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BACKGROUND: Skeletal muscle synthesizes, stores, and releases body L-glutamine (GLN). Muscle atrophy due to disabling diseases triggers the activation of proteolytic and pro-apoptotic cell signaling, thus impairing the body's capacity to manage GLN content. This situation has a poor therapeutic prognosis. OBJECTIVE: Evaluating if oral GLN supplementation can attenuate muscle wasting mediated by elevated plasma cortisol and activation of caspase-3, p38MAPK, and FOXO3a signaling pathways in soleus and gastrocnemius muscles of rats submitted to 14-day bilateral hindlimbs immobilization. METHODS: Animals were randomly distributed into six groups: non-immobilized rats (Control), control orally supplemented with GLN (1 g kg-1) in solution with L-alanine (ALA: 0.61 g kg-1; GLN+ALA), control orally supplemented with dipeptide L-alanyl-L-glutamine (DIP; 1.49 g kg-1), hindlimbs immobilized rats (IMOB), IMOB orally GLN+ALA supplemented (GLN+ALA-IMOB), and IMOB orally DIP supplemented (DIP-IMOB). Plasma and muscle GLN concentration, plasma cortisol level, muscle caspase-3 activity, muscle p38MAPK and FOXO3a protein content (total and phosphorylated forms), and muscle cross-sectional area (CSA) were measured. RESULTS: Compared to controls, IMOB rats presented: a) increased plasma cortisol levels; b) decreased plasma and muscle GLN concentration; c) increased muscle caspase-3 activity; d) increased total and phosphorylated p38MAPK protein content; e) increased FOXO3a and decreased phosphorylated FOXO3a protein content; f) reduced muscle weight and CSA befitting to atrophy. Oral supplementation with GLN+ALA and DIP was able to significantly attenuate these effects. CONCLUSIONS: These findings attest that oral GLN supplementation in GLN+ALA solution or DIP forms attenuates rats' skeletal muscle mass wasting caused by disuse-mediated muscle atrophy.
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Glutamina , Hidrocortisona , Atrofia Muscular , Animales , Ratas , Caspasa 3/metabolismo , Suplementos Dietéticos , Dipéptidos/metabolismo , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Glutamina/farmacología , Músculo Esquelético , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , Transducción de Señal , Proteína Forkhead Box O3/efectos de los fármacos , Proteína Forkhead Box O3/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
PURPOSE: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. METHODS: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. RESULTS: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). CONCLUSION: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.
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Glutamina , Síndrome MELAS , Humanos , Glutamina/metabolismo , Síndrome MELAS/diagnóstico por imagen , Síndrome MELAS/tratamiento farmacológico , Síndrome MELAS/metabolismo , Creatina/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Espectroscopía de Resonancia Magnética/métodos , Ácido Glutámico/metabolismo , Espectroscopía de Protones por Resonancia Magnética/métodos , Lactatos , Suplementos DietéticosRESUMEN
We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.
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Glutamina , Neoplasias de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Cisplatino , Quimioradioterapia/efectos adversos , Docetaxel , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels. METHOD: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation. RESULTS: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 µmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 µmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode. DISCUSSION: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. https://clinicaltrials.gov/ct2/show/NCT04948138.
