The CD40/CD40L costimulatory pathway in inflammatory bowel disease.
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Animals↗
Biomedical subjects
M Sans
Publications and source records attributed to M Sans.
The 4G/4G genotype of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene is a determinant of penetrating behaviour in patients with Crohn's disease.
BACKGROUND: Crohn's disease is a heterogeneous disorder with polygenic inheritance. AIM: To assess the effect of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene, the major inhibitor of fibrinolysis, on Crohn's disease susceptibility and phenotype. METHODS: One hundred and fifty-seven patients with Crohn's disease and 350 controls were included prospectively. Medical records were reviewed to determine changes in the Crohn's disease phenotype. The 4G/5G polymorphism was assessed by polymerase chain reaction techniques. RESULTS: The frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes were similar in patients with Crohn's disease and controls. The 4G/4G genotype (P < 0.0001; odds ratio, 4.84) and male sex (P = 0.009; odds ratio, 2.63) were independent risk factors for penetrating behaviour in Crohn's disease. Most Crohn's disease patients had a non-penetrating phenotype at diagnosis. The probability of development of a penetrating phenotype within 5 years of diagnosis was higher in patients with the 4G/4G genotype (72% vs. 19%, P < 0.0001). CONCLUSIONS: The 4G/4G genotype of the PAI-1 gene does not influence Crohn's disease susceptibility, but increases by five-fold the probability of penetrating behaviour. Most patients with the 4G/4G genotype have a non-penetrating phenotype at diagnosis, but develop a penetrating behaviour within 5 years. Genotyping the 4G/5G polymorphism may be useful for the identification of a sub-group of patients with aggressive Crohn's disease, who might benefit from specific therapy.
Adult↗
[Carriers of hepatitis C: should they all be vaccinated for hepatitis A?].
AIM: To investigate the prevalence of immunization against hepatitis A virus (HAV) in persons with hepatitis C virus (HCV) infection, in order to determine who should be vaccinated for the former. DESIGN: Descriptive, cross-sectional study. SETTING: Urban health center serving 12 000 inhabitants. PARTICIPANTS: Patients older than 14 years positive for HCV infection. MAIN MEASURES VARIABLES: presence of chronic liver disease, serological indications of hepatitis B, A, and immune deficiency virus (HIV) infection, vaccination for hepatitis B. RESULTS: A total of 134 persons (70.9% men and 29.1% women) comprised the sample of patients positive for HCV infection. Mean age was 41.75 years (SD, 16.55 years). Nearly all patients (93.3%) had chronic liver disease, 56.7% were intravenous drug users, 56% were positive for Hbc antibodies and 32.8% were positive for HIV. Serological testing for HAV was done in 75 patients (56%); the result was positive in 86.7%. Mean age in this subgroup was 50.4 years (SD, 17.8 years). In the HAV-negative subgroup, mean age was 36.6 years (SD, 15 years; P=.02). Serological testing for HAV could not be done in 44% of the patients: 33.6% did not respond to attempts to contact them by telephone or in writing, 6% were temporarily away from home, and 1 patient declined to be tested. The response to requests to obtain blood samples was better in women (66.7%), HIV-negative patients (34.7%), persons who were not intravenous drug users (43.3%) and persons with chronic liver disease (60%). CONCLUSIONS: In persons younger than 40 years, the proportion of seronegative individuals is similar to that in the general population. Vaccination should be considered for all patients positive for HCV infection. In persons older than 40 years with chronic liver disease, the decision to vaccinate for HAV should be made in the light of serological findings.
Adolescent↗
[Frequent Internet use among Catalan patients with inflammatory bowel disease].
