The effect of intestinal transit time on bacterial translocation

Increase in intraluminal bacterial count, disruption of the mucosal integrity, changes in intestinal immunity and transit time are the factors involved in bacterial translocation. The relationship between intestinal transit time, intra luminal bacterial count and translocation rate were investigated in 40 Wistar-albino rats. The study was conducted in 4 groups with 10 animals in each. Group I (controls): saline + laboratory chow, Group II: saline + oral total parenteral nutrition (TPN) solution, Group III: morphine sulfate (MS) + oral TPN solution, Group IV: neostigmine bromide (NB) + oral TPN solution. Intestinal transit time was measured by using Indium111-labeled diethylene triamine pentaacetic acid (DTPA). It was prolonged in the MS-treated group and shortened in the NB-treated group (p < 0.01). The frequency of bacterial translocation was 60% in the oral TPN solution group, 100% in the MS-treated group, 20% in the NB-treated group and 10% in controls. Bacterial counts in duodenum, jejunum, ileum and caecum were significantly increased (p < 0.001) in the MS-treated group and decreased (p < 0.05) in the NB-treated group in comparison with the control group. In conclusion, the prolongation of intestinal transit time increased the intraluminal bacterial count and augmented bacterial translocation. The decrease in intestinal transit time had a converse effect.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg(-1)/day(-1)). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN- supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

Psychosocial adjustment of children and adults with port wine stains

OBJECTIVE: To find out if lactulose can prevent the bacterial translocation that is induced by obstructive jaundice in rats. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Turkey. MATERIAL: 50 male Wistar-albino rats. INTERVENTIONS: 10 rats were not operated on and used as controls; 20 rats underwent laparotomy and sham ligation of the common bile duct (CBD); 20 had the CBD ligated alone; and 20 had the CBD ligated and were given oral lactulose 2 ml/day until death. All rats were killed after 14 days. MAIN OUTCOME MEASURES: Presence of Escherichia coli in mesenteric lymph nodes (MLN), and bacterial overgrowth as indicated by counts of E coli in the caecum. RESULTS: There was significantly less bacterial translocation to MLN in the group that had been given lactulose compared with CBD-ligated and lactulose not given (2/20 compared with 8/20, p = 0.06). There was also a significant reduction in the number of Gram negative bacteria in that group (p = < 0.01). CONCLUSION: Lactulose seems to reduce the incidence of translocation from the gut to MLN in rats with obstructive jaundice.     

Pentoxifylline and thalidomide fail to reduce hepatic steatosis during total parenteral nutrition and bowel rest in the rat

BACKGROUND: We suggested that the continuous translocation of endotoxin from Gram-negative bacterial overgrowth during bowel rest and total parenteral nutrition (TPN) causes the release of tumor necrosis factor (TNF), resulting in liver damage and hepatic dysfunction. Because TPN-induced hepatic steatosis was significantly reduced by the monoclonal antibodies against TNF, we attempted a more clinically applicable approach using pentoxifylline and thalidomide. METHODS: A control group (group I) fed rat chow and four groups of rats receiving TPN were studied. Group II received TPN only; group III, TPN and 100 mg/kg/d pentoxifylline; group IV, TPN and 200 mg/kg/d pentoxifylline; and group V, TPN and 5 mg/kg/d thalidomide. On day 7, total liver fat was determined. RESULTS: Bowel rest and TPN resulted in a significant (p < .0005) increase in liver fat content that was unaltered by either pentoxifylline or thalidomide. CONCLUSIONS: Our results show no role for pentoxifylline or thalidomide in reducing TPN-associated hepatic steatosis.     

