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G D Prell

Publications and source records attributed to G D Prell.

35 records · Page 2Linked to original sources
PubMed1989

Rostral-caudal concentration gradients of histamine metabolites in human cerebrospinal fluid.

The metabolites of histamine, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), have a large concentration gradient between cisternal and lumbar CSF in the rhesus monkey. The possibility of a t-MH and/or t-MIAA gradient in man was studied in sequential samples of CSF withdrawn from the lumbar space from a healthy male. The mean levels of t-MH and t-MIAA in the 14-16 ml segment of CSF from 6 male volunteers was also measured. pros-Methylimidazoleacetic acid (p-MIAA), an endogenous isomer of t-MIAA that is not derived from histamine, was also measured. Levels of t-MH, t-MIAA and p-MIAA were measured by gas chromatography-mass spectrometry. With increasing volumes of CSF removed, t-MH and t-MIAA levels increased linearly (p less than 0.01) when plotted against the midpoints of each volume segment. Levels of t-MH and t-MIAA from the volunteers showed little variation; the means of the levels were within 15% of the respective regression lines of the points from the single subject. In contrast, p-MIAA levels showed no gradient (p greater than 0.6) in serially removed CSF; the individual levels in CSF from the volunteers on unrestricted diets varied widely, suggestive of a dietary influence on p-MIAA levels in the CNS. The concentration gradient of histamine metabolites in CSF confirms the rostral-caudal gradient observed in monkey and argues against plasma or spinal cord as major sources of these metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Diurnal fluctuation in levels of histamine metabolites in cerebrospinal fluid of rhesus monkey.

In samples of ventricular cerebrospinal fluid (CSF) that were collected from a conscious, restrained rhesus monkey at intervals of 30 90 min, levels of the histamine metabolites, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), were determined by gas chromatography-mass spectrometry. Levels of t-MH and t-MIAA each showed time-related fluctuations. Peak and trough concentrations of t-MIAA, the product of t-MH, paralleled, but lagged about 2 h behind, the levels of t-MH. Within the first 3 h of illumination, metabolite levels increased more than 3-fold; they fell sharply within the first 3 h of darkness. Mean levels of t-MH and t-MIAA were significantly higher during periods of illumination than of darkness. Fluctuations in the levels of pros-methylimidazoleacetic acid (p-MIAA), an endogenous isomer of t-MIAA that is not a histamine metabolite, were markedly different from those of t-MH or t-MIAA; p-MIAA levels peaked only at the middle of the dark period. The time-related fluctuations in levels of t-MH and t-MIAA, but not p-MIAA, are similar to the daily rhythmic changes observed in monkey CSF for the levels of other central neurotransmitters and peptide neurohormones.

Animals↗
PubMed1989

Presence and measurement of imidazoleacetic acid, a gamma-aminobutyric acid agonist, in rat brain and human cerebrospinal fluid.

Imidazoleacetic acid (IAA) was unequivocally demonstrated in rat brain, human CSF, and human plasma by a gas chromatographic-mass spectrometric method that can reliably quantify as little as 8 pmol, i.e., 1 ng. Owing to tautomerism of the imidazole ring, IAA and [15N, 15N]IAA, the internal standard, each formed two chromatographically distinct isomers after derivatization of the ring nitrogens with either ethyl chloroformate or methyl chloroformate. The isomers of n-butyl(N-ethoxycarbonyl)imidazole acetate and n-butyl(N-methoxycarbonyl)imidazole acetate were identified by analysis with methane chemical ionization and electron impact ionization of molecular and fragment ions. The levels (mean +/- SEM) of free IAA were 140 +/- 14 pmol/g and 2.7 +/- 0.2 pmol/ml in brains of untreated rats and human lumbar CSF, respectively. Mean levels of IAA in brains of anesthetized rats, perfused free of blood, did not differ significantly from mean levels of anesthetized, nonperfused controls or from untreated rats. The source or sources of IAA in brain and CSF are unknown. Because IAA is a potent agonist at gamma-aminobutyrate receptors, it merits examination as a regulator in brain.

