• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.355-361
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• 2006

Intraarticular corticosteroid injections for therapy of rheumatic arthritis are administered with the aim of optimal local anti-inflammatory effect at the injection site. Since the side effects of corticosteroidal drug, dexamethasone(DEX), administered at hish dose limited the therapeutic efficacy, there was a need to design a new drug delivery system for controlled release of dexamethasone. As a prodrug for continuous therapeutic efficacy, dexamethasone-21-palmitate(DEX-PAL) was prepared via esterification of palmitoyl chloride and dexamethasone. DEX-PAL was identified by NMR and MASS analysis. DEX-PAL or DEX was entrapped in lipid nanosphere which could be prepared by using a self emulsification-solvent evaporation method. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated with variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter $83{\sim}95$ nm and DEX-PAL loading efficiency of up to 95%. The drug loading efficiency increased with the increase of aliphatic chain length attached to the phospholipid. The incorporation of cationic lipid was very efficient for both reducing particle size of lipid nanospheres and enhancing drug loading efficiency. The lipid nanospheres containing DEX-PAL may be a promising novel drug carrier for the controlled release of the poorly water-soluble drugs.

• Biomedical Science Letters
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• v.20 no.1
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• pp.43-47
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• 2014

To understand the effect of prenatal stress on sex-specific changes in embryonic and placental growth, a synthetic glucocorticoid (dexamethasone) was administered intraperitoneally at a dosage of 1 mg/kg body weight (BW) (Dex1) or 10 mg/kg BW (Dex10) to pregnant ICR mice at the gestational days 7.5, 8.5 and 9.5 post coitum (p.c.). Embryos and placentas were then harvested at days 11.5 and 18.5 p.c., and their body weight and size were measured following the determination of sex through PCR using Sry specific primers in tail tissues. As a result, female embryos presented reduced fetal body weight and size in Dex1- and Dex10-treated groups than those of control group at the embryonic day 11.5 p.c. Interestingly, the growth seems to be recovered at day 18.5 as there was no difference in growth between control and dexamethasone treated groups. In the case of males, Dex1 induced a decrease in fetal weight in day 11.5 and this pattern was maintained until day 18.5, whereas their growth was not affected by Dex10 treatment. Placental growth showed similar patterns to fetal growth in both sexes but the extent of reduction was not statistically significant in most cases. Placental weights in Dex1- and Dex10-treated group were decreased significantly in male only. The results imply that the effect of prenatal stress is largely sex dependent due to different strategies for growth and survival in a stressful environment.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.712-719
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• 2006

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by $^1H$ nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around $50\;nm{\sim}300\;nm$ according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. $^1H-NMR$ spectroscopy using $D_2O$ and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.441-447
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• 2016

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (${\alpha}_2$-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of $10^{-8}{\sim}10^{-6}mol/L$, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or $3{\times}10^{-9}mmol/L$) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial ${\alpha}_2$-adrenoceptor and nitric oxide synthase.

• Proceedings of the Korea Information Processing Society Conference
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• 2012.04a
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• pp.1228-1230
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• 2012

안드로이드 플랫폼에 적합한 어플리케이션 보급이 급증하면서 달빅(dalvik)에 관련된 다양한 연구 시도가 진행되고 있다. 특히, Java 클래스 파일로부터 dx에 의해 생성되는 DEX 파일의 구조 및 상세 정보를 시각적으로 분석하고 이를 응용하기 위한 노력은 다양한 성능 향상의 효과를 기대할 수 있다. 이 논문에서는 달빅 가상머신의 실행 파일인 DEX 파일의 구조 및 정보를 세분화하여 시각적으로 쉽게 접근할 수 있는 브라우저를 설계하고 구현한다. 이를 통해서, DEX 파일의 구조 및 정보를 보다 쉽게 접근하고 이용할 수 있으며 디어셈블러(smali/baksmali) 편리하게 사용할 수 있도록 하였다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.3
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• pp.152-157
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• 2019

Objectives: The number of elderly patients with systemic basal disease requiring invasive dental treatment has increased. Appropriate prediction of surgical invasiveness and combined use of psychosedation are thought to contribute to safe whole-body management. Dexmedetomidine (DEX) exhibits analgesic and anti-anxiolytic properties and causes mild respiratory depression. Studies regarding DEX use in elderly non-intubated patients are scarce. We aimed to use retrospective data to determine an effective dose of DEX to induce adequate sedation in elderly patients undergoing invasive dental surgery under local anesthesia. Materials and Methods: One hundred two patients aged 70 to 96 years were presumably appropriately controlled with sedation. DEX was administered at an initial loading dose of 2.0 to $3.1{\mu}g/kg/hr$ for 10 minutes. We divided the patients into five groups by age and compared their blood pressures and heart rates. Results: In all five groups, blood pressure decreased suddenly at approximately 15 and 20 minutes after DEX administration. A marked decrease in blood pressure was noted in patients aged 75 to 79 years. Conclusion: For elderly patients aged 75 years and above, the initial loading dose of DEX needs to be reduced to lower than half that required for young and middle-age adults.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.36.1-36.12
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• 2022

