Standort in Deutschland, wo man günstige und qualitativ hochwertige Kamagra Ohne Rezept Lieferung in jedem Teil der Welt zu kaufen.

Wenn das Problem der Verringerung der Potenz berührt mich persönlich war ich schockiert, dass das passiert gerade mit mir kamagra Übrigens jeder leisten und gibt eine sofortige Wirkung ohne Hausarbeiten Anwendungen.

Pii: s0753-3322(02)00291-3

Dossier: Free amino acids in human health and pathologies Arginine and immunity: a unique perspective Carmelo Nieves Jr, Bobbi Langkamp-Henken * Food Science and Human Nutrition Department, University of Florida, PO Box 110370, Gainesville, FL 32611-0370, USA Abstract
Arginine functions in the body as a free amino acid, a component of most proteins, and the substrate for several non-protein, nitrogen-containing compounds, many of which function in immunity. Although arginine is synthesized in the body, it is not made insufficient quantities to support growth or meet metabolic requirements during periods of stress. Based on the biochemical and physiologicalrole of arginine in maintaining health and immunity, arginine is being added at pharmacologic concentrations to enteral formulas to boostimmune function. Unfortunately, animal and human studies that investigate enteral arginine supplementation as the single variable do notshow clear immunologic benefit. The inconsistent effects of arginine supplementation on immune function are due to numerous factors, suchas the amount and timing of arginine supplementation, the animal species or strain of species, and the experimental model. Systematic studyis required to determine whether a basal dietary intake of arginine is required to maintain immune function during health and how mucharginine is required to meet metabolic requirements during periods of growth or stress. 2002 Éditions scientifiques et médicales ElsevierSAS. All rights reserved.
Keywords: Arginine; Immune function; Arginase; Nitric oxide 1. Introduction
2. Arginine metabolism
Arginine functions in the body as a free amino acid, a Classification of arginine as an essential or non-essential component of most proteins, and as the substrate for several amino acid has been difficult. By the classical definition, non-protein, nitrogen-containing compounds. As a free essential amino acids cannot be synthesized in the body to amino acid, arginine functions as an intermediate in the urea meet the needs for optimal growth. In 1930, Scull and Rose cycle. As one of the 20 common α-amino acids, arginine is observed that arginine was synthesized in vivo, and classi- an integral component of mammalian proteins. As a sub- fied arginine as a non-essential amino acid . Nitrogen strate for several non-protein, nitrogen-containing com- balance studies, which are currently used to classify an pounds, arginine indirectly participates in the rapid regen- amino acid as essential or non-essential for humans, also classified arginine as non-essential . Some con- vasodilatation, neurotransmission, calcium release, and ulti- sider this to be an inaccurate evaluation and argue that mately immunity. This review will briefly address the arginine may need to be reclassified as a semi-essential or biochemical basis for arginine in health and disease and conditionally essential amino acid (reviewed in ).
discuss animal and human studies available in the literature Support for this argument comes from animal studies (rats that investigate the role of arginine supplementation on and dogs) in which sub-optimal weight gain is observed when arginine is excluded from the diet during growthUnder these conditions (growth) in vivo synthe-sis of arginine is not sufficient, hence the term conditionallyessential. During times of physiologic stress, arginine syn- thesis may not be able to keep up with metabolic demands.
E-mail address: rjhenken@mail.ifas.ufl.edu (B. Langkamp-Henken).
2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved.
PII: S 0 7 5 3 - 3 3 2 2 ( 0 2 ) 0 0 2 9 1 - 3 C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 This is another ‘condition’ where arginine may become virtually all tissues including the kidney, brain, liver, skel- etal muscle and lungs However, the purpose of this One of the major functions of arginine within the body is as an intermediate in the urea cycle. The free amino acid Another function of arginine is protein synthesis. Argin- arginine contains a guanidino group, which is essential for ine can be converted into proline, glutamate and glutamine the synthesis of urea in most mammals. Urea is primarily (see all of which are common amino acids found synthesized in the liver and excreted by the kidneys. In the within most proteins. Synthesis of these three amino acids cytosol of hepatocytes, arginase-I removes the guanidino begins with arginine being converted into ornithine. Orni- group from arginine to produce urea and ornithine (see thine is then converted into pyrroline-5-carboxylate. The Urea is then transported from the hepatocyte into the enzyme for this reaction is ornithine aminotransferase.
bloodstream and ornithine is used to regenerate arginine Pyrroline-5-carboxylate can be converted into either proline within the hepatocyte. It is important to note that a second using pyrroline-5-carboxylate reductase or in two-steps form of arginase (arginase-II) exists and is expressed in converted into glutamyl-γ-semialdehyde, then glutamate.
Fig. 1. Diagram of arginine metabolites. Metabolites are bolded and enzymes/proteins are italicized.
Abbreviations: ADC, arginine decarboxylase; A:GAT, arginine:glycine amidinotransferase; DAO, diamine oxidase; Glu synthase, glutamine synthase; GMT,guanidinoacetate-N-methyltransferase; NOS-1, nitric oxide synthase-1; NOS-2, nitric oxide synthase-2; NOS-3, nitric oxide synthase-3; OAT, ornithineaminotransferase; ODC, ornithine decarboxylase; P-5-C dehydrogenase, pyrroline-5-carboxylate dehydrogenase; P-5-C reductase, pyrroline-5-carboxylatereductase; and PT, polyamine transporter.
C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 The conversion of pyrroline-5-carboxylate into glutamyl-γ- arginine indirectly provide the substrate for polyamine semialdehyde is spontaneous and requires no enzyme; synthesis, it also indirectly stimulates polyamine synthesis however, conversion of glutamyl-γ-semialdehyde into by stimulating the release of growth hormone . In glutamate requires the enzyme pyrroline-5-carboxylate de- turn, growth hormone stimulates the release of insulin-like hydrogenase. Synthesis of glutamine from glutamate is growth factor-1, which stimulates polyamine synthesis by catalyzed by glutamine synthase and requires ammonia. In increasing ornithine decarboxylase activity .
