Adhesion molecules in chronic ulcerative colitis. (2007 Jul)
adhesion molecules in chronic ulcerative colitis . background AND AIMS : The adhesion molecule expression in colonic mucosa is pivotal for transition from quiescent to active stage of ulcerative colitis ( UC ) . The aim of the present study is to reveal the adhesion molecule profile of colonic mucosa in the active stage of UC and in remission . materials AND methods : biopsy specimens obtained from 14 patients with UC ( seven with active disease and seven with UC in remission ) and from seven controls were used . immunohistochemistry was performed with antibodies against ICAM 1 , VCAM 1 , E selectin , LFA 1 , Mac 1 , and VLA 4 . results : In controls , slight ICAM 1 positivity was observed on thety endothelium of blood vessels of the mucosal and submucosal layer and only single ICAM 1 , Mac 1 , and LFA 1 positive cells were found . In all patients with UC , the endothelium of venules in the edematous mucosal and submucosal layers was ICAM 1 , VCAM 1 , and E selectin positive . numerous ICAM 1 and LFA 1 positive and less VCAM 1 , Mac 1 , and VLA 4 positive inflammatory cells were detected in mucous layers of acute UC . In specimens of UC in remission , the inflammatory cells positive for the studied adhesion molecules were significantly less in number in the mucosa and submucosa ( p 0 . 05 ) . conclusions : …

Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase. (1999 Sep)
reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase . background : oxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases . AIMS : To study the role of nitric oxide ( NO ) derived from inducible NO synthase ( iNOS ) in an experimental model of murine enterocolitis . methods : trinitrobenzene sulphonic acid ( TNBS ) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls . The distal colon was evaluated for histological evidence of inflammation , iNOS expression and activity , tyrosine nitration and malondialdehyde formation ( as indexes of nitrosative and oxidative stress ) , myeloperoxidase activity ( as index of neutrophil infiltration ) , and tissue localisation of intercellular adhesion molecule 1 ( ICAM 1 ) . results : TNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration , increased myeloperoxidase activity , increased concentrations of malondialdehyde , and an intense staining for nitrotyrosine and ICAM 1 in wild type mice . genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage , and notably reduced nitrotyrosine formation and concentrations of malondialdehyde ; it did not , however , affect neutrophil infiltration and intestinal ICAM 1 expression in the injured tissue . conclusion : Data show that activation of iNOS is required for nitrosative and oxidative …

Intercellular adhesion molecule 1 ( ICAM 1 ) deficiency protects mice against severe forms of experimentally induced colitis. (2000 Feb)
intercellular adhesion molecule 1 ( ICAM 1 ) deficiency protects mice against severe forms of experimentally induced colitis . ICAM 1 ( CD54 ) , the ligand for LFA 1 and Mac 1 , is up regulated during inflammatory reaction on the activated vascular endothelium . To determine its role in intestinal inflammation , we induced acute experimental colitis in mice with a deleted ICAM 1 gene , by feeding them with 3 dextran sodium sulphate ( DSS ) in drinking water for 7 days . chronic colitis was elicited by DSS similarly , followed by 2 weeks with water . In the acute phase of inflammation , ICAM 1 deficient mice exhibited a significantly lower mortality rate ( 5 ) than control c57bl / 6J mice ( 35 ) . control animals , but not the ICAM 1 deficient mice , exhibited diarrhoea and rectal bleeding . histological examination of large bowel samples evaluated the intensity of inflammatory changes , and type and extent of mucosal lesions . In the acute phase , 33 . 3 of samples from ICAM 1 deficient mice exhibited mucosal defects ( flat and fissural ulcers ) , predominantly mild to moderate inflammatory infiltrate within the lamina propria mucosae and lower grades of mucosal lesions . Much stronger inflammatory changes were present in control animals , flat ulcers ( sometimes multiple ) and fissural ulcers being observed in 62 . 5 of samples . mucosal inflammatory infiltrate was moderate to severe , typically with …

Effects of the anti ICAM 1 monoclonal antibody on dextran sodium sulphate induced colitis in rats. (1999 Jan)
effects of the anti ICAM 1 monoclonal antibody on dextran sodium sulphate induced colitis in rats . increased expression of intercellular adhesion molecule 1 ( ICAM 1 ) in the colon of inflammatory bowel disease ( IBD ) has been reported . We evaluated the effects of monoclonal antibodies to ICAM 1 on acute colitis induced by dextran sodium sulphate ( DSS ) in rats . colitis was induced by feeding rats 3 DSS for 7 days . Anti ICAM 1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6 . On day 7 the rats were killed and colitis was evaluated histologically . prophylactic treatment with anti ICAM 1 significantly attenuated colonic damage , neutrophil infiltration and the shortening of the colon in DSS colitis . Our findings demonstrate that ICAM 1 plays an important role in this model of inflammatory bowel disease . although this study does not directly address the effect of anti ICAM 1 therapy in IBD , our findings encourage experiments using therapies that target ICAM 1 in rats with already developed disease .

