Oral Salicylates Research Articles

News and controversy in inflammatory bowel disease treatment

Background: The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. Discussion: In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti- TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.

Attualità e controversie nella terapia delle malattie infiammatorie croniche intestinali

The treatment of Inflammatory bowel disease comes from many years of esperience, clinical trials and mistakes. In patients with active Crohn disease steroids are considerated the first choice, but recently, the introduction of anti-TNF alfa agents (infliximab and adalimumab) has changed the protocols. Anti-TNF are also used for closing fistula after surgical curettage. An efficently preventive treatment of Crohn disease still has not been found but hight dose of oral salicylates, azatioprine or 6-MP and antibiotics might be useful. In severe attacks of ulcerative colitis, high dose iv treatment of steroids are required for a few days. Later on, a further treatment with anti-TNF might delay the need of surgery. In patients with mild to moderate attacks of ulcerative colitis, topical treatment is preferred, it consists of enemas, suppositories or foams containing 5-aminosalycilic acid, traditional steroids, topical active steroids. Topical treatment can be associated with oral steroids or oral salicylates. Oral salicylates or azatioprine are used for prevention of relaps.

Sulfasalazine and BAY 11-7082 Interfere with the Nuclear Factor-κB and IκB Kinase Pathway to Regulate the Release of Proinflammatory Cytokines from Human Adipose Tissue and Skeletal Muscle in Vitro

There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.

Nonsteroidal antiinflammatory drugs as therapeutic agents for Alzheimer's disease

AbstractOne feature of the end‐stage pathology of Alzheimer's disease (AD) is the presence of numerous inflammatory markers associated with the amyloid β protein (Aβ) deposits in the brain. Experimental data strongly suggests that Aβ aggregates can incite an inflammatory response, but there are also data suggesting that inflammation can promote Aβ production and deposition. Thus, antiinflammatory drugs may have some role in AD therapy. This idea is supported by epidemiologic data, which shows that long‐term use of nonsteroidal antiinflammatory drugs (NSAIDs) confers protection from the development of AD. Significantly, oral salicylates have not been consistently shown to confer protection. Such studies have raised questions regarding the target or targets of NSAIDs that account for their apparent protection from AD. We have recently found that some NSAIDs have a novel mechanism of action, namely, selective lowering of the pathogenic Aβ42 peptide, that could contribute to their efficacy in AD. Further study will be needed to determine if the classic antiinflammatory properties of NSAIDs, the Aβ42‐lowering property, another known or unknown property, or a combination of these contributes to NSAIDs apparent ability to protect individuals from the development of AD. Drug Dev. Res. 56:415–420, 2002. © Wiley‐Liss, Inc.

Corticosteroid Therapy of Eye Disease

It IS HARD TO IMAGINEthe practice of ophthalmology without corticosteroids. Fifty years ago the treatment options for uveitis included atropine drops, oral salicylates, direct application of heat to the eye, and induction of fever with typhoid vaccine or other proteins. Then, in 1949, Hench and associates 1 described the beneficial effects of adrenocorticotropic hormone (ACTH) and cortisone in the treatment of rheumatoid arthritis. Within months of this seminal article it was clear that these drugs could help control ocular inflammation, and case reports began to appear. To read these articles is to share in the excitement and promise of a new era. In 1949, Elkinton and associates 2 described improvement of hemorrhagic retinopathy in a patient treated with ACTH for generalized collagen disease. Three separate reports soon followed. Mann and Markson 3 successfully controlled a patient's uveitis and episcleritis with ACTH therapy. Gordon and McLean 4 described transient improvement

A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

New Oral Salicylates in the Therapy of Chronic Idiopathic Inflammatory Bowel Disease

Sulfasalazine has been the mainstay of therapy for ulcerative colitis and Crohn's disease of the colon. More recently, it has become clear that 5-ASA is the active moiety of the compound and that the sulfapyridine component is responsible for most of the adverse responses to sulfasalazine. The modes of action of sulfasalazine and 5-ASA have not been determined despite active investigations. There has been great current emphasis on the development of delivery systems to allow maximum concentration of therapeutically active 5-ASA in the colon or other gastrointestinal mucosal locations. Olsalazine accomplishes this goal by creatively coupling two molecules of 5-ASA to each other by a diazo bond. Bacterial azoreductases uncouple the parent drug and deliver 5-ASA to the colonic mucosa. Several pharmaceutical manufacturers have devised variations in mesalamine (5-ASA) coatings designed to release in pH and time-related manners. Oral Rowasa, Claversal, and Asacol accomplish distal delivery with acrylic coating of tablets. Oral Pentasa seems unique in distributing 5-ASA throughout the small bowel as well as the colon by utilization of small ethylcellulose-coated microgranules. For this reason, Pentasa may be particularly useful in the treatment of small bowel Crohn's disease. There are no data to suggest that patients unresponsive to oral sulfasalazine will respond to 5-ASA in any form, although it is possible that better toleration of the 5-ASA formulations will allow more effective dosage levels to be delivered. There are also preliminary data supporting synergism between oral and topical rectal 5-ASA in certain patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral Salicylates May Help Reduce Mortality from Ischaemic Heart Disease

Oral Salicylates May Help Reduce Mortality from Ischaemic Heart Disease

Chronic Inflammatory Bowel Disease.

Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene-drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS)

The “Rib Syndrome”

1. It is suggested that the numerous chest-wall syndromes involving painful costal cartilage be identified by the term “Rib syndrome,” to indicate a single entity or process. 2. Selections from 50 cases of the “Rib syndrome” are presented, some of which illustrate the interrelationships of the numerous acute types of chest wall conditions as one entity. Nine cases of the acute type of rib junction pain showed eventual transition into the chronic nodular type previously known as “Tietze's syndrome,” suggesting an origin for this previously baffling condition. 3. The etiology of the “rib syndrome” appears to be occupational and due to a sprain or strain of the rib junction in many cases. The patient is usually unaware of local tenderness until it is found by the examiner. Biopsies and x-ray films are usually normal and unrevealing. 4. Treatment consists of local splinting, local heat and oral salicylates. The more severe cases respond best to local injections of procaine and cortisone mixtures. 5. The “Rib syndrome” appears to be a common condition that is frequently confused with diseases of heart or lungs. The diagnosis is easily confirmed when point compression over the involved costochondral junction or other painful cartilage exactly reproduces the patient's complaints.