From basic science to future medical options for treatment of ulcerative colitis

There is little information concerning the incidence of alveolar bone loss in estrogen-deficient women. Ovariectomized sheep are valid models for study of the effects of estrogen deficiency on bone metabolism. The objective of this study was to compare alveolar bone loss in control (C) and ovariectomized sheep (OVX) at 3 and 12 months following surgery. OVX animals had decreased serum levels of 17-beta-estradiol and increased serum levels of osteocalcin, IL-6, and urinary levels of deoxypyridinoline which, taken together, suggest development of osteoporosis. The mean probing depths and percentage of sites with pocket depths 4 to 6 mm and > 6 mm were significantly greater in OVX than C at each time period and in OVX were significantly greater at 12 months that at 3 months. Gingival tissue interleukin-6 (IL-6) levels (but not the number of IL-6(+) cells) were elevated adjacent to deep periodontal pockets; however, there was no significant elevation of levels of the proinflammatory cytokines IL-1 beta and IL-8 within gingiva. Taken together, the data suggest a systemic contribution for progression of periodontal disease associated with estrogen deficiency. This may involve upregulation of systemic IL-6 synthesis and transfer to gingiva in serum, resulting in enhanced IL-6 accumulation within the gingival tissues or reduced bone density allowing for a greater amount of alveolar bone loss.     

Guidelines for the treatment of ulcerative colitis in remission

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.     

Cyclosporin for the treatment of severe ulcerative colitis

The effect of cyclosporin was evaluated in six patients with severe ulcerative colitis not responding to at least 8 days of standard therapy with intravenous corticosteroids. Cyclosporin (5-7.5 mg/kg/day intravenously) was added while steroid therapy was continued. Five of 6 patients responded after a mean of 7 days and colectomy was not necessary. After 4 weeks three patients achieved clinical remission or had mild symptoms and were weaned from cyclosporin and corticosteroids without exacerbation within the next 7-15 months. Two patients improved and they were put on oral cyclosporin. One of them relapsed after 2 weeks and then responded to high dose corticosteroids. This patient is doing well at 8 months of followup on azathioprine and steroids. One patient stopped oral cyclosporin after 3 months abruptly and then had a relapse. He subsequently improved while refusing any medical therapy. Side effects of cyclosporin occurred in 2 patients but were mild and self limited and did not necessitate discontinuation of the drug. Cyclosporin appears to be effective in a large portion of patients with severe ulcerative colitis who failed to improve on corticosteroids and in whom colectomy would otherwise be considered.     

The topical treatment of distal ulcerative colitis

Two patients with the acquired immunodeficiency syndrome (AIDS) developed psoriasis, one of them presenting the more severe form and the other one the milder form of the disease, were treated with zidovudine per oral via, 200mg 3 times a day. In the first case the therapeutical response was complete. No lesion was verified in the patient after 9 months under maintenance schedule. In the second case, despite the response being clear, after 6 months of treatment, the patient still presented furfuraceous scalings at limbs ever under the medication schedule.     

Ulcerative colitis: medical treatment

Ulcerative colitis is a chronic inflammatory disease of unknown etiology, affecting the mucosa of the rectum and a variable length of colon. There is no medical cure for this disease, however medical therapy offers comfort to the majority of patients and improves their lives. Medical therapy including newer drugs is here reviewed.     

Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis

AIM: To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis. PATIENTS AND METHODS: Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks. RESULTS: Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a nonsignificant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator's global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine. CONCLUSION: Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.     

Risk factors in ulcerative colitis

In 504 Jewish patients with ulcerative colitis the following risk factors were evaluated: sex, age at onset of disease, community group, extent of disease, and duration of disease. The disease was more severe in females. Severe attacks, weight loss, iron deficiency, liver disease and arthritis were significantly more frequent in females than in mles. Mortality was higher in patients who contracted the disease above age 50. The disease appeared to be more severe in patiets of Ashkenazi origin as compared to Orientals. The difference failed to reach statistical signifcance except for mortality. We confirmed the well-known adverse effect of extensive colonic involvement. Severe attacks, a severe course of the disease and extensive colonic involvement are more frequent with increasing duration of the disease.     

X-ray symptoms in ulcerative colitis

Barium enema studies in 200 patients with ulcerative colitis were analyzed according to radiological symptoms. The results of the radiological examination were compared with those of rectoscopy and biopsy. In about 75 per cent of patients good agreement was achieved.     

Nephrotic syndrome in ulcerative colitis

Complicating disorders in various organs outside the intestinal tract are common in ulcerative colitis. This report deals with the occurrence of nephrotic syndrome in two patients with long-standing ulcerative colitis. In the patient studied in most detail, 2 episodes have taken place, the first developing into uremia. After colectomy had been performed, rapid improvement of renal function took place. The morphological changes in kidney biopsies were compatible with the presence of focal glomerular sclerosis. Activity in the complement system and a favorable response to steroid treatment indicate that humoral immune mechanisms are of pathogenetic importance with regard to the renal disease in these two patients. To our knowledge nephrotic syndrome has not previously been described as a complication to ulcerative colitis.     

Appendiceal inflammation in ulcerative colitis

The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC50 values of 0.06-5.5 microM.     

Use of parenteral feeding in the multimodality treatment of Crohn's disease and nonspecific ulcerative colitis

The paper reviews publication on the use of complete parenteral feeding in the multimodality treatment of inflammatory bowel disease. Complete parenteral feeding was performed in patients with skeletization and physical retardation, in severe diseases, in inefficiency or intolerance of conventional therapy with sulfanilamides and steroids, in those who had intestinal fistulas, as well in the preparation of patients for surgical treatment. The use of complete parenteral feeding, under the above circumstances allow one to achieve persistent remission, spontaneous healing of intestinal fistulas, elimination of abnormal metabolism, nutrition, constitution, water-electrolyte balance, to reduce a surgical risk and the incidence of postoperative complications and the length of patients' hospital stay.