Smidtmay3386
onment as a possible mechanism.
The distribution of tacrolimus (TAC), an immunosuppressant used during cord blood transplantation (CBT)-one of the haematopoietic stem cell transplantations, to red blood cell (RBC) is approximately 90% in whole blood. In CBT patients, the total RBC count shows dramatic fluctuation due to conditioning before transplantation, including anticancer agents and total body irradiation, as well as RBC transfusions during the treatment period. Therefore, the amount of TAC in whole blood may show wide variation. However, therapeutic drug monitoring (TDM) of TAC has been performed based on the whole blood concentration. In this study, to contribute to TDM of TAC in CBT, we performed the population pharmacokinetic (PPK) analysis of TAC in 56 CBT patients and investigated the factors that affected the concentration of TAC, focusing the variation of RBC count.
A one-compartment model was applied to the observed whole blood TAC concentrations, and a PPK analysis was conducted with a non-linear mixed effect model.
Our final PPK model indicated good robustness and accuracy. In addition, haemoglobin (Hb) level was an influential covariate on Vd, which was expressed as Vd(L)=91.4×(Hb/8.2)
.
In this study, our results showed the necessity for the Hb level monitoring during TDM of TAC in CBT patients and provided useful information for improving TDM strategy of TAC.
In this study, our results showed the necessity for the Hb level monitoring during TDM of TAC in CBT patients and provided useful information for improving TDM strategy of TAC.Guanine quadruplex recognition has gained increasing attention, inspired by the growing awareness of the key roles played by these non-canonical nucleic acid architectures in cellular regulatory processes. We report here the solution and solid-state studies of a novel planar platinum(II) complex that is easily assembled from a simple ligand, and exhibits notable binding affinity for guanine quadruplex structures, while maintaining good selectivity for guanine quadruplex over duplex structures. A crystal structure of this ligand complexed with a telomeric quadruplex confirms double end-capping, with dimerization at the 5' interface.The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7 days and treated with GLP-1R agonists. selleck inhibitor Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Cells exposed to high glucose showed lower NF-κB and SOD2 methylation levels, increased NF-κB and reduced SOD2 expression compared to normal glucose cells. Co-treatment with GLP-1 agonists prevented methylation and genes expression changes induced by high glucose. Both high glucose and incretins exposure increased DNA methyltransferases and demethylases levels. In diabetics, incretin treatment resulted a significant predictor of NF-κB DNA methylation, independently of age, sex, body mass index (BMI), glucose and plasma lipid levels. NF-κB DNA methylation inversely correlated with IMT after adjusting for multiple covariates. Our results firstly provide new evidences of an additional mechanism by which incretin drugs could prevent vascular diabetic complications.Dual/multi-component organic doped systems with room-temperature phosphorescence (RTP) properties have been developed. However, the unknown luminescence mechanism still greatly limits the development of the doped materials. Herein, a new doped system exhibiting phosphorescence/fluorescence dual emission (Φphos =4-24 % and τphos =101-343 ms) is successfully constructed through prediction and design. A series of isoquinoline derivatives with different alkoxy chains were selected as the guests. Benzophenone was chosen as the host owing to the characteristics of low melting point and good crystallinity. The alkoxy chain lengths of the guests are first reported to be used to control the fluorescence and phosphorescence intensities of the doped materials, which results in different prompt emission colors. Additionally, the doped ratio of the guest and host can also control the luminous intensities of the materials. In particular, the doped materials still exhibit phosphorescent properties even if the ratio of the guest/host is as low as 1100 000.
Purine-degrading enzymes are favorable as medications and diagnostic tools for hyperuricemia. This study aimed to characterize enzymes isolated from microorganisms, which may useful for developing a new prophylaxis for hyperuricemia.
Cellulosimicrobium funkei A153 was found to be a good catalyst for hypoxanthine degradation and could oxidize hypoxanthine to xanthine and further to uric acid. The enzyme catalyzing this oxidation was purified, and its partial amino acid sequences were examined. Based on this information and genome sequencing results, this xanthine dehydrogenase family protein was cloned and expressed in Rhodococcus erythropolis L88. The recombinant enzyme with a His-tag was characterized. The enzyme was a xanthine oxidase as it could utilize molecular oxygen as an electron acceptor. It was stable under 50ºC and exhibited maximum activity at pH 7.0. The k
, K
, and k
/K
values for xanthine were 1.4 s
, 0.22 mmol l
, and 6.4 s
mmol
l, respectively.
Xanthine oxidase is favorable for hyperuricemia medication because it oxidizes hypoxanthine, an easily adsorbed purine, to xanthine and further to uric acid, which are hardly adsorbed purines.
The enzyme is useful for decreasing serum uric acid levels via conversion of easily absorbed purines to hardly absorbed purines in the intestine. Enzymes from microorganisms may be used as a novel prophylaxis for hyperuricemia.
The enzyme is useful for decreasing serum uric acid levels via conversion of easily absorbed purines to hardly absorbed purines in the intestine. Enzymes from microorganisms may be used as a novel prophylaxis for hyperuricemia.
