• Biomolecules & Therapeutics
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• 제6권4호
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• pp.389-394
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• 1998

Cyclosporine (CsA) is a major immunosuppressive drug used widely to prevent organ allograft rejection. fits potential organotoxicity by prolonged use is known to cause both direct tissue damage and indirect pharmacokinetic interactions with other drugs. This study was performed to determine the effect of nicardipine (NCP) on the pharmacokinetic parameters of CsA in Sprague-Dawley rats. Each rat was administered with CsA in saline-treated group or in NCP-treated group which was pretreated with NCP (5 mg/kg/12 hours, i.p.) for 6 days. The plasma CsA concentration were analyzed by reversed HPLC: UV system at 0.5, 1, 2, 4, 6, and 8 hours after bolus injection of CsA (10 mg/kg). Pharmacokinetic parameters (mean$\pm$ SD, n=7) such as initial plasma concentration (C(0)), mean residence time (MRT), steady-state volume of distribution (Vdss), terminal half-life (t$\frac{1}{2}$($\beta$)) and plasma clearance (CLp) of CsA in each groups (saline-group vs NCP-group) were determined as follows: C(0) (5.66$\pm$ 1.98 vs 17.98$\pm$2.36, p<0.01); Vdss (2.68$\pm$ 1.6 vs 0.94 $\pm$ 0.25, p<0.01); CLp (0.53 $\pm$0.18 vs 0.21 $\pm$0.06, p<0.01). Therefore, Our results indicate that nicardipine significantly affects the pharmacokinetic parameters of cyclosporme, especially C(0), Vdss, and CLp in NCP-treated group. We suggest that the significant pharmacokinetic interaction between cyclosporine and nicardipine should be considered and cyclosporine level should be closely monitored and dosage reduction made as necessary in clinical situation that was coadministered with CsA and NCP.

• 한국임상수의학회지
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• 제33권6호
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• pp.392-394
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• 2016

A 2-year-old spayed female Persian cat presented to Kangwon National University Veterinary Medical Teaching Hospital with pruritus and erythema on the tips of both ears, around the eyes, and in the caudal abdomen. This patient had previously been prescribed prednisolone, but did not respond positively to the treatment. A skin screening test revealed that there were no fleas or fungi, and that only cocci were present. Blood testing revealed no remarkable findings. The patient was prescribed antibiotics (amoxicillin-clavulanic acid 25 mg/kg for 2 weeks) with no prednisolone. After 2 weeks, clinical signs were alleviated and the skin screening test showed no signs of cocci. However, clinical signs recurred even with the prescription of antibiotics. Four weeks after the steroid-free interval, Malassezia spp. hypersensitivity was detected upon a serum allergy test, and pathological analysis confirmed eosinophilic and mastocytic superficial dermatitis in the caudal abdomen. Based on these results, we suspected allergic dermatitis and prescribed 7 mg/kg cyclosporine A once a day. After 3 weeks, clinical signs were resolved. Seven weeks after the first trial with cyclosporine A, we reduced the cyclosporine A dose to 7 mg/kg every other day. The patient's symptoms have since been well controlled for 6 months. This study suggests that cyclosporine A can be a good choice for treating cats with suspected allergic dermatitis that has not responded positively to steroid treatment.

• 대한피부과학회지
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• 제56권10호
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• pp.658-659
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• 2018

• Biomolecules & Therapeutics
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• 제7권4호
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• pp.342-346
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• 1999

This study was performed to investigate the effect of cyclosporine (CsA) on glucose tolerance and peripheral insulin sensitivity in normal Sprague-Dawley rats. After daily treament of CsA (10 mg/kg, i.p.) for two weeks, glucose tolerance tests were carried out by the treatment of glucose (Glu, 2 g/kg, i.p.) alone or in conjunction with exogenous insulin (Ins; human regular insulin, 5 U/kg, s.c.) and measured the decrement of area under the time-plasma glucose concentration curve ($AUC_{o\longrightarrow120}$; g.min/ml) by the trapezoidal rule. The rats were divided into three groups (Glu- (Control), Ins+Glu- and CsA+Ins+Glu-, n=7 in each group). The $AUC_{o\longrightarrow120}$ of the CsA+Ins+Glu-group was significantly (p<0.01) lower than that of Glu-group (61.0% of control) and significantly (p<0.05) higher than that of Ins+Glu-group (197.4% of Ins+Glu-). The CsA+Ins+Glu- grou showed higher levels of maximal blood glucose concentration and higher $AUC_{o\longrightarrow120}$ than those of Ins+Glu-group in normal rats. Besides direct pancreatic toxicity of CsA previously reported (Hahn et al., 1972), these results suggest that CsA also make the possibility to induce peripheral insulin insensitivity and glucose intolerance in normal rats.

