Preterm labor: current tocolytic options for the treatment of preterm labor.
Mesalamine had positive effects which were not statistically significant on bursting pressure and statistically different significant effects on hydroxyproline (HP) levels based on the way of administration and statistically significant positive effects on histopathologic anastomotic healing in experimental anastomosis model.
Although sulfasalazine, a 5-aminosalicylic acid (5-ASA) agent, is still the anti-inflammatory agent of choice for ulcerative colitis and Crohn's disease, newer formulations, which release drug to specific regions of the colon for maximal efficacy, also can be appropriate first-line agents. This article reviews recent clinical studies of therapy with older and newer 5-ASA formulations.
The aim of the present study was to develop a multi-unit dosage form containing 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC), optimised on the basis of recent studies indicating that UC patients have higher intestinal pH than was previously thought to be the case. Pellets with a drug content of 77.4% were prepared by a granulation and spheronization process and then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit((R)) FS 30D) to achieve site specific drug release close to the ileocecal valve. Dissolution tests were carried out in a paddle dissolution apparatus in media simulating pH conditions at various locations in the gastrointestinal tract. The pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release was found to be zero order, while at pH 6.5 and below no release occurred. In a biorelevant medium which simulates the fasting proximal small intestine fluid it was shown that neither surfactants (sodium taurocholate and lecithin) nor changes in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the well established Eudragit((R)) S, and to currently marketed products licensed for the treatment of UC, the multi-unit dosage form coated with the new polymer exhibited an in vitro dissolution profile more appropriate to the pH profile of the ileum and the colon observed in UC patients.
Intravenously transplanted MSCs migrate and distribute to the colon to effectively alleviate the symptoms of UC, while G-CSF enhances this effect via an anti-inflammatory effect and improvement in the pathologic features of UC. G-CSF may be a promising therapeutic regulator of MSCs that can improve therapeutic outcomes in patients with UC.
46 steroid refractory patients with active UC and a mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9-23) were treated with nIFN-beta in addition to existing basic medication (5-ASA/SASP plus corticosteroids). During an induction period of eight weeks, 18 patients (group A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta daily intravenously as a bolus injection. Patients who achieved complete remission (decrease of CAI to < or = 4) during the induction period received maintenance therapy with nIFN-beta at the same dose level three times a week and corticosteroids were withdrawn. Remissions and maintenance of remissions were evaluated.
Two patients with ulcerative colitis and a past history of allergic reactions to sulfasalazine had similar reactions when treated with 5-aminosalicylic acid. This suggests that, at least in some patients, the adverse effects of sulfasalazine are due to 5-aminosalicylic acid rather than sulfapyridine. Desensitization to sulfasalazine was successfully carried out in one patient but was not attempted in a second.
The goals for the management of acute ulcerative colitis are the objective evaluation of disease activity, induction of remission, prevention of relapse and treatment of complications. Clinical practice should be guided by simple activity indices, as it is easy to underestimate severity. For the induction of remission, topical treatment with mesalazine (mesalamine) is appropriate initial therapy for distal disease but, if symptoms persist for over a fortnight, decisive treatment is usually appreciated by the patient. For mild to moderate disease, corticosteroids have been the mainstay in Europe, although high-dose aminosalicylates (such as Pentasa, 4 g orally daily and 1 g rectally) are an alternative for symptoms not interfering with daily activity. Novel therapeutic approaches in ulcerative colitis have lagged behind those used for Crohn's disease, but several (epidermal growth factor, RDP 58, basiliximab, leucocytapheresis) are on the horizon. Severe colitis, defined as a bloody stool frequency of more than six per day with any one of tachycardia (pulse > 90 beats/min), temperature (> 37.8 degrees C), anaemia (haemoglobin < 10.5 g/dL) or raised erythrocyte sedimentation rate (> 30 mm/h), is an indication for intensive intravenous treatment. National UK figures indicate that 30% of ulcerative colitis cases progress to colectomy, and objective criteria for predicting the need for colectomy have been validated. The timing of colectomy is the most important decision that a physician is called upon to make, in conjunction with the patient and surgical colleagues. For the maintenance of remission, aminosalicylates continue to be first-line therapy, although the choice of 5-aminosalicylate appears to be influenced as much by geography as by theoretical considerations. Steroids have no place in the maintenance of remission. Indications for azathioprine include patients after a severe relapse of ulcerative colitis, those with early relapse after steroids (dose of < 15 mg/day, or within 6 weeks of stopping) and those needing a second course of steroids within a year. Therapeutic decisions should have a strategy, aimed at navigating the patient around relapses and through to sustained remission. Good management depends on clinical skills, compassion and care of the individual, in addition to pharmaceuticals.