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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 37 records · Page 2Linked to original sources

Effects of some anxiogenic agents on rat brain monoamine oxidase (MAO) A and B inhibitory (tribulin) activity.

Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine, flumazenil and isatin were administered (ip) to rats at doses known to induce anxiety in this species. All the drugs exhibited anxiogenic response on the elevated plus-maze and induced a parallel increase in endogenous brain monoamine oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced anxiety was fairly well correlated with the magnitude of increase in the MAO A inhibitory component of tribulin but not so with its MAO B inhibitory component. Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine > bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ > yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory component, may be responsible for the postulated function of tribulin as an endogenous marker of anxiety.

Animals↗

Tyramine conjugation deficit in migraine, tension-type headache, and depression.

This study was designed to investigate tyramine sulfate conjugation in patients with migraine or tension-type headache, as defined by the newly introduced International Headache Society (IHS) criteria and to examine whether this relationship is mediated by major depression. A total of 62 subjects completed the study: 38 with migraine (22 with aura and 16 without aura), 12 with tension-type headache, and 12 controls. Patients with migraine had significantly lower urinary tyramine sulfate excretion following oral tyramine challenge than normal control. Tension-type headache was also associated with low tyramine conjugation, but only when comorbid with depression. Although mean tyramine sulfate output was lower among subjects with major depression within each of the subtypes of headache, no significant main effect emerged for depression or major subtype thereof. The lower tyramine sulfate excretion values among patients with both migraine and depression compared to those of migraine alone or depression alone in our data and those of others suggests that comorbid migraine with depression may represent a more severe form of migraine than migraine alone. The findings underscore the importance of comorbidity in clinical and epidemiological studies of migraine.

Adult↗

Rat brain monoamine oxidase A and B inhibitory (tribulin) activity during drug withdrawal anxiety.

Morphine (10 mg/kg), ethanol (8% w/v, 2 ml/kg), nicotine (0.1 mg/kg), cannabis extract (200 mg/kg), lorazepam (10 mg/kg) and ondansetron (0.1 mg/kg) were each administered to rats twice daily i.p. for 14 days and the anxiogenic response following their withdrawal was monitored by the elevated plus-maze test 24 h later. Brains were removed and endogenous monoamine oxidase (MAO) A and B inhibitory activity (tribulin) levels measured on day 14 and 24 h after drug withdrawal in different groups of animals. Morphine, ethanol, lorazepam and nicotine withdrawal was associated with significant anxiety and corresponding increase in brain tribulin activity, particularly its MAO A inhibitory component. Cannabis and ondansetron withdrawal were neither associated with anxiety or change in tribulin levels. The investigation supports the postulated role of tribulin as an endogenous correlate of anxiety, its MAO A inhibitory component accounting for a major part of this effect.

Animals↗

5-Hydroxytryptamine release from platelets by different red wines: implications for migraine.

We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high correlation (r = 0.87) between the effect of red wine and that of reserpine in different individuals. Some types of red wine caused a consistently higher release of 5-HT than others in all subjects; one red wine in particular resulted in negligible release. When several brands of this 'low-releasing' red wine were further examined, they all showed a lower activity than all the brands of a 'high-releasing' red wine type. This variation in releasing power was not related to intensity of red colour. Partial purification of red wine was achieved by column chromatography and showed releasing activity to be associated with a low molecular weight orange fraction. Preliminary studies, using solid phase extraction methods, showed that the active components lie mainly in a subgroup of the flavonoid fraction. If any of the adverse effects of red wine, such as headache induction, derive from this 5-HT releasing ability, then it may be possible to prepare red wines free from the chemical substances responsible.

Blood Platelets↗

Prevalence of antibodies against hepatitis A virus among new immigrants in Israel.

Israel, located in a region endemic for hepatitis A virus (HAV), recently absorbed a large population of immigrants who came from the former USSR. To assess the risk of high morbidity in this population a serosurvey of HAV antibodies was undertaken. Serum samples were collected from 965 new immigrants, of whom 664 came from the European, non-endemic region, and 301 from the Asian and Caucasian endemic regions of the former Soviet Union. They were compared to 240 Israelis. Each population was divided into six age groups: 1-9, 10-19, 20-29, 30-39, 40-49, and 50 years of age and older. The Asian/Caucasian immigrants and the Israeli population were found to share similar characteristics. In both groups, antibodies to HAV (anti-HAV) were present in the 1-9-year-old age group and reached maximum prevalence (90% and 86.7%, respectively) in the 20-29-year-old age group. In contrast, among the European immigrants anti-HAV was first found in the 10-19-year-olds and peaked (93%) in the age group of 50 years and older. It is concluded that immigrants originating from the European part of the former USSR may require vaccination against hepatitis A.

