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1.
Applying Recovery Biomarkers to Calibrate Self-Report Measures of Energy and Protein in the Hispanic Community Health Study/Study of Latinos.
Mossavar-Rahmani, Y, Shaw, PA, Wong, WW, Sotres-Alvarez, D, Gellman, MD, Van Horn, L, Stoutenberg, M, Daviglus, ML, Wylie-Rosett, J, Siega-Riz, AM, et al
American journal of epidemiology. 2015;(12):996-1007
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Abstract
We investigated measurement error in the self-reported diets of US Hispanics/Latinos, who are prone to obesity and related comorbidities, by background (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) in 2010-2012. In 477 participants aged 18-74 years, doubly labeled water and urinary nitrogen were used as objective recovery biomarkers of energy and protein intakes. Self-report was captured from two 24-hour dietary recalls. All measures were repeated in a subsample of 98 individuals. We examined the bias of dietary recalls and their associations with participant characteristics using generalized estimating equations. Energy intake was underestimated by 25.3% (men, 21.8%; women, 27.3%), and protein intake was underestimated by 18.5% (men, 14.7%; women, 20.7%). Protein density was overestimated by 10.7% (men, 11.3%; women, 10.1%). Higher body mass index and Hispanic/Latino background were associated with underestimation of energy (P<0.05). For protein intake, higher body mass index, older age, nonsmoking, Spanish speaking, and Hispanic/Latino background were associated with underestimation (P<0.05). Systematic underreporting of energy and protein intakes and overreporting of protein density were found to vary significantly by Hispanic/Latino background. We developed calibration equations that correct for subject-specific error in reporting that can be used to reduce bias in diet-disease association studies.
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The metabolic effect of resistant starch and yoghurt on the renal and faecal nitrogen and ammonia excretion in humans as measured by lactose-[(15)N2]ureide.
Wutzke, KD, Scholübbers, D
Isotopes in environmental and health studies. 2013;(4):464-70
Abstract
Resistant starch (RS) and Lactobacillus acidophilus yoghurt (LC1) were supplemented simultaneously in healthy adults to evaluate the effect on the urinary and faecal nitrogen and ammonia excretion by means of lactose-[(15)N2]ureide ((15)N-LU) degradation. Nineteen subjects received a regular daily diet either without or with supplementation of an RS-LC1-mixture composed of fibre of potatoes (RS type 1), wrinkle pea starch (RS type 2), and LC1 over a 20-day period in randomised order. Thereafter, (15)N-LU was administered together with breakfast. Urine and faeces were collected over a period of 48 and 72 h, respectively. The (15)N abundances were measured by isotope ratio mass spectrometry. The intake of the pre- and probiotic mixture composed of RS of type 1, type 2 and of LC1 significantly lowered the colonic generation and the renal excretion of toxic (15)NH3 and functioned as an ammonia shift from urinary to faecal (15)N excretion when using (15)N-LU as a xenobiotic marker.
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Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T-cell response and durable tumor response in a chemorefractory stage IV-M1c melanoma patient.
Van Nuffel, AM, Benteyn, D, Wilgenhof, S, Corthals, J, Heirman, C, Neyns, B, Thielemans, K, Bonehill, A
Cancer immunology, immunotherapy : CII. 2012;(7):1033-43
Abstract
Dendritic cells (DCs) electroporated with mRNA encoding CD70, CD40L and a constitutively active toll-like receptor 4 (TriMix-DC) have an increased T-cell stimulatory capacity. In a prospective phase IB clinical trial, we treated melanoma patients with intradermal and intravenous injections of autologous TriMix-DC co-electroporated with mRNA encoding full-length MAGE-A3, MAGE-C2, tyrosinase and gp100. We report here the immunological and clinical results obtained in one patient with a particularly favorable outcome. This patient had stage IV-M1c melanoma with documented progression during dacarbazine chemotherapy and received 5 TriMix-DC injections. Following DC therapy, a broad CD8(+) T-cell response against multiple epitopes derived from all four treatment antigens was found in the blood and among T cells derived from DTH biopsy. In addition, CD4(+) T cells recognizing different MAGE-A3-derived epitopes were detected in DTH-derived cells. A spontaneous anti-MAGE-C2 CD8(+) T-cell response was present prior to TriMix-DC therapy and increased during treatment. The tumor response was assessed with 18-fluorodeoxyglucose-positron emission/computed tomography. We documented a partial tumor response according to RECIST criteria with a marked reduction in (18)F-FDG-uptake by lung, lymph node and bone metastases. The patient remains free from progression after 12 months of follow-up. This case report indicates that administration of autologous TriMix-DC by the combined intradermal and intravenous route can mediate a durable objective tumor response accompanied by a broad T-cell response in a chemorefractory stage IV-M1c melanoma patient.
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Hydrolyzed dietary casein as compared with the intact protein reduces postprandial peripheral, but not whole-body, uptake of nitrogen in humans.
