endothelin-1 and Colitis--Ulcerative

Increases in microalbuminuria and endothelin (ET-1) are involved in the development of ulcerative colitis (UC) and in its progress. Because granulocyte and monocyte adsorption apheresis has proven to be useful in the treatment of UC, we examined whether urinary albumin excretion and plasma ET-1 concentrations are altered and whether granulocyte and monocyte adsorption apheresis affects the concentrations of these two factors in patients with active UC.. Twenty patients with active UC and 20 age-matched healthy volunteers (our hospital staffs) were included in this study. UC patients were randomly divided into two treatment groups: a granulocyte and monocyte adsorption treatment group (n = 10) and a conventional treatment group (n = 10). The urine albumin/creatinine ratio, plasma ET-1 concentration and tumor necrosis factor (TNF)-alpha were determined before and after treatment and compared between 2 treatment groups. The 10 adsorption treatment patients underwent 5 consecutive weekly apheresis sessions, each of 60 min duration at a flow rate of 30 ml/min.. The urine albumin/creatinine ratio in UC patients (6.4 +/- 2.2 mg/mmol) were higher than that in healthy subjects (1.0 +/- 0.7 mg/mmol, p < 0.01). In addition, the plasma ET-1 level in UC patients (3.5 +/-1.5 pg/ml) was higher than that in healthy subjects (0.8 +/- 0.4 pg/ml, p < 0.01). Plasma TNF-alpha was detected in UC patients (18.8 +/- 8.4 pg/ml), but not in healthy subjects. The urine albumin/creatinine ratio was highly correlated with the plasma ET-1 level (r = 0.62; p < 0.01) and plasma TNF-a level (r = 0.66, p < 0.01). Granulocyte and monocyte adsorption apheresis reduced the urine albumin/ creatinine ratio from 6.6 +/- 2.4 to 1.8 +/- 0.6 mg/mmol (p < 0.01), reduced the plasma ET-1 level from 3.7 +/- 1.6 to 1.4 +/- 0.6 pg/ml (p < 0.05) and reduced the plasma TNF-alpha from 19.2 +/- 8.6 to 3.8 +/- 1.2 pg/ml (p < 0.01). Conventional treatment did not affect these factors.. Our data suggest that increases in the urine albumin/creatinine ratio, ET-1 and TNF-alpha play an important role in active UC and that granulocyte and monocyte adsorption apheresis is effective in ameliorating such increases.

Topics: Adsorption; Adult; Albuminuria; Colitis, Ulcerative; Creatinine; Defecation; Endothelin-1; Female; Granulocytes; Humans; Leukapheresis; Leukocyte Count; Male; Monocytes; Tumor Necrosis Factor-alpha

BACKGROUND The aim of this study was to investigate the clinical significance of NLRP3 and HMGB1 in patients with active ulcerative colitis. MATERIAL AND METHODS This was a prospective observational study which included a total of 62 cases with active ulcerative colitis during January 2017 to December 2018. The patients were divided into a mild/moderate group or a severe group according to Sutherland Disease Activity Index (DAI) score. Clinical activity index and endoscopic index were used to determine the severity of UC. Serum levels of NLRP3, HMGB1, endothelin-1, IL-1ß, and TNF-alpha were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS Sutherland DAI score, clinical activity index, and endoscopic index were all significantly higher in severe patients than in the mild/moderate group. NLRP3, HMGB1, endothelin-1, IL-1ß, and TNF-alpha were significantly higher in severe UC patients. NLRP3 level was positively correlated with HMGB1, ET-1, IL-1ß, and TNF-alpha levels. Both NLRP3 and HMGB1 were positively correlated with Sutherland DAI score, clinical activity index, and endoscopic index. CONCLUSIONS Both serum NLRP3 and HMGB1 were elevated in UC patients, and the serum levels of NLRP3 were positively correlated with serum levels of HMGB1, ET-1, IL-1ß, and TNF-alpha, as well as severity of UC patients.

Topics: Adult; Colitis, Ulcerative; Cytokines; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; HMGB1 Protein; Humans; Interleukin-1beta; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha

To study the correlation between the pulmonary injury and the ET-1 serum level in ulcerative colitis (UC) patients, and to study the mechanism for UC induced pulmonary injury.. Recruited were 90 UC outpatients from the clinics of Gastroenterology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from Nov. 2009 to Mar. 2011. The course of disease, disease range, serum ET-1 level of UC patients were observed and compared. The correlation between the serum ET-1 level and each pulmonary function index were studied [including vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, peak expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory flow in 25%, 50%, 75% vital capacity (FEF25%, 50%, 75%), diffusion capacity for carbon monoxide of lung (DLCO), diffusion constant (KCO), total lung capacity (TLC), alveolar ventilation (VA), residual volume (RV), function residual volume (FRV), and RV/TLC]. Besides, another 30 healthy volunteers were enrolled as the control group. The pulmonary symptoms, chest X-ray, the lung function, the serum ET-1 level, and liver and kidney functions [including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCr) were compared between the UC group and the control group.. Ten UC patients were accompanied with cough and chest distress (accounting for 11.1%), 25 with abnormal chest films (accounting for 27.8%), and 54 with pulmonary function abnormality (accounting for 60.0%). In the UC group ALT increased in 2 cases (2.2%) and AST increased in 2. They were normal in the control group. The BUN and SCr were normal in the two groups. Compared with the control group, the serum ET-1 level in the UC group was significantly higher than that in the control group (P < 0.05). There was no statistical difference in the serum ET-1 level (P > 0.05). There was statistical difference in the serum ET-1 level in the UC group between those with the disease course > or = 5 years and those with the disease course <5 years, showing statistical difference (P < 0.05). There was negative correlation between the serum ET-1 level and FEF25% and between the serum ET-1 level and KCO (P < 0.05).. Serum ET-1 level could reflect the pulmonary injury of UC patients earlier. Serum ET-1 level might be a sensitive indicator reflecting the pulmonary injury of UC. The pulmonary injury of UC patients might be correlated with small airway obstruction, reduced lung elasticity, and injured lung diffusion.

Topics: Adult; Aged; Case-Control Studies; Colitis, Ulcerative; Endothelin-1; Female; Humans; Lung; Male; Medicine, Chinese Traditional; Middle Aged; Respiratory Function Tests; Serum; Young Adult

Endothelins can act as polyfunctional cytokines. It is therefore possible that endothelins could play an active role in gut inflammation. Elevated levels of endothelin-1 have been reported in ulcerative colitis and Crohn's disease. The aim of this study was to establish the therapeutic effect of a 'new' endothelin receptor antagonist Ro 48-5695 in an animal model of inflammatory bowel disease. This study compares the effect of Ro 48-5695 on colonic damage induced by two haptens: trinitrobenzenesulphonic (TNBS) or dinitrobenzenesulphonic acid (DNBS).. Colitis was induced by intra-rectal administration of TNBS or DNBS. After TNBS/DNBS injury, rats were treated with 10.0, 3.0, 1.0 or 0.3 mg/kg of Ro 48-5695 orally, daily for 5 days. On day 6 post-hapten treatment, colonic tissues were removed and examined in a blinded fashion for macroscopic damage (damage score) and myeloperoxidase (MPO) activity. Stool consistency and adhesions were also measured.. Oral administration of Ro 48-5695 almost completely prevented TNBS-induced damage at a dose of 10 mg/kg. The same dose in this model also had a therapeutic effect as measured by MPO and incidence of diarrhoea and adhesions. In DNBS-induced colonic damage, Ro 48-5695 was more potent and at 1.0 and 3.0 mg/kg decreased the damage score by 50 and 60% respectively; also the incidence of adhesions and diarrhoea was significantly reduced. However, MPO activity in this model was affected only by the highest dose of Ro 48-5695 tested (3.0 mg/kg) where it was reduced by 48%.. These data provide evidence for the involvement of endothelins in the pathophysiology of inflammatory bowel disease and support the possibility of exploring a new therapeutic approach.

Topics: Animals; Benzenesulfonates; Colitis, Ulcerative; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Inflammatory Bowel Diseases; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Sulfonamides; Trinitrobenzenesulfonic Acid

The purpose of this study was to investigate the behavior of circulating endothelin-1, a vasoconstrictor and mitogenic peptide, in patients with inflammatory bowel disease.. We investigated plasma endothelin-1 levels in 29 patients with Crohn's disease, 13 with ulcerative colitis and 26 healthy subjects as controls.. Erythrocyte sedimentation and C-reactive protein were also measured in all patients. Plasma endothelin-1 was measured by specific radioimmunoassay and expressed as pg/ml.. Both Crohn's disease and ulcerative colitis patients showed a significant increase in plasma endothelin-1 concentration (22.3 +/- 8.2 pg/ml and 11.2 +/- 2.7 pg/ml, respectively) when compared to healthy subjects (6.2 +/- 1.5 pg/ml). Moreover, plasma endothelin-1 levels were significantly higher in Crohn's disease patients than those in ulcerative colitis patients (22.3 +/- 8.2 pg/ml vs 11.2 +/- 2.7 pg/ml; p < 0.001, respectively). A weak correlation (r = 0.645; p < 0.013) between erythrocyte sedimentation and endothelin-1 levels was observed in Crohn's disease patients. Age, sex, clinical activity of the disease, duration of history, anatomical localization of disease and therapy had no influence on plasma endothelin-1 levels.. Our results show that plasma endothelin-1 levels increase in chronic inflammatory bowel disease and mainly in Crohn's disease. This observation leads us on to believe that endothelin-1 has a important role in inflammatory bowel disease.

Topics: Adult; Blood Sedimentation; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Endothelin-1; Female; Humans; Male; Middle Aged