Short bowel syndrome--surgical aspects

INTRODUCTION: Long-term survival after massive intestinal resection is now possible with parenteral nutritional support. The expense, morbidity, and inconvenience of this therapy, however, have led to continued interest in alternatives for the treatment of the short bowel syndrome. Patients with short bowel require a multi disciplinary approach over a prolonged period. HISTORICAL CONSIDERATIONS: The history of small bowel transplantation started in 1959 when Lillehei showed that autotransplantation of the small intestine in a dog was feasible. From 1964 to 1971, 7 attempts of small bowel allotransplantations in humans have been reported. All 7 patients died. DEFINITION: Short gut syndrome is a malabsorptive condition occurring after significant loss of intestinal absorptive capacity. The clinical syndrome is manifested by malnutrition, steatorrhea, weight loss, and diarrhea due to decreased absorptive capacity. ETIOLOGY: Etiologic factors leading to the short gut state include necrotizing enterocolitis, midgut volvulus, trauma, embolic phenomenon, and Crohn's disease. PATHOPHYSIOLOGY: Intestinal failure is the end result of several complex interacting mechanisms related to: reduced enterocyte mass, short small bowel length with consequent reduced mucosal contact time for absorption, massive proximal loop dilatation with poor propulsion, and intraluminal stasis and bacterial overgrowth lead to bacterial translocation to the liver systemically. MANAGEMENT: Patients with short bowel must be totally or partly supported with intravenous nutrition until enteral absorption can sustain survival and growth. Autologous bowel reconstruction attempts to reconfigure the residual bowel to eliminate negative factors of bowel dilatation and stasis, and redistribute the absorptive mucosa to enhance the adaptation response. Several procedures have been suggested to: prolong transmitting time and increase mucosal contact time, enhance absorption by bowel tailoring and bowel lengthening, and increasing the Enterocyte mass. CONCLUSION: Autologous gastro-intestinal reconstruction is still in its infacny with prospect of new and different concepts for the future.     

Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome

OBJECTIVES: Massive intestinal resection results in short bowel syndrome and necessitates prolonged parenteral feeding. The purpose of this work was to assess the impact of late complications of short bowel syndrome, including intestinal bacterial overgrowth and enterocolitis, on the duration of parenteral nutrition (PN) in comparison with factors evident in the neonatal period. METHODS: Retrospective chart review. RESULTS: Of 49 children, 42 were weaned from parenteral nutrition after a treatment course of 17 +/- 14 months. In these 42, postresection small intestinal length equaled 81 +/- 65 cm; 45% had an ileocecal valve. Small intestinal length in the seven children who were PN dependent was 31 +/- 30 cm (p < 0.05); none had an ileocecal valve (p < 0.05). Bacterial overgrowth occurred in all seven PN-dependent children and in 23 of 42 children eventually weaned from PN (p < 0.05). When bacterial overgrowth was identified before weaning (n = 12), the duration pf PN was 28 +/- 17 months, but when bacterial overgrowth was first identified only after weaning (n = 11), the duration of PN was 16 +/- 13 months (p < 0.05). Small intestinal inflammation correlated with bacterial overgrowth (r = 0.69). Those children with severe enteritis identified before weaning remained on the PN regimen for 36 +/- 15 months, in comparison with 21 +/- 14 months in those with mild enteritis and 13 +/- 11 months in those without inflammation (p < 0.02). CONCLUSIONS: Although the length of small intestine remaining after resection is the best immediate predictor of final success in terminating PN in children with short bowel syndrome, PN is prolonged by bacterial overgrowth and associated enteritis in those who will ultimately be weaned.     

