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Biomedical subjects

S E Møller

Publications and source records attributed to S E Møller.

At least 37 records · Page 2Linked to original sources
PubMed1989

Neutral amino acid plasma levels in healthy subjects: effect of complex carbohydrate consumed along with protein.

Six healthy fasting females each received, on different days, 0, 25, or 50 g of complex carbohydrate in the form of white spaghetti containing 11-12% protein along with 200 ml water. Blood was collected before and at intervals for 4 hours after the spaghetti ingestion and assayed for plasma levels of large, neutral amino acids (LNAA), insulin and glucose. The area under the curve for the increase of serum insulin was four times greater after the 50-g dose compared to the 25-g dose of carbohydrate, but the respective areas under the curves for the increases of plasma glucose were identical. The plasma ratio tryptophan/LNAA varied significantly and increased 10% above basal level and 25-30% above control level after either carbohydrate dose, but only the difference for the 50-g dose was significant. Although the main effect for plasma ratio tyrosine/LNAA was also significant, the increases of this ratio above control level were marginal. The main effect for the dose of complex carbohydrate for valine, isoleucine and leucine was significant, and the areas above the curves for the decreases of individual branched-chain amino acids were of the same size after the two doses. Plasma tyrosine, phenylalanine and tryptophan showed no significant variation. The study has shown that consumption of complex carbohydrate along with 11-12% protein (the recommended dietary concentration) slightly increases the plasma ratio tryptophan/LNAA for 4 hours, and that the effect is practically maximal after ingestion of 25 g of the test meal.

Adult↗
PubMed1986

Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study.

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.

Adult↗
PubMed1986

Carbohydrate/protein selection in a single meal correlated with plasma tryptophan and tyrosine ratios to neutral amino acids in fasting individuals.

Plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to their respective competing large neutral amino acids (LNAA) for brain uptake, serum insulin and plasma glucose concentrations were determined in 31 fasting healthy female subjects, and in two smaller groups of smokers and oral contraceptive users, who were subsequently allowed to compose individual breakfast meals from a selection of 25 dietary products. Additional blood samples were collected at 2 hr after the meal. Smokers consumed less carbohydrate (-22%) and total calories (-23%) and showed decreased basal serum insulin level, when compared to controls on the same age. Females on oral contraceptives consumed significantly more carbohydrate (+54%) and total calories (+32%) than comparable controls. In the 31 females there was no significant correlation between any of the biological variables and the intake of fat or total calories. The ratio of carbohydrate/protein eaten was significantly and directly correlated with age and with the sum of plasma ratios Trp/LNAA and Tyr/LNAA, and these independent variables associated with 37% of the variance in the ratio carbohydrate/protein consumed, as evaluated by multiple regression analysis. After the meal, the plasma ratio Tyr/LNAA was increased, whereas the ratio Trp/LNAA was decreased in subjects whose ratio carbohydrate/protein consumed was below the mean of the full sample, whereas subjects who consumed meals with a high ratio carbohydrate/protein showed an increase in plasma ratio Trp/LNAA. It is concluded that biological variables in man are significantly associated with the choice between nutrients with different carbohydrate and protein contents for breakfast. The changes in the plasma ratios Trp/LNAA and Tyr/LNAA after consumption were generally moderate.

Amino Acids↗
PubMed1985

Effect of various oral protein doses on plasma neutral amino acid levels.

Six healthy fasting females each received, on different days, 0, 6, 12.5 or 25 g of albumin dissolved in 200 ml water. Blood was collected before and at intervals after the albumin ingestion and assayed for plasma levels of large, neutral amino acids (LNAA), insulin and glucose. Insulin increased significantly after ingestion of 12.5 and 25 g of albumin, whereas changes in serum glucose were small and inconsistent. Increases of plasma LNAA concentrations were dose-related and correlated significantly with the molar percentage in the albumin of the respective amino acids at 1 and 2 hours but not at 3 and 4 hours after consumption. Ratio in plasma of tyrosine to other LNAA increased by 20 to 60%, and still at 4 hours the plasma tyrosine ratio was significantly elevated above control level after all 3 albumin doses. The plasma ratio of tryptophan to other LNAA decreased by 30 to 50%, and at 4 hours the plasma tryptophan ratio was still significantly below control level after the 2 larger albumin doses. The marked changes in the plasma tryptophan and tyrosine ratio suggests that the central serotonin and catecholamine synthesis could possibly be affected following ingestion of pure protein.

