Cranberry Proanthocyanidins Improve Intestinal sIgA During Elemental Enteral Nutrition

Background: Elemental enteral nutrition (EEN) decreases gut‐associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)–4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA. Methods: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL‐4 by enzyme‐linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT‐6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot. Results: Compared with chow, EEN significantly decreased tissue IL‐4, phosphorylated STAT‐6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone. Conclusions: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone.     

Glutamine Improves Innate Immunity and Prevents Bacterial Enteroinvasion During Parenteral Nutrition

Background: Patients receiving parenteral nutrition (PN) are at increased risk of infectious complications compared with enteral feeding, which is in part explained by impaired mucosal immune function during PN. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated. Methods: Forty‐eight hours following venous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 10), PN (n = 12), or PN + GLN (n = 13) for 5 days. Small intestine tissue and luminal fluid were collected for mucin 2 (MUC2), lysozyme, cryptdin 4 analysis, and luminal interleukin (IL)–4, IL‐10, and IL‐13 level measurement. Tissue was also harvested for ex vivo intestinal segment culture to assess tissue susceptibility to enteroinvasive Escherichia coli. Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < .0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal, P < .05; tissue, P < .0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced expression. IL‐4, IL‐10, and IL‐13 decreased significantly with PN compared with chow, whereas GLN significantly increased these cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < .05), while GLN significantly decreased enteroinvasion to chow levels (P < .05). Conclusions: GLN‐supplemented PN improves innate immunity and resistance to bacterial mucosal invasion lost with PN alone. This work confirms a clinical rationale for providing glutamine for the protection of the intestinal mucosa.     

Arginine Supplementation Induces Arginase Activity and Inhibits TNF‐α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction

Background: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor–α (TNF‐α) and interleukin‐10 (IL‐10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow + IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF‐α and IL‐10 levels were analyzed in splenic macrophage cultures. Results: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO–/–, and Arg–/– groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF‐α levels (Arg vs IO group, P < .05) and maintenance of IL‐10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham–/–, IO–/–, and Arg–/– vs other, P < .05). Conclusions: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF‐α levels, which may be directly related to nitric oxide derived from arginine.     

Innate Mucosal Immune System Response of BALB/c vs C57BL/6 Mice to Injury in the Setting of Enteral and Parenteral Feeding

Background: Outbred mice exhibit increased airway and intestinal immunoglobulin A (IgA) following injury when fed normal chow, consistent with humans. Parenteral nutrition (PN) eliminates IgA increases at both sites. Inbred mice are needed for detailed immunological studies; however, specific strains have not been evaluated for this purpose. BALB/c and C57BL/6 are common inbred mouse strains but demonstrate divergent immune responses to analogous stress. This study addressed which inbred mouse strain best replicates the outbred mouse and human immune response to injury. Methods: Intravenously cannulated mice received chow or PN for 5 days and then underwent sacrifice at 0 or 8 hours following controlled surgical injury (BALB/c: n = 16–21/group; C57BL/6: n = 12–15/group). Bronchoalveolar lavage (BAL) was analyzed by enzyme‐linked immunosorbent assay for IgA, tumor necrosis factor–α (TNF‐α), interleukin (IL)–1β, and IL‐6, while small intestinal wash fluid (SIWF) was analyzed for IgA. Results: No significant increase in BAL IgA occurred following injury in chow‐ or PN‐fed BALB/c mice (chow: P = .1; PN: P = .7) despite significant increases in BAL TNF‐α and SIWF IgA (chow: 264 ± 28 vs 548 ± 37, P < .0001; PN: 150 ± 12 vs 301 ± 17, P < .0001). Injury significantly increased mucosal IgA in chow‐fed C57BL/6 mice (BAL: 149 ± 33 vs 342 ± 87, P = .01; SIWF: 236 ± 28 vs 335 ± 32, P = .006) and BAL cytokines. After injury, PN‐fed C57BL/6 mice exhibited no difference in BAL IgA (P = .9), BAL cytokines, or SIWF IgA (P = .1). Conclusions: C57BL/6 mice exhibit similar airway responses to injury as outbred mice and humans, providing an appropriate model for studying mucosal responses to injury. The BALB/c mucosal immune system responds differently to injury and does not replicate the human injury response.     

