• Title/Summary/Keyword: cyclosporin

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THE STUDY OF CORRELATION WITH CYCLOSPORIN A INDUCED GINGIVAL OVERGROWTH AND LOCAL FACTORS (Cyclosporin A 유도 치은증식과 국소적 요인과의 상관관계에 대한 연구)

  • Ko, Eun-Ah;Yoo, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.25 no.1
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    • pp.14-23
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    • 1995
  • Cyclosporin A is a powerful immunosuppressive agent commonly used for patients receiving organ transplants. Like phenytoin and the calcium channel blockers, the drug is associated with gingival overgrowth. The purpose of this study was to compare the correlation with gingival overgrowth score and clinical indices(i.e, : plaque index, papillary bleeding index, probing depth) and correlation with gingival overgrowth score and microorganism distribution in use of phase contrast microscope. After renal tranplant, taking cyclosporin A 40 patients participating in this investigation. Post - transplatation cyclosporin medication period was average $17.53{\pm}15.75$ months. In previous study reported that gingival overgrowth is an adverse side - effects seen in about 25-81% of patient taking cyclosporin A. The results were as follows : 1. Gingival overgrowth prevalence in taking cyclosporin A patients was 77.5%. Prevalence rate of region was anterior region(26 teeth, 55.3%), molar region(14 teeth, 29.8%), premolar region(7 teeth, 14.8%) in turns. Gingival overgrowth score by Angelopoulos & Goaz method was molar region($1.56{\pm}0.81$), anterior region($1.52{\pm}0.75$), premolar region($1.14{\pm}0.90$) in turns. 2. Medication period was not correlation with gingival overgrowth score. 3. Clinical indices and gingival overgrowth score were as follows. 1) Plaque index and gingival overgrowth score was significantly correlated(p

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Bioequivalence of Cyclosporin A Hard Capsules (사이클로스포린 A 경질캅셀제에 대한 생물학적 동등성 평가)

  • 김종국;이은진;이미경;박준규;신희종;김인숙
    • Biomolecules & Therapeutics
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    • v.6 no.3
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    • pp.296-302
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    • 1998
  • The bioequivalence of two cyclosporin A products was evaluated in 26 normal male volunteers (age 25 ~33 yr, body weight 56~84 kg) following single oral administration. Test product was a hard capsule containing the granule of cyclosporin A (Chong Kun Dang Corp., Korea) and reference product, Sandimmun", was a soft capsule containing surfactant, oil, alcohol and cyclosporin A (Sandoz, Swiss). Both products contain 100 mg of cyclosporin A. Four capsules of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). Average drug concentrations at each sampling time and pharmacokinetic parameters were not significantly different between two products (p>0.05); the area under the concentration-time curve to last sampling time (24 hr) (AU $Co_{24}$) (5034.8$\pm$ 1760.6 vs 4635.4$\pm$ 1158.9 ng . h/ml), maximum plasma concentration ( $C_{max}$) (1002.7$\pm$353.1 vs 980. 4$\pm$ 171.7 ng/71), and mean residence time (MRT) (6.16$\pm$0.81 vs 5.64$\pm$0.50 h). The differences of mean AUC 7-,4,7~, T_ and MRT between the two products (7.93,2.22,16 and 8.39%, respectively) were less than 20% given as a guideline. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24}$, $C_{max}$ and MRT were more than 0.8 and less than 0.2, respectively. Although $T_{max}$ of the two products was significantly different each other (p<0.05), $T_{max}$ might be an insignificant parameter because cyclosporin A generally requires long-term administration. From these results, the two products are bioequivalent.alent.t.

