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Mediators of Inflammation 2017(.) is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in...
(.) is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to -induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient ( ), , and mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by .
Topics: Animals; Escherichia coli; Female; Granzymes; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Nucleosomes; Peritonitis; Sepsis
PubMed: 28694562
DOI: 10.1155/2017/4137563 -
The Journal of Biological Chemistry Oct 2006Lipopolysaccharide (LPS)-activated macrophages are pivotal in innate immunity. With LPS treatment, extracellular signals are transduced into macrophages via Toll-like...
Ca2+- and protein kinase C-dependent signaling pathway for nuclear factor-kappaB activation, inducible nitric-oxide synthase expression, and tumor necrosis factor-alpha production in lipopolysaccharide-stimulated rat peritoneal macrophages.
Lipopolysaccharide (LPS)-activated macrophages are pivotal in innate immunity. With LPS treatment, extracellular signals are transduced into macrophages via Toll-like receptor 4 and induce inflammatory mediator production by activating signaling pathways, including the nuclear factor-kappaB (NF-kappaB) pathway and the mitogen-activated protein kinase (MAPK) pathway. However, the mechanisms by which the intracellular free Ca2+ concentration ([Ca2+]i) increases and protein kinase C (PKC) is activated remain unclear. Therefore, we investigated the signaling pathway for Ca2+- and PKC-dependent NF-kappaB activation, inducible nitric-oxide synthase expression, and tumor necrosis factor-alpha (TNF-alpha) production in LPS-stimulated rat peritoneal macrophages. The results demonstrated that the LPS-induced transient [Ca2+]i increase is due to Ca2+ release and influx. Extracellular and intracellular Ca2+ chelators inhibited phosphorylation of PKCalpha and PKCbeta. A PKCbeta-specific and a general PKC inhibitor blunted phosphorylation of serine in mitogen-activated/extracellular signal-regulated kinase kinase kinase (MEKK) 1. Moreover, a MEKK inhibitor reduced activation of inhibitorykappaB kinase and NF-kappaB. Upstream of the [Ca2+]i increase, a protein-tyrosine kinase inhibitor reduced phosphorylation of phospholipase C (PLC) gamma. Furthermore, a PLC inhibitor eliminated the transient [Ca2+]i increase and decreased the amount of activated PKC. Therefore, these results revealed the following roles of Ca2+ and PKC in the signaling pathway for NF-kappaB activation in LPS-stimulated macrophages. After LPS treatment, protein-tyrosine kinase mediates PLCgamma1/2 phosphorylation, which is followed by a [Ca2+]i increase. Several PKCs are activated, and PKCbeta regulates phosphorylation of serine in MEKK1. Moreover, MEKKs regulate inhibitory kappaB kinase activation. Sequentially, NF-kappaB is activated, and inducible nitric-oxide synthase and tumor necrosis factor-alpha production is promoted.
Topics: Animals; Calcium; Gene Expression Regulation, Enzymologic; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C3H; NF-kappa B; Nitric Oxide Synthase Type II; Peritoneum; Protein Kinase C; Rats; Rats, Wistar; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 16923814
DOI: 10.1074/jbc.M602739200 -
Kidney International Jun 2003Patients treated with peritoneal dialysis frequently suffer from recurrent peritonitis episodes. During peritonitis, inflammatory mediators are released and a...
BACKGROUND
Patients treated with peritoneal dialysis frequently suffer from recurrent peritonitis episodes. During peritonitis, inflammatory mediators are released and a serofibrinous exudate is formed in the peritoneal cavity, which promotes fibrosis and abdominal adhesion development. Human peritoneal mesothelial cells (HMC) play a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme tissue-type plasminogen activator (t-PA) and its specific inhibitor, plasminogen activator inhibitor-1 (PAI-1) as well as the procoagulant protein, tissue factor.
METHODS
Cultured HMC were used to examine the effect of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, on the expression of t-PA, PAI-1 and tissue factor after activation of the cells with tumor necrosis factor-alpha (TNF-alpha). Antigen concentrations in the cell supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Northern blot analysis was conducted for mRNA expression. Luciferase reporter gene assays and Western blot analysis in human fibrosarcoma HT1080 cells and HMC were performed to analyze the effect of simvastatin on the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate tissue factor gene expression.
