• Title/Summary/Keyword: Immunosuppressants

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Review of two immunosuppressants: tacrolimus and cyclosporine

  • HyunJong Lee;Hoon Myoung;Soung Min Kim
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.49 no.6
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    • pp.311-323
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    • 2023
  • Immunosuppressants are vital in organ transplantation including facial transplantation (FT) but are associated with persistent side effects. This review article was prepared to compare the two most used immunosuppressants, cyclosporine and tacrolimus, in terms of mechanism of action, efficacy, and safety and to assess recent trials to mitigate their side effects. PubMed and Google Scholar queries were conducted using combinations of the following search terms: "transplantation immunosuppressant," "cyclosporine," "tacrolimus," "calcineurin inhibitor (CNI)," "efficacy," "safety," "induction therapy," "maintenance therapy," and "conversion therapy." Both immunosuppressants inhibit calcineurin and effectively down-regulate cytokines. Tacrolimus may be more advantageous since it lowers the likelihood of acute rejection, has the ability to reverse allograft rejection following cyclosporine treatment, and has the potential to reinnervate nerves. Meanwhile, graft survival rates seem to be comparable for the CNIs. To avoid nephrotoxicity, various immunosuppressants other than CNIs have been studied. Despite averting nephrotoxicity, these medications show increases in acute rejection or other types of adverse effects compared to CNIs. FT has been a topic of interest for oral and maxillofacial surgeons, and the postoperative usage of immunosuppressants is crucial for the long-term prognosis of FT. As contemporary transplantation regimens incorporate novel medications along with CNIs, further research is required.

Effect of Immunosuppressants on Lipopolysaccharide-Induced Changes of Nitric Oxide Synthase Activity in Liver and Brain of Mice (면역억제제가 Lipopolysaccharide에 의한 생쥐의 간 및 뇌조직의 Nitric Oxide Synthase 활성도의 변화에 미치는 영향)

  • Min, Byung-Woo;Han, Hyng-Soo;Park, Jung-Sook;Kim, Choong-Young
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.233-239
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    • 1995
  • To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

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Treatment of immune-mediated keratitis (IMMK) in dogs with immunosuppressants observed with spectral domain optical coherence tomography (SD-OCT)

  • Hyelin Kim ;Youngseok Jeong ;Eunji Lee;Kangmoon Seo ;Seonmi Kang
    • Journal of Veterinary Science
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    • v.24 no.5
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    • pp.66.1-66.7
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    • 2023
  • Two dogs presented with bilateral pattern-forming corneal opacity. Treatment with topical immunosuppressants was initiated after a complete ophthalmic examination. The response to treatment was assessed by analyzing serial images using slit-lamp biomicroscopy and spectral domain optical coherence tomography (SD-OCT). Both dogs responded to topical immunosuppressants; however, the lesions recurred once the treatment was abated or withdrawn. The most effective immunosuppressant in both dogs was 0.03% tacrolimus ointment. Early and continuous treatment with topical immunosuppressants may be necessary to improve corneal clarity and prevent scarring. SD-OCT could provide useful structural information regarding presumed immune-mediated keratitis and aid in monitoring treatment response.

Current Interventions to Improve Adherence to Immunosuppressants in Liver Transplant Recipients: a Systematic Review (간이식 환자의 면역억제제 복용이행 관련 중재에 관한 체계적 문헌고찰)

  • Kim, So Hee;Lee, Young Joo;Lee, Sun Young;Chu, Sang Hui
    • Journal of Korean Biological Nursing Science
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    • v.18 no.1
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    • pp.17-26
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    • 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.

Cell Therapy in Kidney Transplantation (신장이식 분야의 세포 면역치료)

  • Jeon, Hee Jung;Yang, Jaeseok
    • 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.

Effects of immunosuppressants, FK506 and cyclosporin A, on the osteogenic differentiation of rat mesenchymal stem cells

  • Byun, Yu-Kyung;Kim, Kyoung-Hwa;Kim, Su-Hwan;Kim, Young-Sung;Koo, Ki-Tae;Kim, Tai-Il;Seol, Yang-Jo;Ku, Young;Rhyu, In-Chul;Lee, Yong-Moo
    • Journal of Periodontal and Implant Science
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    • v.42 no.3
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    • pp.73-80
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    • 2012
  • Purpose: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs). Methods: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7. Results: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control. Conclusions: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.

Clinical practice pattern on hematuria and proteinuria in children: the report of a survey for the Korean Society of Pediatric Nephrology

  • Jeesu Min;Naye Choi;Yo Han Ahn;Hee Gyung Kang
    • Childhood Kidney Diseases
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    • v.27 no.1
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    • pp.26-33
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    • 2023
  • Purpose: Hematuria and proteinuria have various causes and consequential outcomes in children. Immunosuppressants are needed in some children with biopsy-proven glomerulonephropathy but have many adverse effects. Since the clinical practice patterns of Korean pediatric nephrologists are diverse, we surveyed their opinions. Methods: Using a clinical vignette, the survey was emailed to all Korean Society of Pediatric Nephrology members. The questionnaires included diagnosis, examination, medications, and dietary recommendations for patients with hematuria and proteinuria. Results: A total of 32 clinicians (5.48%, 22 pediatric certificated nephrologists) responded to the survey. Most responders (87.5%) suspected immunoglobulin A nephropathy, and 68.8% replied that kidney biopsies were a diagnostic tool. Renin-angiotensin system inhibition (62.5%) or steroids (18.8%) were selected as the treatment. Salt and protein intakes were usually encouraged as dietary reference intakes (34.4% and 65.6%, respectively). Conclusions: Children with abnormal urinalysis have various causes, treatments, and prognoses. As treatments such as immunosuppressants can have many adverse effects, it is necessary to confirm an accurate diagnosis and indications of treatments before starting the treatment. Recommendations for a diet should not hinder growth.

Generation of Hybrid Polyketides through Combinatorial Biosynthesis of Polyketide Synthase (PKS) and Modification of Post-PKS Tailoring Steps

  • Yoon, Yeo-Joon
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.75-78
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    • 2003
  • Polyketides are a class of structurally diverse natural products which possess a wide range of biological activities. These compounds are used throughout medicine and agriculture as antimicrobials, immunosuppressants, antiparasitics, and anticancer agents. While structurally diverse, polyketides are assembled by a common mechanism of decarboxylative condensations of simple malonate derivatives by polyketide synthases (PKSs) in a manner very similar to fatty acid biosynthesis (Fig 1). (omitted)

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