• Title/Summary/Keyword: %24AT_1%24 receptor

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Study on the Agonistic Effect of Chunmajeongal-tang Extract to the $GABA_A/benzodiazepine$ Receptor Complex (천마전헐탕의 $GABA_A/benzodiazepine$ 신경수용체(神經受容體) 효능활성(效能活性)에 관(關)한 연구(硏究))

  • Kim, Sung-Wook;Gong, Dae-Jong;An, Hyeon-Guk;Kim, Geun-Woo;Koo, Byung-Soo
    • Journal of Oriental Neuropsychiatry
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    • v.15 no.1
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    • pp.77-86
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    • 2004
  • Objective : This study was performed to investigate the agonistic activity of Chunmajeongal-tang extract to the $GABA_A/benzodiazepine$ receptor complex. Methods : Male mice and Sprague-Dawley rats were used for this experiment. Chunmajeongal-tang Prescription was extracted with 80% methanol, evaporated in vacuo and dried with freeze dryer. The agonistic activity to the GABA/ benzodiazepine receptor complex and GABA transaminase activity were measured in vitro. Results : Chunmajeongal-tang extract inhibited dose-dependently the binding of [3H]Ro15-1788, an antagonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $82.4{\pm}4.12%$ inhibition at a dose of 5.0 mg/kg. This extract inhibited dose-dependently the binding of [3H]flunitrazepam, an agonist on GABA/benzodiazepine receptor complex, in rat cerebral cortices, showing $5.6{\pm}1.24%$ inhibition. Furthermore, Chunmajeongal-tang extract inhibited the binding of [3H]flunitrazepam in the presence of GABA/NaCI with $13.2{\pm}0.44%$ inhibition, its inhibitory effect exhibited a positive GABA shift, which means that this extract activates a GABAergic neurotransmission.

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Transient neonatal diabetes mellitus caused by a de novo ABCC8 gene mutation

  • Kong, Jung-Hyun;Kim, June-Bum
    • Clinical and Experimental Pediatrics
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    • v.54 no.4
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    • pp.179-182
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    • 2011
  • Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), have also been implicated in TNDM. Herein, we present the case of a male child with TNDM whose mutational analysis revealed a heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp mutation in the SUR1 protein. The parents were clinically unaffected and did not show a mutation in the ABCC8 gene. This is the first case of a de novo ABCC8 gene mutation in a Korean patient with TNDM. The patient was initially treated with insulin and successfully switched to sulfonylurea therapy at 14 months of age. Remission of diabetes had occurred at the age of 16 months. Currently, the patient is 21 months old and is euglycemic without any insulin or oral hypoglycemic agents. His growth and physical development are normal, and there are no delays in achieving neurological and developmental milestones.

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.

Impact of RGD Peptide Tethering to IL24/mda-7 (Melanoma Differentiation Associated Gene-7) on Apoptosis Induction in Hepatocellular Carcinoma Cells

  • Bina, Samaneh;Shenavar, Fatemeh;Khodadad, Mahboobeh;Haghshenas, Mohammad Reza;Mortazavi, Mojtaba;Fattahi, Mohammad-Reza;Erfani, Nasrollah;Hosseini, Seyed Younes
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6073-6080
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    • 2015
  • Background: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Materials and Methods: Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. Results and Conclusions: In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (P<0.001). Again, flow cytometry analysis showed a significant apoptosis induction by simple mda-7 gene but not for those RGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (P<0.001). Protein modelling analysis revealed that tethering RGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

ATP and Purinergic Receptor Agonists Stimulate the Mitogen-Activated Protein Kinase Pathway and DNA Synthesis in Mouse Mammary Epithelial Cells

