L-Glutamine

BACKGROUND: Glutamine plays an important role in acute catabolic conditions in critically ill patients. This meta-analysis aimed to investigate the effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral feeding (EN) or parenteral feeding (PN). METHODS: PubMed, Web of Science, Scopus, and Embase were explored to identify the studies investigating the effect of glutamine on serum inflammatory markers in intensive care unit patients. All randomized clinical trials that assessed the effect of glutamine supplementation on "inflammatory markers" in EN or PN were included in the study. Because a small number of studies were included, SE was adjusted for overall effect size by using the Knapp-Hartung method. RESULTS: In this study, 2728 eligible studies were initially included, and 10 eligible case-control studies were finally enrolled for further investigations. There was a statistical reduction between preintervention and postintervention CRP levels (standardized mean difference [SMD] = -0.38 mg/L; 95% CI, -0.72 to -0.03). No significant association was found between L-glutamine supplementation in the EN/PN and interleukin 6 (IL-6) (SMD = -0.58 pg/ml; 95% CI, -2.15 to 0.99) and tumor necrosis factor alpha (TNF-α) (SMD = 2.69 pg/ml; 95% CI, -9.66 to 15.03) compared with the control group. CONCLUSIONS: This study identified that glutamine supplementation might have an important effect on CRP in acute conditions and no significant effect on IL-6 and TNF-α in acute conditions. © 2021 American Society for Parenteral and Enteral Nutrition.

OBJECTIVE: To investigate the mechanism of Huiyang Shengji unguent (, HYSJ) for improving inflammation and promoting wound healing in patients with diabetic foot. METHODS: The primary components of the HYSJ unguent were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 20 patients with a diabetic foot wound were divided randomly into either a HYSJ treatment group (10 cases) or control group (10 cases). The HYSJ group was treated for 14 d with Hui Yang Shengji unguent, while the control group was treated for 14 d with basic fibroblast growth factor unguent. Central granulation tissue and wound secretions were collected before treatment and on the 7th and 14th day, respectively. The proteins prospero homeobox protein 1 (PROX-1), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and vascular endothelial growth factor receptor 3 (VEGFR-3) associated with lymphatic angiogenesis were detected by immunohistochemistry, the levels of inflammatory cytokines in wound exudates including interleukin-1β (IL-1β), interleukin-18 (IL-18), and vascular endothelial growth factor C (VEGF-C) were measured using enzyme-linked immunosorbent assay, while the protein levels of NOD-like receptor family, pyrin domain containing protein 3 (NLRP3), caspase-1, gasdermin D, and N-terminal gasdermin D were measured using immunoimprinting. RESULTS: UPLC-MS/MS analysis revealed that the high-abundance peak compounds in HYSJ unguent included coclaurine, glucoraphanin, citric acid, gallic acid, L-glutamine, and gentianose. Following treatment, there was a significant reduction in IL-1β and IL-18 levels in the HYSJ group's wound exudates on day 14 compared to pre-treatment values (P < 0.05). Conversely, VEGF-C levels showed a significant increase from pre-treatment levels (P < 0.05). In addition, the expression of PROX-1, LYVE-1 and VEGFR-3 in wound tissue increased significantly after 14 d of treatment when compared to pre-treatment levels (P < 0.05). Taken together, the results of these analyses provide insights into the dynamic changes of these factors in wound healing processes. On the 7th and 14th day of treatment, the expression

