Ulcerative Colitis: Sasaki M

Sasaki M, Fujiyama Y. · Department of Gastroenterology, Shiga University of Medical Science. · Nippon Rinsho. · Pubmed #15954431 No free full text.

This publication has no abstract.

Tsujikawa T, Urabe M, Bamba H, Andoh A, Sasaki M, Koyama S, Fujiyama Y, Bamba T. · The Second Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. · J Gastroenterol Hepatol. · Pubmed #10921427 No free full text.

Abstract: A 29-year-old man with ulcerative colitis was admitted to our hospital because of convulsions and a headache. Before admission, oral prednisolone had been administered due to his ulcerative colitis relapse. Computed tomography revealed a low-density area in the right frontal pole suggestive of a venous infarction. Once his headache and convulsions improved after the administration of an antiepileptic drug, he began to complain of right arm numbness and right hemianopsia again. An urgent magnetic resonance imaging angiograph showed extensive thrombosis in the superior sagittal sinus. We finally used the anticoagulant agents, heparin and urokinase, which eased his complaints and prevented the development of bloody stools. He was discharged with no neurological symptoms 25 days after admission. This is a rare case of sinus thrombosis complicated by ulcerative colitis, in which anticoagulant therapy was successful. Magnetic resonance imaging angiography was useful for the diagnosis and for evaluating the therapeutic effect.

Tsujikawa T, Andoh A, Ogaẃa A, Sonoda A, Yagi Y, Hata K, Sasaki M, Saito Y, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan. · Ther Apher Dial. · Pubmed #19379165 No free full text.

Abstract: Leukocytapheresis (LCAP) has been applied for the treatment of steroid refractory ulcerative colitis (UC). A standard protocol employs one or two sessions of LCAP per week. Our aim was to determine whether five consecutive LCAP sessions can be performed safely and effectively for UC patients. Six patients with moderately active UC were enrolled. The patients received five days of consecutive LCAP in which the processing volume of blood was limited to 1500 mL per session. The hemoglobin levels in each patient gradually decreased, and the platelet count by the fifth session reached half of the value before the first session. The clinical activity index in two patients improved daily, and they went into remission with an improvement in the colonic endoscopic appearance after one week. This preliminary study showed that five consecutive LCAP sessions are safe and feasible for active UC patients. The therapeutic efficacy and suitable patients for this treatment protocol should be confirmed by further studies.

Matsumoto T, Andoh A, Okawa K, Ito H, Torii A, Yoshikawa S, Nakaoka R, Okuyama Y, Oshitani N, Nishishita M, Watanabe K, Fukunaga K, Ohnishi K, Kusaka T, Yokoyama Y, Sasaki M, Tsujikawa T, Aoki T, Kusaka T, Takeda Y, Umehara Y, Nakamura S, Fujiyama Y. · Division of Lower Gastroenterology Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. · Ther Apher Dial. · Pubmed #19140847 No free full text.

Abstract: Leukocytapheresis (LCAP) has been advocated as a treatment for moderate to severe active ulcerative colitis (UC) in Japan. To clarify the predictive factors for a rapid response to LCAP treatment, we conducted a multicenter prospective open-label study. A total of 105 patients with UC were analyzed. LCAP was performed using a Cellsorba EX column once a week for 5-10 sessions. The response was evaluated by the clinical activity index (CAI). When the CAI score decreased to less than half the pretreatment value or to less than 5 points within 3 weeks, the patient was considered to be a rapid responder. The average CAI significantly decreased from 11.7 to 4.2 (P < 0.01). Seventy-four percent of the patients responded to the therapy, and 53% of these patients were rapid responders. The following significant factors correlated with the rapid LCAP response: (i) steroid resistance (P < 0.05), (ii) severe disease indicated by a CAI score greater than 11 (P = 0.05), (iii) disease duration of less than 1 year (P < 0.05), and (iv) C-reactive protein levels before treatment (P < 0.01). These results suggest that the early initiation of LCAP is beneficial in patients with steroid-resistant UC.

Andoh A, Tsujikawa T, Ban H, Hashimoto T, Bamba S, Ogawa A, Sasaki M, Saito Y, Fujiyama Y. · Department of Medicine, Shiga University of Medical Science, Seta Tukinowa, Japan. · J Gastroenterol Hepatol. · Pubmed #18662197 No free full text.

