• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.137-146
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• 1999

Interactions among dexamethasone, dehydroepiandrosterone (DHEA), lipopolysaccharide (LPS), and antimycin A on the glutamate uptake and the polyamine uptake were investigated in primary cultures of rat cerebral cortical astrocytes to examine the effects of dexamethasone and DHEA on the regulatory role of astrocytes in conditions of increased extracellular concentrations of glutamate or polyamines. 1. $[^3H]Glutamate$ uptake: LPS and antimycin A decreased $V_{max},$ but both drugs had little effect on $K_m.$ Dexamethasone also decreased basal $V_{max}$ without any significant effect on $K_m.$ And dexamethasone further decreased the antimycin A-induced decrease of $V_{max}.$ DHEA did not affect the kinetics of basal glutamate uptake and the change by LPS or antimycin A. 2. $[^{14}C]Putrescine$ uptake: LPS increased $V_{max},$ and antimycin A decreased $V_{max}.$ They showed little effect on $K_m.$ Dexamethasone decreased $V_{max}$ of basal uptake and further decreased the antimycin A-induced decrease of $V_{max},$ and also decreased $V_{max}$ to less than control in LPS-treated astrocytes. DHEA did not affect $K_m$ and the change of $V_{max}$ by LPS or antimycin A. 3. $[^{14}C]Spermine$ uptake: Antimycin A decreased $V_{max},$ and LPS might increase $V_{max}.\;K_m$ was little affected by the drugs. Dexamethasone decreased basal $V_{max}$ and might further decrease the antimycin A-induced decrease of $V_{max}.$ And dexamethasone also decreased $V_{max}$ to less than control in LPS-treated astrocytes. DHEA might increase basal $V_{max}$ and $V_{max}$ of LPS-treated astrocytes. 4. $V_{max}$ of glutamate uptake by astrocytes was increased by putrescine (1000 ${\mu}M$ & 2000 ${\mu}M$) and spermidine (200 ${\mu}M,$ 500 ${\mu}M$ & 2000 ${\mu}M$). Spermine, 200 ${\mu}M$ (and 100 ${\mu}M$), also increased $V_{max},$ but a higher dose of 2000 ${\mu}M$ decreased $V_{max}.\;K_m$ of glutamate uptake was not significantly changed by these polyamines, except that higher doses of spermine showed tendency to decrease $K_m$ of glutamate uptake. In astrocytes, dexamethasone inhibited the glutamate uptake and the polyamine uptake in normal or hypoxic conditions, and the polyamine uptake might be stimulated by LPS and DHEA. Polyamines could aid astrocytes to uptake glutamate.

• Parasites, Hosts and Diseases
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• 제61권1호
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• pp.33-41
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• 2023

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED₅₀ values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

• 방사선산업학회지
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• 제9권4호
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• pp.193-198
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• 2015

Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

• 대한한방내과학회지
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• 제25권3호
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• pp.461-472
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• 2004

Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)

• Journal of Ginseng Research
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• 제23권2호
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• pp.115-121
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• 1999

에탄올 단기 투여로 유발되는 기억획득의 손상에 대한 홍삼 조 사포닌 성분을 비롯한 수종의 뇌기능개선 후보약물의 급성 및 연속 투여 작용을 검토하였다. 에탄올 급성 투여로 유발된 학습획득 손상 흰쥐에 GABA신경 억제 성 약물인 picrotoxin 급성 투여시 에탄올 투여 흰쥐의 학습획득 손상 작용은 유의성 있는 개선효과를 나타내었으나 diazepam, acetyl-L-carnitine 및 apomoiphie투여 군은 현저한 영향을 미치지 않았다. 급성 홍삼 total saponin 투여군은 에탄올 투여 흰쥐의 학습획득 손상을 유의성 있게 억제하였으며 7일간의 연속 투여에 의해 그 효과가 현저하게 증가하였다. 급성 및 연속 deprenyl투여군은 모두 유의성 있는 억제 작용을 나타내었으나 protopanaxatriol, protopanaxadiol 및 centrophenoxine 투여 군은 모두 현저한 억제작용을 나타내지 않았다. 급성 piracetam 투여 및 연속 N-methyl-D-glucamine투여 군은 유의성 있는 억제효과를 나타내었다. 한편, 에탄올 투여 희쥐의 학습획득 손상에 대한 홍삼 total saponin 연속 투여효과는 ${\alpha}-methyl-전 처치에 의해 유의성 있게 차단되었으나 N-methyl-D-glucamine 연속투여에 의한 억제효과는 부분적으로 차단되었으며, 연속 depreny의 효과는 용량에 따라 차단 또는 증강되는 등 전혀 다른 효과를 나타내었다. 이러한 결과는 에탄올 급성 투여 흰쥐의 학습획득 손상은 picrotoxine, 홍삼 조사포닌, N-methyl-D-glucamme및 deprenyl의 급성 또는 연속 투여가 효과적이며 홍삼 조 사포닌과 N-methyl-D-glucamine 및 deprenyl의 연속 투여 효과는 뇌중 도파민 신경활성에 미치는 영향이 상위함을 나타내고 있다. 따라서 에탄올 급성투여 흰쥐의 학습획득 손상은 일차적으로 뇌중 GABA 신경활성의 억제에 기인하며 이차적으로 도파민신경활성과의 균형의 중요성을 시사하고 있다.

