Growth temperature (TG) dependence of the acceptor concentrations (NA) in Al0.1Ga0.9Sb grown by liquid phase epitaxy in a very wide growth temperature range (250–500 °C) was investigated. It was found that NA varies with TG down to 350 °C as NA ∝exp(Ea/kBTG) with Ea=0.47 eV and that below 350 °C NA fluctuates depending highly on growth conditions. Acceptors in Al0.1Ga0.9Sb grown above 350 °C were concluded to be intrinsic. These observations were successfully made using the improved extremely low-temperature growth process. The evaluation technique of measuring the impurity concentration in a thin epitaxial layer on the conductive GaSb substrate by C-V characteristics of metal-insulator-semiconductor structures was employed.
A 4-Gb AG-AND flash memory was fabricated by using a 90-nm CMOS technology. To reduce cell size, an inversion-layer-bit-line technology was developed, enabling the elimination of both shallow trench isolations and diffusion layers from the memory cells. The inversion-layer-bit-line technology combined with a multilevel cell technique achieved a bit area 2F 2 of 0.0162μm 2 , resulting in a chip size of 126mm 2 . Both an address and temperature compensation techniques control the resistance of the inversion-layer local bit line. Source-side hot-electron injection programming with self-boosted charge, accumulated in inversion-layer bit lines under assist gates, reduces the dispersal of programming characteristics and also reduces the time overhead of pre-charging the bit lines. This self-boosted charge-injection scheme achieves a programming throughput of 10MB/s.
The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m<sup>2</sup>, including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment.
In recent years, cancer chemotherapy has been shifted from inpatients to outpatients. In outpatient cancer chemotherapy, patients manage side effects by themselves. Therefore, it is very important that pharmacists provide information of side effects to patients. In Shiga University of Medical Science Hospital, pharmaceutical care to all outpatients by pharmacists was started from October 2010. However, starting the service incurred some problems. One of them was understaffing. When we constructed a novel original outpatient chemotherapy system, the manpower shortage problem was dispelled. Throughout this service, various symptoms caused by chemotherapy were more significantly improved in intervention cases than in non-intervention cases. A medication leaflet was used when providing medical information for pharmaceutical care. It was also expected to provide information to medical facilities outside the hospital. We consider that the medical leaflet may contribute to promoting collaboration between hospital and community pharmacies.
While nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphism Arg139Cys (rs116855232) is known to be a risk factor for thiopurine-induced severe leukopenia, association with the NUDT15 gene polymorphism Arg139His (rs147390019) has not yet been clarified. In addition, the accuracy of TaqMan PCR to assess these two polymorphisms has not been investigated. In this study, we evaluated TaqMan PCR for detection of the NUDT15 single-nucleotide polymorphisms (SNPs) and examined the clinical impact of Arg139His on thiopurine-induced leukopenia. First, we demonstrated that a TaqMan PCR assay successfully detected the Arg139His polymorphism of NUDT15 in clinical samples. Next, the NUDT15 gene polymorphisms (Arg139Cys and Arg139His) were separately analyzed by TaqMan Real-Time PCR in 189 patients from August 2018 to July 2019. The incidences of leukopenia within 2 years were 16.2, 57.9, and 100% for arginine (Arg)/Arg, Arg/cysteine (Cys), and Arg/histidine (His), respectively. The leukopenia was significantly increased in Arg/Cys and Arg/His compared with Arg/Arg. This retrospective clinical study indicated that, in addition to Arg139Cys, Arg139His may be clinically associated with a high risk of leukopenia. Pharmacogenomics will help in selecting drugs and determining the individualized dosage of thiopurine drugs.
The multikinase inhibitor sorafenib has been used in the treatment of hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma. Here we have demonstrated the production of the first specific antibody against sorafenib. Anti-sorafenib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and carboxylic modified 4-(4-aminophenoxy)-N-methyl-2-pyridinecarboxamide (AMPC) using the N-succinimidyl ester method. Enzyme labeling of sorafenib with horseradish peroxidase was similarly performed using carboxylic modified AMPC. A simple competitive enzyme-linked immunosorbent assay (ELISA) for sorafenib was developed using the principle of direct competition between sorafenib and the enzyme marker for anti-sorafenib antibody, which had been adsorbed by the plastic surface of a microtiter plate. Serum sorafenib concentrations lower than 0.04 µg/mL were reproducibly measurable using the ELISA. This ELISA was specific to sorafenib and showed very slight cross-reactivity (2.5%) with a major metabolite, sorafenib N-oxide. The values of serum sorafenib levels from 32 patients measured by this ELISA were comparable with those measured by HPLC, and there was a strong correlation between the values determined by the two methods (Y=1.016X-0.137, r=0.979). The specificity and sensitivity of the ELISA for sorafenib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of sorafenib.
Pb-Ti-Nb-O ferroelectric thin films with various Nb additions are grown on a Pt/Ti/SiO 2 /Si substrate at 400 °C by metal-organic (MO) CVD. A high density of dome-like surface protrusions is observed by scanning electron microscopy (SEM) in all the as-prepared films. Both the shape and the size of the surface defects are found to be Nb-content-dependent. The internal microstructure of the protrusions is further characterized by cross-section transmission electron microscopy (XTEM). The origins of these surface defects are discussed, based on the substrate hillock as well as the crystallization behavior of the film forming precursors during MOCVD. The development of the observed surface defects is modeled using a two-dimensional vector analysis.
