Features of and Mechanisms Underlying Insulitis In aly/aly Male Mice as an Animal Model of Autoimmune Pancreatitis: Activation of CD11c+, CD4+, and Th2 Cells and Predominant Destruction of β-cells

Diabetes mellitus (DM) is observed in patients with autoimmune pancreatitis (AIP). The development of DM in AIP is believed to be due to blood flow obstruction of the endocrine gland that accompanies pancreatitis, as well as injury to the islets caused by inflammation. The latter is called insulitis and the detailed mechanisms underlying its development are not yet clear. The aim of the present study was to elucidate the mechanisms involved in the development of insulitis in AIP using aly mice as an animal model of AIP: results in aly/aly male mice, as the AIP group, were compared with those inaly/+ male mice as a control group. Mice in both groups were killed between 16 and 48 weeks of age, and pancreatitis and insulitis were evaluated histologically. Inflammatory and endocrine cells were evaluated by immunofluorescence staining with anti-CD4, anti-CD8, anti-CD11b, and anti-CD11c antibodies, as well as immunohistochemical analyses using insulin and glucagon antibodies. Plasma levels and the pancreatic content of interferon (IFN)-γ (as a Th1-secreted cytokine) and interleukin (IL)-4 (as a Th2-secreted cytokine) were determined. Pancreatitis was seen in aly/aly mice from 16 weeks of age and it developed gradually thereafter. Insulitis also developed gradually and was seen in mice after 24 weeks of age in association with a decrease in the number of islets. CD11c+ cells and CD4+ T cells were seen to infiltrate into the islets. Although the number of β-cells decreased with time, the number of α-cells was maintained until mice were 48 weeks of age. IFN-γ content peaked in mice at 16 weeks of age and declined rapidly from 20 weeks. There were two peaks in IL-4 content, one at 16 weeks and the other at 32 weeks, suggesting an association between IL-4 content and advanced insulitis after 32 weeks. In conclusion, the results suggest that insulitis in AIP is induced predominantly by the infiltration of CD11c+ cells and CD4+ T cells into the islets, and progression is facilitated by the imbalance of the activation of Th2 rather than Th1. Furthermore, insulitis in AIP predominantly involves β-cells rather than α-cells

4,6-Dihydroxysalicylic Acid-Catalyzed Oxidative Condensation of Benzylic Amines and Aromatic Ketones for the Preparation of 2,4,6-Trisubstituted Pyridines and Its Application to Metal-Free Synthesis of G‑Quadruplex Binding Ligands

4,6-Dihydroxysalicylic acid was activated under air to catalyze the one-pot oxidative condensation reaction of benzylamines with acetophenones in the presence of BF3·Et2O, affording 2,4,6-trisubstituted pyridines in yields of 59–91%. During this metal-free oxidative condensation reaction, the benzylamines not only provided the aryl moiety at the 4-position of the pyridines but also acted as the nitrogen donor. This method can be applied to the metal-free synthesis of G-quadruplex binding ligands by the sequential addition of 4-chlorobutyryl chloride and pyrrolidine to the reaction system of the 2,4,6-trisubstituted pyridine synthesis

Neutrino-induced reactions on Fe-56 and Ni-56, and production of Mn-55 in population III stars

Neutrino-induced reactions on 56 Fe and 56 Ni are investigated based on a new shell-model Hamiltonian for pf shell. The calculated charged current reaction cross section on 56 Fe induced by decay-at-rest (DAR) neutrinos is shown to be consistent with the observation. The Gamow-Teller strength in 56 Ni is found to be more spread compared to previous calculations and result in a considerably large branching ratio for the proton knock-out channel. As a consequence of this, the production yields of heavy elements such as 55 Mn in population III stars are shown to be enhanced for the new Hamiltonian.status: publishe

Metal-Free Oxidative Coupling of Benzylamines to Imines under an Oxygen Atmosphere Promoted Using Salicylic Acid Derivatives as Organocatalysts

The oxidative coupling of benzylamines proceeds efficiently using salicylic acid derivatives as organocatalysts under an oxygen atmosphere, affording the corresponding <i>N</i>-benzylidenebenzylamines in high yields. Electron-rich salicylic acid derivatives such as 4,6-dimethoxysalicylic acid and 4,6-dihydroxysalicylic acid exhibit excellent catalytic activities for the oxidative coupling of benzylamines to give the corresponding imines. This amine oxidation can also be applied to the synthesis of nitrogen-containing heterocycles such as benzimidazole derivatives. Furthermore, to recycle the catalyst, silica gel supported with 4.7 wt % of 4,6-dihydroxysalicylic acid is prepared, which acts as a recyclable catalyst, oxidizing benzylamine to imine four times successfully

Oxidative Synthesis of Acid Blue 7 Dye Catalyzed by CuO/Silicotungstic Acid in Water-Phase

A catalytic oxidation reaction for Acid Blue 7 dye synthesis was evaluated in water. Without lead oxide or manganese oxide derivatives as oxidants, polyoxometalate catalysts were investigated to reduce the usage of harmful heavy metal. A catalyst was prepared by mixing silicotungstic acid with copper oxide, and aqueous hydrogen peroxide (30%) was used as an oxidizing agent. This reaction proceeded to produce Acid Blue 7 from the corresponding leuco acid after 45 min at 95 °C and was viable for a 10 g-scale synthesis