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Biomedical subjects

B A Davis

Publications and source records attributed to B A Davis.

At least 91 records · Page 5Linked to original sources
PubMed1991

Studies on the properties of some peripheral MAO inhibitors.

1. Studies were carried out on three monoamine oxidase (MAO) inhibitors, two of which, debrisoquine and para- hydroxyphenelzine, are purported to be peripheral inhibitors and one, phenelzine, is a peripherally acting inhibitor, which has been included for comparitive purposes. 2. All three showed varying degrees of specificity towards MAO type A. 3. The action of debrisoquine was very rapid as was that of para- hydroxyphenelzine. 4. The inhibition caused by debrisoquine was competitive and reversible, while that caused by both phenelzine and para- hydroxyphenelzine was irreversible. 5. The inhibition caused by debrisoquine appeared to be unaffected by the pH of the medium.

Animals↗
PubMed1991

Deamination of 2-propyl-1-aminopentane and 2-[(2-propyl)pentylamino] acetamide by amine oxidases: formation of valproic acid.

1. 2-Propyl-1-aminopentane and 2-[(2-propyl)pentylamino]acetamide are deaminated by rat liver monoamine oxidase (MAO) and aorta semicarbazide-sensitive amine oxidase (SSAO). 2. The deaminated product, 2-propylpentaldehyde, is further converted to valproic acid in vitro as well as in vivo. 3. The anticonvulsant action of these two compounds could not be substantiated, because both drugs at relatively low doses caused distinct tremor in mice and rats. 4. Both compounds also potentiate the convulsant effect induced by mercaptopropionic acid.

Amine Oxidase (Copper-Containing)↗
PubMed1991

Enzymatic N-methylation of phenelzine catalyzed by phenylethanolamine N-methyltransferase.

1. Phenelzine has been found to be methylated by enzymes obtained from bovine adrenal and some rat tissues in the presence of S-adenosylmethionine (SAM) as methyl group donor. 2. The methylated product was chromatographically (TLC and HPLC) identical with chemically synthesized N-methylphenelzine. The structure of this methylated phenelzine has been confirmed by a GC-MS procedure. 3. The phenelzine methyltransferase in the bovine adrenal has a molecular weight and isoelectric point identical with that of bovine adrenal phenylethanolamine N-methyl-transferase (PNMT). 4. Methylated phenelzine possesses much reduced inhibitory activity towards monoamine oxidase (MAO). It can, however, be deaminated by MAO to produce phenylacetaldehyde, and subsequently phenylacetic acid. 5. Other hydrazine compounds, such as hydralazine, have also been found to be methylated by the adrenal enzyme. 6. Our finding of enzymatic methylation of hydrazine compounds is novel, and it may play a role in the metabolism of hydrazine drugs.

Adrenal Medulla↗
PubMed1990

The role of phospholamban in the regulation of calcium transport by cardiac sarcoplasmic reticulum.

The calcium transport mechanism of cardiac sarcoplasmic reticulum (SR) is (SR) is regulated by a phosphoregulatory mechanism involving the phosphorylation-dephosphorylation of an integral membrane component, termed phospholamban. Phospholamban, a 27,000 Da proteolipid, contains phosphorylation sites for three independent protein kinases: 1) cAMP-dependent, 2) Ca2(+)-calmodulin-dependent, and 3) Ca2(+)-phospholipid-dependent. Phosphorylation of phospholamban by any one of these kinases is associated with stimulation of the calcium transport rates in isolated SR vesicles. Dephosphorylation of phosphorylated phospholamban results in the reversal of the stimulatory effects produced by the protein kinases. Studies conducted on perfused hearts have shown that during exposure to beta-adrenergic agents, a good correlation exists between the in situ phosphorylation of phospholamban and the relaxation of the left ventricle. Phosphorylation of phospholamban in situ is associated with stimulation of calcium transport rates by cardiac SR, similar to in vitro findings. Removal of beta-adrenergic agents results in the reversal of the inotropic response and this is associated with dephosphorylation of phospholamban. These findings indicate that a phospho-regulatory mechanism involving phospholamban may provide at least one of the controls for regulation of the contractile properties of the myocardium.