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Acidosis Láctica , Síndrome MELAS , Accidente Cerebrovascular , Adulto , Femenino , Humanos , Masculino , Estudios de Cohortes , Suplementos Dietéticos , Ácido Glutámico/uso terapéutico , Glutamina/uso terapéutico , Síndrome MELAS/tratamiento farmacológico , Síndrome MELAS/genética , Síndrome MELAS/metabolismoRESUMEN
OBJECTIVES: Glutamine can be beneficial to athletes for its antiinflammatory and antioxidant effects. The present study was designed to investigate the effect of glutamine supplementation on some atherosclerosis markers after exhaustive exercise in young healthy males. METHODS: In an intervention study, 30 healthy males (case = 15 and control = 15) were randomly assigned into two groups. For 14 d, the intervention group received 0.3 g of glutamine per kilogram of body weight per day, with 25 g of sugar in 250 mL of water, and the control group received 25 g of sugar per 250 mL of water. At the end of the intervention, the participants completed one session of exhaustive exercise, and then fasting blood samples were taken to test serum levels of atherosclerosis markers. RESULTS: In the intervention group, the serum levels of leptin, cholesterol, and oxidized low-density lipoprotein were lower than in the control group after 2 wk of glutamine supplementation (P < 0.05). Interleukin-6 serum levels were lower in the intervention group compared to the control group after supplementation, but not significantly. Serum levels of leptin, interleukin-6, cholesterol, and oxidized low-density lipoprotein, as well as the ratio of oxidized low-density lipoprotein to high-density lipoprotein, were significantly decreased in the intervention group compared to the control group after exhaustive exercise (P < 0.05). CONCLUSIONS: Glutamine supplementation has beneficial effects for athletes, particularly those doing strenuous physical exercise, through reducing atherosclerosis-related biomarkers and elevating serum adiponectin levels, and it can potentially play a role in decreasing the initiation and progression of atherosclerosis.
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Aterosclerosis , Glutamina , Aterosclerosis/prevención & control , Biomarcadores , Suplementos Dietéticos , Ejercicio Físico , Humanos , MasculinoRESUMEN
Peritoneal dialysis used to be a common treatment for acute kidney failure that required dialysis. In favor of continuous, extracorporeal renal replacement procedures, it disappeared from the scene in the western world, whereas it continues to be used in structurally poor countries due to its simplicity and low resource intensity. Recently, the shortages in medical care in the context of the coronavirus disease 2019 (COVID-19) pandemic led to renewed worldwide interest in peritoneal dialysis as a safe option in acute kidney failure requiring dialysis. The introduction of biocompatible solutions 20 years ago was expected to reduce mortality or technical failure. Unfortunately, so far this could only be implied but not confirmed in studies. Immunomodulatory adjuvants are an innovative option which have the potential to improve the local immunocompetence and prevent the loss of peritoneal function. Currently, the vision of a wearable artificial kidney is getting closer. Intensification of dialysis dose also appears achievable with minimal dialysate volumes. In times of global warming, the regeneration of dialysates could not only save relevant amounts of water but also have a favorable impact on the CO2 balance. In summary, peritoneal dialysis is currently enjoying a comeback. This article describes the current and future developments of this procedure.
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Adapted nutrition can improve the growth of low birth weight (LBW) piglets. Since maternal milk is thought to provide insufficient glutamine (Gln) for LBW piglets, the current study investigated the influence of Gln supplementation during the early suckling period on development and lipid deposition in skeletal muscle. The weight differences between LBW and normal birth weight (NBW) littermates persisted from birth to slaughter (p < 0.001). However, intramuscular Gln and Ala concentrations were altered in piglets according to the supplementation (p < 0.01). There were larger muscle fibers (p = 0.048) in Gln-supplemented piglets. Capillarization or nuclei number per muscle fiber was not influenced by birth weight (BiW) or Gln supplementation. Abundance of myosin heavy chain (MYH) isoforms was slightly altered by Gln supplementation. LBW piglets had more lipid droplets than NBW piglets at day 5 of life in both muscles (p < 0.01). The differences decreased with age. Adipocyte development increased with age, but was not influenced by BiW or supplementation. The results indicate that BiW differences were accompanied by differences in lipid deposition and muscle fiber structure, suggesting a delayed development in LBW piglets. Supplementation with Gln may support piglets to overcome those disadvantages.
