Biomedical subjects

Ki-Suk Kim

Publications and source records attributed to Ki-Suk Kim.

9 recordsLinked to original sources

PubMed2006

Electrophysiological effects of brompheniramine on cardiac ion channels and action potential.

Some antihistamines (mainly terfenadine and astemizole) have been demonstrated to cause QT interval prolongation and, in some cases, torsade-de-pointes. We investigated the cardiac electrophysiological effects of brompheniramine, a conventional antihistamine. Brompheniramine was reported to prolong QT interval in isolated hearts. To evaluate the electrophysiological effects of brompheniramine, we used whole-cell patch clamp techniques in human ether-a-go-go related gene (hERG)-stably transfected CHO cells, the SCN5A sodium channel transiently transfected CHO cells, and rat myocytes and conventional microelectrode recording techniques in isolated guinea pig papillary muscles. As for the I(hERG), the IC(50) value of brompheniramine was found to be 0.90+/-0.14microM with a Hill coefficient (n(H)) of 1.75+/-0.42. Action potential duration at 90% repolarization (APD(90)) was slightly prolonged by brompheniramine at 10 and 100microM, but APD(50) was shortened by 100microM. Moreover, despite the potent hERG current block, reductions of the V(max) and total amplitude of action potential were observed at high concentrations of brompheniramine. The change in action potential parameters and poor correlations between hERG and APD assay indicated additional effects of brompheniramine on non-hERG channels. In agreement with this hypothesis, the inhibition of I(Na) (IC(50) values: 21.26+/-2.52microM) and I(Ca) (IC(50) values: 16.12+/-9.43microM) by brompheniramine was observed. The results of this study suggest that brompheniramine may possess classes III, Ib and IV properties, especially at high concentrations and that additional studies on non-hERG channels will be necessary to elucidate the complex electrophysiological effects of brompheniramine on the heart.

Action Potentials↗

PubMed2006

The changes of estrogen receptor-beta variants expression in breast carcinogenesis: Decrease of estrogen receptor-beta2 expression is the key event in breast cancer development.

BACKGROUND AND OBJECTIVES: Although more than five variant forms of estrogen receptor-beta (ERbeta) have been identified, their role has not been identified. This study was carried out to investigate the changes of ERbeta variants in breast cancer development. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERbeta variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERbeta variants were compared between normal and cancer tissues, and also compared according to various clinicopathological parameters. RESULTS: Among ERbeta variants, ERbeta2 and ERbeta5 consist of the major proportion of ERbeta expression both in normal and cancer tissues. The ERbeta and ERbeta2 expression levels decreased significantly in the cancers compared with corresponding normal tissues, particularly in ERalpha-expressing cancers. However, ERbeta5 expression level increased significantly in the cancers, especially in those of postmenopausal patients. The relative increase of ERbeta5 expression in cancer tissues was associated with favorable differentiation. CONCLUSIONS: Decrease of ERbeta2 is thought to be the key reason for the decrease in ERbeta expression in cancer tissues, and it is particularly associated with the development of ERalpha-expressing breast cancer.

Breast↗

PubMed2006

Electrophysiological safety of novel fluoroquinolone antibiotic agents gemifloxacin and balofloxacin.

Some fluoroquinolones have been reported to induce QT interval prolongation associated with the onset of torsades de pointes (TdP), resulting in a life-threatening ventricular arrhythmia. We investigated the cardiac electrophysiological effects of two new fluoroquinolones, gemifloxacin and balofloxacin, by using conventional microelectrode recording techniques in isolated rabbit Purkinje fiber and whole-cell patch-clamp techniques in human ether-á-go-go related gene (hERG)-transient transfected CHO cells. Gemifloxacin had no significant effects on the resting membrane potential, total amplitude, action potential, and Vmax of phase 0 depolarization at concentrations up to 30 microM, but gemifloxacin at 100 microM significantly decreased total amplitude (p < 0.01). These values of gemifloxacin (30 and 100 microM) were approximately 25- and 83-fold more than the free plasma concentration of 1.2 microM in a single therapeutic injection in humans. For I(hERG), the IC(50) value was about 300 microM. Balofloxacin had also no significant effects on the resting membrane potential, total amplitude, action potential duration, and Vmax of phase 0 depolarization at concentrations up to 30 microM, but balofloxacin at 100 microM significantly (p < 0.01) prolonged action potentials at both 50% repolarization (APD(50)) and 90% repolarization (APD(90)). These values of balofloxacin (30 and 100 microM) were approximately 6.8- and 23-fold more than the free plasma concentration of 4.4 microM in a single therapeutic injection in humans. For I(hERG), the IC(50) value was 214 +/- 14 microM. Therefore, our data suggested that in the electrophysiological aspect, gemifloxacin and balofloxacin may have no torsadogenic potenties up to 30 microM.

