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PubMed1998

Taurine can ameliorate inflammatory bowel disease in rats.

We previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. To induce IBD, rats were given ethanolic TNBS intracolonically. The rats then received 500 mg/kg/day of taurine per orally. The rats were sacrificed one week after IBD induction. Ulceration and inflammation of the distal colon with formation of granuloma in the vehicle-treated IBD rats after two days of administration of TNBS were observed. Treatment with 0.5 g/kg of taurine by the oral route ameliorated colonic damage and decreased the incidence of diarrhea and adhesions. Colon weight (an index of tissue edema) was markedly increased in the IBD rats after administration of TNBS, but was significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased compared with that of the control. The taurine-treated animals showed reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased basal and formyl-methionyl leucyl phenylalanine (FMLP) stimulated reactive oxygen generation in colonic tissue of the IBD rat compared with vehicle treatment after one week. These results suggest that administration of taurine reduced the inflammatory parameters in this rat model of IBD by increasing the defenses against oxidative insult.

Animals↗
PubMed1996

Expression of protooncogene-encoded mRNA by colonic epithelial cells in inflammatory bowel disease.

Protooncogenes are cell cycle-related genes that are involved in cell growth of proliferation. Alterations in the level of expression of these genes, or expression of aberrant gene productions, have been observed in tumors and precancerous conditions. To determine if expression of these genes is altered in patients with inflammatory bowel disease (IBD) --who are at risk for development of colon cancer--we assayed transcripts of 15 protooncogenes in colonic epithelial cells of IBD patients and controls. Nine of these genes (H-ras, c-myc, c-fos, c-jun, junB, N-myc, c-abl, c-yes, and p53) were expressed in epithelial cells, whereas two (RB1 and N-ras) were not. expression of four other genes (c-src, K-ras, c-raf, and c-myb) was observed, but the intensity of these bands was too low for densitometric analysis. The steady-state levels of transcripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-jun, junB, and N-myc) were lower in epithelial cells from involved or uninvolved IBD samples than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. The level of c-fos mRNA was two- to threefold higher in involved than in uninvolved areas of the colons of two ulcerative colitis (UC) patients, but not in one Crohn's disease (CD) patient. Message abundance of c-abl transcripts was two- to threefold lower in UC epithelial cells than in either the CD or control samples. The steady-state level of c-yes-encoded mRNA was considerably higher in IBD patients resected for colon cancer than in patients resected for active chronic IBD or in controls. The level of p53 message was constant in these samples. Increased levels of c-fos mRNA in involved UC relative to uninvolved UC may be related to the disease process. Decreased expression of c-abl transcript in UC may be a diagnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of c-yes in IBD patients with tumors compared to active chronic IBD and controls suggests that expression of this gene may be a marker for development of colon cancer in IBD.

Adolescent↗
PubMed1998

Protective effect of taurine on TNBS-induced inflammatory bowel disease in rats.

We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.

Animals↗
PubMed2006

Inflammatory bowel disease and Streptococcus bovis.

Evidence suggests a trend for a higher fecal carriage rate of Streptococcus bovis in adult patients with inflammatory bowel disease (IBD). This study defines the fecal carriage rate of S. bovis among children with IBD compared to controls. Subjects with IBD were prospectively enrolled from the patient population of a pediatric gastroenterology practice. Stool samples from IBD patients as well as controls were analyzed within 24 hr for the presence of S. bovis. The study enrolled 47 patients with IBD and 34 controls. Among the 47 IBD patients, 3 had a positive stool culture for S. bovis (6%) and 1 had an equivocal result between S. bovis and S. salivarius. Including this equivocal result, 8.5% of IBD patients were S. bovis carriers. Among the 34 controls, 3 (9%) were found to be fecal carriers of S. bovis. Assuming that the equivocal stool was indeed S. bovis, these groups are not statistically different as determined by Fisher's exact test (P=0.6). We conclude that the fecal carriage rate of S. bovis is not increased among pediatric patients with IBD compared with controls.

Adolescent↗
PubMed2007

Lamina propria and circulating interleukin-8 in newly and previously diagnosed pediatric inflammatory bowel disease patients.

