Acute Enterocolitis Research Articles

Neurologic deficits associated with severe hyponatremia in 2 foals

AbstractObjective: To describe the neurologic deficits associated with profound hyponatremia in 2 critically ill foals.Series summary: A 4‐month‐old Thoroughbred colt and an 11‐day‐old Paint filly presented for acute diarrhea and depression. Severe neurologic deficits including blindness and head pressing were noted upon initial examination along with marked hyponatremia observed on biochemistry profile. Aggressive intravenous sodium replacement increased the serum sodium concentration to subnormal values with concurrent resolution of neurologic deficits. Intensive monitoring and fluid therapy were continued; the Thoroughbred colt was euthanized due to lack of response to the primary disease while the Paint filly was discharged clinically healthy without further complications.New or unique information provided: Mild hyponatremia (122–132 mEq/L) is a common clinicopathologic finding in equine medicine associated with a variety of diseases. The vast majority of horses with mild hyponatremia do not demonstrate direct clinical manifestations as a result of low serum sodium concentration. However, when severe acute hyponatremia occurs (<122 mEq/L), such as with acute enterocolitis, subtle to profound neurologic deficits may be observed and immediate and rapid treatment as well as serial evaluations of serum sodium concentration are warranted. Significant, and potentially permanent, neurologic deficits can occur if water balance and tonicity are not properly addressed. The cases presented here describe additional cases of a previously published disease in foals, acute hyponatremia and associated neurologic deficits, and describe the microscopic examination of the central nervous system in one foal that did not survive.

Two newly identified SipA domains (F1, F2) steer effector protein localization and contribute to Salmonella host cell manipulation

Salmonella Typhimurium causes bacterial enterocolitis. The type III secretion system (TTSS)-1 is a key virulence determinant of S. Typhimurium mediating host cell invasion and acute enterocolitis. The TTSS-1 effector protein SipA is transported into host cells, accumulates in characteristic foci at the bacteria-host cell interface, manipulates signalling and affects virulence. Two functional domains of SipA have previously been characterized: The N-terminal SipA region (amino acids 1-105) mediates TTSS-1 transport and the C-terminal SipA 'actin-binding' domain (ABD; amino acids 446-685) manipulates F-actin assembly. Little is known about the central region of SipA. In a deletion analysis we found that the central SipA region harbours two distinct functional domains, F1 and F2. They are involved in SipA focus formation and host manipulation. The F1 domain (amino acids 170-271) drives SipA focus formation and domain F2 (amino acids 280-394) enhances this process by mediating SipA-SipA interactions. SipA variants lacking the F1-, the F2- or the actin binding domain were attenuated in virulence assays, namely host cell invasion and/or virulence in a mouse model for enterocolitis. Our results show that the newly identified SipA domains have distinct functions. Nevertheless, cooperation between the SipA domains F1, F2 and ABD is required to promote Salmonella virulence.

Acute Enterocolitis Incidence in Patients with Hematological Malignancies Receiving Myelotoxic Therapy Requiring Hematopoietic Stem Cell Support - Palifermin Experience.