Salsalate, morphine, and postoperative ileus

BACKGROUND: Previously, we demonstrated that ketorolac, a nonsteroidal antiinflammatory drug (NSAID), prevented postoperative small bowel ileus in a rodent model. The aim of this study was to evaluate the effect of salsalate, an NSAID without antiplatelet effect, on postoperative ileus alone or in combination with morphine. METHODS: Forty-eight rats underwent placement of duodenal catheters and were then randomly assigned to one of eight groups (n = 6). Four groups had standardized laparotomy following drug administration, whereas 4 groups underwent the same treatment without laparotomy: control and morphine animals received 0.1 mL alcohol via the catheter, whereas salsalate and salsalate-plus-morphine animals received salsalate (15 mg/kg) dissolved in 0.1 mL alcohol. The animals also received 0.5 mg/kg morphine (morphine and salsalate plus morphine) or the same volume of saline (control and salsalate) subcutaneously. Transit was measured following the injection of a nonabsorbed marker via the duodenal catheter and is defined as the geometric center (GC) of distribution. An additional 20 rats had serosal electrodes placed on the jejunum, and were assigned to one of four treatment groups (control, salsalate, morphine, and salsalate plus morphine; n = 5 each group). Myoelectric activity was recorded until the reappearance of the migrating myoelectric complex (MMC) following laparotomy. RESULTS: Laparotomy and morphine independently reduced small bowel transit (P = 0.0006 and 0.006, respectively, by three-way analysis of variance [ANOVA]; GC 4.3 +/- 0.2 control versus 2.2 +/- 0.3 laparotomy versus 3.6 +/- 0.4 morphine), but morphine did not further worsen postoperative transit (GC 2.4 +/- 0.4; P = 0.42). Although salsalate did not alter baseline transit, pretreatment improved postoperative transit (P = 0.0002; GC 3.6 +/- 0.4). This effect was lost with the addition of morphine (GC 2.7 +/- 0.2; P = 0.21). The MMCs returned earlier after laparotomy in salsalate-pretreated rats (63 +/- 18 minutes salsalate versus 160 +/- 12 minutes laparotomy; P < 0.01, one-way ANOVA). However, this effect was also lost in animals receiving morphine (106 +/- 16 min; P > 0.05). CONCLUSION: Salsalate improves postoperative small bowel motility in a rodent model; however, this effect is masked by morphine.     

Clinical trials in the elderly. Should we do more?

In this study, SPF rat models were used. The purpose of the study was to observe the impairment of gut barrier function subsequent to long-term TPN, and evaluate the effect of TPN enriched by alanyl-glutamine (Ala-Gln) on the gut. After 7 day standard TPN, there was a significant decrease of CD3+, CD4+, CD8+ and IgA-containing plasma cells in lamina propria. The percentage of intestinal bacteria coated by S-IgA declined, and bacterial adherence to intestinal epithelial cells increased with an increased incidence of bacterial translocation to mesenteric lymph nodes. All these adverse effects could be attenuated by addition of Ala-Gln to TPN solutions or oral glutamine (Gln) or Ala-Gln administration. The results of the study suggested that long-term standard TPN impaired the immune gut barrier function and therefor facilitated enterogenic infection, and addition of Gln or Ala-Gln significantly benifited gut barrier protection and infection prevention, which might be important to clinical practice.     

Preservation of intestine protein by peptide YY during total parenteral nutrition

Maintaining rats on TPN for 7 days was associated with a 50% reduction in gut mass and protein content. Co-infusing PYY with total parenteral nutrition (TPN) resulted in significant savings in jejunal wet mass and elevated protein content of jejunum, ileum and colon as compared with rats maintained on TPN alone. No significant effects of PYY on plasma amino acid profile were noted. Although minor alterations in mucosal polyamines were observed in rats maintained on TPN, co-infusion of PYY had no significant effect on gut polyamine concentrations. These results suggest that PYY has trophic effects upon the gut during otherwise catabolic conditions. Therefore, co-infusion of PYY with TPN may suggest methods whereby loss of intestinal mucosa and atrophy-associated complications of TPN may be modulated.     

Risk factors for a positive tuberculin skin test among employees of an urban, midwestern teaching hospital

This study was performed to investigate: (1) the role of gut-derived endotoxin/bacterial translocation in the pathogenesis of sepsis, and (2) the possible effects of selective decontamination of the digestive tract (SDD) on mortality in rats following 40 per cent full-thickness scald injury. In the SDD-treated group, Enterobacteriaceae and yeasts were eradicated from the caecal mucosa, while the mucosal flora consisting of mainly anaerobes was well preserved, within 3 days. The incidence of bacterial translocation to the mesenteric lymph nodes (MLN) and viscerae was significantly lowered on postburn days 1, 3 and 5 (P < 0.05-0.01). Meanwhile, pretreatment with SDD resulted in reductions of the faecal endotoxin levels in different segments of intestinal tract to less than 0.5 per cent (0.04-0.45 per cent) of the untreated control; there was also a significant attenuation of the elevation of endotoxin concentrations in both portal and systemic blood. Intestinal diamine oxidase (DAO) activity returned to baseline on day 5 in rats receiving SDD but not in controls. The 5-day survival rate in the SDD-treated group was elevated by 26.7 per cent as compared with controls (P < 0.05). These data suggested that endotoxin/bacterial translocation took place early and commonly, which in turn contributed to postburn sepsis and mortality. SDD was effective in preventing gut origin endotoxaemia and bacterial translocation, and improving the survival rate in rats following severe thermal injuries.     

