Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte adhesion to mesothelium is an important step during peritonitis, which is mediated by adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1). We investigated the effect of exogenous nitric oxide (NO) on VCAM-1 expression in cultured human peritoneal mesothelial cells and its signal transduction pathway. Mesothelial cells were exposed to tumor necrosis factor-alpha (TNF-alpha) in the presence or absence of NO donors, 3-morpholino-sydnonimine (SIN-1) and nitroprusside (NP). VCAM-1 mRNA and protein expression were measured by Northern blot analysis and flow cytometry. Nuclear factor-kappaB (NF-kappaB) binding activity was determined by electrophoretic mobility shift assay. Both SIN-1 and NP inhibited the TNF-alpha induced VCAM-1 mRNA expression in a dose dependent manner (0.25-2 mM). SIN-1 also suppressed the cell surface expression of VCAM-1 molecule. Furthermore, SIN-1 and NP inhibited the VCAM-1 mRNA expression induced by interleukin-1beta or lipopolysaccharide as well. NF-kappaB inhibitor, PDTC dose dependently inhibited the TNF-alpha induced VCAM-1 mRNA expression. SIN-1 inhibited the TNF-alpha- induced NF-kappaB binding activity. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-alpha-induced VCAM-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no significant influence on the inhibitory effect of SIN-1. These results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-kappaB through a cGMP-independent pathway.
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PMID:Exogenous nitric oxide inhibits VCAM-1 expression in human peritoneal mesothelial cells. Role of cyclic GMP and NF-kappaB. 1196 4

Peritonitis, a common complication of peritoneal dialysis, is followed by acute changes in the function of the peritoneum. The role of inflammatory cytokines in these processes is not clearly identified. We used adenoviral-mediated gene transfer to transiently overexpress interleukin (IL)-1 beta (AdIL-1 beta) or tumor necrosis factor (TNF)-alpha (AdTNF-alpha) in the rat peritoneum then used a modified equilibrium test to study the histological and functional changes. Overexpression of IL-1 beta or TNF-alpha led to an acute inflammatory response. Both inflammatory cytokines induced an early expression of the angiogenic cytokine, vascular endothelial growth factor, along with increased expression of the profibrotic cytokine, transforming growth factor-beta1, along with fibronectin expression and collagen deposition in peritoneal tissues. Both inflammatory cytokines induced angiogenesis, increased solute permeability, and ultrafiltration dysfunction at earlier time points. Changes in structure and function seen in AdTNF-alpha-treated animals returned to normal by 21 days after infection, whereas AdIL-1 beta-treated animals had persistently increased vasculature with submesothelial thickening and fibrosis. This was associated with up-regulation TIMP-1. TNF-alpha or IL-1 beta both induce acute changes in the peritoneum that mimic those seen in peritoneal dialysis patients who experience an episode of peritonitis. These functional changes were associated with early angiogenesis that resolved rapidly after exposure to TNF-alpha. IL-1 beta exposure, however, led to a different response with sustained vascularization and fibrosis. IL-1 beta inhibition may be a therapeutic goal in acute peritonitis to prevent peritoneal damage.
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PMID:Inflammatory cytokines, angiogenesis, and fibrosis in the rat peritoneum. 1205 31

The purpose of the study was to investigate the course of the zymosan-induced multiple organ dysfunction syndrome (MODS) in the absence of tumor necrosis factor (TNF) in a murine model. Tumor Necrosis Factor-alpha-lymphotoxin-a knockout (TNF/LT-/-) mice (n = 36) and wild-type (TNF/LT+/+) mice (n = 36) received 40 microg of lipopolysaccharide (LPS) intraperitoneally followed by zymosan at a dose of 1 mg/g body weight 6 days later (day 0). Animals were monitored daily for body weight and temperature and clinical symptoms. At day 22, most of the surviving mice were killed to examine organ weight and histology. A small number of animals were followed until day 48. In all animals, zymosan induced an acute sterile peritonitis phase followed by an apparent recovery. From day 8 onwards the TNF/LT+/+ mice entered a third-MODS-like-phase, characterized by loss of body weight, decreased body temperature, and significant mortality. At day 22, survival in the TNF/LT-/- mice (92%) was significantly (P = 0.01) higher than in the TNF/LT+/+ mice (60%). In addition, average body temperature and average relative (vs. weight at day 0) body weight were higher in the TNF/LT-/- mice than in the TNF/LT+/+ mice (35.9 degrees C and 100% vs. 33.3 degrees C and 84%, respectively). However, at this time point, surviving animals from both groups showed similar and significant organ damage, indicated by an increase in absolute and relative (vs body weight) weight of lung, spleen, and liver (liver only in the TNF/LT-/- mice). Moreover, histopathological examination of organs from the surviving animals showed a similar degree of microscopic damage in both groups. Interestingly, besides mononuclear cells, inflammatory infiltrates in lungs and livers of TNF/LT+/+ but not of TNF-/- mice contained neutrophils. In conclusion, TNF-deficient mice exhibit significantly improved morbidity and mortality during zymosan-induced MODS. However, the absence of TNF does not completely protect against MODS in this murine model.
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PMID:Improved survival of TNF-deficient mice during the zymosan-induced multiple organ dysfunction syndrome. 1206 82

