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PubMed1989

Inflammatory bowel disease and male infertility: effects of sulfasalazine and 5-aminosalicylic acid on sperm-fertilizing capacity and reactive oxygen species generation.

To investigate the mechanism of the antifertility action of sulfasalazine, we prospectively measured sperm density, motility, hamster oocyte penetration capacity, and reactive oxygen species production in six men with inflammatory bowel disease being treated with sulfasalazine and 8 and 16 weeks after changing to 5-aminosalicylic acid (5-ASA). An improvement was observed after changing to 5-ASA in those with poor (n = 3), but not in those with normal (n = 3), sperm function on sulfasalazine. There was no correlation between reactive oxygen species production or acetylator phenotype with egg penetration capacity, sperm motility, or sperm density. We conclude that the mechanism of impairment and recovery of sperm function on and off sulfasalazine treatment is not related to an excess in reactive oxygen species.

Adult↗
PubMed1992

Mesalamine and olsalazine: 5-aminosalicylic acid agents for the treatment of inflammatory bowel disease.

The history, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, and dosage and administration of rectal mesalamine and oral olsalazine in the treatment of inflammatory bowel disease (IBD) are reviewed. The high incidence of toxicity associated with sulfasalazine led to the development of the nonsulfonamide 5-aminosalicylic acid products mesalamine and olsalazine. The exact mechanism of action of these agents in the treatment of IBD is unknown. In clinical trials, mesalamine was shown to be as effective as or more effective than sulfasalazine or corticosteroids in treating active ulcerative colitis, proctitis, and proctosigmoiditis. Mesalamine is effective in the maintenance of remission in patients with ulcerative colitis. Several studies have demonstrated the effectiveness of olsalazine in the treatment of active mild to moderate ulcerative colitis. Olsalazine is also effective in the maintenance of remission of ulcerative colitis. The most common adverse effect associated with mesalamine enemas is perianal irritation or trauma secondary to insertion. The most common adverse effects associated with olsalazine are dose-dependent watery diarrhea and gastrointestinal upset. The recommended dosage of the mesalamine enema for the treatment of active mild to moderate ulcerative colitis is one 4-g (60-mL) retention enema daily for three to six weeks. The dosage of mesalamine suppositories for the treatment of active ulcerative proctitis is one 500-mg suppository inserted rectally twice daily for three to six weeks. The dosage of olsalazine is 1 g daily in divided doses for the maintenance of remission of ulcerative colitis. Both rectal mesalamine and oral olsalazine provide clinicians with an effective therapeutic option for the treatment of ulcerative colitis, proctosigmoiditis, and proctitis in patients unresponsive to or intolerant of the effects of sulfasalazine or corticosteroids.

Administration, Oral↗
PubMed1992

8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid.

Oxidative DNA damage, as expressed by 8-hydroxydeoxyguanosine (8-OHdG), was investigated in calf thymus DNA exposed to either ultraviolet radiation or to FeCl2/H2O2 in a Fenton-like reaction. The influence of iron (absent in the UV system and present in the FeCl2/H2O2 system) and pH (7.4 and 4.0) on the effect of glutathione (GSH), ascorbate, and 5-aminosalicylic acid (5-ASA, a drug used in the treatment of chronic inflammatory bowel diseases) was examined in these systems. Without iron, all three compounds considerably reduced 8-OHdG formation (i.e., acted as scavengers), while in the presence of iron salts, 8-OHdG formation was accelerated (except for GSH at pH 7.4), i.e., the compounds acted as prooxidants. This effect was augmented at low pH. The prooxidant property of 5-ASA may have implications for its clinical use. Maximum scavenging effect for all the compounds investigated was obtained at much lower doses than the maximum enhancing effect. This demonstrates that to the end of oxy-radical scavenging, the concentration of the GSH, ascorbate, and 5-ASA, respectively, should be chosen to obtain maximum antioxidant effect and minimum prooxidant effects. The significance of this finding for the selection of antioxidant dose is important but remains to be investigated further.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

[Activity of the antioxidant system in patients with idiopathic proctocolitis and the effect of 5-aminosalicylic acid (Salofalk)].

There is a close relationship between inflammation and reactive oxygen species (ROS). Primary source of ROS are activated leucocytes. Antioxidant system protects organism against the deleterious effect of ROS. The aim of the present study was to follow the activity of antioxidant system in blood and colonic mucosa of 17 patients with idiopathic proctocolitis. All patients were treated with 5-aminosalicylic acid (Salofalk), 7 patients with a combination of prednison. The following biochemical parameters were ascertained: malondialdehyde (MDA) and ceruloplasmin in serum, glutathione (GSH) and activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes and colonic mucosa. Before treatment there was found: an increase of MDA and all antioxidant enzyme activities, an a decrease of GSH. After 3 weeks of therapy in 59% of patients, initial clinical remission was observed without serious improvement of biochemical parameters. After 10 weeks of therapy the clinical course improved in all patients, a significant decrease of MDA and activities of all antioxidant enzymes as well as an increase of GSH were stated. The authors assume that IP was positively affected by 5-ASA, and in some patients by its combination with prednisom. The effect of 5-ASA is based on its known antiinflammatory impact and its functioning as a "scavanger" of free radicals (or ROS). (Tab. 1, Fig. 3, Ref. 23.)

