salicylates and Colitis--Ulcerative

Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing.

Topics: Adrenal Cortex Hormones; Biological Therapy; Colitis, Ulcerative; Crohn Disease; Endoscopy, Gastrointestinal; Humans; Immunologic Factors; Intestinal Mucosa; Salicylates; Severity of Illness Index; Terminology as Topic; Wound Healing

The Authors review and critically discuss the most recent published evidence on treatment of mild-moderate ulcerative colitis both in the induction and maintenance of remission. Evidence on each drug is introduced by the related statement of ECCO guidelines. A brief introduction on disease classification and the need of standardizing indexes of clinical and endoscopic activity is also provided. Concluding remarks stress the heterogeneity of available studies both in the selection of patients and the outcomes evaluated and suggest the development of an international consensus in setting standards which will allow studies' results to be compared and combined to produce high quality clinical recommendations.

Topics: Administration, Oral; Administration, Rectal; Adrenal Cortex Hormones; Algorithms; Colitis, Ulcerative; Humans; Randomized Controlled Trials as Topic; Remission Induction; Salicylates; Severity of Illness Index

The classical aim of the treatment of ulcerative colitis is to induce and maintain remission. However, this aim has not been shown to prevent long-term complications. Current treatment goals attempt to prevent complications. In some studies, healing of the intestinal mucosa has been shown to improve long-term outcomes. In ulcerative colitis, mucosal healing reduces recurrence, the risk of colorectal cancer and the need for surgery, and improves patients' quality of life. The drugs for which there is greatest evidence of their efficacy in inducing and maintaining mucosal healing are salicylates and biological agents. In the near future, endoscopic monitoring may be required to evaluate response to the treatment and decisions may have to be taken according to the persistence or disappearance of these lesions.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Biological Therapy; Colectomy; Colitis, Ulcerative; Colorectal Neoplasms; Combined Modality Therapy; Disease Progression; Gastrointestinal Hemorrhage; Humans; Immunosuppressive Agents; Intestinal Mucosa; Outcome Assessment, Health Care; Prognosis; Quality of Life; Recurrence; Regeneration; Salicylates; Severity of Illness Index

Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Colorectal Neoplasms; Humans; Probiotics; Remission Induction; Salicylates; Tacrolimus; Thiazolidines

Although new salicylates are now available for the treatment of ulcerative colitis, sulphasazaline still has an important therapeutic role. The role of salicylates in Crohn's disease is limited to the mild activity phase; further data are required to clarify its role in maintenance on remission. New steroids are a real alternative to traditional steroids in active ulcerative colitis and Crohn's disease.

Topics: Acute Disease; Aspirin; Beclomethasone; Budesonide; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Glucocorticoids; Humans; Inflammatory Bowel Diseases; Prednisolone; Randomized Controlled Trials as Topic; Salicylates; Sulfasalazine

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Bacterial Agents; Anti-Inflammatory Agents; Colitis, Ulcerative; Crohn Disease; Cyclosporine; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Methotrexate; Recurrence; Salicylates; Severity of Illness Index; Steroids

This article reviews the role of corticosteroids, sulfasalazine and mesalazine (5-aminosalicylic acid, mesalamine), immunosuppressive agents and alternative novel drugs for the treatment of distal ulcerative colitis. Short cycles of traditional, rectally administered corticosteroids (methylprednisolone, betamethasone, hydrocortisone) are effective for the treatment of mild to moderately active distal ulcerative colitis. In this context, their systemic administration is limited to patients who are refractory to either oral 5-amino-salicylates, topical mesalazine or topical corticosteroids. Of no value in maintaining remission, the long term use of either or topical corticosteroids may be hazardous. A new class of topically acting corticosteroids [budesonide, fluticasone, beclomethasone dipropionate, prednisolone-21-methasulphobenzoate, tixocortol (tixocortol pivalate)] represents a valid alternative for the treatment of active ulcerative colitis, and may be useful in the treatment of refractory distal ulcerative colitis. Although there is controversy concerning dosage or duration of therapy, oral and topical mesalazine is effective in the treatment of mild to moderately active distal ulcerative colitis. Sulfasalazine and mesalazine remain the first-choice drugs for the maintenance therapy of distal ulcerative colitis. Evidence exists showing a trend to a higher remission rate with higher doses of oral mesalazine. Topical mesalazine (suppositories or enemas) also is effective in maintenance treatment. For patients with chronically active or corticosteroid-dependent disease, azathioprine and mercaptopurine are effective in reducing either the need for corticosteroids or clinical relapses. Moreover, they are effective for long term maintenance remission. Cyclosporin may be useful in inducing remission in patients with acutely severe disease who do not achieve remission with an intensive intravenous regimen. Existing data suggest that azathioprine and mercaptopurine may be effective in prolonging remission in these patients. The role of alternative drugs for the treatment of distal ulcerative colitis and its different forms is reviewed. In particular data are reported concerning the effectiveness of 5-lipoxygenase inhibitors, topical use of short chain fatty acids, nicotine, local anaesthetics, bismuth subsalicylate enema, sucralfate, clonidine, free radical scavengers, heparin and hydroxychloroquine.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Colitis, Ulcerative; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lipoxygenase Inhibitors; Mesalamine; Quality of Life; Salicylates; Sulfasalazine

