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Biomedical subjects

G H Anderson

Publications and source records attributed to G H Anderson.

At least 127 records · Page 7Linked to original sources

5-Hydroxytryptamine : a modulator of food composition but not quantity?

After a meal of protein, in contrast to a meal of carbohydrate (CHO) at 1915 hr, rats allowed to choose from high carbohydrate and high protein diets during 2000-2100 hr prefer CHO (1). Thus the hypothesis that this regulation of macronutrient selection involves brain 5-hydroxytryptamine (5-HT) metabolism was tested. Compared to three baseline days during which rats (250- 300g ) consumed 1 g CHO, rats fed tryptophan (TRP, 5-HT precursor; 15 mg in 1 g CHO) selected meals higher in protein concentration (35.4% vs 46.6%, F (1,12) = 20.05, p less than 0.001) from 10% and 60% casein diets during 2000-2100 hr. Associated with the higher protein selection was an elevated brain 5-HT turnover in rats killed 30 minutes after consuming CHO + TRP. Pretreating rats with p-chlorophenylalanine, an inhibitor of TRP hydroxylase, blocked this effect of TRP (36.3% vs 37.0%). Fenfluramine (1 and 2 mg/kg i.p. at 1945 hr), which transiently enhances neuronal 5-HT release, increased the rat's relative preference for protein from 28.8% to 37.5% (2 mg/kg, t = 3.21, p less than 0.025) during 2000-2100 hr. These rats, also exhibited a selective preference for CHO between 3-12 hrs post injection which paralleled the known subsequent depletion of 5-HT by fenfluramine. We conclude that the relative proportion of protein and carbohydrate selected in a meal is controlled, at least in part, by prior food effects on brain 5-HT metabolism.

Animals↗

Altered methionine metabolism in streptozotocin-diabetic rats.

We examined the origin of hypermethioninaemia in streptozotocin-diabetic rats. In rats administered streptozotocin over a range from 55 to 75 mg/kg, the dose of drug injected correlated directly with the plasma methionine concentration and inversely with the plasma insulin level. Although insulin administration prevented hypermethioninaemia in streptozotocin-diabetic rats, discontinuing insulin treatment resulted in a time-dependent increase in the plasma methionine level. Plasma methionine concentration was, however, normal in insulin-deprived BB Wistar rats despite severe hyperglycaemia. Thus, although insulin deficiency may be a contributing factor, it does not cause hypermethioninaemia independent of other drug-related effects. Administering a loading dose of methionine (100 mg/kg) indicated that streptozotocin-diabetic rats have a reduced metabolic capacity. Since dietary intake is the primary source of methionine, it is likely that hyperphagia combined with limited disposal produces hypermethioninaemia. Methionine is the most toxic amino-acid; therefore, metabolic studies using the streptozotocin model of insulin deficiency must be interpreted with caution.

Animals↗

Brain mechanisms and the quantitative and qualitative aspects of food intake.

The brain receives a large number of signals from the ingestion of food. They provide the brain with information on both the adequacy of energy ingested and the macronutrient composition of the food. From this information brain feeding control systems are able to respond and direct the animal to make appropriate food choices so that both the quantitative (energy) needs as well as the qualitative (nutrient) needs are met. An understanding of brain mechanisms regulating feeding will only emerge if their dual purposes are recognized.

Amino Acids↗

Excretion of urinary catecholamine metabolites in anorexia nervosa: effect of body composition and energy intake.

