Cardiovascular Safety Pharmacology of Sibutramine

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC₅₀ of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD₅₀, and 9% and 17% decreases in APD₉₀, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.     

Optimal combinations of systolic and diastolic blood pressure in Korea: A nationwide population‐based cohort study

We investigated the optimal combinations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels for lowest mortality in participants not taking hypertensive medication at the study baseline using nationwide representative databases. Survival rates and hazard ratios (HRs) were calculated using Kaplan‐Meier curves and multivariable Cox regression analyses. The discriminatory ability for clinical outcomes was assessed by Harrell's C‐index analysis. A survival spline curve was presented, and Classification and Regression Tree (CART) analysis was performed. SBP ≥ 140 group and DBP ≥ 90 group had the highest risk of mortality. Within SBP < 120, the HR (95% CIs) for all‐cause mortality (ACM) was the lowest for DBP 70‐79. Within SBP 120‐139, the HR (95% CIs) for ACM was significantly lower for DBP 70‐79. Within SBP ≥ 140, the HR (95% CIs) for ACM was significantly lower for DBP 80‐89. Conversely, within SBP ≥ 140, DBP < 70 showed the highest risk for ACM. Similar relationships were observed when survival spline curves and CART analysis were used. The combination of SBP and DBP discriminated better than SBP or DBP alone for mortality. The effect of DBP on mortality varies according to the SBP range. It is more effective to evaluate the effect of SBP and DBP jointly for clinical outcomes.     

(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors

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The effect of electron density in furan pendant group on thermal-reversible Diels–Alder reaction based self-healing properties of polymethacrylate derivatives

Herein, we discuss the effect of electron density in a furan pendant group on the thermally reversible Diels–Alder (DA) reaction based self-healing efficiency in polymethacrylate derivatives. First, the furan-functionalized polymethacrylates (rPFMA and dPFMA) having different electron density in the furan pendant groups were prepared through free-radical polymerization. The healing efficiency of rPFMA, which was expected to have high healing efficiency due to the high reactivity of DA reaction originating from the electron density in the furan moiety, was shown to be 95.89% in the first and 69.86% in the second healing process, respectively, where it is higher than that of dPFMA having relatively low electron density in the furan moiety. To illustrate these results, kinetic tests of the DA reaction for rPFMA64 and dPFMA64 were performed, where the reactivity of the DA reaction for rPFMA64 was much higher than that for dPFMA64. This could be explained by the electron density in the furan pendant groups which controls the reactivity of DA reaction having a major effect on the efficiency of self-healing performance in furan-functionalized polymethacrylates.

Herein, we discuss the effect of electron density in a furan pendant group on the thermally reversible Diels–Alder (DA) reaction based self-healing efficiency in polymethacrylate derivatives.     

Spatial Decomposition of a Broadband Pulse Caused by Strong Frequency Dispersion of Sound in Acoustic Metamaterial Superlattice

An acoustic metamaterial superlattice is used for the spatial and spectral deconvolution of a broadband acoustic pulse into narrowband signals with different central frequencies. The operating frequency range is located on the second transmission band of the superlattice. The decomposition of the broadband pulse was achieved by the frequency-dependent refraction angle in the superlattice. The refracted angle within the acoustic superlattice was larger at higher operating frequency and verified by numerical calculated and experimental mapped sound fields between the layers. The spatial dispersion and the spectral decomposition of a broadband pulse were studied using lateral position-dependent frequency spectra experimentally with and without the superlattice structure along the direction of the propagating acoustic wave. In the absence of the superlattice, the acoustic propagation was influenced by the usual divergence of the beam, and the frequency spectrum was unaffected. The decomposition of the broadband wave in the superlattice’s presence was measured by two-dimensional spatial mapping of the acoustic spectra along the superlattice’s in-plane direction to characterize the propagation of the beam through the crystal. About 80% of the frequency range of the second transmission band showed exceptional performance on decomposition.     

Differentiation of hepatic abscess from metastasis on contrast-enhanced dynamic computed tomography in patients with a history of extrahepatic malignancy: emphasis on dynamic change of arterial rim enhancement

Abdominal Radiology - The objective of the study is to identify computed tomography (CT) findings that differentiate hepatic abscess from hepatic metastasis in a patient with a history of...