  • Yuh In-Sub
    • Reproductive and Developmental Biology
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    • v.28 no.4
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    • pp.211-219
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    • 2004
  • The effects of adenosine 5'-triphosphate (ATP) and ATP analogs, P/sub 2y/ purinoceptor agonists, on growth of normal mouse mammary epithelial cells (NMuMG) were examined. Cells were plated onto 24 well plates in DMEM supplemented with 10 % fetal calf serum. After serum starvation for 24 hours, ATP, P/sub 2y/ purinoceptor agonists (AdoPP[NH]P, ATP-α-S, ATP-γ-S, β, γ-me-ATP and 2me-S-ATP), P/sub 2u/ purinoceptor agonist (UTP) and P/sub 2y/ purinoceptor antagonists (Reactive Blue 2, more selective to P/sub 2y/ receptor than PPADS; PPADS) were added. DNA synthesis was estimated as incorporation of 3H-thymidine into DNA (1 hour pulse with 1 μ Ci/ml, 18~19 hours after treatment). ATP, Adopp[NH]P, ATP-α-S or ATP-γ-S, significantly increased DNA synthesis at 1, 10 and 100 μM concentrations with dose-dependency (P<0.05), and the maximum responses of ATP and ATP analogs were shown at 100 μM concentration (P<0.05). The potency order of DNA synthesis was ATP≥ATP- γ -S>Adopp [NH]P>ATP-α-S. β, γ -me-ATP, 2me-S-ATP and UTP did not increase DNA synthesis. In autoradiographic analysis of percentage of S-phase cells, similar results were observed to those of DNA synthesis. Addition of 1, 10 or 100 μM Reactive Blue 2 or PPADS significantly decreased ATP (100 μM)-induced DNA synthesis, however, PPADS was less effective than Reactive Blue 2. In Elvax 40P implant experiment, ATP directly stimulated mammary endbud growth in situ suggesting the physiological regulator of ATP in mammary growth. ATP 100 μM rapidly increased MAPK activity, reaching a maximum at 5 min and then gradually decreasing to the base level in 30 min. ATP analogs, Adopp[NH]P and ATP-γ-S also increased MAPK activity, however, β, γ-me-ATP and 2me-S-ATP did not. The inhibitor of the upstream MAPK kinase (MEK), PD 98059 (25 μM), effectively reduced ATP (100 μM) or EGF(10 ng/ml, as positive control)-induced MAPK activity and DNA synthesis (P<0.05). These results indicate that ATP-induced DNA synthesis was prevented from the direct inhibition of MAPK kinase pathway. Overall results support the hypothesis that the stimulatory effects of normal mouse mammary epithelial growth by addition of ATP or ATP analogs are mediated through mammary tissue specific P/sub 2y/ purinoceptor subtype, and MAPK activation is necessary for the ATP-induced cell growth.

Source Identification of Gaseous Mercury Measured in New York State Using Hybrid Receptor Modeling (수용원 모델을 사용한 대기 중 수은 오염원의 위치 추정에 대한 연구)

  • Han Young-Ji
    • Journal of Korean Society for Atmospheric Environment
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    • v.22 no.2
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    • pp.179-189
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    • 2006
  • Ambient gas phase mercury concentrations including elemental mercury ($Hg^0$) were measured at the Potsdam, Stockton, and Sterling sites in NY from 2000 to 2003. Also, concentrations of ambient reactive gaseous mercury (RGM; $Hg^{2+}$) were measured at the Potsdam site during one year. The contribution of RGM($4.2{\pm}6.4pg/m^3$) was about $0.2{\sim}3%$ of the total gas phase mercury concentration measured (TGM: $1.84{\pm}1.24,\;1.83{\pm}0.32,\;3.02{\pm}2.14ng/m^3$ in Potsdam. Stockton, and Sterling, respectively) at the receptor sites. Potential Source Contribution Function (PSCF), a hybrid receptor modeling incorporating backward trajectories was performed to identify source areas of TGM. Using PSCF, southern New York, North Carolina, and eastern Massachusetts were identified as important source areas in the United States, while the copper smelters and waste incinerators located in eastern Quebec and Ontario were determined to be significant sources in Canada. The Atlantic Ocean was suggested to be a possible mercury source. PSCF incorporating back-dispersion and deposition was applied for RGM , as well as PSCF based on 2-days back-trajectories. Two different approaches yielded considerably different results, primarily due to the consideration of dispersion rather than deposition. Using back-trajectory based PSCF, eastern Ohio, southern New York, and southern Pennsylvania where large coal -fired power plants area located were identified as the large sources in US. Metallurgical industry located in eastern Quebec was resolved as well. From the result of back-dispersion and deposition based PSCF, Pennsylvania, mining facilities around Lake Superior, Toronto, Boston, MA, Quebec, and coal power plants in NY were identified to be the significant source areas for Potsdam site.

