Increased mortality and altered local immune response in secondary peritonitis after previous visceral operations in mice

AbstractPostoperative peritonitis is characterized by a more severe clinical course than other forms of secondary peritonitis. The pathophysiological mechanisms behind this phenomenon are incompletely understood. This study used an innovative model to investigate these mechanisms, combining the models of murine Colon Ascendens Stent Peritonitis (CASP) and Surgically induced Immune Dysfunction (SID). Moreover, the influence of the previously described anti-inflammatory reflex transmitted by the vagal nerve was characterized. SID alone, or 3 days before CASP were performed in female C57BL/6 N mice. Subdiaphragmatic vagotomy was performed six days before SID with following CASP. The immune status was assessed by FACS analysis and measurement of cytokines. Local intestinal inflammatory changes were characterized by immunohistochemistry. Mortality was increased in CASP animals previously subjected to SID. Subclinical bacteremia occurred after SID, and an immunosuppressive milieu occurred secondary to SID just before the induction of CASP. Previous SID modified the pattern of intestinal inflammation induced by CASP. Subdiaphragmatic vagotomy had no influence on sepsis mortality in our model of postoperative peritonitis. Our results indicate a surgery-induced inflammation of the small intestine and the peritoneal cavity with bacterial translocation, which led to immune dysfunction and consequently to a more severe peritonitis.

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Intra-Individual Variation in Serum AZT Concentration is Not Related to Intestinal Absorption or Small Intestinal Inflammatory Changes in Human Immunodeficiency Virus-Infected Subjects

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029700800405 ◽

1997 ◽

Vol 8 (4) ◽

pp. 327-332 ◽

Cited By ~ 6

Author(s):

RA Sherwood ◽

JT Marsden ◽

CA Stein ◽

S Somasundaram ◽

C Aitken ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Urinary Excretion ◽

Intestinal Permeability ◽

Absorptive Capacity ◽

Individual Variation ◽

Half Life ◽

Intestinal Inflammation ◽

Immunodeficiency Virus ◽

Small Intestinal ◽

Inflammatory Changes

3′-Azido-3′-deoxythymidine (AZT; zidovudine) either alone or in combination with didanosine or another nucleoside analogue is the first-line treatment for patients with human immunodeficiency virus (HIV) infection, many of whom have concurrent gastrointestinal (GI) disease. This study assessed whether the absorption of AZT was affected by GI disease. The absorption and pharmacokinetics of AZT in 23 HIV-infected individuals was measured after a single dose of AZT and was related in 12 patients to small intestinal function. Levels of AZT and its metabolite 5′-glucopyranuronosylthymidine (G-AZT) were measured by radioimmunoassay. Intestinal permeability was assessed by differential urinary excretion of orally administered lactulose/1-rhamnose; absorptive capacity was measured simultaneously by the urinary excretion of 3-o-methyl-D-glucose, d-xylose and 1-rhamnose. Small intestinal inflammation was assessed by faecal excretion of indium-labelled neutrophils. Peak levels of AZT in serum varied between 170 and 1820 ng mL−1. The metabolite G-AZT was present in serum at peak concentrations varying from 1020 to 9930 ng mL−1. There was up to a sevenfold variation in the area under the curve (AUC). The time to maximum serum concentration for AZT was between 30 and 120 min, with an absorption half-life of between 2 and 38 min. The median elimination half-life was 57 min (range 46–72 min), close to the predicted half-life of 60 min. Intestinal permeability was increased in six of the 12 subjects studied and eight had evidence of reduced absorptive capacity. Ten of the 12 patients had evidence of small intestinal inflammation. We concluded that neither changes in permeability nor absorptive capacity influenced the absorption of AZT. There was no relationship between the presence of intestinal inflammation and AZT absorption. This study showed a significant intra-individual variation of serum AZT levels which cannot be explained on the basis of altered intestinal absorptive capacity or intestinal inflammatory changes.