Action Potentials↗

PubMed2005

The phenothiazine drugs inhibit hERG potassium channels.

Cardiovascular adverse effects from phenothiazine drugs are common. The most serious consequences of treatment, arrhythmias and sudden death, are probably rare and most likely to be caused primarily by blockade of cardiac potassium channels such as the human ether-a-go-go-related gene (hERG) channel, which plays a central role in arrhythmogenesis. This phenomenon has been previously reported to occur with a few phenothiazine drugs. However, phenothiazine drugs are composed of pharmacologically and structurally diverse groups. The effects of many of the phenothiazine drugs on hERG channels expressed in mammalian cell lines remain unknown. Therefore, we investigated the effects of four distinct phenothiazine drugs (thioridazine, chlorpromazine, trifluoperazine, and perphenazine) on hERG channel expressed in chinese hamster ovary (CHO) cells. HERG channels were expressed in CHO cells, and ion currents were measured using the patch-clamp technique. Thioridazine, perphenazine, trifluoperazine, and chlorpromazine blocked hERG potassium channels with the following IC(50) values: IC(50) values were 224 +/- 42 nM for thioridazine, 1003 +/- 71 nM for perphenazine, 1406 +/- 124 nM for trifluoperazine, and 1561 +/- 281 nM for chloropromazine. Inhibition of hERG channels by thioridazine was characterized by significant changes in voltage dependence, the value of V(1/2), the half-maximal activation potential, and shift into negative potential, that is, the amount of block was greater at more positive potential. No significant changes were noted in other drugs.

Animals↗

PubMed2005

Electrophysiological safety of DW-286a, a novel fluoroquinolone antibiotic agent.

Inhibition of the potassium current I(Kr) and QT prolongation has been known to be associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of DW-286a, a new class of fluoroquinolone antibiotics reported to prolong the QT interval. To investigate the electrophysiological safety of DW-286a, we used conventional microelectrode recording techniques in isolated guinea pig papillary muscles, whole-cell patch clamp techniques in human ether-à-go-go related gene (hERG)-transient transfected Chinese hamster ovary cells, and in vivo electrocardiogram (ECG) measurements in Sprague-Dawley (SD) rats by the use of a telemetry system. DW-286a at 300 microM significantly (P<0.01) prolonged action potentials at 50% repolarization (APD50) and 90% repolarization (APD90). For IHERG, the IC50 value was 89.00+/-37.85 microM with a Hill coefficient (nH) of -0.97+/-0.49. However, when DW-286a was orally administered to conscious SD rats at a high dose (1000 mg/kg), no significant effect on ECG in vivo was detected. From a previous study, we know that concentration at 19.8 microM is the antimicrobial end-point of DW-286a. Therefore, our data suggest that in the electrophysiological aspect, it can be thought that the effective concentrations of DW-286a are between 19.8 and 100 microM (concentration in serum).

Action Potentials↗

PubMed2005

[Distribution of calcaneal bone density according to the mechanical strain of exercise and calcium intake in premenarcheal girls].

OBJECTIVES: The effects of exercise on bone density have been found to be inconsistent in previous studies. We conducted a cross-sectional study in premenarcheal girls to test two hypotheses to explain these inconsistencies. Firstly, "the intensity of mechanical strain, in terms of the ground reaction force(GRF), has more important effects on the bone mass at a weight-bearing site", and secondly, "calcium intake modifies the bone response to exercise". METHODS: The areal bone mineral density was measured at the Os calcis, using peripheral dual energy X-ray absorptiometry, in 91 premenarcheal girls aged between 9 and 12 years. The intensity of mechanical strain of exercise was assessed by a self-report questionnaire and scored by the GRF as multiples of body weight, irrespective of the frequency and duration of exercise. The energy and calcium intake were calculated from the 24-hour dietary recall. An analysis of covariance(ANCOVA) was used to determine the interaction and main effects of exercise and calcium on the bone density, after adjusting for age, weight, height and energy intake. RESULTS: The difference in the bone density between moderate and low impact exercise was more pronounced in the high than low calcium intake group. The bone density for moderate impact exercise and high calcium intake was significantly higher than that for low impact exercise (p=0.046) and low calcium intake, after adjusting for age, weight, height and energy intake. CONCLUSIONS: Our study suggests that the bone density at a weight-bearing site is positively related to the intensity of mechanical loading exercise, and the calcium intake may modify the bone response to exercise at the loaded site in premenarcheal girls.

