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Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.
Costa, G, Shushanof, M, Bouskela, E, Bottino, D
Journal of vascular research. 2022;(1):24-33
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Abstract
OBJECTIVE The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM). METHODS Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day). RESULTS L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups. CONCLUSION L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.
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Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.
Adiamah, A, Rollins, KE, Kapeleris, A, Welch, NT, Iftikhar, SY, Allison, SP, Lobo, DN
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5482-5485
Abstract
BACKGROUND & AIMS Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.
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Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency.
Coughlin, CR, Tseng, LA, Abdenur, JE, Ashmore, C, Boemer, F, Bok, LA, Boyer, M, Buhas, D, Clayton, PT, Das, A, et al
Journal of inherited metabolic disease. 2021;(1):178-192
Abstract
Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided.
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Protein arginine phosphorylation in organisms.
Huang, B, Zhao, Z, Zhao, Y, Huang, S
International journal of biological macromolecules. 2021;:414-422
Abstract
Protein arginine phosphorylation (pArg), a novel molecular switch, plays a key role in regulating cellular processes. The intrinsic acid lability, hot sensitivity, and hot-alkali instability of "high-energy" phosphoamidate (PN bond) in pArg, make the investigation highly difficult and challenging. Recently, the progress in identifying prokaryotic protein arginine kinase/phosphatase and assigning hundreds of pArg proteins and phosphosites has been made, which is arousing scientists' interest and passions. It shows that pArg is tightly connected to bacteria stress response and pathogenicity, and is probably implied in human diseases. In this review, we highlight the strategies for investigation of this mysterious modification and its momentous physiological functions, and also prospect for the potentiality of drugs development targeting pArg-relative pathways.
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Acute Inositol-Stabilized Arginine Silicate Improves Cognitive Outcomes in Healthy Adults.
Gills, JL, Campitelli, A, Jones, M, Paulson, S, Myers, JR, Madero, EN, Glenn, JM, Komorowski, J, Gray, M
Nutrients. 2021;(12)
Abstract
Inositol-stabilized arginine silicate (ASI) is an ergogenic aid that upregulates nitric oxide. Acute ASI supplementation improves working memory and processing speed in young adults but there is a lack of data examining other cognitive tasks. Therefore, the purpose of this study was to examine acute ASI effects on young healthy adults by assessing multiple cognitive domains. Nineteen young adults (20.9 ± 3.2 years) completed this randomized, double-blind, crossover study consuming ASI (1.5 g ASI + 12 g dextrose) and placebo (12 g dextrose). The participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and two digital cognitive assessments before consuming the supplement and then completed the same battery of tests 60 min post-supplementation. Repeated measures ANOVA demonstrated that ASI consumption significantly improved total RBANS and immediate memory scores compared to the placebo (p < 0.05). However, no significant differences were displayed between trials for other cognitive domains (p > 0.05). Acute ASI ingestion increased overall RBANS scores and immediate memory scores in young adults. More research is needed to examine the acute effects of ASI on other domains of cognition, in older populations, and its long-term effects on cognition.
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Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure.
Salmani, M, Alipoor, E, Navid, H, Farahbakhsh, P, Yaseri, M, Imani, H
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3037-3044
Abstract
BACKGROUND & AIMS Heart failure (HF), as a major cardiac disease, is associated with considerable mortality, morbidities and poor quality of life. The aim of this study was to investigate the effect of l-arginine supplementation on cardiac outcomes and quality of life in patients with ischemic HF. METHODS This double-blind randomized controlled clinical trial was conducted in 50 patients with ischemic HF. Patients were randomly assigned to receive either 3 gr/d l-arginine or placebo, for 10 weeks. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. RESULTS The results showed significant improvements in ejection fraction (-6.5 ± 8.7 vs. -0.7 ± 7.8%, P = 0.037), left ventricular function (P = 0.043), diastolic dysfunction (P = 0.01) and marginally improvement in changes of left ventricular dimension during diastole (LVDd) (4 ± 6 vs. 0.3 ± 6.9 mm, P = 0.065) in the l-arginine compared to the placebo group. At the end of the study, physical aspect (5.7 ± 3.3 vs. 1.2 ± 6.1, P = 0.002) and total score (10 ± 6.7 vs. 4.1 ± 9.4, P = 0.011) of quality of life improved significantly in the l-arginine compared with the placebo group. Additionally, pre-to post-values of diastolic blood pressure, mean arterial pressure, LVDd, LV ejection fraction, left ventricular function, diastolic dysfunction as well as physical and total scores of quality of life improved significantly within the intervention, but not the placebo, group (all P < 0.05). CONCLUSION This study showed that 3 gr/d l-arginine supplementation for 10 weeks could improve cardiac recovery and function, and quality of life in patients with HF. This study was registered at the Iranian Clinical Trial Registration Center (www.irct.ir) with IRCT20170202032367N4 code.
