PubMed Health⌕ Search

Biomedical subjects

M W Duncan

Publications and source records attributed to M W Duncan.

46 records · Page 3Linked to original sources
PubMed1985

Precise GC/MS assays for salsolinol and tetrahydropapaveroline: the question of artifacts and dietary sources and the influence of alcohol.

The use of GC/MS with appropriate deuterated internal standards has enabled the development of highly precise assays for salsolinol and THP. The deuterated standards we have prepared for the present assays are entirely free of contamination by non-deuterated species. The extraction and analytical techniques used in these studies do not lead to artifactual formation of either salsolinol or THP due to dopamine cyclization since neither alkaloid was detected in a variety of samples that contained high concentrations of dopamine. Examples are tomato, certain urine samples, rat brain samples including hypothalami from animals treated with pharmacological doses of l-dopa. While we have found little analytical support, at least in urine, for significant in vivo formation of salsolinol from endogenous dopamine and acetaldehyde, there is clear evidence that dietary sources of salsolinol contribute to its detection in biological samples. Whatever the origin of alkaloids such as salsolinol and THP in mammalian samples, their potential for affecting behavioural and physiological systems merit their continued study.

Alcoholism↗
PubMed1984

Comparison of high-performance liquid chromatography with electrochemical detection and gas chromatography-mass fragmentography for the assay of salsolinol, dopamine and dopamine metabolites in food and beverage samples.

High-performance liquid chromatography with electrochemical detection (HPLC-ED) and combined gas chromatography--mass spectrometry in the single-ion monitoring mode (GC--MS-SIM) have been used for the determination of salsolinol, dopamine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol and norepinephrine in a selection of food and beverage samples. The unique specificity of the SIM mode allows a simple one-step extraction to be used even for complex sample matrices. We have been able to demonstrate the quantitative and qualitative advantages offered by GC--MS over HPLC--ED by direct comparison of the chromatographic data obtained. We demonstrate that the specificity of SIM and the benefits offered by the incorporation of deuterated internal standards make GC--MS-SIM the method of choice for valid identification and precise quantitation of salsolinol, dopamine and dopamine metabolites in a complex sample matrix.

Beer↗
PubMed1983

Effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline and yohimbine on hypothalamic monoamine status and pituitary hormone release in the rat.

Shortly after administration of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeOTHBC) and yohimbine to normal or hypothyroid rats [the latter exhibiting chronically elevated levels of serotonin (5-HT) neuronal activity in the hypothalamus] there was a highly significant increase in hypothalamic noradrenaline (NA) activity and in ACTH release concomittant with a reduction in hypothalamic 5-HT activity (P less than 0.01) and in growth hormone (GH) (P less than 0.01) and in thyroid stimulating hormone (TSH) (P less than 0.01) release from the pituitary. Both compounds caused an increase in hypothalamic dopamine (DA) metabolism and in pituitary prolactin (PRL) release in normal rats (P less than 0.01) but only yohimbine exerted this action in hypothyroid rats. Lower doses of 6-MeOTHBC exerted a relatively specific effect in hypothyroid rats, reducing (P less than 0.01) 5-HT neuronal activity in parallel with pituitary TSH secretion (P less than 0.05). While gross effects of 6-MeOTHBC and yohimbine were similar with respect to their effects on NA and 5-HT status in the hypothalamus, there were quantitative differences. 6-MeOTHBC always caused a greater decrease in 5-HT turnover and a lesser increase in NA turnover than did yohimbine. On the basis of these studies we suggest that the effect of tetrahydro-beta-carboline-related alkaloids on pituitary hormone release may be due to their influence on hypothalamic monoamine status and the subsequent alteration of the hypothalamic-pituitary control system.

Adrenocorticotropic Hormone↗
PubMed1979

Infectious arthritis.

One hundred thirteen patients with 120 episodes of septic arthritis were seen during a 14-year period. The most common bacteria cultured from joint fluid or blood during the acute episodes were gonococci, staphylococci, and streptococci. Seventeen other bacteria were the infecting organisms in one or more cases each. Other infections and medical conditions frequently were present. In some instances the septic arthritis was a complication of another infection. In other patients septic arthritis appeared to occur because of diminished resistance to infection. The majority of patients responded well to medical treatment, but eight died and 26 had persistence of articular pain at follow-up examination.

Adolescent↗
PubMedDate not supplied

Aspirin and delayed type hypersensitivity.