Animals↗
PubMed1989

pros-methylimidazoleacetic acid in rat brain: its regional distribution and relationship to metabolic pathways of histamine.

pros-Methylimidazoleacetic acid (p-MIAA; 1-methylimidazole-5-acetic acid), an isomer of the histamine metabolite, tele-methylimidazoleacetic acid (t-MIAA), is present in brain and CSF. Its relationship to histamine synthesis and catabolism was assessed in brains of rats. p-MIAA distribution in brain regions was heterogeneous although the concentrations in regions with the highest (hypothalamus) and the lowest (medulla-pons) levels differed less than four-fold. There was no significant correlation between the regional distributions of p-MIAA with those of histamine or its metabolites. pros-Methylhistidine (1 g/kg, i.p.) produced a 20-fold increase in mean levels of p-MIAA and up to a 50-fold increase in levels of pros-methylhistamine (p-MH), a putative intermediate; levels of histamine and its metabolites were unaltered. L-Histidine (1 g/kg, i.p.) or alpha-fluoromethylhistidine (100 mg/kg, i.p.), the irreversible inhibitor of histamine synthesis, did not alter the levels of p-MIAA in brain. Like the levels of t-MIAA, the levels of p-MIAA were unaltered after probenecid administration. Contrary to its effects in lowering t-MIAA levels, pargyline (75 mg/kg, i.p.) produced a slight rise in levels of p-MIAA in all regions. These findings suggest that, in brain, the metabolic pathways of histamine are independent of pathways that generate p-MIAA. Further, since brain is capable of p-MH formation, its use as an internal standard in analytical methods merits caution.

Animals↗
PubMed1989

Prenatal radiation risk to the brain.

The Central Nervous System (CNS) exhibits a high sensitivity to ionizing radiation from conception until after birth. X-irradiation damage of the nervous system during development has been well documented and exposure to ionizing radiation above approximately 10 cGy during perinatal development is contraindicated. Shielding of the embryo or fetus usually prevents gross malformations but high energy irradiation of the pregnant female may result in embryonic growth retardation. This may be especially true when the irradiation is coupled with an ethanol-induced reduction in SOD activity. The synergistic interactions between other drugs and ionizing radiation also have been demonstrated. However, the concentration of endogenous compounds such as histamine and serotonin may be increased in the maternal circulation following irradiation and reach the fetal CNS through a blood-brain-barrier that is more permiable than normal. The introduction of histamine and/or serotonin into the fetal circulation may result in fetal hypotension, edema, cerebral ischemia, and damage to the developing CNS.

Animals↗
PubMed1988

Histamine metabolites in cerebrospinal fluid of the rhesus monkey (Macaca mulatta): cisternal-lumbar concentration gradients.

Similar to metabolites of other aminergic transmitters, histamine metabolites of brain, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), could have a concentration gradient between rostral and caudal sites of CSF. To test this hypothesis, cisternal and lumbar CSF samples were collected in pairs from eight monkeys (Macaca mulatta), and levels of t-MH and t-MIAA were measured by gas chromatography-mass spectrometry. pros-Methylimidazoleacetic acid (p-MIAA), an endogenous isomer of t-MIAA that is not a histamine metabolite, was also measured. Cisternal levels (in picomoles per milliliter, mean +/- SEM) of t-MH (9.9 +/- 1.4) and t-MIAA (40.8 +/- 7.6), but not of p-MIAA (9.7 +/- 1.2), exceeded those in lumbar CSF (t-MH, 1.8 +/- 0.3; t-MIAA, 6.8 +/- 0.9; p-MIAA, 8.6 +/- 0.6) in every monkey. The magnitudes of the mean cisternal-lumbar concentration gradients for t-MH (6.6 +/- 1.1) and t-MIAA (6.5 +/- 1.3) were indistinguishable. These gradients exceed those of metabolites of most other transmitters. There was no gradient for the levels of p-MIAA. The cisternal, but not lumbar, levels of t-MH and t-MIAA were correlated. There was no significant difference between the means of the metabolite concentration ratios (t-MIAA/t-MH) in cisternal (4.0 +/- 0.4) and lumbar (4.4 +/- 0.9) CSF. The steepness of these gradients suggests that levels of t-MH and t-MIAA in lumbar CSF might be useful probes of histaminergic metabolism in brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Elevated levels of histamine metabolites in cerebrospinal fluid of aging, healthy humans.

The metabolites of histamine, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), were measured in lumbar cerebrospinal fluid of healthy, normal volunteers aged 20-31 (n = 4) and 60-72 (n = 8) by gas chromatography-mass spectrometry. Mean levels (pmol/ml) of t-MH, t-MIAA and the sum of t-MH and t-MIAA (2.9, 6.4 and 9.4, respectively) were significantly higher in CSF from older subjects than from younger subjects (1.1, 4.5 and 5.5, respectively). Another older subject had yet higher levels of metabolites (6.7, 15.1 and 21.8, respectively). The sum of the levels of the known metabolites of histamine in brain, i.e. t-MH and t-MIAA, did not overlap between the younger and older subjects. The levels of pros-methylimidazoleacetic acid, an endogenous isomer of t-MIAA that is not derived from metabolism of histamine, did not differ significantly between the two groups. These findings contrast with results of similar studies of metabolites of other aminergic transmitters in showing elevated levels of metabolites of histamine in cerebrospinal fluid with increasing age.