Adult↗
PubMed1986

Endotoxaemia in active Crohn's disease. Treatment with whole gut irrigation and 5-aminosalicylic acid.

Endotoxins in plasma were monitored during treatment in 18 patients hospitalised for acute exacerbation of Crohn's disease: systemic endotoxaemia was found on admission in all but one. The patients were randomly divided into two groups: one receiving treatment with total parenteral nutrition and steroids. To decrease the absorbable endotoxin pool, the other group was additionally treated with whole gut irrigation and 5-aminosalicylic acid was added to the lavage fluid. In most of these patients endotoxaemia cleared after intestinal lavage and they needed shorter hospitalisation. Earlier improvement was also indicated by a faster decrease of the Crohn's disease activity index and vanHees index. In the group receiving conservative treatment alone, endotoxaemia was controlled within three weeks. We conclude that endotoxaemia occurs in most patients suffering from active Crohn's disease. Control of endotoxaemia after intestinal lavage suggests that systemic endotoxaemia is caused by absorption of endotoxins from the gut. Earlier improvement after whole gut irrigation indicates its beneficial effect in active Crohn's disease.

Adolescent↗
PubMed1992

Low doses of drugs able to alter intestinal mucosal permeability to food antigens (5-aminosalicylic acid and sodium cromoglycate) do not reduce proteinuria in patients with IgA nephropathy: a preliminary noncontrolled trial.

In an uncontrolled trial, patients with IgA nephropathy (IgAN) were treated with drugs that can alter the intestinal mucosal permeability to food antigens. These drugs are known to ameliorate urinary abnormalities and histological lesions of IgAN associated with ulcerative colitis or Crohn's disease [5-aminosalicylic acid (5-ASA)] or to prevent, in mice, the induction of IgAN-like disease by oral immunization [disodium cromoglycate (SCG)]. Nine patients [serum creatinine (s-Cr) less than 2 mg/dl; 24-hour proteinuria higher than 1.5 g, but not nephrotic) were treated with 5-ASA (2.4 g/day for 6 months); 9 similar patients were treated with SCG (400 mg/day for 6 months); the follow-up extended to 6 months after stopping therapy. The 5-ASA group showed a slight but not significant decrease in s-Cr, 24-hour/proteinuria, IgA circulating immune complexes (IgA-CIC) and IgA rheumatoid factor (IgA-RF); serum beta 2-microglobulin and serum IgA were unchanged; 2 of 9 treated patients showed, after 6 months of therapy, a reduction in proteinuria of more than 50% that lasted for the subsequent 18 months. The SCG-treated group showed a slight but not significant increase in 24-hour proteinuria and a significant decrease in serum IgA; unchanged were s-Cr, IgA-CIC, IgA-RF, serum beta 2-microglobulin; no patient treated with SCG showed a reduction in proteinuria of more than 50%. At the dosages and for the periods used, 5-ASA and SCG did not show a significant influence on clinical and laboratory parameters of disease in IgAN; other trials with increased dosages are warranted to definitely ascertain the possible therapeutic role of these drugs in IgAN.

Adult↗
PubMed1983

Cytogenetic effects of chemotherapy with three combinations of anti-tubercular drugs involving isoniazid, thiacetazone, para-aminosalicylic acid and streptomycin on human lymphocytes: chromosome aberrations, sister chromatid exchanges and mitotic index.

Cytogenetic effects of three combinations of anti-tubercular drugs were evaluated on human lymphocytes in vivo and were compared with controls of two types: (1) newly diagnosed tuberculosis patients before starting therapy and (2) individuals from the general population. The drugs used were: isoniazid (INH), thiacetazone (TAZ), para-aminosalicylic acid (PAS), and streptomycin (SM). These drugs were tested in the following combinations: (a) INH + TAZ + SM, (b) INH + PAS + SM, (c) INH + SM. The frequency of chromosome aberrations was significantly increased in patients treated with both the triple drug combinations, i.e., with INH + TAZ + SM and INH + PAS + SM, whereas patients treated with INH + SM did not exhibit an increase in the frequency of chromosome aberrations as compared to the controls. Although both the triple drug combinations were clastogenic, none of the three drug combinations tested induced an increase in the frequency of sister chromatid exchanges (SCEs). In other words, the mechanisms leading to SCEs and chromosome aberrations may be different. SM appeared to depress the mitotic index in patients treated with INH + SM and INH + PAS + SM, though it was found to possess a mild anti-clastogenic effect. INH + TAZ + SM, on the other hand, enhanced the mitotic index. This enhanced mitotic index was probably due to the presence of TAZ.