Randomized Clinical Trial

Background:When intestinal microbiota is imbalanced, a patient becomes more vulnerable to infectious complications; intervention with beneficial probiotics may help lower risk for infection. The aim of this study was to measure levels of inflammatory cytokine messenger RNA (mRNA) in surgical samples of intestinal mucosal tissues from patients who were given the probiotic Saccharomyces boulardii before undergoing colon surgery. Methods: Thirty‐three patients undergoing colon resection were randomly assigned to receive at least 7‐day preoperative probiotic treatment (n = 15) or conventional (n = 18) treatment. Probiotic treatment consisted of oral lyophilized S boulardii. Cytokine mRNA levels (interleukin [IL]–10, IL‐1β, IL‐23A, tumor necrosis factor [TNF]–α, IL‐12B, interferon‐γ [INF‐γ], and IL‐17A) were measured in samples obtained during the operation. Postoperative infections were also assessed. Results: Patients who received probiotics had significantly lower mucosal IL‐1β, IL‐10, and IL‐23A mRNA levels than the control group (P = .001, P = .04, and P = .03, respectively). However, mRNA expression of other cytokines did not differ between the 2 groups (P > .05). The incidence of postoperative infectious complications was 13.3% and 38.8% in probiotic and control groups, respectively (P > .05). There was no perioperative mortality in either group. The mean total length of hospital stay was similar between the groups (P > .05). Conclusions: Probiotic treatment with S boulardii downregulates both pro‐ and anti‐inflammatory cytokines in the intestinal colonic mucosa with no statistical impact on postoperative infection rates.     

Exploring and Enhancing the Anti‐Inflammatory Properties of Polymeric Formula

Background: Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti‐inflammatory properties of EEN. Methods: Glutamine, arginine, vitamin D₃, and α linolenic acid (ALA), present in PF, along with curcumin, were identified as immunoactive nutrient therapies. Tumor necrosis factor (TNF)–α–exposed HT‐29 colonic epithelial cells were used to investigate the immunosuppressive activity of the nutrients by assessing their effect on cell viability, cell activity, chemokine response (interleukin‐8 [IL‐8]), nuclear factor (NF)–κB, P38 mitogen‐activated protein kinase, IκB kinase (Iκκ), and nitric oxide (NO). Results: Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D₃, but not ALA, significantly attenuated IL‐8 production. Glutamine and arginine led to phosphorylation blockade of the signaling components in NF‐κB and P38 pathways, reduction in kinase activity, and enhancement in NO production. Combining glutamine, arginine, and curcumin at optimal concentrations completely abolished the IL‐8 response. Conclusions: These data indicate that glutamine, arginine, and vitamin D₃ can suppress inflammation at concentrations equivalent to those used in PF. The mechanisms of this action were mediated through influencing the NF‐κB and P38 cascades. Glutamine and arginine‐fortified PF with curcumin might be a promising option to enhance the effectiveness and expand the scope of EEN therapy in CD treatment.     

Vitamin E in New‐Generation Lipid Emulsions Protects Against Parenteral Nutrition–Associated Liver Disease in Parenteral Nutrition–Fed Preterm Pigs

Introduction: Parenteral nutrition (PN) in preterm infants leads to PN‐associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Hypothesis: Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. Methods: We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d‐α‐tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, β‐sitosterol, campesterol, and stigmasterol). Results: Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low‐density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7‐hydroxylase and organic solute transporter–α expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo ¹³C‐CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance‐associated protein 2, were higher in ILE, OV, and PS vs IL. Conclusions: α‐tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.     

Intravenous Fish Oil and Pediatric Intestinal Failure–Associated Liver Disease: Changes in Plasma Phytosterols,Cytokines, and Bile Acids and Erythrocyte Fatty Acids

Background: Soybean oil (SO) emulsions are associated with intestinal failure–associated liver disease (IFALD); fish oil (FO) emulsions are used to treat IFALD. SO and FO differ with respect to their fatty acid and phytosterol content. In children with IFALD whose SO was replaced with FO, we aimed to (1) quantify changes in erythrocyte fatty acids and plasma phytosterols, cytokines, and bile acids and (2) correlate these changes with direct bilirubin (DB). Design: This study enrolled IFALD children who received 6 months of FO. Blood samples were collected prior to FO, and after 2 weeks and 3 and 6 months of FO. The primary outcome was 3‐month vs baseline biomarker concentrations. Results: At study initiation, the median patient age was 3 months (interquartile range, 3–17 months), and mean ± standard deviation DB was 5.6 ± 0.7 mg/dL (n = 14). Cholestasis reversed in 79% of subjects. Eicosapentaenoic and docosahexaenoic acid was greater than baseline (P < .001, all time points). Linoleic and arachidonic acid and sitosterol and stigmasterol were less than baseline (P < .05, all time points). Three‐ and 6‐month interleukin‐8 (IL‐8) and total and conjugated bile acids were less than baseline (P < .05). Baseline IL‐8 was correlated with baseline DB (r = 0.71, P < .01). Early changes in stigmasterol and IL‐8 were correlated with later DB changes (r = 0.68 and 0.75, P < .05). Conclusion: Specific fat emulsion components may play a role in IFALD. Stigmasterol and IL‐8 may predict FO treatment response.     