Metabolites of norepinephrine and dopamine were measured in urine from 12 women of normal body weight and from six women undergoing treatment for anorexia nervosa. The women with anorexia nervosa had 48% less body fat (14 +/- 1 versus 27 +/- 1%, p less than 0.001), 9% less fat-free mass (36 +/- 1 versus 40 +/- 1 kg, p = 0.05), and 26% higher energy intake (2217 +/- 147 versus 1750 +/- 43 kcal, p less than 0.01) on collection days compared to the normal weight women. Twenty-four-hour excretions of norepinephrine metabolites, 3-methoxy-4-hydroxyphenylethylglycol, 3,4-dihydroxyphenylethylglycol, and vanilmandelic acid were reduced (p less than 0.01) in anorexia nervosa by 44, 48, and 39%, respectively. Excretion of homovanillic acid, the dopamine metabolite, was the same for both groups. Urinary 3-methoxy-4-hydroxyphenylethylglycol content was best predicted by percentage body fat in the normals (r = 0.63, p less than 0.05) and for both groups combined (r = 0.79, p less than 0.001). Urinary vanilmandelic acid showed a strong relationship with fat-free mass in the normal group (r = 0.84, p less than 0.001) and for both groups combined (r = 0.79, p less than 0.001). In contrast, urinary 3-methoxy-4-hydroxyphenylethylglycol and vanilmandelic acid and energy intakes were only weekly associated in the normals, but unrelated in the anorexics, or when the data from both groups were combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Free tyrosine levels of rat brain and tissues with sympathetic innervation following administration of L-tyrosine in the presence and absence of large neutral amino acids.

The tyrosine concentration of fasted rats was measured in plasma, brain and tissues receiving sympathetic innervation after L-tyrosine (200 mg/kg) was administered alone or in the presence of an equimolar cocktail containing isoleucine, leucine and valine. In the samples taken at 15, 30, 45, 60, 120 or 180 minutes, the highest concentrations of L-tyrosine were observed in plasma, heart, adrenal gland and kidney at 15 minutes, but in interscapular brown adipose tissue at 15 and 30 minutes and in brain at 15-60 minutes. The decline from peak concentrations was slower in brain, kidney and interscapular brown adipose tissue than in plasma, but in all tissues examined, control levels of free tyrosine were attained by 180 minutes postadministration . Competing large neutral amino acids reduced the maximal uptake of tyrosine in the brain by 48% but had no effect in the other tissues examined.

Adipose Tissue, Brown↗

Dietary tyrosine supplementation enhances weight gain in streptozotocin-diabetic rats.

The effect of dietary protein concentration and tyrosine supplementation on growth in streptozotocin (65 mg/kg, ip) diabetic rats was evaluated. When rats were fed diets ranging from 15 to 60% protein, weight gain and feed efficiency were greatest in rats fed the 45% protein diet. Adding tyrosine to this diet (8%, incorporated as a percentage of protein) did not promote further weight gain relative to nonsupplemented diabetic animals. In contrast, rats choosing 45% of total calories as protein by selecting from 10 and 60% protein diets supplemented with either 0, 4, or 8% tyrosine demonstrated a 35% (4% tyrosine) to 45% (8% tyrosine) increase in weight gain. Proximate analysis indicated similar body composition in tyrosine supplemented and nonsupplemented diabetic animals. Including tryptophan (1.45%) with tyrosine in the self-selection diet was without effect. Thus, tyrosine supplementation promoted a modest but consistent and specific increase in weight gained by self-selecting diabetic rats.

Animals↗

A role for vagus nerve in regulation of protein and carbohydrate intake.

The effects of vagotomy on long-term protein and carbohydrate selection or on short-term food selection following cholecystokinin octapeptide (CCK-8) injections, protein, or carbohydrate premeals and on brain 5-hydroxytryptamine (5HT) and catecholamine metabolism were examined in adult rats. Vagotomy was followed by a reduction in daily protein intake that by 3 wk had fallen to 50% of preoperative levels. A corresponding increase in carbohydrate intake occurred so that total food intake was maintained at approximately 93% of that consumed by the sham-operated controls. These changes in day-to-day macronutrient selection from a choice of high- and low-protein diets were associated with a vagotomy-induced decreased turnover of 5HT in the hypothalamus. In meal consumption studies vagotomy prevented a further reduction in meal size by CCK-8 but did not block decreased consumption of total food or of protein preference of the rats in meals taken subsequent to a protein meal. It was concluded that the vagus nerve plays a role in regulating long-term protein and carbohydrate preferences but not in the relationships among meal-to-meal composition and intake.