The treatment of ulcerative colitis (UC) remains empiric because of undetermined etiology and pathogenesis and incomplete understanding of the underlying immunoinflammatory events. However, considerable progress has been made in the management of this disease with the availability and wider use of newer aminosalicylates and immunomodulating agents. The clinician confronted with a patient with chronic ulcerative colitis must weigh the advantages of continued medical therapy against the potential curability with improved surgical techniques. After a brief discussion of the current classes of medicines and their pathophysiological basis of action, we focus on standard approaches to the different clinical syndromes and their complications.

Topics: Anti-Inflammatory Agents; Colectomy; Colitis, Ulcerative; Female; Humans; Immunosuppressive Agents; Male; Pregnancy; Salicylates; Treatment Outcome

Delivery of 5-aminosalicylic acid to the colon by sulphasalazine, other azo-bonded compounds and controlled-release preparations is introduced in the context of metabolism by epithelial cells and therapeutic efficacy in ulcerative colitis. Potential modes of action are then reviewed, including actions on luminal bacteria, epithelial cell surface receptors, cellular events (such as nitric oxide release or butyrate oxidation), electrolyte transport and epithelial permeability. Evidence for an influence of salicylates on circulating and lamina propria inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides and inflammatory mediators, such as eicosanoids, platelet-activating factor, cytokines or reactive oxygen metabolites. The precise mechanism will remain uncertain as long as the aetiology of ulcerative colitis is unknown, but a pluripotential mode of action of salicylates is an advantage when influencing the network of events that constitute chronic inflammation.

Topics: Cell Adhesion Molecules; Colitis, Ulcerative; Colon; Cytokines; Delayed-Action Preparations; Eicosanoids; Epithelial Cells; Epithelium; Humans; Prodrugs; Reactive Oxygen Species; Salicylates; Sulfasalazine; Tablets, Enteric-Coated

Topics: Adrenal Cortex Hormones; Adult; Colitis, Ulcerative; Colostomy; Crohn Disease; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Proctocolectomy, Restorative; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Child; Colitis, Ulcerative; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Pregnancy; Pregnancy Complications; Salicylates

Topics: Colitis, Ulcerative; Crohn Disease; Humans; Salicylates

Recently, oenological prejudices were challenged by the use of a points scoring system (from 50 to 100) to evaluate wine in a book now widely regarded as one of the most authoritative. On this scale, a 1981 Chateau Citran described as 'emaciated' scored 65, a 1983 Chateau Kirwan scored 85, and a 1982 Petrus 100. If the same approach were used for drugs used in ulcerative colitis to quantify an advance over conditions existing at the time of its introduction how would they score? Because they were the first available drugs in their class and clearly constituted major advances, corticosteroids and sulphasalazine both score 95, the score being limited by a high level of side effects. The new salicylates score 75, because they extend the benefits of sulphasalazine to a minority of patients but they have the potential to score 90 if increased dosing and greater effectiveness over sulphasalazine can be achieved. Salicylate enemas score 80, because they advance treatment over topical corticosteroids for patients with resistant distal disease, but the mode of delivery needs improvement. Steroid foams also score 80, particularly if the patient's vote is taken into account. Azathioprine's score cannot be calculated because there is doubt over its efficacy, but it is potentially 88 if it saves patients with difficult disease from colectomy. We can only guess what an oral non-absorbed steroid would score, but if response rates for relapse were substantially improved, or if corticosteroids could be used as effective maintenance treatment, it could be as high as 95. There are indications that we should 'watch this space'.

