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Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.
Ma, C, Tsai, H, Su, W, Sun, L, Shih, Y, Wang, J
Journal of postgraduate medicine. 2018;(3):155-163
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Abstract
BACKGROUND Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. MATERIALS AND METHODS This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. RESULTS No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). CONCLUSION Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.
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Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of L-arginine study).
Monti, LD, Galluccio, E, Villa, V, Fontana, B, Spadoni, S, Piatti, PM
European journal of nutrition. 2018;(8):2805-2817
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Abstract
PURPOSE This study aimed to determine whether L-arginine supplementation lasting for 18 months maintained long-lasting effects on diabetes incidence, insulin secretion and sensitivity, oxidative stress, and endothelial function during 108 months among subjects at high risk of developing type 2 diabetes. METHODS One hundred and forty-four middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an L-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. The primary outcome was a diagnosis of diabetes during the 108 month study period. Secondary outcomes included changes in insulin secretion (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress (AOPPs), and vascular function. After the 18 month participation, subjects that were still free of diabetes and willing to continue their participation (104 subjects) were further followed until diabetes diagnosis, with a time span of about 9 years from baseline. RESULTS Although results derived from the 18 month of the intervention study demonstrated no differences in the probability of becoming diabetics, at the end of the study, the cumulative incidence of diabetes was of 40.6% in the L-arginine group and of 57.4% in the placebo group. The adjusted HR for diabetes (L-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP (p < 0.05) levels were ameliorated in L-arginine compared to placebo. CONCLUSIONS These results may suggest that the administration of L-arginine could delay the development of T2DM for a long period. This effect could be mediated, in some extent, by L-arginine-induced reduction in oxidative stress.
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Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou's general pseudo amino acid composition.
Ju, Z, Wang, SY
Gene. 2018;:78-83
Abstract
As one of the most important and common protein post-translational modifications, citrullination plays a key role in regulating various biological processes and is associated with several human diseases. The accurate identification of citrullination sites is crucial for elucidating the underlying molecular mechanisms of citrullination and designing drugs for related human diseases. In this study, a novel bioinformatics tool named CKSAAP_CitrSite is developed for the prediction of citrullination sites. With the assistance of support vector machine algorithm, the highlight of CKSAAP_CitrSite is to adopt the composition of k-spaced amino acid pairs surrounding a query site as input. As illustrated by 10-fold cross-validation, CKSAAP_CitrSite achieves a satisfactory performance with a Sensitivity of 77.59%, a Specificity of 95.26%, an Accuracy of 89.37% and a Matthew's correlation coefficient of 0.7566, which is much better than those of the existing prediction method. Feature analysis shows that the N-terminal space containing pairs may play an important role in the prediction of citrullination sites, and the arginines close to N-terminus tend to be citrullinated. The conclusions derived from this study could offer useful information for elucidating the molecular mechanisms of citrullination and related experimental validations. A user-friendly web-server for CKSAAP_CitrSite is available at 123.206.31.171/CKSAAP_CitrSite/.
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l-Arginine supplementation does not improve muscle function during recovery from resistance exercise.
Andrade, WB, Jacinto, JL, da Silva, DK, Roveratti, MC, Estoche, JM, Oliveira, DB, Balvedi, MCW, da Silva, RA, Aguiar, AF
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(9):928-936
Abstract
The purpose of this study was to investigate the effects of l-arginine supplementation on muscle recovery after a single session of high-intensity resistance exercise (RE). Twenty healthy young adult participants (22.8 ± 3.4 years old) were assigned to 1 of 2 groups (N = 10 per group): a placebo-supplement group or an l-arginine-supplement group. The groups completed a session of high-intensity RE (0 h) and 3 subsequent fatigue test sessions (at 24, 48, and 72 h postexercise) to assess the time course of muscle recovery. During the test sessions, we assessed the following dependent variables: number of maximum repetitions, electromyographic signal (i.e., root mean square (RMS) and median frequency (MF) slope), muscle soreness, perceived exertion, blood levels of creatine kinase (CK) and lactate, and testosterone:cortisol ratio. Number of maximum repetitions increased at 48 and 72 h postexercise in both groups (time, P < 0.05). CK levels and muscle soreness increased at 24 h postexercise and then progressively returned to baseline at 72 h post exercise in both groups (time, P < 0.05). Lactate levels increased immediately postexercise but were reduced at 24 h postexercise in both groups (time, P < 0.05). Testosterone:cortisol ratio, RMS, and MF slope remained unchanged during the recovery period in both groups (time, P > 0.05). No significant (P > 0.05) group × time interaction was found for all dependent variables during the recovery period. In conclusion, our data indicate that l-arginine supplementation does not improve muscle recovery following a high-intensity RE session in young adults.
