[Studies on the metabolism of para-aminosalicylic acid in the body. VI. Absorption, tolerance and therapeutic effect of Napashin in double gastro-enteric coating].
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Tissues from 6 operation specimens were incubated at 37 degrees C for 30 min +/- ricinoleic acid 6.25-100 micrograms/ml. PAF was determined in the incubates by scintillation proximity assay (Amersham) after extraction and purification. No PAF was detected in control samples (less than 0.4 ng/g/30 min), whereas ricinoleic acid 12.5-100 micrograms/ml stimulated PAF output (18.3 +/- 2.1 ng/g/30 min, mean +/- sem). 5-ASA 25-100 micrograms/ml caused a 5-100% inhibition of the PAF release by 50 micrograms/ml ricinoleic acid. The authors conclude that PAF can be released by damage to human colonic mucosa/submucosa, and that the inhibition of PAF release in ulcerative colitis may at least partly explain the therapeutic effect of 5-ASA.
Enemas containing 1000 mg 5-ASA were administered to patients with active distal colitis in three separate studies: as a single dose in a neutral solution (pH 7.4); as a single dose in a slightly acidic, buffered suspension (pH 4.8); and as multiple doses once a day for 10 days with the acidic enema. 5-ASA was relatively rapidly absorbed from the neutral solution, resulting in plasma concentrations of 5-ASA sometimes two to three times higher than those found after peroral salazosulphapyridine (SASP) treatment. In contrast, absorption from the acidic enema was reduced and/or prolonged, giving plasma concentrations similar to those found during oral SASP treatment. After repeated doses of the acidic enema, plasma concentrations after an enema resembled those seen after the single dose. Urinary excretion was significantly lower, suggesting a reduced fraction of absorption at steady-state conditions. No side effects were observed, and no local irritation was reported. An acidic buffer suspension with 5-ASA seems to be safe for use as enema and deserves further clinical testing for treatment of distal ulcerative colitis.
The preparation of quaternary ammonium derivatives of sulfanilamide and of tertiary amines containing an aliphatic chain up to c-18 is described. Some members of this series show greater antimicrobial activity than the parent substances. This is found also in comparison with other analogous series which have been prepared.
In a comparison of home and sanatorium treatment for tuberculous patients in India, pretreatment cultures of tubercle bacilli showed a higher average level of resistance to p-aminosalicyclic acid (PAS) than pretreatment cultures from a representative sample of patients in Great Britain. The investigation described in the present paper was therefore undertaken to find out the nature of the difference in the PAS sensitivity of cultures from Indian and British patients. In this investigation, carried out jointly at the Tuberculosis Chemotherapy Centre, Madras, and the Postgraduate Medical School of London, sputum specimens from 147 Indian and 93 British patients were cultured and subjected to sensitivity tests. The tests were set up on slopes containing various concentrations of PAS and inoculated with 10(5) viable units of the cultures, and the minimal concentrations of PAS inhibiting the growth of 20, 50 and 100 colonies were determined. According to the 20-colony end-point-the one commonly used in routine sensitivity tests-the Indian strains were significantly more resistant than the British strains. This difference in sensitivity was not apparent, however, in either the 50-colony or the 100-colony results. The presence of a small proportion of resistant organisms was found to be a general characteristic of the Indian strains, but did not appear to be related to any special tendency for the patient to fail to respond to treatment with PAS. Since a chance increase in the inoculum size might well affect the 20-colony results, the authors recommend a tenfold decrease in the size of the inoculum used in routine PAS-sensitivity tests on Indian patients.
An 81-year-old women presented with monstrous subcutaneous mobile masses on the ventral and ventrolateral surfaces of her thighs. Radiography as well as computer tomography showed extensive soft tissue calcifications. We interpreted these alterations as dystrophic calcinosis cutis, most likely resulting from repeated subcutaneous PAS infusions for the treatment of pulmonary tuberculosis.
The mechanism of action of 5-ASA and its derivatives remains obscure. The most likely mechanisms would appear to be an interrelationship between local production of eicosanoids and reactive oxygen metabolites, in conjunction with activated neutrophils, though the nature of the initial triggering factor/s remains to be determined. The possibility that bacterial-derived chemotactic peptides, such as FMLP, might be a triggering factor is an attractive possibility, made possible by an underlying defect in mucosal permeability.
The aim of the study was to compare the efficacy and side-effects of 5-ASA and SASP in the treatment of active ulcerative colitis. An improvement was seen in 71.4% (5-ASA) and 70.3% (SASP) but there were no complete remissions. The incidence of improvements was only 36.3% (5-ASA) and 37.5% (SASP) in pancolitis. The side-effects appeared in 14.2% (5-ASA) and 21% (SASP).
A case of acute renal failure with characteristics of interstitial nephritis associated to treatment with mesalazine (5-ASA bound to resin) in a 26-year old patient with a 7-year history of Crohn's disease is presented. The patient had been previously treated with 5-ASA with no alterations in renal function being observed. Renal failure became manifest several days after initiation of maintenance therapy with 5-ASA during the latest outbreak of intestinal inflammatory disease and disappeared upon suppression of the drug.
A controlled trial has been carried out in order to compare the efficacy of enemas containing a high dosage of 5-ASA (4 g) versus enemas containing hydrocortisone 100 mg. The trial was conducted on 86 patients, 44 of whom received 5-ASA and 42 received hydrocortisone. The results were favorable in terms of clinical, sigmoidoscopic, and histologic criteria for 5-ASA treatment. Other aspects have been investigated, such as retrograde spread of enemas which have been shown to reach the left colon. No nephrotoxicity was detected. The long term experience confirmed the preliminary positive results.
In an open clinical trial 71 patients with ulcerative colitis and 27 patients with Crohn's disease were treated with mesalazine (5-ASA). After four to eight weeks of acute phase treatment, maintenance therapy was ensued by treatment over a period of maximal 48 weeks. The activity of both inflammatory bowel disease clearly decreased. Relapse was not observed during maintenance treatment in ulcerative colitis. Pathological changes of clinical findings were not observed during treatment. Pathologic changes before treatment, which were associated with the disease, returned to normal during treatment. All potential side effects during treatment were recorded. The rate of side effects was low and all normalized when therapy was continued. The study confirms that mesalazine was safe, efficient and almost well tolerable.
We report results of a prospective study of daily 5-ASA enema therapy in patients with proctocolitis that was unresponsive to conventional therapy. Forty-seven patients with active colonic inflammation distal to the splenic flexure have been followed for three months to three years. Rapid improvement was noted within three months in 41 of 47 (87%) patients, while six failed therapy. Of the 41 patients responding to therapy, 39 achieved complete remission. Nineteen patients have relapsed at least once following discontinuation of 5-ASA, but 23 of 25 (92%) relapse episodes responded to a course of 5-ASA therapy. Complications of 5-ASA therapy were limited to hemorrhoidal irritation and local perianal injury. We conclude that 5-ASA enema is effective in inducing remission in patients with proctocolitis unresponsive to conventional therapy.