• 대한핵의학회지
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• 제27권2호
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• pp.223-232
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• 1993

Technetium labeled isonitrile analogues are widely used as myocardial perfusion imaging agents. We synthesized and characterized a new isonitrile compound, ethyl 3-isocyanobutyrate(EIB). Proton and $^{13}C$ NMR spectroscopy and thin layer chromatography with a $C_{18}$ coat was performed. EIB was easily labeled with $^{99m}TcO_4^-$- with sodium dithionite. The labeling efficiency measured by RP-HPLC was over 95%. The labeled product was stable with dilution in normal saline and with prolonged incubation at room temperature. There was no formation of secondary products or free $^{99m}TcO_4^-$. In vivo kinetics study of $^{99m}Tc$ (I) labeled EIB in rabbits showed adequate myocardial uptake, good contrast against lung background, and relatively rapid liver clearance. The heart to lung ratio was over 2.5 and the heart to liver ratio was approximately from 0.4 to 5 at 60 minutes post injection. Hepatic clearance of $^{99m}Tc-MIBI$ was faster ($t_{1/2}$=6 minutes) than that of $^{99m}Tc-MIBI$. In vivo kinetics observed in dog was similar to that in rabbit but there was faster gallbladder filling, and thus lower liver background. SPECT imaging of the canine myocardium showed favorable imaging characteristics. However, biodistribution in mice demonstrated a myocardial % injected dose/organ of less than 0.1%. This was thought to be due to interspecies difference in plasma esterase activity. In human plasma, $^{99m}Tc$ ( I ) labeled EIB was stable for at least 2 hours, without production of secondary products by HPLC. We conclude that ethyl 3-isocyanobutyrate may be a potential new myocardial perfusion imaging agent and deserves further investigation as to its usefulness for clinical use.

• 대한예방한의학회지
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• 제3권2호
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• pp.151-170
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• 1999

This study was to investigate the metal accumulation from SipJeonDaeBo-Decoction to rat blood of Sprague Dawley. 1. There were no significance in body weight, water dose feed ingestion quantity, liver, kidney, brain, bone weights between the control and the experimental groups. Under the experiment with drinking waters was no metal ${\sim}\;0.65mg/L$ detected. Metal level within feed found 0.0001-376.983mg/kg. 2. In the pack of SipJeonDaeBo-decoction, there detected no metal ${\sim}2.086mg/L$ 3. After P.O(per os) SipJeonDaeBo-decoction, As is detected $2.390{\pm}0.812mg/kg$ in blood; Cd $0.001{\pm}0.001mg/kg$, Co $0.003{\pm}0.001mg/kg$, Cr $0.432{\pm}0.234mg/kg$, Cu $1.013{\pm}0.373mg/kg$, Fe $426.293{\pm}114.842mg/kg$, no Hg, Mn $0.109{\pm}0.082mg/kg$, Ni $0.122{\pm}0.068mg/kg$, Zn $3.584{\pm}1.270mg/kg$. 4. The concentration of Hazardous heavy metal (As, Cd, Co, Cr, Hg, Ni, Pb) within blood control group is searched $0.488{\pm}0.138\;mg/l$; experiment I group $0.432{\pm}0.080mg/l$, experiment II group $0.588{\pm}0.213mg/l$. In the concentration of non hazardous heavy metal(Cu, Fe, Mn, Zn) control group $101.409{\pm}6.832mg/l$; experiment I group $96.062{\pm}5.732\;mg/l$, experiment II group $125.139{\pm}044.820mg/l$. 5. Correlation among every metal in blood Zn and Cr was 0.87956 ; Cd and As -0.02316, Pb and As -0.08738, Ni and As 0.07824, Mn and As 0.07824, Mn and Cd 0.04999. Briefly under the injection of SipJeonDaeBo-decoction, this study was defined within safety in blood level by P.O. during 10 days.