Topics: Adrenal Cortex Hormones; Azathioprine; Colitis, Ulcerative; Humans; Salicylates

Chronic inflammatory bowel diseases are probably due to stimulation of the intestinal immune system by multiple, so far unknown antigens. Chronic inflammatory bowel diseases can be contained but not healed by corticosteroids, sulfasalazine (SASP), azathioprin and metronidazol. Healing may be expected by direct pharmacological intervention in the intestinal immune system, but these are not yet available. -5-aminosalicylic acid may replace SASP in the treatment of ulcerative colitis. When administered locally 5-ASA may be effective in cases of corticosteroid-resistant distal colitis. Controlled studies are needed before the perspectives for 5-ASA in the treatment of Crohn's disease can be assessed.

Topics: Administration, Oral; Aminosalicylic Acids; Anti-Inflammatory Agents; Colitis, Ulcerative; Crohn Disease; Humans; Mesalamine; Pharmaceutical Vehicles; Salicylates

Salicylate intolerance is defined as a nonspecific antigen-induced pseudo-allergic hypersensitivity reaction which can occur upon contact of an organism with salicylic acid, its derivatives or other related organic or inorganic acids of similar chemical structure. Since the effects of nonsteroidal anti-inflammatory drugs (NSAID) intolerance are by no means always severe or life-endangering but may just as well present as oligosymptomatic or local disorders (e.g. abdominal pain, diarrhea, we decided to evaluate the characteristics of patients with salicylate intolerance on the basis of gastroenterological case material of Medical Department I of Erlangen University. On the basis of the findings from the Erlangen interdisciplinary data register of chronic inflammatory gastrointestinal disease, the signs and symptoms of NSAID intolerance were found to constitute a diagnosis of great practical import to clinical medicine (allergology, dermatology, immunology, other disorders etc.) including gastroenterology. For approx. 2-7% of all patients with inflammatory bowel syndrome and food allergies this poses a new diagnostic and therapeutic challenge which may concern physicians from any of the disciplines involved. When presented with patients with chronic active disease who are suffering from these symptoms one should, therefore, in future give greater thought to the possibility of salicylate intolerance, all the more as there are meaningful dietetic, diagnostic and therapeutic options available for these persons.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Colitis, Ulcerative; Crohn Disease; Diet; Drug Hypersensitivity; Food Hypersensitivity; Gastrointestinal Diseases; Humans; Irritable Bowel Syndrome; Lower Gastrointestinal Tract; Malabsorption Syndromes; Mesalamine; Salicylates

Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration. The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed.. Steroid and mesalamine enemas were withdrawn before the study. Forty patients were assigned to 1 of 4 strata: no concomitant therapy, oral steroids, oral salicylates, or oral steroids and salicylates. After stratification, patients were randomized to nightly treatment with 350 mg cyclosporine (n = 20) or placebo (n = 20) enemas. Clinical response was determined at baseline and 4 weeks by endoscopy, physician assessment, and a patient diary of daily symptoms. Trough blood cyclosporine levels were measured by high-performance liquid chromatography.. At 4 weeks, 8 of 20 patients (40%) who received cyclosporine showed clinical improvement compared with 9 of 20 patients (45%) who received placebo. One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine, and another patient receiving cyclosporine was unable to tolerate the enema vehicle. No other toxicity was noted during the trial. Blood cyclosporine levels were detectable in only two patients.. Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Adult; Aged; Aminosalicylic Acids; Colitis, Ulcerative; Cyclosporine; Enema; Female; Humans; Mesalamine; Middle Aged; Placebos; Salicylates

Benzalazine (salicylazobenzoic acid, SAB), a 5-azo derivative of 5-aminosalicylic acid, has been designed as a new therapeutic agent for the treatment of inflammatory bowel disease which might lack the frequent side effects caused by the sulfapyridine moiety of the sulfasalazine molecule (SASP). Here, we report on a prospective, randomized, double-blind comparison of SAB and SASP in patients with an acute relapse of ulcerative colitis. 43 patients with an acute relapse of ulcerative colitis proven by the pertinent endoscopic-macroscopic and histologic criteria were randomized to receive a 6-week course of either 1 g SASP (n = 21) or the equivalent dose of 0.72 g SAB (n = 22) three times a day. Both groups were comparable with respect to demographic data, previous duration and extension of the disease as well as clinical, endoscopic and histologic severity of the relapse. 1 patient on SASP had to be removed from the study due to side effects, while 3 patients on SAB were removed due to rapid worsening of the disease requiring either surgery (1 patient with toxic megacolon) or additional steroid treatment (2 patients). 2 SAB patients were lost to follow-up after substantial improvement had been observed within the first 3 weeks of treatment. In the remaining patients (20 SASP, 17 SAB), stool frequency, stool consistency and macroscopic appearance as well as histology of the diseased mucosa were improved within 6 weeks, with no significant difference between the two groups with respect to any of the parameters recorded. Side effects were recorded in 5 patients on SASP (3 with nausea, 1 with pruritus and 1 with a generalized exanthema) and in 3 patients on SAB (all nausea and vomiting; difference not statistically significant). We conclude that SAB and SASP in equivalent doses are of similar efficacy in the treatment of active ulcerative colitis.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aminosalicylic Acids; Clinical Trials as Topic; Colitis, Ulcerative; Double-Blind Method; Humans; Middle Aged; Random Allocation; Salicylates; Sulfasalazine