addition to protein formation, glutamine prevents the accu- While ornithine decarboxylase is the rate-limiting en- mulation of ammonia in extrahepatic tissue by transporting zyme in polyamine production a second enzyme, arginine ammonia through the bloodstream to the hepatocytes for decarboxylase, also synthesizes polyamines In a study conducted in rats, arginine decarboxylase was shown to Arginine metabolism also generates several essential decarboxylate ornithine (K = 0.25 mM) to produce pu- non-protein, nitrogen-containing compounds. Some ex- trescine or to decarboxylate arginine (K = 0.75 mM) to amples of these compounds are creatine, polyamines, agma- produce agmatine . Moreover, both human and animal tine and nitric oxide. Creatine is primarily synthesized in the studies have shown that the enzyme agmatinase can use liver and transported through the blood stream to muscle agmatine as a substrate to produce putrescine tissue. Creatine functions as a carrier for phosphate and is In addition to being a substrate for polyamine synthesis, needed for the rapid regeneration of adenosine triphosphate agmatine also regulates intracellular concentrations of in the muscles. Synthesis of creatine is dependent on the polyamines. Regulation of intracellular polyamine produc- guanidino group of arginine and is a two-step reaction (see tion is important because high levels of polyamines are ). In the first reaction arginine:glycine amidinotrans- toxic to cells (reviewed in Agmatine regulates ferase, transfers the guanidino group from arginine onto polyamine production by decreasing ornithine decarboxy- glycine, this produces guanidinoacetate and ornithine. Next, lase activity and enhancing the transcription of antizyme the enzyme guanidinoacetate N-methyltransferase transfers . Antizyme is an endogenous protein that decreases a methyl group from S-adenosylmethionine to guanidinoac- intracellular polyamine synthesis through two different etate. Products from this reaction are creatine and mechanisms. First, antizyme decreases ornithine decarboxy- lase activity and second, antizyme accelerates the degrada- (phosphocreatine) occurs at the guanidino group in the tion of ornithine decarboxylase . Although, regulating the production polyamines decreases intracellular Approximately 10% of arginine in the plasma is used to polyamines levels, it does not prevent the uptake of synthesize creatine, even though creatine is regenerated polyamines from extracellular sources via the polyamine when phosphocreatine phophorylates adenosine diphos- transporter. Another function of agmatine and antizyme is to phate . This is due to the fact that phosphocreatine decrease the activity of the polyamine transporter, thus undergoes spontaneous degradation to creatinine. Creatinine limiting the uptake of extracellular polyamines cannot be degraded by mammals and is excreted by the In addition to regulating polyamine levels, agmatine and kidneys. A study conducted by Cockroft and Gault esti- arginine also regulate production of nitric oxide. Nitric mated creatinine excretion to be 23.6 ± 5 mg/kg over 24 h in oxide is an antimicrobial agent that is effective against males 18–29 years old . Using a 70 kg male as a intracellular pathogens, extracellular parasites and bacteria reference, 2.0–3.1 g of arginine is needed daily to replace Nitric oxide is also a neurotransmitter (reviewed creatine loss. A typical gram of dietary protein provides in and vasodilator . The enzyme that produces 54 mg of readily available arginine If our reference nitric oxide is nitric oxide synthase. The substrate for this male consumes the recommended daily allowance of 0.8 g reaction is arginine and the products are nitric oxide and of protein per kg of body weight, this supplies 3.0 g of citrulline (see There are three isoforms of nitric arginine. This means that the dietary intake of arginine may oxide synthase; these are NOS-1, NOS-2 and NOS-3.
only be sufficient to replace arginine lost in creatine NOS-1 (also known as nNOS, NOS-I and Type I NOS) is production. However, keep in mind that protein turnover constitutive and is predominately located in neuronal tissue.
and de novo synthesis also add to plasma arginine levels.
NOS-2 (also known as iNOS, NOS-II and Type II NOS) is Another metabolic pathway that involves arginine is the inducible and is located in a variety of tissue. NOS-3 (also synthesis of polyamines. Polyamines (putrescine, spermine known as eNOS, NOS-3 and Type III) is constitutive and is and spermidine) function in membrane transport, (reviewed primarily localized in endothelial tissue. Both NOS-1 and in ), cell growth, cell proliferation and cell differentia- NOS-3 produce low levels of nitric oxide and are calcium tion . Arginine and products of arginine metabo- dependent. Agmatine increases activity of NOS-1 and lism are necessary in both the regulation and the synthesis NOS-3 by stimulating the release of calcium (reviewed in However, agmatine indirectly decreases NOS-2 activ- C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 ity. Agmatine is converted to agmatine aldehyde by diamine the control diet. Researchers have used arginine-free diets or oxidase, in turn, agmatine aldehyde inhibits NOS-2 “standard” diets. The standard diets vary in arginine content from 0.4 to 2% arginine. Ronnenberg et al. compared anarginine-free diet to a standard diet (1% arginine) in‘healthy’ young and aged rats . They showed an 3. Arginine and immunity
increase in concanavalin A-induced splenocyte inter-leukin-2 production with the standard diet compared withthe arginine-free diet. Supplementing arginine in the diet The importance of arginine in metabolic pathways result- (3% arginine) did not increase interleukin-2 production ing in protein formation and removal of nitrogenous waste above that seen with the standard diet . Kobayashi et al.
as well as cell signaling, proliferation and differentiation has compared antigen-specific mucosal immune responses in been well established. What remains to be clarified is mice fed an arginine-free diet with verses fed an arginine- whether dietary arginine can be supplemented at pharmaco- supplemented diet containing 8.7 g/l of arginine Mice logic levels to manipulate metabolic outcome. Currently, fed the arginine-supplemented diet had a higher level of clinicians are adding arginine to enteral formulas at a antigen-specific fecal immunoglobulin A. Mice fed the concentration of five times that found in a typical diet in arginine-free and arginine-supplemented diets did not differ attempt to boost immune function and improve clinical in daily consumption of the diet or in body weight .
outcome in critically ill patients. The rationale for thispractice is based on a number of studies demonstrating the While arginine may not be required in the diet of a benefit of arginine supplementation on immune function.
