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As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.

Objective: To investigate the association between aortic stiffness and incident albuminuria and the decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Research Design and Methods: We investigated 461 Japanese type 2 diabetic patients, comprising 199 women and 262 men, with a mean age of 59 ± 11 years. Patients were divided into two groups according to the median value of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness. The end point was defined as the transition from normo- to microalbuminuria or micro- to macroalbuminuria. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% CI. The correlation between cf-PWV and rate of change in eGFR was also determined by linear regression analysis.Results: The baseline mean (± SD) cf-PWV was 9.6 ± 2.4 m/s. During a median follow-up period of 5.9 years (range 0.3-8.6), progression of albuminuria was observed in 85 patients. The 5-year cumulative incidence of the end point in patients with cf-PWV below and above the median was 8.5 and 19.4%, respectively (P = 0.002, log-rank test). cf-PWV was significantly associated with incident albuminuria (HR 1.23, 95% CI 1.13-1.33, P < 0.001) by multivariate Cox regression analysis. A significant association between cf-PWV and annual change in eGFR was also suggested by multiple linear regression analysis (standardized estimate -0.095, P = 0.031).Conclusions: Aortic stiffness is associated with incident albuminuria and the rate of decline in glomerular filtration rate in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Abstract: The interfacial resistance between the composite electrode and PEO-based solid polymer electrolyte was examined using two different symmetrical cells and AC impedance measurements in the temperature range of 30–60°C. Of the four major resistance components identified in our previous study, three components due to the resistances of the polymer electrolyte and the charge transfer resistance between LiFePO4-C and the electrolyte were assigned; however, one resistance component, in the medium frequency range has not yet been assigned. In this report, the medium frequency range resistance component was investigated using a symmetrical cell with composite electrodes composed of active and inactive materials (LiCoO2, LiMn2O4 and SiO2), solid polymer electrolyte, and carbon fiber as an electron conductor. The resistance was not affected by the carbon coating in LiFePO4-C and the conductive carbon additive (VGCF). An electron blocking cell was also prepared and the resistance was measured in the temperature range of 30–60°C to confirm the effect of the electrode thickness and the electrode composition. The resistance was not affected by the thickness, and decreased with decreasing PEO-LiTFSI electrolyte content in the composite electrode. However, no significant change in the activation energy was evident with the change in the electrode composition. [Copyright &y& Elsevier]

Purpose: We investigated whether images of stationary objects obtained by segmental acquisition with positron emission tomography using 2-deoxy-2-[(18)F]-fluoro-D: -glucose (FDG-PET) are of a quality equivalent to those obtained by conventional continuous acquisition.Materials and Methods: Phantoms filled with FDG and mid-abdominal regions of 18 patients who underwent FDG-PET tests were imaged by both continuous and segmental acquisition methods. The total acquisition time was set to 3 min; in the segmental acquisition mode, imaging for 15 s was repeated 12 times. Segmental images (SIs) obtained by superimposition of the reconstructed images were compared quantitatively and visually with continuous images (CIs).Results: In all the phantom and clinical studies, SIs were never worse than CIs. The variances of the background counts of SIs were 9.8% and 13.0% less those of CIs in phantom and clinical studies, respectively. Visual assessments showed that SIs provided better detection of hot areas and superior image quality when compared to CIs.Conclusion: For stationary objects, the quality of images obtained by the segmental method is equivalent to that of images obtained conventionally by continuous acquisition. Moreover, under some conditions SIs provide better results than CIs. [ABSTRACT FROM AUTHOR]

Abstract: The interface resistance between Li x FePO4 and poly(ethylene oxide) (PEO)–Li(CF3SO2)2N (LiTFSI) was examined by AC impedance measurement of a Li x FePO4/PEO–LiTFSI/Li x FePO4 cell in the temperature range of 30–60°C. Four types of resistance, R0, R1, R2 and R3 were proposed according to analysis of the cell impedance using an equivalent circuit. The sum of R0 and R1 in the high frequency range is consistent with the resistance of the PEO electrolyte. R2 in the middle frequency range is related to lithium ion transport to an active point for charge transfer inside the composite electrode, and R3 in the low frequency range is considered to be the charge transfer resistance. The activation energy for R2 was affected by the thickness and composition of the electrode, whereas that for R3 was not. [Copyright &y& Elsevier]

Abstract: LiFePO4/carbon composite electrode was prepared and applied to the dry polymer electrolyte. Enhanced low-temperature performance of LiFePO4 was achieved by modifying the interface between LiFePO4 and polymer electrolyte. The molecular weight of the polymer and the salt concentration as the Li/O ratio were optimized at 3×105 and 1/10, respectively. Impedance analysis revealed that a small resistive component occurred in the frequency range of the charge transfer process. The reversible capacity of the laminate cell was 140mAhg−1 (C/20) and 110mAhg−1 (C/2) at 40°C, which is comparable to the performance in the liquid electrolyte system. [Copyright &y& Elsevier]

Dispersing ultrafine silicon particles within a ductile graphite matrix by means of high-energy mechanical milling (HEMM) provides an effective way to alleviate the volume effects of silicon upon the repeated electrochemical Li insertion and extraction, resulting in a significantly improved mechanical strength. However, HEMM increases the initial irreversible capacity to unaccepted levels. This deterrent can be overcome by introducing a certain amount of hexagonal Li2.6Co0.4N into above silicon–graphite hosts. The Si–graphite–Li2.6Co0.4N composite synthesized from two HEMM steps demonstrates a large reversible capacity of ca. 1Ahg-1 accompanied with a high cycling stability. Research reveals that the elastic graphite–Li2.6Co0.4N matrix with a good electrical/ionic conductivity can permit the silicon in the matrix to operate while maintaining the morphology integrity. More important, fully lithiated Li2.6Co0.4N plays a role in the capacity compensation in the first cycle that leads to a high initial coulombic efficiency. [Copyright &y& Elsevier]

Objective: To clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D).Research Design and Methods: This was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.Results: Patients with low or high leptin levels had a steeper eGFR decline (-2.07 and -2.14 mL/min/1.73 m(2)/year) than those with midrange leptin levels (-0.82 mL/min/1.73 m(2)/year; P < 0.01), whereas patients with low leptin levels had an elevated risk of progression of albuminuria as compared with those with high leptin levels (hazard ratio 3.125 [95% CI 1.302-7.499]).Conclusions: Both low and high serum leptin levels were risk factors for kidney function decline. Meanwhile, lower serum leptin levels were associated with progression of albuminuria. [ABSTRACT FROM AUTHOR]