• The Korean Journal of Pain
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• v.23 no.2
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• pp.116-123
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• 2010

Background: Pamidronate is a potent inhibitor of osteoclast-mediated bone resorption. Recently, the drug has been known to relieve bone pain. We hypothesized that direct epidural administration of pamidronate could have various advantages over oral administration with respect to dosage, side effects, and efficacy. Therefore, we evaluated the neuronal safety of epidurally-administered pamidronate. Methods: Twenty-seven rats weighing 250-350 g were equally divided into 3 groups. Each group received an epidural administration with either 0.3 ml (3.75 mg) of pamidronate (group P), 0.3 ml of 40% alcohol (group A), or 0.3 ml of normal saline (group N). A Pinch-toe test, motor function evaluation, and histopathologic examination of the spinal cord to detect conditions such as chromatolysis, meningeal inflammation, and neuritis, were performed on the 2nd, 7th, and 21st day following administration of each drug. Results: All rats in group A showed an abnormal response to the pinch-toe test and decreased motor function during the entire evaluation period. Abnormal histopathologic findings, including neuritis and meningeal inflammation were observed only in group A rats. Rats in group P, with the exception of 1, and group N showed no significant sensory/motor dysfunction over a 3-week observation period. No histopathologic changes were observed in groups P and N. Conclusions: Direct epidural injection of pamidronate (about 12.5 mg/kg) showed no neurotoxic evidence in terms of sensory/motor function evaluation and histopathologic examination.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.26 no.2
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• pp.150-158
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• 1993

In order to investigate the content and seasonal variation of the extractive components including taste compounds, free amino acids, nucleotides and related compounds, quanternary ammonium bases, and guanidino compounds of ascidian collected from the south coast of Korea were determined bimonthy from April to October in 1990. The extractive nitrogen was composed of $60{\sim}62\%$ as free amino acids, $12{\sim}16\%$ as betaines, $5{\sim}9\%$ as nucleotides, and others as trimethylamine oxide(TMAO) and total creatinine. The muscle of ascidian was rich in such free amino acids as taurine, proline, glutamic acid, glycine and glycinebetaine. Most of nitrogenous compounds in the extractives showed a marked seasonal variation with a maximum in summer or autumn. AMP content was relatively high among nucleotides. Succinic acid, malic acid, lactic acid and pyroglutaric acid were the major organic acids in ascidian. The results of omission test suggested that the taste of ascidian is attributed to mainly free amino acid, betaines, nucleotides and nonvolatile organic acid in order.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• The Korean Journal of Mycology
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• v.25 no.4 s.83
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• pp.330-339
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• 1997

Botrytis cinerea T91-1 has shown to produce at least four different polygalacturonases in a liquid medium containing citrus pectin as a carbon source. One of the enzymes, its molecular weight was estimated as 37 kDa by denatured polyacrylamide gel electrophoresis, was purified by a series of procedures including acetone precipitation, ion exchange, heparin affinity, and reverse phase column chromatographies. By viscometric analysis, the enzyme was revealed as an endo-polygalacturonase. The enzyme activity was inhibited by divalent cations such as $Ca^{2+}$, $Co^{2+}$, and $Cu^{2+}$. Km and Vmax for polygalacturonic acid hydrolysis were 0.33 mg/ml and 28.6 nM/min, respectively. The optimum temperature for enzymatic activity was $55^{\circ}C$ and the enzyme showed optimal pH values between 4.0 and 4.5. The enzyme was stable up to 12 hours in the range of pH 4 to 7 and at the temperature below $30^{\circ}C$. Amino acid sequence from N-terminal up to 6 amino acids determined by Edman degradation showed little homology with polygalacturonases from fungi and plants.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.4
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• pp.788-796
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• 1998

The purpose of this study was to investigate the effect of various electroacupuncture duration induced by acupuncture point-Zusanli ($S_{36}$) electrical stimulation on inhibition of amplitude of digastric electromyogram (dEMG) evoked by noxious electrical stimuli around the mental foramen. intraperitoneal sodium pentobarbital in an initial dose of 50mg/kg and maintenance doses of 4.5mg/kg/h were given through a cannula in the femoral vein using a constant infusion pump. A pair of stimulating electrodes were inserted for noxious stimuli around the mental foramen. An irritant electronic stimuli pulse (0.2 Hz, 0.1 ms duration) was produced with an intensity of about $1.5{\times}2$ times threshold for evoking the dEMG. The anterior belly of the digastric muscle was exposed and a pair of 0.1mm wire electrodes were inserted for dEMG recording. Acupuncture point stimulation on Zusanli (2 Hz, 250 ${\mu}s$, biphasic pulse, 2 V) was delivered by Dental Electronic Anesthesia (3M, U.S.A). For periods of electronic stimulation of 10, 20, and 30min, the amplitudes of dEMG were measured on the oscilloscope and on the monitor connected to the amplifier. The following results were obtained: The dEMG was decreased to 73.4% of that in the control set after 10 min electroacupunture stimulation (Group I); The dEMG was decreased to 77.1% (10min), 54.0.% (20min) of that in the control set after 20minutes of electroacupunture stimulation (Group II). The dEMG was decreased to 73.3% (10min), 61.9% (20min), 76.2% (30min) of that in the control set after 30 min of electroacupunture stimulation (Group III). From these results, it may be that in the electroacupuncture stimulation on the Zusnali resulted in a reduction of amplitude of dEMG and that the most effective electroacupuncture stimulation period was 20min.

