• Korean Journal of Veterinary Service
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• v.47 no.2
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• pp.89-94
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• 2024

A 5-year-old spayed female mixed-breed dog, previously receiving 7 months of immunosuppressive therapy for pemphigus foliaceus, presented to our referral hospital with a history of dog bites on the right forelimb, chest, and flank 4 days prior to presentation. Physical examination revealed a rectal temperature of 38.6℃; heart rate of 130 beats per minute; panting; systolic blood pressure of 60 mmHg; and swelling, purulent discharge, warmth, pain, and lameness in the right forelimb. The laboratory investigation revealed neutropenia and elevated C-reactive protein levels. Suppurative neutrophilic infiltration with bacterial infection was detected by impression cytology of the pus on the right forelimb. Based on the results of the clinical examinations and laboratory tests, the dog was diagnosed with dog bite-induced sepsis with pemphigus. Meropenem and metronidazole were prescribed. Clinical signs, neutropenia, and C-reactive protein levels markedly improved after 5 days. Subsequently, pemphigus foliaceus relapsed in the dog, and it is currently undergoing re-administration of immunosuppressive medications. To the best of our knowledge, this is the first case report of successful management of dog bite-induced sepsis in a dog undergoing long-term immunosuppressive therapy.

• 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.

• Annals of Clinical Neurophysiology
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• v.9 no.2
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• pp.51-58
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• 2007

Autoimmune myasthenia gravis (MG) is the neuromuscular junction disorder mostly caused by antibody against the acetylcholine receptor (AChR antibody) at the muscle endplate. The goal of treatment is to induce and maintain remission, i.e., absence of symptoms, with the least cost-to-benefit ratio. Although corticosteroids are effective in inducing remission in most patients, they have numerous potentially serious adverse effects with their long-term use. In addition, some patients do not respond or are intolerant to the conventional treatment. In this article, we discuss the difficulties encountered in long-term immunosuppressive treatment of MG, and review useful tips for the use of corticosteroids. Long-term immunosuppressive agents that can be used in steroid-refractory or -dependent patients will be reviewed with their safety profiles and efficacy in MG.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.598-602
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• 2008

Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.

• Korean Journal of Transplantation
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• v.28 no.3
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• pp.121-134
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• 2014

Current immunosuppressants have nonspecific immuosuppressive effects, and are not helpful for tolerance induction. Consequently, transplant patients cannot discontinue using them, and their nonspecific immunosuppressive effects result in many side effects, including infection and malignancy. However, most of cellular immunotherapy can have donor antigen-specific immunsuppressive effects. Therefore, cell therapy could be an alternative or adjunctive to nonspecific immunosuppressants. Polyclonal or antigen-specific Foxp3+ regulatory T cells have been actively tried for prevention of acute rejection, treatment of chronic rejection, or tolerance induction in clinical trials. Regulatory macrophages are also under clinical trials for kidney transplant patients. IL-10-secreting type 1 regulatory T cells and donor- or recipient-derived tolerogenic dendritic cells will also be used for immunoregulation in clinical trials of kidney transplantation. These cells have antigen-specific immunoregulatory effects. Mesenchymal stromal cells (MSCs) have good proliferative capacity and immunosuppressive actions independently of major histocompatibility complex; therefore, even third-party MSCs can be stored and used for many patients. Cell therapy using various immunoregulatory cells is now promising for not only reducing side effects of nonspecific immunosuppressants but also induction of immune tolerance, and is expected to contribute to better outcomes in transplant patients.

• Annals of Clinical Neurophysiology
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• v.14 no.2
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• pp.76-79
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• 2012

Statin is commonly used for lowering cholesterols and can be myotoxic to cause drug-induced necrotizing myopathy. Statin-induced myopathy ranges from asymptomatic hyperCKemia to lethal rhabdomyolysis but is usually reversed by withdrawal of causative drugs. The patient in this study presented with statin-induced necrotizing myopathy, which was finally improved with immunosuppressive therapy, but not just with drug withdrawal. Since statin can induce myopathy through autoimmune processes, we should consider using immunomodulating agents in cases with statin-induced myopathy, which is refractory to drug withdrawal.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• 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 Veterinary Clinics
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• v.25 no.5
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• pp.415-419
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• 2008

The purpose of this study was to determine clinical features of canine episcleritis and outcomes of therapy in Korea. The medical records of dogs with episcleritis presented at the Veterinary Medical Teaching Hospital of Seoul National University from January 2006 to December 2007 were reviewed. Episcleritis was diagnosed in 17 eyes of 12 dogs. The most frequently affected breed was Shih Tzu (n = 6). The median affected age was 5 years with a range from 3 years to 12 years. Simple episcleritis was identified in 8 dogs, nodular granulomatous episcleritis (NGE) in 3 dogs, and secondary episcleritis caused by panophthalmitis in a dog. The combination immunosuppressive therapy of topical corticosteroids, topical cyclosporine A, and intralesional injection of triamcinolone (4 mg) and gentamicin (4 mg) was performed. Most of the patients with episcleritis were resolved within 30 days following the therapy. Surgical excision was performed in 1 NGE case which was not responded to the medical therapy. Recurrence was observed in 4 dogs between 5 and 8 months after the first visit. It is considered that strong immunosuppressive therapy and periodic ocular examination are needed to control episcleritis.

• 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.