BACKGROUND: Preoperative physical frailty is a significant predictor of adverse postoperative outcomes in older patients undergoing cardiac surgery. Inflammation plays a crucial role in the development of frailty and contributes to postoperative complications. This study investigated the effects of preoperative beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine supplementation on inflammatory markers, nutritional status, and renal function in older patients undergoing cardiac surgery. METHODS: This was a secondary analysis of a single-center, open-label, randomized controlled trial. Patients aged ≥65 years scheduled for elective cardiac surgery were randomized to receive either HMB supplementation (1200 mg HMB, 7000 mg l-glutamine, and 7000 mg L-arginine, twice daily) or routine care for at least two weeks before surgery. Serum levels of tumor necrosis factor-alpha (TNF-α), and other biochemical markers were measured at baseline, pre-surgery, and two weeks post-surgery. RESULTS: Forty-four patients (mean age 72.5 years, 36 % women) were analyzed. Preoperative HMB supplementation significantly reduced pre-surgery serum TNF-α levels compared to the control group (0.85 ± 0.28 pg/mL vs. 1.10 ± 0.44 pg/mL, p = 0.039). However, this difference was not observed two weeks post-surgery. No significant differences were observed in C-reactive protein levels or other nutritional markers between the two groups at any time point. CONCLUSIONS: Preoperative supplementation with a combination of HMB, glutamine, and arginine was effective in reducing preoperative TNF-α levels in older patients undergoing cardiac surgery, suggesting a potential anti-inflammatory effect. This anti-inflammatory effect suggests a potential mechanism for improving postoperative outcomes and warrants further investigation. Registration number of Clinical Trial: UMIN000030490 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034773).

PURPOSE: Radiation-induced oral mucositis (RIOM) severely impacts patients with head and neck cancer (HNC) undergoing radiotherapy, often leading to pain and malnutrition. L-arginine and glutamine are immune-enhancing amino acids with potential benefits in wound healing and inflammation control. This study evaluated the efficacy of L-arginine versus L-glutamine oral suspensions in managing RIOM. METHODS: In this triple-blind, randomized controlled trial, 69 HNC patients with RIOM were allocated to three groups (n = 23 each): Group I (L-arginine 5 g + maltodextrin 5 g), Group II (glutamine 5 g + maltodextrin 5 g), or Group III (maltodextrin 10 g). Outcomes, assessed at weeks 2, 5, and 7 of radiotherapy, included the WHO oral mucositis scale, Pain Visual Analogue Scale (Pain-VAS), body mass index (BMI), and Oral Health Impact Profile (OHIP-14) questionnaire. RESULTS: By week 5, WHO scale scores differed significantly among groups (p < 0.001), with arginine and glutamine groups exhibiting lower mucositis severity than the maltodextrin group. Pain-VAS scores at weeks 5 and 7 were significantly lower in the arginine and glutamine groups compared to maltodextrin (p = 0.004 and p < 0.001, respectively). By 7th week of radiotherapy, BMI was significantly decreased in the maltodextrin group than in either the arginine (p = 0.028) or glutamine (p = 0.001) groups, indicative of treatment-mediated weight loss. In contrast, the BMI over time in the arginine (p = 0.87) and glutamine (p = 0.170) groups were almost constant. This indicates that compared to maltodextrin alone, both amino acid supplements prevented a decline in BMI during radiotherapy. OHIP-14 scores improved significantly in the arginine and glutamine groups at weeks 5 and 7 (p < 0.001), indicating better quality of life. CONCLUSIONS: Both L-arginine and glutamine significantly reduced RIOM severity, pain, and weight loss compared to maltodextrin, while improving quality of life in patients with head and neck cancer. Although no statistically significant difference was found between the two, a higher proportion of patients receiving L-arginine achieved complete healing by week 7, suggesting a potential late adva