Sixty-four patients with proven ulcerative colitis who had been maintained on sulphasalazine as their sole form of treatment for a minimum period of one year were entered into a controlled trial of sulphasalazine versus dummy tablets for a period of six months. All the patients admitted were not only symptom-free but also showed no evidence of inflammation on sigmoidoscopy and rectal biopsy. A patient was judged to have relapsed when there was a recurrence of colitic symptoms accompanied by sigmoidoscopic and histological evidence of inflammation. The patients who received dummy tablets had more than four times the relapse rate of those receiving sulphasalazine. The results were similar in patients who had been on maintenance treatment with sulphasalazine for less than three years before entry into the trial and in those who had been on this treatment for more than three years. It is concluded that maintenance treatment of ulcerative colitis with sulphasalazine should be continued indefinitely unless contraindicated by side effects.

Topics: Biopsy; Blood Cell Count; Blood Sedimentation; Clinical Trials as Topic; Colitis, Ulcerative; Headache; Hemoglobins; Humans; Inflammation; Nausea; Placebos; Prednisolone; Psychology; Rectum; Remission, Spontaneous; Salicylates; Sigmoidoscopy; Sulfasalazine

Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated.. Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei Radix et Rhizoma and Coptidis Rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC.. TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system.. TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis.. Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.

Topics: Animals; Antineoplastic Agents; Benzopyrans; Berberine; China; Colitis; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Mice; Salicylates; Tannins; Tight Junction Proteins; Tissue Distribution

Poor adherence to mesalamine is common and driven by a combination of lifestyle and behavioral factors, as well as health beliefs. We sought to develop a valid tool to identify barriers to patient adherence and predict those at risk for future nonadherence.. A 10-item survey was developed from patient-reported barriers to adherence. The survey was administered to 106 patients with ulcerative colitis who were prescribed mesalamine, and correlated with prospectively collected 12-month pharmacy refills (medication possession ratio (MPR)), urine levels of salicylates, and self-reported adherence (Morisky Medication Adherence Scale (MMAS)-8).. From the initial 10-item survey, 8 items correlated highly with the MMAS-8 score at enrollment. Computer-generated randomization produced a derivation cohort of 60 subjects and a validation cohort of 46 subjects to assess the survey items in their ability to predict future adherence. Two items from the patient survey correlated with objective measures of long-term adherence: their belief in the importance of maintenance mesalamine even when in remission and their concerns about side effects. The additive score based on these two items correlated with 12-month MPR in both the derivation and validation cohorts (P<0.05). Scores on these two items were associated with a higher risk of being nonadherent over the subsequent 12 months (relative risk (RR) =2.2, 95% confidence interval=1.5-3.5, P=0.04). The area under the curve for the performance of this 2-item tool was greater than that of the 10-item MMAS-8 score for predicting MPR scores over 12 months (area under the curve 0.7 vs. 0.5).. Patients' beliefs about the need for maintenance mesalamine and their concerns about side effects influence their adherence to mesalamine over time. These concerns could easily be raised in practice to identify patients at risk of nonadherence (Clinical Trial number NCT01349504).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Attitude to Health; Cohort Studies; Colitis, Ulcerative; Female; Humans; Maintenance Chemotherapy; Male; Medication Adherence; Mesalamine; Middle Aged; Salicylates; Self Report; Surveys and Questionnaires; Young Adult

In this study, the syntheses of 4-aminophenylbenzoxazol-2-yl-5-acetic acid, (an analogue of a known nonsteroidal anti-inflammatory drug [NSAID]) and 5-[4-(benzoxazol-2-yl-5-acetic acid)phenylazo]-2-hydroxybenzoic acid (a novel mutual azo prodrug of 5-aminosalicylic acid [5-ASA]) are reported. The structures of the synthesized compounds were confirmed using infrared (IR), hydrogen-1 nuclear magnetic resonance (1H NMR), and mass spectrometry (MS) spectroscopy. Incubation of the azo compound with rat cecal contents demonstrated the susceptibility of the prepared azo prodrug to bacterial azoreductase enzyme. The azo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were evaluated for inflammatory bowel diseases, in trinitrobenzenesulfonic acid (TNB)-induced colitis in rats. The synthesized diazo compound and the 4-aminophenylbenzoxazol-2-yl-5-acetic acid were found to be as effective as 5-aminosalicylic acid for ulcerative colitis. The results of this work suggest that the 4-aminophenylbenzoxazol-2-yl-5-acetic acid may represent a new lead for treatment of ulcerative colitis.

