• Biomolecules & Therapeutics
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• 제13권2호
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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.

• Archives of Pharmacal Research
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• 제24권2호
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• pp.150-158
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• 2001

The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assays we observed that NSAIDs were slightly less active [$EC_{50}~10^{-5}-10^{-4}$ M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

• Journal of Korean Neurosurgical Society
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• 제46권3호
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• pp.226-231
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• 2009

Objective : We describe our clinical experiences and outcomes in patients who had thromboembolic complications occurring during endovascular treatment of intracerebral aneurysms with a review of the literature. The types of thromboembolic complications were divided and the treatment modalities for each type were described. Methods : Between August 2004 and March 2009 we performed endovascular embolization with Guglielmi detachable coils for 173 patients with 189 cerebral aneurysms, including ruptured and unruptured aneurysms at our hospital. Sixty-eight patients were males and 105 patients were females. The age of patients ranged from 22-82 years (average, 58.8 years). We retrospectively evaluated this group with regard to complication rates and outcomes. The types of thromboembolic complications were classified into the following three categories: mechanical obstruction, distal embolic stroke, and stent-induced complications, which corresponded to types I, II, and III, respectively. A comparison of the clinical results was made for each type of complication. Results : Only eight patients had a thromboembolic complication during or after a procedure (4.6%). Of the eight patients, two had a mechanical obstruction as the causative factor; the other three patients had distal embolic stroke as the causative factor. The remaining three patients had stent-induced complications. In cases of mechanical obstruction, recanalization occurred due to the use of intra-arterial thrombolytic agents in one of two patients. Nevertheless, a poor prognosis was seen. In the cases of stent-induced complications, in one of three patients in whom a thrombus developed following stent insertion, a middle cerebral artery territory infarct developed with a poor prognosis despite the use of wiring and an intra-arterial thrombolytic agent. In the cases of distal embolic stroke, all three patients achieved good results following the use of antiplatelet agents. Conclusion : Treatment for thromboemboic complications due to mechanical obstruction and stent-induced complications include antiplatelet and intra-arterial thrombolytic agents; however, this cannot guarantee a sufficient extent of effectiveness. Therefore, active treatments, such as balloon angioplasty, stent insertion, and clot extraction, are helpful.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권3호
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• pp.228-238
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• 2005

Purpose: Several cryoprotectants are in use to help the survival of cells during cryopreservation of bone in maxillofacial region. Among them, $Me_2SO$(dimethyl sulfoxide), EG(ethylene glycol), sucrose were used for experimentally created defects with accompanying cryopreserved bone graft in the rabbit model. The aim of this study is to analyze the effect of above mentioned agents on bone formation using histologic and histomorphometrical methods, thus to provide experimental support for clinical application of these agents. Materials and methods: Nine rabbits were used as experimental animals. Surgical defects were created on the distal femoral heads and mesial tibial heads of each animal using trephine drill(5mm diameter and 5mm length). The harvested bones were cryopreserved in $-80^{\circ}C$ refrigerator for one week. The defects were filled with cryopreserved bone with cryoprotectants as experimental groups and cryopreserved bone without cryoprotectant as control. Then, the animals were sacrificed at 1, 2, and 3 weeks after surgery. With Goldner's modified Masson trichrome staining and semiautomatic image analysis system, we observed the change of the cells and bone formation. Results: After bone graft, bone formation and active remodeling process were examined in all experimental groups and the control. But the intensity of such activities of the control were somewhat weaker than that of the experiments. Especially $Me_2SO$+sucrose group was the best in bone formation and bone remodeling. $Me_2SO$ group was more than that of EG group in bone fomation. Sucrose seems to be helpful in survival of the bone cell. Histologic findings showed superior bony quantity and quality in experimental groups than that in control. Conclusions: The data from this study provides the basis for future studies for evaluating the effect of cryoprotectants in the cryopreservation of bone and clinical study for predictable use of these agents.

