• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.54-58
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• 2009

Background: Obstructive sleep apnea (OSA) is associated with several cardiovascular diseases. However, the mechanisms are not completely understood. The measure of common carotid artery intima-media thickness (IMT) has been extensively used as an early marker of atherosclerosis. The aim of this study was to test the hypothesis that early signs of atherosclerosis are present in patients with OSA and correlate with OSA severity Methods: Eleven male patients with OSA were studied by using full standard overnight polysomnography and high-definition echo-tracking device to measure intima-media thickness and carotid artery diameter. Eight healthy volunteers matched for age and sex were studied by portable respiratory monitoring device. All participants were free of hypertension, diabetes, and were not on any medications. Patients with OSA were naive to treatment. Results: All patients and normal controls were male. There was no significant difference of age between patients and controls ($48.4{\pm}8.85$ and $48.0{\pm}9.77$). Significant differences existed between control subjects and patients with mild to moderate and severe OSA (apnea-hypopnea index, $1.51{\pm}1.15$ and $38.51{\pm}19.13$ respectively) in intima-media thickness ($0.59{\pm}0.064$ and $0.93{\pm}0.16$; P=0.0023), and carotid diameter ($5.79{\pm}0.44$ and $6.47{\pm}0.51$; P=0.0227). Multivariate analyses showed that the apnea-hypopnea index correlated independently with intima-media thickness and carotid diameter (r=0.79, P=0.0008, and r=0.47, P=0.0482). Conclusions: Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis, which further supports the hypothesis that OSA plays an independent role in atherosclerosis progression.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.117-122
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• 2005

After establishing improved HPLC analytical method of cefaclor in human plasma samples, a bioavailability study of cefaclor capsules was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). The standard calibration curve using an HPLC with UV detector was constructed in a range of $0.0324{\sim}16\;{\mu}g/ml$. The 6% perchloric acid instead of 6% trichloroacetic acid was used to precipitate plasma protein. The HPLC chromatograms were precisely and accurately resolved when spiked with human plasma spiked with cefaclor and cephalexin (internal standard). Twenty healthy male Korean volunteers received two commercial cefaclor capsules, $Neocef^{\circledR}$ capsule (Jinyang Pharm. Co., Ltd) or $Ceclor^{\circledR}$ capsule (Lilly Korea. Co., Ltd.) at the 250 mg cefaclor in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of cefaclor were monitored for 8 hours after oral drug administration. $AUC_t$ the area under the plasma concentration-time curve from time zero to 8 hr (13 points), was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Neocef^{\circledR}/Ceclor^{\circledR}$ were $0.9049{\leq}{\delta}{\leq}1.226$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Neocef^{\circledR}/Ceclor^{\circledR}$ with respect to the extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.197-203
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• 2007

A bioequivalence study of $Dilast^{TM}$ Capsule (Chong Kun Dang Pharma. Co., Ltd.) to $Ketas^{(R)}$ Capsule (Han Dok Pharma. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty eight healthy male Korean volunteers received each medicine at the ibudilast dose of 20 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of ibudilast were monitored by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Dilast^{TM}$ $Capsule/Ketas^{(R)}$ Capsule were $log0.93{\sim}log1.06$ and $log0.93{\sim}log1.11$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Dilast^{TM}$ Capsule and $Ketas^{(R)}$ Capsule with respect to the rate and extent of absorption.

• The Korean Journal of Food And Nutrition
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• v.11 no.3
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• pp.303-311
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• 1998

