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Sample records for intravenous glutamine decreases

  1. Intravenous glutamine enhances COX-2 activity giving cardioprotection.

    LENUS (Irish Health Repository)

    McGuinness, Jonathan

    2009-03-01

    Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.

  2. Effect of intravenous GLutamine supplementation IN Trauma patients receiving enteral nutrition study protocol (GLINT Study): a prospective, blinded, randomised, placebo-controlled clinical trial.

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    Al Balushi, Ruqaiya M; Paratz, Jennifer D; Cohen, Jeremy; Banks, Merrilyn; Dulhunty, Joel; Roberts, Jason A; Lipman, Jeffrey

    2011-01-01

    Background Trauma patients are characterised by alterations in the immune system, increased exposure to infectious complications, sepsis and potentially organ failure and death. Glutamine supplementation to parenteral nutrition has been proven to be associated with improved clinical outcomes. However, glutamine supplementation in patients receiving enteral nutrition and its best route are still controversial. Previous trials have been limited by a small sample size, use of surrogate outcomes or a limited period of supplementation. The aim of this trial is to investigate if intravenous glutamine supplementation to trauma patients receiving enteral nutrition is associated with improved clinical outcomes in terms of decreased organ dysfunction, infectious complications and other secondary outcomes. Methods/design Eighty-eight critically ill patients with multiple trauma receiving enteral nutrition will be recruited in this prospective, triple-blind, block-randomised, placebo-controlled clinical trial to receive either 0.5 g/kg/day intravenous undiluted alanyl-glutamine or intravenous placebo by continuous infusion (24 h/day). Both groups will be receiving the same standard enteral nutrition protocol and the same standard intensive care unit care. Supplementation will continue until discharge from the intensive care unit, death or a maximum duration of 3 weeks. The primary outcome will be organ-dysfunction evaluation assessed by the pattern of change in sequential organ failure assessment score over a 10-day period. The secondary outcomes are: the changes in total sequential organ failure assessment score on the last day of treatment, infectious complications during the ICU stay, 60-day mortality, length of stay in the intensive care unit and body-composition analysis. Discussion This study is the first trial to investigate the effect of intravenous alanyl-glutamine supplementation in multiple trauma patients receiving enteral nutrition on reducing severity of organ

  3. Enteral glutamine supplementation for very low birth weight infants decreases morbidity.

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    Neu, J; Roig, J C; Meetze, W H; Veerman, M; Carter, C; Millsaps, M; Bowling, D; Dallas, M J; Sleasman, J; Knight, T; Auestad, N

    1997-11-01

    Glutamine, described as a "conditionally essential" amino acid for critically ill patients, has not been routinely added to parenteral amino acid formulations for critically ill neonates and is provided in only small quantities by the enteral route when enteral intake is low. We conducted a blinded, randomized study of enteral glutamine supplementation in 68 very low birth weight neonates randomly assigned to receive glutamine-supplemented premature formula versus premature formula alone between days 3 and 30 of life. Primary end points consisted of hospital-acquired sepsis, tolerance to subsequent enteral feedings (days with no oral intake), and duration of hospital stay. Hospital acquired sepsis was 30% (control group) and 11% (glutamine group). Logistic regression with birth weight as a covariate showed that: (1) feeding group was significant (p = 0.048) in determining the probability of developing proven sepsis over the course of hospitalization and (2) the estimated odds of developing sepsis were 3.8 times higher for infants in the control group than for those treated with glutamine. Glutamine-supplemented infants had better tolerance to enteral feedings as measured by percent of days on which feedings needed to be withheld (mean percentage of 8.8 vs 23.8, p = 0.007). Analysis of T cells demonstrated a blunting of the rise in HLA-DR+ and CD16 subsets in glutamine-supplemented infants. There were no differences in growth; in serum ammonia, urea, liver transaminase, or prealbumin concentrations; or in mean hospital stay. This study provides evidence for decreased morbidity in very-low-birth-weight neonates who receive enteral glutamine supplementation.

  4. Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats.

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    Olde Damink, S W; de Blaauw, I; Deutz, N E; Soeters, P B

    1999-06-01

    Glutamine is considered to be a 'conditionally' essential amino acid. During situations of severe stress like sepsis or after trauma there is a fall in plasma glutamine levels, enhanced glutamine turnover and intracellular muscle glutamine depletion. Under these conditions, decreased intramuscular glutamine concentration correlates with reduced rates of protein synthesis. It has therefore been hypothesized that intracellular muscle glutamine levels have a regulatory role in muscle protein turnover rates. Administration of the glutamine synthetase inhibitor methionine sulphoximine (MSO) was used to decrease glutamine levels in male Wistar rats. Immediately after the MSO treatment (t=0 h), and at t=6 h and t=12 h, rats received intraperitoneal injections (10 ml/100 g body weight) with glutamine (200 mM) to test whether this attenuated the fall in plasma and intracellular muscle glutamine. Control animals received alanine and saline after MSO treatment, while saline was also given to a group of normal rats. At t=18 h rats received a primed constant infusion of L-[2,6-3H]phenylalanine. A three-pool compartment tracer model was used to measure whole-body protein turnover and muscle protein kinetics. Administration of MSO resulted in a 40% decrease in plasma glutamine and a 60% decrease in intracellular muscle glutamine, both of which were successfully attenuated by glutamine infusions. The decreased intracellular muscle glutamine levels had no effect on whole-body protein turnover or muscle protein kinetics. Also, glutamine supplementation did not alter these parameters. Alanine supplementation increased both hindquarter protein synthesis and breakdown but the net balance of phenylalanine remained unchanged. In conclusion, our results show that decreased plasma and muscle glutamine levels have no effect on whole-body protein turnover or muscle protein kinetics. Therefore, it is unlikely that, in vivo, the intracellular muscle concentration of glutamine is a major

  5. Single Prolonged Stress Decreases Glutamate, Glutamine, and Creatine Concentrations In The Rat Medial Prefrontal Cortex

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    Knox, Dayan; Perrine, Shane A.; George, Sophie A.; Galloway, Matthew P.; Liberzon, Israel

    2010-01-01

    Application of Single Prolonged Stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of Post Traumatic Stress Disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetyl aspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC. PMID:20546834

  6. Glutamine treatment decreases plasma and lymph cytotoxicity during sepsis in rats

    Institute of Scientific and Technical Information of China (English)

    Xuemin Wang; Ying Xue; Menfan Liang; Wei Jiang

    2012-01-01

    Glutamine (Gin) is considered as a conditionally essential amino acid.Pharmacological supplementation of Gln helps to maintain the intestinal mucosal barrier,modulate cytokine production,and prevent organ injury during sepsis.Our previous study demonstrated the different effects of Gln on macrophage cytokine production in vitro or in vivo.The purpose of this study was to investigate the potential mechanism of Gln treatment to protect cells and modulate inflammation during sepsis in vivo.The results showed that administration of Gln significantly attenuated plasma-induced macrophage cytokine production and endothelial cell necrosis after cecal ligation and puncture in rats.In addition,it preserved human umbilical vein endothelial cell (HUVEC) viability and migration ability. Gln treatment also reduced lymph cytotoxicity by restoring macrophage tumor necrosis factor-α production, maintainingHUVEC viability,and decreasing endothelial cell necrosis.Mesenteric lymph duct ligation did not alleviate plasma cytotoxicity. Plasma lipopolysaccharide and D-lactate levels were suppressed after Gln treatment.Taken together,these results indicated that Gin administration can protect cells by attenuating the cytotoxicity of plasma and mesenteric lymph during sepsis.

  7. Early intravenous ibuprofen decreases narcotic requirement and length of stay after traumatic rib fracture.

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    Bayouth, Lilly; Safcsak, Karen; Cheatham, Michael L; Smith, Chadwick P; Birrer, Kara L; Promes, John T

    2013-11-01

    Pain control after traumatic rib fracture is essential to avoid respiratory complications and prolonged hospitalization. Narcotics are commonly used, but adjunctive medications such as nonsteroidal anti-inflammatory drugs may be beneficial. Twenty-one patients with traumatic rib fractures treated with both narcotics and intravenous ibuprofen (IVIb) (Treatment) were retrospectively compared with 21 age- and rib fracture-matched patients who received narcotics alone (Control). Pain medication requirements over the first 7 hospital days were evaluated. Mean daily IVIb dose was 2070 ± 880 mg. Daily intravenous morphine-equivalent requirement was 19 ± 16 vs 32 ± 24 mg (P pain scores were lower in the Treatment group (P rib fractures significantly decreases narcotic requirement and results in clinically significant decreases in hospital length of stay. IVIb therapy should be initiated in patients with traumatic rib fractures to improve patient comfort and reduce narcotic requirement.

  8. Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange

    NARCIS (Netherlands)

    M. Timmerman (Michelle); C. Teng; R.B. Wilkening; P.V. Fennessey (Paul); F.C. Battaglia (Frederick); G. Meschia

    2000-01-01

    textabstractIntravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanis

  9. Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange

    NARCIS (Netherlands)

    M. Timmerman (Michelle); C. Teng; R.B. Wilkening; P.V. Fennessey (Paul); F.C. Battaglia (Frederick); G. Meschia

    2000-01-01

    textabstractIntravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying

  10. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy.

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    Veverka, Megan; Marsh, Kourtney; Norman, Susan; Brock, Michael Alan; Peng, Monica; Shenk, Jennifer; Chen, Jerome Gene

    2016-01-01

    OBJECTIVES: Diabetic ketoacidosis (DKA) is a leading cause of morbidity and mortality in children with type 1 diabetes. We implemented a standardized DKA management protocol by using a 2-bag intravenous (IV) fluid system. The purpose of the study was to examine if the protocol improved clinical outcomes and process efficiency. METHODS: This was a retrospective study of patients who did and did not undergo the protocol. Patients were included if they were 18 years of age or younger, were diagnosed with DKA, admitted to an intensive care unit or stepdown unit, and received continuous IV insulin. RESULTS: Of 119 encounters evaluated, 46 (38.7%) received treatment with the protocol and 73 (61.3%) did not. The median time to normalization of ketoacidosis was 9 hours (IQR 5-12) and 9 hours (IQR 6.5-13) for protocol and non-protocol groups, respectively (p = 0.14). The median duration of IV insulin therapy was 16.9 hours (IQR 13.7-21.5) vs. 21 hours (IQR 15.3-26) for protocol and non-protocol groups (p = 0.03). The median number of adjustments to insulin drip rate was 0 (IQR 0-1) and 2 (IQR 0-3) for protocol and non-protocol groups (p = 0.0001). There was no difference in the incidence of hypokalemia, hypoglycemia, or cerebral edema. CONCLUSIONS: The protocol did not change time to normalization of ketoacidosis but did decrease the duration of insulin therapy, number of adjustments to insulin drip rate, and number of wasted IV fluid bags without increasing the incidence of adverse events.

  11. Enteral glutamine pretreatment does not decrease plasma endotoxin level induced by ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Arda Demirkan; Erkin Orazakunov; Berna Savas; M Ayhan Kuzu; Mehmet Melli

    2008-01-01

    AIM: To investigate whether oral glutamine pretreatment prevents impairment of intestinal mucosal integrity during ischemia-reperfusion (I/R) in rats. METHODS: The study was performed as two series with 40 rats in each. Each series of animals was divided into four groups. The first group was used as a control. Animals in the second group were only pretreated with oral glutamine, 1 g/kg for 4 d. The third group received a normal diet, and underwent intestinal I/R, while the fourth group was pretreated with oral glutamine in the same way, and underwent intestinal I/R. Intestinal mucosal permeability to 51Cr-labeled EDTA was measured in urine in the first series of animals. In the second series, histopathological changes in intestinal tissue and plasma endotoxin levels were evaluated. RESULTS: Intestinal I/R produced a significant increase in intestinal permeability, plasma endotoxin level and worsened histopathological alterations. After intestinal I/R, permeability was significantly lower in glutamine- treated rats compared to those which received a normal diet. However, no significant change was observed in plasma endotoxin levels or histopathological findings. CONCLUSION: Although glutamine pretreatment seems to be protective of intestinal integrity, upon I/R injury, such an effect was not observable in the histopathological changes or plasma endotoxin level.

  12. Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation.

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    Nigel A Morrison

    Full Text Available RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q. Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005. Femoral neck BMD was measured in all subjects (-0.6SD, p = 0.0007. The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q. Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.

  13. Decreased nitric oxide production after intravenous immunoglobulin treatment in patients with Kawasaki disease.

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    Wang, Chih-Lu; Wu, Yu-Tsun; Lee, Chia-Jung; Liu, Hsiu-Chin; Huang, Li-Tung; Yang, Kuender D

    2002-10-01

    To assess nitric oxide (NO) production and different displays of NO synthase (NOS) isoforms in patients with Kawasaki disease (KD) before and after intravenous immunoglobulin (IVIG) treatment. Blood and urine samples were collected from patients with KD before IVIG treatment and 3 days afterward. Age-matched febrile patients with various diseases served as control patients. Plasma NOx (NO3- + NO2-) levels were measured as NO production. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining were used to detect differential NOS isoform expression in mononuclear leukocytes (MNCs). Patients with KD (n = 40) had higher levels of NOx than the non-KD febrile control patients. The elevated NOx levels in patients with KD were significantly associated with the occurrence of coronary artery dilation (>3 mm). These elevated NOx levels significantly decreased after IVIG treatment (157.8 +/- 15.9 micromol/L vs 57.0 +/- 4.27 micromol/L, P urinary NOx levels was not changed after IVIG treatment. Inducible but not constitutive NOS mRNA and protein in MNCs were prominently expressed but significantly decreased after IVIG treatment. IVIG may suppress iNOS expression of MNCs in patients with KD, thus decreasing NO-mediated inflammatory responses and coronary artery dilation.

  14. Astrocytes and Glutamate Homoeostasis in Alzheimer's Disease: A Decrease in Glutamine Synthetase, But Not in Glutamate Transporter-1, in the Prefrontal Cortex

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    Magdalena Kulijewicz-Nawrot

    2013-09-01

    Full Text Available Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system. Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease. AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex. Here, we analyzed the expression of GS (glutamine synthetase and GLT-1 (glutamate transporter-1 in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD. GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3 of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals in parallel with a reduced expression of GS (determined by Western blots, which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  15. Astrocytes and glutamate homoeostasis in Alzheimer's disease: a decrease in glutamine synthetase, but not in glutamate transporter-1, in the prefrontal cortex

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    Alexei Verkhratsky

    2013-10-01

    Full Text Available Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system. Being principal homoeostatic cells, astroglia are fundamental for various forms of neuropathology, including AD (Alzheimer's disease. AD is a progressive neurodegenerative disorder characterized by the loss of cognitive functions due to specific lesions in mnesic-associated regions, including the mPFC (medial prefrontal cortex. Here, we analyzed the expression of GS (glutamine synthetase and GLT-1 (glutamate transporter-1 in astrocytes in the mPFC during the progression of AD in a triple-transgenic mouse model (3xTg-AD. GS is an astrocyte-specific enzyme, responsible for the intracellular conversion of glutamate into glutamine, whereas the removal of glutamate from the extracellular space is accomplished mainly by astroglia-specific GLT-1. We found a significant decrease in the numerical density (Nv, cells/mm3 of GS-positive astrocytes from early to middle ages (1–9 months; at the age of 1 month by 17%, 6 months by 27% and 9 months by 27% when compared with control animals in parallel with a reduced expression of GS (determined by Western blots, which started at the age of 6 months and was sustained up to 12 months of age. We did not, however, find any changes in the expression of GLT-1, which implies an intact glutamate uptake mechanism. Our results indicate that the decrease in GS expression may underlie a gradual decline in the vital astrocyte-dependent glutamate–glutamine conversion pathway, which in turn may compromise glutamate homoeostasis, leading towards failures in synaptic connectivity with deficient cognition and memory.

  16. Clinical use of glutamine supplementation.

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    Wernerman, Jan

    2008-10-01

    Endogenous production of glutamine may become insufficient during critical illness. The shortage of glutamine is reflected as a decrease in plasma concentration, which is a prognostic factor for poor outcome in sepsis. Because glutamine is a precursor for nucleotide synthesis, rapidly dividing cells are most likely to suffer from a shortage. Therefore, exogenous glutamine supplementation is necessary. In particular, when i.v. nutrition is given, extra glutamine supplementation becomes critical, because most present formulations for i.v. use do not contain any glutamine for technical reasons. The major part of endogenously produced glutamine comes from skeletal muscle. For patients staying a long time in the intensive care unit (ICU), the muscle mass decreases rapidly, which leaves a tissue of diminishing size to maintain the export of glutamine. The metabolic and nutritional adaptation in long-staying ICU patients is poorly studied and is one of the fields that needs more scientific evidence for clinical recommendations. To date, there is evidence to support the clinical use of glutamine supplementation in critically ill patients, in hematology patients, and in oncology patients. Strong evidence is presently available for i.v. glutamine supplementation to critically ill patients on parenteral nutrition. This must be regarded as the standard of care. For patients on enteral nutrition, more evidence is needed. To guide administration of glutamine, there are good arguments to use measurement of plasma glutamine concentration for guidance. This will give an indication for treatment as well as proper dosing. Most patients will have a normalized plasma glutamine concentration by adding 20-25 g/24 h. Furthermore, there are no reported adverse or negative effects attributable to glutamine supplementation.

  17. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery.

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    Grigoras, Anca

    2012-09-01

    Breast cancer surgery is associated with a high incidence of persistent postsurgical pain (PPSP). The aim of this study was to evaluate the impact of intravenous (IV) lidocaine on acute and PPSP, analgesic requirements, and sensation abnormalities in patients undergoing surgery for breast cancer.

  18. Glutamine Modulates Macrophage Lipotoxicity

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    Li He

    2016-04-01

    Full Text Available Obesity and diabetes are associated with excessive inflammation and impaired wound healing. Increasing evidence suggests that macrophage dysfunction is responsible for these inflammatory defects. In the setting of excess nutrients, particularly dietary saturated fatty acids (SFAs, activated macrophages develop lysosome dysfunction, which triggers activation of the NLRP3 inflammasome and cell death. The molecular pathways that connect lipid stress to lysosome pathology are not well understood, but may represent a viable target for therapy. Glutamine uptake is increased in activated macrophages leading us to hypothesize that in the context of excess lipids glutamine metabolism could overwhelm the mitochondria and promote the accumulation of toxic metabolites. To investigate this question we assessed macrophage lipotoxicity in the absence of glutamine using LPS-activated peritoneal macrophages exposed to the SFA palmitate. We found that glutamine deficiency reduced lipid induced lysosome dysfunction, inflammasome activation, and cell death. Under glutamine deficient conditions mTOR activation was decreased and autophagy was enhanced; however, autophagy was dispensable for the rescue phenotype. Rather, glutamine deficiency prevented the suppressive effect of the SFA palmitate on mitochondrial respiration and this phenotype was associated with protection from macrophage cell death. Together, these findings reveal that crosstalk between activation-induced metabolic reprogramming and the nutrient microenvironment can dramatically alter macrophage responses to inflammatory stimuli.

  19. Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

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    Ahmad Ghanizadeh

    2013-01-01

    Full Text Available There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids.

  20. Glutamine and glutamate supplementation raise milk glutamine concentrations in lactating gilts

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    Manso Helena

    2012-02-01

    Full Text Available Abstract Glutamine is the most abundant amino acid in milk, and lactation is associated with increased glutamine utilization both for milk synthesis and as a fuel for the enlarged small intestine. A number of recent studies have indicated that lactation is accompanied by a mild catabolic state in which skeletal muscle proteins are degraded to provide amino acids that are used to synthesize additional glutamine. In this study we tested the hypothesis that supplemental L-glutamine or the commercially available glutamine supplement Aminogut (2.5% by weight mixed into daily feed provided to gilts from 30 days prior to parturition until 21 days post-parturition would prevent a decrease in skeletal muscle glutamine while increasing the glutamine content of the milk. Muscle glutamine content decreased (P P P = 0.053. Milk glutamate remained constant between day 7 and 21 of lactation in the control and L-glutamine supplemented groups, but by day 21 of lactation the free glutamine, glutamate, and glutamine plus glutamate concentrations in milk from Aminogut-treated gilts were higher than those of control gilts. Thus dietary glutamine supplementation can alleviate the fall in intramuscular glutamine content during lactation in gilts, and may alleviate some of the catabolic effects of lactation. Furthermore, the increased milk glutamine content in the supplemented gilts may provide optimum nutrition for piglet development.

  1. Comparison of Intravenous Ranitidine with Pantoprazole in Decreasing Gastric Fluid Acidity in Emergency Cesarean Section

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    Alipour M

    2013-10-01

    Full Text Available Objectives: Peri-operative aspiration of gastric contents is a problem that causes certain respiratory problems including ARDS. Prophylaxis against aspiration of gastric contents is performed routinely in elective surgeries, but there is rare evidence on the efficacy of this method in emergency cesarean section. Materials and Methods: This is a randomized, controlled, double-blinded clinical trial. 60 parturients undergoing emergency cesarean section were randomly assigned into three groups of 20 each. They were allocated into two study and one placebo groups. The study group one and two received intravenous ranitidine (IV 50 mg or IV pantoprazole 40 mg, half an hour before induction of GA, respectively. The placebo group was administered just 5 ml of isotonic saline half an hour before GA induction. After intubation and confirmation of endotracheal tube insertion, the gastric contents were aspirated through a nasogastric tube for evaluation of acidity and volume. Results: A statistical difference between group one and two with the control group was observed in the acidity of gastric contents, but there was no difference in volume. Also, the PH level of gastric contents in patients receiving pantoprazole was significantly higher than the isotonic saline (p

  2. Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy

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    Peter Stehle

    2015-01-01

    Full Text Available Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care.

  3. Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy

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    Stehle, Peter; Kuhn, Katharina S.

    2015-01-01

    Critical illness is characterized by glutamine depletion owing to increased metabolic demand. Glutamine is essential to maintain intestinal integrity and function, sustain immunologic response, and maintain antioxidative balance. Insufficient endogenous availability of glutamine may impair outcome in critically ill patients. Consequently, glutamine has been considered to be a conditionally essential amino acid and a necessary component to complete any parenteral nutrition regimen. Recently, this scientifically sound recommendation has been questioned, primarily based on controversial findings from a large multicentre study published in 2013 that evoked considerable uncertainty among clinicians. The present review was conceived to clarify the most important questions surrounding glutamine supplementation in critical care. This was achieved by addressing the role of glutamine in the pathophysiology of critical illness, summarizing recent clinical studies in patients receiving parenteral nutrition with intravenous glutamine, and describing practical concepts for providing parenteral glutamine in critical care. PMID:26495301

  4. Intravenous Iron Repletion Does Not Significantly Decrease Platelet Counts in CKD Patients with Iron Deficiency Anemia

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    Neville R. Dossabhoy

    2013-01-01

    Full Text Available Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT counts in CKD patients with iron deficiency anemia (IDA. Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb, iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg; age years and Creatinine  mg/dL. All CKD stages were represented (stage 4 commonest. Hgb and Fe stores improved post-TDI (. There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, . The mild reduction in PLT after TDI remained non-significant ( when data was stratified by molecular weight (MW of iron dextran used (low versus high, as well as by dose administered (<1000 versus ≥1000 mg. Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.

  5. Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models

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    Jain, Meenu; Gamage, Nipuni-Dhanesha H.; Alsulami, Meshal; Shankar, Adarsh; Achyut, Bhagelu R.; Angara, Kartik; Rashid, Mohammad H.; Iskander, Asm; Borin, Thaiz F.; Wenbo, Zhi; Ara, Roxan; Ali, Meser M.; Lebedyeva, Iryna; Chwang, Wilson B.; Guo, Austin; Bagher-Ebadian, Hassan; Arbab, Ali S.

    2017-01-01

    Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model. PMID:28139732

  6. Intestinal and hepatic metabolism of glutamine and citrulline in humans.

    Science.gov (United States)

    van de Poll, Marcel C G; Ligthart-Melis, Gerdien C; Boelens, Petra G; Deutz, Nicolaas E P; van Leeuwen, Paul A M; Dejong, Cornelis H C

    2007-06-01

    Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.

  7. Glutamine metabolism in uricotelic species: variation in skeletal muscle glutamine synthetase, glutaminase, glutamine levels and rates of protein synthesis.

    Science.gov (United States)

    Watford, Malcolm; Wu, Guoyao

    2005-04-01

    High intracellular glutamine levels have been implicated in promoting net protein synthesis and accretion in mammalian skeletal muscle. Little is known regarding glutamine metabolism in uricotelic species but chicken breast muscle exhibits high rates of protein accretion and would be predicted to maintain high glutamine levels. However, chicken breast muscle expresses high glutaminase activity and here we report that chicken breast muscle also expresses low glutamine synthetase activity (0.07+/-0.01 U/g) when compared to leg muscle (0.50+/-0.04 U/g). Free glutamine levels were 1.38+/-0.09 and 9.69+/-0.12 nmol/mg wet weight in breast and leg muscles of fed chickens, respectively. Glutamine levels were also lower in dove breast muscle (4.82+/-0.35 nmol/mg wet weight) when compared to leg muscle (16.2+/-1.0 nmol/mg wet weight) and much lower (1.80+/-0.46 nmol/mg wet weight) in lizard leg muscle. In fed chickens, rates of fractional protein synthesis were higher in leg than in breast muscle, and starvation (48 h) resulted in a decrease in both glutamine content and rate of protein synthesis in leg muscle. Thus, although tissue-specific glutamine metabolism in uricotelic species differs markedly from that in ureotelic animals, differences in rates of skeletal muscle protein synthesis are associated with corresponding differences in intramuscular glutamine content.

  8. Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation.

    Science.gov (United States)

    Bott, Alex J; Peng, I-Chen; Fan, Yongjun; Faubert, Brandon; Zhao, Lu; Li, Jinyu; Neidler, Sarah; Sun, Yu; Jaber, Nadia; Krokowski, Dawid; Lu, Wenyun; Pan, Ji-An; Powers, Scott; Rabinowitz, Joshua; Hatzoglou, Maria; Murphy, Daniel J; Jones, Russell; Wu, Song; Girnun, Geoffrey; Zong, Wei-Xing

    2015-12-01

    c-Myc is known to promote glutamine usage by upregulating glutaminase (GLS), which converts glutamine to glutamate that is catabolized in the TCA cycle. Here we report that in a number of human and murine cells and cancers, Myc induces elevated expression of glutamate-ammonia ligase (GLUL), also termed glutamine synthetase (GS), which catalyzes the de novo synthesis of glutamine from glutamate and ammonia. This is through upregulation of a Myc transcriptional target thymine DNA glycosylase (TDG), which promotes active demethylation of the GS promoter and its increased expression. Elevated expression of GS promotes cell survival under glutamine limitation, while silencing of GS decreases cell proliferation and xenograft tumor growth. Upon GS overexpression, increased glutamine enhances nucleotide synthesis and amino acid transport. These results demonstrate an unexpected role of Myc in inducing glutamine synthesis and suggest a molecular connection between DNA demethylation and glutamine metabolism in Myc-driven cancers.

  9. Intravenous glutamine support downmodulats the release of plasma LPS and the activities of PLA2 and neutrophil elastase in taurocholate-induced acute severe pancreatitis in pigs%静脉内谷氨酰胺支持下调牛磺胆酸钠诱导急性重症胰腺炎猪血浆内毒素水平及磷酸酶A2和弹性蛋白酶活性

    Institute of Scientific and Technical Information of China (English)

    屠伟峰; 郄文斌; 何洹; 陈茜

    2011-01-01

    Objective To observe the effects of intravenous glutamine (Gln) support on plasma lipopolysaccharide (LPS,endotoxin) concentration and acitvities of phospholipase A2(PLA2) and neutrophil elastase (NE) in taurocholate-induced acute severe pancreatitis (ASP) in pigs. Methods Twenty-one pigs weighed 16 kg-22 kg were randomly divided into four groups: including sham-controlled group (sham group, n=5), ASP-controlled group(ASP group, n=5), ASP+glycine controlled group(Gly group, n=5) and ASP+Gln supported group (Gln group, n=6). Anesthesized pigs were subjected to ASP induced by injecting 1 ml/kg of mixed solution of 5% sodium taurocholate and 8 000~10 000 BAEE units trypsin/ml into pancreas via pancreatic duct, which was replaced by 0.9% sodium chloride phosphate buffer solution to be taken as sham group. Blood samples from caval vein was collected for the determinations of Gln, LPS, NE and PLA2. Plasma glutamine were measured by high performance liquid chromatography. Systemic plasma endotoxin levels was quantified by the chromogenic limulus amebocyte lysate (LAL) technique. All pigs were intravenously sacrificed by injecting 20 ml of 10%KCl. Anything involved in the processes of the sampling, preserving, measuring and so on had to be depyrogenated and to be asepsis. Results ASP porcine induced by sodium taurocholate mixed solution was associated with awfully lowed glutamine concentration but higher LPS, PLA2 and neutrophil elastase (NE) activities in plasma. There existed highly significant difference compared with the normal values (all P<0.01 ). Intravenous glutamine support could effectively prevent the decrease of systemic plasma glutamine level (P<0.01), and reduced the higher levels of systemic plasma LPS and the activities of plasma NE and PLA2 followed by acute severe pancreatitis induced by the mixed solusion of 5% sodium taurocholate and trypsin in pigs (all P<0.01), but all were still higher than the normal values except for NE activities at 72 h

  10. Virtual reality distraction decreases routine intravenous sedation and procedure-related pain during preoperative adductor canal catheter insertion: a retrospective study.

    Science.gov (United States)

    Pandya, Pooja G; Kim, T Edward; Howard, Steven K; Stary, Erica; Leng, Jody C; Hunter, Oluwatobi O; Mariano, Edward R

    2017-08-01

    Virtual reality (VR) distraction is a nonpharmacological method to prevent acute pain that has not yet been thoroughly explored for anesthesiology. We present our experience using VR distraction to decrease routine intravenous sedation for patients undergoing preoperative perineural catheter insertion. This 1-month quality improvement project involved all elective unilateral primary total knee arthroplasty patients who received a preoperative adductor canal catheter. Clinical data were analyzed retrospectively. For the first half of the month, all patients received usual care; intravenous sedation was administered at the discretion of the regional anesthesiologist. For the second half of the month, patients were offered VR distraction with intravenous sedation upon request. The primary outcome was fentanyl dosage; other outcomes included midazolam dosage, procedure-related pain, procedural time, and blood pressure changes. Seven patients received usual care and seven used VR. In the VR group, 1/7 received intravenous sedation versus 6/7 who received usual care (P = 0.029). The fentanyl dose was lower (median [10th-90th percentiles]) in the VR group (0 [0-20] µg) versus the non-VR group (50 [30-100] µg; P = 0.008). Midazolam use was lower in the VR group (0 [0-0] mg) than in the non-VR group (1 [0-1] mg; P = 0.024). Procedure-related pain was lower in the VR group (1 [1-4] NRS) versus the non-VR group (3 [2-6] NRS; P = 0.032). There was no difference in other outcomes. VR distraction may provide an effective nonpharmacological alternative to intravenous sedation for the ultrasound-guided placement of certain perineural catheters.

  11. Effects of Intravenous Indomethacin on Reduction of Symptomatic Patent Ductus Arteriosus Cases and Decreasing the Need for Prolonged Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Jannatdoust Abdollah

    2014-12-01

    Full Text Available Introduction: We decided to investigate the effects of injecting Indomethacin on reducing complications of Patent Ductus Arteriosus (PDA and the need for prolonged mechanical ventilation. Methods: During this randomized clinical trial, 70 premature infants with matched gestational age and birth weight were divided into case and control groups. In the study group, intravenous indomethacin started from the first 2-12 hours of birth. All patients were followed by echocardiography at the fourth day and skull ultrasound in the second week. Results: Symptomatic PDA rate was significantly higher in the control group (25.7% vs. 0%; P≤0.001. Incidence of grade 1-3 intraventricular hemorrhage was higher in the control group and the ratio of needed time for respiratory support in the control group to the case group was approximately 2.1. Conclusion: Intravenous Indomethacin reduced the number of PDA cases and incidence of grade 2 and 3 intraventricular hemorrhage, without any short term side effects.

  12. Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase-1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats.

    Science.gov (United States)

    Fernandez-Bustamante, Ana; Agazio, Amanda; Wilson, Paul; Elkins, Nancy; Domaleski, Luke; He, Qianbin; Baer, Kaily A; Moss, Angela F D; Wischmeyer, Paul E; Repine, John E

    2015-01-01

    Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macrophages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS). Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN+IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1 g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50 ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-α and interleukin (IL)-10 concentrations. Histology and immunofluorescence studies were also performed. Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL protein and LDH concentrations, but not BAL neutrophil counts, compared to non-GLN pretreated rats. The number of alveolar macrophages and the number of CD163+ macrophages were significantly increased in GLN pretreated IL-1/LPS-insufflated rats compared to non-GLN pretreated, IL-1/LPS-insufflated rats. GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages. Immunofluorescence localized CD163 and HO-1 in alveolar macrophages. Short-term GLN pretreatment activates the anti-inflammatory CD163/HO-1/p38-MAPK dephosphorylation pathway of alveolar macrophages and decreases capillary damage but not neutrophil recruitment in IL-1/LPS-insufflated rats.

  13. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

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    Mechteld A. R. Vermeulen

    2016-01-01

    Full Text Available Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%. Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  14. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis.

    Science.gov (United States)

    Vermeulen, Mechteld A R; Brinkmann, Saskia J H; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M; Houdijk, Alexander P J; van Goudoever, Johannes B; van Leeuwen, Paul A M

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  15. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    Science.gov (United States)

    Vermeulen, Mechteld A. R.; Brinkmann, Saskia J. H.; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M.; Houdijk, Alexander P. J.; van Goudoever, Johannes B.; van Leeuwen, Paul A. M.

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285. PMID:27200186

  16. De Novo Glutamine Synthesis

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    Qiao He MD

    2016-04-01

    Full Text Available Purpose: The aim of this study was to investigate the role of de novo glutamine (Gln synthesis in the proliferation of C6 glioma cells and its detection with 13N-ammonia. Methods: Chronic Gln-deprived C6 glioma (0.06C6 cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS inhibitor. 13N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0.06C6 xenografts by micro–positron emission tomography (PET scanning. The expression of GS in C6 cells and xenografts was assessed by Western blotting and immunohistochemistry, respectively. Results: The Gln-deprived C6 cells showed decreased proliferation ability but had a significant increase in GS expression. Furthermore, we found that low concentration of ammonia was sufficient to maintain the proliferation of Gln-deprived C6 cells, and 13N-ammonia uptake in C6 cells showed Gln-dependent decrease, whereas inhibition of GS markedly reduced the proliferation of C6 cells as well as the uptake of 13N-ammoina. Additionally, microPET/computed tomography exhibited that subcutaneous 0.06C6 xenografts had higher 13N-ammonia uptake and GS expression in contrast to C6 xenografts. Conclusion: De novo Gln synthesis through ammonia–glutamate reaction plays an important role in the proliferation of C6 cells. 13N-ammonia can be a potential metabolic PET tracer for Gln-dependent tumors.

  17. Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthritis who initiated intravenous abatacept: results from the 2-year ACTION study

    Science.gov (United States)

    Alten, Rieke; Nüßlein, Hubert; Galeazzi, Mauro; Lorenz, Hanns-Martin; Nurmohamed, Michael T; Bensen, William G; Burmester, Gerd R; Peter, Hans-Hartmut; Pavelka, Karel; Chartier, Mélanie; Poncet, Coralie; Rauch, Christiane; Elbez, Yedid; Le Bars, Manuela

    2016-01-01

    Introduction Prolonged glucocorticoid use may increase the risk of adverse safety outcomes, including cardiovascular events. The European League Against Rheumatism and the Canadian Rheumatology Association advise tapering glucocorticoid dose as rapidly as clinically feasible. There is a paucity of published data on RA that adequately describe concomitant treatment patterns. Methods ACTION (AbataCepT In rOutiNe clinical practice) is a non-interventional cohort study of patients from Europe and Canada that investigated the long-term retention of intravenous abatacept in clinical practice. We assessed concomitant glucocorticoids in patients with established RA who had participated in ACTION and received ≥1 biological agent prior to abatacept initiation. Results The analysis included 1009 patients. Glucocorticoids were prescribed at abatacept initiation in 734 (72.7%) patients at a median 7.5 mg/day dose (n=692). Of the patients who remained on abatacept at 24 months, 40.7% were able to decrease their dose of glucocorticoids, including 26.9% who decreased their dose from >5 mg/day to ≤5 mg/day. Conclusion Reduction and/or cessation of glucocorticoid therapy is possible with intravenous abatacept in clinical practice. PMID:26925253

  18. Glutamine as an immunonutrient.

    Science.gov (United States)

    Kim, Hyeyoung

    2011-11-01

    Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.

  19. Glutamine transport in submitochondrial particles

    Energy Technology Data Exchange (ETDEWEB)

    Sastrasinh, S.; Sastrasinh, M.

    1989-12-01

    Glutamine transport was studied in submitochondrial particles (SMP) to avoid interference from glutamine metabolism. Phosphate-dependent glutaminase activity in SMP was only 0.04% of that in intact mitochondria. The uptake of glutamine in SMP represented both the transport into vesicles and membrane binding (about one-third of total uptake). Sulfhydryl reagents inhibited glutamine uptake in SMP. The uptake of L-({sup 3}H)glutamine increased more than twofold in SMP preloaded with 1 mM L-glutamine, an effect that was not seen with 1 mM D-glutamine. The uptake of L-({sup 3}H)glutamine was inhibited in the presence of either L-glutamine or L-alanine in the incubation medium. Other amino acids did not inhibit glutamine uptake. Alanine was also shown to trans-stimulate glutamine transport in SMP and cis-inhibit glutamine transport in both SMP and intact mitochondria. Glutamine transport showed a positive cooperativity effect with a Hill coefficient of 1.45. Metabolic acidosis increased the affinity of the transporter for glutamine without any change in other kinetic parameters. These data indicated that mitochondrial glutamine transport occurs via a specific carrier with multiple binding sites and that the transport of glutamine into mitochondria has an important role in increased ammoniagenesis during metabolic acidosis.

  20. Glutamine facilitates chemotherapy while reducing toxicity.

    Science.gov (United States)

    Klimberg, V S; Nwokedi, E; Hutchins, L F; Pappas, A A; Lang, N P; Broadwater, J R; Read, R C; Westbrook, K C

    1992-01-01

    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.

  1. Route of administration (enteral or parenteral) affects the contribution of L-glutamine to de novo L-arginine synthesis in mice: a stable-isotope study.

    Science.gov (United States)

    Boelens, Petra G; Melis, Gerdien C; van Leeuwen, Paul A; ten Have, Gabrie A; Deutz, Nicolaas E

    2006-10-01

    A pathway from enteral L-glutamine as substrate for L-arginine synthesis is suggested by previous studies. L-Glutamine and L-glutamine dipeptides exhibit numerous beneficial effects in experimental and clinical studies. In trauma patients, enteral L-glutamine supply increased plasma L-arginine. The present study was designed to quantify the contribution of L-glutamine to the de novo L-citrulline and L-arginine synthesis in mice when L-glutamine is administered in a high dose of labeled L-glutamine or L-alanyl-L-glutamine by the enteral or parenteral route. For this purpose, male Swiss mice (n = 43) underwent a laparotomy, and catheters were inserted for sampling and infusion. A primed, constant, and continuous infusion of L-alanyl-L-[2-(15)N]glutamine (dipeptide groups) or L-[2-(15)N]glutamine (free L-glutamine groups), simultaneously with L-[ureido-(13)C,(2)H(2)]citrulline and L-[guanidino-(15)N(2),(2)H(2)]arginine, was given (steady-state model). Mice received the L-glutamine tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by LC-MS. Arterial L-glutamine concentrations were the highest in the intravenous dipeptide group. L-Glutamine was converted to L-citrulline and L-arginine when L-[2-(15)N]glutamine and L-alanyl-L-[2-(15)N]glutamine were given by enteral or parenteral route. The contribution of L-glutamine to the de novo synthesis of L-citrulline and L-arginine was higher in the enteral groups when compared with the intravenous groups (P glutamine, provided as free molecule or dipeptide, to the de novo synthesis of L-arginine in mice.

  2. Commonly used intravenous anesthetics decrease bladder contractility: An in vitro study of the effects of propofol, ketamine, and midazolam on the rat bladder

    Science.gov (United States)

    Ceran, Canan; Pampal, Arzu; Goktas, Ozgur; Pampal, H. Kutluk; Olmez, Ercument

    2010-01-01

    Aim: This study was designed to test the hypothesis that propofol, ketamine, and midazolam could alter the contractile activity of detrusor smooth muscle. Materials and Methods: Four detrusor muscle strips isolated from each rat bladder (n = 12) were placed in 4 tissue baths containing Krebs-Henseleit solution. The carbachol (10 −8to 10−4mol/L)-induced contractile responses as well as 5, 10, 20, 30, 40, 50 Hz electrical field stimulation (EFS)-evoked contractile responses of the detrusor muscles were recorded using isometric contraction measurements. After obtaining basal responses, the in vitro effects of propofol, ketamine, midazolam (10−5 to 10−3 mol/L), and saline on the contractile responses of the detrusor muscle strips were recorded and evaluated. Results: All the 3 drugs reduced the carbachol-induced and/or EFS-evoked contractile responses of rat detrusor smooth muscles in different degrees. Midazolam (10−4 to 10−3 mol/L) caused a significant decrease in the contractile responses elicited by either EFS or carbachol (P=0.000−0.013). Propofol (10−3mol/L) caused a decrease only in EFS-evoked contractile responses (P=0.001−0.004) and ketamine (10−3mol/L) caused a decrease only in carbachol-induced contractile responses (P=0.001−0.034). Conclusion: We evaluated the effects of the 3 different intravenous anesthetics on detrusor contractile responses in vitro and found that there are possible interactions between anesthetic agents and detrusor contractile activity. The depressant effects of midazolam on the contractile activity were found to be more significant than ketamine and propofol. Despite the necessity of further studies, it could be a piece of wise advice to clinicians to keep the probable alterations due to intravenous anesthetics in mind, while evaluating the results of urodynamic studies in children under sedation. PMID:21116355

  3. Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats.

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    Adriana C Lambertucci

    Full Text Available In this study, we investigated the effect of glutamine (Gln supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1 and the degradation pathways (MuRF-1 and MAFbx were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1 control, non-supplemented with glutamine; 2 control, supplemented with glutamine; 3 diabetic, non-supplemented with glutamine; and 4 diabetic, supplemented with glutamine. Diabetes was induced by the intravenous injection of 65 mg/kg bw STZ in citrate buffer (pH 4.2; the non-diabetic controls received only citrate buffer. After 48 hours, diabetes was confirmed in the STZ-treated animals by the determination of blood glucose levels above 200 mg/dL. Starting on that day, a solution of 1 g/kg bw Gln in phosphate buffered saline (PBS was administered daily via gavage for 15 days to groups 2 and 4. Groups 1 and 3 received only PBS for the same duration. The rats were euthanized, and the soleus muscles were removed and homogenized in extraction buffer for the subsequent measurement of protein and mRNA levels. The results demonstrated a significant decrease in the muscle Gln content in the diabetic rats, and this level increased toward the control value in the diabetic rats receiving Gln. In addition, the diabetic rats exhibited a reduced mRNA expression of regulatory proteins in the protein synthesis pathway and increased expression of those associated with protein degradation. A reduction in the skeletal muscle mass in the diabetic rats was observed and was alleviated partially with Gln supplementation. The data suggest that glutamine supplementation is potentially useful for slowing the progression of muscle atrophy in patients with diabetes.

  4. Effect of glutamine supplementation on neutrophil function in male judoists.

    Science.gov (United States)

    Sasaki, Eiji; Umeda, Takashi; Takahashi, Ippei; Arata, Kojima; Yamamoto, Yousuke; Tanabe, Masaru; Oyamada, Kazuyuki; Hashizume, Erika; Nakaji, Shigeyuki

    2013-01-01

    Glutamine is an important amino acid for immune function. Though high intensity and prolonged exercise decreases plasma glutamine concentration and causes immune suppression, the relationship between neutrophil functions and glutamine has not yet been found. The purpose of this study was to investigate the impacts of glutamine supplementation on neutrophil function. Twenty-six male university judoists were recruited. Subjects were classified into glutamine and control groups. The glutamine group ingested 3000 mg of glutamine per day and the control group ingested placebo for 2 weeks. Examinations were performed at the start of preunified loading exercise (pre-ULE), then 1 and 2 weeks after ULE (post-ULE). Reactive oxygen species (ROS) production, phagocytic activity, serum opsonic activity and serum myogenic enzymes were measured. Differences between the levels obtained in pre-ULE and post-ULE for the two groups were compared. In the glutamine group, ROS production activity increased 1 week after ULE, whereas it was not observed in the control group (P Glutamine supplementation has prevented excessive muscle damage and suppression of neutrophil function, especially in ROS production activity, even during an intensive training period.

  5. II. Glutamine and glutamate.

    Science.gov (United States)

    Tapiero, H; Mathé, G; Couvreur, P; Tew, K D

    2002-11-01

    Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and

  6. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn's patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Lecleire, Stéphane; Hassan, Aktham; Marion-Letellier, Rachel; Antonietti, Michel; Savoye, Guillaume; Bôle-Feysot, Christine; Lerebours, Eric; Ducrotté, Philippe; Déchelotte, Pierre; Coëffier, Moïse

    2008-12-01

    Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18-39) y] with active colonic CD (mean CD activity index: 383.7 +/- 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg(low) or Arg(high), respectively) and Gln (0.6 or 10 mmol/L designated as Gln(low) or Gln(high), respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor-alpha (TNFalpha), IL-1beta, interferon-gamma) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-kappaB p65 subunit, inhibitor of NFkappaB-alpha, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg(high)/Gln(high) decreased the production of TNFalpha, IL-1beta, IL-8, and IL-6 (each P < 0.01). Arg(low)/Gln(high) decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg(high)/Gln(low) did not affect cytokine and NO production. Arg(low)/Gln(high) and Arg(high)/Gln(high) decreased NF-kappaB p65 subunit expression, whereas p38 MAPK was decreased only by Arg(high)/Gln(high). Combined pharmacological doses of Arg and Gln decreased TNFalpha and the main proinflammatory cytokines release in active colonic CD biopsies via NF-kappaB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.

  7. Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

    Science.gov (United States)

    Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

    2014-05-01

    To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and

  8. Glutamine deprivation initiates reversible assembly of mammalian rods and rings.

    Science.gov (United States)

    Calise, S John; Carcamo, Wendy C; Krueger, Claire; Yin, Joyce D; Purich, Daniel L; Chan, Edward K L

    2014-08-01

    Rods and rings (RR) are protein assemblies composed of cytidine triphosphate synthetase type 1 (CTPS1) and inosine monophosphate dehydrogenase type 2 (IMPDH2), key enzymes in CTP and GTP biosynthesis. Small-molecule inhibitors of CTPS1 or IMPDH2 induce RR assembly in various cancer cell lines within 15 min to hours. Since glutamine is an essential amide nitrogen donor in these nucleotide biosynthetic pathways, glutamine deprivation was examined to determine whether it leads to RR formation. HeLa cells cultured in normal conditions did not show RR, but after culturing in media lacking glutamine, short rods (5 μm) formed after 48 h. Upon supplementation with glutamine or guanosine, these RR underwent almost complete disassembly within 15 min. Inhibition of glutamine synthetase with methionine sulfoximine also increased RR assembly in cells deprived of glutamine. Taken together, our data support the hypothesis that CTP/GTP biosynthetic enzymes polymerize to form RR in response to a decreased intracellular level of glutamine. We speculate that rod and ring formation is an adaptive metabolic response linked to disruption of glutamine homeostasis.

  9. CD8⁺ Treg cells associated with decreasing disease activity after intravenous methylprednisolone pulse therapy in lupus nephritis with heavy proteinuria.

    Directory of Open Access Journals (Sweden)

    Yi-Giien Tsai

    Full Text Available We focus on the role of CD8(+ Treg cell in Intravenous methyl-prednisolone (IVMP pulse therapy in forty patients with active Class III/IV childhood lupus nephritis (LN with heavy proteinuria. IVMP therapy for five days. From peripheral blood mononuclear cells (PBMCs and renal tissues, we saw IVMP therapy definitely restoring both CD4(+CD25(+FoxP3(+ and CD8(+CD25(+Foxp3(+ Treg cell number plus greater expression with intracellular IL-10 and granzyme B in CD8(+FoxP3(+ Treg from PBMCs. IVMP-treated CD8(+CD25(+ Treg cells directly suppressed CD4(+ T proliferation and induced CD4(+CD45RO(+ apoptosis. Histologically, CD4(+FoxP3(+ as well as CD8(+FoxP3(+ Treg cells appeared in renal tissue of LN patients before IVMP by double immunohistochemical stain. CD8(+FoxP3(+ Treg cells increased in 10 follow-up renal biopsy specimens after IVMP. Reverse correlation of serum anti-C1q antibody and FoxP3(+ Treg cells in PBMNCs (r = -0.714, P<0.01. After IVMP, serum anti-C1q antibody decrease accompanied increase of CD4(+FoxP3(+ Treg cells. CD8(+Treg cells reduced interferon-r response in PBMCs to major peptide autoepitopes from nucleosomes after IVMP therapy; siRNA of FoxP3 suppressed granzyme B expression while decreasing CD8(+CD25(+Treg-induced CD4(+CD45RO(+ apoptosis. Renal activity of LN by SLEDAI-2k in childhood LN was significantly higher than two weeks after IVMP (P<0.01. CD8(+FoxP3(+ Treg cells return in post-IVMP therapy and exert crucial immune modulatory effect to control autoimmune response in LN.DMR97-IRB-259.

  10. Have we enough glutamine and how does it work? A clinician's view.

    Science.gov (United States)

    Soeters, P B; Grecu, I

    2012-01-01

    There is a gap between the scientific basis of the claim that in several disease states glutamine is lacking and the widespread belief that supplementation of glutamine to the nutritional regimen is beneficial in severely ill patients. Glutamine shortage exists when consuming tissues, playing a crucial role in the response to trauma and disease, receive insufficient amounts of glutamine. In these tissues (immune system, wound), glutamine is only partly oxidized but has more specific roles as nontoxic nitrogen carrier, precursor of several crucial metabolites required for cell proliferation and for maintenance of the redox potential, and as osmolyte. In inflammatory states, glutamine concentrations in plasma and tissues are decreased due to many disease-related factors, precluding its use as a reliable indicator of shortage. Isotope studies have yielded equivocal results, precluding their use as a reliable indicator of glutamine shortage or adequacy. The increase in the net release of glutamine from peripheral tissues to central tissues (immune system, liver, spleen, wound) in inflammatory states provides a better basis for the necessity to supplement the organism with extra glutamine in these conditions. Glutamine supplementation was beneficial in a few studies in burn or trauma patients. The clinical benefit of parenteral glutamine supplementation in patients with severe inflammation has been demonstrated more convincingly. The amounts of glutamine supplemented approximate the amounts released by peripheral tissues and utilized by central organs operative in host defense and are therefore in the physiological range.

  11. [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic fluid at placental insufficiency].

    Science.gov (United States)

    Pogorelova, T N; Gunko, V O; Linde, V A

    2014-01-01

    Metabolism of glutamine and glutamic acid has been investigated in the placenta and amniotic fluid under conditions of placental insufficiency. The development of placental insufficiency is characterized by the increased content of glutamic acid and a decrease of glutamine in both placenta and amniotic fluid. These changes changes were accompanied by changes in the activity of enzymes involved in the metabolism of these amino acids. There was a decrease in glutamate dehydrogenase activity and an increase in glutaminase activity with the simultaneous decrease of glutamine synthetase activity. The compensatory decrease in the activity of glutamine keto acid aminotransferase did not prevent a decrease in the glutamine level. The impairments in the system glutamic acid-glutamine were more pronounced during the development of premature labor.

  12. Supplementation with L-Glutamine and L-Alanyl-L-Glutamine Changes Biochemical Parameters and Jejunum Morphophysiology in Type 1 Diabetic Wistar Rats.

    Directory of Open Access Journals (Sweden)

    Carlos Vinicius D da Rosa

    Full Text Available We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage during thirty days: non diabetic rats (Control + saline, diabetic + saline; Control + L-glutamine (248 mg/kg, Diabetic + L-glutamine (248 mg/kg, Control + GDP (400 mg/kg, Diabetic + GDP (400 mg/kg. Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia. Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica. The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the

  13. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Directory of Open Access Journals (Sweden)

    Morteza Talebi Doluee

    2015-01-01

    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  14. Interrelationships between glutamine and citrulline metabolism

    Science.gov (United States)

    This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter ran...

  15. Dosing and efficacy of glutamine supplementation in human exercise and sport training.

    Science.gov (United States)

    Gleeson, Michael

    2008-10-01

    Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes. However, several recent glutamine feeding intervention studies indicate that although the plasma glutamine concentration can be kept constant during and after prolonged strenuous exercise, the glutamine supplementation does not prevent the postexercise changes in several aspects of immune function. Although glutamine is essential for lymphocyte proliferation, the plasma glutamine concentration does not fall sufficiently low after exercise to compromise the rate of proliferation. Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect in healthy adult humans and no harm was reported in 1 study in which athletes consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels. However, the suggested reasons for taking glutamine supplements (support for immune system, increased glycogen synthesis, anticatabolic effect) have received little support from well-controlled scientific studies in healthy, well-nourished humans.

  16. The clinical role of glutamine supplementation in patients with multiple trauma: a narrative review.

    Science.gov (United States)

    Al Balushi, R M; Cohen, J; Banks, M; Paratz, J D

    2013-01-01

    Glutamine is considered an essential amino acid during stress and critical illness. Parenteral glutamine supplementation in critically ill patients has been shown to improve survival rate and minimise infectious complications, costs and hospital length-of-stay. However, glutamine supplementation in patients receiving enteral nutrition and the best method of administration are still controversial. The purpose of this article is to provide a narrative review of the current evidence and trials of enteral and parenteral glutamine supplementation in multiple trauma patients. A search in PubMed and EMBASE was conducted and relevant papers that investigated the effect of enteral or parenteral glutamine supplementation in patients with multiple trauma were reviewed. Although recent nutritional guidelines recommend that glutamine supplementation should be considered in these patients, further well-designed trials are required to provide a confirmed conclusion. Due to the inconclusive results of enteral glutamine supplementation trials in patients receiving enteral nutrition, future trials should focus on intravenous glutamine supplementation in patients requiring enteral nutrition and on major clinical outcome measures (e.g. mortality rate, infectious complications).

  17. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Lai

    2014-08-01

    Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

  18. Exogenous glutamine: the clinical evidence.

    Science.gov (United States)

    Bongers, Thomas; Griffiths, Richard D; McArdle, Anne

    2007-09-01

    We know that critically ill patients suffering from undernutrition with a limited nutritional reserve have a poorer outcome. Furthermore, having a low body mass index has been shown to be an independent predictor of excess mortality in multiple organ failure. Therefore, nutritional support has gained increasing interest in critical illness with the hope of preventing or attenuating the effects of malnutrition. A negative nitrogen balance is the characteristic metabolic feature in critical illness, with the major protein loss derived from skeletal muscle. In particular, glutamine concentrations are rapidly reduced in plasma and muscle. Over the last 20 yrs or so, increasing evidence is emerging to support the use of glutamine supplementation in critical illness. Clinical trials have found a mortality and morbidity advantage with glutamine supplementation. The advantage appears to be greater the more glutamine is given and greater again when given parenterally. Various modes of action have been postulated. Glutamine seems to have an effect on the immune system, antioxidant status, glucose metabolism, and heat shock protein response. However, the benefit of exogenous glutamine on morbidity and mortality is not universally accepted. This review critically appraises the current clinical evidence regarding glutamine supplementation in critical illness.

  19. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

    Many cancer cells depend on glutamine as a fuel for proliferation,yet the mechanisms by which glutamine supports cancer metabolism are not fully understood.Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

  20. Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Baumann, Sven [Department of Metabolomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Schorsch, Katrin [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Trump, Saskia; Lehmann, Irina [Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Bergen, Martin von [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg (Denmark); Tomm, Janina M., E-mail: Janina.tomm@ufz.de [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany)

    2013-06-15

    There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells.

  1. Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats.

    Science.gov (United States)

    Ardawi, M S

    1992-04-01

    1. The effects of parenteral nutrition with or without xylitol and/or glutamine supplementation were studied in septic rats after 4 days of treatment. 2. Septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition survived sepsis significantly better than other parenteral nutrition-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5% compared with 54.5% in septic rats given parenteral nutrition without xylitol and glutamine, and 52.4% in septic rats treated with parenteral nutrition supplemented with glucose. 3. Xylitol- and/or glutamine-supplemented parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was positive in the rats given xylitol-supplemented parenteral nutrition and more positive when rats were treated with xylitol-glutamine-supplemented parenteral nutrition, as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P less than 0.001) in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 5. Hepatic protein and RNA contents were increased in septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein and RNA contents were markedly increased in muscles of septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. 6. The rates of incorporation of leucine/tyrosine into liver/muscle proteins in vitro were increased and the rate of muscular tyrosine release was decreased in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 7. It is concluded that the administration of xylitol- and/or glutamine-supplemented parenteral nutrition is beneficial to septic rats and possibly to septic patients.

  2. Characterization of Glutamine-Requiring Mutants of Pseudomonas aeruginosa

    NARCIS (Netherlands)

    Janssen, Dick B.; Joosten, Han M.L.J.; Herst, Patricia M.; Drift, Chris van der

    1982-01-01

    Revertants were isolated from a glutamine-requiring mutant of Pseudomonas aeruginosa PAO. One strain showed thermosensitive glutamine requirement and formed thermolabile glutamine synthetase, suggesting the presence of a mutation in the structural gene for glutamine synthetase. The mutation conferri

  3. Regulation of glutamine synthetase, aspartokinase, and total protein turnover in Klebsiella aerogenes.

    Science.gov (United States)

    Fulks, R M; Stadtman, E R

    1985-12-13

    When suspensions of Klebsiella aerogenes are incubated in a nitrogen-free medium there is a gradual decrease in the levels of acid-precipitable protein and of aspartokinase III (lysine-sensitive) and aspartokinase I (threonine-sensitive) activities. In contrast, the level of glutamine synthetase increases slightly and then remains constant. Under these conditions, the glutamine synthetase and other proteins continue to be synthesized as judged by the incorporation of [14C]leucine into the acid-precipitable protein fraction and into protein precipitated by anti-glutamine synthetase antibodies, by the fact that growth-inhibiting concentrations of chloramphenicol also inhibit the incorporation of [14C]leucine into protein and into protein precipitated by anti-glutamine synthetase antibody, and by the fact that chloramphenicol leads to acceleration in the loss of aspartokinases I and III and promotes a net decrease in the level of glutamine synthetase and its cross-reactive protein. The loss of aspartokinases I and III in cell suspensions is stimulated by glucose and is inhibited by 2,4-dinitrophenol. Glucose also stimulates the loss of aspartokinases and glutamine synthetase in the presence of chloramphenicol. Cell-free extracts of K. aerogenes catalyze rapid inactivation of endogenous glutamine synthetase as well as exogenously added pure glutamine synthetase. This loss of glutamine synthetase is not associated with a loss of protein that cross-reacts with anti-glutamine synthetase antibodies. The inactivation of glutamine synthetase in extracts is not due to adenylylation. It is partially prevented by sulfhydryl reagents, Mn2+, antimycin A, 2,4-dinitrophenol, EDTA, anaerobiosis and by dialysis. Following 18 h dialysis, the capacity of extracts to catalyze inactivation of glutamine synthetase is lost but can be restored by the addition of Fe2+ (or Ni2+) together with ATP (or other nucleoside di- and triphosphates. After 40-60 h dialysis Fe3+ together with NADH (but

  4. Effects of glutamine supplementation on the immune status in weaning piglets with intrauterine growth retardation.

    Science.gov (United States)

    Zhong, Xiang; Li, Wei; Huang, Xuexin; Wang, Yuanxiao; Zhang, Lili; Zhou, Yanmin; Hussain, Ahmad; Wang, Tian

    2012-10-01

    Neonates with intrauterine growth retardation (IUGR) often suffer from impaired cellular immunity, and weaning may further aggravate adverse effects of IUGR on development and function of the immune system. In this study, we investigated effects of glutamine supplementation on immune status in the intestines of weaning pigs with IUGR, focusing on molecular mechanisms underlying altered immune response. Piglets with IUGR were weaned at 21 days of age and received orally 1.22 g alanine or 1 g glutamine per kg body weight every 12 h. Weight gain and intestinal weight of weaning piglets were increased by glutamine supplementation. Levels of serum IgG in piglets supplemented with glutamine were increased compared with Control piglets. The production of IL-1 and IL-8 in the serum and jejunum was decreased by glutamine supplementation, whereas the levels of IL-4 in the serum and the concentrations of IL-4 and IL-10 in the jejunum were increased. The expression of heat shock protein 70 (Hsp70) in the jejunum was increased by glutamine supplementation, but the degradation of inhibitor κB and the activity of nuclear factor-κB (NF-κB) were decreased. In conclusion, glutamine supplementation enhanced immune response in weaning piglets with IUGR. The effects of glutamine in IUGR are associated with increased Hsp70 expression and suppression of NF-κB activation.