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Skeletal muscle disuse results in myofibrillar atrophy and protein degradation, via inflammatory and oxidative stress-mediated NF-kB signaling pathway activation. Nutritional interventions, such as l-glutamine (GLN) supplementation have shown antioxidant properties and cytoprotective effects through the modulation on the 70-kDa heat shock protein (HSP70) expression. However, these GLN-mediated effects on cell signaling pathways and biochemical mechanisms that control the myofibrillar protein content degradation in muscle disuse situations are poorly known yet. This study investigated the effects of oral GLN plus l-alanine (ALA; GLN â+ âALA-solution) supplementation, either in their free or dipeptide (L-alanyl-l-glutamine-DIP) form, on GLN-glutathione (GSH) axis and cytoprotection mediated by HSP70 protein expression in the slow-twitch soleus and fast-twitch gastrocnemius skeletal muscle of rats submitted to 14-days of hindlimb immobilization-induced disuse muscle atrophy. Forty-eight Wistar rats were distributed into 6 groups: hindlimb immobilized (IMOB group) and hindlimb immobilized orally supplemented with either GLN (1â¯gâ¯kg-1) plus ALA (0.61â¯gâ¯kg-1) â(GLN â+ âALA-IMOB group) or 1.49 âg âkg-1 of DIP (DIP-IMOB group) and; no-immobilized (CTRL) and no-immobilized supplemented GLN â+ âALA and DIP baselines groups. All animals, including CTRL and IMOB rats (water), were supplemented via intragastric gavage for 14 days, concomitantly to immobilization period. Plasma and muscle GLN levels, lipid (thiobarbituric acid reactive substances-TBARS) and protein (carbonyl) peroxidation, erythrocyte concentration of reduced GSH and GSH disulfide (GSSG), plasma and muscle pro-inflammatory TNF-α levels, muscle IKKα/ß-NF-kB signaling pathway and, the myofibrillar protein content (MPC) were measured. The MPC was significantly lower in IMOB rats, compared to CTRL, GLN â+ âALA, and DIP animals (p â< â0.05). This finding was associated with reduced plasma and muscle GLN concentration, equally in IMOB animals. Conversely, both GLN â+ âALA and DIP supplementation restored plasma and muscle GLN levels, which equilibrated GSH and intracellular redox status (GSSG/GSH ratio) in erythrocytes and skeletal muscle even as, increased muscle HSP70 protein expression; attenuating oxidative stress and TNF-α-mediated NF-kB pathway activation, fact that reverberated on reduction of MPC degradation in GLN â+ âALA-IMOB and DIP-IMOB animals (p â< â0.05). In conclusion, the findings shown herein support the oral GLN â+ âALA and DIP supplementations as a therapeutic and effective nutritional alternative to attenuate the deleterious effects of the skeletal muscle protein degradation induced by muscle disuse.
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Glutamina/farmacología , Inflamación/tratamiento farmacológico , Músculo Esquelético/metabolismo , Estrés Oxidativo/efectos de los fármacos , Administración Oral , Animales , Antioxidantes/farmacología , Creatina Quinasa/genética , Suplementos Dietéticos , Modelos Animales de Enfermedad , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Músculo Esquelético/patología , FN-kappa B/genética , Proteolisis/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.
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Suplementos Dietéticos , Glutamina/administración & dosificación , Obesidad/terapia , Sobrepeso/terapia , Adulto , Animales , Biomarcadores/metabolismo , Peso Corporal/fisiología , Dieta Alta en Grasa/efectos adversos , Método Doble Ciego , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Mediadores de Inflamación/metabolismo , Resistencia a la Insulina/fisiología , Hígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Obesidad/etiología , Obesidad/fisiopatología , Sobrepeso/etiología , Sobrepeso/fisiopatología , Ratas , Ratas Wistar , Circunferencia de la Cintura/fisiologíaRESUMEN
Prophylactic antibiotics and growth promoters have been substituted, mainly for livestock, by immunomodulators and intestinal health promoters - such as ß-D-glucans and glutamine. The aim of this study was to verify the beneficial effects of ß-D-glucans and glutamine against Cytarabine/Ara-C, evaluating the DNA damage in leukocytes, the leukogram, and the mitotic index of intestinal crypts cells. Balb/C mice received treatment with ß-D-glucan (80â¯mg/Kg), glutamine (150â¯mg/Kg), or both, for 21â¯days. On the last two days of this period, Ara-C was administered (1.8â¯mg/animal) by intraperitoneal injection every 12â¯h. The animals submitted to the treatment with Ara-C presented the highest genotoxic index, a significant leukopenia, and a decrease in the mitotic index of the intestinal crypts cells. Treatment with ß-D-glucan protected the leukocytes against DNA fragmentation induced by Ara-C. Glutamine alone promoted maintenance of the mitotic index and, in association with ß-Dglucan, reduced leukopenia. Thus, the use of ß-D-glucan and glutamine proved to be beneficial to intestinal tropism. This can happen once the damage to the genetic material, prevented by the treatments with ß-D-glucan and glutamine, can result in genotoxicity. Not only this, but it might be capable of turning into a mutagenesis, with consequential physiopathological alterations.