Background: Chemotherapeutic agents can cause severe oral and gastrointestinal mucositis, for which there is currently no treatment. Previous research demonstrates that palifermin - keratinocyte growth factor - is potentially antimucotoxic, reducing the duration and severity of oral mucositis after intense chemotherapy in hematological cancers. The primary aim of this study was to determine palifermin effectiveness in ameliorating chemotherapy-induced diarrhoea and oral mucositis incidence. Palifermin adverse events were also assessed.Methods: Retrospective observational study involving patients with hematological malignancies undergoing autologous hematopoietic stem-cell transplantation after myelotoxic therapy. All the patients received antibiotic, antifungal, and antiviral prophylaxis. Patients being treated with palifermin to decrease the incidence and duration of severe oral mucositis (Palifermin Group) were compared to a control group of patients who did not receive palifermin (Control Group). Palifermin was administered during 3 consecutive days, before and after myelotoxic therapy in a 60 μg/Kg daily intravenous dose.Results: Twenty-four patients were included, 8 in Palifermin Group and 16 in Control Group. Baseline malignancies were Hodgkin and non Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. All patients underwent autologous hematopoietic stem-cell transplantation after the following conditioning regimes: BEAM, BuCy, and Mel200 respectively. In Palifermin Group, 62.5% were male, mean age 47.6±13.0 years, mean disease duration of 22.3±10.1 months (N=8). In Control Group 56.3% were male, mean age 45.8±12.1 years (N=16). Mean performance status (Karnofsky Index) was 80±14.1% and 71.3±15.1%, in each group, respectively. No statistically significant differences between Palifermin and Control Groups were found regarding the degree of diarrhoea, although in the Palifermin Group the majority of patients presented a grade 2 (N=3) and in the Control Group a grade 3 (N=6). In the Palifermin Group there was a tendency for a lower incidence of hypoalbuminemia [12.5% (Palifermin Group) vs. 50% (Control Group)], which corresponded to a significant lower difference in the needs for receiving parenteral nutrition (P=0.011). Nevertheless, these findings were not translated in less febrile episodes or less iv antibiotic therapy days. There were no significant differences between the two groups regarding the degree of oral mucositis, the number of days of analgesic opioids use, and the number of hospitalization days, most probably due to the small sample considered. The most common adverse events in the Palifermin Group were reversible erythema and edema of the face and upper trunk that have occurred only in 3 patients. Weight increase was mild and similar in both groups of patients [Median weight increase±SD: 1,0±1,7 Kg (Palifermin Group) vs 2,0±2,5 Kg (Control group)].Conclusion: Gastrointestinal and oral mucositis are common consequences of cancer therapy with a direct and significant impact on the quality of life and care costs, also affecting patient's survival. Our exploratory study shows that palifermin treatment is well tolerated, potentially reducing diarrhoea and the incidence of hypoalbuminemia, and significantly reducing the needs for parenteral nutrition. However further studies with an increased number of patients will be necessary to provide more evidence concerning palifermin efficacy in the management of these cancer therapy's debilitating side-effects.

Malabsorption Following a Brief Fast

Purpose: Diarrheal diseases are considered an important inducers of malnutrition because they affect nutrition through a number of mechanisms; (1) reduced food intake, (2) altered digestion and absorption, (3) impaired utilization of nutrients, (4) other metabolic alterations. During the initial treatment for acute diarrhea, patients are fasted for 24 to 72 hours to provide rest for the gastrointestinal tract. A routine progressive diet, beginning with a clear-liquid diet, is a frequent diet order. However, there are no scientific data to support the use of clear-liquid diets following a brief fast. We investigated malabsorption in patients with acute infectious entero-colitis who were fasted for a few days. Methods: Studies were performed in 22 patients (mean age 38 years, male/female = 13/9). Their diseases diagnosed were acute entero-colitis in 16 patients, colonic diverticulitis in 5, and osteoarthritis in 1. Patients are fasted during the initial treatment. The mean duration of fasting was 2.7 days (1–6). Diets began with mechanical soft diets in 18 patients, full-liquid diets in 3, solid foods in 1 (osteoarthritis). They all were asked to inflate a breath-collecting bag before taking breakfast, lunch, and dinner. Breath hydrogen concentrations were measured by using breath analyzer and compared to the fasting values. Results: Breath hydrogen concentrations before meals varied from 0 to 12ppm. An increase in breath hydrogen concentration after the beginning of serving meals was found in 20 of 22 patients (91%), with a mean value of 17.4ppm (1–53). Ten patients (46%) had an increase of more than 10ppm, 24 to 36 hours after meals. No abdominal symptom was developed despite of a frequent increase in breath hydrogen concentration. Although diets progressed gradually to a common solid foods as tolerated, breath hydrogen concentrations were decreased to the baseline a several days after serving meals. There were no significant differences among three kinds of diets. Conclusions: Malabsorption following a brief fast was detected more frequently than expected in the present study. Apart from the undesirable metabolic effects of even a brief fast, withholding oral intake may alter intestinal absorption.

