• Title/Summary/Keyword: Receptor model

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Association of DR4 (TRAIL-R1) Polymorphisms with Cancer Risk in Caucasians: an Updated Meta-analysis

  • Chen, Wei;Tang, Wen-Ru;Zhang, Ming;Chang, Kwenjen;Wei, Yun-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2889-2892
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    • 2014
  • Death receptor 4 (TRAIL-R1 or DR4) polymorphisms have been associated with cancer risk, but findings have been inconsistent. To estimate the relationship in detail, a meta-analysis was here performed. A search of PubMed was conducted to investigate the association between DR4 C626G, A683C and A1322G polymorphisms and cancer risk, using odds ratios (ORs) with 95% confidence intervals. The results suggested that DR4 C626G and A683C polymorphisms were indeed associated with cancer risk (for C626G, dominant model, OR 0.991, 95%CI 0.866-1.133, p=0.015; for A683C, additive model, OR=1.140, 95%CI: 0.948-1.370, p=0.028; dominant model, OR=1.156, 95%CI: 0.950-1.406, p=0.080) in the Caucasian subgroup. However, the association was not significant between DR4 polymorphism A1322G with cancer risk in Caucasians (For A1322G, additive model: OR 1.085, 95%CI 0.931-1.289, p=0.217; dominant model: OR 1.379, 95%CI 0.934-2.035, p=0.311; recessive model: OR 1.026, 95%CI 0.831-1.268 p=0.429.). In summary, our finding suggests that DR4 polymorphism C626G and A683 rather than A1322G are associated with cancer risk in Caucasians.

Survival Analysis of Patients with Breast Cancer using Weibull Parametric Model

  • Baghestani, Ahmad Reza;Moghaddam, Sahar Saeedi;Majd, Hamid Alavi;Akbari, Mohammad Esmaeil;Nafissi, Nahid;Gohari, Kimiya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8567-8571
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    • 2016
  • Background: The Cox model is known as one of the most frequently-used methods for analyzing survival data. However, in some situations parametric methods may provide better estimates. In this study, a Weibull parametric model was employed to assess possible prognostic factors that may affect the survival of patients with breast cancer. Materials and Methods: We studied 438 patients with breast cancer who visited and were treated at the Cancer Research Center in Shahid Beheshti University of Medical Sciences during 1992 to 2012; the patients were followed up until October 2014. Patients or family members were contacted via telephone calls to confirm whether they were still alive. Clinical, pathological, and biological variables as potential prognostic factors were entered in univariate and multivariate analyses. The log-rank test and the Weibull parametric model with a forward approach, respectively, were used for univariate and multivariate analyses. All analyses were performed using STATA version 11. A P-value lower than 0.05 was defined as significant. Results: On univariate analysis, age at diagnosis, level of education, type of surgery, lymph node status, tumor size, stage, histologic grade, estrogen receptor, progesterone receptor, and lymphovascular invasion had a statistically significant effect on survival time. On multivariate analysis, lymph node status, stage, histologic grade, and lymphovascular invasion were statistically significant. The one-year overall survival rate was 98%. Conclusions: Based on these data and using Weibull parametric model with a forward approach, we found out that patients with lymphovascular invasion were at 2.13 times greater risk of death due to breast cancer.

Development of Source Profiles and Estimation of Source Contribution for VOCs by the Chemical Mass Balance Model in the Yeosu Petrochemical Industrial Complex (여수석유화학산단 내 VOCs에 대한 오염원 분류표의 개발 및 CMB 모델에 의한 기여도 산정)

