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Biomedical subjects

I Ramirez

Publications and source records attributed to I Ramirez.

At least 37 records · Page 2Linked to original sources

Does dietary hyperphagia contradict the lipostatic theory?

It has frequently been suggested that body weight or fat somehow exerts an inhibitory influence on food intake in a way that acts to maintain a stable body weight or fat. The principal evidence supporting this idea is that animals that have been induced to overeat and become overweight by various means, eat less than control rats when they are permitted to eat freely. If the degree of suppression of appetite by overweight is as large as several experiments suggest, then dietary hyperphagia should be self-limiting. Any overeating induced by dietary treatments should disappear after animals become moderately overweight. Animals fed some kinds of hyperhagia-promoting diets do show this pattern. However, animals fed other kinds of diets do not show this pattern, and with most diets, dietary hyperphagia continues for extended periods. This implies that either 1) overweight does not suppress appetite as much as suggested by various authorities, 2) dietary manipulations can override normal regulatory mechanisms, or 3) certain diets induce irreversible changes in body fat that are not evident from changes in body weight.

Adipose Tissue

Why do sugars taste good?

The preference humans and animals show for sweet solutions has been the subject of hundreds of publications. Nevertheless, the evolutionary origin of sweet preference remains enigmatic because of the relatively low nutritional value of sugars and the absence of specific tastes for other, more essential, nutrients. Moderate concentrations of sugars are found in most plant foods because sugars play an important role in plant physiology. Widespread occurrence of sugars in plants is paralleled by widespread preference for sugar solutions in mammals. These observations suggest that preference for sugars evolved because they are common in plants and easy to detect rather than because of any special nutritional merits they offer. Perception of sweetness cannot be used to accurately meter the metabolizable energy or nutritive value of a food.

Animals

Stimulation of energy intake and growth by saccharin in rats.

Rats fed wet diets containing saccharin consumed 12-14% more energy and gained 24-55% more weight than rats fed the same diets without saccharin. Saccharin-induced stimulation of intake was usually not so pronounced during the first week as during subsequent weeks of each experiment. Similar results were obtained using diets high in starch and fat. However, these effects could be obliterated by simply exposing the rats to unsweetened (plain) diet or to saccharin in water for several days before the sweetened diets were introduced. Furthermore, although stimulation of intake by saccharin was observed with diets containing 80% water, no such effect was observed with a diet containing 60% water. Rats given low-energy sweetened water in addition to their 80% water diet consumed substantially more fluid but not more or less energy than rats given unsweetened water. Preference tests suggest that saccharin increases diet palatability only very slightly; this finding is one of several observations suggesting that stimulation of intake by saccharin cannot be interpreted in terms of increased diet palatability. These results suggest that dietary hyperphagia results from the interaction between innate and learned responses to the taste of foods. Osmotic factors did not seem to exert a major influence in these experiments.

Analysis of Variance

Fuel partitioning and food intake: role for mitochondrial fatty acid transport.

Administration of methyl palmoxirate (MP; 10 mg/kg po), an inhibitor of carnitine palmitoyltransferase I (CPT I), increased the food intake of rats maintained on a diet high in triglycerides comprised of long-chain fatty acids, which require CPT I for mitochondrial uptake and oxidation. MP did not affect food intake in rats fed a comparable diet high in medium-chain fatty acids, which do not require CPT I for mitochondrial uptake and oxidation. The feeding response to MP was reduced more effectively by an intragastric preload of medium-chain triglyceride (MCT) oil than a preload of a long-chain triglyceride (LCT) oil. Food intake of MCT- and LCT-fed rats differed under control conditions (no MP), and this appeared to reflect differences in the diurnal distribution of feeding. Measurement of plasma ketone body concentrations indicated that the dietary manipulations and MP had their intended metabolic effects. The results strongly suggest that mitochondrial transport of fatty acids plays a role in the control of food intake. CPT I participates in that control by regulating the partitioning of long-chain fatty acids between pathways of storage and intramitochondrial oxidation.

Adipose Tissue

Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials.

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.

Adolescent

Hepatic endothelial lipase activity in neonatal rat liver.

Hepatic endothelial lipase (HEL) activity is as high in the neonatal (1-day old) rat liver as in adults. Most of the HEL activity is located at the capillaries since 75% of the total activity is released by heparin or collagenase perfusion. The residual activity (non-releasable) is located in hepatocytes and not in hemopoietic cells, which are the major cell type in neonatal liver. Per mg of protein, the HEL activity is 50% higher in neonatal than in adult hepatocytes. We suggest that neonatal hepatocytes have an increased capacity to synthesize and secrete HEL activity, so maintaining a high activity in the whole organ. It might contribute to the hepatic uptake of cholesterol from circulating lipoproteins, in a period in which endogenous cholesterol synthesis is known to be inhibited in the liver.

Animals

Dietary hyperphagia and obesity: what causes them?

