Park, Sun-Mi;Han, Sang-Bae;Hong, Dong-Ho;Lee, Chang-Woo;Park, Se-Hyung;Jeon, Young-Jin;Kim, Hwan-Mook
Archives of Pharmacal Research
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v.23
no.1
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pp.59-65
/
2000
Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemica. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined bycell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic dose of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.
Pharmacokinetic and pharmacodynamic properties of gliclazide were studied after an oral administration of gliclazide tablets in healthy volunteers. After an overnight fasting, gliclazide tablet was orally administered to 11 volunteers; Additional 10 volunteers were used as a control group (i.e., no gliclazide administration). Blood samples were collected, and the concentration determined for gliclazide and glucose up to 24 after the administration. Standard pharmacokinetic analysis was carried out for gliclazide. Pharmacodynamic activity of the drug was expressed by increase of glucose concentration ($\Delta$PG), by area under the increase of glucose concentration-time curve ($AUC_{$\Delta$PG}$) or by the difference in increase of glucose concentration ($D_{$\Delta$PG}$) at each time between groups with and without gliclazide administration. Pharmacokinetic analysis revealed that $C_{max}, T_{max}$, CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of gliclazide were $4.69\pm1.38 mg/L, 3.45\pm1.11 h, 1.26\pm0.35 L/h, 17.78\pm5.27 L, and 9.99\pm2.15 h$, respectively. When compared with the no drug administration group, gliclazide decreased significantly the $AUC_{$\Delta$PG}$ s at 1, 1.5, 2, 2.5, 3 and 4 h (p<0.05). The $\Delta$PGs were positively correlated with $AUC_{gliclazide}$ at 1 and 1.5 h (p<0.05), and the correlation coefficient was maximum at 1 h (r = 0.642) and gradually decreased at 4 h after the administration. The $AUC_{$\Delta$PG}$s were positively correlated with $AUC_{gliclazide}$ at 1, 2, 3 and 4 h (p<0.05), and the maximum correlation coefficient was obtained at 2 h (r=0.642) after the administration. The $D_{$\Delta$PG}$ reached the maximum at 1 h, remained constant from 1 h to 3 h, and decreased afterwards. Therefore, these observations indicated that maximum hypoglycemic effect of gliclazide was reached at approximately at 1.5 h after the administration and the effect decreased, probably because of the homeostasis mechanism, in health volunteers.
IL-10 is an important anti-inflammatory cytokine that can inhibit the production of many pro-inflammatory cytokines. Both human and animal studies have shown that pro-inflammatory cytokines play an important role in pneumonia and other inflammatory lung diseases. In the present study, IL-10 knockout(KO) and wild-type mice were infected with Corynebacterium kutscheri to determine whether the severity of pathogenesis and whether protective immunity could be altered in the absence of IL-10. The survival rate was significantly lower in IL-10 KO mice than wild-type mice. The number of neutrophils in bronchoalveolar lavage fluid and blood were found to be higher in IL-10 KO mice than wild-type mice. IL-10 KO mice showed greater neutrophil infiltration, excessive inflammation, and weight-loss compared with wild-type mice. Furthermore, upregulation of IFN-$\gamma$ in bronchoalveolar lavage fluid, and upregulation of MIP-$1{\alpha}$ and IP-10 mRNA in the lungs of IL-10 KO mice compared with wild-type mice after C. kutscheri infection were observed. These results suggest that IL-10 plays an important role in the anti-inflammatory properties against C. kutscheri infection, and that lack of IL-10 leads to a more severe pulmonary inflammatory response. This increased susceptibility to C. kutscheri pneumonia is at least in part caused by IL-10 deficiency and severe recruitment of neutrophils.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.34
no.6
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pp.588-593
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2008
There are increasing reports regarding regeneration of the defected tissues using tissue engineering technique. In this technique, multipotential stem cells are essential. There are many potential sources of adult stem cells, such as bone marrow, umbilical cord blood, fat, muscle, dental tissues and skin. Among them, skin is highly accessible and easily obtained with a minimum of donor site complications. Moreover, skin is an abundant adult stem cell sources and has the potential for self-replication and immune privilege. In this study, we isolated skin-derived precursor cells (SKPs) from the ear of adult miniature pigs. In these SKPs, the expression of transcriptional factors, Oct-4, Sox-2, and Nanog were detected by RT-PCR. In vitro osteogenesis and adipogenesis were observed at 3 weeks after transdifferentiations as assayed by positive von Kossa and Oil-red O staining, respectively. In addition, expression of osteocalcin and osteonectin in the osteogenic differentiation medium and $PPAR{\gamma}2$ and aP2 in the adipogenic differentiation medium were detected by RT-PCR. In vitro neurogenesis of porcine SKPs was observed during 24 and 72 hours after treatment of neurogenic differentiation medium. The results of this study suggest that SKPs demonstrate the properties of pluripotence or multipotence and multi-lineage differentiation. This indicates that autogenous SKPs are a reliable and useful source of adult stem cells for regenerative medicine.