• 대한약리학회지
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• 제7권1호
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.493-497
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• 2013

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to $30{\mu}g$ of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

• 미생물학회지
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• 제31권1호
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• pp.72-78
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• 1993

Human cytomegalovirus (HCMV) 의 immediate early(IE) 유전자의 promoter/enhancer 부위에 cAMP response element가 있다는 것으부터 caMP 가 HCMV 의 증식에 관여할 것이라고 생각할 수 있다. 이러한 가능성을 알아보기 위해 8-bromoadenosine 3', 5'-cyclic monophosphate (BrA) 와 papaverine 같은 세포내 cAMP 농도를 변화시키는 약제를 사용하여 HCMV 의 증식, DNA 합성 및 IE 유전자 발현에 대한 영향을 알아보았다. HCMV 증식과 DNA 합성은 papaverine 에 의해 억제된 반면, BrA 는 HCMV 의 증식에는 큰 영향을 주지 않았고 DNA 합성은 오히려 촉진시키는 것을 알 수 있었다. HCMV IE promoter 에 의해 작동되는 CAT 유전자를 함유한 plasmid pCMVIE/CAT 을 세포내로 transfection 시켰을 때, papaverine 을 처리한 세포에서는 CAT 효소 활성도가 감소한 반면 BrA 를 처리한 세포에서는 증가하였다. HCMV 에 감수성이 없는 HeLa 세포에서는 CAT 활성도가 감소성 세포인 HEL 세포에서보다 높게 나타난 반면, Vero 세포에서는 낮게 나타났다. 이들 비감수성 세포인 HEL 세포에서 보다 높게 나타난 반면 Vero 세포에서는 낮게 나타났다. 이 들 비감수성 세포에서의 CAT 활성도는 BrA 를 처리하여 주었을 때 모두 증가하였다. 이상과 같은 결과로부터 cAMP 는 HCMV 증식과 IE 유전자 발현에 어느 정도 관여한다는 것을 알 수 있다.

• 대한약리학회지
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• 제9권2호
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• pp.1-6
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• 1973

Although numerous drugs are available for the treatment of superficial fungi infections of skin, the clinical effects of the majority of such drugs are not satisfactory. In the hope of searching the effective drugs for superficial fungi infections, authors studied whether Veratrum rhizoma extracts had any effect on fungi, with water extract (VRWE), ethanol extract (VREE) and methanol extract (VRME) from Veratrum album L. var. grandiflorum Max. In in vitro studies, the spores of fungi were inoculated on Sabouraud's glucose agar media which contained three extracts of Veratrun rhizoma in each concentration of $500\;{\mu}g/ml$, $1,000\;{\mu}g/ml$ and $5,000\;{\mu}g/ml$ respectively, and the growth of the fungi were observed for 3 weeks. The species of the fungi used in these experiments were Epidermophyton floccosum, Microsporum canis, Microsporum nanum, Microsporum gypseum, Microsporum cookei, Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Trichophyton verrucosum. The results of the studies were as follows: 1. The growth of M. canis, M. nanum, T mentagrophytes and T. tonsurans were slightly inhibited by VRWE $1,000\;{\mu}g/ml$, and with VRWE $5,000\;{\mu}g/ml$, the growth of E. floccosum, M. gypseum and T. rubrum were slightly inhibited, moderate inhibition on the growth of M. canis, M. nanum, M. cookei, T. mentagrophytes and T. tonsurans were showed by VRWE $5,000\;{\mu}g/ml$. 2. With $500\;{\mu}g/ml$ of VREE, the inhibition on growth of E. floccosum, M. nanum and M. gypseum were slight, however significant inhibition on the growth of M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed. The growth of M. nanum and M. gypseum were moderately inhibited, and significant inhibition on the growth of E. floccosum, M. canis, M. cookei, T. mentagrophytes, T. rubrum and T. tonsurans were observed by VREE $1,000\;{\mu}g/ml$. By VREE $5,000\;{\mu}g/ml$, the growth of all tested fungi were significantly inhibited except T. verrucosuia being showed slight inhibition. 3. Significant inhibition on the growth of M. canis, T, mentagrophytes, T. rubrum and T. tonsurans were noted, and moderate inhibition of M. nanum, slight inhibition of E. floccosum and M. gypseum in growth were observed by VRME $500\;{\mu}g/ml$. The growth of E. floccosum, M. canis, M. nanum, M. cookei, T. mentsgrophytes, T. rubrum and T. tonsurans were significantly inhibited by VRME $1,000\;{\mu}g/ml$, and that of M. gypseum was moderate. With $5,000\;{\mu}g/ml$ of VRME, significant inhibition on the growth of E. floccosum, M. canis, M. nanum, M. gypseum, M. cookei, T mentagrophytes, T. rubrum and T. tonsurans were observed, and T. verrucosum was showed only slight inhibition. From the above results, it was found that the extracts of organic solvents from Veratrum rhizoma (VREE & VRME) exerted significant antifungal activity, and their effects were probably derived from the pharmacological action of steroidal alkaloids.

• 대한의생명과학회지
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• 제12권3호
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• pp.153-160
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• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.