Diets that cause animals to overeat and become obese have been used in many investigations of obesity. Most of this research, however, has concentrated on the consequences rather than the causes of overeating. Furthermore, in most studies, several nutritional variables were manipulated simultaneously, making cause and effect relationship impossible to disentangle. Consequently, progress has been slow. Diets could alter energy intake by virtue of their effects on oral-sensory, gastrointestinal or postabsorptive effects. Palatability is the most popular oralsensory hypothesis but the empirical basis for this hypothesis is particularly weak. A substantial body of evidence is consistent with the possibility that the osmotic effects of diets in the gastrointestinal tract and metabolic postabsorptive factors may play a major role in dietary hyperphagia and obesity. Suggestions for future research directions are offered.

Animals

Resistance to dietary hyperphagia in juvenile rats.

Adult rats (12 wk of age) fed a wet, high starch diet consumed more energy, gained more weight, and had more carcass fat than rats fed the same diet in a dry form. In contrast, juvenile rats (3.5 wk of age) did not consume more energy, gain more weight, or become fatter when fed the wet, high starch diet than when fed the same diet in dry form. Although rats of both age groups fed high fat diets consumed more energy than rats fed high starch diets, the effect of the high fat diets was much smaller in juvenile than in adult rats. The level of dietary protein (20 vs. 8%) in the diets did not interact with diet type, but juvenile rats fed low protein diets gained less weight than juvenile rats fed standard protein diets. Additional experiments showed that juvenile rats fed a 20% protein diet were capable of increasing fluid intake and energy intake when given sweetened water or insulin, respectively. Thus, low susceptibility to dietary hyperphagia in juvenile rats cannot be explained by assuming that juvenile rats already eat as much as they can. These data are consistent with the possibility that developmental changes in taste responsiveness may contribute to this effect of age.

Aging

Overeating, overweight and obesity induced by an unpreferred diet.

Rats fed diets containing 50-71% added water (liquid diets) eat more energy and gain more weight than rats fed the same diets without added water (solid diets). The present experiments examined the effects of making a liquid diet less palatable. The first experiment examined the effects of sucrose octaacetate on diet preference. Rats, given a choice of a liquid diet containing 0.5% sucrose octaacetate and a plain solid diet, preferred the plain solid diet for three weeks. When the concentration of sucrose octaacetate was reduced to 0.05%, the rats did not show a reliable preference for either the sucrose octaacetate liquid or plain dry diet. In subsequent experiments, each rat was given only one diet at a time. In the second experiment, rats were fed 0.5% sucrose octaacetate liquid diet for three weeks followed by 0.05% sucrose octaacetate liquid diet for another four weeks. The rats fed the sucrose octaacetate liquid diet overate and became obese compared to the rats fed plain solid diet throughout. In the third experiment, rats fed 0.5% sucrose octaacetate liquid diet for six weeks became obese compared to rats fed plain solid diet throughout. Thus, the overeating and obesity induced by liquid diets cannot be attributed solely to their high palatability.

Animals

Insulin counteracts the satiating effect of a fat meal in rats.

The effects of insulin administration of the reduction on food intake which follows a meal of corn oil was examined in normal and streptozotocin-diabetic rats. In the first experiment, a single injection of long-acting, protamine zinc insulin (3 IU) curtailed the decrease in 24-hr food intake that occurred in normal and diabetic rats after ingestion of 2.0 ml of oil. In a second experiment, injection of short-acting, regular insulin (0.5 IU) prevented the depression of food intake which occurred 6-24 hr after ingestion of 1.5 ml of corn oil, but not at earlier time intervals. In a third experiment, the short-term suppression of food intake in diabetic rats that occurred within 6 hr after a 1.5 ml meal of oil was reduced by chronic administration of insulin (3 IU/day) via a subcutaneously implanted osmotic pump. The results indicate that a relatively long-lasting effect of insulin counteracts the satiation from ingested fat and suggest that insulin's role in the control of food intake may depend on the composition of the diet.

Animals

Diet texture, moisture and starch type in dietary obesity.

A series of experiments demonstrated that the texture of a diet has less effect on growth than does the water content. Rats fed diets containing 50-71% water become obese. On the other hand, diets containing as little as 30% or as much as 75% water failed to increase growth. Varying the concentration of the suspending agent (xanthan gum) from 0.5% to 2% greatly altered the viscosity of liquid diets but had no reliable effect on growth. Diets containing gelatinized starch became semi-solid when water was added but the rats still grew faster when fed the moist rather than the dry gelatinized starch diets. However, feeding a diet containing a very high level of gelatinized starch reduced growth independently of the moisture content. Rats fed a dry powdered diet gained weight at about the same rate as rats fed a pelleted diet. These results indicate that the moisture content of a diet has a major influence on its ability to induce obesity. The type of starch fed to the rats also seems to be an important determinant of growth rate.

Animals

Practical liquid diets for rats: effects on growth.

Liquid diets based on the AIN-76 formula are described. The diets employ xanthan gum as a stabilizer. Information is provided on how these diets may be modified to meet the requirements of a particular experiment (e.g., variations in water content, type of protein or carbohydrate or fat, etc.). These diets are superior to widely used diets with regard to nutritional adequacy, cost, ease of preparation, versatility, stability, osmolality, and use of natural ingredients. An experiment is described which compares the effects of feeding rats a solid diet or a liquid diet prepared three different ways. The results confirm that a properly prepared liquid diet can produce overweight and obesity.