Adult↗
PubMed1985

Plasma tyrosine/neutral amino acid ratio correlated with clinical response to nortriptyline in endogenously depressed patients.

Ratios in plasma of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 26 endogenous depressives before and after treatment with nortriptyline in doses adequate to achieve a steady-state serum level between 70 and 130 ng/ml, i.e., within the recommended therapeutic range. Pretreatment plasma Trp ratio and Tyr ratio were normal and did not change significantly during treatment. The plasma Trp and Tyr concentrations and the plasma Trp ratio showed no significant association with the therapeutic response. However, the pretreatment plasma Tyr ratio correlated significantly and directly with the final Hamilton rating score, and inversely with the per cent reduction of Hamilton rating score. Moreover, depressives with plasma Tyr ratio below the normal mean showed significantly greater clinical improvement than patients with higher plasma Tyr ratio with comparable serum nortriptyline levels. Evidence has been presented that biochemical variables in depressed patients are important determinants of clinical improvement following pharmacotherapeutic treatment. Moreover, the results suggest that the plasma Tyr ratio may be a guideline for antidepressant response to nortriptyline.

Adult↗
PubMed1985

Biochemical and diagnostic classification and serum drug levels: relation to antidepressive effect of imipramine.

The relationship between clinical effect of imipramine (IP) in 39 depressed patients and biochemical distinction, serum drug levels, and diagnostic classification was investigated retrospectively. Based on pretreatment plasma ratios of tryptophan and tyrosine to competing amino acids, which reflect the availability of the precursor amino acids to the brain, the patient sample was separated in two halfparts. The one group with low net availability of tryptophan and tyrosine improved significantly more than the other group with comparable mean serum drug levels. In the former group there was no association between clinical improvement and serum drug levels, whereas in the latter group the patients with serum IP plus desipramine (DMI) above 180 ng/ml improved significantly more than patients with lower levels. There was an indication that a serum ratio of IP:DMI below 0.2 was associated with a poor response. Patients classified as nonendogenous depressives by means of the Newcastle II scale showed about the same response pattern as endogenous depressives with comparable plasma amino acid profiles and serum drug levels. Based on amino acid patterns and serum drug levels only half of the patients received an optimal therapy on the applied schematic dosage schedule. Thus, biochemical classification rather than diagnostic may be a useful remedy for the adjustment of serum IP plus DMI to appropriate levels in individual depressives.

Adjustment Disorders↗
PubMed1985

Tryptophan to competing amino acids ratio in depressive disorder: relation to efficacy of antidepressive treatments.

The relationship between the ratio in plasma of tryptophan to competing amino acids, which indicates brain serotonin synthesis, and the clinical response in depressed patients to treatments that act by enhancing brain serotoninergic function has been studied. There was a significantly positive correlation between the pretreatment plasma tryptophan ratio and the final depression score in patients treated with L-tryptophan or amitriptyline, and a trend towards a positive correlation in patients treated with lithium plus L-tryptophan or clomipramine. Patients with a low plasma tryptophan ratio generally showed greater clinical improvement than patients with a high ratio. When the plasma tryptophan ratio and the ratio in plasma of tyrosine to competing amino acids were considered together there was also a significant relationship between clinical and biochemical findings in patients treated with imipramine. These studies strongly indicate that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression. Evidence has furthermore been presented which suggests that, rather than a low brain serotonin level per se, the hypofunction may be associated with disturbances in adaptive and regulatory mechanisms, e.g. postsynaptic serotonin receptors.

Amino Acids↗
PubMed1983

Tryptophan and tyrosine ratios to neutral amino acids in endogenous depression. Relation to antidepressant response to amitriptyline and lithium + L-tryptophan.