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Daño del ADN/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Inestabilidad Genómica/efectos de los fármacos , beta-Glucanos/administración & dosificación , Animales , Citarabina/toxicidad , Glutamina/administración & dosificación , Inyecciones Intraperitoneales , Leucocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB CRESUMEN
OBJECTIVES: The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. METHODS: Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn + EN + GLN-free amino acid (AA; n = 10), sham burn + EN + GLN (n = 10), burn + EN + AA (n = 10), and burn + EN + GLN (n = 10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back, burned rats in two of the experimental groups (burn + EN + AA and burn + EN + GLN groups) were fed with a conventional EN solution by oral gavage for 7 d. Simultaneously, rats in the burn + EN + GLN group were given 0.35 g GLN/kg body weight/d once via a tail vein injection for 7 d and rats in the burn + EN + AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. Rats in two sham burn control groups (sham burn + EN + AA and sham burn + EN + GLN groups) were treated in the same manner except for the burn injury. All rats in the four groups were given 175 kcal/kg body wt/d. There was isonitrogenous, isovolumic, and isocaloric intake among the four groups. At the end of the seventh day after completion of the nutritional program, all rats were anesthetized and samples were collected for further analysis. PP apoptosis was measured by terminal deoxyuridine nick-end labeling (TUNEL). The expression of Hsp90 in PPs was analyzed by western blotting. Caspase-3 activity of PPs was also assessed. Levels of proinflammatory cytokines of gut tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). The intestinal immunoglobulin A (IgA) content was also determined by ELISA. RESULTS: The results revealed that intestinal IgA content in rats of the burn + EN + GLN group were significantly increased compared with those in the burn + EN + AA group (P < 0.05). The expression of Hsp90 of PPs in rats in the burn + EN + GLN group was significantly upregulated compared with those in the burn + EN + AA group (P < 0.05). On the other hand, levels of proinflammatory cytokines of gut tissues, caspase-3 activity, and the number of TUNEL-stained cells of PPs in rats of the burn + EN + GLN group were markedly decreased compared with those of the burn + EN + AA group (P < 0.05). CONCLUSIONS: The results of this study show that parenteral glutamine supplementation combined with EN may upregulate the expression of Hsp90, reduce caspase-3 activity, lessen the release of proinflammatory cytokines, attenuate PP apoptosis, and improve intestinal IgA response in burned rats. Clinically, therapeutic efforts to improve intestinal immunity may contribute to a favorable outcome in severely burned patients.
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Quemaduras/terapia , Suplementos Dietéticos , Glutamina/farmacología , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Ganglios Linfáticos Agregados/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Nutrición Enteral , Mucosa Intestinal/metabolismo , Masculino , Nutrición Parenteral , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: Glutamine is needed for optimal cell growth and for the immune system, especially in the enterocytes of gut mucosal immune responses. Low birth weight makes infants susceptible to glutamine depletion because nutrition is limited in the first week of life. To determine the effect of enteral glutamine supplementation on weight gain patterns and fecal secretory immunoglobulin A. MATERIAL AND METHODS: This study is a double-blind, randomized controlled trial. Infants were randomly assigned to the glutamine group and placebo group. The glutamine group was supplemented with glutamine 400 mg/kg/day for 14 days, and placebo group received glucose 400 mg/kg/day for 14 days. The infants were observed for 30 days. Return-to-birth-weight, weight gain velocity, and fecal secretory immunoglobulin A levels were monitored during the study. RESULTS: Thirty-seven low-birth-weight infants were randomly assigned to the glutamine and placebo groups. The glutamine group had a shorter return-to-birth-weight time than the placebo group (8.1±0.9 vs. 11.0±1.6 days) and faster weight gain velocity (20.0±1.8 vs. 15.5±2.2 g/kg/day) (p<0.001). Secretory immunoglobulin A levels after glutamine supplementation were higher than in the placebo group (0.456±0.057 vs. 0.376±0.035 mg/g) (p<0.001). Levels of secretory immunoglobulin A after treatment in each group were increased. However, there was a significant difference before and after supplementation between the glutamine and placebo groups (0.247±0.024 vs. 0.140±0.016 mg/g) (p<0.001). CONCLUSION: Enteral glutamine supplementation in low-birth-weight infants accelerates return to birth weight, increases the weight gain velocity, and the levels of fecal secretory immunoglobulin A.