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Effects of single and combined metformin and L-citrulline supplementation on L-arginine-related pathways in Becker muscular dystrophy patients: possible biochemical and clinical implications.
Hanff, E, Hafner, P, Bollenbach, A, Bonati, U, Kayacelebi, AA, Fischer, D, Tsikas, D
Amino acids. 2018;(10):1391-1406
Abstract
The L-arginine/nitric oxide synthase (NOS) pathway is considered to be altered in muscular dystrophy such as Becker muscular dystrophy (BMD). We investigated two pharmacological options aimed to increase nitric oxide (NO) synthesis in 20 male BMD patients (age range 21-44 years): (1) supplementation with L-citrulline (3 × 5 g/d), the precursor of L-arginine which is the substrate of neuronal NO synthase (nNOS); and (2) treatment with the antidiabetic drug metformin (3 × 500 mg/d) which activates nNOS in human skeletal muscle. We also investigated the combined use of L-citrulline (3 × 5 g/d) and metformin (3 × 500 mg/d). Before and after treatment, we measured in serum and urine samples the concentration of amino acids and metabolites of L-arginine-related pathways and the oxidative stress biomarker malondialdehyde (MDA). Compared to healthy subjects, BMD patients have altered NOS, arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) pathways. Metformin treatment resulted in concentration decrease of arginine and MDA in serum, and of homoarginine (hArg) and guanidinoacetate (GAA) in serum and urine. L-Citrulline supplementation resulted in considerable increase of the concentrations of amino acids and creatinine in the serum, and in their urinary excretion rates. Combined use of metformin and L-citrulline attenuated the effects obtained from their single administrations. Metformin, L-citrulline or their combination did not alter serum nitrite and nitrate concentrations and their urinary excretion rates. In conclusion, metformin or L-citrulline supplementation to BMD patients results in remarkable antidromic changes of the AGAT and GAMT pathways. In combination, metformin and L-citrulline at the doses used in the present study seem to abolish the biochemical effects of the single drugs in slight favor of L-citrulline.
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Perioperative Nutritional Support With Beta-hydroxy-beta-methylbutyrate, Arginine, and Glutamine in Surgery for Abdominal Malignancies.
Wada, N, Kurokawa, Y, Tanaka, K, Miyazaki, Y, Makino, T, Takahashi, T, Wada, H, Yamasaki, M, Yamasaki, M, Nakajima, K, et al
Wounds : a compendium of clinical research and practice. 2018;(9):251-256
Abstract
UNLABELLED Although beta-hydroxy-beta-methylbutyrate (HMB), arginine (Arg), and glutamine (Gln) may contribute to wound healing, no prospective studies have investigated the efficacy of a compound consisting of HMB, Arg, and Gln (HMB/Arg/Gln) for reducing wound complications following open abdominal surgery. OBJECTIVE This study evaluates the usefulness of perioperative nutrition using HMB/Arg/Gln in patients who were scheduled to undergo open surgery for abdominal malignancies in a randomized controlled trial. MATERIALS AND METHODS Patients scheduled for open surgery for abdominal malignancies were randomized to receive HMB/Arg/Gln (1.2 g HMB, 7 g L-Arg, and 7 g L-Gln) or placebo (isocaloric juice). The supplements were provided once daily for 3 days preoperatively and once daily for 7 days postoperatively. The primary endpoint was the incidence of wound complications. Secondary endpoints included the incidence of other complications, postoperative duration of hospital stay, total-body skeletal muscle mass, handgrip strength, and skin water content. RESULTS Sixty-one patients were randomly assigned to either the HMB/Arg/Gln (n = 31) or the placebo (n = 30) group. One patient in the HMB/Arg/Gln group was ineligible because laparoscopic surgery was performed; thus, 60 patients were analyzed. The incidence of wound complications (20%) was the same in both groups (P = 1.000). There were no significant differences in the incidence of other complications, body composition, handgrip strength, or skin water content between the 2 groups. Serum growth hormone (GH) levels were significantly higher for patients whose total intake was > 80% of planned volume in the HMB/Arg/Gln group. CONCLUSIONS The incidence of wound complications would not be reduced by perioperative HMB/Arg/Gln administration in patients who underwent open surgery. The efficacy of HMB/Arg/Gln for increasing serum GH levels needs to be validated in another large-scale randomized controlled trial.
