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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 145 records · Page 8Linked to original sources
PubMed1985

Red wine contains a potent inhibitor of phenolsulphotransferase.

Many ethanolic drinks, especially red wine, contain potent inhibitors of phenolsulphotransferase. At a dilution of 1/75 from the original beverage, extracts from six types of red wine inhibited human platelet phenolsulphotransferase P by a mean of 99% and human platelet phenolsulphotransferase M by 12%. Such extracts had no significant effect on rat liver monoamine oxidase A or human platelet monoamine oxidase B. The inhibitors, which have not yet been identified, can be extracted into ethyl acetate at acid or neutral pH. Thus, they are not monoamines. Flavonoid phenols are plausible candidates. As phenolsulphotransferase M and P are involved in the metabolism of many phenols, including drugs, the inhibition of these enzymes could result in the enhancement of pharmacological potency and have important clinical consequences.

Alcoholic Beverages↗
PubMed1985

Triazolam, an anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding.

Both alprazolam and triazolam displaced clonazepam (but not Ro 5-4864) from rat brain membranes with high affinity, showing them to act at central but not peripheral benzodiazepine receptors. At 0 degrees C, 10 microM gamma-aminobutyric acid (GABA) increased the ability of alprazolam, but not of triazolam, to displace ethyl-beta-carboline-3-carboxylate (beta-CCE) and Ro 15-1788 from these receptors. At 37 degrees C, GABA increased the affinity of the receptors for both drugs, with a +GABA/-GABA ratio of 1.5 for each in promoting Ro 15-1788 binding displacement. As both triazolam and alprazolam act as anxiolytics in vivo, the results at 37 degrees C would be compatible with the hypothesis that GABA causes an increase in affinity of drugs that act in this way, but the results at 0 degrees C would not be compatible. At 37 degrees C, alprazolam had a higher IC50 for the benzodiazepine receptor than at 0 degrees C, whereas triazolam showed the reverse effect. The relative IC50 values in vitro at 37 degrees C correlated better with the potency in vivo than those obtained at 0 degrees C. At 0 degrees C, both drugs showed Hill plots with slopes of 0.9-1 with beta-CCE and Ro 15-1788. At 37 degrees C, the slopes with triazolam were much reduced, indicating that the drug may have a selective action on a subclass of central benzodiazepine receptors. In the studies reported here, alprazolam behaved like other benzodiazepines, whereas triazolam showed several anomalous properties. It would be of interest if these properties could be related either to the drug's use as a hypnotic or to the side effects it sometimes induces.

Alprazolam↗
PubMed1985

Tribulin: an endogenous monoamine oxidase inhibitor/benzodiazepine receptor ligand.

Tribulin is a low molecular weight inhibitor both of monoamine oxidase and of benzodiazepine receptor binding. It has been highly purified from human urine and has also been isolated from human plasma and animal brain. Its structure is still unknown but its properties do not appear to correspond with any known monoamine or benzodiazepine receptor binding inhibitor. Tribulin output has been found to be increased in a variety of states associated with stress and anxiety, including lactate-induced panic attacks, alcohol or benzodiazepine withdrawal and generalized anxiety disorder.

Animals↗
PubMed1985

The role of salsolinol in alcohol intake and withdrawal.

We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

Acetaldehyde↗
PubMed1984

The genetics of diabetes mellitus, including the South African perspective.

By and large, essential diabetes mellitus is thought to be 50% inherited and 50% environmental. In insulin-dependent diabetes mellitus (IDDM) there is a strong link with the HLA system with regard to the inheritance of 'susceptible' diabetic genes, especially the DR3 and DR4 alleles. In IDDM environmental factors act in a predisposed individual to initiate an immune response with resultant beta-cell damage and destruction. Non-insulin-dependent diabetes mellitus (NIDDM) has no clear HLA link, but has been shown in studies of twins to have a stronger genetic basis than IDDM. In NIDDM environmental factors (race, ethnicity, diet, obesity) have an important influence on the clinical expression of the disease and the severity of complications in a genetically predisposed individual. The non-insulin-dependent diabetes of the young (NIDDY) variant and the phenomenon of chlorpropamide-primed alcohol-induced flushing both underline the heterogeneity of NIDDM. Because of the heterogeneous nature and multifactorial inheritance pattern of diabetes mellitus, accurate genetic counselling is not possible as yet. However, data to date suggest that it is unwise to advise prospective parents not to procreate, since the overall risk of the development of clinical diabetes mellitus is extremely low.

Black People↗
PubMed1984

Platelet monoamine oxidase and phenolsulphotransferase M and P in cancer.

Phenolsulphotransferase and monoamine oxidase inactivate a wide range of dietary and endogenous phenols/monoamines by sulphoconjugation and oxidative deamination respectively. In this study, both enzymes were measured in platelets from cancer patients and controls. Of the two variants of phenolsulphotransferase, activity of the P form was normal in all groups. Activity of the M form was, however, significantly less than control values in patients with cancer of the rectum and bowel but not in other cancer patient groups. If this finding reflects enzyme activity elsewhere in the body and is not merely a manifestation of an abnormal platelet population, the deficit could expose affected subjects to the action of potentially carcinogenic dietary phenols. Platelet monoamine oxidase activity was significantly raised in the cancer group as a whole, and in all sub-types investigated apart from breast cancer. The increase in the cancer group as a whole was independent of sex, age, drugs, radiotherapy, smoking or platelet count. Its mechanism and significance are unknown but there may be links with the patients' psychiatric state.