healthy adult animal to maintain weight or nitrogen balance, However, missing from critical reviews and possibly even it may be required in the diet to maintain normal immune the literature in general have been the studies showing no function. In fact, some studies using lymphocytes from effect or a detrimental effect of arginine supplementation on healthy animals demonstrate depressed in vitro lymphocyte immune function or outcome. Twenty-one animal studies in proliferation when cultured in media containing low levels which arginine was supplemented enterally are summarized of arginine and maximal proliferation when arginine is in The effect of arginine supplementation on added back to the media at physiologic plasma concentra- various immune parameters is listed as an increase, no tions If a minimal amount of arginine is required change, or a decrease in the immune parameter. From this to maintain immune function, the question becomes how table it becomes evident that the effects of arginine supple- much arginine is enough? This question is difficult to mentation on immune function are not consistent. For answer due to the lack of uniformity in the amount of example, five studies report an increase in thymus weight arginine supplemented in the experimental diets, the large with arginine supplementation while five studies report no variation in arginine content of the “standard” control diets, change in thymus weight with supplementation. Two studies and the nitrogen source and/or content of diets.
report an increase in mitogen-induced in vitro interleukin-2 Nutritionists tend to compare arginine supplementation production while five studies report no change in to an isonitrogenous control diet to differentiate between the interleukin-2 production with arginine supplementation.
non-specific effects of arginine (high nitrogen content) and Recommendations for pharmacologic supplementation of the specific effects of arginine and arginine metabolites.
arginine to enhance immunity in human health and patholo- While normalizing the nitrogen load between treatment gies cannot be made until we have a clearer picture of the groups may not be as big of a concern in healthy animals basis for and/or outcomes of these recommendations.
and humans, it does become an issue with stress models Many factors contribute to the inconsistent effects of (e.g. sepsis and trauma), which result in negative nitrogen enteral arginine supplementation on immune function. One of the most evident factors is the amount of arginine Commonly, glycine, alanine, or a mixture of nonessential supplemented in the diet. Researchers have provided 5 g of amino acids is added to the control diet to balance the arginine per kg diet (with half provided in the diet and half nitrogen load between arginine-supplemented and control provided in the drinking water) to 17 g of arginine per liter diets. Because arginine is a nitrogen-rich amino acid, of liquid diet. Others have provided 100 mg arginine HCl non-physiologic concentrations of single amino acids must via gavage (see The different concentrations of be added to make the control diet to make it isonitrogenous.
supplemental arginine and methods of administration may Unfortunately this is not without consequence. Pharmaco- contribute to the inconsistent effects of arginine supplemen- logic doses of glycine have been reported to alter free amino tation on immunity. Additionally, these differences also acid patterns and intestinal enzyme activity in a sepsis make it difficult to compare studies.
model Glycine may also have cytoprotective effects Another factor that may contribute to the inconsistent (reviewed in While the addition of alanine for a effects of arginine supplementation on immune function is nitrogen control in a sepsis model appears to preserve Table 1Summary of animal studies showing the effect of arginine administered enterally on various immune parameters and outcomes Effect of arginine on immune parameters and outcomes Standard a diet with added arginine (2% total arginine) vs. a standard diet a madeisonitrogenous with added alanine for 14 d Purified amino acid diet with 3% total arginine vs. 1.1% total arginine (control diet) vs.
Standard diet with 1% arginine in the drinking NK activity, IL-2R expression, T DTH, IL-2 productionwater vs. standard diet with an isonitrogenous cell cytotoxicity level of glycine in the drinking water for 10 d Standard diet (1.8% arginine) with added 0.5, 1, 2, or 3% arginine—half provided in the diet proliferation d and half in the drinking water vs. standard diet(1.8% arginine) for 6 d Liquid diet with 8.7 g/l arginine vs. arginine- free liquid diet made isonitrogenous withadded non-essential amino acids for 14–21 d Standard diet with 1.2 vs. 0% arginine in the Liquid diet with 7.7 g/l vs. 0 g/l total arginine Isonitrogenous liquid diets with 2.4, 4.5, 7.2 or DTH with 7.2 g/l 12 g total arginine per l via gastrostomy for14 d Standard diet with added 2% arginine vs.
standard diet made isonitrogenous with added Standard diet with added 2% arginine vs.
with E. coli, and 20% whole standard diet made isonitrogenous with added Standard diet (1.6% arginine) with 0.75 vs. 0% Liquid diet via gastrostomy containing 5, 11, or 17 g/l arginine HCl vs. 0.7 g/l total arginine Standard diet (1.8% arginine) with 100 mg arginine HCl vs. water via gavage for 4–7 d Standard diet plus 1, 2, or 5% arginine vs.
Splenocyte proliferation, survival Survival with 5% arginine Effect of arginine on immune parameters and outcomes Standard diet (2% arginine) with 1.8 vs. 0% arginine in the drinking water (0% madeisonitrogenous with added glycine) for 21 d Standard diet with added arginine (3% total arginine) vs. standard diet (1.6% arginine) made isonitrogenous with added alanine for Liquid diet with 2.93 g/l total arginine vs.
arginine-free liquid diet made isonitrogenous bacterial killing, splenocyteproliferation, IL-2 production Standard diet (1.8% arginine) with added 1% arginine—half provided in the diet and half in proliferation the drinking water vs. standard diet (1.8%arginine) for 6 d Standard diet plus 49 g/kg arginine vs.
standard diet made isonitrogenous with added Chemical-induced colorectal Standard diet with 1 vs. 0% arginine in the Thymus weight after 10 week of Thymus weight after 22 week of Tumor incidence, burden, and Standard diet with 1% arginine in drinking water vs. standard diet with an isonitrogenous IL-2 production, splenocytelevel of glycine in the drinking water for a Unless otherwise noted, standard diets contain approximately 0.4 to 0.98% arginine.
b Abbreviations: DTH, delayed-type hypersensitivity; IgA, immunoglobulin A; IL-1 , interleukin-1 beta; IL-2R, interleuking-2 receptor; mRNA, messenger RNA; NK, natural killer; and TNF-α, c In vitro production of IL-2 from mitogen-stimulated lymphocyte cultures.
d Unless stated otherwise splenocyte and thymocyte proliferation is mitogen induced.