Brain endothelial adhesion molecule expression in experimental colitis. (2001 May)
brain endothelial adhesion molecule expression in experimental colitis . objectives : 1 ) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis , and 2 ) to investigate whether leukocyte infiltration occurs in the brain of colitic animals . methods : endothelial vascular cell adhesion molecule 1 ( VCAM 1 ) and intercellular adhesion molecule 1 ( ICAM 1 ) expression was quantified , using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid ( TNBS ) induced colitis , in mice with dextran sulfate sodium ( DSS ) induced colitis , in SCID mice reconstituted with cd45rbhigh T cells , and in IL 10 / mice . leukocyte infiltration in the brain of TNBS induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti CD45 monoclonal antibody . results : marked upregulation of brain endothelial VCAM 1 ( 2 to 5 . 5 fold ) was consistently found in colitic animals in the four models studied . brain VCAM 1 strongly correlated with colon VCAM 1 and colon weight . By contrast , upregulation of brain ICAM 1 in colitic animals was only observed in the cd45rbhigh transfer ( 3 fold ) and the TNBS induced ( 1 . 5 fold models ) . heart and muscle VCAM 1 and ICAM 1 were not upregulated in colitic animals in the majority of models studied . there was …

Association between k469e allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a japanese population. (2002 Dec)
association between k469e allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a japanese population . background AND AIMS : The genetic contribution to inflammatory bowel disease ( IBD ) is under investigation . recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD . We investigated the association between an intercellular adhesion molecule 1 gene ( ICAM 1 ) polymorphism located on chromosome 19p13 and IBD in a japanese population . methods : We compared 207 japanese patients who had IBD ( 79 with crohn s disease ( CD ) ; 128 with ulcerative colitis ( UC ) ) with 103 unrelated japanese controls . We determined r241g and k469e polymorphisms of the ICAM 1 gene using polymerase chain reaction ( PCR ) techniques . results : Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls ( allelic frequency , p ( c ) 0 . 0026 ; carriage rate , p ( c ) 0 . 0034 ; odds ratio 2 . 59 ; 95 confidence interval 1 . 42 4 . 68 ) . furthermore , the frequency of the K469 allele was significantly increased in both CD and UC . subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls . conclusions : We identified an overall …

Antiadhesion molecule therapy in inflammatory bowel disease. (2002 Jul)
antiadhesion molecule therapy in inflammatory bowel disease . adhesion molecules regulate the influx of leukocytes in normal and inflamed gut . Some of these molecules such as madcam 1 are specific for the gastrointestinal endothelium , but in inflammatory bowel diseases most of the adhesion factors are up regulated . adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa . recently , therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed , and are being developed as a novel class of drugs in the treatment of crohn s disease ( CD ) and ulcerative colitis . This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells . secondly , the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed . finally , we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules . Both antiintercellular adhesion molecule 1 ( ICAM 1 ) and anti alpha4 integrin strategies are being developed . trials with the anti ICAM 1 antisense oligonucleotide , ISIS 2302 , in steroid refractory CD have provided conflicting efficacy data . The anti alpha4 integrin antibodies natalizumab ( antegren ) and LDP 02 are in phase III and phase II trials , respectively . In the near future , these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD .