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-alpha, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.
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PMID:Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis. 1239 48

Pro-inflammatory cytokines attract leukocytes to inflamed tissues and activate them. Few attempts have been made to identify the sources of cytokines in vivo. We examined the importance of peritoneal macrophages in the mobilization and homing of neutrophils to a sterile peritonitis in the rat, with emphasis on their cytokine production. Macrophages, present in virtually all tissues, are known to be easily activated and to serve as an important source of cytokines. Flow cytometric analysis of cells stained intracellularly with tagged antibodies against various cytokines revealed that the peritoneal macrophages were stimulated to produce the following cytokines: interleukin (IL)-1beta, macrophage inflammatory protein-2 (MIP-2), and keratinocyte-derived cytokine (KC). High numbers of neutrophils, activated on arrival into the peritoneal cavity, also produced IL-1beta, whereas lower numbers contained interleukin-6, tumor necrosis factor-alpha, MIP-2, KC, and MIP-1alpha. This marked activation of peritoneal neutrophils was also reflected by increased surface expression of CD11b. On the other hand, peritoneal macrophages expressed high basal levels of CD11b, which were reduced 24 h after the onset of inflammation. In rats selectively depleted of macrophages by i.p. injection of liposome-containing clodronate, the massive influx of neutrophils to the peritoneal cavity was markedly reduced, as was the rapid mobilization of mature bone marrow neutrophils. Local macrophages are important both for the accumulation of neutrophils in the inflamed peritoneal cavity and for the early mobilization of neutrophils from the bone marrow. Macrophage-derived IL-1beta, MIP-2, and KC are possible mediators of neutrophil homing to inflamed tissues.
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PMID:Macrophage-dependent regulation of neutrophil mobilization and chemotaxis during development of sterile peritonitis in the rat. 1246 Feb 33

In vitro exposure of Gram-negative bacilli (GNB) to antimicrobial agents may induce endotoxin (ET) release, that may cause various reactions in vivo resulting in endotoxic shock. We used the antimicrobial agents, flomoxef (FMOX) and gentamicin (GM), to investigate the kinetics of ET released from in-vitro-cultured Escherichia coli and to examine the ET effect on tumor necrosis factor (TNF) production by macrophages. In a rabbit model of E. coli peritonitis, we measured plasma ET, TNF and blood bacterial counts under the administration of FMOX or GM. In our in vitro experiment, ET levels under FMOX were significantly higher than those under GM, and ET induced TNF production in a dose-dependent manner. However, in vivo, plasma ET, TNF, and blood bacterial counts under antimicrobial agents were significantly lower than those of the controls, and those under FMOX treatment did not differ from those under GM treatment. Thus, ET release may not be a critical problem in GNB infections if appropriate antimicrobial agents are administered.
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PMID:Relevance of antimicrobial agent-induced endotoxin release from in vitro cultured Escherichia coli and in vivo experimental infection with Gram-negative bacilli. 1272 81

Continuous ambulatory peritoneal dialysis (CAPD) carries a risk of peritonitis which is accompanied by mild symptomatology. Culture of effluent has yielded organism in 50% of cases. Peritoneal phagocytes produce tumor necrosis factor-alpha and interleukin (IL)-1 in response to contact with bacteria, initiating an inflammatory cascade which leads to IL-6 and IL-8 secretion. Additonally, neutrophils undergo an increase in oxidative metabolism. We have evaluated the diagnostic accuracy of effluent measurements of TNF-alpha, IL-6, IL-8, and oxidative metabolism markers in these patients. Dialysate fluids (n = 65) were collected from non-infected patients and those presenting with acute peritonitis. Positive culture proved the diagnosis. Oxidative markers and nitric oxide were measured by chemiluminescence. Cytokines were measured by solid phase chemiluminescent immunometric assay (Immulite, DPC, USA). Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy and the areas under curves were calculated for comparison. All effluent cytokines and oxidative markers were significantly higher in patients with peritonitis when compared to those without (p < 0.05). Significant correlations were evident between IL-6 and IL-8, lucigenin chemiluminescence and luminol chemiluminescence, lucigenin chemiluminescence and IL-6 or IL-8, and luminol chemiluminescence and IL-6 or IL-8. ROC curves showed that the ability of IL-6, IL-8, lucigenin chemiluminescence, and luminol chemiluminescence to differentiate CAPD patients with peritonitis from non-infected cases exceeds that of polymorphonuclear leukocyte count.
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PMID:Early detection of peritonitis in continuous ambulatory peritoneal dialysis patients by cytokine measurements. 1281 61