• BMB Reports
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• 제45권8호
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• pp.482-487
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• 2012

To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3,280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at $4{\sigma}$ standard score). However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress.

• Childhood Kidney Diseases
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• 제21권2호
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• pp.160-164
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• 2017

C3 glomerulopathy (C3G) is a recently defined pathological entity characterized by C3 accumulation with absent or scant immunoglobulin deposition, leading to variable glomerular inflammation. The clinical presentation of patients with C3G is highly variable, as they may present with symptoms ranging from microscopic or mild proteinuria to full-blown nephrotic syndrome, with or without renal impairment. However, there is no consensus recommendation for specific treatment in children with C3G. Recently, new therapies have been suggested to target complement pathways, owing to an improvement in the understanding of the pathogenesis of C3G. C3G complement blockade with eculizumab, a monoclonal antibody targeted against complement C5, inhibits activation of the alternative complement pathway. We could not use eculizumab owing to its high price; thus, we administered oral prednisolone and mycophenolate mofetil (MMF). MMF was replaced with cyclosporine because proteinuria persisted, with a consistently low serum C3 level; we tapered off the prednisolone because of a Cushingoid appearance and amenorrhea. Thereafter, proteinuria improved, and the serum C3 level returned to normal. Thus, we report the effectiveness of cyclosporine in a patient with C3G and an inadequate response to prednisolone and MMF, who was detected via school urinary screening.

• Tuberculosis and Respiratory Diseases
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• 제59권3호
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• pp.315-320
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• 2005

폐쇄성세기관지염기질화폐렴은 스테로이드에 반응을 매우 잘하는 질환으로 알려져 있지만, 본 두 증례에서는 충분한 용량의 스테로이드에 반응을 보이지 않고 이차적 약제인 cyclosporine에 의해 임상적, 방사선학적 호전을 보여 문헌 고찰과 함께 보고하는 바이다.

• Childhood Kidney Diseases
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• 제11권1호
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• pp.92-99
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• 2007

후두엽 가역성 뇌병증 증후군은 고혈압, 자간증, 신부전으로 인한 고혈압 및 면역억제약물 등 의 병력과 함께 두통, 구토, 경련, 시야장애 등 임상적 증상을 보이고 뇌 자기공명영상에서 특징적인 소견을 보이는 질환군이다. 저자들은 스테로이드 저항성 신증후군 환아에서 사이클로스포린 투여 중 발생한 후두엽 가역성 뇌병증 증후군을 경험하였기에 보고하는 바이다.

• 대한핵의학회지
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• 제23권2호
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• pp.225-230
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• 1989

According to the development of monoclonal antibodies against cyclosporine, it became available to replace the conventional polyclonal antibody method with new monoclonal antibody method to measure the blood level of cyclosporine by radioimmunoassay. We compared the results obtained by the two methods: polyclonal antibody and monoclonal antibody method. The results were obtained as follows: 1) We obtained mean value 137.3 ng/ml and CV 16.1% from plasma sample, and mean values 495.7 ng/ml and 1053.8 ng/ml and CVs 19.3% and 17.4% respectively from whole blood sample by polyclonal antibody method. 2) For the two control groups, 100 ng/ml 400 ng/ml each, we obtained that the CVs were 20.2% and 14.0% respectively from plasma sample, and 11 9% and 13.1% respectively from whole blood sample by monoclonal antibody method. In conclusion, we found that cyclosporine RIA was a relatively reliable method to measure blood or plasma concentration. Especially RIA using monocloanl antibody showed less degree of error in measurement compared to polyclonal antibody method.

