Biomedical subjects
Publications and source records attributed to M Sandler.
In a group of 30 patients with major unipolar depressive disorder urinary excretion of tyramine sulphate was measured after an oral dose of tyramine. There was a significant correlation between impaired tyramine conjugation and response to tricyclic antidepressant medication.
Quinolinic acid (QA) content was measured in postmortem frontal and temporal cortex, putamen and cerebellum obtained from patients with senile dementia of Alzheimer type (SDAT), Huntington's disease (HD) and controls, using a gas chromatography/mass spectrometry method. There were no significant group differences in QA content of any of the regions examined. The data do not support the hypothesis that an accumulation of QA plays a role in neuronal degeneration occurring in the frontal and temporal cortex, putamen and cerebellum of patients with SDAT.
In this study, urinary output of both neutral (tribulin) and basic monoamine oxidase inhibitory activity was measured in parkinsonian patients, other neurological patients and controls. No significant differences in output were found between these different groups. In general, tribulin output rose with age, in parallel with known changes in monoamine oxidase B activity.
A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported.
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Tyramine sulfoconjugation following an oral tyramine load was determined in 30 patients suffering from migraine and 14 controls not regularly suffering from headache. Reduced tyramine sulfoconjugation was found in those patients with a history of major depressive disorder compared with controls. When the patients with a history of major depression were removed from the analysis, no differences were found between diet-sensitive and non-diet sensitive migraine patients and controls.
A 55-year-old diabetic female treated with a combination of a short- and intermediate-acting insulin, developed sterile furunculoid lesions at the injection sites which eventually healed with atrophic scars. Histopathologically, an initial neutrophilic stage was followed by granulomatous and fibrotic stages. It was considered that zinc, a component of the intermediate-acting insulin, was responsible for the cutaneous reaction and granuloma formation. Zinc-induced granuloma is a rare histopathological complication of insulin therapy.
1-Methyl-4-phenylpyridinium (MPP+) was taken up into human and rat striatal synaptosomes by a saturable system, similar to that for dopamine, with Km values of 0.24 and 0.17 microM, respectively, and similar Vmax values. Uptake of MPP+ and dopamine into both rat and human synaptosomes was inhibited by cocaine and amfonelic acid, with the latter being five to 10 times more potent than the former. MPP+ uptake was potently inhibited by dopamine in preparations from both species. In general, the characteristics of human and rat synaptosomal MPP+ uptake were very similar It seems unlikely that species differences in toxicity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or reaction to dopamine uptake blockers stem from this system.
We investigated possible alterations in serum alpha 1-protease inhibitor (alpha 1-PI) concentration and activity from insulin-dependent diabetic subjects (IDDs) and in vitro in serum samples containing high glucose concentrations. The in vivo measurements were compared to others taken from normal reference subjects and the in vitro measurements were performed in serum samples containing 0, 10, 20, and 40 mmol/l of glucose. The diabetics had a significantly lower mean alpha 1-PI concentration in their serum than did the reference subjects (1.74 +/- 0.1 g/l vs. 2.1 +/- 0.1 g/l, P less than 0.05), as well as a lower total alpha 1-PI inhibitory activity (201 +/- 0.7 vs. 246.9 +/- 13.5 U/l, P less than 0.02). Addition of glucose to the serum samples in the in vitro study significantly reduced the mean alpha 1-PI concentrations (P less than 0.01 in the case of 10 mmol/l glucose, and P less than 0.001 in the cases of 20 and 40 mmol/l). Added glucose also significantly reduced the mean serum alpha 1-PI activity as determined by the percentage of elastase inhibition in 1, 2, and 3 microliters of reference serum (P less than 0.02 in the case of 10 mmol/l glucose, P less than 0.01 in 20 mmol/l, and P less than 0.001 in 40 mmol/l). Hyperglycaemia thus impaired serum alpha 1-PI concentration and activity both in vivo and in vitro. While the underlying mechanisms and clinical implications of these observations are unknown, the abnormally low alpha 1-PI activity in diabetics may worsen the severity and contribute to the chronicity of their infections.
