Biomedical subjects

R Fukushima

Publications and source records attributed to R Fukushima.

At least 19 recordsLinked to original sources

PubMed1999

Prophylactic treatment with growth hormone and insulin-like growth factor I improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis.

The purpose of this investigation was to evaluate the effects of GH and IGF-I administration in a murine model of burn-induced gut-derived sepsis. BALB/C mice were treated with 4.8 mg/kg/day of GH, 24 mg/kg/day of IGF-I or saline for 4 days. They were then administered 10(10) E. coli by gavage and subjected to 20% full thickness flame burn. All mice received allogeneic blood transfusion 5 days before burn injury to induce mild immunosuppression. Seventy-three mice were observed for survival and 51 mice were sacrificed at 4 and 20 h postburn. Blood, mesenteric lymph nodes (MLN), spleen and liver were harvested aseptically, and viable bacterial counts in the organs were determined. The small intestine was harvested for the evaluation of villus height and mitoses in the crypts. GH and IGF-I groups showed a significantly better survival than the control group. GH and IGF-I groups had significantly greater villus height and mitoses/crypt than the control group. Translocation of bacteria was not significantly different among groups, however, the relation between the numbers of viable bacteria in MLN and blood suggests that both GH and IGF-I reduced systemic spread of translocated bacteria. It is concluded that GH and IGF-I had positive effects on outcome in this model of burn-induced gut-derived sepsis. It appears that GH and IGF-I may have immune-enhancing effects and that administration of these agents may be useful for burn injury.

Animals↗

PubMed1999

Borna disease virus infection in domestic cats: evaluation by RNA and antibody detection.

Borna disease virus (BDV) infection has been suggested to cause spontaneous neurological disease in cats referred to as staggering disease. However the evaluation of BDV infection in neurologically asymptomatic cats remained unclear. In the present study, BDV infected, asymptomatic cats in Tokyo were surveyed both by the presence of plasma antibodies against BDV-p24 and -p40 and by RNA detection in peripheral blood mononuclear cells. Seven of 32 domestic cats (21.9%) were serologically or genetically judged to be BDV-infected. Six cats were positive for anti-BDV antibody and two cats were positive for BDV RNA. Within the 2 RNA-positive cats, only one was positive for anti-BDV antibodies. Furthermore, the findings of anti-BDV-p40 and anti-BDV-p24 antibody-positive cats did not completely overlap. These results suggest that there are neurologically asymptomatic domestic cats infected with BDV present in the Tokyo area.

Animals↗

PubMed1998

Reperfusion induces sublethal endothelial injury.

BACKGROUND: Endothelial cells are pivotal in regulating thrombosis and hemostasis. In this study, we sought to characterize endothelial dysfunction and endothelial cell injury in vitro after hypoxia/reoxygenation. MATERIALS AND METHODS: Cultured human umbilical vein endothelial cells (ECs) were exposed to 120 min of hypoxia followed by reoxygenation. The release of thrombomodulin (TM) and the production of prostaglandin I2 (PGI2) were measured. Endothelial cell injury in hypoxia/reoxygenation was measured by two assays, the Fura-2 release assay and the 51chromium (51Cr) release assay. RESULTS: TM release from ECs during normoxic incubation was undetectable, while it was slightly increased during hypoxic incubation. After reoxygenation, the release of TM increased, and it became significantly higher at 120 min after reoxygenation compared with hypoxic incubation. The production of PGI2 significantly decreased during hypoxic incubation and further decreased within 30 min after reoxygenation, but returned to normoxic levels at 120 min after reoxygenation. In the Fura-2 release assay, a rapid and significantly greater release of Fura-2 was observed in hypoxia/reoxygenation compared with hypoxic incubation. In the 51Cr release assay which demonstrates cell death, 51Cr release did not increase in hypoxia/reoxygenation. CONCLUSIONS: The present study suggests that 120 min of hypoxia/reoxygenation induces endothelial dysfunction of ECs but does not cause cell death.