Levels of Serum Zinc in Children With Enterocolitis and Chronic Malabsorption Syndrome

Background: Serum zinc concentration is the most widely used marker of zinc status. Methods: We used a spectrophotometric method with chromogen 4-(2-pyridylazo) resorcinol sodium salt to measure serum zinc concentrations. Results: Zinc level in serum was measured in children with acute enterocolitis (AE)— 12.87±2.42 μmol/L, chronic malabsorption syndrome (MS)—8.59±2.30 μmol/L, and control groups of healthy children—18.90 ± 5.75 μmol/L. The zinc levels in children with AE and MS were significantly lower compared to those in healthy controls. Conclusion: Serum zinc is a widely used clinical and laboratory indicator for assessment of low levels of zinc and zinc deficiency. With its good analytical parameters and accuracy, the applied spectophotometric method for measurement of serum zinc could be used for diagnosing of zinc deficiency. In the present study, it is applied for the first time in children with AE and MS.

Acute enterocolitis following partial gastrectomy.

Acute enterocolitis following partial gastrectomy.

Efficacy of Saccharomyces boulardii for treatment of horses with acute enterocolitis

To evaluate the viability of Saccharomyces boulardii after PO administration in clinically normal horses and its efficacy as a treatment for horses with acute enterocolitis. Prospective study. 5 clinically normal horses and 14 horses with acute enterocolitis. Feces were collected from 5 clinically normal horses and submitted for microbial culture for 2 days prior to administration of a lyophilized form of S. boulardii (25 or 50 g, PO, q 12 h) for 10 days. Feces were collected for microbial culture 5 and 10 days after treament initiation and 10 days after treatment was discontinued. Fourteen horses with acute enterocolitis were randomly allocated to receive a placebo or S. boulardii (25 g), PO, every 12 hours for 14 days. S. boulardii was not detected in feces of clinically normal horses. After administration, yeast survived within the gastroinestinal tract but did not permanently colonize it. In horses with acute enterocolitis, the severity and duration of gastrointestinal tract disease during hospitalization were significantly decreased in horses receiving S. boulardii, compared with horses receiving the placebo. Administration of S. boulardii may help decrease the severity and duration of clinical signs in horses with acute enterocolitis.

Serum cytokines in differentiating between viral and bacterial enterocolitis

It is difficult to distinguish clinically between bacterial and viral causes of enterocolitis. The aim of the study was to investigate if serum cytokines can distinguish bacterial from viral enterocolitis. We prospectively enrolled 147 paediatric in-patients with acute enterocolitis. Blood was taken for leucocyte count, CRP, ESR, IL-6, IL-8, IFN-alpha and TNF-alpha on the day of admission. A pathogen was identified in 115 of the 147 children, 72 of whom had a bacterial pathogen (bacterial group) and 43 rotavirus (viral group). Mean values of the serum markers IL-6, IL-8 and CRP were significantly higher in the bacterial group. Receiver-operating characteristic curves demonstrated that a cut-off of 15 pg/ml for IL-6 had a sensitivity of 0.75 and a specificity of 0.91 for bacterial diarrhoea. Comparable values for CRP at a cut-off of 13 mg/L demonstrated a sensitivity of 0.54 and a specificity of 0.72. Values for IL-8 at a cut-off of 80 pg/ml had a sensitivity of 0.46 and a specificity of 0.71. Despite the small sample size, our data suggest that serum IL-6, IL-8 and CRP are significantly elevated in children with bacterial enterocolitis. IL-6 has a higher sensitivity, specificity and positive predictive value than IL-8 and CRP. Determination of serum cytokines might be a useful way of differentiating viral from bacterial gastro-enteritis.

Intestinal epithelial antigen induces mucosal CD8 T cell tolerance, activation, and inflammatory response.