Dexamethasone (DEX) was the first drug shown to save lives of critically ill coronavirus disease 2019 (COVID-19) patients suffering from respiratory distress. A hyperactivated state of neutrophils was found in COVID-19 patients compared to non-COVID pneumonia cases. Given the beneficial effects of DEX in COVID-19 patients, we investigated the effects of DEX and of other immunomodulatory drugs vitamin D3 (VD3) and retinoic acid (RA) on neutrophil function. DEX, but not VD3 or RA, significantly inhibited all tested aspects of neutrophil function, e.g., degranulation, intracellular ROS production, CXCL8 release and NETosis. Interestingly, RA displayed the opposite effect by significantly increasing both CXCL8 and NET release by neutrophils. Taken together, these data suggest that the lower COVID-19 mortality in DEX-treated patients may in part be due to the dampening effect of DEX on the inflammatory neutrophil response, which could prevent neutrophil plugs with NETS in the lungs and other inflamed organs of patients.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.106-115
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• 2010

Phosphorylated dextran (P-Dex) is an acidic polysaccharide that functions as an immune adjuvant. P-Dex is known to regulate immune response by maintaining a balance between Th1 and Th2 cells in vitro, and thus may also be important in the control of allergic reactions. In the current study, we report the optimum conditions required for the efficient phosphorylation of dextran without toxicity. We found that when dextran was heated at 160${^{\circ}C}$ for 24 h in phosphate buffer (pH 5.0), the resulting P-Dex demonstrated the highest phosphorus content (6.8%). We also report that P-Dex enhances mitogenic activity in mouse splenocytes and induces expression of CD69 and CD86 on the surface of B cells and dendritic cells (DC) in vitro. Oral administration of P-Dex to ovalubmin (OVA)-immunized mice was found to reduce antigen-induced cell proliferation and suppress the expression of CD86 on Th2-inducing DC via exogenous OVA stimulation. P-Dex was also found to increase IL-10 expression in the splenocytes of treated mice. These findings suggest that oral administration of P-Dex increases immunological tolerance and improves the specificity of immunological response to specific antigens.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.272-278
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• 1997

Many investigators are trying to elucidate the pathogenesis of psychiatric disorders on the basis of neuroendocrine responses to stimulation or perturbation. Dexamethasone(DEX) suppression has been the most widely utilized as the prototypical challenge test. Dexamethasone suppression test(DST) has proven to be valuable in diagnosing the depressive spectrum disorder. Reported specificity of diagnosis of depression is relatively high, but sensitivity is limited. Some researchers used the combination of dexamethasone and corticotropin releasing hormone(CRH) in order to improve the sensitivity. They reported that combined DEX/CRH test is more sensitive than DST alone. In this study the authors modified the DEX/CRH test, i.e., we administered the insulin instead of CRH. Total subjects were 28(7 normal controls, 10 manic patients, 11 schizophrenic patients). Subjects were taken DEX(1.5mg p.o.) at 11 p.m., insulin 16 hours later(0.1 unit/kg i.v.). Five blood samples for the determination of cortisol and ACTH were serially drawn at 15 minute interval. The results are as followings : 1) The cortisol and ACTH levels of manic subjects increased following insulin administration. Manic subjects showed higher levels of cortisol and ACTH than schizophrenic and normal control subjects. The cortisol and ACTH levels of schizophrenic and normal control subjects did not show gross changes. 2) The sensitivity of the test was lower than that of reported DEX/CRH test.

• Journal of Periodontal and Implant Science
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• v.43 no.4
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• pp.168-176
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• 2013

Purpose: The purpose of the current study was to examine the effect of dexamethasone (Dex) at various concentrations on the apoptosis and mineralization of human periodontal ligament (hPDL) cells. Methods: hPDL cells were obtained from the mid-third of premolars extracted for orthodontic reasons, and a primary culture of hPDL cells was prepared using an explant technique. Groups of cells were divided according to the concentration of Dex (0, 1, 10, 100, and 1,000 nM). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for evaluation of cellular viability, and alkaline phosphatase activity was examined for osteogenic differentiation of hPDL cells. Alizarin Red S staining was performed for observation of mineralization, and real-time polymerase chain reaction was performed for the evaluation of related genes. Results: Increasing the Dex concentration was found to reduce cellular viability, with an increase in alkaline phosphatase activity and mineralization. Within the range of Dex concentrations tested in this study, 100 nM of Dex was found to promote the most vigorous differentiation and mineralization of hPDL cells. Dex-induced osteogenic differentiation and mineralization was accompanied by an increase in the level of osteogenic and apoptosis-related genes and a reduction in the level of antiapoptotic genes. The decrease in hPDL cellular viability by glucocorticoid may be explained in part by the increased prevalence of cell apoptosis, as demonstrated by BAX expression and decreased expression of the antiapoptotic gene, Bcl-2. Conclusions: An increase in hPDL cell differentiation rather than cellular viability at an early stage is likely to be a key factor in glucocorticoid induced mineralization. In addition, apoptosis might play an important role in Dex-induced tissue regeneration; however, further study is needed for investigation of the precise mechanism.