• Pediatric Infection and Vaccine
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• v.18 no.2
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• pp.109-116
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• 2011

Purpose : Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model. Methods : Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for ${\beta}$-lactams and macrolide. For the ${\beta}$-lactams, exposure of fT >MIC (time that free drug concentrations remain above the MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model. Results : Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC ${\leq}$1.0 ${\mu}g$/mL and 19 (82.6%) were MIC ${\leq}$2 ${\mu}g$/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC ${\leq}$1.0 ${\mu}g$/mL but PTA decreased to 52% at MIC 2 ${\mu}g$/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 ${\mu}g$/mL. Overall, oral amoxicillin 90 mg/ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion : Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.33-37
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• 2010

Purpose: In the early stage of using PET/CT, it was used to damper revision but recently shows that CT with MDCT is commonly used and works well for an anatomical diagnosis. This hospital makes the accuracy and convenience more higher in the diagnosis and evaluate of coronary heart disease through concurrently running myocardial perfusion SPECT examination, myocardial PET examination with FDG, and CT coronary artery CT angiography(coronary CTA) used PET/CT with 64-slice. This report shows protocol and image based on results from about 400 coronary heart disease examinations since having 64 channels PET/CT in July 2007. Materials and Methods: An Equipment for this examination is 64-slice CT and Discovery VCT (DVCT) that is consisted of PET with BGO ($Bi_4Ge_3O_{12}$) scintillation crystal by GE health care. First myocardial perfusion SPECT with pharmacologic stress test to reduce waiting time of a patient and get a quick diagnosis and evaluation, and right after it, myocardial FDG PET examination and coronary CTA run without a break. One-stop evaluation protocol of ischemic heart disease is as follows. 1)Myocardial perfusion SPECT with pharmacologic stress: A patient is injected with $^{99m}Tc$-MIBI 10 mCi and does not have any fatty food for myocardial PET examination and drink natural water with ursodeoxcholic acid 100 mg and we get SPECT image in an hour. 2)Myocardial FDG PET: To reduce blood fatty content and to increase uptake of FDG, we used creative oral glucose load using insulin and Acipimox to according to blood acid content. A patient is injected with $^{18}F$-FDG 5 mCi for reduction of his radiation exposure and we get a gated image an hour later and get delay image when we need. 3) Coronary CTA: The most important point is to control heart rate and to get cooperation of patient's breath. In order to reduce a heart rate of him or her below 65 beats, let him or her take beta blocker 50 mg ~ 200 mg after a consultation with a doctor about it and have breath-practices then have the examination. Right before the examination, we spray isosorbide dinitrate 3 to 5 times to lower tension of bessel wall and to extension a blood wall of a patient. It makes to get better the shape of an anatomy. At filming, a patient is injected CT contrast with high pressure and have enough practices before the examination in order to have no problem. For reduction of his radiation exposure, we have to do ECG-triggered X-ray tube modulation exposure. Results: We evaluate coronary artery stenosis through coronary CTA and study correlation (culprit vessel check) of a decline between stenosis and perfusion from the myocardial perfusion SPECT with pharmacologic stress, coronary CTA, and can check viability of infarction or hibernating myocardium by FDG PET. Conclusion: The examination makes us to set up a direction of remedy (drug treatment, PCI, CABG) because we can estimate of effect from remedy, lesion site and severity. In addition, we have an advantage that it takes just 3 hours and one-stop in that all of process of examinations run in succession and at the same time. Therefore it shows that the method is useful in one stop evaluation of ischemic heart disease.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.293-302
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• 1994

