-
Dialysis solution containing hyaluronan: effect on peritoneal permeability and inflammation in rats.Kidney International Mar 2000Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In...
BACKGROUND
Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks.
METHODS
Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment.
RESULTS
After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals.
CONCLUSIONS
The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.
Topics: Animals; Biomarkers; Cytokines; Dialysis Solutions; Hyaluronic Acid; Male; Peritoneal Dialysis; Peritoneum; Peritonitis; Permeability; Rats; Rats, Wistar
PubMed: 10720971
DOI: 10.1046/j.1523-1755.2000.00946.x -
Digestive Surgery 2012The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units....
BACKGROUND
The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units. Nevertheless, infected necrosis or persistent multi-organ dysfunction are predictors of poor outcome. In these patients, there is still a need to perform necrosectomy. Open surgery results in extensive operative trauma and is associated with high morbidity and mortality. Therefore, several minimally invasive techniques have been developed recently. Retroperitoneal necrosectomy has been shown to be safe and to reduce morbidity and mortality compared to the open procedure.
METHODS AND RESULTS
In an instructive video, we show the technique of video-assisted retroperitoneal necrosectomy with minimal access, including the preoperative percutaneous drainage and several accesses to the necrosis. We discuss the indication for retroperitoneal necrosectomy as well as the optimal time point of the intervention.
CONCLUSION
In the management of acute necrotizing pancreatitis, the multidisciplinary approach is crucial. The initial treatment by the intensive care units should be extended to intervention or surgery in case of infected necrosis or persistent multi-organ dysfunction. We show here a minimal access solution with the placement of a percutaneous drain followed by video-assisted retroperitoneal necrosectomy.
Topics: Drainage; Humans; Pancreatectomy; Pancreatitis, Acute Necrotizing; Peritoneum; Video-Assisted Surgery
PubMed: 23328030
DOI: 10.1159/000345620 -
Kidney International Aug 2006Loss of function of the peritoneal membrane is associated with peritonitis. Adenosine levels in sites of inflammation were shown to increase and exhibit immunoregulatory...
Loss of function of the peritoneal membrane is associated with peritonitis. Adenosine levels in sites of inflammation were shown to increase and exhibit immunoregulatory effects. Our aim was to elucidate the regulatory role of adenosine during peritonitis and to test the involvement of peritoneal mesothelial cells (PMC) in adenosine regulation. In a mice model of Escherichia coli peritonitis, the adenosine A(2A) receptor (A(2A)R) agonist (CGS21680) prevented leukocyte recruitment and reduced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Peritonitis induced the elevation of adenosine with a peak at 24 h. Analysis of adenosine receptor levels on peritoneum showed that A(1) receptor (A(1)R) protein levels peak at 12 h after inoculation and then return to baseline at 24 h, whereas high affinity A(2A)R protein levels peak at 24 h concomitantly with the peak of adenosine concentration. Low affinity A(2B) receptor (A(2B)R) levels elevated slowly, remaining elevated up to 48 h. In human PMC (HPMC), the early cytokines, IL-1-alpha, and TNF-alpha upregulated the A(2B) and A(2A) receptors. However, interferon-gamma (IFN-gamma) upregulated the A(2B)R and decreased A(2A)R levels. Treatment with the A(2A)R agonist reduced IL-1-dependent IL-6 secretion from HPMC. In conclusion, the kinetics of adenosine receptors suggest that at early stage of peritonitis, the A(1)R dominates, and later its dominance is replaced by the G stimulatory (Gs) protein-coupled A(2A)R that suppresses inflammation. Early proinflammatory cytokines are an inducer of the A(2A)R and this receptor reduces their production and leukocyte recruitment. Future treatment with adenosine agonists should be considered for attenuating the damage to mesothelium during the course of acute peritonitis.