Deglaire, A, Fromentin, C, Fouillet, H, Airinei, G, Gaudichon, C, Boutry, C, Benamouzig, R, Moughan, PJ, Tomé, D, Bos, C
The American journal of clinical nutrition. 2009;(4):1011-22
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Abstract
BACKGROUND Compared with slow proteins, fast proteins are more completely extracted in the splanchnic bed but contribute less to peripheral protein accretion; however, the independent influence of absorption kinetics and the amino acid (AA) pattern of dietary protein on AA anabolism in individual tissues remains unknown. OBJECTIVE We aimed to compare the postprandial regional utilization of proteins with similar AA profiles but different absorption kinetics by coupling clinical experiments with compartmental modeling. DESIGN Experimental data pertaining to the intestine, blood, and urine for dietary nitrogen kinetics after a 15N-labeled intact (IC) or hydrolyzed (HC) casein meal were obtained in parallel groups of healthy adults (n = 21) and were analyzed by using a 13-compartment model to predict the cascade of dietary nitrogen absorption and regional metabolism. RESULTS IC and HC elicited a similar whole-body postprandial retention of dietary nitrogen, but HC was associated with a faster rate of absorption than was IC, resulting in earlier and stronger hyperaminoacidemia and hyperinsulinemia. An enhancement of both catabolic (26%) and anabolic (37%) utilization of dietary nitrogen occurred in the splanchnic bed at the expense of its further peripheral availability, which reached 18% and 11% of ingested nitrogen 8 h after the IC and HC meals, respectively. CONCLUSIONS The form of delivery of dietary AAs constituted an independent factor of modulation of their postprandial regional metabolism, with a fast supply favoring the splanchnic dietary nitrogen uptake over its peripheral anabolic use. These results question a possible effect of ingestion of protein hydrolysates on tissue nitrogen metabolism and accretion. This trial was registered at clinicaltrials.gov as NCT00873951.
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Increased protein maintains nitrogen balance during exercise-induced energy deficit.
Pikosky, MA, Smith, TJ, Grediagin, A, Castaneda-Sceppa, C, Byerley, L, Glickman, EL, Young, AJ
Medicine and science in sports and exercise. 2008;(3):505-12
Abstract
PURPOSE This study examined how a high-protein diet affected nitrogen balance and protein turnover during an exercise-induced energy deficit. METHODS Twenty-two men completed a 4-d (D1-4) baseline period (BL) of an energy balance diet while maintaining usual physical activity level, followed by 7 d (D5-11) of 1000 kcal.d increased energy expenditure via exercise (50-65% V O2peak). One group consumed 0.9 g of protein per kilogram per day and maintained energy balance throughout the 11-d intervention (BAL, N = 8). The other two groups consumed their BL energy intake throughout the 11 days, resulting in a 7-d, 1000-kcal.d energy deficit. These groups consumed either 0.9 g of protein per kilogram per day (DEF, N = 7) or 1.8 g of protein per kilogram per day (DEF-HP, N = 7). Mean nitrogen balance (NB), calculated per kilogram of fat-free mass (FFM), was determined for BL, days 5-8 (EX1), and days 9-11 (EX2). Whole-body protein turnover was derived from phenylalanine and tyrosine kinetics assessed while fasting at rest on days 4, 7, and 12, using a priming dose of L-[ring-N]tyrosine and a 4-h, primed, continuous infusion of L-[N]phenylalanine and L-[ring-H4]tyrosine. RESULTS DEF experienced a decrease in NB from BL to EX 1 that was maintained in EX 2. No changes in NB occurred for BAL or DEF-HP over time. No within- or between-group differences were found over time for Phe flux (Qp), conversion rate of Phe to Tyr (Qpt), or the derived protein synthesis value (Sp). CONCLUSION Increased dietary protein maintained NB during exercise-induced energy deficit, but this did not impact resting whole-body protein turnover.
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The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon.
Geboes, KP, De Hertogh, G, De Preter, V, Luypaerts, A, Bammens, B, Evenepoel, P, Ghoos, Y, Geboes, K, Rutgeerts, P, Verbeke, K
The British journal of nutrition. 2006;(6):1078-86
Abstract
In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.
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Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial.
Albers, MJ, Steyerberg, EW, Hazebroek, FW, Mourik, M, Borsboom, GJ, Rietveld, T, Huijmans, JG, Tibboel, D
Annals of surgery. 2005;(4):599-606
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Abstract
OBJECTIVE To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery. SUMMARY BACKGROUND DATA Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results. METHODS Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources. RESULTS Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects. CONCLUSIONS In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise.
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Amino acid administration to premature infants directly after birth.
te Braake, FW, van den Akker, CH, Wattimena, DJ, Huijmans, JG, van Goudoever, JB
The Journal of pediatrics. 2005;(4):457-61
Abstract
OBJECTIVES To test the hypothesis that the administration of 2.4 g amino acids (AA)/(kg.d) to very low birth weight infants is safe and results in a positive nitrogen balance. STUDY DESIGN We conducted a randomized, clinical trial. Preterm infants with birth weights <1500 g received either glucose and 2.4 g AA/(kg.d) from birth onward (n=66) or solely glucose during the first day with a stepwise increase in AA intake to 2.4 g AA/(kg.d) on day 3 (n=69). Blood gas analysis was performed daily during the first 6 postnatal days; blood urea nitrogen levels were determined on days 2, 4, and 6; AA plasma concentrations and nitrogen balances were determined on days 2 and 4. Student t tests, Mann-Whitney tests, and chi2 tests were performed to compare groups. RESULTS Infants supplemented with AA had no major adverse side effects. Their blood urea nitrogen levels were higher, nitrogen balance turned positive upon AA administration, and more AA concentrations were within reference ranges. CONCLUSIONS High-dose AA administration to very low birth weight infants can be introduced safely from birth onward and results in an anabolic state.
