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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During hemorrhagic shock, increased uptake of NH3 from the gut with inadequate compensation by the liver results in hyperammonemia. The effect on brain metabolism of acute hyperammonemia alone, as compared with normocapnic hypoxia, was investigated in 11 pentobarbital anesthetized (30 mg/kg) dogs. These animals were paralyzed (pancuronium bromide) and artificially ventilated to maintain the end-tidal fraction of FETCO2) CO2 constant. Arterial blood and cerebrospinal fluid (CSF) samples were obtained following control, 30-minute hypoxia, 60-minute NH3 infusion, and 30-minute hypoxia combined with NH3 infusion. These were analyzed for PaO2, PCO2, pH, and NH3. CSF samples were further analyzed for glutamine, urea, lactate, pyruvate, and citrate. There were no significant changes in urea or citrate. Glutamine, lactate, and the lactate/pyruvate ratio were significantly elevated by hypoxia and by NH3 infusion. (formula: see text). Thus, an acute NH3 load is capable of disrupting aerobic glycolytic metabolism. Hence, hyperammonemia may affect brain function during shock.
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PMID:Hypoxia, hyperammonemia, and cerebrospinal fluid metabolites. 26 84

1. Inter-organ relationships between glucose, lactate and amino acids were studied by determination of plasma concentrations in different blood vessels of anaesthetized rats fed on either a high-carbohydrate diet [13% (w/w) casein, 79% (w/w) starch] or a high-protein diet [50% (w/w) casein, 42% (w/w) starch]. The period of food intake was limited (09:00-17:00h), and blood was collected 4h after the start of this period (13:00h). 2. Glucose absorption was considerable only in rats fed on a high-carbohydrate diet. Portal-vein-artery differences in plasma lactate concentration were higher in rats fed on this diet, but not proportional to glucose absorption. Aspartate, glutamate and glutamine were apparently converted into alanine, but when dietary protein intake was high, a net absorption of glutamine occurred. 3. The liver removed glucose from the blood in rats fed on a high-carbohydrate diet, but glucose was released into the blood in rats fed on the high-protein diet, probably as a result of gluconeogenesis. Lactate uptake was very low when amino acid availability was high. 4. In rats on a high-protein diet, increased uptake of amino acids, except for ornithine, was associated with a rise in portal-vein plasma concentrations, and in many cases with a decrease in hepatic concentrations. 5. Hepatic concentrations of pyruvate and 2-oxo-glutarate decreased without a concomitant change in the concentrations of lactate and malate in rats fed on the high-protein diet, in spite of an increased supply of pyruvate precursors (e.g. alanine, serine, glycine), suggesting increased pyruvate transport into mitochondria. 6. High postprandial concentrations of plasma glucose and lactate resulted in high uptakes of these metabolites in peripheral tissues of rats on both diets. Glutamine was released peripherally in both cases, whereas alanine was taken up in rats fed on a high-carbohydrate diet, but released when the amino acid supply increased. 7. It is concluded that: the small intestine is the main site of lactate production, and the peripheral tissues are the main site for lactate utilization; during increased ureogenesis in fed rats, lactate is poorly utilized by the liver; the gut is the main site of alanine production in rats fed on a high-carbohydrate diet and the liver utilizes most of the alanine introduced into the portal-vein plasma in both cases.
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PMID:Inter-organ relationships between glucose, lactate and amino acids in rats fed on high-carbohydrate or high-protein diets. 63 46

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.
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PMID:Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation. 65 52

In fasting dogs, significant uptake by the jejunal wall from arterial blood was found for glutamine and eight other amino acids. Significant release into the mesenteric vein of ammonium, alanine, citrulline, and proline occurred, equal in nitrogen content to glutamine nitrogen taken up. The keto analogues of leucine, valine, and isoleucine, infused for 1 h into the lumen at initial concentrations of 10mM, disappeared from the lumen at 20.2 +/- 1.6, 18.6 +/- 2.0, and 15.7 +/- 2.8 mumol/cm in 1h, respectively. Eight fifteen and seventeen percent, respectively, of these absorbed quantities were released into mesenteric blood as leucine, valine, and isoleucine plus alloisoleucine, indicating significant amination of the keto acids by the gut wall. No significant changes were detected in the arteriovenous differences of any other amino acids or ammonium. The remainder of the absorbed analogues of valine and isoleucine appeared as such in the blood. In the case of the keto analogue of leucine, there was apparent degradation by the gut wall of 34% of the absorbed compound.
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PMID:Amino acid metabolism of dog jejunum before and during absorption of keto analogues. 84 61