Translocation and multiple organ failure

A review of bacterial translocation and multiple organ failure (MOF) is presented. Splanchnic ischaemia plays a central role in the development of MOF, but the exact mechanism of translocation is unclear. The concentration of endotoxins and bacteria in the gut is high. The critically ill patient is often treated with antibiotics with a broad antibacterial spectrum and overgrowth of Gram negative bacteria will take place in the gut favouring the translocation phenomenon. The regime of selective gut decontamination is discussed. Regional and systemic oxygen kinetics together with metabolic markers are important in detecting splanchnic ischaemia. Hepatic vein catheterisation and gastric mucosa pHi are discussed. The regional inflammation in the gut is often initiated by endotoxins, which stimulate the cytokines IL-1, IL-6 and TNF. Another important factor that can accentuate inflammation of the gut is reperfusion injury. A proposal for treatment of splanchnic ischaemia and translocation is discussed i.e.: optimizing central haemodynamic parameters, optimizing the regional microcirculation, treatment with antibodies to endotoxins, gut decontamination and early enteral nutrition. When splanchnic hypoperfusion is detected it cannot be ignored. It may be possible to correct the hypoperfusion with early gastrointestinal resuscitation and to thereby reduce the duration and mortality of MOF. The above mentioned suggestions are all very demanding of resources, but have to be considered in gut directed therapy.     

Effect of lipid-free total parenteral nutrition on hepatic drug conjugation in rats

The effect of total parenteral nutrition (TPN) on drug conjugation in male Sprague-Dawley rats was examined using a nutrition solution composed of amino acids and glucose. The overall disposition of acetaminophen including the formation kinetics of the sulfate and glucuronide metabolites was used as an in vivo probe. Selected drug metabolizing enzyme activities also were examined in vitro. TPN, 200 kcal/kg/day, was administered by continuous i.v. infusion for 14 days and changes elicited were compared to control animals allowed free access to rat chow. TPN decreased the total clearance of acetaminophen by 34% and the formation clearance to acetaminophen sulfate by 47%. The formation clearance of acetaminophen to acetaminophen glucuronide was unaffected by TPN. Cytochrome P450 concentration and oxidative demethylase activity toward p-nitroanisole were decreased in parallel, 47 and 53%, respectively, and UDP-glucuronosyltransferase activity with p-nitrophenol and acetaminophen as the acceptor aglycones was decreased 44 and 25%, respectively in the animals receiving TPN. Sulfotransferase activity toward both p-nitrophenol and acetaminophen decreased 28% in animals receiving TPN vs. ad libitum rat chow. Administration of the parenteral nutrition solution as a continuous enteral infusion via a doudenal catheter slightly decreased p-nitroanisole demethylase activity (26%), but had no other significant effects on either cytochrome P450 concentration or on drug conjugating enzyme activities determined in vitro. These results show that parenteral nutrition administered i.v. depresses drug conjugation and suggest that alterations in both hepatic oxidative and conjugative biotransformation arising from total parenteral nutrition are largely attributable to bypassing the intestinal route for nutrient intake.     

