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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 109 records · Page 6Linked to original sources
PubMed1988

Isatin: identity with the purified endogenous monoamine oxidase inhibitor tribulin.

Purified tribulin, an endogenous monoamine oxidase (MAO) inhibitor, has been identified by direct probe insertion mass spectrometry as the indole-2,3-dione, isatin. A gas chromatographic-mass spectrometric assay for isatin has been developed and used to measure its relatively high concentrations in unpurified human urine, and in rat heart and brain. Isatin is a known compound with a broad range of biological activity; this is the first report of its presence in the animal body. Isatin is a potent inhibitor of MAO, particularly of MAO B (IC50, 3 microM), and also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 microM).

Animals↗
PubMed1988

Brain quinolinic acid in Huntington's disease.

Concentrations of the endogenous neurotoxic tryptophan metabolite, quinolinic acid (QA), were measured in postmortem brain tissue obtained from patients with Huntington's disease (HD) and matched controls, using a gas chromatography/mass spectrometry method. There was no significant difference in either the putamen or the frontal cortex between the HD and control groups. These results do not support the hypothesis that increased QA is responsible for neuronal degeneration in HD.

Brain↗
PubMed1988

Platelet phenolsulphotransferase activity and 'abdominal migraine'.

Low platelet phenolsulphotransferase activity has been reported in adult patients with dietary sensitive migraine. Platelet activity of this enzyme was therefore measured in children having 'abdominal migraine' with probable dietary trigger and in controls. No significant difference was found in activity between the two groups. There was no significant correlation between platelet phenolsulphotransferase activity and age.

Abdomen↗
PubMed1988

The analysis of urinary meta- and para-tyramine by gas chromatography with electron-capture detection.

A simple, reliable method for the analysis of urinary meta- and para-tyramine has been developed. Sample purification was achieved by a weak anion-exchange column, followed by extraction into ethyl acetate at pH 10.2. The heptafluorobutyryl derivative was measured by packed column gas chromatography with electron-capture detection, using para-hydroxyphenylpropylamine as internal standard. The results agreed well with those obtained by gas chromatography-mass spectrometry. The daily output of unconjugated and conjugated meta- and para-tyramine by 23 adults was measured. In consecutive 24 h urine samples from a single subject there was little day-to-day variation in the level of excretion of unconjugated meta- and para-tyramine, whereas the conjugated amines exhibited marked fluctuations.

Adult↗
PubMed1988

Urinary catecholamine metabolite and tribulin output during lactate infusion.

Urinary output of homovanillic acid and 4-hydroxy-3-methoxymandelic acid was decreased both in patients with panic attacks and in normal controls during lactate infusion, whereas that of tribulin (an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor) was increased. There was no change in urinary excretion of any of these compounds during saline infusion. These findings provide further evidence of a link between tribulin output and stress and anxiety in man and point to its possible in vivo action as a monoamine oxidase inhibitor.

Anxiety Disorders↗
PubMed1987

In vitro inhibition of phenolsulphotransferase by food and drink constituents.

Several natural and synthetic food and drink constituents were tested in vitro for their inhibitory actions on phenolsulphotransferase P and M (PST P, PST M) and monoamine oxidase A and B (MAO A, MAO B). Cyanidin 3-rutinoside, a simple anthocyanin, (+)-catechin, a flavanol, and carmoisine, a synthetic food colorant, were found to be particularly potent, reversible inhibitors of PST P. All inhibited this enzyme by 100% at a concentration of 5 microM and had an IC50 in the microM range. The effects of these compounds on PST M and MAO A and B were less pronounced. There was a considerable difference in the inhibitory ability of different purified anthocyanins but all were selective for PST P. Several other phenolic food colorants were also found to be specific inhibitors of PST P, though less potent in their actions. Tartrazine, a non-phenolic food colorant, had little effect. The phenolic extracts from two red wines were also found selectively to inhibit PST P in vitro, suggesting that it is within this fraction that these inhibitors are to be found. PST is an important enzyme involved in the inactivation of a wide range of exogenous and endogenous phenols. If such a degree of inhibition were to occur in vivo, potentially toxic concentrations of some phenolic substrates might result.

Anthocyanins↗
PubMed1987

Analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as monoamine oxidase substrates: a second ring is not necessary.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is oxidised to a neurotoxic metabolite by monoamine oxidase B (MAO B). Using two colorimetric assays, we have examined a range of its structural analogues as possible further substrates of this enzyme in order to identify the types of environmental or endogenous compounds that might also be neurotoxic. Compounds with fully saturated or unsaturated pyridine rings were not substrates; nor were a range of tetrahydro-beta-carbolines or isoquinolines. Four substrates for MAO were found, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-Me-MPTP), 4-phenyl-1,2,3,6-tetrahydropyridine (PTP), 4-(p-chlorophenyl)-1,2,3,6-tetrahydropyridine (Cl-PTP) and ethyl-1-methyl-1,2,3,6-tetrahydro-4-pyridine-carboxylate (ethyl-MTP-carboxylate). Ethyl-MTP-carboxylate is of particular interest as it shows that a tetrahydropyridine without a phenyl ring can also be a substrate. Cl-PTP, PTP and ethyl-MTP-carboxylate appeared to be partially metabolised by MAO A. The inhibitor sensitivity of 2'-Me-MPTP oxidation was more complex.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Psychiatric morbidity and platelet monoamine oxidase activity in cancer patients.

