• Journal of Periodontal and Implant Science
• /
• 제24권2호
• /
• pp.238-254
• /
• 1994

Cyclosporine A is an immunosuppressant commonly used for patients receiving organ transplants. Gingival overgrowth is an adverse side-effect seen in about 8-26% of patients taking cyclosporine A which have been shown to increase the DNA synthesis of gingival fibroblast at the concentration of $10^{-9}g/ml$ in vitro. Glycyrrhetinic acid is the active pharmacological ingredients of licorice which exerts steroid-like action and anti-viral activity. Oleanolic acid, which were isolated from Glechoma hederacea, has been shown to act as inhibitors of tumor promotion in vivo and to be less cytotoxic retinoic acid. This study has been performed to evaluate the effects of glycyrrhetinic acid and oleanolic acid on cyclosporine A induced cell activity in vitro. Human gingival fibroblasts were isolated from explant cultures of healthy gingiva of orthodontic patients. Gingival fibroblasts were trypsinized and transferred to the walls of microtest plates. Fibroblasts were cultured in growth medium added $10^{-9}g/ml$ cyclosporineA and $50{\mu}l/ml$ lipopolysaccharides. Cells between the 4th and 6th transfer in culture were used for this study. The morphology of gingival fibroblst were examined by inverted microscope. The effects of cyclosporine A on the time course of DNA sythesis by human gingival fibroblasts were assessed by $[^3H]-thymidine$ uptake assays. Cyclosporine A was found to stimulate DNA synthesis of human gingival fibroblast at a concentration of $10^{-9}g/ml$. In the presence of lipopolysaccharide derived from Fusobacterium nucleatum, addition of cyclosporine A results in reversal of inhibition at the concentration which normally inhibits gingival fibroblast proliferation. The cell acitivities in the presence of glycyrrhetinic acid and oleanolic acid were decreased, and increased cell acitivities by cyclosporine A were decreased by glycyrrhetinic acid and oleanolic acid at the concentration of $200{\mu}g/ml$. These results suggested that the increased cell activities by cyclosporine A modulated by glycyrrhetinic acid and oleanolic acid.

• Journal of Korean Biological Nursing Science
• /
• 제18권1호
• /
• pp.17-26
• /
• 2016

Purpose: Adherence to immunosuppressants is the key to prevent organ rejection in organ transplant recipients. The purpose of this study was to investigate current interventions to improve adherence to immunosuppressants in liver transplant recipients. Methods: A systemic literature search was done using PubMed, Embase, Cochrane Library, CINAHL and four Korean databases to identify experimental studies reported in English or Korean up to and including 2015. We identified eight intervention studies on the adherence to immunosuppressants in liver transplant recipients independently reviewed by two reviewers. The quality and risk of bias of the selected studies were assessed. Results: Education, conversion of regimen, and text messaging were identified as intervention techniques to improve adherence. We found positive results in three out of four studies implementing educational strategies, but the results were not sufficient to draw a definite conclusion. Conversion from a twice-daily tacrolimus-based regimen to a once-daily tacrolimus extended-release formula was used in three adult-only studies and its effectiveness was confirmed. One study showed that improved adherence and outcomes were effected by using text messaging with pediatric patients. Conclusion: Future research is needed to facilitate interventions to improve adherence to immunosuppressants in various ages of patients including pediatric/adolescent liver transplant recipients.

• Biomolecules & Therapeutics
• /
• 제13권2호
• /
• pp.65-77
• /
• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• 대한한방내과학회지
• /
• 제41권5호
• /
• pp.787-799
• /
• 2020

Objectives: Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder with unknown etiology. Studies on adults have not been conducted yet in Korean medicine. We report the progress of Korean medicine treatment for adult-type pityriasis rubra pilaris. Methods: A 62-year-old female patient was diagnosed with PRP in June 2019. After the diagnosis of PRP, retinoid treatment was continued for about 6 months, and then the drug was switched to an oral immunosuppressant. However, the patient's symptoms did not improve, but instead worsened. The patient was treated with Mihudeungsikjang-tang and acupuncture therapy. We evaluated her treatment progress based on the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS), and the changes in the patient's subjective symptoms. Results: After Korean medicine treatment, the DLQI and VAS scores improved from 18 points to 16 points and from 6 points to 4 points, respectively. The whole-body itching and scaling were reduced by 30% compared to pretreatment. The itching and pain in the neck, which had been severely symptomatic, decreased by 50%. The pain and dysesthesia in the upper and lower extremities disappeared, but the erythema still remained. Conclusions: Conventional treatments for PRP have limitations due to adverse effects and difficulty in treating refractory forms. Korean medicine treatment is worth considering as it can complement the limitations of conventional treatments, although more studies will be needed.

