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T Pyles

Publications and source records attributed to T Pyles.

At least 19 recordsLinked to original sources
PubMed1996

Steroid therapy can modulate gut barrier function, host defense, and survival in thermally injured mice.

Prednisone may be immunosuppressive and dehydroepiandrosterone may stimulate the immune response, but their effect on gut-origin sepsis caused by bacterial translocation has not been studied. Balb/c mice were treated orally with prednisone (1 or 10 mg/kg/day) or saline for 4 days before receiving gavage with 10 (10) 14 C-labeled Escherichia coli and a 20% thermal injury. Mice were transfused with allogeneic blood and given dehydroepiandrosterone (5 or 25 mg/kg/day) or vehicle subcutaneously for 4 days before bacterial gavage and thermal injury. Some groups in each experiment were observed 10 days for mortality and others were sacrificed 4 hr postburn to measure translocation and survival of translocated bacteria. Survival in prednisone treated animals was 25% (10 mg/kg/day) and 75% (1 mg/kg/day) versus 80% for controls. Following dehydroepiandrosterone administration, survival was 72% (25 mg/kg/day/group) and 30% (5 mg/kg/day/group) versus 16% for controls. High dose prednisone increased bacterial translocation to the intestinal wall and mesenteric lymph nodes and greatly impaired killing of translocated E. coli. In contrast, dehydroepiandrosterone (25 mg/kg) did not affect translocation but significantly improved bacterial killing. Prednisone and dehydroepiandrosterone exert opposite effects during gut-derived sepsis.

Animals↗
PubMed1996

High protein diets are associated with increased bacterial translocation in septic guinea pigs.

During sepsis, body protein stores are decreased due to an increase in protein catabolism. The utilization of nutritional support with high-protein diets has been used as a solution to the problem of sepsis-induced protein loss. Work from our laboratory, however, has shown that diets low in protein (5% of total calories) improve survival in septic animals as compared to high protein (20%) diets. The present study investigated the relationship between low-protein diets and improved survival by determining whether septic animals receiving high-protein diets have increased bacterial translocation. Sepsis was induced in guinea pigs by the implantation of an osmotic minipump into the peritoneal cavity containing an equal mixture of Escherichia coli (10(8)) and Staphylococcus aureus (10(8)) or saline. On Day 3 postlaparotomy, the animals were randomized to one of four groups. The groups consisted of septic and nonseptic animals that received a diet with 5 or 20% of total calories as protein. Following 4 days of diet all animals received an instillation of 14C labeled E. coli (10(10)). Four hours later the animals were sacrificed and blood, mesenteric lymph nodes, spleen, lungs, and liver were removed for determination of radionuclide counts. Results indicated that the septic animals that received the high protein diet had more bacterial translocation, as indexed by higher radionuclide counts in the MLN, liver, lung and blood. These findings suggest that a low protein, enterally fed diet may improve survival in septic patients by decreasing the incidence of bacterial translocation.

Animals↗
PubMed1995

Bacterial translocation-related mortality may be associated with neutrophil-mediated organ damage.

Balb/c mice were transfused with .2 mL of C3H/HeJ mouse blood. 5 days later, the mice were gavaged with 10(10) 14C-labeled Escherichia coli, and a 20% full thickness flame burn was inflicted. Additional animals were treated with enisoprost (prostaglandin E1 (PGE1) analog) 200 micrograms/kg/day orally for 3 days before burn. Bacterial translocation was determined by both radionuclide counts (dpm) and viable colony counts 24 h post burn. Neutrophil accumulation was evaluated by the measurement of myeloperoxidase (MPO) in the liver. In addition, splenic macrophages were separated and cultured for 24 h with or without 10 micrograms/mL of LPS. Tumor necrosis factor, interleukin-1 (IL-1), IL-6, and PGE2 were measured in the cell culture supernatants. Consistent with previous work, enisoprost significantly reduced translocation. MPO in the liver was significantly greater in the control group compared to the enisoprost group. There was a significant correlation between MPO content and the degree of bacterial translocation (p < .05). Lipopolysaccharide-stimulated macrophage production of IL-1, IL-6, and PGE2 were significantly greater in the enisoprost group.

