Korean Oncology Nursing Society Guidelines on Oral Chemotherapy

PURPOSE: In 2008, the Korean Oncology Nursing Society (KONS) published standards for the safe use of chemotherapy in clinical settings, including extravastion management. Although the medical environment has rapidly changed, KONS standards have not been revised since then. In 2017, the KONS planned to revise the practice guidelines on oral chemotherapy METHODS: A clinical expert group developed recommended guidelines, using officially accepted standards based on all relevant publications. The draft was discussed and accepted in a consensus conference. The final recommendations were reviewed and approved by the KONS Boards of Directors. RESULTS: There were 4 chapters and 50 recommendations in the final version of the guidelines. Recommendations include those associated with general practice, patient consent and education, order assessment and administration, and side effects and complication management. CONCLUSION: The revised KONS guidelines on oral chemotherapy will contribute to the improvement of staff and patient safety related to oral chemotherapy. KONS guidelines revisions should be carried out at regular intervals.

Taxifolin Glycoside Blocks Human ether-a-go-go Related Gene K+ Channels

Taxifolin glycoside is a new drug candidate for the treatment of atopic dermatitis (AD). Many drugs cause side effects such as long QT syndrome by blocking the human ether-a-go-go related gene (hERG) K+ channels. To determine whether taxifolin glycoside would block hERG K+ channels, we recorded hERG K+ currents using a whole-cell patch clamp technique. We found that taxifolin glycoside directly blocked hERG K+ current in a concentration-dependent manner (EC50=9.6+/-0.7 microM). The activation curve of hERG K+ channels was negatively shifted by taxifolin glycoside. In addition, taxifolin glycoside accelerated the activation time constant and reduced the onset of the inactivation time constant. These results suggest that taxifolin glycoside blocks hERG K+ channels that function by facilitating activation and inactivation process.

Expression of Ca2+ -activated K+ Channels and Their Role in Proliferation of Rat Cardiac Fibroblasts

Cardiac fibroblasts constitute one of the largest cell populations in the heart, and contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, their cardiac functions, especially electrophysiological properties, have often been disregarded in studies. Ca2+-activated K+(KCa) channels can control Ca2+influx as well as a number of Ca2+-dependent physiological processes. We, therefore, attempted to identify and characterize KCa channels in rat Cardiac fibroblasts. First, we showed that the cells cultured from the rat ventricle were cardiac fibroblasts by immunostaining for discoidin domain receptor 2 (DDR-2), a specific fibroblast marker. Secondly, we detected the expression of various KCa channels by reverse transcription polymerase chain reaction (RT-PCR), and found all three family members of KCa channels, including large conductance KCa (BK-alpha 1- and -beta 1~4 subunits), intermediate conductance KCa (IK), and small conductance KCa (SK1~4 subunits) channels. Thirdly, we recorded BK, IK, and SK channels by whole cell mode patch clamp technique using their specific blockers. Finally, we performed cell proliferation assay to evaluate the effects of the channels on cell proliferation, and found that the inhibition of IK channel increased the cell proliferation. These results showed the existence of BK, IK, and SK channels in rat ventricular fibroblasts and involvement of IK channel in cell proliferation.

Effects of Pharmacological Modulators of Ca2+ -activated K+ Channels on Proliferation of Human Dermal Fibroblast

Employing electrophysiological and cell proliferation assay techniques, we studied the effects of Ca2+ -activated K+ channel modulators on the proliferation of human dermal fibroblasts, which is important in wound healing. Macroscopic voltage-dependent outward K+ currents were found at about -40 mV stepped from a holding potential of -70 mV. The amplitude of K+ current was increased by NS1619, a specific large-conductance Ca2+ -activated K+ (BK) channel activator, but decreased by iberiotoxin (IBTX), a specific BK channel inhibitor. To investigate the presence of an intermediate-conductance Ca2+ -activated K+ (IK) channels, we pretreated the fibroblasts with low dose of TEA to block BK currents, and added 1-EBIO (an IK activator). 1-EBIO recovered the currents inhibited by TEA. When various Ca2+ -activated K+ channel modulators were added into culture media for 1~3 days, NS1619 or 1-EBIO inhibited the cell proliferation. On the other hand, IBTX, clotrimazole or apamin, a small conductance Ca2+ -activated K+ channel (SK) inhibitor, increased it. These results suggest that BK, IK, and SK channels might be involved in the proliferation of human dermal fibroblasts, which is inversely related to the channel activation.

