Effect of Am-80, A Novel Retinoid Derivative, On Contact Hypersensitivity Caused by Repeated Applications of Hapten in Mice

Some retinoids show an anti-inflammatory action through regulation of transcription of various genes. In the present study, the inhibitory effect of 4-((5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) carbamoyl) benzoic acid (Am-80), a synthetic retinoid, on mouse contact hypersensitivity provoked by repeated applications of 2,4-dinitrofluorobenzene (DNFB) to the ear was investigated. Five-fold applications of DNFB on ears once per week elicited severe contact dermatitis with marked infiltration of inflammatory cells and elevation of anti-dinitrophenyl (DNP)-IgE antibody in the serum. The Am-80 significantly inhibited ear swelling in a dose-dependent manner. In the histopathologic study, infiltration of inflammatory cells was clearly decreased by Am-80. However, Am-80 did not affect the production of DNP-specific IgE antibody both at the transcriptional and post-transcriptional levels. The effects of Am-80 on the transcriptional level of cytokines, interferon (IFN)-γ, interleukin (IL)-1 and IL-4 in cervical lymph nodes were investigated. Marked elevation of mRNA for all cytokines was observed and Am-80 potently inhibited the expression of IFN-γ mRNA, but not IL-1 and IL-4 mRNA. These findings indicated that Am-80 may inhibit the contact dermatitis at the post-sensitization phase by inhibiting IFN-γ production at the transcriptional level in mice

Drug Binding Dynamics of the Dimeric SARS-CoV-2 Main Protease, Determined by Molecular Dynamics Simulation

We performed molecular dynamics simulation of the dimeric SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) main protease (Mpro) to examine the binding dynamics of small molecular ligands. Seven HIV inhibitors, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir, were used as the potential lead drugs to investigate access to the drug binding sites in Mpro. The frequently accessed sites on Mpro were classified based on contacts between the ligands and the protein, and the differences in site distributions of the encounter complex were observed among the ligands. All seven ligands showed binding to the active site at least twice in 28 simulations of 200 ns each. We further investigated the variations in the complex structure of the active site with the ligands, using microsecond order simulations. Results revealed a wide variation in the shapes of the binding sites and binding poses of the ligands. Additionally, the C-terminal region of the other chain often interacted with the ligands and the active site. Collectively, these findings indicate the importance of dynamic sampling of protein- ligand complexes and suggest the possibilities of further drug optimisations. Raw trajectory data analysed in this paper and movie examples are available at the zenodo repository. </div

Endoscopic transpapillary gallbladder drainage with replacement of a covered self-expandable metal stent

Endoscopic self-expandable metal stent (SEMS) placement has become a standard palliative therapy for patients with malignant biliary obstruction. Acute cholecystitis after SEMS placement is a serious complication. We report a patient with an acute cholecystitis after covered SEMS placement, who was managed successfully with endoscopic transpapillary gallbladder drainage (ETGBD) and replacement of the covered SEMS. An 85-year-old man with pancreatic cancer suffered from acute cholecystitis after covered SEMS placement. It was impossible to perform percutaneous transhepatic gallbladder drainage. After removal of the covered SEMS with a snare, a 7Fr double pigtail stent was placed between the gallbladder and duodenum, subsequently followed by another covered SEMS insertion into the common bile duct beside the gallbladder stent. The cholecystitis improved immediately after ETGBD. ETGBD with replacement of the covered SEMS thus proved to be effective for treatment of patients with acute cholecystitis after covered SEMS placement

Evaluation of Rate of Adhesion of Lactobacillus namurensis Strain GYP-74 to Porous Fine Ceramics

This study aimed to evaluate the ratio of adherence of lactic acid bacteria (LAB) to porous fine ceramics in order to develop a novel LAB-rich pickle container for the production of functional fermented vegetables. Some LAB were isolated from the salted rice bran used for pickling (Nukadoko in Japanese). These isolates were classified in Lactobacillus namurensis by phylogenetic analysis. Some pottery-shard (PS) samples were prepared by varying the mixing rate of polyacetal (POM) resin to clay (0–30% (v/v)) and the burning temperature (1000 °C or 1100 °C). A test of the adherence of strain GYP-74 to the PSs was performed. The results showed that the adherence rate was significantly higher in the PSs burned at 1100 °C as compared with those burned at 1000 °C. A pore distribution analysis showed that pore sizes of less than a few µm and pore sizes in the range of a few µm to a few hundred µm were mainly distributed in the PSs without and with POM, respectively. X-ray diffraction analysis showed that both PSs with and without POM contained quartz and hematite. The PSs burned at 1000 °C and 1100 °C specifically contained microcline and mullite, respectively. This study revealed the basal information regarding what makes PSs adequate for LAB adhesion

Clinical analysis of high serum IgE in autoimmune pancreatitis

AIM: To clarify the clinical significance of high serum IgE in autoimmune pancreatitis (AIP)