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L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.
Castejón-Vega, B, Rubio, A, Pérez-Pulido, AJ, Quiles, JL, Lane, JD, Fernández-Domínguez, B, Cachón-González, MB, Martín-Ruiz, C, Sanz, A, Cox, TM, et al
Cells. 2021;(11)
Abstract
AIMS: Tay-Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay-Sachs and Sandhoff diseases. RESULTS Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of mature cathepsins and HexA into the cytosol, indicating increased lysosomal permeability. GM2 fibroblasts showed diminished mTOR signalling with reduced basal mTOR activity. Accordingly, provision of a positive nutrient signal by L-arginine supplementation partially restored mTOR activity and ameliorated the cytopathological abnormalities. INNOVATION Our data provide a novel molecular mechanism underlying GM2 gangliosidosis. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for these diseases. CONCLUSIONS We contend that the expression of autophagy/lysosome/mTOR-associated molecules may prove useful peripheral biomarkers for facile monitoring of treatment of GM2 gangliosidosis and neurodegenerative disorders that affect the lysosomal function and disrupt autophagy.
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Arginine methylation: the promise of a 'silver bullet' for brain tumours?
Samuel, SF, Barry, A, Greenman, J, Beltran-Alvarez, P
Amino acids. 2021;(4):489-506
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Abstract
Despite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT-protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours.
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Effects of Inositol-Enhanced Bonded Arginine Silicate Ingestion on Cognitive and Executive Function in Gamers.
Sowinski, R, Gonzalez, D, Xing, D, Yoo, C, Jenkins, V, Nottingham, K, Dickerson, B, Humphries, M, Leonard, M, Ko, J, et al
Nutrients. 2021;(11)
Abstract
Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7-14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.
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L-Arginine Improves Endurance to High-Intensity Interval Exercises in Overweight Men.
Daraei, A, Ahmadizad, S, Rahmani, H, Hackney, AC, Johnson, KE, Laher, I, Saeidi, A, Zouhal, H
International journal of sport nutrition and exercise metabolism. 2021;(1):46-54
Abstract
The effects of acute consumption of L-Arginine (L-Arg) in healthy young individuals are not clearly defined, and no studies on the effects of L-Arg in individuals with abnormal body mass index undertaking strenuous exercise exist. Thus, we examined whether supplementation with L-Arg diminishes cardiopulmonary exercise testing responses, such as ventilation (VE), VE/VCO2, oxygen uptake (VO2), and heart rate, in response to an acute session of high-intensity interval exercise (HIIE) in overweight men. A double-blind, randomized crossover design was used to study 30 overweight men (age, 26.5 ± 2.2 years; body weight, 88.2 ± 5.3 kilogram; body mass index, 28.0 ± 1.4 kg/m2). Participants first completed a ramped-treadmill exercise protocol to determine VO2max velocity (vVO2max), after which they participated in two sessions of HIIE. Participants were randomly assigned to receive either 6 g of L-Arg or placebo supplements. The HIIE treadmill running protocol consisted of 12 trials, including exercise at 100% of vVO2max for 1 min interspersed with recovery intervals of 40% of vVO2max for 2 min. Measurements of VO2 (ml·kg-1·min-1), VE (L/min), heart rate (beat per min), and VE/VCO2 were obtained. Supplementation with L-Arg significantly decreased all cardiorespiratory responses during HIIE (placebo+HIIE vs. L-Arg+HIIE for each measurement: VE [80.9 ± 4.3 L/min vs. 74.6 ± 3.5 L/min, p < .05, ES = 1.61], VE/VCO2 [26.4 ± 1.3 vs. 24.4 ± 1.0, p < .05, ES = 1.8], VO2 [26.4 ± 0.8 ml·kg-1·min-1 vs. 24.4 ± 0.9 ml·kg-1·min-1, p < .05, ES = 2.2], and heart rate [159.7 ± 6.3 beats/min vs. 155.0 ± 3.7 beats/min, p < .05, d = 0.89]). The authors conclude consuming L-Arg before HIIE can alleviate the excessive physiological strain resulting from HIIE and help to increase exercise tolerance in participants with a higher body mass index who may need to exercise on a regular basis for extended periods to improve their health.