RNA

(Ribonucleic Acid)
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Published Clinical Studies

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Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.
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Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer.
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Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome.
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Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.
*
Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.
*
Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.
*
The metabolic effects of enterally administered ribonucleic acids.

1
Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.

Kemen M, Senkal M, Homann HH, Mumme A, Dauphin AK, Baier J, Windeler J, Neumann H, Zumtobel V.



Department of Surgery, Ruhr-University Bochum, St. Josef Hospital, FRG.

OBJECTIVE: To evaluate the effect of early postoperative feeding with a nutritionally complete enteral diet supplemented with the nutrients arginine, ribonucleic acid (RNA), and omega-3 fatty acids on the immune function in patients undergoing surgery for upper gastrointestinal (GI) malignancies. DESIGN: Prospective, randomized, placebo-controlled, double-blind study. SETTING: Surgical intensive care unit (ICU) in a German university hospital. PATIENTS: Forty-two consecutive patients receiving an enteral diet via needle catheter jejunostomy after GI surgery for cancer. INTERVENTIONS: Patients were randomized to receive either the arginine, RNA, and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet. Early enteral nutrition was started on postoperative day 1 in the surgical ICU with 20 mL/hr and progressed to the optimal goal of 80 mL/hr by postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse GI symptoms were recorded on a daily basis. Body weight was determined twice weekly. Immunoglobulin concentrations were determined by laser nephelometry. Interferon-gamma concentrations were measured with a modified enzyme-linked immunosorbent assay method. Fluorescence-activated cell scan flow cytometry was performed to analyze B cells, T lymphocytes and their subsets. Clinical patient characteristics and mean caloric intake were similar between the two groups and both formulas were well tolerated. The number of T lymphocytes and their subsets, helper T cells (CD4) and activated T cells (CD3, HLA-DR), were significantly higher in the supplemented diet group on postoperative days 10 and 16 (p < .05). Mean interferon-gamma concentration after phytohemagglutinin stimulation was higher in the supplemented diet group on postoperative day 16. In the supplemented diet group, mean immunoglobulin M concentrations were significantly higher on postoperative day 10 and mean immunoglobulin G concentrations were higher on postoperative day 16 (p < .05) compared with the results in the placebo group. B-lymphocyte indices were significantly higher in the supplemented vs. the placebo diet group on postoperative days 7 and 10 (p < .05). CONCLUSIONS: Supplementation of enteral diet with arginine, RNA, and omega-3 fatty acids in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma.

Publication Types:

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Clinical Trial
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Randomized Controlled Trial

PMID: 7536138 [PubMed - indexed for MEDLINE]



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2
Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer.

Senkal M, Kemen M, Homann HH, Eickhoff U, Baier J, Zumtobel V.



Department of Surgery, Ruhr-University Bochum, St. Josef Hospital, Germany.

OBJECTIVE: To find out whether an enteral diet supplemented with arginine, RNA, and omega-3 fatty acids modulated the production of interleukin-1 (IL-1), interleukin-2 (IL-2), IL-2 receptor, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha) after operations for upper gastrointestinal cancer. DESIGN: Prospective double blind clinical study. SETTING: University hospital, Germany. SUBJECTS: 42 patients randomised into two groups (n = 21 each), one of which was given an isocaloric and isonitrogenous placebo diet and one of which was fed the same diet supplemented with arginine, RNA, and omega-3 fatty acids. INTERVENTIONS: The cytokines were measured before operation and on postoperative days 1, 3, 7, 10, and 16. MAIN OUTCOME MEASURES: Comparison of concentrations of cytokines in the two groups. RESULTS: Among those receiving the placebo diet (after spontaneous stimulation) IL-6 concentrations were significantly higher on days 3 and 7 (p < 0.05) and TNF-alpha concentrations on day 7. In contrast (after stimulation with phytohaemagglutinin) mean concentrations of IL-2 receptor were significantly higher on days 3 and 7, and of IL-1 beta and IL-2 on day 16 (p < 0.05) in the group receiving the supplemented diet. CONCLUSION: Supplementation of an enteral diet with arginine, RNA and omega-3 fatty acids can modulate the acute phase reaction as indicated by the reduction in concentrations of TNF-alpha and IL-6 in the group fed the supplemented diet. Patients receiving the supplemented diet also showed accelerated recovery in the concentrations of IL-1 beta and IL-2 receptor.