Intestinal autoimmune diseases are thought to be associated with a breakdown in tolerance, leading to mucosal lymphocyte activation perhaps as a result of encounter with bacterium-derived Ag. To study mucosal CD8(+) T cell activation, tolerance, and polarization of autoimmune reactivity to self-Ag, we developed a novel (Fabpl(4x at -132)-OVA) transgenic mouse model expressing a truncated form of OVA in intestinal epithelia of the terminal ileum and colon. We found that OVA-specific CD8(+) T cells were partially tolerant to intestinal epithelium-derived OVA, because oral infection with Listeria monocytogenes-encoding OVA did not elicit an endogenous OVA-specific MHC class I tetramer(+)CD8(+) T cell response and IFN-gamma-, IL-4-, and IL-5-secreting T cells were decreased in the Peyer's patches, mesenteric lymph nodes, and intestinal mucosa of transgenic mice. Adoptive transfer of OVA-specific CD8(+) (OT-I) T cells resulted in their preferential expansion in the Peyer's patches and mesenteric lymph nodes and subsequently in the epithelia and lamina propria but failed to cause mucosal inflammation. Thus, CFSE-labeled OT-I cells greatly proliferated in these tissues by 5 days posttransfer. Strikingly, OT-I cell-transferred Fabpl(4x at -132)-OVA transgenic mice underwent a transient weight loss and developed a CD8(+) T cell-mediated acute enterocolitis 5 days after oral L. monocytogenes-encoding OVA infection. These findings indicate that intestinal epithelium-derived "self-Ag" gains access to the mucosal immune system, leading to Ag-specific T cell activation and clonal deletion. However, when Ag is presented in the context of bacterial infection, the associated inflammatory signals drive Ag-specific CD8(+) T cells to mediate intestinal immunopathology.

Campylobacter infection in 682 bulgarian patients with acute enterocolitis, inflammatory bowel disease, and other chronic intestinal diseases

The aim of the study was to assess Campylobacter infections in 309 patients with acute enterocolitis, 272 patients with relapses of chronic enterocolitis, 70 patients with inflammatory bowel disease (involving Crohn's disease and ulcerative colitis) and 31 patients with other chronic intestinal illnesses. Isolation and identification were performed conventionally. Limited agar dilution method was used for susceptibility testing of the strains. Campylobacter species were isolated in patients with acute enterocolitis (7.8%), chronic enterocolitis (6.2%), Crohn's disease (6.2%), ulcerative colitis (3.7%), and irritable bowel syndrome (8.3%). Hippurate-positive Campylobacter jejuni isolates accounted for 62.2% of Campylobacter strains. One tetracycline resistant Campylobacter upsaliensis isolate was detected from a girl with acute enterocolitis. Resistance rates to erythromycin (31.1%) and clarithromycin (22.2%) were high, whereas those to amoxicillin/clavulanate (4.4%), ampicillin/sulbactam (13.3%), tetracycline (24.4%) and ciprofloxacin (22.2%) were relatively low. Resistance to erythromycin and either tetracycline or ciprofloxacin was detected in 8.9% and 6.7%. The involvement of Campylobacter infection in relapses of chronic intestinal disorders and the susceptibility patterns of the strains strongly emphasize the role of Campylobacter as a cause of infection in this group of patients.

Active Crohn's Disease Patients Show a Distinctive Expansion of Circulating Memory CD4+CD45RO+CD28nullT Cells

In a previous study we found an expansion of circulating memory (CD45RO(+)) CD4(+) T cells in patients with Crohn's disease (CD). The aim of this work was to investigate the phenotypic and functional characteristics of this T-cell subset in CD. We analyzed in peripheral blood CD4(+)CD45RO(+) T cells from CD patients the expression of surface markers associated to immune activation, costimulation, and apoptosis. In sorted CD4(+)CD45RO(+) T cells apoptosis was quantified by fluorescent annexin V binding. Healthy subjects and patients with ulcerative colitis and acute bacterial enterocolitis served as control groups. An increased percentage of memory CD4(+)CD45RO(+) T cells lacking the expression of costimulatory receptor CD28 was detected in patients with active CD when compared to the other groups evaluated. This expanded CD4(+)CD45RO(+)CD28(null) T-cell subset expressed mostly the effector-cell marker CD57(+). Both CD28 downregulation and CD57 expression correlated to CDAI and surrogate markers of disease activity. These phenotypic changes observed on CD4(+)CD45RO(+) T cells from active CD returned to values similar to healthy controls after clinical remission. Moreover, this memory CD28(null) T-cell subset might express more intracytoplasmic TNF and IFN-gamma than their CD28(+) counterpart. Significantly lower frequencies of memory CD4(+)CD45RO(+) T cells expressing CD95 apoptosis receptor were found in patients with active CD. Moreover, sorted CD4(+)CD45RO(+)and CD4(+)CD45RO(+) CD28(null) T cells from patients with active CD exhibited a lower apoptotic rate than that found in healthy controls and inactive CD patients. According to our data, circulating T lymphocytes from active CD patients show distinctive phenotypic and functional changes, characterized by an expansion of memory CD4(+)CD45RO(+)CD28(null) T cells expressing effector-associated cell surface molecules and displaying enhanced resistance to apoptosis.