OBJECTIVE: To investigate whether the application of L-glutamine (L-G) and hyaluronic acid (HA) associated with photobiomodulation (PBM) and the Preventive Oral Care Protocol (POCP) would present similar efficacy as the exclusive use of PBM, associated with POCP, in the prevention and control of severe oral mucositis (OM). STUDY DESIGN: Patients with head and neck cancer undergoing radiochemotherapy (RCT) were randomized into two groups: group A, patients that received PBM + POCP (n = 24), and group B, patients that received PBM + POCP + L-G + HA (n = 24). OM was assessed using the National Cancer Institute (NCI) and World Health Organization (WHO) scales. The impact of oral health on patients' quality of life and perception of OM symptoms was evaluated. Assessments were made at the 1st, 7th, 14th, 21st, and 30th radiotherapy (RT) sessions. RESULTS: When the severity of OM was assessed according to the WHO scale in the 30th RT, group B showed lower rates of severe OM than group A. There were no differences when using the NCI scale. The impact of oral health on quality of life and the symptoms reported by patients were lower in group B at all times evaluated. CONCLUSION: The combination of PBM + POCP + L-G + HA resulted in a significantly lower severity of OM than PBM + POCP alone, according to the WHO scale at the 30th RT. TRIAL REGISTRATION: Brazilian Clinical Trials Registry-REBEC no. RBR-6ybmgcv. Registration March 27, 2022. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: L-glutamine and linoleic acid (LA) can suppress inflammatory cytokine expression; however, studies on their simultaneous application are limited due to polarity differences. AIMS: To investigate the effect of glutamine linoleate vesicles (QLAsomes) on skin sensitization by assessing their impact on sensitization-related protein expression, bacterial growth, and clinical efficacy in relieving skin itchiness. METHODS: After synthesizing and analyzing QLAsomes, their inhibitory effects on capsaicin-induced cytokine expression and Staphylococcus aureus growth were evaluated. In a double-blind clinical trial, 24 participants (ages 22-63) with sensitized skin applied 10 wt% QLAsome cream on one side and a vehicle or no cream on the other twice daily for 2 weeks. Itchiness in the elbow area was assessed using a visual analog scale and expert evaluation. Skin barrier changes were measured using transepidermal water loss (TEWL), skin erythema, and stratum corneum (SC) hydration. RESULTS: QLAsomes, formed by L-glutamine and LA through hydrogen bonding, were spherical vesicles (164.6 ± 3.1 nm). Based on the inhibitory effects of L-glutamine and LA on inflammation-related factors, QLAsomes inhibited the capsaicin-induced expression of these factors more effectively than the individual components. IL-4 inhibition was improved by over 26%. Matrix metalloproteinase-1, which degrades collagen, showed 32% and 23% improvements compared to L-glutamine and LA, respectively. In a clinical evaluation, 10 wt% QLAsome cream reduced itching by 45% compared to before application, which is a 67% improvement compared to placebo. Skin evaluations revealed improvements in erythema (12%), TEWL (15%), and SC hydration (19%), suggesting that QLAsomes enhance the skin barrier function. CONCLUSIONS: QLAsomes showed up to 32% higher expression inhibition of key skin sensitization-related factors than individual components, and based on this, improved pruritus by 67% more than placebo. As nanovesicles with skin-soothing properties, they are effective for drug encapsulation and managing skin sensitivity in pharmaceutical and cosmetic industries. © 2025 The Author(s). Journal of Cosmetic

BACKGROUND & AIMS: In older patients undergoing cardiac surgery, physical function is a critical determinant of postoperative outcomes. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has been shown to promote muscle protein anabolism and inhibit catabolism, thereby preventing muscle weakness. However, its efficacy in older patients undergoing cardiac surgery remains unknown. This study aimed to examine the effects of preoperative HMB supplementation on postoperative physical function and complications in this population. METHODS: In this single-center, open-label, randomized controlled trial, patients aged ≥65 years scheduled for cardiac surgery were randomized to receive HMB supplementation or no nutritional intervention. The HMB group received HMB 1200 mg, l-glutamine 7000 mg, and l-arginine 7000 mg, once or twice daily, for at least 2 weeks before surgery. Evaluations were performed at baseline and before and after surgery. The primary outcome was the 6-min walking distance (6MWD) before and after surgery. Secondary outcomes included the incidence of complications, muscle mass and strength, physical performance, and length of hospital stay. RESULTS: Forty-four patients with a mean age of 72.5 years (women, 38 %) were randomized to the HMB (n = 22) or control (n = 22) group. Compared with the control group, the HMB group demonstrated a statistically significant improvement in the 6MWD both at the pre-surgery (448.0 ± 73.5 m vs. 375.5 ± 58.8 m; P = 0.01) and post-surgery time points (428.9 ± 76.4 m vs. 304.5 ± 52.3 m; P = 0.001). Muscle strength and physical performance also showed significant improvements in the HMB group. However, no significant difference in muscle mass was observed between the groups at any time point. The HMB group had a shorter hospital length of stay compared with that of the control group (16.1 ± 3.8 days vs. 20.4 ± 7.6 days, P = 0.03), and no adverse events were observed with the intervention. CONCLUSIONS: Preoperative HMB supplementation in older adults undergoing cardiac surgery resulted in significant improvements in postoperative exercise capacity and physical function, along with a reduction in the length of hospital stay,