Dysregulation of interleukin-8 (IL-8) production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies, which evaluate adult patients with long-standing or steroid-modulated disease, have reported conflicting results regarding the role of IL-8 in IBD pathogenesis. The present study evaluates IL-8 in colonic organ cultures and sera of newly and previously diagnosed pediatric IBD patients with various degrees of histopathologic activity. Colon and terminal ileum biopsies were obtained from 26 patients with Crohn's disease, 12 with ulcerative colitis, 4 with indeterminate colitis, and 12 age-matched normal controls. IBD patients were additionally characterized as newly or previously diagnosed. Supernatants from organ-cultured lamina propria biopsies and sera were evaluated by ELISA for IL-8 protein. IL-8 increased with degree of histologic inflammation regardless of diagnosis (no pathologic diagnosis, 62.6 ng/ml, interquartile range [IQR] 30.4-94.6 ng/ml; mild, 92.0 ng/ml, IQR 21.9-170.0 ng/ml; moderate, 676.2 ng/ml, IQR 46.4-2967.7 ng/ml; severe, 585.6 ng/ml, IQR 149.7-1602.2 ng/ml; P < 0.01). Lamina propria IL-8 was significantly elevated in moderately and severely inflamed tissue segments (603.26 ng/ml; IQR, 72.15-2240.4 ng/ml) compared to noninflamed and mildly inflamed segments (67.70 ng/ml; IQR, 30.38-124.1 ng/ml; P = 0.0009). There was no significant trend in IL-8 concentration when compared by clinical diagnosis. No significant difference was found in IL-8 concentrations in organ cultures from newly diagnosed patients versus those from previously diagnosed patients. There was no significant correlation between serum IL-8 concentration and organ culture IL-8 concentration. We conclude that higher concentrations of IL-8 are found in more histologically inflamed tissue segments from pediatric IBD patients. IL-8 does not appear to be associated with clinical IBD subtype. IL-8 appears to be an integral part of both early and established mucosal inflammation in pediatric IBD patients. These findings suggest that IL-8-specific therapies may universally modify inflammatory activity in IBD patients.

Adolescent↗
PubMed2001

Inflammatory Bowel Disease During Pregnancy.

The management of both male and female patients with inflammatory bowel disease (IBD) who wish to have a baby is challenging. For women, the most important factor to bear in mind is that the outcome of pregnancy is largely influenced by disease activity at the time of conception. Women with quiescent disease are likely to have an uncomplicated pregnancy with the delivery of a healthy baby, whereas women with active disease are more likely to have complications such as spontaneous abortions, miscarriages, stillbirths, and exacerbation of the disease. This is more true of patients with Crohn's disease than of patients with ulcerative colitis. Although the safety of medications used during pregnancy is an important issue, the impact of the medications used to treat IBD is less important in comparison to disease activity itself. 5-Aminosalicylic acid (5-ASA) products appear to be safe during pregnancy; corticosteroids are probably safe; 6-mercaptopurine and azathioprine should be used with caution; and methotrexate is contraindicated. There are inadequate data on the use of infliximab during pregnancy. In regard to men with IBD, the disease itself does not seem to have any negative impact on fertility. However, there is controversy about the effects of using 6-mercaptopurine and azathioprine prior to and during fertilization. In view of possible adverse pregnancy outcomes, it would be prudent to withhold 6-mercaptopurine and azathioprine therapy in men with IBD for 3 months prior to conception, when feasible. Most IBD medications should be continued before, during, and after pregnancy, with careful attention to the known cautions and exceptions. If IBD in a pregnant patient is in remission, the prognosis for pregnancy is the same as if she did not have IBD. Active disease should therefore be treated aggressively and remission accomplished before pregnancy is attempted. Similarly, a woman who unexpectedly becomes pregnant while her IBD is active should be treated aggressively, as remission remains the greatest investment for a favorable pregnancy outcome.

Journal Article↗
PubMed1994

Mucosal biopsy diagnosis of colitis: acute self-limited colitis and idiopathic inflammatory bowel disease.