  5. Plasma glutamine levels and falciparum malaria.

    Science.gov (United States)

    Cowan, G; Planche, T; Agbenyega, T; Bedu-Addo, G; Owusu-Ofori, A; Adebe-Appiah, J; Agranoff, D; Woodrow, C; Castell, L; Elford, B; Krishna, S

    1999-01-01

    Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P sepsis and dyserythropoeisis.

  6. Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia.

    Science.gov (United States)

    Verlander, Jill W; Chu, Diana; Lee, Hyun-Wook; Handlogten, Mary E; Weiner, I David

    2013-09-01

    Renal glutamine synthetase catalyzes the reaction of NH4+ with glutamate, forming glutamine and decreasing the ammonia available for net acid excretion. The purpose of the present study was to determine glutamine synthetase's specific cellular expression in the mouse kidney and its regulation by hypokalemia, a common cause of altered renal ammonia metabolism. Glutamine synthetase mRNA and protein were present in the renal cortex and in both the outer and inner stripes of the outer medulla. Immunohistochemistry showed glutamine synthetase expression throughout the entire proximal tubule and in nonproximal tubule cells. Double immunolabel with cell-specific markers demonstrated glutamine synthetase expression in type A intercalated cells, non-A, non-B intercalated cells, and distal convoluted tubule cells, but not in principal cells, type B intercalated cells, or connecting segment cells. Hypokalemia induced by feeding a nominally K+ -free diet for 12 days decreased glutamine synthetase expression throughout the entire proximal tubule and in the distal convoluted tubule and simultaneously increased glutamine synthetase expression in type A intercalated cells in both the cortical and outer medullary collecting duct. We conclude that glutamine synthetase is widely and specifically expressed in renal epithelial cells and that the regulation of expression differs in specific cell populations. Glutamine synthetase is likely to mediate an important role in renal ammonia metabolism.

  7. Effect of parenteral glutamine supplementation in premature infants

    Institute of Scientific and Technical Information of China (English)

    LI Zheng-hong; WANG Dan-hua; DONG Mei

    2007-01-01

    Background Glutamine, proposed to be conditionally essential for critically ill patients, is not added routinely to parenteral amino acid formulations for premature infants and is provided in only small quantities by the enteral route when enteral feeding is Iow. Parenteral feeding is the basic way of nutrition in the first days of life of premature infants. In this study, we evaluated the effects of glutamine supplemented parenteral nutrition for premature infants on growth and development, feeding toleration, and infective episodes.Methods From December 2002 to July 2006, 53 premature infants were given either standard or glutamine supplemented parenteral nutrition for more than 2 weeks. Twenty-eight infants were in glutamine supplemented group, whose gestational age (31.4±2.0) weeks, birth weight range (1386±251) g; twenty-five infants were in control group, gestational age (31.1 ± 1.7) weeks, with birth weight range (1346± 199) g. There were no differences between the two groups. Various growth and biochemical indices were monitored throughout the duration of hospital stay. Data between groups were analyzed with Student's t test. Nonparametric data were analyzed using a Chi-square test. A two-tailed P value < 0.05 was considered statistically significant.Results The level of serum albumin was lower in the glutamine groups on the second week (3.0 vs 3.2 g/dl, P=0.028), and blood urea nitrogen was higher in glutamine groups on the fourth week (8.1 vs 4.9 mg/dl, P=0.014), but normal. Glutamine group infants took fewer days to regain birth weight (8.1 vs 10.4 days, P=0.017), required fewer days on parenteral nutrition (24.8 vs 30.8 days, P=0.035), with shorter stays in hospital (32.1 vs 38.6 days, P=0.047). Episodes of hospital acquired infection in glutamine supplemented infants were lower than that in control group (0.96 vs 1.84 times, P=0.000).Conclusion Parenteral glutamine supplementation in premature infants can shorten days on parenteral nutrition and

  8. Glutamate and CO2 production from glutamine in incubated enterocytes of adult and very old rats.

    Science.gov (United States)

    Meynial-Denis, Dominique; Bielicki, Guy; Beaufrère, Anne-Marie; Mignon, Michelle; Mirand, Philippe Patureau; Renou, Jean-Pierre

    2013-04-01

    Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial cells (~300×10(6) cells) were incubated in oxygenated Krebs-Henseleit buffer for 30 min containing [1-(13)C] glutamine (~17 M) for analysis of glutamine metabolites by (13)C nuclear magnetic resonance ((13)C NMR). An aliquot fraction was incubated in the presence of [U-(14)C] glutamine to measure produced CO2. Glutamine pretreatment increased glutamate production and decreased CO2 production in very old rats. The ratio CO2/glutamate, which was very high in control very old rats, was similar at both ages after glutamine pretreatment, as if enterocytes from very old rats recovered the metabolic abilities of enterocytes from adult rats. Our results suggest that long-term treatment with glutamine started before advanced age (a) prevented the loss of rat body weight without limiting sarcopenia and (b) had a beneficial effect on enterocytes from very old rats probably by favoring the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis, which was not detected in (13)C NMR spectra in our experimental conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance.

    Science.gov (United States)

    Ko, Ying-Hui; Lin, Zhao; Flomenberg, Neal; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2011-12-15

    Glutamine metabolism is crucial for cancer cell growth via the generation of intermediate molecules in the tricarboxylic acid (TCA) cycle, antioxidants and ammonia. The goal of the current study was to evaluate the effects of glutamine on metabolism in the breast cancer tumor microenvironment, with a focus on autophagy and cell death in both epithelial and stromal compartments. For this purpose, MCF7 breast cancer cells were cultured alone or co-cultured with non-transformed fibroblasts in media containing high glutamine and low glucose (glutamine +) or under control conditions, with no glutamine and high glucose (glutamine -). Here, we show that MCF7 cells maintained in co-culture with glutamine display increased mitochondrial mass, as compared with control conditions. Importantly, treatment with the autophagy inhibitor chloroquine abolishes the glutamine-induced augmentation of mitochondrial mass. It is known that loss of caveolin-1 (Cav-1) expression in fibroblasts is associated with increased autophagy and an aggressive tumor microenvironment. Here, we show that Cav-1 downregulation which occurs in fibroblasts maintained in co-culture specifically requires glutamine. Interestingly, glutamine increases the expression of autophagy markers in fibroblasts, but decreases expression of autophagy markers in MCF7 cells, indicating that glutamine regulates the autophagy program in a compartment-specific manner. Functionally, glutamine protects MCF7 cells against apoptosis, via the upregulation of the anti-apoptotic and anti-autophagic protein TIGAR. Also, we show that glutamine cooperates with stromal fibroblasts to confer tamoxifen-resistance in MCF7 cancer cells. Finally, we provide evidence that co-culture with fibroblasts (1) promotes glutamine catabolism, and (2) decreases glutamine synthesis in MCF7 cancer cells. Taken together, our findings suggest that autophagic fibroblasts may serve as a key source of energy-rich glutamine to fuel cancer cell mitochondrial

  10. Efficacy of Enteral Supplementation Enriched with Glutamine, Fiber, and Oligosaccharide on Mucosal Injury following Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Satoshi Iyama

    2014-10-01

    Full Text Available The combination of glutamine, fiber and oligosaccharides (GFO is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT. Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days; the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days. Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test. Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p Enterococcus species developed in the GFO group (p = 0.0728 than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.

  11. Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm Neonates.

    Science.gov (United States)

    El-Shimi, M S; Awad, H A; Abdelwahed, M A; Mohamed, M H; Khafagy, S M; Saleh, G

    2015-01-01

    Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ≤34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1), after 14 days of enrollment (sample 2), and at time of diagnosis of NEC (sample 3). Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P > 0.05). NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041).

  12. Enteral L-Arginine and Glutamine Supplementation for Prevention of NEC in Preterm Neonates

    Directory of Open Access Journals (Sweden)

    M. S. El-Shimi

    2015-01-01

    Full Text Available Objective. Evaluating the efficacy and safety of arginine and glutamine supplementation in decreasing the incidence of NEC among preterm neonates. Methods. Prospective case-control study done on 75 preterm neonates ≤34 weeks, divided equally into L-arginine group receiving enteral L-arginine, glutamine group receiving enteral glutamine, and control group. Serum L-arginine and glutamine levels were measured at time of enrollment (sample 1, after 14 days of enrollment (sample 2, and at time of diagnosis of NEC (sample 3. Results. The incidence of NEC was 9.3%. There was no difference in the frequency of NEC between L-arginine and control groups (P>0.05. NEC was not detected in glutamine group; L-arginine concentrations were significantly lower in arginine group than control group in both samples while glutamine concentrations were comparable in glutamine and control groups in both samples. No significant difference was found between groups as regards number of septic episodes, duration to reach full oral intake, or duration of hospital stay. Conclusion. Enteral L-arginine supplementation did not seem to reduce the incidence of NEC. Enteral glutamine may have a preventive role against NEC if supplied early to preterm neonates. However, larger studies are needed to confirm these findings. This work is registered in ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01263041.

  13. Encapsulation of glutamine synthetase in mouse erythrocytes: a new procedure for ammonia detoxification.

    Science.gov (United States)

    Kosenko, Elena A; Venediktova, Natalia I; Kudryavtsev, Andrey A; Ataullakhanov, Fazoil I; Kaminsky, Yury G; Felipo, Vicente; Montoliu, Carmina

    2008-12-01

    There are a number of pathological situations in which ammonia levels increase leading to hyperammonemia, which may cause neurological alterations and can lead to coma and death. Currently, there are no efficient treatments allowing rapid and sustained decrease of ammonia levels in these situations. A way to increase ammonia detoxification would be to increase its incorporation in glutamine by glutamine synthetase. The aim of this work was to develop a procedure to encapsulate glutamine synthetase in mouse erythrocytes and to assess whether administration of these erythrocytes containing glutamine synthetase (GS) reduce ammonia levels in hyperammonemic mice. The procedure developed allowed the encapsulation of 3 +/- 0.25 IU of GS / mL of erythrocytes with a 70% cell recovery. Most metabolites, including ATP, remained unaltered in glutamine synthetase-loaded erythrocytes (named ammocytes by us) compared with native erythrocytes. The glutamine synthetase-loaded ammocytes injected in mice survived and retained essentially all of their glutamine synthetase activity for at least 48 h in vivo. Injection of these ammocytes into hyperammonemic mice reduced ammonia levels in the blood by about 50%. The results reported indicate that ammocytes are able to keep their integrity, normal energy metabolism, the inserted glutamine synthetase activity, and can be useful to reduce ammonia levels in hyperammonemic situations.

  14. [Cellular immunity changes after total parenteral nutrition enriched with glutamine in patients with sepsis and malnutrition].

    Science.gov (United States)

    Słotwiński, R; Pertkiewicz, M; Lech, G; Szczygieł, B

    2000-06-01

    The influence of glutamine on human immune system is multidirectional but the exact changes still remain unclear. In this study the effect of total parenteral nutrition (TPN) enriched with glutamine on some selected immunological and nutritional parameters was examined in twelve surgical patients with sepsis and malnutrition. The reason for glutamine supplementation was lack of clinical improvement after standard TPN. All patients received TPN enriched with glutamine for 10 days. Phenotypic analysis of peripheral blood mononuclear subsets (CD4, CD8, CD16, CD56, HLA-DR) were measured before, during (on days 2, 4, 6) glutamine administration and two days after (day 12) glutamine withdrawal. Simultaneously some nutritional parameters were assessed. The number and percentage of CD4, CD16, CD56 mononuclear subsets increased significantly on day 2 and stayed on the same level during observation (with exception in CD4 on day 6, 12 and CD56 on day 4). No significant differences in CD8 and HLA-DR number and percentages were observed after TPN enriched with glutamine. BIA examination revealed on days 2 and 12 significant decrease of total body water and significant increase of body cell mass, intracellular water on day 12. It was correlated with significant higher total lymphocytes count and significantly higher total protein, serum albumin, transferrin, cholesterol and CRP concentration. Results demonstrated that TPN supplemented with glutamine improved rapidly some immunological and nutritional parameters in surgical, malnutrition patients with sepsis.

  15. Effect of glutamine-supplemented total parenteral nutrition on the small bowel of septic rats.

    Science.gov (United States)

    Ardawi, M S

    1992-08-01

    In order to study the effect of total parenteral nutrition (TPN) with or without glutamine supplementation in septic rats, septic Wistar albino rats were randomly assigned to receive 0.23 g of nitrogen and 113 kJ (100 g BW)(-1) per day in the form of amino acids with (group 2) or without (group 1) glutamine supplementation or 10% (w/v) glucose only (group 3). After 4 days of TPN treatments, rats receiving glutamine-supplemented TPN had a cumulative nitrogen balance of -24.4 +/- 3.3 mg N, which was significantly (P sepsis significantly (P < 0.001) better than those in groups 1 and 3. Glutamine-supplemented TPN treatment resulted in significant increases in jejunal weight (P < 0.001), DNA and protein contents (P < 0.001), villous height (P < 0.001) and crypt depth (P < 0.001) when compared with septic rats of group 1. Septic rats of group 2 extracted and metabolised glutamine by the small bowel at higher rates (P < 0.001) than that observed in septic rats of group 1. Increases in jejunal glutaminase (38.2%, P < 0.001) and decreases in glutamine synthetase (41.7%, P < 0.001) activities were observed in response to glutamine-supplemented TPN treatment. It is concluded that the administration of glutamine-supplemented TPN is beneficial to the small bowel of septic rats.

  16. Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity

    Institute of Scientific and Technical Information of China (English)

    Mechteld AR Vermeulen; Jeffrey de Jong; Mathijs J Vaessen; Paul AM van Leeuwen; Alexander PJ Houdijk

    2011-01-01

    AIM: To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity. METHODS: The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied. Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate (PDB) apically, after which the effects of glutamine and glutamate on horseradish peroxidase (HRP) diffusion were studied. An inhibitor of glutamate transport (L-trans-pyrrolidine-2,4-dicarboxylic acid: trans-PDC) and an irreversible blocker (acivicin) of the extracellular glutamine to glutamate converting enzyme, γ-glutamyltransferase, were used. RESULTS: Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n = 30, P < 0.001). Glutamine application reduced hyperpermeability by 19% and 39% in the respective cell lines. Glutamate application reduced hyperpermeability by 30% and 20%, respectively. Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels. Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels. CONCLUSION: Apical glutamate -similar to glutaminecan decrease induced paracellular hyperpermeability. Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.

  17. Effects of glutamine supplementation on muscle function and stress responses in a mouse model of spinal cord injury.

    Science.gov (United States)

    Chamney, Carissa; Godar, Michelle; Garrigan, Ethan; Huey, Kimberly A

    2013-03-01

    Spinal cord injury (SCI) results in loss of muscle function due to rapid breakdown of contractile proteins. Glutamine supplementation improves clinical outcomes, but its effects on muscle function after SCI are unknown. The benefits of glutamine in non-skeletal muscle tissues involve elevated heat shock protein (Hsp)70 and Hsp25, but the muscle response may differ because it is the largest contributor to plasma glutamine. We tested the hypothesis that glutamine preserves muscle function after SCI and that this is associated with increased heat shock protein and reduced inflammatory factors, interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Changes in plantarflexor force, fatigability and total myofibrillar, Hsp70, Hsp25, IL-6 and TNFα muscle protein levels were measured 7 days after sham or spinal cord transection surgery in mice receiving daily placebo or glutamine. Compared with placebo, after SCI glutamine significantly attenuated the reductions in maximal isometric force (0.22 ± 0.01 versus 0.31 ± 0.03 N, respectively) and fatigue resistance (34 ± 4 versus 59 ± 4% of initial force, respectively). Glutamine significantly ameliorated the loss of myofibrillar protein with spinal cord transection. Spinal cord transection was associated with decreased Hsp70 and Hsp25 with glutamine only (45 ± 3 and 44 ± 5% of placebo, respectively). Glutamine significantly reduced spinal cord transection-associated increases in IL-6 and TNFα compared with placebo (38 ± 6 and 37 ± 8% of placebo, respectively). Functionally, early reductions in contractile protein, force and fatigue resistance after SCI were reversed with glutamine. Spinal cord transection-associated reductions in Hsp70, Hsp25, IL-6 and TNFα with glutamine versus placebo suggest lower stress in the muscle, possibly related to a reduced need to produce glutamine. These findings support glutamine as a therapeutic intervention to accelerate recovery of muscle function after SCI.

  18. Glutamine attenuates post-traumatic glutathione depletion in human muscle.

    Science.gov (United States)

    Fläring, U B; Rooyackers, O E; Wernerman, J; Hammarqvist, F

    2003-03-01

    Glutathione is quantitatively the most important endogenous scavenger system. Glutathione depletion in skeletal muscle is pronounced following major trauma and sepsis in intensive care unit patients. Also, following elective surgery, glutathione depletion occurs in parallel with a progressive decline in muscle glutamine concentration. The present study was designed to test the hypothesis that glutamine supplementation may counteract glutathione depletion in a human trauma model. A homogeneous group of patients (n = 17) undergoing a standardized surgical procedure were prospectively randomly allocated to receive glutamine (0.56 g x day(-1) x kg(-1)) or placebo as part of isonitrogenous and isocaloric nutrition. Percutaneous muscle biopsies and blood samples were taken pre-operatively and at 24 and 72 h after surgery. The concentrations of muscle glutathione and related amino acids were determined in muscle tissue and plasma. In the control (unsupplemented) subjects, total muscle glutathione had decreased by 47+/-8% and 37+/-11% and reduced glutathione had decreased by 53+/-10% and 45+/-16% respectively at 24 and 72 h after surgery (P glutamine supplementation attenuates glutathione depletion in skeletal muscle in humans following standardized surgical trauma.

  19. Dietary L-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus.

    Science.gov (United States)

    Ren, Wenkai; Luo, Wei; Wu, Miaomiao; Liu, Gang; Yu, Xinglong; Fang, Jun; Li, Teijun; Yin, Yulong; Wu, Guoyao

    2013-09-01

    Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% L-glutamine or 1.22% L-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% L-glutamine or 1.22% L-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.

  20. Repression of nitrogen catabolic genes by ammonia and glutamine in nitrogen-limited continuous cultures of Saccharomyces cerevisiae

    NARCIS (Netherlands)

    ter Schure, E G; Silljé, H H; Vermeulen, E E; Kalhorn, J W; Verkleij, A J; Boonstra, J; Verrips, C T

    1998-01-01

    Growth of Saccharomyces cerevisiae on ammonia and glutamine decreases the expression of many nitrogen catabolic genes to low levels. To discriminate between ammonia- and glutamine-driven repression of GAP1, PUT4, GDH1 and GLN1, a gln1-37 mutant was used. This mutant is not able to convert ammonia in

  1. Mutation of glutamine to arginine at position 548 of IE2 86 in human cytomegalovirus leads to decreased expression of IE2 40, IE2 60, UL83, and UL84 and increased transcription of US8-9 and US29-32.

    Science.gov (United States)

    Burgdorf, Sarah W; Clark, Charles L; Burgdorf, James R; Spector, Deborah H

    2011-11-01

    The IE2 86 protein of human cytomegalovirus (HCMV) is essential for productive infection. The mutation of glutamine to arginine at position 548 of IE2 86 causes the virus to grow both slowly and to very low titers, making it difficult to study this mutant via infection. In this study, Q548R IE2 86 HCMV was produced on the complementing cell line 86F/40HA, which allowed faster and higher-titer production of mutant virus. The main defects observed in this mutant were greatly decreased expression of IE2 40, IE2 60, UL83, and UL84. Genome replication and the induction of cell cycle arrest were found to proceed at or near wild-type levels, and there was no defect in transitioning to early or late protein expression. Q548R IE2 86 was still able to interact with UL84. Furthermore, Q548R IE2 40 maintained the ability to enhance UL84 expression in a cotransfection assay. Microarray analysis of Q548R IE2 HCMV revealed that the US8, US9, and US29-32 transcripts were all significantly upregulated. These results further confirm the importance of IE2 in UL83 and UL84 expression as well as pointing to several previously unknown regions of the HCMV genome that may be regulated by IE2.

  2. Effect of Liver Damage and Hyperbaric Oxygenation on Glutamine Synthetase of Hepatocytes.

    Science.gov (United States)

    Savilov, P N; Yakovlev, V N

    2016-01-01

    Activity of glutamine synthetase in the hepatocytes of healthy animals and animals with chronic CCl4-induced hepatitis was studied on white mature female rats after liver resection (15-20% of organ weight) and hyperbaric oxygenation (3 atm, 50 min, 3 times). Surgically operated left and non-operated middle lobes of the liver were analyzed on day 3 after liver resection and exposure to hyperbaric oxygenation. On day 65 of CCl4 poisoning, activity of glutamine synthetase decreased in both lobes and did not recover on day 3 after toxin cessation. Liver resection under conditions of CCl4-induced hepatitis restored reduced activity of glutamine synthetase in both liver lobes to the normal level. In healthy rats, the increase in glutamine synthetase activity after liver resection was found only in the middle lobe of the liver. Hyperbaric oxygenation enhanced the stimulatory effect of liver resection on glutamine synthetase activity in hepatocytes during chronic CCl4-induced hepatitis. In healthy animals with liver resection, activity of glutamine synthetase did not change after hyperbaric oxygenation, while normally oxygenation inhibited glutamine synthetase activity.

  3. Glutamine is required for snakehead fish vesiculovirus propagation via replenishing the tricarboxylic acid cycle.

    Science.gov (United States)

    Sun, Lindan; Yi, Lizhu; Zhang, Chi; Liu, Xiaodan; Feng, Shuangshuang; Chen, Wenjie; Lan, Jiangfeng; Zhao, Lijuan; Tu, Jiagang; Lin, Li

    2016-11-01

    Snakehead fish vesiculovirus (SHVV), a member of the family Rhabdoviridae, has caused mass mortality in snakehead fish culture in China. Previous transcriptomic sequencing of SHVV-infected and non-infected striped snakehead fish cells (SSN-1) showed that glutaminase (GLS), the critical enzyme of glutamine metabolism, was upregulated upon SHVV infection. It therefore drew our attention to investigating the role of glutamine in SHVV propagation. Glutamine deprivation significantly reduced the expression of the mRNAs and proteins of SHVV, and the production of virus particles, indicating that glutamine was required for SHVV propagation. Glutamine can be converted to glutamate by GLS, and then be converted to α-ketoglutarate, to join in the tricarboxylic acid (TCA) cycle. Addition of the TCA cycle intermediate α-ketoglutarate, oxaloacetic acid or pyruvate significantly restored SHVV propagation, indicating that the requirement of glutamine for SHVV propagation was due to its replenishment of the TCA cycle. Inhibiting the activity of GLS in SSN-1 cells by an inhibitor, bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, decreased SHVV propagation, while overexpression of GLS increased SHVV propagation. Taken together, our data have revealed the relationship between glutamine metabolism and SHVV propagation.

  4. Repression of nitrogen catabolic genes by ammonia and glutamine in nitrogen-limited continuous cultures of Saccharomyces cerevisiae.

    Science.gov (United States)

    ter Schure, E G; Silljé, H H; Vermeulen, E E; Kalhorn, J W; Verkleij, A J; Boonstra, J; Verrips, C T

    1998-05-01

    Growth of Saccharomyces cerevisiae on ammonia and glutamine decreases the expression of many nitrogen catabolic genes to low levels. To discriminate between ammonia- and glutamine-driven repression of GAP1, PUT4, GDH1 and GLN1, a gln1-37 mutant was used. This mutant is not able to convert ammonia into glutamine. Glutamine-limited continuous cultures were used to completely derepress the expression of GAP1, PUT4, GDH1 and GLN1. Following an ammonia pulse, the expression of GAP1, PUT4 and GDH1 decreased while the intracellular glutamine concentration remained constant, both in the cytoplasm and in the vacuole. Therefore, it was concluded that ammonia causes gene repression independent of the intracellular glutamine concentration. The expression of GLN1 was not decreased by an ammonia pulse but solely by a glutamine pulse. Analysis of the mRNA levels of ILV5 and HIS4 showed that the response of the two biosynthetic genes, GDH1 and GLN1, to ammonia and glutamine in the wild-type and gln1-37 was not due to changes in general transcription of biosynthetic genes. Ure2p has been shown to be an essential element for nitrogen-regulated gene expression. Deletion of URE2 in the gln1-37 background prevented repression of gene expression by ammonia, showing that the ammonia-induced repression is not caused by a general stress response but represents a specific signal for nitrogen catabolite regulation.

  5. [Ammonia, glutamine and glutamic acid content of rat tissues during and after hyperoxia].

    Science.gov (United States)

    Gabibov, M M

    1975-01-01

    The content of ammonia, glutamine, glutamic acid was measured in the brain, liver, heart, spleen, kidneys, skeletal muscles and blood rats exposed to a 4 atm oxygen atmosphere and during aftereffects. The hyperoxic atmosphere resulted in an increase of ammonia and glutamic acid and in a decrease of glutamine in the tissues. The return to the norm of the compounds occurred slowly and nonuniformly, lasting for 40 to 60 posthyperoxic days.

  6. Streptomyces hygroscopicus Has Two Glutamine Synthetase Genes

    NARCIS (Netherlands)

    Kumada, Y.; Takano, E.; Nagaoka, Kozo; Thompson, C.J.

    1990-01-01

    Streptomyces hygroscopicus, which produces the glutamine synthetase inhibitor phosphinothricin, possesses at least two genes (glnA and glnB) encoding distinct glutamine synthetase isoforms (GSI and GSII). The glnB gene was cloned from S. hygroscopicus DNA by complementation in an Escherichia coli gl

  7. The Glutamine-Glutamate/GABA Cycle

    DEFF Research Database (Denmark)

    Walls, Anne B; Waagepetersen, Helle S; Bak, Lasse Kristoffer;

    2015-01-01

    inhibitor methionine sulfoximine and the tricarboxylic acid cycle (aconitase) inhibitors fluoro-acetate and -citrate. Acetate is metabolized exclusively by glial cells, and [(13)C]acetate is thus capable when used in combination with magnetic resonance spectroscopy or mass spectrometry, to provide......The operation of a glutamine-glutamate/GABA cycle in the brain consisting of the transfer of glutamine from astrocytes to neurons and neurotransmitter glutamate or GABA from neurons to astrocytes is a well-known concept. In neurons, glutamine is not only used for energy production and protein...... synthesis, as in other cells, but is also an essential precursor for biosynthesis of amino acid neurotransmitters. An excellent tool for the study of glutamine transfer from astrocytes to neurons is [(14)C]acetate or [(13)C]acetate and the glial specific enzyme inhibitors, i.e. the glutamine synthetase...

  8. Effect of carbohydrate supplementation on plasma glutamine during prolonged exercise and recovery

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Saris, W H; Wagenmakers, A J

    1998-01-01

    Muscle glycogen and glucose have been suggested to be carbon-chain precursors for glutamine synthesis in skeletal muscle. Therefore, the aim of the present study is to investigate whether carbohydrate supplementation affects plasma glutamine and other amino acids during exercise and 7 h of recovery....... Eight well-trained subjects cycled at an alternating workload of 50 and 80% Wmax until exhaustion (59 to 140 min). During the exercise bout the subjects received either water (control) or a carbohydrate (CHO) drink (83 g CHO x l(-1), 2 ml x kg(-1) per kg body weight every 15 min). Plasma glutamine...... concentration appeared not to be affected by exercise, as a significant increase was only observed at some points in time during the control test. During recovery, however, plasma glutamine concentration decreased from 682+/-24 and 685+/-19 micromol x l(-1) at exhaustion to 552+/-19 and 534+/-12 micromol x l(-1...

  9. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Marta Spodenkiewicz

    2016-10-01

    Full Text Available Glutamine synthetase (GS is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS can cause an ultra-rare recessive inborn error of metabolism—congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.

  10. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis.

    Science.gov (United States)

    Spodenkiewicz, Marta; Diez-Fernandez, Carmen; Rüfenacht, Véronique; Gemperle-Britschgi, Corinne; Häberle, Johannes

    2016-10-19

    Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism-congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition.

  11. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

    Science.gov (United States)

    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  12. Effects of glutamine and asparagine on recombinant antibody production using CHO-GS cell lines.

    Science.gov (United States)

    Xu, Ping; Dai, Xiao-Ping; Graf, Erica; Martel, Richard; Russell, Reb

    2014-01-01

    A unique and nontraditional approach using glutamine and asparagine supplements for CHO-glutamine synthetase (GS) cell lines was studied. In our experiments, we found that a decrease in pH and an increase in cell death occurred in production phase of a GS cell line, leading to reduced antibody expression and lower antibody yields. The experimental results and the statistical analysis (ANOVA) indicated that additions of glutamine and asparagine in the basal and feed media were effective to buffer the cell culture pH, reduce lactate generation, maintain a higher cell viability profile, and improve antibody productivity. In bench-top bioreactors, glutamine and asparagine supplementation helped to prevent cell death, improve antibody yield, and reduce base usage. Glutamine is normally excluded from culture media for GS cell lines to prevent the bypass of selection pressure. In this study, however, the addition of glutamine did not affect cell population homogeneity, protein quality, or decrease antibody yield of two GS cell lines.

  13. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    Directory of Open Access Journals (Sweden)

    Yan-Ren Lin

    2016-01-01

    Full Text Available Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2 were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n=20 and control (normal saline, n=20 groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5 or to culture medium (control. Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p<0.05. In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53 and apoptosis (caspase-3, Bcl-xL markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR. L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5. More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells’ beating function at a low pH level.

  14. Effects of glutamine supplementation, GH, and IGF-I on glutamine metabolism in critically ill patients.

    Science.gov (United States)

    Jackson, N C; Carroll, P V; Russell-Jones, D L; Sönksen, P H; Treacher, D F; Umpleby, A M

    2000-02-01

    During critical illness glutamine deficiency may develop. Glutamine supplementation can restore plasma concentration to normal, but the effect on glutamine metabolism is unknown. The use of growth hormone (GH) and insulin-like growth factor I (IGF-I) to prevent protein catabolism in these patients may exacerbate the glutamine deficiency. We have investigated, in critically ill patients, the effects of 72 h of treatment with standard parenteral nutrition (TPN; n = 6), TPN supplemented with glutamine (TPNGLN; 0.4 g x kg(-1) x day(-1), n = 6), or TPNGLN with combined GH (0.2 IU. kg(-1). day(-1)) and IGF-I (160 microg x kg (-1) x day(-1)) (TPNGLN+GH/IGF-I; n = 5) on glutamine metabolism using [2-(15)N]glutamine. In patients receiving TPNGLN and TPNGLN+GH/IGF-I, plasma glutamine concentration was increased (338 +/- 22 vs. 461 +/- 24 micromol/l, P requirement for glutamine in critically ill patients. Combined GH/IGF-I treatment with TPNGLN did not have adverse effects on glutamine metabolism.

  15. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Science.gov (United States)

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  16. Plasma Glutamine Concentrations in Liver Failure.

    Directory of Open Access Journals (Sweden)

    Gunnel Helling

    Full Text Available Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.Four different groups of patients were studies; chronic liver failure (n = 40, acute on chronic liver failure (n = 20, acute fulminant liver failure (n = 20, and post-hepatectomy liver failure (n = 20. Child-Pugh and Model for End-stage Liver Disease (MELD scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100, severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

  17. Regulation of glutamine synthetase activity in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 by the nitrogen source: effect of ammonium.

    Science.gov (United States)

    Mérida, A; Candau, P; Florencio, F J

    1991-07-01

    Glutamine synthetase activity from Synechocystis sp. strain PCC 6803 is regulated as a function of the nitrogen source available in the medium. Addition of 0.25 mM NH4Cl to nitrate-grown cells promotes a clear short-term inactivation of glutamine synthetase, whose enzyme activity decreases to 5 to 10% of the initial value in 25 min. The intracellular levels of glutamine, determined under various conditions, taken together with the results obtained with azaserine (an inhibitor of transamidases), rule out the possibility that glutamine per se is responsible for glutamine synthetase inactivation. Nitrogen starvation attenuates the ammonium-mediated glutamine synthetase inactivation, indicating that glutamine synthetase regulation is modulated through the internal balance between carbon-nitrogen compounds and carbon compounds. The parallelism observed between the glutamine synthetase activity and the internal concentration of alpha-ketoglutarate suggests that this metabolite could play a role as a positive effector of glutamine synthetase activity in Synechocystis sp. Despite the similarities of this physiological system to that described for enterobacteria, the lack of in vivo 32P labeling of glutamine synthetase during the inactivation process excludes the existence of an adenylylation-deadenylylation system in this cyanobacterium.

  18. Cytosolic glutamine synthetase in barley

    DEFF Research Database (Denmark)

    Thomsen, Hanne Cecilie

    Improving crop nitrogen (N) utilization efficiency (NUE) is of major importance in modern agriculture in order to reduce the amount of N fertilizer used for crop production. There is a high demand for development of crops which are able to produce high yields but with a concomitantly lower N...... fertilizer requirement. The enzyme glutamine synthetase (GS) has been a major topic in plant nitrogen research for decades due to its central role in plant N metabolism. The cytosolic version of this enzyme (GS1) plays an important role in relation to primary N assimilation as well as in relation to N...... and wildtype control. However, when grown to maturity the differences between transgenic lines and wildtype were highly dependent on the growth conditions applied. The transgenic lines had a higher N utilization efficiency (NUtE) than wildtype control, but only when exposed to a mild N stress following...

  19. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate...... or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...

  20. Enhanced mitochondrial glutamine anaplerosis suppresses pancreatic cancer growth through autophagy inhibition

    Science.gov (United States)

    Jeong, Seung Min; Hwang, Sunsook; Park, Kyungsoo; Yang, Seungyeon; Seong, Rho Hyun

    2016-01-01

    Cancer cells use precursors derived from tricarboxylic acid (TCA) cycle to support their unlimited growth. However, continuous export of TCA cycle intermediates results in the defect of mitochondrial integrity. Mitochondria glutamine metabolism plays an essential role for the maintenance of mitochondrial functions and its biosynthetic roles by refilling the mitochondrial carbon pool. Here we report that human pancreatic ductal adenocarcinoma (PDAC) cells have a distinct dependence on mitochondrial glutamine metabolism. Whereas glutamine flux into mitochondria contributes to proliferation of most cancer cells, enhanced glutamine anaplerosis results in a pronounced suppression of PDAC growth. A cell membrane permeable α-ketoglutarate analog or overexpression of glutamate dehydrogenase lead to decreased proliferation and increased apoptotic cell death in PDAC cells but not other cancer cells. We found that enhanced glutamine anaplerosis inhibits autophagy, required for tumorigenic growth of PDAC, by activating mammalian TORC1. Together, our results reveal that glutamine anaplerosis is a crucial regulator of growth and survival of PDAC cells, which may provide novel therapeutic approaches to treat these cancers. PMID:27477484

  1. Glutamine supplementation does not improve protein synthesis rate by the jejunal mucosa of the malnourished rat.

    Science.gov (United States)

    Tannus, Andrea Ferreira S; Darmaun, Dominique; Ribas, Durval F; Oliveira, José Eduardo D; Marchini, Julio Sergio

    2009-08-01

    It has been demonstrated that glutamine, a conditionally essential amino acid, improves nitrogen balance, acts as a stimulant of protein synthesis, and decreases proteolysis in myopathic children. In contrast, other studies have shown no beneficial effect of glutamine supplementation on burn victims or critically ill patients. Nonetheless, we hypothesized that glutamine supplementation would increase the fractional protein synthesis rate (FSR) in the jejunal mucosa of malnourished male Wistar rats. Thus, the objective of the present study was to test the effect of daily oral glutamine supplementation (0.42 g kg(-1) d(-1) for 14 days) on the FSR of the jejunal mucosa of healthy and malnourished rats. A 4-hour kinetic study with l-[1-(13)C]leucine was subsequently performed, and jejunal biopsies were obtained 1.5 cm from the Treitz angle and analyzed. Malnourished rats showed a 25% weight loss and increased urinary nitrogen excretion. Plasma amino acid concentration did not differ between groups. (13)C enrichment in plasma and jejunal cells was higher in the malnourished groups than in the healthy group. The FSR (percent per hour) was similar for the control and experimental groups (P > .05), with a mean range of 22%/h to 27%/h. Oral glutamine supplementation alone did not induce higher protein incorporation by the jejunal mucosa in malnourished rats, regardless of total food intake or the presence or absence of glutamine supplementation.

  2. Visualization of glutamine transporter activities in living cells using genetically encoded glutamine sensors.

    Directory of Open Access Journals (Sweden)

    Katrin Gruenwald

    Full Text Available Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level.

  3. Preventive oral supplementation with glutamine and arginine has beneficial effects on the intestinal mucosa and inflammatory cytokines in endotoxemic rats.

    Science.gov (United States)

    Zhou, Xihong; Wu, Xin; Yin, Yulong; Zhang, Cui; He, Liuqin

    2012-08-01

    The objective of this study was to evaluate the effect of oral supplementation with a combination of arginine and glutamine on the intestinal mucosa and inflammatory cytokines of lipopolysaccharide (LPS)-induced adult rats. Fifty Sprague-Dawley rats (average weight of 185 ± 15 g) were randomly divided into five groups: control group A (CA) and control group B (CB), both orally supplemented with 0.9% saline; group Arg, supplemented with 300 mg/kg day(-1) arginine; group Gln, supplemented with 300 mg/kg day(-1) glutamine; group AG, supplemented with 150 mg/kg day(-1) arginine and 150 mg/kg day(-1) glutamine. The experiment lasted for 2 weeks. Food intake and body weight were measured during the experiment. At 10.00 h of day 15, animals were injected with 4 mg/kg LPS (group CB, Arg, Gln, and AG) or sterile saline (group CA) after supplementation. Then at 14.00 h, all animals were killed and blood and tissue collected. The results showed that compared with group CB, arginine concentration tended to be increased (P > 0.05) in group Arg and AG, while there was no significant difference in glutamine concentration among the groups challenged with LPS. Oral supplementation with arginine or/and glutamine mitigated morphology impairment (lower villus height, P Arginine only significantly decreased TNF-α mRNA abundance in the ileum, while glutamine significantly decreased both TNF-α and IL-10 mRNA in the ileum. A combination of arginine and glutamine significantly decreased TNF-α and IL-1β mRNA abundance in both the jejunum and ileum, while they also significantly decreased anti-inflammatory IL-10 in the ileum. These results revealed that an oral supply of combined arginine and glutamine had more favorable effects on the intestinal mucosa and inflammatory cytokines than a supply of arginine or glutamine alone.

  4. Glutamine synthetase of Streptomyces cattleya: purification and regulation of synthesis.

    Science.gov (United States)

    Paress, P S; Streicher, S L

    1985-08-01

    Glutamine synthetase (GS; EC 6.3.1.2) from Streptomyces cattleya was purified using a single affinity-gel chromatography step, and some of its properties were determined. Levels of GS in S. cattleya cells varied by a factor of 8 depending upon the source of nitrogen in the growth medium. Of 24 nitrogen sources examined only glutamine or NH4Cl utilization resulted in very low GS activity. Addition of NH4Cl to a culture with high GS levels appeared to stop further synthesis and resulted in a progressive decrease in the specific activity of the enzyme. The GS inhibitor methionine sulphoximine (MSX) inhibited GS activity but had no effect on exponentially growing cells. The presence of MSX either lengthened or shortened the period between spore inoculation and initiation of exponential growth, depending on the source of nitrogen. In glutamine minimal medium MSX produced earlier and more efficient spore germination while in glutamate or nitrate minimal medium germination was delayed by its presence.

  5. The effect of portacaval anastomosis on the expression of glutamine synthetase and ornithine aminotransferase in perivenous hepatocytes.

    Science.gov (United States)

    da Silva, Robin; Levillain, Oliver; Brosnan, John T; Araneda, Silvia; Brosnan, Margaret E

    2013-05-01

    There is functional zonation of metabolism across the liver acinus, with glutamine synthetase restricted to a narrow band of cells around the terminal hepatic venules. Portacaval anastomosis, where there is a major rerouting of portal blood flow from the portal vein directly to the vena cava bypassing the liver, has been reported to result in a marked decrease in the activity of glutamine synthetase. It is not known whether this represents a loss of perivenous hepatocytes or whether there is a specific loss of glutamine synthetase. To answer this question, we have determined the activity of glutamine synthetase and another enzyme from the perivenous compartment, ornithine aminotransferase, as well as the immunochemical localization of both glutamine synthetase and ornithine aminotransferase in rats with a portacaval shunt. The portacaval shunt caused a marked decrease in glutamine synthetase activity and an increase in ornithine aminotransferase activity. Immunohistochemical analysis showed that the glutamine synthetase and ornithine aminotransferase proteins maintained their location in the perivenous cells. These results indicate that there is no generalized loss of perivenous hepatocytes, but rather, there is a significant alteration in the expression of these proteins and hence metabolism in this cell population.

  6. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis.

    Science.gov (United States)

    Crespo, Irene; San-Miguel, Beatriz; Prause, Carolina; Marroni, Norma; Cuevas, María J; González-Gallego, Javier; Tuñón, María J

    2012-01-01

    Endoplasmic reticulum (ER) stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Glutamine (25 mg/dL) was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio) and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression) increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM). The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine against damage

  7. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis.

    Directory of Open Access Journals (Sweden)

    Irene Crespo

    Full Text Available Endoplasmic reticulum (ER stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD. We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS. Glutamine (25 mg/dL was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM. The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine

  8. Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.

    Science.gov (United States)

    Brinkmann, Saskia J H; Buijs, Nikki; Vermeulen, Mechteld A R; Oosterink, Efraim; Schierbeek, Henk; Beishuizen, Albertus; de Vries, Jean-Paul P M; Wisselink, Willem; van Leeuwen, Paul A M

    2016-09-01

    Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

  9. Peripheral intravenous line (image)

    Science.gov (United States)

    A peripheral intravenous line is a small, short plastic catheter that is placed through the skin into a vein, ... or foot, but occasionally in the head. A peripheral intravenous line is used to give fluids and ...

  10. Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study

    DEFF Research Database (Denmark)

    Samocha-Bonet, Dorit; Chisholm, Donald J; Gribble, Fiona M

    2014-01-01

    /mol) received glutamine (15 g bd)+ sitagliptin (100 mg/d) or glutamine (15 g bd) + placebo for 4 weeks in a randomized crossover study. RESULTS: HbA1c (P = 0.007) and fructosamine (P = 0.02) decreased modestly, without significant time-treatment interactions (both P = 0.4). Blood urea increased (P

  11. Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat.

    Science.gov (United States)

    Blanc, Marie-Céline; Moinard, Christophe; Béziel, Aurélie; Darquy, Sylviane; Cynober, Luc; De Bandt, Jean-Pascal

    2005-01-01

    Increased susceptibility to infections in obese patients may be related to decreased availability of arginine and glutamine, which may affect immune cell functions. Our aim was to evaluate the in vitro effects of these amino acids on the function of macrophages from obese insulin-resistant Zucker rats. Macrophages, isolated from male Zucker obese or lean rats by peritoneal lavage, were incubated in Dulbecco's modified Eagle medium (DMEM) without arginine or glutamine. Arginine or glutamine was added to the medium at increasing final concentrations (0, 0.25, 0.5, 1 or 2 mM). After stimulation by lipopolysaccharide (LPS) from E. coli (40 microg/ml), productions of tumour necrosis factor alpha (TNFalpha) and of nitric oxide (NO) were measured after 3 or 48 h incubation, respectively. NO production, lower in macrophages from obese rats, decreased in macrophages from lean rats (0 mM: 2,423 +/- 1,174 vs. 2 mM: 198 +/- 31 microM/mg protein/24 h; P glutamine was added. TNFalpha production, lower in macrophages from obese rats, was inversely correlated with glutamine concentration. In the presence of arginine, NO production was constantly higher in macrophages from obese rats. It peaked at 0.5 mM arginine and decreased thereafter in both groups. TNFalpha production in macrophages from lean rats was unaffected by arginine, but decreased in macrophages from obese rats (0 mM: 1920 +/- 450 vs. 2 mM: 810 +/- 90 microM/mg protein/3 h; P arginine and glutamine metabolism in macrophages of obese rats, resulting in decreased TNFalpha production and increased NO release, may contribute to increased susceptibility to infection in insulin-resistant states.

  12. The Glutamine Transporters and Their Role in the Glutamate/GABA-Glutamine Cycle

    DEFF Research Database (Denmark)

    Leke, Renata; Schousboe, Arne

    2016-01-01

    Glutamine is a key amino acid in the CNS, playing an important role in the glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from astrocytes to neurons, where it will replenish the inhibitory and excitatory neurotransmitter pools. Different transporters participate...... acids and cationic amino acids (y(+)LAT2 isoform) and have been associated with glutamine efflux from astrocytes. ASCT2 is a Na(+)-dependent antiporter, the participation of which in the GGC also remains to be better characterized. All these isoforms are tightly regulated by transcriptional...... and translational mechanisms, which are induced by several determinants such as amino acid deprivation, hormones, pH, and the activity of different signaling pathways. Dysfunctional glutamine transporter activity has been associated with the pathophysiological mechanisms of certain neurologic diseases...

  13. Glutamine synthetase desensitizes differentiated adipocytes to proinflammatory stimuli by raising intracellular glutamine levels.

    Science.gov (United States)

    Palmieri, Erika Mariana; Spera, Iolanda; Menga, Alessio; Infantino, Vittoria; Iacobazzi, Vito; Castegna, Alessandra

    2014-12-20

    The role of glutamine synthetase (GS) during adipocyte differentiation is unclear. Here, we assess the impact of GS on the adipocytic response to a proinflammatory challenge at different differentiation stages. GS expression at the late stages of differentiation desensitized mature adipocytes to bacterial lipopolysaccharide (LPS) by increasing intracellular glutamine levels. Furthermore, LPS-activated mature adipocytes were unable to produce inflammatory mediators; LPS sensitivity was rescued following GS inhibition and the associated drop in intracellular glutamine levels. The ability of adipocytes to differentially respond to LPS during differentiation negatively correlates to GS expression and intracellular glutamine levels. Hence, modulation of intracellular glutamine levels by GS expression represents an endogenous mechanism through which mature adipocytes control the inflammatory response.

  14. Glutamine enhances glucose-induced mesangial cell proliferation.

    Science.gov (United States)

    Lagranha, Claudia J; Doi, Sonia Q; Pithon-Curi, Tania C; Curi, Rui; Sellitti, Donald F

    2008-05-01

    The proliferation of mesangial cells (MC) in the presence of glutamine (0-20 mM) was determined in both low (5 mM) and high (25 mM) glucose-containing medium. Glutamine in a high glucose (HG) environment increased cell proliferation in a dose-dependent manner. Inhibition of glutamine:fructose 6-phosphate amidotransferase (GFAT) and of phosphodiesterase significantly reduced glutamine-induced proliferation. Supraphysiologic levels of glutamine increase MC proliferation in a HG milieu via GFAT and cAMP-dependent pathways, suggesting that glutamine could pose a risk for diabetic nephropathy.

  15. Effects of adding different levels of Glutamine to modified Beltsville extender on the survival of frozen rooster semen.

    Science.gov (United States)

    Khiabani, Aytak Bakhshayesh; Moghaddam, Gholamali; Kia, Hossein Daghigh

    2017-09-01

    The aim of the present study was to investigate the effects of l-glutamine on the quality of frozen-thawed rooster semen. Semen samples were collected from eight mature roosters (Ross 308). After initial semen assessments, samples of adequate quality were mixed together and diluted with modified Beltsville extender without l-glutamine (control) and supplemented with 2.5, 5, and 7.5mM l-glutamine. Semen straws were subjected to cryopreservation and evaluated twice at 15-day intervals. After thawing, sperm viability, total and progressive sperm motilities were measured by Eosin-Nigrosine and Computer-Aided Sperm Analysis (CASA), respectively. The results showed that sperm functions decreased on day 30 compared to day 15. The extender supplemented with 5mM glutamine improved (p<0.05) sperm viability, total and progressive sperm motilities compared to other treatments and the control group. The best level of glutamine appeared to be 2.5mM, as it provided the highest sperm membrane integrity and the lowest level of abnormalities. The results of this study suggest that the addition of glutamine to the diluent improves semen quality and using glutamine allows rooster sperm to be frozen for longer. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Impact of Glutamine in Drinking Water on Performance and Intestinal Morphology of Broiler Chickens under High Stocking Density

    Directory of Open Access Journals (Sweden)

    Majid SHAKERI

    2016-01-01

    Full Text Available This work sought to look into the impacts of glutamine in drinking water on performance, intestinal morphology and corticosterone level of chickens under different stocking densities. A total 300 male chicks randomly were divided to battery cages as 10 birds/(normal stocking density and 15 birds/(high stocking density. The chicks received feed as (i control diet and (ii control diet + 5g glutamine/ liter in drinking water under normal and high stocking density for the whole experiment. On d 42, 3 chicks from each cage were randomly selected and slaughtered to collect blood and duodenal samples. The results showed significant improvement in growth performance and longer villi when chicken were supplemented with glutamine via drinking water. High stocking density impaired performance of chicks in the control diet, but not in chicken supplemented with glutamine under high stocking density condition. Moreover, high stocking density increased the level of corticosterone in the both groups. More interestingly, the rate of mortality significantly decreased in chickens fed with glutamine supplemented diet (2% when supplemented with glutamine and 5.33% without supplementation. In conclusion, glutamine supplementation via drinking water resulted in better growth performance of birds subjected to high stocking density.

  17. Glutamine supplementation in bone marrow transplantation.

    Science.gov (United States)

    Ziegler, Thomas R

    2002-01-01

    An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens.

  18. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    Science.gov (United States)

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-01-01

    Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required. PMID:27308070

  19. Glutamine supplementation in the critically ill: friend or foe?

    Science.gov (United States)

    Oudemans-van Straaten, Heleen M; van Zanten, Arthur R H

    2014-05-19

    In the previous issue of Critical Care, Mori and colleagues demonstrate that glutamine supplementation in mechanically ventilated patients as part of parenteral nutrition increases plasma glutamine concentration and glutamine utilization, but does not mitigate protein degradation and even increases de novo glutamine production. Studies suggest that protein degradation is regulated by the degree of inflammation. Immune cells utilize large amounts of glutamine and derive their glutamine requirements from muscle protein degradation. We hypothesize that the effects of glutamine supplementation depend on the degree of inflammation. Infusing large amounts of exogenous glutamine into patients with inflammatory conditions like sepsis and multiple organ failure may not only enhance immune competence, but may potentially augment the inflammatory response and thereby negatively influence outcome.

  20. Glutamine Synthetase: Role in Neurological Disorders.

    Science.gov (United States)

    Jayakumar, Arumugam R; Norenberg, Michael D

    2016-01-01

    Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete. This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and astroglial neoplasms. This review also explores the possibility of targeting GS in the therapy of these conditions.

  1. Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

    Science.gov (United States)

    Yoshida, S.; Leskiw, M. J.; Schluter, M. D.; Bush, K. T.; Nagele, R. G.; Lanza-Jacoby, S.; Stein, T. P.

    1992-01-01

    The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

  2. Enteral glutamine: a novel mediator of PPARgamma in the postischemic gut.

    Science.gov (United States)

    Ban, Kechen; Kozar, Rosemary A

    2008-09-01

    Early enteral nutrition supplemented with glutamine, arginine, omega-3 fatty acids, and nucleotides has been shown to decrease infection complications in critically injured patients. Concern has been raised, however, that under conditions of hyperinflammation, these diets may be injurious through the induction of inducible NO synthase by enteral arginine. In a rodent model of gut ischemia/reperfusion, inflammation and injury are intensified by enteral arginine and abrogated by glutamine. These findings correlate with the degree of metabolic stress imposed upon the gut by hypoperfusion. Glutamine is metabolized by the gut and therefore, can contribute back energy in the form of ATP, whereas arginine is a nonmetabolizable nutrient, using but not contributing energy. Recent data suggest that one of the molecular mechanisms responsible for the gut-protective effects of enteral glutamine is the activation of peroxisome proliferator-activated receptor gamma. This anti-inflammatory transcription factor belongs to the family of nuclear receptors, plays a key role in adipocyte development and glucose homeostasis, and has been recognized as an endogenous regulator of intestinal inflammation. Preliminary clinical studies support the use of enteral glutamine in patients with gut hypoperfusion.

  3. MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase.

    Science.gov (United States)

    Liu, Zhenyang; Wang, Junyu; Li, Yunjun; Fan, Juan; Chen, Lihua; Xu, Ruxiang

    2017-02-01

    Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.

  4. Glutamine inhibits CCl4 induced liver fibrosis in mice and TGF-β1 mediated epithelial-mesenchymal transition in mouse hepatocytes.

    Science.gov (United States)

    Shrestha, Nirajan; Chand, Lokendra; Han, Myung Kwan; Lee, Seung Ok; Kim, Chan Young; Jeong, Yeon Jun

    2016-07-01

    Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.

  5. A tracer bolus method for investigating glutamine kinetics in humans.

    Directory of Open Access Journals (Sweden)

    Maiko Mori

    Full Text Available Glutamine transport between tissues is important for the outcome of critically ill patients. Investigation of glutamine kinetics is, therefore, necessary to understand glutamine metabolism in these patients in order to improve future intervention studies. Endogenous glutamine production can be measured by continuous infusion of a glutamine tracer, which necessitates a minimum measurement time period. In order to reduce this problem, we used and validated a tracer bolus injection method. Furthermore, this method was used to measure the glutamine production in healthy volunteers in the post-absorptive state, with extra alanine and with glutamine supplementation and parenteral nutrition. Healthy volunteers received a bolus injection of [1-13C] glutamine, and blood was collected from the radial artery to measure tracer enrichment over 90 minutes. Endogenous rate of appearance (endoRa of glutamine was calculated from the enrichment decay curve and corrected for the extra glutamine supplementation. The glutamine endoRa of healthy volunteers was 6.1±0.9 µmol/kg/min in the post-absorptive state, 6.9±1.0 µmol/kg/min with extra alanyl-glutamine (p = 0.29 versus control, 6.1±0.4 µmol/kg/min with extra alanine only (p = 0.32 versus control, and 7.5±0.9 µmol/kg/min with extra alanyl-glutamine and parenteral nutrition (p = 0.049 versus control. In conclusion, a tracer bolus injection method to measure glutamine endoRa showed good reproducibility and small variation at baseline as well as during parenteral nutrition. Additionally, we showed that parenteral nutrition including alanyl-glutamine increased glutamine endoRa in healthy volunteers, which was not attributable to the alanine part of the dipeptide.

  6. Is there a role for glutamine supplementation in the management of acute pancreatitis?

    Science.gov (United States)

    Castro-Gutiérrez, Victoria; Rada, Gabriel

    2016-08-17

    There is no consensus about the effects of glutamine supplementation for acute pancreatitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 15 systematic reviews including 31 randomized controlled trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded glutamine supplementation might decrease infectious complications in acute pancreatitis, but it is not clear if it affects mortality or length of hospital stay because the certainty of the evidence is very low.

  7. Exogenous glutamine increases lipid accumulation in developing seeds of castor bean (Ricinus communis L. cultured in vitro

    Directory of Open Access Journals (Sweden)

    Zhang Yang

    2015-01-01

    Full Text Available This report describes biomass production and compositional changes of developing castor seeds in response to change in the nitrogen resource (glutamine of the medium. During the early developmental period (24-36 days after pollination, oil was found to initially accumulate in the developing seeds. Carbohydrates and oil were inversely related after glutamine provision (35 mM, in the culture medium. [U-14C] sucrose labeling was used to investigate the effect of metabolic fluxes among different storage materials. Addition of glutamine led to a 7% increase of labeling in lipids and an inverse decrease of labeling in carbohydrates. It was postulated that changes in the glutamine concentration in the medium are likely to influence the partitioning of resources between the various storage products, especially carbohydrates and oil. These observations will contribute to a better understanding of assimilate partitioning in developing castor seeds and the development of molecular strategies to improve castor bean seed quality and plant breeding studies.

  8. Noncoding RNA of Glutamine Synthetase I Modulates Antibiotic Production in Streptomyces coelicolor A3(2)

    OpenAIRE

    D'Alia, Davide; Nieselt, Kay; Steigele, Stephan; Mueller, Jonas; Verburg, Ilse; Takano, Eriko; Alia, Davide D’; Müller, Jonas

    2010-01-01

    Overexpression of antisense chromosomal cis-encoded noncoding RNAss (ncRNAs) in glutamine synthetase I resulted in a decrease in growth, protein synthesis, and antibiotic production in Streptomyces coelicolor. In addition, we predicted 3,597 cis-encoded ncRNAs and validated 13 of them experimentally, including several ncRNAs that are differentially expressed in bacterial hormone-defective mutants.

  9. Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury.

    Science.gov (United States)

    Zhang, Yong; Yan, Hong; Lv, Shang-Gun; Wang, Lin; Liang, Guang-Ping; Wan, Qian-Xue; Peng, Xi

    2013-01-01

    Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis.

  10. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  11. Intravenous paracetamol (acetaminophen).

    Science.gov (United States)

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text].

  12. Protective effects of l-glutamine against toxicity of deltamethrin in the cerebral tissue

    Science.gov (United States)

    Varol, Sefer; Özdemir, Hasan Hüseyin; Çevik, Mehmet Uğur; Altun, Yaşar; Ibiloğlu, Ibrahim; Ekinci, Aysun; Ibiloğlu, Aslıhan Okan; Balduz, Metin; Arslan, Demet; Tekin, Recep; Aktar, Fesih; Aluçlu, Mehmet Ufuk

    2016-01-01

    Background Deltamethrin (DLM) is a broad-spectrum synthetic dibromo-pyrethroid pesticide that is widely used for agricultural and veterinary purposes. However, human exposure to the pesticide leads to neurotoxicity. Glutamine is one of the principal, free intracellular amino acids and may also be an antioxidant. This study was undertaken in order to examine the neuroprotective and antioxidant potential of l-glutamine against DLM toxicity in female Wistar albino rats. Materials and methods The rats were divided into the following groups (n=10): Group I: control (distilled water; 10 mL/kg, po one dose), Group II: l-glutamine (1.5 g/kg, po one dose), Group III: DLM (35 mg/kg, po one dose), and Group IV: DLM (35 mg/kg, po one dose) and l-glutamine (1.5 g/kg, po one dose after 4 hours). Total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels and apoptosis were evaluated in brain tissue. Results DLM-treated animals had a significant increase in brain biochemical parameters, as well as TOS and TAS. Furthermore, the histopathological examination showed neuronal cell degeneration in the cerebral tissue. l-Glutamine treatment decreased the elevated brain levels of TOS and neuronal cell degeneration. There was no difference in tumor necrosis factor-α, IL-1β, and IL-6 levels between the groups. Conclusion l-Glutamine may reduce the toxic effects of DLM in the cerebral tissue through antioxidant properties. PMID:27143900

  13. L-Arginine but not L-glutamine likely increases exogenous carbohydrate oxidation during endurance exercise.

    Science.gov (United States)

    Rowlands, David S; Clarke, Jim; Green, Jackson G; Shi, Xiaocai

    2012-07-01

    The addition of L-arginine or L-glutamine to glucose-electrolyte solutions can increase intestinal water, glucose, and sodium absorption in rats and humans. We evaluated the utility of L-arginine and L-glutamine in energy-rehydration beverages through assessment of exogenous glucose oxidation and perceptions of exertion and gastrointestinal distress during endurance exercise. Eight cyclists rode 150 min at 50% of peak power on four occasions while ingesting solutions at a rate of 150 mL 15 min(-1) that contained (13)C-enriched glucose (266 mmol L(-1)) and sodium citrate ([Na(+)] 60 mmol L(-1)), and either: 4.25 mmol L(-1) L-arginine or 45 mmol L(-1) L-glutamine, and as controls glucose only or no glucose. Relative to glucose only, L-arginine invoked a likely 12% increase in exogenous glucose oxidation (90% confidence limits: ± 8%); however, the effect of L-glutamine was possibly trivial (4.5 ± 7.3%). L-Arginine also led to very likely small reductions in endogenous fat oxidation rate relative to glucose (12 ± 4%) and L-glutamine (14 ± 4%), and relative to no glucose, likely reductions in exercise oxygen consumption (2.6 ± 1.5%) and plasma lactate concentration (0.20 ± 0.16 mmol L(-1)). Effects on endogenous and total carbohydrate oxidation were inconsequential. Compared with glucose only, L-arginine and L-glutamine caused likely small-moderate effect size increases in perceptions of stomach fullness, abdominal cramp, exertion, and muscle tiredness during exercise. Addition of L-arginine to a glucose and electrolyte solution increases the oxidation of exogenous glucose and decreases the oxygen cost of exercise, although the mechanisms responsible and impact on endurance performance require further investigation. However, L-arginine also increases subjective feelings of gastrointestinal distress, which may attenuate its other benefits.