Activation of nuclear factor kappa B and effects of pyrrolidine dithiocarbamate on TNBS induced rat colitis. (2005 Mar)
activation of nuclear factor kappa B and effects of pyrrolidine dithiocarbamate on TNBS induced rat colitis . AIM : To explore the changes of nuclear factor kappa B ( NF kappab ) DNA binding activity , the expression of intercellular adhesion molecule 1 ( ICAM 1 ) regulated by NF kappab at various times and to evaluate the effects of pyrrolidine dithiocarbamate ( PDTC ) on trinitrobenzene sulfonic acid ( TNBS ) induced rat colitis . methods : TNBS of 0 . 6 mL was mixed with ethanol of 0 . 3 mL solution and instilled into the lumen of the rat colon . The rat models were divided into 6 groups , which were killed at 24 h , 3 , 7 , 14 , and 21 d after enema . colonic inflammation and damage were assessed by macroscopical and histological criteria . activity of NF kappab DNA binding was analyzed by electrophoresis mobility shift assays ( EMSA ) . expression of ICAM 1 was detected by in situ hybridization ( ISH ) and immunohistochemistry ( IH ) . Then various doses of PDTC were injected into rat abdomen 30 min before enema with TNBS / ethanol as pretreatment . The rats were killed 4 h after enema and the colonic inflammation , myeloperoxidase ( MPO ) activity , malondialdehyde ( MDA ) level , and DNA binding activity of NF kappab were assessed . finally , PDTC was injected intraperitoneally after colitis was induced . changes of morphology …

Circulating soluble intercellular adhesion molecule 1 ( sicam 1 ) in active inflammatory bowel disease. (1994 Oct)
circulating soluble intercellular adhesion molecule 1 ( sicam 1 ) in active inflammatory bowel disease . intercellular adhesion molecule ( ICAM ) 1 promotes the initial interaction between macrophages and T cells during immune activation . We have measured serum levels of soluble ICAM 1 ( sicam 1 ) by elisa in 27 patients with ulcerative colitis ( UC ) , 31 with crohn s disease ( CD ) , and 29 healthy subjects . The median sicam 1 serum concentration was significantly increased in inflammatory bowel disease ( IBD ) patients ( 355 ng / ml , range 195 855 ) compared to controls ( 245 ng / ml , 155 580 ) ( P 0 . 001 ) . variance analysis for trend showed that sicam 1 levels were significantly higher in patients with active CD and UC , compared to those with inactive disease and controls ( P 0 . 00002 ) . The concentration of sicam 1 was higher in CD patients ( 365 ng / ml 230 470 ) compared to UC ( 300 ng / ml 195 855 ) ( P 0 . 01 ) . furthermore , weak but significant correlations were found between serum levels of sicam 1 and : soluble IL 2 receptors , orosomucoid , and C reactive protein . It is suggested that increased circulating sicam 1 levels may reflect increased adhesiveness and signal transmission across cells , probably as a result of shedding of the parent molecule during …

Comparative studies of the colonic in situ expression of intercellular adhesion molecules ( ICAM 1 , 2 , and 3 … (2000 Aug)
comparative studies of the colonic in situ expression of intercellular adhesion molecules ( ICAM 1 , 2 , and 3 ) , beta2 integrins ( LFA 1 , Mac 1 , and p150 , 95 ) , and pecam 1 in ulcerative colitis and crohn s disease . A dysregulated local immune defense with a constant influx of leukocytes provides a basis for continuous intestinal inflammation in ulcerative colitis ( UC ) and crohn s disease ( CD ) . Cell adhesion molecules are pivotal for the migration of leukocytes from the circulation toward the colonic epithelium . A study quantifying the cells expressing intercellular adhesion molecules ( icams ) , beta2 integrins , and platelet endothelial cell adhesion molecule 1 ( pecam 1 ) in the colon was performed to illustrate the leukocyte migration pathway in inflammatory bowel disease . serial colonic sections ( 10 UC , 10 CD , and 10 controls ) were stained immunohistochemically for ICAM 1 , ICAM 2 , ICAM 3 , cd11a , cd11b , CD18 , and pecam 1 . Cell adhesion molecule expression was evaluated quantitatively with reference to topographic localization . In UC , polymorphonuclear leukocytes ( PMNs ) in contact with the crypt epithelium and in crypt abscesses expressed cd11b . CD tissue was characterized by cd11a , cd11c , and ICAM 1 expressing cells . ICAM 1 was detected on endothelial cells , leukocytes , and apical parts of epithelial membranes , whereas ICAM 2 was expressed on …

Serum proinflammatory cytokines and adhesion molecules in ulcerative colitis. (2006 Dec)
serum proinflammatory cytokines and adhesion molecules in ulcerative colitis . background / AIMS : The aim of this study was to define the correlation between serum markers , such as proinflammatory cytokines and adhesion molecules , and disease activity in ulcerative colitis ( UC ) . methodology : nineteen patients with UC treated in our hospital from april 2003 to June 2004 , were enrolled into this study . We measured serum interleukin 6 ( IL 6 ) , interleukin 8 ( IL 8 ) , tumor necrosis factor alpha ( TNF alpha ) , intercellular adhesion molecule 1 ( ICAM 1 ) , and vascular cell adhesion molecule ( VCAM 1 ) from a blood sample . We investigated the correlation between these cytokine molecules and clinical activity . results : serum levels of IL 6 after treatment were significantly decreased proportionately as disease activity improved . serum levels of IL 8 also significantly correlated with disease activity . On the other hand , serum levels of TNF alpha were within the normal range in most of cases despite being in the active phase . there were also no significant differences between before and after treatment in serum levels of ICAM 1 or VCAM 1 . conclusions : serum IL 6 and IL 8 significantly reflected disease activity in patients with UC .