The objective of this study was to establish a good methodology to isolate single smooth muscle cells that are alive and respond properly to pharmacological agents. Canine urinary bladders were employed as the source of single cells, and acetylcholine, atropine and imipramine were used as indicators of pharmacological responsiveness. Imipramine, an antidepressant drug exhibited the anticholinergic and calcium antagonizing properties on rat detrusor muscle. To establish a control value for a further experiment to elucidate the mechanism of action of imipramine on detrusor muscle, we measured the concentration-response of single cells to acetylcholine in the presesnce of imipramine by length of the cells and compared the result with the response in the presence of atropine. Tiny chops of smooth muscle taken from anesthetized canine urinary bladder were incubated in collagenase solution at $36^{\circ}C$ for 17-20 minutes. The collagenase solution included collagenase 1.2 mg/ml, soybean tryspin inhibitor 0.08 mg/ml, bovine serum albumin 2% in 10 ml Krebs-Henseleit buffer solution aerated with a consistent breeze of 95/5% $O_2/CO_2$, to maintain the pH at 7.4. After washing with plain K-H solution on 450 mesh, cells were dissociated from the digested tissue for 12-15 minutes. Cell suspension was transfered in 5 ml test tubes and acetylcholine was added for the final concentration to be $10^{-14}M{\sim}10^{-9}M$. To find the optimal time to fix the cells to determine the contractile responses, 1% acrolein was added 5, 10, 20, 30, 60 and 120 seconds after the administration of ACh. The length of cells fixed by acrolein were measured by microscaler via CCTV camera on phaes-contrast microscope. The average length of 50 cells from a slide glass was taken as the value of a sample at the very concentration point. Single cells were isolated from canine detrusor. The length of untreated cells varied from 82 ${\mu}m$ to 94 ${\mu}m$. The maximal response to actylcholine $10^{-9}M$ was accomplished within 5 seconds of exposure, and the shortening was $19{\pm}3$%. Atropine reduced the contraction of the cells concentration-dependently. Imipramine which exerts a cholinergic blocking action on some smooth muscles also reduced the contraction concentration-dependently and by a similar pattern as atropine. These findings document that imipramine may exerts a cholinergic blocking activity in the single smooth muscle cells isolated from canine urinary bladder.

• Progress in Medical Physics
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• v.24 no.2
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• pp.119-126
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• 2013

Due to the introduction of CR and DR, it has been neglected the use of the X-ray beam collimator and field size. This study examines nationwide survey of the proper use of collimator and field size by area in a specific field of plain radiography and the current status. Authors emphasized the need for the field size criteria, and propose a standard reference field size in each specific radiologic examination. Total 333 medical institutions (included in Seoul, Gyeonggi-do, Jeolla, Chungcheong, Gangwon-do, Busan area), were investigated in relation to the status of the X-ray beam collimation field size, type specific inspection areas, medical facilities, and image analyses by type to figure out whether they use the adjustment of image field to the specific examination. To assess the awareness and the impact of radiation exposure to the collimation adjustable, 168 radiographers who was working in 10 general hospitals, 10 hospitals, and 10 clinics, were surveyed how they haver adjusted the actual field size. We examine that 61.3% of medical institutions used the "Proper collimation" and only 49.9% of them employed proper one in lumbar spine densely crowded by major organs. 69% among general hospitals, and 65% among hospitals using DR system were using proper collimation. Radiographers recognized that proper adjustment of collimation could reduce the harmful radiation dose on patients. In the survey, 97.6% of respondents were aware of this fact, but only 83.3% of respondents did the adjustment of the size of the collimation field. The using of proper collimation field was low in the nationwide survey, so the effort to reduce the radiation dose on the patients is urgently needed. A unified standard for the field accompanied by thorough education should be needed.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.686-693
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• 2007

Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro). Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% $O_2$ incubator for hypoxia. MPA ($10{\mu}g/mL$) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% $O_2$). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3. Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury, Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.29-34
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• 1993

Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diammihedichloroplatinum (cis-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of $10^3$ cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vitro studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 6.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was when cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cis-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 ${\mu}M$ cis-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adjuvant treatment.

• Journal of Preventive Medicine and Public Health
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• v.35 no.3
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• pp.245-254
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• 2002