  14. Glutamine: precursor or nitrogen donor for citrulline synthesis?

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-07-01

    Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, l-[2-(15)N]- and l-[5-(15)N]glutamine and (15)N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the delta-nitrogen. D(5)-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2-0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-(13)C(n) tracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for approximately 40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis.

  15. Dietary glutamine supplementation partly reverses impaired macrophage function resulting from overload training in rats.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Dong, Jingmei; Wang, Ru; Luo, Beibei

    2015-04-01

    The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training.

  16. Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

    Institute of Scientific and Technical Information of China (English)

    Liliana Belmonte; Philippe Ducrotté; Pierre Déchelotte; Mo(i)se Co(e)ffier; Florence Le Pessot; Olga Miralles-Barrachina; Martine Hiron; Antony Leplingard; Jean-Fran(c)ois Lemeland; Bernadette Hecketsweiler; Maryvonne Daveau

    2007-01-01

    AIM:To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock.METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder.Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed.RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ±0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation.CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

  17. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide.

    Science.gov (United States)

    Zhao, J; Verwer, R W H; van Wamelen, D J; Qi, X-R; Gao, S-F; Lucassen, P J; Swaab, D F

    2016-11-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neuronal/glial glutamate transporters was determined by qPCR in postmortem prefrontal cortex. The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) were selected from young MDD patients who had committed suicide (MDD-S; n = 17), from MDD patients who died of non-suicide related causes (MDD-NS; n = 7) and from matched control subjects (n = 12). We also compared elderly depressed patients who had not committed suicide (n = 14) with matched control subjects (n = 22). We found that neuronal located components (EAAT3, EAAT4, ASCT1, SNAT1, SNAT2) of the glutamate-glutamine cycle were increased in the ACC while the astroglia located components (EAAT1, EAAT2, GLUL) were decreased in the DLPFC of MDD-S patients. In contrast, most of the components in the cycle were increased in the DLPFC of MDD-NS patients. In conclusion, the glutamate-glutamine cycle - and thus glutamine transmission - is differentially affected in depressed suicide patients and depressed non-suicide patients in an area specific way. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Functional hepatocyte heterogeneity. Vascular 2-oxoglutarate is almost exclusively taken up by perivenous, glutamine-synthetase-containing hepatocytes.

    Science.gov (United States)

    Stoll, B; Hüssinger, D

    1989-05-15

    1. In isolated perfused rat liver maximal rates of 2-[1-14C]oxoglutarate uptake were about 0.4 mumol.g-1 .min-1; half-maximal rates of 2-[14C]oxoglutarate uptake were observed with influent concentrations of about 100 microM. 2-[14C]Oxoglutarate uptake by the liver was not affected by the direction of perfusion, but was decreased by about 80-90% when Na+ in the perfusion fluid was substituted by choline+, suggesting a Na+-dependence of hepatic 2-oxoglutarate uptake. In the absence of added ammonia, [14C]oxoglutarate uptake by the liver was about twice the net oxoglutarate uptake, indicating a simultaneous release of unlabeled oxoglutarate from perfused rat liver. 2. 14C-Labeled metabolites derived from [1-14C]oxoglutarate and recovered in the effluent perfusate were 14CO2 and 14C-labeled glutamate and glutamine; they accounted for 85-100% of the radiolabel taken up by the liver. 14CO2 was the major product (more than 70%) from [1-14C]oxoglutarate taken up the liver, provided glutamine synthesis was either inhibited by methionine sulfoximine or the endogenous rate of glutamine production was below 40 nmol.g-1.min-1. 3. Stimulation of glutamine synthesis by ammonia did not affect [14C]oxoglutarate uptake by the liver, but considerably increased net hepatic oxoglutarate uptake, indicating a decreased release of unlabeled oxoglutarate from the liver. Stepwise stimulation of hepatic glutamine synthesis led to a gradual decrease of 14CO2 production and radiolabel was recovered increasingly as [14C]glutamine in the effluent. At high rates of glutamine formation (i.e. about 0.6 mumol.g-1.min-1), about 60% of the [1-14C]oxoglutarate taken up by the liver was recovered in the effluent as [14C]glutamine. 14CO2 and [14C]glutamine production from added [1-14C]oxoglutarate were dependent on the rate of hepatic glutamine synthesis but not on the direction of perfusion. Extrapolation of 14C incorporation into glutamine to maximal rates of hepatic glutamine synthesis yielded an

  19. Key Roles of Glutamine Pathways in Reprogramming the Cancer Metabolism

    Directory of Open Access Journals (Sweden)

    Krzysztof Piotr Michalak

    2015-01-01

    Full Text Available Glutamine (GLN is commonly known as an important metabolite used for the growth of cancer cells but the effects of its intake in cancer patients are still not clear. However, GLN is the main substrate for DNA and fatty acid synthesis. On the other hand, it reduces the oxidative stress by glutathione synthesis stimulation, stops the process of cancer cachexia, and nourishes the immunological system and the intestine epithelium, as well. The current paper deals with possible positive effects of GLN supplementation and conditions that should be fulfilled to obtain these effects. The analysis of GLN metabolism suggests that the separation of GLN and carbohydrates in the diet can minimize simultaneous supply of ATP (from glucose and NADPH2 (from glutamine to cancer cells. It should support to a larger extent the organism to fight against the cancer rather than the cancer cells. GLN cannot be considered the effective source of ATP for cancers with the impaired oxidative phosphorylation and pyruvate dehydrogenase inhibition. GLN intake restores decreased levels of glutathione in the case of chemotherapy and radiotherapy; thus, it facilitates regeneration processes of the intestine epithelium and immunological system.

  20. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    Science.gov (United States)

    Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

    1986-01-01

    The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

  1. Effects of dietary L-glutamine supplementation on specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine.

    Science.gov (United States)

    Chen, Shuai; Liu, Shuping; Zhang, Fengmei; Ren, Wenkai; Li, Nengzhang; Yin, Jie; Duan, Jielin; Peng, Yuanyi; Liu, Gang; Yin, Yulong; Wu, Guoyao

    2014-10-01

    Little is known about effects of dietary glutamine supplementation on specific and general defense responses in a vaccine-immunized animal model. Thus, this study determined roles for dietary glutamine supplementation in specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine. The measured variables included: (1) the production of pathogen-specific antibodies; (2) mRNA levels for pro-inflammatory cytokines, toll-like receptors and anti-oxidative factors; and (3) the distribution of P. multocida in tissues and the expression of its major virulence factors in vivo. Dietary supplementation with 0.5 % glutamine had a better protective role than 1 or 2 % glutamine against P. multocida infection in vaccine-immunized mice, at least partly resulting from its effects in modulation of general defense responses. Dietary glutamine supplementation had little effects on the production of P. multocida-specific antibodies. Compared to the non-supplemented group, dietary supplementation with 0.5 % glutamine had no effect on bacterial burden in vivo but decreased the expression of major virulence factors in the spleen. Collectively, supplementing 0.5 % glutamine to a conventional diet provides benefits in vaccine-immunized mice by enhancing general defense responses and decreasing expression of specific virulence factors.

  2. Intravenous caffeine versus intravenous ketorolac for the management of moderate to severe migraine headache

    Directory of Open Access Journals (Sweden)

    Alireza Baratloo

    2016-06-01

    Full Text Available The aim of this study was to determine if intravenous caffeine is as effective as intravenous ketorolac for the treatment of moderate to severe migraine headaches. Eligible patients randomly received 60 mg caffeine citrate or 60 mg ketorolac infused intravenously. Their pain score were measured at baseline, one hour and two hours after infusion. Therapeutic success was defined as decreasing of at least 3 points on the pain score. In total 110 patients were enrolled (75.5% women. Therapeutic success after 60 min was achieved by 63.6% of patients in the caffeine and 70.1% of patients in the ketorolac group (p = 0.23. After 120 min, 87.3% of the caffeine group and 83.6% of the ketorolac group achieved therapeutic success (p = 0.49. In this multi-center, randomized double blind study, intravenous caffeine was as effective as intravenous ketorolac for first line abortive management of acute migraine.

  3. Rotational Study of Natural Amino Acid Glutamine

    Science.gov (United States)

    Varela, Marcelino; Cabezas, Carlos; Alonso, José L.

    2014-06-01

    Recent improvements in laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) have allowed the investigation of glutamine (COOH-CH(NH2)-CH2-CH2-CONH2), a natural amino acid with a long polar side chain. One dominant structure has been detected in the rotational spectrum. The nuclear quadrupole hyperfine structure of two 14N nuclei has been totally resolved allowing the conclusive identification of the observed species.

  4. Regulation of glutamine synthetase activity in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 by the nitrogen source: effect of ammonium.

    OpenAIRE

    Mérida, A; Candau, P; Florencio, F J

    1991-01-01

    Glutamine synthetase activity from Synechocystis sp. strain PCC 6803 is regulated as a function of the nitrogen source available in the medium. Addition of 0.25 mM NH4Cl to nitrate-grown cells promotes a clear short-term inactivation of glutamine synthetase, whose enzyme activity decreases to 5 to 10% of the initial value in 25 min. The intracellular levels of glutamine, determined under various conditions, taken together with the results obtained with azaserine (an inhibitor of transamidases...

  5. Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.

    Science.gov (United States)

    Nguyen, T Van; Lee, J Eugene; Sweredoski, Michael J; Yang, Seung-Joo; Jeon, Seung-Je; Harrison, Joseph S; Yim, Jung-Hyuk; Lee, Sang Ghil; Handa, Hiroshi; Kuhlman, Brian; Jeong, Ji-Seon; Reitsma, Justin M; Park, Chul-Seung; Hess, Sonja; Deshaies, Raymond J

    2016-03-17

    Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4(CRBN) that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.

  6. Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver

    Institute of Scientific and Technical Information of China (English)

    Soledad Gonzales; Ariel H. Polizio; María A. Erario; María L. Tomaro

    2005-01-01

    AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat liver.METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

  7. A Novel Preparation Method of C-Terminal Glutamine Dipeptides

    Institute of Scientific and Technical Information of China (English)

    QIAN Shao-Song; LIU Yi; CHEN Ran; LI Jia-You; WU Xiao-Yan; JIAO Qing-Cai

    2006-01-01

    A novel synthesis method of dipeptides containing glutamine is reported. Protected L-amino acids were prepared by using inexpensive phthaloyl as the protecting group. Then the phthaloyl-L-amino acids were condensed with glutamine salts by the mixed anhydride method to afford phthaloyl dipeptides. Subsequently, the phthaloyl was removed from the dipeptides with hydrazine hydrate. As a result, optically pure glutamine-containing dipeptides were obtained in good yields.

  8. GLUTAMINE AND HYPERAMMONEMIC CRISES IN PATIENTS WITH UREA CYCLE DISORDERS

    Science.gov (United States)

    Lee, B.; Diaz, G.A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S.A.; Le Mons, C.; Bartley, J.; Longo, N.; Nagamani, S.C.; Berquist, W.; Gallagher, R.C.; Harding, C.O.; McCandless, S.E.; Smith, W.; Schulze, A.; Marino, M.; Rowell, R.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

    2016-01-01

    Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. Methods The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. Results The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8–29%) as compared with 56% (28%–154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2] µmol/L) than patients with baseline glutamine ≤900 µmol/L (26.6 [18.0] µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). Conclusions The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels. PMID:26586473

  9. Blockade of Glutamine Synthetase Enhances Inflammatory Response in Microglial Cells

    Science.gov (United States)

    Palmieri, Erika M.; Menga, Alessio; Lebrun, Aurore; Hooper, Douglas C.; Butterfield, D. Allan

    2017-01-01

    Abstract Aims: Microglial cells are brain-resident macrophages engaged in surveillance and maintained in a constant state of relative inactivity. However, their involvement in autoimmune diseases indicates that in pathological conditions microglia gain an inflammatory phenotype. The mechanisms underlying this change in the microglial phenotype are still unclear. Since metabolism is an important modulator of immune cell function, we focused our attention on glutamine synthetase (GS), a modulator of the response to lipopolysaccharide (LPS) activation in other cell types, which is expressed by microglia. Results: GS inhibition enhances release of inflammatory mediators of LPS-activated microglia in vitro, leading to perturbation of the redox balance and decreased viability of cocultured neurons. GS inhibition also decreases insulin-mediated glucose uptake in microglia. In vivo, microglia-specific GS ablation enhances expression of inflammatory markers upon LPS treatment. In the spinal cords from experimental autoimmune encephalomyelitis (EAE), GS expression levels and glutamine/glutamate ratios are reduced. Innovation: Recently, metabolism has been highlighted as mediator of immune cell function through the discovery of mechanisms that (behind these metabolic changes) modulate the inflammatory response. The present study shows for the first time a metabolic mechanism mediating microglial response to a proinflammatory stimulus, pointing to GS activity as a master modulator of immune cell function and thus unraveling a potential therapeutic target. Conclusions: Our study highlights a new role of GS in modulating immune response in microglia, providing insights into the pathogenic mechanisms associated with inflammation and new strategies of therapeutic intervention. Antioxid. Redox Signal. 26, 351–363. PMID:27758118

  10. Short time L-glutamine supplementation of malnourished rats Suplementação de ratos desnutridos com L-glutamina por tempo curto

    OpenAIRE

    Andréa Ferreira Schuwartz Tannus; Márcia Morandi Junqueira-Franco; Vivian Marques Miguel Suen; Guilherme Vannucchi Portari; Júlio Sérgio Marchini

    2005-01-01

    OBJETIVE: Considering that in malnourished patients supplemented with L-glutamine the negativity of the nitrogen balance tends to decrease, the present study aimed to determine whether malnourished Wistar rats supplemented with L-glutamine would show lower urinary nitrogen excretion, a greater deposition of nitrogen content in different tissues, and/or an alteration in the plasma amino acid levels. METHODS: The rats were divided into groups: 1) protein-energy malnutrition, 2) protein malnutri...

  11. Protective effects of L-glutamine against toxicity of deltamethrin in the cerebral tissue

    Directory of Open Access Journals (Sweden)

    Varol S

    2016-04-01

    Full Text Available Sefer Varol, Hasan Hüseyin Özdemir, Mehmet Uğur Çevik, Yaşar Altun, Ibrahim Ibiloğlu, Aysun Ekinci, Aslıhan Okan Ibiloğlu, Metin Balduz, Demet Arslan, Recep Tekin, Fesih Aktar, Mehmet Ufuk Aluçlu Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey Background: Deltamethrin (DLM is a broad-spectrum synthetic dibromo-pyrethroid pesticide that is widely used for agricultural and veterinary purposes. However, human exposure to the pesticide leads to neurotoxicity. Glutamine is one of the principal, free intracellular amino acids and may also be an antioxidant. This study was undertaken in order to examine the neuroprotective and antioxidant potential of L-glutamine against DLM toxicity in female Wistar albino rats. Materials and methods: The rats were divided into the following groups (n=10: Group I: control (distilled water; 10 mL/kg, po one dose, Group II: L-glutamine (1.5 g/kg, po one dose, Group III: DLM (35 mg/kg, po one dose, and Group IV: DLM (35 mg/kg, po one dose and L-glutamine (1.5 g/kg, po one dose after 4 hours. Total oxidant status (TOS, total antioxidant status (TAS, tumor necrosis factor-α, interleukin (IL-1β, and IL-6 levels and apoptosis were evaluated in brain tissue. Results: DLM-treated animals had a significant increase in brain biochemical parameters, as well as TOS and TAS. Furthermore, the histopathological examination showed neuronal cell degeneration in the cerebral tissue. L-Glutamine treatment decreased the elevated brain levels of TOS and neuronal cell degeneration. There was no difference in tumor necrosis factor-α, IL-1β, and IL-6 levels between the groups. Conclusion: L-Glutamine may reduce the toxic effects of DLM in the cerebral tissue through antioxidant properties. Keywords: deltamethrin, L-glutamine, rat

  12. Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis

    Institute of Scientific and Technical Information of China (English)

    Rodrigo Goulart Pacheco; Christiano Costa Esposito; Lucas CM Müller; Morgana TL Castelo-Branco; Leonardo Pereira Quintella; Vera Lucia A Chagas; Heitor Siffert P de Souza

    2012-01-01

    AIM:To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.METHODS:Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine,butyrate,or saline.Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure.Follow-up colonoscopy was performed every 4 wk for 12 wk.The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β,tumor necrosis factor-alpha,and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.RESULTS:Colonoscopies of the diverted segment showed mucosa with hyperemia,increased number of vessels,bleeding and mucus discharge.Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P =0.015; P =0.001),the number of goblet cells (P =0.021; P =0.029),and the rate of apoptosis within the epithelium (P =0.043; P =0.011) to normal values.The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.CONCLUSION:The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

  13. Dietary L-glutamine supplementation modulates microbial community and activates innate immunity in the mouse intestine.

    Science.gov (United States)

    Ren, Wenkai; Duan, Jielin; Yin, Jie; Liu, Gang; Cao, Zhong; Xiong, Xia; Chen, Shuai; Li, Tiejun; Yin, Yulong; Hou, Yongqing; Wu, Guoyao

    2014-10-01

    This study was conducted to determine effects of dietary supplementation with 1 % L-glutamine for 14 days on the abundance of intestinal bacteria and the activation of intestinal innate immunity in mice. The measured variables included (1) the abundance of Bacteroidetes, Firmicutes, Lactobacillus, Streptococcus and Bifidobacterium in the lumen of the small intestine; (2) the expression of toll-like receptors (TLRs), pro-inflammatory cytokines, and antibacterial substances secreted by Paneth cells and goblet cells in the jejunum, ileum and colon; and (3) the activation of TLR4-nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), and phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt) signaling pathways in the jejunum and ileum. In the jejunum, glutamine supplementation decreased the abundance of Firmicutes, while increased mRNA levels for antibacterial substances in association with the activation of NF-κB and PI3K-Akt pathways. In the ileum, glutamine supplementation induced a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes, and enhanced mRNA levels for Tlr4, pro-inflammatory cytokines, and antibacterial substances participating in NF-κB and JNK signaling pathways. These results indicate that the effects of glutamine on the intestine vary with its segments and compartments. Collectively, dietary glutamine supplementation of mice beneficially alters intestinal bacterial community and activates the innate immunity in the small intestine through NF-κB, MAPK and PI3K-Akt signaling pathways.

  14. Prolonging the survival of Tsc2 conditional knockout mice by glutamine supplementation.

    Science.gov (United States)

    Rozas, Natalia S; Redell, John B; McKenna, James; Moore, Anthony N; Gambello, Michael J; Dash, Pramod K

    2015-02-20

    The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. TSC patients exhibit developmental brain abnormalities and tuber formations that are associated with neuropsychological and neurocognitive impairments, seizures and premature death. Mechanistically, TSC1 and TSC2 loss of function mutations result in abnormally high mTORC1 activity. Thus, the development of a strategy to inhibit abnormally high mTORC1 activity may have therapeutic value in the treatment of TSC. mTORC1 is a master regulator of growth processes, and its activity can be reduced by withdrawal of growth factors, decreased energy availability, and by the immunosuppressant rapamycin. Recently, glutamine has been shown to alter mTORC1 activity in a TSC1-TSC2 independent manner in cells cultured under amino acid- and serum-deprived conditions. Since starvation culture conditions are not physiologically relevant, we examined if glutamine can regulate mTORC1 in non-deprived cells and in a murine model of TSC. Our results show that glutamine can reduce phosphorylation of S6 and S6 kinase, surrogate indicators of mTORC1 activity, in both deprived and non-deprived cells, although higher concentrations were required for non-deprived cultures. When administered orally to TSC2 knockout mice, glutamine reduced S6 phosphorylation in the brain and significantly prolonged their lifespan. Taken together, these results suggest that glutamine supplementation can be used as a potential treatment for TSC.

  15. The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress.

    Science.gov (United States)

    Aldarini, Nohaiah; Alhasawi, Azhar A; Thomas, Sean C; Appanna, Vasu D

    2017-01-17

    Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls. The enhanced activities of such enzymes as acetate kinase, adenylate kinase and nucleotide diphosphate kinase ensured the efficacy of this ATP producing-machine by transferring the high energy phosphate. The elevated amounts of phosphoenol pyruvate carboxylase and pyruvate orthophosphate dikinase recorded in the H2O2 exposed cells provided another route to ATP independent of the reduction of O2. This is the first demonstration of a metabolic pathway involving GS dedicated to ATP synthesis. The phospho-transfer network that is pivotal to the survival of the microorganism under oxidative stress may reveal therapeutic targets against infectious microbes reliant on glutamine for their proliferation.

  16. 1,25-Dihydroxyvitamin D inhibits glutamine metabolism in Harvey-ras transformed MCF10A human breast epithelial cell.

    Science.gov (United States)

    Zhou, Xuanzhu; Zheng, Wei; Nagana Gowda, G A; Raftery, Daniel; Donkin, Shawn S; Bequette, Brian; Teegarden, Dorothy

    2016-10-01

    Breast cancer is the second most common cancer among women in the US. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), is proposed to inhibit cellular processes and to prevent breast cancer. The current studies investigated the effect of 1,25(OH)2D on glutamine metabolism during cancer progression employing Harvey-ras oncogene transformed MCF10A human breast epithelial cells (MCF10A-ras). Treatment with 1,25(OH)2D significantly reduced intracellular glutamine and glutamate levels measured by nuclear magnetic resonance (NMR) by 23±2% each. Further, 1,25(OH)2D treatment reduced glutamine and glutamate flux, determined by [U-(13)C5] glutamine tracer kinetics, into the TCA cycle by 31±0.2% and 17±0.4%, respectively. The relative levels of mRNA and protein abundance of the major glutamine transporter, solute linked carrier family 1 member A5 (SLC1A5), was significantly decreased by 1,25(OH)2D treatment in both MCF10A-ras cells and MCF10A which overexpress ErbB2 (HER-2/neu). Consistent with these results, glutamine uptake was reduced by 1,25(OH)2D treatment and the impact was eliminated with the SLC1A5 inhibitor L-γ-Glutamyl-p-nitroanilide (GPNA). A consensus sequence to the vitamin D responsive element (VDRE) was identified in silico in the SLC1A5 gene promoter, and site-directed mutagenesis analyses with reporter gene studies demonstrate a functional negative VDRE in the promoter of the SLC1A5 gene. siRNA-SLC1A5 transfection in MCF10A-ras cells significantly reduced SLC1A5 mRNA expression as well as decreased viable cell number similar to 1,25(OH)2D treatment. SLC1A5 knockdown also induced an increase in apoptotic cells in MCF10A-ras cells. These results suggest 1,25(OH)2D alters glutamine metabolism in MCF10A-ras cells by inhibiting glutamine uptake and utilization, in part through down-regulation of SLC1A5 transcript abundance. Thus, 1,25(OH)2D down-regulation of the glutamine transporter, SLC1A5, may facilitate vitamin D prevention of breast

  17. Glutamine Reduces the Apoptosis of H9C2 Cells Treated with High-Glucose and Reperfusion through an Oxidation-Related Mechanism.

    Directory of Open Access Journals (Sweden)

    Kai Li

    Full Text Available Mitochondrial overproduction of reactive oxygen species (ROS in diabetic hearts during ischemia/reperfusion injury and the anti-oxidative role of glutamine have been demonstrated. However, in diabetes mellitus the role of glutamine in cardiomyocytes during ischemia/reperfusion injury has not been explored. To examine the effects of glutamine and potential mechanisms, in the present study, rat cardiomyoblast H9C2 cells were exposed to high glucose (33 mM and hypoxia-reoxygenation. Cell viability, apoptosis, intracellular glutamine, and mitochondrial and intracellular glutathione were determined. Moreover, ROS formation, complex I activity, membrane potential and adenosine triphosphate (ATP content were also investigated. The levels of S-glutathionylated complex I and mitochondrial apoptosis-related proteins, including cytochrome c and caspase-3, were analyzed by western blot. Data indicated that high glucose and hypoxia-reoxygenation were associated with a dramatic decline of intercellular glutamine and increase in apoptosis. Glutamine supplementation correlated with a reduction in apoptosis and increase of glutathione and glutathione reduced/oxidized ratio in both cytoplasm and mitochondria, but a reduction of intracellular ROS. Glutamine supplementation was also associated with less S-glutathionylation and increased the activity of complex I, leading to less mitochondrial ROS formation. Furthermore, glutamine supplementation prevented from mitochondrial dysfunction presented as mitochondrial membrane potential and ATP levels and attenuated cytochrome c release into the cytosol and caspase-3 activation. We conclude that apoptosis induced by high glucose and hypoxia-reoxygenation was reduced by glutamine supplementation, via decreased oxidative stress and inactivation of the intrinsic apoptotic pathway.

  18. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...... but more recent research has seriously questioned this.This volume of Advances in Neurobiology is intended to provide a detailed discussion of recent developments in research aimed at delineating the functional roles of the cycle taking into account that in order for this system to work there must...

  19. Release of arginine, glutamate and glutamine in the hippocampus of freely moving rats: Involvement of nitric oxide.

    Science.gov (United States)

    Watts, Jo; Fowler, Leslie; Whitton, Peter S; Pearce, Brian

    2005-05-30

    Using in vivo microdialysis, we have monitored the release of three amino acids (arginine, glutamate and glutamine) in the hippocampus of freely moving rats in response to various drugs. In response to N-methyl-d-aspartate (NMDA) infusion, extracellular glutamate was increased, glutamine was decreased and arginine remained unchanged. By contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) elicited an increase in arginine release but had no effect on either glutamate or glutamine. When S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was infused into the hippocampus, an increase in glutamate, a decrease in glutamine and no change in arginine were recorded. The effect of SNAP on extracellular glutamine levels was reversed by prior infusion of the guanylate cyclase inhibitor oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), however its effect on glutamate release was unchanged. Interestingly, SNAP was found to promote the release of arginine in the presence of ODQ. We also assessed the effect of two nitric oxide synthase inhibitors, N-nitro-l-arginine methylester (l-NAME) and 7-nitroindazole (7-NI), on the release of these amino acids. l-NAME was found to increase arginine and glutamate levels but decrease those of glutamine. In contrast, 7-NI reduced the release of all three amino acids. The results presented here confirm some but not all of the findings previously obtained using in vitro preparations. In addition, they suggest that complex relationships exist between the release of these amino acids, and that endogenous NO plays an important role in regulating their release.

  20. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise.

    Science.gov (United States)

    Legault, Zachary; Bagnall, Nicholas; Kimmerly, Derek S

    2015-10-01

    The study aimed to examine the effects that L-glutamine supplementation has on quadriceps muscle strength and soreness ratings following eccentric exercise. It was hypothesized that glutamine ingestion would quicken the recovery rate of peak force production and decrease muscle soreness ratings over a 72-hr recovery period. Sixteen healthy participants (8♀/8♂; 22 ± 4 years) volunteered in a double-blind, randomized, placebo-controlled crossover study. Supplement conditions consisted of isoenergetic placebo (maltodextrin, 0.6 g·kg-1·day-1) and L-glutamine (0.3 g·kg-1·day-1 + 0.3 g·kg-1·day-1 maltodextrin) ingestion once per day over 72 hr. Knee extensor peak torque at 0°, 30°, and 180° per second and muscle soreness were measured before, immediately following, 24, 48, and 72 hr posteccentric exercise. Eccentric exercise consisted of 8 sets (10 repetitions/set) of unilateral knee extension at 125% maximum concentric force with 2-min rest intervals. L-glutamine resulted in greater relative peak torque at 180°/sec both immediately after (71 ± 8% vs. 66 ± 9%), and 72 hr (91 ± 8% vs. 86 ± 7%) postexercise (all, p eccentric exercise. The effect of L-glutamine on muscle force recovery may be greater in men than women.

  1. Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

    Science.gov (United States)

    Oliveira, Gisele P; de Abreu, Marcelo Gama; Pelosi, Paolo; Rocco, Patricia R M

    2016-02-04

    Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting.

  2. Comparative aspects of tissue glutamine and proline metabolism.

    Science.gov (United States)

    Bertolo, Robert F; Burrin, Douglas G

    2008-10-01

    The cellular metabolism of glutamine and proline are closely interrelated, because they can be interconverted with glutamate and ornithine via the mitochondrial pathway involving pyrroline-5-carboxylate (P5C). In adults, glutamine and proline are converted via P5C to citrulline in the gut, then citrulline is converted to arginine in the kidney. In neonates, arginine is a semiindispensable amino acid and is synthesized from proline completely in the gut; because of low P5C synthase activity, glutamine is not an important precursor for neonatal arginine synthesis. Thus, splanchnic metabolism of glutamine and proline is important, because both amino acids serve as key precursors for arginine synthesis with some developmental differences. Studies investigating splanchnic extraction demonstrate that about two-thirds of dietary glutamine and almost all dietary glutamate are extracted on first pass and the vast majority is oxidized in the gut. This capacity to extract glutamine and glutamate appears to be very large, so diets high in glutamine or glutamate probably have little impact on circulating concentrations and consequent potential toxicity. In contrast, it appears that very little proline is extracted by the gut and liver, at least in the neonate, which may result in hyperprolinemia and potential toxicity. Therefore, the upper limits of safe dietary intake for glutamine and proline, and other amino acids, appear to be substantially different depending on the extent of first-pass splanchnic extraction and irreversible catabolism.

  3. Glutamine Synthetase Deficiency in Murine Astrocytes Results in Neonatal Death

    NARCIS (Netherlands)

    Y. He; T.B.M. Hakvoort; J.L.M. Vermeulen; W.T. Labruyere; D.R. de Waart; W.S. van der Hel; J.M. Ruijter; H.B.M. Uylings; W.H. Lamers

    2010-01-01

    Glutamine synthetase (GS) is a key enzyme in the "glutamine-glutamate cycle" between astrocytes and neurons, but its function in vivo was thus far tested only pharmacologically. Crossing GS(fl/lacZ) or GS(fl/f)l mice with hGFAP-Cre mice resulted in prenatal excision of the GS(fl) allele in astrocyte

  4. Exogenous Glutamine in Respiratory Diseases: Myth or Reality?

    Directory of Open Access Journals (Sweden)

    Gisele P. Oliveira

    2016-02-01

    Full Text Available Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF, asthma, chronic obstructive pulmonary disease (COPD, acute respiratory distress syndrome (ARDS, and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting.

  5. In vivo modification of Azotobacter chroococcum glutamine synthetase.

    Science.gov (United States)

    Muñoz-Centeno, M C; Cejudo, F J; Paneque, A

    1994-03-15

    A monospecific anti-(glutamine synthetase) antibody raised against glutamine synthetase of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 immunoreacted with glutamine synthetase from the N2-fixing heterotrophic bacterium Azotobacter chroococcum. In Western-blotting experiments this antibody recognized a single protein of a molecular mass of 59 kDa corresponding to glutamine synthetase subunit. This protein was in vivo-labelled in response to addition of ammonium, both [3H]adenine and H(3)32PO4 preincubation of the cells being equally effective. Nevertheless, the amount of glutamine synthetase present in A. chroococcum was independent of the available nitrogen source. Modified, inactive glutamine synthetase was re-activated by treatment with snake-venom phosphodiesterase but not by alkaline phosphatase. L-Methionine-DL-sulphoximine, an inhibitor of glutamine synthetase, prevented the enzyme from being covalently modified. We conclude that, in A. chroococcum, glutamine synthetase is adenylylated in response to ammonium and that for the modification to take place ammonium must be metabolized.

  6. Glutamine: A novel approach to chemotherapy-induced toxicity

    Directory of Open Access Journals (Sweden)

    Kumar Gaurav

    2012-01-01

    Full Text Available Treatment of cancer is associated with short- and long-term side-effects. Cancer produces a state of glutamine deficiency, which is further aggravated by toxic effects of chemotherapeutic agents leading to increased tolerance of tumor to chemotherapy as well as reduced tolerance of normal tissues to the side-effects of chemotherapy. This article reviews the possible role of glutamine supplementation in reducing the serious adverse events in patients treated with anticancer drugs. The literature related to the possible role of glutamine in humans with cancer and the supportive evidence from animal studies was reviewed. Searches were made and the literature was retrieved using PUBMED, MEDLINE, COCHRANE LIBRARY, CENAHL and EMBASE, with a greater emphasis on the recent advances and clinical trials. Glutamine supplementation was found to protect against radiation-induced mucositis, anthracycline-induced cardiotoxicity and paclitaxel-related myalgias/arthralgias. Glutamine may prevent neurotoxicity of paclitaxel, cisplatin, oxaplatin bortezomib and lenolidamide, and is beneficial in the reduction of the dose-limiting gastrointestinal toxic effects of irinotecan and 5-FU-induced mucositis and stomatitis. Dietary glutamine reduces the severity of the immunosuppressive effect induced by methotrexate and improves the immune status of rats recovering from chemotherapy. In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. Current data supports the usefulness of glutamine supplementation in reducing complications of chemotherapy; however, paucity of clinical trials weakens the clear interpretation of these findings.

  7. Corticosteroids increase glutamine utilization in human splanchnic bed

    Science.gov (United States)

    Glutamine is the most abundant amino acid in the body and is extensively taken up in gut and liver in healthy humans. To determine whether glucocorticosteroids alter splanchnic glutamine metabolism, the effect of prednisone was assessed in healthy volunteers using isotope tracer methods. Two groups ...

  8. Astrocyte glutamine synthetase: pivotal in health and disease.

    Science.gov (United States)

    Rose, Christopher F; Verkhratsky, Alexei; Parpura, Vladimir

    2013-12-01

    The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate-glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.

  9. Glutamine synthetase induced spinal seizures in rats.

    Science.gov (United States)

    Shin, Dong Won; Yoon, Young Sul; Matsumoto, Masato; Huang, Wencheng; Ceraulo, Phil; Young, Wise

    2003-02-01

    Glutamine synthetase (GS) is a key enzyme in the regulation of glutamate neurotransmission in the central nervous system. It is responsible for converting glutamate to glutamine, consuming one ATP and NH3 in the process. Glutamate is neurotoxic when it accumulates in extracellular fluids. We investigated the effects of GS in both a spinal cord injury (SCI) model and normal rats. 0.1-ml of low (2- micro M) and high (55- micro M) concentrations of GS were applied, intrathecally, to the spinal cord of rats under pentobarbital anesthesia. Immediately after an intrathecal injection into the L1-L3 space, the rats developed convulsive movements. These movements initially consisted of myoclonic twitches of the paravertebral muscles close to the injection site, repeated tonic and clonic contractions and extensions of the hind limbs (hind limb seizures) that spread to the fore limbs, and finally rotational axial movements of the body. An EMG of the paravertebral muscles, fore and hind limbs, showed the extent of the muscle activities. GS (2- micro M) caused spinal seizures in the rats after the SCI, and GS (6- micro M) produced seizures in the uninjured anesthetized rats. Denatured GS (70 degrees C, 1 hour) also produced spinal seizures, although higher concentrations were required. We suggest that GS may be directly blocking the release of GABA, or the receptors, in the spinal cord.

  10. Noncoding RNA of Glutamine Synthetase I Modulates Antibiotic Production in Streptomyces coelicolor A3(2)▿ ‡

    OpenAIRE

    D'Alia, Davide; Nieselt, Kay; Steigele, Stephan; Müller, Jonas; Verburg, Ilse; Takano, Eriko

    2009-01-01

    Overexpression of antisense chromosomal cis-encoded noncoding RNAss (ncRNAs) in glutamine synthetase I resulted in a decrease in growth, protein synthesis, and antibiotic production in Streptomyces coelicolor. In addition, we predicted 3,597 cis-encoded ncRNAs and validated 13 of them experimentally, including several ncRNAs that are differentially expressed in bacterial hormone-defective mutants.

  11. Effect of dietary glutamine on growth performance, non-specific immunity, expression of cytokine genes, phosphorylation of target of rapamycin (TOR), and anti-oxidative system in spleen and head kidney of Jian carp (Cyprinus carpio var. Jian).

    Science.gov (United States)

    Hu, Kai; Zhang, Jing-Xiu; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Zhou, Xiao-Qiu

    2015-06-01

    This study was designed to investigate the effects of dietary glutamine on the growth performance, cytokines, target of rapamycin (TOR), and antioxidant-related parameters in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed the basal (control) and glutamine-supplemented (12.0 g glutamine kg(-1) diet) diets for 6 weeks. Results indicated that the dietary glutamine supplementation improved the growth performance, spleen protein content, serum complement 3 content, and lysozyme activity in fish. In the spleen, glutamine down-regulated the expression of the interleukin 1 and interleukin 10 genes, and increased the level of phosphorylation of TOR protein. In the head kidney, glutamine down-regulated the tumor necrosis factor α and interleukin 10 gene expressions, phosphorylated and total TOR protein levels, while up-regulated the transforming growth factor β2 gene expression. Furthermore, the protein carbonyl content was decreased in the spleen of fish fed glutamine-supplemented diet; conversely, the anti-hydroxyl radical capacity and glutathione content in the spleen were increased by glutamine. However, diet supplemented with glutamine did not affect the lipid peroxidation, anti-superoxide anion capacity, and antioxidant enzyme activities in the spleen. Moreover, all of these antioxidant parameters in the head kidney were not affected by glutamine. Results from the present experiment showed the importance of dietary supplementation of glutamine in benefaction of the growth performance and several components of the innate immune system, and the deferential role in cytokine gene expression, TOR kinase activity, and antioxidant status between the spleen and head kidney of juvenile Jian carp.

  12. A phase I trial of intravenous catumaxomab

    DEFF Research Database (Denmark)

    Mau-Sørensen, Morten; Dittrich, Christian; Dienstmann, Rodrigo;

    2015-01-01

    design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab. Key DLTs were ≥grade 3 optimally treated non-hematological toxicity; ≥grade 3 infusion-related reactions refractory to supportive....... A reversible decrease in liver function test (prothrombin time) at the 7-µg dose level was considered a DLT. The first patient at 10 µg experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study. CONCLUSIONS: The MTD of weekly intravenous catumaxomab was 7 µg. Major...

  13. N-carbamylglutamate augments ureagenesis and reduces ammonia and glutamine levels in patients with propionic acidemia

    Science.gov (United States)

    Mew, Nicholas Ah; McCarter, Robert; Daikhin, Yevgeny; Nissim, Itzhak; Yudkoff, Marc; Tuchman, Mendel

    2012-01-01

    Objective To determine whether N-carbamylglutamate reduces plasma levels of ammonia and glutamine and increases ureagenesis rate in patients with propionic acidemia Patients and Methods Identical four-hour studies were performed before and immediately after a 3-day trial of oral N-carbamylglutamate in 7 patients with propionic acidemia. An oral bolus of [13C]-sodium acetate was administered at the start of each study, and sequential blood samples were obtained to measure [13C]-urea, ammonia, urea and amino acids. Results With longitudinal mixed effects linear regression, peak [13C]urea increased following treatment with N-carbamylglutamate (from 2.2 μM to 3.8 μM; p carbamylglutamate augments ureagenesis and decreases plasma ammonia and glutamine in patients with propionic acidemia. The drug may serve as an important therapeutic adjunct in the treatment of acute hyperammonemia in this disorder. PMID:20566609

  14. Carnosine modulates glutamine synthetase expression in senescent astrocytes exposed to oxygen-glucose deprivation/recovery.

    Science.gov (United States)

    Shi, Xiaojie; Wang, Bingyu; Liu, Yuan; Zhang, Jingjing; Huang, Yuyan; Cao, Pei; Shen, Yao; Lyu, Jianxin

    2017-01-20

    Carnosine is believed to be neuroprotective in cerebral ischemia. However, few reports concern its function on senescent astrocytes during cerebral ischemia. The aim of this study was to investigate the effects of carnosine on cell damage and glutamine synthetase (GS) expression in D-galactose-induced senescent astrocytes exposed to oxygen-glucose deprivation/recovery (OGD/R). The results showed that OGD/R caused massive cell damage and a significant decrease in GS expression both in the young and senescent astrocytes. The GS expression level was partly recovered whereas it continued to decline in the recovery stage in the young and senescent astrocytes, respectively. Decreased GS expression significantly inhibited glutamate uptake and glutamine production and release. Carnosine prevented the cell damage, rescued the expression of GS and reversed the glutamate uptake activity and glutamine production in the senescent astrocytes exposed to OGD/R. The modulatory effect of carnosine on GS expression was partly antagonized by pyrilamine, a selective histamine H1 receptors antagonist, but not bestatin. Bisindolylmaleimide II, a broad-spectrum inhibitor of PKC could also reverse the action of carnosine on GS expression. Thus, histamine H1 receptors and PKC pathway may be involved in the modulatory action of carnosine in GS expression in the senescent astrocytes exposed to OGD/R.

  15. H-independent glutamine transport in plant root tips.

    Directory of Open Access Journals (Sweden)

    Huaiyu Yang

    Full Text Available BACKGROUND: Glutamine is one of the primary amino acids in nitrogen assimilation and often the most abundant amino acid in plant roots. To monitor this important metabolite, a novel genetically encoded fluorescent FRET-reporter was constructed and expressed in Arabidopsis thaliana. As a candidate for the glutamine fluxes, the root tip localized, putative amino acid transporter CAT8 was analyzed and heterologously expressed in yeast and oocytes. PRINCIPAL FINDINGS: Rapid and reversible in vivo fluorescence changes were observed in reporter-expressing root tips upon exposure and removal of glutamine. FRET changes were detected at acid and neutral pH and in the presence of a protonophore, suggesting that part of the glutamine fluxes were independent of the pH. The putative amino acid transporter CAT8 transported glutamine, had a half maximal activity at approximately 100 microM and the transport was independent of external pH. CAT8 localized not only to the plasma membrane, but additionally to the tonoplast, when tagged with GFP. Ultrastructural analysis confirmed this dual localization and additionally identified CAT8 in membranes of autophagosomes. Loss-of function of CAT8 did not affect growth in various conditions, but over-expressor plants had increased sensitivity to a structural substrate analog, the glutamine synthetase inhibitor L-methionine sulfoximine. CONCLUSIONS: The combined data suggest that proton-independent glutamine facilitators exist in root tips.

  16. Glutamine dipeptide for parenteral nutrition in abdominal surgery: A meta-analysis of randomized controlled trials

    Institute of Scientific and Technical Information of China (English)

    Ya-Min Zheng; Fei Li; Ming-Ming Zhang; Xiao-Ting Wu

    2006-01-01

    AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition(PN) in patients undergoing abdominal surgery.METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases:the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of <0.05 was considered statistically significant.RESULTS: Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002),decreasing postoperative infectious morbidity (OR = 0.24,95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P<0.00001). No serious adverse effects were found.CONCLUSION: Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.

  17. Glutaminólise em astrocitomas

    OpenAIRE

    2014-01-01

    O metabolismo da glutamina (Gln) é alvo de atenções recentes para a compreensão da reprogramação metabólica para o suprimento energético das células tumorais em proliferação e para o desenvolvimento de novas estratégias terapêuticas em câncer. Tanto a absorção de glutamina quanto a taxa de glutaminólise, o catabolismo da Gln para gerar adenosina trifosfato (ATP) e lactato na mitocôndria estão aumentados em diferentes tumores. A Gln e glicose participam do processo da proliferação de células t...

  18. Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro

    Science.gov (United States)

    Max, Stephen R.; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa; Konagaya, Masaaki

    1987-01-01

    The regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture is studied. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

  19. The glutamine synthetase gene family in Populus

    Directory of Open Access Journals (Sweden)

    Cánovas Francisco M

    2011-08-01

    Full Text Available Abstract Background Glutamine synthetase (GS; EC: 6.3.1.2, L-glutamate: ammonia ligase ADP-forming is a key enzyme in ammonium assimilation and metabolism of higher plants. The current work was undertaken to develop a more comprehensive understanding of molecular and biochemical features of GS gene family in poplar, and to characterize the developmental regulation of GS expression in various tissues and at various times during the poplar perennial growth. Results The GS gene family consists of 8 different genes exhibiting all structural and regulatory elements consistent with their roles as functional genes. Our results indicate that the family members are organized in 4 groups of duplicated genes, 3 of which code for cytosolic GS isoforms (GS1 and 1 which codes for the choroplastic GS isoform (GS2. Our analysis shows that Populus trichocarpa is the first plant species in which it was observed the complete GS family duplicated. Detailed expression analyses have revealed specific spatial and seasonal patterns of GS expression in poplar. These data provide insights into the metabolic function of GS isoforms in poplar and pave the way for future functional studies. Conclusions Our data suggest that GS duplicates could have been retained in order to increase the amount of enzyme in a particular cell type. This possibility could contribute to the homeostasis of nitrogen metabolism in functions associated to changes in glutamine-derived metabolic products. The presence of duplicated GS genes in poplar could also contribute to diversification of the enzymatic properties for a particular GS isoform through the assembly of GS polypeptides into homo oligomeric and/or hetero oligomeric holoenzymes in specific cell types.

  20. Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

    Science.gov (United States)

    Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

    2014-01-01

    Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

  1. Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

    Science.gov (United States)

    Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

    2014-08-01

    Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

  2. Inhibition of glutamine synthesis induces glutamate dehydrogenase-dependent ammonia fixation into alanine in co-cultures of astrocytes and neurons.

    Science.gov (United States)

    Dadsetan, Sherry; Bak, Lasse K; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Leke, Renata; Schousboe, Arne; Waagepetersen, Helle S

    2011-09-01

    It has been previously demonstrated that ammonia exposure of neurons and astrocytes in co-culture leads to net synthesis not only of glutamine but also of alanine. The latter process involves the concerted action of glutamate dehydrogenase (GDH) and alanine aminotransferase (ALAT). In the present study it was investigated if the glutamine synthetase (GS) inhibitor methionine sulfoximine (MSO) would enhance alanine synthesis by blocking the GS-dependent ammonia scavenging process. Hence, co-cultures of neurons and astrocytes were incubated for 2.5h with [U-(13)C]glucose to monitor de novo synthesis of alanine and glutamine in the absence and presence of 5.0 mM NH(4)Cl and 10 mM MSO. Ammonia exposure led to increased incorporation of label but not to a significant increase in the amount of these amino acids. However, in the presence of MSO, glutamine synthesis was blocked and synthesis of alanine increased leading to an elevated content intra- as well as extracellularly of this amino acid. Treatment with MSO led to a dramatic decrease in glutamine content and increased the intracellular contents of glutamate and aspartate. The large increase in alanine during exposure to MSO underlines the importance of the GDH and ALAT biosynthetic pathway for ammonia fixation, and it points to the use of a GS inhibitor to ameliorate the brain toxicity and edema induced by hyperammonemia, events likely related to glutamine synthesis.

  3. Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux

    NARCIS (Netherlands)

    F. Grüne (Frank); S. Kazmaier (Stephan); B. Sonntag (Barbara); R.J. Stolker (Robert); A. Weyland (Andreas)

    2014-01-01

    textabstractBACKGROUND:: Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cer

  4. The effect of intravenous preemptive paracetamol on postoperative ...

    African Journals Online (AJOL)

    2014-07-12

    Jul 12, 2014 ... Aim: We investigated the efficacy of intravenous (IV) preemptive paracetamol on postoperative total .... rate below 50 bpm) and hypotension (a decrease of >30% ... to treatment groups in the post‑anesthesia recovery room.

  5. Glutamate and CO2 production from glutamine in incubated enterocytes of adult and very old rats

    OpenAIRE

    Meynial-Denis, Dominique; Bielicki, Guy; Beaufrere, Anne-Marie; MIGNON, Michelle; Patureau Mirand, Philippe; Renou, Jean-Pierre

    2013-01-01

    Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial ce...

  6. Proximal Tubule Glutamine Synthetase Expression is Necessary for the Normal Response to Dietary Protein Restriction.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Verlander, Jill W; Weiner, I David

    2017-03-22

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The current study's purpose was to determine proximal tubule GS's role in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule glutamine synthetase expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

  7. Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats.

    Science.gov (United States)

    Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

    2016-08-04

    Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p carbamylglutamate significantly increased the urine levels of creatinine, ethanol, indoxyl sulfate, lactate, methymalonate, acetoacetate, m-hydroxyphenylacetate, and sarcosine, and decreased the urine levels of acetamide, acetate, citrulline, creatine, glycine, hippurate, homogentisate, N-acetylglutamate, phenylacetyglycine, acetone, and p-hydroxyphenylacetate (p carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats.

  8. Evolution of the Maillard Reaction in Glutamine or Arginine-Dextrinomaltose Model Systems

    Directory of Open Access Journals (Sweden)

    Silvia Pastoriza

    2016-12-01

    Full Text Available Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o-phtaldialdehyde (OPA, 5-Hydroximethylfurfural (HMF, furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm. The systems were prepared by mixing glutamine or arginine with dextrinomaltose (similar ingredients to those used in special enteral formula, and heated at 100 °C, 120 °C and 140 °C for 0 to 30 min. The recorded changes in the concentration of furanic compounds was only useful for longer heating times of high temperatures, while absorbance and fluorescence measurements were useful in all the assayed conditions. In addition, easiness and sensitivity of absorbance and fluorescence make them useful techniques that could be implemented as indicators for monitoring the manufacture of special enteral formulas. Glucosylisomaltol is a useful indicator to monitor the manufacture of glutamine-enriched enteral formulas.

  9. Evolution of the Maillard Reaction in Glutamine or Arginine-Dextrinomaltose Model Systems

    Science.gov (United States)

    Pastoriza, Silvia; Rufián-Henares, José Ángel; García-Villanova, Belén; Guerra-Hernández, Eduardo

    2016-01-01

    Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o-phtaldialdehyde (OPA), 5-Hydroximethylfurfural (HMF), furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm. The systems were prepared by mixing glutamine or arginine with dextrinomaltose (similar ingredients to those used in special enteral formula), and heated at 100 °C, 120 °C and 140 °C for 0 to 30 min. The recorded changes in the concentration of furanic compounds was only useful for longer heating times of high temperatures, while absorbance and fluorescence measurements were useful in all the assayed conditions. In addition, easiness and sensitivity of absorbance and fluorescence make them useful techniques that could be implemented as indicators for monitoring the manufacture of special enteral formulas. Glucosylisomaltol is a useful indicator to monitor the manufacture of glutamine-enriched enteral formulas.

  10. Kinetic properties of a phosphate-bond-driven glutamate-glutamine transport system in Streptococcus lactis and Streptococcus cremoris.

    Science.gov (United States)

    Poolman, B; Smid, E J; Konings, W N

    1987-06-01

    In Streptococcus lactis ML3 and Streptococcus cremoris Wg2 the uptake of glutamate and glutamine is mediated by the same transport system, which has a 30-fold higher affinity for glutamine than for glutamate at pH 6.0. The apparent affinity constant for transport (KT) of glutamine is 2.5 +/- 0.3 microM, independent of the extracellular pH. The KTS for glutamate uptake are 3.5, 11.2, 77, and 1200 microM at pH 4.0, 5.1, 6.0, and 7.0, respectively. Recalculation of the affinity constants based on the concentration of glutamic acid in the solution yield KTS of 1.8 +/- 0.5 microM independent of the external pH, indicating that the protonated form of glutamate, i.e., glutamic acid, and glutamine are the transported species. The maximal rates of glutamate and glutamine uptake are independent of the extracellular pH as long as the intracellular pH is kept constant, despite large differences in the magnitude and composition of the components of the proton motive force. Uptake of glutamate and glutamine requires the synthesis of ATP either from glycolysis or from arginine metabolism and appears to be essentially unidirectional. Cells are able to maintain glutamate concentration gradients exceeding 4 X 10(3) for several hours even in the absence of metabolic energy. The t1/2s of glutamate efflux are 2, 12, and greater than 30 h at pH 5.0, 6.0, and 7.0, respectively. After the addition of lactose as energy source, the rate of glutamine uptake and the level of ATP are both very sensitive to arsenate. When the intracellular pH is kept constant, both parameters decrease approximately in parallel (between 0.2 and 1.0 mM ATP) with increasing concentrations of the inhibitor. These results suggest that the accumulation of glutamate and glutamine is energized by ATP or an equivalent energy-rich phosphorylated intermediate and not by the the proton motive force.

  11. Oral Glutamine Supplementation Benefits Jejunum but Not Ileum

    Directory of Open Access Journals (Sweden)

    Paul E Hardy

    1994-01-01

    Full Text Available Glutamine is the primary metabolic fuel of the small intestine. The ability of enteral glutamine to support jejunal architecture and metabolism is well established, but its effect on intestinal absorptive function, especially in the terminal ileum, remains undetermined. The purpose of this study was to develop a functional ileal fluid absorption surgical injury model and to determine if oral glutamine supplementation would be beneficial in accelerating healing and restoring function. The effects of either 1 cm resection and ileal end-to-end anastomosis or sham laparotomy on rat in vivo fluid absorption at study start (day 0, one and two days was investigated. In sham-operated rats, fluid absorption was not altered. In contrast, ileal fluid absorption was significantly reduced at days 0 (17.2±4.8 μL/cm/h and 1 (31.4±13.6 μL/cm/h, but returned to normal by day 2 (71.0±6.2 μL/cm/h in anastomosed rats. To examine the effects of glutamine in this model, rats were fed either glutamine (2.4 g/kg/day or an isonitrogenous glycine-supplemented elemental oral diet for five days before their randomization to sham or anastomotic groups. This dose of glutamine reached the ileum and was completely absorbed along the small intestine. Glutamine-fed rats demonstrated no difference in recovery of in vivo ileal fluid absorption, ileal villus morphometric measurements, mg DNA:mg protein ratio, degree of inflammation or glutaminase activity. In contrast, jejunal, but not ileal, villus morphometry, mg DNA:mg protein ratio and glutaminase activity were increased in glutamine-fed ‘not operated’ rats (P<0.01, indicating that the jejunum, but not the ileum, responded to the glutamine-supplemented diet. These studies demonstrate that ileal resection and anastomosis causes transient impairments in in vivo fluid absorption, and oral glutamine supplementation offers a beneficial effect to jejunal, but not ileal, intestinal mucosa. These results suggest

  12. Efeitos metabólicos da L-alanil-glutamina em ratos submetidos à isquemia da pata traseira esquerda seguida de reperfusão Metabolic effects of L-alanyl-glutamine in rats subjected to left hind leg ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    João Martins de Souza Torres

    2003-01-01

    Full Text Available OBJETIVO: Objetivou-se investigar os efeitos metabólicos da L-alanil glutamina no tecido muscular e sangue arterial de ratos Wistar submetidos à isquemia aguda da pata traseira. MÉTODOS: Utilizaram-se 48 ratos machos distribuídos em 4 grupos (1- controle / 2 - experimento, redistribuídos em 2 subgrupos (n=06. Trinta minutos após a injeção de uma solução a 20% de L-alanil-glutamina (0,75mg/ grupo 2 ou solução salina (grupo 1 na veia jugular direita ocluiu-se a artéria ilíaca comum esquerda por 30 minutos, por pinçamento. Amostras musculares e de sangue arterial foram obtidas logo após a remoção da pinça (tempo 0 e 5, 15 e 30 mais tarde. RESULTADOS: Observou-se redução significativa (p PURPOSE: An experimental study has been conducted to investigate acute ischemic changes in concentrations of glucose, piruvate, lactate and ketone bodies in rat hind leg muscle and arterial blood after intravenous injection of l-alanil-glutamine solution. METHODS: Forty-eight male Wistar rats were distributed into two groups: Group 1 (Control and Group 2 (Experiment. Each group was divided into 4 subgroups (n=6. Thirty minutes after administration of 20% solution of L-alanil-glutamine (0,75g/Kg, group 1 or saline solution (group 2 into right jugular vein, a clamp was placed across left common iliac artery for 30 minutes. Samples from left thigh muscle and arterial blood from abdominal aorta were collected at the end of ischemic period (subgroup 0 and 5, 15 and 30 minutes later. RESULTS: Glucose concentrations were decreased (p<0.05 in experiment group muscles, compared to respective control (subgroup 15 min and significantly increased in subgroups 15 and 30 min as compared to subgroup 0 min. There was no difference in glycemia and pyruvate concentrations when comparing experiment versus control rats. Decreased lactate concentrations might be related to L-alanyl glutamine effects. CONCLUSIONS: Increased availability of L-alanil-glutamine

  13. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis.

    OpenAIRE

    Levine, R L; Oliver, C N; Fulks, R M; Stadtman, E R

    1981-01-01

    We partially purified a preparation from Escherichia coli that proteolytically degrades the enzyme glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. The degradation is at least a two-step process. First, the glutamine synthetase undergoes an oxidative modification. This modification leads to loss of catalytic activity and also renders the protein susceptible to proteolytic attack in the second step. The oxidative step displays characteristics of a mixed-function oxi...

  14. Secondary NAD+ deficiency in the inherited defect of glutamine synthetase.

    Science.gov (United States)

    Hu, Liyan; Ibrahim, Khalid; Stucki, Martin; Frapolli, Michele; Shahbeck, Noora; Chaudhry, Farrukh A; Görg, Boris; Häussinger, Dieter; Penberthy, W Todd; Ben-Omran, Tawfeg; Häberle, Johannes

    2015-11-01

    Glutamine synthetase (GS) deficiency is an ultra-rare inborn error of amino acid metabolism that has been described in only three patients so far. The disease is characterized by neonatal onset of severe encephalopathy, low levels of glutamine in blood and cerebrospinal fluid, chronic moderate hyperammonemia, and an overall poor prognosis in the absence of an effective treatment. Recently, enteral glutamine supplementation was shown to be a safe and effective therapy for this disease but there are no data available on the long-term effects of this intervention. The amino acid glutamine, severely lacking in this disorder, is central to many metabolic pathways in the human organism and is involved in the synthesis of nicotinamide adenine dinucleotide (NAD(+)) starting from tryptophan or niacin as nicotinate, but not nicotinamide. Using fibroblasts, leukocytes, and immortalized peripheral blood stem cells (PBSC) from a patient carrying a GLUL gene point mutation associated with impaired GS activity, we tested whether glutamine deficiency in this patient results in NAD(+) depletion and whether it can be rescued by supplementation with glutamine, nicotinamide or nicotinate. The present study shows that congenital GS deficiency is associated with NAD(+) depletion in fibroblasts, leukocytes and PBSC, which may contribute to the severe clinical phenotype of the disease. Furthermore, it shows that NAD(+) depletion can be rescued by nicotinamide supplementation in fibroblasts and leukocytes, which may open up potential therapeutic options for the treatment of this disorder.

