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Biomedical subjects

I N Mefford

Publications and source records attributed to I N Mefford.

At least 55 records · Page 3Linked to original sources
PubMed1987

Chromatographic approaches to signal and selectivity enhancement for determination of biogenic amines by liquid chromatography with amperometric detection.

A variety of chromatographic approaches are detailed for enhancement of signal and selectivity for determination of biogenic amines by HPLC with amperometric detection. Microbore HPLC columns offer significant signal enhancement due to the reduced elution volume. Selection of novel surfactants such as N-methyl oleoyl taurate allows conversion of reverse phase materials to strong cation exchangers, adding selectivity. Large injection volumes can be applied to these columns due to their strong cationic nature using a noneluting matrix. Additional sensitivity can be obtained by using a mobile phase of relatively high pH to take advantage of intramolecular cyclization.

Animals↗
PubMed1987

Are there epinephrine neurons in rat brain?

The present model of epinephrine containing and PNMT containing neurons in rat brain (and by extension other species) implies that epinephrine is primarily a postsynaptic metabolite of norepinephrine in forebrain due to the probable postsynaptic localization of PNMT. As a result the most physiologically relevant pool is found in extracellular space with the bulk of tissue epinephrine found co-stored in noradrenergic terminals. Changes in the extracellular pool of epinephrine are effected by changes in the extracellular norepinephrine concentration as in times of increased release, reuptake blockade or inhibition of degradation. alpha 2-Adrenergic receptors associated with cells not necessarily in synaptic contact with the noradrenergic terminal containing epinephrine could be stimulated through this extracellular pool. The majority of PNMT containing cells in the brainstem/medulla appear to also contain other catecholamine biosynthetic enzymes. The present model suggests that epinephrine formed in these neurons is primarily used as a co-transmitter with norepinephrine formed in these same terminals. The balance of norepinephrine to epinephrine found in vesicles in these terminals would be a function of intraneuronal PNMT activity, MAO activity and reuptake which would be the major regulator of intraneuronal norepinephrine concentrations. The literature is reviewed in these contexts, questioning the existence of classical epinephrine neurons. Evidence is presented in support of a model for postsynaptic synthesis of epinephrine in the forebrain, especially during times of high norepinephrine release. The classic model of compartmentalization of biosynthetic enzymes is used in support of a co-transmitter role of epinephrine in the brainstem/medulla. Epinephrine is considered a unique metabolite of norepinephrine with important pharmacological actions and a receptor subtype in brain which monitors and regulates its formation. Epinephrine is recognized by the uptake system on noradrenergic terminals and vesicles and can therefore compete for storage in these noradrenergic neurons. Based on the distribution of PNMT and its association with major noradrenergic fiber tracts, epinephrine can be considered a site-selective metabolite of physiological and neuronal importance. Due to the compartmentalization of synthetic enzymes, it is probably not a classical neurotransmitter in the central nervous system, although it may be the primary catecholamine neurotransmitter in some medullary neurons.

Animals↗
PubMed1986

Modification of reversed-phase separations of small molecules using non-ionic surfactants and mixed ionic-non-ionic surfactants.

The effects of non-ionic surfactants, Tween 20 and Tween 60, on reversed-phase separations of small molecules have been examined. Tween compounds were found to partition irreversibly into the ODS material used, markedly decreasing capacity factors for the compounds tested. Compounds which could hydrogen bond were less affected. Ion pairing using either anionic or cationic surfactants was possible in the presence of the non-ionic surfactants. While reversed-phase effects predominate under these conditions, secondary effects on retention order were observed and attributed to hydrogen bonding. Primary amines were retained longer than the corresponding secondary amine while catechols were retained longer than the corresponding methoxyphenols.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF.

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.

Adolescent↗
PubMed1986

CSF dopamine levels correlate with extraversion in depressed patients.

Cerebrospinal fluid (CSF) dopamine levels were studied in 16 male patients who also were tested for self-reported extraversion using the Eysenck Personality Inventory. Log CSF dopamine was significantly correlated with extraversion as predicted by recent theoretical work integrating mesolimbic dopamine function and active responding to external incentives as psychobiological traits. CSF dopamine levels were uncorrelated with the total score on the Hamilton Rating Scale for Depression, self-reported neuroticism, and age. The results are discussed in relation to other biological models of extraversion such as the construct of sensation-seeking behavior.

Bipolar Disorder↗
PubMed1985

Determination of catecholamines in tissue and body fluids using microbore HPLC with amperometric detection.

Performance of microbore reverse phase HPLC coupled with amperometric detection is detailed for the analysis of catecholamines in small tissue samples and human blood plasma and cerebrospinal fluid. Extraction procedures for pre-concentration and clean-up of these samples are described. Marked signal enhancement is observed due to the smaller column volume as well as the increased coulometric yield which results from the lower flow rates used with this technique. Detection limits of 0.2 to 0.5 picograms are obtained allowing analysis of catecholamines in extremely small tissue samples or small volumes of cerebrospinal fluid or plasma.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Epinephrine accumulation in rat brain after chronic administration of pargyline and LY 51641--comparison with other brain amines.