• Korean Journal of Clinical Pharmacy
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• v.13 no.1
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• pp.1-4
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• 2003

Cyclosporine (CsA) has become well established as a potent immunosuppressive agent in the renal transplantation. However, therapy is complicated by large intraindividual and interindividual variability in pharmacokinetics of CsA and frequent undesirable clinical outcomes such as graft rejection and nephrotoxicity. The objective of this study was to determine the CsA trough blood concentrations that were associated with acute graft rejection and renal toxicity in renal transplant patients. Also, the ability of the current recommendation of therapeutic range for CsA to prevent graft rejections and CsA-associated renal toxicity was assessed. The clinical courses of the patients on CsA as an immusuppressive agent for preventing the graft rejection with renal ransplantation performed at Seoul National University Hospital from January 1995 to September 1998 were retrospectively reviewed. Total of 78 patients were included and three of them were retransplantation cases. Twenty-two acute episodes of rejection were identified, but only 16 episodes were clinically significant. Of these all the episodes occurred during the first month after transplantation except one. Mean daily doses of CsA were $427.2\pm72.1,\;352.6\pm56.8,\;308.62\pm48.3\;and\;268.47.1\;mg$ at posttransplant 1, 3, 6, and 12 months, respectively. Mean CsA whole blood though levels were $259.8\pm36.2,\;238.5\pm39,\;200.8\pm45.8\;and\;161.9\pm25.8\;ng/ml$ at posttransplant 1, 3, 6 and 12 months, respectively. Mean daily doses/weight were $7.9\pm1,\;6.4\pm1,\;5.3\pm0.7\;and\;4.6\pm0.7\;mg/kg$ at posttransplant 1, 3, 6 and 12 months, respectively. CsA doses decreased significantly as months progressed (p<0.001). During the first month after transplantation, only $12.5\%$ of the patients in rejection group had CsA concentration in therapeutic range, and 87.5, 93.8, and $100\%$ were within the therapeutic range at posttransplant 3, 6, and 12 months, respectively. These results suggested that CsA concentrations of $250\sim300\;ng/ml$ might be appropriate for preventing the acute rejection during the first posttransplant month.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.694-702
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• 1995

Using the Korean red ginseng saponin, which is known to world-wide and thd effects of it have been investigated by many reserachers for years. Ginseng saponin, one of the major components of Korea ginseng root, has many various biologic effects, such as cytotoxic effect, tumorcidal activity, protein biosynthesis and membrane modifying effect. The purpose of this study was to evaluate effects of ginseng saponin on the alkaline phosphatase activity of ROS cells in culture. After ROS cells were seeded into a 96-well plate, 96-well plate cultured until confluence was obtained. To evaluate cytotoxic effect of total saponin in cultured ROS cells, the plates were added to each total saponin concentration (0-1mg/ml). After 48hr., cells were counted by stain with 0.2% trypan blue at randomly selected field microscopically. Also, to evaluate alkaline phosphatase(ALP) activity of total saponin in cultured ROS cell, the plate was added to each total saponin concentration (0-1mg/ml) and ALP activity was assayed. To evaluate time-course of ALP activity, $31.25{\mu}g/ml$ of saponin added to 96-well plate. After culture of 6, 12, 24 and 48hr., ALP activity test was performed. To evaluate effect of cycloheximide in ALP activity, 96-well plate was added to saponin and cycloheximide. In control group, the plate was added saponin only. The results were as follows. 1. After the various concentration of total saponin was added in the medium, 500 and $1000{\mu}g/ml$ of total saponin showed cytotoxic effect of ROS(P<0.005). 2. In contrast to control group, 7.6, 15.6, 31.25, 62.5 and $250{\mu}g/ml$ of total saponin increased ALP activity significantly. 3. Otherwise, 500 and $1000{\mu}g/ml$ of total saponin decreased ALP activity significantly(P<0.005). 4. As the time span increases, $31.25{\mu}g/ml$ of total saponin increased ALP activity. 5. Cycloheximide decreased saponin-indueced ALP actitity in ROS(P<0.005). These results suggest that Ginseng total saponin stimulates the ALP activity of rat osteoblastic cells.