Topics: Acetates; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoxazoles; Colitis, Ulcerative; Disease Models, Animal; Female; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mesalamine; Prodrugs; Rats; Rats, Wistar; Salicylates; Spectrophotometry, Infrared; Trinitrobenzenesulfonic Acid

The study is carried out to identify the expression pattern of indoleamine 2,3-dioxygenase (IDO) in human Crohn's disease and ulcerative colitis and to investigate the effect of different therapies (salicylates, steroids, and antitumor necrosis factor antibody) on the intestinal expression of IDO.. Immunohistochemistry was used. A total of 10 high power fields were counted for each patient.. IDO was expressed in the both lamina propria and epithelium. IDO expression increased in the lesions from ulcerative colitis and Crohn's disease and was positively related to the severity of inflammation. IDO-positive mononuclear cells also expressed CD11c, CD68, and TLR4. IDO expression decreased significantly after treatment with steroids and salicylates, but remained unchanged after infliximab therapy.. IDO was over-expressed in human inflammatory bowel disease. It may be a bridge between innate immunity and adaptive immunity. Steroids and salicylates may act through the inhibition of IDO expression. IDO upregulation may be a promising therapy to achieve inflammatory bowel disease remission.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD11c Antigen; Colitis, Ulcerative; Crohn Disease; Epithelial Cells; Female; Gastrointestinal Agents; Glucocorticoids; Humans; Immunoenzyme Techniques; Indoleamine-Pyrrole 2,3,-Dioxygenase; Inflammatory Bowel Diseases; Infliximab; Intestinal Mucosa; Male; Middle Aged; Salicylates; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Several drugs are currently available to maintain remission in patients who have responded after one or other type of induction therapy, depending on the initial severity of the outbreak. Salicylates are the drugs of choice to maintain remission after a mild-to-moderate outbreak controlled by salicylates or oral corticosteroids. To maintain remission after a severe outbreak or in patients with corticosteroid dependence or resistance, thiopurines are the drugs of choice. In patients who have failed to respond to thiopurines and in those with thiopurine intolerance, biological agents, mainly infliximab, can be used to maintain remission in patients after induction therapy with infliximab for a severe outbreak. However, these scenarios may not reflect reality of gastroenterologists' daily clinical practice. Treatment will therefore be based on the patient's individual characteristics (age, clinical course, previous treatment, adverse effects and personal preferences) as well as the physician's medical art.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Azathioprine; Colitis, Ulcerative; Disease Management; Disease Progression; Humans; Immunosuppressive Agents; Infliximab; Maintenance Chemotherapy; Mercaptopurine; Methotrexate; Patient Preference; Practice Patterns, Physicians'; Salicylates; Tumor Necrosis Factor-alpha

Adjusting therapy of patients with ulcerative colitis (UC) regarding their cytomegalovirus (CMV)--status.. 40 patients were included, mean age--44.3 +/- 3.2 yo. DNA CMV was detected in mucosal tissue samples from rectum using real-time PCR.. 4 (10%) were CMV-positive. CMV-positive status rate was higher among patients on therapy with immunomodulators 3 (23.1%) vs 1 in patients on steroids and/or salicylates. There was significantly higher rate of severe disease and steroid dependence among CMV-positive patients than among CMV-negative: 75% vs 13.9%, 75% vs 8.3% correspondently.. CMV-infection is associated with severe and steroid-dependent UC.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Azathioprine; Colitis, Ulcerative; Cytomegalovirus; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Infliximab; Male; Rectum; Reverse Transcriptase Polymerase Chain Reaction; Salicylates; Severity of Illness Index