Antisense oligonucleotides offer great therapeutic potential provided adequate intracellular penetration can be achieved. In this study, we evaluated the effectiveness of microencapsulating antisense oligonucleotides to tumor necrosis factor (TNF) in suppressing TNF release in vitro and in vivo. Microencapsulation of TNF oligomers was performed using albumin to produce microcapsules 0.6-1.0 mum in size that target phagocytic cells. Albumin microcapsules containing fluoresceinated TNF oligomers were incubated with U-937 cells to observe uptake. Microcapsules were added to whole blood and stimulated with Escherichia coli endotoxin. Endotoxin was given intravenously (i.v.) to rats along with 100 mug microencapsulated TNF oligomers to determine TNF inhibition and animal survival. E. coli was given intraperitoneally (i.p.) along with gentamicin and microencapsulated TNF oligomers to assess TNF inhibition and animal survival. The duration of microencapsulated antisense TNF oligomers was also determined in vivo. The results demonstrated rapid uptake of the microcapsules by macrophages after 2 h and 4 h incubation. There was improvement in TNF inhibition in vitro and improved animal survival by microencapsulated antisense in both endotoxin (100% survival) and peritonitis models (70% survival) compared with free antisense oligomers in solution. Microencapsulation extended the duration of action of the oligomers to 72 h. Intracellular targeting of macrophages with antisense oligomers to TNF by microencapsules as a delivery system improves TNF inhibition using the models of whole blood endotoxin stimulation and endotoxic shock and peritonitis in rats.
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PMID:Microencapsulation of tumor necrosis factor oligomers: a new approach to proinflammatory cytokine inhibition. 1456 62

Immunotherapy using tumor antigen-loaded dendritic cells is a new approach for the treatment of various types of malignant tumors. Here, we describe a patient with advanced gastric carcinoma who received immunotherapy using fused autologous dendritic cells and carcinoma cells (fusions) and showed effective clinical responses to the treatment. A 74-year-old man showed massive ascitic effusion due to peritonitis carcinomatosa after surgical operation for gastric carcinoma. A gastric carcinoma cell line was established from the patient's tumor tissue. Dendritic cells were obtained by cultivation of the adherent cell fraction of the patient's peripheral blood mononuclear cells (PBMCs) with granulocyte macrophage-colony stimulating factor, interleukin-4, and tumor necrosis factor-alpha. The cells were mixed with irradiated tumor cells and treated with 50% polyethyleneglycol (PEG) for the generation of fusions, as described previously. The PEG-treated cells were injected subcutaneously every 2 weeks. Low-grade fever was observed after the first and second treatments. After the third treatment, ascitic effusion and leg edema decreased markedly, without any other treatments. Serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 decreased to levels lower than those at the initiation of treatment. PBMCs collected after the fifth treatment elicited cytotoxic activity against autologous tumor cells. Although treatment was continued in the same way, recurrence of the disease was observed about 5 months after the start of the treatment. This is the first report of immunotherapy utilizing fusions of autologous dendritic cells and tumor cells resulting in effective clinical responses in advanced gastric carcinoma, without severe adverse effects.
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PMID:Immunotherapy using fusions of autologous dendritic cells and tumor cells showed effective clinical response in a patient with advanced gastric carcinoma. 1461 8

Despite significant advances in intensive care therapy and antibiotics, severe sepsis accounts for 9% of all deaths in the United States annually. The pathological sequelae of sepsis are characterized by a systemic inflammatory response, but experimental therapeutics that target specific early inflammatory mediators [tumor necrosis factor (TNF) and IL-1beta] have not proven efficacious in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late mediator of endotoxin-induced lethality that exhibits significantly delayed kinetics relative to TNF and IL-1beta. Here, we report that serum HMGB1 levels are increased significantly in a standardized model of murine sepsis, beginning 18 h after surgical induction of peritonitis. Specific inhibition of HMGB1 activity [with either anti-HMGB1 antibody (600 microg per mouse) or the DNA-binding A box (600 microg per mouse)] beginning as late as 24 h after surgical induction of peritonitis significantly increased survival (nonimmune IgG-treated controls = 28% vs. anti-HMGB1 antibody group = 72%, P < 0.03; GST control protein = 28% vs. A box = 68%, P < 0.03). Animals treated with either HMGB1 antagonist were protected against the development of organ injury, as evidenced by improved levels of serum creatinine and blood urea nitrogen. These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame.
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PMID:Reversing established sepsis with antagonists of endogenous high-mobility group box 1. 1469 89


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