Animals↗
PubMed1990

Some pharmacological implications of MAO-mediated deamination of branched aliphatic amines: 2-propyl-1-aminopentane and N-(2-propylpentyl)glycinamide as valproic acid precursors.

2-Propyl-1-aminopentane (2-PAP) and N-(2-propylpentyl)glycinamide (PPG) were readily deaminated by rat liver monoamine oxidase B and rat aorta semicarbazide-sensitive amine oxidase. The deaminated product, valproic acid (VPA), was identified by HPLC-fluorometric assessment. Absorption and biotransformation of these compounds and their VPA metabolite into the brain were rapid processes. An investigation was conducted to examine whether these compounds can be used as VPA prodrugs. Both compounds, however, at relatively low doses exhibited distinct tremor effects in mice and rats. They also potentiate the convulsant effect induced by mercaptopropionic acid (MPA).

3-Mercaptopropionic Acid↗
PubMed1989

Biogenic amines and their metabolites in body fluids of normal, psychiatric and neurological subjects.

The biogenic monoamines and their metabolites have been isolated, identified and quantified in human body fluids over the past forty years using a wide variety of chromatographic separation and detection techniques. This review summarizes the results of those studies on normal, psychiatric and neurological subjects. Tables of normal values and the methods used to obtain them should prove to be useful as a reference source for benchmark amine and metabolite concentrations and for successful analytical procedures for their chromatographic separation, detection and quantification. Summaries of the often contradictory results of the application of these methods to psychiatric and neurological problems are presented and may assist in the assessment of the validity of the results of experiments in this field. Finally, the individual, environmental and the methodological factors affecting the concentrations of the amines and their metabolites are discussed.

Biogenic Amines↗
PubMed1989

Isolation, separation and analysis in neurochemistry: trace amines and acids as an illustrative example.

In this brief overview various neurochemical isolation procedures that can be adopted for the analysis of several monoamine neurotransmitters/neuromodulators and their principal oxidatively deaminated metabolites are outlined. With respect to the trace amines, they can be identified and quantitated as their so-called dansyl derivatives after thin-layer chromatographic separation by mass spectrometric (MS) electron-impact (EI) ionisation followed by selected-ion monitoring (SIM) of their molecular ions. Deuterated homologues are added as internal standards at the start of the analytical procedure. The MS-EI-SIM procedure offers a tissue extract or releasate sensitivity of about 100 pg/g of tissue or fluid. In the case of tryptamine or phenylethylamine, by utilising different derivatives (N-acetylpentafluoropropionyl or N-acetylpentafluorobenzoyl), which cyclise to form perfluorinated spirocyclic compounds, it is possible using MS negative chemical ionisation techniques coupled with monitoring of the (M-HF) ions to achieve sensitivities for tissue extracts of 1 pg/g or less. Acidic and neutral metabolites (up to twelve of them can be assayed simultaneously) can be detected and quantitated in tissue extracts, releasates or biological fluids as their methylpentafluoropropionyl or trifluoroethyl-pentafluoropropionyl derivatives in the 100-1000 pg range using gas chromatographic-MS-SIM procedures.

Amines↗
PubMed1989

Community nutrition in Canada: an overview.

This paper provides an overview of the scope and diversity of community nutrition in Canada today and illustrates the many community organizations that include a nutrition component. The relationship of public health nutrition to the broader field of community nutrition is outlined, and health promotion concepts and strategies are described as a basis for community nutrition programs. Strategies such as education, mass communication/social marketing, advocacy, self-help/mutual aid, community organization, economic support, policy development/legislation, and environmental change are identified with some examples from programs in Canadian communities. Future directions are proposed as research, better surveillance and monitoring, more effective program evaluation, and a forum for the exchange of community nutrition information.

Canada↗
PubMed1988

Effects of long-term storage on the concentrations of the unconjugated acidic metabolites of the trace amines, indoleamines and catecholamines.

The concentrations of urinary phenylacetic, m- and p-hydroxyphenylacetic, mandelic (MA), p-hydroxymandelic, indoleacetic, homovanillic, vanillylmandelic, 5-hydroxyindoleacetic and 3,4-dihydroxyphenylacetic (DOPAC) acids and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the concentrations of the above plasma acids (except MA, MHPG and DOPAC) were determined by gas chromatography-mass spectrometry with selected-ion monitoring at the time of receipt of the samples and after three, six and nine months storage at -18 degrees C. The samples were not treated in any way before storage. The concentrations of most of the urinary metabolites declined significantly (analysis of variance) over the nine-month storage period, whereas most of the plasma metabolites did not.

