Infliximab- and Immunosuppressant-Resistant Crohn's Disease Successfully Treated with Adsorptive Granulocyte Apheresis Combined with Prednisolone

Activated granulocytes, monocytes, and platelets appear to be closely involved in active Crohn's disease (CD). Adsorptive granulocyte apheresis (GCAP) is a new treatment for inflammatory bowel disease. GCAP was used to treat a 23-year-old female patient with CD resistant to both infliximab (IFX) and azathioprine (AZA). At 16 years of age, the patient underwent a partial ileal resection for peritonitis caused by perforative ileitis. On pathological examination of the resected specimen, the diagnosis was CD. Mesalazine was started, but the patient did not comply with therapy. She was admitted to our hospital again in 2007 due to an acute exacerbation. IFX induction therapy was started. The combination of both AZA daily and IFX every 8 weeks was continued as maintenance therapy. However, she developed severe abdominal pain in September 2009. Computed tomography revealed ileitis and ascending colitis, and blood tests showed high inflammatory response marker levels. She was considered to have IFX- and AZA-resistant CD. Initial intravenous steroid therapy did not result in any improvement. Therefore, weekly GCAP therapy was given for 5 weeks, which immediately improved the inflammatory response markers. GCAP combined with prednisolone could be effective for IFX- and AZA-refractory CD

Localization of the ultraviolet-sensor Opn5m and its effect on myopia-related gene expression in the late-embryonic chick eye

Recent studies show that exposure to ultraviolet (UV) light suppresses ocular elongation, which causes myopia development. However, the specific mechanisms of this process have not been elucidated. A UV-sensor, Opsin 5 (Opn5) mRNA was shown to be present in extraretinal tissues. To test the possibility that UV-signals mediated by Opn5 would have a direct effect on the outer connective tissues of the eye, we first examined the expression patterns of a mammalian type Opn5 (Opn5m) in the late-embryonic chicken eye. Quantitative PCR showed Opn5m mRNA expression in the cornea and sclera. The anti-Opn5m antibody stained a small subset of cells in the corneal stroma and fibrous sclera. We next assessed the effect of UV-A (375 nm) irradiation on the chicken fibroblast cell line DF-1 overexpressing chicken Opn5m. UV-A irradiation for 30 min significantly increased the expression of Early growth response 1 (Egr1), known as an immediate early responsive gene, and of Matrix metalloproteinase 2 (Mmp2) in the presence of retinal chromophore 11-cis-retinal. In contrast, expression of Transforming growth factor beta 2 and Tissue inhibitor of metalloproteinase 2 was not significantly altered. These results indicate that UV-A absorption by Opn5m can upregulate the expression levels of Egr1 and Mmp2 in non-neuronal, fibroblasts. Taken together with the presence of Opn5m in the cornea and sclera, it is suggested that UV-A signaling mediated by Opn5 in the extraretinal ocular tissues could influence directly the outer connective tissues of the chicken late-embryonic eye

A novel PI3K inhibitor iMDK suppresses non-small cell lung Cancer cooperatively with A MEK inhibitor

The PI3K–AKT pathway is expected to be a therapeutic target for non-small cell lung cancer (NSCLC) treatment. We previously reported that a novel PI3K inhibitor iMDK suppressed NSCLC cells in vitro and in vivo without harming normal cells and mice. Unexpectedly, iMDK activated the MAPK pathway, including ERK, in the NSCLC cells. Since iMDK did not eradicate such NSCLC cells completely, it is possible that the activated MAPK pathway confers resistance to the NSCLC cells against cell death induced by iMDK. In the present study, we assessed whether suppressing of iMDK-mediated activation of the MAPK pathway would enhance anti-tumorigenic activity of iMDK. PD0325901, a MAPK inhibitor, suppressed the MAPK pathway induced by iMDK and cooperatively inhibited cell viability and colony formation of NSCLC cells by inducing apoptosis in vitro. HUVEC tube formation, representing angiogenic processes in vitro, was also cooperatively inhibited by the combinatorial treatment of iMDK and PD0325901. The combinatorial treatment of iMDK with PD0325901 cooperatively suppressed tumor growth and tumor-associated angiogenesis in a lung cancer xenograft model in vivo. Here, we demonstrate a novel treatment strategy using iMDK and PD0325901 to eradicate NSCLC

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

Degos 病の関与が疑われた腸管気腫症の一例

症例は70歳代男性．既往に脳梗塞，パーキンソン病があり抗凝固薬を内服していた．デイサービス利用中に倦怠感および血圧低下を認め近医を受診し入院加療となった．入院２日目に40℃の熱発があり，腹部造影CT を施行したところfree air を認め外科的治療目的に当院へ救急搬送された．造影CT では肝彎曲部から脾彎曲部にかけての横行結腸に腸間膜気腫および腸管壁内ガスを認めた．明らかな腸間膜虚血および壊死を示唆する所見はなかった．消化管穿孔または腸管気腫症が考えられ緊急手術が検討されたが，腹部症状に乏しく液体成分など腸管内容の流出を示唆する所見がないことから一旦保存的加療を行った．また，体幹部を中心に小豆大までの皮膚潰瘍が多発していた．皮膚病理所見，既往および今回の病態からDegos 病と診断された．入院６日目に注腸造影および腹部CT を施行したところ，free air はほぼ消失しており，造影剤の腸管外漏出は認めず８日目に退院となった．Degos 病は皮膚の萎縮性丘疹を呈し，消化管の多発性潰瘍や穿孔，中枢神経系の出血や梗塞を特徴とし，病態としては末梢の血栓性血管炎が主体と考えられている．今回我々は，Degos病の関連が疑われた腸管気腫症の一例を経験したので文献的考察を加えて報告する．The patient was a 70 year-old-male. His past medical history was significant for cerebral infarction and Parkinson’s disease. He presented with malaise and hypotension and had been admitted to a local hospital three days ago. After admission，he had a fever of 40℃ and a computed tomography (CT) showed free air in the upper abdomen，he was referred to our hospital for an operation. A contrast-enhanced computed tomography also showed free air and pneumatosis intestinalis in transverse colon, with no evidence of mesenteric ischemia such as superior mesenteric artery occlusion (SMA) or non-occulusive mesenteric ischemia. Due to no abdominal pain and intraperitoneal fluid, we assessed that pneumatosis cystoides intestinalis was more probable than intestinal perforation. It was observed that the patient had many skin ulcers the size of red beans which were located around the chest and abdomen. A skin biopsy was performed，indicating Degos’ disease by a pathological exam. On day 6 of admission，we performed a barium enema exam and plain abdomen computed tomography (CT), it was seen that the free air almost disappeared and there was no leakage of the contrast medium. He was discharged on day 8. Patients with Degos’ disease present atrophic papula with perforation of intestinal or cerebral vascular accidents such as hemorrhage or infarction. This is considered a cause for bythrombotic angiitis of the peripheral vessels. We present a report with reference to the relevant literature