Cell Death↗

PubMed1998

[Bacterial translocation in multiple organ failure].

Bacterial translocation has been defined as the passage of both viable and nonviable bacteria and their products (e.g., endotoxins) across the intestinal barrier to extraintestinal sites such as the mesenteric lymph nodes, liver, etc. It has been hypothesized that intestinally derived bacteria or endotoxins serve as triggers to initiate, perpetuate, or exacerbate the septic state and thereby promote the development of multiple organ failure (MOF). In various animal studies, bacterial translocation has been associated with mortality and septic complications. Although most data on translocation have been derived from animal studies, convincing evidence has been provided that translocation may occur in humans during various disease states. The question still remains, however, of whether bacterial translocation is an important pathophysiological event in human disease or simply an epiphenomenon of severe disease, since the results are variable. Recent studies have indicated that the gut can produce important amounts of immunoinflammatory factors and that intestinal injury predisposes to distant organ injury even in the absence of detectable bacteria or endotoxins in the portal blood or tissues. This hypothesis may in part explain the inconsistent causal relationship between bacterial translocation and MOF.

Animals↗

PubMed1997

Genomic structure and expression analyses of serine acetyltransferase gene in Citrullus vulgaris (watermelon).

The genomic clones of Sat gene encoding serine acetyltransferase (SATase), a key enzyme in cysteine biosynthesis in plants, were isolated from the genomic library of Citrullus vulgaris (watermelon). The determination of nucleotide sequence of 5.7 kilobase pair (kbp) length revealed the presence of two introns of 1939 basepair (bp) and 515 bp length in the gene. The transcription start point was determined by primer extension experiments. Southern blot analysis indicated the presence of a single copy of the Sat gene and a couple of additional related sequences in the genome of C. vulgaris. The expression of Sat was analyzed in watermelon plants growth under sulfur- and/or nitrogen-starved conditions and in the presence of pyrazole, O-acetylserine and N-acetylserine. Only slight increment (ca. 1.5-2-fold) of Sat gene expression was observed upon sulfur starvation for 48 h. Interestingly, the addition of pyrazole, which is a precursor of beta-pyrazolealanine (beta-PA) synthesized by SATase and cysteine/beta-PA synthase, enhanced the expression of Sat by ca. 2-fold.

Acetyltransferases↗

PubMed1997

Preoperative total parenteral nutrition influences postoperative systemic cytokine responses after colorectal surgery.

Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide. However, it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery. This study was designed to investigate whether preoperative total parental nutrition (TPN) influences systemic interleukin-6 (IL-6) and interleukin-8 (IL-8) responses in patients following surgery for colorectal cancer. Patients with colorectal cancer received TPN (TPN group, n = 6) or an oral diet (oral group n = 6) for more than 7 d before the operation. Patients in the TPN group received standard TPN. Patients in the oral group received an ordinary hospital diet. Blood samples were collected before the operation, on postoperative day 1 (POD1), POD3, and POD7. Levels of IL-6, IL-8, and C-reactive protein (CRP) in plasma were determined. The characteristics of patients in the TPN and oral groups were comparable. Mean carbohydrate intake was greater (28 versus 19 kCal/kg), and lipid intake was smaller (0 versus 7 kCal/kg) in the TPN group than in the oral group. Plasma CRP levels did not differ between the two groups. Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group. The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group (P < 0.05, r = 0.881). The slope of the regression line was steeper in the TPN group than in the total enteral nutrition (TEN) group (P < 0.01). In conclusion, routes of nutritional supply have an impact on the production of systemic cytokines after insult. The postoperative systemic IL-6 and IL-8 responses in patients who received standard TPN preoperatively were greater than in patients who received an oral diet. Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition.

Colorectal Neoplasms↗

PubMed1997

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis.

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

Amino Acids↗

PubMed1997

Interleukin-1 and tumor necrosis factor alter plasma concentration and interorgan fluxes of taurine in dogs.