Animals↗

Normal and abnormal function of the hypothalamic-pituitary-adrenocortical system in man.

The first half of this manuscript is devoted to a review of the methods used and the results obtained in the published measurements of the normal responses to tests of the three main types of hypothalamic-pituitary-adrenocortical (HPA) activity in man. These are, I, basal, unstressed activity leading to appropriate levels of total daily production of cortisol in the characteristic circadian pattern; II, responses to feedback stimulation of HPA activity by metyrapone administration; and III, responses to tests of the effects of stress on the HPA system including the effects of hypoglycemia, induced fever, vasopressin administration, and ACTH injections and infusions. The advantages and shortcomings of each type of procedure are discussed. The second half of this paper describes the authors' attempts to establish the limits of normality of standard and modified methods of evaluating the HPA system. The defined limits of normality have been used to assess the HPA function in 158 patients with known or suspected disorders of the HPA system. In normal controls, halfhourly plasma cortisol determinations established the normality of circadian and postprandial fluctuations and of mean plasma cortisol concentration, 6.2 +/- 0.3 (SEM) micrograms/dl, which were closely approximated by determinations every 6 h. Metyrapone, given in a dose of 500 mg every 2 h for 24 h increased urinary 17-OHCS excretion to 10.5-32.6 mg/day or to 1.7-7.8 times basal excretion rate. Increasing rates of insulin infusion disclosed significant relationships between resulting plasma glucose and cortisol concentrations. The slopes of the delta cortisol/delta glucose responses were similar after insulin infusions (0.46 +/- 0.05) and after insulin injections, 0.15 U/kg (0.43 +/- 0.09), and were always greater than 0.20 micrograms/mg. This index provides a useful objective measure of the normality of responses to hypoglycemic stress, 0.20-0.87 micrograms/mg. Adrenocortical responses to iv infusions of ACTH (cosyntropin 0.25 mg) may be equivocal at 2 h but are clear cut at 4, 6 and 8 h. Of 158 patients in whom hypopituitarism was known or suspected because of the presence of a pituitary tumor, acromegaly, hyperprolactinemia, or clinical features, HPA function was found to be entirely normal in 88 patients and partially or severely abnormal in the remaining 70 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxycorticosteroids↗

The effect of prematurity on milk composition and its physiological basis.

The composition of milk obtained from mothers giving birth prematurely is of current interest because of the use of this milk as a nutrient source for the premature infant. During the past 5 years research has established that the milk produced by mothers of infants of very low birth weight (e.g., 28-32 wk of gestation) is different from the milk of women giving birth at term. Preterm milk of early lactation is generally found to have higher levels of protein, nonprotein nitrogen, fat, energy, sodium, and chloride, but lower levels of lactose and greater interindividual variation. However, by the end of the first month of lactation the preterm mother's milk is very similar in nutrient composition to term milk, at least based on the incomplete information available at present. Many of the initial differences in composition of preterm compared with term milk may be explained provisionally from animal studies of mammary gland development. Possible explanations include reduced blood flow to the gland and hence milk volume, incomplete differentiation of mammary epithelial cells, and the absence of tight junctions between epithelial cells.

Animals↗

Acute effects of captopril on cardiopulmonary hemodynamics and renin-angiotensin-aldosterone and bradykinin profile in hypertension.

