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Biomedical subjects

J D Fernstrom

Publications and source records attributed to J D Fernstrom.

At least 109 records · Page 6Linked to original sources
PubMed1979

Diet-induced changes in plasma amino acid pattern: effects on the brain uptake of large neutral amino acids, and on brain serotonin synthesis.

Tryptophan is transported into brain by a competitive carrier system it shares with such other large neutral amino acids as tyrosine, phenylalanine, leucine, isoleucine, and valine. Physiologic variations in the plasma neutral amino acid pattern (either as a change in plasma tryptophan, or in the plasma concentration of one or more of its competitors) directly alter this competitive process, and thereby modify the uptake of tryptophan into brain. Such variations in tryptophan uptake influence brain tryptophan levels, and thus serotonin synthesis. Food intake, by influencing directly the plasma levels of large neutral amino acids, ca- therefore predictably modify brain trypotphan uptake and serotonin synthesis. The effect of food intake on the competitive uptake of tryptophan into brain, and on brain tryptophan levels, has recently been shown not to be limited to this amino acid, but also holds for other large neutral amino acids, and for certain large neutral amino acid drugs (e.g., methyldopa). Hence, following a meal, the brain concentration of any large neutral amino acid appears to depend on how the food modifies the plasma level of that amino acid relative to the plasma concentrations of its competitors. The binding of tryptophan to albumin in blood has also been suggested to influence brain tryptophan uptake. However, this notion has not been sustained by the results of nutritional studies, in which meal-induced changes in brain tryptophan levels were readily shown not to be predicted by the alterations in the size of the serum free tryptophan pool. Taken together, these data affirm the importance of competitive transport in determining brain tryptophan uptake and levels, but question whether serum albumin binding and the size of the free tryptophan pool function physiologically to modulate brain tryptophan concentrations.

Animals↗
PubMed1979

Free amino acid, protein, and fat contents of breast milk from Guatemalan mothers consuming a corn-based diet.

Diet compositions and breast milk levels of free amino acids, protein, and lipid were compared in lactating American and Guatemalan women. The protein in the American diet derived principally from animal sources, whereas that in the Guatemalan diet was based most exclusively on cereal grains and legumes. Corn, in the form of cornmeal, was the predominant food. Because of these dietary differences, the Guatemalan women consumed significantly smaller amounts of protein than the American women. The concentrations of most of the free amino acids in aliquots of breast milk from the Guatemalan women were lower than those in samples from the American women. In particular, tryptophan and lysine levels were 23% and 29%, respectively, of the levels in the American breast milk samples. The Guatemalan samples contained less protein, and, when values from Guatemalan women who had nursed only for 6 mth or less were considered, the fat content was also less than in the American samples. The lipid content of the milk, however, did not differ between the two groups when the length of the lactation period was not controlled. The substantial cultural differences between the two groups in the frequency and duration of nursing probably prevented the identification of a clear dietary influence on milk lipid content. The correlations found between diet composition and either the amount of protein or the levels of free amino acids in breast milk suggest that, if a mother's diet is deficient in high-quality protein, the deficiency may be reflected in the composition of her milk, perhaps to the detriment of the nursing infant.

Amino Acids↗
PubMed1979

Tyrosine administration reduces blood pressure and enhances brain norepinephrine release in spontaneously hypertensive rats.

Administration of L-tyrosine to normotensive or spontaneously hypertensive rats reduces blood pressure. The effect is maximal within 2 hr of injection. In spontaneously hypertensive rats, a dose of 50 mg/kg, intraperitoneally, reduces blood pressure by about 12 mm Hg (1 mm Hg = 1.33 x 10(2) pascals); a dose of 200 mg/kg produces the maximal effect, a reduction of about 40 mm Hg. Tryptophan injection (225 mg/kg) also lowers blood pressure in spontaneously hypertensive rats, but only by about half as much as an equivalent dose of tyrosine. Other amino acids tested (leucine, isoleucine, valine, alanine, arginine, and aspartate) do not affect blood pressure. Tyrosine injection appears to reduce blood pressure via an action within the central nervous system, since the effect can be blocked by co-administering other large neutral amino acids that reduce tyrosine's uptake into the brain. That tyrosine's antihypertensive action is mediated by an acceleration in norepinephrine or epinephrine release within the central nervous system is suggested by the concurrent increase that its injection produces in brain levels of methoxyhydroxyphenylethylglycol sulfate.

