Biomedical subjects

B A Davis

Publications and source records attributed to B A Davis.

At least 19 recordsLinked to original sources

PubMed1995

Aliphatic propargylamines, a new series of potent selective, irreversible non-amphetamine-like MAO-B inhibitors. Their structures, function and pharmacological implications.

1-Deprenyl, a selective irreversible MAO-B inhibitor, has been shown to prolong the onset of disability in Parkinson's patients and to improve cognitive behavior in Alzheimer's disease. It has been claimed that 1-deprenyl exhibits neuroprotective and neurorescue effects in several animal models. The precise mechanism of these effects is unknown. It is yet to be established whether or not the effects are unique to 1-deprenyl; a drug which possesses, in addition to inhibition of MAO-B activity, an amphetamine moiety. Based on the fact that several N-methylpropargylamine derivatives have been shown to be MAO inhibitors and that aliphatic amines are typical MAO-B substrates with a high affinity for the enzyme, we have synthesized a series of aliphatic propargylamines which have turned out to be highly potent, selective and irreversible MAO-B inhibitors, structurally unrelated to amphetamine. The potency of these inhibitors is related to their chain length and the substitution of a hydrogen on the terminal carbon of the aliphatic chain. MAO-I activity, as assessed in vitro, increased as the aliphatic carbon chain length increased; substitution of the hydrogen at the aliphatic chain terminal by hydroxyl, carboxyl or carboethoxyl groups or replacement of the methyl group on the nitrogen atom by an ethyl group considerably reduced their inhibitory activity. Stereospecific effects were observed with the R-(-)-enantiomer being 20-fold more active than the S-(+)-enantiomer. Inhibitors with relatively short carbon chain lengths (i.e. four to six carbons) were found to be more potent at inhibiting brain MAO-B activity in vivo especially after oral administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1995

Folic acid absorption in women with a history of pregnancy with neural tube defect.

Folic acid absorption was compared in nonpregnant women with a history of pregnancy with a neural tube defect (cases)(n = 10) with that of control women (n = 10) with a normal pregnancy history. [2H4]folic acid was administered in an oral dose (400 micrograms) to fasting case and control subjects after a 30-d saturation protocol involving daily ingestion of two 1-mg folic acid supplements. Serum and red blood cell folate concentrations were not different for case and control subjects before or during the saturation protocol (P > 0.05). The percentage (x +/- SD) of the oral dose of [2H4]folic acid excreted in 24-h urine collections postdose was not different (P > 0.05) for case compared with control subjects (9.05 +/- 2.25% and 11.10 +/- 3.41%, respectively). These data suggest that the absorption of folic acid routinely consumed in supplements and fortified food products is not impaired in women with a history of a pregnancy with a neural tube defect. Further case-controlled studies are needed to compare the absorption of the predominant dietary form of the vitamin.

Administration, Oral↗

PubMed1995

Controlled dietary folate affects folate status in nonpregnant women.

In a study designed to estimate the requirement for dietary folate in nonpregnant women, 17 women (21-27 y) consumed 200, 300, or 400 micrograms/d of total folate for 70 d which was provided by low folate conventional foods (30 micrograms) plus supplemental folic acid. Group means for initial serum and erythrocyte folate and plasma homocysteine concentrations were not significantly different. Serum and erythrocyte folate decreased relative to the initial value in the 200 micrograms/d group (43.4 +/- 12.1%, 13.6 +/- 16.6%, respectively; mean +/- SD), in contrast to an increase in the 400 micrograms/d group (16.8 +/- 52.0%, 10.2 +/- 18.5%, respectively). The final serum folate in the 200 and 300 micrograms/d groups (6.4 +/- 0.8 nmol/L, 7.3 +/- 1.1 nmol/L, respectively) was significantly lower than that of the 400 micrograms/d group (14.3 +/- 2.0 nmol/L), with evidence in the 200 micrograms/d and 300 micrograms/d groups of low ( < 6.8 nmol/L) serum folate concentrations. Differences in final erythrocyte folate did not reach statistical significance, although low values ( < 362 nmol/L) were frequent in subjects with 200 micrograms/d intake. In the 200 micrograms/d group, plasma homocysteine was negatively correlated with serum and erythrocyte folate, and final mean plasma homocysteine (12.6 +/- 1.7 mumol/L) was significantly higher than that of the 300 or 400 micrograms/d groups. Elevated plasma homocysteine levels ( > 16 mumol/L) were observed in the 200 micrograms/d group only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Developing effective measurement tools: a case study of the Consumer Emergency Care Satisfaction Scale.