• Childhood Kidney Diseases
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• 제2권2호
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• pp.138-144
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• 1998

목 적 : 면역억제제로 사용되는 cyclosporine과 항암제로 사용되는 mitomycin의 신장에 미치는 직접적인 독성여부를 확인하고 이들 약제의 사용으로 초래되는 신장병변의 발생기전을 알아보고자 본 연구를 시행하였다. 대상 및 방법 : 실험동물은 체중 250-300gm의 Sprague-Dawley계 흰쥐를 암수 구별없이 사용하였으며 약물 투여는 Hoyer등이 기술한 방법을 다소 변형한 일측성 신관류 방법을 사용하여 좌측 신장을 대동맥과 대정맥의 혈류로부터 차단하고 좌측 신동맥을 통하여 좌측신을 관류시켰다. Cyclosporine은 4 mL에 2.5 mg, mitomycin은 4 mL에 1.6mg의 농도로 하였고 대조군은 생리적 식염수를 .사용하였으며 혈관 clamping으로부터 감자제거까지 소요된 총 ischemic time은 15분을 초과하지 않았다. 약제 투여후 48시간에 실험 동물을 도살하고 좌측 신장을 적출하여 광학 및 전자 현미경 검사를 시행하였다. 결 과 : Cyclosporine투여군에서는 사구체 내피세포 및 상피세포의 심한 종창이 있었으며 간질내 모세혈관의 내피세포도 심한 종창을 보였다. Mitomycin투여군에서는 사구체 내피세포 및 상피세포의 심한 종창을 보였으며 일부의 모세 혈관에는 혈소판의 응집, 종창 및 탈과립 현상과 섬유소 물질도 포함된 혈전성 미세혈관 병변의 소견을 보였다. 결 론 : Cyclosporine과 mitomycin은 신장 내피세포에 직접적인 손상을 초래하며 그러므로 이들 약제 사용으로 인한 혈전성 미세혈관 병변 (용혈성 요독증)의 발생 기전에는 이들 약제의 신장 내피세포에의 직접적인 손상이 중요한 시발점이 되는 것으로 생각된다.($41.4\%$)이 신초음파에서 이상소견을 보였다. 방광요관역류가 있었던 32명(53역류신장)은 역류정도에따라 Grade $I:25.0\%,\;II:44.5\%,\;III:64.3\%,;IV:92.9\%,\;V:100\%$에서 초기 DMSA 신주사상 이상소견을 보였다. 53역류신장중 전체적으로 DMSA신주사에서 36신장($68.0\%$), 신초음파에서 26신장($49.1\%$)이 이상소견을 보여 유의한 차이를 보였으며(P<0.05). 특히 Grade IV 역류신장에서 유의한 차이가 있었다(P<0.05). 결 론 : DMSA신주사를 이용한 급성신우신염의 진단은 신초음파검사 보다 유용하며, 초기 DMSA신주사 소견상 이상소견을 보인 경우 약 8-12주 후 추적검사를 시행하여 변화를 관찰하고 섭취결손 부분이 남아있는 경우에는 향후 새로운 병소의 출현 혹은 정상화 여부를 보기 위한 추적검사가 필요하리라 사료된다. 방광요관역류 환아에서 DMSA신주사소견은 방광요관역류의 정도가 심할수록 이상소견을 보일 확률이 높으며 신초음파 검사보다 민감도가 높은 것을 알 수 있었다.이는 혈압을 조절시키지 못하였고 저단백식이 항고혈압제투여군은 저단백식이 단독투여군보다 혈압조절 및 단백뇨의 감소 소견은 유의한 차이를 보였으나, mesangial matrix expansion score,대상성 사구체비대는 통계적으로 유의한 차이를 보이지 않았다. 그러므로 만성신부전의 진행을 지연시키는데 있어서 저단백식이와 함께 항고혈압제를 추가하였을 때 항고혈압제에 의한 추가적인 지연 효과는 관찰되지 않았다.학생이 남학생보다 높고, 물리치료과를 타의로