Publication Types:

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Clinical Trial
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Randomized Controlled Trial
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Review
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Review, Tutorial

PMID: 7539633 [PubMed - indexed for MEDLINE]



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3
Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome.

Daly JM, Lieberman MD, Goldfine J, Shou J, Weintraub F, Rosato EF, Lavin P.



Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.

The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune function, but prospective trials have not demonstrated their effects on clinical outcome. Patients (n = 85) who underwent operation for upper gastrointestinal malignancies were randomized to receive the supplemental diet or a standard enteral diet after surgery. Clinical patient characteristics were similar between the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs -6.6 gm/day) measured in the first 20 patients were significantly greater in the supplemented group than in the standard group (p = 0.05). In vitro lymphocyte mitogenesis was measured in the first 31 patients and was decreased on postoperative day 1 in both groups, but normal levels were regained only in the supplemented group. In the cohort of 77 eligible patients, infectious and wound complications occurred significantly less often (11% vs 37%) in the supplemented group than in the standard group (p = 0.02). Linear logistic models for infectious/wound complications with control for the amount of nitrogen suggested (p = 0.10) dietary treatment as the major factor. Mean length of stay in the hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/- 5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids instead of a standard enteral diet significantly improved immunologic, metabolic, and clinical outcomes in patients with upper gastrointestinal malignancies who were undergoing major elective surgery.

Publication Types:

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Clinical Trial
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Randomized Controlled Trial

PMID: 1377838 [PubMed - indexed for MEDLINE]



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4
Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.

Tepaske R, Velthuis H, Oudemans-van Straaten HM, Heisterkamp SH, van Deventer SJ, Ince C, Eysman L, Kesecioglu J.



Department of Intensive, University of Amsterdam, Academic Medical Centre, Amsterdam, Netherlands. r.tepaske@amc.uva.nl

BACKGROUND: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. METHODS: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. FINDINGS: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. INTERPRETATION: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

Publication Types:

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Clinical Trial
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Randomized Controlled Trial

PMID: 11551575 [PubMed - indexed for MEDLINE]



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5
Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact.

Kemen M, Senkal M, Homann HH, Mumme A, Dauphin AK, Baier J, Windeler J, Neumann H, Zumtobel V.



Department of Surgery, Ruhr-University Bochum, St. Josef Hospital, FRG.

OBJECTIVE: To evaluate the effect of early postoperative feeding with a nutritionally complete enteral diet supplemented with the nutrients arginine, ribonucleic acid (RNA), and omega-3 fatty acids on the immune function in patients undergoing surgery for upper gastrointestinal (GI) malignancies. DESIGN: Prospective, randomized, placebo-controlled, double-blind study. SETTING: Surgical intensive care unit (ICU) in a German university hospital. PATIENTS: Forty-two consecutive patients receiving an enteral diet via needle catheter jejunostomy after GI surgery for cancer. INTERVENTIONS: Patients were randomized to receive either the arginine, RNA, and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet. Early enteral nutrition was started on postoperative day 1 in the surgical ICU with 20 mL/hr and progressed to the optimal goal of 80 mL/hr by postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Clinical examination and adverse GI symptoms were recorded on a daily basis. Body weight was determined twice weekly. Immunoglobulin concentrations were determined by laser nephelometry. Interferon-gamma concentrations were measured with a modified enzyme-linked immunosorbent assay method. Fluorescence-activated cell scan flow cytometry was performed to analyze B cells, T lymphocytes and their subsets. Clinical patient characteristics and mean caloric intake were similar between the two groups and both formulas were well tolerated. The number of T lymphocytes and their subsets, helper T cells (CD4) and activated T cells (CD3, HLA-DR), were significantly higher in the supplemented diet group on postoperative days 10 and 16 (p < .05). Mean interferon-gamma concentration after phytohemagglutinin stimulation was higher in the supplemented diet group on postoperative day 16. In the supplemented diet group, mean immunoglobulin M concentrations were significantly higher on postoperative day 10 and mean immunoglobulin G concentrations were higher on postoperative day 16 (p < .05) compared with the results in the placebo group. B-lymphocyte indices were significantly higher in the supplemented vs. the placebo diet group on postoperative days 7 and 10 (p < .05). CONCLUSIONS: Supplementation of enteral diet with arginine, RNA, and omega-3 fatty acids in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma.

