Increased levels of circulating adrenomedullin following treatment with TU­100 in patients with Crohn's disease.

Daikenchuto (TU­100) is a traditional Japanese medicine that is widely used to treat intestinal symptoms. The mechanisms underlying it effects on the circulating levels of adrenomedullin (ADM) are of interest. In addition, the effect of TU­100 in the treatment of Crohn's disease (CD) in humans remains to be elucidated. The primary objective of the present study was to evaluate the effect of TU­100 on the circulating ADM levels in patients with active CD. An additional objective was to assess the effect of the drug on the disease activity and its potential side effects. In an open­label study, 10 patients with active CD received 15 g TU­100 per day for 8 consecutive weeks, and baseline anti­inflammatory therapy was continued. The pre­ and post­treatment blood plasma levels of total ADM (t­ADM) and mature­ADM (m­ADM) were determined using enzyme­linked immunosorbent assays. The response of patients to the treatment was evaluated clinically using the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score. The plasma levels of t­ADM (16.4±1.1 vs. 20.2±1.7 fmol/ml, P=0.0218) and m­ADM (1.7±0.1 vs. 2.2±0.1 fmol/ml, P=0.0284) increased following 8 weeks of TU­100 treatment, compared with control. The IOIBD score of patients also improved, with a significant decrease in the score from 3.9±0.5 at 0 weeks to 2.4±0.4 at 8 weeks (P=0.0284). Out of the 10 components of the IOIBD scoring system, the scores for abdominal pain and tenderness, decreased significantly (P=0.014 and P=0.046). Therefore, TU­100 was safe and well­tolerated by the patients that participated in the current study. The present study determined that the pharmacologic action of TU­100 is associated with changes in the circulating ADM levels and that treatment with TU­100 may aid in the management of CD. These promising findings warrant further investigation in larger, multicenter studies.

Univariate analysis to examine predictors of response to leukocytapheresis in ulcerative colitis patients.

Leukocytapheresis (LCAP) is reportedly effective for the treatment of active ulcerative colitis (UC) and is a therapeutic option for steroid-dependent or steroid-resistant patients with UC. However, a consensus regarding the use of LCAP for UC patients has not yet been established. Therefore, we analyzed patients' records to identify predictors of response to LCAP therapy and subsequent recurrence. Between October 2001 and March 2011, we recruited 41 patients who had been diagnosed as having UC and had received LCAP therapy. Patients diagnosed with moderate to severe UC with left-side or total colitis and received LCAP therapy for the first time were enrolled. We retrospectively performed a univariate analysis using the patients' medical records to identify factors affecting the therapeutic effect of LCAP. Body mass index exceeding 18.5 kg/m(2) was found to influence the therapeutic effect of LCAP. Male sex was correlated with a rapid response to LCAP treatment and the maintenance of remission. UC patients experiencing their first attack or had an elevated C-reactive protein level prior to LCAP therapy exhibited a relatively long remission period. In the "after LCAP therapy" group, a low Rachmilewitz endoscopic score, low erythrocyte sedimentation rate, or high white blood cell count was associated with a long remission period. Our results suggest that LCAP should be performed for the treatment of early-onset UC. LCAP can be expected to induce a long remission period, enabling mucosal healing, although the factors that affected the remission period did not influence the therapeutic effect and responsiveness.

Successful treatment of rectal ulcers in a patient with systemic lupus erythematosus using corticosteroids and tacrolimus.

Systemic lupus erythematosus (SLE) is frequently accompanied by gastrointestinal symptoms. Although all parts of the gastrointestinal tract may be affected, colonic involvement is quite rare. Colonic ulceration, particularly in the rectum, is associated with a high mortality rate in patients with SLE, despite immunosuppressive therapy. While a standard regimen for treating rectal ulcers as a complication of SLE has not been established, combination therapy with steroids and immunosuppressive agents is necessary because of the associated high mortality rate. In this report, we describe a patient with SLE whose condition was complicated with ulcerative lesions in the rectum and sigmoid colon; the lesions were successfully treated with a combination of corticosteroids and tacrolimus therapy. Tacrolimus could be a useful additional or alternative modality for treating rectal involvement in SLE.

Possible diagnostic role of antibodies to Crohn's disease peptide (ACP): results of a multicenter study in a Japanese cohort.

BACKGROUND: Various noninvasive tests have been studied to screen for patients with Crohn's disease (CD), and were found to have limited accuracy and sensitivity, particularly in Asian populations. The aim of our study was to explore the possible diagnostic utility of antibodies to the CD peptide (ACP) in patients with CD. METHODS: In a multicenter study using enzyme-linked immunosorbent assay, serum ACP levels were determined in 196 patients with CD, 210 with ulcerative colitis, 98 with other intestinal diseases, 132 with other inflammatory diseases, and 183 healthy controls. and then examined for correlation to clinical variables. The diagnostic utility of ACP was evaluated by receiver operating characteristics analysis and compared with anti-Saccharomyces cerevisiae antibodies (ASCA). RESULTS: ACP levels were significantly elevated in the CD patients, but not in the other groups that included UC, other intestinal diseases, other inflammatory diseases and the healthy controls. Among these other groups, ACP levels were not significantly different. In the CD patients, ACP had a higher sensitivity and specificity (63.3 and 91.0 %, respectively) than ASCA (47.4 and 90.4 %). ACP levels were negatively associated with disease duration, but not with CDAI, disease location, or medical treatment. CONCLUSIONS: ACP, a newly proposed serologic marker, was significantly associated with CD and was highly diagnostic. Further investigation is needed across multiple populations of patients and ethnic groups, and more importantly, in prospective studies.