• The Korean Journal of Pain
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• 제18권2호
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• pp.113-117
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• 2005

Background: Serotonin 3 receptor is involved in the modulation of nociceptive transmission in the spinal cord. The serotonin 3 receptor antagonist has been used for the management of opioid-induced nausea and vomiting. The aim of this study was to examine whether the analgesic effect of morphine is antagonized by serotonin 3 receptor antagonists at the spinal level. Methods: Rats were implanted with lumbar intrathecal catheters. For nociception, a formalin solution (5%, $50{\mu}l$) was injected into the hind paw of male Sprague-Dawley rats. To determine whether the effect of intrathecal morphine was mediated via serotonin 3 receptors, serotonin 3 receptor antagonists were intrathecally administered 10 min prior to the morphine delivery. Following the formalin injection, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. Results: Intrathecal morphine produced a dose-dependent suppression of the flinches in both phases during the formalin test. The analgesic action of morphine was not reversed by serotonin 3 receptor antagonists (LY-278,584, ondansetron), which had little per se effect on the formalin-induced nociception. Conclusions: Spinal serotonin 3 receptors may not be involved in the analgesia of morphine on a nociceptive state evoked by a formalin stimulus.

• 대한약리학회지
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• 제32권3호
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• pp.381-388
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• 1996

패혈증 환자에 흡입마취제를 투여하는 것은 혈역동학에 심각한 영향을 초래할 수 있다. 흡입마취제 투여시 내독소혈증흰쥐 대동맥 수축반응에 미치는 hydroxocobalamin의 영향을 알아보기위해, 내독소 (1.5 mg/kg)를 복강내 투여한 뒤 18시간 후에 대동맥을 적출하여 phenylephrine에 대한 수축반응과 이에 대한 흡입마취제 및 hydroxocobalamin의 작용을 알아보았다. 패혈증이 적절히 유발되었는 지를 확인하기 위해 RT-PCR을 이용하여 혈관 평활근에서 iNOS유도를 확인하였다. 내독소 처치에 의해 수축기 및 확장기 혈압이 대조군에 비해 유의하게 감소되었으나, 심박동수는 영향이 없었다. Phenylephrine에 대한 수축반응은 $10^{-8}\;M$부터 $10^{-5}\;M$까지 용량 의존적으로 증가했으며, 내독소혈증흰쥐 대동맥에서 수축반응이 억제되었다. halothane과 enflurane은 1 MAC 농도에서 phenylephrine에 의한 수축반응을 유의하게 억제했으나 isoflurane은 영향이 없었다. Hydroxocobalamin $(10^{-5}\;M)$은 흡입마취제의 종류 및 투여 유무에 관계없이 내독소혈증흰쥐 대동맥 수축반응을 증가시켰다. 이상의 결과로 미루어보아 hydroxocobalamin은 패혈증 환자의 흡입마취시 혈역동을 개선시킬 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• 제25권3호
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• pp.239-244
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• 1998

The purpose of this study is compare IVF cycle outcome in poor responders between clomiphene citrate (CC) stimulated and controlled ovarian hyperstimulation (COH) protocol. A total of 94 patients responding poorly in previous IVF cycles (estradiol<600 pg/ml or less than 3 oocytes retrieved) subsequently underwent either COH (COH group: 122 cycles, 68 patients) or CC-stimulated cycles (CC group: 43 cycles, 26 patients). CC was administered for five consecutive days starting on cycle day 3 at a dose of 100 mg daily. Serial transvaginal ultrasound examination was done from cycle day 8. Urine was collected $3\sim4$ times before hCG injection for the detection of LH surge. The hCG was administered when serum estradiol reached greater than 150 pg/ml and mean follicle diameter>16 mm. In COH group, ovarian stimulation was done using short protocol (GnRH-a/FSH/HMG/hCG). No difference in age or number of transferred embryos was found between CC group and COH group. COH group had significantly (p<0.05) higher mean peak level of $E_2$ ($810{\pm}112$ vs $412{\pm}55$ pg/ml) and greater number of retrieved oocytes ($3.0{\pm}0.2$ vs $2.0{\pm}0.2$) than CC group. CC group had transferred embryos $(1.8{\pm}0.2)$ compared with $(2.1{\pm}0.2)$ in COH group. However, CC group had higher pregnancy rate than COH group per retrieval [26.9% (7/26) vs 6.2% (6/97)], or per transfer [31.8% (7/22) vs 7% (6/86)]. Although cycle cancellation rate in CC group (48.8%) was higher than that of COH group (21.3%), the pregnancy rate per cycle in CC group was still higher (16.3%) than COH group (4.9%). In addition, implantation rate in CC group was 17.5% (7/40), which was significantly (p<0.01) higher than 3.9% (7/180) in COH group. These data suggest that oocyte and embryo quality are lower in COH cycles of poor responders than CC cycles. We suggest that clomiphene citrate stimulated IVF cycle may be more efficient than COH IVF cycle in poor responders in terms of lower costs and higher pregnancy performance.