Psychometric ratings for both anxiety and depression in 30 cancer patients were significantly elevated compared with values in 16 controls. The scores were especially high in the 14 patients who did not have breast cancer. This group also had significantly greater platelet monoamine oxidase activity than either the breast cancer patients or controls. Platelet monoamine oxidase activity values correlated significantly with both depression and anxiety scores in the whole cancer group.

Adult↗
PubMed1987

Serum alpha-1-protease inhibitor activity and pulmonary function in young insulin-dependent diabetic subjects.

Abnormalities of lung function have previously been described in patients with impaired alpha 1-protease inhibitor (alpha 1-PI) function and more recently in insulin-dependent diabetic subjects. This study was undertaken to test the hypothesis that impaired alpha 1-PI activity may be implicated in the pathogenesis of lung function abnormalities in young insulin-dependent diabetic patients. Twelve young (16.23 +/- 4.51 years), non-smoking insulin-dependent diabetic subjects and 12 reference subjects were evaluated in respect of lung mechanics, absolute serum alpha 1-PI levels and the functional ability of alpha 1-PI to inhibit elastase. Results of the ventilatory mechanics showed that the mean value for the volume-independent index of lung elasticity Kst(L) was significantly greater in the diabetic group (0.149 +/- 0.05 vs. 0.116 +/- 0.03; p less than 0.05). The absolute serum alpha 1-PI levels in the insulin-dependent diabetic subjects was significantly lower than in reference subjects (1.74 +/- 0.11 vs. 2.06 +/- 0.09 g/l; p less than 0.05). While the specific alpha 1-PI activity of the diabetic sera showed no significant difference from that of the reference sera, the total alpha 1-PI inhibitory activity in the diabetic sera was significantly lower than reference values (201.9 +/- 9.7 vs. 246.9 +/- 13.5 U/L; p less than 0.02). Although these findings indicate impairment of both ventilatory mechanics and alpha 1-PI activity in the insulin-dependent diabetic subjects, the pathogenesis of these findings and their functional implications are at present unknown.

Adolescent↗
PubMed1987

Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus.

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1987

Interference by naproxen in the urinary 5-hydroxyindoleacetic acid assay is due to a metabolite, desmethylnaproxen.

Interference by naproxen in the spectrophotometric assay for urinary 5-hydroxyindoleacetic acid has been investigated. Gas chromatography-mass spectrometry demonstrated that ingestion of naproxen was associated with the production of four urinary components, unchanged drug and three metabolites, the major one being desmethylnaproxen. Unlike naproxen, this metabolite reacted in the spectrophotometric assay giving a product with the same absorption spectrum as that observed in urine samples obtained after naproxen ingestion. Unlike 5-hydroxyindoleacetic acid, the colour due to desmethylnaproxen is thermolabile and so the interference may be overcome by performing the incubation at 100 degrees C.

Adult↗
PubMed1987

Alcoholic ketoacidosis: a case report.

A 43-year-old alcoholic presented in coma with ketoacidosis, after three days of nausea and feeling generally unwell, which had been preceded by a prolonged three-week period of heavy alcohol consumption with poor dietary intake. The acidosis responded rapidly to intravenous dextrose. This is the first Scottish report of a case of alcoholic ketoacidosis.

Acidosis↗
PubMed1987

Selegiline and the prophylaxis of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration causes a Parkinson's disease like syndrome in man and primates, with selective degeneration of the substantia nigra. This discovery has raised the possibility that some environmental or endogenous toxin causes idiopathic Parkinson's disease. MPTP is oxidised to its neurotoxic metabolite, 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase B (MAO B). MPTP toxicity is prevented by pretreatment with the MAO B inhibitor selegiline ((-)-deprenyl). We have screened a range of structural analogues of MPTP as possible alternative substrates for the enzyme. All compounds which were found to be substrates for MAO B were tetrahydropyridines, some with substituents on the phenyl ring. The most interesting substrate, ethyl-MTP-carboxylate, did not have a phenyl ring. The precise histochemical localisation of MAO B within the rat and marmoset brain has been established. There was substantial activity within the nigrostriatal pathway of the marmoset; in comparison, the rat had only a low background MAO B level. These results may partially explain why the marmoset is more susceptible to the action of MPTP than the rat.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