C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 plasma and tissue-free amino acid concentrations In addition to differences in lymphocyte cytokine pro- observations from our laboratory suggest that alanine is not duction between different strains of mice, macrophages from different strains of mice respond differently. Resident In 2000, we showed that arginine supplementation en- peritoneal macrophages from C57BL/6 are more easily hanced delayed-type hypersensitivity responses in young, activated to produce nitric oxide upon stimulation with adult, and aged male CB6F1 (BALB/c × C57BL/6) mice interferon-γ than macrophages from BALB/c mice given a 2% arginine diet versus an isonitrogenous control Based on differences in lymphocyte cytokine production diet The control diet was made isonitrogenous with the and macrophage activation among strains of mice, it may be addition of alanine. Recently we have repeated this experi- possible that arginine supplementation yields different im- ment in female BALBc mice, but this time a third diet was mune outcomes in different strains of mice. Similar obser- added to the protocol. Mice received the standard diet with vations may also become apparent between species with added arginine (2% total arginine), the standard diet made arginine supplementation (and reviewed in ).
isonitrogenous to the arginine diet with the addition of Up until this point in the review, the experimental model alanine, or the standard diet. Delayed-type hypersensitivity used to examine the effect of arginine supplementation on responses were not different between mice receiving the 2% immune function has been largely ignored. The amount of arginine diet and the mice that received the standard diet.
arginine required in the diet and ultimately the effect of However, the delayed-type hypersensitivity response was arginine supplementation on outcome might largely depend significantly lower in the mice fed the alanine-supplemented on the experimental model. Sepsis and inflammation in- (isonitrogenous diet) than the standard diet (unpublished crease nitric oxide production via upregulation of NOS-2 data). These data in conjunction with the previously re- Mice that lack NOS-2 are susceptible to infection ported data suggest that arginine supplementation did Trauma, on the other hand, is associated with not enhance delayed-type hypersensitivity responses but decreased nitric oxide production and increased extrahe- that the addition of alanine to the standard diet depressed patic arginase-I expression and activity these responses. Other explanations for these data could be The greatest increase in extrahepatic arginase activity is that male and female mice or different strains of mice found in splenic macrophages . In humans, general respond differently to arginine supplementation. The latter surgery and trauma increase peripheral mononuclear cell explanation could also help justify some of the conflicting arginase-I activity and decrease plasma nitric oxide effects of arginine supplementation on immune function that In general surgery patients, the increase in mononuclear arginase activity was only evident when the T 2 cytokine, Mitogen-stimulated splenocytes from different strains of interleukin 10, was increased Bernard et al. demon- mice have a propensity to secrete different cytokines. For strated that in vitro macrophage arginase activity increases example, splenocytes from C57BL/6 mice secrete higher concentrations of interferon-γ and lower concentrations of -adrenoceptor blockade prior to trauma decreases murine interleukin-4, while splenocytes from BALB/c mice secrete splenic arginase activity These data suggest a role for lower concentrations of interferon-γ and higher concentra- catecholamines and cytokines in switching arginine metabo- tions of interleukin-4 Helper T lymphocytes that lism between an antimicrobial and a tissue repair pathway.
Since arginase and nitric oxide synthase utilize arginine interleukin-2 and tumor-necrosis factor- are referred to as as a substrate, increased expression of arginase-I increases T helper-1 (T 1) cells, whereas T lymphocytes that pre- intracellular ornithine and polyamines and reduces basal dominantly produce interleukin-4, -5, -6 and -10 are re- nitric oxide synthesis by endothelial cells . Nitric oxide ferred to as T 2 cells. Cell-mediated immune functions, derived from NOS-3 produces vasorelaxation and inhibits such as delayed-type hypersensitivity and activation of platelet aggregation and neutrophil infiltration—important cytotoxic T lymphocytes and inflammatory macrophages, functions for maintaining organ blood flow following are associated with T 1 responses, while B lymphocyte, trauma A series of studies examined whether mast cell and eosinophil activation are associated with T 2 intravenous arginine administration during resuscitation responses. The balance between T 1 and T 2 responses improved blood flow to various organs following trauma predicts the metabolic fate of arginine and possibly the and hemorrhage . Rats underwent a sham operation or difference between cell proliferation and connective tissue laparotomy (trauma), were bled to a mean arterial pressure production or antimicrobial capacity. In vitro and in vivo of 40 mmHg, and resuscitated. Arginine (300 mg/kg) or studies demonstrate that NOS-2 and arginase-1 are differ- saline was infused intravenously during the first 15 min of entially regulated by T 1- and T 2-driven immune reac- resuscitation. At 3 h post trauma-hemorrhage and resusci- tions with T 1 cytokines inducing NOS-2 and T 2 cytok- tation, plasma arginine (corrected for the plasma protein concentration) decreased 87% compared with shamoperated C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 group. Infusion of arginine during resuscitation temporarily Two of the trials show an increase in mitogen-induced corrected plasma arginine concentrations and significantly lymphocyte proliferation, while three of the trials show no increased corrected plasma citrulline concentrations increase or a decrease in lymphocyte proliferation with Cardiac output and blood flow to the heart, skin, muscle, arginine supplementation. No studies demonstrate improved kidneys, stomach, pancreas, small intestine, large intestine, clinical outcomes with arginine supplementation.
mesentery, brain, liver, and spleen were increased with A large part of the rationale for supplementing arginine to intravenous arginine administration during resuscitation enhance immune function is based on studies that show an . Arginine infusion during resuscitation was also asso- increase in mitogen-induced in vitro lymphocyte prolifera- ciated with decreased liver injury and plasma interleukin-6 tion (see In vitro lymphocyte proliferation and increased splenocyte interleukin-2 production com- is a convenient measure of immune function, especially in pared with animals resuscitated without arginine human studies, and appears to correlate with mortality Mitogen-induced splenocyte proliferation was significantly However, the mechanism by which arginine supplementa- lower following trauma-hemorrhage and resuscitation with- tion in vivo may enhance in vitro lymphocyte proliferation out arginine infusion compared with sham-operated con- is still unknown. Is it possible that mitogen-induced in vitro trols. Arginine infusion prevented this decrease Based lymphocyte proliferation represents a completely artificial on the kinetics of nitric oxide produc tion in the blood flow condition? For example, Barbul et al. gave healthy volun- studies, the authors concluded that the intravenous arginine teers 24.8 g of free arginine per day for 14 d . Plasma increased blood flow via the production of nitric oxide by arginine concentrations were 66.3 µM at baseline and in- creased to 114 µM after 14 d of supplementation. Peripheral While this series of studies showed benefit of intravenous blood lymphocytes were obtained at baseline and day 14 infusion of arginine at the time of resuscitation, it is and stimulated with mitogen in culture media (RPMI 1640) unknown and perhaps doubtful that enteral arginine would containing approximately 1150 µM arginine Any have the same affect. In a healthy animal, approximately changes that occur in vivo due to the difference in plasma 40% of dietary arginine is degraded in the intestine in the arginine concentrations may be abolished in vitro. Ochoa et al. demonstrated that interleukin-2 accumulation was sig- hemorrhage, blood flow to the intestines and portal blood nificantly less when splenocytes, stimulated with anti-CD3, flow are reduced which may alter the absorption process were cultured in media containing 100 or 1000 µM arginine Madden et al. demonstrated that providing arginine compared with cells cultured with 0 or 10 µM arginine (100 mg arginine HCl every 12 h) via gavage immediately Additionally, CD45RA negative CD8+ (memory) T cells after and for 4 d following cecal ligation and puncture that and the number of CD8 and CD3 receptors were upregu- overall survival was not altered compared with unsupple- lated with the addition of arginine to the culture media mented controls When the arginine was gavaged daily Rodriguez et al. demonstrated that T cell receptor CD3 for 3 d prior to and after the insult following the same chain expression was regulated by arginine in the culture administration regimen, survival improved significantly.