Cronkhite-Canada syndrome complicated with multiple gastric cancers and multiple colon adenomas.

BACKGROUND: We experienced a case in which Cronkhite-Canada Syndrome presented with complications of multiple gastric cancers and multiple colon adenomas. CASE REPORT: Our case is a 64-year-old male who visited a nearby hospital with diarrhea and weight loss. The patient was anemic and hypoproteinemic, with multiple polyps in the stomach, duodenum, and large intestine. He also presented with alopecia, onychatrophia, cutaneous pigmentation, and dysgeusia, and was diagnosed with Cronkhite-Canada Syndrome. Follow-up examinations found multiple gastric cancers and colon adenomas. We performed a total gastrectomy and a polypectomy of the large intestine lesions, revealing 4 well-differentiated adenocarcinomas in the resected stomach, and tubular adenomas in the large intestine lesions. Intraoperative findings included scattered melanoid pigmentation on the mesentery and the small intestinal wall. Tumor cells were positive for p53 and Ki67 and partially positive for MUC5AC and MUC2. Cronkhite-Canada Syndrome polyps are generally classified as juvenile type polyps, and these polyps rarely become cancerous. However, of the 383 cases of Cronkhite-Canada Syndrome reported in Japan, complications of gastric cancer were found in 39 cases (10.2%), and only 8 cases with multiple gastric cancer were reported in Japan. including the cases we have personally experienced. There were only two English literatures on Cronkhite-Canada Syndrome complicated with gastric cancer. So it is necessary to notify this information of Cronkhite-Canada Syndrome to the world. CONCLUSIONS: Close gastrointestinal examination and strict follow-up are believed to be essential for Cronkhite-Canada Syndrome patients.

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: effects of leukocytapheresis.

Complementary DNA microarray technology allows the simultaneous analysis of the expression of hundreds to thousands of genes. We applied this technique to clarify the molecular mechanisms underlying the therapeutic effects of leukocytapheresis (LCAP) therapy in patients with ulcerative colitis (UC). A 776-gene microarray analysis was performed using whole blood cells from six normal subjects and six patients with active UC who had undergone filtration LCAP. Widespread gene upregulation was observed in patients with UC, compared with normal subjects. After LCAP, genes with proinflammatory actions, such as CD97, CD74, human leukocyte antigen-DRß1 and -DP light chain, were downregulated, while genes responsible for antimicrobial actions, such as neutrophil gelatinase-associated lipocalin, and acute phase reactions, such as haptoglobin α1S and α1-acid glycoprotein, were upregulated. In conclusion, we identified several genes expressed in the whole blood cells of UC patients as well as the transcriptional events following LCAP. Following LCAP, the gene profile shifted toward a pattern indicating disease improvement. These results suggest a basis for the molecular mechanisms leading to the therapeutic effects of LCAP and also indicate new therapeutic targets, providing important prognostic information.

A new therapeutic approach using a schizophyllan-based drug delivery system for inflammatory bowel disease.

Antisense technologies for the targeted inhibition of gene expression could provide an effective strategy for the suppression of inflammation. However, the effective use of antisense oligonucleotides (ODN) has been limited because of several problems. Therefore, a delivery system for antisense ODNs that enhances antisense stability, while maintaining the specificity of antisense for its target RNA or DNA is needed. We have developed a delivery system for antisense ODN using schizophyllan (SPG), a polysaccharide that belongs to the ß-(1-3) glucan family. This system has several advantages enabling the effective suppression of targeted RNA or DNA: the SPG complex is stable in vivo and does not dissolve in the presence of deoxyribonuclease, and the SPG complex is effectively taken up into macrophages by phagocytosis through Dectin-1. Macrophage-migration inhibitory factor (MIF), which is mainly produced by macrophages has been shown to have a pathogenetic role in inflammatory bowel disease (IBD). We developed a technique to create an SPG complex that highly conformed to the antisense MIF. The administration of antisense MIF/SPG complex effectively suppressed MIF production and significantly ameliorated intestinal inflammation. Our result demonstrated a possible new therapeutic approach, i.e., the administration of antisense MIF/SPG complex, for the treatment of IBD.

Study on simultaneous speciation of arsenic and antimony by HPLC-ICP-MS.

A method was developed for the simultaneous speciation of arsenic and antimony with HPLC-ICP-MS using C30 reversed phase column. Eight kinds of arsenic compounds (As(III), As(V), monomethylarsonic acid (MMAA), dimethylarsinic acid (DMAA), arsenobetaine (AB), arsenocholine (AsC), trimethylarsine oxide (TMAO) and tetramethylarsonium (TeMA)), Sb(III) and Sb(V) were simultaneously separated by the special mobile phase containing ammonium tartrate. Especially for the species of organic As, a C30 column was better than a C18 column in the effect of separation. Limits of detection (LOD) for these elements were 0.2 ng ml(-1) for the species of each As, and 0.5 ng ml(-1) for the species of each Sb, when a 10 microl of sample was injected, respectively. The proposed method was applied to a hot spring water and a fish sample.