• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.471-477
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• 1998

Cyclosporin A (CsA), a widely used immunosuppressant, is well known to cause nephrotoxicity and hypertension as major side effects. The present study was aimed at investigating the effects of CsA-pretreatment on the activities of cytosolic guanylate cyclase (cGC) in relation to the alteration of relaxant responses in the rat thoracic aorta. CsA $(10\;{\mu}M)-preincubation$ for 90 min significantly attenuated the vasodilatation induced by sodium nitroprusside (SNP), a cytosolic guanylate cyclase activator, shifting the dose-response curve to the right. The increase in cGMP contents induced by SNP was markedly attenuated by CsA. SNP ($1\;{\mu}M{\sim}\;mM$) increased the cGC activity dose-dependently, and the increase was completely abolished by CsA. CsA attenuated the SNP-induced cGC activation dose-dependently. The abolishing effect of CsA-pretreatment on the SNP-induced cGC activation was not affected by washing the preparation, suggesting that the inhibition is irreversible. When CsA was added simultaneously with SNP, cGC activation was not attenuated. 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine (H-7), a protein kinase C (PKC) inhibitor, decreased SNP-induced cGC activation and blocked the CsA-attenuation of cGC activation. These results suggest that CsA directly inhibits cGC participating in the CsA-induced impairment of vasodilatation, and that PKC is involved in the inhibitory action of CsA on cGC.

• Journal of Chest Surgery
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• 제27권1호
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• pp.15-23
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• 1994

This study examined the effects of cyclosporin A [CsA] and methylprednisolone[MP] on the viability of the devascularized trachea after heterotopic transplantation. Fourty-two tracheal segments were harvested from 21 donor Wistar rats. Those tracheal segments were heterotopically implanted into the abdomen of recipient rats after wrapping in omentum. Heterotopical implantation was performed in six groups of rats:Group I was Wistar syngeneic controls, and five groups of Sprague Dawley recipients, receiving no immunosuppression[Group II], CsA alone[Group III, V], and CsA in combination with MP[Group IV, VI]. After 14 days, the tracheal segments were histologically evaluated.Epithelial thickness and the degree of epithelial regeneration were significantly different between group I and group II, III, VI, VI [p< 0.05]. There were significant differences in the epithelial thickness between group II, III, IV and group V, VI. In the degree of epithelial regeneration, there were significant differences in group II, group III-IV, and group V-VI. Without immunosuppression there was virtually no epithelium, whereas low-dose immunosuppression yielded intermediated viability, and with high dose CsA and MP we observed improved tracheal viability. Our results suggest that optimal combination of CsA and MP may improve the viability in heterotopic tracheal allografts.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권6호
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• pp.526-529
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• 2006

The aim of this study was to prepare cyclosporin A-loaded liposome (CyA-Lip) as an oral delivery carrier, with their encapsulation into microspheres based on alginate or extracellular polysaccharide (EPS) p-m10356. The main advantage of liposomes in the microspheres (LIMs) is to improve the restricted drug release property from liposomes and their stability in the stomach environment. Alginate microspheres containing CyA-Lip were prepared with a spray nozzle; CyA-Liploaded EPS microspheres were also prepared using a w/o emulsion method. The shape of the LIMs was spherical and uniform, and the particle size of the alginate-LIMs ranged from 5 to $10\;{\mu}m$, and that of the EPS-LIMs was about $100\;{\mu}m$. In a release test, release rate of CyA in simulated intestinal fluid (SIF) from the LIMs was significantly enhanced compared to that in simulated gastric fluid (SGF). In addition, the CyA release rates were slower from formulations containing the liposomes compared to the microspheres without the liposome. Therefore, alginate-and EPS-LIMs have the potential for the controlled release of CyA and as an oral delivery system.