Two hours of cold restraint stress in rats resulted in significantly increased brain concentrations of endogenous monoamine oxidase inhibitor (tribulin). Young and old rats showed the same order of response. Tribulin levels were also increased by immobilisation stress alone but to a lesser extent.
This study describes the histochemical localisation of monoamine oxidase (MAO) in marmoset brain. No MAO A staining was observed but MAO B was found in many areas, with medium intensity of staining in the substantia nigra, and high intensity staining in the striatum and nucleus accumbens, among other regions. The high activity in the nigrostriatal tract, compared with the rat, may partially explain the greater sensitivity of the marmoset to MPTP toxicity. As in the rat, high activity was present in the raphe nuclei. However, unlike the rat, no enrichment of MAO B was observed in blood vessels or ventricular linings.
Patients with migraine who believed that red wine but not alcohol in general had a headache-provoking effect on them were challenged either with red wine or with a vodka and diluent mixture of equivalent alcohol content, both consumed cold out of dark bottles to disguise colour and flavour. The red wine, which had a negligible tyramine content, provoked a typical migraine attack in 9 of 11 such patients, whereas none of the 8 challenged with vodka had an attack. Neither red wine nor vodka provoked such episodes in other migrainous subjects or controls. These findings show that red wine contains a migraine-provoking agent that is neither alcohol nor tyramine.
Blood pressure and heart rate responses to oral tyramine have been measured in healthy volunteers before and after administration of the selective monoamine oxidase B inhibitor selegiline at high dosage (30 mg/day). Treatment brought about a 2 to 4-fold increase in tyramine sensitivity and a concomitant small but significant reduction in plasma 4-hydroxy-3-methoxyphenylglycol concentration, pointing to the emergence of some degree of monoamine oxidase A inhibition. It is suggested that patients treated with selegiline 30 mg/day or more should be placed on a tyramine-free diet.
Urinary output of an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor (tribulin) was raised in a group of patients with generalised anxiety disorder compared with controls. Tribulin levels remained relatively constant in individual patients over the 6-week period of observation, mean values remaining high even after reduction of anxiety following non-drug behaviour therapy.
The histochemical distribution of monoamine oxidase A and B in rat brain was investigated using a coupled peroxidatic technique with benzylamine and tyramine as substrates and clorgyline and (-)-deprenyl as selective inhibitors. Benzylamine oxidase was absent in all areas. Both forms of monoamine oxidase were present, at low levels, in all areas; in addition several regions showed high activity of one or other form or both. Substantial activity of monoamine oxidase B was identified in the pineal gland, the lining of the ventricles, several hypothalamic regions, and the raphe nuclei. The locus coeruleus and interpeduncular nucleus possessed considerable type A activity. The substantia nigra and striatum showed no staining above the low general level, although the ventral tegmental area showed higher levels of both A and B. In general, noradrenaline-containing neuronal cell body areas showed monoamine oxidase A, and 5-hydroxytryptamine-rich areas monoamine oxidase B. There was no consistent enrichment of either in corresponding dopamine-rich regions. Monoamine oxidase thus appears to have a different role in these three types of neuron. The low level of monoamine oxidase B in the nigrostriatal tract may help to explain the resistance of the rat to MPTP toxicity.
Tribulin (endogenous monoamine oxidase inhibitor/benzodiazepine receptor binding inhibitor) output was measured in the urine of 18 patients with post-traumatic stress disorder (PTSD) and 13 controls. The level of the two inhibitory activities was highly significantly correlated in the group as a whole. There was no difference between output of either inhibitor in patients and controls. However, when the PTSD group was subdivided according to various psychometric ratings, a pattern of output did emerge. Levels of both inhibitory activities were higher in agitated compared with non-agitated subjects, and lower in extroverts compared with introverts. This finding supports the view that tribulin output is raised in conditions of greater arousal.
Patients with arteriovenous malformations of the bowel may have multiple symptoms secondary to chronic blood loss. A case of ileal cavernous hemangioma detected by Tc-99m labeled red blood cell imaging in the absence of active gastrointestinal bleeding is presented.