BACKGROUND/AIMS: Rectal biopsy specimen changes distinguish acute self-limited colitis (ASLC) from idiopathic inflammatory bowel disease (IBD). This study aimed to determine whether these histological criteria are also valid for acute-onset IBD. METHODS: Blind analysis of colorectal biopsy specimens from 52 patients with ASLC, 51 patients with acute-onset (< 3 months) IBD, and 30 patients with chronic IBD was performed. RESULTS: Histological features of ASLC are normal crypt architecture and acute lamina propria inflammation, but mixed acute and chronic inflammation can be found. Histological features of IBD are diffusely abnormal crypt architecture, crypt atrophy, mixed lamina propria inflammation, basal plasmacytosis, basal lymphoid aggregates, basal lymphoid hyperplasia, isolated giant cells, epithelioid granulomas, goblet cell mucus depletion, and reactive epithelial hyperplasia. Changes of chronic IBD were present in biopsy specimens as early as 7 days after the onset of symptoms. CONCLUSIONS: Rectal biopsy specimens are useful in distinguishing ASLC from acute-onset IBD even if the biopsy specimens are not obtained during the first 4 days of the illness. There were no significant differences in histology between acute-onset and chronic IBD.

Acute Disease↗
PubMed1995

Impaired response of activated mononuclear phagocytes to interleukin 4 in inflammatory bowel disease.

BACKGROUND/AIMS: In inflammatory bowel disease (IBD), peripheral monocytes and intestinal macrophages show an increased state of priming and activation. The aim of this study was to test the hypothesis that the response of IBD mononuclear phagocytes to the contrainflammatory cytokine interleukin (IL) 4 may be altered. METHODS: The in vitro secretion of proinflammatory cytokines (IL-1 beta, tumor necrosis factor alpha [TNF-alpha], and IL-1-receptor antagonist [IL-1ra]) by peripheral monocytes and by intestinal lamina propria mononuclear cells (LPMNCs) was assessed by enzyme-linked immunosorbent assay. In parallel, superoxide anion release, macrophage mannose receptor, and IL-4 receptor expression were investigated. RESULTS: IBD peripheral monocytes and intestinal LPMNCs in vitro secrete increased amounts of proinflammatory cytokines (IL-1 beta and TNF-alpha) with decreased IL-1ra/IL-1 beta ratios. IL-4 down-regulates proinflammatory cytokine (IL-1 beta and TNF-alpha) and superoxide anion secretion in a dose-dependent manner. In contrast to normal and disease-specific controls, IBD peripheral monocytes and IBD intestinal LPMNCs show a diminished responsiveness to the inhibitory effect of IL-4. The IL-1ra/IL-1 beta ratios in normal monocytes are increased by IL-4, whereas in IBD monocytes low IL-1ra/IL-1 beta ratios persist after IL-4 treatment. IL-4-induced expression of macrophage mannose receptor, which is a molecule pivotal to macrophage-mediated host defense, again appeared to be impaired in IBD monocytes. CONCLUSIONS: IL-4-mediated regulation of mononuclear phagocyte effector functions is disturbed in IBD.

Cellular Senescence↗
PubMed2005

Surgical outcome in patients with primary sclerosing cholangitis undergoing ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: The outcome of restorative proctocolectomy in the setting of chronic ulcerative colitis complicated by primary sclerosing cholangitis (PSC) is not clear. The purpose of this study was to determine the surgical outcome, risk of dysplasia/cancer, morbidity/mortality, long-term results, and functional and quality of life results in patients with inflammatory bowel disease (IBD) and PSC who underwent restorative proctocolectomy with ileal pouch-anal anastomosis and compare them in a case-matched study. METHODS: Patients with PSC-associated IBD undergoing restorative proctocolectomy between 1983 and 2002 were included in the study. This study group was matched for age, gender, diagnosis, duration of disease, anastomosis technique, and proximal diversion to a cohort of IBD patients with no associated PSC who underwent restorative proctocolectomy during the same period of time. Postoperative morbidity, incidence of neoplasia/cancer in the resected specimen, pouchitis, pouch failure, long-term mortality, and 5-year survival rates were compared between the groups. The functional and quality of life records were prospectively collected and compared between the groups. For each group, matched Kaplan-Meier survival analysis was also conducted comparing 5-year survival between the 2 cohorts, matching for diagnosis, duration of disease, age, gender, anastomosis type, and proximal diversion. RESULTS: Sixty-five patients with PSC and IBD underwent restorative proctocolectomy with ileal pouch-anal anastomosis during the study period. Two hundred sixty IBD patients with no associated PSC who matched with the outlined criteria comprised the control group. The follow-up period was 68 +/- 50 months for the PSC group and 102 +/- 62 months for the control group. A higher incidence of cancer (14% vs 5%, P = .02) and dysplasia in the resected specimen (40% vs 7%, P < .001), an associated increased risk of postoperative pelvic sepsis (14% vs 5%, P = .02), and higher long-term mortality (35% vs 4%, P < .001) were found in the PSC group compared with control group with no associated PSC. The majority, 13 of 23 (57%), of the deaths in the PSC group were a result of liver disease. Five-year survival for the PSC group was significantly poorer than the 5-year survival for the control group with no associated PSC. No significant differences were found in functional and quality of life results between the groups in the short- and long-term follow-up periods. CONCLUSIONS: PSC-associated IBD patients after restorative proctocolectomy have a higher risk of neoplasia/cancer in the resected specimen, postoperative pelvic sepsis, and higher long-term mortality. Functional and quality of life remains similar in IBD patients after restorative proctocolectomy with or without associated PSC in the follow-up. However, patients with IBD and PSC have a significantly poorer survival than patients with no associated PSC after restorative proctocolectomy.