Amino Acids↗
PubMed1979

Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.

Adult↗
PubMed1979

Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.

The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.

Adult↗
PubMed1979

Reduction in blood pressure in normal and spontaneously hypertensive rats by lergotrile mesylate.

The acute administration of lergotrile mesylate to normal or spontaneously-hypertensive rats (SHR) causes a prompt reduction in blood pressure. In SHR, doses as small as 0.05 mg kg-1 are effective; maximal reductions in blood pressure are obtained at a dose of 0.25 mg kg-1. Lergotrile may be administered intraperitoneally or orally. Its efficacy as an antihypertensive agent in rats does not diminish significantly when administered twice daily for 7 days. Although lergotrile has been reported to be a dopamine agonist, the present data do not establish the mechanism by which the drug lowers blood pressure.

Animals↗
PubMed1978

Serotonin receptor antagonists block a natural, short term surge in serum growth hormone levels.

Serum GH levels in untreated rats were found to increase spontaneously to over 300 ng/ml around the onset of darkness (1900 h) and then decrease to under 100 ng/ml by 2000 h. Pretreatment with the serotonin receptor blockers, metergoline (0.2, 0.5, 1, or 2 mg/kg) or cyproheptadine (1, 2, or 5 mg/kg), at 1800 h significantly blunted this physiological rise in serum GH. In rats bearing chronic right atrial cannulae from which blood samples were drawn every 15 min for 5 h, the administration of metergoline (1 mg/kg) was also observed to reduce plasma GH levels over a 3.25-h period. Serotonin-containing neurons in the brain thus seem to be involved in the physiological secretion of GH.

Animals↗
PubMed1978

Diurnal variations in plasma insulin concentrations in normal and cirrhotic subjects: effect of dietary protein.

Concentrations of immunoreactive insulin and of glucose were measured in plasma samples taken at 4-hour intervals from cirrhotic and normal control subjects ingesting diets containing various amounts of protein. In both groups, insulin levels were highest after meals, between 11 a.m. and 7 p.m.; in cirrhotic subjects, but not in controls, plasma glucose levels were also higher at these times. Insulin and glucose concentrations in plasma from cirrhotic subjects were higher than those from control subjects at all times measured. Peak daytime insulin levels were about 150 muU/ml in plasma from cirrhotic subjects, and 40--50 muU/ml in plasma from controls; nocturnal levels were 20--30 muU/ml in cirrhotics versus 10 muU/ml or less in controls. The protein content of the diet was unrelated to plasma insulin levels at all times of day or night examined. These data thus show that plasma insulin levels are persistently elevated in cirrhotics, remaining higher than normal throughout the 24-hour period.

Adolescent↗
PubMed1977

Diet and uptake of aldomet by the brain: competition with natural large neutral amino acids.

The rise in levels of aldomet in the brains of rats after an injection of the alpha-methylated amino acid was depressed when large neutral amino acids, but not acidic amino acids, were coadministered with the drug. This result suggests that aldomet is transported into brain by the carrier for natural large neutral amino acids. The prior ingestion of a carbohydrate meal, which lowers levels of neural amino acids in the serum, enhanced the uptake of aldomet into brain; the consumption of a protein-containing meal inhibited the subsequent uptake of aldomet into the brain. Antecedent diet can thus affect the availability of aldomet to the central nervous system; the mechanism of this effect probably involves the blood-brain barrier uptake system for large neutral amino acids.

Amino Acids↗
PubMed1977

Effects on the diet on brain neurotransmitters.