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OBJECTIVE: The aim of this study is to investigate the effects of parenteral glutamine(GLN) supplementation combined with enteral nutrition (EN) on heat shock protein 90(Hsp90) expression, apoptosis of lymphoid organs and circulating lymphocytes, immunological function and survival in severely burned rats. METHODS: Male SD rats were randomly assigned into 4 groups: a sham burn+EN+GLN-free amino acid (AA) group (n=10), a sham burn+EN+GLN group (n=10), a burn+EN+AA group (n=10), and a burn +EN +GLN group (n=10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back was made, the burned rats in two experimental groups (the burn+EN+AA group and the burn+EN +GLN group) were fed with a conventional enteral nutrition solution by oral gavage for 7 days. Simultaneously, the rats in the burn+EN+GLN group were given 0.35g GLN/kg body weight/day once via a tail vein injection for 7 days, whereas those in the burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. The rats in two sham burn control groups (the sham burn+EN+AA group and the sham burn+EN +GLN group) were treated in the same procedure as above, except for burn injury. All rats in each of the four groups were given 175kcal/kg body wt/day. There was isonitrogenous, isovolumic and isocaloric intake among four groups. At the end of the 7th day after nutritional programme were finished, all rats were anesthetized and samples were collected for further analysis. Serum immunoglobulin quantification was conducted by ELISA. Circulating lymphocyte numbers were counted by Coulter LH-750 Analyzer. The percentages and apoptotic ratio of CD4 and CD8T lymphocytes in circulation were determined by flow cytometry (FCM). The neutrophil phagocytosis index (NPI) was examined. The GLN concentrations in plasma, thymus, spleen and skeletal muscle were measured by high performance liquid chromatography (HPLC). The organ index evaluation and TUNEL analysis of thymus and spleen were carried out. The expression of Hsp90 in thymus and spleen was analyzed by western blotting. Moreover, the survival in burned rats was observed. RESULTS: The results revealed that parenteral GLN supplementation combined with EN significantly increased the GLN concentrations of plasma and tissues, the serum immunoglobulin content, the circulating lymphocyte number, the CD4/CD8 ratio, the indexes of thymus and spleen, NPI and survival as compared with the burn+EN+AA group (p<0.05). The expression of Hsp90 in thymus and spleen in the burn+EN+GLN group was significantly up-regulated as compared with the burn+EN+AA group (p<0.05). The apoptosis in circulating CD4 and CD8 lymphocytes, thymus and spleen in the burn+EN+GLN group was significantly decreased as compared with the burn+EN+AA group (p<0.05). CONCLUSION: The results of this study show that parenteral GLN supplementation combined with EN may increase the GLN concentrations of plasma and tissues, up-regulate the expression of Hsp90, attenuate apoptosis in lymphoid organ and circulating lymphocyte, enhance the immunological function and improve survival in severely burned rats. Clinically, therapeutic efforts at the modulation of the immune dysfunction may contribute to a favorable outcome in severely burned patients.