Adult↗
PubMed2006

Measurement of cytokine mRNA expression in intestinal biopsies of cats with inflammatory enteropathy using quantitative real-time RT-PCR.

Inflammatory bowel disease (IBD) is a common condition in cats characterised by infiltration of inflammatory cells into the intestinal mucosa. In this study, real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to quantify cytokine messenger RNA (mRNA) expression in intestinal biopsies from cats. Biopsies were collected from seven cats with chronic diarrhoea and histologically confirmed IBD, five cats with chronic diarrhoea due to non-IBD gastrointestinal (GI) disease, and nine clinically normal cats with or without subclinical inflammatory changes in small intestine. Real-time RT-PCR was developed for quantification of mRNA encoding interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p35 and p40), IL-18, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a 'housekeeper' gene. All real-time PCR efficiencies were>90% (range 90.4-102%) with correlation coefficients >0.99 (range 0.998-1). The results of the study were analyzed on the basis of either clinical presentation or histopathological evidence of intestinal inflammation. The former analysis showed that mRNA encoding IL-10 and TGF-beta (immunoregulatory cytokines), and IL-6, IL-18, TNF-alpha and IL-12 p40 (Th1 and pro-inflammatory cytokines) was significantly higher in clinically normal cats and cats with IBD when compared to cats with other GI diseases. IL-5 mRNA was significantly higher in cats with IBD compared to clinically normal cats. IL-2 mRNA was significantly lower in cats with non-IBD GI disease than in clinically normal cats. Analysis on the basis of histopathological change revealed that cats with intestinal inflammation had significantly more transcription of genes encoding IL-6, IL-10, IL-12p40, TNF-alpha and TGF-beta than those with normal intestinal morphology. The results suggest that immune dysregulation plays a role in feline IBD and that IBD in cats has a complicated pathogenesis with both pro-inflammatory and immunoregulatory features.

Animals↗
PubMed1997

A case-control study of measles vaccination and inflammatory bowel disease. The East Dorset Gastroenterology Group.

BACKGROUND: The cause of inflammatory bowel disease (IBD) remains to be established. Evidence has linked measles infection in early childhood with the subsequent risk of developing IBD, particularly Crohn's disease. A cohort study raised the possibility that immunisation with live attenuated measles vaccine, which induces active immunity to measles infection, might also predispose to the later development of IBD, provoking concerns about the safety of the vaccine. METHOD: We report a case-control study of 140 patients with IBD (including 83 with Crohn's disease) born in or after 1968, and 280 controls matched for age, sex and general practitioner (GP) area, designed to assess the influence of measles vaccination on later development of IBD. Documentary evidence of childhood vaccination history was sought from GP and community health records. FINDINGS: Crude measles vaccination rates were 56.4% in patients with IBD and 57.1% among controls. Matched odds ratios for measles vaccination were 1.08 (95% CI 0.62-1.88) in patients with Crohn's disease, 0.84 (0.44-1.58) in patients with ulcerative colitis, and 0.97 (0.64-1.47) in all patients with IBD. INTERPRETATION: These findings provide no support for the hypothesis that measles vaccination in childhood predisposes to the later development of either IBD overall or Crohn's disease in particular.

Adult↗
PubMedDate not supplied

[Relationship between patient's subjective stress perception and the course of inflammatory bowel disease].