Hemodynamic variables were measured and plasma renin activity (PRA), angiotensin II (AII), aldosterone, and bradykinin assays performed in 21 hypertensive men on regular diet and thiazide diuretics before and 60 to 90 minutes after 25 mg oral captopril. Heart rate, right and left ventricular filling pressures, mean cardiac index (CI), and pulmonary vascular resistance (PVR) remained unchanged. The mean intra-arterial pressure (MAP) fell from 140 +/- 5 to 116 +/- 6 mm Hg (p less than 0.001) correlating with reduction of systemic vascular resistance (SVR) (r = 0.87, p less than 0.001), control PRA (r = 0.59, p less than 0.01), and All levels (r = 0.72, p less than 0.005) but not with control bradykinin or its postcaptopril rise (p less than 0.01). The fall in SVR correlated with reduction in plasma All (r = 0.80, p less than 0.001) and aldosterone concentrations (r = 0.53, p less than 0.05). Of four patients (19%) with precipitous fall in MAP after captopril, three needed volume expansion for circulatory support. We conclude: (1) All reduction by captpril and not bradykinin potentiation explains most of the agent's hemodynamic response in hypertensive circulation, (2) endogenous All may have a supportive role for SVR and possibly for CI but not for PVR, and (3) extra precaution is warranted while captopril is being started in patients taking diuretics.

Adult↗

Anaplastic thyroid cancer presenting with hyperthyroidism.

Primary thyroid malignancies typically do not interfere with thyroid function. A patient is reported with anaplastic thyroid carcinoma presenting with hyperthyroidism; this is believed to be the first such case described. Prior to the onset of the thyroidal process, the patient was clinically euthyroid. It is concluded that the mechanism of thyrotoxicosis is analogous to that of subacute thyroiditis: rapid tissue necrosis with resultant release of thyroid hormone.

Carcinoma↗

A controlled trial of the effect of parenteral nutritional support on patients with respiratory failure and sepsis.

Energy and protein metabolism was studied in 11 septic patients receiving ventilatory support while on three different intravenous regimens. They received 5% dextrose in water (D5W), and one of two different regimens of parenteral nutritional support (PNS); either amino acid and dextrose (PNA) or amino acid and dextrose and lipid (PNB). All patients were given D5W and PNS in random order. The energy intake was targetted to exceed by 50% the measured metabolic rate. On D5W the mean measured energy expenditure was only 15.2% above the expected energy expenditure (p<0.02). A respiratory quotient of 0.75 while on D5W showed that in the absence of PNS the major part of energy requirements came from fat oxidation. In addition, on D5W these patients were in negative nitrogen and protein (synthesis-catabolism) balance. With PNS the metabolic rate rose significantly (p<0.02). While on PNA, the CO2 production was significantly higher than with PNB, and despite receiving all non-protein energy as glucose, the patients continued to oxidise fat to meet about 30% of their energy requirements. Continued fat oxidation was found to be associated with insulin resistance and high catecholamine levels, suggesting a cause and effect relationship. PNS caused an increase in protein (synthesis - catabolism) and nitrogen balances, and reduced leucine oxidation. The fall in leucine oxidation was greater on PNB than on PNA. Protein and nitrogen balances, expressed per gram of amino acid infused, were significantly better with PNB than PNA. It was concluded that insulin resistance may make fat an efficient source of energy.

Journal Article↗

Macromineral balances in premature infants fed their own mothers' milk or formula.

The premature infant's own mother's milk (preterm milk) and modified infant formula (SMA, 67 and 80 kcal/dl) were fed to paired groups of seven infants, all of whom were of very low birth weight (VLBW) (less than 1.3 kg) and were studied during the first month of life. Sodium, potassium, magnesium, calcium, and phosphorus status was compared. The apparent retention of sodium from their mother's milk paralleled intrauterine retention rates and was greater than retention from SMA formula (P less than 0.01) during the first two weeks of life. However, when the formula was supplemented with NaHCO3 to intakes of 2.7 mmol Na/kg/24 hr after week 2, the infants retained adequate amounts of sodium. Potassium retention was similar to intrauterine retention rates in both groups throughout the four postnatal weeks. Magnesium intake, but not retention, was consistently higher in the group fed SMA (P less than 0.01), and intrauterine retention rates were achieved only in the group given formula. Calcium and phosphorus intakes from SMA were also higher (P less than 0.01) than from human milk. However, retention of calcium and phosphorus in both groups did not meet intrauterine retention rates, and hypophosphatemia developed in infants who received their mothers' milk. Growth in length and head circumference in both groups approximated intrauterine growth rates. If it is assumed that body composition of the growing VLBW infants should be similar to the composition of the fetus at corresponding gestational ages, then their nutrient requirements should be based on knowledge of intrauterine nutrient accretion rates. Based on this premise, we conclude that, for the growing VLBW infant, early maternal milk provided for sufficient retention of sodium, chloride, and potassium during the first four postnatal weeks. Neither human preterm milk nor SMA supplied adequate calcium and phosphorus for the growing VLBW infant.