  15. Glutamine and antioxidants: status of their use in critical illness.

    Science.gov (United States)

    van Zanten, Arthur R H

    2015-03-01

    Many studies in critically ill patients have addressed enteral or parenteral supplementation of glutamine and antioxidants to counteract assumed deficiencies and induce immune-modulating effects to reduce infections and improve outcome. Older studies showed marked reductions in mortality, infectious morbidity and length of stay. Recent studies no longer show beneficial effects and in contrast even demonstrated increased mortality. This opiniating review focuses on the latest information and the consequences for the use of glutamine and antioxidants in critically ill patients. Positive effects in systematic reviews and meta-analyses are based on results from older, smaller and mainly single-centre studies. New information has challenged the conditional deficiency hypothesis concerning glutamine in critically ill patients. The recent REDOXS and MetaPlus trials studying the effects of glutamine, selenium and other antioxidants have shown no benefits and increased mortality. Given that the first dictum in medicine is to do no harm, we cannot be confident that immune-modulating nutrient supplementation with glutamine and antioxidants is effective and well tolerated for critically ill patients. Until more data are available, it is probably better not to routinely administer glutamine and antioxidants in nonphysiological doses to mechanically ventilated critically ill patients.

  16. Understanding the mechanisms of glutamine action in critically ill patients

    Directory of Open Access Journals (Sweden)

    Gisele P. Oliveira

    2010-06-01

    Full Text Available Glutamine (Gln is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.A glutamina (Gln é uma importante fonte de energia e tem sido usada como substrato energético suplementar. Além disso, a Gln é um componente essencial para numerosas funções metabólicas tais como: homeostase ácido-base, gliconeogênese, transporte de nitrogênio e síntese de proteínas e ácidos nucléicos. Portanto, a glutamina desempenha um papel importante na homeostase celular e no metabolismo dos órgãos. Esse artigo objetiva rever os mecanismos de ação da glutamina na doen

  17. Increasing the culture efficiency of hybridoma cells by the use of integrated metabolic control of glucose and glutamine at low levels.

    Science.gov (United States)

    Li, Ling; Mi, Li; Feng, Qiang; Liu, Rong; Tang, Hao; Xie, Li; Yu, Xiaoling; Chen, Zhinan

    2005-08-01

    The metabolism of HAb18 hybridoma cells was shifted to decrease metabolite accumulation and to improve culture efficiency by integrated metabolic control of glucose and glutamine at low levels. When glucose and glutamine levels were decreased to 0.5 and 0.3 mM respectively, lactate and ammonia production were reduced by 62.6 and 74% respectively, glucose-to-cell yield was increased from 0.23x10(9) to 0.66x10(9) cells.mmol-1, and glutamine-to-cell yield from 0.18x10(9) to 1.95x10(9) cells.mmol-1. Compared with high-level glucose and glutamine fed-batch cultures, low-level glucose and glutamine led to higher cell density (1.0x10(7) versus 0.3x10(7) cells.ml-1), longer culture span (14 as opposed to 8 days) and higher antibody yield (250 as against 150 mg.l-1). These results indicate that hybridoma culture efficiency would be increased by the integrated control of glucose and glutamine at 0.5 and 0.3 mM respectively. In contrast with previously reported glucose-and/or-glutamine-level-controlled fed-batch cultures, we demonstrated an efficient strategy of nutrient level selection and amino acid feeding. More importantly, our accurately and well-distributed Equable Feeding Control System opens a new avenue for reducing metabolites to low levels by controlling nutrients at low levels.

  18. {open_quotes}The effects of diabetes on the activity of the enzyme glutamine: fructose-6-phosphate amindotransferase{close_quotes}

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, S.P.

    1994-12-31

    Hexsoamine synthetic pathway (HexNSP) controls the supply of essential substrates for glycoprotein synthesis. In vitro studies suggest that increased flux of glucose via the hexsoamine synthetic pathway may play a role in glucose induced insulin resistance of glucose transport. Glutamine: fructose-6-phosphate amindotransferase (GFAT) controls flux into the hexsoamine synthetic pathway; the major products are UDPN-acetylhexosamines (UDP.HexNac=UDP.GlcNAc= UDP.GalNac). I examined whether diabetes ({approximately} 7 days post intravenous streptozotocin, and genetically linked) affects the activity of glutamine: fructose-6-phosphate in rat and mouse skeletal muscle in vivo. Nucleotide linked HexNAc were analyzed by high pressure liquid chromatography(HPLC) in deproteinized hind limb muscle extracts.

  19. L-glutamine and whole protein restore first-phase insulin response and increase glucagon-like Peptide-1 in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Samocha-Bonet, Dorit; Chisholm, Don J; Holst, Jens Juul

    2015-01-01

    protein low in glutamine, on insulin response in well-controlled T2D patients. In a randomized study with a crossover design, T2D patients (n = 10, 6 men) aged 65.1 ± 5.8, with glycosylated hemoglobin (HbA1c) 6.6% ± 0.7% (48 ± 8 mmol/mol), received oral l-glutamine (25 g), protein (25 g) or water......, followed by an intravenous glucose bolus (0.3 g/kg) and hyperglycemic glucose clamp for 2 h. Blood was frequently collected for analyses of glucose, serum insulin and plasma total and active GLP-1 and area under the curve of glucose, insulin, total and active GLP-1 excursions calculated. Treatments were...

  20. Intravenous magnetic resonance arthrography of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hyeon; Lee, Young Uk; Suh, Jong Dae; Lee, Seung Hee; Kim, Dong Joo [Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    1995-10-15

    Knee MR images were repeatedly obtained after intravenous administration of gadopentetate dimeglumine to evaluate the arthrographic effect and to determine the optimal scan timing and technique. Sagittal T1-weighted (650/15) sequences were repeated before and after intravenous gadolinium enhancement in 26 patients who were divided into exercise (14/26) and nonexercise (12/26) groups. Fourteen patients in exercise group were allowed to move the affected knee joint actively for 10 minutes immediately after the first post-enhancement scan and before repeating scans. The signal intensities in central and peripheral portions of the joint were measured and compared between these two groups. In all cases, enhancement of joint fluid began at peripheral portion and progressed toward central portion. The diffusion rate in exercise group was far faster than that in nonexercise group and homogeneous arthrographic image was revealed within 10 minutes after completion of joint movement. The arthrographic effect continued and the rate of signal decrease was quite slow. MR arthrographic image of knee joint can be obtained within 10 minutes after completion of a few minute exercise following intravenous injection of gadopentetate dimeglumine. Intravenous MR arthrography is expected to become an useful method as a convenient alternative to direct MR arthrography.

  1. Effect of cysteine and glutamine added to extender on post-thaw sperm functional parameters of buffalo bull.

    Science.gov (United States)

    Topraggaleh, T R; Shahverdi, A; Rastegarnia, A; Ebrahimi, B; Shafiepour, V; Sharbatoghli, M; Esmaeili, V; Janzamin, E

    2014-09-01

    Amino acids seem to be crucial components for semen freezing extender due to antioxidant properties. Therefore, this study aimed to assess motility parameters, membrane integrity, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and DNA damage to detect the optimum concentrations of cysteine and glutamine for buffalo semen cryopreservation. Twenty ejaculates of four buffalo bulls were diluted in tris-egg yolk extender and divided into seven equal groups consisting of cysteine (5, 7.5 and 10 mmol), glutamine (10, 15 and 20 mmol) and no additive. Supplementation of 5 and 7.5 mmol cysteine and 15 mmol glutamine in cryopreservation extender significantly increased post-thaw motility and plasma membrane integrity of spermatozoa with significant reduction in intracellular ROS when compared with control groups (P Cysteine at 7.5 mmol concentration elevated progressive motility and MMP, compared with control (P cysteine and 15 mmol glutamine in semen cryopreservation extender has more potential to decrease intracellular ROS, and subsequently elevate motility and membrane integrity of buffalo frozen-thawed spermatozoa.

  2. [¹³N]Ammonia positron emission tomographic/computed tomographic imaging targeting glutamine synthetase expression in prostate cancer.

    Science.gov (United States)

    Shi, Xinchong; Zhang, Xiangsong; Yi, Chang; Liu, Yubo; He, Qiao

    2014-01-01

    The purpose of this study was to investigate the expression of glutamine synthetase (GS) in prostate cancer (PCa) and the utility of [¹³N]ammonia positron emission tomography/computed tomography (PET/CT) in the imaging of PCa. The uptake ratio of [¹³N]ammonia and the expression of GS in PC3 and DU145 cells was measured. Thirty-four patients with suspected PCa underwent [¹³N]ammonia PET/CT imaging, and immunohistochemistry staining of GS was performed. The uptake of [¹³N]ammonia in PC3 and DU145 cells elevated along with the decrease in glutamine in medium. The expression of GS messenger ribonucleic acid and protein also increased when glutamine was deprived. In biopsy samples, the GS expression scores were significantly higher in PCa tissue than in benign tissues (p glutamine. GS is the main reason for the uptake of [¹³N]ammonia, and [¹³N]ammonia is a useful tracer for PCa imaging.

  3. The effact of glutamine supplementation in patients following elective operation and accidental injury%择期手术/意外创伤后补充谷氨酰胺的效应

    Institute of Scientific and Technical Information of China (English)

    DouglasW

    2001-01-01

    The etabolic response to injury,whether a controlled electivesurgical procedure or an accidental injury,is characterized by the breakdown of skeletal muscle protein and the translocation of the amino acids to visceral organs and the wound.At these sites the substrate serves to dnhance host defenses,and support vital organ function and wound repair.Glutamine (GLN) plays a major role in this process,accounting for approximately one-third of the translocated nitrogen.From the data available,GLN supplemented intravenous nutrition in patients undergoing elective surgery improved nitrogen balance,helped correct the decreased GLN concentration found in the free intracellular skeletal muscle amino acid pool and enhanced net protein synthesis (particularly in skeletal muscel).Six rancomized blinded trials(two multicentered investigations) have reported a dereased length in hospital stay in postoperative patients receiving GLN supplementation.Following blunt trauma,GLN supplementation increased plasma concentrations,attenuated the immunosuppression commonly observed and decreased the rate of infection.Patients with burn injury have low GLN plasma and intramuscular concentrations,but turnover and synthesis rate are accelerated,yet apparently inadequate to support normal concentrations.These data suggests that GLN supplementation has important effects in catabolic surgical patients,but the exact mechanisms to explain these events remain unknown and more research is required to explain the apparent benefits of dietary GLN.

  4. Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression in C2C12 myotubes, Hep G2 hepatoma cells and 3T3 L1 adipocytes

    OpenAIRE

    Wang, Yanxin; Watford, Malcolm

    2006-01-01

    The cell-specific regulation of glutamine synthetase expression was studied in three cell lines. In C2C12 myotubes, glucocorticoids increased the abundance of both glutamine synthetase protein and mRNA. Culture in the absence of glutamine also resulted in very high glutamine synthetase protein abundance but mRNA levels were unchanged. Glucocorticoids also increased the abundance of glutamine synthetase mRNA in Hep G2 hepatoma cells but this was not reflected in changes in protein abundance. C...

  5. L-glutamine Induces Expression of Listeria monocytogenes Virulence Genes

    Science.gov (United States)

    Lobel, Lior; Burg-Golani, Tamar; Sigal, Nadejda; Rose, Jessica; Livnat-Levanon, Nurit; Lewinson, Oded; Herskovits, Anat A.

    2017-01-01

    The high environmental adaptability of bacteria is contingent upon their ability to sense changes in their surroundings. Bacterial pathogen entry into host poses an abrupt and dramatic environmental change, during which successful pathogens gauge multiple parameters that signal host localization. The facultative human pathogen Listeria monocytogenes flourishes in soil, water and food, and in ~50 different animals, and serves as a model for intracellular infection. L. monocytogenes identifies host entry by sensing both physical (e.g., temperature) and chemical (e.g., metabolite concentrations) factors. We report here that L-glutamine, an abundant nitrogen source in host serum and cells, serves as an environmental indicator and inducer of virulence gene expression. In contrast, ammonia, which is the most abundant nitrogen source in soil and water, fully supports growth, but fails to activate virulence gene transcription. We demonstrate that induction of virulence genes only occurs when the Listerial intracellular concentration of L-glutamine crosses a certain threshold, acting as an on/off switch: off when L-glutamine concentrations are below the threshold, and fully on when the threshold is crossed. To turn on the switch, L-glutamine must be present, and the L-glutamine high affinity ABC transporter, GlnPQ, must be active. Inactivation of GlnPQ led to complete arrest of L-glutamine uptake, reduced type I interferon response in infected macrophages, dramatic reduction in expression of virulence genes, and attenuated virulence in a mouse infection model. These results may explain observations made with other pathogens correlating nitrogen metabolism and virulence, and suggest that gauging of L-glutamine as a means of ascertaining host localization may be a general mechanism. PMID:28114430

  6. Glutamine versus ammonia utilization in the NAD synthetase family.

    Directory of Open Access Journals (Sweden)

    Jessica De Ingeniis

    Full Text Available NAD is a ubiquitous and essential metabolic redox cofactor which also functions as a substrate in certain regulatory pathways. The last step of NAD synthesis is the ATP-dependent amidation of deamido-NAD by NAD synthetase (NADS. Members of the NADS family are present in nearly all species across the three kingdoms of Life. In eukaryotic NADS, the core synthetase domain is fused with a nitrilase-like glutaminase domain supplying ammonia for the reaction. This two-domain NADS arrangement enabling the utilization of glutamine as nitrogen donor is also present in various bacterial lineages. However, many other bacterial members of NADS family do not contain a glutaminase domain, and they can utilize only ammonia (but not glutamine in vitro. A single-domain NADS is also characteristic for nearly all Archaea, and its dependence on ammonia was demonstrated here for the representative enzyme from Methanocaldococcus jannaschi. However, a question about the actual in vivo nitrogen donor for single-domain members of the NADS family remained open: Is it glutamine hydrolyzed by a committed (but yet unknown glutaminase subunit, as in most ATP-dependent amidotransferases, or free ammonia as in glutamine synthetase? Here we addressed this dilemma by combining evolutionary analysis of the NADS family with experimental characterization of two representative bacterial systems: a two-subunit NADS from Thermus thermophilus and a single-domain NADS from Salmonella typhimurium providing evidence that ammonia (and not glutamine is the physiological substrate of a typical single-domain NADS. The latter represents the most likely ancestral form of NADS. The ability to utilize glutamine appears to have evolved via recruitment of a glutaminase subunit followed by domain fusion in an early branch of Bacteria. Further evolution of the NADS family included lineage-specific loss of one of the two alternative forms and horizontal gene transfer events. Lastly, we identified NADS

  7. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma.

    Science.gov (United States)

    Tardito, Saverio; Oudin, Anaïs; Ahmed, Shafiq U; Fack, Fred; Keunen, Olivier; Zheng, Liang; Miletic, Hrvoje; Sakariassen, Per Øystein; Weinstock, Adam; Wagner, Allon; Lindsay, Susan L; Hock, Andreas K; Barnett, Susan C; Ruppin, Eytan; Mørkve, Svein Harald; Lund-Johansen, Morten; Chalmers, Anthony J; Bjerkvig, Rolf; Niclou, Simone P; Gottlieb, Eyal

    2015-12-01

    L-Glutamine (Gln) functions physiologically to balance the carbon and nitrogen requirements of tissues. It has been proposed that in cancer cells undergoing aerobic glycolysis, accelerated anabolism is sustained by Gln-derived carbons, which replenish the tricarboxylic acid (TCA) cycle (anaplerosis). However, it is shown here that in glioblastoma (GBM) cells, almost half of the Gln-derived glutamate (Glu) is secreted and does not enter the TCA cycle, and that inhibiting glutaminolysis does not affect cell proliferation. Moreover, Gln-starved cells are not rescued by TCA cycle replenishment. Instead, the conversion of Glu to Gln by glutamine synthetase (GS; cataplerosis) confers Gln prototrophy, and fuels de novo purine biosynthesis. In both orthotopic GBM models and in patients, (13)C-glucose tracing showed that GS produces Gln from TCA-cycle-derived carbons. Finally, the Gln required for the growth of GBM tumours is contributed only marginally by the circulation, and is mainly either autonomously synthesized by GS-positive glioma cells, or supplied by astrocytes.

  8. Comparative study among glutamine, acetyl-L-carnitine, vitamin-E and methylcobalamine for treatment of paclitaxel-induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Santu Mondal

    2014-01-01

    Full Text Available Context: One of the major toxicity of paclitaxel is peripheral neuropathy. Sensory components are affected more than motor and autonomic dysfunction. Aims: Acetyl-L-carnitine (ALC, methylcobalamine, vitamin E and glutamine have been used in various trials against placebos. With head on trials among these four drugs missing, this randomized study was conducted to compare the efficacy in relieving symptoms of paclitaxel induced peripheral neuropathy. Settings and Design : This single institutional, prospective, multi-arm, randomized study was conducted as per Helsinki protocol and with local ethical committee clearances. Materials and Methods: Patients of carcinomas of lung, breast and ovary recruited, would receive paclitaxel 175 mg/m 2 intravenous as 1 st or 2 nd line drug. They underwent randomization to any of four treatment arms: Arm A (vitamin E 400 mg OD day 1 of the cycle to 1 month after completion of clinical trial [CT]; Arm B (ALC 250 mg OD from day 1 to day 7 in each cycle of CT; Arm C (glutamine 10 mg TDS from day 2 to day 5 in each cycle and Arm D (methylcobalamine 500 μg TDS from day 1 of the first cycle to 1 month after completion of CT. All drugs were started at the onset of symptoms. CTCAE v 4.02 was used for assessments. Statistical Analysis Used : Changes in scores for sensory, motor and pain symptoms over the study period were compared using repeated measures of General Linear Model of SPSS version 17. Results : 22, 24, 21 and 23 patients were eligible for analysis in four arms. Vitamin E was producing comparable relief as methylcobalamine of peripheral neuropathy. Both vitamin E and methylcobalamine was superior to glutamine and ALC in relieving sensory, motor and pain symptoms. Glutamine and ALC had comparable effects. Conclusions: All four drugs were effective in the alleviation of symptoms with vitamin E and methylcobalaine more effective than glutamine and ALC in control of symptoms of paclitaxel induced peripheral

  9. Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression in C2C12 myotubes, Hep G2 hepatoma cells and 3T3 L1 adipocytes.

    Science.gov (United States)

    Wang, Yanxin; Watford, Malcolm

    2007-04-01

    The cell-specific regulation of glutamine synthetase expression was studied in three cell lines. In C2C12 myotubes, glucocorticoids increased the abundance of both glutamine synthetase protein and mRNA. Culture in the absence of glutamine also resulted in very high glutamine synthetase protein abundance but mRNA levels were unchanged. Glucocorticoids also increased the abundance of glutamine synthetase mRNA in Hep G2 hepatoma cells but this was not reflected in changes in protein abundance. Culture of Hep G2 cells without glutamine resulted in very high levels of protein, again with no change in mRNA abundance. Insulin was without effect in both C2C12 and Hep G2 cells. In 3T3 L1 adipocytes glucocorticoids increased the abundance of both glutamine synthetase mRNA and protein, insulin added alone had no effect but in the presence of glucocorticoids resulted in lower mRNA levels than seen with glucocorticoids alone, although protein levels remained high under such conditions. In contrast to the other cell lines glutamine synthetase protein levels were relatively unchanged by culture in the absence of glutamine. The results support the hypothesis that in myocytes, and hepatomas, but not in adipocytes, glutamine acts to moderate glutamine synthetase induction by glucocorticoids.

  10. Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel.

    Science.gov (United States)

    Sato, N; Moore, F A; Kone, B C; Zou, L; Smith, M A; Childs, M A; Moore-Olufemi, S; Schultz, S G; Kozar, R A

    2006-04-01

    Using a rodent model of gut ischemia-reperfusion (I/R), we have previously shown that the induction of inducible nitric oxide synthase (iNOS) is harmful, whereas the induction of heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is protective. In the present study, we hypothesized that the luminal nutrients arginine and glutamine differentially modulate these molecular events in the postischemic gut. Jejunal sacs were created in rats at laparotomy, filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 min of superior mesenteric artery occlusion and 6 h of reperfusion, and compared with shams. The jejunum was harvested for histology or myeloperoxidase (MPO) activity (inflammation). Heat shock proteins and iNOS were quantitated by Western blot analysis and PPAR-gamma by DNA binding activity. In some experiments, rats were pretreated with the PPAR-gamma inhibitor G9662 or with the iNOS inhibitor N-[3(aminomethyl)benzyl]acetamidine (1400W). iNOS was significantly increased by arginine but not by glutamine following gut I/R and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR-gamma was significantly increased by glutamine but decreased by arginine, whereas heat shock proteins were similarly increased in all experimental groups. The PPAR-gamma inhibitor G9662 abrogated the protective effects of glutamine, whereas the iNOS inhibitor 1400W attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious I/R-mediated gut inflammation and injury. The induction of PPAR-gamma by luminal glutamine is a novel protective mechanism, whereas luminal arginine appears harmful to the postischemic gut due to enhanced expression of iNOS.

  11. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    Science.gov (United States)

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

  12. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

    2016-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.

  13. Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study.

    Directory of Open Access Journals (Sweden)

    Dorit Samocha-Bonet

    Full Text Available L-glutamine is an efficacious glucagon-like peptide (GLP-1 secretagogue in vitro. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients.Type 2 diabetes patients treated with metformin (n = 13, 9 men with baseline glycated hemoglobin (HbA1c 7.1±0.3% (54±4 mmol/mol received glutamine (15 g bd+ sitagliptin (100 mg/d or glutamine (15 g bd + placebo for 4 weeks in a randomized crossover study.HbA1c (P = 0.007 and fructosamine (P = 0.02 decreased modestly, without significant time-treatment interactions (both P = 0.4. Blood urea increased (P<0.001 without a significant time-treatment interaction (P = 0.8, but creatinine and estimated glomerular filtration rate (eGFR were unchanged (P≥0.5. Red blood cells, hemoglobin, hematocrit, and albumin modestly decreased (P≤0.02, without significant time-treatment interactions (P≥0.4. Body weight and plasma electrolytes remained unchanged (P≥0.2.Daily oral supplementation of glutamine with or without sitagliptin for 4 weeks decreased glycaemia in well-controlled type 2 diabetes patients, but was also associated with mild plasma volume expansion.ClincalTrials.gov NCT00673894.

  14. Structural and Dynamic Basis for Low-Affinity, High-Selectivity Binding of L-Glutamine by the Glutamine Riboswitch

    Directory of Open Access Journals (Sweden)

    Aiming Ren

    2015-12-01

    Full Text Available Naturally occurring L-glutamine riboswitches occur in cyanobacteria and marine metagenomes, where they reside upstream of genes involved in nitrogen metabolism. By combining X-ray, NMR, and MD, we characterized an L-glutamine-dependent conformational transition in the Synechococcus elongatus glutamine riboswitch from tuning fork to L-shaped alignment of stem segments. This transition generates an open ligand-binding pocket with L-glutamine selectivity enforced by Mg2+-mediated intermolecular interactions. The transition also stabilizes the P1 helix through a long-range “linchpin” Watson-Crick G-C pair-capping interaction, while melting a short helix below P1 potentially capable of modulating downstream readout. NMR data establish that the ligand-free glutamine riboswitch in Mg2+ solution exists in a slow equilibrium between flexible tuning fork and a minor conformation, similar, but not identical, to the L-shaped bound conformation. We propose that an open ligand-binding pocket combined with a high conformational penalty for forming the ligand-bound state provide mechanisms for reducing binding affinity while retaining high selectivity.

  15. Structural and Dynamic Basis for Low-Affinity, High-Selectivity Binding of L-Glutamine by the Glutamine Riboswitch.

    Science.gov (United States)

    Ren, Aiming; Xue, Yi; Peselis, Alla; Serganov, Alexander; Al-Hashimi, Hashim M; Patel, Dinshaw J

    2015-12-01

    Naturally occurring L-glutamine riboswitches occur in cyanobacteria and marine metagenomes, where they reside upstream of genes involved in nitrogen metabolism. By combining X-ray, NMR, and MD, we characterized an L-glutamine-dependent conformational transition in the Synechococcus elongatus glutamine riboswitch from tuning fork to L-shaped alignment of stem segments. This transition generates an open ligand-binding pocket with L-glutamine selectivity enforced by Mg(2+)-mediated intermolecular interactions. The transition also stabilizes the P1 helix through a long-range "linchpin" Watson-Crick G-C pair-capping interaction, while melting a short helix below P1 potentially capable of modulating downstream readout. NMR data establish that the ligand-free glutamine riboswitch in Mg(2+) solution exists in a slow equilibrium between flexible tuning fork and a minor conformation, similar, but not identical, to the L-shaped bound conformation. We propose that an open ligand-binding pocket combined with a high conformational penalty for forming the ligand-bound state provide mechanisms for reducing binding affinity while retaining high selectivity.

  16. Effect of glutamine on change in early postoperative intestinal permeability and its relation to systemic inflammatory response

    Institute of Scientific and Technical Information of China (English)

    Zhu-Fu Quan; Chong Yang; Ning Li; Jie-Shou Li

    2004-01-01

    AIM: To study the effects of glutamine (Gln) on the change of intestinal permeability and its relationship to systemic inflammatory response in early abdominal postoperative patients.METHODS: A prospective, randomized, double-blind and controlled trial was taken. Twenty patients undergoing abdominal surgery were randomized into Gln group (oral administration of glutamine, 30 g/d, for 7 d, n=10) and placebo group (oral administration of placebo, 30 g/d, for 7 d, n=10). Temperatures and heart rates of all patients were daily recorded. White blood cell counts(WBC) and biochemical variables were measured before operation and 4 and 7 d after drug administration. Serum concentrations of glutamine, endotoxin, diamine oxidase and malondialdehyde and urine lactulose/mannito (L/M) ratio were measured before and 7 d after drug administration.RESULTS: The patients in the 2 groups were comparable prior to drug administration. Serum Gln concentration was significantly decreased in the placebo group and increased in the Gln group 7 d after drug administration. Urine L/M ratio was significantly increased in the placebo group and decreased in the Gln group. The serum concentration of endotoxin, diamine oxidase and malondialdehyde was significantly decreased in the Gln group compared with those in the placebo group. Temperatures, heart rates and WBC counts were significantly lower in the Gln group than those in the placebo group.CONCLUSION: Gut is one of the sources of systemic inflammatory response in abdominal postoperative patients and glutamine can decrease intestinal permeability, maintain intestinal barrier and attenuate systemic inflammatory response in early postoperative patients.

  17. Glutamine analogs promote cytoophidium assembly in human and Drosophila cells

    Institute of Scientific and Technical Information of China (English)

    Kangni Chen; Jing Zhang; (O)mür Yilmaz Tastan; Zillah Anne Deussen; Mayte Yu-Yin Siswick; Ji-Long Liu

    2011-01-01

    CTP synthase is compartmentalized within a subcellular structure,termed the cytoophidium,in a range of organisms including bacteria,yeast,fruit fly and rat.Here we show that CTP synthase is also compartmentalized into cytoophidia in human cells.Surprisingly,the occurrence of cyloophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-L-norleucine (DON),an inhibitor of glutaminedependent enzymes including CTP synthase.Experiments in flies confirmned that DON globally promotes cytoophidium assembly.Clonal analysis via CTP synthase RNA interference in somatic cells indicates that CTP synthase expression level is critical for the formation of cytoophidia.Moreover,DON facilitates cytoophidium assembly even when CTP synthase level is low.A second glutamine analog azaserine also promotes cytoophidum formation.Our data demonstrate that glutamine analogs serve as useful tools in the study of cytoophidia.

  18. 品管圈活动在降低血液透析中补铁所致的透析机空气报警率中的应用%Effect of quality control circle program in decreasing hemodialysis machine air alarm rate because of intravenous iron administration

    Institute of Scientific and Technical Information of China (English)

    李月娥; 赖丽梅; 唐淑杏

    2014-01-01

    目的:探讨品管圈活动在降低血液透析补铁所致的透析机空气报警中的应用,以提高血液透析病人蔗糖铁使用的安全性,保证病人血液透析的顺利进行。方法:由血液净化中心8名医护人员自愿组建品管圈,选定降低血液透析中补铁所致的透析机空气报警率为活动主题,总结分析透析过程中静脉点滴蔗糖铁所致的透析机空气报警原因,同时制定和实施相应的护理对策。结果:应用品管圈活动后,静脉点滴蔗糖铁所致的空气报警率较活动前明显降低,差异有统计学意义(P<0.05)。结论:开展品管圈活动,降低了血液透析中静脉点滴蔗糖铁所致的透析机空气报警次数,提高了圈员的团队精神和质量管理能力。%Objective:To observe the effect of quality control circle ( QCC) program in decreasing the rate of hemodialysis machine air alarm because of in-travenous iron administration during hemodialysis,in order to improve the safety of using iron sucrose and ensure hemodialysis smoothly. Methods:QCC was established by 8 medical personnel voluntarily,and the theme of this program was decreased the rate of hemodialysis machine air alarm. Observed the rate of hemodialysis machine air alarm before this program,and then analyzing its reason. At the same time,the corresponding nursing countermeasures were formu-lated and implemented. Results:The rate of hemodialysis machine air alarm exceeded the targets obviously after implementing QCC was lower than before, the was remarkable different (P<0. 05). Conclusion:QCC program can not only decrease the rate of hemodialysis machine air alarm,but also improve the team spirit and the ability of quality management.

  19. Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformations

    OpenAIRE

    Constantin Jorgete; Suzuki-Kemmelmeier Fumie; Comar Jurandir F; Bracht Adelar

    2010-01-01

    Abstract Background Glutaminase predominates in periportal hepatocytes and it has been proposed that it determines the glutamine-derived nitrogen flow through the urea cycle. Glutamine-derived urea production should, thus, be considerably faster in periportal hepatocytes. This postulate, based on indirect observations, has not yet been unequivocally demonstrated, making a direct investigation of ureogenesis from glutamine highly desirable. Methods Zonation of glutamine metabolism was investig...

  20. Glutamine synthetase 2 is not essential for biosynthesis of compatible solutes in Halobacillus halophilus

    OpenAIRE

    Anna eShiyan; Melanie eThompson; Saskia eKöcher; Michaela eTausendschön; Helena eSantos; Inga eHänelt; Volker eMüller

    2014-01-01

    Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride....

  1. Inhibition of glutamine synthesis induces glutamate dehydrogenase-dependent ammonia fixation into alanine in co-cultures of astrocytes and neurons

    DEFF Research Database (Denmark)

    Dadsetan, Sherry; Bak, Lasse Kristoffer; Sørensen, Michael

    2011-01-01

    of alanine increased leading to an elevated content intra- as well as extracellularly of this amino acid. Treatment with MSO led to a dramatic decrease in glutamine content and increased the intracellular contents of glutamate and aspartate. The large increase in alanine during exposure to MSO underlines...... the importance of the GDH and ALAT biosynthetic pathway for ammonia fixation, and it points to the use of a GS inhibitor to ameliorate the brain toxicity and edema induced by hyperammonemia, events likely related to glutamine synthesis....

  2. How to understand the results of studies of glutamine supplementation.

    Science.gov (United States)

    Wernerman, Jan

    2015-11-03

    The lack of understanding of the mechanisms behind possible beneficial and possible harmful effects of glutamine supplementation makes the design of interventional studies of glutamine supplementations difficult, perhaps even hazardous. What is the interventional target, and how might it relate to outcomes? Taking one step further and aggregating results from interventional studies into meta-analyses does not diminish the difficulties. Therefore, conducting basic research seems to be a better idea than groping in the dark and exposing patients to potential harm in this darkness.

  3. Effects of glutamine on wound healing.

    Science.gov (United States)

    Kesici, Ugur; Kesici, Sevgi; Ulusoy, Hulya; Yucesan, Fulya; Turkmen, Aygen U; Besir, Ahmet; Tuna, Verda

    2015-06-01

    Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  4. Effect of alanyl glutamine on the acute inflammatory reaction and immunological function in elderly patients with intestinal obstruction

    Institute of Scientific and Technical Information of China (English)

    Fei-Guo Ma

    2016-01-01

    Objective:To explore the application value of alanyl glutamine in improving the acute inflammatory reaction and immunological function in elderly patients with intestinal obstruction.Methods:A total of 97 elderly patients with intestinal obstruction who were admitted in our hospital were included in the study and randomized into the treatment group (n=49) and the control group (n=48). The patients in the control group were given total parenteral nutrition (TPN) treatment. On this basis, the patients in the treatment group were given intravenous injection of alanyl glutamine for 1 week. The plasma prealbumin, albumin, serum related cytokines, L/M, and DAO before and after treatment in the two groups were detected. The serum immunoglobulin and T lymphocyte subsets before and after treatment in the two groups were compared.Results:The plasma prealbumin and albumin levels after treatment in the observation group were significantly higher than those in the control group, while the serum CRP, IL-6, and TNF-α levels in the two groups were significantly reduced when compared with before treatment, and those in the observation group were significantly lower than those in the control group. When compared with before treatment, L/M and plasma DAO level after treatment in the control group were significantly elevated, while those in the observation group were significantly reduced, and the comparison between the two groups was statistically significant. The serum IgG and IgA levels after treatment in the observation group were significantly higher than those in the control group. The serum CD4+, CD8+, and CD4+/CD8+ after treatment in the two groups were significantly elevated when compared with before treatment, and those in the observation group were significantly higher than those in the control group.Conclusions:Alanyl glutamine in the treatment of elderly intestinal obstruction can significantly improve the acute inflammatory reaction and immunological function, with a

  5. FOXO1 activates glutamine synthetase gene in mouse skeletal muscles through a region downstream of 3'-UTR: possible contribution to ammonia detoxification.

    Science.gov (United States)

    Kamei, Yasutomi; Hattori, Maki; Hatazawa, Yukino; Kasahara, Tomomi; Kanou, Masanobu; Kanai, Sayaka; Yuan, Xunmei; Suganami, Takayoshi; Lamers, Wouter H; Kitamura, Tadahiro; Ogawa, Yoshihiro

    2014-09-15

    Skeletal muscle is a reservoir of energy in the form of protein, which is degraded under catabolic conditions, resulting in the formation of amino acids and ammonia as a byproduct. The expression of FOXO1, a forkhead-type transcription factor, increases during starvation and exercise. In agreement, transgenic FOXO1-Tg mice that overexpress FOXO1 in skeletal muscle exhibit muscle atrophy. The aim of this study was to examine the role of FOXO1 in amino acid metabolism. The mRNA and protein expressions of glutamine synthetase (GS) were increased in skeletal muscle of FOXO1-Tg mice. Fasting induced FOXO1 and GS expression in wild-type mice but hardly increased GS expression in muscle-specific FOXO1 knockout (FOXO1-KO) mice. Activation of FOXO1 also increased GS mRNA and protein expression in C2C12 myoblasts. Using a transient transfection reporter assay, we observed that FOXO1 activated the GS reporter construct. Mutation of a putative FOXO1-binding consensus sequence in the downstream genomic region of GS decreased basal and FOXO1-dependent reporter activity significantly. A chromatin immunoprecipitation assay showed that FOXO1 was recruited to the 3' region of GS in C2C12 myoblasts. These results suggest that FOXO1 directly upregulates GS expression. GS is considered to mediate ammonia clearance in skeletal muscle. In agreement, an intravenous ammonia challenge increased blood ammonia concentrations to a twofold higher level in FOXO1-KO than in wild-type mice, demonstrating that the capacity for ammonia disposal correlated inversely with the expression of GS in muscle. These data indicate that FOXO1 plays a role in amino acid metabolism during protein degradation in skeletal muscle.

  6. The impact of use of Glutamine on patients with head and neck tumors in radiotherapy and chemotherapy treatment; O Impacto do uso de Glutamina em pacientes com tumores de cabeca e pescoco em tratamento radioterapico e quimioterapico

    Energy Technology Data Exchange (ETDEWEB)

    Boligon, Caroline Schardong, E-mail: caronut@bol.com.b [Hospital de Caridade de Ijui, RS (Brazil); Huth, Adriane, E-mail: adriane.huth@unijui.edu.b [UNIJUI, RS (Brazil). Dept. Ciencias da Saude

    2011-07-01

    Introduction: patients with head and neck neoplasia usually show malnutrition or a nutritional risk, because of common symptoms like: dysphagia, odynophagia and xerostomia. Objective: this study aimed to verify the impact of using amino glutamine in patients with head and neck neoplasia and under radiotherapy and chemotherapy treatment concomitantly. Methods: the research was quantitative, cross-sectional, descriptive and exploratory. The data was collected from nutritional evaluation, and patients chart consultation. The patients were divided in a control group (without use of glutamine) and a test group (with use of glutamine). 16 patients, 13 of which were men and three were women, participated in the research. Results: The control group presented mucositis grades I to IV while patients who used the amino glutamine showed mucositis grades I to II only. It could be observed that the Nutritional Risk Index decreased, which represents higher nutritional risk in patients from the control group only. In patients who used glutamine, this decrease was not significant. Conclusion: these results suggest that the use of glutamine in patients with head and neck tumors and under antineoplastic therapy helps to maintain their nutritional stage and to prevent mucositis throughout their treatment, mainly grades III and IV, which prevents adequate and regular eating and nourishment. (author)

  7. Arginine and glutamine supplementation to culture media improves the performance of various channel catfish immune cells.

    Science.gov (United States)

    Pohlenz, Camilo; Buentello, Alejandro; Mwangi, Waithaka; Gatlin, Delbert M

    2012-05-01

    Specific components of both the innate and adaptive immune systems of channel catfish were evaluated after supplementation of culture media with arginine (ARG) and/or glutamine (GLN). Primary cell cultures of head-kidney macrophages (MØ) were used for phagocytic and bactericidal assays against Edwardsiella ictaluri. Additionally, proliferation assays were conducted with naïve peripheral blood lymphocytes (PBL) exposed to non-specific mitogens. To indirectly assess amino acid utilization of both MØ and PBL, amino acid levels, with emphasis on ARG and GLN, were evaluated in the basal medium before and after activation or mitogenic exposure. After bactericidal and proliferation assays, the sum of the media free amino acid pool significantly (P Glutamine levels in medium decreased by 38% and ARG by 18% during the bactericidal assay. Also, decreases of 52 and 46% from initial values were found after the proliferation assay for GLN and ARG, respectively. Macrophage phagocytosis and killing ability was significantly (P < 0.05) enhanced by ARG supplementation to culture media regardless of GLN supplementation. Proliferation of naïve T- and B-lymphocytes upon mitogenic exposure was significantly (P < 0.05) enhanced by supplementing ARG and GLN to the media, but limited synergistic effects were observed. These results suggest that in vitro, ARG and GLN are important substrates and immunomodulators of both innate and adaptive responses in fish leukocytes, and further highlights the potential use of ARG and GLN as immunonutrients in aquafeeds.

  8. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Lamers, Wouter H; Chaudhry, Farrukh A; Verlander, Jill W; Weiner, I David

    2016-06-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.

  9. Synergistic effects of glutamine and ciprofloxacin in reduction of Pseudomonas aeruginosa-induced septic shock severity.

    Science.gov (United States)

    Mazloomi, Ebrahim; Jazani, Nima Hosseini; Sohrabpour, Mohammad; Ilkhanizadeh, Behrouz; Shahabi, Shahram

    2011-12-01

    Systemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gln) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression. To assess the effect of co-administration of Gln and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice. Six- to eight-week old male BALB/c mice were used. At first, P. aeruginosa susceptibility to ciprofloxacin was determined. Then, 75% lethal dose (LD 75) of P. aeruginosa in a 10-day period was assessed. For determining survival rate, fifty mice were divided into 5 groups which included control (+), control (-), Gln, ciprofloxacin, and "glutamine+ciprofloxacin" group. All mice, except for control (-), were given an LD75 dose of P. aeruginosa and after 30 min each group received its special treatment: control (-) and control (+) groups received only 500λ phosphate buffer saline (PBS). Gln group received 500λ Ala-Gln, Cip group received 500λ ciprofloxacin. The Cip+Gln group received 500λ Gln and ciprofloxacin. Finally serum TNF-α, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined. Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-α concentration and the liver necrosis severity in comparison to control (+) group. Gln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Reversible adenylylation of glutamine synthetase is dynamically counterbalanced during steady-state growth of Escherichia coli.

    Science.gov (United States)

    Okano, Hiroyuki; Hwa, Terence; Lenz, Peter; Yan, Dalai

    2010-12-03

    Glutamine synthetase (GS) is the central enzyme for nitrogen assimilation in Escherichia coli and is subject to reversible adenylylation (inactivation) by a bifunctional GS adenylyltransferase/adenylyl-removing enzyme (ATase). In vitro, both of the opposing activities of ATase are regulated by small effectors, most notably glutamine and 2-oxoglutarate. In vivo, adenylyltransferase (AT) activity is critical for growth adaptation when cells are shifted from nitrogen-limiting to nitrogen-excess conditions and a rapid decrease of GS activity by adenylylation is needed. Here, we show that the adenylyl-removing (AR) activity of ATase is required to counterbalance its AT activity during steady-state growth under both nitrogen-excess and nitrogen-limiting conditions. This conclusion was established by studying AR(-)/AT(+) mutants, which surprisingly displayed steady-state growth defects in nitrogen-excess conditions due to excessive GS adenylylation. Moreover, GS was abnormally adenylylated in the AR(-) mutants even under nitrogen-limiting conditions, whereas there was little GS adenylylation in wild-type strains. Despite the importance of AR activity, we establish that AT activity is significantly regulated in vivo, mainly by the cellular glutamine concentration. There is good general agreement between quantitative estimates of AT regulation in vivo and results derived from previous in vitro studies except at very low AT activities. We propose additional mechanisms for the low AT activities in vivo. The results suggest that dynamic counterbalance by reversible covalent modification may be a general strategy for controlling the activity of enzymes such as GS, whose physiological output allows adaptation to environmental fluctuations.

  11. Glutamine supplemented parenteral nutrition prevents intestinal ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Wu; Hao Wang; Yan-Wei Zhang; Zhao-Han Wu; Zhao-Guang Wu

    2004-01-01

    AIM: To examine whether glutamine prevents the injury to the intestinal mucosa after intestinal ischemia-reperfusion (I/R) in rats.METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups: a standard parenteral nutrition (PN)group (n = 10); an I/R-PN group (n = 10); an I/R-glutamine enriched PN (I/R-Gln) group (n = 10). The superior mesenteric artery (SMA) was clamped. After 60 min of ischemia, reperfusion was initiated and infusion was started. All rats received isocaloric and isonitrogenous nutritional support for 48 h. Spleen, liver, mesenteric lymph nodes (MLN), and intestinal segments were removed for morphological and biochemical analyses, and blood samples were collected for bacterial culture and measurement of endotoxin levels.The permeability of intestinnal mucosa was assayed by measurement of D-(-)-lactate levels in plasma.RESULTS: In I/R-PN group, extensive epithelial atrophy was observed, mucosal thickness, villous height, crypt depth and villous surface area were decreased significantly compared with PN group, whereas these findings did not occur in the I/R-Gln group. The incidence of intestinal bacterial translocation to spleen, liver, MLN, and blood was significantly higher in I/R-PN group than that in other groups.Plasma endotoxin levels significantly increased in the I/R-PN group compared with the I/R-Gln group. Remarkably higher values of D-(-)-lactate were also detected in PN group compared with that in I/R-Gln group.CONCLUSION: Glutamine protects the morphology and function of intestinal mucosa from injury after I/R in rats.

  12. Persistent reduction of hippocampal glutamine synthetase expression after status epilepticus in immature rats.

    Science.gov (United States)

    van der Hel, W Saskia; Hessel, Ellen V S; Bos, Ineke W M; Mulder, Sandra D; Verlinde, Suzanne A M W; van Eijsden, Pieter; de Graan, Pierre N E

    2014-12-01

    Mesiotemporal sclerosis (MTS), the most frequent form of drug-resistant temporal lobe epilepsy, often develops after an initial precipitating injury affecting the immature brain. To analyse early processes in epileptogenesis we used the juvenile pilocarpine model to study status epilepticus (SE)-induced changes in expression of key components in the glutamate-glutamine cycle, known to be affected in MTS patients. SE was induced by Li(+) /pilocarpine injection in 21-day-old rats. At 2-19 weeks after SE hippocampal protein expression was analysed by immunohistochemistry and neuron damage by FluoroJade staining. Spontaneous seizures occurred in at least 44% of animals 15-18 weeks after SE. As expected in this model, we did not observe loss of principal hippocampal neurons. Neuron damage was most pronounced in the hilus, where we also detected progressive loss of parvalbumin-positive GABAergic interneurons. Hilar neuron loss (or end-folium sclerosis), a common feature in patients with MTS, was accompanied by a progressively decreased glutamine synthetase (GS)-immunoreactivity from 2 (-15%) to 19 weeks (-33.5%) after SE. Immunoreactivity for excitatory amino-acid transporters, vesicular glutamate transporter 1 and glial fibrillary acidic protein was unaffected. Our data show that SE elicited in 21-day-old rats induces a progressive reduction in hilar GS expression without affecting other key components of the glutamate-glutamine cycle. Reduced expression of glial enzyme GS was first detected 2 weeks after SE, and thus clearly before spontaneous recurrent seizures occurred. These results support the hypothesis that reduced GS expression is an early event in the development of hippocampal sclerosis in MTS patients and emphasize the importance of astrocytes in early epileptogenesis.

  13. Glutamine, arginine, and leucine signaling in the intestine.

    Science.gov (United States)

    Marc Rhoads, J; Wu, Guoyao

    2009-05-01

    Glutamine and leucine are abundant constituents of plant and animal proteins, whereas the content of arginine in foods and physiological fluids varies greatly. Besides their role in protein synthesis, these three amino acids individually activate signaling pathway to promote protein synthesis and possibly inhibit autophagy-mediated protein degradation in intestinal epithelial cells. In addition, glutamine and arginine stimulate the mitogen-activated protein kinase and mammalian target of rapamycin (mTOR)/p70 (s6) kinase pathways, respectively, to enhance mucosal cell migration and restitution. Moreover, through the nitric oxide-dependent cGMP signaling cascade, arginine regulates multiple physiological events in the intestine that are beneficial for cell homeostasis and survival. Available evidence from both in vitro and in vivo animal studies shows that glutamine and arginine promote cell proliferation and exert differential cytoprotective effects in response to nutrient deprivation, oxidative injury, stress, and immunological challenge. Additionally, when nitric oxide is available, leucine increases the migration of intestinal cells. Therefore, through cellular signaling mechanisms, arginine, glutamine, and leucine play crucial roles in intestinal growth, integrity, and function.

  14. Synthesis of Biobased Succinonitrile from Glutamic Acid and Glutamine

    NARCIS (Netherlands)

    Lammens, T.M.; Nôtre, Le J.; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2011-01-01

    Succinonitrile is the precursor of 1,4-diaminobutane, which is used for the industrial production of polyamides. This paper describes the synthesis of biobased succinonitrile from glutamic acid and glutamine, amino acids that are abundantly present in many plant proteins. Synthesis of the intermedia

  15. Synthesis of Biobased Succinonitrile from Glutamic Acid and Glutamine

    NARCIS (Netherlands)

    Lammens, T.M.; Nôtre, Le J.; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2011-01-01

    Succinonitrile is the precursor of 1,4-diaminobutane, which is used for the industrial production of polyamides. This paper describes the synthesis of biobased succinonitrile from glutamic acid and glutamine, amino acids that are abundantly present in many plant proteins. Synthesis of the intermedia

  16. Transport of glutamine into the xylem of sunflower (Helianthus annuus).

    NARCIS (Netherlands)

    Findenegg, G.R.; Plaisier, W.; Posthumus, M.A.; Melger, W.C.

    1990-01-01

    Sunflower (Helianthus annuus L.) plants were grown on nutrient solution with ammonium nitrogen. After 12 days of growth the ammonium in the nutrient solution was labeled with N (99%). Three hours later glutamine-N in the xylem exudate was labeled for 56% as shown by GC-MS; this percentage increased

  17. Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress.

    Science.gov (United States)

    Lee, Yoon-Mi; Lee, Gibok; Oh, Taek-In; Kim, Byeong Mo; Shim, Do-Wan; Lee, Kwang-Ho; Kim, Young Jun; Lim, Beong Ou; Lim, Ji-Hong

    2016-01-01

    Recent studies have shown anticancer activity of apigenin by suppressing glucose transporter 1 (GLUT1) expression in cultured cancer cells; however, it is not clear whether apigenin can suppress glucose metabolism in lung cancer cells or sensitize them to inhibition of glutamine utilization-mediated apoptosis through metabolic and oxidative stress. We show that apigenin significantly decreases GLUT1 expression in mice. Furthermore, we demonstrate that apigenin induces growth retardation and apoptosis through metabolic and oxidative stress caused by suppression of glucose utilization in lung cancer cells. The underlying mechanisms were defined that the anticancer effects of apigenin were reversed by ectopic GLUT1 overexpression and galactose supplementation, through activation of pentose phosphate pathway-mediated NADPH generation. Importantly, we showed that severe metabolic stress using a glutaminase inhibitor, compound 968, was involved in the mechanism of sensitization by apigenin. Taken together, the combination of apigenin with inhibitors of glutamine metabolism may provide a promising therapeutic strategy for cancer treatment.

  18. Fluorescence study on ligand induced conformational changes of glutamine synthetase from Bacillus brevis Bb G1 under sporulating conditions

    Directory of Open Access Journals (Sweden)

    SUJA ABRAHAM

    2015-04-01

    Full Text Available Glutamine synthetase, an important enzyme of nitrogen metabolism, was purified under sporulating conditions (GSala. The effect of ligands on the tryptophan fluorescence of the purified enzyme GSala was investigated. With increasing concentrations of L-glutamine in GSala, a blue shift in emission maximum with an increase in fluorescence intensity and decrease in life times were observed compared to the emission maximum, fluorescence intensity and life times of GSala. With increasing concentrations of glycine in GSala, a shift in emission maximum, change in fluorescence intensity and change in lifetimes were observed compared to the emission maximum, fluorescence intensity and life times of GSala. These observations strongly support the possibility that GSala undergoes a conformational change on binding with ligands and each ligand produced different conformational changes in GSala. Also, different concentrations of each ligand produced different protein conformations in the enzyme GSala.

  19. Global Transcriptional and Physiological Responses of Saccharomyces cerevisiae to Ammonium, L-Alanine, or L-Glutamine Limitation

    DEFF Research Database (Denmark)

    Usaite, Renata; Patil, Kiran Raosaheb; Grotkjær, Thomas;

    2006-01-01

    The yeast Saccharomyces cerevisiae encounters a range of nitrogen sources at various concentrations in its environment. The impact of these two parameters on transcription and metabolism was studied by growing S. cerevisiae in chemostat cultures with L-glutamine, L-alanine, or L-ammonium in limit......The yeast Saccharomyces cerevisiae encounters a range of nitrogen sources at various concentrations in its environment. The impact of these two parameters on transcription and metabolism was studied by growing S. cerevisiae in chemostat cultures with L-glutamine, L-alanine, or L...... activity in L-alanine-limited cells. The changes in these cells were found to be focused around pyruvate, acetyl coenzyme A, glyoxylate, and alpha-ketoglutarate via increased levels of ALT1, DAL7, PYC1, GDH2, and ADH5 and decreased levels of GDH3, CIT2, and ACS1 transcripts. The transcript profiles were...

  20. The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion.

    Science.gov (United States)

    Odegaard, Matthew L; Joseph, Jamie W; Jensen, Mette V; Lu, Danhong; Ilkayeva, Olga; Ronnebaum, Sarah M; Becker, Thomas C; Newgard, Christopher B

    2010-05-28

    Glucose-stimulated insulin secretion from pancreatic islet beta-cells is dependent in part on pyruvate cycling through the pyruvate/isocitrate pathway, which generates cytosolic alpha-ketoglutarate, also known as 2-oxoglutarate (2OG). Here, we have investigated if mitochondrial transport of 2OG through the 2-oxoglutarate carrier (OGC) participates in control of nutrient-stimulated insulin secretion. Suppression of OGC in clonal pancreatic beta-cells (832/13 cells) and isolated rat islets by adenovirus-mediated delivery of small interfering RNA significantly decreased glucose-stimulated insulin secretion. OGC suppression also reduced insulin secretion in response to glutamine plus the glutamate dehydrogenase activator 2-amino-2-norbornane carboxylic acid. Nutrient-stimulated increases in glucose usage, glucose oxidation, glutamine oxidation, or ATP:ADP ratio were not affected by OGC knockdown, whereas suppression of OGC resulted in a significant decrease in the NADPH:NADP(+) ratio during stimulation with glucose but not glutamine + 2-amino-2-norbornane carboxylic acid. Finally, OGC suppression reduced insulin secretion in response to a membrane-permeant 2OG analog, dimethyl-2OG. These data reveal that the OGC is part of a mechanism of fuel-stimulated insulin secretion that is common to glucose, amino acid, and organic acid secretagogues, involving flux through the pyruvate/isocitrate cycling pathway. Although the components of this pathway must remain intact for appropriate stimulus-secretion coupling, production of NADPH does not appear to be the universal second messenger signal generated by these reactions.

  1. Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke.

    Science.gov (United States)

    Jeitner, Thomas M; Battaile, Kevin; Cooper, Arthur J L

    2015-12-01

    The following article addresses some seemingly paradoxical observations concerning cerebral glutamine synthetase in ischemia-reperfusion injury. In the brain, this enzyme is predominantly found in astrocytes and catalyzes part of the glutamine-glutamate cycle. Glutamine synthetase is also thought to be especially sensitive to inactivation by the oxygen- and nitrogen-centered radicals generated during strokes. Despite this apparent sensitivity, glutamine synthetase specific activity is elevated in the affected tissues during reperfusion. Given the central role of the glutamine-glutamate cycle in the brain, we sought to resolve these conflicting observations with the view of providing an alternative perspective for therapeutic intervention in stroke.

  2. The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, S.M.; Habash, D.Z.

    2009-07-02

    Glutamine synthetase assimilates ammonium into amino acids, thus it is a key enzyme for nitrogen metabolism. The cytosolic isoenzymes of glutamine synthetase assimilate ammonium derived from primary nitrogen uptake and from various internal nitrogen recycling pathways. In this way, cytosolic glutamine synthetase is crucial for the remobilization of protein-derived nitrogen. Cytosolic glutamine synthetase is encoded by a small family of genes that are well conserved across plant species. Members of the cytosolic glutamine synthetase gene family are regulated in response to plant nitrogen status, as well as to environmental cues, such as nitrogen availability and biotic/abiotic stresses. The complex regulation of cytosolic glutamine synthetase at the transcriptional to post-translational levels is key to the establishment of a specific physiological role for each isoenzyme. The diverse physiological roles of cytosolic glutamine synthetase isoenzymes are important in relation to current agricultural and ecological issues.

  3. The importance of cytosolic glutamine synthetase in nitrogen assimilation and recycling.

    Science.gov (United States)

    Bernard, Stéphanie M; Habash, Dimah Z

    2009-01-01

    Glutamine synthetase assimilates ammonium into amino acids, thus it is a key enzyme for nitrogen metabolism. The cytosolic isoenzymes of glutamine synthetase assimilate ammonium derived from primary nitrogen uptake and from various internal nitrogen recycling pathways. In this way, cytosolic glutamine synthetase is crucial for the remobilization of protein-derived nitrogen. Cytosolic glutamine synthetase is encoded by a small family of genes that are well conserved across plant species. Members of the cytosolic glutamine synthetase gene family are regulated in response to plant nitrogen status, as well as to environmental cues, such as nitrogen availability and biotic/abiotic stresses. The complex regulation of cytosolic glutamine synthetase at the transcriptional to post-translational levels is key to the establishment of a specific physiological role for each isoenzyme. The diverse physiological roles of cytosolic glutamine synthetase isoenzymes are important in relation to current agricultural and ecological issues.

  4. Circumstantial evidence for a role of glutamine-synthetase in suicide.

    Science.gov (United States)

    Kalkman, Hans O

    2011-06-01

    Suicide occurs during depression, schizophrenia, diabetes and epilepsy. A common denominator of these disorders is the presence of inflammation. Inflammatory cytokines affect function and expression of the glial enzyme glutamine synthetase and post mortem studies indicate that brain glutamine synthetase function is suppressed in mood disorders and epilepsy. In a study of schizophrenia brains, the expression of glutamine synthetase was reduced in those cases where the cause of death was suicide. The glycogen synthase kinase 3 (GSK3) inhibitor, lithium, which has a proven efficacy against suicide, increased in an animal experiment the expression of glutamine synthetase. Based on these data one could reason that suicide may be prevented by centrally acting GSK3 inhibitors. However, since inhibition of glutamine synthetase may lead to a deficit in glutamine and as consequence a GABA and glutamate deficit, even simple food supplementation with glutamine might help to reduce suicide.

  5. Effects of Glutamine Supplementation on Patients Undergoing Abdominal Surgery

    Institute of Scientific and Technical Information of China (English)

    Yue-ping Fan; Jian-chun Yu; Wei-ming Kang; Qun Zhang

    2009-01-01

    Objective To evaluate the effects of supplementation of glutamine (GLN) on maintaining glutathione (GSH) level, immune system function, liver function, and clinical outcome of patients receiving abdominal operation. Methods Forty patients undergoing elective abdominal surgical treatment were randomly divided into 2 groups: study group (n = 20) and control group (n = 20). All patients received total parenteral nutrition (TPN) for up to 7 days during perioperative period. The study group received TPN supplemented with GLN dipeptide while the control group received TPN without GLN dipeptide. Patients in both groups received equivalent nitrogen and caloric intake. Blood sample was taken on preoperative day, and the 1st, 3rd, 6th postoperative day to measure GSH level, immune indexes, and liver function indexes. Results The decrease of GSH level in plasma and red blood cell (RBC) in study group was less than that in control group during postoperative period. Ratio of GSH/glutathione disulfide (GSSG) in plasma in study group was higher than that in control group on the 3rd postoperative day (52.53 ± 11.46 vs. 31.43 ± 7.27, P = 0.001). Albumin level in study group was higher than that in control group on the 3rd postoperative day (37.7 ± 3.8 g/L vs. 33.8 ± 4.2 g/L, P = 0.02). There was no significant difference in the levels of immunoglobin (IgG, IgM, IgA) or T lymphocyte subgroup (CD4, CD8, CD4/CD8) in both groups during postoperative period. There was one case with infectious complication in control group, while none in study group. A trend of shortened hospital stay was observed in study group compared with control group (22.3 ± 2.1 d vs. 24.9 ± 1.7 d, P = 0.32). Conclusions Supplementation of GLN-enriched TPN has beneficial effects on maintaining GSH levels in plasma and RBC, sustaining GSH/GSSG ratio and albumin level, and keeping antioxidant abilities during postoperative period in patients with abdominal operation, with the trends of decreasing incidence of

  6. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress

    Science.gov (United States)

    Vats, P.; Mukherjee, A. K.; Kumria, M. M. L.; Singh, S. N.; Patil, S. K. B.; Rangnathan, S.; Sridharan, K.

    Exposure to high altitude causes loss of body mass and alterations in metabolic processes, especially carbohydrate and protein metabolism. The present study was conducted to elucidate the role of glutamine synthetase, glutaminase and glycogen synthetase under conditions of chronic intermittent hypoxia. Four groups, each consisting of 12 male albino rats (Wistar strain), were exposed to a simulated altitude of 7620 m in a hypobaric chamber for 6 h per day for 1, 7, 14 and 21 days, respectively. Blood haemoglobin, blood glucose, protein levels in the liver, muscle and plasma, glycogen content, and glutaminase, glutamine synthetase and glycogen synthetase activities in liver and muscle were determined in all groups of exposed and in a group of unexposed animals. Food intake and changes in body mass were also monitored. There was a significant reduction in body mass (28-30%) in hypoxia-exposed groups as compared to controls, with a corresponding decrease in food intake. There was rise in blood haemoglobin and plasma protein in response to acclimatisation. Over a three-fold increase in liver glycogen content was observed following 1 day of hypoxic exposure (4.76+/-0.78 mg.g-1 wet tissue in normal unexposed rats; 15.82+/-2.30 mg.g-1 wet tissue in rats exposed to hypoxia for 1 day). This returned to normal in later stages of exposure. However, there was no change in glycogen synthetase activity except for a decrease in the 21-days hypoxia-exposed group. There was a slight increase in muscle glycogen content in the 1-day exposed group which declined significantly by 56.5, 50.6 and 42% following 7, 14, and 21 days of exposure, respectively. Muscle glycogen synthetase activity was also decreased following 21 days of exposure. There was an increase in glutaminase activity in the liver and muscle in the 7-, 14- and 21-day exposed groups. Glutamine synthetase activity was higher in the liver in 7- and 14-day exposed groups; this returned to normal following 21 days of exposure

  7. Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide.