Concentrations of biogenic amines and metabolites were measured in regions of rat brain following administration of monoamine oxidase (MAO) inhibitors for 21 days. Epinephrine concentrations were increased from 350 to 500% following chronic administration of LY 51641, a selective inhibitor of MAO type A. Norepinephrine, dopamine and serotonin showed much less relative accumulation. The marked relative accumulation of epinephrine may be related to the efficacy of inhibitors of MAO type A in the treatment of depression.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Serotonin and schizophrenia: correlations between serotonergic activity and schizophrenic motor behavior.

Increased serotonergic activity in animals has been associated with a variety of stereotyped motor behaviors. In addition, serotonin facilitates brainstem, reticular, and spinal motor neuronal activity implicated in the expression of these behaviors. This report presents positive correlations between both peripheral (platelet serotonin levels) and central (cerebrospinal concentrations of 5-hydroxy-indoleacetic acid) measures of serotonin metabolism and the symptom of peculiar or unusual mannerisms and posturing in schizophrenic patients. The findings are discussed in light of the animal behavioral correlates of increased serotonergic activity and the stereotyped affectomotor behavior seen in some schizophrenic patients.

Adult↗
PubMed1985

Serum melatonin and pineal indoleamine metabolism in a species with a small day/night N-acetyltransferase rhythm.

Ovine serum and pineal melatonin levels are low during the day, increase five to ten-fold at night, decrease during a light pulse at night, and rapidly increase to night levels following the light-dark transition. N-Acetyltransferase activity increases three-fold at night, falls significantly in response to the light pulse, but does not increase following the light pulse. No significant change in N-acetylserotonin occurs under these conditions. These results suggest that the biochemical mechanisms controlling pineal melatonin synthesis in the sheep pineal gland may be different from those in the rat.

Acetyltransferases↗
PubMed1985

Epinephrine, norepinephrine and dopamine concentrations in amphibian brain.

The whole brain concentrations of epinephrine, norepinephrine and dopamine in North American amphibians, orders Caudata and Salientia, are reported. Epinephrine is the major catecholamine in the Salientia while norepinephrine and epinephrine concentrations are roughly equivalent in suborders of Caudata. Relative regional concentrations are similar to other classes (mammals, reptiles and birds) although the absolute concentration of epinephrine is considerably higher in amphibians than in most other species.

Amphibians↗
PubMed1985

Rapid nocturnal increase in ovine pineal N-acetyltransferase activity and melatonin synthesis: effects of cycloheximide.

Thirty minutes after the onset of darkness, ovine pineal arylalkylamine N-acetyltransferase, N-acetylserotonin, and melatonin increase 5- to 10-fold. No significant changes in hydroxyindole-O-methyltransferase, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxyindoleacetic acid, and 5-methoxytryptophol are detected at this time. Administration of cycloheximide inhibits the rise in N-acetyltransferase and N-acetylserotonin, but not melatonin. Unexpectedly, 5-methoxytryptophol increases after cycloheximide treatment. Taken together, these results, although consistent in part with a role for serotonin N-acetylation in the regulation of melatonin synthesis in sheep, indicate that an N-acetyltransferase-independent mechanism may also be involved.

Acetylserotonin O-Methyltransferase↗
PubMed1985

Ovine pineal indoles: effects of L-tryptophan or L-5-hydroxytryptophan administration.

L-5-Hydroxytryptophan (L-5-HTP) (20 or 200 mg/kg i.p.) but not L-tryptophan (500 mg/kg i.p.) loading substantially increases serum melatonin in sheep. In the present study we examined the effects of these compounds on pineal serotonin and six serotonin metabolites. L-Tryptophan failed to increase 5-hydroxytryptamine (5-HT; serotonin) or any of its metabolites despite a five-fold increase in pineal tryptophan. In contrast, L-5-HTP loading produced a marked increase in pineal 5-HT and its metabolites, including N-acetylserotonin (NAS) and melatonin, indicating that an increased synthesis of melatonin is responsible for the increased serum melatonin concentration after loading with this precursor. No change in pineal indoleamine N-acetyltransferase (NAT) activity was seen. These results are consistent with the suggestion that, during daytime in the sheep, 5-HT availability may limit the production of melatonin.

5-Hydroxytryptophan↗
PubMed1985

Ovine pineal alpha 1-adrenoceptors: characterization and evidence for a functional role in the regulation of serum melatonin.

Plasma melatonin in sheep increases to nocturnal levels rapidly (10-20 min) after dark onset. This increase is blocked by iv prazosin (1 mg), but not propranolol (6 mg). Prazosin also blocks the elevation in pineal melatonin content after dark onset, but does not significantly alter the rise in N-acetyltransferase activity or the elevation in pineal N-acetylserotonin content. Since the nocturnal elevation in N-acetyltransferase, a neurally regulated event, was unaltered, this suggests that prazosin does not significantly impair the transmission of neural signals from the eye to the gland, but does act on pineal alpha 1-adrenoceptors to block melatonin production. This is supported by binding studies in ovine pineal membranes using [125I] iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone, which revealed that binding is rapid, reversible, saturable, and stereo-specific. Saturation studies indicated the presence of a single class of binding sites, with an equilibrium binding constant (Kd) of 32 +/- 6 pM and a maximum binding of 139 +/- 19 fmol/mg protein. The relative potencies of several adrenergic agonists and antagonists in competition studies indicated that the receptor belongs to the alpha 1-subclass of adrenoceptors. Together, these data suggest that melatonin synthesis in the sheep pineal gland is controlled in part by an alpha 1-adrenoceptor mechanism at a step beyond N-acetylation.

Acetyltransferases↗