• 대한두개안면성형외과학회지
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• 제20권5호
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• pp.289-296
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• 2019

Background: Topical hemostatic agents are used when ligation, electrocauterization, or other conventional hemostatic methods are impractical. Because a hemostatic agent is a foreign body, it can cause foreign body reactions, inflammation, and infections that can interfere with the wound healing process. Therefore, we should select hemostatic agents after considering their effects on wound healing. Here, we compared the effects of hemostatic agents on wound healing in a rectus abdominis muscle defect in rats. Methods: Twelve Sprague Dawley rats were subjected to creation of a $6{\times}6mm$ defect in the rectus abdominis muscle and divided into four groups: control group; group A, Tachosil fibrin sealant patch; group B, Surgicel Fibrillar oxidized regenerated cellulose; and group C, Surgicel Snow oxidized regenerated cellulose. For the histologic analysis, biopsies were performed on the 3rd, 7th, and 27th days. Results: The foreign body reaction was the weakest in group A and most significant in group C. The inflammatory cell infiltration was the weakest in group A and similar in groups B and C. Muscle regeneration differed among periods. The rats in group A were the most active initially, while those in group C showed prolonged activity. Conclusion: Tachosil and Surgicel administration increased inflammation via foreign body reactions, but the overall wound healing process was not significantly affected. The increased inflammation in the Surgicel groups was due to a low pH. We recommend using Tachosil, because it results in less intense foreign body reactions than Surgicel and faster wound healing due to the fibrin action.

• 한국수산과학회지
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• 제54권1호
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• pp.111-117
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• 2021

The study was aimed at developing an alternative therapeutic agent against acne vulgaris, one of the most common skin diseases, to meet the continuing demand for new therapies. Acne vulgaris is often associated with the acne-causing bacteria such as Cutibacterium acnes. To investigate the safety of agents against acne vulgaris, we evaluated the potential antibacterial activities of edible seaweeds against C. acnes in Korea. Forty-one edible seaweeds, including the brown, green, and red varieties, were selected for the antibacterial test. In comparison with other seaweeds, 70% ethanolic extracts of brown seaweeds, such as Cladophora wrightiana var. minor, Eisenia bicyclis, Ecklonia cava, Ishige foliacea, Ishige okamurae, Sargassum filicinum, and Sargassum miyabei Yendo, exhibited potential antibacterial activity against C. acnes with minimum inhibitory concentrations ranging between 64 and 128 ㎍/mL. To investigate the active anti-acne agents and to enhance our understanding of the antibacterial activities against C. acnes, further solvent-fractionation experiments are warranted. The findings imply that brown seaweeds can be a potential source of natural agents against acne vulgaris.

• Journal of Microbiology and Biotechnology
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• 제16권5호
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• pp.651-660
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• 2006

Natural products are a rich source of biologically active small molecules and a fertile area for lead discovery of new drugs [10, 52]. For instance, 5% of the 1,031 new chemical entities approved as drugs by the US Food and Drug Administration (FDA) were natural products between 1981 and 2002, and another 23% were natural product-derived molecules [53]. These molecules have evolved through millions of years of natural selection to interact with biomolecules in the cells or organisms and offer unrivaled chemical and structural diversity [14, 37]. Nonetheless, a large percentage of nature remains unexplored, in particular, in the marine and microbial environments. Therefore, natural products are still major valuable sources of innovative therapeutic agents for human diseases. However, even when a natural product is found to exhibit biological activity, the cellular target and mode of action of the compound are mostly mysterious. This is also true of many natural products that are currently under clinical trials or have already been approved as clinical drugs [11]. The lack of information on a definitive cellular target for a biologically active natural product prevents the rational design and development of more potent therapeutics. Therefore, there is a great need for new techniques to expedite the rapid identification and validation of cellular targets for biologically active natural products. Chemical genomics is a new integrated research engine toward functional studies of genome and drug discovery [40, 69]. The identification and validation of cellular receptors of biologically active small molecules is one of the key goals of the discipline. This eventually facilitates subsequent rational drug design, and provides valuable information on the receptors in cellular processes. Indeed, several biologically crucial proteins have already been identified as targets for natural products using chemical genomics approach (Table 1). Herein, the representative case studies of chemical genomics using natural products derived from microbes, marine sources, and plants will be introduced.

