• Title/Summary/Keyword: therapeutic strategy

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Recent Developments in Analytical and Preparative Scale Enantioseparations

  • Chankvetadze, Bezhan
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.161-162
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    • 2002
  • Field of enantioseparations represents one of the actual topics of chemistry. Significant, in some cases dramatic differences in a desired activity as well as in toxic properties of enantiomers of chiral drugs, food additives, agrochemicals, cosmetic products, etc. represents a driving force in this field. The enantiomers of all chiral bioactive compounds have to be isolated and to be tested. Besides the ethical or environmental reasons for developing single enantiomers, it may be a real therapeutic benefit and in some cases, it has been used as a strategy for extending patent life. (omitted)

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A novel potassium channel opener, KR-31378, protects cortex neurons from oxidative injury by restoring antioxidant enzyme activities and glutathione levels

  • Kim, Sun-Ok;Cho, In-Sun;Lee, Dong-Ha;Lim, Hong;Yoo, Sung-Eun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.197.1-197.1
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    • 2003
  • Neuronal hyperexcitability followed by high level of intracellular calcium and oxidative stress play critical roles in neuronal cell death in stroke and neurotrauma. Hence, KR-31378, a novel benzopyran derivative was designed as a new therapeutic strategy for neuroprotection possessing both anti-oxidant and potassium channel modulating activities. In the present study, we tested for its neuroprotective efficacy against oxidative stress-induced cell death in primary cortical cultures and further investigated its neuroprotective mechanism. (omitted)

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Proposed Mechanisms of Photobiomodulation (PBM) Mediated via the Stimulation of Mitochondrial Activity in Peripheral Nerve Injuries

  • Choi, Ji Eun
    • Medical Lasers
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    • v.10 no.4
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    • pp.195-200
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    • 2021
  • Evidence shows that nerve injury triggers mitochondrial dysfunction during axonal degeneration. Mitochondria play a pivotal role in axonal regeneration. Therefore, normalizing mitochondrial energy metabolism may represent an elective therapeutic strategy contributing to nerve recovery after damage. Photobiomodulation (PBM) induces a photobiological effect by stimulating mitochondrial activity. An increasing body of evidence demonstrates that PBM improves ATP generation and modulates many of the secondary mediators [reactive oxygen species (ROS), nitric oxide (NO), cyclic adenosine monophosphate (cAMP), and calcium ions (Ca2+)], which in turn activate multiple pathways involved in axonal regeneration.

Treatment-Resistant Schizophrenia : Pathophysiology and Treatment (치료 저항성 조현병의 이해와 치료)

  • Kim, Euitae
    • Journal of Korean Neuropsychiatric Association
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    • v.57 no.3
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    • pp.230-234
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    • 2018
  • A large proportion of patients with schizophrenia show a poor response to first-line antipsychotic drugs, which is termed treatment-resistant schizophrenia. Previous studies found that a different neurobiology might underlie treatment-resistant schizophrenia, which necessitates the development of different therapeutic approaches for treating treatment-resistant schizophrenia. This study reviewed previous studies on the pathophysiology of treatment-resistant schizophrenia and the pharmacological intervention, and forthcoming investigations of treatment-resistant schizophrenia are suggested.

AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells

  • Im, Jin Young;Min, Woo-Kie;Park, Min Hee;Kim, NamOh;Lee, Jong Kil;Jin, Hee Kyung;Choi, Je-Yong;Kim, Shin-Yoon;Bae, Jae-Sung
    • BMB Reports
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    • v.47 no.8
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    • pp.439-444
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    • 2014
  • Inhibition of an increase of osteoclasts has become the most important treatment for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the mobilization of osteoclast precursors within bone marrow (BM). However, the actual therapeutic impact of AMD3100 in osteoporosis has not yet been ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the treatment of ovariectomy-induced osteoporosis in mice. We found that treatment with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of osteoclasts on bone surfaces. These findings support the hypothesis that treatment with AMD3100 can result in efficient mobilization of HSPCs into blood through direct blockade of the SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.

Bordetella bronchiseptica bateriophage suppresses B. bronchiseptica-induced inflammation in swine nasal turbinate cells

  • Park, Ga Young;Lee, Hye Min;Yu, Hyun Jin;Son, Jee Soo;Park, Sang Joon;Song, Kyoung Seob
    • Genes and Genomics
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    • v.40 no.12
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    • pp.1383-1388
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    • 2018
  • The development of therapeutic bacteriophages will provide several benefits based on an understanding the basic physiological dynamics of phage and bacteria interactions for therapeutic use in light of the results of antibiotic abuse. However, studies on bacteriophage therapeutics against microbes are very limited, because of lack of phage stability and an incomplete understanding of the physiological intracellular mechanisms of phage. The major objective of this investigation was to provide opportunity for development of a novel therapeutic treatment to control respiratory diseases in swine. The cytokine array system was used to identify the secreted cytokines/chemokines after Bordetella bronchiseptica infection into swine nasal turbinate cells (PT-K75). We also performed the real-time quantitative PCR method to investigate the gene expression regulated by B. bronchiseptica infection or bacteriophage treatment. We found that B. bronchiseptica infection of PT-K75 induces secretion of many cytokines/chemokines to regulate airway inflammation. Of them, secretion and expression of IL-$1{\beta}$ and IL-6 are increased in a dose-dependent manner. Interestingly, membrane-bound mucin production via expression of the Muc1 gene is increased in B. bronchiseptica-infected PT-K75 cells. However, cytokine production and Muc1 gene expression are dramatically inhibited by treatment with a specific B. bronchiseptica bacteriophage (Bor-BRP-1). The regulation of cytokine profiles in B. bronchiseptica-induced inflammation by B. bronchiseptica bacteriophage is essential for avoiding inappropriate inflammatory responses. The ability of bacteriophages to downregulate the immune response by inhibiting bacterial infection emphasizes the possibility of bacteriophage-based therapies as a novel anti-inflammatory therapeutic strategy in swine respiratory tracts.

