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Biomedical subjects

M H Fernstrom

Publications and source records attributed to M H Fernstrom.

50 records · Page 3Linked to original sources
PubMed1986

Effect of tyrosine administration on dopa accumulation in light- and dark-adapted retinas from normal and diabetic rats.

The interaction of tyrosine concentration and lighting on in vivo dihydroxyphenylalanine (dopa) accumulation rate was studied in retinas of normal and diabetic rats. In both groups of rats, dopa accumulation and in vitro hydroxylase activity were higher in retinas exposed to light than in those adapted to darkness. In light-adapted diabetic rats, though, retinal tyrosine level, dopa accumulation, and in vitro tyrosine hydroxylase activity were all below normal. In both normal and diabetic rats exposed to light, tyrosine injection raised retinal tyrosine concentrations and stimulated dopa accumulation. Injection of tyrosine into dark-adapted rats raised retinal tyrosine level but did not enhance dopa accumulation. Together, these results suggest that in vivo retinal amacrine cells will vary their dopa accumulation rate as a function of substrate supply, but only in the light, when tyrosine hydroxylase is activated. They further indicate that dopa accumulation rate remains sensitive to tyrosine supply in the light-activated diabetic retina.

Adaptation, Ocular↗
PubMed1986

Chronic imipramine treatment and weight gain.

A study of weight change in subjects treated with imipramine was performed on recurrent depressive outpatients. The patients (n = 52) were treated with imipramine (200-250 mg/day) and psychotherapy for 16 weeks. Each individual was weighed upon entry to the study (drug-free) and then weekly thereafter for 16 weeks. Of the 44 women (85%) and 8 men (15%) in the study, 60% of the total group had a weight gain or loss less than 5 pounds (mean = 1.1 pounds) over this time. A weight gain of 6-10 pounds was observed in 19% of subjects, while 9% of the group gained 11-15 pounds. Only 6% (3 subjects) gained more than 15 pounds. Three subjects (6%) lost 6-10 pounds. No correlations were observed between a change in weight and the subject's age, sex, prior weight, or response to medication.

Adult↗
PubMed1986

Effects of aspartame ingestion on the carbohydrate-induced rise in tryptophan hydroxylation rate in rat brain.

Effects of aspartame (aspartyl-phenylalanine-methylester) on increases in brain-tryptophan level and hydroxylation rate following a high-carbohydrate, protein-free meal were tested. After an overnight fast, rats consumed a protein-free meal containing one of several levels of aspartame. Blood and brain amino acid levels and the in vivo rate of tryptophan hydroxylation in brain were estimated at intervals thereafter. Ingestion of the meal alone increased brain-tryptophan level and hydroxylation rate. Aspartame did not modify these effects, except at doses of 530 mg/kg body weight or more. Results suggest a threshold dose of aspartame can be identified for the rat in single-meal studies above which suppression of carbohydrate-induced increases in brain-tryptophan level and serotonin synthesis occurs. This dose, however, is large and, when corrected for species differences in metabolic rate, is unlikely to be ingested by a human subject as a single load.

Administration, Oral↗
PubMed1986

In vivo inhibition of tyrosine uptake into rat retina by large neutral but not acidic amino acids.

The uptake of tyrosine into rat retina and brain was studied in vivo after its peripheral injection alone or in combination with other amino acids. Both retinal and brain tyrosine levels increased monotonically for at least 60 min after tyrosine administration. When tyrosine was injected along with branched-chain amino acids, but not with acidic amino acids, such increments in retinal and brain tyrosine levels were significantly attenuated. The postinjection tyrosine levels in retina and brain paralleled better the serum ratio of tyrosine to the sum of the other large neutral amino acids (which include the branched-chain amino acids) than the serum tyrosine level alone. These results suggest that tyrosine uptake into rat retina, like that into brain, is mediated by a competitive transport system shared among the large neutral amino acids.

Amino Acids↗
PubMed1985

Absence of chronic effects of dietary protein content on brain tryptophan concentrations in rats.

Groups of young, adult, male rats were given free access for 2 wk to a diet containing 12, 24 or 40% protein (dry weight). During this period, all animals grew considerably; those consuming the 12% protein diet grew less rapidly than those ingesting the higher percent protein diets. At the end of 2 wk, six rats from each diet group were killed every 4 h throughout a 24-h period, and blood samples and whole brains were obtained for analysis. Serum tryptophan levels were lowest in animals consuming the 12% protein diet, intermediate in rats consuming the 24% protein diet and highest in rats consuming the 40% protein diet (at all times studied). Brain tryptophan levels, however, did not differ significantly as a function of dietary protein content. The ratio in serum of the concentration of tryptophan to the sum of the concentrations of its competitors for brain uptake also was not significantly influenced by dietary protein level. Levels of 5-hydroxyindoles in brain showed significant diurnal variations but no evidence of a significant effect of dietary protein content. Since the ratio of serum tryptophan to its competitors and the levels in brain of tryptophan and 5-hydroxyindoles did not vary as a function of dietary protein intake, the results do not support the view that these variables serve as signals to the brain for regulating long-term dietary protein intake.

Animals↗
PubMed1984

Caffeine injection raises brain tryptophan level, but does not stimulate the rate of serotonin synthesis in rat brain.