Development of valid and reliable instruments to assist nurse researchers and clinicians in meeting the needs of consumers is an avenue toward continuous quality improvement (CQI). This article explains validity and reliability and the process of constructing a valid and reliable scale. The development of the Consumer Emergency Care Satisfaction Scale, a measure of quality nursing care in the emergency department, is used as the example.

Consumer Behavior↗

PubMed1994

Characterization of human serum and umbilical artery semicarbazide-sensitive amine oxidase (SSAO). Species heterogeneity and stereoisomeric specificity.

Semicarbazide-sensitive amine oxidases (SSAOs) are located in cardiovascular smooth muscle, cartilage and brown adipose tissues of different species, including human. The enzyme is also present in blood, and its activity appears to be altered under certain pathological conditions. SSAOs from both human umbilical arteries and serum were partially purified, and some of their biochemical properties were investigated. Both human artery and blood SSAO exhibited very similar substrate preference, lack of stereospecificity catalyzing the deamination of pro-R and pro-S benzylamine-deuterated enantiomers, and were very sensitive towards (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (MDL-72974A). It was concluded that circulating serum SSAO is identical to the SSAO from vascular tissues. Human SSAO exhibited distinctly different properties in comparison to bovine and rat SSAOs.

Allyl Compounds↗

PubMed1994

Deamination of aliphatic amines by type B monoamine oxidase and semicarbazide-sensitive amine oxidase; pharmacological implications.

Straight and branched chain aliphatic monoamines, which are not normal tissue constituents, are deaminated selectively by type B monoamine oxidase (MAO-B). They exhibit a high affinity towards the active site of MAO-B and this made them very useful pharmacologically. An anticonvulsant prodrug, Milacemide [2-(N-pentyl)glycinamide] is deaminated by MAO-B and this facilitates a mechanism of delivering glycine into the CNS. We have found that 2-propyl-pentylamine (2-propyl-1-aminopentane) and N-(2-propylpentyl)glycinamide are also converted by MAO-B to valproic acid and glycine both in vitro and in vivo; these compounds, however, cause severe tremor. By attaching a propargylamine group the resultant series of aliphatic propargylamine derivatives have been shown to be very potent selective MAO-B inhibitors. They are chemically quite different from most other MAO-B inhibitors, since they do not possess any aromatic structures. The relatively short chain aliphatic propargylamines, i.e. N-2-pentyl-N-methylpropargylamine and N-2-hexyl-N-methylpropargylamine, are 4 to 5 times more potent and more selective than selegiline (1-deprenyl) with respect to the inhibition of MAO-B in brain following oral administration. Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of not only longer chain aliphatic amines but also short chain aliphatic amines including methylamine. Formaldehyde is produced from methylamine by SSAO. Increased methylamine deamination may cause cellular damage in some pathological conditions, such as uraemia and diabetes. We have observed that cultured human endothelial cells are damaged by methylamine in the presence of SSAO. Inhibition of the SSAO activity completely protects these cells from the methylamine-SSAO induced damage.

Amine Oxidase (Copper-Containing)↗

PubMed1994

The trace amines and their acidic metabolites in depression--an overview.

1. Investigations of the role of the trace amines (phenylethylamine, tryptamine, m- and p-tyramine) and their acidic metabolites (phenylacetic, indoleacetic, m- and p-hydroxyphenylacetic acids) in depression are reviewed. 2. The evidence for the phenylethylamine hypothesis of depression is mixed. 3. Reduced phenylacetic acid levels in urine, plasma and CSF and changes in those levels during treatment with antidepressants show potential as state markers for depression. 4. Impaired p-tyramine conjugation following a tyramine challenge may be a good trait marker for depression.

