ABSTRACT
Background: Inflammatory bowel disease usually presents with gastrointestinal stigmata of weight loss, anaemia, and rectal bleeding, but may exhibit prominent extra-intestinal manifestations also such as joint symptoms, skin signs and some other auto-immune manifestations. During the last few years many authors have reported serious complications of IBD manifesting in the Ear-Nose-Throat (ENT) and influencing disease morbidity. Methods: Twenty four patients with active ulcerative colitis (mean age 45 years) were recruited prospectively along with 24 healthy age- and sex-matched controls. Otoscopy, tympanometry and pure tone audiometry were performed. Otoscopy and tympanometry were normal in all patients and controls. Pure tone audiometry showed sensorineural hearing loss over all frequencies in patients with inflammatory bowel disease and compared with controls. The otologic data including age of onset, family history of otologic problems, exposure to noise and audiometric findings were also reviewed. Results: Out of 48 patients with a history of IBD, 24 had documented SNHL, 17 of these patients had a diagnosis of ulcerative colitis and 7 had Crohn’s disease. 22 patients had bilateral SNHL, and 2 patients had unilateral SNHL. Tinnitis were the most common associated aural complaint. Conclusion: Sensorineural hearing loss is very unusual finding, possibly of auto-immune aetiology. We recommend steroid or immunosuppressive therapy in such a patient. Evidence for an autoimmune basis for this condition is reviewed and the potential benefit of systemic corticosteroids emphasized.
ABSTRACT
The prodrugs (glyceride derivatives) 3a and 3b of diclofenac were prepared by reacting 1, 2, 3-trihydroxy propane-1,3-dipalmitate/stearate with the acid chloride of diclofenac as potential prodrugs to reduce the gastrointestinal toxicity associated with them. These prodrugs were evaluated for their ulcerogenicity, anti-inflammatory and analgesic activity. It was found that the prodrugs were significantly less irritating to the gastric mucosa as indicated by severity index of 0.86, 0.78 compared to 1.6 of diclofenac. The prodrugs 3a and 3b showed better anti-inflammatory and analgesic activity than the parent drugs. The hydrolysis of prodrugs 3a and 3b were studied at pH 3, 4, 5 and 7.4. The HPLC analysis showed that the prodrugs were resistant to hydrolysis at pH 3, 4 and 5 indicating that they did not hydrolyze in acidic environment, whereas at pH 7.4 the prodrugs readily released the parent drug in significant quantities. The plasma levels of diclofenac were also analyzed by HPLC in rats after single oral dose of the prodrugs. The results indicated that the parent drugs were readily released. The concentration of diclofenac during the study was found higher in animals treated with prodrugs 3a and 3b compared with animals treated with diclofenac. The concentration of diclofenac was found to be 38.59, 33.6 and 30.36 microg/ml in animals treated with prodrugs 3a, 3b and diclofenac respectively. In conclusion, all these studies indicated that the glyceride prodrugs of diclofenac might be considered as potential biolabile prodrugs of diclofenac.