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Age Influence in the Prognosis of Bacterial Secondary Peritonitis

Revista de Chimie ◽

10.37358/rc.17.5.5603 ◽

2017 ◽

Vol 68 (5) ◽

pp. 1023-1027

Author(s):

Dorel Firescu ◽

Cristina Serban ◽

Aurel Nechita ◽

Mihaela Dumitru ◽

Laura Rebegea

Keyword(s):

Retrospective Study ◽

Aging Process ◽

The Body ◽

Secondary Peritonitis ◽

Metabolic Alterations ◽

Clinical Hospital ◽

Bacterial Peritonitis ◽

Severe Peritonitis ◽

The Impact

Today the age of 60-65 years old is considered the seniority threshold. The structural, functional and metabolic alterations which occur following to the aging process determine an exacerbation of the impact which any aggression will have on the body. This retrospective study analyses a group of 245 patients with severe peritonitis, which had been hospitalized and treated in Surgery 2nd Clinic of the Sf. Apostol Andrei Emergency Clinical Hospital in the period 2007-2016. The median age 54 years old [range 30-95]; 68 patients (27.76% of cases) were ] 65 years old (65+) and 177 patients (72.24% of cases) with age between [ 65 years old (65-). Out of the results obtained, it is obvious the impact of age in the evolution and prognosis of bacterial peritonitis.

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Intestinal permeability and inflammation in patients on NSAIDs

Gut ◽

10.1136/gut.43.4.506 ◽

1998 ◽

Vol 43 (4) ◽

pp. 506-511 ◽

Cited By ~ 111

Author(s):

G Sigthorsson ◽

J Tibble ◽

J Hayllar ◽

I Menzies ◽

A Macpherson ◽

...

Keyword(s):

Intestinal Permeability ◽

Intestinal Inflammation ◽

Test Dose ◽

Faecal Excretion ◽

Intestinal Integrity ◽

Number Of Patients ◽

Significant Difference ◽

Indium 111 ◽

Small Intestinal ◽

Inflammatory Changes

Background—The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain.Aims—To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs.Methods—Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar). Two hundred and eighty six patients on 12 different NSAIDs underwent indium-111 white cell faecal excretion studies to assess the prevalence and severity of intestinal inflammation.Results—The iso- and hyperosmolar tests showed significant malabsorption of 3–0-methyl-d-glucose, d-xylose, andl-rhamnose. Intestinal permeability changes were significantly more pronounced and frequent with the hypo- and hyperosmolar as opposed to the iso-osmolar test. Sequential studies showed that four and nine patients (of 13) developed inflammation after three and six months treatment with NSAIDs, respectively. There was no significant difference (p>0.1) in the prevalence (54–72%) or severity of intestinal inflammation in the 286 patients taking the various NSAIDs apart from those on aspirin and nabumetone, these having no evidence of intestinal inflammation. There was no significant correlation between the inflammatory changes and age, sex, dose of NSAID, length of disease, or NSAID ingestion.Conclusions—Intestinal permeability test dose composition is an important factor when assessing the effects of NSAIDs on intestinal integrity. All the conventional NSAIDs studied were equally associated with small intestinal inflammation apart from aspirin and nabumetone which seem to spare the small bowel.

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Salmonella entericaEffectors SifA, SpvB, SseF, SseJ, and SteA Contribute to Type III Secretion System 1-Independent Inflammation in a Streptomycin-Pretreated Mouse Model of Colitis

Infection and Immunity ◽

10.1128/iai.00872-18 ◽

2019 ◽

Vol 87 (9) ◽

Cited By ~ 5

Author(s):

Shigeki Matsuda ◽

Takeshi Haneda ◽

Hiyori Saito ◽

Tsuyoshi Miki ◽

Nobuhiko Okada

Keyword(s):