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Colchicine Derivatives Allows Prolonged Survival of Cardiac Allograft in the Rat (백서에서의 동종이형의 심장이식후 Colchicine 변형 물질 투여군의 장기 변존)

  • Kim Young-Hak;Lee Hyung-Chang;Chung Won-Sang;Kang Jung-Ho;Kim Hyuck;Chon Sun-Ho;Shin Sung-Ho
    • Journal of Chest Surgery
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    • v.38 no.9 s.254
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    • pp.595-600
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    • 2005
  • Background: Colchicine with its immunosupressive properties has been used with benefcial effects in autoimmune disease, such as Gout, etc. Whether colchicine, by virtue of the above property, could attenuate the process of cardiac allograft rejection in the rats is investigated in this report. Material and Method: We compared the untreated group (Control, n=6), Cyclosporin A group (10 mg/kg, daily, n=20), and Colchicine derivative group (Colchicine 40 ${\mu}g$/kg, n=20) of cardiac allografts in the rats. Result: In the untreated control group (n=6), all of 6 rats showed rejection within 3 weeks after cardiac allograft. In the cyclosporin A group (n=20), cyclosporin A (10 mg daily oral dose) was administered at a 10 mg daily oral dose and promoted long-term survival (over 100 days). The cyclosporin A group had one mortality at the 18th post-operative day due to infection. Furthermore, in the Colchicine derivatives group (n=20) with a daily IP (Intra Peritoneum) dose (40 ug/kg/day), we observed long-term survival.(> 100 days), except for one rat that died of an anesthetic problem (respiratory failure) at the 9th post-operative day. Conclusion: Experiments have also been performed to evaluate whether the effect of colchicine derivatives allowed prolonged survival of cardiac allografts compared with the cyclosporin A administration group in the rats.

Experimental Intervention to Reverse Inhibition of Nitric Oxide Production by Cyclosporin A in Rat Aortic Smooth Muscle Cells (혈관평활근세포에서 Cyclosporin A에 의한 Nitric Oxide 생성억제를 길항하는 실험적 중재법)

  • Kim, In-Kyeom
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.211-219
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    • 1996
  • The inhibitory effect of cyclosporin A (CsA) on nitric oxide production is not related to the immunosuppressive action of the drug, but to the renal toxicity and arterial hyper-tension. In this study the experimental interventions to reverse the inhibition of nitric oxide production by cyclosporin A in rat aortic smooth muscle cells were examined. CsA inhibited the accumulation of nitrite, the stable end product of nitric oxide, in culture media in a concentration $(0.1{\sim}100{\mu}g/ml)-dependent$ manner. The inhibitory effect of CsA on nitrite accumulation were not antagonized by arginine (10 mM), a substrate of nitric oxide synthase, nor by calcium ionophore A23187 $(7{\mu}M)$. Forskolin, an activator of adenylate cyclase, which enhanced iNOS induction at transcriptional level, completely reversed the inhibitory action of CsA on nitrite accumulation. However, PMA (2 nM) and PDB (50 nM), PKC activators, increased the inhibitory action of CsA on nitrite accumulalion. From these results, it is suggested that cyclic AMP-elevating agents may be candidates of therapeutic agents in prevention and treatment of renal toxicity and arterial hypertension induced by CsA. Among conventional antihypertensive drugs, calcium channel blockers and ${\alpha}-blockers$ are preferred to ${\beta}-blockers$.

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GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY (cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상)

  • Kim, Yong-Kwan;Lee, Jae-Hoon;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.202-212
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    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.

A Case Report on the Treatment of Cyclosporin-A Induced Gingival Enlargement in Renal Transplant Patient (신장이식 환자에 있어서 Cyclosporin-A에 의한 치은비대의 치험례)

  • 장성용
    • Journal of Oral Medicine and Pain
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    • v.23 no.2
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    • pp.119-125
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    • 1998
  • The authors treated a 58-year old female patient who had come to the Department of Oral Medicine, KNUH due to the chief complaints of gingival enlargement and bleeding on the upper and lower jaw. The lesions were diagnosed as cyclosporin-A induced gingival enlargement by patient's history and clinical examination. The patient was treated with gingivectomy using pulsed Nd:YAG laser. After gingivectomy the wound was compressed with 0.1% chlorhexidine-soaked gauze to prevent relapse of the lesion. Good healing process was observed and there were no recurrences until 3-month follow-up visit. From the results of this clinical trial it was suggested that a pulsed Nd:YAG laser gingivectomy would be helpful for the treatment of cyclosporin-A induced gingival enlargement in renal transplant patients.

