Yoshinori Arai

Effect of icatibant, a bradykinin B2 receptor antagonist, on the development of experimental ulcerative colitis in mice.

Dextran sulfate sodium-induced colitis in micehas been recognized as a model for human ulcerativecolitis. Using this model, we carried out a study on thepreventive effect of Icatibant, a bradykinin B receptor antagonist previously called HOE 140,on the development of colitis. Subcutaneousadministration of Icatibant (0.3 or 1.5 mg/kg)significantly suppressed shortening of the largeintestine and worsening of the general health. Oraladministration of Icatibant (50 mg/kg) significantlysuppressed shortening of the large intestine, the onsetof diarrhea, and worsening of the general health. Inaddition, the oral treatment significantly inhibited thedevelopment of colitis that was observedhistopathologically. These results indicate a role of BKin the development of dextran sulfate sodiuminducedcolitis in mice, and suggest that BK could be importantin human ulcerative colitis.

Prostaglandin E2 production by endogenous secretion of interleukin-1 in decidual cells obtained before and after the labor

Previous reports revealed that interleukin-1 (IL-1) was involved in the process of premature labor in the cases with intrauterine infection. However, the roles of the cytokine in normal spontaneous labor remain uncertain. The present studies aimed at determining the involvement of the cytokine in prostaglandin (PG)E2 production during labor by the third trimester decidual cells. The cells were obtained at the time of normal spontaneous delivery (NVD) and elective cesarean section (ECS). The NVD cells produced significantly more amount of PGE2 than the ECS cells and the both cells responded to the addition of IL-1 beta to increase PGE2 production. A specific inhibitor of cyclooxygenase-2 (COX-2), NS398, decreased basal PGE2 production and inhibited the stimulatory effect of IL-1 beta in a dose dependent manner in NVD cells. The NVD cells secreted more amount of IL-1 beta than the ECS cells and contained more amount of preprocessed 31kD IL-1 beta inside the cells. The addition of recombinant soluble human IL-1 receptor (type I) not only blocked the effect of IL-1 beta on PG secretion, but significantly reduced the basal production of PGE2 by NVD cells. These results indicate that decidual PG production depends upon COX-2 after the onset of labor. Besides it seems likely that endogenously produced IL-1 beta may be involved in autocrine or paracrine fashion in inducing COX-2 after the onset of labor.

Frigen II improves the reliability of measurement of interleukin-1 related substances in amniotic fluid

BACKGROUND To investigate the role of interleukin-1 related substances in amniotic fluid in normal term labor without intrauterine infection. METHODS Amniotic fluid samples were collected from forty-one patients with various backgrounds. A novel pre-assay treatment using Frigen II was introduced to improve the recovery rates of cytokines, i.e., interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist, prior to ELISA assay. Urine samples from newborn infants were also tested. RESULTS The concentrations of interleukin-1alpha, interleukin-1beta and interleukin-1ra were significantly higher in samples from normal vaginal delivery. The higher levels of interleukin-1alpha were also observed in samples from preterm labor without infection. Preterm infants produced more of interleukin-1 receptor antagonist in urine compared with term infants. CONCLUSIONS This study provides evidence of the possible involvement of interleukin-1 related substances in labor without signs of infection. The data from newborn urine suggests that amniotic interleukin-1ra originates from the fetus. However, amniotic fluid interleukin-1alpha and interleukin-1beta may be derived from maternal tissue, such as decidua.