    Science.gov (United States)

    Cury-Boaventura, Maria Fernanda; Levada-Pires, Adriana C; Folador, Alessandra; Gorjão, Renata; Alba-Loureiro, Tatiana C; Hirabara, Sandro M; Peres, Fabiano P; Silva, Paulo R S; Curi, Rui; Pithon-Curi, Tania C

    2008-06-01

    Lymphocyte and neutrophil death induced by exercise and the role of hydrolyzed whey protein enriched with glutamine dipeptide (Gln) supplementation was investigated. Nine triathletes performed two exhaustive exercise trials with a 1-week interval in a randomized, double blind, crossover protocol. Thirty minutes before treadmill exhaustive exercise at variable speeds in an inclination of 1% the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus 4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide dissolved in 250 mL water. Cell viability, DNA fragmentation, mitochondrial transmembrane potential and production of reactive oxygen species (ROS) were determined in lymphocytes and neutrophils. Exhaustive exercise decreased viable lymphocytes but had no effect on neutrophils. A 2.2-fold increase in the proportion of lymphocytes and neutrophils with depolarized mitochondria was observed after exhaustive exercise. Supplementation of maltodextrin plus Gln (MGln) prevented the loss of lymphocyte membrane integrity and the mitochondrial membrane depolarization induced by exercise. Exercise caused an increase in ROS production by neutrophils, whereas supplementation of MGln had no additional effect. MGln supplementation partially prevented lymphocyte apoptosis induced by exhaustive exercise possibly by a protective effect on mitochondrial function.

  8. Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.

    Science.gov (United States)

    Momosaki, Sotaro; Ito, Miwa; Tonomura, Misato; Abe, Kohji

    2015-01-01

    Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain.

  9. l-glutamine and l-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise.

    Science.gov (United States)

    Leite, Jaqueline Santos Moreira; Raizel, Raquel; Hypólito, Thaís Menezes; Rosa, Thiago Dos Santos; Cruzat, Vinicius Fernandes; Tirapegui, Julio

    2016-08-01

    In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p < 0.05). The results presented herein demonstrate that l-glutamine supplemented with l-alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.

  10. Benefits of establishing an intravenous team and the standardization of peripheral intravenous catheters.

    Science.gov (United States)

    da Silva, Gislene Aparecida; Priebe, Sheila; Dias, Fábio Nunes

    2010-01-01

    The purpose of this study was to show the importance of a team dedicated to intravenous (IV) insertion and the standardization of peripheral IV catheters in reducing venipuncture attempts, reducing cases of phlebitis, and optimizing costs. The benefits achieved by the team were a decrease in venipuncture attempts, a decrease of phlebitis (from 0.47% to 0.35%), the optimization of the team's time, and a 29.47% reduction in the use of catheters. The study corroborates the IV team's importance in the process of managing nurses' workflow, since it provides important indicators for quality management.

  11. Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin.

    Science.gov (United States)

    Nichols, K E; Chitneni, S R; Moore, J O; Weinberg, J B

    1989-10-01

    Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability

  12. Serum glutamine, set-shifting ability and anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Collier David A

    2010-06-01

    Full Text Available Abstract Background Set-shifting is impaired in people with anorexia nervosa (AN, but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine are associated with set-shifting ability in people with acute AN and those after recovery. Methods Serum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group, 18 women recovered from AN (ANRec group and 28 age-matched healthy controls (HC group. Set-shifting was measured using the Wisconsin Card Sorting Test (WCST and the Trail Making Task (TMT. Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ, the Maudsley Obsessive-Compulsive Inventory (MOCI and the Hospital Anxiety and Depression Scale (HADS. Results Serum glutamine concentrations in the AN group (1,310.2 ± 265.6 μM, mean ± SD were significantly higher (by approximately 20% than those in the HC group (1,102.9 ± 152.7 μM, mean ± SD (F(2, 70 = 6.3, P = 0.003, 95% CI 61.2 to 353.4. Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting. Conclusions Serum

  13. Differential contribution of the proline and glutamine pathways to glutamate biosynthesis and nitrogen assimilation in yeast lacking glutamate dehydrogenase.

    Science.gov (United States)

    Sieg, Alex G; Trotter, Pamela J

    2014-01-01

    In Saccharomyces cerevisiae, the glutamate dehydrogenase (GDH) enzymes play a pivotal role in glutamate biosynthesis and nitrogen assimilation. It has been proposed that, in GDH-deficient yeast, either the proline utilization (PUT) or the glutamine synthetase-glutamate synthase (GS/GOGAT) pathway serves as the alternative pathway for glutamate production and nitrogen assimilation to the exclusion of the other. Using a gdh-null mutant (gdh1Δ2Δ3Δ), this ambiguity was addressed using a combination of growth studies and pathway-specific enzyme assays on a variety of nitrogen sources (ammonia, glutamine, proline and urea). The GDH-null mutant was viable on all nitrogen sources tested, confirming that alternate pathways for nitrogen assimilation exist in the gdh-null strain. Enzyme assays point to GS/GOGAT as the primary alternative pathway on the preferred nitrogen sources ammonia and glutamine, whereas growth on proline required both the PUT and GS/GOGAT pathways. In contrast, growth on glucose-urea media elicited a decrease in GOGAT activity along with an increase in activity of the PUT pathway specific enzyme Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH). Together, these results suggest the alternative pathway for nitrogen assimilation in strains lacking the preferred GDH-dependent route is nitrogen source dependent and that neither GS/GOGAT nor PUT serves as the sole compensatory pathway.

  14. Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

    Science.gov (United States)

    Noth, Rainer; Häsler, Robert; Stüber, Eckhard; Ellrichmann, Mark; Schäfer, Heiner; Geismann, Claudia; Hampe, Jochen; Bewig, Burkhard; Wedel, Thilo; Böttner, Martina; Schreiber, Stefan; Rosenstiel, Philip; Arlt, Alexander

    2013-04-01

    Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

  15. Glutamine synthetase gene evolution: A good molecular clock

    Energy Technology Data Exchange (ETDEWEB)

    Pesole, G.; Lanvave, C.; Saccone, C. (Consiglio Nazionale delle Richerche, Bari (Italy)); Bozzetti, M.P. (Univ. di Bari (Italy)); Preparata, G. (Univ. di Milano (Italy))

    1991-01-15

    Glutamine synthetase gene evolution in various animals, plants, and bacteria was evaluated by a general stationary Markov model. The evolutionary process proved to be unexpectedly regular even for a time span as long as that between the divergence of prokaryotes from eukaryotes. This enabled us to draw phylogenetic trees for species whose phylogeny cannot be easily reconstructed from the fossil record. The calculation of the times of divergence of the various organelle-specific enzymes led us to hypothesize that the pea and bean chloroplast genes for these enzymes originated from the duplication of nuclear genes as a result of the different metabolic needs of the various species. The data indicate that the duplication of plastid glutamine synthetase genes occurred long after the endosymbiotic events that produced the organelles themselves.

  16. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells

    OpenAIRE

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K.; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F.; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E.; Sonveaux, Pierre

    2015-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning th...

  17. Glutamine synthetase localization in cortisol-induced chick embryo retinas

    OpenAIRE

    1980-01-01

    We report here for the first time, in chick retina, Muller cell localization of glutamine synthetase (GS) activity by an immunohistochemical technique, in agreement with previous reports of glial localization of this enzyme in rat brain and retina. Age- dependent changes in the endogenous enzyme activity as well as cortisol- induced changes in GS activity, both in ovo and in vitro, measured biochemically, reflect the changes observed by staining.

  18. Glutamine synthetase activity in the ruminal bacterium Succinivibrio dextrinosolvens.

    OpenAIRE

    Patterson, J A; Hespell, R B

    1985-01-01

    Succinivibrio dextrinosolvens C18 was found to possess glutamine synthetase (GS), urease, glutamate dehydrogenase, and several other nitrogen assimilation enzymes. When grown in continuous culture under ammonia limitation, both GS and urease activities were high and glutamate dehydrogenase activity was low, but the opposite activity pattern was observed for growth in the presence of ample ammonia. The addition of high-level (15 mM) ammonium chloride to ammonia-limited cultures resulted in a r...

  19. Phytogenic additives and glutamine plus glutamic acid in broiler diets

    OpenAIRE

    VC Pelícia; AC Stradiotti; PC Araujo; MK Maruno; FB Carvalho; AC Pezzato; JR Sartori

    2013-01-01

    The objective of this study was to evaluate the effect of the dietary supplementation of phytogenic additives (PAs) and glutamine plus glutamic acid (Gln/Glu), associated or not, in replacement of antibiotic growth promoters and anticoccidials (AGP/AC) on the performance and carcass yield of broilers. Five hundred male Cobb broilers were housed in an experimental house and randomly distributed into five treatments, with four replicates of 25 birds each. Treatments consisted of a control diet ...

  20. Controlling the prion propensity of glutamine/asparagine-rich proteins

    OpenAIRE

    Paul, Kacy R.; Ross, Eric D.

    2015-01-01

    ABSTRACT The yeast Saccharomyces cerevisiae can harbor a number of distinct prions. Most of the yeast prion proteins contain a glutamine/asparagine (Q/N) rich region that drives prion formation. Prion-like domains, defined as regions with high compositional similarity to yeast prion domains, are common in eukaryotic proteomes, and mutations in various human proteins containing prion-like domains have been linked to degenerative diseases, including amyotrophic lateral sclerosis. Here, we discu...

  1. The effect of immunonutrition (glutamine, alanine on fracture healing

    Directory of Open Access Journals (Sweden)

    Abdullah Küçükalp

    2014-11-01

    Full Text Available Background: There have been various studies related to fracture healing. Glutamine is an amino acid with an important role in many cell and organ functions. This study aimed to make a clinical, radiological, and histopathological evaluation of the effects of glutamine on fracture healing. Methods: Twenty rabbits were randomly allocated into two groups of control and immunonutrition. A fracture of the fibula was made to the right hind leg. All rabbits received standard food and water. From post-operative first day for 30 days, the study group received an additional 2 ml/kg/day 20% L-alanine L-glutamine solution via a gastric catheter, and the control group received 2 ml/kg/day isotonic via gastric catheter. At the end of 30 days, the rabbits were sacrificed and the fractures were examined clinically, radiologically, and histopathologically in respect to the degree of union. Results: Radiological evaluation of the control group determined a mean score of 2.5 according to the orthopaedists and 2.65 according to the radiologists. In the clinical evaluation, the mean score was 1.875 for the control group and 2.0 for the study group. Histopathological evaluation determined a mean score of 8.5 for the control group and 9.0 for the study group. Conclusion: One month after orally administered glutamine–alanine, positive effects were observed on fracture healing radiologically, clinically, and histopathologically, although no statistically significant difference was determined.

  2. Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis.

    Science.gov (United States)

    Levine, R L; Oliver, C N; Fulks, R M; Stadtman, E R

    1981-04-01

    We partially purified a preparation from Escherichia coli that proteolytically degrades the enzyme glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2]. The degradation is at least a two-step process. First, the glutamine synthetase undergoes an oxidative modification. This modification leads to loss of catalytic activity and also renders the protein susceptible to proteolytic attack in the second step. The oxidative step displays characteristics of a mixed-function oxidation, requiring both molecular oxygen and a reduced nucleotide. This step can also be catalyzed by a purified, mammalian cytochrome P-450 system, as well as by a model system consisting of ascorbic acid and oxygen. Catalase blocks this oxidative modification step. Thus, the overall process of proteolytic degradation can be observed only if care is taken to remove catalase activity from the extracts. The inactivation reaction is dependent on the state of adenylylation of the glutamine synthetase, suggesting that this a physiologically important reaction. If so, then mixed-function oxidases are now implicated in the process of intracellular protein turnover.

  3. Identification of the glutamine synthetase adenylyltransferase of Azospirillum brasilense.

    Science.gov (United States)

    Van Dommelen, Anne; Spaepen, Stijn; Vanderleyden, Jozef

    2009-04-01

    Glutamine synthetase, a key enzyme in nitrogen metabolism of both prokaryotes and eukaryotes, is strictly regulated. One means of regulation is the modulation of activity through adenylylation catalyzed by adenylyltransferases. Using PCR primers based on conserved sequences in glutamine synthetase adenylyltransferases, we amplified part of the glnE gene of Azospirillum brasilense Sp7. The complete glnE sequence of A. brasilense Sp245 was retrieved from the draft genome sequence of this organism (http://genomics.ornl.gov/research/azo/). Adenylyltransferase is a bifunctional enzyme consisting of an N-terminal domain responsible for deadenylylation activity and a C-terminal domain responsible for adenylylation activity. Both domains are partially homologous to each other. Residues important for catalytic activity were present in the deduced amino acid sequence of the A. brasilense Sp245 glnE sequence. A glnE mutant was constructed in A. brasilense Sp7 by inserting a kanamycin resistance cassette between the two active domains of the enzyme. The resulting mutant was unable to adenylylate the glutamine synthetase enzyme and was impaired in growth when shifted from nitrogen-poor to nitrogen-rich medium.

  4. Glutamine supplementation and immune function during heavy load training.

    Science.gov (United States)

    Song, Qing-Hua; Xu, Rong-Mei; Zhang, Quan-Hai; Shen, Guo-Qing; Ma, Ming; Zhao, Xin-Ping; Guo, Yan-Hua; Wang, Yi

    2015-05-01

    Athletes with heavy training loads are prone to infectious illnesses, suggesting that their training may suppress immune function. This study sought to determine whether supplementation with the amino acid glutamine, which supports immune health, alters immune function in athletes during heavy load training. 24 athletes were randomly assigned to either an experimental group (n = 12) or a control group (n = 12). Athletes exercised using heavy training loads for 6 weeks. Athletes in the experimental group took 10 g glutamine orally once a day beginning 3 weeks after initial testing, while athletes in the control group were given a placebo. Immune function was assessed by measuring the following immunity markers: CD4⁺ and CD8⁺ T cell counts, serum IgA, IgG, and IgM levels, and natural killer (NK) cell activity both before and after the completion of training. The percentages of circulating CD8⁺ T cells were significantly different before (39.13 ± 5.87%) and after (26.63 ± 3.95%) training in the experimental group (p glutamine supplementation may be able to restore immune function and reduce the immunosuppressive effects of heavy-load training.

  5. L-arginine and L-glutamine as immunonutrients and modulating agents for oxidative stress and toxicity induced by sodium nitrite in rats.

    Science.gov (United States)

    El-Sheikh, Nora M; Khalil, Fatma A

    2011-04-01

    Sodium nitrite (NaNO(2)) is a flavoring, coloring and preservative agent in meat and fish products. The study aimed to evaluate the efficacy of L-arginine and L-glutamine supplementation as a potentially novel and useful strategy for the modulation of oxidative stress and toxicity induced by NaNO(2) in male rats. Rats were divided into six groups each of 10 rats and treated for 6 weeks: group 1 as normal control; group 2 fed standard diet containing 0.2% NaNO(2); group 3 and 4 fed the previous diet supplemented with 1% and 2% arginine, respectively; group 5 and 6 fed NaNO(2) diet supplemented with 1% and 2% glutamine, respectively. NaNO(2) treatment induced a significant increase in serum malondialdehyde, nitric oxide, arginase, glutathione-S-transferase activities, urea and creatinine as well as differential leucocytes%. However, a significant decrease was recorded in reduced glutathione, catalase activity, total protein, albumin and some hematological parameters as well as immunoglobulin G. On the other hand, arginine or glutamine showed a remarkable modulation of these abnormalities as indicated by reduction of malondialdehyde and improvement of the investigated antioxidant and hematological parameters. It can be concluded that arginine or glutamine supplementation may reduce oxidative stress and improve the hazard effects of NaNO(2).

  6. Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on tissue content of dopamine and serotonin as well as glutamate and glutamine.

    Science.gov (United States)

    Althobaiti, Yusuf S; Almalki, Atiah H; Das, Sujan C; Alshehri, Fahad S; Sari, Youssef

    2016-11-10

    Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a β-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every 2h×4) followed by either saline or CEF (200mg/kg, i.p, every day×3) post-treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc and PFC. Importantly, dopamine tissue content was completely restored in the NAc following CEF post-treatment. Additionally, METH caused a significant decrease in glutamate and glutamine tissue content in PFC, and this effect was attenuated by CEF post-treatment. These findings demonstrate for the first time the attenuating effects of CEF post-treatment on METH induced alterations in the tissue contents of dopamine, glutamate, and glutamine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy.

    Science.gov (United States)

    Gruenbaum, Shaun E; Wang, Helen; Zaveri, Hitten P; Tang, Amber B; Lee, Tih-Shih W; Eid, Tore; Dhaher, Roni

    2015-10-01

    The prevalence of depression and suicide is increased in patients with mesial temporal lobe epilepsy (MTLE); however, the underlying mechanism remains unknown. Anhedonia, a core symptom of depression that is predictive of suicide, is common in patients with MTLE. Glutamine synthetase, an astrocytic enzyme that metabolizes glutamate and ammonia to glutamine, is reduced in the amygdala in patients with epilepsy and depression and in suicide victims. Here, we sought to develop a novel model of anhedonia in MTLE by testing the hypothesis that deficiency in glutamine synthetase in the central nucleus of the amygdala (CeA) leads to epilepsy and comorbid anhedonia. Nineteen male Sprague-Dawley rats were implanted with an osmotic pump infusing either the glutamine synthetase inhibitor methionine sulfoximine [MSO (n=12)] or phosphate buffered saline [PBS (n=7)] into the right CeA. Seizure activity was monitored by video-intracranial electroencephalogram (EEG) recordings for 21days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21days. Methionine sulfoximine-infused rats exhibited recurrent seizures during the monitoring period and showed decreased sucrose preference over days when compared with PBS-infused rats (pglutamine synthetase activity in the CeA is a possible common cause of anhedonia and seizures in TLE. We propose that the MSO CeA model can be used for mechanistic studies that will lead to the development and testing of novel drugs to prevent seizures, depression, and suicide in patients with TLE.

  8. Expression of glutamine synthetase in balloon cells: a basis of their antiepileptic role?

    Science.gov (United States)

    Buccoliero, Anna Maria; Barba, Carmen; Giordano, Flavio; Baroni, Gianna; Genitori, Lorenzo; Guerrini, Renzo; Taddei, Gian Luigi

    2015-01-01

    Glutamine synthetase is an enzyme involved in the clearance of glutamate, the most potent excitatory neurotransmitter. We studied the immunohistochemical expression of glutamine synthetase in neocortical samples from 5 children who underwent surgery for pharmacoresistant epilepsy and a histological diagnosis of focal cortical dysplasia IIb. In all cases, balloon cells, but not dysmorphic neurons, were immunopositive for glutamine synthetase. This finding suggests that balloon cells can be involved in the neutralization of glutamate and play a protective anti-seizure role.

  9. No benefit of glutamine supplementation on persistent diarrhea in Ugandan children.

    Science.gov (United States)

    Kamuchaki, Justine M; Kiguli, Sarah; Wobudeya, Eric; Bortolussi, Robert

    2013-05-01

    We evaluated the efficacy of oral glutamine supplementation in children 2 to 60 months of age with persistent diarrhea by 1:1 randomization to standard treatment alone or together with twice daily glutamine. The failure rate was similar in both arms (relative risk: 1.8 [95% confidence interval: 0.8-3.7], P = 0.12). Glutamine supplementation showed no benefit on the outcome of persistent diarrhea.

  10. Sustained response to intravenous alendronate in postmenopausal osteoporosis.

    Science.gov (United States)

    Vasikaran, S D; Khan, S; McCloskey, E V; Kanis, J A

    1995-12-01

    We studied the effects of alendronate (amino-hydroxybutylidene bisphosphonate) on biochemical indices of bone turnover and on lumbar spinal bone mineral density in 15 postmenopausal women with vertebral osteoporosis. Alendronate 7.5 mg daily was administered intravenously as a slow infusion for four consecutive days. Treatment was associated with a significant decrease in serum calcium (p transient lymphopenia or leucopenia was noted in eight patients and a short-lived fever in six. No other side effects were observed. This study demonstrates that shortterm exposure to high intravenous doses of alendronate induces suppression of bone resorption in osteoporosis that persists for at least 6 months after infusion. We conclude that a short exposure to high intravenous doses induces sustained effects on bone turnover in much the same manner as that observed in Paget's disease of bone.

  11. Initial pharmacology and toxicology of intravenous desmethylmisonidazole

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, C.N. (Stanford Univ., CA); Wasserman, T.H.; Phillips, T.L.; Strong, J.M.; Urtasun, R.C.; Schwade, J.G.; Johnson, R.J.; Zagars, G.

    1982-03-01

    Since January 1981, 52 patients have entered the Radiaton Therapy Oncology Group Phase I trial with intravenous (i.v.) desmethylmisonidazole (DMM). DMM is less lipophilic than misonidazole (MISO) and theoretically will be less neurotoxic due to lower penetration into neural tissue and more rapid elimination. The drug is administered intravenously to achieve the maximum drug concentration in tumor for a given dose. The protocol slowly escalates the total dose of drug administered. At this time the planned dose on the three week schedule is 1 g/m/sup 2/ twice weekly to a total dose of 17.5g/m/sup 2/. The preliminary plasma pharmacokinetic data demonstrates high peak plasma levels within five minutes of the end of the drug infusion. Compared to MISO the percent of DMM excreted in the urine is increased, 63% vs 10%, and the elimination half-life is decreased: DMM, i.v. 5.3h; MISO, i.v. 9.3h; MISO, oral 10 to 13h. Neurotoxicity has been observed in approximately 30% of patients given a cumulative dose of >11g/m/sup 2/. This is in comparison to a 50% incidence in RTOG Phase 1 study with oral MISO at doses of 12g/m/sup 2/. There is not sufficient data to evaluate the relationship between neurotoxicity and drug exposure. Further patient accrual on this study is required to better define the properties of DMN.

  12. Bacterial Type I Glutamine Synthetase of the Rifamycin SV Producing Actinomycete, Amycolatopsis mediterranei U32, is the Only Enzyme Responsible for Glutamine Synthesis under Physiological Conditions

    Institute of Scientific and Technical Information of China (English)

    Wen-Tao PENG; Jin WANG; Ting WU; Jian-Qiang HUANG; Jui-Shen CHIAO; Guo-Ping ZHAO

    2006-01-01

    The structural gene for glutamine synthetase, glnA, from Amycolatopsis mediterranei U32 was cloned via screening a genomic library using the analog gene from Streptomyces coelicolor. The clone was functionally verified by complementing for glutamine requirement of an Escherichia coli glnA null mutant under the control of a lac promoter. Sequence analysis showed an open reading frame encoding a protein of466 amino acid residues. The deduced amino acid sequence bears significant homologies to other bacterial type I glutamine synthetases, specifically, 71% and 72% identical to the enzymes of S. coelicolor and Mycobacterium tuberculosis, respectively. Disruption of this glnA gene in A. mediterranei U32 led to glutamine auxotrophy with no detectable glutamine synthetase activity in vivo. In contrast, the cloned glnA+ gene can complement for both phenotypes in trans. It thus suggested that in A. mediterranei U32, the glnA gene encoding glutamine synthetase is uniquely responsible for in vivo glutamine synthesis under our laboratory defined physiological conditions.

  13. [Intravenous remifentanyl for labor analgesia].

    Science.gov (United States)

    Arnal, D; Serrano, M L; Corral, E M; García del Valle, S

    2009-04-01

    Intravenous remifentanil may be the preferred analgesic when regional techniques are contraindicated. To perform a systematic review on the use of remifentanil for analgesia in labor. We searched MEDLINE (January 1995-August 2007) for studies on obstetric analgesia with remifentanil. We found 32 references representing the use of remifentanil in 257 women in labor. In most cases, patients reported relief of pain and a high level of satisfaction, with no severe side effects in mothers or neonates. When compared with meperidine and nitrous oxide in clinical trials, remifentanil provided better analgesia with fewer adverse effects. Analgesia with intravenous remifentanil is more effective and safer than other alternatives to regional analgesic techniques in obstetrics. Nevertheless, the optimum system for infusing the drug must b e established and further studies of maternal and fetal safety should be carried out.

  14. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  15. Anaphylactic reaction to intravenous diclofenac

    Directory of Open Access Journals (Sweden)

    Ranju Singh

    2011-01-01

    Full Text Available Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used as an opioid sparing agent for postoperative analgesia. Anaphylaxis due to intravenous diclofenac sodium is very rare. We report a case of anaphylactic reaction to IV diclofenac sodium, occurring postoperatively in a 25-year-old primigravida, the clinical features of which mimicked pulmonary embolism. The rarity, clinical importance and the diagnostic dilemma associated prompted us to report this case.

  16. New developments in glutamine delivery%谷氨酰胺给药的新进展

    Institute of Scientific and Technical Information of China (English)

    PeterFuerst,MD

    2001-01-01

    Free glutamine-a critical issueNumerous studies demonstrate that free glutamine can be added to commercially available crystalline amino acid based preparations prior to their administration.Instability during heat sterilization and prolonged storage and linited solubility (35 g/L at 20℃) hampers the use of free glutamine in routine clinical setting.Indeed,there are many well controlled and valuable trials with free glutamine,yet its use is restricted to clinical research.How to solve the problem?The obvious linitations of using free glutamine initiated an intensive search for alternative substrates.Indeed,glutamic acid is a poor precursor;its in vivo transformation to glutamine is restricted to yield only 5-6%.Similarly,the transformation of α-ketoglutarate or the salt ornthine-α-ketoglutarate to glutamine is confined since they are primarily precursors for glutamic acid.Parenterally supplied acetyl glutamine is poorly utilized in man;the large urinary excretion (45-50%) being associated with considerable accumulation of acetyl glutamine in body fluids.It can be concluded that N-acetylated glutamine is not suitable as alternative glutamine source in humans due to restricted acylase capacities.Synthetic glutamine dipeptides are stable under heat sterilization and highly soluble;these properties qualify the dipeptides as suitable constituents of nutritional preparations.Industrial production of these dipeptides at a reasonable price is an essential prerequisite for implications of dipeptide-containing solutions in clinical practice.Recent development of novel synthesis procedures allows increased capacity in industrial-scale production.Basic studies with synthetic glutamine-containing short-chain peptides provide convincing evidence that these new substrates are rqpidly cleared from plasma after parenteral administration,without being accumulated in tissues,and with negligible loss of urine.The presence of membrane-bound as well as tissue free extracellular

  17. Glutamine supplementation prevents exercise-induced neutrophil apoptosis and reduces p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression.

    Science.gov (United States)

    Lagranha, Claudia J; Hirabara, Sandro M; Curi, Rui; Pithon-Curi, Tania C

    2007-01-01

    We have previously shown that a single session of exercise induces DNA fragmentation, mitochondrial membrane depolarization, increases expression of pro-apoptotic genes (bax and bcl-xS) and decreases expression of anti-apoptotic genes (bcl-xL) in rat neutrophils. Glutamine supplementation had a protective effect in the apoptosis induced by a single session of exercise. The mechanism involved in the effect of single session of exercise to induce apoptosis was investigated by measuring expression of p53 and caspase 3 and phosphorylation of p38 mitogen-activated protein kinases (MAPK) and cJun NH(2)-terminal kinase (JNK) in neutrophils from rats supplemented or not with glutamine. Exercise was carried out on a treadmill for 1 h and the rats were killed by decapitation. Neutrophils were obtained by intraperitoneal (i.p.) lavage with PBS, 4 h after injection of oyster glycogen solution. Glutamine supplementation (1g per Kg b.w.) was given by gavage 1 h before the exercise session. Gene expression and protein phosphorylation were then analyzed by reverse transcriptase chain reaction (RT-PCR) and Western blotting, respectively. A single session of exercise increased p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression. Glutamine supplementation partially prevented the increase in p38 MAPK and JNK phosphorylation and p53 expression, and fully abolished the increase in caspase 3 expression. Thus, neutrophil apoptosis induced by a single session of exercise is accompanied by increased p53 and caspase 3 expression and p38 MAPK and JNK phosphorylation. Glutamine supplementation prevents these effects of exercise and reduces apoptosis.

  18. Effects of glutamine on intestinal permeability and bacterial translocation in TPN-rats with endotoxemia

    Institute of Scientific and Technical Information of China (English)

    Lian-An Ding; Jie-Show Li

    2003-01-01

    AIM: To evaluate the protective effect and mechanism ofglutamine on the intestinal barrier function in totalparenteral nutrition (TPN) rats with trauma or endotoxemia. METHODS: To perform prospective, randomized andcontrolled animal experimentation of rats with surgicaltrauma, TPN and endotoxemia, thirty-four male, adultSprague Dawley rats were divided into four groups: control group (n=8), TPN group (n=9), trauma and endotoxemia group (LPS, n=8) and trauma plus endotoxemia supplemented with glutamine in TPN solution group (Gin.group, n=9). All groups except the control group were given TPN solutions in 7-day experimental period. For Gin group, 1 000 mg/kg/d of glutamine was added to TPN solution during day 1-6. On the 7th day all the animals were gavaged with lactulose (66 mg) and mannitol (50 mg)in 2 mi of normal saline. Then 24 h urine with preservative was collected and kept at -20 ℃. On day 8, under intraperitoneal anesthesia using 100 mg/kg ketamin, the intestine, liver, mesenteric lymph nodes and blood were taken for examination. RESULTS: The body weight of LPS group decreased most among the four groups. The structure of small intestinal mucosa in TPN group, LPS group and Gln group showed impairments of different degrees, and the damage of small intestinal mucosa in Gln group was remarkably alleviated.The concentrations of interleukins in small intestine mucosa were lower (for IL-4 and IL-6) or the lowest (IL-10) in Gln group. The IgA level in the blood plasma and the mucosa of Gln group was the highest among all of the groups. The urine lactulose/mannitol test showed that the intestinal permeability in LPS group was lower than that in TPN group (P<0.001), but there was no difference between LPS group and Gln group. The rate of bacterial translocation in Gln group was lower than that in LPS group (P<0.02). CONCLUSION: Prophylactic treatment with glutamine could minimize the increments of intestinal permeability and bacterial translocation caused by

  19. Arginine synthesis from enteral glutamine in healthy adults in the fed state.

    Science.gov (United States)

    Tomlinson, Chris; Rafii, Mahroukh; Ball, Ronald O; Pencharz, Paul

    2011-08-01

    Recent studies have documented transfer of labeled nitrogen from [2-(15)N]glutamine to citrulline and arginine in fasting human adults. Conversely, in neonates and piglets we have shown no synthesis of arginine from [2-(15)N]glutamate, and others have shown in mice that glutamine is a nitrogen, but not a carbon donor, for arginine synthesis. Therefore, we performed a multitracer study to determine whether glutamine is a nitrogen and/or carbon donor for arginine in healthy adult men. Two glutamine tracers, 2-(15)N and 1-(13)C, were given enterally to five healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two glutamine tracers. 1-(13)C isotopomers of citrulline and arginine were synthesized from [1-(13)C]glutamine. Three isotopomers each of citrulline and arginine were synthesized from the [2-(15)N]glutamine tracer: 2-(15)N, 5-(15)N, and 2,5-(15)N(2). Significantly greater enrichment was found of both [5-(15)N]arginine (0.75%) and citrulline (3.98%) compared with [2-(15)N]arginine (0.44%) and [2-(15)N]citrulline (2.62%), indicating the amino NH(2) from glutamine is mostly transferred to arginine and citrulline by transamination. Similarly, the enrichment of the 1-(13)C isotopomers was significantly less than the 2-(15)N isotopomers, suggesting rapid formation of α-ketoglutarate and recycling of the nitrogen label. Our results show that the carbon for 50% of newly synthesized arginine comes from dietary glutamine but that glutamine acts primarily as a nitrogen donor for arginine synthesis. Hence, studies using [2-(15)N]glutamine will overestimate arginine synthesis rates.

  20. Response of transgenic poplar overexpressing cytosolic glutamine synthetase to phosphinothricin.

    Science.gov (United States)

    Pascual, María Belén; Jing, Zhong Ping; Kirby, Edward G; Cánovas, Francisco M; Gallardo, Fernando

    2008-01-01

    Glutamine synthetase (GS) is the main enzyme involved in ammonia assimilation in plants and is the target of phosphinothricin (PPT), an herbicide commonly used for weed control in agriculture. As a result of the inhibition of GS, PPT also blocks photorespiration, resulting in the depletion of leaf amino acid pools leading to the plant death. Hybrid transgenic poplar (Populus tremula x P. alba INRA clone 7171-B4) overexpressing cytosolic GS is characterized by enhanced vegetative growth [Gallardo, F., Fu, J., Cantón, F.R., García-Gutiérrez, A., Cánovas, F.M., Kirby, E.G., 1999. Expression of a conifer glutamine synthetase gene in transgenic poplar. Planta 210, 19-26; Fu, J., Sampalo, R., Gallardo, F., Cánovas, F.M., Kirby, E.G., 2003. Assembly of a cytosolic pine glutamine synthetase holoenzyme in leaves of transgenic poplar leads to enhanced vegetative growth in young plants. Plant Cell Environ. 26, 411-418; Jing, Z.P., Gallardo, F., Pascual, M.B., Sampalo, R., Romero, J., Torres de Navarra, A., Cánovas, F.M., 2004. Improved growth in a field trial of transgenic hybrid poplar overexpressing glutamine synthetase. New Phytol. 164, 137-145], increased photosynthetic and photorespiratory capacities [El-Khatib, R.T., Hamerlynck, E.P., Gallardo, F., Kirby, E.G., 2004. Transgenic poplar characterized by ectopic expression of a pine cytosolic glutamine synthetase gene exhibits enhanced tolerance to water stress. Tree Physiol. 24, 729-736], enhanced tolerance to water stress (El-Khatib et al., 2004), and enhanced nitrogen use efficiency [Man, H.-M., Boriel, R., El-Khatib, R.T., Kirby, E.G., 2005. Characterization of transgenic poplar with ectopic expression of pine cytosolic glutamine synthetase under conditions of varying nitrogen availability. New Phytol. 167, 31-39]. In vitro plantlets of GS transgenic poplar exhibited enhanced resistance to PPT when compared with non-transgenic controls. After 30 days exposure to PPT at an equivalent dose of 275 g ha(-1), growth

  1. True hyponatremia secondary to intravenous immunoglobulin.

    Science.gov (United States)

    Nguyen, Minhtri K; Rastogi, Anjay; Kurtz, Ira

    2006-06-01

    Hyponatremia is characterized as either "true hyponatremia," which represents a decrease in the Na(+) concentration in the water phase of plasma, or "pseudohyponatremia," which is due to an increased percentage of protein or lipid in plasma, with a normal plasma water Na(+) concentration ([Na(+)]). Pseudohyponatremia is a known complication of intravenous immunoglobulin (IVIG). Because IVIG has been reported to result in post-infusional hyperproteinemia, IVIG-induced hyponatremia has been attributed to pseudohyponatremia. In this case report, we demonstrate that IVIG therapy can result in true hyponatremia, resulting from sucrose-induced translocation of water from the intracellular compartment (ICF) to the extracellular compartment (ECF), as well as the infusion of a large volume of dilute fluid, in patients with an underlying defect in urinary free water excretion.

  2. Butachlor impact on protein, free amino acid and glutamine contents, and on activity levels of aminotransferases, glutamate dehydrogenase and glutamine synthetase in the fresh water snail, Pila globosa (Swainson).

    Science.gov (United States)

    Rajyalakshmi, T; Srinivas, T; Swamy, K V; Mohan, P M

    1996-08-01

    Biochemical changes followed in the freshwater snail Pila globosa (Swainson) during exposure to sublethal concentrations of the herbicide butachlor (26.6 ppm) in the ambient medium, at 3,6,12,24 and 48 h intervals, were marked by a significant decrease in total and soluble proteins, and an increase in free amino acids in foot and hepatopancreas up to 12 h before gradually recovering. Aminotransferase activities and glutamine content decreased during the early periods of exposure, while glutamate dehydrogenase activity increased. After an initial elevation, glutamate synthetase activity decreased at later intervals. Maximum effect of butachlor on the enzymes was seen after 12 h exposure. The extent of increase or decrease in different parameters examined varied between the two tissues studied. These changes are discussed in relation to the toxic stress of butachlor.

  3. Systematic review: intravenous Ibuprofen in preterm newborns.

    Science.gov (United States)

    Aranda, J V; Thomas, Ronald

    2006-06-01

    Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic, antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose-dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in preterm newborns with patent ductus arteriosus. Clinical trials have compared IV ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug before and after its administration have also been evaluated. Compared with placebo, IV ibuprofen effectively closed PDA with minimal effect on renal function. One study using intravenous ibuprofen-THAM showed decreased renal function and increased risk of NEC and PPHN. Compared with indomethacin, IV ibuprofen lysine exerted similar efficacy (75% to 93% closure). However, indomethacin increased abnormal renal function and decreased mesenteric and cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen did not reduce the incidence of intraventricular hemorrhage compared with placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours), suggesting that once daily dosing is appropriate. Dose finding studies indicate that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and indomethacin indicate that, on the first day of life when IVH prevention is desired, indomethacin and not ibuprofen should be used since ibuprofen has no effect on IVH risk. On or after the second day of postnatal life, when early or therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the first choice due to its better adverse event profile.

  4. Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia

    DEFF Research Database (Denmark)

    Kempaiah, Prakasha; Dokladny, Karol; Karim, Zachary

    2016-01-01

    Severe malarial anemia [SMA, hemoglobin (Hb) SMA was characterized...... in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70...... was correlated with reticulocyte production and Hb. Since glutamine (Gln) up-regulates Hsp70, modulates NF-κB activation, and attenuates over-expression of pro-inflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA...

  5. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  6. Impairment of glutamine/glutamate-γ-aminobutyric acid cycle in manganese toxicity in the central nervous system.

    Science.gov (United States)

    Sidoryk-Wegrzynowicz, M

    2014-01-01

    Manganese (Mn) is an essential trace element that is required for maintaining the proper function and regulation of many biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system. The overdose accumulation of Mn in specific brain areas, such as the substantia nigra, the globus pallidus and the striatum, triggers neurotoxicity resulting in a neurological brain disorder, referred to as manganism. Manganese toxicity is associated with the disruption of glutamine (Gln)/glutamate (Glu) GABA cycle (GGC). The GGC represents a complex process, since Gln efflux from astrocytes must be met by its influx in neurons. Mn toxicity is associated with the disruption of both of these critical points in the cycle. In cultured astrocytes, pre-treatment with Mn inhibits the initial net uptake of Gln in a concentration-dependent manner. Manganese added directly to astrocytes induces deregulation in the expression of SNAT3, SNAT2, ASCT2 and LAT2 transporters and significantly decreases in Gln uptake mediated by the transporting Systems N and ASC, and a decrease in Gln efflux mediated by Systems N, ASC and L. Further, Mn disrupts Glu transporting systems leading to both a reduction in Glu uptake and elevation in extracellular Glu levels. Interestingly, there appear to be common signaling targets of Mn in GGC cycling in glial cells. Namely, the PKC signaling is affected by Mn in Gln and Glu transporters expression and function. Additionally, Mn was identified to deregulate glutamine synthetase (GS) expression and activity. Those evidences could triggers depletion of Gln synthesis/metabolism in glia cells and consequently diminish astrocytic-derived glutamine, while disruption of Glu removal/transport can mediate dyshomeostasis in neurotransmission of functioning neurons. Overdose and excessive Mn accumulations in astrocytes not only culminate in pathology, but also affect astrocytic protective properties and defect or

  7. Inactivation of Glutamine Synthetase by Ammonia Shock in the Gram-Positive Bacterium Streptomyces cattleya.

    Science.gov (United States)

    Wax, R; Synder, L; Kaplan, L

    1982-10-01

    In cultures of the gram-positive bacterium Streptomyces cattleya, a rapid inactivation of glutamine synthetase was seen after ammonia shock. pH activity curves for ammonia-shocked and control cultures are shown. A peak of glutamine synthetase activity was seen during fermentation for production of the antibiotic thienamycin.

  8. Regulation of Amidase Formation in Mutants from Pseudomonas aeruginosa PAO Lacking Glutamine Synthetase Activity

    NARCIS (Netherlands)

    Janssen, Dick B.; Herst, Patricia M.; Joosten, Han M.L.J.; Drift, Chris van der

    1982-01-01

    The formation of amidase was studied in mutants from Pseudomonas aeruginosa PAO lacking glutamine synthetase activity. It appeared that catabolite repression of amidase synthesis by succinate was partially relieved when cellular growth was limited by glutamine. Under these conditions, a correlation

  9. The effect of glutamine infusion on the inflammatory response and HSP70 during human experimental endotoxaemia

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Pedersen-Skovsgaard, Theis; Mortensen, Ole Hartvig;

    2009-01-01

    INTRODUCTION: Glutamine supplementation has beneficial effects on morbidity and mortality in critically ill patients, possibly in part through an attenuation of the proinflammatory cytokine response and a stimulation of heat shock protein (HSP)70. We infused either alanine-glutamine or saline dur...

  10. Effect of L-glutamine levels in piglets diets challenged with Escherichia coli lipopolysacharides

    Directory of Open Access Journals (Sweden)

    Arturo Pardo L.

    2014-09-01

    Full Text Available Objective. To evaluate the effect of different levels of L-glutamine on weaned and immunologically challenged piglets with Escherichia coli lipopolysaccharides (LPS on performance parameters, serum cortisol and defense cells. Materials and methods. Four levels of L –glutamine were evaluated (0, 1.0, 1.5, 2.0% as well as the addition, or no addition, of LPS (0.3μg. 96 piglets were used (48 castrated males and 48 females of Agroceres x PenArlan lineage, with an initial age of 21 days and 6.06±0.852 kg live weight. An experimental design was used on randomized blocks in a factorial setting 4 x 2 (levels of L- glutamine with or without challenge. Results. Cubic effect was shown for daily weight gain of unchallenged animals, and was better with the addition of 0.41% L- glutamine. Feed conversion improved with increased levels of L -glutamine for challenged animals. In the evaluation of defense cells, there was interaction of leukocytes with the levels of L- glutamine and the immune challenge. Eosinophils and lymphocytes showed a quadratic effect for the levels of L –glutamine, with a maximum value of 1.30% and 0.5%, respectively. Conclusions. L -glutamine supplementation of up to 2% in the diet improves feed conversion and favors the immune serum of weaned piglets challenged with LPS of E. coli.

  11. Plasma glutamine is a minor precursor for the synthesis of citrulline: A multispecies study

    Science.gov (United States)

    Glutamine is considered the main precursor for citrulline synthesis in many species, including humans. The transfer of 15N from 2[15N]-glutamine to citrulline has been used as evidence for this precursor-product relationship. However, work in mice has shown that nitrogen and carbon tracers follow di...

  12. Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Efrossini Briassouli

    2012-01-01

    Full Text Available Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups, premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

  13. Inactivation of Glutamine Synthetase by Ammonia Shock in the Gram-Positive Bacterium Streptomyces cattleya

    OpenAIRE

    Wax, Richard; Synder, Linda; Kaplan, Louis

    1982-01-01

    In cultures of the gram-positive bacterium Streptomyces cattleya, a rapid inactivation of glutamine synthetase was seen after ammonia shock. pH activity curves for ammonia-shocked and control cultures are shown. A peak of glutamine synthetase activity was seen during fermentation for production of the antibiotic thienamycin.

  14. Regulation of Amidase Formation in Mutants from Pseudomonas aeruginosa PAO Lacking Glutamine Synthetase Activity

    NARCIS (Netherlands)

    Janssen, Dick B.; Herst, Patricia M.; Joosten, Han M.L.J.; Drift, Chris van der

    1982-01-01

    The formation of amidase was studied in mutants from Pseudomonas aeruginosa PAO lacking glutamine synthetase activity. It appeared that catabolite repression of amidase synthesis by succinate was partially relieved when cellular growth was limited by glutamine. Under these conditions, a correlation

  15. Glutamine randomized studies in early life: the unsolved riddle of experimental and clinical studies.

    Science.gov (United States)

    Briassouli, Efrossini; Briassoulis, George

    2012-01-01

    Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of "glutamine-heat shock proteins-stress response" in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

  16. Effects of glutamine on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis

    Directory of Open Access Journals (Sweden)

    Brenda Carla Luquetti

    2016-08-01

    Full Text Available ABSTRACT This study aimed to assess the effects of glutamine as feed additive on performance and intestinal mucosa morphometry of broiler chickens vaccinated against coccidiosis. A total of 400 day-old male chicks were randomly assigned to four treatments (NVNG – no vaccination, no glutamine supplementation; NVG – no vaccination, glutamine supplementation (10 g kg−1; VNG – vaccination, no glutamine supplementation; VG – vaccination, glutamine supplementation replicated four times with 25 birds per replicate. A commercial sprayed-on vaccine against coccidiosis containing Eimeria acervulina, E. maxima, E. mivati, and E. tenella was administered at the hatchery. Broiler performance was evaluated from 1-28 days, and morphometric parameters were analyzed at 14, 21, and 28 days of age. Body weight gain and feed intake were negatively affected by vaccination, but not by glutamine. Vaccination increased crypt depth in the duodenum and jejunum at 21 and 28 days. In conclusion, this study showed that glutamine was not able to increase weight gain of broiler chickens, irrespective of whether the animals were vaccinated or not against coccidiosis. Glutamine supplementation was able to improve feed conversion in vaccinated birds suggesting trophic effect on intestinal epithelium improving.

  17. Cytokine responses in very low birth weight infants receiving glutamine-enriched enteral nutrition

    NARCIS (Netherlands)

    A. van den Berg; R.M. van Elburg; L. Vermeij; A. van Zwol; G.R. van den Brink; J.W.R. Twisk; E.E.S. Nieuwenhuis; W.P.F. Fetter

    2009-01-01

    Objective: Very low birth weight (VLBW) infants receiving glutamine-enriched enteral nutrition may present with a lower infection rate, which may result from enhanced antimicrobial innate or Th1 cytokine responses. We investigated whether glutamine-enriched enteral nutrition in VLBW infants increase

  18. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

    DEFF Research Database (Denmark)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne

    2014-01-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains...

  19. Oral supplementations with free and dipeptide forms of L-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins.

    Science.gov (United States)

    Cruzat, Vinicius F; Pantaleão, Lucas C; Donato, José; de Bittencourt, Paulo Ivo Homem; Tirapegui, Julio

    2014-03-01

    Sepsis is a leading cause of death in intensive care units worldwide. Low availability of glutamine contributes to the catabolic state of sepsis. L-Glutamine supplementation has antioxidant properties and modulates the expression of heat shock proteins (HSPs). This study investigated the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP), on glutamine-glutathione (GSH) axis and HSPs expression in endotoxemic mice. B6.129F2/J mice were subjected to endotoxemia (lipopolysaccharides from Escherichia coli, 5 mg.kg(-1), LPS group) and orally supplemented for 48 h with either L-glutamine (1 g.kg(-1)) plus L-alanine (0.61 g.kg(-1)) (GLN+ALA-LPS group) or 1.49 g.kg(-1) of DIP (DIP-LPS group). Endotoxemia reduced plasma and muscle glutamine concentrations [relative to CTRL group] which were restored in both GLN+ALA-LPS and DIP-LPS groups (P<.05). In supplemented groups were re-established GSH content and intracellular redox status (GSSG/GSH ratio) in circulating erythrocytes and muscle. Thiobarbituric acid reactive substance was 4-fold in LPS treated mice relative to the untreated CTRL group, and plasma TNF-α and IL-1β levels were attenuated by the supplements. Heat shock proteins 27, 70 and 90 (protein and mRNA) were elevated in the LPS group and were returned to basal levels (relative to CTRL group) in both GLN+ALA-LPS and DIP-LPS groups. Supplementations to endotoxemic mice resulted in up-regulation of GSH reductase, GSH peroxidase and glutamate cysteine ligase mRNA expression in muscle. In conclusion, oral supplementations with GLN+ALA or DIP are effective in reversing the conditions of LPS-induced deleterious impact on glutamine-GSH axis in mice under endotoxemia.

  20. IMMUNOREGULATORY EFFECTS OF INTRAVENOUS IMMUNOGLOBULINS

    Directory of Open Access Journals (Sweden)

    S. A. Sel'kov

    2013-01-01

    Full Text Available Treatment with intravenous immunoglobulins (IVIG is widely used in modern clinical practice inorder to cure different clinical disorders, including obstetric conditions. Currently, IVIGs have become drugs of  choice  for  treatment of  anti-phospholipid  syndrome  in pregnant women,  like  as  in  cases of  intrauterine cytomegalovirus infection.

  1. SAT1, a glutamine transporter, is preferentially expressed in GABAergic neurons

    Directory of Open Access Journals (Sweden)

    Tom Tallak Solbu

    2010-02-01

    Full Text Available Subsets of GABAergic neurons are able to maintain high frequency discharge patterns, which requires efficient replenishment of the releasable pool of GABA. Although glutamine is considered a preferred precursor of GABA, the identity of transporters involved in glutamine uptake by GABAergic neurons remains elusive. Molecular analyses revealed that SAT1 (Slc38a1 features system A characteristics with a preferential affinity for glutamine, and that SAT1 mRNA expression is associated with GABAergic neurons. By generating specific antibodies against SAT1 we show that this glutamine carrier is particularly enriched in GABAergic neurons. Cellular SAT1 distribution resembles that of GAD67, an essential GABA synthesis enzyme, suggesting that SAT1 can be involved in translocating glutamine into GABAergic neurons to facilitate inhibitory neurotransmitter generation.

  2. Influence of glutamine on the effect of resistance exercise on cardiac ANP in rats

    Directory of Open Access Journals (Sweden)

    Romeu Rodrigues de Souza

    2015-03-01

    Full Text Available Various nutritional supplements (herbs, vitamins, and micronutrients improve responses and adaptations to resistance exercise. ANP is a heart hormone that contributes to fluid, electrolyte and blood pressure homeostasis through its natriuretic and vasodilative actions. In the present study, the adaptation of ANP in response to resistance exercise was investigated in rats supplemented with glutamine for five weeks. The results showed that supplementation with glutamine did not influence the number of ANP granules per atrial cardiocyte in sedentary animals. In exercised-trained rats, the number and diameter of the granules was significantly higher in comparison with the control group and in exercised animals supplemented with glutamine there was significant increase in the number and diameter of ANP granules compared with controls. Altogether, these data indicated that in resistance exercise rats, glutamine significantly enhances cardiac ANP thus implicating the beneficial effects of glutamine supplementation to the ANP system.

  3. Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis.

    Science.gov (United States)

    Fedorova, Ksenia; Kayumov, Airat; Woyda, Kathrin; Ilinskaja, Olga; Forchhammer, Karl

    2013-05-02

    The Bacillus subtilis glutamine synthetase (GS) plays a dual role in cell metabolism by functioning as catalyst and regulator. GS catalyses the ATP-dependent synthesis of glutamine from glutamate and ammonium. Under nitrogen-rich conditions, GS becomes feedback-inhibited by high intracellular glutamine levels and then binds transcription factors GlnR and TnrA, which control the genes of nitrogen assimilation. While GS-bound TnrA is no longer able to interact with DNA, GlnR-DNA binding is shown to be stimulated by GS complex formation. In this paper we show a new physiological feature of the interaction between glutamine synthetase and TnrA. The transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in vivo and in vitro, while the GlnR protein does not affect the activity of the enzyme.

  4. Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Samocha-Bonet, Dorit; Wong, Olivia; Synnott, Emma-Leigh;

    2011-01-01

    glutamine, with or without sitagliptin (SIT), on postprandial glycemia and GLP-1 concentration in 15 type 2 diabetes patients (glycated hemoglobin 6.5 ± 0.6%). Participants ingested a low-fat meal (5% fat) after receiving either water (control), 30 g l-glutamine (Gln-30), 15 g L-glutamine (Gln-15), 100 mg...

  5. Kinetic Properties of a Phosphate-Bond-Driven Glutamate-Glutamine Transport System in Streptococcus lactis and Streptococcus cremoris

    NARCIS (Netherlands)

    POOLMAN, B; SMID, EJ; KONINGS, WN

    1987-01-01

    In Streptococcus lactis ML3 and Streptococcus cremoris Wg2 the uptake of glutamate and glutamine is mediated by the same transport system, which has a 30-fold higher affinity for glutamine than for glutamate at pH 6.0. The apparent affinity constant for transport (KT) of glutamine is 2.5 ± 0.3 μM, i

  6. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.; Wamelen, D.J. van; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neu

  7. Cloning, expression, and purification of glutamine synthetase from Clostridum acetobutylicum

    Energy Technology Data Exchange (ETDEWEB)

    Usdin, K.P.; Zappe, H.; Jones, D.T.; Woods, D.R.

    1986-09-01

    A glutamine synthetase (GS) gene, glnA, from the gram-positive obligate anaerobe Clostridium acetobutylicum was cloned on recombinant plasmid pHZ200 and enabled Escherichia coli glnA deletion mutants to utilize (NH/sub 4/)/sub 2/ as a sole source of nitrogen. The cloned C. acetobutylicum gene was expressed from a regulatory region contained within the cloned DNA fragment. glnA expression was subject to nitrogen regulation in E. coli. This cloned glnA DNA did not enable an E. coli glnA ntrB ntrC deletion mutant to utilize arginine or low levels of glutamine as sole nitrogen sources, and failed to activate histidase activity in this strain which contained the Klebsiella aerogenes hut operon. The GS produced by pHZ200 was purified and had an apparent subunit molecular weight of approximately 59,000. There was no DNA or protein homology between the cloned C. acetobutylicum glnA gene and GS and the corresponding gene and GS from E. coli. The C. acetobutylicum GS was inhibited by Mg/sup 2 +/ in the ..gamma..-glutamyl transferase assay, but there was no evidence that the GS was adenylylated.

  8. Glutamine as an energy substrate in cultured neurons during glucose deprivation.

    Science.gov (United States)

    Peng, Liang; Gu, Li; Zhang, Hongliang; Huang, Xueshi; Hertz, Elna; Hertz, Leif

    2007-11-15

    During glucose deprivation an increase in aspartate formation from glutamine has been observed in different brain preparations, including synaptosomes and cultured astrocytes. To what extent this reaction, which provides a substantial amount of energy, occurs in different types of neurons is unknown. The present study shows that (14)CO(2) formation from [U-(14)C]glutamine in cerebellar granule neurons, a glutamatergic preparation, increased by 60% during glucose deprivation, indicating enhanced aspartate formation or increased complete oxidative degradation of glutamine. In primary cultures of cerebrocortical interneurons, a GABAergic preparation, the rate of (14)CO(2) production from [U-(14) C] glutamine was four times lower and not stimulated by glucose deprivation. During incubation with glutamine (0.8 mM) as the only metabolic substrate, cerebellar granule cells maintained an oxygen consumption rate of 12 nmol/min/mg protein, corresponding to an aspartate formation of 8 nmol/min/mg protein (three oxidations occur between glutamine and aspartate) or to a total oxidative degradation of 3 nmol/min/mg protein. During glucose deprivation, the rate of aspartate formation increased, and during a 20-min incubation in phosphate-buffered saline it amounted to 3.3 nmol/min/mg protein at 0.2 mM glutamine, which might have been more if measured at 0.8 mM glutamine. These values are consistent with the rate of glutamine utilization calculated based on oxygen consumption and leaves open the possibility that some glutamine is completely degraded oxidatively, as has been shown by other authors based on pyruvate recycling and labeling of lactate from aspartate in cerebellar granule neurons.

  9. Effect of dietary supplementation with glutamine and a combination of glutamine-arginine on intestinal health in twenty-five-day-old weaned rabbits.

    Science.gov (United States)

    Chamorro, S; de Blas, C; Grant, G; Badiola, I; Menoyo, D; Carabaño, R

    2010-01-01

    The effect of dietary supplementation with 1% l-glutamine and a combination of 1% l-glutamine and 0.5% l-arginine on intestinal health was examined in weaned rabbits. A basal diet was formulated to meet nutrient recommendations. Another 2 diets were formulated by adding 1% (as-fed basis) Gln or a mixture of 1% (as-fed basis) Gln + 0.5% (as-fed basis) Arg (Gln-Arg) to the basal diet. In Exp. 1, a total of 357 rabbits were blocked by litter and assigned at random to the experimental diet to determine mortality (119 per diet) and growth performance (35 per diet; from weaning at 25 to 56 d of age). Rabbits were fed the experimental diets for a 2-wk period and thereafter received a commercial diet. Rabbits weaned at 25 d (blocked by litter and assigned at random to diets) were slaughtered at 35 d and used to determine apparent ileal digestibility of DM, CP, and AA (Exp. 2, a total of 60 rabbits), intestinal morphology, N-aminopeptidase and myeloperoxidase intestinal activity, the expression of PPARgamma at the ileum and kidney, serum immunoglobulin in healthy and sick rabbits (Exp. 3, a total of 24 rabbits), and ileal and cecal microbial composition by PCR-RFLP (Exp. 4, a total of 45 rabbits). Dietary treatment did not affect ADG, ADFI, or G:F, during the entire fattening period. Supplementation with Gln reduced mortality during the first 2 wk and the whole fattening period from 18.5 to 8.4% (P = 0.023) and from 31.9 to 20.2% (P = 0.039), respectively, whereas no effect was detected for Arg supplementation. Among all the variables studied, the reduction on mortality due to Gln was related to a reduced intestinal colonization (Eimeria lesions) and changes on microbial ecosystem in the ileum and cecum, reducing the frequency of detection of Clostridium spp. (from 86.7 to 33.3%, P = 0.003) at the ileum, and Helicobacter spp. at the ileum (from 86.7 to 46.7%, P = 0.003) and at the cecum (from 86.7 to 46.7, P = 0.028), whereas no effect was detected for Arg supplementation

  10. Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study.

    Science.gov (United States)

    Hashimoto, K; Bruno, D; Nierenberg, J; Marmar, C R; Zetterberg, H; Blennow, K; Pomara, N

    2016-03-01

    Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N=28; age- and gender-matched comparison group, N=19) at baseline and 3-year follow-up (MDD group, N=19; comparison group, N=17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by high-performance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.

  11. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Table IV. Different morbidity scores as a percentage of total visits. Morbidity score ... to bronchodilators with or without antibiotics (no intravenous therapy or .... admissions needed surgery; almost 50% needed more than one ...

  12. Intravenous injections in neonatal mice.

    Science.gov (United States)

    Gombash Lampe, Sara E; Kaspar, Brian K; Foust, Kevin D

    2014-11-11

    Intravenous injection is a clinically applicable manner to deliver therapeutics. For adult rodents and larger animals, intravenous injections are technically feasible and routine. However, some mouse models can have early onset of disease with a rapid progression that makes administration of potential therapies difficult. The temporal (or facial) vein is just anterior to the ear bud in mice and is clearly visible for the first two days after birth on either side of the head using a dissecting microscope. During this window, the temporal vein can be injected with volumes up to 50 μl. The injection is safe and well tolerated by both the pups and the dams. A typical injection procedure is completed within 1-2 min, after which the pup is returned to the home cage. By the third postnatal day the vein is difficult to visualize and the injection procedure becomes technically unreliable. This technique has been used for delivery of adeno-associated virus (AAV) vectors, which in turn can provide almost body-wide, stable transgene expression for the life of the animal depending on the viral serotype chosen.

  13. Differential protein analysis of serum exosomes post-intravenous immunoglobulin therapy in patients with Kawasaki disease.

