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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.
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PMID:Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study. 898 63

Heparin has been shown to ameliorate inflammatory bowel disease in several series. In addition to its anticoagulant properties, heparin has numerous other effects that may be beneficial in inflammatory bowel disease. Other sulfated polysaccharides, such as dextran sulfate, cause colitis in mice through unknown mechanisms. We postulate that dextran sulfate and heparin may act via similar pathways with opposite effects. To examine this thesis, the effect of heparin on dextran sulfate-induced colitis was studied. Swiss-Webster mice were given 5% dextran sulfate in their drinking water for five days to induce colitis. Heparin was given both therapeutically after the induction of colitis and prophylactically by subcutaneous injections, with saline injections given in controls. Histologic sections of colon were randomized and graded for colitis. Heparinized animals showed no significant difference in the pattern or severity of colitis when compared to control animals. It is concluded that heparin does not ameliorate the murine colitis induced by dextran sulfate in the doses given.
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PMID:Effect of heparin on dextran sulfate sodium-induced colitis. 972 72

Oral glucosamine has anti-inflammatory activity in rodents, and anecdotal evidence suggests that it may be clinically useful in inflammatory bowel disorders. A possible explanation is that supplemental glucosamine increases production of heparan sulfate (HS) proteoglycans by the vascular endothelium, thereby improving the endothelium's barrier function. Extravasation of leukocytes and metastatic cancer cells requires degradation of HS. Heparin can inhibit neutrophil activation, adhesion, and chemotaxis, and--like glucosamine--has been reported effective for managing inflammatory bowel syndromes. Cytokine-mediated loss of endothelial HS may be a key factor in the coordinated inflammatory response. These considerations suggest that glucosamine may have clinical utility in a range of inflammatory disorders, and should be assessed with regard to its impact on cancer metastasis and peripheral ischemic disease. In inflammatory bowel disease, fish oil, ginkgolides, and enteric-coated 5-aminosalicylic acid may safely complement the efficacy of glucosamine.
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PMID:Vascular heparan sulfates may limit the ability of leukocytes to penetrate the endothelial barrier--implications for use of glucosamine in inflammatory disorders. 988 30

Heparin apparently aids healing in ulcerative colitis although its mechanism of action is unknown. The purpose of this study was to investigate the hypothesis that heparin functions as a coreceptor molecule for basic fibroblast growth factor, a role usually performed by heparan sulfate chains on syndecan-1. A marked reduction of syndecan-1 immunostaining was found in reparative epithelium from inflammatory bowel disease patients. Removal of heparan sulfate on gastrointestinal epithelial cells in vitro reduced the proliferative response to basic fibroblast growth factor. The response to basic fibroblast growth factor was completely restored by the addition of heparin. Loss of syndecan-1 expression occurs in the regenerative mucosa in inflammatory bowel disease. Although this may facilitate tissue motility, its loss probably adversely affects the ability of cells to bind basic fibroblast growth factor. The present data show that heparin may substitute the loss of functional activity of syndecan-1 in the binding of basic fibroblast growth factor.
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PMID:Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy. 1063 May 5

Recent reports suggest that unfractionated heparin may be a useful adjunct in the treatment of inflammatory bowel disease (IBD). We report the successful use of subcutaneous unfractionated heparin to treat a moderate-to-severe flare of Crohn's disease during pregnancy, which was refractory to standard therapy. The patient received 10,000 units of unfractionated heparin subcutaneously twice a day after her Crohn's colitis failed to come under remission with intravenous corticosteroids. Heparin was continued throughout her pregnancy. Following initiation of adjunctive heparin therapy, the patient experienced a rapid clinical response, was able to discontinue intravenous steroids, discharge from the hospital, and ultimately deliver a healthy term newborn. Although there is extensive obstetric experience with heparin in the treatment of thrombosis associated with pregnancy, there is limited information regarding its use in IBD patients during pregnancy. Because heparin has an established track record in maternal-fetal medicine, this agent may be considered in women who suffer an inflammatory flare of IBD during pregnancy who have not responded to standard treatment.
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PMID:Successful treatment of an acute flare of steroid-resistant Crohn's colitis during pregnancy with unfractionated heparin. 1197 40

The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% CI, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95%o CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients.
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PMID:Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. 1294 75

Patients who undergo colorectal surgery are at a substantially higher risk for deep vein thrombosis (DVT) than their general surgery counterparts. The incidence of DVT in colorectal surgery patients who do not receive prophylaxis is approximately 30%; a four-fold increase exists in the incidence of pulmonary embolism. The precise reasons for the increased risk are uncertain; likely, contributing factors are the need for pelvic dissection, patient positioning (eg, use of stirrups), and indications for surgery (eg, inflammatory bowel disease, cancer). Despite the clear evidence that supports the safety and efficacy of DVT prophylaxis, appropriate preventive measures are frequently not used. Heparin preparations and mechanical compression in combination likely represents the most appropriate prophylactic regimen in these high-risk patients. Standard heparin appears to be as effective as low-molecular-weight heparin and considerably less costly. In the presence of relatively poor adherence to consensus guidelines for prophylaxis, critical pathways or electronic alerts may be useful to facilitate compliance with appropriate preventive measures.
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PMID:Venous thromboembolism prophylaxis in colorectal surgery. 1652 69

