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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 19 recordsLinked to original sources

Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: evidence for a monoamine oxidase A inhibiting component of tribulin.

Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin.

Animals

Inhibitory potency of some isatin analogues on human monoamine oxidase A and B.

Isatin is an endogenous compound which acts as a selective inhibitor of monoamine oxidase (MAO) B. In this study a range of isatin analogues were tested for their in vitro inhibition of human MAO A and B. Most of the analogues were less potent than isatin. Hydroxylation of the aromatic ring changed the inhibitory potency in favour of MAO A, with 5-hydroxyisatin being a potent and selective MAO A inhibitor (IC50 8 microM). Isatinic acid, which is formed reversibly from isatin at alkaline pH, showed no inhibition.

Blood Platelets

Pergolide can induce soluble superoxide dismutase in rat striata.

Pergolide, a dopamine receptor agonist, given daily i.p. for three weeks at 0.04 mg/kg and 0.4 mg/kg, significantly induced soluble (Cu-Zn) superoxide dismutase in the rat striatum, while having no effect on the mitochondrial (Mn) form of the enzyme. Such induction, which can also be effected by (-)-deprenyl, may help to protect against nigrostriatal degeneration.

Animals

Abnormal platelet 5-hydroxytryptamine uptake and imipramine binding in postnatal dysphoria.

Platelet 14C-5-hydroxytryptamine (14C-5-HT) uptake, 3H-imipramine binding and monoamine oxidase (MAO) activity were measured in women 5 days postpartum and compared with depression scores (Edinburgh Postnatal Depression Scale) at that time and 6 weeks later. Mean Km of 14C-5-HT uptake was significantly reduced in the group showing dysphoria at 5 days (p less than 0.01). Mean Kd of 3H-imipramine binding was significantly increased in the group who later went on to become depressed at 6 weeks postpartum (p less than 0.03). Vmax for 14C-5-HT uptake, Bmax for 3H-imipramine binding and MAO activity did not differ between depressed and non-depressed patients on either occasion. Although the observed changes manifested in a system known to be disturbed in other forms of depression, they were in affinity rather than Bmax or Vmax. Even though probably not of direct physiological significance, such results, if confirmed, together with other pointers in the literature, suggest biochemical abnormalities specific to the puerperal period.

Adult

Is the tyramine test for depressive illness useful in elderly patients?

There were no significant differences in tyramine sulphate excretion following tyramine ingestion between elderly depressed, demented or control patient groups, in contrast with younger subjects where this test is a trait marker for unipolar endogenous depression. There are inherent problems in urine collection studies in the elderly and the results may have been influenced by the medication that elderly patients have to take for other disorders. This study suggests that the tyramine test is unlikely to be of clinical usefulness in the over 65 age group.

Aged

Amiodarone dosage in older patients with atrial fibrillation: an open, multi-centre study.

An open, multi-centre study was carried out to assess the effectiveness and tolerability of amiodarone at a lower dose than routinely used in the clinical and symptomatic treatment of older patients with atrial fibrillation who were resistant to other therapy or in whom other therapy was either poorly tolerated or contraindicated. Suitable patients for dose adjustment were selected from a dosing survey population of those aged 60 years or over who were currently receiving amiodarone at a dosage of 200 mg or more daily. Periodic 100 mg dose reductions were made at 6-weekly intervals until there were signs of exacerbation or recurrence of the arrhythmia or until a daily dose of 100 mg was reached. Evaluation of the results from 167 patients showed that 156 (94%) were stabilized on a final dose of 100 mg daily and the remaining 11 (6%) on 200 mg daily. The majority of these patients were either in sinus rhythm or atrial fibrillation with a ventricular rate less than 100 beats per min. Twenty-one patients reported 22 adverse events. The majority of adverse events were not considered serious by the investigators, while approximately half were considered as 'probably unrelated' to amiodarone treatment. Six deaths were recorded during the treatment period but none was linked to amiodarone or 'probably related' to dose reduction.

Aged

Links between early post-partum mood and post-natal depression.

The Edinburgh Postnatal Depression Scale (EPDS) was used to rate 217 patients at five days and six weeks post-partum. There was a highly significant positive correlation between the two scores, together with similar symptom profiles. Of the 25 women who suffered post-natal depression (6-week EPDS score greater than or equal to 13), 17 had similar symptoms in the first week post-partum (5-day EPDS score greater than or equal to 10). Low birth weight of the baby, delivery by Caesarean section, a delivery much more difficult than expected, and bottle feeding were all significantly associated with a high EPDS score in the first week post-partum. Bottle feeding and delivery by Caesarean section were the only factors associated with depression at the sixth week. A recollection of low mood after a previous birth was also associated with post-natal depression after the current birth. This, together with an EPDS score of 13 or more at five days post-partum, increased the risk of post-natal depression at six weeks 85-fold.

Adult

Training experience and views of recently appointed consultants in geriatric medicine.

A postal survey of 71 recently appointed consultant geriatricians was undertaken in spring 1991. Several respondents were concerned about the adequacy of training in domiciliary visiting and continuing care, and about the time allocated for research and study. A high proportion felt they had been poorly prepared for the administrative and organisational components of their consultant post, and 75% of respondents advocated training in managerial skills for senior registrars. These findings are relevant to the planning of future training for senior registrars in geriatric medicine.

Attitude of Health Personnel

Effect of aromatic amino acids, pentylenetetrazole and yohimbine on isatin and tribulin activity in rat brain.