Na+/H+ exchanger isoform 3 (NHE-3) is responsible for net uptake of NaCl and water from the gastrointestinal (GI) tract. However, its status in human inflammatory bowel diseases (IBDs) such as ulcerative colitis(UC) and Crohn's disease (CD) remains poorly understood. The aim of this study was to investigate the underlying mechanism of NHE-3 isoform expression and its modulation by 5'-aminosalicylate in human CD and UC.. Subjects were divided into three groups: 1) controls; 2) untreated/new IBD cases (n = 13) and 3) 5'-aminosalicylate-treated IBD patients (n = 13). Subjects presenting with abdominal pain but with endoscopically normal colons served as normal controls. Inflammation was confirmed by the level of myeloperoxidase (MPO) activity, malondialdehyde (MDA) concentrations and by histologic evaluation. Expressions of NHE-3 protein and mRNA, sodium pump activity and IL-1beta and TNF-alpha mRNA were estimated in the colonic biopsies using ECL-Western blot analysis,reverse transcription-polymerase chain reaction (RT-PCR) and enzyme assays.. The level of NHE-3 protein and sodium pump activity was reduced (p < 0.05) in both the untreated and treated CD and UC patients. NHE-3 mRNA was reduced only in CD patients but not in those with UC. The treatment reversed the symptoms, but levels of MPO activity, MDA concentration, IL-1beta, TNF-alpha and infiltration of inflammatory cells remained high with the exception of IL-1beta mRNA in the treated patients.. NHE-3 suppression is regulated differentially in CD and UC, which together with suppression of sodium pump activity will reduce NaCl and water uptake from the colonic lumen. These findings suggest a role of TNF-a in the regulation of NHE-3 expression in IBD.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Blotting, Western; Case-Control Studies; Colitis, Ulcerative; Colon; Crohn Disease; Female; Humans; Inflammatory Bowel Diseases; Interleukin-1beta; Male; Malondialdehyde; Middle Aged; Peroxidase; Protein Isoforms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salicylates; Sodium Chloride; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase; Tumor Necrosis Factor-alpha; Water

The aim of the present study was to evaluate the inmunomodulatory effects of UR-1505, a new salicylate derivative, on the T helper (Th)2/humoral response produced during dextran sodium sulfate (DSS)-induced rat colitis. In the in vitro studies, UR-1505 (300 microM) inhibited both the production of interleukin (IL)-10 and IL-5 in concanavalin A (Con A)-activated splenocytes and the production of immunoglobulin (Ig) G and IgA by B-lymphocytes. However, in contrast to the in vitro results, the administration of UR-1505 (10 and 30 mg/kg per day) to rats with established DSS-colitis enhanced both IL-10 and IgA production, whereas it inhibited IgG production, thus ameliorating the intestinal inflammation.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Immunoglobulin A; Immunoglobulin G; Rats; Salicylates; Th2 Cells

To study the method for synthesis of 2-hydroxyl-5- butyramidobenzoic acid and test its effect on acetic acid-induced colitis in rats.. 2-hydroxyl-5-butyramidobenzoic acid was synthesized from 5-aminosalicylic acid and butyric acid by amidation, esterification and hydrolization. The effect of 2-hydroxyl-5-butyramidobenzoic acid on acetic acid enema-induced colitis in rats was investigated.. The structure of 2-hydroxyl-5-butyramidobenzoic acid was identified by IR and 1H-NMR. After treatment with acetic acid, the colon mucosal damage index (CMDI), fecal occult blood (OB) test, and activity of myelperoxidase (MPO) increased significantly in the rats as compared to the control levels. 2-hydroxyl-5- butyramidobenzoic acid obviously reduced the CMDI and OB, and reduced the level of MPO in the rats with colitis.. The synthesis of 2-hydroxyl-5-butyramidobenzoic acid requires only mild conditions with simple procedures, and the synthesized 2-hydroxyl-5-butyramidobenzoic acid shows obvious therapeutic effects on mucosal damage of in rats with acetic acid-induced colitis.

Topics: Acetic Acid; Aminobenzoates; Animals; Colitis, Ulcerative; Male; Protective Agents; Rats; Rats, Sprague-Dawley; Salicylates