Acute caffeine injection (100 mg/kg) elevates brain levels of tryptophan (TRP), serotonin (5HT), and 5-hydroxyindoleacetic acid (5HIAA). Experiments were performed to determine if the increases in 5HT and 5HIAA result from a stimulation of the rate of 5HT synthesis. Both the rate of 5-hydroxytryptophan (5HTP) accumulation following NSD-1015 injection, and the rate of 3H-5-hydroxyindole synthesis from 3H-tryptophan were measured in vivo following caffeine administration and found to be normal. Tryptophan hydroxylase activity, as measured in vitro in brain homogenates, was also unaffected by caffeine. The results suggest that the elevations in brain 5HT and 5HIAA levels produced by caffeine do not reflect enhanced 5HT synthesis, despite significant elevations in brain TRP level. Some other mechanism(s) must therefore be responsible for these elevations in brain 5-hydroxyindole levels.

5-Hydroxytryptophan↗
PubMed1984

In vivo tyrosine hydroxylation in the diabetic rat retina: effect of tyrosine administration.

The in vivo rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation was measured in light-adapted retinas of normal and diabetic albino rats. DOPA accumulation was significantly below normal in diabetic retinas; tyrosine levels were also reduced. In vitro tyrosine hydroxylase activity was normal. The administration of tyrosine methylester (500 mg/kg i.p.) to diabetic animals significantly raised retinal tyrosine levels and enhanced DOPA accumulation. Reduced tyrosine levels may therefore contribute to the observed reduction in in vivo tyrosine hydroxylation rate in the diabetic retina.

Animals↗
PubMed1983

Effects of acute and chronic trazodone administration on serum prolactin levels in adult female rats.

Trazodone was tested for its ability to elevate serum prolactin levels in mature female rats. When the drug was administered acutely to female rats at doses up to 80 mg/kg ip, it induced a clear rise in serum prolactin levels, with a minimum effective dose of 20 mg/kg; blood trazodone levels at these doses were between 1.6-2.4 micrograms/ml. However, trazodone could not be considered to be a potent stimulator of prolactin secretion, since the injection of haloperidol at 2 mg/kg elevated serum prolactin to values twice those seen in animals receiving the 80 mg/kg dose of trazodone. When trazodone was administered chronically in the diet for two or four weeks, at an average daily dose of 80 mg/kg, serum trazodone levels were found to be 100-200 ng/ml when measured at each stage of the estrous cycle. Serum prolactin levels in trazodone-treated animals, however, did not differ from those in control rats. Moreover, drug-treated animals showed normal proestrus surges in serum prolactin. The results of these studies thus indicate that acutely, at very high doses, trazodone probably can stimulate prolactin secretion modestly in female rats. However, when consumed chronically at 80 mg/kg/day, the drug has no effects on serum prolactin levels. Therefore, if trazodone stimulates prolactin secretion by altering neurotransmission across dopamine and/or serotonin synapses in brain, it is probably not potent in these actions, at least as concerns those dopamine and serotonin neurons that influence the secretion of prolactin.

Animals↗
PubMed1983

Acute effects of aspartame on large neutral amino acids and monoamines in rat brain.

The dipeptide aspartame (APM; aspartylphenylalanine methylester), an artificial sweetener, was studied in vivo for its ability to influence brain levels of the large neutral amino acids and the rates of hydroxylation of the aromatic amino acids. The administration by gavage of APM (200 mg/kg) caused large increments in blood and brain levels of phenylalanine and tyrosine by 60 minutes. Brain tryptophan level was occasionally reduced significantly, but the brain levels of the branched-chain amino acids were always unaffected. Smaller doses (50, 100 mg/kg) also raised blood and brain tyrosine and phenylalanine, but did not reduce brain tryptophan levels. At the highest dose (200 mg/kg), APM gavage caused an insignificant increase in dopa accumulation (after NSD-1015), and a modest reduction in 5-hydroxytryptophan accumulation. No changes in the brain levels of serotonin, 5-hydroxyindoleacetic acid, dopamine, dihydroxyphenylacetic acid, homovanillic acid, or norepinephrine were produced by APM administration (200 mg/kg). These results thus indicate that APM, even when administered in amounts that cause large increments in brain tyrosine and phenylalanine, produce minimal effects on the rates of formation of monoamine transmitters.

Amino Acids↗
PubMed1981

The regional distribution of somatostatin, substance P and neurotensin in human brain.

The regional distribution of somatostatin-, substance P- and neurotensin-like immunoreactivity was determined in 41 areas of 10 human brains. Each peptide is distributed widely in the human central nervous system and for each the pattern of distribution is unique. No significant relationship was found between peptide levels and patient age, interval between death and autopsy, and tissue storage time prior to assay. The regional distribution of these peptides is similar to that seen in several animal species and the pattern of this distribution is consistent with the idea that peptides function as neurotransmitters within the central nervous system. The problems of using human post-mortem material for peptide assay are discussed.

Adult↗
PubMed1981

Immunoreactive neurotensin levels in pancreas: elevation in diabetic rats and mice.

Neurotensin levels in pancreas, but not other tissues, were increased in diabetic animals. The concentration of pancreatic immunoreactiveneurotensin was 138% higher in streptozotocin-diabetic rats, and 68% higher in genetically diabetic (db/db) mice as compared to their respective control animals. Daily administration of insulin (10-15 IU/kg) to diabetic rats completely reversed this effect, and pancreatic neurotensin levels in these animals returned to control values. These findings suggest that elevated levels of pancreatic neurotensin may contribute to some of the metabolic and hormonal disturbances occurring in diabetes.

Animals↗