Abstract: BACKGROUND AND AIM: There have been no reports on 6-thioguanine nucleotide (6-TGN) concentrations in Japanese patients with inflammatory bowel disease (IBD) undergoing azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy. The aim of this study was to assess 6-TGN concentrations in Japanese IBD patients. METHODS: Eighty-three patients with Crohn's disease (n = 42) and ulcerative colitis (n = 41) were enrolled. In 69 patients, AZA was prescribed at 50 mg/day, and seven patients were given 75 (n = 5) or 100 mg/day (n = 2). 6-MP was administered at 30 mg/day (n = 7). The 6-TGN concentrations were then assayed by high-performance liquid chromatography. RESULTS: The mean 6-TGN concentrations of the entire study population (n = 83) were 277.9 +/- 179.8 pmol/8 x 10(8) red blood cells (RBC). The mean 6-TGN concentrations in those patients with active disease (n = 38) and those in remission (n = 45) were 232.9 +/- 159.7(mean +/- SD) and 342.8 +/- 184.6 pmol/8 x 10(8) RBC, respectively (P < 0.05). The odds ratio of being in remission and having a 6-TGN value >235 pmol/8 x 10(8) RBC was 2.6 (95% CI 1.05-6.2). A significant inverse correlation was found between the white blood cell (WBC) counts and 6-TGN concentrations (r = -0.301, P < 0.05, n = 83); the mean WBC counts of the active patients (6780 +/- 2412) were significantly higher than the patients in clinical remission (5468 +/- 1920, P < 0.05). Three patients with severe leukopenia and 10 patients with high 6-TGN concentrations had no thiopurine S-methyl transferase mutations. CONCLUSION: The 6-TGN concentrations in Japanese patients with IBD on low-dose AZA and 6-MP therapy were comparable to those reported from Western countries. The monitoring of 6-TGN concentrations may be helpful for developing a therapeutic strategy for Japanese IBD patients.

Ban H, Andoh A, Tanaka A, Tsujikawa T, Sasaki M, Saito Y, Fujiyama Y. · Department of Medicine, Shiga University of Medical Science, Otsu. · Intern Med. · Pubmed #18827410 links to  free full text

Abstract: BACKGROUND AND AIMS: Myelosuppression observed in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the genetic polymorphism of high-versus low-metabolizing alleles. We investigated the association between TPMT genotypes and myelosuppression in Japanese IBD patients. METHODS: Forty-one healthy volunteers and 70 IBD patients (UC, n = 50; CD, n = 20) were recruited. All IBD patients were treated with AZA. The TPMT genotypes were determined by polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses. RESULTS: One healthy volunteer showed a heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBD patients were of the wild alleleotype (TPMT*1/*1). In the IBD patients, 7 patients developed leucopenia (<3,000/microL). One of them developed severe leucopenia (<1,000 microL) with agranulocytosis on day 14 after drug initiation. CONCLUSION: TPMT mutations are not associated with myelosuppression in Japanese IBD patients. Even in IBD patients with a wild TPMT genotype, clinicians should pay attention for the possible development of myelosuppression.

Osaki R, Andoh A, Tsujikawa T, Ogawa A, Koizumi Y, Nakahara T, Hata K, Sasaki M, Saito Y, Fujiyama Y. · Department of Medicine, Shiga University of Medical Science, Otsu. · Intern Med. · Pubmed #18628583 links to  free full text

Abstract: Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by a reactivation of a latent virus; acute CMV infections are rare. Treatment with immunosuppressive agents further increases the infection risk. Here, we present a 32-year-old man with acute CMV-mononucleosis and colitis, superimposed on corticosteroid-naïve ulcerative colitis (UC). The diagnosis was confirmed by a viral-like prodrome, positive CMV antigenemia (C7-HRP), a positive CMV IgM titer, the presence of atypical lymphocytes, mild transaminase elevation, and immunohistological detection of CMV positive cells in his colonic mucosa. Gancyclovir was intravenously administered, and all symptoms were improved.

Tajiri H, Tomomasa T, Yoden A, Konno M, Sasaki M, Maisawa S, Sumazaki R, Shimizu T, Toyoda S, Etani Y, Nakacho M, Ushijima K, Kobayashi A, Anonymous00112. · Department of Pediatrics, Osaka General Medical Center, Osaka, Japan. · Digestion. · Pubmed #18577852 No free full text.

