Nucleotides are low molecular weight biological molecules key to biochemical processes. Sources include de novo synthesis, recovery via salvage mechanisms, and dietary intakes. Although endogenous production serves as the main nucleotide source, evidence suggests that exogenous sources are essential to immune competence, intestinal development, and recovery. Dietary nucleotides serve a marked role in rapidly proliferating cells where they are necessary for optimal function. Accordingly, dietary nucleotides are deemed conditionally essential in the presence of various physiological stresses, including growth and development, recovery from injury, infection, and certain disease states. Clinical studies that evaluated nutrition formulations of nucleotides in combination with other specific nutrient substances demonstrated improved clinical outcomes in patients characterized as critically ill, injured, immune suppressed, or with chronic gastrointestinal conditions. However, conclusions regarding specific benefits of nucleotides are limited. Scientific substantiation of nucleotide supplementation in infant formula has been reported to improve the maturation and development of the intestinal tract as well as immune function. All medical nutrition products except for one immune-modulating formulation are devoid of nucleotides. In an effort to build on this, the current review presents the data to support potential clinical applications for nucleotides in enteral nutrition that may contribute to improved outcomes in physiologically stressed patients.
Atrophy of skeletal muscle reduces both the quality and quantity of life of patients with cancer cachexia. Loss of muscle mass is thought to arise from a reduction in protein synthesis combined with an enhanced rate of protein degradation, and few treatments are available to counteract this process. Eicosapentaenoic acid (EPA) has been shown to attenuate the enhanced protein degradation, but to have no effect on protein synthesis. This study examines the effect of EPA combined with a protein and amino-acid supplementation on protein synthesis and degradation in gastrocnemius muscle of mice bearing the cachexia-inducing MAC16 tumour. Muscles from cachectic mice showed an 80% reduction in protein synthesis and about a 50-fold increase in protein degradation compared with muscles from nontumour-bearing mice of the same age and weight. Treatment with EPA (1 g kg−1) daily reduced protein degradation by 88%, but had no effect on protein synthesis. Combination of EPA with casein (5.35 g kg−1) also had no effect on protein synthesis, but when combined with the amino acids leucine, arginine and methionine there was almost a doubling of protein synthesis. The addition of carbohydrate (10.7 g kg−1) to stimulate insulin release had no additional effect. The combination involving the amino acids produced almost a doubling of the ratio of protein synthesis to protein degradation in gastrocnemius muscle over that of EPA alone. No treatment had a significant effect on tumour growth rate, but the inclusion of amino acids had a more significant effect on weight loss induced by the MAC16 tumour than that of EPA alone. The results suggest that combination therapy of cancer cachexia involving both inhibition of the enhanced protein degradation and stimulation of the reduced protein synthesis may be more effective than either treatment alone.
The abilities of picric, sulfosalicylic (SSA), tricbloroacetic (TCA), and tungstic acids to precipitate a partial hydrolysate of egg albumin and several proteins were examined. After precipitation of the hydrolysate with SSA, TCA, and tungstic acid respectively, it was found that 88%, 79%, and 69% of the nitrogen remained in solution. The average size of the peptides in the supernatants varied from 330 to 380 daltons. The ability to precipitate native proteins varied with the precipitant and the protein. Tungstic acid precipitated both bovine serum albumin and p-lactoglobulin completely at low concentration (0.5% final concentration, w/v). Bovine serum albumin was precipitated by 3% TCA or SSA but, p-lactoglobulin was not completely precipitated until the concentrations had been increased to 10% and 20%, respectively. Pretreating p-lactoglobulin with sodium dodecylsulfate increased the amount precipitated by SSA and TCA.
Crude p-galatosidase was produced by lysis of cells of Streptococcus thermophilus grown on deproteinized whey. The enzyme was partially purified by ammonium sulfate precipitation and ion-exchange chromatography to yield a preparation free of protease activity. Highest activity was observed at pH 7.1, in the presence of potassium and manganese ions. Both monovalent and divalent cations were required for maximum activity but not for stability. The Km for o-nitrophenyl-p-galactopyranoside and lactose was 0.98 mM and 6.9 mM, respectively. Galactose was a competitive inhibitor with Ki of 60 mM. Gel-filtration indicated a molecular weight of 530,000. The enzyme seems well suited to hydrolysis of lactose in milk.
Phytoestrogens are a normal constituent of soy protein and have been shown to have anti-inflammatory activity in various in vitro and in vivo models. The present study was designed to determine if a diet enriched in the phytoestrogen isoflavones, genistin and daidzin, would alter the antigen-induced cellular infiltration, particularly eosinophilia, characteristic of a guinea pig model of asthma. Throughout the duration of the study, guinea pigs were maintained on a control diet (standard guinea pig chow) or the same diet enriched in isoflavones. The animals were placed on the diet 2 weeks prior to active sensitization with ovalbumin (OA). Three weeks after sensitization, animals were challenged with OA aerosol. The cellular infiltration into the lung and protein and red blood cells (RBC) in the bronchoalveolar lavage fluid (BAL) were determined 17 hr later. In animals maintained on the control diet, OA aerosol challenge resulted in the expected increase in eosinophils in both the BAL and the lung tissue, an increase in neutrophils in the BAL, and an increase in protein and the number of RBC in the BAL. In contrast, in animals maintained on the isoflavone diet, the OA-induced eosinophilia in the lung tissue was significantly attenuated. In addition, OA challenge caused a greater increase in BAL protein in animals maintained on the isoflavone diet compared with animals on the control diet. Our results indicated that a diet enriched in isoflavones results in reduced antigen-induced eosinophilia in the lung in the guinea pig model of asthma. However, this beneficial anti-inflammatory effect of dietary phytoestrogens is accompanied by a potentially detrimental increase in antigen-induced leakage of protein into the airspace.
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