Prognostic value of energy expenditure and respiratory quotient measuring in patients with liver cirrhosis.

BACKGROUND & AIMS: Resting energy expenditure (REE) and respiratory quotient (RQ) as measured by indirect calorimetry (IC) may correlate with muscle mass and represent prognostic indicators in treating patients with liver cirrhosis. We aimed to assess the correlation of IC-measured REE and RQ with skeletal muscle mass (SM), mortality, and REE values as estimated by Harris-Benedict, European guidelines (EG), and Brazilian guidelines-DITEN (BG) equations in patients with liver cirrhosis. METHODS: In this prospectively designed study, REE was measured in 126 male patients with liver cirrhosis by IC and predicted by Harris-Benedict, EG (35 kcal/kg current weight), and BG (30 kcal/kg current weight) guidelines. Measurements were obtained at the time of admission to the study. Body composition was determined by whole-body dual-energy X-ray absorptiometry. The association between REE and 3-year survival was investigated. RESULTS: Cirrhosis etiology was classified as alcohol related (59.0%), viral (20.1%), cryptogenic (11.8%), or other (9.0%). Mean Child-Pugh and MELD indexes were 8.30 ± 2.0 and 14.38 ± 6.12, respectively. RQ showed a moderate correlation with SM (r = 0.64), while IC-measured REE was inversely associated with mortality (multivariate Cox Regression, HR = 0.88, 95% CI: 0.78; 1, p = 0.04). Among the predictive equations for REE, only Harris-Benedict yielded values close to the IC, with a positive Pearson correlation (r = 0.77), excellent accuracy (Cb = 0.98), and positive Lin's concordance correlation (CCC = 0.75). However, a large standard deviation was observed; HB-measured REE did not correlate with mortality. CONCLUSIONS: RQ and REE, as measured by IC, may be valuable tools for evaluating the severity of cirrhosis, by reflecting SM and predicting mortality, respectively. The predictive equations for REE included in this study cannot replace IC for this purpose. REGISTERED AT: www.clinicalTrials.gov (NCT02421848).

Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women.

INTRODUCTION: Prebiotics positively affect gut microbiota composition, thus improving gut function. These properties may be useful for the treatment of constipation. OBJECTIVES: This study assessed the tolerance and effectiveness of a prebiotic inulin/partially hydrolyzed guar gum mixture (I-PHGG) for the treatment of constipation in females, as well as its influence on the composition of intestinal microbiota and production of short chain fatty acids. METHODS: Our study enrolled 60 constipated female health worker volunteers. Participants reported less than 3 bowel movements per week. Volunteers were randomized to treatment with prebiotic or placebo. Treatment consisted of 3 weeks supplementation with 15 g/d IPHGG (fiber group) or maltodextrin (placebo group). Abdominal discomfort, flatulence, stool consistency, and bowel movements were evaluated by a recorded daily questionnaire and a weekly interview. Changes in fecal bacterial population and short chain fatty acids were assessed by real-time PCR and gas chromatography, respectively. RESULTS: There was an increased frequency of weekly bowel movements and patient satisfaction in both the fiber and placebo groups with no significant differences. Total Clostridium sp significantly decreased in the fiber group (p = 0.046) and increased in the placebo group (p = 0.047). There were no changes in fecal short chain fatty acid profile. CONCLUSIONS: Consumption of I-PHGG produced clinical results comparable to placebo in constipated females, but had additional protective effects on gut microbiota by decreasing the amount of pathological bacteria of the Clostridium genera.

Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion.

Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (Mφ) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium-chain trygliceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by addition time: no INF-γ addition, 18 hours before, or at the time of LE addition. HLA-DR expression on Mφ surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 0.5%: 100) FO decreased the expression of HLA-DR when added alone [in simultaneously-activated Mφ, for 0.1%: 70 (59 ± 73); for 0.25%: 51 (48 ± 56); and for 0.5%: 52.5 (50 ± 58)] or in association with MCTSO [in simultaneously-activated Mφ, for 0.1%: 50.5 (47 ± 61); for 25%: 49 (45 ± 52); and for 0.5%: 51 (44 ± 54) and in previously-activated Mf, for 1.0%: 63 (44 ± 88); for 0.25%: 70 (41 ± 88); and for 0.5%: 59.5 (39 ± 79)] in culture medium (Friedman p < 0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated Mφ [for 0.1%: 87.5 (75±93); for 0.25%: 111 (98 ± 118); and for 0.5%: 101.5 (84 ± 113)]. Results show that parenteral FO modulates the expression of HLA-DR on human Mφ surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.

Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion.

Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (Mphi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium chain triglyceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-gamma addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on Mphi surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 0.5%: 100) FO decreased the expression of HLA-DR when added alone [in simultaneously-activated Mphi, for 0.1%: 70 (59+/-73); for 0.25%: 51 (48+/-56); and for 0.5%: 52.5 (50+/-58)] or in association with MCTSO [in simultaneously-activated Mphi, for 0.1%: 50.5 (47+/-61); for 25%: 49 (45+/-52); and for 0.5%: 51 (44+/-54) and in previously-activated Mphi, for 1.0%: 63 (44+/-88); for 0.25%: 70 (41+/-88); and for 0.5%: 59.5 (39+/-79)] in culture medium (Friedman p<0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated Mphi [for 0.1%: 87.5 (75+/-93); for 0.25%: 111 (98+/-118); and for 0.5%: 101.5 (84+/-113)]. Results show that parenteral FO modulates the expression of HLA-DR on human Mphi surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.

Parenteral lipid emulsions and phagocytic systems.

Lipid emulsions (LE) for parenteral use are complex emulsions containing fatty acids, glycerol, phospholipids and tocopherol in variable amounts and concentrations. In clinical practice, LE have been employed for more than 30 years. Fatty acids may have different impacts on phagocytic cells according to their structure. Experimental and clinical studies have consistently shown that LE modify monocyte/macrophage and polymorphonuclear phagocytosis. The inhibitory effect of LE on the functional activity of the phagocytic system, although still clinically controversial, may have a harmful impact because total parenteral nutrition with lipids may be recommended in hypercatabolic conditions where inflammation and infection are present. LE based on triglycerides containing long chain fatty acids (termed long chain triglycerides or LCT) are the main parenteral fat source and are typically rich in n-6 polyunsaturated fatty acids. They may have adverse effects on the immune system, especially when given in high doses over a short period of time. However when administered properly they can be used safely. LE containing medium chain triglycerides (MCT) may have some advantages because of their positive effects on polymorphonuclear cells, macrophages, and cytokine production, particularly in critically ill or immunocompromised patients. New parenteral LE containing n-3 polyunsaturated fatty acids or monounsaturated olive oil are already available in Europe. Judicious use of these new LE is mandatory especially relating on their potential impact on the immune system. New experimental and clinical studies are required to further establish the role of LE in clinical nutrition.

Impact of parenteral n-3 fatty acids on experimental acute colitis.

The present study was undertaken to investigate the effects of parenteral lipid emulsions (LE) enriched with n-3 fatty acids (n-3 FA) in experimental acute colitis. Seventy-four adult male Wistar rats were randomized into six groups, five of which had acetic acid-induced colitis. The animals received a fat-free diet and water ad libitum in individual metabolic cages. By a central venous catheter, saline was infused (0.5 ml/h) into the control groups CS (without colitis) and CC (with colitis), while the test groups received specific LE for 7 days. The n-3/n-6 FA ratio and the lipidic compositions regarding long chain (LCT) and medium chain (MCT) triglycerides were: group L--1:7.7 (LCT, n = 12), M--1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus n-3 FA, n = 12) and MW-3--1:3.0 (MCT and LCT plus n-3 FA, n = 13). The frequency of diarrhea, oral intake/body weight ratio, intestinal alterations, macrophage cellularity were evaluated and colonic concentrations of leukotrienes (LTB4, LTC4), prostaglandins (PGE2) and thromboxanes (TXB2) were measured. Groups M, MW-3 and LW-3 had less diarrhea than the CC group (P<0.05). Average oral intake/body weight ratio in MW-3 animals was comparable to the CS and better than the CC group. n-3 FA treated rats (LW-3 and MW-3) presented less intestinal inflammatory alterations than CC rats. Mucosal ulcer formation in MW-3 group did not differ from CS rats. M and MW-3 rats had less macrophages in the colon than the CC group. Compared with CC group, lower concentrations of LTB4 in the CS, LW-3 and MW-3 groups; of PGE2 in the CS, M and MW-3 groups; and of TXB2 in the CS and MW-3 groups were found. Mean concentrations of LTC4 did not differ among the groups. Thus, a LCT-containing LE with a low n-3-n-6 ratio does not modify inflammatory colitis manifestations; LE with a high n-3-n-6 ratio reduces diarrhea, preserves oral intake-weight ratio, attenuates morphological consequences and decreases colonic concentrations of inflammatory mediators; MCT/LCT-containing LE with 1:3 n-3-n-6 ratio exerts the most profound beneficial impact on the inflammatory response.