Park, Jeong-Eun;Kim, Hwa-Sun;Chang, Min-Jung;Hong, Hae-Sook
Journal of Korean Academy of Nursing
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v.44
no.3
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pp.294-304
/
2014
Purpose: The influence of dietary composition on blood pressure is an important subject in healthcare. Interactions between antihypertensive drugs and diet (IBADD) is the most important factor in the management of hypertension. It is therefore essential to support healthcare providers' decision making role in active and continuous interaction control in hypertension management. The aim of this study was to implement an ontology-based clinical decision support system (CDSS) for IBADD management (IBADDM). We considered the concepts of antihypertensive drugs and foods, and focused on the interchangeability between the database and the CDSS when providing tailored information. Methods: An ontology-based CDSS for IBADDM was implemented in eight phases: (1) determining the domain and scope of ontology, (2) reviewing existing ontology, (3) extracting and defining the concepts, (4) assigning relationships between concepts, (5) creating a conceptual map with CmapTools, (6) selecting upper ontology, (7) formally representing the ontology with Protege (ver.4.3), (8) implementing an ontology-based CDSS as a JAVA prototype application. Results: We extracted 5,926 concepts, 15 properties, and formally represented them using Protege. An ontology-based CDSS for IBADDM was implemented and the evaluation score was 4.60 out of 5. Conclusion: We endeavored to map functions of a CDSS and implement an ontology-based CDSS for IBADDM.
Han, Sung Joon;Han, Woosik;Song, Hee-Jung;Kim, Cuk-Seong;Jeong, Seong-Mok;Kang, Min Woong
Journal of Chest Surgery
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v.51
no.2
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pp.114-121
/
2018
Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.
Taurine is one of the most abundant free ${\beta}$-amino acids in the human body that accounts for 0.1% of the human body weight. It has a sulfonic acid group in place of the more common carboxylic acid group. Mollusks and meat are the major dietary source of taurine, and mother's milks also include high levels of this amino acid. The leukocytes, heart, muscle, retina, kidney, bone, and brain contain more taurine than other organs. Furthermore, taurine can be synthesized in the brain and liver from cysteine. There are no side effects of excessive taurine intake in humans; however, in case of taurine deficiency, retinal abnormalities, reduced plasma taurine concentration, and other abnormalities may occur. Taurine enters the cell via a cell membrane receptor. It is excreted in the urine (approximately 95%) and feces (approximately 5%). Taurine has a number of features and functions, including conjugation with bile acid, reduction of blood cholesterol and triglyceride levels, promotion of neuron cell differentiation and growth, antioxidant effects, maintenance of cell membrane stability, retinal development, energy generation, depressant effects, regulation of calcium level, muscle contraction and relaxation, bone formation, anti-inflammatory effects, anti-cancer and anti-atherogenic effects, and osmotic pressure control. However, the properties, functions, and effects of taurine require further studies in future.
In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.
The Journal of the Society of Korean Medicine Diagnostics
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v.11
no.1
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pp.48-60
/
2007
Palpation of the pulse has been used in Korean traditional medicine since ancient times to assess physical health. Pulse wave contour may be obtained by measuring arterial pressure or blood volume change of skin. The latter is called as Photoplethysmography(PPG) or digital volume pulse(DVP). The PPG signal is measured by a device comprising an infrared light sourece and a photodetector. Although less widely used, this technique deserves further consideration because of its simplicity and ease of use. The contour of the PPG is formed as a result of a complex interaction between the left ventricle and the systemic circulation. It usually exhibits an early systolic peak and an early diastolic peak. the first peak is formed mainly by pressure trasmitted along a direct path from the left ventricle to the finger. The second peak is formed in part by pressure transmitted along the aorta and large arteries to sites of impedance mismatch in the lower body. The contour of the PPG is sensitive to changes in arterial tone and is influenced by ageing and large artery stiffness. Measurements taken directly from the PPG or from its second derivative can be used to assess these properties. In some mathematical approaches, the extraction of periodic components using frequency analysis was tried to analysis of the PPG. But we don't understand yet what kind of factor in the cardiovascular system or human body is related with the respective specific Fourier components of PPG. This review describes the background to measurement principles, representative contour, contour analysis and frequency domain analysis of PPG, and current and future.
Hematotoxicity and vascular irritation of DA-125, a new anthracycline antitumor antibiotic, were investigated in mice and rabbits. In hematotoxicity study, healthy male ICR mice were treated with DA-125 by a single intravenous injection at doses of 18 and 24 mg/kg. After 4, 8, 12 and 16 days WBC count, RBC count, hemoglobin concentration, hematocrit value, and platelet counts were measured respectively. As a positive control, 12 mg/kg of doxorubicin (DXR) was used in the same manner. Remakable reductions of WBC counts in groups treated with DA-125 or DXR were observed 4 days after administration and returned to normal range 8 days after injection in groups of DA-125 18 mg/kg and DXR 12 mg/kg. The recovery of leukopenia induced in a group of DA-125 24 mg/kg took about 16 days after administration. The RBC counts, hemoglobin concentrations and hematocrit values also decreased in all drug treated groups on day 8 and recovered thereafter. The platelet counts of groups treated with DA-125 or DXR decreased on day 4 and recovered from day 8 of experiment. Local vascular irritation of DA-125 was also assessed in rabbits. The obtained results can be summarized as follows. 1. Thrombophlebitis was not induced even after daily intravenous administration of 0.4% solution of DA-125 or 0.2% solution of DXR for 7 days. 2. Macro- and microscopic observations revealed that the irritative activity of 0.4% solution of DA-125 in blood vessels was not so much different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 7 days. 3. Mild inflammatory reaction was noted around vessels in rabbits treated with 0.2% solution of DXR after consecutive intravenous infusion for more than 5 days. 4. The potencies of vascular irritation of the test solutions were summarized in the following order; saline = 0.4% DA-125<0.2% DXR. These results indicated that DA-125 showed similar pattern of hematotoxicity with DXR but was less hematotoxic than DXR, and that 0.4% solution of DA-125 did not elicit unusual toxic properties when injected through intravenous route for clinical practice.
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