• Title/Summary/Keyword: Immunomodulating agents

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In vitro response of rat microglia and human polymorphonuclear cells (PMN) to immunoactive compounds

  • Lombardi, Valter RM;Eetcheverria, Ignacio;Fernandez-Novoa, Lucia;Diaz, Joaquin;Seoane, Silvia;Cacabelos, Ramon
    • Advances in Traditional Medicine
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    • v.5 no.3
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    • pp.216-230
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    • 2005
  • Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.

Analysis of Pharmacogenetic Information in Korea Drug Labels (국내 허가사항에 반영된 약물 유전정보 분석)

  • Lee, Mijin;Kim, Sukyung;Yee, Jeong;Gwak, Hye Sun;Choi, Kyung Hee
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.1
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    • pp.21-26
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    • 2021
  • Background: Pharmacogenomics is the study of how genetic mutations in patients affect their response to drugs. Pharmacogenomic studies aim to maximize drug effects and minimize adverse drug events. The Food and Drug Administration and the European Medicine Agency published guidelines for pharmacogenetics in 2005 and 2006, respectively; the Korean Ministry of Food and Drug Safety followed suit in 2015. Methods: This study analyzed pharmacogenomic information in the Korean Ministry of Food and Drug Safety's integrated drug information system to evaluate whether domestic pharmaceutical products reflect the current research on pharmacogenomic differences. Results: In June 2020, the Korean pharmacogenomic database contained genomic data on 90 compounds. Of these, 45 compounds were classified as "Antineoplastic and immunomodulating agents." The other 45 non-antineoplastic agents were in the following categories: Anti-infectives, Mental & behavior disorder, Hormone & metabolism related diseases, Cardiovascular system, Skin & subcutaneous tissue disease, Genito-urinary system and sex hormones, Blood and blood forming organs, Nervous system, Alimentary tract and metabolism, Musculo-skeletal system, and Other conditions including the respiratory system. In addition, 30 additives unrelated to the main ingredient were associated with genetic precautions. Conclusion: This study showed that antineoplastic and immunomodulating agents accounted for half the drugs associated with pharmacogenetic information. For antitumor and immunomodulatory drugs, genomic tests were recommended depending on the indication; this was in contrast to genomic testing recommendations for non-antineoplastic medications. Genomic tests were rarely requested or recommended for non-antineoplastic medications because the relationships between genotype and efficacy among those drugs were relatively weak.

Current Status of Anti-HBV Chemotherapy

  • Hong, Joon H.;Choi, Yong-Seok;Chun, Byoung K.;Lee, Kyeong;Chu, Chung K.
    • Archives of Pharmacal Research
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    • v.21 no.2
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    • pp.89-105
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    • 1998
  • In the past decade, significant progress has been achieved in the battle against hepatitis B virus. In addition to the immunomodulating agents such as interferon-.alpha., and thymosin, many novel antiviral agents have been discovered, among which nucleoside analogues are the mainstay. New-generation compounds such as 3TC and famciclovir have shown promise in the treatment of patients chronically infected by this virus, and are on the line for approval. However, viral rebound after cessation of therapy still remains a major problem. Additionally, the reports on the drug resistance to these antiviral agents suggest that combination therapy will be the eventual strategy (Bartholomew et al., 1997; Tipples et al., 1996). Therefore, developments of safe and effective antiviral agents which do not cross-resist with currently available antiviral drugs are still much needed.

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Effects of PALMIWON on Cell Viability of Immune Cell and ${\beta}-cell$ (취장소도세포와 면역세포에 미치는 팔미원의 영향)

  • 이인순;이인자
    • YAKHAK HOEJI
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    • v.39 no.5
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    • pp.541-547
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    • 1995
  • In order to investigate the usability of PALMIWON as antidiabetic immuno-modulating prescription for Insulin-dependent diabetes, we studies the effects of PALMIWON on immune cell and ${\beta}-cell$. U937 was used as the model of immune cell and RINm5F as the model of ${\beta}-cell$. The effects of PALMIWON was measured by cell viability in terms of MIT assay. As a result, PALMIWON and the compositional drugs showed the different effects m immune cell and ${\beta}-cell$. Cell viability of U937 was significantly decreased wheras that of RINm5F was no significantly difference between drug treated group and control, or significantly less reduction compared with U937. It implies that PALMIWON is useful as immunotherapeutic agents in the prevention and therapy of type 1 diabetes.

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Surgical Management of Pyoderma Gangrenosum: A Case Report (괴저성 농피증의 수술적 치험례)

  • Seul, Chul Hwan;Kim, Bom Jin;Lee, Sung Joon;Kim, Sug Won;Chung, Yoon Kyu
    • Archives of Plastic Surgery
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    • v.32 no.1
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    • pp.135-138
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    • 2005
  • Pyoderma gangrenosum(PG) is an uncommon cutaneous vascular disease that typically presents as a painful and destructive ulceration on the anterior surface of the legs. The etiology of PG is currently unknown. But, the association with many immunologic disorders and its clinical response to immunomodulating agents suggest an immune etiology. A common feature of patients with PG is the presence of pathergy(the induction of lesion following injury of the skin). The trauma of surgery can be sufficient to induce pathergy, thus paradoxically limiting the usefulness of surgical treatment of PG. For that reason, medical treatments have been commonly used, while surgical treatments have been regarded not suitable. However, the use of the classic systemic agents is limited by their side effects and contraindications. Moreover, the large, problematic ulcers take too long to heal with medical management only. We present our experience in closing large wounds with the goal of decreasing morbidity, drug side effects and hospital stay by combination of medical and surgical therapy(split thickness skin graft). And authors advocate that surgical management is not a contraindication and may be considered as a selective modality in treatment of PG.

