Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine.

Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K(+)-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mM. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na(+)-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased.

Interactions of cephradine and cefaclor with the intestinal absorption of D-galactose.

Oral cephalosporins are frequently prescribed beta-lactam antibiotics. Although it has been well established that cephalosporins compete with dipeptides for absorption in the intestine, using the same transport mechanism, little is known about the action of the drugs on the absorption of other nutrients. In this work the effect of cephradine and cefaclor on the absorption of D-galactose has been studied. Intestinal sugar uptake was measured in-vitro in pieces of intestine (50 mg) and brush-border membrane vesicles, and in-vivo in intestinal loops. Galactose uptake was inhibited by cephalosporins in a dose-related, time-dependent manner. In-vivo the inhibition appeared when the antibiotics were on the luminal side of the enterocyte and when they reached the gut from the basolateral side. Only the active transport of the sugar was modified; passive transfer did not change in the presence of cephalosporins. In brush-border membrane vesicles, cephradine and cefaclor did not alter sugar uptake in either sodium or potassium gradients. Both antibiotics non-competitively inhibited basolateral Na+,K(+)-ATPase activity. These findings show that cephradine and cefaclor inhibit the active-transport component of galactose absorption because they reduce the activity of the basolateral Na+,K(+)-ATPase.

Influence of cephalosporins on intestinal enzymatic activity.

The effect of the broad spectrum antibiotics cefaclor, cefadroxil, cephradine, cefatrizine, cephaloglycine and cefroxadine was examined on rat intestinal brush border enzymes, aminopeptidase N (E.C. 3.4.11-2), dipeptidyl peptidase IV (E.C. 3.4.14.5) and alkaline phosphatase (E.C. 1.3.1.3.). All the cephalosporins assayed -except cefaclor- inhibit the aminopeptidase N activity, in an uncompetitive manner. Cefatrizine showed the most important inhibitory effect (52.5%; p < 0.001). Cefaclor and cefadroxil have no effect on the activity of the dipeptidyl peptidase IV, while cephaloglycine and cephradine showed a non competitive type inhibition. In contrast, cefatrizine and cefroxadine showed a competitive inhibition for this enzyme. None of the cephalosporins assayed had any effect on alkaline phosphatase activity.

[Development of a computer program to assess nutritional status of infants and preschool children]. / Desarrollo de un programa para la valoración del estado nutricional del lactante y del niño de corta edad por ordenador.

A computer program named INFANDIET has been designed with a Window's application (ToolBook software vs. 1.53), based upon object-oriented programming, and devised to assess the nutritional status of infants by using compatible computers PC. Additionally, it is a useful tool to elaborate personalized diets. This program has been developed to assist health professionals and students in the evaluation of the infant nutritional status by a) creating and managing clinical histories with anthropometrical, immunological and clinical data; b) showing infant dietary guidelines, with the ability to update the nutritional and food composition database of the program; c) giving information about infant nutrition; d) and presenting a complete list of references.

Growth, hormonal status and protein turnover in rats fed on a diet containing peas (Pisum sativum L.) as the source of protein.

The inclusion of peas (Pisum sativum L.) as the source of protein in the diet of growing rats brings about a reduction in growth rate as well as the impairment in the liver, muscle and spleen weights as compared with casein fed controls. Also, a fall in plasma glucose, triglycerides and protein was observed in the legume fed animals, while no changes in cholesterol levels were found. Furthermore, the rats fed on the diet containing peas showed lower levels of plasma insulin, corticosterone, IGF-I and T4 as compared with casein controls. Liver and muscle total protein (mg) and total DNA (mg) were markedly decreased in the legume fed animals, but DNA/g, protein/DNA and RNA/protein ratios were similar in both dietary groups. Likewise, liver and muscle fractional synthesis rates were similar in the casein and legume groups, while the whole body protein synthesis is assumed to be lower in the legume fed animals due to differences in body weights. It is concluded that animals fed on a diet containing peas (Pisum sativum L.) as the only source of protein showed less adverse effects than those found with other legumes such as Vicia faba L. or Phaseolus vulgaris L., in which protein quality, antinutritional factors and nutrient availability could be involved.

Immunological changes in growing mice fed on diets containing casein or peas (Pisum sativum var. Belinda) as the source of protein.