Nitrogen-free analogues of essential amino acids, when administered with those essential amino acids for which analogues are ineffective or unavailable, exert three actions that may be beneficial in protein-deficient or protein-intolerant subjects. First, they bring about an increase in the concentrations of essential amino acids in the blood at the expense of the concentrations of certain non-essential amino acids, notably alanine and glutamine. This effect is most readily demonstrated in children with congenital defects of the urea cycle enzymes, but can also be seen during daily therapy of adults with portal-systemic encephalopathy. Second, these compounds promote nitrogen balance through their suppressive effect on urea synthesis (an effect not attributable to re-utilization of ammonia derived from urease action in the gut). This action is demonstrable in obese subjects who are already conserving nitrogen maximally at the end of a prolonged fast and can also be shown in the first week of fasting when the branched-chain keto acids alone are administered. In both situations, improved nitrogen conservation persists long after the analogues are metabolized, suggesting enzyme adaptations. In chronic uremics, nitrogen balance can be maintained in some (but not all) patients on very low nitrogen intakes. Third, these mixtures may delay or reverse the progressive decline in glomerular filtration rate characteristic of chronic renal failure in some cases: thus, for example, 5 of 6 patients taken off chronic dialysis have maintained lower serum urea concentrations without evidence of protein malnutrition for periods of 2-24 months.
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PMID:Evidence for an anabolic action of essential amino acid analogues in uremia and starvation. 107 39

The antidiuretic action of a number of vasopressin analogues has been measured in the rat and man in water diuresis. These analogues had the following categories of structural alteration: a) substitution of -CH2CH2-(dicarba) and -SCH2-(6-monocarba) for the natural -SS- bridge between residues 1 and 6, b) changes in the nature of the C-terminal tripeptide produced by substitution of D-arginine and L-Nalpha-methylarginine for L-arginine in sequence position 8 and L-leucine for proline in position 7, and c) combinations of a and b. In addition, a highly active analogue which results when valine is substituted for glutamine in position 4 was tested. Trained, unanesthetized rats and normal human volunteers were complemented by a volunteer patient with posttraumatic diabetes insipidus (DI) in the total group of experimental subjects. The only change in the C-terminal tripeptide which was associated with a high antidiuretic action was D-Arg substitution. The meArg and Leu analogues showed low to very little activity and no signs of antidiuretic antagonist action. All of the carba analogues showed both high potency and prolongation of antidiuretic action in the following order (for both potency and duration): monocarba + 8-D-Arg greater than 4-Val + 8-D-Arg greater than 8-D-Arg alone, all in deamino form. None of the 8-D-Arg analogues had any side effects on the cardiovascular system, gut, uterus, bladder, etc. The prolongation was such that even with a DI patient refractory to the action of lysine-vasopressin and relatively resistant to deamino-[8-D-Arg]-vasopressin, water turnover could be reduced from untreated levels of 20 to 30 liters/day to less than 2 liters/day with only a single administration of deamino-6-carba-[8-D-Arg]-vasopressin as nose drops. The significance of these structural alterations in the vasopressin molecule for interaction with both antidiuretic and smooth muscle receptors was discussed.
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PMID:Role of the disulfide bridge and the C-terminal tripeptide in the antidiuretic action of vasopressin in man and the rat. 119 61

Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.
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PMID:Glutamine facilitates chemotherapy while reducing toxicity. 128 30