Alprostadil↗
PubMed1994

Effects of antimurine interleukin-6 on bacterial translocation during gut-derived sepsis.

BACKGROUND: Recent studies have shown that interleukin-6 (IL-6) is involved in the systemic changes that are associated with infection and tissue injury and that there is a correlation between high levels of IL-6 and poor outcome during several pathologic conditions. OBJECTIVE: The effects of antimurine IL-6 antibody on survival and host defense were studied in a clinically relevant model of infection. METHODS: Balb/c mice were treated with 10 micrograms of antimurine interleukin-6, a nonspecific mouse IgG, or placebo 1 hour before they underwent bacterial challenge by gavage of 10(10) Escherichia coli and burn injury. Survival and the extent of translocation of E coli were determined as well as the correlation between the IL-6 levels and survival times. RESULTS: Survival after burn and gavage was 90% in animals treated with antimurine interleukin-6 vs 50% in animals treated with nonspecific IgG and 30% in saline-treated controls. A significant correlation between the levels of IL-6 and survival time was observed. Less translocation and better killing of bacteria were observed in the tissues of animals treated with antimurine interleukin-6. CONCLUSIONS: Interleukin-6 appears to play a major role in both the intensity of translocation of E coli from the intestine following burn injury and the host's ability to kill translocated organisms. Improved outcome was associated with a reduction of IL-6 levels by anti-IL-6 antibody.

Analysis of Variance↗
PubMed1994

Role of early enteral feeding and acute starvation on postburn bacterial translocation and host defense: prospective, randomized trials.

OBJECTIVES: To investigate the effect of: a) starvation during the preburn period and b) immediate postburn enteral nutrition on the permeability of the gut to microorganisms and the ability of the host to kill translocated bacteria. DESIGN: Prospective, randomized, experimental trials. SETTING: Laboratory. SUBJECTS: Balb/c mice and Hartley guinea pigs. INTERVENTIONS: In the first experiment, mice were starved for 0, 6, 12, 18, or 24 hrs before receiving gavage with 10(10) 14C-labeled Escherichia coli and a 20% burn injury. In the second experiment, guinea pigs received a 40% burn injury and were randomized to receive a complete enteral diet (175 kcal/kg/day) or infusion of an equal volume of lactated Ringer's solution via a previously placed gastrostomy for 6, 24, or 48 hrs. After each feeding period, 10(10) 14C Escherichia coli were infused intragastrically. In both experiments, the animals were killed 4 hrs after gavage, and mesenteric lymph nodes, spleen, liver, lungs, peritoneal fluid, and blood were harvested aseptically. MEASUREMENTS: For each tissue or fluid, the number of viable E. coli and radionuclide counts of the 14C E. coli were measured and the percentage of translocated bacteria that remained alive was calculated. MAIN RESULTS: In mice, 18 and 24 hrs of preburn starvation increased translocation only to the mesenteric lymph nodes, but it also enhanced bacterial killing in all tested tissues. Guinea pigs that were fed enterally for 6, 24, and 48 hrs postburn had significantly lower bacterial translocation in all tissues compared with animals infused with lactated Ringer's solution. Additionally, enhanced killing of translocating organisms was observed after 24 and 48 hrs of feeding. CONCLUSIONS: Starvation preburn has different consequences than starvation postburn on translocation and bacterial killing. Postburn enteral nutrition decreases the load of viable bacteria in the tissues via a double mechanism: an initial decreased translocation and a subsequent improved ability to kill bacteria that do translocate.

Acute Disease↗
PubMed1993

Reduction of bacterial translocation with oral fibroblast growth factor and sucralfate.