Topics: Adenosine; Adenosine A1 Receptor Agonists; Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Animals; Antihypertensive Agents; Cells, Cultured; Disease Models, Animal; Down-Regulation; Epithelium; Escherichia coli; Female; Humans; Inflammation; Interleukin-6; Leukocytes; Mice; Mice, Inbred Strains; Peritonitis; Phenethylamines; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; RNA, Messenger; Receptor, Adenosine A1; Receptor, Adenosine A2A; Receptors, Purinergic P1; Theobromine; Tumor Necrosis Factor-alpha; Up-Regulation; Xanthines
PubMed: 16788688
DOI: 10.1038/sj.ki.5001609 -
Journal of the National Medical... Feb 2005Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases.
BACKGROUND
Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases.
METHOD AND PATIENTS
We studied tumor necrosis factor-alpha, tumor necrosis factor receptor and C-reactive protein levels in both ascitic fluid and serum in patients with spontaneous bacterial peritonitis (SBP) (n = 22), and in the malignant (n = 38) and cirrhotic (n = 32) ascites.
RESULTS
C-reactive protein, tumor necrosis factor-alpha and tumor necrosis factor receptor levels in the ascitic fluid were found to be elevated in the SBP (p < 0.001) and malignant groups (p < 0.005) when compared with the sterile cirrhotic group. C-reactive protein levels in the serum were found to be elevated in the SBP group when compared with the sterile cirrhotic (p < 0.001) and malignant group (p < 0.005). Tumor necrosis factor-alpha in the serum was significantly elevated in the SBP when compared with the cirrhotic (p < 0.005) and malignant ascites (p < 0.001). Sensitivity and specificity of ascitic fluid CRP in discriminating malignant 84% and 67% and SBP from sterile ascites were 90% and 76%, respectively. Sensitivity and specificity of ascitic fluid TNF-alpha in discriminating malignant 77% and 60% and SBP from sterile ascites were 82% and 66%, respectively. Sensitivity and specificity of TNF-r p60 in discriminating malignant 74% and 70% and SBP from sterile ascites were 80% and 76%, respectively.
CONCLUSION
The sensitivity and specificity of ascitic fluid CRP, TNF-alpha and TNF-r values were found to be similar. Ascitic fluid Creactive protein to differentiate SBP and malignant ascitic from cirrhotic ascites are cheap, practical and safe tests used in the differential diagnosis of ascites.
Topics: Adult; Ascites; Ascitic Fluid; C-Reactive Protein; Cytokines; Enterococcus; Escherichia coli; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Peritonitis; Receptors, Tumor Necrosis Factor; Sensitivity and Specificity; Staphylococcus aureus; Time Factors; Tumor Necrosis Factor-alpha
PubMed: 15712792
DOI: No ID Found -
BMJ Case Reports Aug 2017A 27-year-old female heroin addict presented with a peritonitic and distended abdomen. Her medical history included depression and a 3-year history of heroin abuse with...
A 27-year-old female heroin addict presented with a peritonitic and distended abdomen. Her medical history included depression and a 3-year history of heroin abuse with attendant constipation. CT scan showed free intraperitoneal gas, massive faecal distension of the rectum and sigmoid colon and likely bowel necrosis. She underwent an emergency Hartmann's procedure for perforation of the sigmoid colon. Pathology identified two areas of stercoral ulceration, one of them being the area of perforation. Postoperatively, the patient developed a deep vein thrombosis and is now on anticoagulant therapy. She was discharged 4 weeks after admission. The patient has been reviewed at follow-up clinic by the surgical team and specialist stoma nurses. She is coping well with good stoma function. We will perform a colonoscopy to identify any further areas of stercoral ulceration but there are no plans for further surgery at present.
Topics: Adult; Colon, Sigmoid; Fecal Impaction; Female; Heroin Dependence; Humans; Intestinal Perforation; Peritonitis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28765178
DOI: 10.1136/bcr-2016-218875 -
World Journal of Gastroenterology Jun 2010The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal...
The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal disease that fails to respond to a gluten-free diet. Splenic hypofunction may also be present. The cause is not known but its development during the clinical course of celiac disease is usually indicative of a poor prognosis for the intestinal disorder, a potential for significant complications including sepsis and malignancy, particularly T-cell lymphoma, and significant mortality. Modern abdominal imaging modalities may permit earlier detection in celiac disease so that earlier diagnosis and improved understanding of its pathogenesis may result.