This study was carried out to determine the blood glucose responses to 10 kinds of typical Korean domestic meals, 9 kinds of eating out meals and 5 kinds of diabetic meals recommended by hospitals. The levels of blood glucose were measured at 15, 30, 60, 90 and 120 minutes after taking 24 kinds of meals(500$\pm$10㎉) and 50g of glucose to healthy volunteers. The blood glucose response areas and glycemic index(GI) were calculated. There was no invariable tendency of blood glucose responses among diabetic meals, general domestic meals and eating out meals. As the units of grain groups were increased, the GI of meals was increase. When the units of grain groups are same, the side dishes also affected the blood glucose responses, however, it is yet unknown what kinds of food materials of side dishes affected the blood glucose responses. Noodles (Chinese style, kalgugsu(Korean home made) and ramen) lowered blood glucose responses compared to steamed rice. Mixing barley and brown rice with polished rich also lowered blood glucose responses, especially when the mixing ratio of them was over the 15%. The lowering efficiency of barely was greater than brown rice. More than three grain units of rice increased the blood glucose response. The GI was significantly correlated with left area ratio(LAR), right area ratio(RAR) and blood glucose levels at 15, 30, 60, 90 minutes. The RAR and blood glucose levels at 30 minutes profoundly affected the GI.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.303-308
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two talniflumate tablets, SOMALGEN tablet (Kun Wha Pharm. Co., Ltd., Seoul, Korea, reference drug) and FLUTAL tablet (Kukje Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the talniflumate dose of 740 mg in a $2{\pm}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of niflumic acid were monitored by an HPLC-UV for over a period of 14 hr after the administration. $AUC_t$(the area under the plasma concentration-time curve from time zero to 14 hr) was calculated by the linear trapezoidal rule method. $C_{max}$(maximum plasma drug concentration) and $T_{max}$(time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$, ratio and the $C_{max}$ ratio for SOMALGEN/FLUTAL were $log0.8510{\sim}log1.0318$ and $log0.9264{\sim}log1.0607$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Taken together, our study demonstrated the bioequivalence of SOMALGEN and FLUTAL with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.193-199
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• 2006

A bioequivalence study of $Sudo^{TM}$ Ranitidine HCI tablet (Sudo Pharma. Ind. Co., Ltd.) to $Curan^{TM}$ tablet (Il Dong Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the ranitidine hydrochloride dose of 150 mg in a 2x2 crossover study. There was a one week wash-out period between the doses. Plasma concentrations of ranitidine were monitored by a high-turbulent liquid chromatography (HTLC) for over a period of 12 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found far all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Sudo^{TM}$ Ranitidine $HCl/Curan^{TM}$ were 0.92-1.00 and 0.90-1.03, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Sudo^{TM}$ Ranitidine HCI and $Curan^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.413-419
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• 2006

In this study, the main purpose was to evaluate the bioequivalence of two thioctic acid tablests, Thioctacid HR tablet(Bukwang Pharm. Co., Ltd.) and Daewon thioctic acid HR tablet 600 mg(Daewon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four, healthy Korean volunteers were divided into two groups, randomized and treated by $2{\times}2$ crossover study. After the administration of one thioctic acid tablet containing 600 mg thioctic acid, blood samples were taken until 8 hr after the oral administration. LC-MS/MS was applied to determination of thioctic acid, and we calculated the $AUC_t,\;C_{max},\;T_{max}$ from the plasma concentration-time data. Analysis of variance(ANOVA) was carried out using logarithmically transformed $AUC_t\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Daewon thioctic acid tablet 600 mg/Thioctacid HR were log 0.9877$\sim$log 1.1938 and log 0.8169$\sim$log 1.2237, respectively. These values were within the acceptable bioequivalence intervals of log 0.80$\sim$log 1.25, recommended by KFDA. In all of these results we concluded that Daewon thioctic acid tablet 600 mg was bioequivalent to Thioctacid HR tablet, in terms of rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.413-418
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• 2004

A bioequivalence of $Melax^{TM}$ capsules (Chong Kun Dang Pharm., Korea) and $Mobic^{TM}$ capsules (Boehringer Ingelheim Korea) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 15 mg dose of meloxicam of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2\;{\times}\;2$ crossover design. Concentrations of meloxicam in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 72 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Melax^{TM}/Mobic^{TM}$ were 0.95 - 1.04 and 0.98 - 1.14, respectively. This study demonstrated a bioequivalence of $Melax^{TM}$ and $Mobic^{TM}$ with respect to the rate and extent of absorption.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.75-84
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• 2014

Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.