The aim of this study was to evaluate the ability of basic fibroblast growth factor (bFGF) and sucralfate to prevent bacterial translocation after burn injury. Four groups of Balb/c mice (n = 10/group) were treated by gavage with bFGF (10 micrograms/kg/d), sucralfate (15 mg/kg/d), bFGF plus sucralfate, or saline for 4 days prior to receiving a gavage with 1 x 10(10) 14C-radiolabeled Escherichia coli and a 20% full-thickness burn. Four hours after burn, the mesenteric lymph nodes, liver, spleen, and blood were harvested aseptically. For each tissue, the number of viable bacteria and radionuclide counts of the translocated 14C-labeled E. coli were measured, and the percentage of translocated organisms that remained alive was calculated. The results indicated that treatment with either bFGF or sucralfate alone had a partial effect on translocation, whereas the combined treatment with bFGF plus sucralfate significantly decreased the magnitude of translocation in all tested tissues (p < 0.05, ANOVA), which was associated with complete preservation of gut mucosal integrity. None of the treatments affected the ability of the host to kill translocated bacteria when the results were compared with those of the controls. The additive effect of the combined therapy may be due to the high affinity of sucralfate for bFGF, decreasing the degradation of bFGF by gastric acid.

Animals↗
PubMed1993

Identification of the blood component responsible for increased susceptibility to gut-derived infection.

It has previously been reported that the transfusion of allogeneic whole blood increases sepsis-related mortality and decreases the ability of the host to kill bacteria that have translocated from the intestinal tract. To determine which blood component contributes to this adverse effect, the impact of the transfusion of white cells (WBCs), red cells (RBCs), and plasma on microbial translocation, bacteria killing, and mortality rate was studied. Blood from C3H/HeJ mice was separated into WBCs, RBCs, and plasma, and these fractions were transfused to Balb/c mice. Controls received sterile saline. Five days after transfusion, all Balb/c mice underwent a 20-percent burn and gavage with 1 x 10(10) Escherichia coli labeled with 14C-glucose. Mortality was observed for 10 days. Four additional groups, receiving the same treatment as above, were sacrificed 4 hours after the burn, and mesenteric lymph nodes, liver, kidney, and blood were harvested aseptically. For each tissue, quantitative colony counts, radionuclide counts, and percentage of translocated bacteria that remained alive were calculated. By radionuclide counts, no difference was observed in the degree of 14C E. coli translocation among the groups. In contrast, the percentage of viable bacteria and the mortality rate were significantly higher in the group receiving allogeneic WBCs than in all other groups (p < 0.05). It is concluded that WBCs are the component in transfused blood that has an adverse effect on host resistance to gut-derived infection.

Animals↗
PubMed1993

Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide.

OBJECTIVE: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega-Nitro-L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. RESULTS: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine. Treatment with NNA reversed the beneficial effects of arginine on immune defense. CONCLUSIONS: The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway.

Animals↗
PubMed1993

Prostaglandin E1 analogues misoprostol and enisoprost decrease microbial translocation and modulate the immune response.

The aim of this study was to investigate the ability of two prostaglandin E1 (PGE1) analogues, misoprostol and enisoprost, to alter bacterial translocation following burn injury. Balb/c mice were treated with misoprostol (n = 36) or enisoprost (n = 36) for 3 days with different doses (20 or 200 micrograms/kg/day) prior to receiving a 20% full-thickness burn and simultaneous gavage with 1 x 10(10) 14C-Escherichia coli. Animals were sacrificed 4 and 24 hr postburn, and blood, peritoneal fluid, mesenteric lymph nodes, spleen, liver, and lungs were harvested aseptically. Radionuclide counts, number of viable bacteria, and percentage of translocating bacteria remaining alive in each tissue suggested that the high doses of misoprostol or enisoprost decreased the magnitude of 14C-E. coli translocation, while the low dose of both drugs enhanced bacterial clearance. Therefore, both misoprostol and enisoprost reduce bacterial translocation, and modulate bacterial clearance in a dose-dependent manner.

Alprostadil↗
PubMed1992

Impact of blood transfusion and burn injury on microbial translocation and bacterial survival.