Mouse Model ◽

Type Iii Secretion ◽

Intestinal Inflammation ◽

Type Iii Secretion System ◽

Secretion System ◽

Time Range ◽

Content Type ◽

Type Iii ◽

System 1 ◽

Inflammatory Changes

ABSTRACTSalmonella entericaserovar Typhimurium (S.Typhimurium) induces inflammatory changes in the ceca of streptomycin-pretreated mice. In this mouse model of colitis, the type III secretion system 1 (T3SS-1) has been shown to induce rapid inflammatory change in the cecum at early points, 10 to 24 h after infection. Five proteins, SipA, SopA, SopB, SopD, and SopE2, have been identified as effectors involved in eliciting intestinal inflammation within this time range. In contrast, a T3SS-1-deficient strain was shown to exhibit inflammatory changes in the cecum at 72 to 120 h postinfection. However, the effectors eliciting T3SS-1-independent inflammation remain to be clarified. In this study, we focused on two T3SS-2 phenotypes, macrophage proliferation and cytotoxicity, to identify the T3SS-2 effectors involved in T3SS-1-independent inflammation. We identified a mutant strain that could not induce cytotoxicity in a macrophage-like cell line and that reduced intestinal inflammation in streptomycin-pretreated mice. We also identified five T3SS-2 effectors, SifA, SpvB, SseF, SseJ, and SteA, associated with T3SS-1-independent macrophage cytotoxicity. We then constructed a strain lacking T3SS-1 and all the five T3SS-2 effectors, termed T1S5. TheS.Typhimurium T1S5 strain significantly reduced cytotoxicity in macrophages in the same manner as a mutantinvA spiBstrain (T1T2). Finally, the T1S5 strain elicited no inflammatory changes in the ceca of streptomycin-pretreated mice. We conclude that these five T3SS-2 effectors contribute to T3SS-1-independent inflammation.

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Rapid Fecal Calprotectin Level Assessment and the SIBDQ Score Can Accurately Detect Active Mucosal Inammation in IBD Patients in Clinical Remission: a Prospective Study

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.233.thv ◽

2014 ◽

Vol 23 (3) ◽

pp. 273-278 ◽

Cited By ~ 12

Author(s):

Theodor Voiosu ◽

Andreea Bengus ◽

Roxana Dinu ◽

Andrei M. Voiosu ◽

Paul Balanescu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Clinical Remission ◽

Intestinal Inflammation ◽

Activity Index ◽

Fecal Calprotectin ◽

Clinical Activity ◽

Inflammatory Bowel ◽

Inflammatory Changes

Background & Aims: Mucosal healing is an important predictor of disease-related outcome in inflammatory bowel disease (IBD) patients, including those in clinical remission. However, colonoscopy is an invasive procedure and many patients decline repeated endoscopic examinations. We aimed to assess whether noninvasive biomarkers could accurately detect endoscopic mucosal inflammatory activity in IBD patients in clinical remission.Methods: We conducted a prospective observational cohort study on IBD patients in clinical remission at Colentina Hospital, Bucharest. Clinical activity was assessed using the Mayo score and Crohns Disease Activity Index (CDAI), quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Serum C-reactive protein (CRP) and fecal calprotectin (FC) levels were determined. All patients underwent ileo-colonoscopy to assess mucosal inflammatory activity.Results: 48 patients were included in this study, with 67% showing endoscopic disease activity. SIBD questionnaire and FC performed well as noninvasive markers of intestinal inflammation (AUROC 0.78 and 0.77, respectively), while CRP could not accurately predict endoscopic disease activity. Fecal calprotectin levels > 30 ľg/g showed a 93% sensitivity and a 50% specificity for detecting inflammatory changes of the mucosa while a combined test using FC > 30µg/g and a SIBDQ score < 6 achieved 81.2% sensitivity and 75% specificity, respectively, in detecting active endoscopic disease.Conclusion: Fecal calprotectin and SIBDQ have good diagnostic accuracy in detecting mucosal inflammatory changes in IBD patients in clinical remission. Combining simple, noninvasive tests such as the SIBDQ and FC levels appears to be a practical method for monitoring disease activity in these patients, possibly reducing the need for repeat endoscopic examinations.

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Genetic and Pharmacological Dissection of the Role of Spleen Tyrosine Kinase (Syk) in Intestinal Inflammation and Immune Dysfunction in Inflammatory Bowel Diseases

Inflammatory Bowel Diseases ◽

10.1093/ibd/izx031 ◽

2017 ◽

Vol 24 (1) ◽

pp. 123-135 ◽

Cited By ~ 3

Author(s):

Michele Biagioli ◽

Andrea Mencarelli ◽

Adriana Carino ◽

Sabrina Cipriani ◽

Silvia Marchianò ◽

...