The effects of aspirin on delayed hypersensitivity were assessed in 40 healthy subjects who were randomly assigned to two equal groups. In a double-blind format, the individuals in one group were placed on 4 gm aspirin daily for 5 days, and individuals in the other group were given placebo. Lymphocyte proliferation was measured before and 72 hours after the initiation of drug, by using three mitogens and four antigens. The percentages of T and B lymphocytes were likewise measured before and during therapy. The subjects were skin tested with the same four antigens 72 hours after the initiation of drug, and the skin tests were read 48 hours later. No significant differences between the two groups were detected when skin tests, lymphocyte proliferation, and percentage of T lymphocytes were compared.

Adult↗
PubMedDate not supplied

2-Amino-3-(methylamino)propanoic acid (BMAA) bioavailability in the primate.

2-Amino-3-(methylamino)-propanoic acid (BMAA) is a low potency excitatory amino acid present in the cycad plant that has been proposed as a factor in the high incidence of amyotrophic lateral sclerosis-parkinsonism dementia (ALS-PD) in the western Pacific region. We employed stable isotopic forms of BMAA to assess the oral bioavailability of this compound in cynomolgous monkeys (n = 3). The stable isotope labeled BMAA ([15N]-BMAA) was injected i.v. at the same time that the unlabeled compound was administered orally. Both forms of BMAA were then quantified in a 48h urine sample by gas chromatography-mass spectrometry (GC/MS). Following oral dosing, 80% of the administered BMAA was absorbed into the systemic circulation; thus, oral bioavailability was high and other routes of administration could not result in significantly higher circulating levels of BMAA for a given administered dose.

Administration, Oral↗
PubMedDate not supplied

Quantification of the putative neurotoxin 2-amino-3-(methylamino)propanoic acid (BMAA) in cycadales: analysis of the seeds of some members of the family Cycadaceae.

Over the past 30 years there have been attempts to link the unusually high incidence of amyotrophic lateral sclerosis (ALS) among the Chamorros native to the island of Guam to the consumption of the seeds of Cycas circinalis L., the false sago palm. In support of this relationship it was recently shown that, when given to primates, 2-amino-3-(methylamino)-propanoic acid (BMAA), a minor cycad component, can cause selective degeneration of upper and lower motor neurons in the spinal cord and clinical features similar to those of ALS. In order to test the relationship between ALS and cycads, we have developed a sensitive and precise gas chromatographic/mass spectrometric (GC/MS) assay for BMAA which allows direct assessment of the BMAA content in foods and is directly applicable to the assay of BMAA in biologic tissues and fluids. After the addition of a deuterated isotopomer as an internal standard and transesterication with 2-methyl-1-propanol, BMAA was extracted into dichloromethane and then acylated with pentafluoropropionic anhydride before GC/MS. This method permits precise quantification of BMAA in the low picogram/sample range. Direct quantification of the BMAA content in the female gametophyte tissue (endosperm) of a range of cycad seeds collected from Guam confirmed the presence of BMAA at levels of approximately 1 g/g (dry weight). The presence of BMAA in the seed extract was confirmed after derivatization of an aliquot of the extract and GC/MS analysis in the scanning mode. BMAA was found to be present, albeit at lower levels, in the endosperm of the seeds of C. revoluta (0.32 mg/g) and C. media (0.29 mg/g).

Amino Acids, Diamino↗
PubMedDate not supplied

Analysis of the neurotoxic plasticizer n-butylbenzenesulfonamide by gas chromatography combined with accurate mass selected ion monitoring.

The plasticizer, n-butylbenzenesulfonamide (NBBS), is reported to be neurotoxic when inoculated intracisternally or intraperitoneally into rabbits. Because NBBS is commonly used in the production of polyamide (nylon) plastics and is soluble in water, the disposal of NBBS-containing plastics in landfill sites could result in NBBS appearing in the leachate. Further, NBBS could also be leached from packaging into their contents. To allow us to examine the risks posed by NBBS in the environment, we have developed a quantitative assay for this compound. The assay employs a one-step extraction into dichloromethane followed by gas chromatography with accurate mass selected ion recording. The assay incorporates [13C6]NBBS as an internal standard to allow precise quantitation, and four separate ion chromatograms are recorded. NBBS was found in some Australian domestic solidwaste landfill leachate (from less than 0.3 to 94.6 ng/mL), but ground water in the vicinity of a landfill had only trace quantities of NBBS. NBBS was also quantitated in some bottled and cask wines, and levels varied from not detected to 2.17 ng/mL (n = 14). Additional studies are required to assess the public health risks associated with the use of NBBS as a plasticizer.

Gas Chromatography-Mass Spectrometry↗