• The Korean Journal of Physiology and Pharmacology
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• 제10권5호
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• pp.273-282
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• 2006

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.413-422
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• 2012

The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine HCl. Lidocaine HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.

• 생명과학회지
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• 제12권3호
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• pp.332-339
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• 2002

옻나무(Rhus verniciflua Stokes)로부터 간섬유화에 따른 간독성의 경감기전을 추구할 목적으로 ethyl acetate 분획에서 분리한 fustin 및 sulfuretin을 실험동물에 투여하고서 혈액학적 변화 및 간장 중 활성산소에 미치는 영향 검토한 결과 담도결찰하여 간섬유화를 유도한 군에서는 AST, ALT, SDH, ${\gamma}$-GT활성 및 total bilirubin의 양이 현저히 증가되던 것이 옻나무의 메탄을 엑스(250 mg/kg), 에틸아세테이트 엑스(250 mg/kg), fustin(10 mg/kg) 및 sulfuretin(10 mg/kg)을 2주간 각각 경구투여 하므로서 유의성 있게 억제되었다. Hydroxyproline양 및 MDA 농도에서도 간섬유화를 유도하므로서 현저히 증가되던 것이 옻나무의 분획 및 sulfuretin과 fustin의 투여로서 각각 약 60% 및 47%정도 감소되었다. 간섬유화를 유도한 cytosolic계 효소인 xanthine oxidase 및 aldehyde oxidase의 활성이 현저히 증가되었으며 한편 superoxide dismutase, glutathione peroxidase 및 catalase은 간섬유화의 유도로 감소되었으나 옻나무의 분획(메탄올, 에틸아세테이트) 및 성분(fustin, sulfuretin)의 투여로서 조절되었다.

• 대한의용생체공학회:의공학회지
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• 제27권5호
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• pp.210-217
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• 2006

Many types of interspinous distraction devices (IDDs) have been recently developed as an alternative surgical treatment to laminectomy and fusion with pedicle screws for the treatment of the lumbar spinal stenosis (LSS). They are intended to keep the lumbar spine in a slightly flexed posture to relieve pain caused by narrowing of the spinal canal and vertebral foramen. However, their biomechanical efficacies are not well known. In this study, we evaluated the kinematic behaviors and changes in intradiscal pressure (IDP) of the porcine lumbar spine implanted with IDD. For kinematics analysis, five porcine lumbar spines (L2-L6) were used and the IDD was inserted at L4-L5. Three markers (${\phi}{\le}0.8mm$) were attached on each vertebra to define a rigid body motion for stereophotogrammetric assessment of the spinal motion in 3-D. A moment of 7.5Nm in flexion-extension, lateral bending, and axial rotation were imparted with a compressive force of 700N. Then, IDD was implanted at L3-L4. IDPs were measured using pressure transducer under compression (700N) and additional extension moment (700N+7.5Nm). In kinematic behaviors, insertion of IDD resulted in statistically significant decrease 42.8% at the implanted level in extension. There were considerable changes in ROM at the adjacent levels, but statistically insignificant. In other motions, there were no significant changes in ROM as well regardless of levels. IDPs at the surgical level (L3-L4) under compression and extension moment decreased by 12.9% and 18.8% respectively after surgery (p<0.05). At the superiorly adjacent levels, IDPs increased by 19.4% and 12.9% under compression and extension, respectively (p<0.05). Corresponding changes at the inferiorly adjacent levels were 29.4% and 6.9%, but they were statistically insignificant (p>0.05). The magnitude of pressure changes due to IDD, both at the operated and adjacent levels, were far less than the previously reported values with conventional fusion techniques. Our experimental results demonstrated the IDDs can be very effective in limiting the extension motion that may cause narrowing of the spinal canal and vertebral foramens while maintaining kinematic behaviors and disc pressures at the adjacent levels.