Keyword(s):

Tyrosine Kinase ◽

Inflammatory Bowel Diseases ◽

Intestinal Inflammation ◽

Adaptor Protein ◽

Immune Dysfunction ◽

Trinitrobenzene Sulfonic Acid ◽

Spleen Tyrosine Kinase ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Background The DNAX adaptor protein 12 (DAP12) is a transmembrane adaptor molecule that signals through the activation of Syk (Spleen Tyrosine Kinase) in myeloid cells. The purpose of this study is to investigate the role of DAP12 and Syk pathways in inflammatory bowel diseases (IBDs). Methods DAP12 deficient and DAP12 transgenic, overexpressing an increased amount of DAP12, mice and Syk deficient mice in the C57/BL6 background were used for these studies. Colitis was induced by administering mice with dextran sulfate sodium (DSS), in drinking water, or 2,4,6-trinitrobenzene sulfonic acid (TNBS), by intrarectal enema. Results Abundant expression of DAP12 and Syk was detected in colon samples obtained from Crohn’s disease patients with expression restricted to immune cells infiltrating the colonic wall. In rodents development of DSS colitis as measured by assessing severity of wasting diseases, global colitis score,and macroscopic and histology scores was robustly attenuated in DAP12-/- and Syk-/- mice. In contrast, DAP12 overexpression resulted in a striking exacerbation of colon damage caused by DSS. Induction of colon expression of proinflammatory cytokines and chemokines in response to DSS administration was attenuated in DAP12-/- and Syk-/- mice, whereas opposite results were observed in DAP12 transgenic mice. Treating wild-type mice with a DAP-12 inhibitor or a Syk inhibitor caused a robust attenuation of colitis induced by DSS and TNBS. Conclusions DAP12 and Syk are essential mediators in inflammation-driven immune dysfunction in murine colitides. Because DAP12 and Syk expression is upregulated in patients with active disease, present findings suggest a beneficial role for DAP12 and Syk inhibitors in IBD.

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Surgically induced hormonal, metabolic and inflammatory changes in laparoscopic hysterectomy: a comparison with abdominal hysterectomy

Gynaecological Endoscopy ◽

10.1046/j.1365-2508.2002.00566.x ◽

2002 ◽

Vol 11 (5) ◽

pp. 299-304 ◽

Cited By ~ 4

Author(s):

Zdenek Holub ◽

Antonin Jabor ◽

Ludik Sprongl ◽

Lev Kliment ◽

Drahomira Fischlova ◽

...

Keyword(s):

Laparoscopic Hysterectomy ◽

Abdominal Hysterectomy ◽

Inflammatory Changes ◽

Surgically Induced

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Quantification of gold labeled cell surface antigens by SEM: Current progress and remaining problems

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015770x ◽

1990 ◽

Vol 48 (3) ◽

pp. 34-35

Author(s):

Etienne de Harven ◽

Davide Soligo ◽

Roy McGroarty ◽

Hilary Christensen ◽

Richard Leung ◽

...

Keyword(s):

Cell Surface ◽

Immunogold Labeling ◽

Target Antigen ◽

Facs Analysis ◽

Becton Dickinson ◽

Cell Surface Antigens ◽

Human T Lymphocyte ◽

Backscattered Electron ◽

Imaging Mode ◽

Electron Imaging

Taking advantage of the high elemental contrast of particles of colloidal gold observed in the backscattered electron imaging(BEI) mode of the SEM (1,2), the human T lymphocyte was chosen as a model system to study the potential value of immunogold labeling for the quantification of cell surface expressed molecules. The CD3 antigen which is expressed on all human T lymphocytes and is readily identified by the LEU-4 murine monoclonal antibody (Becton Dickinson, Mountain View, CA) followed by a gold conjugated goat anti-mouse Ig polyclonal antibody was chosen as a model target antigen. When quantified by non-EM methods, using radio-iodinated probes or FACS analysis, approximately 30,000 to 50,000 copies of this antigen per cell are enumerated.The following observations were made while attempting to quantify the same molecule by SEM after specific immunogold labeling:Imaging in the SE vs BE mode: The numbers of gold markers counted in the secondary electron (SE) imaging mode are considerably lower than those counted on the same cells in the backscattered electron (BE) imaging mode.

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