    Science.gov (United States)

    Zhang, Li; Song, Qi-Fang; Jin, Jing-Jie; Huang, Ping; Wang, Zhou-Ping; Xie, Xiao-Fei; Gu, Xiao-Qiong; Gao, Xue-Juan; Jia, Hong-Ling

    2017-08-14

    Kawasaki disease, which is characterised by systemic vasculitides accompanied by acute fever, is regularly treated by intravenous immunoglobulin to avoid lesion formation in the coronary artery; however, the mechanism of intravenous immunoglobulin therapy is unclear. Hence, we aimed to analyse the global expression profile of serum exosomal proteins before and after administering intravenous immunoglobulin. Two-dimensional electrophoresis coupled with mass spectrometry analysis was used to identify the differentially expressed proteome of serum exosomes in patients with Kawasaki disease before and after intravenous immunoglobulin therapy. Our analysis revealed 69 differential protein spots in the Kawasaki disease group with changes larger than 1.5-fold and 59 differential ones in patients after intravenous immunoglobulin therapy compared with the control group. Gene ontology analysis revealed that the acute-phase response disappeared, the functions of the complement system and innate immune response were enhanced, and the antibacterial humoral response pathway of corticosteroids and cardioprotection emerged after administration of intravenous immunoglobulin. Further, we showed that complement C3 and apolipoprotein A-IV levels increased before and decreased after intravenous immunoglobulin therapy and that the insulin-like growth factor-binding protein complex acid labile subunit displayed reverse alteration before and after intravenous immunoglobulin therapy. These observations might be potential indicators of intravenous immunoglobulin function. Our results show the differential proteomic profile of serum exosomes of patients with Kawasaki disease before and after intravenous immunoglobulin therapy, such as complement C3, apolipoprotein A-IV, and insulin-like growth factor-binding protein complex acid labile subunit. These results may be useful in the identification of markers for monitoring intravenous immunoglobulin therapy in patients with Kawasaki disease.

  14. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Gabriela Beatriz Acosta; María Alejandra Fernández; Diego Martín Roselló; María Luján Tomaro; Karina Balestrasse; Abraham Lemberg

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions.

  15. Intravenous nutrition during a twin pregnancy.

    Science.gov (United States)

    Karamatsu, J T; Boyd, A T; Cooke, J; Vinall, P S; McMahon, M J

    1987-01-01

    A case is reported of a woman in the third trimester of a twin pregnancy who required intravenous nutrition because of inadequate absorption of nutrients due to a jejunoileal bypass. Weight gain was poor, and there was evidence of intrauterine growth retardation before commencement of intravenous feeding. She received overnight intravenous nutrition for 6 weeks and gained weight with ultrasound evidence of fetal growth. During the 33rd week of gestation, she was delivered of healthy twin males who were at appropriate birth weights and development for their age of gestation. The considerations in intravenous nutrition for a twin pregnancy after jejunoileal bypass are discussed.

  16. Pancreatic enzyme secretion during intravenous fat infusion.

    Science.gov (United States)

    Burns, G P; Stein, T A

    1987-01-01

    The nutritional support of patients with pancreatic and high gastrointestinal fistulas and severe pancreatitis frequently involves intravenous fat infusion. There are conflicting reports on the effect of intravenous fat on pancreatic exocrine secretion. In 10 dogs with chronic pancreatic fistulas, pancreatic juice was collected during secretin (n = 10) or secretin + cholecystokinin (n = 4) stimulation, with and without intravenous fat infusion (5 g/hr). The hormonal-stimulated secretion of lipase, amylase, trypsin, total protein, bicarbonate, and water was unchanged during fat infusion. This study supports the use of intravenous fat as a nutritional source when it is desirable to avoid stimulation of the pancreas.

  17. Repercussões da L-alanil-glutamina sobre as concentrações de lactato e lactato desidrogenase (LDH em pacientes com isquemia crítica dos membros inferiores submetidos a revascularização distal Repercussions of l-alanyl-glutamine upon the concentrations of lactate and lactate dehydrogenase (LDH in patients with critical ischemia of lower limbs subjected to distal revascularization

    Directory of Open Access Journals (Sweden)

    Wellington Forte Alves

    2003-06-01

    Full Text Available OBJETIVO: Investigar efeitos da L-alanil-glutamina nas concentrações musculares de lactato, e nas concentrações sanguíneas de LDH, em pacientes com isquemia crítica dos membros inferiores submetidos à revascularização distal. MÉTODOS: Dezesseis adultos (12-homens/4-mulheres foram distribuídos em 2 grupos (1-controle/2-estudo. Três horas após injeção endovenosa de 250 ml de L-alanil-glutamina a 20% adicionados a 750 ml de soro fisiológico (Grupo 2, ou 1000 ml de solução salina (Grupo 1, iniciava-se a revascularização, sob raquianestesia. Amostras musculares e de sangue (arterial/venoso foram coletadas no início do procedimento (TI, no final (TF, e 10 e 20 minutos após isquemia (T1/T2. RESULTADOS: Observou-se redução significante (pPURPOSE: Investigate the repercussions of L-alanyl-glutamine in muscular tissue concentrations of lactate, and venous and arterial blood concentrations of LDH, in patients with critical ischemia of the lower limbs submitted to distal revascularization. METHODS: Sixteen adults (12 male/4 female were distributed in 2 groups (1-Control/2-Experiment. Three hours after the intravenous injection of 250 ml of a 20% solution of L-alanyl-glutamine added to 750 ml of saline solution (Group 2; or 1000 ml of saline solution (Group 1, distal bypass was carried out under spinal anesthesia. Muscle and blood samples (arterial/venous were collected at the beginning of the surgical procedure (TI, at the end (TF, and 10 and 20 minutes after re-establishment of blood flow. RESULTS: Significant reduction (p<0,05 of lactate concentration was observed in healthy muscle tissue in L-alanyl-glutamine treated patients in comparison to control group, at all times studied. There was a significant reduction (p <0,05 in venous concentrations of LDH in treated patients at all times studied (TI/TFV/T1V/T2V; and in arterial blood during reperfusion (T1A/T2A. CONCLUSIONS: 1. Decreased lactate concentrations in healthy skeletal

  18. Increased glutamine catabolism mediates bone anabolism in response to WNT signaling.

    Science.gov (United States)

    Karner, Courtney M; Esen, Emel; Okunade, Adewole L; Patterson, Bruce W; Long, Fanxin

    2015-02-01

    WNT signaling stimulates bone formation by increasing both the number of osteoblasts and their protein-synthesis activity. It is not clear how WNT augments the capacity of osteoblast progenitors to meet the increased energetic and synthetic needs associated with mature osteoblasts. Here, in cultured osteoblast progenitors, we determined that WNT stimulates glutamine catabolism through the tricarboxylic acid (TCA) cycle and consequently lowers intracellular glutamine levels. The WNT-induced reduction of glutamine concentration triggered a general control nonderepressible 2-mediated (GCN2-mediated) integrated stress response (ISR) that stimulated expression of genes responsible for amino acid supply, transfer RNA (tRNA) aminoacylation, and protein folding. WNT-induced glutamine catabolism and ISR were β-catenin independent, but required mammalian target of rapamycin complex 1 (mTORC1) activation. In a hyperactive WNT signaling mouse model of human osteosclerosis, inhibition of glutamine catabolism or Gcn2 deletion suppressed excessive bone formation. Together, our data indicate that glutamine is both an energy source and a protein-translation rheostat that is responsive to WNT and suggest that manipulation of the glutamine/GCN2 signaling axis may provide a valuable approach for normalizing deranged protein anabolism associated with human diseases.

  19. Effect of glutamine limitation on the death of attached Chinese hamster ovary cells

    Energy Technology Data Exchange (ETDEWEB)

    Sanfeliu, A.; Stephanopoulos, G. (Massachusetts Inst. of Tech., Cambridge, MA (United States))

    1999-07-05

    The effect of glutamine depletion on the death of attached Chinese hamster ovary (CHO) cells was investigated. Experiments were performed using an anchorage dependent CHO cell line expressing [gamma]-IFN and a second cell line obtained by transfection of that cell line with the human bcl-2 (hbcl-2). Either cell line could grow in media devoid of glutamine with minimal cell death due to endogenous glutamine synthetase activity that allowed cells to synthesize glutamine from glutamic acid in the medium. However, compared to control cultures in glutamine-containing media, the cell growth rate in glutamine-free media was slower with an increased fraction of cells distributed in the G[sub 0]/G[sub 1] phase. The slower rate of cell cycling apparently protected the cells from entering apoptosis when they were stimulated to proliferate in an environment devoid of other protective factors, such as serum or over-expressed hbcl-2. The depletion of both glutamine and glutamic acid did cause cell death, which could be mitigated by hbcl-2 over-expression.

  20. The Effect of One-week Glutamine Supplementation on Oxidative Stress Indices in Healthy Young Men

    Directory of Open Access Journals (Sweden)

    Rasool Javanamani

    2015-04-01

    Full Text Available Background &objectives: Glutamine has antioxidant properties and can be used to treat some diseases. This study was conducted to assess the effect of one-week glutamine supplementation on oxidative stress indices in young healthy men.   Methods: Nineteen active healthy men volunteered for this study. This study was conducted in biochemistry lab of Ardabil branch of Islamic Azad University in Spring 2014. Participants were randomized in a double-blind placebo-controlled method into two groups: Glutamine (n = 9 and placebo group (n = 10. The participants took supplement (0.15 g/kg glutamine + 15g sweetener + 250ml water or placebo (15g sweetener + 250ml water daily for 7 days before main trial.Fasting blood samples were taken before and after supplementation. Total antioxidant capacity (TAC of plasma, reduced glutathione (GHS level of serum, and malondialdehyde (MDA of plasma were measured.   Results: GHS significantly increased after treatment compared with pre-treatment in Glutamine group (p0.05.   Conclusions: These results showed that one-week daily oral supplementation of glutamine has been able to increase GHS probably because of greater glutamine availability .

  1. Liver regeneration with l-glutamine supplemented diet: experimental study in rats

    Directory of Open Access Journals (Sweden)

    Cibelle Ribeiro Magalhães

    2014-04-01

    Full Text Available OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and without supplementation of L-glutamine through liver weight changes, laboratory parameters and histological study. METHODS: 36 male rats were divided into two groups: glutamine group and control group. Each group was subdivided into three subgroups, with death in 24h, 72h and seven days. The glutamine group received water and standard diet supplemented with L-glutamine, and the control recieved 0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and indirect bilirubin and albumin and analysis of cell mitosis by hematoxylin-eosin. RESULTS: In both groups there was liver regeneration by weight gain. Gamma-GT increased significantly in the control group (p < 0.05; albumin increased in the glutamine group. The other indicators of liver function showed no significant differences. Histological analysis at 72h showed a higher number of mitoses in the glutamine group, with no differences in other subgroups. CONCLUSION: Diet supplementation with L glutamine is beneficial for liver regeneration.

  2. Pharmacokinetic interaction of intravenous fentanyl with ketoconazole.

    Science.gov (United States)

    Ziesenitz, Victoria C; König, Sonja K; Mahlke, Nina S; Skopp, Gisela; Haefeli, Walter E; Mikus, Gerd

    2015-06-01

    Fentanyl is primarily metabolized by CYP3A, but has also been suggested to act as a weak inhibitor of CYP3A. We investigated the influence of CYP3A inhibition by ketoconazole on the pharmacokinetics of intravenously administered fentanyl and the effect of fentanyl on CYP3A activity. A prospective, open-label, randomized, monocentre, crossover study was conducted in 16 healthy volunteers. They received fentanyl alone (5 microgram per kilogram) or fentanyl plus ketoconazole (200 milligram orally B.I.D. over 2 days). Naloxone (2 × 0.2 milligram i.v.) was given simultaneously with fentanyl to mitigate any opioid effect. Midazolam was administered as a CYP3A probe drug. Fentanyl and its metabolites were quantified by LC/MS/MS in blood and urine samples obtained over 24 hour. Exposure of fentanyl (AUC0- ∞ ) was significantly increased to 133% and systemic clearance was reduced to 78% by ketoconazole, norfentanyl formation was significantly delayed and partial metabolic clearance decreased to 18%. Fentanyl had no influence on midazolam exposure and CYP3A activity whereas ketoconazole decreased CYP3A activity to 13%. Although fentanyl N-dealkylation is substantially inhibited by ketoconazole, exposure of fentanyl itself increased by one third only. Clinically fentanyl dosage adjustments may become necessary when ketoconazole or other strong CYP3A inhibitors are given simultaneously. Fentanyl itself does not influence CYP3A activity.

  3. Effects of Supplementation with BCAA and L-glutamine on Blood Fatigue Factors and Cytokines in Juvenile Athletes Submitted to Maximal Intensity Rowing Performance.

    Science.gov (United States)

    Koo, Ga Hee; Woo, Jinhee; Kang, Sungwhun; Shin, Ki Ok

    2014-08-01

    [Purpose] This study was conducted to understand the impacts of BCAA (branched-chain amino acid) and glutamine supplementation on the degree of blood fatigue factor stimulation and cytokines along with performance of exercise at the maximal intensity. [Subjects] Five male juvenile elite rowing athletes participated in this study as the subjects; they took 3 tests and received placebo supplementation (PS), BCAA supplementation (BS), and glutamine supplementation (GS). [Methods] The exercise applied in the tests was 2,000 m of rowing at the maximal intensity using an indoor rowing machine, and blood samples were collected 3 times, while resting, at the end of exercise, and after 30 min of recovery, to analyze the blood fatigue factors (lactate, phosphorous, ammonia, creatine kinase (CK)) and blood cytokines (IL (interleukin)-6, 8, 15). [Results] The results of the analysis showed that the levels of blood phosphorous in the BS and GS groups at the recovery stage were decreased significantly compared with at the end of exercise, and the level of CK appeared lower in the GS group alone at recovery stage than at the end of exercise. The level of blood IL-15 in the PS and BS groups appeared higher at the end of exercise compared with the resting stage. [Conclusion] It seemed that glutamine supplementation had a positive effect on the decrease in fatigue factor stimulation at the recovery stage after maximal intensity exercise compared with supplementation with the placebo or BCAA. Besides, pre-exercise glutamine supplementation seemed to help enhance immune function and the defensive inflammatory reaction.

  4. Effect of Glutamine Supplementation on Abilities of Antioxidative and γ-glutamyl Transpeptidase Activities in Liver and Intestine of Piglets Fed Diets Containing Raw Soybean

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun-min; GAO Zhen-chuan; WANG Lian-di; JIANG Yun-xia; ZHANG Qi

    2003-01-01

    Eighteen male piglets weaned at 28 days age were randomly assigned to one of three treatments(1% glutamate, 1% and 2 % glutamine supplementation). The basal diet contained 5 % raw soybean. The di-ets were calculated to be isonitrogenous and isoenergetic. The level of plasma glutahione (GSH) increasedmarkedly in piglets fed glutamine, and the response was related to dose. In treatments Ⅰ and Ⅱ, the levels ofplasma GSH were significantly higher than that in the control at the 35 days age (P<0.05). The level of plas-ma GSH in treatment Ⅱ was significantly higher than that in the control at 42 days age (P<0.05). At 49days age, there was no significantly difference of the level of GSH in plasma, liver, spleen, intestine and mes-enteric lymph node. The level of superoxide dismutase (SOD) in liver and spleen was higher than that of thecontrol, however, the difference wasn't significant. Dietary glutamine supplementation decreased γ-glutamyltranspeptidase(γ-GT) activities in liver. The activities of γ-GT of liver protein in treatment Ⅱ were signifi-cantly lower than that in the control (P<0. 05). The activities of γ-GT of duodenum in treatments Ⅰ and Ⅱwere also significantly lower than that in the control (P<0.05). But there were no significant differences ofthe activities of γ-GT in jejunum and ileum. The results showed that dietary glutamine supplementation in-creased the level of plasma GSH, and decreased γ-GT activities.

  5. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress.

    Directory of Open Access Journals (Sweden)

    Jianmin Chen

    Full Text Available Glutamine is the most abundant free amino acid in the human blood stream and is 'conditionally essential' to cells. Its intracellular levels are regulated both by the uptake of extracellular glutamine via specific transport systems and by its intracellular synthesis by glutamine synthetase (GS. Adding to the regulatory complexity, when extracellular glutamine is reduced GS protein levels rise. Unfortunately, this excess GS can be maladaptive. GS overexpression is neurotoxic especially if the cells are in a low-glutamine medium. Similarly, in low glutamine, the levels of multiple stress response proteins are reduced rendering cells hypersensitive to H(2O(2, zinc salts and DNA damage. These altered responses may have particular relevance to neurodegenerative diseases of aging. GS activity and glutamine levels are lower in the Alzheimer's disease (AD brain, and a fraction of AD hippocampal neurons have dramatically increased GS levels compared with control subjects. We validated the importance of these observations by showing that raising glutamine levels in the medium protects cultured neuronal cells against the amyloid peptide, Aβ. Further, a 10-day course of dietary glutamine supplementation reduced inflammation-induced neuronal cell cycle activation, tau phosphorylation and ATM-activation in two different mouse models of familial AD while raising the levels of two synaptic proteins, VAMP2 and synaptophysin. Together, our observations suggest that healthy neuronal cells require both intracellular and extracellular glutamine, and that the neuroprotective effects of glutamine supplementation may prove beneficial in the treatment of AD.

  6. Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.

    Science.gov (United States)

    Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B

    2010-06-01

    The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.

  7. ZINC AND GLUTAMINE IMPROVE BRAIN DEVELOPMENT IN SUCKLING MICE SUBJECTED TO EARLY POST-NATAL MALNUTRITION

    Science.gov (United States)

    Ladd, Fernando V.L.; Ladd, Aliny A.B.L.; Ribeiro, Antônio Augusto C.M.; Costa, Samuel B.C.; Coutinho, Bruna P.; Feitosa, George André S.; de Andrade, Geanne M.; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C.; Castro, Ibraim C.; Oliveira, Bruna B.; Guerrant, Richard L.; Lima, Aldo Ângelo M.; Oriá, Reinaldo B.

    2009-01-01

    Objective The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Methods Malnutrition was induced by clustering the litter size from 6–7 pups/dam (nourished control) to 12–14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40–80μl) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin (SYN) and myelin basic protein (MBP) brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Results Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal GABA and SYN levels on day 14. Conclusion We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. PMID:20371167

  8. Bisphosphonic acids as effective inhibitors of Mycobacterium tuberculosis glutamine synthetase.

    Science.gov (United States)

    Kosikowska, Paulina; Bochno, Marta; Macegoniuk, Katarzyna; Forlani, Giuseppe; Kafarski, Paweł; Berlicki, Łukasz

    2016-12-01

    Inhibition of glutamine synthetase (GS) is one of the most promising strategies for the discovery of novel drugs against tuberculosis. Forty-three bisphosphonic and bis-H-phosphinic acids of various scaffolds, bearing aromatic substituents, were screened against recombinant GS from Mycobacterium tuberculosis. Most of the studied compounds exhibited activities in micromolar range, with N-(3,5-dichlorophenyl)-2-aminoethylidenebisphoshonic acid, N-(3,5-difluorophenyl)-2-aminoethylidene-bisphoshonic acid and N-(3,4-dichlorophenyl)-1-hydroxy-1,1-ethanebisphosphonic acid showing the highest potency with kinetic parameters similar to the reference compound - L-methionine-S-sulfoximine. Moreover, these inhibitors were found to be much more effective against pathogen enzyme than against the human ortholog. Thus, with the bone-targeting properties of the bisphosphonate compounds in mind, this activity/selectivity profile makes these compounds attractive agents for the treatment of bone tuberculosis.

  9. Glutamine Supplementation in Sick Children: Is It Beneficial?

    Directory of Open Access Journals (Sweden)

    Elise Mok

    2011-01-01

    Full Text Available The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.

  10. Autoxidation of oxymyoglobin with the distal (E7) glutamine.

    Science.gov (United States)

    Suzuki, T

    1987-08-05

    We reported previously that the distal(E7) histidine is replaced by glutamine in myoglobin from the shark, Galeorhinus japonicus. The amino-acid sequence of myoglobin from another shark, Heterodontus japonicus, has been determined. The myoglobin is composed of 148 residues, is acetylated at the N-terminus, and contains the distal(E7) histidine at position 59. Although the sequence homologies between G. japonicus, H. japonicus, and sperm-whale myoglobins were about 40-55%, their hydropathy profiles were very similar, indicating that they have a similar geometry in their globin folding. The autoxidation rates of the two shark oxymyoglobins were examined in 0.1 M buffer at 25 degrees C over pH range 4.5-11.5. The pH dependence for the autoxidation of H. japonicus myoglobin was very similar to that of sperm-whale myoglobin, although the rate was about 10-times higher over the pH range examined. In both myoglobins, autoxidation was largely accelerated by H+. On the other hand, the pH dependence of G. japonicus myoglobin, which has the distal glutamine in the place of histidine, was quite different from those of sperm-whale and H. japonicus myoglobins. One of the most remarkable features is the fact that the autoxidation rate is not enhanced with an increase in the concentration of H+ in the acidic range of pH, where the autoxidation of sperm-whale and H. japonicus myoglobins is most accelerated. This finding suggests that the distal(E7) histidine participates in the autoxidation reaction as a catalytic residue facilitating the movement of a catalytic proton.

  11. Phytogenic additives and glutamine plus glutamic acid in broiler diets

    Directory of Open Access Journals (Sweden)

    VC Pelícia

    2013-12-01

    Full Text Available The objective of this study was to evaluate the effect of the dietary supplementation of phytogenic additives (PAs and glutamine plus glutamic acid (Gln/Glu, associated or not, in replacement of antibiotic growth promoters and anticoccidials (AGP/AC on the performance and carcass yield of broilers. Five hundred male Cobb broilers were housed in an experimental house and randomly distributed into five treatments, with four replicates of 25 birds each. Treatments consisted of a control diet (CD; CD+AGP/AC; CD+Gln/Glu; CD+PAs; CD+Gln/ Glu+PAs. Diets were formulated only with plant feedstuffs, i.e., they did not contain any animal byproducts. Performance data were collected for the accumulated periods of 1-7, 1-21, and 1-42 days of age. Carcass yield and parts yield were determined at 42 days of age. Treatments did not influence performance during none of the evaluated periods. The greatest carcass yield (p<0.05 was obtained in birds in the treatments CD+Gln/Glu and CD+Gln/Glu+PAs relative to CD, but not different from birds in the AGP+AC and PAs treatments, which were not different from the CD treatment. Birds fed the CD+Gln/Glu diet presented greater breast yield (p<0.05 compared with those in the CD and AGP/AC treatments, but there was no difference in comparison with the other treatments. Under the conditions of the present experiment, the dietary supplementation with phytogenic additives and with glutamine plus glutamic acid does not affect the performance, but improves carcass yield and breast yield of broilers.

  12. Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1.

    Science.gov (United States)

    Cardaci, Simone; Rizza, Salvatore; Filomeni, Giuseppe; Bernardini, Roberta; Bertocchi, Fabio; Mattei, Maurizio; Paci, Maurizio; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2012-09-01

    Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy.

  13. Partial intravenous anesthesia in cats and dogs.

    Science.gov (United States)

    Duke, Tanya

    2013-03-01

    The partial intravenous anesthesia technique (PIVA) is used to lower the inspired concentration of an inhalational anesthetic by concurrent use of injectable drugs. This technique reduces the incidence of undesirable side-effects and provides superior quality of anesthesia and analgesia. Drugs commonly used for PIVA include opioids, alpha-2 adrenergic agonists, injectable anesthetic agents, and lidocaine. Most are administered by intravenous infusion.

  14. Intravenous Laser Therapy in Young Children with Thermal Injuries

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    R. V. Bocharov

    2014-01-01

    Full Text Available Objective: to evaluate the laboratory and clinical effects of combined intravenous laser therapy in young children with thermalinjuries in the acute period of burn disease.Subjects and methods. Forty children whose mean age was 2.67±0.35 years were examined; thermal injuries accounted for 25.05±1.01% of the total body surface area; of them degrees IIIaIIIb was 19.04±0.85%. A comparison group (n=15 received conventional therapy without taking into account and correcting baseline and current hemostasiological disorders. On day 1, a study group (n=25 had programmed anticoagulant therapy and intravenous laser therapy at different radiation frequencies with a Mustang 20002+ laser therapy apparatus (patent for invention No. 2482894 in addition to the conventional therapy. The laser therapy cycle was 6 to 16 sessions. The investigators estimated and compared the following examined parameters: white blood cell count; leukocytic index of intoxication; plasma average mass molecules at a wavelength of 254 nm; toxogenic granularity of neutrophils; wound exudate discharge time; surgical plasty area; and hospitalization time.Results. The positive laboratory and clinical effects of the performed combined intravenous laser therapy in the combined therapy of burn disease in young children were comparatively shown in the study group patients. The significant decrease in the level of an inflammatory response and endogenous intoxication led to a rapider burn wound cleansing, active epithelization, and reduced surgical plasty volumes.Conclusion. Combined intravenous laser therapy signif icantly exerts antiinflammatory and detoxifying effects in young children with 40% thermal injuries in the acute period of burn disease. Abolishing a systemic inflammatory response by combined intravenous laser therapy initiated early regenerative processes in the burn wound and caused reductions in surgical plasty volumes and hospitalization time, which optimizes ther

  15. 谷氨酰胺和精氨酸配合放疗对肺癌病人免疫和临床影响的相关研究%Research of glutamine and arginine on immunity and clinical effect for patients of lung cancer radiotherapy

    Institute of Scientific and Technical Information of China (English)

    高彩霞; 乔田奎

    2012-01-01

    目的:研究谷氨酰胺(Gln)和精氨酸(Arg)配合放疗对肺癌病人营养状况的影响和机体免疫功能的变化.方法:收集临床确诊为非小细胞肺癌病人36例,随机分为单独放疗组(n=18例)和联合治疗组(n=18例).单独放疗组病人行单独放疗,联合治疗组病人在放疗同时的第1~10天,静脉给予Gln和Arg.所有病人在放疗期间饮食由医院营养师统一制订,保证热量供给基本相同.所有病人分别于放疗前、中、后抽取静脉血,检测血清清蛋白、前清蛋白、淋巴细胞计数、C反应蛋白、补体C3、IgG和CD3+、CD4+、CD8+和CD4+/CD8+.结果:联合治疗组病人放疗中和放疗结束时血清前清蛋白较单独放疗组升高,且有显著性差异(P<0.05),C反应蛋白和补体C3放疗中较放疗前降低.联合治疗组CD3+、CD4+放疗中较放疗前上升,CD8+下降,与单独放疗组比,放疗中、放疗后CD4+/CD8+升高明显,并且有显著性差异(P<0.01).结论:Gln和Arg配合放疗可以提高肺癌病人CD4+/CD8+水平,增强细胞免疫功能;同时阻止机体蛋白质降解速度,提高放疗中的营养状况.%Objective: The study was designed to observe the effect of glutamine and arginine in the patients of lung cancer radiotherapy. Methods: 36 cases diagnosed non-small cell lung cancer clinically were randomly divided into the radiotherapy group (n = 18) and the combined treatment group (n = 18). Radiotherapy group received radiotherapy alone. Combined treatment group received intravenous arginine and glutamine, Arg 25 g/d [0.5 g/(kg·d) ] , glutamine 20 g/d [0.4 g/(kg·d) ] in 1 ~ 10 days while accepting radiotherapy. All patients were detected about ALB,PA ,LC ,CRP,complement C3, IgG and T cells Subsets CD3 + , CD4 + , CD8+ and CD4+ /CD8+. Results: PA of the combined treatment group increased significantly P <0. 05 than in radiotherapy group. CD3+ and CD4 + cells in the combined treatment group increased and CD8 + cells decreased

  16. Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): a dynamic 1H-MRS study.

    Science.gov (United States)

    Maddock, Richard J; Casazza, Gretchen A; Buonocore, Michael H; Tanase, Costin

    2011-08-15

    Vigorous exercise increases lactate and glucose uptake by the brain in excess of the increase in brain oxygen uptake. The metabolic fate of this non-oxidized carbohydrate entering the brain is poorly understood, but accumulation of lactate in the brain and/or increased net synthesis of amino acid neurotransmitters are possible explanations. Previous proton magnetic resonance spectroscopy (1H-MRS) studies using conventional pulse sequences have not detected changes in brain lactate following exercise. This contrasts with 1H-MRS studies showing increased brain lactate when blood lactate levels are raised by an intravenous infusion of sodium lactate. Using a J-editing 1H-MRS technique for measuring lactate, we demonstrated a significant 19% increase in lactate in the visual cortex following graded exercise to approximately 85% of predicted maximum heart rate. However, the magnitude of the increase was insufficient to account for more than a small fraction of the non-oxidized carbohydrate entering the brain with exercise. We also report a significant 18% increase in Glx (combined signal from glutamate and glutamine) in visual cortex following exercise, which may represent an activity-dependent increase in glutamate. Future studies will be necessary to test the hypothesis that non-oxidized carbohydrate entering the brain during vigorous exercise is directed, in part, toward increased net synthesis of amino acid neurotransmitters. The possible relevance of these findings to panic disorder and major depression is discussed.

  17. Prevention of methionine and ammonia-induced coma by intravenous infusion of a branched chain amino acid solution to rats with liver injury.

    Directory of Open Access Journals (Sweden)

    Shiota,Tetsuya

    1984-10-01

    Full Text Available The prevention of hepatic encephalopathy by the intravenous infusion of a branched chain amino acid (BCAA-enriched solution was investigated in methionine and ammonium acetate-treated rats whose liver was already injured with carbon tetrachloride. A BCAA-enriched solution protected the rats from entering a coma. The brain BCAA contents became higher, and the brain methionine and tyrosine levels and the ratio of glutamine to glutamic acid in the brain diminished after administering the BCAA-enriched solution.

  18. Phosphotransferase-dependent accumulation of (p)ppGpp in response to glutamine deprivation in Caulobacter crescentus

    Science.gov (United States)

    Ronneau, Séverin; Petit, Kenny; De Bolle, Xavier; Hallez, Régis

    2016-01-01

    The alarmone (p)ppGpp is commonly used by bacteria to quickly respond to nutrient starvation. Although (p)ppGpp synthetases such as SpoT have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. Here, we describe an essential role of the nitrogen-related phosphotransferase system (PTSNtr) in controlling (p)ppGpp accumulation in Caulobacter crescentus. We show that cells sense nitrogen starvation by way of detecting glutamine deprivation using the first enzyme (EINtr) of PTSNtr. Decreasing intracellular glutamine concentration triggers phosphorylation of EINtr and its downstream components HPr and EIIANtr. Once phosphorylated, both HPr∼P and EIIANtr∼P stimulate (p)ppGpp accumulation by modulating SpoT activities. This burst of second messenger primarily impacts the non-replicative phase of the cell cycle by extending the G1 phase. This work highlights a new role for bacterial PTS systems in stimulating (p)ppGpp accumulation in response to metabolic cues and in controlling cell cycle progression and cell growth. PMID:27109061

  19. The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme.

    Science.gov (United States)

    Moreadith, R W; Lehninger, A L

    1984-05-25

    Little evidence has been available on the oxidative pathways of glutamine and glutamate, the major respiratory substrates of cancer cells. Glutamate formed from glutamine by phosphate-dependent glutaminase undergoes quantitative transamination by aerobic tumor mitochondria to yield aspartate. However, when malate is also added there is a pronounced decrease in aspartate production and a large formation of citrate and alanine, in both state 3 and 4 conditions. In contrast, addition of malate to normal rat heart, liver, or kidney mitochondria oxidizing glutamate causes a marked increase in aspartate production. Further analysis showed that extramitochondrial malate is oxidized almost quantitatively to pyruvate + CO2 by NAD(P)+-linked malic enzyme, present in the mitochondria of all tumors tested, but absent in heart, liver, and kidney mitochondria. On the other hand intramitochondrial malate generated from glutamate is oxidized quantitatively to oxalacetate by mitochondrial malate dehydrogenase of tumors. Acetyl-CoA derived from extramitochondrial malate via pyruvate and oxalacetate derived from glutamate via intramitochondrial malate are quantitatively converted into citrate, which is extruded. No evidence was found that malic enzyme of tumor mitochondria converts glutamate-derived malate into pyruvate as postulated in other reports. Possible mechanisms for the integration of mitochondrial malic enzyme and malate dehydrogenase activities in tumors are discussed.

  20. Glutamine synthetase plays a role in D-galactose-induced astrocyte aging in vitro and in vivo.

    Science.gov (United States)

    Shen, Yao; Gao, Hongchang; Shi, Xiaojie; Wang, Na; Ai, Dongdong; Li, Juan; Ouyang, Li; Yang, Jianbo; Tian, Yueyang; Lu, Jianxin

    2014-10-01

    Astrocytes play multiple roles in physiological and pathological conditions in brain. However, little is known about the alterations of astrocytes in age-related changes, and few aging models of the astrocytes in vitro have been established. Therefore, in the present study, we used d-galactose (D-Gal) to establish astrocyte aging model to explore the alterations of astrocytes in brain aging. We also used (1)H nuclear magnetic resonance ((1)H NMR) spectra to verify the metabolic changes in the cerebral cortex of mice injected with D-gal. The results showed that D-gal (55mM) treatment for 1 week induced senescence characteristics in cultured cortical astrocytes. Real-time PCR and western blot analysis showed that the levels of glutamine synthetase (GS) mRNA and protein were strikingly decreased in the cultured senescent astrocytes, and the senescent astrocytes showed less resistance to the glutamate-induced gliotoxicity. The impairments of glutamate-glutamine cycle and astrocytes were also found in the cerebral cortex of mice treatment with D-gal (100mg/kg) for 6 weeks, and the level of GS mRNA was also found to be reduced markedly, being consistent with the result obtained from the senescent astrocytes in vitro. These results indicate that astrocyte may be the predominant contributor to the pathogenic mechanisms of D-gal-induced brain aging in mice, and GS might be one of the potential therapeutic targets of the aged brain induced by D-gal.

  1. Phosphotransferase-dependent accumulation of (p)ppGpp in response to glutamine deprivation in Caulobacter crescentus.

    Science.gov (United States)

    Ronneau, Séverin; Petit, Kenny; De Bolle, Xavier; Hallez, Régis

    2016-04-25

    The alarmone (p)ppGpp is commonly used by bacteria to quickly respond to nutrient starvation. Although (p)ppGpp synthetases such as SpoT have been extensively studied, little is known about the molecular mechanisms stimulating alarmone synthesis upon starvation. Here, we describe an essential role of the nitrogen-related phosphotransferase system (PTS(Ntr)) in controlling (p)ppGpp accumulation in Caulobacter crescentus. We show that cells sense nitrogen starvation by way of detecting glutamine deprivation using the first enzyme (EI(Ntr)) of PTS(Ntr). Decreasing intracellular glutamine concentration triggers phosphorylation of EI(Ntr) and its downstream components HPr and EIIA(Ntr). Once phosphorylated, both HPr∼P and EIIA(Ntr)∼P stimulate (p)ppGpp accumulation by modulating SpoT activities. This burst of second messenger primarily impacts the non-replicative phase of the cell cycle by extending the G1 phase. This work highlights a new role for bacterial PTS systems in stimulating (p)ppGpp accumulation in response to metabolic cues and in controlling cell cycle progression and cell growth.

  2. Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina.

    Science.gov (United States)

    Zeng, Kaihong; Yang, Na; Wang, Duozi; Li, Suping; Ming, Jian; Wang, Jing; Yu, Xuemei; Song, Yi; Zhou, Xue; Yang, Yongtao

    2016-05-01

    This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy.

  3. Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

    Science.gov (United States)

    Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

    2016-01-01

    Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

  4. Intravenous clarithromycin: A valuable immunomodulator for severe infections

    Directory of Open Access Journals (Sweden)

    Leventogiannis Konstantinos

    2014-01-01

    Full Text Available There are many studies suggesting that intake of a macrolide in the treatment regimen is linked with improved outcomes for patients with community-acquired pneumonia. However this was never proved through one randomized clinical study (RCT. We reviewed all pre-clinical and clinical development from 2003 to 2014 for intravenous clarithromycin as adjunctive treatment of severe infections. This process ended with the conduct of two RCTs; the first in 200 patients with ventilator-associated pneumonia; and the second in 600 patients with proven or suspected Gram-negative infections of non-pulmonary origin. The two RCTs has similar findings; significant decrease of mortality of patients with septic shock and multiple organ dysfunctions; and shorter resolution of severe infections. The second RCT also showed significant savings for survivors. These data support the use of intravenous clarithromycin as adjunctive treatment of severe infections.

  5. A novel glutamine biosensor based on zinc oxide nanorod and glutaminase enzyme from Hypocria jecorina.

    Science.gov (United States)

    Albayrak, Dilruba; Karakuş, Emine

    2016-01-01

    A novel biosensor for determination of L-glutamine in pharmaceutical glutamine powder was developed via immobilizing our produced glutaminase enzyme from Hypocria jecorina onto our prepared zinc oxide (ZnO) nanorod and chitosan. ZnO nanorods were prepared as surface-dependent and surface-independent and both were used. The biosensor is specific for L-glutamine and the peculiar analytical properties (linearity range, reproducibility, and accuracy) of it were experimentally determined. The optimum operating conditions of the biosensor such as buffer concentration, buffer pH, and medium temperature effect on the response of biosensor were studied. Km and Vmax values for the our-producing glutaminase enzyme from Hypocria jecorina immobilized on the biosensor were also determined as 0.29 mM and 208.33 mV/min., respectively, from Lineweaver-Burk plot. The biosensor was then used for the determination of glutamine contained in pharmaceutical formulations.

  6. 3-substituted anilines as scaffolds for the construction of glutamine synthetase and DXP-reductoisomerase inhibitors

    CSIR Research Space (South Africa)

    Mutorwa, M

    2009-01-01

    Full Text Available -1 Synthetic Communications Volume 39, Issue 15, 2009 3-Substituted Anilines as Scaffolds for the Construction of Glutamine Synthetase and DXP-Reductoisomerase Inhibitors Marius Mutorwaa, Sheriff Salisua, Gregory L. Blatchbc, Colin Kenyond & Perry T...

  7. GLUTAMINE SUPPLEMENTATION DID NOT BENEFIT ATHLETES DURING SHORT-TERM WEIGHT REDUCTION

    Directory of Open Access Journals (Sweden)

    Mona Rosene-Treadwell

    2003-12-01

    Full Text Available The purpose was to determine if glutamine supplementation would prevent a loss of lean mass in athletes during a 12-day weight reduction program. It was hypothesized that supplementation would spare lean body mass. Subjects (n=18 exercised and dieted to create a 4186kJ·day-1 energy deficit and a 8372 kJ·day-1 energy deficit on days 1-5, days 6-12, respectively. The glutamine (GLN group (n=9 ingested 0.35 g·kg-1 body mass of glutamine while a placebo was administered to the remaining subjects. Body mass (BM, lean body mass (LBM and fat mass (FM, were measured at days 0, 6, and 12. GLN and placebo groups both lost significant amounts of BM, LBM and FM. There were no significant differences between groups. The findings indicate little benefit for retention of lean mass with supplementation of glutamine during a short-term weight reduction program.

  8. Ion exclusion chromatography for the purification of L-glutamine; Ion haijo chromatography ni yoru L-glutamine no seiseiho no kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Ito, H.; Nishi, A.; Naruse, M. [Ajinomoto Co. Inc., Kawasaki (Japan)

    1998-09-05

    Ion exclusion chromatography for the purification of L-glutamine is studied. L-glutamine is usually produced by fermentation and used in pharmaceuticals. By using a model solution of L-glutamine and L-glutamic acid, the optimum cation exchange resin is examined. As a result of the experiments, it is found that a cation exchange resin which has smaller crosslinkage and smaller diameter is better. Ammonium sulfate, L-glutamic acid and pyrrolidonecarboxylic acid, which are usually contained in fermentation broth as impurities, are effectively separated by this method. Moreover, the experimental data of the chromatography is expressed fairly well by the differential equations which express the mass transfer in the fixed bed. 8 refs., 5 figs., 2 tabs.

  9. Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a β-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation.

    Science.gov (United States)

    Berry, Ryan S; Gullapalli, Rama R; Wu, Jin; Morris, Katherine; Hanson, Joshua A

    2014-08-01

    Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, β-catenin activated, and unclassifiable. β-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for β-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a β-catenin wild-type hepatocellular adenoma but harbored a β-catenin mutation by molecular analysis. The tumor lacked nuclear β-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.

  10. Disruption of glutamate-glutamine-GABA cycle significantly impacts on suicidal behaviour: survey of the literature and own findings on glutamine synthetase.

    Science.gov (United States)

    Bernstein, Hans-Gert; Tausch, Anne; Wagner, Rebecca; Steiner, Johann; Seeleke, Patrick; Walter, Martin; Dobrowolny, Henrik; Bogerts, Bernhard

    2013-11-01

    The aetiology of suicide is complex and still not completely understood. The present communication, which consists of two parts, aims to shed some light on the role of amino acidergic neurotransmission in suicide. In the first part we provide an overview of the literature showing that with the exception of certain gamma-aminobutyric acid transporters, virtually all components of the glutamate-glutamine- gamma-aminobutyric acid cycle are, in some way or other, abnormal in suicide victims, which indicates a prominent involvement of the glutamatergic and gammaaminobutyric acidergic neurotransmitter systems in suicidal behaviour. In the second part we present own immunohistochemical findings showing that densities of glutamine synthetase expressing glial cells in the mediodorsal thalamus as well as in the dorsolateral prefrontal and orbitofrontal cortex of schizophrenic suicide completers are significantly elevated compared with controls and non-suicide individuals with schizophrenia, thus calling into question the belief that cerebral glutamine synthetase deficit is indicative of suicidal behaviour.

  11. Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation.

    Science.gov (United States)

    Vandresen-Filho, Samuel; Martins, Wagner C; Bertoldo, Daniela B; Mancini, Gianni; Herculano, Bruno A; de Bem, Andreza F; Tasca, Carla I

    2013-06-01

    Oxygen-glucose deprivation (OGD) in brain cells increases extracellular glutamate concentration leading to excitotoxicity. Glutamate uptake from the synaptic cleft is carried out by glutamate transporters, which are likely to be modulated by oxidative stress. Therefore, oxidative stress is associated with reduced activity of glutamate transporters and glutamine synthetase, thus increasing extracellular glutamate levels that may aggravate damage to brain cells. Atorvastatin, a cholesterol-lowering agent, has been shown to exert neuroprotective effects. The aim of this study was to investigate if in vivo atorvastatin treatment would have protective effects against hippocampal slices subjected to OGD, ex vivo. Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS). Atorvastatin pretreatment also prevented the OGD-induced decrease in glutamate uptake and glutamine synthetase activity, although it had no effect on OGD-induced excitatory aminoacids release. Addition of cholesterol before OGD and reoxygenation, abolished the protective effect of atorvastatin on cellular viability as well as on glutamate uptake and glutamine synthetase activity. Therefore, atorvastatin is capable of preventing OGD-induced cell death, an effect achieved due to modulation of glutamate uptake and glutamine synthetase activity, and associated with diminished oxidative stress. Additionally, atorvastatin effects were dependent on its action on cholesterol synthesis inhibition. Thus, atorvastatin might be a useful strategy in the prevention of glutamate exitotoxicity involved in brain injuries such as vascular disorders.

  12. Clinical applications of intravenous immunoglobulins in neurology

    Science.gov (United States)

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  13. Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformations

    Directory of Open Access Journals (Sweden)

    Constantin Jorgete

    2010-01-01

    Full Text Available Abstract Background Glutaminase predominates in periportal hepatocytes and it has been proposed that it determines the glutamine-derived nitrogen flow through the urea cycle. Glutamine-derived urea production should, thus, be considerably faster in periportal hepatocytes. This postulate, based on indirect observations, has not yet been unequivocally demonstrated, making a direct investigation of ureogenesis from glutamine highly desirable. Methods Zonation of glutamine metabolism was investigated in the bivascularly perfused rat liver with [U-14C]glutamine infusion (0.6 mM into the portal vein (antegrade perfusion or into the hepatic vein (retrograde perfusion. Results Ammonia infusion into the hepatic artery in retrograde and antegrade perfusion allowed to promote glutamine metabolism in the periportal region and in the whole liver parenchyma, respectively. The results revealed that the space-normalized glutamine uptake, indicated by 14CO2 production, gluconeogenesis, lactate production and the associated oxygen uptake, predominates in the periportal region. Periportal predominance was especially pronounced for gluconeogenesis. Ureogenesis, however, tended to be uniformly distributed over the whole liver parenchyma at low ammonia concentrations (up to 1.0 mM; periportal predominance was found only at ammonia concentrations above 1 mM. The proportions between the carbon and nitrogen fluxes in periportal cells are not the same along the liver acinus. Conclusions In conclusion, the results of the present work indicate that the glutaminase activity in periportal hepatocytes is not the rate-controlling step of the glutamine-derived nitrogen flow through the urea cycle. The findings corroborate recent work indicating that ureogenesis is also an important ammonia-detoxifying mechanism in cells situated downstream to the periportal region.

  14. Glutamine-Loaded Liposomes: Preliminary Investigation, Characterization, and Evaluation of Neutrophil Viability.

    Science.gov (United States)

    Costa, Larissa Chaves; Souza, Bárbara Nayane Rosário Fernandes; Almeida, Fábio Fidélis; Lagranha, Cláudia Jacques; Cadena, Pabyton Gonçalves; Santos-Magalhães, Nereide Stela; Lira-Nogueira, Mariane Cajubá de Britto

    2016-04-01

    Glutamine has received attention due to its ability to ameliorate the immune system response. Once conventional liposomes are readily recognized and captured by immune system cells, the encapsulation of glutamine into those nanosystems could be an alternative to reduce glutamine dosage and target then to neutrophils. Our goals were to nanoencapsulate glutamine into conventional liposomes (Gln-L), develop an analytical high-performance liquid chromatography (HPLC) method for its quantification, and evaluate the viability of neutrophils treated with Gln-L. Liposomes were prepared using the thin-film hydration technique followed by sonication and characterized according to pH, mean size, zeta potential, and drug encapsulation efficiency (EE%). We also aimed to study the effect of liposomal constituent concentrations on liposomal characteristics. The viability of neutrophils was assessed using flow cytometry after intraperitoneal administration of free glutamine (Gln), Gln-L, unloaded-liposome (UL), and saline solution as control (C) in healthy Wistar rats. The selected liposomal formulation had a mean vesicle size of 114.65 ± 1.82 nm with a polydispersity index of 0.30 ± 0.00, a positive surface charge of 36.30 ± 1.38 mV, and an EE% of 39.49 ± 0.74%. The developed chromatographic method was efficient for the quantification of encapsulated glutamine, with a retention time at 3.8 min. A greater viability was observed in the group treated with glutamine encapsulated compared to the control group (17%), although neutrophils remain viable in all groups. Thus, glutamine encapsulated into liposomes was able to increase the number of viable neutrophils at low doses, thereby representing a promising strategy for the treatment of immunodeficiency conditions.

  15. Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver.

    OpenAIRE

    Smith, D. D.; Campbell, J. W.

    1988-01-01

    Mitochondrial glutamine synthetase (EC 6.3.1.2) is the primary ammonia-detoxifying enzyme in avian liver and is therefore analogous in function to carbamoyl-phosphate synthetase I (ammonia) (EC 6.3.4.16) in mammalian liver. In mammalian liver, glutamine synthetase is cytosolic and its distribution is restricted to a few hepatocytes around the terminal venules. These cells do not express carbamoyl-phosphate synthetase I. Using immunocytochemistry, we show here that there is little or no zonati...

  16. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study.

    Science.gov (United States)

    Laviano, A; Molfino, A; Lacaria, M T; Canelli, A; De Leo, S; Preziosa, I; Rossi Fanelli, F

    2014-11-01

    Glutamine supplementation improves insulin sensitivity in critically ill patients, and prevents obesity in animals fed a high-fat diet. We hypothesized that glutamine supplementation favors weight loss in humans. Obese and overweight female patients (n=6) were enrolled in a pilot, cross-over study. After recording anthropometric (that is, body weight, waist circumference) and metabolic (that is, glycemia, insulinemia, homeostatic model of insulin resistance (HOMA-IR)) characteristics, patients were randomly assigned to 4-week supplementation with glutamine or isonitrogenous protein supplement (0.5 g/KgBW/day). During supplementation, patients did not change their dietary habits nor lifestyle. At the end, anthropometric and metabolic features were assessed, and after 2 weeks of washout, patients were switched to the other supplement for 4 weeks. Body weight and waist circumference significantly declined only after glutamine supplementation (85.0±10.4 Kg vs 82.2±10.1 Kg, and 102.7±2.0 cm vs 98.9±2.9 cm, respectively; P=0.01). Insulinemia and HOMA-IR declined by 20% after glutamine, but not significantly so. This pilot study shows that glutamine is safe and effective in favoring weight loss and possibly enhancing glucose metabolism.

  17. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen;

    2008-01-01

    AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated...... with a rise in the glutamine concentration and ICP. PATIENTS AND METHODS: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion...... pressure (CPP). RESULTS: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate...

  18. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats.

    Science.gov (United States)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  19. The effect of glial glutamine synthetase inhibition on recognition and temporal memories in the rat.

    Science.gov (United States)

    Kant, Deepika; Tripathi, Shweta; Qureshi, Munazah F; Tripathi, Shweta; Pandey, Swati; Singh, Gunjan; Kumar, Tankesh; Mir, Fayaz A; Jha, Sushil K

    2014-02-07

    The glutamate neurotransmitter is intrinsically involved in learning and memory. Glial glutamine synthetase enzyme synthesizes glutamine, which helps maintain the optimal neuronal glutamate level. However, the role of glutamine synthetase in learning and memory remains unclear. Using associative trace learning task, we investigated the effects of methionine sulfoximine (MSO) (glutamine synthetase inhibitor) on recognition and temporal memories. MSO and vehicle were injected (i.p.) three hours before training in separate groups of male Wistar rats (n=11). Animals were trained to obtain fruit juice after following a set of sequential events. Initially, house-light was presented for 15s followed by 5s trace interval. Thereafter, juice was given for 20s followed by 20s inter-presentation interval. A total of 75 presentations were made over five sessions during the training and testing periods. The average number of head entries to obtain juice per session and during individual phases at different time intervals was accounted as an outcome measure of recognition and temporal memories. The total head entries in MSO and vehicle treated animals were comparable on training and testing days. However, it was 174.90% (p=0.08), 270.61% (pGlutamine synthetase inhibition did not induce recognition memory deficit, while temporal memory was altered, suggesting that glutamine synthetase modulates some aspects of mnemonic processes.

  20. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

    Science.gov (United States)

    Eid, Tore; Ghosh, Arko; Wang, Yue; Beckström, Henning; Zaveri, Hitten P; Lee, Tih-Shih W; Lai, James C K; Malthankar-Phatak, Gauri H; de Lanerolle, Nihal C

    2008-08-01

    An excess of extracellular glutamate in the hippocampus has been linked to the generation of recurrent seizures and brain pathology in patients with medically intractable mesial temporal lobe epilepsy (MTLE). However, the mechanism which results in glutamate excess in MTLE remains unknown. We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically involved in the pathophysiology of the disease. To further explore the role of glutamine synthetase in MTLE we created a novel animal model of hippocampal glutamine synthetase deficiency by continuous (approximately 28 days) microinfusion of methionine sulfoximine (MSO: 0.625 to 2.5 microg/h) unilaterally into the hippocampus in rats. This treatment led to a deficiency in hippocampal glutamine synthetase activity by 82-97% versus saline. The majority (>95%) of the MSO-treated animals exhibited recurrent seizures that continued for several weeks. Some of the MSO-treated animals exhibited neuropathological features that were similar to mesial temporal sclerosis, such as hippocampal atrophy and patterned loss of hippocampal neurons. However, many MSO-treated animals displayed only minimal injury to the hippocampus, with no clear evidence of mesial temporal sclerosis. These findings support the hypothesis that a deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, and that restoration of glutamine synthetase may represent a novel approach to therapeutic intervention in this disease.

  1. Pilot study with a glutamine-supplemented enteral formula in critically ill infants

    Directory of Open Access Journals (Sweden)

    Barbosa Eliana

    1999-01-01

    Full Text Available Seriously ill infants often display protein-calorie malnutrition due to the metabolic demands of sepsis and respiratory failure. Glutamine has been classified as a conditionally essential amino acid, with special usefulness in critical patients. Immunomodulation, gut protection, and prevention of protein depletion are mentioned among its positive effects in such circumstances. With the intent of evaluating the tolerance and clinical impact of a glutamine supplement in seriously ill infants, a prospective randomized study was done with nine patients. Anthropometric and biochemical determinations were made, and length of stay in the intensive care unit (ICU, in the hospital, and under artificial ventilation, and septic morbidity and mortality were tabulated. Infants in the treatment group (n=5 were enterally administered 0.3 g/kg of glutamine, whereas controls received 0.3 g/kg of casein during a standard period of five days. Septic complications occurred in 75% of the controls (3/4 versus 20% of the glutamine-treated group (1/5, p<=0.10, and two patients in the control group died of bacterial infections (50% vs. 0%, p<=0.10. Days in the ICU, in the hospital, and with ventilation numerically favored glutamine therapy, although without statistical significance. The supplements were usually well tolerated, and no patient required discontinuation of the program. The conclusion was that glutamine supplementation was safe and tended to be associated with less infectious morbidity and mortality in this high-risk population.

  2. The complexity of prescribing intravenous lipid emulsions.

    Science.gov (United States)

    Waitzberg, Dan Linetzky; Torrinhas, Raquel Susana

    2015-01-01

    Intravenous lipid emulsions (LEs) are relevant for patients receiving parenteral nutrition because they prevent the depletion of essential fatty acids (FAs) and, as a highly dense energy source, enable the reduction of glucose provision, thereby decreasing the risks of hyperglycemia and hepatic impairment. The prescription of LEs is complex, due mainly to their distinct FA components, which may alter the immune response in different ways and distinctly influence inflammation, oxidative stress and blood coagulation according to their biochemical properties. In addition, an excess of other LE components, such as phospholipids and phytosterols, may be associated with hepatic steatosis and dysfunction. These associations do not represent direct risks or obstacles to LE use in metabolically stable patients but can render the choice of the best LE for hypermetabolic patients difficult. The infusion of LEs according to the available guidelines provides more benefit than harm and should be part of exclusive parenteral nutrition regimens or complement enteral nutrition when appropriate. The patient's metabolic profile should guide the type of FA and amount of lipids that are provided. For critically ill hypermetabolic patients, growing evidence indicates that standard LEs based solely on soybean oil should be avoided in favor of new LEs containing medium-chain triglycerides, olive oil, or fish oil to decrease the provision of potentially oxidative, inflammatory/immunosuppressive, and prothrombotic n-6 FAs. In addition, as sources of eicosapentaenoic and docosahexaenoic acids, LEs containing fish oil may be important for critically ill patients because they allow better modulation of the immune response and likely reduce the length of intensive care unity stay. However, current evidence precludes the recommendation of a specific LE for clinical use in this patient population.

  3. Effect of proanthocyanidin, arginine and glutamine supplementation on methotrexate-induced gastrointestinal toxicity in rats.

    Science.gov (United States)

    Gulgun, M; Karaoglu, A; Kesik, V; Kurt, B; Erdem, O; Tok, D; Kismet, E; Koseoglu, V; Ozcan, O

    2010-11-01

    Methotrexate is a folate antagonist that is commonly used as an antitumor and antiarthritic drug. The aim of this study was to investigate the possible roles of exogenous glutamine (Glu), arginine (Arg) and proanthocyanidin (PA) on gut protection from methotrexate-induced intestinal damage in rats. Experimental rats were separated into eight groups. The first (sham) group received a 0.9% NaCl solution alone. The second group received intraperitoneal injections of methotrexate (20 mg/kg/day) administered on day 4 of the experiment and continued for 5 days. Rats in the other six groups were administered PA, Glu, Arg, Glu+PA, Arg+PA or Glu+Arg orally by gavage together with methotrexate and animals were sacrificed on day 8 of the experiment. All animals were sacrificed 4 days after methotrexate injection for histopathological analysis, tissue glutathione peroxidase, malondialdehyde and superoxide dismutase assays. Proanthocyanidin and Glu decreased the severity of intestinal injury and oxidant injury as evident by histopathology and changes in malondialdehyde levels. Histological analysis confirmed that PA and to a lesser extent Glu supplementation were more favorable than Arg for the protection of the small intestine from methotrexate-induced injury.

  4. Stability of Minimum Essential Medium functionality despite L-glutamine decomposition.

    Science.gov (United States)

    Jagušić, Maja; Forčić, Dubravko; Brgles, Marija; Kutle, Leonida; Šantak, Maja; Jergović, Mladen; Kotarski, Ljerka; Bendelja, Krešo; Halassy, Beata

    2016-08-01

    L-Glutamine (L-Gln) instability in liquid media is a well-known fact. Also, negative effect of ammonia, one of the L-Gln degradation products, on viability of many cell cultures and on replication of different viruses has been described. However, negative effects of ammonia have been reported in doses excessively exceeding those that could be generated in regularly used liquid culture media due to spontaneous L-Gln breakdown (below 2 mM). Traditional virus vaccine production processes have been established and registered involving L-Gln containing media use. Eventual culture media replacement in the regular production process belongs to the major regulative changes that require substantial financial expenses. The aim of this study was to evaluate the effect of storage of Minimum Essential Media with Hanks salts on their relevant biological functions during virus vaccine production process in relation to L-Gln decrease. Our results show a cell type dependent effect of spontaneous L-Gln degradation during medium storage. They also suggest that for cell cultures used in measles, mumps, and rubella virus production the media retain their functionality in respect to cell viability or virus growth over a certain time window despite L-Gln degradation.

  5. Glutamine synthetase in Durum Wheat: Genotypic Variation and Relationship with Grain Protein Content.

    Science.gov (United States)

    Nigro, Domenica; Fortunato, Stefania; Giove, Stefania L; Paradiso, Annalisa; Gu, Yong Q; Blanco, Antonio; de Pinto, Maria C; Gadaleta, Agata

    2016-01-01

    Grain protein content (GPC), is one of the most important trait in wheat and its characterized by a very complex genetic control. The identification of wheat varieties with high GPC (HGPC), as well as the characterization of central enzymes involved in these processes, are important for more sustainable agricultural practices. In this study, we focused on Glutamine synthetase (GS) as a candidate to study GPC in wheat. We analyzed GS expression and its enzymatic activity in different tissues and phenological stages in 10 durum wheat genotypes with different GPC. Although each genotype performed quite differently from the others, both because their genetic variability and their adaptability to specific environmental conditions, the highest GS activity and expression were found in genotypes with HGPC and vice versa the lowest ones in genotypes with low GPC (LGPC). Moreover, in genotypes contrasting in GPC bred at different nitrogen regimes (0, 60, 140 N Unit/ha) GS behaved differently in diverse organs. Nitrogen supplement increased GS expression and activity in roots of all genotypes, highlighting the key role of this enzyme in nitrogen assimilation and ammonium detoxification in roots. Otherwise, nitrogen treatments decreased GS expression and activity in the leaves of HGPC genotypes and did not affect GS in the leaves of LGPC genotypes. Finally, no changes in GS and soluble protein content occurred at the filling stage in the caryopses of all analyzed genotypes.

  6. The role of glutamine supplementation in thoracic and upper aerodigestive malignancies.

    Science.gov (United States)

    Papanikolopoulou, Amalia; Syrigos, Konstantinos N; Drakoulis, Nikolaos

    2015-01-01

    In cancer patients, marked glutamine (gln) depletion develops over time. Host tissues (epithelial cells and lymphocytes) that depend upon adequate stores of gln for optimal functioning can be negatively influenced. In addition, radiation and/or chemotherapy cause normal tissues damage that might be enhanced by this depletion effect. The present review evaluates in vivo clinical data about the potential beneficial role of gln administration in the prevention of host tissue toxicity, in a patient group with thoracic and upper aerodigestive malignancies (T&UAM) during cancer treatment. Publications were identified in a systematic review of MEDLINE Database from the last 2 decades (1994-2014) using key search terms and through manual searches. Overall, 13 clinical studies (9 oral/4 parenteral) evaluated the safety and tolerance of gln supply, showing a beneficial effect in the grade, duration of mucositis and esophagitis, decreased gut permeability, and weight loss. Only 1 Phase 1 clinical trial had negative results because the chemo-radiotherapy combined treatment was not feasible. The use of oral gln may especially have an important role in the prevention of acute radiation toxicities, the weight loss and the need for analgesics in patients with T&UAM, especially if the treatment plan includes combined modality therapy with chemo-radiation.

  7. Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats.