INTRODUCTION: Studies examining the relationship between stress secondary to adverse life events (ALE) and inflammatory bowel disease (IBD) have produced controversial data. The aim of this study was to explore the subjective perception of this relationship in IBD patients. PATIENTS AND METHODS: Seventy consecutive patients suffering from IBD (40 Crohn's disease, 30 ulcerative colitis) were assessed using a self-rating questionnaire related to demographic variables, clinical characteristics, subjective perception of the influence of ALE on the course of IBD, psychiatric background, and the HAD scale. The results of this scale were compared with a group of 25 relatives. RESULTS: Forty-two patients (60%) perceived that there was relationship between ALE and the onset of their disease, forty-nine (70%) between ALE and the increasing IBD symptoms severity, and fifty-one patients (72.9%) with disease activity. Sixteen of the patients (22.9%) had been visited by a psychiatrist during relapses of IBD. Twenty-five patients (42.4%) reached a score of 11 or higher on the depression or anxiety subscales of the HAD, indicating a probable psychological disorder. CONCLUSIONS: IBD patients perceive a strong relationship between ALE and the course of IBD. We have found a high prevalence of anxiety and depression symptoms in these patients. If this observation is confirmed with objective measurements, it will be important to consider psychiatric intervention for these patients.

Activities of Daily Living↗
PubMed2001

Acute and late radiotherapy toxicity in patients with inflammatory bowel disease.

PURPOSE: To evaluate the incidence of gastrointestinal complications in patients with inflammatory bowel disease (IBD) receiving radiotherapy (RT) and to identify possibly avoidable factors associated with these complications. METHODS AND MATERIALS: Twenty-four patients were identified and their records reviewed; all had a history of IBD before receiving RT to fields encompassing some portion of the gastrointestinal tract (Crohn's disease) or to the abdomen or pelvis (ulcerative colitis or IBD not otherwise specified). RESULTS: Five of 24 patients (21%) experienced Grade > or =3 acute gastrointestinal toxicity; all 5 received concurrent chemotherapy. Two of 24 patients (8%) experienced Grade > or =3 late gastrointestinal toxicity. There were no significant correlations between complications and IBD type, prior IBD-related surgery, use of medications for IBD, or status of IBD. CONCLUSION: Patients with IBD may have an increased risk for severe acute RT-related gastrointestinal complications that is more modest than generally perceived, because all patients who had Grade > or =3 acute complications in this study had received concurrent chemotherapy (p = 0.04). Further study is needed to assess this risk, as well as the impact of RT on these patients' future gastrointestinal morbidity.

Adolescent↗
PubMed2000

Anemia in inflammatory bowel disease - the role of recombinant human erythropoietin.

Anemia is a common problem in inflammatory bowel disease (IBD). It is related to low Karnofsky scores, loss of weight, impaired physical activity, low tolerance to the underlying disease, and a poor growth rate in children. Multiple factors can contribute to the anemia in IBD, such as iron, folic acid or B(12) deficiency, treatment with immunosuppressive drugs or sulfasalazine, hemolysis, and anemia of chronic disease. Anemia of chronic disease is characterized by impaired iron utilization, lower erythropoietin (EPO) production than needed, and a low response of bone marrow erythroid progenitor cells to EPO. In recent years, recombinant human erythropoietin (rhEPO) has been used in combination with iron for the correction of refractory anemia in IBD patients (adults or children) with good results. There is increasing evidence that rhEPO may correct refractory anemia in IBD (both ulcerative colitis (UC) and Crohn's disease (CD)). In addition, such therapy may give IBD patients the opportunity to predonate blood before surgery and to avoid blood transfusions. One must not forget to exclude or correct other causes of anemia in IBD patients before administering rhEPO. Furthermore, the enhancement of erythropoiesis by EPO makes it mandatory to administer oral or intravenous iron supplementation during therapy to meet the increased demand. rhEPO is safe in IBD patients. Further studies with larger numbers of patients are needed to optimize the therapy with rhEPO in the refractory anemia of IBD.