RESULTS
Incubation of HMC with TNF-alpha resulted in significantly decreased t-PA and increased PAI-1 synthesis. In the presence of simvastatin t-PA synthesis in control and TNF-alpha-treated cells dose-dependently increased, reaching 5.8-fold and 7.7-fold higher t-PA levels, respectively, at 5 micromol/L simvastatin after 48 hours. Simvastatin dose-dependently suppressed PAI-1 production in both control and TNF-alpha-treated cells. At 5 micromol/L, simvastatin lowered PAI-1 synthesis 3.4-fold and 4.0-fold, respectively, thereby also completely suppressing the TNF-alpha effect itself. Similarly, simvastatin down-regulated the expression of tissue factor and also completely opposed the TNF-alpha-induced tissue factor expression. The effects of simvastatin on t-PA, PAI-1 and tissue factor expression were prevented by mevalonate and geranylgeraniol (GG), suggesting the involvement of geranylgeranyl-modified intermediates in simvastatin's mode of action. Also, simvastatin reduced NF-kappa B- and AP-1-dependent reporter gene activity in TNF-alpha-treated HT-1080 fibrosarcoma cells and reduced the nuclear levels of p50-NF-kappa B, p65-NF-kappa B, and the AP-1 components c-fos and c-jun in HMC.
CONCLUSION
The HMG-CoA reductase inhibitor simvastatin is an effective stimulator of the mesothelial fibrinolytic capacity and suppresses the procoagulant activity both under normal and inflammatory conditions. Our findings provide a molecular explanation for the anti-inflammatory properties of statins in HMC and a rationale for the use of these drugs to protect peritoneal dialysis patients from peritoneal fibrosis and adhesion development during bacterial peritonitis.
Topics: Antineoplastic Agents; Cells, Cultured; Diterpenes; Epithelial Cells; Epithelium; Fibrinolysis; Gene Expression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mevalonic Acid; Omentum; Peritoneal Dialysis; Peritoneum; Peritonitis; Plasminogen Activator Inhibitor 1; Simvastatin; Thromboplastin; Tumor Necrosis Factor-alpha
PubMed: 12753293
DOI: 10.1046/j.1523-1755.2003.t01-2-00004.x -
World Journal of Gastroenterology Apr 2020Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is...
BACKGROUND
Hepatic portal venous gas (HPVG) generally indicates poor prognoses in patients with serious intestinal damage. Although surgical removal of the damaged portion is effective, some patients can recover with conservative treatments.
AIM
To establish an optimal treatment strategy for HPVG, we attempted to generate computed tomography (CT)-based criteria for determining surgical indication, and explored reliable prognostic factors in non-surgical cases.
METHODS
Thirty-four cases of HPVG (patients aged 34-99 years) were included. Necessity for surgery had been determined mainly by CT findings (. free-air, embolism, lack of contrast enhancement of the intestinal wall, and intestinal pneumatosis). The clinical data, including treatment outcomes, were analyzed separately for the surgical cases and non-surgical cases.
RESULTS
Laparotomy was performed in eight cases (surgical cases). Seven patients (87.5%) survived but one (12.5%) died. In each case, severe intestinal damage was confirmed during surgery, and the necrotic portion, if present, was removed. Non-occlusive mesenteric ischemia was the most common cause ( = 4). Twenty-six cases were treated conservatively (non-surgical cases). Surgical treatments had been required for twelve but were abandoned because of the patients' poor general conditions. Surprisingly, however, three (25%) of the twelve inoperable patients survived. The remaining 14 of the 26 cases were diagnosed originally as being sufficiently cured by conservative treatments, and only one patient (7%) died. Comparative analyses of the fatal ( = 10) and recovery ( = 16) cases revealed that ascites, peritoneal irritation signs, and shock were significantly more frequent in the fatal cases. The mortality was 90% if two or all of these three clinical findings were detected.
CONCLUSION
HPVG related to intestinal necrosis requires surgery, and our CT-based criteria are probably useful to determine the surgical indication. In non-surgical cases, ascites, peritoneal irritation signs and shock were closely associated with poor prognoses, and are applicable as predictors of patients' prognoses.
Topics: Adult; Aged; Aged, 80 and over; Ascites; Conservative Treatment; Embolism, Air; Female; Gases; Humans; Intestinal Mucosa; Male; Mesenteric Ischemia; Necrosis; Pneumatosis Cystoides Intestinalis; Portal Vein; Prognosis; Retrospective Studies; Risk Factors; Shock; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32327911
DOI: 10.3748/wjg.v26.i14.1628 -
The American Journal of Pathology Sep 2008The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that...