UNLABELLED: No data are available on the use of the Internet by Spanish patients with chronic diseases. AIM: To determine the extent to which patients with inflammatory bowel disease (IBD) in Barcelona (Spain) make use of the Internet and the relationship between Internet use and demographic characteristics. METHOD: A questionnaire on Internet use was administered to 200 patients attending an information session on IBD organized by the Gastroenterology Department of a university referral hospital in the city of Barcelona. RESULTS: Replies were received from 86% of those surveyed. The mean age was 40 years and 60% were women. Sixty-eight percent had home computers and 49% had an Internet connection. Forty-four percent sporadically or regularly obtained information on IBD from the web. A positive correlation was found between availability and Internet use and young age and higher educational level. No differences were found between men and women. Eighty-four percent expressed interest in having a web site on IBD supported by the physicians of their referral center and 65% were prepared to pay a subscription for this service. CONCLUSION: Patients with IBD from Barcelona frequently looked for information on their disease on the Internet and were receptive to initiatives concerning electronic information from physicians of their local referral center.
Adolescent↗
Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center.
BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS: One hundred and sixteen patients with non-cirrhotic chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital between 1971 and 1977 were followed until December 1998 or until death. Patients with significant alcohol intake were excluded from the study. Variables obtained at the time of diagnosis, including epidemiological, clinical, laboratory, and histological data were recorded to determine risk factors associated with the development of liver cirrhosis and hepatic decompensation. RESULTS: Based on complete follow-up data, the development of liver cirrhosis and hepatic decompensation was evaluated in 94 and 114 of the 116 patients, respectively. Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate aminotransferase (AST) value higher than 70 IU/L was associated with development of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at 10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently associated to the development of hepatic decompensation was the presence of fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9). Liver-related death occurred only in seven (6%) of 114 patients. In comparison with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C diagnosed in 1999 were younger, more often asymptomatic, had lower AST and alanine aminotransferase (ALT) values and had significantly lower grade and stage histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate of progression to liver cirrhosis over a prolonged follow-up. However, this might be related to the fact that two decades ago the diagnosis was made at a significantly more advanced stage of the disease. Patients at high risk of progression can be identified by biochemical and histological variables at the time of diagnosis.
Adult↗
Differential role of selectins in experimental colitis.
BACKGROUND AND AIMS: The role of selectins in experimental colitis remains unknown. The aims of this study were to characterize the time-course expression of selectins in trinitrobenzene sulfonic acid (TNBS)-induced colitis, the functional role of selectins in colonic leukocyte-endothelial cell interactions, and the therapeutic usefulness of selectin blockade in this model. METHODS: Control and TNBS-induced colitic rats were studied. Expression of P- and E-selectin was assessed by the radiolabeled antibody technique, and L-selectin by flow cytometry. Leukocyte-endothelial cell interactions were studied in colonic venules by using intravital microscopy under basal conditions and after P-, E-, or L-selectin immunoblockade. Additional groups of animals were treated with anti-P-selectin antibody, a nonbinding antibody, or dexamethasone, for 7 days. RESULTS: P-selectin and E-selectin expression were markedly up-regulated in colitic rats. Increased leukocyte rolling was abrogated by anti-P-selectin, but only attenuated by anti-E- or anti-L-selectin antibodies. Only pretreatment with anti-P- selectin decreased leukocyte adhesion. Animals chronically treated with dexamethasone, but not with anti- P-selectin, had significantly lower macroscopic and histologic damage scores, colon weight, and myeloperoxidase (MPO) activity than those treated with nonbinding antibody. CONCLUSIONS: P-selectin plays a key role on leukocyte rolling and its blockade attenuates leukocyte adhesion in TNBS-induced colitis. However, treatment with an anti-P-selectin antibody does not significantly improve colitis.
Animals↗
Preconditioning protects against systemic disorders associated with hepatic ischemia-reperfusion through blockade of tumor necrosis factor-induced P-selectin up-regulation in the rat.