Anti inflammatory mechanism of oxymatrine in dextran sulfate sodium induced colitis of rats. (2005 Aug)
Anti inflammatory mechanism of oxymatrine in dextran sulfate sodium induced colitis of rats . AIM : To investigate the anti inflammatory mechanism of oxymatrine in dextran sulfate sodium ( DSS ) induced colitis of rats . methods : acute colitis was induced by giving 2 DSS orally in drinking water for 8 d . twenty six male rats were randomized into oxymatrine treated group ( group A , 10 rats ) , DSS control ( group B , 10 rats ) and normal control ( group C , 6 rats ) . The rats in group A were injected muscularly with oxymatrine at the dosage of 63 mg / ( kg . d ) from d 1 to 11 and drank 2 DSS solution from d 4 to 11 . The rats in group B were treated with 0 . 9 saline in an equal volume as group A and drank 2 DSS solution from d 4 to 11 . The rats in group C were treated with 0 . 9 saline as group B from d 1 to 11 and drank water normally . diarrhea and bloody stool as well as colonic histology were observed . The levels of serum tumor necrosis factor alpha ( TNF alpha ) and interleukin 6 ( IL 6 ) were determined by elisa , and nuclear factor kappab ( NF kappab ) activity and the expression of inter cellular adhesion molecule 1 ( ICAM 1 ) in colonic mucosa were detected by immunohistochemistry …

Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. (1991 Jan)
expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease . leukocyte adhesion molecules are important in cell cell interactions of the immune system . lymphocyte function associated antigen 1 ( cluster designation 11a ) mediates interactions between T cells and mononuclear phagocytes through its ligand , the intercellular adhesion molecule 1 ( CD54 ) , whereas complement receptors 3 ( CD 11b ) and 4 ( cd11c ) are involved in complement mediated phagocytosis . expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls . In normal colon , few mononuclear phagocytes expressed lymphocyte function associated antigen 1 and intercellular adhesion molecule 1 at high densities . The major adhesion molecule was cd11c . Thus , the largest population of normal colonic mononuclear phagocytes was represented by quiescent , resident macrophages with likely phagocytic function . In inflammatory bowel disease , mononuclear phagocytes showed only a slight increase in cd11a expression and no significant change in expression of cd11b and cd11c . By contrast , the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6 . 9 / 3 . 9 in controls to 69 . 2 / 12 . 8 in ulcerative colitis ( P less than 0 . 001 ) and to 45 . 7 / 22 . 8 in crohn s disease ( P less than 0 . 01 ) , showing …

Beta2 integrin / ICAM expression in crohn s disease. (1998 Mar)
beta2 integrin / ICAM expression in crohn s disease . We have previously reported on the expression of the beta2 integrin family of adhesion molecules and their ligands , the ICAM molecules , in the normal human intestine . these molecules likely have a role to play in the inflammatory response and , therefore , were studied in a group of patients with crohn s disease . A comprehensive study was undertaken in both colon ( n 8 ) and ileum ( n 10 ) specimens from 15 patients who underwent surgical resections . immunohistochemistry was performed for CD18 , cd11a , cd11b , cd11c , alphad , ICAM 1 , ICAM 2 , and ICAM 3 . Each of the mucosal , submucosal , muscle , and adventitial layers were scored for expression . specimens from normal colon ( n 15 ) , normal ileum ( n 6 ) , and ulcerative colitis ( n 7 ) were used for comparisons . compared with normal , the expression in the colon mucosa and submucosa in crohn s disease was increased for all beta2 integrins . mucosal cd11c expression was significantly greater in crohn s disease than in ulcerative colitis . In the colon muscle and adventitial layers the expression in crohn s disease was similar to normal but increased compared with ulcerative colitis . In crohn s disease ileum , the beta2 integrin mucosal and submucosal expression was similar to normal ; however , muscle and adventitial expression was …

