Immunoregulation of Inflammatory and Inhibitory Cytokines by Vitamin D3 in Patients with Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of vitamin D3 in patients with IBD exerts both direct and indirect regulatory roles on the naïve T cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of vitamin D3 on naïve T cells result in the proliferation of more regulatory T cells and inhibitory cytokines such as IL-4, IL-10 and IL-5. The binding of vitamin D to dendritic cells (DCs) through vitamin D receptors inhibits the action of IL-12 on DCs, resulting in the downregulation of Th1 and Th17. On the other hand, this interaction favours Th2 and Treg upregulation and facilitates the maintenance of immune homoeostasis between inflammatory and inhibitory cytokines which is essentially significant in the management of patients with IBD. The aim of this review was to explore the current and mounting scientific evidence on the roles of vitamin D3 in immunoregulation of inflammatory and inhibitory cytokines in patients with IBDs. An extensive literature search was conducted using keywords such as Vitamin D3*, IBD*, inflammatory cytokines*, inhibitory cytokines*, naïve-T-cells* and antigen presenting cells* through PubMed, SCOPUS and MEDLINE search engines. The results of the accumulated bodies of research that have been conducted demonstrate that vitamin D3 plays a major role not only in the immunoregulation of cytokines involved in the pathogenesis of IBDs but also in many other inflammatory disorders.

Immunomodulatory and Immunosuppressive Roles of 1α,25(OH)2D3 in Autoimmune Diseases.

Autoimmune diseases are pathological conditions characterized by abnormal responses, accompanied by autoantibodies to self-molecules. The role of vitamin D in autoimmune diseases has increased significantly in the recent past from its functions in calcium and phosphate homoeostasis, and it is now involved in the regulations and proliferations of Th1 and Th17 lymphocyte. 1α,25(OH)2D3 is very important in ameliorations of inflammatory disorders arising from autoimmune diseases, but the mechanism by which this is performed is still a bone of contentions. This review aimed to highlight the existing facts about the roles of Vitamin D in the treatment and management of autoimmune diseases. An extensive online literature search was conducted using PubMed, MEDLINE and Scopus. Accumulated bodies of research evidence are available which demonstrates that Vitamin D has a very important part to play in the regulation of immune responses in autoimmune diseases. Some of the authors suggested that Vitamin D3 carry-out its immunosuppressive and immune modulatory action, through its actions on antigen-presenting cells and activated T and B cells with the help of Vitamin D receptors present on the each of these cells. Vitamin D supplementation assists in autoimmune disorders by making qualitative and quantitative changes in the immune system (downregulation of Th1 and upregulations of Th2 cells). This resulted in the body to be more tolerant of self and less likely to mount autoimmune responses.

Irritable bowel syndrome: a review article.

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder noted in the general population worldwide. Its chronic nature, signs and symptoms which vary periodically from mild to severe have many negative effects on the quality of life for the sufferer; therefore the appropriate treatment of these patients is highly important. Patients should be informed by their doctors that the nature of the disease is benign, and educated on how to deal with and control symptoms of the disease. This article sets out a review of recent studies on the prevalence of IBS in Iran and appropriate methods for management of patients affected by IBS.

Clinical trial: the effect of amitriptyline in patients with diarrhoea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome is the most common disorder diagnosed by gastroenterologists. Although several randomized-controlled trials have assessed the therapeutic role of antidepressant drugs, there is insufficient evidence to support their use. AIM: To compare the effects of low-dose amitriptyline in the treatment of diarrhoea-predominant irritable bowel syndrome in a double-blind randomized-controlled trial. METHODS: Fifty-four patients who fulfilled Rome II criteria for diarrhoea-predominant irritable bowel syndrome were included in this study. Organic causes were ruled out by standard laboratory and radiological tests, and rectosigmoidoscopy. Patients were randomly assigned to receive either 10 mg amitriptyline daily or placebo. Subjects were followed up for 2 months and symptoms were assessed using a questionnaire. Intention-to-treat and per-protocol analysis was performed. RESULTS: Fifty patients completed the study. At 2 months, the amitriptyline group showed greater (P < 0.05) reduction in the incidence of loose stool and feeling of incomplete defecation. Patients receiving amitriptyline showed greater complete response, defined as loss of all symptoms, compared with those receiving placebo (68% vs. 28%, P = 0.01). Adverse effects were similar between the two groups. CONCLUSION: Amitriptyline may be effective in the treatment of diarrhoea-predominant irritable bowel syndrome and at low dose is well tolerated.

The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study.