Topics: Celiac Disease; Diet, Gluten-Free; Humans; Lymph Nodes; Mesentery; Necrosis; Syndrome
PubMed: 20572301
DOI: 10.3748/wjg.v16.i24.2991 -
Aging Feb 2019Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Methane has been reported to have anti-oxidative,...
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Methane has been reported to have anti-oxidative, anti-apoptotic and anti-inflammatory properties. We investigated the potential protective effects of methane on sepsis-induced injury and determined the related mechanisms. C57BL/6 mice received laparotomy with cecal ligation and puncture (CLP) to create a septic model, followed by methane-rich saline (MRS) treatment after CLP. MRS treatment improved the 5-day survival rate and organ functions and alleviated pathological damage of the mice, as well as reduced excessive inflammatory mediators, such as tumor necrosis factor-α and interleukin-6. MRS treatment also decreased the levels of oxidative stress index proteins, decreased the apoptosis of cells and inhibited nod-liker receptor protein (NLRP)3-mediated pyroptosis in the lung and intestine. In in vitro experiments, RAW264.7 and primary peritoneal macrophages were treated with lipopolysaccharide (LPS) plus adenosine-triphosphate (ATP) to induce inflammation and pyroptosis. Consistent with the in vivo results, methane-rich medium (MRM) treatment also reduced the levels of excessive inflammatory mediators, and decreased the levels of ROS, inhibited apoptosis and pyroptosis. Our results indicate that methane offers a protective effect for septic mice via its anti-inflammation, anti-oxidation, anti-pyroptosis and anti-apoptosis properties.
Topics: Animals; Apoptosis; Cytokines; Gene Expression Regulation; Macrophages, Peritoneal; Male; Methane; Mice; Mice, Inbred C57BL; Peritonitis; Pyroptosis; RAW 264.7 Cells; Saline Solution; Sepsis
PubMed: 30779706
DOI: 10.18632/aging.101831 -
Nature Communications Apr 2018Despite anti-TNF therapy advancements for inflammatory diseases such as rheumatoid arthritis, the burden of diseases remains high. An 11-mer TNF peptide, TNF, is known...
Despite anti-TNF therapy advancements for inflammatory diseases such as rheumatoid arthritis, the burden of diseases remains high. An 11-mer TNF peptide, TNF, is known to stimulate selective functional responses compared to the parent TNF molecule. Here, we show that TNF binds to the TNF receptor, activating p38 MAP kinase through TNF receptor-associated factor 2. Using truncated TNFR mutants, we identify the sequence in TNFRI which enables p38 activation by TNF. Peptides with this TNFRI sequence, such as TNFRI bind to TNF and inhibit TNF-induced p38 activation, respiratory burst, cytokine production and adhesion receptor expression but not F-Met-Leu-Phe-induced respiratory burst in neutrophils. TNFRI does not prevent TNF binding to TNFRI or TNF-induced stimulation of ERK, JNK and NF-κB. TNFRI inhibits bacterial lipopolysaccharide-induced peritonitis, carrageenan-induced and antigen-induced paw inflammation, and respiratory syncytial virus-induced lung inflammation in mice. Our findings suggest a way of targeting TNF-p38 pathway to treat chronic inflammatory disorders.
Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Neutrophils; Peptide Fragments; Peritonitis; Platelet Glycoprotein GPIb-IX Complex; Pneumonia; Pneumonia, Viral; Protein Binding; Receptors, Tumor Necrosis Factor; Respiratory Burst; Respiratory Syncytial Viruses; Signal Transduction; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
PubMed: 29636466
DOI: 10.1038/s41467-018-03640-y -
Arthritis and Rheumatism Feb 2011To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo.
OBJECTIVE
To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo.
METHODS
OCP crystal-induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin-1 (IL-1) secretion (IL-1α(-/-) , IL-1β(-/-) , ASC(-/-) , and NLRP3(-/-) mice) or in mice pretreated with IL-1 inhibitors (anakinra [recombinant IL-1 receptor antagonist] and anti-IL-1β). The production of IL-1α, IL-1β, and myeloid-related protein 8 (MRP-8)-MRP-14 complex was determined by enzyme-linked immunosorbent assay. Peritoneal neutrophil recruitment and cell viability were determined by flow cytometry. Depletion of mast cells or resident macrophages was performed by pretreatment with compound 48/80 or clodronate liposomes, respectively.