Body Composition↗

Obesity and precursor availability affect urinary catecholamine metabolite production in women.

The effect of obesity and tyrosine (tyr) supplements on catecholamine metabolism in 12 normal weight and nine obese adult women was studied. Protein intake was maintained at 1.4 g protein/kg fat-free mass daily for 4 days with tyr added (0.26 g/kg fat-free mass) to the liquid diet on the last 2 days. In the 12 normal subjects, but not the obese, base-line urinary excretion of the norepinephrine metabolite, 3-methoxy-4-hydroxy phenylethyleneglycol was related to body fat whereas excretion of the norepinephrine metabolite vanilmandelic acid was related to fat-free mass and to total energy intake. Normal subjects responded to tyr with elevations in plasma tyr/neutral amino acid, plasma 3-methoxy-4-hydroxy phenylethyleneglycol, urinary vanilmandelic acid, and homovanillic acid, a dopamine metabolite, but not the norepinephrine metabolite, dihydroxy phenylethyleneglycol. The obese showed no increase in plasma or urinary 3-methoxy-4-hydroxy phenylethyleneglycol during tyr supplementation, although vanilmandelic acid and homovanillic acid increased. We conclude that urinary catecholamine metabolite production is related to body composition and to tyr intake in normal weight women. These relationships however, are altered in the obese, suggesting an association of obesity with abnormal catecholamine metabolism.

Adult↗

The influence of oral tyrosine and tryptophan feeding on plasma catecholamines in man.

We investigated the effects of oral tyrosine (7.5 g/day) and oral tryptophan (3 g/day) feeding with regular meals in normal male volunteers using a double-blind cross-over design with a "run in" period for acclimatization. Oral tyrosine feeding significantly decreased both free and conjugated plasma norepinephrine concentrations while oral tryptophan feeding did not have such an effect. Since alpha adrenergic stimulation in certain areas of the CNS has been shown to decrease peripheral sympathetic tone, we postulate that dietary tyrosine supplementation in man causes an increase in brain catecholaminergic activity which in turn leads to a decrease in peripheral sympathetic activity as evidenced by the decrease in plasma catecholamines.

Adult↗

Effect of dietary protein manipulation in subclinical portal-systemic encephalopathy.

Eight stable cirrhotic patients with mild or subclinical portal-systemic encephalopathy (PSE) were studied after shunt surgery when they were off all antiencephalopathic therapy. Equal amounts of mixed proteins were alternated with animal or vegetable protein in a crossover protocol under metabolic conditions for five consecutive, one week periods. The different dietary periods were not associated with either a change in the neurological impairment score or the Trailmaking Tests, which showed a learning effect. The peak frequencies of the computer analysed EEG (CAEEG) were lower during the animal (6.58 +/- 0.42 Hz) than the vegetable (7.10 +/- 0.44 Hz) diet (p 0.01). Neither arterial ammonia levels nor plasma amino acid ratios changed with the diets, whereas urinary 3-methyl-histidine excretion increased during the animal diet. During the vegetable diet the apparent nitrogen balance tended to be more positive than during either the mixed or animal diets associated with decrease in the urinary nitrogen excretion. The peak frequency of the CAEEG is the most sensitive test to monitor methods of treatment in portal-systemic encephalopathy. A vegetable protein diet, rather than overall protein restriction, should be considered in the management of this disorder, particularly when the nutritional state is poor.

Adult↗