• 동국한의학연구소논문집
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• 제6권2호
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• pp.99-107
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• 1998

본 실험은 cyclosporin A(CsA)에 의한 시간의 경과에 따른 림프절에서의 세포성 면역억제를 조사하기 위해서 시행된 것으로 BALB/C계 생쥐에 10일동안 CsA(45mg/kg/day) 투여 후 림프절에서의 T 림프구, IL-2 수용기 그리고 자연살해(NK)세포의 분포 변화를 관찰하였다. 대조군의 림프절에서는 L3T4(CD4)에 양성반응을 보이는 도움 T림프구, Ly2(CD8)에 양성반응을 보이는 세포독성 T 림프구 그리고 CD25R에 양성반응을 보이는 IL-2 수용기를 가진 세포는 곁피질(paracortex)과 수질동(medullary sinus)에서 분포하였다. CsA 투여 후 처음 3일까지는 이들 양성반응세포의 분포 변화는 없었으며 양성반응성의 변화도 없었다. 그러나 CsA 투여 7일부터 양성반응 세포수의 감소와 양성반응성의 약화가 관찰되기 시작하였으며 이러한 변화는 시간이 경과하여 14일에 이르렀을 때 가장 큰 감소추세로 나타났다. 한편 NK1.1(CD56)에 양성반응을 보이는 자연살해세포는 피질과 수질에 분포하였으며 CsA 투여 후 시간의 경과에 따라 양성반응 세포수가 감소하였으며, 이러한 감소는 14일에서 가장 큰 것으로 나타났다. 이상의 결과로 미루어보아 CsA 투여는 림프절에서의 IL-2 분비저해를 통해 T 림프구와 NK세포의 활성을 차단하여 선택적이면서 효과적인 세포성 면역억제작용을 하고 있는 것으로 사료된다.

• 대한수의학회지
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• 제38권3호
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• pp.441-449
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• 1998

This study was carried out to investigate the fine structural changes of rat hepatocytes by repeated treatment of cyclosporin A that has been widely used for immunosuppressive drug in organ transplantation. Sprague-Dawley rats were kept in experimental circumstances for 2 weeks and 50mg/kg B.W of cyclosporin A was injected once a day subcutaneously for 7 days and sacrificed at 1 hour, 1 day, 3 days, 7 days, 14 days, 28 days after the last injection. Fine structural changes were observed by transmission electron microscope (JEM 1200EX II) and the results obtained were as follows. 1. Accumulation of lipid droplets in hepatocytes was prominently increased in 1 hour and 1 day lapse groups, and this finding was slightly reduced in 3 days lapse group and remarkably reduced from 7 days lapse group enough to be recovered completely in 14 days lapse group. 2. Dilatation of rough endoplasmic reticule cisternae, detachment of membrane bound ribosomes, proliferation of smooth endoplasmic reticula were observed in 1 hour and 1 day lapse groups, and these findings were mild in 3 days lapse group and abruptly reduced from 7 days lapse group enough to be recovered completely in 28 days lapse group. 3. Small myelin figures were observed in 3 days lapse group after CsA-treatment. 4. Swelling of mitochondria and destruction of their cristae were observed in 1 hour and 1 day lapse groups, and these findings were recovered from 3 days lapse group. 5. Dilatation of bile canaliculi and remarkable loss of microvilli in the pericanalicular wall were observed in 1 hour lapse group and the most severe change was shown in 1 day lapse group and lasted to 3 days lapse group, and these findings were reduced gradually from 7 days lapse group enough to recovered completely in 28 days lapse group.

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 1997년도 제37회 종합학술대회 연제초록
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• pp.113-113
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• 1997

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 1994년도 제34회 종합학술대회
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• pp.35-35
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• 1994

• 대한치주과학회:학술대회논문집
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• 대한치주과학회 1994년도 제34회 종합학술대회
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• pp.36-37
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• 1994

• 대한흉부심장혈관외과학회:학술대회논문집
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• 대한흉부외과학회 1993년도 제25차년차학술대회 및 총회
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• pp.47-47
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• 1993

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.285-285
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• 1996

Cyclosporin A (CyA) is widely used in the inhibition of graft rejection in organ transplantation. However, the bioavailability of CyA after oral administration is very low due to its poor solubility and dispersability hi water. To improve the solubility of CyA, microemulsion systems were developed and its physicochemical characteristics were evaluated by phase studies, solubility and dispersability tests. Phase studies on the systems composed of ethyl oleate (EO), PPG-20 methyl glucose ether (GP-20), poloxamer 123 (PL) and water U) were carried out to make stable w/o emulsions. Besides, based on CyA solubility test in various compositions of surfactant systems, a reasonable surfactant composition (GP-20/PL=4/1) was selected to enhance its solubility.