RESULTS
OCP crystals induced peritoneal inflammation, as demonstrated by neutrophil recruitment and up-modulation of IL-1α, IL-1β, and MRP-8-MRP-14 complex, to levels comparable with those induced by monosodium urate monohydrate crystals. This OCP crystal-induced inflammation was both IL-1α- and IL-1β-dependent, as shown by the inhibitory effects of anakinra and anti-IL-1β antibody treatment. Accordingly, OCP crystal stimulation resulted in milder inflammation in IL-1α(-/-) and IL-1β(-/-) mice. Interestingly, ASC(-/-) and NLRP3(-/-) mice did not show any alteration in their inflammation status in response to OCP crystals. Depletion of the resident macrophage population resulted in a significant decrease in crystal-induced neutrophil infiltration and proinflammatory cytokine production in vivo, whereas mast cell depletion had no effect. Finally, OCP crystals induced apoptosis/necrosis of peritoneal cells in vivo.
CONCLUSION
These data indicate that macrophages, rather than mast cells, are important for initiating and driving OCP crystal-induced inflammation. Additionally, OCP crystals induce IL-1-dependent peritoneal inflammation without requiring the NLRP3 inflammasome.
Topics: Animals; Bone Density Conservation Agents; Bone Substitutes; Calcium Phosphates; Carrier Proteins; Cell Survival; Clodronic Acid; Crystallization; Disease Models, Animal; Female; Injections, Intraperitoneal; Interleukin-1; Macrophages, Peritoneal; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Neutrophils; Peritoneum; Peritonitis; p-Methoxy-N-methylphenethylamine
PubMed: 21279999
DOI: 10.1002/art.30147 -
Proceedings of the National Academy of... Dec 2014Sepsis is characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state, defining a complex clinical scenario that...
Sepsis is characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state, defining a complex clinical scenario that explains the lack of successful therapeutic options. Here we tested whether the formyl-peptide receptor 2/3 (Fpr2/3)--ortholog to human FPR2/ALX (receptor for lipoxin A4)--exerted regulatory and organ-protective functions in experimental sepsis. Coecal ligature and puncture was performed to obtain nonlethal polymicrobial sepsis, with animals receiving antibiotics and analgesics. Clinical symptoms, temperature, and heart function were monitored up to 24 h. Peritoneal lavage and plasma samples were analyzed for proinflammatory and proresolving markers of inflammation and organ dysfunction. Compared with wild-type mice, Fpr2/3(-/-) animals exhibited exacerbation of disease severity, including hypothermia and cardiac dysfunction. This scenario was paralleled by higher levels of cytokines [CXCL1 (CXC receptor ligand 1), CCL2 (CC receptor ligand 2), and TNFα] as quantified in cell-free biological fluids. Reduced monocyte recruitment in peritoneal lavages of Fpr2/3(-/-) animals was reflected by a higher granulocyte/monocyte ratio. Monitoring Fpr2/3(-/-) gene promoter activity with a GFP proxy marker revealed an over threefold increase in granulocyte and monocyte signals at 24 h post-coecal ligature and puncture, a response mediated by TNFα. Treatment with a receptor peptido-agonist conferred protection against myocardial dysfunction in wild-type, but not Fpr2/3(-/-), animals. Therefore, coordinated physio-pharmacological analyses indicate nonredundant modulatory functions for Fpr2/3 in experimental sepsis, opening new opportunities to manipulate the host response for therapeutic development.
Topics: Adaptor Proteins, Signal Transducing; Animals; Chemokine CCL2; Chemokine CXCL1; Disease Models, Animal; Granulocytes; Humans; Mice; Mice, Knockout; Monocytes; Peritoneum; Receptors, Formyl Peptide; Sepsis; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha
PubMed: 25512512
DOI: 10.1073/pnas.1410938111