Previous studies indicate that ischemic preconditioning protects against lung injury resulting from hepatic ischemia-reperfusion (I/R) through inhibition of tumor necrosis factor (TNF) release from Kupffer cells. The present study investigated whether this effect is limited to the lung or is a generalized systemic response and explores the molecular mechanisms involved. Hepatic I/R led to an increase in neutrophil accumulation in liver, lung, and splanchnic organs. Although preconditioning did not modify neutrophil infiltration in liver during reperfusion, it conferred protection against hepatic injury associated with I/R. In remote organs, preconditioning abrogated the increase in P-selectin up-regulation, preventing neutrophil infiltration and thus reducing the oxidative stress and microvascular disorders following hepatic I/R in these organs. Administration of Abs against P-selectin or TNF previous to ischemia had the same effects as preconditioning. The effects of preconditioning on the blockade of P-selectin up-regulation probably results from inhibition of systemic TNF release from Kupffer cells. Supplementation of TNF abolished the benefits of preconditioning, whereas the injurious effects of TNF were prevented by previous blockade of P-selectin. The results of the present study suggest that ischemic preconditioning protects the liver against I/R injury by a mechanism independent of adhesion molecule expression and neutrophil accumulation. In remote organs, however, hepatic preconditioning prevents inflammatory damage by reducing the systemic TNF release from the liver and thus preventing P-selectin up-regulation.
Animals↗
123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis.
OBJECTIVES: To evaluate the usefulness of 123I-labelled anti-vascular cell adhesion molecule-1 (VCAM-1) monoclonal antibody (MAb) scintigraphy in the assessment of colonic inflammatory damage. DESIGN: Colitis was induced by intracolonic administration of 30 mg trinitrobenzenesulphonic acid in 0.5 ml of 50% (v/v) ethanol. Rats injected with vehicle served as controls. Animals were studied at day 7 after induction of colitis. METHODS: Scintigraphy was performed in control and trinitrobenzenesulphonic acid-induced colitic rats 2, 4 and 24 h after intravenous administration of 123I-anti-VCAM-1 MAb. Scintigraphic uptake was quantified in selected areas on scintigraphs. Animals were killed, tissue 123I radioactivity accumulation was measured, and accumulation of anti-VCAM-1 MAb in each organ was calculated. 99mTc-hexamethyl propylene amine oxime-labelled leucocyte scintigraphy was performed in additional groups of animals for comparison. RESULTS: Colonic tracer uptake was visible in scans of colitic, but not control animals. Quantification of scintigraphic uptake in the colon was significantly higher in colitic rats than in control animals (P< 0.0001). The specificity of the increase was demonstrated by lack of 123I-labelled non-binding MAb uptake in the colon, and by displacement of 123I-anti-VCAM-1 MAb colonic uptake by pre-treatment with unlabelled MAb. Accumulation of anti-VCAM-1 MAb in the colon of colitic rats was eightfold higher than in control animals. Strong correlations were found between quantification of scintigraphic uptake, anti-VCAM-1 MAb accumulation, histological damage and myeloperoxidase activity in the colon. CONCLUSION: 123I-labelled anti-VCAM-1 MAb scintigraphy allows an accurate evaluation of colonic inflammatory damage in trinitrobenzenesulphonic acid-induced colitis, suggesting a potential role for this imaging technique in the assessment of human IBD.
Animals↗
Hydrocolonic sonography for evaluating inflammatory bowel disease.
OBJECTIVE: The purpose of our study was to compare the usefulness of hydrocolonic sonography and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)--labeled leukocyte scintigraphy in the examination of patients with inflammatory bowel disease, using precise sonographic criteria of bowel involvement. SUBJECTS AND METHODS: Sixty-eight consecutive patients with active inflammatory bowel disease (34 ulcerative colitis and 34 Crohn's disease), 12 with inactive inflammatory bowel disease, and 10 control subjects were prospectively studied. Patients with active disease underwent clinical assessment, hydrocolonic sonography, scintigraphy, and colonoscopy within 72 hr, whereas patients with inactive disease and control subjects underwent clinical examination and hydrocolonic sonography. RESULTS: Involvement of a colonic segment by active inflammatory bowel disease was best defined by mucosal thickness greater than 1.5 mm, bowel wall thickness greater than 4 mm, mucosal irregularity, or the absence of haustra; and involvement of the terminal ileum by bowel wall thickness greater than 4 mm. Using these criteria, hydrocolonic sonography had 100% sensitivity for identifying patients with active inflammatory bowel disease and a greater overall accuracy (87%) than scintigraphy (77%) in the assessment of disease extension. In addition, strong correlation was shown between a hydrocolonic sonography activity index and clinical and endoscopic activity indexes. CONCLUSION: This prospective study provides precise sonographic criteria for the definition of bowel involvement by active inflammatory bowel disease. Hydrocolonic sonography has a greater accuracy than scintigraphy for assessing disease extension and activity. Therefore, hydrocolonic sonography should be considered a first-choice technique to complete the study of inflammatory bowel disease after confirmation of the diagnosis by histology.