  • Jeon Jun-Min;Hur Dong;Kim Dong-Sul
    • Journal of Korean Society for Atmospheric Environment
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    • v.21 no.1
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    • pp.83-96
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    • 2005
  • The purposes of this study were to characterize the local levels of VOCs (volatile organic compounds), to develop source profiles of VOCs, and to quantify the source contribution of VOCs using the CMB (chemical mass balance) model. The concentration of VOCs had been measured every 6-day duration in the SRO monitoring site in the Yeosu Petrochemical Industrial Complex from September 2000 to August 2002. The total of 35 target VOCs, which were included in the TO-14 designated from the U.S. EPA, was selected to be monitored in the study area. During a 24-h period, the ambient VOCs were sampled by using canisters placing about 10 ~ 15 m above the ground level. The collected canisters were then analyzed by a GC-MS in the laboratory. Aside from ambient sampling at the SRO site, the VOCs had been intensively and massively measured from 8 direct sources and 4 general sources in the study area. The results obtained in the study were as follows; first, the annual mean concentrations of the target VOCs were widely distributed regardless of monitoring sites in the Yeosu Petrochemical Industrial Complex. In particular, the concentrations of BTX (Benzene, Toluene, Xylene), vinyl chloride were higher than other target compounds. Second, based on these source sample data, source profiles for VOCs were developed to apply a receptor model, the CMB model. Third, the results of source apportionment study for the VOCs in the SRO Site were as follows; The source of petrochemical plant was apportioned by 31.3% in terms of VOCs mass. The site was also affected by 16.7% from wastewater treatment plant, 14.0% from iron mills, 8.4% from refineries, 4.4% from oil storage, 3.8% from automobiles, 2.3% from fertilizer, 2.3% from painting, 2.2% from waste incinerator, 0.6% from graphic art, and 0.4% from gasoline vapor sources.

The Antiallodynic Effect and the Change of the α2 Adrenergic Receptor Subtype mRNA Expression by Morphine Administration in a Spinal Nerve Ligation Rat Model (백서의 척수신경결찰모델에서 Morphine의 투여가 항이질통 효과와 척수 α2 아드레날린계 수용체 아형 mRNA 발현에 미치는 영향)

  • Chung, Kyu Yeon;Shin, Sang Wook;Kwon, Su Ah;Kim, Tae Kyun;Baek, Seung Hoon;Baik, Seong Wan
    • The Korean Journal of Pain
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    • v.22 no.1
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    • pp.21-27
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    • 2009
  • Background: The neuropathic pain arising from nerve injury is difficult to treat and the therapeutic effects of opioid drugs remain debatable. Agonists acting at the ${\alpha}_2$ adrenergic and opioid receptors have analgesic properties and they act synergistically when co-administered in the spinal cord. The lack of subtype-selective pharmacological agents has previously impeded the synergistic effects that are mediated by the adrenergic receptor subtypes. Methods: We created neuropathic pain model by ligating the L5 spinal nerve in Sprague-Dawley rats (n = 18). We divided the rats into three groups (n = 6 for each group), and we administered intraperitoneal morphine (1 mg/kg, 3 mg/kg, 5 mg/kg) and then we measured the mechanical allodynia with using von-Frey filaments for 8 hours. We then injected morphine (5 mg/kg) intraperitoneally, twice a day for 2 weeks. We measured the tactile and cold allodynia in the morphine group (n = 9) and the saline group (n = 9). After 2 weeks, we decapitated the rats and harvested the spinal cords at the level of lumbar enlargement. We compared the ${\alpha}_2$ subtype mRNA expression with that of control group (n = 6) by performing real time polymerase chain reaction (RTPCR). Results: Intraperitoneal morphine reduced the neuropathic pain behavior in the dose-dependent manner. Chronic morphine administration showed an antiallodynic effect on the neuropathic pain rat model. The rats did not display tolerance or hyperalgesia. The expression of the mRNAs of the ${\alpha}_{2A}$, ${\alpha}_{2B}$, ${\alpha}_{2C}$ subtypes decreased, and morphine attenuated this effect. But we could not get statistically proven results. Conclusions: Systemic administration of morphine can attenuate allodynia during both the short-term and long-term time course. Morphine has an influence on the expression of ${\alpha}_2$ receptor subtype mRNA. Yet we need more research to determine the precise effect of morphine on the ${\alpha}_2$ subtype gene expression.

Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies for Identification of New Inverse Agonists of Human Histamine H1 Receptor

  • Thangapandian, Sundarapandian;Krishnamoorthy, Navaneethakrishnan;John, Shalini;Sakkiah, Sugunadevi;Lazar, Prettina;Lee, Yu-No;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.31 no.1
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    • pp.52-58
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    • 2010
  • Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.

A Regional Source-Receptor Analysis for Air Pollutants in Seoul Metropolitan Area (수도권지역에서의 권역간 대기오염물질 상호영향 연구)

  • Lee, Yong-Mi;Hong, Sung-Chul;Yoo, Chul;Kim, Jeong-Soo;Hong, Ji-Hyung;Park, Il-Su
    • Journal of Environmental Science International
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    • v.19 no.5
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    • pp.591-605
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    • 2010
  • This study were to simulate major criteria air pollutants and estimate regional source-receptor relationship using air quality prediction model (TAPM ; The Air Pollution Model) in the Seoul Metropolitan area. Source-receptor relationship was estimated by contribution of each region to other regions and region itself through dividing the Seoul metropolitan area into five regions. According to administrative boundary, region I and region II were Seoul and Incheon in order. Gyeonggi was divided into three regions by directions like southern(region III), northern(IV) and eastern(V) area. Gridded emissions ($1km{\times}1km$) by Clean Air Pollicy Support System (CAPSS) of National Institute of Environmental Research (NIER) was prepared for TAPM simulation. The operational weather prediction system, Regional Data Assimilation and Prediction System (RDAPS) operated by the Korean Meteorology Administration (KMA) was used for the regional weather forecasting with 30km grid resolution. Modeling period was 5 continuous days for each season with non-precipitation. The results showed that region I was the most air-polluted area and it was 3~4 times more polluted region than other regions for $NO_2$, $SO_2$ and PM10. Contributions of $SO_2$ $NO_2$ and PM10 to region I, II and III were more than 50 percent for their own sources. However region IV and V were mostly affected by sources of region I, II and III. When emissions of all regions were assumed to reduce 10 and 20 percent separately, air pollution of each region was reduced linearly and the contributions of reduction scenario were similar to those of base case. As input emissions were reduced according to different ratio - region I 40 percent, region II and III 20 percent, region IV and V 10 percent, air pollutions of region I and III were decreased remarkably. The contributions to region I, II, III were also reduced for their own sources. However, region I, II and III affected more regions IV and V. Shortly, graded reduction of emission could be more effective to control air pollution in emission imbalanced area.

Estimation of Quantitative Source Contribution of Ambient PM-10 Using the PMF Model (PMF모델을 이용한 대기 중 PM-10 오염원의 정량적 기여도 추정)

  • 황인조;김동술
    • Journal of Korean Society for Atmospheric Environment
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    • v.19 no.6
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    • pp.719-731
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    • 2003
  • In order to maintain and manage ambient air quality, it is necessary to identify sources and to apportion its sources for ambient particulate matters. The receptor methods were one of the statistical methods to achieve reasonable air pollution strategies. Also, receptor methods, a field of chemometrics, is based on manifold applied statistics and is a statistical methodology that analyzes the physicochemical properties of gaseous and particulate pollutant on various atmospheric receptors, identifies the sources of air pollutants, and quantifies the apportionment of the sources to the receptors. The objective of this study was 1) after obtaining results from the PMF modeling, the existing sources of air at the study area were qualitatively identified and the contributions of each source were quantitatively estimated as well. 2) finally efficient air pollution management and control strategies of each source were suggested. The PMF model was intensively applied to estimate the quantitative contribution of air pollution sources based on the chemical information (128 samples and 25 chemical species). Through a case study of the PMF modeling for the PM-10 aerosols, the total of 11 factors were determined. The multiple linear regression analysis between the observed PM-10 mass concentration and the estimated G matrix had been performed following the FPEAK test. Finally the regression analysis provided quantitative source contributions (scaled G matrix) and source profiles (scaled F matrix). The results of the PMF modeling showed that the sources were apportioned by secondary aerosol related source 28.8 %, soil related source 16.8%, waste incineration source 11.5%, field burning source 11.0%, fossil fuel combustion source 10%, industry related source 8.3%, motor vehicle source 7.9%, oil/coal combustion source 4.4%, non-ferrous metal source 0.3%. and aged sea- salt source 0.2%, respectively.