Abstract: BACKGROUND AND AIMS: Azathioprine (AZA) and 6-mercaptopurine (6-MP) have recently been used in Japanese pediatric patients with ulcerative colitis. The aims of this study were to evaluate both the therapeutic efficacy and safety of AZA/6-MP in this group of patients. METHODS: Fourteen members of the Japanese Society for Pediatric Inflammatory Bowel Disease reported 35 retrospective cases that received AZA/6-MP and were evaluated for adverse drug effects. In those who tolerated AZA/6-MP, disease activity and corticosteroid doses before and during the first 6 months of therapy were assessed. RESULTS: AZA or 6-MP was safely used in 21 of 35 patients (60%) without adverse drug effects. The disease activity began to decrease from the first month of therapy and the maximum effect was achieved after 3 months. The mean daily prednisolone dose was decreased from 26.9 to 11.6 mg and dose reduction was achieved in 58% of patients after 6 months of therapy. Fourteen of the 35 patients (40%) experienced adverse drug effects, including leukopenia (n = 11), aplastic anemia (n = 1), pancreatitis (n = 1) and liver dysfunction (n = 1). CONCLUSIONS: The majority of Japanese children with ulcerative colitis tolerated AZA/6-MP and experienced favorable effects. However, 40% experienced adverse drug effects, mainly myelosuppression.

Yagi Y, Andoh A, Ogawa A, Bamba S, Tsujikawa T, Sasaki M, Mitsuyama K, Fujiyama Y. · Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan. · Ther Apher Dial. · Pubmed #17845392 No free full text.

Abstract: To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we performed microarray analysis for gene expression patterns in peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in patients with ulcerative colitis (UC). Four patients with UC were enrolled. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first session of LCAP therapy. Cells were stimulated with IL-1beta for 12 h, and gene expression patterns were analyzed by an IntelliGene HS Human Expression Chip. The LCAP session reduced various genes, such as proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, and IFN-gamma), cytokine receptors (IL-1R and IL-2Ralpha), chemokines, chemokine receptors, and intracellular signal transduction molecules. Genes which had increased after the LCAP session included those regulating anti-inflammatory cytokines and proteins (TGF-beta1 and IL-R antagonist), receptors for anti-inflammatory cytokines (IL-10R and IL-4R), growth factor receptors (IGF-R1, R2) and antioxidant proteins. Total changes in gene expression patterns after LCAP session were a combination of a decrease in pro-inflammatory genes and an enhancement of anti-inflammatory genes. These changes may explain some parts of the mechanisms by which LCAP improves clinical symptoms of UC patients.

Sasaki M, Sitaraman SV, Babbin BA, Gerner-Smidt P, Ribot EM, Garrett N, Alpern JA, Akyildiz A, Theiss AL, Nusrat A, Klapproth JM. · Internal Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA. · Lab Invest. · Pubmed #17660846 links to  free full text

Abstract: Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory conditions of the gut. Our goal was to investigate if invasive Escherichia coli strains were present in patients with inflammatory bowel disease (IBD). Bacterial strains were isolated from biopsy material obtained from normal controls, and patients with a clinical diagnosis of CD and UC. Invasive bacteria were characterized by gentamicin protection assay and biochemical profiling (Api-20E). Strains were characterized by induction of cytokine expression in epithelial and macrophage cell cultures, measurement of epithelial barrier function, and confocal microscopy. Of all invasive bacterial strains in CD 98.9% were identified as E. coli as opposed to 42.1% in UC and 2.1% in normal controls. Epithelial invasion in vitro was significantly higher for CD-associated E. coli (8.4%, +/-5.5 of initial inoculum (I/O)) in comparison to UC (2.5%, +/-0.4 I/O), but highest for strains from inflamed CD tissue (11.3%, +/-4.3 I/O). Both, CD and UC E. coli strains induced high mean TNF-alpha expression in macrophage cell lines (2604.8 pg/10(5) cells, +/-447.4; 2,402.6 pg/10(5) cells, +/-476.3, respectively), but concentrations were significantly higher for isolates from inflamed CD tissue (3071.3 pg/10(5) cells, +/-226.0). Invasive E. coli from IBD tissue induced similar concentrations of interleukin (IL)-8 in epithelial cell cultures, but strains from inflamed CD tissue induced significantly less epithelial IL-8 (674.1 pg/10(5) cells, +/-58.0 vs 920.5 pg/10(5) cells, +/-94.6). IBD-associated E. coli strains significantly decreased transepithelial resistance, induced disorganization of F-actin and displacement of ZO-1, and E-cadherin from the apical junctional complex (AJC). In comparison to normal controls and UC, E. coli are more prevalent in CD, are highly invasive, and do not encode for known effector proteins. E. coli strains from IBD patients regulate cytokine expression and epithelial barrier function, two pathological features of IBD.