The plasma ratios of tryptophan and tyrosine to those amino acids that compete with them during transport across the blood-brain barrier have been determined in depressed patients before and after treatment for four weeks with amitriptyline or lithium + L-tryptophan. There was no relation between the absolute plasma concentrations of free or total tryptophan or tyrosine and the clinical response to amitriptyline. There was also no relation between pre-treatment ratio of plasma tyrosine to competing amino acids and response to amitriptyline, but depressives with subnormal tryptophan ratio improved significantly more than patients with supernormal tryptophan ratio with comparable serum drug levels. The therapeutic response to lithium + L-tryptophan was predicted neither by the absolute plasma concentrations of free or total tryptophan or tyrosine nor by the tyrosine ratio, but there was also a trend towards greater improvement in patients with subnormal compared with supernormal tryptophan ratio. The results suggest that the pre-treatment plasma ratio of tryptophan to competing amino acids is a useful predictor of clinical response to amitriptyline. The possible mode of action of amitriptyline and lithium + L-tryptophan is briefly discussed.

Amino Acids↗
PubMed1983

Tryptophan and tyrosine availability: relation to food choice and sleeping habits of man. A preliminary study.

Brain serotonin and noradrenaline may be involved in the regulation of sleep and of food choice. The precursor amino acids tryptophan and tyrosine and their ratios to large, neutral amino acids (LNAA) were determined in plasma of 60 healthy females and related to sleeping and eating habits as reported on a questionnaire. There was no relation between biochemical findings and the habits of going early to bed and rising early versus late rising and going late to bed. The ratios tryptophan:LNAA and tyrosine:LNAA together were significantly related to the choice of between-meal snacks in the forenoon; the subjects with supernormal net availability of tryptophan and tyrosine selected snacks with low proportions of protein to carbohydrate contents in preference to snacks with relatively high proportions as compared with subjects with subnormal net availability. Although designed as a pilot study, the results suggest an involvement of both serotoninergic and noradrenergic mechanisms in the regulation or protein and carbohydrate intake in man.

Adult↗
PubMed1982

Tryptophan tolerance and metabolism in endogenous depression.

The concentration of free and total tryptophan and kynurenine in plasma from 49 female depressives and 26 female controls was measured following oral loading with L-tryptophan, 100 mg/kg body weight. There was no significant difference between five depressives and six controls in the area under curve for free or total tryptophan or kynurenine in plasma. The peak concentration of kynurenine occurred 4 h after loading and in correlated significantly with the area under curve for kynurenine. There was no significant correlation between the L-tryptophan dose (g) and the plasma concentration of kynurenine a 4 h in the 49 depressives or 26 controls. The mean plasma levels of tryptophan and kynurenine at 4 h in the depressives were not significantly different from control levels. There was no clear relationship between the plasma levels of tryptophan or kynurenine at 4 h and the therapeutic response in 13 depressives treated with L-tryptophan for 15 days. It is concluded that the absorption, the plasma clearance, and the degradation to kynurenine of loading doses of L-tryptophan are normal in depressed patients. Results furthermore suggest that the plasma levels of tryptophan and kynurenine at 4 h are poor predictors of the response to L-tryptophan treatment in depressives.

Adult↗
PubMed1982

Lithium + L-tryptophan compared with amitriptyline in endogenous depression.

Endogenously depressed in-patients were treated for four weeks with either lithium + L-tryptophan (N = 22) or amitriptyline (N = 21) in an open study. Before and weekly during treatment the patients were evaluated by means of Hamilton rating scale, and blood samples were collected for determination of serum concentration of lithium, or amitriptyline and nortriptyline. Both groups responded significantly and the two treatments were not significantly different in antidepressive efficacy. No significant correlation could be demonstrated between clinical improvement and steady-state serum drug levels. From this study it appears that lithium combined with L-tryptophan may be effective in the treatment of endogenous depression.

Adult↗
PubMed1981

Pharmacokinetics of tryptophan, renal handling of kynurenine and the effect of nicotinamide on its appearance in plasma and urine following L-tryptophan loading of healthy subjects.