Chronic inflammatory diseases are common and still remain a therapeutic challenge for both efficacy and safety reasons. Hence, novel therapeutics addressing these issues would for example improve treatment of severe diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Inappropriate leukocyte homing to the affected compartments is a common feature of these diseases. Heparin and related polysaccharides have been shown to interfere with leukocyte homing through a variety of effects distinct from their anticoagulant properties. In this review, data on heparin as an anti-inflammatory agent are presented. In addition, structure-activity requirements for the anti-inflammatory properties of heparin are discussed, which should aid the drug development based on structurally modified heparin or other sulfated carbohydrates for treatment of inflammatory diseases.
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PMID:Structural requirements of heparin and related molecules to exert a multitude of anti-inflammatory activities. 1701

Low molecular weight heparins (LMWH) have shown efficacy in the treatment of inflammatory bowel disease after parenteral administration however risking severe hemorrhagic adverse effects. Therefore, an oral colonic targeted heparin dosage form allowing the release of LMWH directly in the inflamed tissue would be of major interest. Enoxaparin was entrapped into pH-sensitive microspheres using Eudragit P4135F that dissolves at pH>7.2. Particle preparation was based on a double emulsion technique with either solvent extraction or evaporation. In order to increase the entrapment efficacy several preparation parameters were optimized, such as inner phase volume, polymer concentration, stabilization of the internal interface by surfactants. Solvent evaporation led to higher entrapment rates (evaporation: 70.1+/-9.9%; extraction: 46.5+/-6.4%). When increasing the volume of the inner aqueous heparin phase, lower encapsulation rates and larger microspheres ( approximately 100-400 microm) were obtained. Sorbitan monostearate (1.75-28% of the total particle mass) had a stabilizing effect on the primary water/oil emulsion. Indeed, higher encapsulation rates (7%: 78.2+/-3.5%; 14%: 76.4+/-10.1%) and smaller particles ( approximately 120-160 microm) were obtained whereas hexadecyltrimethylammonium bromide destabilized the primary emulsion. Interfacial tension studies at a simulated internal water/oil interface confirmed these results. As expected, in vitro drug release was found to be strongly pH-dependent; LMWH was retained in microspheres at pH<6 (<20% release within 4h) whereas a fast drug release was obtained at pH 7.4. The developed microspheres exhibited a particle size adapted to the needs of inflammatory bowel disease therapy, an efficient LMWH encapsulation, and a pH-controlled drug release. These microspheres represent a promising tool for the selective oral delivery of heparin to the colon, especially interesting in the treatment of inflammatory bowel disease.
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PMID:Low molecular weight heparin loaded pH-sensitive microparticles. 1715 Mar 17

Low-molecular-weight heparins (LMWH) have been shown to be efficient in the treatment of inflammatory bowel disease (IBD). Parenteral heparin therapy, however, may cause hemorrhagic adverse effects. To reduce this risk, epithelial LMWH delivery in combination with a system ensuring selective drug release to the inflamed tissue was tested here. Enoxaparin loaded microspheres (MS) were administered orally to male BALB mice suffering from a pre-existing experimental colitis, whereas control groups received subcutaneous or rectal LMWH solution. Colon weight/length index and alkaline phosphatase and myeloperoxidase activities were assessed to determine the inflammation. Tissue penetration experiments elucidated the processes involved in the proposed new therapeutic approach. Oral LMWH-MS proved to be equally efficient in mitigating experimental colitis as rectally administered LMWH solution when quantified by myeloperoxidase activity (MS, 10.2+/-1.5 U/mg tissue; rectal, 9.2+/-1.6 U/mg) and to be superior to subcutaneous LMWH (s.c., 21.6+/-5.6 U/mg; untreated colitis control, 30.0+/-3.8 U/mg). Pharmacokinetic studies found a notably low systemic availability of oral LMWH delivered from MS (<5%) indicating a low potential for adverse effects. The tissue permeability was selectively enhanced in the inflamed regions where a 9-fold higher LMWH penetration was found compared with healthy tissue. Epithelial LMWH delivery has been found a promising anti-inflammatory therapeutic approach. The use of LMWH-MS in this context offers a promising tool for IBD therapy by enhancing specifically drug availability at inflamed tissue sites while reducing the risk for systemic adverse effects to a negligibly low level.
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PMID:Epithelial heparin delivery via microspheres mitigates experimental colitis in mice. 1732 27


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