[Aerosol administration of para-aminosalicylic acid].
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Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease.
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Two cases of chronic manganese poisoning were treated with sodium para-aminosalicylic acid (PAS-Na; 6 g/day in 500 ml of 10% glucose solution by intravenous drip). The results indicated that one had been clinically cured and that the other had obviously improved in clinical symptoms and signs. Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning.
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Since the discovery that 5-aminosalicylic acid (5-ASA) is the active moiety of sulphasalazine in the treatment of chronic inflammatory bowel disease, several new 5-ASA based drugs have been developed. These consist either of slow- or delayed-release formulations of plain 5-ASA or sulpha-free azo compounds of 5-ASA. The different formulations and compounds have varying bioavailabilities, which makes it possible to use them alternatively in different clinical situations. A review of the literature is given, together with suggestions as to how the new drugs might be used in different clinical situations.
BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.
Gastrointestinal transit of an enteric-coated, delayed-release 5-aminosalicylic acid tablet radiolabelled with indium-111 has been monitored in a preliminary study with eight healthy subjects using gamma scintigraphy. Gastric emptying of the tablet was delayed by the presence of food in the stomach. Disintegration occurred about 5 hours after the tablet left the stomach. There was close agreement between the tablet disintegration times and the initial detection of drug in the blood. The site of disintegration could be established in most instances; approximately 80% of the doses resulted in drug dispersion within the ascending colon. The coated tablets provide an effective means of drug delivery to the proximal colon.
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The activities of six derivatives of a new class of isonicotinoylhydrazones were investigated in vitro against Mycobacterium tuberculosis H37Rv ATCC 27294, isoniazid-resistant M. tuberculosis ATCC 35822, rifampicin-resistant ATCC 35838, pyrazinamide-resistant ATCC 35828, streptomycin-resistant ATCC 35820 and 16 clinical isolates of M. tuberculosis. Several compounds showed interesting antimycobacterial activity against both ATCC strains and clinical isolates, but were less active against isoniazid-resistant M. tuberculosis. Combinations of five isonicotinoylhydrazone derivatives and rifampicin, ethambutol, para-aminosalicylic acid, isoniazid and clofazimine were also investigated against M. tuberculosis H37Rv ATCC 27294 and against ATCC drug-resistant strains. Addition of sub-MICs of some isonicotinoylhydrazone derivatives resulted in a four- to 16-fold reduction in MICs of ethambutol, para-aminosalicylic acid and rifampicin with fractional inhibitory concentrations (FICs) ranging between 0.17 and 0.37, suggesting a synergic interaction against M. tuberculosis H37Rv. Increased activity was also observed with other combinations (FICs 0.53-0.75), including isoniazid, and a synergic interaction between one of the isonicotinoylhydrazone derivatives and isoniazid (FIC 0.26) was shown against isoniazid-resistant M. tuberculosis ATCC 35822, whereas no effects were observed on combining the isonicotinoylhydrazones with clofazimine. The ability of isonicotinoylhydrazones to inhibit specifically the growth of M. tuberculosis, the high selectivity index and their ability to enhance the activity of standard antituberculous drugs in vitro indicate that they may serve as promising lead compounds for future drug development for the treatment of M. tuberculosis infections.
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