We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and interorgan fluxes of taurine and taurine precursors, including methionine and serine, using chronically catheterized awake dogs. In the first study, the dogs received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and arteriovenous differences during infusion and for 2 h after discontinuation of the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in 60 and 90% increases, respectively, in the arterial plasma taurine concentration. Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1 infusion. In the second study, we investigated whether Ala-Gln infusion affects taurine metabolism under normal and stress conditions. The dogs were given a constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was infused simultaneously during the second hour. Plasma concentrations and fluxes, across the liver, gut, and lung, of taurine and taurine precursors were studied. IL-1 administration increased the plasma concentration, hepatic release, and lung uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations or organ fluxes of taurine. These data suggest that cytokines play a role in taurine metabolism under stress conditions.

Alanine↗

PubMed1997

Effect of exogenous growth hormone on in vitro proliferation of thymic lymphocytes from the hypophysectomized rats.

Thymus weight and total thymic lymphocyte (TL) number decreased markedly after hypophysectomy (HX). Serum level of insulin-like growth factor-I (IGF-I), one of mediators brought about by growth hormone (GH), reduced considerably after the operation. Exogenous GH stimulation enhanced significantly DNA synthetic activity of TLs from HX group only at lower cell concentrations, less than 5 x 10(5) cell/ml. However, there was not a significant difference in the percentage increase of the TL-DNA synthetic activity with exogenous GH between HX and sham-operated (SO) groups. Since GH-responding TLs appeared to be mature cells and to exist in thymus medulla, the results suggest that rate of the responding cells in the thymus medulla of HX animals is similar to that of SO ones. Furthermore, there was not a significant difference in the percentages of rosette-forming cells and non-rosette-forming cells, reflecting nearly the maturation steps of TLs, between groups. It is difficult to explain such an aspect in spite of severe reduction of TLs after hypophysectomy, since the proliferative-responding rate of TLS to exogenous GH stimulation and the constitutive ratio of each maturation step of TLs in the HX group were almost same as those of SO group. The contradictory data found in thymus after hypophysectomy are discussed from the point of view of the compensatory effects of growth hormone-releasing hormone on TLs from the operated animals.

Animals↗

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

Interleukin-6 and stress hormone responses after uncomplicated gasless laparoscopic-assisted and open sigmoid colectomy.

PURPOSE: Laparoscopic colectomy has increasingly been advocated as an option for treatment of colonic disease. The purpose of this study was to compare effects of laparoscopic-assisted sigmoid colectomy (LAS) and conventional open colectomy (OPEN) on postoperative cytokine and stress hormone responses. METHODS: Fourteen patients with sigmoid colon cancer, apparently free of preoperative complications, were analyzed. Patients in both groups underwent sigmoid colectomy with lymphadenectomy. LAS was performed by the gasless abdominal wall-lifting method. A 5 cm incision was placed at the beginning of the operation. Blood samples were taken preoperatively and postoperatively for measurement of interleukin-6, glucagon and C-reactive protein. Urinary catecholamine excretions were also determined postoperatively. RESULTS: The two groups of patients were similar with respect to age (61 +/- 7 for LAS vs. 64 +/- 9 for OPEN) and sex. Intraoperative blood loss did not differ significantly between groups (112 +/- 97 ml for LAS vs. 366 +/- 380 ml for OPEN). Operative times for LAS tended to be longer than those for OPEN (231 +/- 67 vs. 169 +/- 45 minutes; P = 0.08). Similar time courses of postoperative interleukin-6, C-reactive protein, and stress hormone responses were observed in both groups. No significant differences were observed in the magnitude of changes except that the serum interleukin-6 level on day of surgery (postoperative day 0) was significantly higher in LAS patients than in those receiving OPEN. In addition, interleukin-6 levels showed a significant positive correlation with operative duration (r = 0.582; P < 0.05). CONCLUSIONS: Data suggest that stress responses after sigmoid colectomy, in patients undergoing LAS, are comparable with those of patients receiving OPEN and that the early interleukin-6 response after surgery appears to be associated with operative time.