Multifocal bone tuberculosis: apropos of a case

OBJECTIVE: To review recent experience of gastroschisis at the Royal Children's Hospital, Melbourne. METHODOLOGY: Retrospective review of admissions over a 13 year period, June 1980-June 1993 inclusive, including an analysis of those factors influencing mortality, morbidity and complications. RESULTS: There were 49 infants, of whom two died (4%), both having an associated bowel atresia. Mode of delivery, age at operative repair, birthweight centile and silo repair had no significant effect on the duration of total parenteral nutrition (TPN) or hospital stay. The presence of short gut and/or gut resection and localized bowel narrowing or bowel atresia resulted in a significant increase in the duration of TPN and hospital stay. The presence of a central venous line was a highly significant risk factor for the development of systemic sepsis. CONCLUSION: Currently gastroschisis has a good outlook with a low mortality. Infants with short gut/resection and bowel atresia have a long duration of TPN and hospitalization, with significant morbidity and complications.     

The intestine as an immunological organ]

The intestinal mucosa is in close contact with a large number of foreign antigens and mitogenic substances in the gut lumen. To protect the host against invasion of potential pathogens or an inappropriate immune response to the enormous number of antigens, a highly specialized immune system in the intestinal mucosa has developed, the so-called gut-associated lymphoid tissue (GALT). The passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa is called bacterial translocation. Bacterial translocation in critically ill patients may lead to a significant incidence of systemic sepsis. This has attracted much clinical interest, as it has been shown that disturbances of the GALT and malnutrition itself, impair various aspects of barrier function. Enteral nutrition seems to be superior to parenteral nutrition in maintaining the functional barrier of the gut. Defined dietary variable (fibre, glutamine) influence bacterial translocation. Future therapeutic strategies should therefore concentrate on early enteral feeding in traumatised patients to reduce the incidence of bacterial translocation and septic complications.     

Topical gentamicin and ethacrynic acid: effects on cochlear function

OBJECTIVE: To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window. STUDY DESIGN: The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone. METHODS: Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. RESULTS: After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds. CONCLUSIONS: This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.     

Arginine-supplemented diets inhibit endotoxin-induced bacterial translocation in mice

We studied the effects of supplemental dietary arginine (ARG) on endotoxin-induced bacterial translocation. Mice were fed a 20%-casein diet (control) or a 20%-casein diet supplemented with 2% or 4% ARG and then injected with lipopolysaccharide (1 mg/500 microliters). The incidence of bacterial translocation was noted by the recovery of viable organisms from the mesenteric lymph node (MLN) and spleen. The mortality rates of the mice were 40%, 10%, and 20% in the control group and 2%- and 4%-ARG groups, respectively. Of the surviving mice, bacterial translocation occurred in 100% of the control group, in 56% (MLN) and 56% (spleen) in the 2%-ARG group, and in 36% (MLN) and 25% (spleen) in the 4%-ARG group. Quantitative colony counts and median numbers of viable bacteria were lower (p < 0.05) in the 2%-ARG group and slightly lower in the 4%-ARG group compared with the control group. MLN and spleen weights expressed as a percentage of body weight were heavier (p < 0.05) only in the 2%-ARG group. These results support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infection after injury, and that supplementation with 2% or 4% ARG could improve outcome.     

Elemental diet-induced immune suppression is caused by both bacterial and dietary factors

Because it is unclear whether elemental diet-induced immune suppression is an indirect effect caused by the translocating bacteria or is directly caused by the elemental diet, we tested whether prevention of diet-induced bacterial translocation or disruption of the gut microflora ecology would prevent diet-induced impaired lymphocyte function in a rat elemental diet model. Prevention of diet-induced bacterial translocation was accomplished by the addition of cellulose fiber or oral antibiotics (penicillin and streptomycin) to the elemental diet feeding regimen. Control groups consisted of rat food-fed and elemental diet-fed (4.25% amino acids; 28% glucose) rats. Immune function was quantitated by measuring the mitogen-induced blastogenic response of peripheral blood or splenic mononuclear cells to the mitogens concanavalin A and phytohemagglutinin. Bacterial translocation from the gut to the mesenteric lymph node and cecal bacterial population levels were measured in all groups. Although the incidence of elemental diet-induced bacterial translocation was reduced from 100% to 25% (p < .01) by the addition of dietary fiber, fiber did not prevent diet-induced impaired lymphocyte function. Because fiber supplementation of the elemental diet did not completely prevent diet-induced intestinal bacterial overgrowth or bacterial translocation, the experiment was repeated in antibiotic-decontaminated rats. Antibiotic decontamination completely prevented diet-induced intestinal bacterial overgrowth and bacterial translocation. Although antibiotic decontamination reduced the magnitude of lymphocyte mitogen suppression (p < .05), it was not fully effective in reversing the diet-induced lymphocyte suppression. These results indicate that elemental diet-induced lymphocyte blastogenic suppression is related to both bacterial and dietary factors.     

