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Wounds : a Compendium of Clinical... Oct 2016This study investigated and compared the effects of antibiotic and steroid lavage on survival and cytokine levels in an experimental abdominal sepsis model.
OBJECTIVE
This study investigated and compared the effects of antibiotic and steroid lavage on survival and cytokine levels in an experimental abdominal sepsis model.
BACKGROUND
In abdominal sepsis, abdominal lavage with saline or antibiotic solutions is a well-documented intervention known to have positive impact on survival; however, the effects of steroid lavage in abdominal sepsis have not yet been investigated.
MATERIALS AND METHODS
Ninety-six Wistar rats were divided into 4 groups (n = 24). Abdominal sepsis was induced by cecal ligation and puncture. Six hours after laparotomy, the authors performed a relaparatomy followed by cecal resection and an abdominal lavage. Abdominal lavage was performed using saline in group 1, equal volumes of cefazolin sodium in group 2, low-dose methylprednisolone (1 mg/kg) in group 3, and high-dose methylprednisolone (2 mg/kg) in group 4. After division of 2 subgroups from each of the 4 groups, the first of the rats (n = 12) were euthanized 6 hours later for evaluation of cytokines (ie, interleukin [IL] 1β, 2, 4, 10, and tumor necrosis factor alpha [TNF-α]), and the others were followed for 30 days for analysis of mortality rates.
RESULTS
The mortality rate of the rats in group 2 was significantly higher than group 4, which had no mortality (P = 0.032). Although insignificant, the lowest mean value of IL-1β, IL-2, and TNF-α were in group 1, and the highest was in group 2. The lowest IL-4 level was in group 3, and the highest level was in group 2 (P = 0.41). Interleukin-10 levels were significantly lower in group 4 and higher in group 2 (P = 0.014).
CONCLUSION
The authors state that peritoneal lavage with prednisolone improved survival rates with increasing doses in abdominal sepsis.
Topics: Abdomen; Animals; Cecum; Disease Models, Animal; Ligation; Male; Peritoneal Lavage; Peritonitis; Prednisolone; Rats; Rats, Wistar; Sepsis
PubMed: 27768573
DOI: No ID Found -
Nephron. Experimental Nephrology 2012Experimental peritonitis is a frequently used inflammatory model to evaluate leukocyte recruitment. By the intrinsic characteristics of the peritoneal cavity, the... (Review)
Review
Experimental peritonitis is a frequently used inflammatory model to evaluate leukocyte recruitment. By the intrinsic characteristics of the peritoneal cavity, the various resident cell populations have a role to play in the initiation, the modulation and the resolution of peritoneal inflammation. Through various manipulations of these cell populations, we gained important knowledge on their respective roles in peritoneal inflammation. In this brief review, we will focus on the cellular regulation of leukocyte recruitment in experimental peritonitis.
Topics: Animals; Dendritic Cells; Humans; Interferon-gamma; Interleukin-2; Lymphocytes; Macrophages, Peritoneal; Models, Immunological; Peritonitis; Tumor Necrosis Factor-alpha
PubMed: 22222207
DOI: 10.1159/000334169 -
Biological & Pharmaceutical Bulletin 2022Macrophages have important roles in the progression of inflammation. Ajania purpurea Shih. is a member of the Ajania Poljakor family that grows in Tibet (China)....
Macrophages have important roles in the progression of inflammation. Ajania purpurea Shih. is a member of the Ajania Poljakor family that grows in Tibet (China). Extracts from plants in this genus have anti-bacterial and anti-inflammatory properties. However, there are few reports on the activity and mechanism of Ajania purpurea. Here, we confirmed the anti-inflammatory effect of Ajania purpurea Shih. ethanol extract (EAPS) by examining the levels of inflammatory factors in a mouse model of peritonitis and RAW264.7 cells. The main components of EAPS detected by LC-MS analysis included piperine and chlorogenic acid. In particular, in lipopolysaccharide (LPS)-induced RAW264.7 cells, EAPS inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, lowered the levels of nitric oxide (NO) and prostaglandin E2 (PGE), as well as the release of inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6. In addition, Western blot analysis and immunofluorescence staining verified that EAPS inhibited the activity of the nuclear factor-kappaB (NF-κB) pathway by reducing the nuclear translocation of the p65 subunit. Furthermore, in a mouse model of peritonitis, EAPS inhibited the release of inflammatory factors, as well as the recruitment of immune cells including neutrophils and macrophages. These findings indicated that EAPS suppressed LPS-induced inflammation via inhibiting the NF-κB pathway in RAW264.7 cells and mice with peritonitis. Thus, EAPS may be a viable therapeutic method for the treatment of inflammation and related disorders.
Topics: Mice; Animals; Lipopolysaccharides; NF-kappa B; Inflammation; Peritonitis; Dinoprostone; Disease Models, Animal; Plant Extracts
PubMed: 36450537
DOI: 10.1248/bpb.b22-00388 -
Scientific Reports Aug 2018Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood....
Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols. H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.