INTRODUCTION: Hand-foot-skin reaction (HFSR) is the most common side effect of multi-tyrosine kinase inhibitor therapy for unresectable hepatocellular carcinoma (uHCC). Sarcopenia has been reported to be a poor prognostic factor for HCC. Here, we performed a randomized controlled trial (RCT) of the efficacy of a β-hydroxy-β-methyl butyrate/l-arginine/l-glutamine (HMB/Arg/Gln) beverage and locomotion training as supportive care in the treatment of uHCC with lenvatinib. METHODS: A total of 20 patients were enrolled from the jRCTs031190252 trial in this pilot study. HFSR was the primary endpoint, and other adverse events and skeletal muscle index at the third lumbar level (L3-SMI) were secondary endpoints. RESULTS: Twelve patients had albumin-bilirubin grade 1, and eight had grade 2. No difference in HFSR was observed. Although interesting differences were observed in the secondary endpoints, a slight retention of L3-SMI values in the intervention group compared with that in the control group was observed (96.5 % vs. 89.9 %, p = 0.407). CONCLUSION: Although the HMB/Arg/Gln beverage and locomotion training did not reduce adverse events caused by lenvatinib, they might be useful in maintaining skeletal muscle mass. Further validation studies with a larger number of patients are warranted.

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities. © 2024. The Author(s).

BACKGROUND: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance. METHODS: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects (n = 40; four groups, n = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake. RESULTS: Statistical analyses displayed ten significant main effects (p < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group (p < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level. CONCLUSIONS: Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

Erratum in Cancer Lett. 2022 Feb 1;526:363. doi: 10.1016/j.canlet.2021.11.029. Proteasome inhibitors (PIs), used in the treatment of plasma cell myeloma (PCM), interfere with the degradation of misfolded proteins leading to activation of unfolded protein response (UPR) and cell death. However, despite initial strong antimyeloma effects, PCM cells eventually develop acquired resistance to PIs. The pleiotropic role of ʟ-glutamine (Gln) in cellular functions makes inhibition of Gln metabolism a potentially good candidate for combination therapy. Here, we show that PCM cells, both sensitive and resistant to PIs, express membrane Gln transporter (ASCT2), require extracellular Gln for survival, and are sensitive to ASCT2 inhibitors (ASCT2i). ASCT2i synergistically potentiate the cytotoxic activity of PIs by inducing apoptosis and modulating autophagy. Combination of ASCT2 inhibitor V9302 and proteasome inhibitor carfilzomib upregulates the intracellular levels of ROS and oxidative stress markers and triggers catastrophic UPR as shown by upregulated spliced Xbp1 mRNA, ATF3 and CHOP levels. Moreover, analysis of RNA sequencing revealed that the PI in combination with ASCT2i reduced the levels of Gln metabolism regulators such as MYC and NRAS. Analysis of PCM patients' data revealed that upregulated ASCT2 and other Gln metabolism regulators are associated with advanced disease stage and with PIs resistance. Altogether, we identified a potent therapeutic approach that may prevent acquired resistance to PIs and may contribute to the improvement of treatment of patients suffering from PCM.

BACKGROUND: Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. MATERIALS AND METHODS: We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. RESULTS: Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC50s) of 0.12->10 IU/ml. Erwinaze at <1 IU/ml reduced temozolomide IC50s by 3.6- to 13-fold (300-1,200 μM to 40-330 μM). Seven-week-old SMO/SMO mice treated with Erwinaze (regardless of temozolomide treatment) had better survival 11 weeks post-therapy, compared to those not treated with Erwinaze (81.25% vs. 46.15, p=0.08). Temozolomide-treated mice developed 10% weight loss, impairing survival. All 16 mice treated with temozolomide (regardless of Erwinaze treatment) succumbed by 40-weeks of age, whereas 5/8 animals treated with Erwinaze alone and 2/6 controls survived (p=0.035). CONCLUSION: Erwinaze enhances cytotoxicity of temozolomide in vitro, and improves survival in SMO/SMO mice, likely by reducing cerebrospinal fluid glutamine. Temozolomide-associated toxicity prevented demonstration of any potential combinatorial advantage with Erwinaze in vivo.

