Pharmacologic levels of dietary arginine in CB6F1 mice increase serum ammonia in the healthy state and serum nitrite in endotoxemia.

BACKGROUND: Therapeutic or pharmacologic doses of arginine are used to enhance blood flow and immune function despite the lack of dose-response studies and the potential for adverse effects. This study determined the optimal level of oral arginine supplementation required to elevate serum arginine concentrations yet limit adverse effects in healthy and endotoxemic mice. METHODS: Male CB6F1 mice were fed one of the following diets: The standard AIN93G (3 g arginine/100 g of protein) or this diet modified to provide 10 g, 20 g, or 30 g arginine/100 g of protein. On day 14, mice were injected with lipopolysaccharide (endotoxemic) or saline (healthy) and 4 hours later were exsanguinated. RESULTS: Weight gain was reduced 50% in the group fed the 30 g arginine vs standard diet. Serum arginine, ornithine, citrulline, histidine, lysine, serine, threonine, tyrosine, and phenylalanine were greater and glutamate levels were lower in healthy supplemented mice; lipopolysaccharide treatment negated these changes. Serum ammonia concentration was 52% greater in healthy mice fed the 30 g arginine vs standard diet. Serum nitrite and urea were unaffected by supplementation in healthy mice. Serum nitrite was 37% greater in endotoxemic mice fed 30 g vs 10 g arginine, and serum urea was 27% greater in mice fed 20 g or 30 g vs 10 g arginine. CONCLUSIONS: Changes in serum arginine or its metabolites were observed with all of the modified diets; however, a 30-g arginine diet was associated with an initial impairment of growth and potential adverse effects.

Oxidative stress and antioxidant capacity in smoking and nonsmoking men with HIV/acquired immunodeficiency syndrome.

BACKGROUND: Past studies document decreased levels of antioxidants and selenium and increased levels of oxidative stress in people living with HIV/acquired immunodeficiency syndrome (AIDS). Cigarette smoking is another source of oxidative stress. Excessive oxidative stress can induce HIV replication, resulting in disease progression. The purpose of this study was to determine whether subjects with HIV/AIDS who smoke cigarettes have increased oxidative stress and decreased antioxidant status compared with nonsmokers with HIV/AIDS. METHODS: Thirty-one men with HIV/AIDS (adhering to highly active antiretroviral therapy for the previous 3 months) were recruited during regular visits to a Veterans Affairs Medical Center Infectious Disease Clinic in a southeastern US city. Plasma was obtained from a 1-time blood draw for this comparison study. Plasma lipid peroxide (LPO) was used as a marker of oxidative stress. Indicators of antioxidant capacity included plasma glutathione peroxidase (GPx, the functional indicator of selenium status), vitamin C, and antioxidant potential (AOP). RESULTS: Fifteen smokers and 10 nonsmokers with HIV/AIDS were enrolled. Median plasma LPO level was above the normal range of 0-1.3 micromol/L in both nonsmokers (2.5 [0-23.4] micromol/L, median [range]) and smokers (4.0 [0-47.5] micromol/L), but there was no difference between groups. Plasma GPx concentration was significantly lower in smokers (169 [118-295] mumol/min/L) compared with nonsmokers (197 [149-414] micromol/min/L). Vitamin C and AOP levels were not different between groups. CONCLUSIONS: This pilot study suggests that effects of smoking on oxidative stress are not additive, as no striking differences were observed in oxidative stress or antioxidant capacity between clinically stable smoking and nonsmoking men with HIV/AIDS.

Mini nutritional assessment and screening scores are associated with nutritional indicators in elderly people with pressure ulcers.

OBJECTIVE: To determine the association between the Mini Nutritional Assessment (MNA) or MNA Screening Form and standard indicators of nutritional status in male elders with pressure ulcers. DESIGN: Cross-sectional study. MNA and MNA Screening Form scores were related to nutritional indicators using the Pearson correlation. SUBJECTS/SETTING: Residents (79+/-1 years, N=23 men) of Veterans Affairs medical center nursing home care units with stage I to IV pressure ulcers were enrolled. MAIN OUTCOME MEASURES: Correlation coefficients were obtained from correlations between the MNA or MNA Screening Form scores and biochemical and anthropometric indices of nutritional status or measures of body composition normalized for height by dividing by height in meters(2). RESULTS: Hemoglobin (106+/-4 g/L; r=0.43, P=.0409, mean, standard error of the mean, Pearson's r, P value), hematocrit (0.32+/-0.01; r=0.44, P=.0358), body mass index (23.1+/-1.0; r=0.66, P=.0006), calf circumference (30.4+/-1.1 cm; r=0.46, P=.0286), fat-free mass index (18.3+/-0; r=0.60, P=.0063), body cell mass index (8.3+/-0.5; r=0.64, P=.0033), and fat mass index (3.7+/-0.4; r=0.50, P=.0275) positively correlated with MNA score. Serum albumin (31+/-1 g/L) and prealbumin (180+/-17 mg/L) did not correlate with MNA, but prealbumin inversely correlated with erythrocyte sedimentation rate (r=-0.52, P=.0134), a marker of inflammation. The inverse correlation between albumin and erythrocyte sedimentation rate approached statistical significance (r=-0.42, P=.0542). The MNA Screening Form showed similar correlations or lack of correlations observed with the MNA with the exception of hemoglobin and hematocrit. CONCLUSIONS: The MNA and MNA Screening Form provide advantages over using visceral proteins in screening and assessing nutritional status of elderly people with pressure ulcers.