Beneficial effects on survival were also observed when the signal transduction element and the rate-limiting step in the arginine was infused intravenously immediately after insult.
assembly and membrane expression of the T cell receptor These data suggest that enteral arginine supplementation prior to injury or intravenous arginine supplementation at not interleukin-2 production or interleukin-2 receptor the time of injury may provide the most benefit . Thus chains) was reduced when Jurkat cells (helper T-cell line) timing of enteral arginine supplementation appears to be were cultured in arginine-free media. The inhibition of the another factor contributing to the inconsistent outcomes chain expression was completely reversed with the addition associated with arginine supplementation.
of arginine to the culture media This arginine-mediated The strongest evidence supporting the role of arginine effect was attributed to a change in CD3 mRNA half-life supplementation on immune-modulation in humans comes from double-blind, randomized controlled trials. However, Changes in macrophage function with altered cell culture there are few such trials and fewer that investigate or arginine concentrations have also been described. Albina et demonstrate clinical outcomes (this does not include clinical al. demonstrated that macrophage superoxide production, trials that compare immune-enhancing enteral formulas of phagocytosis, protein synthesis, and tumoricidal activity which arginine is one of many added nutrients). Of 15 were greatest in culture media containing 6 µM arginine, clinical trials that examined the effect of arginine supple- decreased as the arginine concentration in the media ap- proached physiologic concentrations (∼100 µM), and con- tinued to decrease or maintained lower levels of function at the study was a double-blind, randomized controlled trial.
pharmacologic concentrations observed in common cell C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 Table 2Double-blind, randomized controlled trials investigating the effect of enteral arginine supplementation on immune function No differences in lymphocyte No difference in preoperatively via oral intake proliferation or endotoxin- lymphocyte proliferation and complications 20, 10, or 0 g/d for 4 weeks, No change in viral load and 17, 8.5, or 0 g/d for 4 weeks No change to possibly a in residents with pressure ulcers via oral intake lymphocyte proliferation andno change in IL-2 production a Abbreviations: IL-2, interleukin-2; GI, gastrointestinal.
culture media (∼1200 µM) These data suggest that arginine supplementation, the animal species or strain of macrophage function would be enhanced at low plasma species, and the experimental model. Systematic study is arginine concentrations and inhibited at concentrations typi- required to determine whether a basal dietary intake of cally found in plasma or culture media. While there are very arginine is required to maintain immune function during few in vivo measures of immune function that can be used health and how much arginine is required to meet metabolic to assess the immune effects of arginine supplementation requirements during periods of growth or stress.
(especially in humans), caution should be used wheninterpreting in vitro studies with immune cells cultured inmedia containing nonphysiologic concentrations of argin- Acknowledgments
In summary, arginine functions in the body as a free This research was supported by the Florida Agricultural amino acid, a component of most proteins, and the substrate Experiment Station, and approved for publication as Journal for several non-protein, nitrogen-containing compounds, many of which function in immunity. Although arginine issynthesized in the body, it is not made in sufficient quanti-ties to support growth or meet metabolic requirements References
during periods of stress. Based on the biochemical andphysiological role of arginine in maintaining health and Albina JE, Caldwell MD, Henry Jr WL, Mills CD. Regulation of immunity, arginine is being added at pharmacologic con- macrophage functions by L-arginine. J Exp Med 1989;169:1021–9.
centrations to enteral formulas to boost immune function.
Albina JE, Henry Jr L. Suppression of lymphocyte proliferation Unfortunately, animal and human studies that investigate through the nitric oxide synthesizing pathway. J Surg Res 1991;50: enteral arginine supplementation as the single variable do not show clear immunologic benefit. The inconsistent ef- Alheid U, Frolich JC, Forstermann U. Endothelium-derived relaxing fects of arginine supplementation on immune function are factor from cultured human endothelial cells inhibits aggregation of due to numerous factors, such as the amount and timing of human platelets. Thromb Res 1987;47:561–71.
C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 Angele MK, Fitzal F, Smail N, Knoferl MW, Schwacha MG, Cui X, Iwasa M, Iwasa Y, Ogoshi S. Arginine-supplemented diet Ayala A, et al. L-Arginine attenuates trauma-hemorrhage-induced decreases expression of inflammatory cytokines and improves sur- liver injury. Crit Care Med 2000;28:3242–8.
vival in burned rats. JPEN J Parenter Enteral Nutr 2000;24:89–96.
Angele MK, Smail N, Knoferl MW, Ayala A, Cioffi WG, Daly JM, Reynolds J, Thom A, Kinsley L, Dietrick-Gallagher M, Chaudry IH. L-Arginine restores splenocyte functions after trauma Shou J, et al. Immune and metabolic effects of arginine in the and hemorrhage potentially by improving splenic blood flow. Am J surgical patient. Ann Surg 1988;208:512–23.
Elitsur Y, Strom J, Luk GD. Inhibition of ornithine decarboxylase Angele MK, Smail N, Wang P, Cioffi WG, Bland KI, Chaudry IH.
activity decreases polyamines and suppresses DNA synthesis in L-Arginine restores the depressed cardiac output and regional human colonic lamina propria lymphocytes. Immunopharmacology perfusion after trauma-hemorrhage. Surgery 1998;124:394–401 Fong WF, Heller JS, Canellakis ES. The appearance of an ornithine Babal P, Ruchko M, Campbell CC, Gilmour SP, Mitchell JL, decarboxylase inhibitory protein upon the addition of putrescine to Olson JW, et al. Regulation of ornithine decarboxylase activity and cell cultures. Biochim Biophys Acta 1976;428:456–65.
polyamine transport by agmatine in rat pulmonary artery endothelial Gennari R, Alexander JW. Arginine, glutamine, and dehydroepi- cells. J Pharmacol Exp Ther 2001;296:372–7.
androsterone reverse the immunosuppressive effect of prednisoneduring gut-derived sepsis. Crit Care Med 1997;25:1207–14.
