Biomedical subjects

B A Davis

Publications and source records attributed to B A Davis.

At least 55 records · Page 3Linked to original sources

PubMed1995

Inhibition of MAO-B by (-)-deprenyl alters dopamine metabolism in the macaque (Macaca facicularis) brain.

The present study has examined whether MAO-B has a role in DA metabolism in the primate CNS in situ. Eleven macaques (macaca facicularis) were used in this study to examine the effects of (-)-deprenyl (1 mg/kg, i.v., 2 and 24 hours). (-)-Deprenyl administration completely and selectively blocked MAO-B activity and blocked DA metabolism in the caudate nucleus and frontal cortex. DA metabolism in the substantia nigra was not affected by MAO-B inhibition. Changes in DA metabolism were accompanied by changes in 5-hydroxytryptamine (5HT) turnover: 5-hydroxyindole acetic acid (5HIAA) levels increased in the caudate and decreased in the frontal cortex. Levels of 2-phenylethylamine (PE), a putative modulator of dopaminergic transmission, were increased by MAO-B inhibition in all three brain regions examined. It is concluded that in some regions of the primate brain, in contrast to the rat, MAO-B has an important role in DA metabolism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Neurochemical, neuroprotective and neurorescue effects of aliphatic N-methylpropargylamines; new MAO-B inhibitors without amphetamine-like properties.

A series of aliphatic N-methylpropargylamine MAO-B inhibitors have been synthesized and their structural and functional relationships have been investigated. 2-Hexyl-N-methylpropargylamine (2-HxMP), for example, has been found to be a highly potent, irreversible, selective, MAO-B inhibitor both in vitro and in vivo. The R-(-)-enantiomers are much more active than the S-(+)-enantiomers at inhibiting MAO-B activity. Some of these compounds protect mouse nigrostriatal dopamine neurons against the neurotoxin MPTP and the mouse hippocampal noradrenergic system against the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). They rescue hippocampal neurons after damage induced by ischemia and kainic acid treatment, as well as motoneurons in young mice following facial nerve axotomy. Such rescue effects are, interestingly, unrelated to inhibition of MAO-B activity. Some of the aliphatic propargylamines enhance the survival of neuroblastoma cells co-cultured with astrocytes following serum depletion. They stimulate the expression of AADC mRNA and inhibit GFAP mRNA expression. They do not possess amphetamine-like properties and exhibit no effect on noradrenaline or dopamine uptake nor do they increase hypertensive effects in the tyramine pressor test. Unlike R(-)-deprenyl, 2-HxMP does not potentiate dopamine toxicity in vitro. These new MAO-B inhibitors may possess significant chemotherapeutic implications for certain psychiatric and neurodegenerative disorders.

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↗

PubMed1995

Color stability of hybrid ionomers after accelerated aging.

PURPOSE: The color stability and surface roughness of three commercial hybrid ionomers were determined in vitro after accelerated aging. Three shades of each hybrid ionomer prepared in light-cured and dark-cured conditions were tested. MATERIALS AND METHODS: Samples were aged in an artificial aging chamber by subjecting them to total ultraviolet light irradiation of 150 kJ/m2 over a period of 77 hours. Color (CIE LAB system) was measured before and after aging on a reflection spectrophotometer. Surface roughness was measured with a profilometer. RESULTS: After accelerated aging, all samples became lighter. Photac-Fil Aplicap (ESPE-Premier, Norristown, PA) and Fuji II LC (GC America, Chicago, IL) also became less chromatic (less red and less yellow). Among the light-cured samples, Fuji II LC had the greatest change in color followed by Photac-Fil Aplicap and Vitremer (3M Dental Products, St Paul, MN). For the dark-cured samples, Fuji II LC had the greatest change in color followed by Vitremer and Photac-Fil Aplicap. There were no differences in delta E* between the two lightest shades, but the darker shades of each product showed the greatest changes in color. All samples became significantly rougher after aging. CONCLUSIONS: Hybrid ionomers changed color significantly and perceptibly after in vitro accelerated aging. Surfaces became significantly rougher and showed evidence of cracking and degradation.

Analysis of Variance↗

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

Effect of structural modification of alkyl N-propargylamines on the selective inhibition of monoamine oxidase B activity.

A series of alkyl N-methyl-propargylamine derivatives has been discovered recently to be very potent selective irreversible monoamine oxidase B inhibitors (MAO-B). In the present study, we used a simple compound in this series, namely N-2-butyl-N-methylpropargylamine.HCl (2-BuMP), as the basic structure to investigate the effect of structural modification on the effectiveness and selectivity of the inhibition of MAO activities. When the N-methyl group was replaced by a hydrogen atom, an ethyl group or a propargyl group, MAO inhibitory activity was abolished. The modification of the propargyl group, e.g. to 3-butynyl, N-cyanomethyl or to allyl groups, also destroyed the inhibitory activity. The potency of the inhibitors was related to the carbon chain length of the alkyl group as well as to the substitution of the alpha or the terminal carbon atoms. Substitution of hydroxyl, carboxyl or carboethoxyl groups on the terminal carbon of the alkyl chain drastically reduced the inhibitory activity. More potent MAO inhibitory activity was observed for molecules with a single methyl group substitution on the alpha carbon in comparison with those substituted with two hydrogen or two methyl groups. Other branched alkyl N-methylpropargylamines, e.g. N-methyl-N-(3-pentyl)propargylamine, appeared to be slightly less selective in the inhibition of MAO-B activity. Some of these alkyl propargylamine MAO-B inhibitors, which do not possess the amphetamine-like moiety of L-deprenyl, may have significant neuropsychopharmacological implications.

Alkylation↗

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↗