• 한국약용작물학회지
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• 제17권3호
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• pp.217-222
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• 2009

The purpose of this study evaluated the immunoregulatory effect of phellinus linteus ethanol (PLE) extracts on liver damage on carbon tetrachloride ($CCl_4$) induced in rats. Four-week old Male Sprague-Dawley rats were divided into the three experimental groups randomly; Control group, $CCl_4$ group, $CCl_4$ + PLE group. We found that effect of PLE on $IFN-\gamma$, STAT1 and pSTAT1 was decrease in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. IL-4, STAT6 and pSTAT6 decreased significantly lower in $CCl_4$ + PLE than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group with $CCl_4$ + PLE group. In our data indicate that IgA levels in MLN lymphocytes were low, while IgE was high in $CCl_4$ + PLE group compared with $CCl_4$ group. Therefore, the results of this study show that PLE can be proposed to protect the liver against $CCl_4$-induced immunoregulatory activity in rats.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.1.1-1.14
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• 2018

DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

• Clinical and Experimental Reproductive Medicine
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• 제24권2호
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• pp.167-177
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• 1997

Oocyte donation program developed to reach the pregnancy in those patients suffering from premature ovarian failure or surgery induced menopause, particularly in their reproductive age. With technical advances and popularity of ART (assisted reproductive technology), the indication of oocyte donation program extended to low responders, and even to naturally menopaused patients that has led them quite successfully to getting in pregnancy. The purpose of this study was to evaluate which one is involved in the decline of fertility between the oocyte and uterine factor. One hundred five cycles of oocyte donation program were performed in 84 patients from Jan., 1993 to Dec., 1996. Oocytes were donated from healthy, young, fertile anonymous donors or relatives or infertile patients with supernumerary oocytes. The study population was divided into 3 groups according to the age of recipients. Group 1 was less than 35 years old, Group 2 was between 35 to 39 years old, and Group 3 was more than 39 years old. The results were as follows: The mean age of oocyte donor was $31.5{\pm}3.3$ (range; 25-36). The mean concentration of basal serum FSH and peak serum estradiol were not different among groups. The mean number of oocytes retrieved from donors, embryos transferred to recipients, and fertilization rate were not different among groups. The clinical pregnancy rate was 37.3% in Group 1, 31.6% in Group 2, and 31.6% in Group 3, respectively. The spontaneous abortion rate was 16.0% in Group 1, 16.7% in Group 2, and 16.7 in Group 3, respectively. The multiple pregnancy rate was 20.0% in Group 1, 16.7% in Group 2, 16,7% in Group 3, respectively, The implantation rate was 11.3% in Group 1, 10.3% in Group 2 and 10.0% in Group 3, respectively. All of the pregnancy outcomes were not different statistically among groups. In conclusion, endometrial receptivity does not seem to be impaired as age increases with transfer of good quality embryos and adequate endometrial preparation.

• 한국방사선학회논문지
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• 제15권2호
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• pp.239-246
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• 2021

기존 연구인 선량평가의 임상 적용 및 신뢰도 확보를 위하여 EPID를 이용하여 Portal Dosimetry를 검증하였다. 뇌정위방사선수술 2.5 cm cone을 장착하여 360° 회전조사에 의한 측정치와 Geant4의 선량분포를 비교하였다. 뇌전이 환자의 선량분포를 확인하기위해 두부인체 팬톰에 Gafchromic EBT필름을 삽입하여 조사한 선량분포와 VMAT을 이용한 두부인체 팬톰에서 얻은 선량분포를 비교하여 실제 환자에 적용하고자 한다. 분석결과 beam center와 couch의 center가 정확하게 일치하는가를 pin ball을 통해 QA한 결과 1 mm 이내의 오차로 정밀함을 확인할 수 있었다. 또한 EBT3 Film에 다양한 선량조사에 따라 0 ~ 10 Gy영역까지 우수한 선형성임을 확인할 수 있었다. 두경부 팬텀과 같은 설정에서 광자 빔을 사용한 Geant4에 기반한 선량 계산 도구의 구현과 시뮬레이션 결과 계산치는 치료계획용적(PTV)내에서 실험 데이터와 일치함을 확인하였다. 따라서 체적변조 아크치료(VMAT) 360° 회전 조사를 실시하여 회전조사에 의한 등선량분포 분석결과 가상 종양을 포함하기에 적절함을 확인하였다.