Animal Feed

When does sucrose increase appetite and adiposity?

Two methods of sucrose feeding have been employed in studies with rodents. In the nutritional method, part or all of the starch in a diet is replaced with sucrose. In the solution method, animals maintained on a nutritionally complete diet are given a sucrose solution to drink. The solution method is generally a more effective and reliable method of producing obesity except for weanling rodents. These two methods yield different results with regard to interactions with the fat and protein content of the diet, efficiency of weight gain, disaccharide effects and effects of meal feeding. It is suggested that for the nutritional method, sucrose alters food intake and adiposity via its effects on fat oxidation. For the solution method, the critical factor may be presenting a wet source of calories rather than sucrose per se. Differences in the way sucrose is fed do not account for all divergent results. Different investigators conducting similar experiments have often obtained different results. For these and other reasons, animal studies do not support the idea that sucrose intake causes obesity in humans.

Animals

Feeding a liquid diet increases energy intake, weight gain and body fat in rats.

Studies were undertaken to analyze the role of moisture content of foods in producing dietary obesity. Female CD rats consumed more energy when offered a sucrose solution and plain water to drink than when they were only given plain water, regardless of the sugar content of their diet (0-65%). This suggested that the overeating that commonly occurs when sucrose solutions are offered may not be due to sucrose per se. In subsequent experiments, rats were fed modified AIN-76 diets high in sucrose, starch or fat for 28-42 d. For some rats, the diet was liquefied by adding water to make a 32% suspension. Plain drinking water was always available. Rats fed high carbohydrate liquid diets, with or without solid diet, consumed 8-15% more energy than rats fed solid diet only. Rats fed liquid diets also gained 43-206% more weight than did rats fed solid diets. Analysis of carcass composition revealed that the liquid diets increased body fat. For high fat diets, the results were more complicated. Addition of water to a low cellulose, high fat diet did not increase adiposity, whereas addition of water to a high cellulose, high fat diet did increase adiposity. These results suggest that the obesity-inducing effects of feeding sugar solutions or cafeteria diets may be due, in part, to the high water content of these foods.

Adipose Tissue

Second malignant neoplasm in treated Hodgkin's disease. Report of a patient and scope of the problem.

The condition of a 6-year-old boy was diagnosed as mixed-cellularity Hodgkin's disease that involved the right side of the neck. Five years after the completion of radiation therapy for the involved area, followed by six courses of chemotherapy with mechlorethamine hydrochloride (nitrogen mustard), vincristine sulfate, procarbazine hydrochloride, and prednisone, he developed cerebral gliosarcoma. Numerous second malignant neoplasms have been reported in adults following treatment for Hodgkin's disease; however, the sequence of events in our patient is a new finding that has not, to our knowledge, been reported previously. While the second malignant tumor may have been induced by prior treatment, direct evidence is lacking.

Antineoplastic Combined Chemotherapy Protocols

Hypophagia following dietary obesity.

Two experiments examined the hypophagia that occurs when rats are switched from a high-fat to a low-fat diet. In the first experiment, rats fed a high-fat diet for eight weeks weighed 79 g more than rats fed a low-fat diet. Removal of the high-fat diet led to reduced food intake for at least four weeks. Reducing the body weight of the rats by a 24 hour fast did not alter the time course of the hypophagia. Plasma levels of free glycerol, free fatty acids and ketones were elevated during and after feeding the high-fat diet; suggesting that feeding a high-fat diet increases fat oxidation even after the high-fat diet is withdrawn. In the second experiment, feeding rats the high-fat diet for four weeks increased body weight and body fat. Starving the rats for two days after feeding the high-fat diet did not alter subsequent hypophagia and did not alter the percentage of body fat. This pattern of results is similar to that previously seen following termination of obesity-inducing insulin treatment. The results are consistent with the idea that a persistent increase in fat oxidation is responsible for the hypophagia.

Animals

Intragastric feeding differentially affects apparent rate of gastric emptying of phenol red and carbohydrate.

The effects of intragastric feeding on subsequent gastric emptying of glucose and glucose polymer solutions were investigated in rats having chronic gastric catheters. Rats were tested by a modification of the serial test meal method of Hunt. Six ml of solution was fed by mouth or gastric catheter and stomach contents were drained 15 to 60 minutes later. Dilution of stomach contents by gastric secretions and the fluid used to rinse the stomach was assessed by measurement of phenol red and direct assay of the carbohydrate. These two indicators gave very different results. Intragastric feeding of severely food deprived rats appeared to accelerate gastric emptying 30 to 60 minutes after feeding when phenol red was used but not when carbohydrate was used as a marker. Intragastric feeding did not significantly affect the apparent rate of gastric emptying in this same 30-60 minute period in mildly food deprived rats. Even though phenol red and glucose usually give similar results, it is probably inappropriate to estimate the emptying of glucose solely on the basis of measurements of phenol red. When carbohydrate was used as a marker, the chief effect of intragastric feeding is to produce some dumping of gastric contents within 15 minutes after the beginning of intragastric infusion.

Animals