Madcam mediates lymphocyte endothelial cell adhesion in a murine model of chronic colitis. (2001 Oct)
madcam mediates lymphocyte endothelial cell adhesion in a murine model of chronic colitis . previous studies have revealed that the expression of several endothelial cell adhesion molecules e . g . , intercellular adhesion molecule 1 ( ICAM 1 ) , vascular cell adhesion molecule 1 ( VCAM 1 ) , and mucosal addressin cell adhesion molecule 1 ( madcam 1 ) is dramatically elevated in the chronically inflamed colonic vasculature of severe combined immunodeficient ( SCID ) mice reconstituted with congenic CD4 , cd45rb ( high ) T lymphocytes . The objective of this study was to define the contribution of different endothelial cell adhesion molecules to the lymphocyte endothelial cell ( L / E ) adhesion observed in the colonic microvasculature in this experimental model of inflammatory bowel disease . fluorescently labeled T lymphocytes , isolated from spleens of normal BALB / C mice , were injected intravenously into SCID mice that had been reconstituted with CD4 , cd45rb ( high ) T lymphocytes either before ( 3 wk after reconstitution ) or after ( 7 wk postreconstitution ) the onset of clinical signs of colitis ( i . e . , diarrhea , loss of body wt ) . intravital fluorescence microscopy was used to quantify L / E adhesion in different sized venules of the colonic submucosa during the development of colitis . L / E adhesion was noted in some segments of the vasculature in precolitic SCID mice ( 3 wk after reconstitution ) but …

In situ endothelial cell adhesion molecule expression in ulcerative colitis. (1998 Apr)
In situ endothelial cell adhesion molecule expression in ulcerative colitis . E selectin in situ expression correlates with clinical , endoscopic and histological activity and outcome . background AND objectives : little is known of the in situ expression of adhesion molecules in ulcerative colitis ( UC ) according to disease activity . In the present study we investigate the vascular expression of endothelial leucocyte adhesion molecule 1 ( ELAM 1 / E selectin ) , vascular cell adhesion molecule ( VCAM 1 ) and intercellular adhesion molecules ( ICAM 1 and ICAM 3 ) on the rectal mucosa of patients with UC in order to identify links between in situ expression of these adhesion molecules and clinical , endoscopic and histological parameters . design AND methods : At inclusion , 16 untreated patients with UC at different stages of disease activity were assessed clinically and endoscopically and underwent rectal biopsy . Ten patients had similar assessments during follow up . quantitative histological and immunohistochemical scores were established with anti E selectin , VCAM 1 , ICAM 1 , ICAM 3 and HLA DR monoclonal antibodies on frozen biopsy specimens . results : ( 1 ) At inclusion , E selectin in situ expression correlated with clinical activity ( r 0 . 7 , P 0 . 05 ) , endoscopic severity ( r 0 . 74 , P 0 . 04 ) , the histological score ( r 0 . 57 , P 0 . 02 ) and in …

Activation of nuclear factor kappa B and its modulalorg effects on intercellular adhesion molecule 1 expression in mice with dextran … (2008 May)
activation of nuclear factor kappa B and its modulalorg effects on intercellular adhesion molecule 1 expression in mice with dextran sulphate sodium induced rat colitis objective : To investigate the changes in the activity of nuclear factor kappab ( NF kappa B ) in mice with dextran sulphate sodium ( DSS ) induced rat colitis and its modulalorg effect on intercellular adhesion molecule 1 ( ICAM 1 ) expression . methods : twenty normal male mice were randomized into DSS group and normal saline ( NS ) control group according to a matched pair design . From days 1 to 7 , the mice in DSS group were subjected to oral administration of 5 DSS solution , and from days 8 to 20 , NS was given instead , for a total of 3 cycles . In the control group , only NS was administered . The colonic pathology was observed using HE staining and the mucosa 1 damage was scored for each mouse . The DNA binding activity of NF kappa B was tested by electrophoretic mobility shift assay , and the expressions of ICAM 1 and NF kappa B p65 were detected using immunohistochemistry . results : The DNA binding activity of NF kappa B was significantly increased in DSS group as compared with NS group . ICAM 1 and p65 expressions were detected in the nuclei of the vascular endothelial and inflammatory cells , especially in the mucosa and submucosa , but such positive cells were seldom …