Adolescent↗

Monoamine oxidase A-inhibiting components of urinary tribulin: purification and identification.

The endogenous monoamine oxidase (MAO) inhibitory activity, termed tribulin, contains several components. We have previously identified one of them, isatin, which is a selective inhibitor of MAO B. In the present study we have purified several further components of human urinary tribulin which act as selective inhibitors of MAO A. They have been identified by gas chromatography-mass spectrometry (GC-MS) as ethyl indole-3-acetate (and/or methyl indole-3-propionate), methyl indole-3-acetate and ethyl 4-hydroxyphenylacetate. IC50 values for MAO A were found to be 44 microM (105 microM for methyl indole-3-propionate), 88 microM and 120 microM, respectively, whilst those for MAO B were each greater than 1 mM. The artificial formation of these esters was excluded by carrying the parent acids, from which they are presumably synthesized, through the purification procedure. As tribulin output is increased during stress or anxiety, these results point to a possible role for tryptamine and tyramine pathways in such disorders.

Blood Platelets↗

Isatin is a potent endogenous antagonist of guanylate cyclase-coupled atrial natriuretic peptide receptors.

Isatin (indole-2,3-dione) is an endogenous compound with anxiogenic properties. In the brain, highest levels (0.1 microgram/g) have been found in the rat hippocampus. In the present study, we show that isatin has little effect on a wide range of neurotransmitter and hormonal receptors but that it acts as an inhibitor of atrial natriuretic peptide (ANP) binding, with an IC50 of 4x 10(-7) M. It also inhibits ANP-activated particulate guanylate cyclase from rat kidney, heart and brain membranes in dose-dependent fashion, varying also with ANP concentration. These findings suggest that isatin is a new endogenous regulator of mammalian ANP activity, with potential implications for the control of both anxiety and natriuresis.

Animals↗

Dietary migraine: recent progress in the red (and white) wine story.

The concept of dietary migraine as a clinical entity remains controversial. We review here such objective evidence that has been put forward for its existence. Red wine, in particular, is commonly alleged to initiate attacks in susceptible individuals. We discuss how some of its recently described pharmacological properties might trigger off the sequence of events leading to migrainous headache.

Clinical Trials as Topic↗

Migraine to the year 2000.

Although migraine is inextricably bound up with 5-hydroxytryptamine and its many receptors, its precise mechanisms continue to elude us and there is still no clear evidence supporting either a vascular or neurogenic hypothesis unequivocally. What appears to distinguish migraine sufferers from normal subjects may be a greater gentic sensitivity to a wide variety of triggering agents--even including nitric oxide and the migraine aura, as well as those more usually recognized. Attention is drawn to a possible role for neurotrophins, such as the hyperalgesia-provoking nerve growth factor (NGF) in particular, as well as basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF).

Humans↗

Gut flora and the origin of some urinary aromatic phenolic compounds.

The concentration of several phenolic acids and alcohols was measured in urine from germ-free and specific pathogen-free (SPF) rats before and after inoculation with faecal microorganisms, and from conventional rats before and after gut sterilization. The rate of excretion of benzoic acid, phenylacetic acid, and m- and p-hydroxyphenylpropionic acid in the germ-free animals was markedly increased after inoculation. Some acids showed no increase, including the endogenously generated homovanillic, vanilmandelic and p-hydroxyphenyllactic acids. Most others sought showed a small but significant increase. Some of the compounds excreted by the germ-free animals may have been in the food pellets, either as such or as precursors. The pattern was somewhat different in the SPF rats. The excretion of p-hydroxyphenylpropionic, p-hydroxyphenylacetic and m-hydroxyphenylacetic acids was initially much higher than in the germ-free animals and their excretion decreased after inoculation, presumably because of an altered pattern of gut flora. This work quantifies the effect of gut flora in the formation of some of the more important phenolic acids found in rat urine.

Animals↗

Mild hypomania (the highs) can be a feature of the first postpartum week. Association with later depression.

