Biomedical subjects

R Fukushima

Publications and source records attributed to R Fukushima.

At least 37 records · Page 2Linked to original sources

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

Dietary fatty acids modulate host bacteriocidal response,microbial translocation and survival following blood transfusion and thermal injury.

The effect of dietary lipids on bacterial translocation, killing of translocated organisms and host survival was studied in a burned animal model. Balb/c mice were fed with one of the three experimental AIN-76A diets (containing 15% of energy from fish oil, safflower oil or a 50:50 mixture), AIN-76A without added lipids or a nonpurified stock diet. All animals were transfused on day 10. On day 15, the animals were gavaged with 10(10) 14C radiolabelled Escherichia coli and given a 20% burn injury. Survival was 84% in the fish oil group versus 36% in the safflower oil and 50:50 diet groups, and 25% and 20% in the two control groups (P < 0.0001). The numbers of viable translocating bacteria were reduced in all tested organs in the fish oil groups compared to the other groups. It is concluded that a diet enriched in fish oil has beneficial effects during gut-derived sepsis.

Journal Article↗

PubMed1996

Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis.

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.

Journal Article↗

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↗

PubMed1994

The primary site of bacterial translocation.

OBJECTIVE: To establish the primary anatomic site of bacterial translocation in the intestinal tract. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Hartley guinea pigs. INTERVENTIONS: In guinea pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were created. The animals then received intraluminal injections of Escherichia coli labeled with radioactive carbon (14C) before a 50% full-thickness burn was inflicted. Four hours after the burn injury, the animals were killed, and the intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested. Intestinal loops were irrigated and then treated with ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes from the lamina propria. Radionuclide counts were determined in the effluents, the enterocytes (or colonocytes), lamina propria, and other organs. Colony-forming units of E coli were also determined in mesenteric lymph nodes, spleen, liver, and lung. MEASUREMENTS AND MAIN RESULTS: No significant differences were noted in the radionuclide counts in the lamina propria and epithelial cell fraction related to the type of loop. In addition, no significant differences were noted in the radionuclide counts in the mesenteric lymph nodes, liver, spleen, and lung related to the type of loop, but more viable bacteria were recovered when bacteria were injected into the jejunal loop. CONCLUSIONS: Translocation of bacteria occurred with similar intensity throughout the gut, but more bacteria were killed in the process of translocation across the lower part of the intestinal tract.

Animals↗

PubMed1994

Isolated pulmonary infection acts as a source of systemic tumor necrosis factor.

OBJECTIVE: To investigate the local secretion of tumor necrosis factor (TNF) in the lung as a source for systemic TNF. DESIGN: Prospective, randomized experimental trials. SETTING: Laboratory. SUBJECTS: Hartley guinea pigs. INTERVENTIONS: Female guinea pigs were challenged intratracheally with 10(3) to 10(9) Escherichia coli. Two and eight hrs after the bacterial challenge, colony-forming units of bacteria in the lung and blood, TNF and prostaglandin E2 (PGE2) in the bronchoalveolar lavage fluid, and serum TNF concentrations were determined. At the same time, alveolar macrophages were harvested and cultured in vitro, and TNF and PGE2 secretions were measured. MEASUREMENTS AND MAIN RESULTS: TNF and PGE2 concentrations were either not detected in bronchoalveolar lavage fluid or were found in very low levels in control animals. High concentrations of TNF and PGE2, however, were found in bacteria-challenged animals. Two hours after inoculation of bacteria, TNF in the bronchoalveolar lavage fluid had a significant correlation with TNF values in the serum. The TNF concentration in aortic blood was significantly higher than TNF concentration in right atrial blood. For comparable inocula, TNF in the bronchoalveolar lavage fluid after 8 hrs was significantly lower than at 2 hrs, but PGE2 levels remained high. Lipopolysaccharide-stimulated alveolar macrophage secretion of TNF in vitro was depressed in animals with high PGE2 levels in bronchoalveolar lavage fluid and high numbers of viable bacteria in the lungs. CONCLUSIONS: During pulmonary Gram-negative infection, the lungs may be a major source of TNF in the blood. The magnitude of TNF secretion by the lungs is highly dependent on the intensity of infection during its early stages. By 8 hrs after onset of infection, TNF secretion appears to downregulate, possibly by endogenous PGE2.

Animals↗

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↗

PubMed1994

Time course of production of cytokines and prostaglandin E2 by macrophages isolated after thermal injury and bacterial translocation.

The relationship of translocation of bacteria from the gut of burned guinea pigs and the in vitro production of tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated mesenteric lymph node and splenic macrophages was investigated at two early times after thermal injury. Two hr postburn, there was a large number of translocated bacteria in the mesenteric lymph nodes and a large proportion was killed; at 24 hr postburn, there were fewer translocated bacteria, but a large proportion was viable. In some cases, there were very large differences compared to controls in the amounts of TNF, IL-6, and PGE2, but not of IL-1, produced by the macrophages at different times postburn and at different in vitro incubation times. The results suggest that the macrophages were primed by the burn or the translocated bacteria to produce in vitro different and sometimes large amounts of cytokines or PGE2 after further stimulation with LPS. Although there was no direct correlation between production of cytokines or PGE2 and time postburn, the early increased production of PGE2 by splenic macrophages could have depressed the animal's ability to kill translocated bacteria by 24 hr postburn, and could be one of the mechanisms of the cause of systemic infection after burn injury.

Animals↗

PubMed1993

The activation of bone marrow macrophages 24 hours after thermal injury.

We determined the effect of thermal injury on the in vitro production of the immunoactive substances tumor necrosis factor, interleukin 1, prostaglandin E2, and complement component C3 by lipopolysaccharide-stimulated guinea pig bone marrow macrophages and on the cytotoxicity of these cells. Macrophages from burned animals produced different amounts of these mediators compared with unburned animals at certain culture times, suggesting that thermal injury could program the bone marrow cells to respond differently from normal cells to in vitro stimulation with lipopolysaccharide. Also, the macrophages from burned animals displayed greater cytotoxicity towards L929 target cells. These results suggest that there is a complex interaction among cellular secretory products, especially after thermal injury, that may be important in host defense.

Animals↗

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

[Localization of salazopyrin in colonic mucosa patients with ulcerative colitis].

In this study SASP metabolite levels were measured in colonic mucosal specimens and plasma samples from 31 patients with ulcerative colitis (UC) under treatment with the drug. Colonic tissue specimens were obtained by endoscopically guided biopsy and plasma was isolated from peripheral blood. Measurements were performed by HPLC according to the procedure of Fischer et al. The levels of 5-ASA and SP in either of colonic tissue or plasma were significantly lower than those of Ac-5-ASA and Ac-SP, respectively. The tissue level of 5-ASA had a significant correlation to the dosage of 5-ASA. The tissue levels of 5-ASA and Ac-5-ASA were low in an active stage of UC than during a remission period and the difference observed with respect to the latter metabolite was significant. These findings suggest that acetylation of 5-ASA is inhibited in the colonic mucosa in an active stage of the disease.

Adult↗