The effects of two different sources of protein: peas (Pisum sativum var. Belinda) and casein on immunocompetence, nutritional utilization and growth performance have been investigated in recently weaned mice. Feeding these animals on a pea diet resulted in an impairment in growth and significant decreases in the weights of liver, muscle, kidneys and femur, while intestine weights increased. No differences in food consumption were observed, but food conversion efficiency (food intake: weight gain) was increased in pea-fed animals compared with those offered the casein diet. Packed cell volume and serum Fe and Zn levels fell significantly after legume-protein intake, and, by contrast, Cu values increased slightly. Serum albumin levels showed a statistically significant reduction in mice fed on the diet containing peas. However, gamma-globulins and immunoglobulin G titres were markedly increased. The characterization of spleen-cell subsets using monoclonal antibodies revealed a significantly higher percentage of T-lymphocytes in the pea group compared with casein-fed animals, while no changes were observed in the proportions of B-lymphocytes and macrophages. In vitro mitogenic responses to phytohaemagglutinin, concanavalin A and Escherichia coli lipopolysaccharide S were slightly, but not significantly, lower in the pea-fed animals. Our results describe, apparently for the first time in mice, some immunological disturbances after peak intake. These results may lead to a better understanding of the possible role of antigenic proteins in gastrointestinal disorders and the poor individual performance after legume intake.

Insulin-like growth factor I (IGF-I) affects plasma lipid profile and inhibits the lipolytic action of growth hormone (GH) in isolated adipocytes.

The actions of insulin-like growth factor I (IGF-I) and growth hormone (GH) on lipid metabolism have been investigated in hormonally intact rats. The subcutaneous injection of IGF-I (100 micrograms) and GH (100 micrograms) lowered total cholesterol plasma levels. The in vitro assays on isolated rat adipocytes showed an antilipolytic effect of IGF-I on GH induced lipolysis. All these data support an important role for IGF-I and GH on the regulation of lipid metabolism.

Organ-specific effects and interactions of acute insulin-like growth factor I (IGF-I) and growth hormone (GH).

The acute organ-specific and metabolic actions of Insulin-like Growth Factor-I (IGF-I) and Growth Hormone (GH) were investigated in normal rats. Rats received a single subcutaneous injection of IGF-I (100 micrograms), GH (100 micrograms) or a combined treatment with IGF-I (100 micrograms) plus GH (100 micrograms) following a 2(2) factorial design. The acute treatment with IGF-I produced an increase in its plasma concentration along with a reduction in insulin levels. Plasma glucose and total cholesterol decreased in all treated groups as well as triglycerides in IGF-I treated animals as compared to controls. The rates of protein synthesis, measured by amino acid incorporation were not affected by any of these treatments in muscle or liver. However, GH treatment raised the rate of protein synthesis in the jejunum, while IGF-I treatment produced an increase in tibia protein synthesis rate. Negative interactions between GH and IGF were noted concerning tibia and jejunum protein formation. Thus, GH appeared to inhibit the response to IGF-I in bone, while IGF-I inhibited the response of the jejunum to GH administration. Also, liver cathepsin activity was reduced, while bone alkaline phosphase was increased by the GH treatment. Therefore, these results have demonstrated some acute organ-specific anabolic effects and interactions of IGF-I and GH on different aspects of metabolism in normal rats.

Acute effects of insulin-like growth factor-I (IGF-I) on bone protein synthesis in rats.

The acute systemic effects of IGF-I on bone protein metabolism from hormonally intact rats have been investigated by measuring the fractional rate of protein synthesis. The animals received a single subcutaneous injection of rhIGF-I (100 micrograms). Treatment with IGF-I increased the rate of tibia protein synthesis (Ks) while plasma glucose and insulin concentrations were decreased. These results are in favor of an endocrine role of IGF in stimulating bone growth.

[A computer program for assessing nutritional status and diet preparation]. / Programa informático para la valoración del estado nutritivo y la confección de dietas.

This computer program has been written in a BASIC language and designed to assess the nutritional status by means of anthropometrical, immunological and clinical data. Additionally, it is useful for the design and elaboration of personalized diets. The use of this program will allow to work with a great amount of nutritional information, besides, it will outstandingly reduce work time and increase accuracy to diagnose specific nutritional problems. The data base of this program has been made on the basis of current nutritional information and it can be easily updated when necessary.

Free intracellular and protein bound amino acids in tissues as affected by a mixed beta-adrenergic agonist.

The administration of metaproterenol induced an increase in gastrocnemius muscle weight without change in body growth rate or tissue protein concentrations, while epididymal fat was reduced. This effect was accompanied by an enhancement in the levels of intracellular amino acids in muscle. By contrast, liver amino acids were unaffected by treatment with the mixed beta-adrenergic agonist.

Skeletal growth after oral administration of demineralized bone matrix.