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Apoptosis/efectos de los fármacos , Quemaduras/terapia , Nutrición Enteral , Glutamina/farmacología , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Bazo/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Timo/efectos de los fármacos , Administración Intravenosa , Animales , Western Blotting , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Suplementos Dietéticos , Citometría de Flujo , Proteínas HSP90 de Choque Térmico/metabolismo , Etiquetado Corte-Fin in Situ , Recuento de Linfocitos , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fagocitosis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Bazo/metabolismo , Linfocitos T/citología , Timo/metabolismoRESUMEN
La glutamina es un aminoácido condicionalmente esencial considerado actualmente como un importante fármaco-nutriente. Niveles plasmáticos bajos de glutamina han demostrado comportarse como un factor independiente de mortalidad en el paciente crítico, y su adición al soporte nutricional ha probado disminuir las complicaciones infecciosas, la mortalidad y la estancia hospitalaria. En los últimos años han aparecido nuevos estudios que indicanla necesidad de individualizar la vía de acceso y la dosis y el período de suplementación para determinados grupos de pacientes candidatos a la suplementación con glutamina, y por otra parte, a tenor de los resultados, es aconsejable evitarla en situaciones deshock hipovolémico inestable, fallo multiorgánico o insu¬ciência renal no sometida a técnicas de depuración.
Glutamine is a conditionally essential aminoacid which is nowadays considered an important pharmaco nutrient. Low serum levels of glutamine have proven to be an independent predictor of mortality in the critically ill patient. Supplementation with glutamine as a part of a nutritional therapy has demonstrated to reduce infectious complications, length of stay in hospital and mortality. Recent new published data show the need to individualize the route, dose, length of supplementation for determined groups of candidate patients to glutamine administration. On the other hand, according to results, glutamine is not recommended in case of unstable hypovolemic shock, multiorgan faillure, or renal failure not subjected to depuration techniques.
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Humanos , Enfermedad Crítica/terapia , Glutamina/farmacología , Nutrición Parenteral/efectos adversos , Pacientes , Glutamina , Fenómenos Fisiológicos Nutricionales del Lactante/normasRESUMEN
Marked alterations in systemic glutamate-glutamine metabolism characterize the catabolic state, in which there is an increased breakdown and decreased synthesis of skeletal muscle protein. Among these alterations are a greatly increased net release of glutamine (Gln) from skeletal muscle into blood plasma and a dramatic depletion of intramuscular Gln. Understanding the catabolic state is important because a number of pathological conditions with very different etiologies are characterized by its presence; these include major surgery, sepsis, trauma, and some cancers. Acetaminophen (APAP) overdose is also accompanied by dramatic changes in systemic glutamate-glutamine metabolism including large drops in liver glutathione (for which glutamate is a precursor) and plasma Gln. We have constructed a mathematical model of glutamate and glutamine metabolism in rat which includes liver, blood plasma and skeletal muscle. We show that for the normal rat, the model solutions fit experimental data including the diurnal variation in liver glutathione (GSH). We show that for the rat chronically dosed with dexamethasone (an artificial glucocorticoid which induces a catabolic state) the model can be used to explain empirically observed facts such as the linear decline in intramuscular Gln and the drop in plasma glutamine. We show that for the Wistar rat undergoing APAP overdose the model reproduces the experimentally observed rebound of liver GSH to normal levels by the 24-h mark. We show that this rebound is achieved in part by the action of the cystine-glutamate antiporter, an amino acid transporter not normally expressed in liver but induced under conditions of oxidative stress. Finally, we explain why supplementation with Gln, a Glu precursor, assists in the preservation of liver GSH during APAP overdose despite the fact that under normal conditions only Cys is rate-limiting for GSH formation.
Asunto(s)
Acetaminofén/efectos adversos , Sobredosis de Droga/metabolismo , Glutatión/metabolismo , Hígado/metabolismo , Modelos Biológicos , Músculo Esquelético/metabolismo , Acetaminofén/farmacología , Animales , Sobredosis de Droga/patología , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Hígado/patología , Músculo Esquelético/patología , Ratas , Ratas WistarRESUMEN
OBJECTIVES: The gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohistochemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. RESULTS: The results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). CONCLUSION: The results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis.