Major thermal injury is associated with extreme hypermetabolism and catabolism as the principal metabolic manifestations encountered following successful resuscitation from the shock phase of the burn injury. Substrate and hormonal measurements, indirect calorimetry, and nitrogen balance are biochemical metabolic parameters which are useful and more readily available biochemical parameters worthy of serial assessment for the metabolic management of burn patients. However, the application of stable isotopes with gas chromatography/mass spectroscopy and more recently, new immunoassays for growth factors and cytokines has increased our understanding of the metabolic manifestations of severe trauma. The metabolic response to injury in burn patients is biphasic wherein the initial ebb phase is followed by a hypermetabolic and catabolic flow phase of injury. The increased oxygen consumption/metabolic rate is in part fuelled by evaporative heat loss from wounds of trauma victims, but likely also by a direct central effect of inflammation upon the hypothalamus. Although carbohydrates in the form of glucose appear to be an important fuel source following injury, a maximum of 5-6 mg/kg/min only is beneficial. Burn patients have accelerated gluconeogenesis, glucose oxidation, and plasma clearance of glucose. Additionally, considerable futile cycling of carbohydrate intermediates occurs which includes anaerobic lactate metabolism and Cori cycle activity arising from wound metabolism of glucose and other substrates. Similarly, accelerated lipolysis and futile fatty acid cycling occurs following burn injury. However, recent evidence suggests that lipids in the diet of burned and other injured patients serve not only as an energy source, but also as an important immunomodulator of prostaglandin metabolism and other immune responses. Amino acid metabolism in burn patients is characterized by increased oxidation, urea synthesis, and protein breakdown which is prolonged and difficult to reduce with current nutritional therapy. However, the current goal of nutritional support is to optimize protein synthesis. Specific unique requirements may exist for supplemental glutamine and arginine following burn injury but further research is needed before enhanced branched chain amino acids supplements can be recommended for burn patients. Recent research investigations have revealed the importance of enteral feeding to enhance mucosal defense against gut bacteria and endotoxin. Similarly, research has demonstrated that many of the metabolic perturbations of burns and sepsis may be due, at least in part, to inflammatory cytokines. Investigation of their pathogenesis and mechanism of action both at a tissue and a cellular level offer important prospects for improved understanding and therapeutic control of the metabolic disorders of burn patients.
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PMID:The metabolic effects of thermal injury. 129 Feb 69

In two recent clinical trials in surgical patients, supplementation of total parenteral nutrition with daily doses of 12 or 20 g of glutamine resulted in a diminished loss of free glutamine in skeletal muscle tissue. Studies in animals exploring the use of both enteral and parenteral glutamine supplementation suggest that glutamine may be an essential nutrient in the maintenance of gut structure and function during critical illness. These findings have led to heightened interest in the glutamine content of enteral formulas. This article describes a method for estimating the glutamine content of whole-protein enteral formulas. The average amount of glutamine in selected, whole-protein formulas ranges from a minimum of 3.55 g/4200 kJ to a maximum of 5.15 g/4200 kJ. Although it is still too early to define the safest and most effective dose of glutamine, there are two points regarding glutamine supplementation that clearly merit further investigation: no clinical trials have been conducted to assess the potential benefits of glutamine supplementation of an enteral diet or to assess the effects of using diets containing protein-bound glutamine rather than free glutamine.
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PMID:Glutamine content of whole proteins: implications for enteral formulas. 129 89

In recent years, considerable research has focused on the physiologic effects and clinical uses of three dietary constituents thought to be trophic to the intestinal tract in human beings: glutamine, short-chain fatty acids (SCFAs), and dietary fiber. Glutamine is an important nitrogen-carrying amino acid that may be "conditionally essential" in certain disease states to support the gut barrier and immune function and overall protein use. Colonic irrigations with SCFA preparations have demonstrated enhanced healing of bowel tissue in animals and human beings. Dietary fiber supports bacterial SCFA production, normal stool output, and the gut barrier and immune function. However, optimal fiber doses for various medical conditions are not known, and the risk for gastrointestinal (GI) obstruction, diarrhea, gas, and bloating necessitates careful selection of patients and daily monitoring of fiber tolerance. A review of the current literature indicates that widespread use of glutamine and SCFA additives parenterally and enterally awaits further evidence of safety and efficacy in human beings, establishment of appropriate doses, and advances in formulation technology. Administration of dietary fiber to enhance bowel motility should be considered in long-term tube-fed patients with intact GI function and sufficient fluid tolerance to permit hydration of fiber. Industrywide agreement on fiber analysis methods and labeling standards (eg, fiber fermentability vs solubility) would facilitate selection of enteral products. To streamline studies and optimize research efforts in future clinical trials, standard criteria for evaluating GI function, diarrheagenic factors, and intestinal outcome variables should be established.
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PMID:Intestinal fuels: glutamine, short-chain fatty acids, and dietary fiber. 839 Oct 33


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