Baligan M, Giardina A, Giovannini G, Laghi MG, Ambrosioni G.
Gianotti L, Alexander JW, Pyles T, Fukushima R. Arginine- L-Arginine and immunity. Study of pediatric subjects. Minerva supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G.
oxide. Ann Surg 1993;217:644–53 discussion 653-654.
Arginine enhances wound healing and lymphocyte immune Gobert AP, Daulouede S, Lepoivre M, Boucher JL, Bouteille B, responses in humans. Surgery 1990;108:331–6 [discussion 336–7].
Buguet A, et al. L-Arginine availability modulates local nitric oxide Barbul A, Sisto DA, Wasserkrug HL, Efron G. Arginine stimulates production and parasite killing in experimental trypanosomiasis.
lymphocyte immune response in healthy human beings. Surgery Gonce SJ, Peck MD, Alexander JW, Miskell PW. Arginine supple- Barbul A, Wasserkrug HL, Seifter E, Rettura G, Levenson SM, mentation and its effect on established peritonitis in guinea pigs.
Efron G. Immunostimulatory effects of arginine in normal and JPEN J Parenter Enteral Nutr 1990;14:237–44.
injured rats. J Surg Res 1980;29:228–35.
Hall JC. Glycine. JPEN J Parenter Enter Nutr 1998;22:393–8.
Barbul A, Wasserkrug HL, Sisto DA, Seifter E, Rettura G, Leven- Hayashi S, Murakami Y, Matsufuji S. Ornithine decarboxylase son SM, Efron G. Thymic stimulatory actions of arginine. JPEN J antizyme: a novel type of regulatory protein. Trends Biochem Sci Parenter Enteral Nutr 1980;4:446–9.
Bauer H, Jung T, Tsikas D, Stichtenoth DO, Frolich JC, Neumann C.
Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Nitric oxide inhibits the secretion of T-helper 1- and T-helper Cheever AW, et al. Differential regulation of nitric oxide synthase-2 2-associated cytokines in activated human T cells. Immunology and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Bermudez LE. Differential mechanisms of intracellular killing of Mycobacterium avium and Listeria monocytogenes by activated Heys SD, Segar A, Payne S, Bruce DM, Kernohan N, Eremin O.
human and murine macrophages. The role of nitric oxide. Clin Exp Dietary supplementation with L-arginine: modulation of tumour- infiltrating lymphocytes in patients with colorectal cancer. Br J Surg Bernard AC, Fitzpatrick EA, Maley ME, Gellin GL, Tsuei BJ, Arden WA, et al. Beta adrenoceptor regulation of macrophage Iyer RK, Kim HK, Tsoa RW, Grody WW, Cederbaum SD. Cloning arginase activity. Surgery 2000;127:412–8.
and characterization of human agmatinase. Mol Genet Metab Bernard AC, Mistry SK, Morris Jr SM, O’Brien WE, Tsuei BJ, Maley ME, et al. Alterations in arginine metabolic enzymes in Kennedy JA, Kirk SJ, McCrory DC, Halliday MI, Barclay GR, Rowlands BJ. Modulation of immune function and weight loss byL-arginine in obstructive jaundice in the rat. Br J Surg 1994;81: Blantz RC, Satriano J, Gabbai F, Kelly C. Biological effects of arginine metabolites. Acta Physiol Scand 2000;168:21–5.
Kirk SJ, Hurson M, Regan MC, Holt DR, Wasserkrug HL, Barbul A.
Borman A, Wood TR, Black HC, Anderson EG, Oesterling MJ, Arginine stimulates wound healing and immune function in elderly Wommack E, et al. The role of arginine in growth with some human beings. Surgery 1993;114:155–9 [discussion 160].
observations on the effects of argininic acid. J Biol Chem 1946;166: Kirk SJ, Regan MC, Wasserkrug HL, Sodeyama M, Barbul A.
Arginine enhance T-cell responses in athymic nude mice. JPEN Brittenden J, Park KG, Heys SD, Ross C, Ashby J, Ah-See A, et al.
Parenter Enteral Nutr 1992;16:429–32.
L-Arginine stimulates host defenses in patients with breast cancer.
Kles KA, Wallig MA, Tappenden KA. Luminal nutrients exacerbate intestinal hypoxia in the hypoperfused jejunum. JPEN J Parenter Castillo L, Chapman TE, Yu YM, Ajami A, Burke JF, Young VR.
Dietary arginine uptake by the splanchnic region in adult humans.
Knopf RF, Conn JW, Fajans SS, Floyd JC, Guntsche EM, Rull JA.
Plasma growth hormone response to intravenous administration of Chambon-Savanovitch C, Felgines C, Farges MC, Raul F, amino acids. J Clin Endocrinol Metab 1965;25:1140–4.
Cezard JP, Davot P, et al. Comparative study of glycine, alanine or Kobayashi T, Yamamoto M, Hiroi T, McGhee J, Takeshita Y, casein as inert nitrogen sources in endotoxemic rats. J Nutr 1999; Kiyono H. Arginine enhances induction of T helper 1 and T helper 2 cytokine synthesis by Peyer’s patch alpha beta T cells and Cockcroft DW, Gault MH. Prediction of creatinine clearance from antigen-specific mucosal immune response. Biosci Biotechnol Bio- serum creatinine. Nephron 1976;16:31–41.
C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 Kubes P, Kanwar S, Niu XF, Gaboury JP. Nitric oxide synthesis Murasko DM, Weiner P, Kaye D. Association of lack of mitogen- inhibition induces leukocyte adhesion via superoxide and mast cells.
induced lymphocyte proliferation with increased mortality in the elderly. Aging Immunol Infect Dis 1988;1:1–6.