Topics: Acute Kidney Injury; Animals; Catechols; Dimethyl Sulfoxide; Dimethylamines; Disease Models, Animal; Fatty Alcohols; Feces; Humans; Injections, Intraperitoneal; Male; Metabolome; Metabolomics; Oxidative Stress; Peritonitis; Rats; Rats, Wistar; Sepsis; Sulfones; Survival Analysis; Treatment Outcome
PubMed: 30108263
DOI: 10.1038/s41598-018-30522-6 -
PloS One 2016Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional...
Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects.
Topics: Animals; Antibodies, Monoclonal; CA-125 Antigen; Collagen; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Granulocytes; Hyaluronic Acid; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peritoneal Dialysis; Peritoneum; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II
PubMed: 27755542
DOI: 10.1371/journal.pone.0163314 -
Scientific Reports Sep 2016Toll-like receptors (TLRs) have critical roles in innate immunity and inflammation and the detailed mechanisms by which TLR signaling is fine tuned remain unclear....
Toll-like receptors (TLRs) have critical roles in innate immunity and inflammation and the detailed mechanisms by which TLR signaling is fine tuned remain unclear. Keratin 8 (CK8) belongs to the type II keratin family and is the major compontent of the intermediate filaments of simple or single-layered epithelia. Here we report that down-regulation of CK8 in mice enhanced TLR-mediated responses, rendering mice more susceptible to lipopolysaccharide (LPS)-induced endotoxin shock and Escherichia coli-caused septic peritonitis with reduced survival, elevated levels of inflammation cytokines and more severe tissue damage. We found that CK8 suppressed TLR-induced nuclear factor (NF)-κB activation and interacted with the adaptor tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) to prevent its polyubiquitination. Our findings demonstrate a novel role of CK8 in negative regulation of TLR/NF-κB signaling and highlight a previously unidentified nonclassical function for CK8 in limiting inflammatory responses.
Topics: Animals; Cytokines; Disease Models, Animal; Endotoxins; Escherichia coli Infections; Inflammation; Keratin-8; Mice; NF-kappa B; Peritonitis; Shock, Septic; Survival Analysis; TNF Receptor-Associated Factor 6; Toll-Like Receptors; Ubiquitination
PubMed: 27586056
DOI: 10.1038/srep32710 -
Infection and Immunity Jan 2009A progressive increase in infections with multiresistant Enterococcus faecium has been reported, especially in cancer patients and neutropenic patients. Despite its...
A progressive increase in infections with multiresistant Enterococcus faecium has been reported, especially in cancer patients and neutropenic patients. Despite its increasing importance as a nosocomial pathogen, knowledge of the pathogenesis of E. faecium infections is highly limited. In this study, we investigated the role of neutrophils during peritonitis with subsequent bacteremia caused by E. faecium. Therefore, we depleted neutrophils by intraperitoneal injections of monoclonal antibody RB6-8C5. Mice were followed for 5 days, and the enterococcal outgrowth and inflammatory response were compared between neutropenic mice and immunoglobulin G-injected control mice. Neutropenic mice demonstrated a severe delay in enterococcal clearance from all cultured organs (peritoneal fluid, blood, and lung and liver tissue). In particular, neutropenic mice remained bacteremic for up to 3 days, whereas all nonneutropenic mice had cleared the bacteria from circulation by 2 days. Furthermore, neutropenic mice displayed elevated peritoneal cytokine and chemokine levels 1 day after the infection and attracted fewer macrophages into the peritoneal cavity. In the circulation, a prolonged elevation of tumor necrosis factor alpha, interleukin-6, and the acute-phase proteins serum amyloid A and complement 3 were measured in neutropenic mice. In conclusion, attraction of neutrophils to the primary site of E. faecium infection is important for a rapid clearance of this bacterium, thereby attenuating a systemic inflammatory response.
Topics: Animals; Ascitic Fluid; Bacteremia; Blood; Colony Count, Microbial; Cytokines; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Leukocyte Count; Leukocyte Reduction Procedures; Liver; Lung; Mice; Neutrophils; Peritonitis
PubMed: 19001080
DOI: 10.1128/IAI.00863-08 -
Kidney International Sep 1994Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study...
Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study examines the regulation of prostaglandin production by human peritoneal mesothelial cells (HPMC) following stimulation with peritoneal macrophage-conditioned medium and the cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). IL-1 beta and TNF-alpha stimulated significant release of prostaglandin above background levels in a time and dose dependent manner. Stimulation of HPMC with IL-1 beta (500 pg/ml) or TNF-alpha (100 pg/ml) for 24 hours resulted in the release of 24.5 +/- 4.3 (N = 11) (z = 3.40, P < 0.001 vs. control) and 19.4 +/- 4.5 (N = 10; z = 3.29, P < 0.001 vs. control) pg 6-keto-PGF1 a/micrograms cellular protein, respectively. Pretreatment of HPMC with dexamethasone (10(-6) to 10(-9) M) inhibited both constitutive and cytokine stimulated prostaglandin synthesis in a dose dependent manner. Both PMø-CM and PMø-S.epiCM stimulated 6-keto-PGF1 alpha and PGE2 synthesis by HPMC in a time and dose dependent manner (PMø-S.epiCM >> PMø-CM). Co-incubation of HPMC with PMø-S.epiCM in the presence of anti-IL-1 beta and/or anti-TNF-alpha antibody, interleukin-1 receptor antagonist or soluble TNF receptor (TNF p75) significantly reduced the capacity of these supernatants to stimulate prostaglandin synthesis. Exposure of HPMC to cytokines or PMø-S.epiCM resulted in the time dependent increase in the levels of both Cox-1 and Cox-2 mRNA as assessed by RT/PCR analysis with the greatest increase being seen for Cox-2. These data demonstrate specific stimulation of eicosanoid metabolism in HPMC by peritoneal macrophage derived cytokines, indicating the possible importance of these mediators in the activation of intraperitoneal prostaglandin synthesis. HPMC prostaglandins might act as important pro/anti-inflammatory mediators contributing to a cytokine network in the peritoneal cavity during CAPD peritonitis.