Adolescent↗
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 no leukocyte infiltration into the brain of TNBS-induced colitic rats. CONCLUSIONS: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not associated with an infiltration of leukocytes into brain tissue.
Animals↗
[Temporal disability caused by psychiatric pathology at a health center].
OBJECTIVE: To find the incidence, duration, diagnosis and treatment of time off work for psychiatric reasons. DESIGN: Retrospective, descriptive study. SETTING: The Dr. Pujol i Capsada Health Centre in Baix Llobregat county, Barcelona. PARTICIPANTS: All the records of time off occurring between January 1992 and December 1996 were reviewed. Time off for psychiatric reasons, and its length, follow-up, relapses and treatment were analysed. MEASUREMENTS AND MAIN RESULTS: 71 patients had had time off on some occasion for psychiatric reasons (34% men, 66% women). The mean age was 38 (SD 10). The mean number of days off in the first period of time off (n = 71) was 155 days (SD = 302), in the second (n = 21) 209 (SD = 268), in the third (n = 8) 187 (SD = 327), and in the fourth (n = 3) 206 days (SD = 326). Total number of days off came to 16,894. 4% obtained invalidity status for psychiatric reasons. The most common initial reasons for the first period of time off were, by pathology: psychiatric (58%), osteo-muscular (17%), nervous system and sense organs (7%) and digestive system (6%). The psychiatric reasons for the first period off were: anxiety (48%), depression (38%), anxiety-depression (10%), schizoid disorders (3%) and personality disorders (1%). Half the patients were referred and almost all were supervised by the general practitioner. The most commonly used drugs were the benzodiazepines (75%) and serotonin re-uptake inhibitors (38%). CONCLUSIONS: Time off for psychiatric reasons tends to last a long time and to recur. 42% of these periods of time off was not initially classified as for psychiatric reasons. Half the patients are shared and supervised jointly with the psychiatrist: thus, the need for good coordination between the two areas.
Adult↗
Optimization of technetium-99m-HMPAO leukocyte scintigraphy in evaluation of active inflammatory bowel disease.
Although [99mTc]HMPAO-labeled leukocyte scintigraphy is widely used in the assessment of IBD, the time point chosen for imaging is still controversial. The aim of the present study was to determine the optimal scanning sequence to assess IBD extension and activity. Sixty-two consecutive patients with active and 18 with inactive IBD were prospectively studied. Clinical evaluation, colonoscopy, radiology, and scintigraphy were performed within three days, without changes in the patient's treatment. Compared to early scan (45 min), late scan (3 hr) had a higher sensitivity (85% vs 100%) and accuracy (85% vs 95%) in identifying patients with active IBD and in defining IBD extension. Combinations of values from both scans did not improve accuracy of scintigraphy, which is lower in Crohn's disease than in ulcerative colitis and also in patients receiving steroid treatment. In conclusion, a single late scintigraphy scan provides the best means to identify patients with active IBD and to assess disease extension.
Adolescent↗
Replenishment of glutathione levels improves mucosal function in experimental acute colitis.