Amines↗
PubMed1988

Interaction of biogenic amines with components of cigarette smoke. Formation of cyanomethylamine derivatives.

A reaction of the biogenic amines 5-hydroxytryptamine, dopamine, histamine, p-tyramine, beta-phenylethylamine and tryptamine with components of cigarette smoke was observed. The adducts formed from 5-hydroxytryptamine and beta-phenylethylamine were purified by chromatographic procedures and identified by high resolution mass spectrometry. The structures of some of these compounds were established as cyanomethylamine derivatives, i.e. RCH2CH2NHCH2CN. In the case of 5-hydroxytryptamine, a cyanomethyl-beta-1,2,3,4-tetrahydrocarboline product formed via a Pictet-Spengler condensation reaction was isolated. The mass spectra of such adducts and their fragment ions were observed to be identical to those of chemically synthesized cyanomethylamines. Both formaldehyde and cyanide, which are known to be present in cigarette smoke, were involved in the reaction with the primary amines. The reaction was time dependent and was enhanced by an increase in temperature or by incubation under alkaline conditions. Cyanomethyl adduct formation was increased when smoke from cigarettes with higher tar and nicotine content was used. When the amines were incubated with human saliva obtained after cigarette smoking, cyanomethylamine products were readily detected.

Acetonitriles↗
PubMed1988

Stereospecific deamination of benzylamine catalyzed by different amine oxidases.

1. Stereospecific deuterated benzylamine enantiomers, R(alpha-2H1)-and S(alpha-2H1)-benzylamine, were synthesized by a combined chemical and enzymatic method. 2. The retention or cleavage of the deuterium atom during deamination of benzylamine catalyzed by amine oxidases from different sources was assessed by a GC-MS procedure and confirmed by HPLC separation of the products and by the observation of a deuterium isotope effect. 3. Three types of stereospecific abstraction of hydrogen atoms from the alpha-carbon of benzylamine during deamination were observed: (a) In the first type of deamination the pro-R hydrogen is removed from the alpha-carbon. Enzymes in this category are mitochondrial MAO from different tissues; (b) The second type of deamination involves the abstraction of pro-S hydrogen. Soluble enzymes such as rat aorta benzylamine oxidase or diamine oxidase from hog kidney and pea seedling have been found to belong to this group; and (c) Bovine plasma amine oxidase exhibits the third type of deamination where no absolute stereospecificity is required. 4. The kinetic deuterium isotope effect during the deamination of benzylamine by the different amine oxidase varies greatly, i.e. VH/VD ranged from 1.7 to 4.0.

Amine Oxidase (Copper-Containing)↗
PubMed1987

A comparison of the gas chromatographic and mass spectrometric properties of the pentafluoropropionyl and heptafluorobutyryl derivatives of the methyl, trifluoroethyl, pentafluoropropyl and hexafluoroisopropyl esters of twelve acidic metabolites of biogenic amines.

The gas chromatographic and mass spectrometric properties of the methyl, trifluoroethyl, pentafluoropropyl and hexafluoroisopropyl esters of the pentafluoropropionyl and heptafluorobutyryl derivatives of twelve important acidic metabolites of biogenic amines have been investigated. The optimum derivatization conditions for the different classes of metabolites have been established and the byproducts formed in some of the derivatizations have been identified. Under certain derivatizing conditions, back-exchange of deuterium in the labelled internal standards was observed. No single derivative appears to be ideally suitable for the simultaneous quantitative analysis by GC/MS of all twelve metabolites, so extracts of plasma and urine were split and a combination of the methyl or trifluoroethyl esters of the pentafluoropropionyl derivatives were used.

Biogenic Amines↗
PubMed1987

The metabolism of ingested deuterium-labelled p-tyramine in normal subjects.

