Differential effects of FK506 and methotrexate on inflammatory cytokine levels in rat adjuvant-induced arthritis

OBJECTIVE: To investigate the effects of prophylactic and therapeutic treatments with FK506 (tacrolimus), an immunosuppressive drug that specifically inhibits T cell activation, and methotrexate (MTX) on inflammatory cytokines, tumor necrosis factor (TNF)-a, interleukin (IL)-1beta, and IL-6 levels in rat adjuvant-induced arthritis (AIA). METHODS: AIA was induced in female Lewis rats. Arthritis was assessed by hindpaw swelling. TNF-a, IL-1beta, and IL-6 levels in paw extracts were determined by ELISA. To assess the effects on cytokine levels, rats were treated prophylactically with FK506 (3 mg/kg) or MTX (0.1 mg/kg) from day 1 to day 17, and therapeutically with FK506 (5 mg/kg) or MTX (1 mg/kg) from day 15 to day 17 (3-day treatment) or day 15 to 20 (6-day treatment) by oral administration. RESULTS: TNF-a, IL-1beta, and IL-6 levels in paw tissue were found to significantly increase between day 15 and day 21 after adjuvant injection, when the arthritis was in a developed stage. Prophylactic treatment with FK506 and MTX suppressed arthritis and reduced the levels of those inflammatory cytokines. FK506 caused a marked reduction of TNF-a and IL-1beta levels in paw tissue even in short-term (3-day) therapeutic treatment. It reduced all levels of TNF-a, IL-1beta, and IL-6 in paws in 6-day therapeutic treatment. In contrast, therapeutic treatment with MTX affected neither TNF-a or IL-6 levels in paws. MTX reduced IL-1beta levels only in the 6-day treatment. CONCLUSION: FK506 is more effective than MTX in reducing elevated levels of inflammatory cytokines TNF-a, IL-1beta, and IL-6 in established stages of AIA. Our findings suggest that inhibition of T cell activation results in a rapid reduction of inflammatory cytokine levels even after the arthritis is established in AIA.     

Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

Usefulness of magnifying narrow-band imaging endoscopy for the diagnosis of gastric and colorectal lesions

A series of studies about the potential usefulness of magnifying endoscopy with narrow-band imaging (NBI) for the diagnosis of gastric and colonic lesion is reviewed. Concerning the magnifying NBI appearances of gastric lesions, a light blue crest is a highly accurate sign of the presence of histological intestinal metaplasia. Also, the degree of irregularity of the mucosal and vascular pattern is correlated with the histological severity of Helicobacter pylori-associated chronic gastritis. According to the 'VS classification', an irregular microvascular pattern and/or an irregular microsurface pattern together with a clear demarcation line are characteristic for early gastric carcinoma, and a multicenter prospective randomized controlled trial demonstrated that magnifying endoscopy with NBI is superior to ordinary white light endoscopy for making a differential diagnosis of a small depressed lesion between carcinoma and non-carcinoma. Concerning the magnifying NBI appearances of colonic tumor, the vague or invisible microvascular pattern is mostly observed in hyperplastic polyp. The regular meshed microvascular pattern is mostly observed in adenoma. The irregular meshed microvascular pattern is mostly observed in intramucosal or shallow submucosal-invasive carcinoma. The decreased or loose microvasucular pattern is mostly observed in deep submucosal-invasive carcinoma. Thus, magnifying NBI endoscopy is useful for the differentiation of colorectal non-adenomatous lesions from adenoma, the differentiation of adenoma from carcinoma, and the assessment of invasion depth of early colorectal carcinoma. At present, several magnifying NBI classifications for the diagnosis of early colorectal neoplasia have been proposed in Japan. Recently, the NICE classification based on NBI findings with/without magnification for colorectal tumor was established by an international group.     

Formation of a long-lived electron-transfer state in mesoporous silica-alumina composites enhances photocatalytic oxygenation reactivity

A simple donor-acceptor linked dyad, 9-mesityl-10-methylacridinium ion (Acr⁺-Mes) was incorporated into nanosized mesoporous silica-alumina to form a composite, which in acetonitrile is highly dispersed. In this medium, upon visible light irradiation, the formation of an extremely long-lived electron-transfer state (Acr^•-Mes^•+) was confirmed by EPR and laser flash photolysis spectroscopic methods. The composite of Acr⁺-Mes-incorporated mesoporous silica-alumina with an added copper complex [(tmpa)Cu^II] (tmpa = tris(2-pyridylmethyl)amine) acts as an efficient and robust photocatalyst for the selective oxygenation of p-xylene by molecular oxygen to produce p-tolualdehyde and hydrogen peroxide. Thus, incorporation of Acr⁺-Mes into nanosized mesoporous silica-alumina combined with an O₂-reduction catalyst ([(tmpa)Cu^II]²⁺) provides a promising method in the development of efficient and robust organic photocatalysts for substrate oxygenation by dioxygen, the ultimate environmentally benign oxidant.     

Diabetes and life expectancy among Japanese - NIPPON DATA80

Life expectancy (LE) among the Japanese population with or without diabetes mellitus was estimated. LE in 40-year old men and women was 41.1 and 47.5 years in those without diabetes and 32.3 and 40.9 years in those with diabetes. The LE of 40-year old men and women with diabetes was 8.8 and 6.6 years shorter than in those without diabetes. Diabetes mellitus leads to a decrease in LE. The presence of impaired glucose tolerance also affected LE inversely.     

Effect of sumatriptan on gastric emptying: a crossover study using the BreathID system

AIM:To determine the effect of oral sumatriptan on gastric emptying using a continuous 13 C breath test(BreathID system).METHODS:Ten healthy male volunteers participated in this randomized,2-way crossover study.The subjects fasted overnight and were randomly assigned to receive a test meal(200 kcal/200 mL) 30 min after pre-medication with sumatriptan 50 mg(sumatriptan condition),or the test meal alone(control condition).Gastric emptying was monitored for 4 h after administration of the test meal by the 13 C-acetic acid breath test performed continually using the BreathID system.Then,using Oridion Research Software(β version),the time taken for emptying of 50% of the labeled meal(T 1/2) similar to the scintigraphy lag time for 10% emptying of the labeled meal(T lag),the gastric emptying coefficient(GEC),and the regression-estimated constants(β and κ) were calculated.The statistical significance of any differences in the parameters were analyzed using Wilcoxon’s signed-rank test.RESULTS:In the sumatriptan condition,significant differences compared with the control condition were found in T 1/2 [median 131.84 min(range,103.13-168.70) vs 120.27 min(89.61-138.25);P = 0.0016],T lag [median 80.085 min(59.23-125.89) vs 61.11 min(39.86-87.05);P = 0.0125],and β [median 2.3374(1.6407-3.8209) vs 2.0847(1.4755-2.9269);P = 0.0284].There were no significant differences in the GEC or κ between the 2 conditions.CONCLUSION:This study showed that oral sumatriptan significantly delayed gastric emptying of a liquid meal.