About 10% of women show elation and associated features of hypomania in the first 5 days following childbirth. These symptoms can be detected using a self-rating scale (the 'Highs') based on SADS-L criteria. This phenomenon has been confirmed using the observer-rated Comprehensive Psychopathological Rating Scale, which also revealed a high degree of related irritability. Significantly more women scoring > or = 8 on the Highs scale at 3 days postpartum went on to manifest depression at 6 weeks than did subjects with no psychopathology in the early puerperium. It is suggested that the 'highs' followed by depression may be a mild and common form of bipolar disorder.

Adult↗

Metabolism of dopamine analogues in rat.

1. The metabolism of dopamine analogues, differing in their ring substituents and length of side chain, has been examined in rat. 2. Both benzylamines and phenethylamines were converted to their analogous acids. Where sought, the corresponding alcohols were present only in minute traces, or were undetectable. 3. Benzylamines were largely excreted as such, possibly conjugated, and this output, together with acid metabolites, accounts for most of the dose. In contrast, only a minor part of the phenethylamine dose was excreted unchanged, and much of what was given remains unaccounted for. 4. With increasing chain length the proportion of the dose found as urinary metabolites decreases markedly; long-chain (hydrophobic) amines may be sequestered in fat depots rendering them largely unavailable for metabolism. 5. beta-Oxidation of long-chain aromatic acids is observed. 6. Catechols showed evidence of O-methylation, and some O-methyl compounds were demethylated. N-methylation and N-demethylation were, at best, very minor pathways. 7. No overall pattern emerged between the position of substituents and the extent of oxidation by monoamine oxidase. No pattern at all was apparent with the benzylamines. Phenethylamines showed a trend towards a lower rate of metabolism for secondary and tertiary amines. Phenethylamines and propylamines with ortho substituents exhibited a lower rate of metabolite excretion than did their analogues.

Animals↗

The effect of pergolide and MDL 72974 on rat brain CuZn superoxide dismutase.

It has previously been shown that both the dopamine receptor agonist, pergolide, and the monoamine oxidase inhibitor, (-)-deprenyl, can cause induction of CuZn superoxide dismutase in the rat striatum. We have now confirmed this effect of pergolide (0.04 mg/kg i.p.) as being localised to the striatum, but not the cerebellum, and shown it to take 3 weeks to develop. Furthermore, we have found that MDL 72974, a more specific monoamine oxidase inhibitor than (-)-deprenyl, failed to bring about such an induction either at a low selective monoamine oxidase B inhibitory dose, or at a higher non-selective dose.

Allyl Compounds↗

Phenylpyruvic acid may be a direct precursor of mandelic acid without intermediate transamination of phenylalanine.

A series of compounds related to phenylalanine was administered to rats. Output of mandelic acid, a major but unexplained metabolite in phenylketonuria, was increased after the administration of phenylethanolamine or phenylpyruvic acid, whereas phenylethylamine or phenylalanine increased its excretion only marginally. Phenylacetic acid, previously suggested as a possible precursor in man, was almost without effect. It seems likely that mandelic acid can be formed from phenylpyruvic acid directly, without intermediate transamination to phenylalanine.

Animals↗

Platelet monoamine oxidase B activity in Parkinson's disease: a re-evaluation.

An increase in platelet monoamine oxidase (MAO) B activity in drug-free parkinsonians (n = 6) compared with healthy controls (n = 10) has been confirmed using both phenylethylamine (PEA) and dopamine as substrates, reaching statistical significance in the case of PEA oxidising activity (p < 0.05). Thus, certain reports of raised platelet MAO B activity towards PEA but decreased activity towards dopamine in parkinsonians, raising the possibility of the existence of an abnormal form of MAO B in this condition, cannot be supported.

Aged↗

Critical components of obstetric management of chemically dependent women.

Providing prenatal care to chemically dependent women presents multiple dilemmas and challenges to clinicians. It is a complex task and one that is incongruent with the usual perceptions of the obstetric experience. However, it must be viewed as an opportunity to bring these alienated women into the health care system. Pregnancy represents a period in most women's lives when they recognize the need for and are receptive to caring and responsive intervention. By optimizing the prenatal experience of chemically dependent women, maternal-fetal outcomes will be improved and the groundwork laid for the ongoing therapeutic services that are needed to maintain the health and well-being of the mother and child.

Adolescent↗