Evaluation of Dermal Absorption Rate of Pesticide Chlorpyrifos Using In Vitro Rat Dermal Tissue Model and Its Health Risk Assessment

  • Kim, Su-Heyun;Jang, Jae-Bum;Park, Kyung-Hun;Paik, Min-Kyoung;Jeong, Sang-Hee
    • Biomedical Science Letters
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    • v.22 no.4
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    • pp.140-149
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    • 2016
  • All pesticides must be assessed strictly whether safe or not when agricultural operators are exposed to the pesticides in farmland. A pesticide is commonly regarded as safe when estimated dermal absorption amount is lower than the acceptable operator's exposure level (AOEL). In this study, dermal absorption rate of chlorpyrifos, a widely used organophosphate insecticide, was investigated using rat dermal tissue model. Chlorpyrifos wettable powder solved in water (250, 500 and 2,500 ppm) was applied to freshly excised rat dermal slices ($341{\sim}413{\mu}m$ thickness) on static Franz diffusion cells at $32^{\circ}C$ for 6 hours. After exposure period of 6 hours, and then washing-at residual amount of chlorpyrifos was analyzed in dermal tissues, tape strips, washing solution, washing swabs of receptor bottles and receptor fluids at 1, 2, 4, 8 and 24 hours. Chlorpyrifos was only detected in dermal tissue but not found in receptor fluid at each concentration and time point, and the absorption rate of 250, 500 and 2,500 ppm was 2.36%, 1.96% and 1.69%, respectively. The estimated exposure level of chlorpyrifos was calculated as 0.012 mg/kg bw/day. The health risk for farmers in this condition is a level of concern because the estimated exposure level is 12 times higher than AOEL 0.001 mg/kg bw/day. However, actual health risk will be alleviated than estimated because absorbed chlorpyrifos is not permeated into internal body system and only retained in skin layer.

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

  • Son, Ji-Seon;Kwon, Young-Bae
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.6
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    • pp.359-364
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    • 2010
  • Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

The effect of cetirizine, a histamine 1 receptor antagonist, on bone remodeling after calvarial suture expansion

  • Hwang, Soonshin;Chung, Chooryung J.;Choi, Yoon Jeong;Kim, Taeyeon;Kim, Kyung-Ho
    • The korean journal of orthodontics
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    • v.50 no.1
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    • pp.42-51
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    • 2020
  • Objective: The objective of this study was to evaluate the effects of cetirizine, a histamine 1 receptor antagonist, on bone remodeling after calvarial suture expansion. Methods: Sixty male Sprague-Dawley rats were divided into 4 groups; the phosphate-buffered saline (PBS)-injected no expansion group, cetirizine-injected no expansion group, PBS-injected expansion group, and cetirizine-injected expansion group, and were observed at 7, 14, and 28 days. Five rats per group were examined at each observation day. Daily injections of cetirizine or PBS were administered to the relevant groups starting 2 weeks prior to expander insertion. A rapid expander was inserted in the calvarial bone to deliver 100 cN of force to the parietal suture. The specimens were prepared for hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining. Suture opening and bone regeneration were evaluated using microcomputed tomography and bone histomorphometric analysis. Serum blood levels of osteocalcin and carboxy-terminal collagen crosslinks (CTX) were also evaluated. Results: TRAP-positive cell counts and CTX levels decreased while osteocalcin levels increased in the cetirizine-injected expansion group at observation day 28. In the expansion groups, the mineralized area gradually increased throughout the observation period. At day 28, the cetirizine-injected expansion group showed greater bone volume density, greater mineralized area, and narrower average suture width than did the PBS-injected expansion group. Conclusions: Cetirizine injection facilitated bone formation after suture expansion, mostly by suppressing osteoclastic activity. Histamine 1 receptor antagonists may aid in bone formation after calvarial suture expansion in the rat model.