Oshima T, Joh T, Kataoka H, Sasaki M, Fujita F, Togawa S, Wada T, Iio E, Itoh M. · Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya, Japan. · Dig Dis Sci. · Pubmed #17404878 No free full text.

This publication has no abstract.

Tsujikawa T, Kitoh K, Andoh A, Sasaki M, Koyama S, Fujiyama Y. · Internal Medicine, Shiga University of Medical Science. · Nippon Ronen Igakkai Zasshi. · Pubmed #17233463 links to  free full text

Abstract: AIM: Ulcerative colitis (UC) primarily affects young adults, but the proportion of elderly patients with UC seems to be increasing. It is important that the clinical characteristics of elderly patients be analyzed. METHODS: In the older group consisted of 32 outpatients (23 aged 50-64 years old, 9 aged 65 or over) in our hospital, we evaluated disease duration, severity, therapeutic efficacy and other clinical problems. RESULTS: The age distributions of the disease onset showed a peak at early age and decreased with aging. The degree of severity was mainly mild, and left-sided or pancolitis were more frequent than expected in the older group. Most elderly patients suffered other diseases, and care was required in the administration of steroids. CONCLUSION: The clinical features of elderly patients with UC were similar to those of younger patients. However, It should be considered that elderly patients often have complications requiring care in the use of steroids.

Andoh A, Yoshida T, Yagi Y, Bamba S, Hata K, Tsujikawa T, Kitoh K, Sasaki M, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan. · J Gastroenterol. · Pubmed #16501857 No free full text.

Abstract: BACKGROUND: Platelets play an important role in hemostatic and inflammatory responses. To evaluate any potential enhancement of platelet activity in patients with inflammatory bowel disease (IBD), we measured the platelet aggregation responses to various stimuli. METHODS: Twenty-two healthy controls, 24 patients with ulcerative colitis (UC) and 25 patients with Crohn's Disease (CD) were studied. The aggregation responses induced by three agonists (epinephrine, collagen, and ADP) were measured by an 8-channel aggregometer. The platelet-derived microparticles (PDMP) levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Twenty-one out of the 22 healthy controls did not respond to epinephrine (0.1 microg/ml), collagen (0.2 microg/ml), or ADP (1.0 microM). Eight out of the 12 active UC patients were sensitive to all agonists, and 4 patients showed increased sensitivity to epinephrine/collagen or epinephrine/ADP. Three out of the 12 inactive UC patients were normal, but 9 of these patients showed increased sensitivity, mainly to epinephrine. Ten out of the 12 active CD patients were sensitive to all agonists, and 2 active CD patients were sensitive to epinephrine/collagen or epinephrine/ADP. Eight out of the 13 inactive CD patients were sensitive to two or all agonists. Even after remission, almost all of the UC and CD patients showed some increased sensitivity to the agonists. The platelet number and the plasma PDMP levels were significantly higher in the active IBD patients than in the control group. CONCLUSIONS: Platelet aggregation responses are enhanced in IBD, even in inactive-phase patients. This increased sensitivity of the platelets may play an important role in the pathophysiology of IBD.

Andoh A, Tsujikawa T, Hata K, Araki Y, Kitoh K, Sasaki M, Yoshida T, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Seta Tukinowa, Otsu, Japan. · Am J Gastroenterol. · Pubmed #16128950 No free full text.

Abstract: OBJECTIVES: Platelet-derived microparticles (PDMPs) are active molecules involved in the hemostatic and inflammatory responses. To evaluate the changes in the platelet function in patients with inflammatory bowel disease (IBD), we measured circulating PDMP levels. METHODS: Twenty-five healthy controls, 44 patients with ulcerative colitis (UC), and 43 patients with Crohn's Disease (CD) were studied. The PDMP and soluble P-selectin (sP-selectin) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the healthy controls, the PDMP levels were 17.2 +/- 6.2 U/mL. Significant differences were not observed between the healthy controls and inactive UC patients (20.8 +/- 9.5 U/mL, n = 25) or between the healthy controls and inactive CD patients (17.6 +/- 7.8 U/mL, n = 24). In contrast, the PDMP levels were significantly higher in both active UC (49.2 +/- 33.6 U/mL, n = 19) and active CD (48.6 +/- 42.8 U/mL, n = 19) patients than in the healthy controls. A significant correlation was found between the PDMP levels and the clinical activity indexes (CAI) of UC patients (r = 0.65, p < 0.01, n = 44), and between the PDMP levels and Crohn's disease activity indexes (CDAI) (r = 0.72, p < 0.01, n = 43). Elevated PDMP levels in active patients were significantly reduced after remission. A significant correlation was observed between the PDMP levels and the sP-selectin levels (r = 0.60, p < 0.01, n = 122). CONCLUSION: Elevated circulating PDMPs in active IBD patients suggest a role for platelets in the pathogenesis of IBD.