Objective : To test if the intake of $H_2$ receptor antagonists ($H_2$-RAs) increases the risk of gastric cancer in the elderly. Methods : The source population for this study was drawn from the responders to a questionnaire survey administered to the Korea Elderly Pharmacoepidemiological Cohort (KEPEC), who were beneficiaries of the Korean Medical Insurance Corporation, were at least 65 years old, and residing in Busan in 1999. The information on $H_2$-RAs exposure was obtained from a drug prescription database compiled between inn. 1993 and Dec. 1994. The cases consisted of 76 gastric cancer patients, as confirmed from the KMIC claims data, the National Cancer Registry and the Busan Cancer Registry. The follow-up period was from Jan. 1993 to Dec. 1998. Cancer free controls were randomly selected by 1:4 individual matching, which took in to consideration the year of birth and gender. Information on confounders was collected by a mail questionnaire survey. The odds ratios, and their 95% confidence intervals, were calculated using a conditional logistic regression model. Results : After adjusting for a history of gastric ulcer symptoms, medication history, and body mass index, the adjusted OR (aOR) was 4.6 (95% CI=1.72-12.49). The odds ratio of long term use (more than 7 days) was 2.3 (95% CI=1.07-4.82). The odds ratio of short term use was 4.6 (95% CI=1.26-16.50). The odds ratio of parenteral use was 4.4 195% CI=1.16-17.05) and combination use between the oral and parenteral routes (aOR, 16.8; 95% CI=1.21-233.24) had the high risk of gastric cancer. The aOR of cimetidine was 1.7 (95% CI=1.04-2.95). The aOR of ranitidine was 2.0 (95% CI=1.21-3.40). The aOR of famotidine was 1.7 (95% CI=0.98-2.80). Conclusion : The intake of $H_2$-RAs might increase the risk of gastric cancer through achlorhydria in the elderly.

• Journal of Food Hygiene and Safety
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• v.31 no.4
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• pp.227-249
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• 2016

Arsenic and its compounds vary in their toxicity according to the chemical forms. Inorganic arsenic is more toxic and known as carcinogen. The provisional tolerable weekly intake (PTWI) of $15{\mu}g/kg$ b.w./week established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has been withdrawn, while the EFSA panel suggested $BMDL_{0.1}$ $0.3{\sim}8{\mu}g/kg\;b.w./day$ for cancers of the lung, skin and bladder, as well as skin lesions. Rice, seaweed and beverages are known as food being rich in inorganic arsenic. As(III) is the major form of inorganic arsenic in rice and anaerobic paddy soils, while most of inorganic arsenic in seaweed is present as As(V). The inorganic arsenic in food was extracted with solvent such as distilled water, methanol, nitric acid and so on in heat-assisted condition or at room temperature. Arsenic speciation analysis was based on ion-exchange chromatography and high-performance liquid chromatography equipped with atomic absorption spectrometry and inductively coupled plasma mass spectrometry. However, there has been no harmonized and standardized method for inorganic arsenic analysis internationally. The inorganic arsenic exposure from food has been estimated to range of $0.13{\sim}0.7{\mu}g/kg$ bw/day for European, American and Australian, and $0.22{\sim}5{\mu}g/kg$ bw/day for Asian. The maximum level (ML) for inorganic arsenic in food has established by EU, China, Australia and New Zealand, but are under review in Korea. Until now, several studies have conducted for reduction of inorganic arsenic in food. Inorganic arsenic levels in rice and seaweed were reduced by more polishing and washing, boiling and washing, respectively. Further research for international harmonization of analytical method, monitoring and risk assessment will be needed to strengthen safety management of inorganic arsenic of foods in Korea.

• Journal of Life Science
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• v.23 no.2
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• pp.197-206
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• 2013

The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.

• Molecules and Cells
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• v.21 no.1
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• pp.52-62
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• 2006

In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent $Ca^{2+}$ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned $Ca^{2+}$ channel subtypes such as ${\alpha}_{1C}$(L)-, ${\alpha}_{1B}$(N)-, ${\alpha}_{1A}$(P/Q)-, ${\alpha}_{1E}$(R)- and ${\alpha}_{1G}$(T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on $Ba^{2+}$ currents ($I_{Ba}$) in Xenopus oocytes expressing five different $Ca^{2+}$ channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the ${\alpha}_{1G}$-type. Of the various ginsenosides, $Rb_1$, Rc, Re, Rf, $Rg_1$, $Rg_3$, and $Rh_2$, ginsenoside $Rg_3$ also inhibited all five channel subtypes and ginsenoside $Rh_2$ had most effect on the ${\alpha}_{1C}$- and ${\alpha}_{1E}$-type $Ca^{2+}$ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the ${\alpha}_{1G}$-type of $Ca^{2+}$ channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. $Rg_3$, $Rh_2$, and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the ${\alpha}_{1B}$- and ${\alpha}_{1A}$-types. These results reveal that $Rg_3$, $Rh_2$ and CK are the major inhibitors of $Ca^{2+}$ channels in Panax ginseng, and that they show some $Ca^{2+}$ channel selectivity.