Eight normal subjects ingested 125 mg of p-tyramine-beta,beta-2H2 hydrochloride and the 3 h and following 21 h urine collections were analysed by mass spectrometry with selected ion monitoring for the deuterated metabolites: free and conjugated p-tyramine-beta,beta-2H2, free p-octopamine-beta-2H1, free and conjugated p-hydroxyphenylacetic acid-alpha-2H1 and -alpha,alpha-2H2, and free p-hydroxymandelic acid-alpha-2H1. These metabolites accounted for 72% of the ingested label, of which conjugated p-tyramine and free p-hydroxyphenylacetic acid constituted 90%. Approximately 50% of the total deuterated tyramine and 70% of the total deuterated p-hydroxyphenylacetic acid were excreted in the first three hours, although there was considerable variation between individuals. The presence of a small amount of p-hydroxyphenylacetic acid-alpha-2H1 suggests that some exchange of deuterium occurred at the intermediate p-hydroxyphenylacetaldehyde stage. These results, based as they are on metabolites labelled with the stable isotope deuterium, ought to be more reliable than earlier studies in which unlabelled tyramine was ingested with the resultant metabolites, indistinguishable from their endogenous metabolic counterparts, being measured by fluorimetry or gas chromatography.

Administration, Oral↗
PubMed1987

Antilipolytic activity of viprostol, a transdermally active antihypertensive PGE2 analog.

Viprostol, a novel prostaglandin E2 congener, was assessed for in vitro antilipolytic activity in the spontaneously obese rat. In isolated epididymal adipocytes, viprostol exhibited a dose-dependent inhibition of catecholamine-stimulated lipolysis at concentrations ranging from 10 microM to 1 mM, but was ineffective at lower concentrations. Additionally, viprostol exhibited approximately 50% of the antilipolytic activity of naturally-occurring PGE1 and PGE2 at similar concentrations, but was as potent as PGF2 alpha. At 10 microM, viprostol inhibited maximum catecholamine-stimulated lipolysis by approximately 35% of the total, hormone-stimulated glycerol release. The results of these experiments indicate that viprostol exhibits antilipolytic activity in vitro, but is less potent than the naturally-occurring PGE's to which it is most closely related structurally.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Standards of gerontological/long term care nursing practice.

The Academic Nursing Home Care Unit of the West Los Angeles Veterans Administration Medical Center developed standards of gerontological/long term care (LTC) nursing practice. The standards can be used by nurses who practice in LTC settings and who care for the diverse needs of patients who are elderly or who have chronic illnesses: medical, psychiatric, or both. The standards describe how the philosophy, mission, and goals of the facility should be translated into action, and they supply a framework for evaluating the quality of nursing care.

Aged↗
PubMed1987

Deuterium isotope effect in gamma-aminobutyric acid transamination: determination of rate-limiting step.

The rate of transamination of gamma-aminobutryic acid (GABA) catalyzed by hog brain gamma-aminobutyrate aminotransferase was substantially reduced when the hydrogen at the gamma-carbon position was replaced by deuterium. The deuterium isotope effect of this reaction has been substantiated by fluorometric, radiometric, and mass spectrometric procedures and assessed kinetically. The ratios of Vmax of the nonlabeled substrate/Vmax of the deuterated substrate obtained under different conditions ranged from 6 to 7. This indicates that the cleavage of the hydrogen from the gamma-carbon is the rate-determining step in GABA transamination. Similar isotope effects have also been shown to occur in the peripheral system in vivo.

4-Aminobutyrate Transaminase↗
PubMed1986

Simultaneous analysis of twelve biogenic amine metabolites in plasma, cerebrospinal fluid and urine by capillary column gas chromatography-high-resolution mass spectrometry with selected-ion monitoring.

A procedure is described for the simultaneous determination of twelve acidic and alcoholic metabolites of trace and catecholic biogenic amines in plasma, cerebrospinal fluid and urine by capillary column gas chromatography--high-resolution mass spectrometry. Protein precipitation with sulphosalicylic acid, derivatization with two different reagent systems, final sample clean-up with a buffer wash and a program for automatically changing the reference mass of the mass spectrometer to suit each group of compounds as they are eluted from the column, are the main novel features of the procedure. A brief description of the synthesis of the deuterium-labelled internal standards is provided. The procedure is applied to biological samples and a comparison to reported values is given.

Biogenic Amines↗