An ICAM 1 antisense oligonucleotide prevents and reverses dextran sulfate sodium induced colitis in mice. (1997 Mar)
An ICAM 1 antisense oligonucleotide prevents and reverses dextran sulfate sodium induced colitis in mice . Mice treated p . o . with 5 dextran sodium sulfate develop a mild to moderate colitis characterized by focal areas of inflammation and crypt abscesses . immunohistological analysis of colons from dextran sodium sulfate treated mice revealed an increased expression of intercellular adhesion molecule 1 ( ICAM 1 ) and infiltration of lymphocyte function antigen 1 positive cells . A murine specific antisense oligonucleotide , ISIS 3082 , was used to determine the role of ICAM 1 expression in the development of colitis . prophylactic treatment of dextran sodium sulfate treated mice with ISIS 3082 reduced the clinical signs of colitis in a dose dependent manner , with maximal effects occurring at a dose of 1 mg / kg / day . reductions in ICAM 1 immunostaining and infiltrating leukocytes were observed in colons of animals treated with 1 mg / kg ISIS 3082 . scrambled control oligonucleotides failed to modify the course of the disease . The ICAM 1 oligonucleotide also diminished the clinical severity of colitis in mice with established colitis . The toxicity of ISIS 3082 was assessed in normal CD 1 mice by administering the oligonucleotide intravenously every other day for 2 weeks . At pharmacologically relevant doses of ISIS 3082 ( 1 and 10 mg / kg ) , there were no signs of toxicity with respect to body and organ weights , clinical chemistry or hematology . …

Attenuation of colitis in the cotton top tamarin by anti alpha 4 integrin monoclonal antibody. (1993 Aug)
attenuation of colitis in the cotton top tamarin by anti alpha 4 integrin monoclonal antibody . recent studies have demonstrated the induced expression of endothelial adhesion molecules including E selectin ( also called endothelial leukocyte adhesion molecule 1 ) , vascular cell adhesion molecule and intercellular adhesion molecule in actively involved mucosa of patients with ulcerative colitis and crohn s disease . similar induction has been demonstrated in the colon of the cotton top tamarin ( CTT ) , a New world primate that experiences a spontaneous acute and chronic colitis resembling ulcerative colitis . To assess the potential importance of leukocyte adhesion as a necessary step in acute colitis , the effect of parenteral mAb directed against adhesion molecules on CTT colitis was evaluated in placebo controlled blinded trials . serial administration of either of two anti E selectin mAb designated BB11 and EH8 effectively coated endothelial surfaces expressing this vascular adhesion molecule . although colitis activity was slightly diminished after the 10 d treatment period in CTT receiving either BB11 or EH8 , this reduction was not significantly different than that seen in animals given a placebo control when assessed by a previously validated standardized scale of inflammatory activity : mean histologic activity grade 2 . 2 / 0 . 2 pretreatment vs 1 . 5 / 0 . 5 posttreatment in group receiving mAb and 2 . 1 / 0 . 1 pretreatment vs 1 . 3 / 0 . 5 posttreatment in the placebo group ( …

Blockade of Poly ( ADP ribose ) synthetase inhibits neutrophil recruitment , oxidant generation , and mucosal injury in murine … (1999 Feb)
blockade of Poly ( ADP ribose ) synthetase inhibits neutrophil recruitment , oxidant generation , and mucosal injury in murine colitis . background AIMS : inflammatory bowel disease is characterized by oxidative and nitrosative stress , leukocyte infiltration , and up regulation of intercellular adhesion molecule 1 ( ICAM 1 ) expression in the colon . recent data show that oxidative and nitrosative stress in isolated enterocytes produces DNA single strand breaks that activate the nuclear enzyme poly ( ADP ribose ) synthetase ( PARS ) , resulting in depletion of intracellular energetics and increased paracellular permeability . The aim of the present study was to examine the in vivo relevance of this injury pathway . methods : colitis was induced by rectal instillation of trinitrobenzenesulfonic acid ( TNBS ) in mice with a genetic deficiency of PARS ( PARS / ) and in wild type littermates . results : In wild type mice , TNBS treatment resulted in colonic erosion and ulceration that was maintained up to 7 days . neutrophil infiltration ( indicated by myeloperoxidase activity in the mucosa ) was associated with up regulation of ICAM 1 and high levels of malondialdehyde and nitrotyrosine . TNBS treated PARS / mice experienced a similar colonic injury that was , however , completely resolved by 6 days . resolution of the damage was associated with absence of ICAM 1 up regulation , reduction of neutrophil infiltration , lipid peroxidation , and nitrosative damage . conclusions : these data show …