Adult↗
PubMed1984

Excretion of catecholamines and their metabolites in transplantable rat phaeochromocytoma.

The urinary excretion pattern of catecholamines and their metabolites was studied in rats bearing a subcutaneous transplantable phaeochromocytoma. Compared with normal rats, tumour-bearing animals showed a markedly raised excretion of dopamine, noradrenaline and adrenaline, together with certain of their major acidic and alcoholic metabolites. No evidence of increased octopamine production could be obtained. There was a significant correlation between the output of dopamine and its metabolites, allowing accurate assessment of dopamine turnover rates which were comparable with those observed in human phaeochromocytoma. Tumour development, as determined by tumour weight, also correlated significantly with urinary excretion of noradrenaline and dopamine. Rat phaeochromocytoma appears to be a useful model for the human tumour.

3-Methoxy-4-hydroxyphenylethanol↗
PubMed1984

Isolated adrenocorticotrophic hormone deficiency in the absence of polyglandular endocrinopathy. A case report.

A 64-year-old woman presented with recurrent episodes of confusion and nonspecific abdominal symptoms associated with hyponatraemia, which prompted a provisional diagnosis of the syndrome of inappropriate antidiuretic hormone secretion. Further investigation revealed evidence of hypocortisolaemia secondary to isolated adrenocorticotrophic hormone (ACTH) deficiency, which was successfully treated with steroid therapy. The clinical spectrum and aetiological associations of isolated ACTH deficiency are reviewed.

Adrenal Glands↗
PubMed1984

The prevalence of diet-induced migraine.

Nineteen percent of about 490 patients with classical or common migraine reported that headaches can be precipitated by chocolate, 18% by cheese and 11% by citrus fruit, and a highly significant majority of these patients were sensitive to all three foods. Twenty-nine percent of the patients reported sensitivity to alcohol; again this was significantly associated with sensitivity to the three food stuffs, though a substantial number of patients were sensitive to alcohol but not foods. Thirty-one percent of 331 female patients believed that oral contraceptives precipitated headaches, but this could not be related to any dietary response. Patients with affected relatives were significantly more likely to report sensitivity to alcohol and chocolate; sensitivity to cheese and citrus fruit was less strongly related, and there was no relationship at all for oral contraceptives. These correlations suggest that food induced headaches are mediated by chemical constituents common to these foods.

Alcoholic Beverages↗
PubMed1984

Variation of the spleen-liver activity ratio due to a change in position.

The ratio of splenic to hepatic activity in the posterior view of a Tc-99m SC liver-spleen scan has been used as an indicator of parenchymal disease. Analysis of liver-spleen scans from a series of patients acquired in both the supine and erect positions revealed that the spleen-liver ratio varied considerably with a change in the patient position. Qualitatively there was a shift of colloid from the liver to the spleen in five of 18 supine views and ten of 18 erect views. Quantitative analysis of 37 cases showed that the median erect spleen-liver ratio was 20% greater than the spleen-liver ratio observed in supine patients. Criteria for an abnormal spleen-liver ratio need to be established in each position.

Colloids↗
PubMed1984

Characterization of human brain phenolsulphotransferase.

Both human phenolsulphotransferase M (for monoamines) and P (for phenol) were detected in eight out of twelve brains examined postmortem. Activity values were low compared with those in other human tissues and in brains from other species. The activity of both forms was unevenly distributed in different brain regions in a pattern different from that of the monoamines. From a study of substrate specificity, Km values, and inhibitor sensitivity, the two forms of the human brain enzyme did not appear to differ from their counterparts in platelet.

Adult↗
PubMed1984

Low platelet monoamine oxidase activity in headache: no correlation with phenolsulphotransferase, succinate dehydrogenase, platelet preparation method or smoking.

Platelet monoamine oxidase activity in male migrainous and cluster headache patients was significantly lower than in male controls, confirming our previous study. The activity range showed a normal distribution and low mean values could not be attributed to a subgroup with particularly low activity. When Corash 's platelet preparation method was used, with its high platelet yield, specific enzyme activities of a similar order were obtained. Thus, the low values encountered were not due to abnormal recovery within the platelet population. Two other enzyme activities, phenolsulphotransferase M and succinate dehydrogenase, were also measured in the same platelet samples. Although low succinate dehydrogenase activity was identified in the headache groups, it appeared to represent a separate phenomenon and there was no significant correlation between activity of either enzyme and that of monoamine oxidase. This shows that the low activity of platelet monoamine oxidase in headache is not related to a generalised platelet enzyme deficit. It was also shown that the low monoamine oxidase activity in the headache patients could not be attributed to smoking.

Arylsulfotransferase↗