Lipid and lipid-free total parenteral nutrition: differential effects on macrophage phagocytosis in rats.

Lipid emulsions provided with total parenteral nutrition (TPN) have been associated with mononuclear phagocytic system functional changes. The aim of the present investigation was to assess the influence of TPN with added lipid emulsions on macrophage (M phi) phagocytosis. Wistar rats (n = 70) with external jugular vein cannulation were randomized into seven groups. The rats received an oral diet or six different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30% non-protein calories) TPN regimens: (a) an oral diet with intravenous infusion of saline (OS); (b) non-lipid TPN (glucose); (c) TPN with 10% long chain triacylglycerol emulsions (LCT); (d) TPN with 90% LCT and 10% fish oil (FO) emulsion; (e) TPN with 50% LCT and 50% FO; (f) TPN with 10% lipid emulsion with 50% medium chain triacylglycerol (MCT) and 50% LCT; and (g) TPN with 45% MCT, 45% LCT, and 10% FO. After 96 h of TPN or saline infusion, colloidal carbon (Pelikan, Germany) was injected intravenously at 1.0 mL/kg body weight, and the rats were killed after 3 h. Liver, spleen, and lung were weighed and prepared by immunohistochemistry analyses with the HAM-56 anti-M phi antibody. Under light microscopy, the total M phi number (MT) and the colloidal carbon phagocytic M phi number (MP) were established, and the phagocytic index was calculated as MP/MT x 100. There were no statistical (P < 0.05) differences in liver, spleen, or lung weights among the seven groups in comparison with the OS group. Non-lipid TPN inhibited spleen and lung M phi phagocytosis when compared with the OS and lipid-TPN groups. Lipid TPN supplemented with fish oil emulsion increased total liver and lung M phi number and phagocytosis. These results indicate that TPN supplemented with fish oil increases M phi phagocytosis in rats.

Small bowel adaptation with growth hormone and glutamine after massive resection of rat's small bowel.

The use of glutamine (GLN) and growth hormone (GH) improves intestinal adaptation in short bowel syndrome (SBS). The present study aimed to assess the effect of a diet rich in glutamine and the use of GH on intestinal adaptation in experimental SBS. 80 Wistar rats (240 g) were randomized into 6 groups: 1) RGLN (20)--95% small bowel resection and fed on GLN diet; 2) RGLNGH (20)--95% SBR, GLN diet and GH; 3) RC (10)--95% SBR and fed on a low GLN control diet (C); 4) RCGH (10)--95% SBR and C diet and GH; 5) TAGLIN (10)--intestinal transection and anastomosis (Ta) and fed on a GLN diet; 6) TAGLNGH (10)--Ta and GLN diet and GH. GH was given SC at a dose of 0.14 mg/kg/day. The rats were weighed daily and nitrogen balance was made. Rats were sacrificed after 15 days and mucosa cell proliferation was studied with PC10 antibody. Statistical analysis was performed. All SBR rats lost weight as compared to their initial weight (8% to 13%). GH improved Ta rats weight (18.98 x 5.04%). The use of GLN diet and GH improved nitrogen balance and bowel growth on SBR groups, as compared to controls, but not cell proliferation. In conclusion, the use of GLN enriched diet and GH improves intestinal adaptation after massive resection of the small bowel in rats.