• Journal of Yeungnam Medical Science
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• 제3권1호
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• pp.279-285
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• 1986

가토의 Ouabain유발 부정맥에 미치는 Carbamazepine의 영향을 검색한 결과 다음과 같은 결론을 얻었다. 1. Ouabain을 지속적으로 정맥 주사하여 64+$8.8{\mu}g/kg$이 투여되었을 때 부정맥이 발생 했으며, 이 양을 부정맥 유발 가능용량으로 정했다. 2. Ouabain $64{\mu}g/kg$을 단회 정맥 주사했을 때 발생한 부정맥은 약 7~9분간 지속된 후 모든 예에서 자연 소실되었고, 정상 심박동으로 회복된 지 20분 후 다시 동량의 Ouabain을 정맥 주사했을 때 모든 예에서 다시 나타났다. 3. 부정맥 유발 용량($64{\mu}g/kg$)의 Ouabain을 단회 정맥 주사한 후 부정맥이 나타난 것을 관찰 즉시 Carbamazepine을 투여한 결과 즉시 정상 신박동으로 환원되었으며 어느 정도 지속된 후 모든 예에서 부정맥이 발생했으나 즉시 동량의 Carbamazepine 투여로 다시 정상 심박동으로 환원되었다. 한편, Carbamazepine의 양이 증가되면서 항 부정백 작용의 기간은 길어졌으나 항 부정맥 작용없이 사망한 예가 많아졌다. 4. Carbamazepine을 단독 투여 해 본 결과 그 양이 증가함에 따라 심한 서맥, A-V block, 심방 세동 등이 나타나면서 심장이 정지함을 볼 수 있었다. 이상의 실험 결과로 미루어 Carbamazepine은 Ouabain의 독작용에 의한 심한 부정맥을 일시적으로 억제할 수 있으며, 보다 대량에서는 그 항 부정맥 작용이 보다 오래 지속할 수 있으나 Carbamazepine 자체의 심장에 대한 부작용이 발현될 위험이 존재한다고 생각된다.

• 한국응용과학기술학회지
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• 제32권3호
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• pp.488-496
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• 2015

Streptozotocin(STZ)으로 유도된 당뇨 흰쥐에게 구척 에탄올 추출물을 1일 1회 7일간 1,000 mg/kg.b.w의 용량으로 투여 후 glucose함량과 당대사에 관여하는 효소인 glucose-6-phosphatase(G-6-Pase), glucose-6-phosphate dehydrogenase(G-6-PDH)과 glucokinase(GK)활성과 glycogen 함량과 triglyceride(T.G), total cholesterol 등의 지질대사에 관여하는 물질들과 항산화작용에 관여하는 glutathione-s-transferase(GST),Catalase(CAT), glutathione peroxidase(GSH-Px)활성과 glutathione(GSH)함량을 측정한 결과 구척 에탄올 추출물 투여군이 glucose, T.G, total cholesterol 등의 함량과 G-6-Pase 활성의 유의적인 감소(p<0.05)를 나타내었으며 glycogen 함량과 G-6-PDH, GK의 활성이 유의적인 증가(p<0.05)를 나타내었다. 이와 같이 구척 에탄올 추출물이 항당뇨, 항산화작용의 개선효과를 갖는 유효성분을 함유하고 있음을 알 수 있었다.