Pretreatment and Treatment With L‐Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis

Background: Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. Methods: C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L ‐arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L ‐arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). Results: The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine‐supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Conclusions: Arginine attenuates weight loss and BT in mice with colitis.     

The Role of L‐Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation

Background: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L‐arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow +IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. Results: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg–/– groups vs Sham and Sham–/– groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO–/– groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. Conclusion: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.     

Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels

BACKGROUND: Total parenteral nutrition (TPN) prevents progressive malnutrition but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or established respiratory antiviral or antibacterial mucosal immunity. Our previous work demonstrated that decreases in intestinal immunoglobulin A (IgA) were associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)-4 and IL-10. Because glutamine supplementation of TPN partially preserves respiratory defenses and normalizes GALT, we investigated the ability of parenteral glutamine to normalize respiratory and intestinal IgA levels and measured Th2 cytokines in intestinal homogenates. METHODS: Animals were cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an isonitrogenous, isocaloric TPN solution formulated by removing the appropriate amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days. Respiratory tract and intestinal washings were obtained for IgA and the intestine homogenized and analyzed for IL-4 and IL-10. RESULTS: TPN decreased intestinal and respiratory IgA in association with decreases in intestinal IL-4 and IL-10 compared with chow-fed animals. Glutamine significantly improved respiratory and intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and maintained IL-10 levels midway between chow-fed and TPN animals. CONCLUSIONS: Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels and had a normalizing effect on Th2-type IgA-stimulating cytokines.     

Influence of Preoperative Feeding on the Healing of Colonic Anastomoses in Malnourished Rats

Background: Malnutrition influences healing of gastrointestinal anastomoses. The authors hypothesize that colonic anastomotic healing is decreased by malnutrition and might be improved by preoperative feeding. Methods: Eighty adult male Wistar rats were divided into 4 groups: (1) control rats 1 (C1), fed regular chow ad libitum for 21 days; (2) malnourished pair‐fed rats (M), fed 50% of the food ingested by the control rats for 21 days; (3) preoperative nutrition rats (PRE), fed 50% of the average of the controls for 21 days and then fed preoperative nutrition with regular chow ad libitum for 1 week before the operation; and (4) control rats 2 (C2), fed regular chow ad libitum for 28 days. On days 21 (C1 and M) and 28 (PRE and C2), rats underwent 2 colonic transections and, subsequently, 2 end‐to‐end anastomoses. Rats were killed on postoperative day 5. The anastomoses were ressected for tensile strength and histological analysis. Results: PRE rats showed increased maximal tensile strength vs the M group (0.09 ± 0.01 vs 0.15 ± 0.01; P < .05) and similar values of maximal tensile strength as the controls (0.15 ± 0.01 vs 0.15 ± 0.02; P = .91). Collagen type I was higher in controls vs the PRE group (6.13 ± 0.39 vs 4.90 ± 1.53; P < .05); nevertheless, the PRE group showed higher collagen type I than M rats (4.90 ± 0.36 vs 3.83 ± 0.35; P < .05). Conclusions: Preoperative feeding for 7 days increases the maximal tensile strength, as well as the percentage area of mature collagen, approaching similar values as the control group.     

Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia‐Inducible Factor‐1 Activation in Rats With Burn Injury

Background: Recent studies have suggested that pyruvate‐enriched oral rehydration solution (Pyr‐ORS) may be superior to the standard bicarbonate‐based ORS in the protection of intestine from ischemic injury. The aim of this study was to compare the effects of Pyr‐ORS with citrate‐enriched ORS (Cit‐ORS) on the intestinal hypoxia‐inducible factor‐1 (HIF‐1)–erythropoietin (EPO) signaling pathway for enteral rehydration in a rat model of burn injury. Methods: Rats were randomly assigned to 4 groups (N = 20, 2 subgroups each: n = 10): scald sham (group SS), scald with no fluid resuscitation (group SN), scald and resuscitation with enteral Cit‐ORS (group SC), and scald and resuscitation with enteral Pyr‐ORS (group SP). At 2.5 and 4.5 hours after a 35% total body surface area (TBSA) scald, intestinal mucosal blood flow (IMBF), contents of HIF‐1, EPO, endothelial nitric oxide synthase (eNOS), nitric oxide (NO), barrier protein (ZO‐1), levels of serum diamine oxidase (DAO), and intestinal mucosal histology injury score were determined. Results: Serum DAO activities in the scalded groups were significantly elevated, but less raised in group SP than in group SC, at 2.5 hours and at 4.5 hours after the scald. Further, group SP more profoundly preserved intestinal HIF‐1 expression compared with group SC at the 2 time points. Compared with group SC, group SP had markedly elevated intestinal EPO, eNOS, and NO levels at the same time points, respectively (P < .05). Similarly, IMBF and ZO‐1 levels were significantly higher in group SP than in group SC. Intestinal mucosal histopathological scores were statistically higher at 2.5 hours and 4.5 hours after scalding but were more attenuated in group SP than in group SC (P < .05). Immunofluorescence expression of intestinal mucosal ZO‐1 was consistent with the above changes. The above parameters were also significantly different between groups SC and SN (all P < .05). Conclusion: Pyr‐ORS provides a superior option to Cit‐ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF‐1‐EPO signaling cascades.     

Glutamine Restores Tight Junction Protein Claudin‐1 Expression in Colonic Mucosa of Patients With Diarrhea‐Predominant Irritable Bowel Syndrome

Background:Recent studies showed that patients with diarrhea‐predominant irritable bowel syndrome (IBS‐D) had an increased intestinal permeability as well as a decreased expression of tight junctions. Glutamine, the major substrate of rapidly dividing cells, is able to modulate intestinal permeability and tight junction expression in other diseases. We aimed to evaluate, ex vivo, glutamine effects on tight junction proteins, claudin‐1 and occludin, in the colonic mucosa of patients with IBS‐D. Materials and Methods: Twelve patients with IBS‐D, diagnosed with the Rome III criteria, were included (8 women/4 men, aged 40.7 ± 6.9 years). Colonic biopsy specimens were collected and immediately incubated for 18 hours in culture media with increasing concentrations of glutamine from 0.6–10 mmol/L. Claudin‐1 and occludin expression was then measured by immunoblot, and concentrations of cytokines were assessed by multiplex technology. Claudin‐1 expression was affected by glutamine (P < .05, analysis of variance). In particularly, 10 mmol/L glutamine increased claudin‐1 expression compared with 0.6 mmol/L glutamine (0.47 ± 0.04 vs 0.33 ± 0.03, P < .05). In contrast, occludin expression was not significantly modified by glutamine. Interestingly, glutamine effect was negatively correlated to claudin‐1 (Pearson r = ‐0.83, P < .001) or occludin basal expression (Pearson r = ‐0.84, P < .001), suggesting that glutamine had more marked effects when tight junction protein expression was altered. Cytokine concentrations in culture media were not modified by glutamine treatment. Conclusion: Glutamine increased claudin‐1 expression in the colonic mucosa of patients with IBS‐D. In addition, glutamine effect seems to be dependent on basal expression of tight junction proteins.     

Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

正常妊娠和妊娠期活动性TORCH感染者的细胞免疫功能及Th亚群激活状态研究

目的:研究活动性TORCH感染孕妇细胞免疫及Th亚群激活状态,以进一步探讨其发生机制。方法:用流式细胞仪结合微珠捕获法(cytometric bead array,CBA)测定血清6种Th1/Th2源细胞因子水平,流式细胞术计数外周血淋巴细胞及其亚群。结果:①正常孕妇的CD8+细胞〔(30.0±0.8)%〕较非孕对照〔(27.5±4.9)%〕增多、CD19+细胞〔(9.4±2.0)%〕较非孕对照〔(11.8±3.9)%〕减少;活动感染孕妇CD3+〔(65.6±6.5)%〕、CD4+〔(32.6±7.6)%〕和CD8+〔(27.7±5.1)%〕细胞数量均显著低于正常孕妇(P<0.05)。②正常孕妇的TNF-α〔(4.4±1.3)pg/ml〕及IL-2〔(4.0±1.1)pg/ml〕较非孕对照组显著降低,除IFN-γ外,多数Th1源与Th2源细胞因子的比值下降;活动感染孕妇IL-2水平〔(5.0±1.5)pg/ml〕及IL-2/IL-10比值(0.67±0.14)高于正常孕妇(P<0.05)。结论:①正常妊娠时机体处于免疫抑制状态,尤其以Th1细胞抑制明显,Th1/Th2平衡向Th2偏移。②活动感染孕妇以IL-2水平升高为主,似有Th1细胞激活,提示妊娠期活动性TORCH感染的发生可能与该阶段的Th1细胞抑制及Th亚群激活状态改变有关。     

