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Background The clinical dosing method for tolvaptan in patients with acute heart failure (HF) is still unclear. We aimed to compare the differences in clinical effect between two dosing regimens: once-daily 7.5 mg and twice-daily 3.75 mg. Methods In this randomized trial, tolvaptan was administered within 12 h from hospital admission. The primary outcome was the serial change in congestion scores measured every day from enrollment until dosing day 7. Outcomes including safety parameters were also evaluated. Results The subjects were assigned to either the once-daily 7.5 mg dosing regimen ( N = 15) or the twice-daily 3.75 mg dosing regimen ( N = 16). The time-course changes in body weight, serum sodium and creatinine levels, systolic blood pressure, daily urine output, and congestion scores were similar between the two groups. In the twice-daily 3.75 mg dosing group, the serum sodium levels on days 3 and 4 were significantly ( p < 0.05) increased compared with those on day 1. The congestion scores significantly ( p < 0.05) decreased from day 2 to day 7 in both groups compared with those on day 1. However, the difference in the serial change in the congestion scores did not reach statistical significance. Conclusions Our present results suggest that the early administration of tolvaptan within 12 h after hospital admission significantly improved congestion from the first day after administration by either dosing regimen, i.e. once-daily 7.5 mg or twice-daily 3.75 mg in patients with acute HF. [ABSTRACT FROM AUTHOR]

The knowledge of excess electron binding mechanisms in biomolecules is very important for molecular-level understanding of DNA damage by low-energy electrons. We here focus on two different excess electron binding mechanisms from the theoretical side; diffuse dipole-bound and valence-bound anionic states. We have found that long-range corrected (LC) density-functional theory (DFT) methods combined with a set of diffuse basis functions can reasonably describe electronic transformation processes between these two different anionic states. The applicability of the LC-DFT calculations is demonstrated for uracil, guanine–cytosine base pair, fructose, and uracil-iodide anion complex. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of 1-bromo-2-(1-isothiocyanatoalkyl)benzenes, which are easily derived from 2-bromophenyl ketones or (2-bromophenyl)methanamine, with butyllithium generates 1-(1-isothiocyanatoalkyl)-2-lithiobenzenes, which immediately underwent intramolecular cyclization to give rise to the corresponding 3-substituted and 3,3-disubstituted 2,3-dihydro-1H-isoindole-1-thiones in good yields. [Copyright &y& Elsevier]

Abstract: An efficient one-pot method for the synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-dihydro-3,1-benzoxazine-2-thiones has been developed. Treatment of 2-bromophenyl isothiocyantes with butyllithium in THF at −78 °C generates 2-lithiophenyl isothiocyanates, which are allowed to react with various carbonyl compounds, including aldehydes, ketones, and butanolide, to give the corresponding desired products in moderate to good yields. [ABSTRACT FROM AUTHOR]

There are several in vitro systems that enable evaluation of the absorption direction, but there are few quantitative systems that enable easy evaluation of the excretion direction. Enteroids, organoids derived from intestine, have been frozen and passaged for various research. But it is not clear how the freezing and passaging affect the expression and function of transporters. We investigated the effects of passage and cryopreservation of enteroids. We focused on P-gp (P-glycoprotein) and compared the transfer rates of rhodamine 123 (Rh123) into the lumen of enteroids with and without a P-gp inhibitor. mRNA expression levels did not change significantly before and after passage and cryopreservation. Accumulation of Rh123 in the lumen of enteroids was observed. With some P-gp inhibitors, excretion of Rh123 into the lumen of enteroids was inhibited and the nonexcreted Rh123 accumulated in enteroids epithelial cells. The transfer rate of Rh123 into the lumen of enteroids with a P-gp inhibitor was significantly decreased compared to that of without a P-gp inhibitor. Before and after passage and cryopreservation, the transfer rate was almost the same as that of primary cultured enteroids. We succeeded in easily evaluating whether a component is a substrate of P-gp using enteroids. [Display omitted] • mRNA expression level of efflux intestinal transporter was not changed before and after passage and number of culture days. • This method allows semi-quantitative evaluation of efflux transporters function regardless of the shapes of enteroids. • Our method enables to easily evaluate whether a component is a substrate of P-gp using enteroids. [ABSTRACT FROM AUTHOR]