Oral administration of bone extracts obtained from bovine demineralized bone matrix to rats has a direct effect on bone metabolism, affecting bone proportions and some markers of bone formation such as bone malate dehydrogenase, serum alkaline phosphatase and serum osteocalcin. Furthermore collagen deposition, bone protein synthesis and nucleic acids content were significantly increased by the treatment.

Homeorhetic actions on tissue protein metabolism after the administration of rat growth hormone to normal rats.

An acute treatment with rat growth hormone (1 microgram/g) to intact female rats produced immediate changes in muscle and bone protein synthesis as well as in muscle protein breakdown, while glucose and glutamate-piruvate transaminase plasma levels were not altered. These effects, apparently, are not mediated by systemic insulin-like growth factor I. Also a long-term treatment with somatotropin (0.1 microgram/g/d) for 22 days was performed, in which protein synthesis rates in muscle, liver and bone remained unchanged. However, the growth hormone long-term treatment induced a decrease in muscle proteolytic activity and an increase in tibia weight. In this context, this experiment describes, apparently for the first time, the systemic effect of growth hormone in entire female rats. Data suggest that a single dose of rat growth hormone produces immediate changes in tissue protein metabolism, through a direct effect of growth hormone. These effects were not observed after the long-term growth hormone treatment, although these animals showed an increased in tibia proportions.

Tissue protein turnover in animals treated with the mixed beta-agonist metaproterenol: influence of dose, route and pattern of administration.

beta-Adrenergic agonists have been shown to increase protein deposition as a result of changes in the balance between protein synthesis and degradation rates. The aim of this study is to investigate the effect of the treatment with the non-selective beta-adrenergic agonist, metaproterenol, on protein metabolism in rats as well as the influence of the route and pattern of administration. A short- and long-term experimental trial were carried out. After the short-term treatment with the beta-agonist (1 mg/kg), neither protein nor nucleic acids were affected in liver or gastrocnemious muscle, while cathepsin A activity, an index of protein degradation, significantly increased in muscle. However, cathepsin A activity was reduced in muscle by the oral administration during 21 days of metaproterenol (2 ppm/day), but not by the subcutaneous injections (0.1 mg/kg/day). On the other hand, RNA/DNA, an index of protein synthesis capacity, and protein/DNA, an indicator of cell size, significantly diminished in muscle after the subcutaneous long-term treatment but did not change in the liver of treated rats. Our study has demonstrated a different outcome of a mixed beta-adrenergic agonist on protein metabolism depending on the duration of the treatment and the route of administration.

Potential induction of osteogenesis by systemic administration of bovine bone proteins.

This study shows, apparently for the first time, that the administration of bone derived proteins (putative bone growth factors) obtained from bovine demineralized maxillaries has a direct effect on osteogenesis, affecting significantly some markers of bone formation such as lactate dehydrogenase activity and serum osteocalcin. Also, collagen deposition and bone protein turnover were markedly increased by the treatment, which may have important biological and clinical applications.

Nutritional outcome and immunocompetence in mice fed on a diet containing raw field beans (Vicia faba, var. minor) as the source of protein.

Feeding growth mice on diets containing raw field beans (Vicia faba var. minor) as the only source of protein brought about an impairment in growth, muscle mass and liver weight. No changes in food consumption were observed, but the food intake:weight gain ratio was increased in those animals. Plasma protein, triacylglycerols and cholesterol values were not affected by the dietary treatment although serum glucose and zinc levels fell after legume intake as well as the number of circulating erythrocytes. The relative enlargement of thymus and spleen in the legume-fed mice was apparently accompanied by a reduction in the cell number and an increase in cell size, while the protein synthesis capacity followed differentiated patterns in both tissues when assessed through protein, DNA and RNA determinations. The haemagglutination titres and the number of rosette-forming cells were lower in those animals fed on the field bean diet as well as the splenic lymphocyte responses to phytohaemagglutinin, Concanavalin A or lipopolysaccharide mitogens used to evaluate the functional status of T and B lymphocytes. The present study describes, apparently for the first time in mice, the involvement of field bean intake in some immunological disturbances affecting both humoral- and cell-mediated aspects of the immune response.

Changes in serum and urinary amino acids after the administration of a mixed beta-adrenergic agonist.

The administration of the repartitioning agent metaproterenol, with affinity for beta 1- and beta 2-receptors, induced marked increases in gastrocnemius muscle and heart weights. The renal loss of essential amino acids was reduced in animals treated with beta-adrenergic agonists and a significant reduction in total serum amino acids was found as well. The assessment of urinary 3-methylhistidine suggests, that those changes were accompanied by a lower myofibrillar protein breakdown, while hydroxyproline output was increased as an indirect index of collagen turnover.