TASK-1 Channel Promotes Hydrogen Peroxide Induced Apoptosis

Hydrogen peroxide (H2O2) causes oxidative stress and is considered as an inducer of cell death in various tissues. Two-pore domain K+ (K2p) channels may mediate K+ efflux during apoptotic volume decreases (AVD) in zygotes and in mouse embryos. In the present study, we sought to elucidate linkage between K2p channels and cell death by H2O2. Thus K2p channels (TASK-1, TASK-3, TREK-1, TREK-2) were stably transfected in HEK-293 cells, and cytotoxicity assay was preformed using cell counting kit-8 (CCK-8). Cell survival rates were calculated using the cytotoxicity assay data and dose-response curve was fitted to the H2O2 concentration. Ionic currents were recorded in cell-attached mode. The bath solution was the normal Ringer solution and the pipette solution was high K+ solution. In HEK-293 cells expressing TREK-1, TREK-2, TASK-3, H2O2 induced cell death did not change in comparison to non-transfected HEK-293. In HEK-293 cells expressing TASK-1, however, dose-response curve was significantly shifted to the left. It means that H2O2 induced cell death was increased. In cell attached-mode recording, application of H2O2 (300micrometer) increased activity of all K2P channels. However, a low concentration of H2O2 (50micrometer) increased only TASK-1 channel activity. These results indicate that TASK-1 might participate in K+ efflux by H2O2 at low concentration, thereby inducing AVD.

Modulation of Large Conductance Ca2+-activated K+ Channel of Skin Fibroblast (CRL-1474) by Cyclic Nucleotides

Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in Ca2+ homeostasis and/or Ca2+-activated kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific K+ channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance Ca2+-activated K+ (BKCa) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance K+ channels (106 pS of chord conductance at +40 mV in physiological K+ gradient). The 106 pS channels were activated by membrane potential and [Ca2+]i, consistent with the known properties of BKCa channels. BKCa channels in CRL-1474 were positively regulated by adenylate cyclase activator (10microM forskolin), 8-Br-cyclic AMP (300microM) or 8-Br-cyclic GMP (300microM). These results suggest that human skin fibroblasts (CR-1474) have typical BKCa channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

Nitric Oxide Synthase Mediates Carbon Monoxide-Induced Stimulation of L-type Calcium Currents in Human Jejunal Smooth Muscle Cells

Exogenous carbon monoxide (0.2%) increases L-type calcium (Ca2+) current in human jejunal circular smooth muscle cells. The stimulatory effect of carbon monoxide (CO) on L-type Ca2+ current is inhibited by pre-application of L-NNA, a classical competitive inhibitor of nitric oxide synthase (NOS) with no significant isoform selectivity (Lim, 2003). In the present study, we investigated which isoform of NOS affected CO induced stimulation of L-type Ca2+ current in human jejunal circular smooth muscle cells. Cells were voltage clamped by whole-cell mode patch clamp technique, and membrane currents were recorded with 10 mM barium as the charge carrier. Before the addition of CO, cells were pretreated with each inhibitor of three NOS isoforms for 15 minutes. CO-stimulating effect on L-type Ca2+ current was partially blocked by N- (3- (Amino-methyl) benzyl) acetamidine-2HCl (1400W, an iNOS inhibitor). On the other hand, 3-bromo-7-nitroindazole (BNI, a nNOS inhibitor) or N5- (1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO, an eNOS inhibitor) completely blocked the CO effect. These data suggest that low dose of exogenous CO may stimulate all NOS isoforms to increase L-type Ca2+ channel through nitric oxide (NO) pathway in human jejunal circular smooth muscle cells.

Elk dander-induced occupational asthma / 알레르기

We experienced two cases of occupational asthma induced by Elk dander in Elk-feeders and confirmed these cases by the bronchial provocation test with Elk dander. Both of them showed dual asthmatic response. They also showed positive reaction to the skin prick test with EIK dander. Now one of them has no asthmatic symptoms at all after complete avoidnce of EIK dander.