18F-FDG positron emission tomography in the early diagnosis of enterocolitis: preliminary results

Collagenous and eosinophilic colitis are rare diseases characterised by chronic watery diarrhoea. Radiographic evaluation of the gastrointestinal tract and colonoscopy are usually non-diagnostic since as many as one-third of patients will have minor abnormalities. To date a few investigators have reported increased fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography (PET) in patients with acute enterocolitis, but there have been no reports on the use of (18)F-FDG PET for the diagnosis of collagenous or eosinophilic colitis in an early clinical stage. The aim of this preliminary study was to evaluate the usefulness of (18)F-FDG PET in the early diagnosis of patients with colitis. We investigated five women (mean age 61.2+/-12.1 years) who had been diagnosed as having colitis in an early clinical stage. In all but one of the patients, the diagnosis of colitis was based on biopsy. Magnetic resonance colonography, ultrasonography and colonoscopy were performed in all but one of the patients. Two women were identified as having collagenous colitis in an early clinical stage. Another two patients had eosinophilic colitis. The morphological imaging methods, magnetic resonance colonography and ultrasonography, yielded no suspicious findings, and the results of colonoscopy similarly showed no abnormalities. One patient had colitis due to bacterial infection. In all patients (18)F-FDG PET showed a pathological increase in tracer uptake in the large bowel, suggestive of colitis. In four of the five patients, colitis was confirmed by histology, and in one, by bacterial analysis. (18)F-FDG PET was able to detect colitis in an early clinical stage, when morphological imaging methods and colonoscopy were non-diagnostic. The early performance of (18)F-FDG PET imaging in patients with possible colitis is encouraging.

Pediatric Salmonella enterocolitis in a teaching hospital in Taitung: A four-year analysis.

In order to understand the childhood Salmonella enterocolitis in Taitung, we retrospectively collected the patients with the diagnosis of acute enterocolitis who were admitted to the pediatric wards of Taitung branch of Mackay Memorial Hospital from January 1, 1995 to December 31, 1998. Salmonella enterocolitis accounted for 16.8% of the total cases of acute enterocolitis. The mean age of the patients was 14.6 +/- 14.1 months old. Seventy-nine patients were male and 78 patients were female. Eighty-two patients lived in the urban area and 75 patients lived in the suburbs. The mean duration from onset of illness to admission was 2.6 +/- 1.9 days. The mean duration of hospitalization was 6.6 +/- 4.8 days. The peak incidence was in August and September. The most common clinical manifestations were fever (74.5%) and blood stool (46.5%). In 157 patients, Salmonella serogroup B was isolated from stool in 115 patients. The rate of bacteremia was 4.5%. Serogroup D accounted for 28.6% of the bacteremia. Two patients developed meningitis and one patient had osteomyelitis. Of 88 patients examined for rotavirus, 12 had positive results. There was neither bowel perforation nor mortality recorded in our study.

Equine monocytic Ehrlichiosis (Potomac horse fever) in horses in Uruguay and southern Brazil.

A disease named locally as churrío or churrido equino (i.e., equine scours) has occurred for at least 100 years in Uruguay and southern Brazil in farms along both shores of the Merín lake. This report describes cases of churrido equino and provides serologic, pathologic, and DNA-based evidence indicating that the disease is in fact equine monocytic ehrlichiosis (Potomac horse fever). Results of an epidemiological investigation conducted on an endemic farm are also presented. Clinical signs in 12 horses were fever, depression, diarrhea, dehydration, and sometimes colic and distal hind limb edema. Postmortem findings of 3 horses were of acute enterocolitis. Inclusion bodies containing ehrlichial organisms were found in the cytoplasm of macrophages of the large colon of 1 horse. Eleven of the 12 horses were serologically positive to Ehrlichia risticii (indirect fluorescent antibody assay) and, of 3 paired samples, 2 showed seroconversion. Ehrlichia risticii DNA was identified by a nested polymerase chain reaction in peripheral blood of an affected horse. A healthy horse inoculated with peripheral blood from an affected horse developed the disease and antibodies to E. risticii. The disease had a peak incidence in March (summer) and was statistically associated with a marshy ecosystem near the Merín lake, where large numbers of Pomacea spp. (Ampullariidae) snails were found. Incidence density was almost 8 times higher in nonnative horses than in native horses. It was concluded that the previous diarrheic disease of horses known in Uruguay and southern Brazil as churrido equino is equine monocytic ehrlichiosis.