Tissue manganese concentrations and antioxidant enzyme activities in rats given total parenteral nutrition with and without supplemental manganese

BACKGROUND: Manganese is an essential but potentially toxic mineral. Parenteral administration of manganese via total parenteral nutrition (TPN) bypasses homeostatic mechanisms (intestinal absorption and presystemic hepatic elimination). Our objective in this study was to determine the effect of supplemental manganese in TPN solutions on manganese status in a rat model. METHODS: Male Sprague-Dawley rats underwent jugular catheterization and were given 61.0 +/- 0.4 g/d TPN solution providing 0.5 +/- 0.2 nmol manganese/g (Mn-; n = 6) or 16 +/- 3 nmol manganese/g (Mn+; n = 7) for 7 days. Reference rats (RF; n = 8) were fed a purified diet containing 1.3 mmol manganese/g. RESULTS: Liver manganese decreased in both TPN groups, but tibia, spleen, and pancreas manganese concentrations were greater in Mn+ rats than in Mn- or RF rats. Although no treatment differences were seen in heart or liver manganese superoxide dismutase activity, heart copper-zinc superoxide dismutase activity was lower in the Mn+ rats than in Mn- or RF rats (p < .05). Glutathione peroxidase activity was depressed in livers of both Mn- and Mn+ rats relative to RF rats (p < .0001), which was not due to selenium deficiency. CONCLUSIONS: Supplemental parenteral manganese is taken up to a greater extent by peripheral tissues than the liver. In this first report of antioxidant enzyme activities in animals maintained with TPN, we found that TPN as well as supplemental manganese can influence antioxidant enzyme activities. We conclude that it is generally unnecessary and potentially toxic to supplement TPN solutions with manganese during short-term usage.     

Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition

OBJECTIVE: The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA: The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. METHODS: Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. RESULTS: Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. CONCLUSIONS: Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.     

Addition of glucagon to lipid-free total parenteral nutrition reduces production of prostaglandin E2 by stimulated splenic macrophages

Sepsis is a major complication of total parenteral nutrition (TPN). Impaired immunity has been suggested as being responsible for TPN-related sepsis, but it is unknown how the immune system is affected by TPN. We recently found that administration of lipid-free TPN resulted in an increase in prostaglandin E2 (PGE2) release by stimulated splenic macrophages. This observation suggested that TPN may impair immunity through the prominent immunosuppressive effects of PGE2. In the present study, we tested the hypothesis that addition of glucagon to TPN solution may protect against the immunosuppressive effect of TPN by modifying PGE2 secretion. Adult, male Sprague-Dawley rats (n = 18) underwent jugular vein cannulation: group 1 (n = 7) received intravenous saline and chow ad libitum; group 2 (n = 6) received TPN (80 mL/24 h); and group 3 (n = 5) received TPN (80 mL/24 h) plus glucagon (100 micrograms/24 h). After 10 days, spleens were removed and splenic macrophages were isolated and cultured for 24 h in plain M199 medium (nonstimulated) or in medium containing Escherichia coli lipopolysaccharide (5 micrograms/mL) (stimulated). PGE2 release was determined by enzyme-linked immunosorbent assay. There were no differences in PGE2 release between the groups of nonstimulated cells, but when stimulated with lipopolysaccharide, the macrophages from the TPN rats (group 2) released more PGE2 (81.68 +/- 25.99 ng/2.5 x 10(6) cells) than the control group (16.04 +/- 3.26 ng/2.5 x 10(6) cells). The release of PGE2 was normalized in the TPN animals treated with glucagon (15.71 +/- 3.33 ng/2.5 x 10(6) cells). This difference was significant, with p < .05 by Tukey's test after analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)