Fermentable fiber ameliorates fermentable protein-induced changes in microbial ecology, but not the mucosal response, in the colon of piglets

Dietary inclusion of fermentable carbohydrates (fCHO) is reported to reduce large intestinal formation of putatively toxic metabolites derived from fermentable proteins (fCP). However, the influence of diets high in fCP concentration on epithelial response and interaction with fCHO is still unclear. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP/low fCHO [14.5% crude protein (CP)/14.5% total dietary fiber (TDF)]; low fCP/high fCHO (14.8% CP/16.6% TDF); high fCP low fCHO (19.8% CP/14.5% TDF); and high fCP/high fCHO (20.1% CP/18.0% TDF) as dietary treatments. After 21-23 d, pigs were killed and colon digesta and tissue samples analyzed for indices of microbial ecology, tissue expression of genes for cell turnover, cytokines, mucus genes (MUC), and oxidative stress indices. Pig performance was unaffected by diet. fCP increased (P < 0.05) cell counts of clostridia in the Clostridium leptum group and total short and branched chain fatty acids, ammonia, putrescine, histamine, and spermidine concentrations, whereas high fCHO increased (P < 0.05) cell counts of clostridia in the C. leptum and C. coccoides groups, shifted the acetate to propionate ratio toward acetate (P < 0.05), and reduced ammonia and putrescine (P < 0.05). High dietary fCP increased (P < 0.05) expression of PCNA, IL1β, IL10, TGFβ, MUC1, MUC2, and MUC20, irrespective of fCHO concentration. The ratio of glutathione:glutathione disulfide was reduced (P < 0.05) by fCP and the expression of glutathione transferase was reduced by fCHO (P < 0.05). In conclusion, fermentable fiber ameliorates fermentable protein-induced changes in most measures of luminal microbial ecology but not the mucosal response in the large intestine of pigs.     

Total phenolic contents in selected fruit and vegetable juices exhibit a positive correlation with interferon-γ, interleukin-5, and interleukin-2 secretions using primary mouse splenocytes

We hypothesized that some fruits and vegetables have an immuno-modulatory potential on T helper type 1 (Th1) and Th2 cytokine secretions. Therefore, Th1 cytokines including interleukin (IL)-2, and interferon (IFN)-γ, and Th2 cytokines including IL-4 and IL-5, produced by mouse splenocytes administrated with 13 selected fruits and vegetables were determined. The results showed that low dose (10 μg/ml) administration with oriental plum, mulberry, peppers (including green, yellow, and red color varieties), ceylon spinach, and red onion significantly (P<0.05) increased IL-2 secretion. Administration with high dose (500 μg/ml) strawberry significantly increased the secretion ratio of IFN-γ/IL-5 (Th1/Th2). Further analysis showed that the stimulatory effects of selected fruits and vegetables on IL-2, IFN-γ, and IL-5 secretions demonstrated a significantly (P<0.05) positive correlation with the total phenolic (including flavonoid) content in the selected fruits and vegetables. The correlation coefficient (r) between total phenolic content (including flavonoid) and cytokine secretions varied in magnitude: IFN-γ>IL-5>IL-2. The coefficients from total phenolic content were much greater than those from the total flavonoid content. The total phenolic and flavonoid contents of oriental plum, mulberry, green pepper, and red onion II showed a significantly positive correlation with the IFN-γ secretion. This study suggests that in vitro supplementation with phenolic-rich fruits and vegetables might demonstrate an immuno-modulatory potential via the regulation of Th1/Th2 cytokine secretions, especially Th1 cytokines. The Th1/Th2 immuno-modulatory potentials of these selected fruits and vegetables will be important and useful for the future exploitation of food materials to develop a novel functional food.