To evaluate the role of azathioprine (AZA) in Indian patients with ulcerative colitis over longer duration of time.. One hundred fifty six patients with ulcerative colitis who were treated with AZA from January 1995 to December 2003 were reviewed. The indications for its use were as follows: (1) steroid dependent and steroid refractory disease; (2) Azathioprine monotherapy for naive patients with severe disease; and (3) combination therapy (AZA + sulfasalazine or 5-aminosalicylates) for naive patients with severe disease. The data included patient and disease demographics, efficacy and toxicity profile of AZA. Patients with a minimum duration of 6 mo use of AZA were included in this report.. Of a total of 156 patients treated with AZA, 45 were excluded from analysis for the following reasons- (follow up less than 6 mo, n = 9; poor follow up, n = 18; adverse affects, n = 18). In steroid refractory/dependent group the mean number of relapses prior to and post initiation of AZA therapy were 3.28 (+/- 0.81) and 0.94 (+/- 0.29) respectively. Discontinuation of steroids could be accomplished in 12 of the 15 steroid dependent patients. The proportion of patients with sustained remission of 1, 2, 3, 4 and 5 years duration were calculated. Eighteen patients experienced adverse effects necessitating withdrawal of AZA (pancreatitis, n = 7; hepatitis, n = 3; gastrointestinal intolerance, n = 2; alopecia, n = 2; and hematological, n = 4) while 13 patients needed dose reduction or temporary withdrawal of the drug.. Azathioprine is well tolerated and has therapeutic benefits lasting as long as 4 years. Adverse effects such as pancreatitis, hepatitis, cytopenias and gastrointestinal symptoms do occur but are controlled by drug withdrawal only.

Topics: Azathioprine; Colitis, Ulcerative; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; India; Retrospective Studies; Salicylates; Sulfasalazine

Topics: Bismuth; Colitis, Ulcerative; Humans; Hydrogen Sulfide; Organometallic Compounds; Salicylates

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p < 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.

Topics: Adult; Aged; alpha-Glucosidases; Bismuth; Colitis, Ulcerative; Crohn Disease; Feces; Female; Humans; Longitudinal Studies; Male; Middle Aged; Organometallic Compounds; Salicylates; Sulfatases

Topics: Clinical Trials as Topic; Colitis, Ulcerative; Drug Administration Schedule; Humans; Salicylates

In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.). Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks treatment. Sigmoidoscopoic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time. Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required.

Topics: Administration, Rectal; Adolescent; Adult; Bismuth; Colitis, Ulcerative; Colon; Female; Humans; Male; Middle Aged; Organometallic Compounds; Salicylates

The therapeutic efficacy of salicylate drugs for ulcerative colitis in vivo is related to the capacity of each drug to suppress fatty acid oxidation in colonocytes in vitro. The suppression index of fatty acid oxidation (SIFO) was assessed with 17 salicylate drugs of either known or unknown therapeutic efficacy. The high SIFO value of 5-aminosalicylic acid (5-ASA) was reduced to zero when the amino group was replaced with a methyl, nitro, hydroxyl or bromine group. The SIFO of 3-ASA was dose-related and 2- to 3-fold greater than the SIFO of 5-ASA. The antioxidants methyl- or propyl-4-hydroxybenzoate have a high SIFO, but show a 'toxic' action towards colonocytes not observed with 3-ASA, 4-ASA or 5-ASA. A new cellular action proposed for 5-ASA is that acetylation of the amino group of 5-ASA in colonocytes releases free CoA countering sequestration of CoA observed in epithelial cells during active colitis.

Topics: Aminosalicylic Acids; Animals; Carbon Dioxide; Colitis, Ulcerative; Colon; Epithelial Cells; Fatty Acids; Mesalamine; Oxidation-Reduction; Rats; Rats, Inbred Strains; Salicylates; Sodium Nitrite

Topics: Adrenal Cortex Hormones; Colitis, Ulcerative; Crohn Disease; Cyclosporins; Humans; Salicylates

Topics: Colitis, Ulcerative; Humans; Salicylates; Sulfasalazine

Sulfasalazine (SASP) consists of salicylic acid azo linked at the 5-position to a pyridine-containing sulfonamide. This drug, currently used in inflammatory bowel disease treatment, is reductively cleaved by anaerobic bacteria in the lower bowel to 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP). Recent reports indicate that 5-ASA is the active therapeutic moiety and that SP is responsible for a variety of adverse clinical side effects. Water-soluble polymer 7, which contains salicylate residues azo linked at the 5-position to an inert polymer backbone, has been synthesized for the site-specific reductive release of 5-ASA in the lower bowel. Preparations of 7 deliver (chemical reduction) greater than 1.96 mmol of 5-ASA/g of polymer. In vitro studies with the polymer in anaerobic rat cecal bacteria demonstrated a reduction rate of approximately 1 mu equiv of azo bond h-1 (mL of cecal content)-1. A pharmacokinetic comparison of polymer and SASP showed similar deliveries of 5-ASA and metabolites to the lower bowel, blood, and urine of orally dosed rats. Polymer 7 proved more active than SASP or 5-ASA in the guinea pig ulcerative colitis model. Potential therapeutic advantages of 7 include nonabsorption/nonmetabolism in the small intestine, direct 5-ASA release at the disease site, and nonabsorption/nonmetabolism of the reduction-released carrier polymer.

Topics: Aminosalicylic Acid; Animals; Biotransformation; Colitis, Ulcerative; Guinea Pigs; Intestines; Polymers; Salicylates; Sulfapyridine; Sulfasalazine

Topics: Adult; Aged; Colitis, Ulcerative; Enema; Female; Humans; Male; Middle Aged; Salicylates; Sulfasalazine

In four patients with inactive ulcerative proctocolitis, oral administration of non-steroidal anti-inflammatory drugs appeared to precipitate relapse. These observations suggest that inhibitors of prostaglandin synthesis should be used with care in patients with this disease, and are consistent with the hypothesis that prostaglandins may have a protective role in the lower as well as the upper gastrointestinal tract.

Topics: Adult; Anti-Inflammatory Agents; Colitis, Ulcerative; Female; Flurbiprofen; Humans; Ibuprofen; Indomethacin; Male; Middle Aged; Recurrence; Salicylates

In addition to proctocolectomy, new surgical techniques for treating ulcerative colitis include the Kock internal ileal reservoir and endorectal pullthrough of the ileum. In children three forms of Crohn's disease requiring operation have been identified. Ileocecal disease may be treated with resection and anastomosis; colorectal disease is best managed by primary proctocolectomy cutaneous ileostomy; and Crohn's disease of the small bowel should be managed by medical therapy in most cases.

Topics: Cecal Diseases; Child; Colectomy; Colitis, Ulcerative; Colostomy; Crohn Disease; Female; Humans; Ileostomy; Inflammation; Male; Methods; Prednisone; Proctitis; Salicylates; Sulfapyridine

Topics: Adult; Colitis, Ulcerative; Drug Combinations; Female; Humans; Male; Salicylates; Sulfanilamides

Aetiology of ulcerative colitis and Crohn's disease is unknown. Therefore causal therapy is not possible. Conservative treatment for both diseases is of antiinflammatory, symptomatic and substituting nature. Surgical intervention is indicated if conservative treatment fails or if dangerous complications occur. The right moment for an operation can only be determined in close cooperation between internist and surgeon.

Topics: Adrenocorticotropic Hormone; Anemia; Anti-Inflammatory Agents; Blood Transfusion; Colitis, Ulcerative; Colonic Neoplasms; Crohn Disease; Dietary Proteins; Drug Combinations; Humans; Lactose Intolerance; Parenteral Nutrition; Psychotherapy; Salicylates; Sulfonamides; Vitamins

Topics: Allergens; Antigen-Antibody Reactions; Cell Migration Inhibition; Colitis, Ulcerative; Complement Fixation Tests; Hemagglutination Tests; Humans; Immunoglobulins; Leukocytes; Male; Middle Aged; Precipitin Tests; Pyridines; Respiratory Function Tests; Respiratory Hypersensitivity; Salicylates; Skin Tests; Sulfonamides

Topics: Adult; Azo Compounds; Colitis, Ulcerative; Diet Therapy; Drug Evaluation; Humans; Middle Aged; Salicylates; Sulfanilamides

Topics: Acute Disease; Adolescent; Adult; Aged; Colitis, Ulcerative; Ethanol; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Salicylates; Stress, Physiological

Topics: Adolescent; Adult; Child; Colitis, Ulcerative; Escherichia coli; Feces; Female; Humans; Male; Middle Aged; Salicylates; Sulfonamides

Topics: Adult; Colitis, Ulcerative; Female; Humans; Male; Salicylates

Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Child; Colitis, Ulcerative; Humans; Prognosis; Psychotherapy; Salicylates; Sulfanilamides

Topics: Arthritis; Colitis, Ulcerative; Humans; Male; Middle Aged; Psoriasis; Salicylates

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Colitis, Ulcerative; Female; Humans; Male; Middle Aged; Pyridines; Salicylates; Sulfonamides

Topics: Adrenal Cortex Hormones; Atropine; Child; Colitis, Ulcerative; Conjunctivitis; Corneal Ulcer; Drug Therapy; Eye; Eye Manifestations; Humans; Iridocyclitis; Iritis; Keratitis; Penicillin G; Penicillin G Procaine; Procaine; Salicylates; Sclera

Topics: Arthritis; Arthritis, Rheumatoid; Colitis; Colitis, Ulcerative; Erythema Nodosum; Humans; Salicylates

Topics: Chronic Disease; Colitis; Colitis, Ulcerative; Humans; Salicylates

Topics: Colitis, Ulcerative; Humans; Salicylates; Sulfasalazine