Andoh A, Tsujikawa T, Inatomi O, Deguchi Y, Sasaki M, Obata H, Mitsuyama K, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. · Ther Apher Dial. · Pubmed #15967005 No free full text.

Abstract: The aim of this study was to elucidate the molecular mechanisms responsible for the therapeutic effects of leukocytapheresis (LCAP). We investigated the alterations in circulating T cell subsets after LCAP therapy in ulcerative colitis (UC) patients. Eighteen patients with UC were enrolled. Fourteen patients were responders, and four patients were non-responders. Peripheral venous blood was obtained within 5 min before and 5 min after LCAP therapy. Flow cytometric analysis for T cell markers and intracellular interferon (IFN)-gamma (Th1) and interleukin (IL)-4 (Th2) was then performed. The average numbers of lymphocytes, T and B cells were significantly decreased after LCAP therapy, respectively (P < 0.01). The numbers of CD4+ and CD8+ T cells were also significantly decreased, respectively (P < 0.01), but the CD4+/CD8+ ratio was not changed. The number of CD45RO+ CD4+ memory T cells was significantly decreased. The number of CD25+ CD4+ T cells tended to decrease after LCAP therapy (not significant). However, the ratio of CD25+ CD4+-cells/CD25- CD4+-cells was significantly increased (P < 0.05). The number of IFN-gamma-positive (Th1) cells was significantly decreased after LCAP therapy, but there was no significant change in the number of IL-4-positive (Th2) cells. The Th1/Th2 ratio was significantly decreased after LCAP therapy. Some of the immuno-suppressive effects of LCAP therapy may be associated with a modulation of circulating T cell subsets.

Andoh A, Hirashima M, Maeda H, Hata K, Inatomi O, Tsujikawa T, Sasaki M, Takahashi K, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. · Nutrition. · Pubmed #15850963 No free full text.

Abstract: OBJECTIVE: Selenoprotein-P is a selenium-rich serum protein that carries more than 50% of serum selenium. We evaluated changes in serum selenoprotein-P levels in patients with inflammatory bowel disease. METHODS: Serum selenoprotein-P levels were measured by enzyme-linked immunosorbent assay. Twenty healthy individuals (controls), 34 patients with ulcerative colitis, and 37 patients with Crohn's disease (CD) were studied. RESULTS: A highly significant correlation was found between the serum selenium and selenoprotein-P levels. There was no significant difference in serum selenoprotein-P levels between healthy controls (average 3.4+/-0.8 microg/mL, n=20) and patients with ulcerative colitis (3.0+/-1.0 microg/mL, n=34). Serum selenoprotein-P levels were significantly lower in patients with CD (average 1.8+/-0.5 microg/mL, n=37). Serum selenoprotein-P levels were significantly lower in the elemental diet group of patients who had CD (average 1.4+/-0.4 microg/mL, n=17) than in the non-elemental diet group of patients who had CD (average 2.1+/-0.3 microg/mL, n=20). CONCLUSION: We found that the serum selenoprotein-P level is decreased in patients with CD. It may be a useful marker to monitor the systemic selenium status in various disorders.

Andoh A, Tsujikawa T, Inatomi O, Deguchi Y, Hata K, Kitoh K, Sasaki M, Mitsuyama K, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan. · Ther Apher Dial. · Pubmed #15828923 No free full text.

Abstract: To elucidate the molecular mechanisms involved in the therapeutic effects of granulocyte/monocyte adsorption apheresis, changes were investigated in the cytokine responses of peripheral blood mononuclear cells (PBMC) before and after granulocyte/monocyte adsorptive apheresis in ulcerative colitis (UC) patients. Four patients with active UC were enrolled. All patients responded to granulocyte/monocyte adsorptive apheresis. A total of 20 sessions of four patients were analyzed. Peripheral blood mononuclear cells were isolated from peripheral venous blood within 5 min before and after each session of granulocyte/monocyte adsorptive apheresis. The cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the secreted IL-8 and IL-6 levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1beta-induced IL-8 and IL-6 secretion was significantly decreased after granulocyte/monocyte adsorptive apheresis. TNF-alpha-induced IL-8 secretion was also significantly decreased after apheresis, but there was no significant difference in TNF-alpha-induced IL-6 secretion (P = 0.052). In conclusion, granulocyte/monocyte adsorptive apheresis down-regulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMC. The induction of hyporesponsiveness to pro-inflammatory cytokines may be an important factor mediating the clinical effects of granulocyte/macrophage adsorptive apheresis in UC patients.

