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Biomedical subjects

R Wurtman

Publications and source records attributed to R Wurtman.

17 recordsLinked to original sources
PubMed1995

Choline ingestion increases the resonance of choline-containing compounds in human brain: an in vivo proton magnetic resonance study.

Choline is a crucial intermediate in several clinically relevant neurochemical processes. In this study, choline-containing compounds in human brain (principally phosphocholine, glycero-phosphocholine, and choline) were measured by 1H-magnetic resonance spectroscopy, before and after the ingestion of 50 mg/kg choline in four normal control subjects. Substantial and remarkably similar increases in the brain choline resonance occurred in each subject, with a nearly two-fold rise in the choline resonance observed 3 hr following choline ingestion (p = 0.008 versus baseline). One subject also received a dose of 200 mg/kg choline, and exhibited a proportionally larger increase in the brain choline resonance. The results are consistent with animal data reporting a rise in choline-containing compounds following choline administration. This is the first study to our knowledge where an oral nutrient has been shown to produce a detectable change in human brain composition in vivo. Studying choline transport and biotransformation in human brain may have relevance to several neuropsychiatric disorders, including affective disorders and dementia.

Acetylcholine↗
PubMed1995

The effect of a carbohydrate-rich beverage on mood, appetite, and cognitive function in women with premenstrual syndrome.

OBJECTIVE: To test the efficacy of a specially-formulated, carbohydrate-rich beverage (one known to increase the serum ratio of tryptophan to other large neutral amino acids) on the mood, cognitive, and appetitive disturbances of premenstrual syndrome (PMS). METHODS: Twenty-four women with confirmed PMS were enrolled in a double-blind, crossover study to test the efficacy of the specially-formulated beverage compared with two other isocaloric products on PMS symptoms. The study was conducted over three menstrual cycles preceded by a 1-month placebo run-in. Patients were tested at home or work using an interactive computer-telephone system. Standardized measurements of mood, cognitive performance, and food cravings were made before and 30, 90, and 180 minutes after consumption of active and placebo beverages during the late luteal phase of the menstrual cycle. RESULTS: The experimental carbohydrate intervention significantly decreased self-reported depression, anger, confusion, and carbohydrate craving 90-180 minutes after intake. Memory word recognition was also improved significantly compared with scores obtained during the placebo run-in month (P < .05). The isocaloric placebo interventions had no significant effect on any of these measures. CONCLUSION: The results suggest that the psychological and appetitive symptoms of PMS can be relieved after consuming a specially-formulated, carbohydrate-rich beverage known to increase serum tryptophan levels.

Adult↗
PubMed1995

Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation.

We tested whether 14 wk of dexfenfluramine (30 mg) or fluoxetine (40 mg) treatment would prevent weight gain after subjects quit smoking. Normal-weight women (n = 144) were randomly assigned to drug or placebo on a double-blind basis for 2 wk before quitting smoking and 12 wk thereafter. The fluoxetine group had more dropouts (28/49, 57.1%) than the dexfenfluramine group (17/47, 36.2%), with an intermediate number of dropouts from the placebo group (21/48, 43.8%). All groups gained weight during treatment, but their amount and pattern of weight gain differed. In the first month after quitting smoking, the placebo group gained more weight than either the dexfenfluramine or fluoxetine group (P < 0.05). By 2 mo postcessation, dexfenfluramine still suppressed weight gain in comparison with placebo (P < 0.05); weight gain with fluoxetine was not differentiable from either dexfenfluramine or placebo. By 3 mo postcessation, the dexfenfluramine group had gained 1.0 +/- 0.7 kg, significantly less than either the placebo (3.5 +/- 0.7 kg) or fluoxetine (2.7 +/- 0.5 kg) groups. Three months after drug discontinuation, formerly medicated, but not placebo patients, showed additional weight gain, eliminating differences between groups. Results indicate that weight gain, an adverse accompaniment of smoking cessation, can be minimized to some degree by serotoninergic drugs, although only for the duration of drug treatment.

Adult↗
PubMed1993

Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.

The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for 21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/- 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.

Adult↗
PubMed1991

Mineral homeostasis in obesity: effects of euglycemic hyperinsulinemia.

We explored the effects of insulin on mineral homeostasis in five lean and six moderately obese nondiabetic premenopausal women. Serum and urine minerals were measured before and during the steady-state phase of a euglycemic insulin clamp. Each subject participated in two insulin clamp studies on separate days at insulin infusion rates of 10 and 40 mU/m2/min. Euglycemic hyperinsulinemia was associated with (1) a significant increase in urinary calcium excretion when expressed per minute with no change in total serum calcium; (2) a decrease in urine and serum phosphate; (3) a decrease in serum potassium with no change in urine potassium; and (4) no measurable effects on urine or serum sodium. At any given insulin level, the obese individuals excreted significantly more calcium, phosphate, and potassium per minute than lean controls. While insulin administration had no effect on serum parathyroid hormone (PTH) or vitamin D levels, baseline serum 1,25(OH)2D concentration was significantly higher and serum ultrafilterable calcium was significantly lower in obese subjects than in lean controls.

Adult↗
PubMed1991

Weight gain and withdrawal symptoms after smoking cessation: a preventive intervention using d-fenfluramine.