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Potentiometric performances of polymer membrane electrode based on cyclosporin (싸이크로스포린을 이용한 고분자막 전위차 전극)

  • Rhee Paeng, Insook
    • Analytical Science and Technology
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    • v.18 no.6
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    • pp.491-494
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    • 2005
  • The main component governing selectivity in ion-selective electrodes and optodes is the ionophore. For this reason, a member of natural products that possess selective ion-binding properties have long been sought after. By applying this principle, the performance of cyclosporin used as neutral carriers for calcium selective polymeric membrane electrode was investigated. The calcium ion-selective electrode based on cyclosporin gave a good Nernstian response of 26.6 mV per decade for calcium ion in the activity range $1{\times}10^{-6}M$ to $1{\times}10^{-2}M$. The optimized calcium ion-selective electrode displayed very comparable selectivity for $Ca^{2+}$ ion against alkali and alkaline earth metal ions, $Na^{2+}$, and $Mg^{2+}$ in particular.

Acute Leukoencephalopathy During Cyclosporin A Therapy in a Pediatric Patient with Nephrotic Syndrome (신 증후군 환아에서 Cyclosporin A 치료 중 발생한 급성 백색질 뇌증 1례)

  • Jung Suk-Won;Rhee Kyung-Hwa;Kwon Young-Se;Kim, Soon-Ki;Son Byong-Kwan;Lee Ji-Eun
    • Childhood Kidney Diseases
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    • v.9 no.1
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    • pp.91-96
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    • 2005
  • Cyclosporin A-induced central neurotoxicity has been rarely reported in patients with nephrotic syndrome. We report a pediatric patient who developed acute leukoencephalopathy diagnosed by MRI during CsA therapy for nephrotic syndrome.

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Neuroprotective Effect of Cyclosporin A on Spinal Cord Ischemic Injury in Rabbits (토끼를 이용한 척수 허혈 손상 모델에서 Cyclosporin A의 척수 손상에 대한 보호 효과)

  • Shin Yoon-Cheol;Choe Ghee-Young;Kim Won-Gon
    • Journal of Chest Surgery
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    • v.39 no.10 s.267
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    • pp.739-748
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    • 2006
  • Background: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses, Material and Method: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control 12 group (n=8), the control 17 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The 12 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the 17 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the End day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. Result: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 ($2.75{\pm}0.89$) were significantly higher than those of group 17 ($1.25{\pm}1.39$) on the 7th day (p<0,05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 ($1,0{\pm}0.53$) was less than those of group 17 ($2.13{\pm}1.36$, p<0.05). TUNEL staing showed apoptosis of the specimen in group 12 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group. Conclusion: We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spiral cord in the rabbit.

Targeted Gene Disruption and Functional Complementation of Cytochrome P450 Hydroyxlase Involved in Cyclosporin A Hydroxylation in Sebekia benihana

  • Lee, Mi-Jin;Han, Kyu-Boem;Kim, Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.21 no.1
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    • pp.14-19
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    • 2011
  • A cyclic undecapeptide-family natural product, cyclosporin A (CyA), which is one of the most valuable immunosuppressive drugs, is produced nonribosomally by a multifunctional cyclosporin synthetase enzyme complex in a filamentous fungal strain named Tolypocladium niveum. Previously, structural modifications of cyclosporins such as a regionspecific hydroxylation at the $4^{th}$ N-methyl leucine in a rare actinomycetes called Sebekia benihana were reported to lead to dramatic changes in their bioactive spectra. However, the reason behind this change could not be determined since a system to genetically manipulate S. benihana has not yet been developed. To address this limitation, in this study, we utilized the most commonly practiced gene manipulation techniques including conjugation-based foreign gene transfer-and-expression as well as targeted gene disruption to genetically manipulate S. benihana. Using these optimized genetic manipulation systems, a putative cytochrome P450 hydroxylase (CYP) gene named CYP506, which is involved in CyA hydroxylation in S. benihana, was specifically disrupted and genetically complemented. The S. benihana${\Delta}$CYP506 exhibited a significantly reduced CyA hydroxylation yield as well as considerable yield restoration by functional complementation of the S. benihana CYP506 gene, suggesting that the genetically manipulated S. benihana CYP mutant strains may serve as a more efficient bioconversion host for various valuable metabolites including CyA.