Amines↗

PubMed1994

Phenylethylamine and schizophrenia.

1. The evidence that phenylethylamine (PEA) plays a role in the etiology of schizophrenia is reviewed. 2. PEA shares structural and physiological similarities with the amphetamines, the administration of which can induce a schizophrenia-like psychosis. 3. While there are a number of reports of high urinary PEA excretion in schizophrenic patients, the measurement of PEA in other body fluids and the measurement of phenylacetic acid (the major metabolite of PEA) has resulted in inconsistent findings. 4. The use of neuroleptic medication is a major confounding variable in most of the clinical studies. If PEA does have a role in the etiology of schizophrenia, the mechanism may involve PEAs ability to amplify dopamine responses.

Antipsychotic Agents↗

PubMed1994

Neurochemical and neuroprotective effects of some aliphatic propargylamines: new selective nonamphetamine-like monoamine oxidase B inhibitors.

Aliphatic N-propargylamines have recently been discovered to be highly potent, selective, and irreversible monoamine oxidase B (MAO-B) inhibitors. N-Methyl-N-(2-pentyl)propargylamine (M-2-PP) and N-methyl-N-(2-hexyl) propargylamine (2-HxMP), for example, are approximately fivefold more potent that l-deprenyl at inhibiting mouse brain MAO-B activity following oral administration. These inhibitors are nonaromatic compounds and are chemically quite different from other known MAO-B inhibitors. Some of their neurochemical and neuroprotective properties have been evaluated and compared with those of l-deprenyl. We have confirmed that these new inhibitors selectively inhibit MAO-B activity both in vitro and in vivo. 2-Phenylethylamine levels were substantially increased following administration of M-2-PP, but the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid were not affected except at high, nonselective doses. Chronic oral administration of l-deprenyl and M-2-PP causes selective inhibition of MAO-B activity and increases dopamine levels in mouse caudate. M-2-PP, like l-deprenyl, has been shown to be potent in protecting against MPTP-induced damage in the mouse. N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenaline neurotoxin, is not an MAO substrate. Its noradrenaline-depleting effects were substantially mitigated by l-deprenyl as well as by M-2-PP and 2-HxMP in the mouse hippocampus. Administration of 2-phenylethylamine, however, failed to reverse the effect of DSP-4. The neuroprotective effect of M-2-PP and 2-HxMP is apparently unrelated to the uptake of DSP-4.

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

PubMed1994

Neuroprotective effects of some monoamine oxidase-B inhibitors against DSP-4-induced noradrenaline depletion in the mouse hippocampus.

DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenaline (NA) uptake blocker, is capable of inducing long-lasting depletion of NA in some noradrenergic axon terminals and of subsequently causing cell death to NA neuronal cell bodies in rodents. R(-)-Deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, has been shown to be capable of protecting animals against this DSP-4-induced neuronal degeneration. Its action, however, has been claimed to be unrelated to the inhibition of MAO-B activity but rather due to competition for the NA uptake sites. The effects of several types of MAO inhibitors against DSP-4 toxicity, MAO-B activity both in vivo and in vitro, and NA uptake into the hippocampus have been assessed. N-(2-Hexyl)-N-methylpropargylamine (2-HxMP), a potent MAO-B inhibitor, for example, exerts no appreciable effect on NA uptake but is quite potent in counteracting the NA-depleting effect of DSP-4. Such results rule out the possibility that the neuroprotective effect of the MAO-B inhibitors is due mainly to their effect on NA uptake. The in vitro inhibition of MAO-B activity seems to correlate positively with their neuroprotective effects against DSP-4. In comparison to the MAO-B inhibitors, NA uptake blockers, such as desipramine and S(+)-deprenyl, exhibit relatively low efficacy in protecting the NA axon terminals from the effects of DSP-4-induced damage. The restoration of hippocampal NA levels is significantly enhanced with repeated treatments of R(-)-deprenyl or 2-HxMP even at very low doses following the DSP-4 insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of immersion disinfection on properties of impression materials.

