Decrease In Glutamine Levels Research Articles

Enteral Glutamine Supplementation is Associated with Lowering Wound Infection Morbidity and Length of Hospital Stay among Burn Patients: A Meta-analysis and Systematic Review

Background. Significant nutritional support to meet increased energy expenditure is vital for burn patient's survival. Burn injury may lead to a significant decrease in Glutamine levels, which inspired the hypothesis that glutamine supplementation following burn injury would improve outcomes. Hence, the purpose of this meta-analysis study was to provide the rationale for determining the efficacy and safety of enteral glutamine in burn patients.
 
 Methods. We conducted a meta-analysis based on PRISMA design to assess the potency of enteral glutamine supplementation as adjuvant treatment in patients with burn trauma. PubMed, Sciencedirect, and Google scholar were searched systematically using the following keywords: "enteral glutamine" and "burn patients" and "critical ill" and "infection" and "length of stay". Newcastle-Ottawa Scale (NOS) was used to assess the quality of papers included in our meta-analysis. A Z test was used to determine the significance of pooled effect estimates. Publication bias was assessed using Egger's. We used Comprehensive Meta-Analysis (CMA) version 2.1 to analyze the data.
 
 Results: A total of 12 studies recording 344 cases and 335 controls were enrolled for our analysis. Data on hospital Length of Stay (LOS) was found that enteral glutamine supplementation provided a significant result in reducing the LOS (Std mean diff: 0.70, 95%CI: 0.16 – 1.24; p=0.0100). We also found that a higher risk of positive wound culture was significantly observed in patients without the supplementation of enteral glutamine (OR 2.15, 95% CI: 1.41 – 3.27; p=0.0003) compared to patients receiving enteral glutamine supplementation among burn patients.
 
 Conclusion: In our meta-analysis study, enteral glutamine in burn patients confers significantly shorter LOS and lower risk of wound infection among burn patients. We suggest that enteral glutamine supplementation may be a beneficial intervention for the management of burn patients.

Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes.

Glutamine synthetase (GS) is a key enzyme that metabolizes glutamate into glutamine. While GS is highly enriched in astrocytes, expression in other glial lineages has been noted. Using a combination of reporter mice and cell type-specific markers, we show that GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells of the mouse and human ventral spinal cord. To investigate the role of GS in mature OL, we used a conditional knockout (cKO) approach to selectively delete GS-encoding gene (Glul) in OL, which caused a significant decrease in glutamine levels on mouse spinal cord extracts. GS cKO mice (CNP-cre+ :Glulfl/fl ) showed no differences in motor neuron numbers, size or axon density; OL differentiation and myelination in the ventral spinal cord was normal up to 6months of age. Interestingly, GS cKO mice showed a transient and specific decrease in peak force while locomotion and motor coordination remained unaffected. Last, GS expression in OL was increased in chronic pathological conditions in both mouse and humans. We found a disease-stage dependent increase of OL expressing GS in the ventral spinal cord of SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Moreover, we showed that GLUL transcripts levels were increased in OL in leukocortical tissue from multiple sclerosis but not control patients. These findings provide evidence towards OL-encoded GS function in spinal cord sensorimotor axis, which is dysregulated in chronic neurological diseases.

Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena

The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 μg/kg bw/day and 300 μg/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet- specific. Then the 1H NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the diet-specificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP.

Amino acid profiles as potential biomarkers for pediatric cancers: a preliminary communication.

Childhood cancer remains one of the main cause of death in the pediatric population. Amino acids (AAs) level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease. Seventy-seven children with cancer, including 47 with hematological and 30 with solid tumors were enrolled in this study and compared with healthy children. Twenty-two plasma-free AAs were determined by HPLC with fluorometric detection. The results revealed significant decrease in glutamine levels for oncological patients and significant increase in aspartic acid, glutamic acid, asparagine, serine, citrulline, alanine, GABA, tryptophan, methionine, valine, phenylalanine and isoleucine levels in cancer children versus control. Plasma-free AA profile as a biomarker, which combines metabolic and clinical data, as an innovative and interdisciplinary approach, may allow for faster detection of tumor occurrence, and in the future for monitoring patient during treatment, and possible prediction of cancer recurrence.