Directly measured food intake in 31 overweight female smokers to test whether (a) calorie and carbohydrate intakes increase after smoking cessation and (b) double-blind d-fenfluramine (30 mg), a serotonin-releasing drug, suppresses weight gain, overeating, and dysphoric mood associated with stopping smoking. Placebo-treated patients grew dysphoric after smoking withdrawal and ate 300 kcal/day more from 2 to 28 days after, showing a 3.5-lb weight gain. Fat and protein intakes did not change, but carbohydrate intake increased (30% to 40%). D-fenfluramine prevented postcessation dysphoria. Although drug-treated patients ate more carbohydrate snacks just after quitting, they returned to baseline by 4 weeks, showing a 1.8-lb weight loss. Agents that enhance brain serotonin-mediated neurotransmission may help prevent weight gain, overeating, and dysphoric mood after smoking withdrawal.

Adult↗
PubMed1991

Selection of carbohydrate to protein ratio and correlations with weight gain and body fat in rats allowed three dietary choices.

In order to determine the spontaneous macronutrient choice of a normal rat population, we allowed growing animals to choose their food among three isocaloric diets: 5% protein - 40% carbohydrate; 45% protein - 40% carbohydrate and 5% protein - 70% carbohydrate, and we measured macronutrient intake, carbohydrate to protein (C/P) ratio and weight gain twice weekly during 9 weeks. At the end of the study, final body weight gain and fat accretion as well as brain serotonin content were measured. Protein consumption increased and fat intake decreased steadily during the assay (from 18.8 to 29 kcal% vs. 35.7 to 25.2 kcal%) whereas carbohydrate consumption remained constant (approx. 46 kcal%) ("carbohydrate homeostasis"), and as a consequence the C/P ratio dropped. There were great variations in total protein consumption between animals (13-32 kcal%) and an inverse relationship with fat intake because carbohydrate consumption was constant. Daily weight gain was negatively correlated with the corresponding C/P ratio, as were final weight gain and body fat content with the global C/P ratio characterizing the food choice of each rat. The concentrations of brain serotonin and 5-hydroxyindole acetic acid were rather uniform and did not show any correlations with any of the other variables. The percent food protein chosen by the animal determined the outcome of the trial at 9 weeks, i.e. food intake, weight gain and body fat accretion. In this experimental model, body fat accumulation is, therefore, directly linked to the protein content of the diet, inversely proportional to the fat level and not related to the carbohydrate content. Since the animals increase the proportion of protein in their food with age above basic nutritional requirements, it is postulated that the macronutrient choice of the rat is also determined by the need of the brain for a proper and balanced supply of neurotransmitter precursors adapted to the situation of each animal.

Adipose Tissue↗
PubMed1985

d-Fenfluramine selectively suppresses carbohydrate snacking by obese subjects.

Twenty obese inpatients who claimed to crave carbohydrate-rich foods were given d-fenfluramine (15 mg p.o., twice daily) or its placebo, double-blind, for two consecutive eight-day periods. Food choices were measured on treatment days 1, 7, and 8 by giving the subjects access to unlimited portions of six isocaloric meal foods (three high in carbohydrate and three high in protein) and of 10 isocaloric snack foods (five high in protein and five high in carbohydrate) available 24 hours a day in a computerized vending machine. d-fenfluramine reduced mealtime calorie intake by only 16% (from 1940 +/- 94 to 1630 +/- 92; p < .001), mealtime carbohydrate by 22%, and had no significant effect on mealtime protein consumption; in contrast, snack calorie intake was reduced by 41% (from 707 +/- 97 to 414 +/- 46; p < .001), and snack carbohydrate intake by the same proportion. The mean number of carbohydrate-rich snacks consumed per day decreased from 5.8 +/- 0.8 to 3.4 +/- 0.4 (p < .01), while that of protein-rich snacks failed to change signficantly (i.e., from 0.7 +/- 0.2 to 0.5 +/- 0.2).

Adult↗
PubMed1981

Characterization of neuropeptides by reversed-phase, ion-pair liquid chromatography with post-column detection by radioimmunoassay. Application to thyrotropin-releasing hormone, substance P, and vasopressin.

Neuropeptide contents of rat brain samples were determined by radioimmunoassay (RIA) after fractionation of tissue extracts by high-performance liquid chromatography (HPLC). Solvent systems were composed of acetic acid, acetonitrile and short-chain (5--8 carbons) alkylsulfonic acids. Separate solvent systems were developed for thyrotropin-releasing hormone, substance P. arginine vasopressin and biologic analogs, and the enkephalins. All separation systems tested gave 80--90% recovery of picogram quantities of peptides. When lyophilized, the HPLC solvents did not interfere significantly with the RIAs, allowing quantitation of tissue concentrations of isolated neuropeptides using the lyophilized eluent from the HPLC. The combination of liquid chromatography with RIA should allow for very accurate identification and quantification of peptides in biologic samples containing large numbers of potentially cross-reacting species of molecules.

Animals↗
PubMed1975

Rotational behavior in gerbils following unilateral common carotid artery ligation.

Unilateral cerebral infarctions are produced in 30-50% of all gerbils subjected to ipsilateral ligation of a common carotid artery. It has previously been shown that this infarction is associated with a major depletion if ipsilateral brain dopamine. The present studies characterize the spontaneous and drug-induced rotational behavior manifested by these animals and attempt to relate it to the functional activity of dopaminergic synapses. The tendency of animals to turn towards the side of the lesion 2-3 hours after surgery was found to correlate highly with the unilateral dopamine depletion observed after 24 hours. Two patterns of rotational responses were observed among animals showing symptoms that were treated with d-amphetamine or apomorphine; these could be correlated with mortality 24 hours after surgery.

Amphetamine↗