James Thomsen (monkeyhose25)

A novel high-performance liquid chromatography-mass spectrometry method was developed to determine the quantities of pyridine, 4-dimethylaminopyridine, and N, N-dimethylaniline impurities in vildagliptin drug material. These impurities are reactive bases that may be used in synthesis of vildagliptin pharmaceutical ingredients. They are considered as potentially genotoxic impurities since they contain electrophilic functional groups. Therefore, these impurities should be monitored at the allowed limits in vildagliptin. Hence a high-performance liquid chromatography-mass spectrometry method was developed to quantify the amounts of these impurities in vildagliptin. The column was KROMASIL CN (250 mm × 3.9 mm, 3.5 μm) in reversed-phase mode. The mobile phase was a mixture of water-methanol (5545) containing 2.5 mM ammonium acetate and 0.1% formic acid. The mass spectrometer was used to detect the amounts of impurities using selected ionization monitoring mode at m/z = 80, 122, and 123 for pyridine, N, N-dimethylaniline, and 4-dimethylaminopyridine, respectively. The flow rate was 0.5 mL/min. The sensitivity of the method was excellent at levels very less than the allowed limits. The method had excellent linearity in the concentration ranges of limit of quantification-150% of the permitted level with coefficients of determination above 0.9990. The recovery ratios were in the range of 93.70-108.63%. Results showed good linearity, precision, accuracy, sensitivity, selectivity, robustness, and solution stability.When performing living-donor lobar lung transplantation on small children of height 100 cm or under, accommodation of an oversized adult lobar graft is problematic, sometimes necessitating single lobar transplantation in combination with contralateral pneumonectomy. We here report a unique case of living-donor lobar lung transplantation in a 9-year-old boy with congenital pulmonary hypoplasia. Although he was 104 cm tall, and the available adult lower lobe graft appeared to be oversized, his right lung was hypoplastic, resulting in his mediastinum being shifted to the right and thus already showing "postpneumonectomy-like" anatomy. His father's left lower lobe was successfully transplanted into the left thorax without performing a contralateral pneumonectomy. Three-dimensional reconstruction of computed tomography images and computed tomography volumetry were extremely helpful in matching the size of the graft and planning this unique surgery.IL-12 (p35/p40) and IL-23 (p19/p40) signal through IL-12R (IL-12Rβ2/β1) and IL-23R (IL-23Rα/IL-12Rβ1), respectively, which can promote pathogenic T lymphocyte activation, differentiation, and function in graft-versus-host disease (GVHD). With the use of murine models of allogeneic hematopoietic cell transplantation (HCT), we found that IL-12Rβ1 on donor T cells was dispensable to induce acute GVHD development in certain circumstances, while IL-23Rα was commonly required. This observation challenges the current paradigm regarding IL-12Rβ1 as a prerequisite to transmit IL-23 signaling. We hypothesized that p19/EBI3 (IL-39) may have an important role during acute GVHD. With the use of gene transfection and immunoprecipitation approaches, we verified that p19 and EBI3 can form biological heterodimers. We found that IL-39 levels in recipient serum positively correlated with development of acute GVHD in experimental models and in clinical settings, thereby implicating IL-39 in the pathogenesis of acute GVHD. Furthermore, we observed that human T cells can signal in response to IL-39. In chronic GVHD, IL-23Rα and IL-12Rβ1 were similarly required for donor T cell pathogenicity, and IL-39 levels were not significantly different from controls without GVHD. Collectively, we identify a novel cytokine, IL-39, as a pathogenic factor in acute GVHD, which represents a novel potential therapeutic target to control GVHD and other inflammatory disorders. Arable crops in temperate climatic regions su