Attenuation Of Exertional Muscle Damage With A Nutritional Supplement

Previous research suggests that glutamine (GLN) administration either during or following strenuous exercise modulates post-exercise inflammatory responses and may facilitate recovery. PURPOSE: This study studied the effects of GLN added to a beverage containing a carbohydrate (CHO) and an essential amino acid (EAA) mixture consumed during and after exercise on markers of EMD and performance in subjects following a strenuous physical training event. METHODS: Male subjects (n = 33; mean age of 24 years ± 1) completed this blinded-crossover study. Subjects were randomized to ingest either a placebo or treatment beverage during and after two identical events (modified physical fitness test), with the alternate beverage provided at the second event. Beverages were matched for CHO and EAA content (42 grams of CHO, 6 grams of EAA per liter) providing 192 calories. The GLN containing (4 grams) treatment beverage provided 208 calories per liter. RESULTS: No significant differences were noted (p ≤ 0.05) between groups with respect to muscle damage or inflammation, to include changes in creatine kinase, lactate dehydrogenase, white blood cell counts, C-reactive protein and select pro- and anti-inflammatory cytokines, as measured at baseline and after exercise. Creatine kinase, the primary variable of interest, increased after the training event in both groups indicating muscle damage had occurred. The treatment beverage did not significantly attenuate the response (p = 0.28). Plasma GLN levels remained relatively unchanged between placebo and treatment conditions, with both beverages blunting post-exercise induced decreases in GLN levels. Physical performance measures and pain scores were not significantly affected by the addition of GLN. CONCLUSIONS: Our findings suggest that the addition of GLN to a CHO/EAA beverage provided during and after exercise does not confer any significant benefit over a CHO/EAA beverage alone. The intervention failed to alter circulating GLN levels or measurably affect markers of EMD and the inflammatory response, and did not improve physical performance.

Glutamine and arginine metabolism in tumor-bearing rats receiving total parenteral nutrition

Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 × 10 6) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U- 14C-glutamine (2.0 μCi/h) or U- 14C-arginine (2.0 μCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U- 14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U- 14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 ± 11.9 μmol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 ± 66.1 μmol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% ± 10.9% v 77.4% ± 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.

Valproate Increases Glutaminase and Decreases Glutamine Synthetase Activities in Primary Cultures of Rat Brain Astrocytes

It has been proposed that hyperammonemia may be associated with valproate therapy. As astrocytes are the primary site of ammonia detoxification in brain, the effects of valproate on glutamate and glutamine metabolism in astrocytes were studied. It is well established that, because of compartmentation of glutamine synthetase, astrocytes are the site of synthesis of glutamine from glutamate and ammonia. The reverse reaction is catalyzed by the ubiquitous enzyme glutaminase, which is present in both neurons and astrocytes. In astrocytes exposed to 1.2 mM valproate, glutaminase activity increased 80% by day 2 and remained elevated at day 4; glutamine synthetase activity was decreased 30%. Direct addition of valproate to assay tubes with enzyme extracts from untreated astrocytes had significant effects only at concentrations of 10 and 20 mM. When astrocytes were exposed for 4 days to 0.3, 0.6, or 1.2 mM valproate and subsequently incubated with L-[U-14C]glutamate, label incorporation into [14C]glutamine was decreased by 11, 25, and 48%, respectively, and is consistent with a reduction in glutamine synthetase activity. Label incorporation from L-[U-14C]glutamate into [14C]aspartate also decreased with increasing concentrations of valproate. Following a 4-day exposure to 0.6 mM valproate, the glutamine levels increased 40% and the glutamate levels 100%. These effects were not directly proportional to valproate concentration, because exposure to 1.2 mM valproate resulted in a 15% decrease in glutamine levels and a 25% increase in glutamate levels compared with control cultures. Intracellular aspartate was inversely proportional to all concentrations of extracellular valproate, decreasing 60% with exposure to 1.2 mM valproate.(ABSTRACT TRUNCATED AT 250 WORDS)