Pathogenesis of enteric Campylobacter infection.

Campylobacter jejuni and related species are important human pathogens, causing acute human enterocolitis, and they are the most common cause of food-borne diarrhoea in many industrialized countries. Previous infection with certain strains of C. jejuni is also linked with the development of the neurological disorder Guillain-Barre syndrome (GBS). Despite its importance as a human pathogen, relatively little is understood of the mechanisms of C. jejuni-associated disease. The recent release of the complete genome sequence of C. jejuni strain NCTC 11168, together with new strategies for random and directed mutagenesis, have allowed a better insight into some of the genetic determinants of C. jejuni virulence. In this review current knowledge on the pathogenesis of C. jejuni infection is summarized, and possible directions of future research indicated.

Crohn's disease in Japan: diagnostic criteria and epidemiology.

New diagnostic criteria for Crohn's disease and a review of Japanese epidemiologic studies are presented. New diagnostic criteria for Crohn's disease were established by the Research Committee of Inflammatory Bowel Disease, set up by the Japanese Ministry of Health and Welfare. For a definite diagnosis one of the following three conditions is required: 1) longitudinal ulcer or luminal deformity induced by longitudinal ulcer or cobblestone pattern, 2) intestinal small aphthous ulcerations arranged in a longitudinal fashion for at least three months plus noncaseating granulomas, and 3) multiple small aphthous ulcerations in both the upper and lower digestive tract not necessarily with longitudinal arrangement, for at least three months, plus noncaseating granulomas. Moreover, ulcerative colitis, ischemic enterocolitis, and acute infectious enterocolitis should be excluded. Data from the Japanese Ministry of Health and Welfare, in addition to data collected from two study groups, these being the two largest studies in Japan, are reviewed with regard to epidemiology. The number of patients with Crohn's disease has increased remarkably. The prevalence and the annual incidence of patients with Crohn's disease in Japan were estimated to be approximately 2.9 and 0.6 per 10(5) population in 1986, respectively, and 13.5 and 1.2 per 10(5) population in 1998. Characteristic features of Crohn's disease in Japan are that the male-female ratio exceeds 2, and that there is no second peak of incidence in the age group of 55 to 65 years. Clinically, Crohn's disease with only multiple small aphthous ulcerations, which is the earliest stage of the disease that is diagnosable, was found in 5 percent of patients.

A Campylobacter Colifoodborne Outbreak in Belgium

In May 1995, the Scientific Institute of Public Health was informed of an outbreak of gastrointestinal illness in a congregational school in the Brussels area. The field investigation identified 24 cases with mild to severe gastrointestinal and general symptoms of acute bacterial enterocolitis. Campylobacter coli was detected in the stools of 5 patients. A retrospective cohort study suggested that a mixed salad (containing ham and feta cheese) was the probable source of infection, but the route of contamination remained unknown. The rapid investigation of such episodes of collective foodbome infections is essential for the implementation of adequate control measures.

Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-α in ulcerative colitis

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a newly described neutrophil lipocalin that may bind the proinflammatory bacterial tripeptide N-formylmethionyl-leucyl-phenylalanine. In situ hybridization and immunohistochemical studies have shown a strong NGAL expression in colonocytes and neutrophils in ulcerative colitis (UC). Because NGAL is highly protease resistant, it should be ideal for in vivo fecal and dialysate studies. Our aim was to investigate the potential of NGAL as a disease activity marker in UC and to compare it with IL-8 and TNF-α. METHODS: Twenty-three patients with UC, 14 with Crohn’s disease (CD), 19 patients with acute infectious enterocolitis, and 20 healthy controls were included. The disease activity of UC and CD was scored semiquantitatively. Concentrations of NGAL, IL-8, and TNF-α were determined in rectal dialysis fluid, feces, and serum using sandwich enzyme-linked immunosorbent assays. The total protein concentration in feces and dialysate fluid was measured, and the amount of markers was expressed as ng/mg protein. RESULTS: In healthy controls and non-IBD (irritable bowel disease) colitis, the median values for NGAL in feces were 183 ng/mg protein and 546 ng/mg protein ( p < 0.01), respectively. When separating UC into clinical activity groups (remission, mild/moderate, and severe disease activity) the corresponding values of NGAL were 442 ng/mg ( p > 0.05), 605 ng/mg ( p < 0.02), and 3646 ng/mg ( p < 0.001, compared with controls), respectively, and in quiescent colonic CD 368 ng/mg ( p > 0.05) and in active stages 751 ng/mg ( p < 0.01). NGAL levels in dialysis fluid listed in the same order were: 11 ng/mg for controls, 71 ng/mg ( p > 0.05) for non-IBD colitis, 100 ng/mg ( p < 0.02), 179 ng/mg ( p < 0.01), and 2053 ng/mg ( p < 0.001) for UC, and 14 ng/mg ( p > 0.05) and 121 ng/mg ( p < 0.02) for CD, respectively. Serum NGAL concentrations did not differ between UC and CD in quiescent versus active stages. A significant increase of NGAL in both feces and dialysate with increasing disease activity of UC was found ( p = 0.02 and p = 0.003, respectively). CONCLUSIONS: The NGAL content in rectal dialysate and particularly in feces seems to be a reliable marker for severe disease activity in UC, whereas serum NGAL concentrations do not reflect disease activity.

Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-alpha in ulcerative colitis.

Neutrophil gelatinase-associated lipocalin (NGAL) is a newly described neutrophil lipocalin that may bind the proinflammatory bacterial tripeptide N-formylmethionyl-leucyl-phenylalanine. In situ hybridization and immunohistochemical studies have shown a strong NGAL expression in colonocytes and neutrophils in ulcerative colitis (UC). Because NGAL is highly protease resistant, it should be ideal for in vivo fecal and dialysate studies. Our aim was to investigate the potential of NGAL as a disease activity marker in UC and to compare it with IL-8 and TNF-alpha. Twenty-three patients with UC, 14 with Crohn's disease (CD), 19 patients with acute infectious enterocolitis, and 20 healthy controls were included. The disease activity of UC and CD was scored semiquantitatively. Concentrations of NGAL, IL-8, and TNF-alpha were determined in rectal dialysis fluid, feces, and serum using sandwich enzyme-linked immunosorbent assays. The total protein concentration in feces and dialysate fluid was measured, and the amount of markers was expressed as ng/mg protein. In healthy controls and non-IBD (irritable bowel disease) colitis, the median values for NGAL in feces were 183 ng/mg protein and 546 ng/mg protein (p < 0.01), respectively. When separating UC into clinical activity groups (remission, mild/moderate, and severe disease activity) the corresponding values of NGAL were 442 ng/mg (p > 0.05), 605 ng/mg (p < 0.02), and 3646 ng/mg (p < 0.001, compared with controls), respectively, and in quiescent colonic CD 368 ng/mg (p > 0.05) and in active stages 751 ng/mg (p < 0.01). NGAL levels in dialysis fluid listed in the same order were: 11 ng/mg for controls, 71 ng/mg (p > 0.05) for non-IBD colitis, 100 ng/mg (p < 0.02), 179 ng/mg (p < 0.01), and 2053 ng/mg (p < 0.001) for UC, and 14 ng/mg (p > 0.05) and 121 ng/mg (p < 0.02) for CD, respectively. Serum NGAL concentrations did not differ between UC and CD in quiescent versus active stages. A significant increase of NGAL in both feces and dialysate with increasing disease activity of UC was found (p = 0.02 and p = 0.003, respectively). The NGAL content in rectal dialysate and particularly in feces seems to be a reliable marker for severe disease activity in UC, whereas serum NGAL concentrations do not reflect disease activity.