57. Med Lett Drugs Ther. 2018 Jan 29;60(1539):21-22. L-glutamine (Endari) for sickle cell disease. [No authors listed]

Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC.

Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC.

Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-l-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virus-endosome fusion. These findings both rationalize the great anti-influenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance. Glutamine inhibits ammonia-induced accumulation of cGMP in rat striatum limiting arginine supply for NO synthesis. Hilgier W(1), Freśko I, Klemenska E, Beresewicz A, Oja SS, Saransaari P, Albrecht J, Zielińska M. Author information: (1)Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. Brain L-glutamine (Gln) accumulation and increased activity of the NO/cGMP pathway are immediate consequences of acute exposure to ammonia. This study tested whether excess Gln may influence NO and/or cGMP synthesis. Intrastriatal administration of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine or the system A-specific Gln uptake inhibitor methylaminoisobutyrate increased microdialysate Gln concentration and reduced basal and ammonia-induced NO and cGMP accumulation. Gln applied in vivo (via microdialysis) or in vitro (to rat brain cortical slices) reduced NO and cGMP accumulation in the presence and/or absence of ammonia, but not cGMP synthesis induced by

38. Neurobiol Dis. 2009 Jul;35(1):75-81. doi: 10.1016/j.nbd.2009.04.004. Epub 2009 Apr 18. Glutamine inhibits ammonia-induced accumulation of cGMP in rat striatum limiting arginine supply for NO synthesis. Hilgier W(1), Freśko I, Klemenska E, Beresewicz A, Oja SS, Saransaari P, Albrecht J, Ziel

Our study aimed to find more effective protective agents against mucosa toxicity induced by methotrexate and 5-fluorouracil. We focused on the relationship between oral mucositis and keratinocyte injury and examined methotrexate and 5-fluorouracil-induced cytotoxicity in normal human epidermal keratinocyte cell lines. Cell viability and superoxide radical activity were measured based on converting WST-1 (4-[3-(4-indophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzen disulfonate) to a water-soluble formazan dye. DNA synthesis by 5-bromo-2'-deoxyuridine incorporation was measured as an indirect parameter of cell proliferation. Allopurinol and amifostine were used as the radical scavengers. l-glutamine was used as a mucosa-protective agent. A cyclooxygenase inhibitor interrupting the production of hydroxyl radicals in the arachidonic acid cascade was also examined. 5-fluorouracil and methotrexate caused cytotoxicity due to the activation of intracellular superoxide radicals specifically on normal human epidermal keratinocytes. From the electron spin resonance study, it was found that allopurinol was a superoxide radical scavenger, while amifostine was hydroxyl radical scavenger. Allopurinol showed no effect on the cytotoxicity due to 5-fluorouracil and methotrexate. The cell injury induced by methotrexate was restored by amifostine. However, the cell injury induced by 5-fluorouracil was markedly recovered by a selective cyclooxygenase-1 inhibitor compared to amifostine. It was suggested that amifostine and cyclooxygenase-1 inhibitor could be useful protective agents against methotrexate and 5-fluorouracil chemotherapeutic toxicity. Additionally, this in vitro cell injury model using normal human epidermal keratinocytes may be useful for understanding the pathophysiology of oral mucositis induced by chemotherapeutic agents.

Prolonged or excessive exposure to corticosterone leads to neuronal damages in the brain regions, including hippocampus. We reported that astrocyte-conditioned medium (ACM) protected the neurons of the primary hippocampal cultures against the corticosterone-induced damages. Corticosterone added to the cultures resulted in a significant number of TUNEL-positive cells. However, corticosterone-induced TUNEL labeling was suppressed as for ACM-cultured neurons. To delineate the molecular basis underlying the neuroprotection of ACM, we assessed the activation of ERK1/2 and (PI3-K)/Akt signal pathways in response to corticosterone-induced neuronal damages. Western blot test revealed that corticosterone increased the phosphorylation of ERK1/2 and PI3-K/Akt in hippocampal neurons grown in Neurobasal medium supplemented with B27 and 500 microm L-glutamine (NBM+). Interestingly, the increase of phospho-ERK1/2 and Akt levels was much pronounced and the time course of phosphorylation was altered in ACM, suggesting that both signaling pathways might participate in ACM protection. Furthermore, the selective inhibitor of Akt, rather than ERK1/2, blocked the neuroprotective activity against corticosterone in ACM-cultured neurons. In summary, our data showed that ACM had a potent neuroprotective effect in cultured neurons. PI3-K/Akt signal pathway, but not ERK1/2, was involved in the protective activity against the corticosterone-induced damages.

Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play a role in the increased risk for gastrointestinal cancers in alcoholics. In the present study, the effect of acetaldehyde on tyrosine phosphorylation, immunofluorescence localization, and detergent-insoluble fractions of the tight junction and the adherens junction proteins was determined in the human colonic mucosa. The role of EGF and L-glutamine in prevention of acetaldehyde-induced effects was also evaluated. Acetaldehyde reduced the protein tyrosine phosphatase activity, thereby increasing the tyrosine phosphorylation of occludin, E-cadherin, and beta-catenin. The levels of occludin, zonula occludens-1, E-cadherin, and beta-catenin in detergent-insoluble fractions were reduced by acetaldehyde, while it increased their levels in detergent-soluble fractions. Pretreatment with EGF or L-glutamine prevented acetaldehyde-induced protein tyrosine phosphorylation, redistribution from intercellular junctions, and reduction in the levels of detergent-insoluble fractions of occludin, zonula occludens-1, E-cadherin, and beta-catenin. These results demonstrate that acetaldehyde induces tyrosine phosphorylation and disrupts tight junction and adherens junction in human colonic mucosa, which can be prevented by EGF and glutamine.

From this detailed analysis of the main dietary trials conducted over the last 30 years in the secondary prevention of coronary heart disease, it can be said that the older trials were conducted on low risk patients and used high fat diets (about 40% of energy as lipids), comprising low saturated fat and cholesterol intake but very high (15 to 20% of energy) polyunsaturated fat intake, particularly from the omega-6 fatty acid family. These experimental diets were designed to reduce blood cholesterol and failed to improve prognosis. By contrast, recent trials were not primarily designed to reduce cholesterol, were conducted in medium- and high-risk patients and used low fat diets supplemented by omega-3 fatty acids from various sources. In two of these trials, the consumption of natural antioxidants, oligoelements and vegetable proteins was increased. Recurrence rate was reduced in the range of 30 to 70%. One conclusion from these well-conducted recent experiments on more than 3000 patients is that new and more specific dietary recommendations are clearly warranted in secondary prevention of coronary heart disease. They should be more specific and more clearly defined and therefore different from those generally provided in the U.S.A. and Europe at present. In a recent Consensus Panel statement, authors wrote less than one line to describe a cardioprotective diet in patients with coronary heart disease, summarized as < or = 30% fat, < 7% saturated fat, < 200 mg.day-1 cholesterol. This is both too much (too restrictive to hope that white European and American patients will adhere in the long-term) and insufficient because dietary counselling cannot be restricted to three factors. Ulbricht and Southgate recently emphasized that the relationship between diet and coronary heart disease is more complex than the current cholesterol hypothesis. They identified at least seven major dietary factors, including fibres, although the evidence of an effect on coronary heart disease is weak. However, they did not mention vegetable and fish proteins which are rich in arginine and L-glutamine, major regulators of cardiovascular function. Thus, new dietary advice should include: r

This systematic review aims to summarise the clinical outcomes of l-glutamine, crizanlizumab, and voxelotor in the treatment of sickle cell disease (SCD) based on clinical trials and real-world data and to identify any gaps in the observations. The review identified 97 studies reporting data until 31 May 2024. A pivotal phase III study of l-glutamine showed that patients treated with l-glutamine had a 25 % reduction in pain crises and 33 % fewer hospital days compared to placebo. l-glutamine was generally well tolerated with minimal side effects. Real-world studies of l-glutamine emphasize patient adherence and obstacles to medication accessibility and approval as key concerns. In the SUSTAIN study, a 5-mg/kg dose of crizanlizumab reduced the occurrence of vaso-occlusive crises (VOCs) and hospitalizations by 45 % and 41 %, respectively. Real-world studies of crizanlizumab showed a reduction in complicated VOC events. The high discontinuation rate and results of the STAND trial led to a significant decrease in the use of crizanlizumab. The HOPE trial demonstrated a 51 % improvement in hemoglobin response and a reduction in hemolytic markers in patients treated with voxelotor. While some real-world studies have reported a decrease in VOCs and hospitalizations, the results are inconsistent and not conclusive. Further studies are needed to assess the impact of these novel therapies on end-organ-specific complications of SCD.

Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection. AIM: The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer. MATERIALS AND METHOD: A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines. RESULTS: A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies. CONCLUSION: Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes. Publisher: La mucositis oral (MO) es una complicación frecuente en pacientes oncológicos sometidos a quimioterapia o radioterapia. Se manifiesta como una inflamación de la mucosa oral, provocando en ocasiones graves consecuencias como limitaciones en la alimentación, dificultad para hablar y posiblemente sobreinfección. Objetivo: El objetivo de esta revisión fue actualizar la evidencia publicada durante los últimos cinco años sobre el tratamiento de la mucositis oral inducida por radioterapia y/o quimioterapia, en pacientes con cáncer. Materiales y Método: Se realizó una búsqueda en Pubmed, Scielo y Scopus, con las palabras de búsqueda

BACKGROUND: Sickle cell disease (SCD) is a hemoglobinopathy with increasing global prevalence resulting in pain episodes and multiorgan complications. Complications of SCD have been shown to adversely impact health-related quality of life (HRQOL) comprised of physical, social, and emotional domains; hence, HRQOL measures can serve as an effective evaluator of disease burden. Hydroxyurea (HU) and other disease-modifying therapies have demonstrated to significantly improve clinical outcomes in patients with SCD. Medication adherence is an essential mediator of the clinical benefits of these therapies; low adherence has been shown to increase disease burden and healthcare utilization. This systematic literature review intends to determine the association between adherence to disease-modifying therapies and HRQOL in patients with SCD. METHODS: We found a total of 12 articles involving 788 participants, which included both patients with SCD and caregivers/parents. Adherence was measured using self-report instruments, laboratory markers, such as fetal hemoglobin and mean corpuscular volume, and mHealth medication trackers. HRQOL was measured using self-report instruments. RESULTS: All studies demonstrated a correlation between higher HU adherence and better HRQOL scores. Higher HU adherence was associated with lower pain impact, less frequent pain episodes, less fatigue, and improved physical function and mobility, reflecting better physical HRQOL outcomes. Higher adherence was also associated with improved emotional response, decreased anxiety and depressive symptoms, and better social functioning and peer relationships. In addition, our findings indicated that having less frequent barriers to HU adherence was associated with better HRQOL scores. No studies evaluated HRQOL outcomes in relation to adherence to l-glutamine, voxelotor, or crizanlizumab. CONCLUSIONS: Optimizing HU adherence has the potential to improve HRQOL in patients with SCD in addition to reducing healthcare utilization and improving treatment satisfaction. Addressing barriers to HU adherence can positively strengthen the relationship between adherence and HRQOL to potentially improve patient outcom

BACKGROUND: Myalgia reflects generalized inflammation and cytokine response and can be the onset symptom of 36% of patients with COVID-19. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) levels in plasma and upper respiratory secretions directly correlate with the magnitude of viral replication, fever, and respiratory and systemic symptoms, including musculoskeletal clinical manifestations. OBJECTIVE: The aim of our work is to report literature scientific investigation clinical protocol to reduce the immunomodulation and inflammatory response nutraceutical therapy associated with dexamethasone and how can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19. METHODS: We searched in Pubmed and Cochrane the nautriceutical drugs to treat the immune modulation of organism to COVID-19. We put these keywords: immune inflammation, desease descriptions, epidemiology COVID-19; immunomodulations; IL-6; Rheumatic Symptoms; Joint; Musculoskeletal Disorders; dexamethasone; Polydatin; Zinc; Melatonin; N- Acetyl Cysteine; Colostrum; L- Glutamine; Vitamin D3. RESULTS: We found 61 papers. All the authors analyze them. After the Analyze we suggest the use of response nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19. CONCLUSION: According the scientific literature nutraceutical therapy associated with dexamethasone can reduce the expression of Interlukina-6(IL-6) and myalgia due to COVID-19. © 2022 Umberto Ripani, Michele Bisaccia, Luigi Meccariello.