Adult↗
PubMed1986

Brain histamine response to stress in 12 month old rats.

The regional brain histamine regulation in response to stress was investigated in 12 month old Sprague-Dawley male rats. Air blast exposure (15 min) induced significant (26.5%) elevation in hypothalamic HA level; midbrain and cortical HA concentrations were not affected. Histamine methyltransferase activity was not altered by stress in any of the brain regions investigated. Plasma corticosterone levels of stressed rats were significantly elevated (6.5 fold). Hence, the response of hypothalamic HA to stress is still evident in 12 month old rats.

Animals↗
PubMed1984

Age-related changes in brain histamine.

The effect of age on brain histamine levels and histamine methyltransferase activity (HMT) was investigated. Male Sprague-Dawley rats (12 months old) displayed significantly higher hypothalamic, midbrain and cortical histamine concentrations than three-month-old animals. In contrast, HMT activity was significantly decreased in all three brain regions. The increase in brain histamine concentration of old rats could have been partially attributed to decreased activity of HMT since elevated levels of brain histamine are known to occur following HMT inhibition. Present results indicate that similarly to the reported changes in the concentration, synthesis and/or metabolism of other central neurotransmitters in old rats, brain histamine regulation may also be affected in the process of aging.

Age Factors↗
PubMed1980

Brain histamine: plasma corticosterone spontaneous locomotor activity and temperature.

Hypothalamic histamine exhibited circadian fluctuations in male Sprague-Dawley rats; low values were found during the dark period when spontaneous locomotor activity (S.L.A.) and temperature were elevated. A relatively high hypothalamic histamine level was observed during the early period of the light cycle and was associated with decreased S.L.A. and temperature. Histamine concentration was high when corticosterone levels were low at the end of the dark cycle and during the morning hours (4 a.m.-1 p.m.); but histamine levels were relatively constant while corticosterone concentration dropped during afternoon and early night hours (4 p.m.-10 p.m.). Furthermore, the lowest hypothalamic histamine level (at 1 a.m.) was associated with the average plasma corticosterone value, thus no consistent relationship between histamine and corticosterone levels could be observed. Circadian fluctuations in brain histamine may support its role in brain function.

Animals↗
PubMedDate not supplied

Influence of age and gender on the levels of histamine metabolites and pros-methylimidazoleacetic acid in human cerebrospinal fluid.

The metabolites of histamine, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), were measured in cerebrospinal fluid (CSF) from 47 subjects with neurological disorders and healthy controls. In lumbar CSF, concentrations of these metabolites were significantly correlated. Levels of t-MH, t-MIAA and their sum (which represents virtually all histamine metabolized in brain) were significantly higher in CSF from older subjects and were positively correlated with age. Females had higher levels of histamine metabolites than males. Males had higher levels of pros-methylimidazoleacetic acid (p-MIAA), an isomer of t-MIAA that is not a metabolite of histamine. Levels of p-MIAA increased with age among men. These results are in contrast to those of age-related effects on levels of other aminergic transmitter metabolites in CSF and suggest that metabolic activity of histamine in brain may increase with age.

Journal Article↗
PubMedDate not supplied

Influence of age and gender on the levels of histamine metabolites and pros-methylimidazoleacetic acid in human cerebrospinal fluid.

The metabolites of histamine, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), were measured in cerebrospinal fluid (CSF) from 47 subjects with neurological disorders and healthy controls. In lumbar CSF, concentrations of these metabolites were significantly correlated. Levels of t-MH, t-MIAA and their sum (which represents virtually all histamine metabolized in brain) were significantly higher in CSF from older subjects and were positively correlated with age. Females had higher levels of histamine metabolites than males. Males had higher levels of pros-methylimidazoleacetic acid (p-MIAA), an isomer of t-MIAA that is not a metabolite of histamine. Levels of p-MIAA increased with age among men. Analysis of covariance indicated that the subjects' health status had little or no effect on age- or sex-related differences in levels of analytes in CSF; sex-related differences were independent of changes attributed to age. These results are in contrast to those of age-related effects on levels of other aminergic transmitter metabolites in CSF and suggest that metabolic activity of histamine in brain may increase with age.

Journal Article↗