Acute Pancreatitis due to pH-Dependent Mesalazine That Occurred in the Course of Ulcerative Colitis

We report the case of a 26-year-old male who presented with acute pancreatitis during the course of treatment for pancolitic ulcerative colitis (UC) with a time-dependent mesalazine formulation, prednisolone and azathioprine (AZA). Despite a review of his clinical history and various tests, the cause of pancreatitis could not be determined. Since drug-induced pancreatitis was considered possible, administration of the time-dependent mesalazine preparation and AZA was discontinued, and conservative treatment for acute pancreatitis was performed. The pancreatitis promptly improved with these treatments, but drug lymphocyte stimulation test (DLST) for both the time-dependent mesalazine formulation and AZA was negative. A pH-dependent mesalazine formulation was given for maintenance therapy of UC. Subsequently, as the pancreatitis relapsed, drug-induced pancreatitis was strongly suspected. Administration of mesalazine was discontinued, and pancreatitis was smoothly in remission by conservative treatment. According to the positive DLST result for the pH-dependent mesalazine formulation and the clinical course, a diagnosis of pH-dependent mesalazine-induced pancreatitis due to this formulation was made. During the clinical course of UC, occurrence of drug-induced pancreatitis must always be considered.

Prostaglandin E2 Production by Endogenous Secretion of Interleukin-1 in Decidual Cells from Term Fetal Membrane

The intrauterine tissues including decidua have been investigated as the sites of prostaglandin (PG) production in connection with its involvement in the onset or progress of labor (1–4). The recent papers suggested that the intrauterine infection was responsible for the pathophysiology of preterm labor through the set of events from the generation of various types of cytokines such as interleukin-1 (IL-1), the induction of cyclooxygenase (COX) to the PG synthesis in these tissues (5–7). On the other hand, IL-1 has been reported to induce COX-2, an inducible type of COX in cultured decidual cells (8). Therefore, COX-2 induction in decidua by IL-1 would play a role in the initiation of spontaneous labor as well as preterm labor. Though the physiological role of IL-1 secreted in decidual cells remains still uncertain (9), this study was aimed to reveal endogenous role of IL-1 synthesized and secreted by decidual cells in the formation of PGE2. In addition, we investigated the selective role of COX-2 in decidual cells for the initiation or maintenance of labor by using a specific inhibitor for the enzyme, NS-398.

Unusual images of mass-forming intrahepatic cholangiocarcinoma.

We experienced a case of mass-forming intrahepatic cholangiocarcinoma which could not been diagnosed accurately without pathologic findings. A 78-year-old Japanese woman with no particular symptoms was admitted for changes in liver function tests. Ultrasonography revealed a solid liver tumor. When there are no typical imaging features, no pathognomonic clinical findings and no obvious risk factors for any specific hepatic tumor, it may be difficult to make an accurate diagnosis before surgical resection. The lesion was resected on the basis of a high degree of suspicion for malignancy and submitted for pathologic evaluation. Microscopically, the neoplasm was a moderately differentiated adenocarcinoma with abundant fibrous stroma, consistent with a mass-forming cholangiocarcinoma. This case exemplifies the importance of considering the various tumorous and non-tumorous diseases in the differential diagnosis of a liver mass with atypical features, especially when malignancy cannot be excluded.

Endoscopic Findings during the Early Induction Phase of Infliximab Therapymay Predict its Efficacy for Refractory Ulcerative Colitis

Background and Aims: Infliximab (IFX) is one of the most potent and effective treatments for steroid- or immunomodulator-refractory ulcerative colitis (UC). We evaluated the early efficacy of IFX, based on endoscopic findings, and also attempted to define endoscopic findings predictive of IFX efficacy. Methods: Nine patients were treated with IFX induction therapy at weeks 0, 2, and 6. Early efficacy was evaluated, using endoscopic and clinical findings, at week 1 (n=9) and again at weeks 3 (n=3) or 7 (n=4). Efficacy was evaluated using the Mayo, Schroeder, and Rachmilewitz endoscopic (RES) scores. Results: At week 1, 8 of 9 (89%) patients showed a clinical response, and 11% (1 of 9) experienced clinical remission. The mean Mayo score was significantly decreased at week 1 (10 ± 1.2 at baseline vs. 5.6 ± 1.9 at week 1, p 0.3 mg/dl) in the non-remission group, but were negative in the remission group.