Journal Article↗
PubMed2005

Rectal mucosal nitric oxide in differentiation of inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND & AIMS: Differentiating patients with functional bowel disorders from those with inflammatory bowel disease (IBD) can be difficult. Rectal luminal levels of nitric oxide (NO) are greatly increased in IBD. To further evaluate this disease marker, we compared NO in patients with irritable bowel syndrome (IBS) with those found in patients with active IBD and in healthy control subjects. METHODS: Rectal NO was measured with chemiluminescence technique by using a tonometric balloon method in 28 healthy volunteers, 39 patients with IBS, 86 with IBD (Crohn's disease and ulcerative colitis), and 12 patients with collagenous colitis. In addition, NO was measured before and after a 4-week treatment period in patients with active ulcerative colitis and repeatedly during 2 weeks in healthy volunteers. RESULTS: NO was low in healthy control subjects (median, 45; 25th-75th percentile, 34-64 parts per billion [ppb]), and variations over time were small. In IBS patients NO was slightly increased (150, 53-200 ppb; P < .001), whereas patients with active IBD or collagenous colitis had greatly increased NO levels (3475, 575-8850 ppb, and 9950, 4475-19,750 ppb, respectively; P < .001). With a cutoff level of 250 ppb, NO had a sensitivity of 95% and a specificity of 91% in discriminating between active bowel inflammation and IBS. Rectal NO correlated with disease activity in IBD and collagenous colitis and decreased markedly in IBD patients responding to anti-inflammatory treatment. CONCLUSIONS: Rectal NO is a minimally invasive and rapid tool for discriminating between active bowel inflammation and IBS and a possibly useful add-on for monitoring patients with IBD.

Adolescent↗
PubMed1998

IL-10 synergizes with IL-4 and IL-13 in inhibiting lysosomal enzyme secretion by human monocytes and lamina propria mononuclear cells from patients with inflammatory bowel disease.

Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated with enhanced monocytic lysosomal enzyme release. In this study, peripheral monocytes and lamina propria mononuclear cells (LPMNC) were isolated from IBD patients and normal controls. Cells were stimulated with lipopolysaccharide after treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using the corresponding p-nitrophenyl glycosides as substrates. Molecular forms of cathepsin D were examined to describe the mode of enzyme release. IL-10 and IL-4 strongly down-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte response was not found with combinations of IL-13 and IL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretion compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressed enzyme release by these cells. Both the precursor and mature forms of cathepsin D were elevated in IBD patients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both the precursor and mature form of cathepsin D. Our results favor the potent clinical utility of combined treatment, thus improving chances of developing effective treatments for human IBD.

Adult↗
PubMed2003

Extraintestinal symptoms in irritable bowel syndrome and inflammatory bowel diseases: nature, severity, and relationship to gastrointestinal symptoms.

Patients suffering from the irritable bowel syndrome (IBS) tend to have extraintestinal symptoms. The purposes of this study were to compare the nature and severity of these symptoms in IBS patients in relation to patients with inflammatory bowel disease (IBD) and to nonpatients and to clarify the relationship between intestinal and extraintestinal symptoms. A consecutive group of male patients and a control group of age-matched male subjects were studied. Symptoms were graded for severity using a validated, self-administered inventory. There were 53 IBS patients, 55 IBD patients (32 Crohn's disease), and 56 controls. IBS patients scored significantly higher than IBD patients on constipation, dyspepsia, and reflux scales. Musculoskeletal symptoms, neurasthenia, and sleep scores were similar in IBS and IBD patients, and both groups scored significantly higher than the controls. The scores of urinary, thoracic, and oral symptoms were similar in IBD patients and in controls. However, IBS patients scored significantly higher than both groups on all these scales. Reflux symptoms were the most powerful predictors of extraintestinal symptoms, both in IBS and in IBD. Diarrhea was predictive of extraintestinal symptoms only in IBD. In conclusion, IBS patients experienced extraintestinal symptoms to the same extent, or even more than patients with IBD. However, the relationship between intestinal and extraintestinal symptoms differed in the two conditions.

Adult↗
PubMed2004

Are Helicobacter species and enterotoxigenic Bacteroides fragilis involved in inflammatory bowel disease?

The aim of this study was to determine if either Helicobacter or enterotoxigenic Bacteroidesfragilis (ETBF) was linked to inflammatory bowel disease (IBD), using PCR. We analyzed the luminal washings and colonic biopsies of 35 patients with IBD and 37 control patients. The presence of Helicobacter was confirmed in the luminal washing of one IBD patient and three control patients and in the biopsies of two IBD patients. Ten of 28 control patients and 8 of 32 IBD patients had a positive luminal washing for the enterotoxin gene. Six of 33 control patients and 4 of 32 IBD patients had positive biopsies. The prevalence of the enterotoxin gene was higher in IBD patients with active disease compared with patients with inactive disease, although it did not achieve statistical significance. In conclusion, Helicobacter was not associated with IBD in our population of patients, although ETBF may be associated with active disease.

Adult↗