Asunto(s)
Suplementos Dietéticos , Nutrición Enteral/métodos , Glutamina/farmacología , Inmunidad Mucosa/efectos de los fármacos , Mucosa Intestinal/inmunología , Nutrición Parenteral/métodos , Sepsis/inmunología , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Glutamina/administración & dosificación , Inmunoglobulina A/metabolismo , Mucosa Intestinal/efectos de los fármacos , Linfocitos/efectos de los fármacos , Masculino , Ganglios Linfáticos Agregados/efectos de los fármacos , Células Plasmáticas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sepsis/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to assess clinical relevance of long-term oral glutamine supplementation on lipid profile and inflammatory and metabolic factors in patients with diabetes. METHOD: Sixty-six patients with type 2 diabetes between the ages of 18 and 65 y were randomized to receive glutamine 30 g/d (10 g powder, three times a day) or placebo, in a double-blind, placebo-controlled trial during a 6-wk treatment period. Fifty-three patients completed the trial. Independent samples t test and analysis of covariance were used. RESULTS: After a 6-wk treatment period, a significant difference was observed between the two groups in body fat mass (P = 0.01) and percentage of body fat (P = 0.008). Moreover, a significant reduction in waist circumference (P < 0.001) and a tendency for an increase in fat-free mass (P = 0.03), with no change in body weight and body mass index (BMI) was found. Enhancement in body fat-free mass was mainly attributed to trunk (P = 0.03). There was a downward trend in systolic blood pressure (P = 0.005) but not diastolic. Fasting blood glucose (mmol/L) concentration significantly decreased after the 6-wk intervention (P = 0.04). Mean hemoglobin A1c was significantly different between the groups at week 6 (P = 0.04). No significant difference was detected for fasting insulin, homeostasis model assessment for insulin resistance and quantitative insulin sensitivity index between groups (P > 0.05). No significant difference was observed between groups in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride. No treatment effect on C-reactive protein was found (P = 0.44). CONCLUSION: We demonstrated that the 6-wk supplementation with 30 g/d glutamine markedly improved some cardiovascular risk factors, as well as body composition, in patients with type 2 diabetes. Future glutamine dose-response studies are warranted in these areas.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Glutamina/administración & dosificación , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Adulto , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Composición Corporal , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Dieta , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Glutamina/sangre , Hemoglobina Glucada/metabolismo , Homeostasis , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Actividad Motora , Factores de Riesgo , Triglicéridos/sangreRESUMEN
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 < 0.001). Though myogenic enzymes increased significantly after ULE (P < 0.001), the glutamine group remained unchanged by supplementation during ULE. Glutamine supplementation has prevented excessive muscle damage and suppression of neutrophil function, especially in ROS production activity, even during an intensive training period.
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Suplementos Dietéticos , Glutamina/administración & dosificación , Glutamina/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Glutamina/inmunología , Humanos , Masculino , Proteínas Opsoninas/sangre , Fagocitosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: To investigate whether supplementation of carbohydrate together with peptide glutamine would increase exercise tolerance in soccer players. METHODS: Nine male soccer players (mean age: 18.4 ± 1.1 years; body mass: 69.2 ± 4.6 kg; height: 175.5 ± 7.3 cm; and maximum oxygen consumption of 57.7 ± 4.8 ml.kg-1.min-1) were evaluated. All of them underwent a cardiopulmonary exercise test and followed a protocol that simulated the movements of a soccer game in order to evaluate their tolerance to intermittent exercise. By means of a draw, either carbohydrate with peptide glutamine (CARBOGLUT: 50g of maltodextrin + 3.5g of peptide glutamine in 250 ml of water) or carbohydrate alone (CARBO: 50g of maltodextrin in 250 ml of water) was administered in order to investigate the enhancement of the soccer players' performances. The solution was given thirty minutes before beginning the test, which was performed twice with a one-week interval between tests. RESULTS: A great improvement in the time and distance covered was observed when the athletes consumed the CARBOGLUT mixture. Total distance covered was 12750 ± 4037m when using CARBO, and 15571 ± 4184m when using CARBOGLUT (p<0.01); total duration of tolerance was 73 ± 23 min when using CARBO and 88 ± 24 min when using CARBOGLUT (p<0.01). CONCLUSION: The CARBOGLUT mixture was more efficient in increasing the distance covered and the length of time for which intermittent exercise was tolerated. CARBOGLUT also reduced feelings of fatigue in the players compared with the use of the CARBO mixture alone.