Arginine supplementation enhances mitogen-induced splenocyte proliferation but does not affect in vivo indicators of antigen-specific immunity in mice.

Arginine is a conditionally essential amino acid with many physiologic roles. Its role in immune function has been one of major focus with conflicting results. Early in vitro immune studies demonstrated increased mitogen-induced lymphocyte proliferation with dietary arginine supplementation; however, not all studies confirmed this effect. Even less is known about the effect of arginine supplementation on in vivo immune responses. To test whether arginine supplementation enhances in vivo indicators of immune function, young female BALB/c mice were fed either the AIN-93G rodent diet (6.4 g arginine/kg diet) or the same diet with 20 g total arginine/kg diet for 15 d before delayed-type hypersensitivity (DTH) testing with 2,4-dinitrofluorobenzene (n = 16-18/diet group). The same mice were challenged with influenza virus A/Port Chalmers/1/73 (H3N2) 15 d later. Mice were killed 3, 6, or 31 d postinfluenza challenge (5-6/diet group on each day). Mitogen-induced splenocyte proliferation, body weight, anti-influenza serum antibody, lung viral titers, and serum arginine were measured. DTH did not differ between diet groups. On d 6 and 31 postchallenge, mitogen-induced proliferation of splenocytes from mice fed the arginine diet was >1.5-fold that of mice fed the control diet (P < 0.05). Body weight and influenza lung viral and serum antibody titers did not differ between diet groups. These data suggest that despite significant enhancement of in vitro mitogen-induced splenocyte proliferation, arginine supplementation does not have a biologically significant effect on antigen-specific in vivo indicators of immune function in this model.

Arginine supplementation does not enhance serum nitric oxide levels in elderly nursing home residents with pressure ulcers.

The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen-induced proliferation decreased significantly at Week 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.

Immune function is impaired with a mini nutritional assessment score indicative of malnutrition in nursing home elders with pressure ulcers.

BACKGROUND: Malnutrition is prevalent in elders with pressure ulcers and is associated with increased morbidity and mortality. This study compared nutritional status, assessed by the Mini Nutrition Assessment (MNA), to immune function in nursing home elders with pressure ulcers. METHODS: Nutritional status was assessed in nursing home residents (>65 years) with a stage II or more severe pressure ulcer. Subjects were classified as well nourished, at risk of malnutrition, or malnourished according to MNA score. Blood was drawn to assess whole blood mitogen-induced lymphocyte proliferation and neutrophil respiratory burst. Delayed-type hypersensitivity to 3 antigens was measured. MNA status was compared with immune parameters using the Kruskall-Wallis test. RESULTS: Of the 24 subjects (23 men, 1 woman) who completed the study protocol, only 4 (17%) were classified as well nourished, whereas 7 (29%) were at risk and 13 (54%) were malnourished according to MNA score. Whole blood lymphocyte proliferation was significantly lower in the malnourished vs at risk subjects with both pokeweed (median [25th, 75th percentile], 0.6 [0.3, 0.9] vs 1.8 [1.2, 2.1] disintegrations per minute [dpm]/cell, p < .05); and concanavalin A (1.7 [0.9, 2.0] vs 2.8 [2.6, 3.9] dpm/cell, p < .05) mitogens. Neutrophil respiratory burst normalized to a young control was significantly lower in malnourished subjects vs well-nourished subjects (0.8 [0.5, 0.9] vs 1.4 [1.0, 1.7], p < .05). Total induration to 3 skin-test antigens was 13.4 +/- 4.6, 3.5 +/- 2.6, and 3.8 +/- 1.8 (mean +/- SEM) for well-nourished, at risk, and malnourished, respectively (p = .059). CONCLUSIONS: Immune function is impaired with an MNA score indicative of malnutrition in nursing home elders with pressure ulcers.

Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors.

OBJECTIVES: To assess whether an experimental nutritional formula, given as a supplement, would reduce days of symptoms of upper respiratory tract infection (URTI) and affect antibody and lymphocyte proliferative responses to influenza vaccine. DESIGN: A prospective, randomized, double-blind, controlled trial was conducted between October 1999 and April 2000. SETTING: Assisted- and independent-living facilities in North Central Florida. PARTICIPANTS: Sixty-six individuals, aged 65 and older. INTERVENTION: Subjects received 8 oz/d of an experimental formula containing antioxidants, zinc, selenium, fermentable oligosaccharides, and structured triacylglycerol or an isoenergetic, isonitrogenous control formula for 183 days. MEASUREMENTS: Subjects recorded daily symptoms of URTI. Antibody titers and lymphocyte proliferation to three influenza vaccine components were measured on Days 57 and 183. RESULTS: Eighteen subjects in the control group and 16 subjects in the experimental group consumed an average of 7 ounces of formula daily and completed the 183-day study. Median days of symptoms of URTI were 3 (range 0-69, total days=156) and 0 (range 0-49, total days=78) for the control and experimental groups, respectively (P=.049). On Day 57, seven of 17 (41%) subjects in the control group and 13 of 15 (87%) subjects in the experimental group achieved a fourfold or greater increase in serum antibody titer to A/Beijing (P=.012). Lymphocyte proliferation to influenza vaccine components was greater in the experimental (median=1,365 cpm, range=0-14,955 cpm) than the control group (median=136 cpm, range=0-4,270 cpm) (P=.013). CONCLUSION: Subjects consuming an experimental nutritional formula experienced enhanced immune function and fewer days of URTI symptoms.