• Applied Microscopy
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• v.25 no.3
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• pp.51-62
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• 1995

It has been well known that ischemia and reperfusion injury to skeletal muscle following an acute arterial occlusion causes significant morbidity and mortality. The skeletal muscle, which contains high energy phosphate compounds, has ischemic tolerance. During the ischemia, the ATP is catalyzed to hypoxanthine anaerobically and hypoxanthine dehydrogenase is converted to xanthine oxidase. During reperfusion, the hypoxanthine is catalyzed to xanthine by xanthine oxidase under $O_2$, presence and that results in production of cytotoxic oxygen free radicals. These cytotoxic free radicals, $O_2^-,\;H_{2}O_2,\;OH^-$, are toxic and make lesions in skeletal muscle during reperfusion. The authors perform the present study to investigate the effects of allopurinol, the inhibitor of xanthine oxidase, on reperfused ischemic skeletal muscles by observing the ultrastructural changes of the muscle fibers. A total of 48 healthy Sprague-Dawley rats weighing from 200 g to 250 g were used as experimental animals. Under urethane(3.0mg/kg., IP) anesthesia, lower abdominal incision was done and the left common iliac artery were ligated by using vascular clamp for 1, 2 and 6 hours. The left rectus femoris muscles were obtained at 6 hours after the removal of vascular clamp. In the allopurinol pretreated group, 50mg/kg of allopurinol was administered once a day for 2 days and before 2 hours of ischemia. The specimens were sliced into $1mm^3$ and prepared by routine methods for electron microscopic observations. All preparations were stained with uranyl acetate and lead citrate, and then observed with Hitachi -600 transmission electron microscope. The results were as follows: 1. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats, decreased glycogen particles and electron density of mitochondrial matrix and dilated terminal cisternae are seen. In 2 hours ischemia/6 hours repersed rectus femoris muscles of rats, mitochondria with electron lucent matrix, irregularly dilated triad and spheromembranous bodies are observed. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats, irregularly arranged myofibrils, and many spheromembranous bodies, fat droplets and lysosome are seen. 2. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, decreased glycogen particle and dilated cisternae of sarcoplasmic reticulum and triad are observed. In 2 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol decreased electron density of mitochondrial matrix and spheromembranous bodies are seen. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, mitochondria with electron lucent matrix, spheromembranous bodies and dilated cisternae of sarcoplasmic reticulum and terminal cistern are observed. The results suggest that the allopurinol attenuates the damages of the skeletal muscles of rats during ischemia and reperfusion.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.27-30
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• 1994

잠재적으로 항감염 약제로 사용될 가능성이 있는 약제들의 초기 연구과정에서 주된 관심사는 이들이 미생물(세균, 바이러스, 기타 기생충)에 대한 작용들이 있는가 하는 점이다. 이러한 작용들이 실험적으로 충분히 연구가 된 후에야 실험동물에서 그 효과를 연구한다. 항 바이러스 제제의 경우에는 세포배양을 통한 연구가 그 약제의 독성과 효용성을 나타내는데 필수적인 것이 된다. 여러 종류의 동물을 이용한 생체실험에서 약제의 일반적인 흡수와 배설, 분포 등에 관한 정보와 약제 자체와 동물 내에서의 대사적 변화에 대한 정보가 제공된다. 여러 가지 미생물로 감염을 시킨 적합한 동물과 여러 가지 용량으로 치료하는 실험을 통하여 약제의 항 감염 능력이 알려지게 된다. 동물에서의 생체실험과 실험관내에서 실험을 하고 나서야 사람에서의 연구가 이루어지게 된다. 소위 전임상시험에서 대표적 병원성 미생물에 대한 생물학적효과, 약리학적 효과와 독성 그리고 동물실험모델에서의 가능한 효과가 결정된 후에 임상시험에 들어가기 마련이다. 항균제의 임상시험에는 각각의 감염질환에 대한 진단 및 치료기준을 반영하는 것이 기본이다. 새로운 항균제의 임상시험에서는 안전성과 효과가 반드시 밝혀져야 한다. 1상에서는 인체에서의 약리효과, 안전성이 주목적이며, 2상과 3상은 겹쳐지는 점도 있으나 하나 또는 그 이상의 적응증에 대한 항균제의 효과와 단기간의 부작용은 2상에서 관찰하여야하며, 다수의 환자에서 제안된 적응질환의 무작위임상시험과 다수에서의 안전성도 3상에서 관찰하여야 한다. 4상에서는 이상에서의 자료로 시판된 후에도 계속해서 감시하는 것으로 지속적으로 안전성을 관찰하는 것이다. 이러한 기본사항외에도 소아, 임산부, 고령자등에서의 임상시험도 넓은 의미에서 포함되어야 할 것이며 또한 질적인 면에서 조절하는 Quality Assurance도 중요하다.양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.5주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 모든 처리군들이 대조군에 비하여 높게 발현되는. 것이 관찰되었으나 시험개시후 26주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 대조군에 비하여 차이가 거의 없었다. 따라서 랫드에서 화학적으로 유도한 간암발생 과정에서 NK 세포활성이 현저하게 억제되는 것으로 생각되며, c-myc 종양단백의 발현은 시험개시후 15주에 그 발현이 확실한 것으로 사료되어 진다.에 영향을 주는 성분이 있음을 제시하였다.1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.바와 같이 MCl에서 작은 Dv 값을 갖는데, 이것은 CdCl$_{4}$$^{2-}$ 착이온을 형성하거나 ZnCl$_{4}$$^{2-}$ , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서던지 NH$_{4}$$^{+}$의 경우 Dv값이 제일 작았다. 바. 본 연구의 목적중의 하나인 인체유