The synthesis of neurotransmitters in mammalian brain responds rapidly to changes in precursor availability. Serotonin synthesis depends largely on the brain concentrations of L-tryptophan, its precursor amino aicd. This relationship appears to be physiologic: when brain tryptophan levels vary because of insulin secretion or meal ingestion, corresponding alterations occur in the rate of serotonin formation. The ability of any food to modify brain tryptophan (and serotonin) depends on how its ingestion changes the serum concentration of not only tryptophan, but also several other large neutral amino acids that compete with tryptophan for uptake into the brain. Such precursor-induced changes in brain serotonin appear to be functionally important: animals having a reduced level of brain serotonin (caused by the chronic ingestion of a naturally tryptophan-poor diet, such as corn) demonstrate a heightened sensitivity to painful stimuli; this pain sensitivity can be acutely restored to normal values by a single injection of L-tryptophan, which rapidly elevates brain serotonin. The synthesis of catecholamines (e.g., dopamine, norepinephrine) in the brain also varies with the availability of the precursor amino acid L-tyrosine. Single injections of this amino acid increase brain tyrosine levels and accelerate brain catechol synthesis, while injections of a competing neutral amino acid (e.g., leucine, tryptophan) reduce brain tyrosine and its rate of conversion to dopa. The rate of catecholamine synthesis, however, appears to be influenced less by precursor levels than is serotonin formation: tyrosine hydroxylase, whcih catalyzes the rate-limiting step in catecholamine synthesis, responds strongly to end-product inhibition and to other controls that reflect variations in neuronal activity. The synthesis of acetylcholine in brain responds to substrate (choline) availability much like serotonin synthesis. Short-term alterations in brain choline levels are mirrored by similar changes in brain acetylcholine concentration. Variations in the daily dietary intake of choline also modify brain choline and acetylcholine. The relationship between choline availability and acetylchyoline synthesis has already foudn a cletween choline availability and acetylchyoline synthesis has already found a clinical application: choline has been used successfully in the treatment of tardive dyskinesia, a disorder of the central nervous system thought to reflect a deficiency in cholinergic transmission. These relationships between precursor availability from the periphery and brain neurotransmitter synthesis may ultimately provide the brain with information about peripheral metabolic state.

Acetyl Coenzyme A↗
PubMed1977

L-Dopa inhibits prolactin secretion in proestrous rats.

Female rats received an ip injection of L-dopa on the afternoon of proestrus. L-Dopa reduced serum prolactin concentrations within 1 h, whether administered just prior to, or during, the normal surge in serum hormone level. This inhibition lasted for 2-3 h, after which serum prolactin concentrations rose substantially. Pretreatment of proestrous rats with MK-486, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, did not block the effect of L-dopa on serum prolactin levels. In fact, MK-486 pretreatment appeared to prolong the effectiveness of L-dopa. Pretreatment with RO4-4602 at a dose sufficient to block central decarboxylase activity, however, did prevent dopa from inhibiting the proestrous surge in serum prolactin. These data are consistent with a role for dopamine in the control of prolactin secretion and suggest that the mechanism of action of L-dopa apparently does not require peripheral decarboxylation.

Animals↗
PubMed1976

Tryptophan concentrations in rat brain. Failure to correlate with free serum tryptophan or its ratio to the sum of other serum neutral amino acids.

Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation. Sera from animals fed carbohydrate plus fat contained 2.5 times as much free tryptophan concentrations did not differ. Similarly, sera from rats fed on carbohydrate, large neutral amino acids, and 40% fat contained 5 times as much free tryptophan as those from rats given this meal without fat, but brain tryptophan concentrations increased by only 26%. Correlations were made between brain tryptophan and (1) free serum tryptophan, (2) the ratio of free serum tryptophan to the sum of the other large neutral amino acids in serum that compete with it for uptake into the brain, (3) total serum tryptophan or (4) the ratio of total serum tryptophan to the sum of its circulating competitors. The r values for correlations (3) and (4) (i.e. those involving total serum tryptophan) were appreciably higher than those for correlations (1) and (2). Brain tyrosine concentrations also were found to correlate well with the ratio of serum tyrosine to the sum of its competitors. Competition for uptake into the brain among large neutral amino acids (represented here by serum ratios) thus appears to determine the changes in the brain concentrations of these amino acids under physiological conditions(i.e. after food consumption). Total, not free, serum tryptophan is the relevant index for predicting brain tryptophan concentrations.

Amino Acids↗