PURPOSE: Dimensional change and wettability were determined for three addition silicones and a polyether impression material after disinfection by immersion for two 30-minute cycles in 2% acid-potentiated glutaraldehyde. MATERIALS AND METHODS: Contact angles of water on disks were measured on a goniometer. Dimensional change was determined by change in distance between two reference lines. Contact angle (degree) and dimensional change (percent) of five samples were measured after 0-, 30-, 60-, and 1,440-minute intervals of storage in air and disinfectant. RESULTS: The contact angle in air increased for two addition silicones and remained constant for the remaining materials. In disinfectant, the contact angle increased for all four materials, with the contact angle of the polyether increasing the least. In air, dimensional change decreased significantly for an addition silicone and a polyether. In disinfectant, the dimensional changes of the addition silicones were not significant, but the polyether increased in dimension after 1,440 minutes. CONCLUSIONS: Two 30-minute cycles of disinfection in 2% acid-potentiated glutaraldehyde reduced wettability, but had little effect on the dimensional change of the addition silicones and polyethers tested.

Analysis of Variance↗

PubMed1994

Shrinkage-induced activation of Na(+)-H+ exchange in barnacle muscle fibers.

We examined the effect of shrinkage on Na(+)-H+ exchange in single muscle fibers at intracellular pH (pHi) values of 6.8, 7.2, and 7.6 using pH microelectrodes and internal dialysis. Under normotonic conditions (975 mosmol/kgH2O) at pHi 6.8, the amiloride-sensitive acid-extrusion rate (JAmil/s) averaged 17 microM/min. Exposure to hypertonic solutions (1,600 mosmol/kgH2O) increased JAmil/s to 304 microM/min at pHi 6.8. At pHi approximately 7.2 and 7.6, hypertonicity increased JAmil/s from approximately 0 to approximately 172 microM/min (pHi 7.2) and approximately 0 to approximately 90 microM/min (pHi 7.6). Thus, under normotonic conditions, Na(+)-H+ exchange activity is slight at pHi approximately 6.8 and virtually nil at higher pHi values. Shrinkage stimulated Na(+)-H+ exchange, more at low pHi values. We also examined the Cl- dependence of the Na(+)-H+ exchanger's response to shrinkage. Our results indicate that shrinkage-induced activation of Na(+)-H+ exchange requires Cl-, specifically intracellular Cl-. These results establish that shrinkage is both pHi dependent and requires intracellular Cl-.

Animals↗

PubMed1994

Correlations of plasma and urinary phenylacetic acid and phenylethylamine concentrations with eating behavior and mood rating scores in brofaromine-treated women with bulimia nervosa.

Women with bulimia nervosa undergoing treatment with the reversible monoamine oxidase type A inhibitor, brofaromine, were rated for mood and eating behaviour and their plasma and urine were assessed for phenylacetic acid (unconjugated and total) and unconjugated phenylethylamine prior to and after four weeks of drug treatment. Changes in plasma unconjugated phenylacetic acid concentrations were significantly and negatively correlated with the corresponding changes in Hamilton Depression scores but not with eating behavior measures. There were no significant correlations between changes in phenylethylamine levels and changes in rating scores. Patients diagnosed as suffering concurrently from severe depression (Hamilton Depression score of 17 or higher) had lower plasma and urinary phenylacetic acid levels than did those whose depression was not severe (Hamilton score less than 17). Phenylethylamine concentrations were not different between the severely and mildly depressed subgroups. The results confirm earlier studies on the relationship between phenylacetic acid and depression while showing that a similar relationship does not pertain to phenylacetic acid and eating behavior in bulimia nervosa.

Adult↗

PubMed1993

Inhibition of tryptophan hydroxylase by 6,7-dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline, a cyanomethyl derivative of dopamine formed from cigarette smoke.

6,7-Dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline, a cyanomethyl derivative of dopamine formed from cigarette smoke, was found to inhibit the activity of tryptophan hydroxylase. The inhibition was non-competitive to the substrate L-tryptophan (the Ki value 7.25 +/- 0.81 microM), but not to the biopterin cofactor. The inhibition is irreversible. 6-Hydroxy-N-cyanomethyl-tetrahydro-beta-carboline, a cyanomethyl derivative of serotonin, is inactive towards the hydroxylase. 6,7-Dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline may affect the serotonin biosynthesis in vivo as a consequence of cigarette smoking.

