Electrophysiological analysis of mammalian cells expressing hERG using automated 384-well-patch-clamp

BACKGROUND: An in vitro electrophysiological assay system, which can assess compound effects and thus show cardiotoxicity including arrhythmia risks of test drugs, is an essential method in the field of drug development and toxicology. METHODS: In this study, high-throughput electrophysiological recordings of human embryonic kidney (HEK 293) cells and Chinese hamster ovary (CHO) cells stably expressing human ether-a-go-go related gene (hERG) were performed utilizing an automated 384-well-patch-clamp system, which records up to 384 cells simultaneously. hERG channel inhibition, which is closely related to a drug-induced QT prolongation and is increasing the risk of sudden cardiac death, was investigated in the high-throughput screening patch-clamp system. RESULTS: In the automated patch-clamp measurements performed here, K(v) currents were investigated with high efficiency. Various hERG channel blockers showed concentration-dependent inhibition, the 50 % inhibitory concentrations (IC(50)) of those blockers were in good agreement with previous reports. CONCLUSIONS: The high-throughput patch-clamp system has a high potential in the field of pharmacology, toxicology, and cardiac physiology, and will contribute to the acceleration of pharmaceutical drug development and drug safety testing

Structure Effect on Antioxidant Activity of Catecholamines toward Singlet Oxygen and Other Reactive Oxygen Species in vitro

The reactivity of catecholamine neurotransmitters and the related metabolites were precisely investigated toward 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and reactive oxygen species. Catecholamines reacted immediately with DPPH radicals, their reactivity being stronger than that of ascorbic acid as a reference. Superoxide scavenging activities of catecholamines determined by WST-1 and electron spin resonance (ESR) spin trapping methods were also high. Whereas tyrosine, the dopamine precursor showed no reactivity toward superoxide. The reactivity toward singlet oxygen was evaluated by observing specific photon emission from singlet oxygen. The results revealed that reactivity of catecholamines was markedly higher than that of sodium azide, and catechin as catechol reference. The reaction of catecholamines and singlet oxygen was further studied by ESR using 55-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping reagent and rose bengal as photosensitizer. DMPO-OH signal of epinephrine was significantly small compared to other catecholamines, catechin, and 4-methylcatechol as a reference compound and was as small as that of tyrosine. The signal formation was totally dependent on singlet oxygen, and the presence of catechol compounds. These results indicated that epinephrine is the most potent singlet oxygen quencher than other catecholamines, and the secondary amino group in its alkyl side chain could play a role in unique singlet oxygen quenching property of epinephrine

Localized-to-itinerant transition preceding antiferromagnetic quantum critical point and gapless superconductivity in CeRh0.5Ir0.5In5

A fundamental problem posed from the study of correlated electron compounds, of which heavy-fermion systems are prototypes, is the need to understand the physics of states near a quantum critical point (QCP). At a QCP, magnetic order is suppressed continuously to zero temperature and unconventional superconductivity often appears. Here, we report pressure T-c. (P)-dependent In-115 nuclear quadrupole resonance (NQR) measurements on heavy-fermion antiferromagnet CeRh0.5Ir0.5In5. These experiments reveal an antiferromagnetic (AF) QCP at P-c(AF) = 1.2 GPa where a dome of superconductivity reaches a maximum transition temperature Tc. Preceding P-c(AF), however, the NQR frequency nu(Q) undergoes an abrupt increase at P-c* = 0.8 GPa in the zero-temperature limit, indicating a change from localized to itinerant character of cerium's f-electron and associated small-to-large change in the Fermi surface. At P-c(AF) where T-c is optimized, there is an unusually large fraction of gapless excitations well below T-c that implicates spin-singlet, odd-frequency pairing symmetry

Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer

Table S2. Change in NK population in PBL

Perubahan Harga Lahan dalam Kaitannya dengan Pembangunan Pertanian di Pedesaan Lampung

IndonesianDalam pembangunan pertanian diperlukan empat faktor penggerak yaitu sumberdaya lahan, sumberdaya manusia, teknologi dan kelembagaan. Keempat faktor diatas saling terkait satu sama lain, sehingga bila salahsatu faktor diatas mengalami hambatan sulit tercapai sasaran yang diinginkan. Pesatnya laju pembangunan beberapa tahun terakhir, menyebabkan sumberdaya lahan terasa semakin terbatas. Hal ini disebabkan oleh terjadinya Perubahan fungsi lahan untuk kepentingan pembangunan itu sendiri. Bertitik tolak dari permasalahan diatas, sumberdaya lahan khususnya lahan pertanian dapat merupakan permasalahan pada masa mendatang. Sumberdaya lahan untuk pertanian akan merupakan suatu komoditi langka dan mempunyai nilai yang tinggi. Kondisi seperti ini akan banyak membawa dampak, baik terhadap nilai lahan, kelembagaan pertanian dan lain sebagainya. Prubahan-Perubahan yang terjadi sudah tentu akan mempengaruhi pembangunan pertanian pada masa mendatang

Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity

Clinical Usefulness of the VS Classification System Using Magnifying Endoscopy with Blue Laser Imaging for Early Gastric Cancer

Background. Blue laser imaging (BLI) enables the acquisition of more information from tumors’ surfaces compared with white light imaging. Few reports confirm the validity of magnifying endoscopy (ME) with BLI (ME-BLI) for early gastric cancer (EGC). We aimed to assess the detailed endoscopic findings from EGCs using ME-BLI. Methods. We enrolled 386 consecutive patients with 417 EGCs that were diagnosed using ME-BLI and resected by endoscopic submucosal dissection. Using the VS classification system, three highly experienced endoscopists (HEEs) and three less experienced endoscopists (LEEs) evaluated the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) within the endoscopic images of EGCs obtained using ME-BLI, assigning high-confidence (HC) or low-confidence (LC) levels. We investigated the clinicopathological features associated with each confidence level. Results. The HEEs’ evaluations determined the presence of DL in 99%, irregular MSP in 96%, and irregular MVP in 96%, and the LEEs’ evaluations determined the presence of DL in 98%, irregular MSP in 95%, and irregular MVP in 95% of the EGCs. When DL was present, HC levels in the Helicobacter pylori- (H. pylori-) eradicated group and noneradicated group were evident in 65% and 89%, a difference that was significant (p<0.001). Conclusions. In the diagnosis of EGC with ME-BLI, the VS classification system with ME-NBI can be applied, but identifying the DL after H. pylori was difficult