The role of the immune system in microbial translocation must be clarified. In these studies, the effect of blood transfusion-related immunosuppression on translocation was investigated in a burn animal model previously known to increase the gut's permeability to 14C-radiolabeled Escherichia coli. In a first experiment, Balb/c mice underwent transfusion (T) with 0.2 mL per mouse of allogeneic C3H/HeJ mouse blood 5 days prior to undergoing 30-percent burn injury (B) and simultaneous gavage (G) with 10(9) E. coli bacteria labeled with 14C. An additional six groups of Balb/c mice underwent different combinations of T, B, and G procedures (TG, BG, TB, T, B, G). Survival rate was recorded for all groups on Day 10. This experiment suggested that B and T, to a lesser extent, were the factors affecting survival, although the combination of T, B, and G clearly showed a synergistic effect on mortality. In a second experiment, 18 Balb/c mice belonging to TBG, BG, TG, and G groups were sacrificed 1, 4, and 24 hours after burn or gavage. The residual radioactivity and the percentage of viable bacteria were computed for mesenteric lymph nodes, spleen, liver, lungs, blood, and peritoneal fluid. Statistical analysis of the radionuclide counts recognized B as the only variable able to enhance the magnitude of 14C E. coli translocation. The percentage of viable bacteria showed that T and, more moderately, B were the factors leading to the failure of bacterial clearance in the tissues.

Animals↗
PubMed1992

The degree of bacterial translocation is a determinant factor for mortality after burn injury and is improved by prostaglandin analogs.

Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation.

16,16-Dimethylprostaglandin E2↗
PubMed1991

Distribution and survival of Escherichia coli translocating from the intestine after thermal injury.

The present investigation was performed to study the kinetics of tissue distribution and deposition of Escherichia coli and endotoxin translocating from the intestine after thermal injury. Escherichia coli was grown in the presence of 14C glucose and both labeled bacteria and endotoxin prepared from the labeled bacteria were used as translocation probes. Escherichia coli (10(8) to 10(10) bacteria) and E. coli endotoxin (100 micrograms per animal) were gavaged into the stomach immediately before a 30% burn injury was inflicted in mice. Animals were killed 1, 4 and 24 hours after burn injury. Translocation occurred extensively within 1 hour after burn injury. Expressed as amount of radioactivity per gram of tissue, translocation was greatest in the mesenteric lymph node (MLN) followed by spleen, lung, and liver. Translocation of endotoxin was similar to translocation of intact bacteria, with the exception that less radioactivity could be found in the peritoneal cavity and more in the liver. Both intact E. coli and endotoxin translocated directly through the intact bowel wall. Killing of bacteria was greatest in the MLN and spleen, approximating 95% to more than 99% of translocating bacteria. Killing efficiency was lowest in the lungs. It is concluded that estimation of translocation by viable bacterial counts in tissues grossly underestimates the extent of translocation of bacteria and ignores the extent of translocation of endotoxin. Translocation of endotoxin may have biologic significance that is independent of and in addition to translocation of intact bacteria.

Animals↗
PubMed1990

The process of microbial translocation.

The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.

Animals↗
PubMedDate not supplied

Relationship between extent of burn injury and magnitude of microbial translocation from the intestine.

The gut can be a source of sepsis after thermal injury. In the present study the relationship between the extent of burn injury and magnitude of bacterial translocation was investigated. Mice underwent 0%, 10%, 20%, 30%, or 50% total body surface area full-thickness burn and simultaneous gavage with 1 x 10(10) 14C-labeled Escherichia coli. mesenteric lymph nodes, liver, spleen, peritoneal fluid, and burn wound were excised 4 hours after burn injury. Residual radioactivity and bacterial colony counts were measured, and percentages of viable organisms were calculated. Results showed that the rate of translocation of 14C E. coli increased proportionally with the burn size, reaching a maximum at 30%. The cutaneous eschar collected a remarkable amount of labeled bacteria, suggesting enteric microflora as a possible source of contamination of the burn wound via endogenous routes. The percentage of viable organisms in the tissues demonstrated that the ability of mesenteric lymph nodes, liver, and eschar to clear translocated bacteria was directly affected by the severity of the burn injury.