• 한국미생물·생명공학회지
• /
• 제35권1호
• /
• pp.26-29
• /
• 2007

Tautomycetin(TMC)은 국내 토양에서 분리된 방선균(Streptomyces sp. CK4412)로부터 생합성 되는 항진균성 2차 대사산물로서, Cyclosporin및 FK506과 같은 기존의 면역억제제보다 작용 메카니즘 및 효능이 훨씬 탁월한 선형의 폴리케타이드계 면역억제 화합물이다. 고체배지의 pH변화와 TMC생산성과의 상관관계를 규명하기 위하여, 방선균 CK4412를 다양한 pH조건에서 배양하면서 항진균 활성 및 TMC생산량을 비교분석 하였다. 고체배지의 pH를 산성조건(pH 4-5)으로 유지하여 방선균 CK4412 균주를 배양할 경우, 중성 pH 조건에서 배양한 경우보다 훨씬 탁월한 항진균 활성 및 TMC생산성이 관찰되었다. 본 연구결과는 대표적인 방선균 S. coelicolor에서 입증된 pH-shock게 의한 2차대사산물의 생산성 증대효과가 대사산물의 특성과 균주가 전혀 다른 TMC 생산균주 CK4412에서도 관찰됨을 입증함으로써, pH조절에 의한 다양한 종류의 방선균 유래 유용 생리활성물질의 생산성 증대 전략을 제시하고 있다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제9권6호
• /
• pp.353-361
• /
• 2005

The interaction of cyclosporine A (CsA), an immunosuppressant, with rat brain Kv1.5 (Kv1.5) channels, which were stably expressed in Chinese hamster ovary cells, was investigated using the whole-cell patch-clamp technique. CsA reversibly blocked Kv1.5 currents at +50 mV in a reversible concentrationdependent manner with an apparent $IC_{50}$ of 1.0μM. Other calcineurin inhibitors (cypermethrin, autoinhibitory peptide) had no effect on Kv1.5 and did not prevent the inhibitory effect of CsA. Fast application of CsA led to a rapid and reversible block of Kv1.5, and the onset time constants of the CsA-induced block were decreased in a concentration-dependent manner. The CsA-induced block of Kv1.5 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the block exhibited voltage independence over the voltage range in which channels were fully activated. The rate constants for association and dissociation of CsA were $7.0{\mu}M{-1}s^{-1}$ and $8.1s^{-1}$, respectively. CsA slowed the deactivation time course, resulting in a tail crossover phenomenon. Block of Kv1.5 by CsA was use-dependent. CsA also blocked Kv1.3 currents at +50 mV in a reversible concentration-dependent manner with an apparent $IC_{50}$ of $1.1{\mu}M$. The same effects of CsA on Kv1.3 were also observed in excised inside-out patches when applied to the internal surface of the membrane. The present results suggest that CsA acts directly on Kv1.5 currents as an open-channel blocker, independently of the effects of CsA on calcineurin activity.

• 생명과학회지
• /
• 제25권1호
• /
• pp.29-36
• /
• 2015

천연의 붉은 색소인 prodigiosin은 Serratia marcescens에 의해서 생산되며 이는 pyrrolylpyrromethane 골격으로 구성되어 있다. 이 색소는 그 분자가 가진 특성 때문에 넓은 범위에서 활용되고 있다. 또한 항암제, 면역억제제, 항진균제, 살조제 등 다양한 분야의 효과가 보고되소 있다. Methicillin-resistant Staphylococcus aureus (MRSA)는 세계적으로 가장 주요한 원내 감염균으로써, 미국에서 해마다 HIV로 사망하는 수보다 더 많은 사망률을 보이고 있다. 그러므로 MRSA에 대한 새로운 치료제의 개발이 매우 중요하며 급박한 문제이다. 본 연구에서는 중증오염도를 가진 하천수로부터 Serratia sp. PDGS 120915를 분리하였으며 항 MRSA 활성을 가진 prodigiosin에 대하여 연구하였다. 본 연구를 위하여 HPLC를 이용하여 물질을 정제하였으며, 분리된 물질의 항 MRSA 활성을 확인하였다. Prodigiosin의 MRSA에 대한 최소억제농도(Minimal inhibitory concentration; MIC)는 $32{\mu}g/ml$이었으며, 분할저해농도(Fractional inhibitory concentration; FIC)는 ampicillin과 penicillin에서 상승작용이 있는 것으로 나타났다.