• 대한환경공학회지
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• 제22권7호
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• pp.1307-1318
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• 2000

원자력 발전소에서 발생되는 제염폐수에 함유된 Oxalic acid와 Citric acid를 고급산화방법(Advanced Oxidation Process) 중의 하나인 $UV/H_2O_2$를 적용하여 이들 물질의 분해특성 및 최적처리조건을 파악하고자 하였다. 이를 위하여 각각의 물질에 대하여 $H_2O_2$나 UV를 단독사용할 경우, pH 및 과산화수소의 주입량 변화, Oxalic acid와 Citric acid의 농도변화에 따른 분해특성에 대하여 조사하였다. $H_2O_2$나 UV만으로도 완전분해가 가능한 반면 Citric acid는 같은 파장의 UV만으로는 분해가 잘되지 않는 것으로 조사되었다. 또한 과산화수소와는 두 물질 모두 반응성이 없는 것으로 조사되었다. 산화공정에서 반응속도상수, 반응시간, 제거효율, 과산화수소 소모량 등에 대한 결과를 종합한 결과 Oxalic acid의 경우 pH 4 이하의 낮은 pH에서, Citric acid는 pH 4~6 정도의 약산성 부근에서 높은 분해효율을 나타내는 것으로 조사되었다. 최적 pH에서는 과산화수소의 주입량이 증가할수록 두 물질 모두 제거효율이 증가하는 것으로 조사되었으나 과산화수소의 주입량이 200 mg/L 이상을 초과하는 경우에는 과산화수소에 의한 OH radical trap에 의하여 제거효율이 감소하는 것으로 조사되었다. 이상의 결과 $UV/H_2O_2$ 광분해에 의한 Oxalic acid와 Citric acid의 처리시 pH 4에서 과산화수소 주입량 200 mg/L일 경우 가장 효율적인 것으로 조사되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.185-195
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• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.437-442
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• 2015

Aim: To establish a pancreatic cancer stem cell model using human pancreatic cancer cells in nude mice to provide a platform for pancreatic cancer stem cell research. Materials and Methods: To establish pancreatic cancer xenografts using human pancreatic cancer cell line SW1990, nude mice were randomly divided into control and gemcitabine groups. When the tumor grew to a volume of $125mm^3$, they treated with gemcitabine at a dose of 50mg/kg by intraperitoneal injection of 0.2ml in the gemcitabine group, while the mice in control group were treated with the same volume of normal saline. Gemcitabine was given 2 times a week for 3 times. When the model was established, the proliferation of pancreatic cancer stem cells was observed by clone formation assay, and the protein and/or mRNA expression of pancreatic stem cell surface markers including CD24, CD44, CD133, ALDH, transcription factors containing Oct-4, Sox-2, Nanog and Gli, the key nuclear transcription factor in Sonic Hedgehog signaling pathway was detected by Western blot and/or RT-PCR to verify the reliability of this model. Results: This model is feasible and safe. During the establishment, no mice died and the weight of nude mice maintained above 16.5g. The clone forming ability in gemcitabine group was stronger than that of the control group (p<0.01). In gemcitabine group, the protein expression of pancreatic cancer stem cell surface markers including CD44, and ALDH was up-regulated, the protein and mRNA expression of nuclear transcription factor including Oct-4, Sox-2 and Nanog was also significantly increased (P<0.01). In addition, the protein expression of key nuclear transcription factor in Sonic Hedgehog signaling pathway, Gli-1, was significantly enhanced (p<0.01). Conclusions: The pancreatic cancer stem cell model was successfully established using human pancreatic cancer cell line SW1990 in nude mice. Gemcitabine could enrich pancreatic cancer stem cells, simultaneously accompanied by the activation of Sonic Hedgehog signaling pathway.