Aged↗

PubMed1996

Effects of three inhibitors of nitric oxide synthase on host resistance to bacterial infection.

OBJECTIVE: To examine the effects of three nitric oxide synthase inhibitors on survival in a murine sepsis model. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. SUBJECTS: Female Balb/c mice. INTERVENTIONS: Escherichia coli (10(8) colony-forming-units/body) were injected into the peritoneal cavities of Balb/c mice. NG-nitro-L-arginine-methyl-ester, NG-monomethyl-L-arginine, or N-iminoethyl-L-ornithine was given at various concentrations, intraperitoneally, one hour before bacterial challenge. MEASUREMENTS: One hundred and fifteen animals were observed for survival. RESULTS: These inhibitors provided the mice no protection from the bacterial challenge. Notably, pretreatment with NG-nitro-L-arginine-methyl-ester (100 mg/kg i.p.) actually reduced survival time after E. coli challenge. CONCLUSIONS: Inhibition of nitric oxide production improved neither the survival time nor rate in this murine sepsis model.

Animals↗

PubMed1996

Route of nutritional supply influences local, systemic, and remote organ responses to intraperitoneal bacterial challenge.

OBJECTIVE: The authors' aim was to investigate whether antecedent nutritional routes influence immune responses after surgical insult. SUMMARY BACKGROUND DATA: Total parenteral nutrition (TPN) may influence host responses to infection. To the best of the authors' knowledge, however, no study has focused on the mechanisms underlying the influence of nutritional route on local, systemic, and remote organ (lung) responses after surgical insult. METHODS: Sixty-eight rats were divided into TPN and total enteral nutrition (TEN) groups. The two groups received identical nutrients for 7 days and were then challenged intraperitoneally with 3 x 10(8) Escherichia coli. In the first experiment, the rats were observed for survival. In the second experiment, the rats were killed before (0 hours) challenge or 2 or 6 hours after challenge. Peritoneal exudative cells (PEC) and bronchoalveolar cells (BALC) were harvested and cultured in vitro. Colony-forming units of bacteria in the peritoneal lavage fluid (PLF) were determined. Tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha), interferon-gamma (IFN-gamma) levels in serum, PLF, bronchoalveolar lavage fluid (BALF), and cell culture supernatants were measured. RESULTS: The 48-hour survival rate was higher in TEN than in TPN rats. Local immunity was depressed in the TPN group. Bacterial colony counts in PLF were significantly higher in the TPN group than in the TEN group after challenge. The number of PECs was significantly lower, and at 2 hours, local cytokine (TNF and IL-1 alpha) responses were diminished in the TPN group compared with the TEN group at 2 hours. The number of PECs showed a significant positive correlation with levels of local cytokines in the TEN group but not in the TPN group. Elevation of local IFN-gamma was significant from 0 to 6 hours in the TEN group but not in the TPN group. In vitro production of TNF by PEC was impaired in the TPN rats before challenge. Remote organ (lung) responses were suppressed in the TPN group. The number of BALCs and the TNF levels in BALF declined significantly between 0 and 2 hours in the TEN group but not in the TPN group. Interferon-gamma levels in BALF were higher in the TEN group than in the TPN group at 2 hours. Systemic cytokine responses were disturbed in the TPN group. Production of systemic TNF was greater, but the IFN-gamma response was diminished in the TPN group compared with the TEN group after intraperitoneal bacterial challenge. CONCLUSION: Local, systemic, and remote organ (lung) immune responses to intraperitoneal bacterial challenge are suppressed in TPN-treated animals, leading to poor survival after challenge. Enteral nutrition before surgical insult may enhance host immune responses after the insult as compared to parenteral nutrition.

Animals↗

PubMed1996

Distribution and anti-inflammatory effect of mesalazine on carrageenan-induced colitis in the rabbit.

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.