Topics: Base Sequence; Cells, Cultured; Chromatography, High Pressure Liquid; Culture Media, Conditioned; Cytokines; DNA Primers; Enzyme Induction; Epithelium; Gene Expression Regulation, Enzymologic; Humans; Macrophages; Molecular Sequence Data; Peritoneal Cavity; Peritoneum; Polymerase Chain Reaction; Prostaglandin-Endoperoxide Synthases; Prostaglandins; RNA, Messenger; Radioimmunoassay
PubMed: 7996812
DOI: 10.1038/ki.1994.348 -
Laboratory Investigation; a Journal of... Dec 2015Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we...
Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1β, IL-6, transforming growth factor-β1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.
Topics: Adenoviridae; Animals; Body Weight; Disease Models, Animal; Genetic Therapy; Immunomodulation; Interleukin-10; Male; Peritoneal Fibrosis; Peritoneum; Pyruvaldehyde; Random Allocation; Rats, Sprague-Dawley
PubMed: 26367488
DOI: 10.1038/labinvest.2015.110 -
Journal of Vascular Surgery Feb 2013To present the short- to midterm outcomes after management of 14 patients with symptomatic isolated dissection of superior mesenteric artery (SIDSMA) and propose a...
OBJECTIVE
To present the short- to midterm outcomes after management of 14 patients with symptomatic isolated dissection of superior mesenteric artery (SIDSMA) and propose a preliminary treatment algorithm.
BACKGROUND
SIDSMA is a rare but potentially fatal entity. However, most of these reports were isolated case reports, and a consensus treatment protocol remains lacking so far. It would be meaningful to propose a reasonable treatment algorithm for it.
METHODS
Patients with SIDSMA who were treated in our center between July 2007 and June 2011 were retrospectively collected and analyzed. Based upon the abdominal pain and signs, the clinical manifestations have been retrospectively classified into grade I (peritonitis absent) and grade II (peritonitis present). Medical treatment mainly included anticoagulation, antiplatelet, and bowel rest. Endovascular stent placement and surgical fenestration with exploratory laparotomy have been selected according to the grade classification. Computed tomographic angiography, magnetic resonance angiography, or duplex scans have been used for diagnosis and follow-up.
RESULTS
Fourteen consecutive patients with SIDSMA were collected; among them, 13 cases belonged to grade I and one to grade II. The mean duration from the onset to the admission was 12 ± 12 days (range, 0.5-45 days). The mean distance from the primary tear to the ostium of superior mesenteric artery (SMA) was 26 ± 4 mm (range, 15-32 mm). Medical treatment was given for 13 patients of grade I for the first 3 to 5 days after admission, and the abdominal pain remarkably or completely resolved in four patients who received continued medical treatment, whereas the other unresolved nine patients were converted to endovascular stent placement that succeeded in four and failed in five patients. Since these five cases were free from peritoneal signs, medical treatment was given again instead of an immediate surgical intervention, and ultimately achieved complete alleviation of abdominal pain within the following 1 week. The mean duration from the start of medical treatment to the alleviation of symptoms, including the continued medical treatment after the failed endovascular stent placement, was 8 ± 3 days (range, 4-12 days). The grade II patient underwent a successful emergency surgical SMA fenestration without bowel resection. Follow-up was accomplished in all 14 cases, ranging from 2 to 48 months (mean, 30 ± 15 months). No intestinal necrosis, morbidity, or mortality developed during hospitalization. During the follow-up, all patients were free from aneurysmal formation of SMA or chronic intestinal ischemia, and all stents remained patent.
CONCLUSIONS
For grade I SIDSMA, most cases might be successfully treated with medical therapy, and the endovascular stent placement appears to be an acceptable alternative if medical treatment fails. For grade II SIDSMA, the endovascular stenting combined with laparoscopic exploration and/or open surgery could be a reasonable option.
Topics: Abdominal Pain; Adult; Algorithms; Aortic Dissection; Anticoagulants; Endovascular Procedures; Female; Humans; Magnetic Resonance Angiography; Male; Mesenteric Artery, Superior; Middle Aged; Peritonitis; Platelet Aggregation Inhibitors; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Surgical Procedures
PubMed: 23336859
DOI: 10.1016/j.jvs.2012.07.060