PURPOSE: Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures. METHODS: We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database. RESULTS: We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism. CONCLUSIONS: This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.

Different amino acids (AAs) may exert distinct effects on postprandial glucose and insulin concentrations. A quantitative comparison of the effects of AAs on glucose and insulin kinetics in humans is currently lacking. PubMed was queried to identify intervention studies reporting glucose and insulin concentrations after acute ingestion and/or intravenous infusion of AAs in healthy adults and those living with obesity and/or type 2 diabetes (T2DM). The systematic literature search identified 55 studies that examined the effects of l-leucine, l-isoleucine, l-alanine, l-glutamine, l-arginine, l-lysine, glycine, l-proline, l-phenylalanine, l-glutamate, branched-chain AAs (i.e., l-leucine, l-isoleucine, and l-valine), and multiple individual l-AAs on glucose and insulin concentrations. Oral ingestion of most individual AAs induced an insulin response, but did not alter glucose concentrations in healthy participants. Specific AAs (i.e., leucine and isoleucine) co-ingested with glucose exerted a synergistic effect on the postprandial insulin response and attenuated the glucose response compared to glucose intake alone in healthy participants. Oral AA ingestion as well as intravenous AA infusion was able to stimulate an insulin response and decrease glucose concentrations in T2DM and obese individuals. The extracted information is publicly available and can serve multiple purposes such as computational modeling.

OBJECTIVES: Treatment options for preventing vaso-occlusive crises (VOC) among patients with sickle cell disease (SCD) are limited, especially if hydroxyurea treatment has failed or is contraindicated. A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the efficacy and safety of crizanlizumab for older adolescent and adult (≥16 years old) SCD patients. METHODS: The SLR included randomised controlled trials (RCTs) and uncontrolled studies. Bayesian NMA of VOC, all-cause hospitalisation days and adverse events were conducted. RESULTS: The SLR identified 51 studies and 9 RCTs on 14 treatments that met the NMA inclusion criteria. The NMA found that crizanlizumab 5.0 mg/kg was associated with a reduction in VOC (HR 0.55, 95% credible interval (0.43, 0.69); Bayesian probability of superiority >0.99), all-cause hospitalisation days (0.58 (0.50, 0.68); >0.99) and no evidence of difference on adverse events (0.91 (0.59, 1.43) 0.66) or serious adverse events (0.93 (0.47, 1.87); 0.59) compared with placebo. The HR for reduction in VOC for crizanlizumab relative to L-glutamine was (0.67 (0.50, 0.88); >0.99). These results were sensitive to assumptions regarding whether patient age is an effect modifier. CONCLUSIONS: This NMA provides preliminary evidence comparing the efficacy of crizanlizumab with other treatments for VOC prevention. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Hydroxyurea, indicated for managing sickle cell anemia (SCA), and L-glutamine, indicated for treating sickle cell disease (SCD), were the only pharmacotherapeutic options in this patient population before the approval of crizanlizumab by the U.S. Food and Drug Administration in November 2019 to reduce vaso-occlusive crisis (VOC) frequency. This article reviews the evidence pertaining to crizanlizumab in SCD by searching records in Medline, Embase, and International Pharmaceutical Abstracts. Crizanlizumab, a P-selectin inhibitor, mitigates the microvascular vaso-occlusion in SCD. In the multicenter randomized double-blind SUSTAIN trial, a higher dose of crizanlizumab decreased the incidence of VOCs by 45% and prolonged the median time to the first and second VOC. A post hoc subgroup analysis demonstrated that the proportion of patients who had no VOC incidence during the study period was greater in the crizanlizumab group, and this benefit was consistent regardless of concomitant hydroxyurea use, prior categorized history of VOC frequency, or SCD genotype. Crizanlizumab had a safety profile comparable with placebo. Multiple ongoing clinical trials are trying to establish its roles in pediatric patients with SCD and its effects on alleviating other SCD-related complications. As the first parenteral option for SCD, providers need to formulate administration logistics to improve patients' access to crizanlizumab. Current available data suggest crizanlizumab is a promising agent to reduce VOC in patients with SCD. © 2020 Pharmacotherapy Publications, Inc.