BACKGROUND: Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness. AIM: To compare the effects of fluoxetine and placebo in the treatment of pain and constipation-predominant irritable bowel syndrome in a double-blind randomized-controlled trial. METHODS: Forty-four cases meeting Rome II criteria for irritable bowel syndrome with predominance of pain and constipation were included in this study. Organic causes were ruled out by detailed history, physical examination, laboratory tests and colonoscopy. Participants were then randomly assigned to receive either fluoxetine or placebo for 12 weeks. Symptoms addressed by the Rome II criteria were recorded during treatment and 4 weeks after termination of treatment. RESULTS: Fluoxetine was significantly more effective than placebo in decreasing abdominal discomfort, relieving feeling and sense of bloating, increasing frequency of bowel movements and decreasing consistency of stool. Mean number of symptoms per patient decreased from 4.6 to 0.7 in the fluoxetine group vs. 4.5 to 2.9 in controls (P < 0.001). CONCLUSIONS: Fluoxetine is an effective and well-tolerated short-term treatment for pain and constipation-predominant irritable bowel syndrome.

Coeliac disease presenting with symptoms of irritable bowel syndrome.

BACKGROUND: Coeliac disease may easily mimic symptoms which are parts of the criteria used for diagnosing irritable bowel syndrome. AIM: To find the frequency of coeliac disease among patients diagnosed as irritable bowel syndrome. METHODS: During a period of one year, irritable bowel syndrome patients referred to a university clinic in Tehran were studied. For each patient, an asymptomatic sibling was enrolled as control. Serological tests for coeliac disease were performed in all patients and controls. If positive, duodenal biopsy was performed to confirm the diagnosis. Patients subsequently diagnosed as coeliac disease were placed on a gluten free diet and re-evaluated after 6 months. RESULTS: One hundred and five cases of irritable bowel syndrome and 105 controls were enrolled. Coeliac disease was diagnosed in 12 of the irritable bowel syndrome patients and none of the controls. Eleven coeliac disease patients adhered to a gluten free diet. After 6 months, all 11 patients had significant improvement in symptoms and three were totally asymptomatic. Six allowed repeated endoscopy after 6 months of gluten free diet, of which five showed improvement in histological findings. CONCLUSIONS: Coeliac disease is a common finding among patients labelled as irritable bowel syndrome. In this sub-group, a gluten free diet may lead to a significant improvement in symptoms. Routine testing for coeliac disease may be indicated in all patients being evaluated for irritable bowel syndrome.

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial.

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.

Second-line Helicobacter pylori eradication with a furazolidone-based regimen in patients who have failed a metronidazole-based regimen.

BACKGROUND/AIM: In developing countries the standard quadruple therapy containing metronidazole results in suboptimal eradication rates of Helicobacter pylori (<75%). In a retrospective study, we undertook to evaluate efficacy and tolerability of a furazolidone-based regimen (omeprazole, furazolidone, bismuth, and tetracycline) in patients who had previously failed the standard metronidazole-based regimen (omeprazole, metronidazole, bismuth, and amoxicillin). METHODS: The records of H. pylori infected patients who were referred to outpatient clinic (from March 1999 to August 1999) and who underwent previous eradication regimens were studied. A total of 320 cases were noted to have received a metronidazole-based quadruple regimen. From these 320 patients, 80 were noted to have failed this regimen based on a urea breath test. These 80 patients were enrolled in the study and given the furazolidone-based regimen. Side effects were assessed at follow-up visits. At least 2 months after the end of each therapy regimen, a (14)C-urea test was performed in each subject to document the cure of the patients. RESULTS: A total of 80 patients (39 males and 41 females) with a mean age of 43.8 +/- (SD) 13.3 years were studied. The H. pylori eradication rate was 90% with the furazolidone-based regimen. The side effects of this regimen were minor. CONCLUSIONS: A furazolidone-based regimen is effective in patients who do not achieve cure of H. pylori infection with the metronidazole-based quadruple therapy. In areas where the metronidazole resistance is high, initial therapy with a furazolidone-based regimen is recommended.

Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease.

OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.

[Peridural morphine administration in restless legs status]. / Peridurale Morphiumanwendung bei Restless-Legs-Status.

The restless-legs syndrome is known to occur in a familial form. The paraesthesias, which are hard to define, are sometimes compared to a painful sensation that can be alleviated only by movement. The pathomechanism of the syndrome and its aetiology are still unknown. A 67-year old patient was admitted as an emergency with most severe pain in her legs. In her family the syndrome occurred in an autosomal dominant form. A long-standing history of abuse of various analgesics was known. Initially the symptoms could not be influenced by any of the various drugs given; even epidural bupivacaine showed no effect. Dramatic relief, however, was obtained by epidural morphine. The maintenance therapy with oral morphine sulfate provided equally good results.