The pharmacokinetics of tryptophan, the temporal occurrence of kynurenine (KYN) and 3-hydroxykynurenine (3-HK) in plasma and urine, and the effect of nicotinamide on tryptophan metabolism were studied in 6 healthy subjects after oral administration of L-tryptophan 100 mg per kg body weight. The peak concentration of tryptophan in plasma occurred after 1 to 2 h, tryptophan disappeared linearly from 2 to 5 h and exponentially from 5 to 8 h. Urinary tryptophan excretion was negligible. The peak concentration of KYN in plasma occurred after 4 h and it was correlated significantly with the area under the plasma curve (AUC) of KYN of the subjects investigated. The AUC in plasma of KYN was significantly correlated with urinary KYN excretion within individuals, but not in the group as a whole. The data suggest that KYN was reabsorbed by renal tubules and that the degree of reabsorption was subject to large interindividual variation. The peak concentration in plasma of 3-HK occurred 11 min later than that of KYN. The results suggest that the net tubular effect on 3-HK was secretion. Pre-treatment with nicotinamide (0.5 g three times daily) resulted in considerable decreases in AUC in plasma, and in urinary excretion of KYN and 3-HK, indicating inhibition of liver tryptophan pyrrolase. The concomitant increase in AUC in plasma of free and total tryptophan was insignificant. As only a relatively small amount of tryptophan is catabolized by tryptophan pyrrolase following an L-tryptophan load, cautious interpretation is recommended of urinary KYN excretion as an indicator of tryptophan break down in investigation of different subjects.

Adult↗
PubMed1981

Relevance of tryptophan and tyrosine availability in endogenous and 'non-endogenous' depressives treated with imipramine or clomipramine.

This study was performed on 65 depressed in-patients who were included in previously reported trials of imipramine and clomipramine. Before and during treatment, blood samples were collected for estimation of the availability of tryptophan and tyrosine by measurement of their plasma ratios to competing amino acids, and for determination of plasma steady-state concentrations of imipramine, clomipramine and their demethylated metabolites. The patients were classified as endogenous or 'non-endogenous' depressives by means of diagnostic rating scales, and therapeutic efficacy was evaluated by means of the Hamilton rating scales. Neither imipramine nor clomipramine increased the availability of tryptophan or tyrosine. Three biochemical regions were defined: a low region including mostly patients with subnormal availability of both tryptophan and tyrosine, a medium region, and a high region including mostly patients with supernormal precursor availabilities. Endogenous depressives showed about the same biochemical distribution as controls whereas there tended to be a proportionately higher number of 'non-endogenous' depressives within the low region. Patients in the low region, irrespective of diagnostic classification, improved faster and more on imipramine than patients in the medium and high regions with comparable plasma drug levels. Patients on clomipramine tended to show a relationship between precursor availabilities and clinical response but no definite conclusion could be drawn from these data. The results suggest that determination of the pre-treatment tryptophan and tyrosine availability may be superior to diagnostic classification in predicting response to imipramine. The possible mode of action of tricyclic antidepressants is briefly discussed.

Biological Availability↗
PubMed1981

Effect of oral contraceptives on tryptophan and tyrosine availability: evidence for a possible contribution to mental depression.

The plasma concentrations of branched-chain and aromatic amino acids, free tryptophan, and kynurenine have been determined in oral contraceptive users and comparable controls. There were no differences between progestogen users and controls in either of the biochemical measurements. The estrogen-progestogen users showed elevated plasma levels of total tryptophan and decreased levels of tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. There was a clear trend that the incidence of adverse reactions was related to the decrease in tyrosine levels. The plasma ratio of tryptophan to competing amino acids was increased in the estrogen-progestogen users, whereas the ratio of tyrosine to competitors was severely decreased suggesting a decreased brain tyrosine concentration. It is suggested that a substrate-limited reduction in brain noradrenaline synthesis may contribute to the occurrence of depressive symptoms in susceptible individuals on estrogen-progestogen contraceptives.

Adult↗
PubMed1980

Relationship between plasma ratio of tryptophan to competing amino acids and the response to L-tryptophan treatment in endogenously depressed patients.

The ratio of the plasma of total tryptophan to those amino acids that compete with tryptophan during transport into the brain was determined in 60 control subjects and 87 patients suffering from endogenous depression, all females. The plasma ratio in the control subjects showed a significant negative correlation with age. There was no significant difference in the distribution of the biochemical data between the control subjects and the depressed patients. There was a significant higher proportion of bipolar depressed subjects compared to unipolar depressives and patients of uncertain polarity who showed a plasma ratio in the lower normal range. Thirty-two patients were subsequently treated with L-tryptophan. In the patients who showed a particularly low plasma ratio of tryptophan to competing amino acids a remission frequency of 80% was observed on day 14. The efficacy of L-tryptophan in the patients who showed a plasma ratio within the upper normal range was extremely poor. The results suggest that the ratio in the plasma of tryptophan to competing amino acids is a useful predictor of the course of treatment of depressed subjects with L-tryptophan.

Adult↗