The effects of i.p. injection of 3 aromatic amino acids and two anxiogenic agents on rat brain isatin concentration and tribulin (endogenous monoamine oxidase inhibitor) activity were investigated. Isatin levels were significantly increased by pentylenetetrazole, confirming the link with 'anxiety', but were unaffected by the other compounds. In contrast, tribulin activity was significantly increased by phenylalanine and tryptophan as well as by both pentylenetetrazole and yohimbine. Whilst these findings shed no light on the mode of synthesis of isatin, they clearly demonstrate the existence of rat brain monoamine oxidase inhibitory activity that is different from it.

Animals

Augmentation of rat brain endogenous monoamine oxidase inhibitory activity (tribulin) by electroconvulsive shock.

The effects of acute and subacute supramaximal and submaximal electroshock-induced convulsions on rat brain tribulin activity were investigated. Both supramaximal and submaximal shocks induced a marked increase, as measured 30 min after the onset of convulsions, with a significantly greater effect from the former. The effects were no longer present 24 h after stimulus. Repeated electroshock for 5 and 10 days showed that submaximal stimuli produced little change, whereas supramaximal shock brought about a significant increase in tribulin activity, the effect being greater with 10-day exposure. The results are not inconsistent with the clinical observation that a single electroconvulsive therapy (ECT) shock has little clinical usefulness but that repeated shocks, spread over several days, result in therapeutic benefit due, perhaps, to an increase in brain concentrations of tribulin, an endogenous monoamine oxidase inhibitor.

Animals

Isatin (indole-2,3-dione) in urine and tissues. Detection and determination by gas chromatography-mass spectrometry.

A simple procedure based upon capillary column gas chromatography-mass spectrometry (GC-MS) is described for the detection and determination of isatin (indole-2,3-dione) in body fluids and tissues. After addition of 5-methylisatin as internal standard to urine or tissue homogenates, organic extracts are dried and derivatized successively with hydroxylamine hydrochloride and the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). The tert.-butyldimethylsilyl derivatives obtained show good GC-MS properties and allow quantification by selected-ion monitoring of m/z 333 (isatin) and m/z 347 (internal standard). Adult and newborn human urine output values lie in the ranges 0.4-3.2 mg/mmol of creatinine (5-30 mg per 24 h) and 0.002-0.518 mg/mmol of creatinine, respectively. There is a discontinuous regional distribution in rat tissues. The GC-MS properties of a number of derivatives formed by successive reaction of isatin with hydroxylamine hydrochloride (or methoxyaminehydrochloride or ethoxyamine hydrochloride) and MTBSTFA, bis(trimethylsiyl)trifluoroacetamide, pentafluoropropionic anhydride or pentafluorobenzyl bromide are also described.

Acetamides

Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attacks.

Urinary output of endogenous monoamine oxidase (MAO) inhibitory activity, was significantly raised in serial samples collected across a migraine attack compared with collections during attack-free periods and in healthy controls, which did not differ from each other. There was a highly significant correlation in output between isatin, a major fraction of the MAO inhibitory activity, and output of the MAO inhibitory activity itself. However, although there was a tendency towards increased isatin excretion during migraine attacks, it failed to reach statistical significance.

Acute Disease

(-)-Deprenyl can induce soluble superoxide dismutase in rat striata.

(-)-Deprenyl (0.25 or 2 mg/kg) or saline was injected daily into male Wistar rats for 3 weeks. The striata were dissected out and soluble and particulate superoxide dismutase activity measured. (-)-Deprenyl at 2 mg/kg induced a significant increase in the soluble but not the particulate form of the enzyme. The possibility that this action contributes to the ability of (-)-deprenyl to retard nigral degeneration in man and prolong life in rats is discussed.

Animals

Tyramine conjugation test distinguishes unipolar from bipolar depressed patients and controls.

Tyramine sulphate conjugation following oral tyramine administration (the tyramine test) has previously been found to distinguish endogenous unipolar from neurotic depression and appears to be a trait marker. In this study, the test was used in 24 unipolar depressed patients compared with similar sized matched groups of bipolar depressed patients and normal controls. Most of the depressed patients in each group showed endogenous features. The study found that whereas tyramine sulphate conjugation was significantly impaired in unipolar patients, values in the bipolars were similar to those of controls. These results provide further evidence for the biological difference between unipolar and bipolar depression.

Administration, Oral

Platelet [3H]imipramine binding in migraine and tension headache in relation to depression.

Platelet [3H]imipramine binding was measured in 40 migrainous (7 classical and 33 common) and 17 tension headache patients and in 28 normal controls. A significant reduction in Bmax was found in migraine compared with controls (p less than 0.05) but not in tension headache. In migraine, there was no significant relationship between Bmax and depression or anxiety score on the self-rating Hospital Anxiety and Depression (HAD) Scale, suggesting that the reduction in Bmax is a concomitant of migraine itself rather than a manifestation of associated depression. Preliminary evaluation using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) tended to confirm this conclusion.

Adult

Release of (14C)5-hydroxytryptamine from human platelets by red wine.

Red wine, at a final dilution of 1/50, caused release of [14C]5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

Beer

Chocolate is a migraine-provoking agent.

Patients with migraine who believed that chocolate could provoke their attacks were challenged with either chocolate or a closely matching placebo. In a double-blind parallel group study, chocolate ingestion was followed by a typical migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had an attack (p = 0.051). The median time to the onset of the attack was 22 h. This brief study provides some objective evidence that chocolate is able to provoke a migraine attack in certain patients who believe themselves sensitive to it.

Adult