Because reactive oxygen species (ROS) have been implicated as mediators of inflammatory bowel disease (IBD), the purpose of the present work was to determine the functional role of mucosal GSH in the trinitrobenzenesulfonic acid in 50% ethanol (TNBS+ethanol)-induced colitis in rats. Mucosal samples were taken to evaluate the temporal relationship between the extent of injury, the levels of glutathione (GSH) during acute colitis induced by TNBS+ethanol, and the effect of N-acetylcysteine (NAC) administration. In vitro assays revealed the interaction of TNBS with GSH leading to the almost instantaneous disappearance of GSH, while the reductive metabolism of TNBS by GSSG reductase generated ROS. Mucosal samples from TNBS+ethanol-treated rats indicated a direct correlation between GSH depletion and injury detected as soon as 30 minutes after TNBS+ethanol administration that persisted 24 hours post treatment. Although, short term depletion of mucosal GSH per se by diethylmaleate did not result in mucosal injury, the oral administration of NAC (40 mM) 4 hours after TNBS+ethanol treatment increased GSH stores (2-fold), decreasing the extent of mucosal injury (60-70%) examined at 24 hours post treatment. However, an equimolar dose of dithiothreitol failed to increase GSH levels and protect mucosa from TNBS+ethanol-induced injury. Interestingly, GSH levels in TNBS+ethanol-treated rats recovered by 1-2 weeks, an effect that was accounted for by an increase of gamma-glutamylcysteine synthetase (gamma-GCS) activity due to an induction of gamma-GCS-heavy subunit chain mRNA. Thus, TNBS promotes two independent mechanisms of injury, GSH depletion and ROS generation, both being required for the manifestation of mucosal injury as GSH limitation renders intestine susceptible to the TNBS-induced ROS overgeneration. Accordingly, in vivo administration of NAC attenuates the acute colitis through increased mucosal GSH levels, suggesting that GSH precursors may be of relevance in the acute relapse of IBD.
Acetylcysteine↗
VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice.
Adhesion molecule immunoneutralization is envisioned as a promising therapy for inflammatory bowel disease, but the relative value of selective blockade of different adhesion molecules has not been established. The aims of this study were to measure expression and functional relevance of endothelial intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in leukocyte recruitment in experimental colitis and to compare the therapeutic effectiveness of their selective blockade. For this purpose, cell adhesion molecule expression was measured by the dual radiolabeled antibody technique in mice with dextran sulfate sodium-induced colitis and controls. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of chronic treatment with anti-ICAM-1, anti-VCAM-1, or anti-MAdCAM-1 antibodies were also assessed. Whereas colonic endothelial ICAM-1 was constitutively expressed and had a mild up-regulation in colitic animals, constitutive expression of VCAM-1 and MAdCAM-1 was low, but markedly increased after induction of colitis. Leukocyte adhesion was abrogated by immunoneutralization of VCAM-1 or MAdCAM-1 but not by treatment with an anti-ICAM-1 antibody. Chronic administration of anti-VCAM-1 antibody, but not anti-ICAM-1 or anti-MAdCAM-1, resulted in significant attenuation of colitis in terms of disease activity index, colon length, ratio of colon weight to length, and myeloperoxidase activity. In conclusion, VCAM-1 plays a central role in leukocyte recruitment in colitis and blockade of this adhesion molecule has higher therapeutic effect than immunoneutralization of ICAM-1 or MAdCAM-1 in this experimental model.
Animals↗
Tepoxalin inhibits inflammation and microvascular dysfunction induced by abdominal irradiation in rats.
BACKGROUND: Inflammatory cells contribute to the acute and sub-acute sequelae of radiation therapy. Tepoxalin, an inhibitor of cyclooxygenase and 5-lipoxygenase that suppresses NF-kappaB activation, has potent anti-inflammatory activity. AIMS: To assess the effects of tepoxalin on radiation-induced inflammatory damage, and determine its mechanisms of action. METHODS: Leucocyte rolling, adhesion and emigration, and albumin leakage were determined by intra-vital microscopy in rat mesenteric venules. NF-kappaB activation was measured by electrophoretic mobility shift assays, and endothelial intercellular adhesion molecule-1 expression by the radiolabelled antibody technique. Groups of irradiated rats were treated with tepoxalin, N-acetyl-L-cysteine, zileuton (lipoxygenase inhibitor), or vehicle. RESULTS: Irradiated animals had a marked increase in the number of rolling, adherent and emigrated leucocytes in mesenteric venules, and in microvascular permeability. Tepoxalin prevented leucocyte adhesion and the increase in permeability after radiation. Tepoxalin did not inhibit radiation-induced NF-kappaB activation or intercellular adhesion molecule-1 up-regulation, while N-acetyl-L-cysteine, which attenuated NF-kappaB activation, had no effect on leucocyte recruitment. In contrast, tepoxalin inhibited the increase in leukotriene B4 levels after radiation, and the anti-inflammatory effects of the drug were mimicked by zileuton. CONCLUSIONS: Tepoxalin affords significant protection against radiation-induced inflammation and microvascular dysfunction in splanchnic organs through a mechanism dependent on leukotriene synthesis inhibition.