Effects of Vinblastine and Vincristine on the Primary and Secondary Cell-mediated Immunity (Vinblastine과 Vincristine이 1차(次) 및 2차(次) 세포성(細胞性) 면역반응(免疫反應)에 미치는 영향(影響))

  • Pyo, Myoung-Yun
    • Korean Journal of Pharmacognosy
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    • v.17 no.3
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    • pp.248-254
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    • 1986
  • Effects of vinblastine(VLB) and vincristine(VCR) on cell-mediated immunity(CMI) were studied with the microcytotoxicity test(MCT) after normal or pre-sensitized Balb/c mice had been treated in vivo with a combination of two different doses of VLB or VCR(single dose of 20% and 60% $LD_{50}$, i.p.) at different times (from day -6 to day +4) plus allo-transplantation antigen(allo-TA, cells from C3H mice at day 0). The results were that $LD_{50}$ of VLB for female Balb/c mouse was 7.3mg/kg body weight (i.p.) and $LD_{50}$ of VCR was 4.3mg/kg body weight and that VLB and VCR acted as immunosuppressive agents on the primary CMI when administered after allo-TA(antigen-drug-phase), but showed no effect when administered prior to allo-TA(drug-antigen-phase). Change of doses of VLB and VCR(20% $LD_{50}$, 60% $LD_{50}$) caused quantitative or qualitative variations in the immunomodulating effects of these two drugs. Neither VLB nor VCR had any immunomodulating effect on the secondary CMI. Lastly, the results support that the four parameters (type of drug, sensitization status, time of drug treatment in relation to antigen injection, and drug dosis) are significant for the effects of the VLB and VCR on the CMI, and that VLB and VCR may inhibit the proliferation of antigen-stimulated T effector lymphocytes but not memory-cytotoxic T lymphocytes.

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A Case of 1-Month Fever Caused by CMV Infection in a Patient With MIS-C Treated With IVIG, Infliximab, and High-Dose Methylprednisolone

  • Gihun Jeong;Jihye You
    • Pediatric Infection and Vaccine
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    • v.31 no.1
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    • pp.140-146
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    • 2024
  • Multisystem inflammatory syndrome in children (MIS-C) is a rare complication of coronavirus disease 2019 (COVID-19), causing multi-organ damage affecting the heart, lungs, kidneys, digestive tract, and nervous system. As the cases of MIS-C have been increasing following the COVID-19 pandemic, the importance of appropriate management for MIS-C is becoming increasingly apparent. Immunomodulating agents such as anakinra, infliximab, and steroids are regarded as supplementary therapy to the first-line treatment with intravenous immunoglobulin. However, these immunomodulating therapies can potentially precipitate opportunistic infections, including those caused by cytomegalovirus (CMV), Epstein-Barr virus, and tuberculosis, or increase the risk of co-infections. Herein, we report a case of a 3-year-old boy who was treated with immunoglobulin, infliximab, and high-dose methylprednisolone for MIS-C, and subsequently developed a persistent fever lasting 32 days caused by a CMV infection.

Brazilin Augments Cellular Immunity in Multiple Low Dose Streptozotocin (MLD-STZ) Induced Type I Diabetic Mice

  • Yang, Kyoung-Mee;Jeon, Sun-Duck;So, Dhong-Soo;Moon, Chang-Kiu
    • Archives of Pharmacal Research
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    • v.23 no.6
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    • pp.626-632
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    • 2000
  • Brazilin, an active principle of Caesalprenia sappan, was examined for its immunopotentiating effects in multiple low dose streptozotocin (MLD-STZ) induced type diabetic mice. Brazilin was intraperitoneally administered for 5 consecutive days to MLD-STZ induced type 1 diabetic mice. Delayed type hypersensitivity, Con A-induced proliferation of splenocytes and mixed lymphocyte reaction, which had been decreased in diabetic mice, were significantly recovered by the administration of brazilin. Brazilin increased IL-2 production without affecting suppressor cell activity. Con A-induced and IL-2-induced expression of high affinity IL-2 receptors were also enhanced by brazilin. These results indicate that brazilin augments cellular immune responses, which are suppressed in the MLD-STZ induced type I diabetic mice, by increasing IL-2 production and responsiveness of immune cells to IL-2.

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Statin-Induced Autoimmune Necrotizing Myopathy Responsive to Immunosuppressive Therapy (면역억제치료에 반응하는 statin에 의한 자가면역성 괴사성 근병증)

  • Park, Young-Eun;Seo, Jae-Deuk;Kim, Dae-Seong
    • 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.

Trends of clinical trials from 2014 to 2016 in South Korea

  • Huh, Ki Young;Hwang, Jun Gi;Lee, SeungHwan
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.172-176
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    • 2018
  • Mandatory registration of clinical trials in public registry can ensure the transparency of clinical trials. Public clinical trial registry of can provide current chronological and geographical distribution of clinical trial throughout the country. We used public clinical trial registry provided by Ministry of Food and Drug Safety to analyze current status of clinical trial from 2014 to 2016 in South Korea. The number of clinical trials in antineoplastic and immunomodulating agents area was the greatest, followed by cardiovascular system and antiinfectives for systemic use as a whole. From 2014 to 2016, overall number of clinical trials decreased while the number of phase I clinical trials increased. Seoul accounted for more than half number of clinical trials in Korea. Supports for clinical trials in non-metropolitan area needs to be considered.