Langkamp-Henken B, Herrlinger-Garcia KA, Stechmiller JK, Nick- Nakagawa I, Kobayashi K, Suzuki T, Takahashi T. Amino acid erson-Troy JA, Lewis B, Moffatt L. Arginine supplementation is requirements of children—minimal needs of tryptophan, arginine well tolerated but does not enhance mitogen-induced lymphocyte and histidine based on nitrogen balance method. J Nutr 1963;80: proliferation in elderly nursing home residents with pressure ulcers.
JPEN J Parenter Enter Nutr 2000;24:280–7.
Nirgiotis JG, Hennessey PJ, Andrassy RJ. The effects of an Langkamp-Henken B, Johnson LR, Viar MJ, Geller AM, Kotb M.
arginine-free enteral diet on wound healing and immune function in Differential effect on polyamine metabolism in mitogen- and the postsurgical rat. J Pediatr Surg 1991;26:936–41.
superantigen-activated human T-cells. Biochim Biophys Acta1 Nussler AK, Billiar TR. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukocyte Biol 1993;54:171–8.
Laursen JB, Boesgaard S, Trautner S, Rubin I, Poulsen HE, Ochoa JB, Bernard AC, Mistry SK, Morris Jr SM, Figert PL, Aldershvile J. Endothelium-dependent vasorelaxation in inhibited Maley ME, et al. Trauma increases extrahepatic arginase activity.
by in vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase. Free Radic Res 2001;35:387–94.
Ochoa JB, Bernard AC, O’Brien WE, Griffen MM, Maley ME, Lewis B, Langkamp-Henken B. Arginine enhances in vivo immune Rockich AK, et al. Arginase I expression and activity in human responses in young, adult and aged mice. J Nutr 2000;130:1827–30.
mononuclear cells after injury. Ann Surg 2001;233:393–9.
Li H, Meininger CJ, Hawker Jr JR, Haynes TE, Kepka-Lenhart D, Ochoa JB, Strange J, Kearney P, Gellin G, Endean E, Fitzpatrick E.
Mistry SK, et al. Regulatory role of arginase I and II in nitric oxide, Effects of L-arginine on the proliferation of T lymphocyte subpopu- polyamine, and proline syntheses in endothelial cells. Am J Physiol lations. JPEN J Parenter Enter Nutr 2001;25:23–9.
Endocrinol Metab 2001;280(E):75–82.
Ochoa JB, Udekwu AO, Billiar TR, Curran RD, Cerra FB, Sim- Ma Q, Hoper M, Anderson N, Rowlands BJ. Effect of supplemental mons RL, et al. Nitrogen oxide levels in patients after trauma and L-arginine in a chemical-induced model of colorectal cancer. World during sepsis. Ann Surg 1991;214:621–6.
Pacelli R, Wink DA, Cook JA, Krishna MC, DeGraff W, Fried- Madden HP, Breslin RJ, Wasserkrug HL, Efron G, Barbul A.
man N, et al. Nitric oxide potentiates hydrogen peroxide-induced Stimulation of T cell immunity by arginine enhances survival in killing of Escherichia coli. J Exp Med 1995;182:1469–79.
peritonitis. J Surg Res 1988;44:658–63.
Park KG, Hayes PD, Garlick PJ, Sewell H, Eremin O. Stimulationof lymphocyte natural cytotoxicity by L-arginine. Lancet 1991;337: McCann PP, Tardif C, Mamont PS. Regulation of ornithine decar- boxylase by ODC-antizyme in HTC cells. Biochem Biophys ResCommun 1977;75:948–54.
Park KG, Heys SD, Blessing K, Kelly P, McNurlan MA,Eremin O, et al. Stimulation of human breast cancers by dietary McCarter MD, Gentilini OD, Gomez ME, Daly JM. Preoperative L-arginine. Clin Sci (Colch) 1992;82:413–7.
oral supplement with immunonutrients in cancer patients. JPEN J Peck MD, Babcock GF, Alexander JW, Billiar T, Ochoa J. High Parenter Enter Nutr 1998;22:206–11.
doses of dietary arginine during repletion impair weight gain and Merimee TJ, Lillicrap DA, Rabinowitz D. Effect of arginine on increase infectious mortality in protein-malnourished mice. Br J serum-levels of human growth-hormone. Lancet 1965;2:668–70.
Merimee TJ, Rabinowitz D, Riggs L, Burgess JA, Rimoin DL, Regunathan S, Reis DJ. Characterization of arginine decarboxylase McKusick VA. Plasma growth hormone after arginine infusion.
in rat brain and liver: distinction from ornithine decarboxylase. J Clinical experiences. New Engl J Med 1967;276:434–9.
Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-M-2 Reynolds JV, Daly JM, Shou J, Sigal R, Ziegler MM, Naji M.
macrophages and the Th1/Th2 paradigm. J Immunol 2000;164: Immunologic effects of arginine supplementation in tumor-bearing and non-tumor-bearing hosts. Ann Surg 1990;211:202–10.
Minami Y, Weissman AM, Samelson LE, Klausner RD. Building a Reynolds JV, Daly JM, Zhang S, Evantash E, Shou J, Sigal R, multichain receptor: synthesis, degradation, and assembly of the Ziegler MM. Immunomodulatory mechanisms of arginine. Surgery T-cell antigen receptor. Proc Natl Acad Sci USA 1987;84:2688–92.
Morris DR. A new perspective on ornithine decarboxylase Robinson LE, Bussiere FI, Le Boucher J, Farges MC, Cynober LA, regulation: prevention of polyamine toxicity is the overriding theme.
Field CJ, Baracos VE. Amino acid nutrition and immune function in tumour-bearing rats: a comparison of glutamine-, arginine- and Morris Jr SM, Bhamidipati D, Kepka-Lenhart D. Human type II ornithine 2-oxoglutarate- supplemented diets. Clin Sci (Lond) 1999; arginase: sequence analysis and tissue-specific expression. Gene Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Munder M, Eichmann K, Modolell M. Alternative metabolic states Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 2002;277:21123–9.
synthase/arginase balance: competitive regulation by CD4+ T cells Ronnenberg AG, Gross KL, Hartman WJ, Meydani SN, Prior RL.
correlates with Th1/Th2 phenotype. J Immunol 1998;160:5347–54.
Dietary arginine supplementation does not enhance lymphocyte Munder M, Eichmann K, Moran JM, Centeno F, Soler G, Mod- proliferation or interleukin-2 production in young and aged rats. J olell M. Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J Immunol 1999;163: Rose WC. The Nutritive significance of the amino acids and certain related compounds. Science 1937;86:298–300.