The pathophysiology of endometriosis remains unclear but involves a complex interaction between ectopic endometrium and host peritoneal tissues. We hypothesized that disruption of this interaction would suppress endometriotic lesion formation. We hoped to delineate the molecular and cellular dialogue between ectopic human endometrium and peritoneal tissues in nude mice as a first step toward testing this hypothesis. Human endometrium was xenografted into nude mice, and the resulting lesions were analyzed using microarrays. A novel technique was developed that unambiguously determined whether RNA transcripts identified via microarray analyses originated from human cells (endometrium) or mouse cells (mesothelium). Four key pathways (ubiquitin/proteasome, inflammation, tissue remodeling/repair, and ras-mediated oncogenesis) were revealed, demonstrating communication between host mesothelial cells and ectopic endometrium. Morphometric analysis of nude mouse lesions confirmed that necrosis, inflammation, healing and repair, and cell proliferation occurred during xenograft development. These processes were entirely consistent with the molecular networks revealed by the microarray data. The transcripts detected in the xenografts overlapped with differentially expressed transcripts in a comparison between paired eutopic and ectopic endometria from human endometriotic patients. For the first time, components of the interaction between ectopic endometrium and peritoneal stromal tissues are revealed. Targeted disruption of this dialogue is likely to inhibit endometriotic tissue formation and may prove to be an effective therapeutic strategy for endometriosis.
Topics: Adult; Animals; Endometriosis; Endometrium; Female; Gene Expression; Humans; Immunohistochemistry; Mice; Mice, Nude; Middle Aged; Oligonucleotide Array Sequence Analysis; Peritoneum; Transplantation, Heterologous
PubMed: 18688027
DOI: 10.2353/ajpath.2008.071128 -
Fertility and Sterility Jun 2006To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women...
OBJECTIVE
To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women with endometriosis when compared with women without the disease during menstrual and luteal phases of the cycle.
DESIGN
Patients with endometriosis were compared with control patients.
SETTING
University hospital.
PATIENT(S)
A total of 35 patients (20 patients during the luteal phase and 15 patients during the menstrual phase) were selected for this study on the basis of cycle phase and presence or absence of endometriosis.
INTERVENTION(S)
In this study, endometriosis was laparoscopically and histologically confirmed in 24 women with endometriosis of revised American Society for Reproductive Medicine (ASRM) stage I-II (n = 12) and revised ASRM stage III-IV (n = 12), and the presence of a normal pelvis was documented by laparoscopy in 11 control patients. The macroscopically normal peritoneum tissues were collected from lateral wall left or right, near the colon ascendens or descendens.
MAIN OUTCOME MEASURE(S)
The expression levels were determined as ratios between the target molecules and beta-actin as housekeeping gene.
RESULT(S)
In women with endometriosis, peritoneal mRNA levels of matrix metalloproteinase (MMP)-3, transforming growth factor-beta, interleukin (IL)-6, and intercellular adhesion molecule-1 and endometrial mRNA levels of MMP-3, tumor necrosis factor (TNF)-alpha, and IL-8 were significantly higher during the menstrual phase when compared with luteal phase. During the menstrual phase of the cycle, both endometrial expression of TNF-alpha, IL-8, and MMP-3 mRNA levels and peritoneal expression of transforming growth factor-beta, IL-6, and intercellular adhesion molecule-1 mRNA levels were significantly higher in women with endometriosis when compared with controls. Immunohistochemical staining confirmed the presence of TNF-alpha in peritoneum and endometrium in both women with endometriosis and controls.
CONCLUSION(S)
Increased endometrial and peritoneal cytokine mRNA expression during menstruation may contribute to a pelvic inflammatory microenvironment favoring the development of endometriosis.
Topics: Biomarkers; Cytokines; Endometriosis; Endometrium; Female; Gene Expression; Humans; Menstrual Cycle; Peritoneum
PubMed: 16759923
DOI: 10.1016/j.fertnstert.2005.11.060 -
Alimentary Pharmacology & Therapeutics Dec 2007Over the last decades, gastrointestinal endoscopy has transformed from serving purely diagnostic purposes to therapeutic applications. One recent major progress is... (Review)
Review
BACKGROUND
Over the last decades, gastrointestinal endoscopy has transformed from serving purely diagnostic purposes to therapeutic applications. One recent major progress is taking the endoscope beyond the gastrointestinal lumen into the peritoneal cavity for diagnostic and therapeutic procedures. The first step towards Natural Orifice Translumenal Endoscopic Surgery (NOTES) was translumenal endoscopic debridement of pancreatic necrosis.
AIM
To overview current status of endoscopic debridement of organized pancreatic necrosis. Finally, we take a short look into the potential future of translumenal endoscopic procedures.
METHODS
Medical databases were searched for relevant publications, dealing with endoscopic debridement of pancreatic necrosis and NOTES.
RESULTS
All current published studies concerning endoscopic debridement of organized pancreatic necrosis were retrospectively performed and relatively small (largest n = 25). Success rates varies from 80-93% and complication rates from 7-20%. There was no procedure related mortality reported. Published NOTES experiments showed feasibility of a variety of transgastric, transcolonic and transvaginal procedures in the porcine model.
CONCLUSION
Endoscopic debridement seems to be an effective and relatively safe minimally invasive therapy in patients with symptomatic organized pancreatic necrosis and is the first step towards NOTES. Further comparative studies need to define its definitive role in the management of these patients.