• Clinical and Experimental Otorhinolaryngology
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• 제11권4호
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• pp.293-300
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• 2018

Objectives. The current study aims to determine the correlation between nutritional status upon presentation and disease severity, as well as treatment and survival outcomes. Methods. Patients who were diagnosed with deep neck infection, underwent at least one surgical drainage/debridement, and had more than 1 week of hospitalization at a tertiary medical center from 2007 to 2015 were retrospectively included. Thereafter, initial serum albumin, C-reactive protein (CRP), and body mass index (BMI) were reviewed. Results. A total of 135 patients were included in the final analysis. Accordingly, the proportion of patients with simultaneous mediastinitis (21.0%), necrotizing fasciitis (12.9%), disease extent >1 cervical level (72.6%), mean CRP (22.4 mg/dL), mean length of hospitalization (25.0 days), and mean 1-week follow-up CRP (7.2 mg/dL) was significantly higher in the hypoalbuminemia group (initial serum albumin <3.0 g/dL) than in the normoalbuminemia group (all P<0.05). No significant correlations had been observed according to BMI status. After adjusting for age and Charlson comorbidity index, odds ratios for the following outcomes were calculated in patients initially presenting with hypoalbuminemia: simultaneous mediastinitis (3.07), necrotizing fasciitis (7.89), disease extent >1 cervical level (2.12), initial serum CRP over 20 mg/dL (3.79), hospitalization of more than 14 days (4.10), 1-week follow-up CRP over 5 mg/dL (3.78), and increased duration for an over 50% decrease in initial CRP (2.70) (all P<0.05). Although intravascular albumin replenishment decreased the proportion of patients with hypoalbuminemia after 2 weeks (P<0.05), it did not significantly predict better treatment outcomes. Conclusion. Among the markers reflecting an individual's nutritional state, an initial serum albumin of less than 3.0 g/dL was an independent serologic marker predicting increased disease severity and complications in patients with deep neck infection.

• Clinical and Experimental Otorhinolaryngology
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• 제11권4호
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• pp.281-287
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• 2018

Objectives. Regenerative treatment using stem cells may serve as treatment option for empty nose syndrome (ENS), which is caused by the lack of turbinate tissue and deranged nervous system in the nasal cavity. We aimed to assess the efficacy and safety of the autologous stromal vascular fraction (SVF) in the treatment of ENS. Methods. In this prospective observational clinical study, we enrolled 10 ENS patients who volunteered to undergo treatment of ENS through the injection of autologous SVF. Data, including demographic data, pre- and postoperative Sino-Nasal Outcome Test-25 (SNOT-25) scores, overall patient satisfaction, and postoperative complications, were prospectively collected. Nasal secretion was assessed using the polyurethane foam absorption method, and the levels of biological markers were analyzed in both ENS group and control group using enzyme-linked immunosorbent assay. The SVF extracted from abdominal fat was diluted and injected into both inferior turbinates. Results. Among the 10 initial patients, one was excluded from the study. Subjective satisfaction was rated as "much improved" in two and "no change" in seven. Among the improved patients, the mean preinjection SNOT-25 score was 55.0 and the score at 6 months after injection was 19.5. However, the average SNOT-25 score of nine participants at 6 months after injection (mean${\pm}$standard deviation, $62.4{\pm}35.8$) did not differ significantly from the baseline SNOT-25 score ($70.1{\pm}24.7$, P>0.05, respectively). Among the various inflammatory markers assessed, the levels of interleukin $(IL)-1{\beta}$, IL-8, and calcitonin gene-related peptide were significantly higher in ENS patients. Compared with preinjection secretion level, the nasal secretions from SVF-treated patients showed decreased expressions of $IL-1{\beta}$ and IL-8 after injection. Conclusion. Although SVF treatment appears to decrease the inflammatory cytokine levels in the nasal mucosa, a single SVF injection was not effective in terms of symptom improvement and patient satisfaction. Further trials are needed to identify a more practical and useful regenerative treatment modality for patients with ENS.