Acid Dissociation Equilibrium and Singlet Molecular Oxygen Quantum Yield of Acetylated 6,8-Dithioguanosine in Aqueous Buffer Solution.

2',3',5'-Tri- O-acetyl-6,8-dithioguanosine (taDTGuo) is a nucleoside derivative of drug 6-thioguanine and under further development as a potential photochemotherapeutic agent due to its desirable properties of photosensitivity to UVA light and singlet molecular oxygen generation. The photochemical characteristics of taDTGuo under biological conditions (namely in aqueous solution) were intensively investigated by the steady-state absorption and emission, time-resolved near-infrared emission measurements, and quantum chemical calculations. taDTGuo was found to be held in sequential acid dissociation equilibria within pH 3.79-11.93. With the global fitting analysis of the absorption spectra at various pHs, two p Ka values of the equilibria were determined to be 7.02 ± 0.01 and 9.79 ± 0.01. Quantum chemical calculations suggested that its mono- and dianionic species in the ground state should be 1-imide anionic form (N1-taDTGuo-) and 1,7-di-imide anionic form (taDTGuo2-). taDTGuo generates a singlet molecular oxygen effectively and has pH-dependent quantum yields. In conclusion, taDTGuo would be very useful as a potent agent for photochemotherapy under certain carcinomatous pH conditions.

Efficacy, safety and cost analyses in ulcerative colitis patients undergoing granulocyte and monocyte adsorption or receiving prednisolone.

BACKGROUND: Patients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA. METHODS: Forty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY. RESULTS: PSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001). CONCLUSIONS: In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

Large-scale disaster and gastrointestinal diseases.

Many medical investigations, including epidemiological studies, case reports and case series have been conducted in association with large-scale disasters worldwide. Gastrointestinal diseases have been identified in many studies on disaster-related diseases with various problems being encountered especially in the acute (the first 3 days after the onset of a disaster), subacute (approximately the first 2 weeks after the onset of a disaster), and chronic phases. The problems in the acute phase concern food security and nutrition, while those in the subacute phase concern constipation and diarrhea. According to each disease site, the clinically important problems in the chronic phase are peptic ulcer and functional dyspepsia affecting the upper gastrointestinal tract, and inflammatory bowel disease and irritable bowel syndrome affecting the lower gastrointestinal tract. In addition, chronic hepatitis B and alcoholic liver diseases/pancreatitis are major hepatobiliary pancreatic diseases.

[¹8F-fluorodeoxyglucose PET/CT and small bowel endoscopy in a patient with small bowel leiomyoma].

A 49-year-old man was admitted to our hospital because of recurrent gastrointestinal bleeding of unknown origin, after repeated negative endoscopic and radiographic evaluation, including colonoscopy, esophago-gastro-duodenoscopy, CT and angiography. His condition had not been diagnosed for the past 18 years. ¹8F-fluorodeoxyglucose (FDG) on positron emission tomography (PET/CT) showed mild FDG uptake by a tumor of the small bowel (SUVmax 2.83), and capsule endoscopy (CE) and double balloon endoscopy (DBE) revealed a well-defined smooth submucosal tumor in the jejunum. The patient underwent a laparotomy and small bowel resection. The pathologic diagnosis was a small intestinal leiomyoma. Our report suggests the significance of combination of CE, DBE and PET/CT in the diagnosis of small bowel leiomyoma.

Selection of anticoagulants for leukocytapheresis therapy in cases of active ulcerative colitis.

BACKGROUND AND AIM: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment. METHODS: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30-50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP. RESULTS: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30-50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column. CONCLUSIONS: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP.

Nuclear expression of phosphorylated EGFR is associated with poor prognosis of patients with esophageal squamous cell carcinoma.

OBJECTIVES: Although it has been reported that epidermal growth factor receptor (EGFR) is able to translocate from the plasma membrane to the nucleus, the pathophysiological role of this translocation in tumorigenicity is still unclear. In the present study, to elucidate the pathophysiological significance of EGFR translocation, we investigated the expression not only of conventional EGFR but also its phosphorylated form (pEGFR), focusing on its cellular localization in esophageal cancer tissues. METHODS: Fifty-two specimens of esophageal squamous cell carcinoma (SCC) obtained by surgery were examined immunohistochemically for their EGFR and pEGFR immunostaining patterns. The relationships between clinicopathological parameters and EGFR or pEGFR immunostaining patterns were then analyzed. RESULTS: In 37 (71.2%) of the 52 esophageal SCCs, EGFR immunoreactivity was clearly localized at the plasma membrane of the cancer cells, whereas pEGFR immunoreactivity was clearly localized in the nucleus in 19 (36.5%) cases. Nuclear expression of pEGFR significantly correlated with TNM stage and lymph node metastasis, and moreover was associated with a poor outcome of esophageal SCC. CONCLUSIONS: Nuclear translocalization of pEGFR is associated with an increase in the malignant potential of esophageal SCC and may affect prognosis in patients with esophageal SCC.