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The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.
Wolff, MS, Schenkel, AB
Advances in dental research. 2018;(1):93-97
Abstract
Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.
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Domain communication in Thermotoga maritima Arginine Binding Protein unraveled through protein dissection.
Smaldone, G, Balasco, N, Vigorita, M, Ruggiero, A, Cozzolino, S, Berisio, R, Del Vecchio, P, Graziano, G, Vitagliano, L
International journal of biological macromolecules. 2018;:758-769
Abstract
Substrate binding proteins represent a large protein family that plays fundamental roles in selective transportation of metabolites across membrane. The function of these proteins relies on the relative motions of their two domains. Insights into domain communication in this class of proteins have been here collected using Thermotoga maritima Arginine Binding Protein (TmArgBP) as model system. TmArgBP was dissected into two domains (D1 and D2) that were exhaustively characterized using a repertoire of different experimental and computational techniques. Indeed, stability, crystalline structure, ability to recognize the arginine substrate, and dynamics of the two individual domains have been here studied. Present data demonstrate that, although in the parent protein both D1 and D2 cooperate for the arginine anchoring; only D1 is intrinsically able to bind the substrate. The implications of this finding on the mechanism of arginine binding and release by TmArgBP have been discussed. Interestingly, both D1 and D2 retain the remarkable thermal/chemical stability of the parent protein. The analysis of the structural and dynamic properties of TmArgBP and of the individual domains highlights possible routes of domain communication. Finally, this study generated two interesting molecular tools, the two stable isolated domains that could be used in future investigations.
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[Enzymatic production of arginine derivatives: a review].
Sun, A, Song, W, Liu, J, Luo, Q, Chen, X, Liu, L
Sheng wu gong cheng xue bao = Chinese journal of biotechnology. 2018;(2):165-176
Abstract
L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.
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Arginine Deprivation Therapy: Putative Strategy to Eradicate Glioblastoma Cells by Radiosensitization.
Hinrichs, CN, Ingargiola, M, Käubler, T, Löck, S, Temme, A, Köhn-Luque, A, Deutsch, A, Vovk, O, Stasyk, O, Kunz-Schughart, LA
Molecular cancer therapeutics. 2018;(2):393-406
Abstract
Tumor cells-even if nonauxotrophic-are often highly sensitive to arginine deficiency. We hypothesized that arginine deprivation therapy (ADT) if combined with irradiation could be a new treatment strategy for glioblastoma (GBM) patients because systemic ADT is independent of local penetration and diffusion limitations. A proof-of-principle in vitro study was performed with ADT being mimicked by application of recombinant human arginase or arginine-free diets. ADT inhibited two-dimensional (2-D) growth and cell-cycle progression, and reduced growth recovery after completion of treatment in four different GBM cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a three-dimensional (3-D) environment. Migration and 3-D invasion were not unfavorably affected. However, ADT caused a significant radiosensitization that was more pronounced in a GBM cell model with p53 loss of function as compared with its p53-wildtype counterpart. The synergistic effect was independent of basic and induced argininosuccinate synthase or argininosuccinate lyase protein expression and not abrogated by the presence of citrulline. The radiosensitizing potential was maintained or even more distinguishable in a 3-D environment as verified in p53-knockdown and p53-wildtype U87-MG cells via a 60-day spheroid control probability assay. Although the underlying mechanism is still ambiguous, the observation of ADT-induced radiosensitization is of great clinical interest, in particular for patients with GBM showing high radioresistance and/or p53 loss of function. Mol Cancer Ther; 17(2); 393-406. ©2017 AACRSee all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology."