• Title/Summary/Keyword: Drug response

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The Chemopreventive Effects of Antioxidant Enzyme (항산화효소의 암 예방 효과 및 발암 억제 기전)

  • Jung Hwa-Jin;Choi Yoon-Joo;Won Chang-Won;Seo Young-Rok
    • Environmental Mutagens and Carcinogens
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    • v.26 no.2
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    • pp.45-47
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    • 2006
  • The reactive oxygen species (ROS) caused the damage of macro molecules, many degenerative disease and cancer, which was produced in process of the aerotropic metabolic pathway as well as in response to the various genotoxic stresses. Recently, redox systems including the number of antioxidant proteins such as catalase, glutathione peroxidase, heam-containing peroxidase, peroxiredoxin and superoxide dismutase (SOD) has been reported to have chemopreventive effects. Antioxidant proteins has been known to have the activity directly removing ROS and affecting the protein-protein interaction and cell signaling to induce the cellular responses. We need to understand the mechanism of antioxidants prevent DNA damage from oxidative stresses for researching the cancer prevention and providing the development of cancer therapeutic drug.

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Cytochrome P-450 3A4 proximal promoter activity by histone deacetylase inhibitor in HepG2 cell.

  • Kim, Ja-Young;Ahn, Mee-Ryung;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.88-88
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    • 2003
  • Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. Here, we developed luciferase reporter gene assay system to detect SXR-based CYP 3A4 transcriptional activity. We have used CYP3A4-Luc plasmid that contains proximal promoter of human CYP3A4 gene upstream of the luciferase gene. We did transient transfection of 3A4-luciferase gene and SXR. In the HepG2 cells transfected with CYP3A4-Luc, when rifampicin treatment was combined with histone deacetylase inhibitor (HDAC Inhibitor), such as Trichostatin A, Hc-toxin and IN 2001 of the luciferase activity was induced 10-20 fold over control.

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The Assessment of Carbendazim, Cyazofamid, Diethofencarb and Pyrimethanil Residue Levels in P. ginseng (C. A. Meyer) by HPLC

  • Choi, Jeong-Heui;El-Aty, A.M.Abd;Park, Young-Seok;Cho, Soon-Kil;Shim, Jae-Han
    • Bulletin of the Korean Chemical Society
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    • v.28 no.3
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    • pp.369-372
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    • 2007
  • A fast and simple high-performance liquid chromatography (HPLC) method for the simultaneous determination of four pesticides having fungicide properties has been proposed for Panax ginseng, C. A. Meyer grown for 4, 5, or 6 years. Analytical separation was performed on C18 columns using ultraviolet detector under gradient conditions. Spiked blank samples were used as standards to counteract the matrix effect observed in the chromatographic determination. The HPLC response for all pesticides was linear, with determination coefficients > 0.9986. The average rate of recovery for pesticides spiked with 2 fortification levels was > 72% with relative standard deviations < 9%. The limits of quantification (LOQ) ranged from 0.03 to 0.16 ppm. These LOQs were lower than the respective maximum residue limits (MRL) established by the Korean Food and Drug Administration (KFDA), except for cyazofamid. The proposed method was used to determine pesticide residue levels in samples of ginseng obtained from Jeonnam Province (Republic of Korea). None of the pesticides were found in ginseng samples grown for 4, 5, or 6 years.

Application of time-temperature indicators for cooling and frozen food storage and distribution (저장 조건 감지 지표 장치의 특성 및 식품에의 응용 가능성)

  • An, Duek-Jun;Yoo, Seung-Seok
    • KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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    • v.5 no.1
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    • pp.25-29
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    • 1999
  • Time-temperature indicators (TTI) from three different companies obtained and were attached to food packages materials to evaluate degree of their color change according to storage time and temperature. Five temperature (-10 -5, 0, 5 and 10) was selected to represent standard freezing, refrigerating and room temperature, and evaluated performance by color change based on magnitude of color change and hunter system (L, a, b). Response end point was measured and recorded to find characteristic of each indicator. Comparison and discussion were conducted for accuracy and precision of each time-temperature. More research should be conducted at variable temperature and with various food to determine applicability of TTI on various storage condition.

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Nonsteroidal Anti-inflammatory Drugs (비스테로이드 항염제)

  • Lee, Choong-Ki
    • Journal of Yeungnam Medical Science
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    • v.17 no.1
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    • pp.1-11
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    • 2000
  • Inhibition of cyclooxygenase(COX), and thus prevention of the formation of prostaglandins, provided a unifying explanation of the therapeutic and toxic actions of nonsteroidal anti-inflammatory drugs (NSAIDs). Recently, the discovery of the two isoforms of COX was made by molecular biologists studying neoplastic transformation in chick embryo cells. The constitutive enzyme, COX-1, is obviously responsible for the production of prostaglandins involved in housekeeping functions such as maintenance of integrity of the gastric mucosa, renal blood flow and platelet aggregation. The inducible form of COX (COX-2) is responsible for the formation of prostaglandins that pathologically affects inflammation, pain and fever. Clearly, all the experimental and clinical data support the hypothesis that the beneficial effects of NSAIDs are due to inhibition of the COX-2 enzyme, whereas the gastrotoxicity is due to inhibition of COX-1. The cox-2/COX-1 ratios of the NSAIDs in common use have been measured and compared with epidemiological data on their side effects. There is little evidence to suggest that one NSAID is clearly more effective than another, But substantial individual variability is present with respect to the pharmacology and pharmacokinetics of these drugs: therefore it is essential to adjust the dosage and choose specific drug to the patient's response.

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Pancastatin A and B Have Selective Cytotoxicity on Glucose-Deprived PANC-1 Human Pancreatic Cancer Cells

  • Park, Hae-Ryong
    • Journal of Microbiology and Biotechnology
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    • v.30 no.5
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    • pp.733-738
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    • 2020
  • Glucose deprivation and hypoxia frequently occur in solid tumor cells, including pancreatic cancer cells. Glucose deprivation activates the unfolded protein response (UPR) and causes the up-regulation of glucose-regulated protein 78 (GRP78). Induction of GRP78 has been shown to protect cancer cells. Therefore, shutting down of GRP78 expression may be a novel strategy in anticancer drug development. Based on this understanding, a screening system established for anticancer agents that exhibit selective cytotoxicity on pancreatic cancer cells under glucose-deprived conditions. To test this hypothesis, the new compounds isolated, pancastatin A (PST-A) and B (PST-B), from Ponciri Fructus. PST-A and B were identified as glabretal triterpenoid moieties by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopic methods. PST-A and B suppressed the accumulation of the UPR hallmark gene, GRP78, during glucose deprivation. Furthermore, PST-A and B showed selective cytotoxicity on PANC-1 pancreatic cancer cells under glucose deprivation. Interestingly, PST-A and B had no effect on these cells under normal growth conditions. Our results suggest that PST-A and B act as novel therapeutic agents to induce selective cell death in glucose-deprived pancreatic cancer cells.

Cytochrome P-450 3A4 proximal promoter activity by histone deacetylase inhibitor in HepG2 cell.

  • Kim, Ja-Young;Ahn, Mee-Ryung;Sheen, Yhun-Yhong
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.178-178
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    • 2003
  • Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this Is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. Here, we developed luciferase reporter gene assay system to detect SXR-based CYP 3A4 transcriptional activity. We have used CYP3A4-Luc plasmid that contains proximal promoter of human CYP3A4 gene upstream of the luciferase gene. We did transient transfection of 3A4-luciferase gene and SXR. In the HepG2 cells transfected with CYP3A4-Luc, when rifampicin treatment was combined with histone deacetylase inhibitor (HDAC Inhibitor), such as Trichostatin A, Hc-toxin and IN 2001 of the luciferase activity was induced 10-20 fold over control.

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Effect of Mequitazine on the Muscarinic Receptors (Mequitazine의 Muscarine수용체에 대한 작용)

  • 이신웅;장태수
    • Biomolecules & Therapeutics
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    • v.3 no.3
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    • pp.192-198
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    • 1995
  • The affinity of mequitazine, a non-sedating antihistamine, for muscarinic receptors was evaluated in the guinea-pig ventricle and ileum by in vitro binding techniques and functional studies. In binding studies, [$^3$H]quinuclidinyl benzilate (QNB) identified a single class of muscarinic receptors with similar apparent $K_{D}$ value of about 100 pM in two tissues. Mequitazine inhibited [$^3$H]QNB binding to muscarinic receptors competitively. Analysis of the mequitazine inhibition curve of [$^3$H]QNB binding to ventricular microsome and ileal homogenate indicated the presence of a single homogeneous binding site with Ki value of 25 nM and 18 nM, respectively. In functional studies, mequitazine caused parallel rightward shifts of concentration-response curves for carbachol and histamine in the isolated guinea-pig ileum. The slope values obtained from Schild plot analysis for the antagonistic action of mequitazine on muscarinic and histamine $H_1$-receptors were not significantly different from unity. The p $A_2$values of mequitazine for muscarinic and histamine $H_1$-receptors were about 7.6 ( $K_{M}$= 25.1 nM) and 8.88 ( $K_{H}$= 1.32 nM), respectively. These results indicate that the muscarinic receptor blocking action of mequitazine is 15 times less potent than the $H_1$receptor blocking action, but high concentration of this drug may cause the peripheral muscarinic receptor blocking effect.t.t.t.

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Pharmacological Screening of Dikamali Resin Extract

  • Sridhar, S.K.;Ramachandran, S.;Anbalagan, N.;Leonard, J. Thomas;Joanofarc, J.;Kumar, S. Sadish
    • Natural Product Sciences
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    • v.9 no.1
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    • pp.10-12
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    • 2003
  • In the present study, dikamali resin (obtained from the leaf buds and the young shoots of Gardenia gummifera Linn.) was extracted with diethyl ether and the extract was vacuum dried. Qualitative tests confirmed the presence of flavonoids and free phenolic compounds in the extract. The antioxidant property (qualitative) of the extract was performed by TLC method $({\beta}-carotene-linoleate method)$. The $LD_{50}$ of the extract was found to be 2227 mg/kg by Karber's arithmetic method. The extract was screened for analgesic, anti-inflammatory, antipyretic (100, 200 and 400 mg/kg) and anthelmintic (0.1,0.2 and 0.5%w/v) activities by standard methods. The extract exhibited antioxidant property and prevented oxidation of ${\beta}-carotene$. The extract exhibited significant graded dose response for analgesic, anti-inflammatory, antipyretic and anthelmintic activities. The extract caused the death of earthworms in all experimental concentration whereas the standard drug (piperazine) only effected paralysis. The present study proved the claims of dikamali resin mentioned in the Indian system of medicine.

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.