• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1716-1722
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• 2018

Immunosuppressive drugs are used to make the body less likely to reject transplanted organs or to treat autoimmune diseases. In this study, five immunosuppressive drugs including two glucocorticoids (dexamethasone and prednisolone), one calcineurin inhibitor (cyclosporin A), one non-steroid anti-inflammatory drug (aspirin), and one antimetabolite (methotrexate) were tested for their effects on viral proliferation using feline foamy virus (FFV). The five drugs had different cytotoxic effects on the Crandell-Ress feline kidney (CRFK) cells, the natural host cell of FFV. Dexamethasone-pretreated CRFK cells were susceptible to FFV infection, but pretreatment with prednisolone, cyclosporin A, aspirin, and methotrexate showed obvious inhibitory effects on FFV proliferation, by reducing viral production to 29.8-83.8% of that of an untreated control. These results were supported by western blot, which detected viral Gag structural protein in the infected cell lysate. As our results showed a correlation between immunosuppressive drugs and susceptibility to viral infections, it is proposed that immune-compromised individuals who are using immune-suppressive drugs may be especially vulnerable to viral infection originated from pets.

• Journal of Oral Medicine and Pain
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• v.42 no.1
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• pp.20-24
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• 2017

Drug-induced gingival overgrowth (DIGO) is an adverse drug reaction mainly described with three types of commonly prescribed drugs, namely, calcium channel blockers (CCBs) (nifedipine, diltiazem, and verapamil), anti-convulsants (phenytoin), and immunosuppressive agents (cyclosporine). Numerous reports have associated gingival overgrowth with the newer generation of immunosuppressive agents (tacrolimus, sirolimus, and everolimus), and CCBs (amlodipine, felodipine, nicardipine, and manidipine). Especially, patients concomitantly medicated with an immunosuppressive agent and CCB have a higher DIGO chance. Dentists need to be aware of drugs that induce gingival overgrowth, the possibility of DIGO, and risk factors, and also prevent the progression of DIGO by early detection of DIGO, consultation about the drug change, and the maintenance of strict dental hygiene regimes.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.567-571
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• 2016

We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota.

• IMMUNE NETWORK
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• v.4 no.1
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• pp.1-6
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• 2004

Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.

• Molecules and Cells
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• v.22 no.1
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• pp.1-7
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• 2006

The NFAT family of transcription factors plays pivotal roles in the development and function of the immune system. Their activation process is tightly regulated by calcium-dependent phosphatase calcineurin and has been a target of the immunosuppressive drugs cyclosporin A and FK-506. Although the clinical use of these drugs has dramatically increased the success of organ transplantation, their therapeutic use is limited by severe side effects. Recent studies for the calcineurin/NFAT signaling pathway have identified a number of cellular proteins that inhibit calcineurin function. Specific peptide sequences that interfere with the interaction between calcineurin and NFAT have also been characterized. Moreover, diverse approaches to identify small organic molecules that modulate NFAT function have been performed. This review focuses on the recent advances in our understanding of the inhibitory modulation of NFAT function, which may open up the additional avenues for immunosuppressive therapy.

• Archives of Reconstructive Microsurgery
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• v.4 no.1
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• pp.9-15
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• 1995

Free vascularized composite tissue transfer is more frequently underwent for reconstruction of complicated tissue defects with the recent advance of microsurgery. But postoperative result was not satifactory because of donor site morbidity, flap bulkiness and cosmetic problem. So would no longer be a problem if we can obtain the exact donor tissue required for the recipient site as allotransplantation and designing the flap. Allotransplantation has been resolved with the recent development of immunosuppressive agents, while reconstruction has made great progress with the refinement of microsurgical techniques in the last 20 years. The final sucess or failure of the operative procedure in transplantation is so utterly dependent no the availability of strategies that can control the immune system effectively, selectively, safely to allow allotransplantation of a nonvital body part. 1 used 2 strains of rats, BUF and LEW, for the limb allotransplantation as a composite tissue transfer. The primary goal of this program is to improve results in clinical transplantation by accelerating the transformation of new immunological knowledge into useful medicine. Two of the most promising new immunosuppressive compounds are FK-t06(FK) and rapamycin(RPM). Both drugs are antibiotic macrolide fungal fermentation products that presumably suppress the immune system in ways similar to cyclosporin(CyA). This study shows that two new immunosuppressive drugs compare the immunosuppressive activity and effectiveness of FK-506 and RPM for prevention of the limb allograft rejection in the rat. Additional experiments investigate the dose, route of administration and histologic findings. These data demonstrates that rapamycin is far more potent and effective than FK-506 when both compounds are administered by the intraperitoneal route, as well as prolonged graft survival significantly in a dose-route dependent manner. These results lead to the view that vascularized allograft composite tissue transfer can become a reality with the expectation of possible future application in reconstructive surgery of humans.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.476-480
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• 2005

Immunosuppressive therapy in pediatric renal transplant recipients is changing consequence of the increasing number of available immunosuppressive agents. The optimal use of immunosuppressive agents requires a thorough understanding of the pharmacokinetic characteristics, but the information on the pharmacokinetic characteristics of these drugs in pediatric transplant recipients is still limited. In general, patients younger than 5 years old show higher clearance rates, therefore the need for higher dosages in younger patients seems evident. By the therapeutic drug monitoring, trough($C_{min}$) and peak level($C_{max}$) are measured and the area under the blood concentration-time curve(AUC), which is taken as being representative of total systemic exposure can be calculated. Cyclosporine A (CSA) has poor bioavailability, which contributes to high inter- and intra-patient pharmacokinetic variability. CSA concentration measured 2 hours after administration($C_2$) has better correlation with the AUC than $C_{min}$ and is an alternative technique that predicts the AUC. Tacrolimus(Tac) has a great deal of inter-individual variability like CSA but intra-individual variability in systemic exposure is considered to be low. Both CSA and Tac are metabolized by a cytochrome P-450 enzyme isoform(CYP3A4). We should consider changing the dosages when CSA or Tac is used in combination with the medicines that inhibit or induce the CYP3A4. In case of steroid-free immunosuppressive therapy, the blood concentration of Tac should be frequently checked and dosage adjustment may be needed.

• Journal of Haehwa Medicine
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• v.10 no.1
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• pp.29-46
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• 2001

In the result of investigating traditional chinese medical literatures to understand definite immunopharmacologic effects of drugs for clearing away heat and detoxicating such as Ampelopsis Radix, Rhapontici Radix, Cremastrae Appendiculatae Tuber, Rhaseoli Radiati Semen, Potentillae Discolohs Herba, Potentillae Chinensis Herba, Chrysanthemi Indici Flos, Lomcerae Caulis, we could reach conclusions as follows: 1. Rhapontici Radix, Chrysanthemi Indici Flos can increase voracity of leukocytes, macrophages and increase to produce IL-2 by splenocytes. 2. Potentillae Chinensis Herba, Chrysanthemi Indici Flos, Lonicerae Caulis can inhibit activities of B lymphocytes and have anti-inflammatory effects. 3. Drugs for clearing away heat and detoxicating almost have antibiotic, anti-inflammatory effects, and so can be applied to many inflammatory immune diseases. 4. Drugs for clearing away heat and detoxicating also have antifebrile, diuretic, detoxicating effects. Above results indicates that Drugs for clearing away heat and detoxicating have immunosuppressive effect, so that can be applied to many inflammatory immune diseases.

• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.65-77
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• 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.

• Journal of Periodontal and Implant Science
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• v.19 no.1
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• pp.129.1-129.1
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• 1989