[Technical and histological standardization of experimental colitis with trinitrobenzenosulfonic acid (TNBS)]. / Padronização técnica e histológica de colite experimental com ácido trinitrobenzenosulfônico (TNBS).

Attempts to reproduce inflammatory colitis have created many experimental models. Since the pioneer work of Morris et al. (1989), trinitrobenzenosulfonic (TNBS) solutions have been used with different dosages. The aims of this work were standardize the induction of colitis, evaluate the clinical and intestinal effects of different doses and verify the reproducibility of the intestinal inflammatory process. Wistar rats were inoculated endo rectally with 2.5 ml solutions of different concentrations of TNBS and ethanol, and the rats were sacrificed after 14 days. According to the solution concentrations of TNBS (mg) and ethanol (%), six groups of animals were established: Control (saline), 30 mg/30%, 30 mg/40%, 30 mg/50%, 50 mg/10% and 50 mg/30%. Statistical analysis of food ingestion showed no differences between groups (p = 0.247). The 30/50 group presented greater weight loss when compared to 50/10 and 50/30 groups (p = 0.012). Groups 30/50 and 30/40 showed greater degrees of macroscopic lesion than control and 50/10 group (p < 0.05). Histologic lesion was not uniform to all rats regardless of the solution employed. Group 50/10 presented the less severe histologic alterations; on the other hand, 30/40 and 30/50 groups had important changes on mucosal thickness, on vascularization and ulceration. The authors conclude that experimental colitis with TNBS 1) cause intestinal lesions that are not uniform to all animals, although they may be reproduced in many of them; 2) with the same doses of TNBS, the increase in ethanol concentrations leads to a greater inflammatory process, intestinal thickness, vascularization, abscess formation and intestinal ulceration; 3) 50/10 and 50/30 solutions make less severe lesions when compared to 30/40 and 30/50 solutions; 4) 30/50 solution was the best one, as it produces inflammation 90% of the animals, increases in wall thickness in 50%, abscess in 70% and ulceration in 38%.

[Effect of glucidic and fat total parenteral nutrition on macrophage phagocytosis in rats]. / Influência da nutrição parenteral total em regime glicídico e lipídico sobre a fagocitose de macrófagos de ratos.

Fat lipid emulsions in Total Parenteral Nutrition (TPN) have been associated to Mononuclear Phagocytary System (MPS) changes. Intravenous lipid emulsions may alter macrophage membrane composition but there are controversies about their effects on MPS function. The aim of the present investigation was to assess the influence of fat free TPN and fat emulsions TPN on the macrophage phagocytosis. Wistar rats (70) with external jugular vein canulation were divided in seven groups. The rats received, intravenously (i.v.) different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30 to 32% of non-proteic caloric value) TPN regimens or oral diet: 1) Group OS: oral diet with i.v. infusion of saline; 2) Group GLU: fat-free TPN; 3) Group LCT: TPN with 10% long chain triglecide emulsion (TCL); 6) Group MCT: TPN with 10% lipid emulsion with medium chain triglycerides (TCM-50%) and TCL (50%). After 96 hours of TPN or saline infusion, colloidal carbon was i.v. injected at 1.0 mL/kg body weight. The rats were sacrificed after three hours. Liver, spleen and lung were weighted and studied by immunohistochemistry by the avidine-biotine method. Under light microscopy the total macrophage number (MT) and colloidal carbon phagocytic macrophages number (MF) were established. Phagocytic index was MT/MF x 100. The results were statistically analysed (p < 0.05). The group under oral diet (OS) was the only one to gain weight. There were no differences in organ weight in any group. There were changes in MT, MF and phagocytic index in all TPN groups. Fat free TPN inhibited liver, spleen and lung macrophage phagocytosis. Fat TPN with TCL inhibited liver and lung macrophage phagocytosis. At conclusion fat free TPN or with long chain tryglicerides may inhibit MPS phagocytosis. Further studies are necessary to estabilish the effect of TPN on other MPS function.