Murakami Y, Matsufuji S, Miyazaki Y, Hayashi S. Destabilization of Rose WC, Haines WJ, Warner DT. The amino acid requirements of ornithine decarboxylase by transfected antizyme gene expression in man V. The role of lysine, arginine, and tryptophan. J Biol Chem hepatoma tissue culture cells. J Biol Chem 1992;267:13138–41.
C. Nieves Jr, B. Langkamp-Henken / Biomed Pharmacother 56 (2002) 471–482 Rose WC, Rice EE. The significance of the amino acids in canine Torre PM, Ronnenberg AG, Hartman WJ, Prior RL. Oral arginine supplementation does not affect lymphocyte proliferation during Saito H, Trocki O, Wang SL, Gonce SJ, Joffe SN, Alexander JW.
endotoxin-induced inflammation in rats. J Nutr 1993;123:481–8.
Metabolic and immune effects of dietary arginine supplementation Torre PM, Ronnenberg AG, Hartman WJ, Prior RL. Supplemental after burn. Arch Surg 1987;122:784–9.
arginine and ornithine do not affect splenocyte proliferation in Sastre M, Galea E, Feinstein D, Reis DJ, Regunathan S. Metabolism surgically treated rats. JPEN J Parenter Enteral Nutr 1993;17:532–6.
of agmatine in macrophages: modulation by lipopolysaccharide and Torring N, Vinter-Jensen L, Pedersen SB, Sorensen FB, Flyvbjerg A, inhibitory cytokines. Biochem J 1998;330:1405–9.
Nexo E. Systemic administration of insulin-like growth factor I Sastre M, Regunathan S, Galea E, Reis DJ. Agmatinase activity in (IGF-I) causes growth of the rat prostate. J Urol 1997;158:222–7.
rat brain: a metabolic pathway for the degradation of agmatine. J Tsuei BJ, Bernard AC, Shane MD, Shirley LA, Maley ME, Bou- langer BR, et al. Surgery induces human mononuclear cell arginase Satriano J, Matsufuji S, Murakami Y, Lortie MJ, Schwartz D, I expression. J Trauma 2001;51:497–502.
Kelly CJ, et al. Agmatine suppresses proliferation by frameshiftinduction of antizyme and attenuation of cellular polyamine levels.
van Bokhorst-De Van Der Schueren MA, Quak JJ, von Blomberg- van der Flier BM, Kuik DJ, Langendoen SI, Snow GB, et al. Effect Satriano J, Schwartz D, Ishizuka S, Lortie MJ, Thomson SC, of perioperative nutrition, with and without arginine supplementa- Gabbai F, et al. Suppression of inducible nitric oxide generation by tion, on nutritional status, immune function, postoperative morbid- agmatine aldehyde: beneficial effects in sepsis. J Cell Physiol ity, and survival in severely malnourished head and neck cancer patients. Am J Clin Nutr 2001;73:323–32.
Schaefer EL, Seidenfeld J. Effects of polyamine depletion on serum [100] Visek WJ. Arginine needs, physiological state and usual diets. A stimulation of quiescent 3T3 murine fibroblast cells. J Cell Physiol reevaluation. J Nutr 1986;116:36–46.
[101] Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, et al.
Schuber F. Influence of polyamines on membrane functions. Bio- Altered immune responses in mice lacking inducible nitric oxide Scull CW, Rose WCI. The relation of the arginine content of the diet [102] Weissman AM, Ross P, Luong ET, Garcia-Morales P, Jelachich ML, to the increments in tissue arginine during growth. J Biol Chem Biddison WE, et al. Tyrosine phosphorylation of the human T cell antigen receptor zeta-chain: activation via CD3 but not CD2. J Shi O, Kepka-Lenhart D, Morris Jr SM, O’Brien WE. Structure of the murine arginase II gene. Mamm Genome 1998;9:822–4.
[103] Wiesinger H. Arginine metabolism and the synthesis of nitric oxide Snyderman SE, Boyer A, Holt Jr LE. The arginine requirement of in the nervous system. Prog Neurobiol 2001;64:365–91.
the infant. AMA J Dis Child 1959;92:192–5.
[104] Windmueller HG, Spaeth AE. Metabolism of absorbed aspartate, Stechmiller JK, Lentz-Slick A, Bender BS, Hoffinger R, Langkamp- asparagine, and arginine by rat small intestine in vivo. Arch Henken B. Arginine versus protein supplementation in HIV-infected men. Nutr Clin Pract 2001;16:158–64.
Swanson B, Keithley JK, Zeller JM, Sha BE. A pilot study of the [105] Wu CW, Chi CW, Chiu CC, Wu HS, Liu WY, P’Eng FK, et al. Can safety and efficacy of supplemental arginine to enhance immune daily dietary arginine supplement affect the function and subpopu- function in persons with HIV/AIDS. Nutrition 2002;18:688–90.
lation of lymphocytes in patients with advanced gastric cancer? Taheri F, Ochoa JB, Faghiri Z, Culotta K, Park HJ, Lan MS, et al.
L-Arginine regulates the expression of the T-cell receptor zeta chain [106] Wu G, Morris Jr SM. Arginine metabolism: nitric oxide and beyond.
(CD3zeta) in Jurkat cells. Clin Cancer Res 2001;7:958s–65s.

Source: http://belightestarbem.com.br/arquivos/1176932687_07%20-%20Arginine%20and%20immunity.pdf

Microsoft word - october_2013_press.docx

Appel to Wou-Ki: International Art Flexes its Strength at Heffel’s October Online Auction William Scott ~ Still Life with Jug Thursday afternoon brought a flurry of energized bidding that resulted in an exciting close to Heffel’s October online auction of International art. Heffel is proud to announce that the sale totalled $647,000 (all prices are in Canadian dollars and include a

brainsurgeon.com.au

(Affix patient identification label here) Beneficence and Nonmaleficence Neurosurgeon and Spine Surgeon Lumbar Decompression and Pedicle Screw Fusion A. Interpreter / cultural needs • Bladder or bowel problems due to nerve root injury. This may be temporary or permanent. • Injury to the covering of the spinal cord. This may If yes , is a qualified Interpreter present?

Copyright © 2010-2014 Internet pdf articles