Animals↗

PubMed1993

Determination of regional distributions of phenylethylamine and meta- and para-tyramine in rat brain regions and presence in human and dog plasma by an ultra-sensitive negative chemical ion gas chromatography-mass spectrometric (NCI-GC-MS) method.

Using a new ultrasensitive method the trace biogenic amines, phenylethylamine, meta-tyramine and para-tyramine have been quantitated in brain regions obtained from a single rat. Phenylethylamine concentrations in ng/g wet tissue (mean +/- std. error) were as follows: caudate 2.71 +/- 0.73, hypothalamus 0.45 +/- 0.15, cerebellum 0.09 +/- 0.02, olfactory bulb 0.35 +/- 0.11, stem 0.13 +/- 0.03, hippocampus 0.20 +/- 0.11, cortex 0.69 +/- 0.13 and the rest (remainder of the brain) 2.81 +/- 0.41. Mean whole brain was 1.23 +/- 0.19 ng/g, in agreement with previous measurements. meta-Tyramine concentrations (ng/g) were: caudate 2.69 +/- 0.19, hypothalamus 0.32 +/- 0.16, cerebellum 0.07 +/- 0.04, olfactory bulb 0.09 +/- 0.04, stem 0.04 +/- 0.01, hippocampus 0.07 +/- 0.02, cortex 0.18 +/- 0.15 and the rest 0.15 +/- 0.06, with a mean whole brain value of 0.26 +/- 0.05 ng/g and para-tyramine concentrations were: caudate 8.99 +/- 1.60, hypothalamus 0.93 +/- 0.13, cerebellum 0.78 +/- 0.27, olfactory bulb 0.70 +/- 0.13, stem 0.90 +/- 0.36, hippocampus 0.40 +/- 0.06, cortex 1.78 +/- 0.28 and the rest 2.38 +/- 0.12 and mean whole brain was 1.90 +/- 0.25 ng/g. In human plasma the concentrations of the three amines were found to be 31.3 +/- 3.4 pg/ml, 5.3 +/- 1.6 pg/ml and 66.0 +/- 9.9 pg/ml respectively and in dog blood 95.3 +/- 4.6 pg/ml, 24.0 +/- 7.6 pg/ml and 486 +/- 43 pg/ml respectively. When monoamine oxidase inhibitors were added to the blood immediately after collection there were no significant increases in the amine levels indicating that MAO-B is not present in plasma in significant quantities.

Animals↗

PubMed1993

The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog.

Behavioral and pharmacological effects of oral administration of L-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects of L-deprenyl on behavior and cognitive function.

Administration, Oral↗

PubMed1993

Effects of chronic brofaromine administration on biogenic amines including sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa.

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.

Adolescent↗

PubMed1993

A longitudinal study of the relationships between psychometric test scores, offence history and the plasma concentrations of phenylacetic and 5-hydroxyindoleacetic acids in seven inmates of a prison for the psychiatrically disturbed.

1. The plasma concentrations of phenylacetic (PAA) and 5-hydroxyindoleacetic (5HIAA) acids in seven inmates incarcerated in the Regional Psychiatric Centre (Prairies), Correctional Service of Canada, were assessed each weekday for four weeks (i.e., 20 samples each). Psychometric assessments for hostility, anger, depression and anxiety were also performed daily. Mean differences between subjects in psychometric and biochemical measures were subjected to tests of statistical significance. 2. The subject who was clearly most aggressive by offence history/institutional behavior scored significantly highest on scales of anger and hostility and significantly lowest with respect to PAA concentration. It was concluded that PAA may be a trait marker for aggression. 3. Plasma 5HIAA concentrations were invariant between subjects. 4. The psychometric measures were intercorrelated, thus confounding the variables of interest. They also varied little, proving insensitive to subtle mood changes.

Adult↗