Andoh A, Ogawa A, Kitamura K, Inatomi O, Fujino S, Tsujikawa T, Sasaki M, Mitsuyama K, Fujiyama Y. · Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, 520-2192, Japan. · J Gastroenterol. · Pubmed #15622478 No free full text.

Abstract: BACKGROUND: To elucidate the molecular mechanisms involved in the therapeutic effects of leukocytapheresis (LCAP), we investigated the alterations in the cytokine responses of peripheral blood mononuclear cells (PBMCs) before and after LCAP therapy in ulcerative colitis (UC) patients. METHODS: Twelve patients with UC who did not respond to steroid therapy were enrolled. Nine patients responded to LCAP therapy, but 3 patients did not show clinical improvement. PBMCs were isolated from peripheral venous blood obtained within 5 min before and after the first and second session of LCAP treatment. Cells were stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha for 24 h, and the levels of secreted IL-8 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: LCAP induced a significant decrease in peripheral lymphocyte, monocyte, and platelet counts. IL-1beta- and TNF-alpha-induced IL-8 and IL-6 secretion was significantly decreased after the first and second LCAP treatments. These responses were associated with inhibitory effects on nuclear factor (NF)-kappaB DNA-binding activity. CONCLUSIONS: LCAP downregulates the IL-1beta- and TNF-alpha-induced inflammatory responses in PBMCs isolated from UC patients. The induction of hyporesponsiveness to proinflammatory cytokines may be an important factor mediating the clinical effects of LCAP in UC patients.

Andoh A, Fujiyama Y, Yoshioka U, Sasaki M, Araki Y, Tsujikawa T, Bamba T. · Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan. · Int J Mol Med. · Pubmed #11956656 No free full text.

Abstract: An autoimmune mechanism has been postulated for the pathogenesis of ulcerative colitis (UC). The aim of this study was to evaluate the presence of anti-carbonic anhydrase (CA) I and anti-CA II antibodies in a series of inflammatory bowel disease (IBD) patients. We studied 58 IBD patients [36 UC patients and 21 patients with Crohn's disease (CD)]. As a control, 24 healthy individuals and 12 patients with non-IBD diarrheal diseases were tested. Serum anti-CA I and anti-CA II antibodies were quantified by enzyme-linked immunosorbent assay. Anti-CA II antibody was detected in 27.8% of UC patients, whereas anti-CA I antibody was detected in only 5.6% of UC patients. Positive rate of anti-CA II antibody was significantly higher in UC patients as compared to the control. In CD patients and non-IBD diarrheal patients, there were no significant increase in positive rate of either anti-CA I or II antibody. These results suggest that autoimmune responses against CA II may be involved in the pathogenesis of UC, and similar mechanism may participate in the development of pancreatic lesions in UC patients.

Okamoto T, Sasaki M, Tsujikawa T, Fujiyama Y, Bamba T, Kusunoki M. · Second Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan. · J Gastroenterol. · Pubmed #10832668 No free full text.

Abstract: Butyrate enemas have been reported to be effective in ulcerative colitis. However, long-term use is difficult because of the troublesome procedure and the unpleasant smell. We therefore investigated the effects of the oral administration of Clostridium butyricum M588 (CBM588), an enterobacterium producing butyrate, in dextran sodium sulfate (DSS)-induced colitis in rats. First, we confirmed the effects of pre-treatment with a butyrate enema on DSS colitis. We then studied the efficacy of oral administration of CBM588 which was started 1 week prior to the induction of DSS colitis. In the CBM588 group, the ulcer index and myeloperoxidase (MPO) activity in the distal colon were significantly lower than in the control group. Proliferating cell nuclear antigen (PCNA) immuno-positive cells were increased around the ulcer in the CBM588 group. In regard to the contents of the cecum and colon, the proportions of Lactobacillus and Eubacterium were increased in the cecum in the CBM588 group. Further, there were significant increases of n-butyrate, propionate, and acetate concentrations in the cecum in the CBM588 group. These results indicated that the oral administration of CBM588 alleviated DSS-induced colitis, and may be useful instead of butyrate enema.