Topics: Debridement; Endoscopy, Digestive System; Humans; Pancreatitis, Acute Necrotizing; Peritoneal Cavity
PubMed: 18081666
DOI: 10.1111/j.1365-2036.2007.03489.x -
Annals of Surgery Nov 1957
Topics: Colonic Neoplasms; Humans; Infarction; Omentum; Peritoneal Diseases; Vascular Diseases
PubMed: 13479059
DOI: 10.1097/00000658-195711000-00023 -
The Pan African Medical Journal 2018We conducted a retrospective study of 15 patients with complicated Meckel diverticula treated in the emergency surgery at the Aristide Le Dantec Hospital, Dakar, over a...
We conducted a retrospective study of 15 patients with complicated Meckel diverticula treated in the emergency surgery at the Aristide Le Dantec Hospital, Dakar, over a period of 13 years (January 2003-June 2016). The study included 10 men and 5 women, whose average age was 27.8 years, ranging between 1 months and 73 years. The two main circumstances of detection were occlusive syndrome and peritoneal irritation. Emergency laparotomy allowed clinicians to affirm the involvement of Meckel diverticulum in the clinical picture. In the case of occlusion, the mechanism was always a flange. Ten patients had intestinal necrosis with perforation at the time of diagnosis. All 15 patients underwent segmental resection of the intestine with elimination of the diverticulum. This resection was followed by immediate anastomosis in 12 cases. The morbidity was constituted of 2 cases of fistulas and 2 cases of postoperative peritonitis. A case of death due to septic shock was reported. Three patients had heterotopic mucosa, including gastric heterotopia, colic heterotopia and an association between colic heterotopia and gastric heterotopia in the same patient. The complications of Meckel diverticula are digestive emergencies requiring early and adapted surgical treatment. This is characterized by a non-negligible morbidity.
Topics: Adolescent; Adult; Aged; Anastomosis, Surgical; Child; Child, Preschool; Emergencies; Female; Humans; Infant; Laparotomy; Male; Meckel Diverticulum; Middle Aged; Necrosis; Peritonitis; Postoperative Complications; Retrospective Studies; Senegal; Young Adult
PubMed: 29875962
DOI: 10.11604/pamj.2018.29.81.12675 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Nov 2019A rare cause of acute abdomen or intestinal obstruction, the abdominal cocoon syndrome is also described in the literature as sclerosing peritonitis or sclerosing...
BACKGROUND
A rare cause of acute abdomen or intestinal obstruction, the abdominal cocoon syndrome is also described in the literature as sclerosing peritonitis or sclerosing encapsulating peritonitis. Abdominal cocoon is characterized by the total or partial wrapping of the abdominal organs by a fibrous membrane. Although it is usually observed in young women, the etiology is unknown. The diagnosis is usually made during laparotomy. In this case series, we aimed to present seven patients diagnosed with abdominal cocoon syndrome during operation.
METHODS
The records of patients who underwent laparotomy for abdominal pain and/or intestinal obstruction in our hospital and diagnosed as abdominal cocoon during operation between January 2012 and November 2018 were retrospectively reviewed. The demographic characteristics of the patients, etiologic factors, surgical procedures, operative findings and follow-up of the patients were recorded.
RESULTS
Four out of seven patients who were operated for abdominal cocoon were male and 3 of them were female. The median age of patients was 61 (57-63) years in male and 39.6 (28-49) years in female. Six of the patients were operated in emergency conditions with the diagnosis of an acute abdomen or ileus. One of the patients was operated with the diagnosis of an intra-abdominal mass in elective conditions. In five out of seven patients, all of the small intestines were wrapped with a fibrous collagen capsule, while two of the patient intestines were partially wrapped with a fibrous collagen capsule. Four of the patients had no underlying disease, while one of the patients had Familial Mediterranean Fever (FMF), one had Endometriosis and one had beta-blocker medication. One patient who had small bowel necrosis and septic peritonitis were observed during the operation and died post operative 6th days. Postoperative complications were not observed in the follow-up of other patients and reoperation was not required due to recurrence.
CONCLUSION
Abdominal cocoon is a condition that is usually diagnosed during operation in patients that were operated for reasons, such as the acute abdomen or intestinal obstruction. When the diagnose delayed, death can be seen due to small bowel necrosis and septic complications. High clinical suspicion and radiological imaging are important in the preoperative diagnosis. Treatment is required adhesiolysis and excision of the fibrous membranes.
Topics: Abdomen, Acute; Abdominal Pain; Adult; Female; Humans; Intestinal Obstruction; Male; Middle Aged; Peritoneal Fibrosis; Peritonitis; Retrospective Studies
PubMed: 31701503
DOI: 10.14744/tjtes.2019.48380