Chitosan Derivatives for Target of Specific Tissue in the Body (생체 내 특정 조직의 표적을 위한 키토산 유도체)

  • Jang, Mi-Kyeong;Nah, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.21 no.6
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    • pp.593-602
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    • 2010
  • Chitosan as a natural polymer has superior physicochemical properties such as biocompatibility, biodegradability and nontoxicity, but application of chitosan for therapy of cancer and gene related-disease has been limited by poor solubility in aqueous solution. Therefore, low molecular weight water-soluble chitosan (LMWSC) with high reactivity and strong positive charge can be applied as a delivery system having function to carry in the specific tissue the bioactive material like poor solubility drug, or therapeutic gene and developed as a therapeutic system having good therapeutic efficiency. The most important factor for therapy of various diseases is to reveal the antigen or receptor expressed in specific lesion tissue and the antibody and ligand which can bind with antigen is to introduce at the biomaterials for enhancement the therapeutic efficiency. The studies for cationic synthetic polymer as drug or gene delivery have been actively performed, but it has many problems such as toxicity in the body, therapeutic efficiency. From this point of view, this article demonstrated the introduction of functional groups to target the specific tissue and therapeutic strategy using the modification of LMWSC with free-amine group. The development of these delivery system will provide a positive vision for cancer therapy.

Change in the treatment strategy for pediatric Crohn's disease

  • Kim, Mi-Jin;Choe, Yon-Ho
    • Clinical and Experimental Pediatrics
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    • v.53 no.9
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    • pp.830-833
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    • 2010
  • Crohn's disease is characterized by chronic inflammation involving any portion of the gastrointestinal tract. Treating Crohn's disease is a major challenge for clinicians, as no curative therapy currently exists. Pediatric Crohn's disease is characterized by frequent relapses, a wide extent of disease, a high prevalence of extraintestinal manifestations, and a severe clinical course. The classic therapeutic approach is known as the 'step-up' strategy, and follows a progressive course of treatment intensification as disease severity increases. Although this approach is usually effective for symptom control, many patients become either resistant to or dependent on corticosteroids. The efficacy of infliximab suggests that, rather than a progressive course of treatment, early intense induction may reduce complications associated with conventional treatment and improve quality of life. Intensive early therapy with infliximab is known as the 'top-down' strategy. Such therapy offers the potential for altering the natural history of Crohn's disease, and is changing treatment paradigms. However, the relatively new concept of an early aggressive or 'top-down' treatment approach is not yet widely accepted, especially in pediatric patients. The results of our current study demonstrate that early and intensive treatment of pediatric Crohn's disease patients with infliximab, at initial diagnosis, was more effective for maintaining remission and reducing flares.

Correlation of Glasgow Prognostic Score or Procalcitonin to Clinical Variables in Patients with Pretreatment Lung Cancer

  • Kim, Young;Seok, Ji-Yoon;Hyun, Kyung-Yae;Lee, Gil-Hyun;Choi, Seok-Cheol
    • Biomedical Science Letters
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    • v.22 no.1
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    • pp.9-17
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    • 2016
  • Unfortunately, the five-year survival rate of lung cancer is relatively low compared with other cancers. Therefore, better predictors are need for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer. Recently, increasing data suggest that Glasgow Prognostic Score (GPS) and procalcitonin levels are useful predictor cancer prognosis. In this study, we retrospectively investigated the correlation of GPS or procalcitonin to clinical variables in patients with pretreatment lung cancer. In 135 patients with pretreatment lung cancer, GPS, procalcitonin, demographic characteristics, hematological, coagulation, biochemical, inflammatory and cardiac markers were measured. Monocyte, eosinophil, basophil, neutrophil to lymphocyte ratio, red cell distribution width (RDW), platelet to lymphocyte ratio, mean platelet volume to platecrit ratio, D-dimer and prothrombin time (PT) levels were higher, whereas mean platelet volume was lower than their normal ranges. Glucose and sodium levels were low, whereas gamma glutamyl transferase (GGT), total bilirubin, creatinine and inorganic phosphorus concentrations were increase compared their normal ranges. Procalcitonin, high sensitivity C-reactive protein and troponin-I concentrations were elevated compared with their normal ranges. GPS had significantly positive or negative relations to cancer stage, hematological, coagulation, biochemical, inflammatory and troponin-I. Based on the data, we suggest that GPS may be a potent and useful predictor for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer.

Dust particles-induced intracellular Ca2+ signaling and reactive oxygen species in lung fibroblast cell line MRC5

  • Lee, Dong Un;Ji, Min Jeong;Kang, Jung Yun;Kyung, Sun Young;Hong, Jeong Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.327-334
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    • 2017
  • Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.