Bone Density↗

PubMed2004

Safety pharmacology of DW-224a, a novel fluoroquinolone antibiotic agent.

To investigate the safety pharmacology of a novel fluoroquinolone antibiotic agent, DW-224a, on the vital functions, we studied its effects on the central nervous system, cardiovascular system and respiratory system. To determine the effects on the central nervous system, we used a modified Irwin's test at each time point after oral administration of DW-224a to mice. In this test, we found that the treatment of test article had no effects on motor activity, behavioral changes, coordination, and sensory/motor reflex responses. The effects of DW-224a on the cardiovascular system were evaluated by the use of a telemetry system in beagle dogs. At 360 min post-DW-224a (100 mg/kg) administration, QT interval prolongation was observed. However, there were no changes in heart rate, blood pressure, and electrocardiogram at all doses and each time points with the exception of QT-interval prolongation as compared to the vehicle treated group. In experiments designed to determine the changes of respiratory function in rats, we found no changes at all doses and time points. We investigated the effects of DW-224a on the human ether-a-go-go-related gene (hERG) mediated potassium currents to evaluate its potential to induce QT interval prolongation. When whole cell patch-clamp electrophysiology was used, DW-224a inhibited hERG currents with IC50 of 218.12 +/- 39.51 microM though its effect was less potent than that of E-4031, a positive control drug. Our data suggested that DW-224a showed no adverse effects on the central nervous system, cardiovascular system, and respiratory system, with the exception of the effect on the QT interval prolongation.

Animals↗

PubMed2003

Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-beta (ERbeta) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERbeta in BC development and progression. ERbeta expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERbeta mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERbeta mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERbeta expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERbeta expression. Collectively, ERbeta mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

Biomarkers, Tumor↗

PubMed2003

Effects of water flow on dental hard tissue ablation using Er:YAG laser.

OBJECTIVE: The aim of this study was to investigate the effect of water on dental hard tissue ablation using Er:YAG laser as it relates to energy and pulse repetition rate, and determine the water flow rate that produces the most effective ablation at a given irradiation condition. BACKGROUND DATA: Er:YAG laser application leads to volumetric expansion and micro-explosions that result in hard tissue ablation. Ablation efficiency is improved when combined with fine water spray. MATERIALS AND METHODS: Extracted, healthy human molars were sectioned into two pieces and categorized into small groups related to water flow rate (1.69, 6.75, and 13.5 mL/min), pulse energy (250 and 400 mJ), and pulse repetition rate (5, 10, and 20 Hz). Within the combination of irradiation parameters, a laser beam was applied over enamel and dentin surfaces of the specimens, and the ablation amount was determined by differences in weight before and after irradiation. RESULTS: At a pulse energy of 250 mJ, the most effective ablation resulted from a water flow rate of 1.69 mL/min in both enamel and dentin. With 400 mJ/pulse, dentin removal was most effective at the water flow rate of 1.69 mL/min, whereas the efficiency of enamel ablation was the highest at 6.75 mL/min. Dental hard tissue ablated better as energy and pulse repetition rate increased. CONCLUSION: Effective ablation of dental hard tissue using Er:YAG laser requires that the appropriate water flow rate correspond properly to irradiation conditions. The results of this study suggest the following parameters; a water flow rate of 1.69 mL/min for enamel and dentin ablation at a pulse energy of 250 mJ and for dentin ablation at 400 mJ/pulse, and a water flow rate of 6.75 mL/min for enamel ablation at a pulse energy of 400 mJ, regardless of pulse repetition rate of 5, 10, and 20 Hz.

Dentistry, Operative↗