Assessment of the proarrhythmic effects of repurposed antimalarials for COVID-19 treatment using a comprehensive in vitro proarrhythmia assay (CiPA)

Due to the outbreak of the SARS-CoV-2 virus, drug repurposing and Emergency Use Authorization have been proposed to treat the coronavirus disease 2019 (COVID-19) during the pandemic. While the efficiency of the drugs has been discussed, it was identified that certain compounds, such as chloroquine and hydroxychloroquine, cause QT interval prolongation and potential cardiotoxic effects. Drug-induced cardiotoxicity and QT prolongation may lead to life-threatening arrhythmias such as torsades de pointes (TdP), a potentially fatal arrhythmic symptom. Here, we evaluated the risk of repurposed pyronaridine or artesunate-mediated cardiac arrhythmias alone and in combination for COVID-19 treatment through in vitro and in silico investigations using the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The potential effects of each drug or in combinations on cardiac action potential (AP) and ion channels were explored using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and Chinese hamster ovary (CHO) cells transiently expressing cardiac ion channels (Nav1.5, Cav1.2, and hERG). We also performed in silico computer simulation using the optimized O’Hara-Rudy human ventricular myocyte model (ORd model) to classify TdP risk. Artesunate and dihydroartemisinin (DHA), the active metabolite of artesunate, are classified as a low risk of inducing TdP based on the torsade metric score (TMS). Moreover, artesunate does not significantly affect the cardiac APs of hiPSC-CMs even at concentrations up to 100 times the maximum serum concentration (Cmax). DHA modestly prolonged at APD90 (10.16%) at 100 times the Cmax. When considering Cmax, pyronaridine, and the combination of both drugs (pyronaridine and artesunate) are classified as having an intermediate risk of inducing TdP. However, when considering the unbound concentration (the free fraction not bound to carrier proteins or other tissues inducing pharmacological activity), both drugs are classified as having a low risk of inducing TdP. In summary, pyronaridine, artesunate, and a combination of both drugs have been confirmed to pose a low proarrhythmogenic risk at therapeutic and supratherapeutic (up to 4 times) free Cmax. Additionally, the CiPA initiative may be suitable for regulatory use and provide novel insights for evaluating drug-induced cardiotoxicity

Progression from Chronic Atrophic Gastritis to Gastric Cancer; Tangle, Toggle, Tackle with Korea Red Ginseng

Key molecular players that link inflammation to carcinogenesis are prostaglandins, cytokines, nuclear factor-κB (NF-κB), chemokines, angiogenic growth factors, and free radicals, all of which lead to increased mutations and altered functions of important enzymes and proteins, for example, activation of oncogenic products and/or inhibition of tumor suppressor proteins, in inflamed tissues, thus contributing to multi-stage carcinogenesis process. Interpreted reversely, the identification of the molecular mechanisms by which chronic inflammation increases cancer risk or optimal intervention of targeted drugs or agents during the inflammation-associated carcinogenic process could be a necessary basis for developing new strategy of cancer prevention at many sites. In this review, we discuss the possibilities for cancer prevention by controlling inflammation process in Helicobacter pylori (H. pylori)-associated inflamed stomach with Korea red ginseng. Korea red ginseng is a good example of a natural herb that has ubiquitous properties that are conductive to stop inflammatory carcinogenesis that is un wanted outcome of H. pylori infection, rendering rejuvenation of chronic atrophic gastritis

Timarete posteria, a new cirratulid species from Korea (Annelida, Polychaeta, Cirratulidae)

A new cirratulid species, Timarete posteria sp. n., is described from the intertidal habitats of the eastern coast of South Korea. The new species is closely related to Timarete luxuriosa (Moore, 1904) from southern California based on morphological similarity of the branchial and tentacular finalents and the noto- and neuropodial spines. However, T. posteria sp. n. differs from the latter based on the following characteristics: 1) evenly divided peristomium into three annulations; 2) 2–4 neuropodial spines originating in the posterior chaetigers alternated by a few capillaries; and 3) complete shift in branchial finalents located about one-third between the notopodium and the dorsal midline. The new species has a methyl green staining pattern (MGSP) distinct from other Timarete species. Detailed description and illustrations of the new species are provided with molecular information based on the partial sequences of the mitochondrial cytochrome c oxidase subunit I (COI) and 16S ribosomal RNA (16S). This study also includes a key and discussion of known Timarete species from East Asia

Characteristics of high efficiency current charging system for HTS magnet with solar energy

AbstractIn terms of electrical energy, the technical fusion with solar energy system is promisingly applied in order to improve the efficiency in the power applications, since the solar energy system can convert an eternal electric energy in all-year-around. As one of such power applications, we proposed a current charging system for HTS magnet combined with solar energy (CHS). As this system can operate without external utility power to charge the HTS load magnet due to the solar energy, the operating efficiency is practically improved. The power converter, which is interfaced with solar energy and HTS magnet systems, plays an important role to transfer the stable electric energy and thus, the stabilized performance of the converter with solar energy system is one of essential factors. In this study, we investigated various charging performances under different operating conditions of the converter. In addition, operating characteristics have been analyzed by solving solar cell equivalent equations based on circuit simulation program

Hearing Abilities at Ultra-High Frequency in Patients with Tinnitus

ObjectivesTo compare tinnitus patients who have normal hearing between 250 Hz and 8 kHz with normal controls with regard to the ability of each group to hear extended high-frequency pure tone thresholds.MethodsWe enrolled 18 tinnitus patients, each of whom had a threshold of HL <25 dB and threshold differences of <10 dB between ears at frequencies of 250 and 500 Hz and 1, 2, 4, and 8 kHz. We also enrolled age- and gender-matched normal volunteers (10 ears), for each patient. Extended high frequency pure tone audiometry was performed, and the mean hearing thresholds at 10, 12, 14, and 16 kHz of each tinnitus ear were compared with those of the 10 age- and sex-matched normal ears.ResultsOf the 18 patients with tinnitus, 12 had significantly increased hearing thresholds at more than one of the four high frequencies, compared with the normal group. When we assessed results according to frequency, we found that 8 patients had decreased hearing ability at 10 kHz, 10 at 12 kHz, 8 at 14 kHz, and 4 at 16 kHz.ConclusionSome patients with tinnitus who have normal hearing below 8 kHz have decreased hearing ability at extended high-frequencies. Thus, the proportion of patients with tinnitus who have normal hearing over the entire audible range is smaller than in previous reports