Abdomen↗
Diagnosis and management of diffuse leiomyomatosis of the oesophagus.
Diffuse leiomyomatosis of the oesophagus is a rare entity among oesophageal diseases. Histopathologically it is characterized by diffuse hypertrophy of the muscular layer extending to the whole oesophagus predominantly in the lower third, where it can result in tumour formation. Leiomyomatosis can involve the upper part of the stomach and is frequently associated with genital or tracheobronchial (bronchitracheal) muscular localizations. Also, it can be associated with Alport's syndrome in familial cases. For diagnosis, barium swallow, computerized tomography (CT) scan and, in recent years, endoscopic ultrasonography are used. Oesophageal resection is the only suitable treatment in symptomatic cases. We report three observations during 1979-95.
Adult↗
Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis.
BACKGROUND & AIMS: Unfractionated heparin has been found to reduce symptoms and improve healing as adjuvant therapy in patients with ulcerative colitis. The current study evaluated the efficacy and safety of unfractionated heparin in the treatment of ulcerative colitis in comparison with methylprednisolone. METHODS: A multicenter randomized trial with blinded endpoint evaluation was conducted in patients hospitalized for moderate or severe ulcerative colitis. Patients were randomized to receive heparin as a continuous infusion or methylprednisolone (0.75-1 mg x kg(-1) x day(-1)). RESULTS: Twenty-five patients entered the study: 13 received methylprednisolone and 12 received heparin. By day 10, 69% of patients in the methylprednisolone group, but none in the heparin group, achieved significant improvement or remission. C-reactive protein levels significantly decreased in the methylprednisolone group but not in the heparin group. Three patients in the heparin group were withdrawn before day 10 because of an adverse event: rectal bleeding needing transfusion (2 cases) or surgery (1 case). The proportion of patients with persistent rectal bleeding at day 10 was 31% in the methylprednisolone group and 90% in the heparin group (P<0.05). CONCLUSIONS: Unfractionated heparin as monotherapy is not effective in the treatment of moderate or severe ulcerative colitis and is associated with significant bleeding complications.
Adult↗
Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism.
BACKGROUND: In addition to its anticoagulant properties, heparin has anti-inflammatory effects, the molecular and mechanistic bases of which are incompletely defined. AIMS: The current studies were designed to test the hypothesis that heparin abrogates the expression or function of leucocyte-endothelial adherence molecules which are fundamental to the acute inflammatory response. METHODS: The effects of heparin on tumour necrosis factor alpha (TNF-alpha) induced leucocyte rolling, adhesion, and migration as well as vascular permeability were assessed in rat mesenteric venules using intravital microscopy. Expression of adhesion molecules was quantitated using a double radiolabelled monoclonal antibody (mAb) binding technique in vivo (P-selectin, intercellular cell adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1)) or flow cytometry (CD11a, CD11b, and L-selectin). Ex vivo binding of heparin to neutrophils was assessed by flow cytometry. RESULTS: TNF-alpha induced a significant increase in leucocyte rolling, adhesion, and migration, and vascular permeability, coincident with a significant increase in expression of P-selectin, ICAM-1, and VCAM-1. Ex vivo assessment of blood neutrophils showed significant upregulation of CD11a and CD11b and significant downregulation of L-selectin within five hours of TNF-alpha administration. Heparin pretreatment significantly attenuated leucocyte rolling, adhesion, and migration but did not affect expression of cell adhesion molecules or vascular permeability elicited by TNF-alpha administration. Binding of heparin was significantly increased on blood neutrophils obtained five hours after TNF-alpha administration. Preincubation with an anti-CD11b mAb but not with an anti-CD11a or anti-L-selectin antibody significantly diminished heparin binding ex vivo. CONCLUSIONS: Our results support the concept that the anti-inflammatory effects of heparin involve attenuation of a CD11b dependent adherent mechanism.
Animals↗