• 한국식품영양과학회지
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• 제27권3호
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• pp.399-405
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• 1998

This study was carried out to investigate the effects of herb extracts on lipid oxidation and free radical reaction in iron sources reacted with active oxygen species. The catalytic effects of active oxygen on lipid oxidation in oil emulsion tended to show more active in the order of OH, H2O2 and KO2. Herb extracts tended to show a little catalytic effect and active oxygen scavenging ability of herb extracts didn't show. But herb extracts played role as a strong chelating agents to bind iron if Fe2+ ion exist in oil emulsion. The contents of Fe2+ ion and total iron in Salvia miltiorrhiza Bge. and Angelica gigas Nakai were higher than those of Prunus persica Stockes and pinus strobus. The content of asocrbic acid in Pinus strobus showed the highest (26.97ppm) among several herb extracts. Electron donating abilities of Pinus strobus and Salvia miltiorrhiza Bge. were 79.54% and 77.11%, respectively, which were higher contents than those of Prunus persical Stokes and Angelica gigas Nakai. The SOD-like activity of Prunus persca Stokes showed 0.16 optical density (O.D), which means the most strong antioxidant activity among other herb extracts. The nitrite scavening effects tended to be different depending on pH. Pinus strobus and Angelica gigas Nakai showed 99.8% and 98.6% nitrite scavening effects at pH 1.2. And the effects were decreased as pH was increased. Especially, they didn't show the nitrite scavenging effect in pH 6.0. In conculsin, the Prinus strobus extract among herb extracts were the most effective antioxidant by evaluating several functional tests.

• 셀메드
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• 제2권2호
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• pp.20.1-20.5
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• 2012

$Gynura$ $segetum$ (Lour.) Merr. ($Compositae$) is a well recognized medicinal plant in Indonesia and Malaysia. It is believed to have an anticoagulant effect and is used in treating snake-bites, inflammations and other skin afflictions. This study was carried out to evaluate the antimicrobial effects of $Gynura$ $segetum$ leaves extracts and its fractions. The chemical compositions of the active extracts were also determined. The antimicrobial activities of different solvent extracts of leaves of $Gynura$ $segetum$ were evaluated using the agar well-diffusion method. The Minimum Inhibitory Concentration (MIC) of the active subfractions was determined by the tube dilution method. Gas Chromatography-mass spectrometry (GC-MS) analysis was carried out to identify the chemical compositions of the active extracts. The ethyl acetate fraction and its subfraction E4 performed potent antimicrobial activities and fifteen known chemical constituents were identified by GCMS analysis as 4-vinylphenol, 1-tetradecene, phenol, 2,4-bis(1,1-dimethylethyl), 1-hexadecene, E-15-heptadecenal, hexadecanoic acid, 1,2-benzenedicarboxylic acid, dibutyl ester, 1-docosene, octadecanoic acid, 1-eicosene, cyclotetracosane, 1,2-benzenedicarboxylic acid, bis(2-ethylhexyl)ester, butanedioic acid, monomethyl ester, niacin and 4-hydroxy-benzoic acid. The results of this study suggested a connection between the antimicrobial activities and the chemical structures. The plant may be used as a potential source for antimicrobial agents.

• 한국약용작물학회지
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• 제25권5호
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• pp.315-321
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• 2017

Background: Glycyrrhiza uralensis Radix (GR) is a crude drugs used in Asian countries that has been reported to prevent the progression of neurodegenerative diseases such as Alzheimer's disease. The present study examined whether GR and its active compounds, glycyrrhizic acid (GA) and isoliquiritigenin (IL), exerted protective effects on $H_2O_2$-induced oxidative damage in C6 glial cells. Methods and Results: We exposed C6 glial cells to hydrogen peroxide ($H_2O_2$) for 24 h and investigated the cellular response to GR and its active compounds by evaluating cell viability, reactivie oxygen species (ROS) production, and apoptosis-related protein expression. GR successfully mitigated the reduced cell viability and ROS production induced by $H_2O_2$ in C6 glial cells, IL and GA significantly increased the cell viability and decreased ROS production. In addition, IL and GA down-regulated apoptotic Baxdependent caspase-3 activation, but each compound exerted different mechanisms, i.e., IL dose-dependently decreased ROS production and, GA up-regulated anti-apoptotic Bcl-2 expression. Conclusions: These results demonstrated that GR and its active components, IL and GA, exhibit potential for use as natural neurodegenerative agents for the modulation of apoptosis in C6 glial cells.