Lower Incidence but More Aggressive Behavior of Right Sided Breast Cancer in Pakistani Women: Does Right Deserve More Respect?

  • Fatima, Nosheen;Zaman, Maseeh Uz;Maqbool, Aamir;Khan, Shaista H.;Riaz, Nazia
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.43-45
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    • 2013
  • Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population. Materials and Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM. Results: The left to right sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The right sided BC was observed in younger age group (46:52 years; p<0.0001) and with a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM had relatively higher negative receptor status with a significant predominance of right sided BC. The overall incidence of BM on BS was 28% and relatively higher in right than left breast (33%:24% p=0.068). The average number of BM sites was also significantly greater for the right side (6:4, P<0.0001). The % cumulative risk of BM in right breast was noted at significantly smaller PTS than left side with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event free survival of BM in left sided BC was significantly higher than for the right side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right BC. Conclusions: 1) A left sided predominance of BC was seen in local population; 2) right sided BC had a more aggressive behavior with extensive and earlier appearance of BM at relatively younger age, smaller PTS and receptor (s) negativity.

Study on White Ginseng Extract Preparation for Cognition Improvement (인지능 개선 효과 증진을 위한 백삼 추출물 조제 연구)

  • Lee, Seung Eun;Kim, Geum Sook;Lee, Dae Young;Kim, Hyung Don;Lee, Jae Won;Lee, Young Sup;Park, Chun Geun;Ahn, Young Sup
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.5
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    • pp.375-385
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    • 2016
  • Background: The study was conducted to elucidate the extraction conditions under which white ginseng has cognition-improving efficacy. Methods and Results: Extracts from white ginseng under different solvent and temperature conditions were analyzed for ginsenoside content and inhibitory effect on N-methyl-D-aspartate (NMDA) receptor and acetylcholinesterase. The total ginsenoside contents and amounts of ginsenoside Rb1 plus ginsenoside Rg1 from the 1st extracts (prepared with EtOH/$H_2O$ as solvent) were higher than those from the 2nd extracts (extracted with $H_2O$ after the 1st EtOH/$H_2O$ extraction). The contents in the 1st and 2nd extracts produced at $80^{\circ}C$ were also higher than those obtained at $50^{\circ}C$. Samples from the 1st extraction at $80^{\circ}C$ indicated higher inhibitory activities on NMDA receptors-whose excessive activation is thought to mediate the calcium-dependent neurotoxicity associated with several neurodegenerative diseases-than those from the 2nd extraction. Among the samples prepared at varying temperatures, the extract prepared at $50^{\circ}C$ showed the highest suppression activity on NMDA receptors. Note, however, that the extracts from the 2nd extraction at $50^{\circ}C$ inhibited acetylcholinesterase-whose inhibition could be a therapeutic strategy for neurodegenerative diseases with cognitive deficits and memory malfunction-more effectively than those from the 1st extraction. Conclusions: To enhance the cognition-improving activity of white ginseng extract, it is suggested that the extracts be utilized after being combined the 1st extracts (made with EtOH/$H_2O$ solvent) and the 2nd extracts (prepared with $H_2O$) at low temperature.

