopted official first action for both fruit juice and evaporated milk.

Animals↗
PubMed1978

Analysis of total arsenic in urine and blood by high speed anodic stripping voltammetry.

A method for the measurement of parts per billion levels of total arsenic in urine and blood is described. Samples are wet ashed with a mixture of HNO3, HCIO4, and H2SO4 acids. Ashed materials are subjected to a reductillationTM procedure to reduce As (V) to As (III) and to separate arsenic from the sample matrix. Collected arsenic is then quantitated by anodic stripping voltammetry (ASV) at a gold film electrode. ASV analysis time is only 2 minutes. By simultaneous reductillation of 4 samples, ppb arsenic determinations can be accomplished at a rate of about 12 per hour. The method is as accurate, precise and reliable at the nanogram level as the more universally accepted colorimetric techniques are at the microgram and milligram levels. For replicate analysis of real samples, method precision ranged from +/- 1.4 ppb at the 5 ppb level to +/- 0.96 ppb at the 25 ppb level. Accuracy is estimated at +/- 6% over the range 5 to 500 ppb arsenic.

Arsenic↗
PubMed1978

Direct analysis of lead in fruit juice by anodic stripping voltammetry with no prior sample preparation.

A method is presented for determining lead in fruit juice in less than 3 min after instrument calibration. The range examined is 0.01 to 1.3 ppm lead. The method is compared with 3 other methods in general use. Standard error of estimates between the methods compared range from 0.023 to 0.051 ppm for a set of 50 samples and from 0.037 to 0.091 ppm for a set of 9 samples. Regression correlation coefficients between methods range from 0.968 to 0.995. Judged by the comparisons, the direct method is precise and accurate over greater than a 100-fold range of lead concentrations.

Beverages↗