    Science.gov (United States)

    Fan, Jun; Wu, Lidong; Li, Guoping; Tao, Shaoyu; Sheng, Zhiyong; Meng, Qingyan; Li, Fengxin; Yu, Lijuan; Li, Li

    2015-06-14

    The aim of the present study was to investigate the effects of enteral nutrition (EN) with parenteral glutamine (GLN) supplementation on inflammatory response, lymphatic organ apoptosis, immunological function and survival in septic rats by caecal ligation and puncture (CLP). Male rats were randomly assigned into two experimental groups and two sham CLP control groups (n 10 per group). After CLP or sham CLP model and nutrition programme were completed, the GLN concentrations of plasma and tissues and several indices of immunological function including serum Ig content, circulating lymphocyte number, the CD4:CD8 ratio, the neutrophil phagocytosis index (NPI), the organ index and apoptosis of thymus and spleen, and plasma cytokine levels were determined. Moreover, the survival in septic rats was observed. The results revealed that EN with parenteral GLN supplementation remarkably increased the GLN concentrations of plasma and tissues, serum Ig content, the circulating lymphocyte number, the CD4:CD8 ratio, the indexes of thymus and spleen, NPI and survival compared with the control group (P< 0·05). In contrast, the apoptosis of thymus and spleen and the levels of TNF-α, IL-1β and IL-6 in plasma were obviously decreased compared with the control group (P< 0·05). These results show that EN with parenteral GLN supplementation diminished the release of inflammatory cytokines, attenuated lymphatic organ apoptosis, enhanced the immunological function and improved survival in septic rats.

  8. Identification of a phosphinothricin-resistant mutant of rice glutamine synthetase using DNA shuffling.

    Science.gov (United States)

    Tian, Yong-Sheng; Xu, Jing; Zhao, Wei; Xing, Xiao-Juan; Fu, Xiao-Yan; Peng, Ri-He; Yao, Quan-Hong

    2015-10-23

    To date, only bar/pat gene derived from Streptomyces has been used to generate the commercial PPT-resistant crops currently available in the market. The limited source of bar/pat gene is probably what has caused the decrease in PPT-tolerance, which has become the main concern of those involved in field management programs. Although glutamine synthetase (GS) is the target enzyme of PPT, little study has been reported about engineering PPT-resistant plants with GS gene. Then, the plant-optimized GS gene from Oryza sativa (OsGS1S) was chemically synthesized in the present study by PTDS to identify a GS gene for developing PPT-tolerant plants. However, OsGS1S cannot be directly used for developing PPT-tolerant plants because of its poor PPT-resistance. Thus, we performed DNA shuffling on OsGS1S, and one highly PPT-resistant mutant with mutations in four amino acids (A63E, V193A, T293A and R295K) was isolated after three rounds of DNA shuffling and screening. Among the four amino acids substitutions, only R295K was identified as essential in altering PPT resistance. The R295K mutation has also never been previously reported as an important residue for PPT resistance. Furthermore, the mutant gene has been transformed into Saccharomyces cerevisiae and Arabidopsis to confirm its potential in developing PPT-resistant crops.

  9. Comparison of quality of induction of anaesthesia between intramuscularly administered ketamine, intravenously administered ketamine and intravenously administered propofol in xylazine premedicated cats

    Directory of Open Access Journals (Sweden)

    T.B. Dzikiti

    2007-06-01

    Full Text Available The quality of induction of general anesthesia produced by ketamine and propofol, 2 of the most commonly used anaesthetic agents in cats, was assessed. Eighteen cats admitted for elective procedures were randomly assigned to 3 groups and then premedicated with xylazine 0.75 mg/kg intramuscularly before anaesthesia was induced with ketamine 15 mg/kg intramuscularly (KetIM group, ketamine 10 mg/kg intravenously (KetIV group or propofol 4 mg/kg intravenously (PropIV group. Quality of induction of general anaesthesia was determined by scoring ease of intubation, degree of struggling, and vocalisation during the induction period. The quality of induction of anaesthesia of intramuscularly administered ketamine was inferior to that of intravenously administered ketamine, while intravenously administered propofol showed little difference in quality of induction from ketamine administered by both the intramuscular and intravenous routes. There were no significant differences between groups in the ease of intubation scores, while vocalisation and struggling were more common in cats that received ketamine intramuscularly than in those that received intravenously administered ketamine or propofol for induction of anaesthesia. Laryngospasms occurred in 2 cats that received propofol. The heart rates and respiratory rates decreased after xylazine premedication and either remained the same or decreased further after induction for all 3 groups, but remained within normal acceptable limits. This study indicates that the 3 regimens are associated with acceptable induction characteristics, but administration of ketamine intravenously is superior to its administration intramuscularly and laryngeal desensitisation is recommended to avoid laryngospasms.

  10. Intravenous drug delivery in neonates: lessons learnt.

    Science.gov (United States)

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  11. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  12. Failure of intravenous metoprolol to limit acute myocardial infarct size in a nonreperfused porcine model.

    Science.gov (United States)

    Kern, K B; Hilwig, R W; Warner, A; Basnight, M; Ewy, G A

    1995-04-01

    The usefulness of intravenous beta-adrenergic receptor blockade in limiting infarct size when neither reperfusion nor collateral flow occurs is unknown. The effect of intravenous metoprolol on limiting myocardial infarct size was therefore examined in a nonreperfused porcine model. Closed-chest techniques were used to occlude the left anterior descending coronary artery, after which animals were randomized at 20 minutes to receive intravenous metoprolol, 0.75 mg/kg, or placebo. Infarct size examined at 5 hours with Evans blue and triphenyltetrazolium staining techniques was expressed as a percentage of total ventricular myocardium at ischemic risk. This percentage was not significantly different between the groups (84% +/- 5% with metoprolol vs 90% +/- 4% with placebo; p = 0.4). Myocardial infarct size was not significantly decreased at 5 hours by early administration of intravenous metoprolol when the infarct artery remained occluded and collateral flow was minimal.

  13. What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients?

    DEFF Research Database (Denmark)

    Bager, Palle; Dahlerup, Jens Frederik

    for a total of iron-dose was to 233€ to reduce the numbers of infusion from 7 till 2.    Conclusion: The cost of choosing iron carboxymaltose rather than iron sucrose in treatment of iron deficiency in IBD differs depending of the economic perspective chosen. Only the Budget Impact Analysis showed iron......  What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients? It dependent on the economic evaluation perspective!   Aim: To evaluate the health care cost for intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject......®, Vifor) treatment to IBD patients in an outpatient setting.   Background: Intravenous iron sucrose can be given as a maximum of 200 mg Fe++ per infusion vs. intravenous iron carboxymaltose that can be given as a maximum of 1000 mg Fe++ in a single infusion leading to fewer infusions and visits. The drug...

  14. Dietary glutamine supplementation modulates Th1/Th2 cytokine and interleukin-6 expressions in septic mice.

    Science.gov (United States)

    Yeh, Chiu Li; Hsu, Chun-Sun; Yeh, Sung-Ling; Chen, Wei-Jao

    2005-09-01

    Glutamine (Gln) has been demonstrated to have benefit in the modulation of systemic immunity in sepsis. However, the effects of Gln on local immunity and intra-lymphocyte cytokine expression have not been investigated in mice with gut-derived sepsis. This study evaluated the influence of a Gln-enriched diet on interleukin (IL)-6 expression in organs and Th1/Th2 type cytokine production within lymphocytes in septic mice. Male ICR mice were assigned to control and Gln groups. The control group was fed a semi-purified diet, while in the Gln group, Gln replaced part of the casein. After feeding the respective diets for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP). Mice were sacrificed at 0, 6, 12 and 24h after CLP and their organs were harvested for further analysis. Results showed that IL-6 levels in the liver were decreased, whereas levels were increased in the lungs, kidneys and intestines with the progression of sepsis in both groups. Also, intra-lymphocyte interferon (IFN)-gamma expression decreased and IL-4 expression increased during sepsis. Compared to the control group, the Gln group had higher levels of IL-6 in the liver and lower levels in other organs at various time points. Lymphocyte IFN-gamma expression in the Gln group was higher, and IL-4 levels were lower than those of the control group after CLP. These results suggest that Gln supplementation decreased IL-6 production in non-hepatic organs, while reducing intra-lymphocyte IL-4 and enhancing IFN-gamma expressions. This change may reverse the Th2 type response to a more-balanced Th1/Th2 response during sepsis.

  15. Glutamine: a precursor of glutathione and its effect on liver

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To investigate the relationship between alanyl-glutamine (ALA-GLN) and glutathione (GSH) biosynthesis in hepatic protection.METHODS Twenty male Wistar rats were randomly divided into two groups: one receiving standard parenteral nutrition (STD) and the other supplemented with or without ALA-GLN for 7 days. The blood and liver tissue samples were examined after 5-fluorouracil (5-FU) was injected peritoneally.RESULTS The concentration measurements were significantly higher in ALA-GLN group than in STD group in serum GLN (687 μmol/ L±50 μmol/ L vs 505 μmol/ L±39 μmol/ L, P<0.05), serum GSH (14 μmol/ L±5 μmol/ L vs 7 μmol/ L±3 μmol/ L, P<0.01) and in liver GSH content (6.9 μmol/ g±2.5 μmol/ g vs 4.4 μmol/ g±1.6 μmol/ g liver tissue, P<0.05). Rats in ALA-GLN group had lesser elevations in hepatic enzymes after 5-FU administration.CONCLUSION The supplemented nutrition ALA-GLN can protect the liver function through increasing the glutathione biosynthesis and preserving the glutathione stores in hepatic tissue.

  16. Overexpression of glutamine synthetases confers transgenic rice herbicide resistance

    Institute of Scientific and Technical Information of China (English)

    Sun Hui; Huang Qiman; Su Jin

    2005-01-01

    Glutamine synthetase (GS, E.C.6.3.1.2) is a key enzyme involved in the assimilation of inorganic nitrogen in higher plants and gram-negative microorganisms. GS is the targeting enzyme of a herbicide phosphinothricin (PPT) or Basta. In order to generate PPT-resistant transgenic rice via overexpression of GS, we constructed a plant expression vector p2GS harboring two different isoenzymes GS1 and GS2 cDNAs under the control of constitutive promoters of rice Act1 and maize Ubiquitin(Ubi) genes. The p2GS was introduced into rice genome by Agrobacterium-mediated transformation and confirmed by PCR and Southern blot hybridization. GS-transgene expression was first detected by Northern blot analyses. Results from Basta test indicated that GS-transgenic plants can tolerate as high as 0.3% Basta solution. In addition, our results also demonstrated that GS overexpression conferred transformed rice calli PPT resistance. Thus, GS cassette can serve as a selective marker gene instead of bar cassette for selection of PPT transformants.

  17. Controlling the prion propensity of glutamine/asparagine-rich proteins.

    Science.gov (United States)

    Paul, Kacy R; Ross, Eric D

    2015-01-01

    The yeast Saccharomyces cerevisiae can harbor a number of distinct prions. Most of the yeast prion proteins contain a glutamine/asparagine (Q/N) rich region that drives prion formation. Prion-like domains, defined as regions with high compositional similarity to yeast prion domains, are common in eukaryotic proteomes, and mutations in various human proteins containing prion-like domains have been linked to degenerative diseases, including amyotrophic lateral sclerosis. Here, we discuss a recent study in which we utilized two strategies to generate prion activity in non-prion Q/N-rich domains. First, we made targeted mutations in four non-prion Q/N-rich domains, replacing predicted prion-inhibiting amino acids with prion-promoting amino acids. All four mutants formed foci when expressed in yeast, and two acquired bona fide prion activity. Prion activity could be generated with as few as two mutations, suggesting that many non-prion Q/N-rich proteins may be just a small number of mutations from acquiring aggregation or prion activity. Second, we created tandem repeats of short prion-prone segments, and observed length-dependent prion activity. These studies demonstrate the considerable progress that has been made in understanding the sequence basis for aggregation of prion and prion-like domains, and suggest possible mechanisms by which new prion domains could evolve.

  18. Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences.

    Science.gov (United States)

    Walsh, Patrick S; Dean, Jacob C; McBurney, Carl; Kang, Hyuk; Gellman, Samuel H; Zwier, Timothy S

    2016-04-28

    The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I β-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the β-turn not otherwise involved in a hydrogen bond. This β-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y β-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.

  19. Intravenous Clomipramine for Treatment-Resistant Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Karameh, Wael Karameh; Khani, Munir

    2015-07-28

    This open trial was conducted to evaluate the effectiveness of intravenous clomipramine (CMI) in refractory obsessive-compulsive disorder (OCD). Thirty OCD poor responders to previous multiple trials of anti-obsessive medications were selected and admitted to the hospital. Severity of the illness and response to treatment were primarily assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). CMI was gradually administered intravenously for one week. All patients were thereafter switched to oral CMI with a maximum dose of 225 mg/day. The Y-BOCS total score mean at admission was in the severe range (24-31), and dropped on discharge and follow-ups to the moderate range (16-23). At discharge, 23 patients (76.7%) had a decrease in Y-BOCS ≥ 25% and were considered responders, while only 18 (60%) were still responders at 24 weeks. No relevant persistent side effects were reported. Intravenous clomipramine could be of benefit for severe OCD cases that have not adequately responded to several therapies, including oral clomipramine. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  20. Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy

    OpenAIRE

    Swamy, Mahima; Pathak, Shalini; Grzes, Katarzyna M.; Damerow, Sebastian; Sinclair, Linda V.; van Aalten, Daan M.F.; Cantrell, Doreen A.

    2016-01-01

    Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We now show that glutamine and glucose also fuel an indispensible dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of UDP-GlcNAc, a substrate for cellular glycosyltransferases. Immune activated T cells contained higher concentrations of UDP-GlcN...

  1. Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats

    OpenAIRE

    Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

    2016-01-01

    Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution 1H NMR metabolic profiling combined with...

  2. Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats.

    Science.gov (United States)

    Ardawi, M S

    1992-05-01

    1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. A critical role for amino-terminal glutamine/asparagine repeats in the formation and propagation of a yeast prion.

    Science.gov (United States)

    DePace, A H; Santoso, A; Hillner, P; Weissman, J S

    1998-06-26

    The yeast [PSI+] factor propagates by a prion-like mechanism involving self-replicating Sup35p amyloids. We identified multiple Sup35p mutants that either are poorly recruited into, or cause curing of, wildtype amyloids in vivo. In vitro, these mutants showed markedly decreased rates of amyloid formation, strongly supporting the protein-only prion hypothesis. Kinetic analysis suggests that the prion state replicates by accelerating slow conformational changes rather than by providing stable nuclei. Strikingly, our mutations map exclusively within a short glutamine/asparagine-rich region of Sup35p, and all but one occur at polar residues. Even after replacement of this region with polyglutamine, Sup35p retains its ability to form amyloids. These and other considerations suggest similarities between the prion-like propagation of [PSI+] and polyglutamine-mediated pathogenesis of several neurodegenerative diseases.

  4. Regulation of expression from the glnA promoter of Escherichia coli in the absence of glutamine synthetase.

    OpenAIRE

    Rothstein, D M; Pahel, G; Tyler, B.; Magasanik, B

    1980-01-01

    One of the suspected regulators of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] in enteric bacteria is glutamine synthetase itself. We isolated Escherichia coli strains carrying fusions of the beta-galactosidase structural gene to the promoter of the glutamine synthetase gene, with the aid of the Casadaban Mud1 (ApR, lac, cts62) phage. Some aspects of regulation were retained in haploid fusion strains despite the absence of glutamine synthetase, whereas other as...

  5. Dietary L-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice.

    Science.gov (United States)

    Ren, Wenkai; Liu, Shuping; Chen, Shuai; Zhang, Fengmei; Li, Nengzhang; Yin, Jie; Peng, Yuanyi; Wu, Li; Liu, Gang; Yin, Yulong; Wu, Guoyao

    2013-10-01

    This study was conducted to determine the effects of graded doses of L-glutamine supplementation on the replication and distribution of Pasteurella multocida, and the expression of its major virulence factors in mouse model. Mice were randomly assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0 % glutamine. Pasteurella multocida burden was detected in the heart, liver, spleen, lung and kidney after 12 h of P. multocida infection. The expression of major virulence factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5 % glutamine supplementation has little significant effect on these parameters, compared to those with basal diet. However, results showed that a high dose of glutamine supplementation increased the P. multocida burden (P glutamine supplementation inhibited the proinflammatory responses (P glutamine supplementation on different components in TLR signaling depends on glutamine concentration, and high dose of glutamine supplementation activated the proinflammatory response. In conclusion, glutamine supplementation increased P. multocida burden and the expression of its major virulence factors, while affecting the functions of the lung and spleen.

  6. Proline and Glutamine Improvein vitro Callus Induction and Subsequent Shooting in Rice

    Institute of Scientific and Technical Information of China (English)

    Bhausaheb PAWAR; Prashant KALE; Jyoti BAHURUPE; Ashok JADHAV; Anil KALE; Sharad PAWAR

    2015-01-01

    This study was conducted to evaluate the effects of proline and glutamine onin vitro callus induction and subsequent regeneration and to develop a reproducible and highly efficient plant regeneration protocol in four ricegenotypes, viz. Pawana, Jaya, Indrayani and Ambemohar. Considerable variation in response to plant growth regulators and amino acid supplements used was observed in all the four genotypes. Medium supplemented with proline and glutamine was shown to be superior to medium without proline and glutamine. The best callusing from mature embryo was observed on Murashige and Skoog (MS) medium supplemented with 2.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 500 mg/L proline and 500 mg/L glutamine. Shoot induction was higher in the callus obtained from medium supplemented with 500 mg/L proline and 500 mg/L glutamine. The highest shoot regeneration frequency (83.2%) was observed on MS medium with 2.0 mg/L benzylaminopurine, 0.5 mg/L 1-naphthaleneacetic acid, 500 mg/L proline, and 500 mg/L glutamine in the callus obtained from MS medium supplemented with 2.0 mg/L 2,4-D, 500 mg/L proline and 500 mg/L glutamine. Among the four genotypes, Pawana has the highest regeneration efficiency (83.2%), whereas the regeneration efficiency of the rest three rice genotypes was in the range of 32.0% to 72.3%. This optimized regeneration protocol can be efficiently used forAgrobacterium mediated genetic transformation in rice.

  7. Aphid amino acid transporter regulates glutamine supply to intracellular bacterial symbionts.

    Science.gov (United States)

    Price, Daniel R G; Feng, Honglin; Baker, James D; Bavan, Selvan; Luetje, Charles W; Wilson, Alex C C

    2014-01-01

    Endosymbiotic associations have played a major role in evolution. However, the molecular basis for the biochemical interdependence of these associations remains poorly understood. The aphid-Buchnera endosymbiosis provides a powerful system to elucidate how these symbioses are regulated. In aphids, the supply of essential amino acids depends on an ancient nutritional symbiotic association with the gamma-proteobacterium Buchnera aphidicola. Buchnera cells are densely packed in specialized aphid bacteriocyte cells. Here we confirm that five putative amino acid transporters are highly expressed and/or highly enriched in Acyrthosiphon pisum bacteriocyte tissues. When expressed in Xenopus laevis oocytes, two bacteriocyte amino acid transporters displayed significant levels of glutamine uptake, with transporter ACYPI001018, LOC100159667 (named here as Acyrthosiphon pisum glutamine transporter 1, ApGLNT1) functioning as the most active glutamine transporter. Transporter ApGLNT1 has narrow substrate selectivity, with high glutamine and low arginine transport capacity. Notably, ApGLNT1 has high binding affinity for arginine, and arginine acts as a competitive inhibitor for glutamine transport. Using immunocytochemistry, we show that ApGLNT1 is localized predominantly to the bacteriocyte plasma membrane, a location consistent with the transport of glutamine from A. pisum hemolymph to the bacteriocyte cytoplasm. On the basis of functional transport data and localization, we propose a substrate feedback inhibition model in which the accumulation of the essential amino acid arginine in A. pisum hemolymph reduces the transport of the precursor glutamine into bacteriocytes, thereby regulating amino acid biosynthesis in the bacteriocyte. Structural similarities in the arrangement of hosts and symbionts across endosymbiotic systems suggest that substrate feedback inhibition may be mechanistically important in other endosymbioses.

  8. A source of ultrasensitivity in the glutamine response of the bicyclic cascade system controlling glutamine synthetase adenylylation state and activity in Escherichia coli.

    Science.gov (United States)

    Jiang, Peng; Ninfa, Alexander J

    2011-12-20

    Glutamine synthetase (GS) activity in Escherichia coli is regulated by reversible adenylylation, brought about by a bicyclic system comprised of uridylyltransferase/uridylyl-removing enzyme (UTase/UR), its substrate, PII, adenylyltransferase (ATase), and its substrate, GS. The modified and unmodified forms of PII produced by the upstream UTase/UR-PII cycle regulate the downstream ATase-GS cycle. A reconstituted UTase/UR-PII-ATase-GS bicyclic system has been shown to produce a highly ultrasensitive response of GS adenylylation state to the glutamine concentration, but its composite UTase/UR-PII and ATase-GS cycles displayed moderate glutamine sensitivities when examined separately. Glutamine sensitivity of the bicyclic system was significantly reduced when the trimeric PII protein was replaced by a heterotrimeric form of PII that was functionally monomeric, and coupling between the two cycles was different in systems containing wild-type or heterotrimeric PII. Thus, the trimeric nature of PII played a role in the glutamine response of the bicyclic system. We therefore examined regulation of the individual AT (adenylylation) and AR (deadenylylation) activities of ATase by PII preparations with various levels of uridylylation. AR activity was affected in a linear fashion by PII uridylylation, but partially modified wild-type PII activated the AT much less than expected based on the extent of PII modification. Partially modified wild-type PII also bound to ATase less than expected based upon the fraction of modified subunits. Our results suggest that the AT activity is only bound and activated by completely unmodified PII and that this design is largely responsible for ultrasensitivity of the bicyclic system.

  9. 原位氮饥饿发酵工艺中梯度补氮对谷氨酰胺合成酶的调控%REGULATION OF GLUTAMINE SYNTHETASE IN GLUTAMINE PRODUCTION BY FERMENTATION OF Corynebacterium glutamicum WITH in-situ NITROGEN STARVATION AND GRADIENT FED NITROGEN

    Institute of Scientific and Technical Information of China (English)

    李春; 刘雨磊; 陈奎发; 杨艳; 曹竹安

    2004-01-01

    The effects of uniform and gradient fed nitrogen on glutamine synthetase (GS), glutamate dehydrogenase(GDH) and glutamate synthase ((K)GAT)were investigated in glutamine production by fermentation of Corynebacterium glutamicum NS611 after 3 h of in-situ nitrogen starvation. It was shown that the strain in the later growth phase entered naturally into in-situ nitrogen starvation by controlling the initial concentration of urea and the biomass was slightly decreased. The pH value reached 6.5 again in the culture system, which confirmed the beginning of nitrogen starvation in the culture system. After 3 h nitrogen starvation the activity of GS was increased over two folds and the time of high activity of GS persisted three folds longer in the gradient fed nitrogen system than that in the normal fed batch. The higher activity of GDH was also maintained. The glutamine production increased by 72 % than the original technology of nitrogen starvation and the time of fermentation was shortened by above 12 h.

  10. The immediate effects of intravenous specific nutrients on EEG sleep.

    Science.gov (United States)

    Lacey, J H; Stanley, P; Hartmann, M; Koval, J; Crisp, A H

    1978-03-01

    This study examined the immediate influence of intravenous amino acids and glucose on sleep as measured by all-night EEG recording. The study on 9 normal female subjects was of a latin-square design. Slow wave sleep (SWS) was increased by both solutions whilst dream sleep (REM) was decreased by amino acids and increased by glucose. Total sleep time was not affected. Subjective feelings as to restlessness, quality and depth of sleep under the impact of the various solutions were gathered. The work further elucidates the effect of nutrition on sleep and supports certain theories as to the function of the main sleep component.

  11. Glutamine deprivation sensitizes human breast cancer MDA-MB-231 cells to TRIAL-mediated apoptosis.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Jeong, Jin-Woo; Prasad Tharanga Jayasooriya, Rajapaksha Gedara; Neelaka Molagoda, Ilandarage Menu; Lee, Seungheon; Park, Sang Rul; Choi, Yung Hyun; Kim, Gi-Young

    2017-02-13

    Tumor cell metabolism is a promising target for various cancer treatments. Apart from aerobic glycolysis, cancer cell growth is dependent on glutamine (Gln) supply, leading to their survival and differentiation. Therefore, we examined whether treatment with TNF-related apoptosis-inducing ligand (TRAIL) sensitizes MDA-MB-231 cells to apoptosis under Gln deprivation condition (TRAIL/Gln deprivation). Gln deprivation decreased cell proliferation as expected, but did not induce remarkable cell death. TRAIL/Gln deprivation, however, significantly increased growth inhibition and morphological shrinkage of MDA-MB-231 cells compared to those induced by treatment with either Gln deprivation or TRAIL alone. Moreover, TRAIL/Gln deprivation upregulated the apoptotic sub-G1 phase accompanied with a remarkable decrease of pro-caspase-3, pro-caspase-9, and anti-apoptotic xIAP, and Bcl-2. Increased cleavage of PARP and pro-apoptotic Bid protein expression suggests that TRAIL/Gln deprivation triggers mitochondrion-mediated apoptosis in MDA-MB-231 cells. Additionally, TRAIL/Gln deprivation upregulated the expression of endoplasmic reticulum (ER) stress markers such as ATF4 and phosphorylated eIF2α, thereby enhancing the C/EBP homologous protein (CHOP) protein level. Transient knockdown of CHOP partically reversed TRAIL/Gln deprivation-mediated apoptosis. Accordingly, TRAIL/Gln deprivation enhanced the expression of death receptor 5 (DR5) and transient knockdown of DR5 completely restored TRAIL/Gln deprivation-mediated apoptosis. Taken together, our results suggest that Gln deprivation conditions can be used for the development of new therapies for TRAIL-resistant cancers.

  12. Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival.

    Directory of Open Access Journals (Sweden)

    Erica L Sanchez

    2015-07-01

    Full Text Available Kaposi's Sarcoma-associated Herpesvirus (KSHV is the etiologic agent of Kaposi's Sarcoma (KS. KSHV establishes a predominantly latent infection in the main KS tumor cell type, the spindle cell, which is of endothelial cell origin. KSHV requires the induction of multiple metabolic pathways, including glycolysis and fatty acid synthesis, for the survival of latently infected endothelial cells. Here we demonstrate that latent KSHV infection leads to increased levels of intracellular glutamine and enhanced glutamine uptake. Depletion of glutamine from the culture media leads to a significant increase in apoptotic cell death in latently infected endothelial cells, but not in their mock-infected counterparts. In cancer cells, glutamine is often required for glutaminolysis to provide intermediates for the tri-carboxylic acid (TCA cycle and support for the production of biosynthetic and bioenergetic precursors. In the absence of glutamine, the TCA cycle intermediates alpha-ketoglutarate (αKG and pyruvate prevent the death of latently infected cells. Targeted drug inhibition of glutaminolysis also induces increased cell death in latently infected cells. KSHV infection of endothelial cells induces protein expression of the glutamine transporter, SLC1A5. Chemical inhibition of SLC1A5, or knockdown by siRNA, leads to similar cell death rates as glutamine deprivation and, similarly, can be rescued by αKG. KSHV also induces expression of the heterodimeric transcription factors c-Myc-Max and related heterodimer MondoA-Mlx. Knockdown of MondoA inhibits expression of both Mlx and SLC1A5 and induces a significant increase in cell death of only cells latently infected with KSHV, again, fully rescued by the supplementation of αKG. Therefore, during latent infection of endothelial cells, KSHV activates and requires the Myc/MondoA-network to upregulate the glutamine transporter, SLC1A5, leading to increased glutamine uptake for glutaminolysis. These findings

  13. Algorithms for intravenous insulin delivery.

    Science.gov (United States)

    Braithwaite, Susan S; Clement, Stephen

    2008-08-01

    This review aims to classify algorithms for intravenous insulin infusion according to design. Essential input data include the current blood glucose (BG(current)), the previous blood glucose (BG(previous)), the test time of BG(current) (test time(current)), the test time of BG(previous) (test time(previous)), and the previous insulin infusion rate (IR(previous)). Output data consist of the next insulin infusion rate (IR(next)) and next test time. The classification differentiates between "IR" and "MR" algorithm types, both defined as a rule for assigning an insulin infusion rate (IR), having a glycemic target. Both types are capable of assigning the IR for the next iteration of the algorithm (IR(next)) as an increasing function of BG(current), IR(previous), and rate-of-change of BG with respect to time, each treated as an independent variable. Algorithms of the IR type directly seek to define IR(next) as an incremental adjustment to IR(previous). At test time(current), under an IR algorithm the differences in values of IR(next) that might be assigned depending upon the value of BG(current) are not necessarily continuously dependent upon, proportionate to, or commensurate with either the IR(previous) or the rate-of-change of BG. Algorithms of the MR type create a family of IR functions of BG differing according to maintenance rate (MR), each being an iso-MR curve. The change of IR(next) with respect to BG(current) is a strictly increasing function of MR. At test time(current), algorithms of the MR type use IR(previous) and the rate-of-change of BG to define the MR, multiplier, or column assignment, which will be used for patient assignment to the right iso-MR curve and as precedent for IR(next). Bolus insulin therapy is especially effective when used in proportion to carbohydrate load to cover anticipated incremental transitory enteral or parenteral carbohydrate exposure. Specific distinguishing algorithm design features and choice of parameters may be important to

  14. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis.

    Science.gov (United States)

    Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro

    2016-05-18

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

  15. Functional interactions between a glutamine synthetase promoter and MYB proteins.

    Science.gov (United States)

    Gómez-Maldonado, Josefa; Avila, Concepción; Torre, Fernando; Cañas, Rafael; Cánovas, Francisco M; Campbell, Malcolm M

    2004-08-01

    In Scots pine (Pinus sylvestris), ammonium assimilation is catalysed by glutamine synthetase (GS) [EC 6.3.1.2], which is encoded by two genes, PsGS1a and PsGS1b. PsGS1b is expressed in the vascular tissue throughout the plant body, where it is believed to play a role in recycling ammonium released by various facets of metabolism. The mechanisms that may underpin the transcriptional regulation of PsGS1b were explored. The PsGS1b promoter contains a region that is enriched in previously characterized cis-acting elements, known as AC elements. Pine nuclear proteins bound these AC element-rich regions in a tissue-specific manner. As previous experiments had shown that R2R3-MYB transcription factors could interact with AC elements, the capacity of the AC elements in the PsGS1b promoter to interact with MYB proteins was examined. Two MYB proteins from loblolly pine (Pinus taeda), PtMYB1 and PtMYB4, bound to the PsGS1b promoter were able to activate transcription from this promoter in yeast, arabidopsis and pine cells. Immunolocalization experiments revealed that the two MYB proteins were most abundant in cells previously shown to accumulate PsGS1b transcripts. Immunoprecipitation analysis and supershift electrophoretic mobility shift assays implicated these same two proteins in the formation of complexes between pine nuclear extracts and the PsGS1b promoter. Given that these MYB proteins were previously shown to have the capacity to activate gene expression related to lignin biosynthesis, we hypothesize that they may function to co-regulate lignification, a process that places significant demands on nitrogen recycling, and GS, the major enzyme involved in the nitrogen recycling pathway.

  16. Glutamine Supplemented Parenteral Nutrition to Prevent Ventilator-Associated Pneumonia in the Intensive Care Unit

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    Meltem Türkay Aydoğmuş

    2012-12-01

    Full Text Available Objective: Ventilator-associated pneumonia (VAP is a form of nosocomial pneumonia that increases patient morbidity and mortality, length of hospital stay, and healthcare costs. Glutamine preserves the intestinal mucosal structure, increases immune function, and reduces harmful changes in gut permeability in patients receiving total parenteral nutrition (TPN. We hypothesized that TPN supplemented by glutamine might prevent the development of VAP in patients on mechanical ventilator support in the intensive care unit (ICU. Material and Methods: With the approval of the ethics committee and informed consent from relatives, 60 patients who were followed in the ICU with mechanical ventilator support were included in our study. Patients were divided into three groups. The first group received enteral nutrition (n=20, and the second was prescribed TPN (n=20 while the third group was given glutamine-supplemented TPN (n=20. C-reactive protein (CRP, sedimentation rate, body temperature, development of purulent secretions, increase in the amount of secretions, changes in the characteristics of secretions and an increase in requirement of deep tracheal aspiration were monitored for seven days by daily examination and radiographs. Results: No statistically significant difference was found among groups in terms of development of VAP (p=0.622. Conclusion: Although VAP developed at a lower rate in the glutamine-supplemented TPN group, no statistically significant difference was found among any of the groups. Glutamine-supplemented TPN may have no superiority over unsupplemented enteral and TPN in preventing VAP.

  17. LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer

    Science.gov (United States)

    Xu, Pan; Oosterveer, Maaike H.; Stein, Sokrates; Demagny, Hadrien; Ryu, Dongryeol; Moullan, Norman; Wang, Xu; Can, Emine; Zamboni, Nicola; Comment, Arnaud; Auwerx, Johan; Schoonjans, Kristina

    2016-01-01

    Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncanonical glutamine pathway that is reliant on the mitochondrial and cytosolic transaminases glutamate pyruvate transaminase 2 (GPT2) and glutamate oxaloacetate transaminase 1 (GOT1), which fuel anabolic metabolism. In particular, we show that gain and loss of function of hepatic LRH-1 modulate the expression and activity of mitochondrial glutaminase 2 (GLS2), the first and rate-limiting step of this pathway. Acute and chronic deletion of hepatic LRH-1 blunts the deamination of glutamine and reduces glutamine-dependent anaplerosis. The robust reduction in glutaminolysis and the limiting availability of α-ketoglutarate in turn inhibit mTORC1 signaling to eventually block cell growth and proliferation. Collectively, these studies highlight the importance of LRH-1 in coordinating glutamine-induced metabolism and signaling to promote hepatocellular carcinogenesis. PMID:27298334

  18. Response to Dietary Supplementation of Glutamine in Broiler Chickens Subjected to Transportation Stress

    Directory of Open Access Journals (Sweden)

    Majid SHAKERI

    2016-07-01

    Full Text Available The main purpose of this study was to determine effects of glutamine supplementation on performance and blood parameters including Hsp70 and acute phase protein when chicken were subjected to transportation stress. A total of four hundred day-old-male cobb-500 chicks were obtained directly from a local hatchery. The chicks were allotted to two groups as: immediate placement (1 hour after hatching with access to feed and water and placement after 24h transportation without access to feed and water. The experiment consisted of a factorial arrangement of 2 different diets and 2 different time of placement. Chicks from each placement group were fed either basal diet or basal diet + 1% glutamine from 1 to 21 days of age. The results indicated that dietary glutamine improved the body weight gain and feed conversion ratio significantly when chicks were subjected to delayed or immediate placement. In conclusion, supplementing chicken with glutamine in diet can reduce negative effects of delayed access to feed and water during transportation. Moreover, APP concentration and HSP70 level were positively affected when chicks supplemented with glutamine in the diet.

  19. Effect of a short-term infusion of glutamine on muscle protein metabolism postoperatively.

    Science.gov (United States)

    Januszkiewicz, A; Essén, P; McNurlan, M A; Calder, G A; Andersson, K; Wernerman, J; Garlick, P J

    1996-10-01

    The acute effect of a short-term postoperative infusion of glucose supplemented with glutamine (0.285 g/kg body weight), on muscle protein metabolism, was studied by analyses of free amino acid concentrations and determinations of protein synthesis. A glutamine-glucose infusion was given for 5.5 h to 6 patients 2-3 days after elective surgery for colon cancer. The free glutamine concentration was 5.72 +/- 0.96 mmol/kg wet weight (ww) before and 6.14 +/- 1.10 mmol/kg ww 4 h after the glutamine infusion. The rate of protein synthesis was 1.26 +/- 0.15%/24 h before the infusion and 1.12 +/- 0.16%/24 h during its latter part. The percentage of polyribosomes was 42.2 +/- 3.4% before and 40.9 +/- 1.3% after the infusion. The results showed no difference in these biochemical parameters, indicating that a short-term infusion of glutamine given postoperatively is insufficient to affect protein metabolism in human skeletal muscle.

  20. Glutamine synthetase 2 is not essential for biosynthesis of compatible solutes in Halobacillus halophilus.

    Science.gov (United States)

    Shiyan, Anna; Thompson, Melanie; Köcher, Saskia; Tausendschön, Michaela; Santos, Helena; Hänelt, Inga; Müller, Volker

    2014-01-01

    Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride. To address the role of GlnA2 in the biosynthesis of the osmolytes glutamate and glutamine, a deletion mutant (ΔglnA2) was generated and characterized in detail. We compared the pool of compatible solutes and performed transcriptional analyses of the principal genes controlling the solute production in the wild type strain and the deletion mutant. These measurements did not confirm the hypothesized role of GlnA2 in the osmolyte production. Most likely the presence of another, yet to be identified enzyme has the main contribution in the measured activity in crude extracts and probably determines the total chloride-modulated profile. The role of GlnA2 remains to be elucidated.

  1. Glutamine Synthetase Sensitivity to Oxidative Modification during Nutrient Starvation in Prochlorococcus marinus PCC 9511.

    Science.gov (United States)

    Gómez-Baena, Guadalupe; Domínguez-Martín, María Agustina; Donaldson, Robert P; García-Fernández, José Manuel; Diez, Jesús

    2015-01-01

    Glutamine synthetase plays a key role in nitrogen metabolism, thus the fine regulation of this enzyme in Prochlorococcus, which is especially important in the oligotrophic oceans where this marine cyanobacterium thrives. In this work, we studied the metal-catalyzed oxidation of glutamine synthetase in cultures of Prochlorococcus marinus strain PCC 9511 subjected to nutrient limitation. Nitrogen deprivation caused glutamine synthetase to be more sensitive to metal-catalyzed oxidation (a 36% increase compared to control, non starved samples). Nutrient starvation induced also a clear increase (three-fold in the case of nitrogen) in the concentration of carbonyl derivatives in cell extracts, which was also higher (22%) upon addition of the inhibitor of electron transport, DCMU, to cultures. Our results indicate that nutrient limitations, representative of the natural conditions in the Prochlorococcus habitat, affect the response of glutamine synthetase to oxidative inactivating systems. Implications of these results on the regulation of glutamine synthetase by oxidative alteration prior to degradation of the enzyme in Prochlorococcus are discussed.

  2. Pilot study with a glutamine-supplemented enteral formula in critically ill infants.

    Science.gov (United States)

    Barbosa, E; Moreira, E A; Goes, J E; Faintuch, J

    1999-01-01

    Seriously ill infants often display protein-calorie malnutrition due to the metabolic demands of sepsis and respiratory failure. Glutamine has been classified as a conditionally essential amino acid, with special usefulness in critical patients. Immunomodulation, gut protection, and prevention of protein depletion are mentioned among its positive effects in such circumstances. With the intent of evaluating the tolerance and clinical impact of a glutamine supplement in seriously ill infants, a prospective randomized study was done with nine patients. Anthropometric and biochemical determinations were made, and length of stay in the intensive care unit (ICU), in the hospital, and under artificial ventilation, and septic morbidity and mortality were tabulated. Infants in the treatment group (n = 5) were enterally administered 0.3 g/kg of glutamine, whereas controls received 0.3 g/kg of casein during a standard period of five days. Septic complications occurred in 75% of the controls (3/4) versus 20% of the glutamine-treated group (1/5, p glutamine supplementation was safe and tended to be associated with less infectious morbidity and mortality in this high-risk population.

  3. Ornithine decarboxylase expression in the small intestine of broilers submitted to feed restriction and glutamine supplementation

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    AV Fischer da Silva

    2007-06-01

    Full Text Available Six hundred and forty one-day-old Cobb male broilers were used to evaluate ornithine decarboxylase (ODC expression in the mucosa of the small intestine. Birds were submitted to early feed restriction from 7 to 14 days of age. The provided feed was supplemented with glutamine. A completely randomized design with a 2 x 2 factorial arrangement was used (with or without glutamine, with or without feed restriction. Restricted-fed birds were fed at 30% the amount of the ad libitum fed group from 7 to 14 days of age. Glutamine was added at the level of 1% in the diet supplied from 1 to 28 days of age. Protein concentration in the small intestine mucosa was determined, and ODC expression at 7, 14, 21, and 28 days of age was evaluated by dot blotting. ODC was present in the mucosa of broilers, and the presence of glutamine in the diet increased ODC activation. Glutamine prevented mucosa atrophy by stimulating protein synthesis, and was effective against the effects of feed restriction. Dot blotting can be used to quantify ODC expression in the intestinal mucosa of broilers.

  4. Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term

    Science.gov (United States)

    Le Fur, Yann; Viout, Patrick; Ratiney, Hélène; Confort-Gouny, Sylviane; Cozzone, Patrick J.; Girard, Nadine

    2016-01-01

    Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (Pmacromolecules/H2O ratios (Pmacromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis. PMID:27547969

  5. Plasma glutamine and cystine are decreased and negatively correlated with endomysial antibody in children with celiac disease.

    Science.gov (United States)

    Sevinc, Eylem; Sevinc, Nergiz; Akar, Himmet Haluk; Ozelcoskun, Banu Demet; Sezgin, Gülten Can; Arslan, Duran; Kendirci, Mustafa

    2016-01-01

    背景与目的:谷氨酰胺是一种非必需氨基酸,具有提高肠黏膜再生和吸收的 功能。谷胱甘肽是人体一种具有抗氧化的重要分子,由胱氨酸合成。该研究的 主要目的是检测腹腔疾病(CD)患儿血浆谷氨酰胺和胱氨酸水平,并与对照 组比较。其次是探讨这些氨基酸与肌内膜抗体(EMA)是否相关。方法与研 究设计:选择50 名CD 患儿,另选年龄和性别相匹配的50 名健康儿童作为对 照。采用串联质谱法测定儿童血浆谷氨酰胺和胱氨酸的水平。结果:CD 患儿 血浆谷氨酰胺(808 vs 870 μmol/L)和胱氨酸水平(19 vs 48.5 μmol/L)显著 低于对照组儿童(p0.05)。血清EMA 与血浆胱氨酸水平(r=-0,321, p=0.023)和谷氨酰胺 (r=-0.413, p=0.003)呈显著负相关。结论:该研究表明,CD 患儿血浆谷氨酰 胺和胱氨酸含量明显低于健康对照组。另外,这些氨基酸的含量与EMA 水平 呈显著负相关。.

  6. Use of intravenous immunoglobulin in pediatric practice

    Science.gov (United States)

    Zülfikar, Bülent; Koç, Başak

    2014-01-01

    In recent years, human-driven intravenous immunoglobulins (IVIG) administered intravenously have been widely used in treatment of many diseases. Intravenous immunoglobulin is obtained from human-driven plasma pools as in other plasma-driven products and IVIG preperations contain structurally and functionally intact immunoglobulin. Intravenous immunoglobulin was approved by FDA (Food and Drug Administration) in USA in 1981 for the first time and was started to be primarily used in patients with immune deficiency with hypogammaglobulinemia. The effects of intravenous immunoglobulin include complex mechanisms, but it exerts its essential action by eliminating the non-specific Fc receptors found in the mononuclear phagocytic system or by inhibiting binding of immune complexes to Fc receptors in the cells. Their areas of usage include conditions where their anti-inflammatory and immunomudulator effects are utilized in addition to replacement of deficient immunoglobulin. Although the definite indications are limited, it has been shown that it is useful in many diseases in clinical practice. Its side effects include fever, sweating, nausea, tachycardia, eczematous reactions, aseptic meningitis, renal failure and hematological-thromboembolic events. In this article, use of IVIG, its mechanisms of action, indications and side effects were discussed. PMID:26078679

  7. [Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

    Science.gov (United States)

    Cong, Minghua; Song, Chenxin; Zou, Baohua; Deng, Yingbing; Li, Shuluan; Liu, Xuehui; Liu, Weiwei; Liu, Jinying; Yu, Lei; Xu, Binghe

    2015-03-17

    To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.

  8. Efficacy of bolus intravenous iron treatment in peritoneal dialysis patients

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    Jovanović Nataša

    2005-01-01

    Full Text Available Introduction. Normocytic, normochromic anemia is one of the first signs of chronic renal failure and it is common in patients on chronic dialysis treatment. It causes decrease in oxygen supply to tissues, increases cardiac minute volume, causes left ventricular hyperthrophy, cardiac insufficiency, disorders related to cognitive functions and immune response, and increases morbidity and mortality rates. The leading cause of anemia in patients on chronic peritoneal dialysis (PD is iron depletion and most patients on PD need oral or parenteral iron supplementation. The aim of this study was to evaluate our first experience with bolus intravenous ferrogluconate therapy in patients on chronic peritoneal dialysis at the Nephrology Clinic of the Clinical Center of Serbia (CCS. Material and Methods. We examined 11 patients, 7 males and 4 females, mean-age 49 years (range 31 to 68 years on chronic PD. All patients received blood transfusions, oral or intramuscular iron supplementation before 465 to 665 mg ferrogluconate therapy was given in 500 ml. saline intravenous infusion; 5 of them were on erythropoietin therapy and 2 of them started with EPO therapy after the ferrogluconate therapy. Results. The blood count improved during the first 3 months after application of bolus intravenous iron therapy (ferrogluconate; erythropoietin dose was not increased during the follow-up. Some patients suffered from side effects during infusion and 6 patients received the complete treatment. Discussion. Blood count improves in a number of patients affected by end-stage renal disease during the first months on continuous ambulatory peritoneal dialysis (CAPD treatment. But a large number of patients on chronic CAPD treatment are iron-depleted and they require oral or parenteral substitution. Side effects and complications of intravenous iron therapy were not severe and only one patient suffered from allergic manifestations. Ferremia and blood count improved in patients

  9. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

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    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  10. Mercury excretion and intravenous ascorbic acid.

    Science.gov (United States)

    Dirks, M J; Davis, D R; Cheraskin, E; Jackson, J A

    1994-01-01

    We tested the hypothesis that intravenous ascorbic acid increases urinary excretion of mercury in subjects with low mercury levels from dental amalgam, food, and other sources. From 89 adult volunteers we selected 28 subjects with the highest mercury excretions (2 to 14 micrograms/24 h). We administered intravenous infusions of 500 ml lactated Ringer's solution with and without addition of 750 mg of ascorbic acid/kg body weight, up to 60 g ascorbic acid. Average mercury excretion during the 24 h after infusion of ascorbic acid was 4.0 +/- 0.5 micrograms (mean +/- SEM), which was not significantly more than after infusion of Ringer's solution alone (3.7 +/- 0.5 micrograms). Lead excretion was similarly unaffected. If ascorbic acid administered intravenously benefits some persons with suspected adverse reactions to mercury, the benefit in subjects similar to ours appears unrelated to short-term enhanced excretion of mercury or lead.

  11. Glutamine Assimilation and Feedback Regulation of L-acetyl-N-glutamate Kinase Activity in Chlorella variabilis NC64A Results in Changes in Arginine Pools.

    Science.gov (United States)

    Minaeva, Ekaterina; Forchhammer, Karl; Ermilova, Elena

    2015-11-01

    Glutamine is a metabolite of central importance in nitrogen metabolism of microorganisms and plants. The Chlorella PII signaling protein controls, in a glutamine-dependent manner, the key enzyme of the ornithine/arginine biosynthesis pathway, N-acetyl-L-glutamate kinase (NAGK) that leads to arginine formation. We provide evidence that glutamine promotes effective growth of C. variabilis strain NC64A. The present study shows that externally supplied glutamine directly influences the internal pool of arginine in NC64A. Glutamine synthetase (GS) catalyzes the ATP-dependent conversion of glutamate and ammonium to glutamine. The results of this study demonstrate that glutamine acts as a negative effector of GS activity. These data emphasize the importance of glutamine-dependent coupling of metabolism and signaling as components of an efficient pathway allowing the maintenance of metabolic homeostasis and sustaining growth of Chlorella.

  12. On-line gas analysis in animal cell cultivation: II. Methods for oxygen uptake rate estimation and its application to controlled feeding of glutamine.

    Science.gov (United States)

    Eyer, K; Oeggerli, A; Heinzle, E

    1995-01-05

    Different methods for oxygen uptake rate (OUR) determinations in animal cell cultivation were investigated using a high quality mass spectrometer. Dynamic measurements have considerable disadvantages because of disturbances of the growing cells by the necessary variations of dissolved oxygen concentration. Only infrequent discrete measurements are possible using this method. Stationary liquid phase balance yielded better results with much higher frequency. Gas phase balancing has the advantage of not requiring dissolved oxygen measurement and knowledge of K(L)a, both of them are easily biased. It was found that simple gas phase balancing is either very inaccurate (error larger than expected signal) or very slow, with gas phase residence times of several hours. Therefore, a new method of aeration was designed. Oxygen and CO(2) transfer are mainly achieved via sparging. The gas released to the headspace is diluted with a roughly 100-fold stream of an inert gas (helium). Through this dilution, gas ratios are not changed for O(2), CO(2), Ar, and N(2). The measurement of lower concentrations (parts per million and below) is easy using mass spectrometry with a secondary electron multiplier. With this new method an excellent accuracy and sufficient speed of analysis were obtained. All these on-line methods for OUR measurement were tested during the cultivation of animal cells. The new method allowed better study of the kinetics of animal cell cultures as was shown with a hybridoma cell line (HFN 7.1, ATCC CRL 1606) producing monoclonal antibodies against human fibronectin. With the aid of these methods it was possible to find a correlation between a rapid decrease in oxygen uptake rate (OUR) and glutamine concentration. The sudden decrease in OUR can be attributed to glutamine depletion. This provided a basis for the controlled addition of glutamine to reduce the formation of ammonia produced by hydrolysis. This control method based on OUR measurement resulted in

  13. NITRIC OXIDE (NO, CITRULLINE - NO CYCLE ENZYMES, GLUTAMINE SYNTHETASE AND OXIDATIVE STRESS IN ANOXIA (HYPOBARIC HYPOXIA AND REPERFUSION IN RAT BRAIN

    Directory of Open Access Journals (Sweden)

    M. Swamy, Mohd Jamsani Mat Salleh, K. N .S. Sirajudeen, Wan Roslina Wan Yusof, G. Chandran

    2010-01-01

    Full Text Available Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia and reperfusion (reoxygenation, the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.

  14. Lack of cardioprotection from metabolic support with glutamine or glutamate in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Mortensen, Ulrik;

    2005-01-01

    OBJECTIVE: Previous experimental studies indicate that glutamine or glutamate may provide cardioprotection by improving the oxidative metabolism in myocardial ischemia. We investigated the effect of glutamine or glutamate, given during reperfusion, on resulting infarct size and hemodynamic recovery...... vascular resistance, while glutamate preserved cardiac output during infusion. CONCLUSION: Substrate supplementation with the anaplerotic precursors glutamine and glutamate is ineffective as adjunctive therapy for severe myocardial ischemia. Beneficial effects documented in less complex experimental....... DESIGN: A porcine coronary occlusion model was applied. Infusions were initiated 15 min before reperfusion and supplemented with intracoronary bolus doses at reperfusion. The primary outcome measure was infarct size in relation to area at risk determined by a standard tissue staining procedure. Secondary...

  15. p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates.

    Science.gov (United States)

    Nguyen, Thang Van; Li, Jing; Lu, Chin-Chun Jean; Mamrosh, Jennifer L; Lu, Gang; Cathers, Brian E; Deshaies, Raymond J

    2017-03-20

    Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function. Notably, p97 is also required for the degradation of all four known CRBN neo-substrates [Ikaros family zinc finger proteins 1 (IKZF1) and 3 (IKZF3), casein kinase 1α (CK1α), and the translation termination factor GSPT1] whose ubiquitylation is induced by immunomodulatory drugs. Together, these data point to an unexpectedly intimate relationship between the E3 ubiquitin ligase CRL4(CRBN) and p97 pathways.

  16. In vitro reactivation of in vivo ammonium-inactivated glutamine synthetase from Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Mérida, A; Candau, P; Florencio, F J

    1991-12-16

    Glutamine synthetase from Synechocystis sp. strain PCC 6803 is inactivated by ammonium addition to cells growing with nitrate as the nitrogen source. The enzyme can be reactivated in vitro by different methods such as alkaline phosphatase treatment, but not phosphodiesterase, by raising the pH of the crude extract to values higher than 8, by increasing the ionic strength of the cell-free extract, or by preincubation with organic solvents, such as 2-propanol and ethanol. These results suggest that the loss of glutamine synthetase activity promoted by ammonium involves the non-covalent binding of a phosphorylated compound to the enzyme and support previous results that rule out the existence of an adenylylation/deadenylylation system functioning in the regulation of cyanobacterial glutamine synthetase.

  17. Regulation of active site coupling in glutamine-dependent NAD[superscript +] synthetase

    Energy Technology Data Exchange (ETDEWEB)

    LaRonde-LeBlanc, Nicole; Resto, Melissa; Gerratana, Barbara; (Maryland)

    2009-05-21

    NAD{sup +} is an essential metabolite both as a cofactor in energy metabolism and redox homeostasis and as a regulator of cellular processes. In contrast to humans, Mycobacterium tuberculosis NAD{sup +} biosynthesis is absolutely dependent on the activity of a multifunctional glutamine-dependent NAD{sup +} synthetase, which catalyzes the ATP-dependent formation of NAD{sup +} at the synthetase domain using ammonia derived from L-glutamine in the glutaminase domain. Here we report the kinetics and structural characterization of M. tuberculosis NAD{sup +} synthetase. The kinetics data strongly suggest tightly coupled regulation of the catalytic activities. The structure, the first of a glutamine-dependent NAD{sup +} synthetase, reveals a homooctameric subunit organization suggesting a tight dependence of catalysis on the quaternary structure, a 40-{angstrom} intersubunit ammonia tunnel and structural elements that may be involved in the transfer of information between catalytic sites.

  18. Oxidative stress and redistribution of glutamine synthetase in California sea lions (Zalophus californianus) with domoic acid toxicosis.

    Science.gov (United States)

    Madl, J E; Duncan, C G; Stanhill, J E; Tai, P-Y; Spraker, T R; Gulland, F M

    2014-01-01

    The aim of this study was to test the hypothesis that oxidative stress and glutamine synthetase (GS) redistribution occur in domoic acid (DA) toxicosis in California sea lions (CSLs, Zalophus californianus). Sections of archived hippocampi from seven control and 13 CSLs diagnosed with DA toxicosis were labelled immunohistochemically for GS and for two markers of oxidative stress, malondialdehyde (MDA) and 3-nitrotyrosine (NT). The distribution and intensity of labelling were compared with the pathological changes seen in haematoxylin and eosin-stained sections. Increased expression of MDA and NT occurred in neurons of the hippocampal formation of CSLs with lesions consistent with DA toxicosis. The degree of oxidative stress was not affected significantly by the chronicity or severity of hippocampal damage. In six out of seven CSLs with chronic effects of DA toxicosis, in addition to the normal glial distribution of GS, GS expression was very strong in some neurons of the subiculum. However, neuronal GS labelling was also seen in one control CSL, an effect that may have been due to previous exposure to DA. GS expression in neurons was associated with decreases in GS labelling in neighbouring glial cell processes. DA toxicosis therefore induces increased expression of markers of oxidative stress in neurons consistent with oxidative stress contributing to the initial DA insult and also the epilepsy that often develops in chronic DA toxicosis. GS redistribution occurred primarily in chronic DA toxicosis, perhaps leading to alterations of the glutamine-glutamate-GABA (gamma-aminobutyric acid) cycle and contributing to the excitotoxicity and seizures often seen in DA toxicosis.

  19. Gastric residual volume by magnetic ressonance after intake of maltodextrin and glutamine: a randomized double-blind, crossover study.

    Science.gov (United States)

    Brianez, Luigi R; Caporossi, Cervantes; de Moura, Yure W; Dias, Lorena A; Leal, Regis V; de Aguilar-Nascimento, José E

    2014-01-01

    The addition of glutamine in preoperative drinks may enhance the benefits of carbohydrate alone. To evaluate the gastric residual volume after the intake of a beverage containing carbohydrate plus glutamine. Eleven healthy volunteers (24-30 years-old) were randomized in a crossover fashion to intake 400 mL (4h before) and 200 mL (2h before) of a beverage containing either 12.5% maltodextrin (carbohydrate group) or 12.5% maltodextrin plus 15 g of glutamine (glutamine group) in two different moments 7 days apart. Magnetic ressonance was performed to measure the gastric residual volume (mL) 120 and 180 minutes after the last ingestion. Gastric residual volume similar to basal condition was found after 2h and 3h of the intake of beverages. There was no difference in the mean ±SD GRV (mL) found at 120 minutes (carbohydrate group: 22.9±16.6 and glutamine group: 19.7±10.7) and at 180 minutes (carbohydrate group: 21.5±24.1 and glutamine group: 15.1±10.1) between the two drinks. Gastric emptying is efficient, and occurs in up to two hours after the intake of a beverage containing either carbohydrate alone or carbohydrate associated with glutamine. The addition of glutamine to carbohydrate-enriched drink seems to be safe for the use up to 2h before an operation.

  20. The 2007 ESPEN Sir David Cuthbertson Lecture: amino acids between and within organs. The glutamate-glutamine-citrulline-arginine pathway.

    Science.gov (United States)

    Deutz, Nicolaas E P

    2008-06-01

    In daily practice, the plasma concentration of amino acids is usually viewed as a parameter of production. However, both a high production and/or a reduced disposal capacity can result in an increased plasma concentration. In this presentation, I will discuss my research on interorgan relationships of the amino acids glutamate, glutamine, citrulline and arginine to explain the regulation of the plasma arginine level. The reduced glutamine disposal during liver failure is related to enhanced plasma glutamine level without any change in muscle and gut production or consumption rate. In contrast during sepsis, a small reduction in plasma glutamine is related to a substantially enhanced organ glutamate and glutamine production or consumption rate. These observations are a good example that plasma levels are directly related to production or consumption rates. Because glutamine breakdown in the gut produces citrulline, there is a good relation between the amount of metabolically active gut tissue and gut and whole body citrulline production. Arginine is produces from citrulline in the kidney and a reduced gut glutamine to citrulline conversion during sepsis explains the reduced de novo arginine production that is related to the reduced plasma arginine level. The interorgan route between muscle, gut, liver and kidney of the amino acids glutamate, glutamine, citrulline and arginine is a very good example of how complicated the regulation of plasma amino acid levels can be. However, in-depth research is necessary and will give us important clues to new nutritional strategies.

  1. Iatrogenic intravascular pneumocephalus secondary to intravenous catheterization

    Energy Technology Data Exchange (ETDEWEB)

    Yildiz, Altan; Oezer, Caner; Egilmez, Hulusi; Duce, Meltem Nass; Apaydin, Demir F.; Yalcinoglu, Orhan [Department of Radiology, Faculty of Medicine, Mersin University (Turkey)

    2002-03-01

    The presence of pneumocephalus without a history of intracranial or intrathecal procedures is a significant radiographic finding. Although pneumocephalus means a violation of the dural barrier or the presence of infection, intravascular pneumocephalus is different from intraparenchymal pneumocephalus and its benign nature must be known in the presence of intravenous catheterization. Herein, we present a case of iatrogenic intravascular pneumocephalus with CT findings. To our knowledge, there are only a few reported cases of iatrogenic intravascular pneumocephalus in the literature. Careful intravenous catheterization and diagnosis of the condition on imaging helps to prevent unnecessary treatment procedures. (orig.)

  2. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats.

    Science.gov (United States)

    Abraham, Premila; Isaac, Bina

    2011-07-01

    Nephrotoxicity is one of the adverse side effects of cyclophosphamide (CP) chemotherapy. In a recent study, we have demonstrated that oxidative stress and glutathione depletion play important roles in CP-induced renal damage. The aim of the study was to verify whether glutamine, the precursor for glutathione synthesis, prevents CP-induced oxidative stress and renal damage using a rat model. Adult male rats were administered a single dose of 150 mg/ kg body weight of CP intraperitoneally. The glutamine-pretreated rats were administered 1 gm/kg body weight of glutamine orally 2 h before the administration of CP. Vehicle/glutamine-treated rats served as controls. All the rats were killed 16 h after the dose of CP/vehicle. The kidneys were removed and used for light microscopic and biochemical studies. The markers of oxidative stress including malondialdehyde content, protein carbonyl content, protein thiol, reduced glutathione and myeloperoxidase activity, a marker of neutrophil infiltration, were measured in kidney homogenates. CP treatment-induced damage to kidney involved the glomeruli and the tubules. Pretreatment with glutamine reduced CP-induced glutathione depletion and increased myeloperoxidase activity. However, it did not prevent CP-induced lipid peroxidation, protein carbonylation and renal damage. The results of the present study suggest that glutamine pretreatment does not prevent CP-induced lipid peroxidation and renal damage, although it prevents CP-induced glutathione depletion and neutrophil infiltration significantly. It is suggested that mechanisms other than oxidative stress may also be involved and/or oxidative stress may be consequence and not the cause of CP induced renal damage.