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Postprandial metabolic utilization of wheat protein in humans.
Bos, C, Juillet, B, Fouillet, H, Turlan, L, Daré, S, Luengo, C, N'tounda, R, Benamouzig, R, Gausserès, N, Tomé, D, et al
The American journal of clinical nutrition. 2005;(1):87-94
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Abstract
BACKGROUND The quality of cereal protein has been little studied in humans despite its quantitative importance in the diet, particularly in developing countries. OBJECTIVE The objective of this study was to determine the nutritional value of wheat protein in humans as assessed by the measurement of their real ileal digestibility and postprandial retention. DESIGN Healthy young adults (n = 14) were fitted with an intestinal tube to allow the collection of intestinal fluid in the duodenum or terminal ileum. Subjects received a mixed meal of 136 g wheat toast that contained 24.6 g uniformly and intrinsically [(15)N]-labeled wheat protein. Intestinal fluid, blood, and urine were collected for 8 h postprandially. RESULTS The real ileal digestibility of dietary wheat nitrogen amounted to 90.3 +/- 4.3%. The cumulative amount of dietary nitrogen transferred to the deamination pools reached a plateau at 8 h of 24.7 +/- 6.8% of the amount ingested. The urinary excretion of dietary nitrogen in ammonia was high (0.8 +/- 0.3% of ingested dose). The incorporation of dietary nitrogen into serum protein reached 7.0 +/- 1.9% of the meal. Postprandial wheat protein retention was 66.1 +/- 5.8%. CONCLUSIONS Our results show that wheat proteins had the same true ileal digestibility as did most of the plant proteins already studied in humans, but also that they had a lower postprandial nitrogen retention value. However, this low value was higher than that predicted from the calculation of indispensable amino acid scores, ie, 89% rather than 30-40% of the nutritional value of milk proteins.
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Early enteral administration of immunonutrition in critically ill children: results of a blinded randomized controlled clinical trial.
Briassoulis, G, Filippou, O, Hatzi, E, Papassotiriou, I, Hatzis, T
Nutrition (Burbank, Los Angeles County, Calif.). 2005;(7-8):799-807
Abstract
OBJECTIVES In a blinded, prospective, randomized, controlled clinical trial, we compared nitrogen balance (NB), nutritional indices, antioxidant catalysts, and outcome in critically ill children given an immune-enhancing formula (I) or conventional early enteral nutrition (C). METHODS Fifty patients, 103 +/- 7 months old, with disorders prompting admission to the pediatric intensive care unit, including sepsis, respiratory failure, and severe head injury, were enrolled in the study. Within 12 h of admission, patients were randomized to receive I (n=25) or C (n=25). Caloric intake was aimed at meeting patient's predicted basal metabolic rate by day 2 and predicted energy expenditure by day 4, irrespective of group assignment. Outcome endpoints and complications were recorded; NB, transthyretin, retinol-binding protein, transferrin, zinc, copper, and metabolic indices were measured on days 1 and 5 and compared with clinical and nutritional characteristics within and between groups. RESULTS Both diets achieved their initial targets of covering predicted basal metabolic rate by day 2 and predicted energy expenditure by day 4. Twenty four-hour NB became positive in 40% of patients in group C and occurred in 64% of patients in group I by day 5. Only in group I did the mean NB become positive by day 5 (0.07+/-0.07 g/kg versus -0.24+/-0.03 g/kg on day 1, P<0.001) compared with group C in which the mean NB remained negative (-0.06+/-0.04 g/kg versus -0.25+/-0.06 g/kg on day 1, P<0.001). By day 5, nutritional indices and antioxidant catalysts showed a higher increasing trend in group I compared with group C and higher osmolality (P<0.02), sodium (P<0.03), and urea (P<0.04). Diarrhea for group I (P<0.02) and gastric distention for group C (P<0.04) were the most frequently recorded complications. Mortality or length of stay did not differ between groups, but there was a trend for less gastric gram plus isolates (P<0.05) or for Candida species (P<0.04) and nosocomial infections in group I compared with group C. CONCLUSIONS Although less well tolerated, immunonutrition is a feasible method of early enteral nutrition in the pediatric intensive care unit. It has a favorable effect on nutritional indices and antioxidant catalysts, but not on outcome hard endpoints. Although it poses a higher metabolic burden to the patient, it shows a trend to improve colonization and infection rates. Appropriate modifications for specific age populations might improve its tolerability and benefits among critically ill children.