Aminosalicylic Acids↗

PubMed1996

Growth hormone and the immune response to bacterial infection.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1), especially the former, have immunoregulatory effects in addition to anabolic effects. The hormones may act to protect the host from lethal bacterial infection by promoting the maturation of myeloid cells, stimulating phagocyte migration, priming phagocytes for the production of superoxide anions and cytokines, and enhancing opsonic activity. GH administration may be beneficial for the prevention, as well as treatment, of severe sepsis in critical illness.

Animals↗

PubMed1995

Detrimental effects of a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine-methyl-ester) in a murine sepsis model.

OBJECTIVE: To examine the effects of a nitric oxide synthase inhibitor on host elimination of bacteria, tumor necrosis factor (TNF) production, and survival in a murine sepsis model. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Female Balb/c mice. INTERVENTIONS: Balb/c mice were injected with Escherichia coli (10(8) colony-forming units per body) into the peritoneal cavity. N-omega-Nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase, was given intraperitoneally at 10 mg/kg (N10 group) or 100 mg/kg (N100 group) 1 hour before bacterial challenge. MAIN OUTCOME MEASURES: Thirty animals were observed for survival. Samples of peritoneal lavaged fluid (PLF), blood, liver, and lungs were obtained at 4 and 6 hours after bacterial challenge (n = 60). The peritoneal exudative cells were counted. Viable bacterial counts were determined in PLF, blood, and organs. The TNF levels also were determined in plasma, PLF, and supernatant samples of cultured peritoneal exudative cells. RESULTS: Survival times after E coli challenge were significantly reduced by pretreatment with L-NAME (100 mg/kg intraperitoneally). Numbers of viable bacteria in the peritoneal cavity and plasma TNF level 4 hours after E coli challenge were higher in both L-NAME-treated groups than in the control group. The number of bacteria in the blood and the plasma TNF level 6 hours after E coli challenge were higher in the L-NAME-treated group (N100 group) than in the control group. Conversely, the number of hepatic bacteria in the control group was significantly higher than in the L-NAME-treated groups. Plasma TNF level showed significant positive correlations with numbers of bacteria in the PLF and in the blood 4 hours after challenge. No significant differences were noted in TNF levels in PLF and peritoneal exudative cell cultured supernatants. CONCLUSION: Inhibition of nitric oxide production is detrimental in this gram-negative sepsis model.

Animals↗

PubMed1995

Growth hormone and insulinlike growth factor I enhance host defense in a murine sepsis model.

OBJECTIVE: To investigate the effects of exogenous growth hormone (GH) and insulinlike growth factor I (IGF-I) on host defense and survival in a murine model of Escherichia coli sepsis. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Nine-week-old female BALB/c mice. INTERVENTIONS: Mice were injected subcutaneously with 4.8 or 0.48 mg/kg of body weight per day of GH, 24 or 2.4 mg/kg of body weight per day of IGF-I or, as a control, normal saline solution, for 6 days. Mice were then challenged intraperitoneally with 1 x 10(8) colony-forming units per body of E coli. MAIN OUTCOME MEASURES: Fifty mice were observed for survival. In the next experiments, samples from the high-dose GH, high-dose IGF-I, and saline control groups were harvested before or at 4 or 6 hours after challenge. Numbers of peritoneal exudative cells and tissue-viable bacterial counts were determined. Peritoneal exudative cells were cultured with lipopolysaccharide (10 micrograms/mL) for 24 hours. Levels of tumor necrosis factor, interleukin-1, and interleukin-6 in the peritoneal lavage fluid, plasma and supernatants of peritoneal exudative cell culture were measured. RESULTS: Both high and low doses of GH and high-dose IGF-I significantly prolonged survival. Growth hormone and IGF-I significantly increased peritoneal exudative cell numbers and reduced viable bacterial counts in the peritoneal lavage fluid and the liver. These hormones significantly suppressed excessive systemic cytokine production, while enhancing in vitro cytokine production and preserving local cytokine responses. CONCLUSION: The immunomodulation produced by administration of GH or IGF-I leads to improved host defense in this murine model of E coli sepsis.

Analysis of Variance↗

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↗