Application of Representative $PM_{2.5}$ Source Profiles for the Chemical Mass Balance Study in Seoul

  • Kang, Choong-Min;Kang, Byung-Wook;SunWoo, Young;Lee, Hak-Sung
    • Journal of Korean Society for Atmospheric Environment
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    • v.24 no.E1
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    • pp.32-43
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    • 2008
  • Source samples were collected to construct source profiles for 9 different source types, including soil, road dust, gasoline/diesel-powered vehicles, a municipal incinerator, industrial sources, agricultural/biomass burning, marine aerosol, and a coal-fired power plant. Seasonal profiles for 'Chinese aerosol', aerosols derived from the urban area of China, were reconstructed from seasonal $PM_{2.5}$ compositions reported in Beijing, China. Ambient $PM_{2.5}$ at a receptor site was also measured during each of the four seasons, from April 2001 to February 2002, in Seoul. The Chemical Mass Balance receptor model was applied to quantify source contributions during the study period using the estimated source profiles. Consequently, motor vehicle exhaust (33.0%), in particular 23.9% for diesel-powered vehicles, was the largest contributor affecting the $PM_{2.5}$ levels in Seoul, followed by agricultural/biomass burning (21.5%) and 'Chinese aerosol' (13.1%), indicating contributions from long-range transport. The largest contributors by season were: for spring, 'Chinese aerosol' (31.7%); for summer, motor vehicle exhaust (66.9%); and for fall and winter, agricultural/biomass burning (31.1% and 40.1%, respectively). These results show different seasonal patterns and sources affecting the $PM_{2.5}$ level in Seoul, than those previously reported for other cities in the world.

The Effects of Prunus on Diabetic Nephropathy Rats Induced by Unilateral Nephrectomy and Streptozotocin (도인(挑仁)이 일측 신절제와 streptozotocin으로 유발된 당뇨병성 신증 Rat에 미치는 영향)

  • Kim, Nam-Kyu;Oh, Jae-Seon;Jeon, Sang-Yun
    • The Journal of Internal Korean Medicine
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    • v.35 no.4
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    • pp.519-531
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    • 2014
  • Objectives: Diabetic nephropathy is the most common cause of end stage renal disease. Transforming growth factor (TGF)-${\beta}1$, type IV collagen, advanced glycation end-products (AGEs), and angiotensin II type 1 receptor (AT1) are the main factors of diabetic nephropathy. We investigated the effects of Prunus on renal function and histopathological changes of diabetic nephropathy rat model induced by unilateral nephrectomy and streptozotocin. Methods: Diabetes was induced in male Sprague-Dawley rats ($290{\pm}10g$) by injecting streptozotocin (55 mg/kg) into the tail vein after unilateral nephrectomy. Rats were divided into 3 groups (n=6): normal, control, and Prunus. After 8 weeks of oral administration of Prunus extract on the Prunus group from 3 days after streptozotocin injection, we checked weight, 24 hrs urine, blood biochemistry and renal tissue to evaluate renal function and histopathological changes by examining parameters including albuminuria, BUN, creatinine, cholesterol, low density lipoprotein (LDL), triglyceride, TGF-${\beta}1$, type IV collagen, AGEs, and AT1. We also measured mRNA expression of TGF-${\beta}1$, type IV collagen, AGEs, and AT1 by Real Time polymerase chain reaction (RT-PCR). Results: Prunus decreased the amount of 24 hrs proteinuria, and inhibited histopathological changes of diabetic nephropathy including the expression and accumulation of TGF-${\beta}1$, type IV collagen and AGEs which could promote development of diabetic nephropathy. Prunus also inhibited mRNA expression of TGF-${\beta}1$, type IV collagen. Conclusions: These findings suggest that Prunus might protect the renal function and inhibit the development of renal injury by regulating factors including TGF-${\beta}1$, type IV collagen, AGEs, except AT1, so Prunus can be used for diabetic patients to prevent the progression of diabetic nephropathy.