  3. Alteration of plasma glutamate and glutamine levels in children with high-functioning autism.

    Directory of Open Access Journals (Sweden)

    Chie Shimmura

    Full Text Available BACKGROUND: It has recently been hypothesized that hyperglutamatergia in the brain is involved in the pathophysiology of autism. However, there is no conclusive evidence of the validity of this hypothesis. As peripheral glutamate/glutamine levels have been reported to be correlated with those of the central nervous system, the authors examined whether the levels of 25 amino acids, including glutamate and glutamine, in the platelet-poor plasma of drug-naïve, male children with high-functioning autism (HFA would be altered compared with those of normal controls. METHODOLOGY/PRINCIPAL FINDINGS: Plasma levels of 25 amino acids in male children (N = 23 with HFA and normally developed healthy male controls (N = 22 were determined using high-performance liquid chromatography. Multiple testing was allowed for in the analyses. Compared with the normal control group, the HFA group had higher levels of plasma glutamate and lower levels of plasma glutamine. No significant group difference was found in the remaining 23 amino acids. The effect size (Cohen's d for glutamate and glutamine was large: 1.13 and 1.36, respectively. Using discriminant analysis with logistic regression, the two values of plasma glutamate and glutamine were shown to well-differentiate the HFA group from the control group; the rate of correct classification was 91%. CONCLUSIONS/SIGNIFICANCE: The present study suggests that plasma glutamate and glutamine levels can serve as a diagnostic tool for the early detection of autism, especially normal IQ autism. These findings indicate that glutamatergic abnormalities in the brain may be associated with the pathobiology of autism.

  4. Molecular cloning and characterization of glutamine synthetase, a tegumental protein from Schistosoma japonicum.

    Science.gov (United States)

    Qiu, Chunhui; Hong, Yang; Cao, Yan; Wang, Fei; Fu, Zhiqiang; Shi, Yaojun; Wei, Meimei; Liu, Shengfa; Lin, Jiaojiao

    2012-12-01

    Glutamine synthetase catalyzes the synthesis of glutamine, providing nitrogen for the production of purines, pyrimidines, amino acids, and other compounds required in many pivotal cellular events. Herein, a full-length cDNA encoding Schistosoma japonicum glutamine synthetase (SjGS) was isolated from 21-day schistosomes. The entire open reading frame of SjGS contains a 1,095-bp coding region corresponding to 364 amino acids with a calculated molecular weight of 40.7 kDa. NCBIP blast shows that the putative amino acid of SjGS contains a classic β-grasp domain and a catalytic domain of glutamine synthetase. The relative mRNA expression of SjGS was evaluated in 7-, 13-, 21-, 28-, 35-, and 42-day worms of S. japonicum in the final host and higher expression at day 21, and 42 worms were observed. This protein was also detected in worm extracts using Western blot. Immunofluorescence studies indicated that the SjGS protein was mainly distributed on tegument and parenchyma in 28-day adult worms. The recombinant glutamine synthetase with a molecular weight of 45 kDa was expressed in Escherichia coli and purified in its active form. The enzyme activity of the recombinant protein was 3.30 ± 0.67 U.μg-1. The enzyme activity was highly stable over a wide range of pH (6-9) and temperature (25-40 °C) under physiological conditions. The transcription of SjGS was upregulated in praziquantel-treated worms at 2-, 4-, and 24-h posttreatment compared with the untreated control. As a first step towards the clarification of the role of glutamine synthetase in schistosome species, we have cloned and characterized cDNAs encoding SjGS in S. japonicum, and the data presented suggest that SjGS is an important molecule in the development of the schistosome.

  5. Effect of dietary glutamine supplementation on Salmonella colonization in the ceca of young broiler chicks.

    Science.gov (United States)

    Fasina, Y O; Bowers, J B; Hess, J B; McKee, S R

    2010-05-01

    Live poultry is an important vehicle for transmitting Salmonella Typhimurium to humans that have salmonellosis. It is therefore imperative to reduce Salmonella Typhimurium levels in the gastrointestinal tract of live chickens. Glutamine is an established immunonutrient that is capable of alleviating disease conditions in humans and rats. Thus, 2 experiments that used Ross broiler chicks were conducted to evaluate the effect of glutamine supplementation at 1% level of the diet on cecal Salmonella Typhimurium levels in young broiler chicks. Experiment 1 consisted of i) treatment 1 (control, CN), in which chicks were given an unmedicated corn-soybean meal basal starter diet without glutamine supplementation or Salmonella Typhimurium challenge; ii) treatment 2 (CST), in which chicks were given the same diet as CN but challenged with 3.6 x 10(6) cfu Salmonella Typhimurium/mL at 3 d of age; and iii) treatment 3 (GST), in which chicks were given the unmedicated corn-soybean meal basal starter diet supplemented with glutamine at 1% level, and challenged with 3.6 x 10(6) cfu at 3 d of age. Experiment 2 used similar treatments (CN, CST, and GST), except that chicks in CST and GST were challenged with 7.4 x 10(7) cfu Salmonella Typhimurium/mL, and a fourth treatment was added. The fourth treatment consisted of chicks that were not challenged with Salmonella Typhimurium but given the same diet as in GST. Duration of each experiment was 14 d. Growth performance of chicks was monitored weekly, and cecal Salmonella Typhimurium concentration was microbiologically enumerated on d 4, 10, or 11 postchallenge. Results showed that glutamine supplementation improved BW and BW gain in experiment 2 (P 0.05). The optimum supplemental level of glutamine that will enhance intestinal resistance to Salmonella Typhimurium colonization should be determined.

  6. Effects of glutamine and curcumin on bacterial translocation in jaundiced rats

    Institute of Scientific and Technical Information of China (English)

    Oguzhan; Karatepe; Ersin; Acet; Muharrem; Battal; Gokhan; Adas; Ahu; Kemik; Merih; Altiok; Gulcin; Kamali; Safiye; Koculu; Atahan; Catay; Sedat; Kamali; Servet; Karahan

    2010-01-01

    AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used. METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, GroupⅠ received oral normal saline, Group Ⅱ received oral glutamine and Group Ⅲ received oral curcumin for seven day...

  7. Reduced activity of glutamine synthetase in Rhodospirillum rubrum mutants lacking the adenylyltransferase GlnE.

    Science.gov (United States)

    Jonsson, Anders; Nordlund, Stefan; Teixeira, Pedro Filipe

    2009-10-01

    In the nitrogen-fixing bacterium Rhodospirillum rubrum, the GlnE adenylyltransferase (encoded by glnE) catalyzes reversible adenylylation of glutamine synthetase, thereby regulating nitrogen assimilation. We have generated glnE mutant strains that are unable to adenylylate glutamine synthetase (GS). Surprisingly, the activity of GS was lower in the mutants than in the wild type, even when grown in nitrogen-fixing conditions. Our results support the proposal that R. rubrum can only cope with the absence of an adenylylation system in the presence of lowered GS expression or activity. In general terms, this report also provides further support for the central role of GS in bacterial metabolism.

  8. Glutamine and nucleotide supplementation in broiler diets in alternative breeding system

    OpenAIRE

    Zavarize, K C [UNESP; Sartori,José Roberto; Pelícia, V C [UNESP; Pezzato, Antonio Celso [UNESP; Araujo, P C; Stradiotti, A C [UNESP; Madeira, L A [UNESP

    2011-01-01

    The experiment was conducted to evaluate the effect of supplementing glutamine and nucleotides on growth performance and development intestinal morphology in broiler chicks. In the trial, 600 male broiler chicks distributed in randomized blocks in a 3x2 factorial arrangement (consisting of a uniform basal diet supplemented with: 0.0, 0.5 or 1.0% glutamine, and 0.0 or 0.04% nucleotides), for a total of 6 treatments with 25 birds each. Means of performance (weight, weight gain, feed intake, fee...

  9. A commentary on the 2015 Canadian Clinical Practice Guidelines in glutamine supplementation to parenteral nutrition.

    Science.gov (United States)

    Leguina-Ruzzi, Alberto

    2016-01-08

    Glutamine is one of the conditionally essential free amino acids with multiple biological functions. Its supplementation to parenteral nutrition has been widely used for the management of complications in intensive care. However, controversial clinical reports have generated reluctance in the use of this pharmaco-nutrient. In this commentary, we address the impact of four studies that influenced the recommendations on glutamine supplementation by the Canadian Clinical Practice Guide 2015. Because of the importance of this guideline in clinical practice, we strongly believe that a more rigorous and critical evaluation is required to support recommendations in future guidelines.

  10. Metabolic indicators of drought stress tolerance in wheat: glutamine synthetase isoenzymes and Rubisco.

    Science.gov (United States)

    Nagy, Zoltán; Németh, Edit; Guóth, Adrienn; Bona, Lajos; Wodala, Barnabás; Pécsváradi, Attila

    2013-06-01

    Drought stress has a considerable impact on the ecosystem and agriculture. Continuous water deficit induces early leaf senescence in plants. During this process, chloroplasts are degraded and photosynthesis drastically drops. The objective of this investigation was to look into the regulation of nitrogen and carbon metabolism during water deficit. Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase; EC 4.1.1.39) and the total protein contents inform us of the sink-source relation in plants. Glutamine synthetase (GS, EC 6.3.1.2) isoenzymes are good markers of plastid status (GS2) and the nitrogen metabolism (GS1). Tolerant and sensitive wheat (Triticum aestivum L.) genotypes were tested, which are widely used in agriculture. The amount of protein, Rubisco and GS isoforms in leaves were measured during the grain filling period, as indicative traits that ultimately determine the onset and stage of senescence. The symptoms of senescence first appeared on the oldest and finally on the youngest leaves. Drought stress disrupted the sequentiality of senescence in the sensitive varieties. An untimely senescence appeared in flag leaves, earlier than in the older leaves. Total protein and Rubisco contents decreased and the GS2 isoenzyme declined considerably in the youngest leaves. In the tolerant varieties, however, these physiological parameters did not change under drought, only the sequential senescence of leaf levels accelerated in some cases compared to the control, well-watered plants. Our results revealed that GS is a good indicator of drought stress, which can be applied for the characterization of wheat cultivars in terms of drought stress tolerance.

  11. Fibronectin-integrin signaling is required for L-glutamine's protection against gut injury.

    Directory of Open Access Journals (Sweden)

    Stefanie Niederlechner

    Full Text Available BACKGROUND: Extracellular matrix (ECM stabilization and fibronectin (FN-Integrin signaling can mediate cellular protection. L-glutamine (GLN is known to prevent apoptosis after injury. However, it is currently unknown if ECM stabilization and FN-Integrin osmosensing pathways are related to GLN's cell protective mechanism in the intestine. METHODS: IEC-6 cells were treated with GLN with or without FN siRNA, integrin inhibitor GRGDSP, control peptide GRGESP or ERK1/2 inhibitors PD98059 and UO126 under basal and stressed conditions. Cell survival measured via MTS assay. Phosphorylated and/or total levels of cleaved caspase-3, cleaved PARP, Bax, Bcl-2, heat shock proteins (HSPs, ERK1/2 and transcription factor HSF-1 assessed via Western blotting. Cell size and F-actin morphology quantified by confocal fluorescence microscopy and intracellular GLN concentration by LC-MS/MS. RESULTS: GLN's prevention of FN degradation after hyperthermia attenuated apoptosis. Additionally, inhibition of FN-Integrin interaction by GRGDSP and ERK1/2 kinase inhibition by PD98059 inhibited GLN's protective effect. GRGDSP attenuated GLN-mediated increases in ERK1/2 phosphorylation and HSF-1 levels. PD98059 and GRGDSP also decreased HSP levels after GLN treatment. Finally, GRGDSP attenuated GLN-mediated increases in cell area size and disrupted F-actin assembly, but had no effect on intracellular GLN concentrations. CONCLUSION: Taken together, this data suggests that prevention of FN degradation and the FN-Integrin signaling play a key role in GLN-mediated cellular protection. GLN's signaling via the FN-Integrin pathway is associated with HSP induction via ERK1/2 and HSF-1 activation leading to reduced apoptosis after gut injury.

  12. Effect of nitrate on activities and transcript levels of nitrate reductase and glutamine synthetase in rice

    Institute of Scientific and Technical Information of China (English)

    CAO Yun; FAN Xiao-Rong; SUN Shu-Bin; XU Guo-Hua; HU Jiang; SHEN Qi-Rong

    2008-01-01

    Real-time polymerase chain reaction analysis was used to compare the effect of NO-3 on the activities of nitrate reductase (NR) and glutamine synthetase (GS),and the transcript levels of two NR genes,OsNia1 and OsNia2,two cytceolic GS1 genes,OsGln1;1 and OsGln1;2,and one plastid GS2 gene OsGln2,in two rice (Oryza sativa L.) cultivars Nanguang (NG) and Yunjing (YJ).Both cultivars achieved greater biomass and higher total N concentration when grown in a mixed N supply than in sole NH+ nutrition.Supply of NO-3 increased NR activity in both leaves and roots.Expression of both NR genes was also substantially enhanced and transcript levels of OsNia2 were significantly higher than those of OsNia1.NO-3 also caused an increase in GS activity,but had a complex effect on the expression of the three GS genes.In roots,the OsGln1;1 transcript increased,but OsGln1;2 decreased.In leaves,NO-3 had no effect on the GS1 expression,but the transcript for OsGln2 increased both in the leaves and roots of rice with a mixed supply of N.These results suggested that the increase in GS activity might be a result of the complicated regulation of the various GS genes.In addition,the NO-3 induced increase of biomass,NR activity,GS activity,and the transcript levels of NR and GS genes were proportionally higher in NG than in YJ,indicating a stronger response of NG to NO-3 nutrition than YJ.

  13. Quantitative analysis of 15N labeled positional isomers of glutamine and citrulline via electrospray ionization tandem mass spectrometry of their dansyl derivatives

    Science.gov (United States)

    The enteral metabolism of glutamine and citrulline are intertwined because, while glutamine is one of the main fuel sources for the enterocyte, citrulline is one of its products. It has been shown that the administration of 15N labeled glutamine results in the incorporation of the 15N label into cit...

  14. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants : A randomized controlled trial

    NARCIS (Netherlands)

    van den Berg, Anemone; Fetter, Willem P. F.; Westerbeek, Elisabeth A. M.; van der Vegt, Ina M.; van der Molen, Hilda R. A.; van Elburg, Ruurd M.

    2006-01-01

    Background: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as refl

  15. Asymmetric generalization and interaction profiles in rhesus monkeys discriminating intravenous cocaine or intravenous heroin from vehicle.

    Science.gov (United States)

    Platt, Donna M; Rowlett, James K; Spealman, Roger D

    2010-03-01

    Many polydrug abusers combine cocaine with heroin in the form of a "speedball." This study investigated the discriminative stimulus (DS) effects of speedballs in rhesus monkeys trained to discriminate either intravenous cocaine or intravenous heroin from vehicle. Initial substitution tests revealed an asymmetry in the generalization profile of dopamine and opioid agonists such that mu agonists partially substituted for cocaine, but direct and indirect dopamine agonists did not substitute for heroin. Subsequent speedball tests in which drug mixtures were administered by coinjecting the component drugs while keeping the dose-ratio constant revealed an additional asymmetry. In cocaine-trained monkeys, coadministration of cocaine and heroin produced leftward shifts in the cocaine dose-response function. Heroin's cocaine-enhancing effects were mimicked by the mu agonists fentanyl and methadone and less consistently by the delta agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80) and reversed by the mu antagonist naltrexone and the delta antagonist naltrindole. In heroin-trained monkeys, coadministration of cocaine and heroin attenuated the DS effects of heroin. Cocaine's heroin-attenuating effects were mimicked by the D1-like agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine (SKF 81297) and the D2-like agonist R-(-)-propylnorapomorphine and reversed by the D1-like antagonist (6aS-trans)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H- benzo[d] aphtha[2,1-b]azepin-12-ol hydrobromide (SCH 39166) and the D2-like antagonist raclopride. Attenuation of the effects of heroin was accompanied by decreases in response rate. These results suggest that heroin enhances the DS effects of cocaine via mu, and to a lesser extent delta, receptor mechanisms; whereas cocaine-induced inhibition of the DS effects of heroin probably was due at least in part to masking of the heroin DS presumably

  16. Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma.

    Science.gov (United States)

    Hale, Gillian; Liu, Xinxin; Hu, Junjie; Xu, Zhong; Che, Li; Solomon, David; Tsokos, Christos; Shafizadeh, Nafis; Chen, Xin; Gill, Ryan; Kakar, Sanjay

    2016-11-01

    The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and β-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and β-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of the three patterns: (a) diffuse homogeneous: moderate-to-strong cytoplasmic staining in >90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate-to-strong staining in 50-90% of lesional cells, without a map-like pattern, and (c) patchy: moderate-to-strong staining in glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 β-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular carcinoma. The interpretation of β-catenin activation based on glutamine synthetase staining should be performed with caution, and the undetermined significance of various glutamine synthetase patterns should be highlighted in pathology reports.

  17. Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium

    Institute of Scientific and Technical Information of China (English)

    Takayuki Motoki; Hiroshi Tsuchita; Mehmet Gunduz; Hitoshi Nagatsuka; Noriaki Tanaka; Toshiyoshi Fujiwara; Yoshio Naomoto; Junji Hoshiba; Yasuhiro Shirakawa; Tomoki Yamatsuji; Junji Matsuoka; Munenori Takaoka; Yasuko Tomono; Yasuhiro Fujiwara

    2011-01-01

    AIM: To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial cells.METHODS: We developed three kinds of artificial milk with different amounts of glutamine; Complete amino acid milk (CAM), which is based on maternal mouse milk, glutamine-depleted milk (GDM), and glutaminerich milk (GRM). GRM contains three-fold more glutamine than CAM. Eighty-seven newborn mice were divided into three groups and were fed with either of CAM, GDM, or GRM via a recently improved nipple-bottle system for seven days. After the feeding period, the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of apoptosis.Moreover, IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay, flow cytometry, and western blotting to examine the biological effect of glutamine on cell growth and apoptosis.RESULTS: During the feeding period, we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%), but not in the GRM-fed mice, with no differences in body weight gain between each group. Microscopic examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed mice. Intake of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining; GRM: 13.8%, CAM: 10.7%, GDM:1.14%, GRM vs GDM: P < 0.001, CAM vs GDM: P < 0.001)and Ki-67 labeling index (the average percentage of Ki-67-positive staining; GRM: 24.5%, CAM: 22.4% GDM:19.4%, GRM vs GDM: P = 0.001, CAM vs GDM: P =0.049), suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial cells. Glutamine deprivation further caused the

  18. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  19. Homicide by intravenous injection of naphtha.

    Science.gov (United States)

    Case, M E; Poklis, A; Mackell, M A

    1985-01-01

    A case of homicide by the intravenous injection of Energine, a petroleum distillate spot remover, is presented. This case is the only known homicide committed with naphtha. This elderly man had severe natural disease in addition to chest trauma sustained in the assault leading to death; however, the rapid injection of approximately 25 mL of Energine was the overwhelming cause of death.

  20. Pharmacokinetics of intravenous buprenorphine in children.

    OpenAIRE

    1989-01-01

    Buprenorphine (3 micrograms kg-1) was given intravenously as premedication to small children (age 4-7 years) undergoing minor surgery. Because of the rapid decline of the plasma buprenorphine concentrations, the terminal elimination half-life could not be estimated reliably. Given this constraint, values of clearance appeared to be higher than those in adults but values of Vss were similar.

  1. Pharmacokinetics of intravenous buprenorphine in children.

    Science.gov (United States)

    Olkkola, K T; Maunuksela, E L; Korpela, R

    1989-08-01

    Buprenorphine (3 micrograms kg-1) was given intravenously as premedication to small children (age 4-7 years) undergoing minor surgery. Because of the rapid decline of the plasma buprenorphine concentrations, the terminal elimination half-life could not be estimated reliably. Given this constraint, values of clearance appeared to be higher than those in adults but values of Vss were similar.

  2. Benign transient eosinophilia following intravenous urography

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, M.E.; Gerzof, S.G.; Robbins, A.H.

    1977-06-13

    Eosinophilia, a component of the allergic response, may occur after the use of iodinated radiographic contrast media for intravenous urography. A benign transient elevation in differential eosinophil count was seen in 21 of 101 patients following the injection of iodinated contrast agents for that purpose.

  3. Epileptic fits under intravenous midazolam sedation.

    Science.gov (United States)

    Robb, N D

    1996-09-07

    A case is presented of a patient who suffered from recurrent epileptic fits while being treated under intravenous sedation with midazolam. Those using sedation are advised to beware of the patient who gives a history of fits being provoked in the dental environment.

  4. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

    2004-01-01

    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in child

  5. Intravenous and intramuscular magnesium sulphate regimens in ...

    African Journals Online (AJOL)

    1993-09-03

    Sep 3, 1993 ... Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! ... in the treatment of severe pre-eclampsia with the IM regimen of ..... people under the age of 50 years and more men died than women. In 40% of ...

  6. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

    2004-01-01

    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

  7. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  8. The 3' untranslated region of the two cytosolic glutamine synthetase (GS(1)) genes in alfalfa (Medicago sativa) regulates transcript stability in response to glutamine.

    Science.gov (United States)

    Simon, Bindu; Sengupta-Gopalan, Champa

    2010-10-01

    Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia with glutamate to produce glutamine. The GS enzyme is located either in the chloroplast (GS(2)) or in the cytoplasm (GS(1)). GS(1) is encoded by a small gene family and the members exhibit differential expression pattern mostly attributed to transcriptional regulation. Based on our recent finding that a soybean GS(1) gene, Gmglnβ ( 1 ) is subject to its 3'UTR-mediated post-transcriptional regulation as a transgene in alfalfa (Medicago sativa) we have raised the question of whether the 3'UTR-mediated transcript destabilization is a more universal phenomenon. Gene constructs consisting of the CaMV35S promoter driving the reporter gene, GUS, followed by the 3'UTRs of the two alfalfa GS(1) genes, MsGSa and MsGSb, were introduced into alfalfa and tobacco. The analysis of these transformants suggests that while both the 3'UTRs promote transcript turnover, the MsGSb 3'UTR is more effective than the MsGSa 3'UTR. However, both the 3'UTRs along with Gmglnβ ( 1 ) 3'UTR respond to nitrate as a trigger in transcript turnover. More detailed analysis points to glutamine rather than nitrate as the mediator of transcript turnover. Our data suggests that the 3'UTR-mediated regulation of GS(1) genes at the level of transcript turnover is probably universal and is used for fine-tuning the expression in keeping with the availability of the substrates.

  9. Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells

    Directory of Open Access Journals (Sweden)

    Ivan Greguric

    2013-06-01

    Full Text Available DOTA-linked glutamine analogues with a C6- alkyl and polyethyleneglycol (PEG chain between the chelating group and the L-glutamine moiety were synthesised and labelled with 67,68Ga using established methods. High yields were achieved for the radiolabelling of the molecules with both radionuclides (>90%, although conversion of the commercially available 67Ga-citrate to the chloride species was a requirement for consistent high radiochemical yields. The generator produced 68Ga was in the [68Ga(OH4]− form. The 67Ga complexes and the 67Ga complexes were demonstrated to be stable in PBS buffer for a week. Uptake studies were performed with longer lived 67Ga analogues against four tumour cell lines, as well as uptake inhibition studies against L-glutamine, and two known amino acid transporter inhibitors. Marginal uptake was exhibited in the PEG variant radio-complex, and inhibition studies indicate this uptake is via a non-targeted amino acid pathway.

  10. Efeito da suplementação com L-alanil-L-glutamina sobre a resposta de hipersensibilidade do tipo tardio em ratos submetidos ao treinamento intenso Effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH in rats submitted to intense training

    Directory of Open Access Journals (Sweden)

    Marcelo Macedo Rogero

    2002-12-01

    Full Text Available O treinamento intenso e o exercício exaustivo podem ocasionar imunossupressão em atletas por meio da diminuição da concentração plasmática de glutamina. O presente estudo verificou inicialmente o efeito da suplementação com L-glutamina e L-alanilL-glutamina sobre a resposta ao teste de hipersensibilidade do tipo tardio (HTT em ratos submetidos ao treinamento intenso em natação durante seis semanas. Posteriormente, foi avaliado o efeito dessas intervenções nutricionais sobre a contagem total e porcentual de leucócitos e concentração sérica de anticorpos IgG anti-albumina de soro bovino, em animais submetidos ao teste de exaustão e recuperados durante o período de 3 horas. Não houve efeito do treinamento e da suplementação sobre a resposta ao teste de HTT. Animais suplementados apresentaram maior concentração de glutamina no plasma (PIntense training and exhaustive exercise may cause immunesupression in athletes by reducing plasma glutamine concentration. Initially, this study verified the effect of L-glutamine and L-alanyl-L-glutamine supplementation on the response to delayed-type hypersensitivity test (DTH in rats submitted to intense swimming training for six weeks. Later on, we assessed the effect of these nutritional interventions on total and differential white blood cell counts and on concentration of anti-bovine serum albumin IgG antibodies, in animals submitted to exhaustion test and a three-hour recovery period. There was no effect of training and supplementation on the response to DTH. Supplemented animals presented greatest plasma glutamine concentration (p<0.05, though this increase in glutaminemia did not interfere on the serum IgG antibody concentration. The recovery period after intense exercise resulted in decreased glutaminemia as compared with the values obtained immediately after exhaustion test (p<0.05. Increase in corticosterone levels induced by strenuous exercises led to leukocytosis, neutrophilia

  11. Photoperiodic regulation of glycogen metabolism, glycolysis, and glutamine synthesis in tanycytes of the Siberian hamster suggests novel roles of tanycytes in hypothalamic function.

    Science.gov (United States)

    Nilaweera, Kanishka; Herwig, Annika; Bolborea, Matei; Campbell, Gill; Mayer, Claus D; Morgan, Peter J; Ebling, Francis J P; Barrett, Perry

    2011-11-01

    The objective of this study is to investigate the impact of photoperiod on the temporal and spatial expression of genes involved in glucose metabolism in the brain of the seasonal mammal Phodopus sungorus (Siberian hamster). In situ hybridization was performed on brain sections obtained from male hamsters held in long photoperiod (high body weight and developed testes) or short photoperiod (reduced body weight with testicular regression). This analysis revealed upregulation in expression of genes involved in glycogen and glucose metabolism in short photoperiod and localized to the tanycyte layer of the third ventricle. On the basis of these data and a previously identified photoperiod-dependent increase in activity of neighboring hypothalamic neurons, we hypothesized that the observed expression changes may reflect alteration in either metabolic fuel or precursor neurotransmitter supply to surrounding neurons. Gene expression analysis was performed for genes involved in lactate and glutamate transport. This analysis showed that the gene for the lactate transporter MCT2 and glutamate transporter GLAST was decreased in the tanycyte layer in short photoperiod. Expression of mRNA for glutamine synthetase, the final enzyme in the synthesis of the neuronal neurotransmitter precursor, glutamine, was also decreased in short photoperiod. These data suggest a role for tanycytes in modulating glutamate concentrations and neurotransmitter supply in the hypothalamic environment.

  12. Intravenous immunoglobulin treatment of children with autism.

    Science.gov (United States)

    Plioplys, A V

    1998-02-01

    Since autism has been associated with immunologic abnormalities suggesting an autoimmune cause of autistic symptoms in a subset of patients, this study was undertaken to investigate whether intravenous immunoglobulin (i.v.Ig) would improve autistic symptoms. Ten autistic children with immunologic abnormalities, demonstrated on blood tests, were enrolled in this study. Their ages ranged from 4 to 17 years, with two girls and eight boys. Eight children (1 female and 7 male) historically had undergone autistic regression. Intravenous immunoglobulin, 200 to 400 mg/kg, was administered every 6 weeks for an intended treatment program of four infusions. In five children, there was no detectable change in behavior during the treatment program. In four children, there was a mild improvement noted in attention span and hyperactivity. In none of these children did the parents feel that the improvement was sufficient to warrant further continuation of the infusions beyond the termination of the program. Only in one child was there a very significant improvement, with almost total amelioration of autistic symptoms over the time period of the four infusions. Once the treatment program was completed, this child gradually deteriorated over a 5-month time period and fully reverted to his previous autistic state. In this treatment program, five children had no response to intravenous immunoglobulin. In the four children who showed mild improvements, those improvements may simply have been due to nonspecific effects of physician intervention and parental expectation (ie, placebo effect). However, in one child there was a very significant amelioration of autistic symptoms. There were no distinguishing historic or laboratory features in this child who improved. Given a positive response rate of only 10% in this study, along with the high economic costs of the immunologic evaluations and the intravenous immunoglobulin treatments, the use of intravenous immunoglobulin to treat autistic

  13. Intravenous Perfluorocarbon After Onset of Decompression Sickness Decreases Mortality in 20-kg Swine

    Science.gov (United States)

    2010-06-01

    1; A PP Pharmaceuticals, Schaumburg, IL) was administered irltravenously prior to euthanasia . Animals were then euthanized by intra- venous...perfluorocarbon emulsion reduces morbidity and morality in a swine saturation model of decompression sickness. J Appl Physiol 2007; 102:1099-104. 8

  14. Intravenous glucagon beneficial during colonoscopy in patient with IBS

    Directory of Open Access Journals (Sweden)

    Dharmesh H Kaswala

    2014-05-01

    Full Text Available Background and Aim: Irritable bowel syndrome (IBS is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits. Patients with IBS requiring colonoscopy take longer time to cecum with higher need for medications used for conscious sedation. Glucagon is routinely used during endoscopic procedures to reduce peristalsis that interfere with the procedure. However, randomized controlled data using glucagon during endoscopic procedures are lacking. We designed a prospective randomized placebo-controlled trial to study the effect of intravenous glucagon given during colonoscopy. Materials and Methods: We received approval from the FDA for this off-label use of glucagon during colonoscopy. This is a double-blind randomized placebo-controlled study. Patients were selected based on ROME III criteria for IBS; patients who met Rome III criteria and had an indication for colonoscopy for age-specific colon cancer screening or for work up of any alarm signs. We selected 34 patients meeting the Rome III for IBS and randomized into Group A and Group B. Both the performing endoscopist and patients were blinded. These patients in both groups initially received a standard dose of conscious sedation, up to 100 mcg of fentanyl and up to 5 mg of midazolam intravenously. In Group A, 17 patients, in addition to conscious sedation, received 1 ml saline as placebo. In Group B, 17 patients, in addition to conscious sedation, received 1 mg of intravenous glucagon. Parameters evaluated were as follows: 1 Total time required for colonoscopy 2 Completion of colonoscopy as documented by cecal intubation or visualization of appendicular orifice 3 Level of comfort in patient concerned to post- procedure spasmodic pain, which was based on Wong-Baker FACES pain rating scale and 4 Calculate the amount of sedation required in both groups of patients and also at what extent glucagon helped to decrease the requirement of sedatives. Data was

  15. Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model

    Science.gov (United States)

    Das, Sujan C.; Althobaiti, Yusuf S.; Alshehri, Fahad S.; Sari, Youssef

    2016-01-01

    Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4 g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48 hours of withdrawal, P rats were re-exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS. PMID:26821293

  16. The sRNA NsiR4 is involved in nitrogen assimilation control in cyanobacteria by targeting glutamine synthetase inactivating factor IF7.

    Science.gov (United States)

    Klähn, Stephan; Schaal, Christoph; Georg, Jens; Baumgartner, Desirée; Knippen, Gernot; Hagemann, Martin; Muro-Pastor, Alicia M; Hess, Wolfgang R

    2015-11-10

    Glutamine synthetase (GS), a key enzyme in biological nitrogen assimilation, is regulated in multiple ways in response to varying nitrogen sources and levels. Here we show a small regulatory RNA, NsiR4 (nitrogen stress-induced RNA 4), which plays an important role in the regulation of GS in cyanobacteria. NsiR4 expression in the unicellular Synechocystis sp. PCC 6803 and in the filamentous, nitrogen-fixing Anabaena sp. PCC 7120 is stimulated through nitrogen limitation via NtcA, the global transcriptional regulator of genes involved in nitrogen metabolism. NsiR4 is widely conserved throughout the cyanobacterial phylum, suggesting a conserved function. In silico target prediction, transcriptome profiling on pulse overexpression, and site-directed mutagenesis experiments using a heterologous reporter system showed that NsiR4 interacts with the 5'UTR of gifA mRNA, which encodes glutamine synthetase inactivating factor (IF)7. In Synechocystis, we observed an inverse relationship between the levels of NsiR4 and the accumulation of IF7 in vivo. This NsiR4-dependent modulation of gifA (IF7) mRNA accumulation influenced the glutamine pool and thus [Formula: see text] assimilation via GS. As a second target, we identified ssr1528, a hitherto uncharacterized nitrogen-regulated gene. Competition experiments between WT and an ΔnsiR4 KO mutant showed that the lack of NsiR4 led to decreased acclimation capabilities of Synechocystis toward oscillating nitrogen levels. These results suggest a role for NsiR4 in the regulation of nitrogen metabolism in cyanobacteria, especially for the adaptation to rapid changes in available nitrogen sources and concentrations. NsiR4 is, to our knowledge, the first identified bacterial sRNA regulating the primary assimilation of a macronutrient.

  17. Successful usage of intravenous lipid emulsion in treatment of acute verapamil poisoning: A case report

    Directory of Open Access Journals (Sweden)

    Vuković-Ercegović Gordana

    2017-01-01

    Full Text Available Introduction. During the last few years, intravenous lipid emulsions have been effectively used in treatment of acute poisonings with lipophilic substances, including verapamil. Case report. A 37-year-old women presented 1 hour after ingestion of 2.8 g verapamil with hypotension and complete heart block. Because of the applied standard therapy failure and further patients impairment, Intralipid® 20% was used. Sinus rhythm was restored, arterial blood pressure increased and verapamile concentrations, both total and free decreased. Conclusion. Intravenous lipid emulsion can be important in treatment of severe acute intoxication and cardiotoxicity caused by verapamil.

  18. Inhibitory plant serpins with a sequence of three glutamine residues in the reactive center

    DEFF Research Database (Denmark)

    Hejgaard, Jørn

    2005-01-01

    Serpins appear to be ubiquitous in eukaryotes, except fungi, and are also present in some bacteria, archaea and viruses. Inhibitory serpins with a glutamine as the reactive-center P1 residue have been identified exclusively in a few plant species. Unique serpins with a reactive center sequence...

  19. The advantages of combining low-density lipoproteins with glutamine for cryopreservation of canine semen.

    Science.gov (United States)

    Bencharif, D; Amirat, L; Pascal, O; Anton, M; Schmitt, E; Desherces, S; Delhomme, G; Langlois, M-L; Barrière, P; Larrat, M; Tainturier, D

    2010-04-01

    Twenty sperm samples from five dogs were frozen in liquid nitrogen at -196 degrees C in 16 different media, two control media containing 20% egg yolk and 6% low-density lipoproteins (LDL); 10 test media containing 6% LDL (the active cryoprotective ingredient of chicken egg yolk) combined with 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 mmol of glutamine respectively at 4%, 5%, 7%, and 8% LDL. Following thawing, sperm mobility was assessed using an image analyser, HAMILTON THORN CERROS 12. The percentage of mobile spermatozoa was 62.05% in the 6% LDL + 20 mmol glutamine medium compared with 48.90% in the egg yolk-based medium (p < 0.05) or 57.55% for the 6% LDL medium (p < 0.05). Furthermore, in most cases, the motility parameters (average path velocity, curvilinear velocity, straight line velocity) in the 6% LDL + 20 mmol glutamine medium, were superior, to a statistically significant extent, to those in the control media. Finally, the 6% LDL + 20 mmol glutamine combination provides spermatozoa with better protection during freezing than egg yolk or the 6% LDL medium alone in terms of acrosome integrity (fluorescein isothiocyanate--Pisum sativum agglutinin test: p < 0.05), the flagellar plasma membrane (hypo-osmotic test: p < 0.05 for 6% LDL), the DNA (acridine orange test; no significant difference) and the integrity of the acrosome (Spermac test: no significant difference).

  20. Astroglial glutamate-glutamine cycle is involved in the modulation of inflammatory nociception in rats

    Institute of Scientific and Technical Information of China (English)

    Tiancheng Wang; Jing Wang; Bin Geng; Hongyu Guo; Haili Shen; Yayi Xia

    2011-01-01

    Our previous behavioral studies have indicated that the astroglial glutamate-glutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidence. In this study, double-labeling immunofluorescence techniques showed that after rats were intrathecally injected with PBS and plantarly injected with formalin, glial fibrillary acidic protein (GFAP) and glutamine synthesase (GS) expression were increased and GFAP/GS coexpression was changed to include layers III and IV. After intrathecal injection of methionine sulfoximine, a GS specific inhibitor, the formalin-induced change in expression and coexpression of GFAP and GS in spinal cord dorsal horns was inhibited. The morphology, distribution and quantity of astrocytes recovered to normal levels. An intrathecal glutamine injection reversed the inhibitory effect of methionine sulfoximine. Astrocytes showed significant activation and distribution extended to layers V and VI. The present study provides morphological evidence that the astroglial glutamate-glutamine cycle is involved in the process of formalin-induced spinal cord central sensitization.

  1. Expression of glutamine transporter isoforms in cerebral cortex of rats with chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Leke, Renata; Escobar, Thayssa D.C.; Rama Rao, Kakulavarapu V.

    2015-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs due to acute and chronic liver diseases, the hallmark of which is the increased levels of ammonia and subsequent alterations in glutamine synthesis, i.e. conditions associated with the pathophysiology of HE. Under physiological...

  2. Evidence for Tautomerisation of Glutamine in BLUF Blue Light Receptors by Vibrational Spectroscopy and Computational Chemistry.

    Science.gov (United States)

    Domratcheva, Tatiana; Hartmann, Elisabeth; Schlichting, Ilme; Kottke, Tilman

    2016-03-07

    BLUF (blue light sensor using flavin) domains regulate the activity of various enzymatic effector domains in bacteria and euglenids. BLUF features a unique photoactivation through restructuring of the hydrogen-bonding network as opposed to a redox reaction or an isomerization of the chromophore. A conserved glutamine residue close to the flavin chromophore plays a central role in the light response, but the underlying modification is still unclear. We labelled this glutamine with (15)N in two representative BLUF domains and performed time-resolved infrared double difference spectroscopy. The assignment of the signals was conducted by extensive quantum chemical calculations on large models with 187 atoms reproducing the UV-vis and infrared signatures of BLUF photoactivation. In the dark state, the comparatively low frequency of 1,667 cm(-1) is assigned to the glutamine C=O accepting a hydrogen bond from tyrosine. In the light state, the signature of a tautomerised glutamine was extracted with the C=N stretch at ~1,691 cm(-1) exhibiting the characteristic strong downshift by (15)N labelling. Moreover, an indirect isotope effect on the flavin C4=O stretch was found. We conclude that photoactivation of the BLUF receptor does not only involve a rearrangement of hydrogen bonds but includes a change in covalent bonds of the protein.

  3. Studies towards the synthesis of ATP analogs as potential glutamine synthetase inhibitors

    CSIR Research Space (South Africa)

    Salisu, S

    2011-05-01

    Full Text Available -1 Synthetic Communications, 41: 2216?2225 DOI: 10.1080/00397911.2010.501473 Studies Towards the Synthesis of ATP Analogs as Potential Glutamine Synthetase Inhibitors Sheriff Salisu a , Colin Kenyon b & Perry T. Kaye a a Department of Chemistry...

  4. Reaction Mechanism of Mycobacterium Tuberculosis Glutamine Synthetase Using Quantum Mechanics/Molecular Mechanics Calculations.

    Science.gov (United States)

    Moreira, Cátia; Ramos, Maria J; Fernandes, Pedro Alexandrino

    2016-06-27

    This paper is devoted to the understanding of the reaction mechanism of mycobacterium tuberculosis glutamine synthetase (mtGS) with atomic detail, using computational quantum mechanics/molecular mechanics (QM/MM) methods at the ONIOM M06-D3/6-311++G(2d,2p):ff99SB//B3LYP/6-31G(d):ff99SB level of theory. The complete reaction undergoes a three-step mechanism: the spontaneous transfer of phosphate from ATP to glutamate upon ammonium binding (ammonium quickly loses a proton to Asp54), the attack of ammonia on phosphorylated glutamate (yielding protonated glutamine), and the deprotonation of glutamine by the leaving phosphate. This exothermic reaction has an activation free energy of 21.5 kcal mol(-1) , which is consistent with that described for Escherichia coli glutamine synthetase (15-17 kcal mol(-1) ). The participating active site residues have been identified and their role and energy contributions clarified. This study provides an insightful atomic description of the biosynthetic reaction that takes place in this enzyme, opening doors for more accurate studies for developing new anti-tuberculosis therapies.

  5. Glutamine synthetase sequence evolution in the mycobacteria and their use as molecular markers for Actinobacteria speciation

    Directory of Open Access Journals (Sweden)

    Wiid Ian JF

    2009-02-01

    Full Text Available Abstract Background Although the gene encoding for glutamine synthetase (glnA is essential in several organisms, multiple glnA copies have been identified in bacterial genomes such as those of the phylum Actinobacteria, notably the mycobacterial species. Intriguingly, previous reports have shown that only one copy (glnA1 is essential for growth in M. tuberculosis, while the other copies (glnA2, glnA3 and glnA4 are not. Results In this report it is shown that the glnA1 and glnA2 encoded glutamine synthetase sequences were inherited from an Actinobacteria ancestor, while the glnA4 and glnA3 encoded GS sequences were sequentially acquired during Actinobacteria speciation. The glutamine synthetase sequences encoded by glnA4 and glnA3 are undergoing reductive evolution in the mycobacteria, whilst those encoded by glnA1 and glnA2 are more conserved. Conclusion Different selective pressures by the ecological niche that the organisms occupy may influence the sequence evolution of glnA1 and glnA2 and thereby affecting phylogenies based on the protein sequences they encode. The findings in this report may impact the use of similar sequences as molecular markers, as well as shed some light on the evolution of glutamine synthetase in the mycobacteria.

  6. Exploring the Catalytic Mechanism of Human Glutamine Synthetase by Computer Simulations.

    Science.gov (United States)

    Issoglio, Federico M; Campolo, Nicolas; Zeida, Ari; Grune, Tilman; Radi, Rafael; Estrin, Dario A; Bartesaghi, Silvina

    2016-10-13

    Glutamine synthetase is an important enzyme that catalyzes the ATP-dependent formation of glutamine from glutamate and ammonia. In mammals, it plays a key role in preventing excitotoxicity in the brain and detoxifying ammonia in the liver. In plants and bacteria, it is fundamental for nitrogen metabolism, being critical for the survival of the organism. In this work, we show how the use of classical molecular dynamics simulations and multiscale quantum mechanics/molecular mechanics simulations allowed us to examine the structural properties and dynamics of human glutamine synthetase (HsGS), as well as the reaction mechanisms involved in the catalytic process with atomic level detail. Our results suggest that glutamine formation proceeds through a two-step mechanism that includes a first step in which the γ-glutamyl phosphate intermediate forms, with a 5 kcal/mol free energy barrier and a -8 kcal/mol reaction free energy, and then a second rate-limiting step involving the ammonia nucleophilic attack, with a free energy barrier of 19 kcal/mol and a reaction free energy of almost zero. A detailed analysis of structural features within each step exposed the relevance of the acid-base equilibrium related to protein residues and substrates in the thermodynamics and kinetics of the reactions. These results provide a comprehensive study of HsGS dynamics and establish the groundwork for further analysis regarding changes in HsGS activity, as occur in natural variants and post-translational modifications.

  7. Evidence for Tautomerisation of Glutamine in BLUF Blue Light Receptors by Vibrational Spectroscopy and Computational Chemistry

    Science.gov (United States)

    Domratcheva, Tatiana; Hartmann, Elisabeth; Schlichting, Ilme; Kottke, Tilman

    2016-01-01

    BLUF (blue light sensor using flavin) domains regulate the activity of various enzymatic effector domains in bacteria and euglenids. BLUF features a unique photoactivation through restructuring of the hydrogen-bonding network as opposed to a redox reaction or an isomerization of the chromophore. A conserved glutamine residue close to the flavin chromophore plays a central role in the light response, but the underlying modification is still unclear. We labelled this glutamine with 15N in two representative BLUF domains and performed time-resolved infrared double difference spectroscopy. The assignment of the signals was conducted by extensive quantum chemical calculations on large models with 187 atoms reproducing the UV-vis and infrared signatures of BLUF photoactivation. In the dark state, the comparatively low frequency of 1,667 cm−1 is assigned to the glutamine C=O accepting a hydrogen bond from tyrosine. In the light state, the signature of a tautomerised glutamine was extracted with the C=N stretch at ~1,691 cm−1 exhibiting the characteristic strong downshift by 15N labelling. Moreover, an indirect isotope effect on the flavin C4=O stretch was found. We conclude that photoactivation of the BLUF receptor does not only involve a rearrangement of hydrogen bonds but includes a change in covalent bonds of the protein. PMID:26947391

  8. Acute depletion of plasma glutamine increases leucine oxidation in prednisone-treated humans.

    Science.gov (United States)

    To determine whether depletion in plasma glutamine worsens the catabolic response to corticosteroids, seven healthy volunteers received oral prednisone for 6 days on two separate occasions, at least 2 weeks apart, and in random order. On the sixth day of each treatment course, they received 5 h intr...

  9. Evidence for Tautomerisation of Glutamine in BLUF Blue Light Receptors by Vibrational Spectroscopy and Computational Chemistry

    Science.gov (United States)

    Domratcheva, Tatiana; Hartmann, Elisabeth; Schlichting, Ilme; Kottke, Tilman

    2016-03-01

    BLUF (blue light sensor using flavin) domains regulate the activity of various enzymatic effector domains in bacteria and euglenids. BLUF features a unique photoactivation through restructuring of the hydrogen-bonding network as opposed to a redox reaction or an isomerization of the chromophore. A conserved glutamine residue close to the flavin chromophore plays a central role in the light response, but the underlying modification is still unclear. We labelled this glutamine with 15N in two representative BLUF domains and performed time-resolved infrared double difference spectroscopy. The assignment of the signals was conducted by extensive quantum chemical calculations on large models with 187 atoms reproducing the UV-vis and infrared signatures of BLUF photoactivation. In the dark state, the comparatively low frequency of 1,667 cm-1 is assigned to the glutamine C=O accepting a hydrogen bond from tyrosine. In the light state, the signature of a tautomerised glutamine was extracted with the C=N stretch at ~1,691 cm-1 exhibiting the characteristic strong downshift by 15N labelling. Moreover, an indirect isotope effect on the flavin C4=O stretch was found. We conclude that photoactivation of the BLUF receptor does not only involve a rearrangement of hydrogen bonds but includes a change in covalent bonds of the protein.

  10. Changes in Activities of Glutamine Synthetase during Grain Filling and Their Relation to Rice Quality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Four japonica rice varieties differed in cooking and eating qualities were used in a pot experiment to study the relationship between the activities of glutamine synthetase during grain filling and rice quality. The activities of glutamine synthetase gradually increased and then declined as a single peak curve in the course of grain filling. The 15th day after heading was a turning point, before which the enzymatic activities in the inferior rice varieties with high protein content were higher than those in the superior rice varietie with low protein content, and after which it was converse. The activity of glutamine synthetase in grain was correlated with the taste meter value, peak viscosity and breakdown negatively at the early stage of grain filling whereas positively at the middle and late stages. Moreover, it was correlated with the protein content of rice grain and setback positively at the early stage and negatively at the middle and late stages. The correlation degree varied with the course of grain filling. From 15 days to 20 days after heading was a critical stage, in which the direction of correlation between the activity of glutamine synthetase and taste meter value and RVA properties of rice changed.

  11. In vitro enzyme degradation of crosslinked films of poly hydroxyalkyl glutamine

    Institute of Scientific and Technical Information of China (English)

    PAN Shi-rong; WANG Qin-mei; Yi Wu

    2001-01-01

    @@ Polybenzyl glutamate as one of polyα-amino acids displaying excellent biocompatibility and biodegradabi-lity is capable of reacting with hydroxyalkyl-amine byaminolysis and changing the benzyl glutamate to hydro-xyalkyl glutamine, whichproperties can obviously be improved.

  12. Evaluation of the causes and cost impact of returned intravenous ...

    African Journals Online (AJOL)

    intravenous medications at a tertiary care hospital in. Riyadh ... cost impact in an in-patient setting in a Saudi tertiary care hospital. ..... Lean Techniques to Reduce Intravenous Waste. Through Premixed Solutions and Increasing Production.

  13. Glutamine enema regulates colonic ubiquitinated proteins but not proteasome activities during TNBS-induced colitis leading to increased mitochondrial activity.

    Science.gov (United States)

    Bertrand, Julien; Marion-Letellier, Rachel; Azhar, Saïda; Chan, Philippe; Legrand, Romain; Goichon, Alexis; Ghouzali, Ibtissem; Aziz, Moutaz; Vaudry, David; Savoye, Guillaume; Déchelotte, Pierre; Coëffier, Moïse

    2015-07-01

    Ubiquitin proteasome system contributes to the regulation of intestinal inflammatory response as its inhibition is associated with tissue damage improvement. We aimed to evaluate whether glutamine is able to limit inflammation by targeting ubiquitin proteasome system in experimental colitis. Colitis was induced in male rats by intrarectal instillation of 2-4-6-trinitrobenzen sulfonic acid (TNBS) at day 1. From day 2 to day 6, rats daily received either an intrarectal instillation of PBS (TNBS/PBS group) or glutamine (TNBS/Gln). Rats were euthanized at day 7 and colonic samples were taken to evaluate ubiqutinated proteins by proteomic approach combining 2D electrophoresis and immunoblots directed against ubiquitin. Results were then confirmed by evaluating total expression of proteins and mRNA levels. Survival rate, TNFα, and IL-1β mRNA were improved in TNBS/Gln compared with TNBS/PBS (p TNBS but not by glutamine. We identified eight proteins that were less ubiquitinated in TNBS/PBS compared with controls with no effect of glutamine. Four proteins were more ubiquitinated in TNBS/PBS group and restored in TNBS/Gln group. Finally, 12 ubiquitinated proteins were only affected by glutamine. Among proteins affected by glutamine, eight proteins (GFPT1, Gapdh, Pkm2, LDH, Bcat2, ATP5a1, Vdac1, and Vdac2) were involved in metabolic pathways. In conclusion, glutamine may regulate ubiquitination process during intestinal inflammation.

  14. INTRAVENOUS DEXMEDETOMIDINE FOR LABOUR ANALGESIA IN WOMEN WITH PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    Nidhi

    2016-06-01

    Full Text Available BACKGROUND Parenteral opioids and sedatives are the most frequently prescribed agents for women in labour in many poor resource settings. These have shown poor pain relief and a lot of side effects in both the mother and the foetus. In patients with severe pre-eclampsia who are already haemodynamically compromised labour pains and delivery can result in haemodynamic instability, which can compromise both the mother and the neonate. Dexmedetomidine is a highly selective α-2 agonist, which when used in recommended dose in the form of an infusion has several desirable properties like sedation, anxiolysis, sympatholysis, analgesia, decreased anaesthetic requirements, maintains cardiovascular stability and provides a smooth recovery. AIM The aim of this study was to study the haemodynamic effects of intravenous dexmedetomidine when used in patients with severe pre-eclampsia for labour analgesia. MATERIALS AND METHODS The study was conducted in the Department of Obstetrics and Gynaecology of Bundelkhand Medical College, Sagar, between January 2015 and December 2016; 40 labouring patients with severe pre-eclampsia were included in the study; 20 each were allocated to the study and control group. The study group received intravenous Dexmedetomidine in the recommended doses (1 ug/kg loading dose over 10-15 minutes followed by an infusion at 0.2-0.7 ug/kg/hour when in active labour, while the control group received Intravenous Fentanyl. The two groups were compared regarding the duration of labour, the mode of delivery, the neonatal outcome, the onset and duration of analgesia and maternal haemodynamic parameters during labour and delivery. The data obtained in this study was tabulated and analysed using the Chi-square test and the Z test with p value of 0.05 taken as significant. RESULTS It was found out that the group of patients who received Dexmedetomidine were more haemodynamically stable during labour and delivery; there was significant pain relief

  15. Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats

    Directory of Open Access Journals (Sweden)

    Michelle Cruz

    2012-01-01

    Full Text Available The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.

  16. Glutamine, glutamate, and arginine-based acid resistance in Lactobacillus reuteri.

    Science.gov (United States)

    Teixeira, Januana S; Seeras, Arisha; Sanchez-Maldonado, Alma Fernanda; Zhang, Chonggang; Su, Marcia Shu-Wei; Gänzle, Michael G

    2014-09-01

    This study aimed to determine whether glutamine deamidation improves acid resistance of Lactobacillus reuteri, and to assess whether arginine, glutamine, and glutamate-mediated acid resistance are redundant or complementary mechanisms of acid resistance. Three putative glutaminase genes, gls1, gls2, and gls3, were identified in L. reuteri 100-23. All three genes were expressed during growth in mMRS and wheat sourdough. L. reuteri consistently over-expressed gls3 and the glutamate decarboxylase gadB. L. reuteri 100-23ΔgadB over-expressed gls3 and the arginine deiminase gene adi. Analysis of the survival of L. reuteri in acidic conditions revealed that arginine conversion is effective at pH of 3.5 while glutamine or glutamate conversion were effective at pH of 2.5. Arginine conversion increased the pHin but not ΔΨ; glutamate decarboxylation had only a minor effect on the pHin but increased the ΔΨ. This study demonstrates that glutamine deamidation increases the acid resistance of L. reuteri independent of glutamate decarboxylase activity. Arginine and glutamine/glutamate conversions confer resistance to lactate at pH of 3.5 and phosphate at pH of 2.5, respectively. Knowledge of L. reuteri's acid resistance improves the understanding of the adaptation of L. reuteri to intestinal ecosystems, and facilitates the selection of probiotic and starter cultures.

  17. Effects of nitric oxide synthase inhibition on glutamine action in a bacterial translocation model.

    Science.gov (United States)

    Santos, Rosana G C; Quirino, Iara E P; Viana, Mirelle L; Generoso, Simone V; Nicoli, Jacques R; Martins, Flaviano S; Nogueira-Machado, José A; Arantes, Rosa M E; Correia, Maria I T D; Cardoso, Valbert N

    2014-01-14

    Glutamine may be a precursor for NO synthesis, which may play a crucial role in bacterial translocation (BT). The goal of the present study was to investigate the potential effects of glutamine on BT and the immunological response in an experimental model of NO synthase inhibition by NG-nitro-L-arginine methyl ester (l-NAME). Mice were randomly assigned to four groups: sham; intestinal obstruction (IO); IO+500 mg/kg per d glutamine (GLN); IO+GLN plus 10 mg/kg per d l-NAME (GLN/LN). The groups were pretreated for 7 d. BT was induced by ileal ligation and was assessed 18 h later by measuring the radioactivity of 99mTc-Escherichia coli in the blood and organs. Mucosal damage was determined using a histological analysis. Intestinal permeability (IP) was assessed by measuring the levels of 99mTc-diethylenetriaminepentaacetic acid in the blood at 4, 8 and 18 h after surgery. IgA and cytokine concentrations were determined by ELISA in the intestinal fluid and plasma, respectively. BT was increased in the GLN/LN and IO groups than in the GLN and sham groups. IP and intestinal mucosa structure of the sham, GLN and GLN/LN groups were similar. The GLN group had the highest levels of interferon-γ, while IL-10 and secretory IgA levels were higher than those of the IO group but similar to those of the GLN/LN group. The present results suggest that effects of the glutamine pathway on BT were mediated by NO. The latter also interferes with the pro-inflammatory systemic immunological response. On the other hand, IP integrity preserved by the use of glutamine is independent of NO.

  18. Glutamine synthetase/glutamate synthase ammonium-assimilating pathway in Schizosaccharomyces pombe.

    Science.gov (United States)

    Perysinakis, A; Kinghorn, J R; Drainas, C

    1995-06-01

    Kinetic parameters of glutamine synthetase (GS) and glutamate synthase (glutamine-oxoglutarate aminotransferase) (GOGAT) activities, including initial velocity, pH, and temperature optima, as well as Km values, were estimated in Schizosaccharomyces pombe crude cell-free extracts. Five glutamine auxotrophic mutants of S. pombe were isolated following MNNG treatment. These were designated gln1-1,2,3,4,5, and their growth could be repaired only by glutamine. Mutants gln1-1,2,3,4,5 were found to lack GS activity, but retained wild-type levels of NADP-glutamate dehydrogenase (GDH), NAD-GDH, and GOGAT. One further glutamine auxotrophic mutant, gln1-6, was isolated and found to lack both GS and GOGAT but retained wild-type levels of NADP-GDH and NAD-GDH activities. Fortuitously, this isolate was found to harbor an unlinked second mutation (designated gog1-1), which resulted in complete loss of GOGAT activity but retained wild-type GS activity. The growth phenotype of mutant gog1-1 (in the absence of the gln1-6 mutation) was found to be indistinguishable from the wild type on various nitrogen sources, including ammonium as a sole nitrogen source. Double-mutant strains containing gog1-1 and gdh1-1 or gdh2-1 (mutations that result specifically in the abolition of NADP-GDH activity) result in a complete lack of growth on ammonium as sole nitrogen source in contrast to gdh or gog mutants alone.

  19. Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells.

    Science.gov (United States)

    Yao, Kang; Yin, Yulong; Li, Xilong; Xi, Pengbin; Wang, Junjun; Lei, Jian; Hou, Yongqing; Wu, Guoyao

    2012-06-01

    α-Ketoglutarate (AKG) is a key intermediate in glutamine metabolism. Emerging evidence shows beneficial effects of AKG on clinical and experimental nutrition, particularly with respect to intestinal growth and integrity. However, the underlying mechanisms are unknown. Intestinal porcine epithelial cells (IPEC-1) were used to test the hypothesis that AKG inhibits glutamine degradation and enhances protein synthesis. IPEC-1 cells were cultured for 3 days in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 0, 0.2, 0.5 or 2 mM of AKG. At the end of the 3-day culture, cells were used to determine L-[U-14C]glutamine utilization, protein concentration, protein synthesis, and the total and phosphorylated levels of the mammalian target of the rapamycin (mTOR), ribosomal protein S6 kinase-1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1). Compared with 0 mM of AKG (control), 0.2 and 0.5 mM of AKG dose-dependently reduced (P<0.05) glutamine degradation and the production of glutamate, alanine and aspartate in IPEC-1 cells. Addition of 0.5 and 2 mM of AKG to culture medium enhanced protein synthesis (P<0.05) by 78 and 101% without affecting protein degradation, compared to the control group. Rapamycin (50 nM; a potent inhibitor of mTOR) attenuated the stimulatory effect of AKG on protein synthesis. Consistent with these metabolic data, the addition of 0.5 or 2 mM of AKG to culture medium increased (P<0.05) the phosphorylated levels of mTOR, S6k1 and 4E-BP1 proteins. Collectively, these results indicate that AKG can spare glutamine and activate the mTOR signaling pathway to stimulate protein synthesis in intestinal epithelial cells.

  20. The Molecular Basis of TnrA Control by Glutamine Synthetase in Bacillus subtilis.

    Science.gov (United States)

    Hauf, Ksenia; Kayumov, Airat; Gloge, Felix; Forchhammer, Karl

    2016-02-12

    TnrA is a master regulator of nitrogen assimilation in Bacillus subtilis. This study focuses on the mechanism of how glutamine synthetase (GS) inhibits TnrA function in response to key metabolites ATP, AMP, glutamine, and glutamate. We suggest a model of two mutually exclusive GS conformations governing the interaction with TnrA. In the ATP-bound state (A-state), GS is catalytically active but unable to i