Animals↗
PubMedDate not supplied

Translocation and survival of Bacteroides fragilis after thermal injury.

B. fragilis and E. coli were labeled with tritiated (3H) thymidine, and 10(10) of each were given separately by gavage in Balb/c mice immediately before a 20% burn injury was inflicted. Control groups received gavage with 3H-B. fragilis or 3H-E. coli without burn. Four hours after burn or gavage was administered, the animals were killed, and the radionuclide and colony counts were determined in the mesenteric lymph nodes, liver, and spleen. Additional groups of mice receiving gavage (B. fragilis or E. coli) and burn were observed for 10 days to study survival. The results showed that 3H-B. fragilis translocated to a greater extent than 3H-E. coli but that fewer B. fragilis than E. coli survived in tissues. Survival was 86% for animals challenged with B. fragilis versus 53% for animals challenged with E. coli. It is concluded that in this model B. fragilis translocates extensively after burn injury and that survival is closely related to the destruction of translocated bacteria.

Animals↗
PubMedDate not supplied

Oral glutamine decreases bacterial translocation and improves survival in experimental gut-origin sepsis.

BACKGROUND: Glutamine has been shown to be an important dietary component for the maintenance of gut metabolism. The purpose of this study was to assess the potential benefit of glutamine-enriched diets on experimental gut-derived sepsis. METHODS: BALB/c mice were fed either 2% glutamine-supplemented or 1% glycine-supplemented (near-isonitrogenous control) AIN-76A diets. Control mice received either nonsupplemented AIN-76A or regular Purina Rodent Laboratory Mouse Chow 5001 diets. After 10 days of feeding, the mice were transfused with allogeneic blood (from C3H/HeJ mice), and the feeding protocols were continued for an additional 5 days. The mice then underwent gavage with 10(10) Escherichia coli labeled with either indium-111 oxine or [14C]glucose followed immediately by a 20% burn injury. Some mice were observed 10 days postburn for survival rates. Others were killed 4 hours after burn, and the mesenteric lymph nodes, liver, and spleen were harvested to determine radionuclide and bacterial colony counts. The percentages of viable translocated E coli were also calculated. RESULTS: Mice fed glutamine-enriched diets had a lower degree of translocation (as measured by both radionuclide and bacterial counts) to the tissues than did the other groups and had an improvement in the ability to kill translocated E coli (as measured by the percentage of viable bacteria). Survival was significantly higher in the group fed 2% glutamine (81%) compared with the groups fed 1% glycine (36%), AIN-76A (35%), and Purina Rodent Laboratory Mouse Chow 5001 (36%) diets (p < .004). CONCLUSIONS: Glutamine-supplemented enteral diets may exert important benefits in preventing gut-origin sepsis after trauma.

Animals↗
PubMedDate not supplied

Post injury hypermetabolic response and magnitude of translocation: prevention by early enteral nutrition.

The relationship between hypermetabolism and bacterial translocation was investigated in guinea pigs receiving a 40% burn. Animals were infused intragastrically with a complete enteral diet or Ringer's solution for 48 h, given 10(10) 14C-labeled Escherichia coli intragastrically, and killed 4 h later. Resting metabolic expenditure (RME), translocation (dpm of the 14C-labeled E. coli) to the portal blood and ileal mucosa, plasma cortisol, and urinary vanillylmandelic acid (VMA) were determined. Enterally fed animals had significantly lower RME, cortisol, VMA, and dpm, but higher mucosal and body weight than the Ringer's group. Disintegrations per minute (dpm) in the blood were positively correlated with RME (r = 0.856), cortisol (r = 0.872), VMA (r = 0.759), and dpm mucosa (r = 0.836) and inversely correlated with mucosal weight (r = -0.883). We conclude that bacterial translocation is reduced by early feeding and is an important cause of hypermetabolism and stress hormone production after burn injury.

Animals↗