• 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 ${\beta}-blockers$.

• Journal of Microbiology and Biotechnology
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• v.18 no.5
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• pp.913-917
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• 2008

The cyclic undecapeptide, cyclosporin A (CyA), is one of the most commonly prescribed immunosuppressive drugs. It is generated nonribosomally from a multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus Tolypocladium niveum. In order to maximize the production of CyA by wild-type T. niveum (ATCC 34921), each of three culture stages (sporulation culture, growth culture, and production culture) were sequentially optimized. Among the three potential sporulation media, the SSMA medium generated the highest numbers of T. niveum spores. The SSM and SM media were then selected as the optimal growth and production culture media, respectively. The addition of valine and fructose to the SM production medium was also determined to be crucial for CyA biosynthesis. In this optimized three-stage culture system, 3% of the spore inoculum generated the highest level of CyA productivity in a 15-day T. niveum production culture, thereby implying that the determination of an appropriate size of T. niveum spore inoculum plays a critical role in the maximization of CyA production.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.10-21
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• 2010

The overall prognosis of Henoch-Schoenlein purpura (HSP) is favorable, but severe nephritis has a high risk of progression to end stage renal failure. Recent studies emphasize the importance of early treatment in children with severe HSP nephritis, but the treatment of severe HSP nephritis still remains controversial due to the rarity of randomized controlled studies in this field. Nevertheless, several intensive therapies, such as intravenous high-dose methylprednisolone pulse, immunosuppressive/cytotoxic drugs, fibrinolytic therapy, anticoagulants, antiplatelet agent and plasma exchange, have been used in children with severe HSP nephritis. In this review, we focus on the treatment of severe HSP nephritis in children.

• Journal of Veterinary Clinics
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• v.36 no.6
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• pp.345-348
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• 2019

A four-year old, indoor-living neutered male Old English Bulldog was presented for generalized ulcerative dermatitis. Generalized alopecia and multifocal papules and ulcers with crusting were observed mainly in the dorsal trunk. Cytology of the skin lesions revealed a pyogranulomatous inflammation comprising macrophages and nondegenerate neutrophils. Histopathology also revealed a nodular dermatitis characterized by mixed infiltration of monocytes and neutrophils involving the superficial and deep dermis. Neither of bacteria nor fungus was identified in microscopic exam and culture. From those findings, a diagnosis of cutaneous sterile pyogranuloma/granuloma syndrome (SPGS) was made. Treatment with immunosuppressive drugs of prednisone and cyclosporine was performed and visible ulcerative skin lesions were resolved after 4 weeks of initiation of therapy. Treatment with combination of cyclosporine and prednisone may be effective for the case of SPGS.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.10.1-10.17
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• 2022

Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

• Natural Product Sciences
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• v.13 no.1
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• pp.33-39
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• 2007

Eleven polyhydroxyursane triterpenoids (PHUTs) were tested to determine their cytoprotective, immunosuppressive and anti-inflammatory effects. To compare the bioactivities of $19{\alpha}$-hydroxyursane-type triterpenoids {23-hydroxytormentic acid (6), its methyl ester (7), tormentic acid (8), niga-ichigoside $F_1$ (9),euscaphic acid (10) and kaji-ichigoside $F_1$ (11)} of the Rosaceae crude drugs (Rubi Fructus and Rosa rugosae Radix) with PHUTs possessing no $19{\alpha}-hydroxyl$ of Centella asiatica (Umbelliferae), the four PHUTs, asiaticoside (1), madecassoside (2), asiatic acid (3), and madecassic acid (4) were isolated from C. asiatica and 23-hydroxyursolic acid (5) from Cussonia bancoensis. Cytoprotective effects were assessed by measuring cell viabilities against cisplatin-induced cytotoxocity in $LLC-PK_1$, cells (proximal tubule, pig kidney) to determine whether these agents have protective effects against nephrotoxicity caused by cisplatin. The inhibitory effect of 11 PHUTS on nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ were evaluated by measuring nitrite accumulation in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells, and their anti-inflammatory effects were tested in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. Six MHUTs (compounds 1, 2, 4, 6, 10, and 11) exhibited higher cell viabilities during cisplatin-induced cytotoxicity testing even at a concentration of $200\;{\mu}g/ml$ than cisplatin only-treated group, suggesting that ese compounds have the potentcytoprotective efffcts. Compounds 1 and 3 of the C. asiatica and niga-ichigoside $F_1$ exhibited no inhibitory effect on NO and/or $PGE_2$ production whereas other PHUTs produced mild to significant NO and/or $PGE_2$ production.The four compounds (2, 5, 9, and 10) potently inhibited mouse ear edema induced by TPA whereas two compounds (1 and 3) had no activity in this test. These results suggest that many PHUTs are potentchemopreventives. Structure-activity relationship (SAR) was also discussed in each assay with regard to the significant role of OHs at the position of 2, 3, 6, 19, and 23 and to the glycoside linkage at the 28-carboxyl.

• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.105-110
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• 1988

To establish a laboratory animal model for study on development of diagnostic methods for infectious bovine rhinotracheitis virus(IBRV), experimental infection of the virus to rabbits immunosuppressed with dexamethasone(DX) were carried out. Results obtained throughout the experiments were as follows. When lymphocyte activity was measured by lymphocyte transformation to phytohaemagglutinin in parallel with total and differential leucocyte counting, both groups treated with 2.0mg DX once and 1.0mg DX daily showed marked immunosuppression between 5 to 72 hrs. after administration. The degree of suppression of lymphocyte activities was more remarkable in the latter group. IBRV PQ7 strain at $10^{7.5}\;TCID_{50}/0.2ml$ was inoculated into conjunctival sacs of rabbits immunosuppressed with DX and non-treated. During 3 weeks observation, the immunosuppressed groups revealed mild conjunctivitis, viremia and virus recovery by 33.3 to 100%, whereas the DX nontreated group showed viremia and virus recovery with no clinical conjunctivitis by one of three rabbits(33.3%). In conclusion, it was indicated that experimental infection of IBRV PQ7 strain to rabbit was limited in prerequisite to immunologic modification by administration of immunosuppressive drugs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.1
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• pp.69-73
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• 2004

Mucormycosis is an acute opportunistic infection caused by a saprophytic fungus found in soil, decaying fruits and vegetables. Numerous predisposing risk factors are associated with mucormycosis, although most cases have been reported in poorly controlled diabetics or in patients with hematologic malignant conditions. Throughout the history of mucormycosis, from the first case in humans reported in 1885 by Paltauf, through publication by Gregory et al of the first observation of rhino-orbital cerebral mucormycosis in 1943, to the report by Harris in 1955 of the first known survivor, little has changed in the diagnosis and outcome of this disease. Without treatment, the patient may die after an interval ranging from a few days to a few weeks. Regulation of diabetes mellitus and a decrease in the dose of immunosuppressive drugs facilitate the treatment of Mucormycosis. Extensive debridement of craniofacial lesions appears to be very important. intravenous amphotericin B is clearly of value. This is a case report of a patient with mucormycosis in maxilla. He was an uncontrolled DM patient, and for the treatment of intravenous amphotericin B and sequestrectomy were applied.

• Biomolecules & Therapeutics
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• v.6 no.4
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.571-579
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• 2010

The advancement of medical technology has made it possible to treat various incurable diseases. Especially organ transplantation can give another life to the patients who have organ failure and could not find any other ways to treat their diseases. According to the development of medical technology and immunosuppressive drugs, the rate and extent of organ transplantation is increasing these days. New medical technologies like organ transplantation brought on critical issues and these have changed the way of thinking and morals that has been the fundamental rules in our society. Bioethics is already an important field of medicine and oriental medicine should investigate the problem caused by the development of medical technology and life science and should form a view of life in oriental medicine. Oriental medicine is East Asian traditional medicine based on "Huangdi-Neijing", constructed by the system of Jangfu and meridian. The traditional therapies of oriental medicine have completed a scientific system on the point of view that looks on human and nature equally. This process continued to form a new medical theory as the environment was changed and the new diseases were appeared since "Huangdi-Neijing" and "Shoganron" showed a new scope to investigate human and diseases. Therefore, it is important to develop the point of view of oriental medicine as the medical situation was changed. Oriental medicine has a holistic view that considers human as a little cosmos resonated by a big cosmos and regards the possibility to recover and to regulate the energy in our body. This theory is a basic idea of oriental philosophy. Oriental medicine focuses on the balance of yin and yang of the body and tries to harmonize the imbalance of yin and yang caused by the life style and environment. This can solve many problems that cannot be settled by modern medicine and this can accomplish the new paradigm of oriental medicine that is needed these days.