Publication Types:

*
Clinical Trial
*
Randomized Controlled Trial

PMID: 7536138 [PubMed - indexed for MEDLINE]



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6
Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

Bower RH, Cerra FB, Bershadsky B, Licari JJ, Hoyt DB, Jensen GL, Van Buren CT, Rothkopf MM, Daly JM, Adelsberg BR.



Department of Surgery, University of Cincinnati College of Medicine, OH.

OBJECTIVE: To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). DESIGN: A prospective, randomized, double-blind, multicenter trial. SETTING: ICUs in eight different hospitals. PATIENTS: Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age (< 60 or > or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). INTERVENTIONS: Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. MEASUREMENTS AND MAIN RESULTS: Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. CONCLUSIONS: Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections.

Publication Types:

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Clinical Trial
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Multicenter Study
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Randomized Controlled Trial

PMID: 7874893 [PubMed - indexed for MEDLINE]



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The metabolic effects of enterally administered ribonucleic acids.7

Rudolph FB, Van Buren CT.



Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892, USA. fbr@rice.edu

Roles for dietary sources of preformed purines and pyrimidines such as RNA in various systems have been demonstrated in recent years. These include maintenance of a competent immune system, gut development, hepatic function and many others, with a central theme of rapidly dividing cells requiring these compounds for optimal function. These compounds were previously thought to be non-essential but are now considered to be conditionally required when various stresses, including rapid growth and infection, are present. A number of recent studies are summarized that cover a variety of areas and are consistent with critical roles for dietary sources of nucleotides for many cellular functions.

Publication Types:

*
Review
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Review, Tutorial

PMID: 10565405 [PubMed - indexed for MEDLINE]



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Referencesref

1.
Bower RH, Cerra FB, Bershadsky B, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized clinical trial. Crit Care Med 1995;23(3):436-49.
2.
Anon. 2000 www.angelfire.com/co2/slendermummie/madna.html. (Accessed 21 March 2000).
3.
Tepaske R, Velthuis H, Oudemans-van Straaten HM, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet 2001;358:696-701.
4.
Rudolph FB, Van Buren CT. The metabolic effects of enterally administered ribonucleic acids. Current Opinion in Clinical Nutrition and Metabolic Care 1998;1(6):527-30.
5.
Van Buren CT, Rudolph F. Dietary nucleotides: a conditional requirement. Nutr 1997;13(5):470-2.
6.
Schubert R, Hohlweg U, Renz D, Doefler W. On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission o the fetus. Mol Gen Genet 1998;259:569-76.
7.
Li L. Erythematous skin reaction to subcutaneous injection of ribonucleic acid. Contact Dermatitis 1999;41:239.
8.
Saffle JR, Wiebke G, Jennings K, et al. Randomized trial of immune-enhancing enteral nutrition in burn patients. The Journal of Trauma, Injury, Infection and Critical Care 1997;42(5):793-802.
9.
Gianotti L, Braga M, Fortis C, et al. A prospective, randomized clinical trial on perioperative feeding with an arginine, omega-3-fatty acid, and RNA-enriched enteral diet: effect on host response and nutritional status. Journal of Parenteral and Enteral Nutrition 1999;23(6):314-20.
10.
Kemen M, Senkal M, Homann HH, et al. Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet vs placebo in cancer patients: an immunologic evaluation of impact. Crit Care Med 1995;23:652-9.
11.
Senkal M, Kemen M, Homann HH, et al. Modulation of postoperative immune response by enteral nutrition with a diet enriched with arginine, RNA, and omega-3 fatty acids in patients with upper gastrointestinal cancer. Eur J Surg 1995;161:115-22.
12.
Anon. 2000. www.moon-light.com/ (Accessed 21 March 2000).
13.
Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic and clinical outcome. Surgery 1992;112:56-67.

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