Aminosalicylic Acid↗
PubMed1995

A controlled double blind multicenter study of the effectiveness of 5-aminosalicylic acid in patients with Crohn's disease in remission.

We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohn's disease. Included were 59 patients who had proven Crohn's disease of at least 1 year's duration, and who had been in continuous remission for at least 6 months, while taking only 5-aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohn's disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohn's disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years.

Adolescent↗
PubMedDate not supplied

Scavenging effect of 5-aminosalicylic acid on neutrophil-derived oxidants. Possible contribution to the mechanism of action in inflammatory bowel disease.

Inflammatory phagocytic leukocytes produce superoxide and hydrogen peroxide and secrete myeloperoxidase (MPO) into the extracellular medium. MPO catalyzes the oxidation of Cl- by H2O2 to yield chlorinated oxidants (e.g. HOCl and NH2Cl), which have been shown to induce pathologic changes in mucosal function. We examined the ability of 5-aminosalicylic acid (5-ASA), a drug used to treat inflammatory bowel disease (IBD), to inhibit oxidation of L-cysteine by NH2Cl, HOCl and H2O2. NH2Cl and HOCl were especially strong oxidants against L-cysteine. 5-ASA prevented L-cysteine oxidation by NH2Cl and HOCl; an interaction associated with the formation of characteristic absorption spectra due to the oxidation of 5-ASA was observed. NH2Cl and HOCl evoked characteristic increases in short-circuit current (Isc), indicative of net electrolyte transport, when added to the serosal side of stripped rat colon mounted in Ussing chambers. Premixing of NH2Cl with 5-ASA 10 min before addition to the tissue markedly reduced the secretory response to NH2Cl. In contrast, 5-ASA immediately reduced the response to HOCl. The reduction in the functional response to NH2Cl and HOCl by 5-ASA may contribute to its mechanism of action in the treatment of the symptoms of IBD.

Aminosalicylic Acids↗
PubMed1975

Mutational studies of the drug-resistance of M. tuberculosis with special reference to p-aminosalicylic acid, ethambutol, isoniazid and rifampicin.

In the M. tuberculosis H37Rv and in the human tubercular strains isolated from patients, the localization of genetic determinants of drug-resistance to antitubercular chemotherapeutic drugs in current use was studied. Data obtained through the treatment of the resistanct strains with acridine dyes and ethidium bromide, and the analysis of irreversible elimination of resistance markers support the hypothesis of an extrachromosomal locus for the p-aminosalicylic acid (PAS)-resistance and confirm a chromosomal mutation for the isoniazid (INH), ethambutol (EM), rifampicin (R/AMP)-resistances, in all the levels reached in training or selected in wild strains. In the PAS-revertants recovered after treatment with mutagenic agents, a loss by degrees of resistance levels was observed. In a mycobacterial strain biresistant to PAS and streptomycin (Sm) the Authors were able to find a loss of the mono-resistance to Sm only. The significance of these results is discussed in terms of plasmid (s) having separate mutational loci for PAS- and for the aminoglycoside-resistance. These results agree with the previous studies in the field of resistance of Mycobacteria to specific drugs.

Aminosalicylic Acids↗
PubMed1987

Keratoconjunctivitis sicca in the dog following 5-aminosalicylic acid administration.

1 Keratoconjunctivitis sicca (KCS) is an inflammatory eye condition, affecting the cornea and conjunctiva, caused by a deficiency in the aqueous fraction of tears. The condition is relatively common in the dog with a varied aetiology. A number of drugs have been implicated in the production of KCS in the dog including salicylazosulphapyridine (sulphasalazine). 2 This paper details clinically evident KCS in a 12-month oral toxicity study with 5-aminosalicylic acid (5-ASA), the therapeutically active metabolite of sulphasalazine. 3 The condition was first diagnosed at study week 22 and subsequently progressed both in incidence and severity. There was a distinct sex-difference in the response, with treated females being more affected than males. 4 There was a close correlation between the production of KCS and reduced lacrimation as assessed by the Schirmer tear test. 5 Although sulphasalazine causes KCS in dogs there have been no reports of ocular lesions of this type in man with this drug. It is highly probable that the dog is not a predictive model for man with regard to KCS induction by sulphasalazine or its metabolite 5-ASA.

Aminosalicylic Acids↗