• 농약과학회지
• /
• 제18권3호
• /
• pp.181-190
• /
• 2014

곤충병원세균인 Bacillus thuringiensis (비티)는 포자 형성과 더불어 살충성 Cry 독소단백질을 생산한다. Cry 독소단백질은 대상 곤충의 중장에 위치한 수용체와 특이적으로 결합하며 살충작용을 발휘하기에 비티의 적용해 충범위가 비교적 좁다. 본 연구는 비티의 적용해충범위와 살충력을 증가시키기 위한 일환으로 실시되었다. 서로 다른 네 가지 비티 균주에서 분리된 Cry 독소단백질은 각각 좁은 적용해충범위를 나타냈다. 이들 Cry 독소단백질을 혼합한 결과 적용범위가 현격하게 증가했다. 벡큘로바이러스가 비티의 적용범위를 증가시키는 지 알아보기 위해 Cry1Ac 또는 Cry1Ca 독소단백질을 각각 발현시키는 재조합바이러스로 검정한 결과 벡큘로바이러스는 Cry 독소단백질의 적용범위를 증가시키는 데 유효하지 않았다. Xenorhabdus nematophila (Xn) 세균 배양액은 조사된 모든 곤충의 세포성 면역을 억제하고 Cry 독소단백질의 살충력을 증가시켰다. 이 Xn 세균배양액을 혼합 Cry 독소단백질에 추가한 결과 적용해충범위와 살충력을 모두 증가시켰다.

• Journal of Microbiology and Biotechnology
• /
• 제26권2호
• /
• pp.233-240
• /
• 2016

FK506, a widely used immunosuppressant, is a 23-membered polyketide macrolide that is produced by several Streptomyces species. FK506 high-yielding strain Streptomyces sp. RM7011 was developed from the discovered Streptomyces sp. KCCM 11116P by random mutagenesis in our previous study. The results of transcript expression analysis showed that the transcription levels of tcsA, B, C, and D were increased in Streptomyces sp. RM7011 by 2.1-, 3.1-, 3.3-, and 4.1-fold, respectively, compared with Streptomyces sp. KCCM 11116P. The overexpression of tcsABCD g enes in Streptomyces sp. RM7011 gave rise to approximately 2.5-fold (238.1 μg/ml) increase in the level of FK506 production compared with that of Streptomyces sp. RM7011. When vinyl pentanoate was added into the culture broth of Streptomyces sp. RM7011, the level of FK506 production was approximately 2.2-fold (207.7 μg/ml) higher than that of the unsupplemented fermentation. Furthermore, supplementing the culture broth of Streptomyces sp. RM7011 expressing tcsABCD genes with vinyl pentanoate resulted in an additional 1.7-fold improvement in the FK506 titer (498.1 μg/ml) compared with that observed under non-supplemented condition. Overall, the level of FK506 production was increased approximately 5.2-fold by engineering the supply of allylmalonyl-CoA in the high-yielding strain Streptomyces sp. RM7011, using a combination of overexpressing tcsABCD genes and adding vinyl pentanoate, as compared with Streptomyces sp. RM7011 (95.3 μg/ml). Moreover, among the three precursors analyzed, pentanoate was the most effective precursor, supporting the highest titer of FK506 in the FK506 high-yielding strain Streptomyces sp. RM7011.

• Childhood Kidney Diseases
• /
• 제9권1호
• /
• pp.83-90
• /
• 2005

Focal segmental glomerulosclerosis(FSGS) has been detected in approximately 10% of cases of Idiopathic nephrotic syndrome in children, and exhibits a poor response to initial steroid therapy, as well as a higher rate of progression to chronic renal failure and relapse after kidney transplantation. We describe a case of an eleven year-old boy with steroid-resistant FSGS who exhibited a response to a second trial of cyclosporin h(CsA) therapy. At the age of 26 months, this patient was diagnosed with steroid-resistant FSGS. For 9 years, he had undergone a gauntlet of therapies to induce remission; oral steroids, cyclophosphamide, methylprednisolone(mehyIPd) pulse therapy, CsA, and ibuprofen therapy. Although these therapies failed to induce remission, the patient's renal function remained In the normal range during the nine years of treatment. At the age of ten years, the patient's proteinuria decreased, and complete remission was attained with a second administration of CsA, coupled with a low dose of oral steroids. This patient continues to receive CsA without relapse. Therefore, our major concern involves the possibility of relapse after the discontinuation of CsA therapy Our findings in this case suggest that, in cases of refractory FSGS, if renal insufficiency does not emerge, aggressive therapy for the amelioration of proteinuria should be continuously pursued.