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Sample records for propranolol promotes egr1

  1. The study on Egr-1 promoter which is radioactive promoter

    International Nuclear Information System (INIS)

    Zhang Chunzhi; Guo Yang; Lv Zhonghong

    2006-01-01

    Radiogenetic therapy is a heated reaseach on oncotherapy. Early growth response gene-1 (Egr-1) gene promoter is a probably means in radiogenetic therapy. The article review studying on Egr-1 gene promoter and constructing regulating gene expressing system by radiation-inducible Egr-1 gene promoter. (authors)

  2. Construction of recombinant adenovirus with Egr-1 promoter and Smad7 cDNA and study of the Egr-1 promoter's biological activity

    International Nuclear Information System (INIS)

    Cai Xuwei; Fu Xiaolong; Yang Jian; Song Houyan

    2005-01-01

    Objective: To construct a recombinant replication-defective adenovirus containing Egr-1 promoter and Smad7 cDNA, then to evaluate the biological activity of Egr-1 promoter. Methods: Based on Adeno- X TM expression system, CMV promoter of the pShuttle vector was replaced by Egr-1 promoter, and the Smad7 cDNA was subcloned into the MCS(multiple cloning site) of pShuttle. The recombinant pShuttle was then sub-cloned into the Adeno-X TM genome, which was transformed into E. coli to get recombinant Adeno-X TM plasmid DNA. The recombinant adenovirus was packaged and amplified in the transfected HEK293 cells before it was purified and tested for viral titer. The fibroblasts (3T6 cells) infected by the recombinant adenovirus were irradiated , and the activity of Egr-1 promoter was quantitively determined by the amount of Smad7 protein expressed in the 3T6 cells using Western blot. Results: Identified by restriction endonuclease analysis and PCR, the recombinant adenovirus containing Egr-1 promoter and Smad7 cDNA was constructed successfully, with a viral titer of 1.0 x 10 11 TCID 50 /ml. The expressed amount of Smad7 protein varied at different dose levels and different time points post-irradiation in the 3T6 cells infected with the recombinant adenovirus. The amount of Smad7 protein increased along with the rising of the irradiation dose, and remained at a high expression level from 8 Gy to 15 Gy. The amount of Smad7 protein started to increase at 2 hours post-irradiation, and maintained a relatively high level for the next 5 hours before it descended, which was not observed in the control 3T6 cells. Conclusions: With the aid of Adeno-X TM expression system and molecular cloning techniques, construction of recombinant adenovirus could be quick and efficient. The recombined Egr-1 promoter has the activity of regulating the expression of downstream Smad7 cDNA. The increase in Smad7 expression under control of Egr-1 promoter induced by ionizing radiation is time- and dose

  3. The progress of tumor gene-radiotherapy induced by Egr-1 promoter

    International Nuclear Information System (INIS)

    Guo Rui; Li Biao

    2010-01-01

    The promoter of early growth response gene-1 (Egr-1) is a cis-acting element of Egr-1, and its activity is regulated by inducers such as ionizing radiation, free radical. In designated gene-radiotherapy system, radiation combined with therapeutic gene (such as tumor necrosis factor-α gene, suicide gene) can spatially and temporally regulate therapeutic gene expression in the irradiated field, produced a marked effect, while little systemic toxicities were observed. The combination of radiotherapy and gene therapy is promising in tumor therapy. (authors)

  4. Study on cloning of the Egr-1 promoter and its radiation-inducible property

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: Egr-1 promoter was amplified and Egr-PGL plasmid was constructed to study the expression of luciferase in transfected NIH3T3 cells after different doses of X-ray irradiation. Methods: Egr-1p was amplified by PCR and inserted into PGL3-E vector. The expression of luciferase induced by X-ray was studied by counting the light of luciferase and substrate. Results: Egr-1 cDNA was obtained by PCR and was sequenced. The results indicated the sequence was almost correct. The Egr-1p was connected with PGL3 vector and was detected by electrophoresis. The constructs were used to transfect mouse NIH3T3 cells to characterize the regulatory function of Egr-1p after exposure to X-ray irradiation. The results indicate that the expression of luciferase of all groups irradiated is higher than that of 0 Gy group. The expression of groups irradiated is about 5-7.5 times greater than that of 0 Gy group. Conclusion: Egr-1p obtained can induce the expression of its downstream gene after different doses of X-ray irradiation. Low dose irradiation also can do it and it is may be more important in tumor gene therapy

  5. EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair.

    Science.gov (United States)

    Tao, Xu; Liu, Junpeng; Chen, Lei; Zhou, You; Tang, Kanglai

    2015-01-01

    The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.

  6. EGR1 Induces Tenogenic Differentiation of Tendon Stem Cells and Promotes Rabbit Rotator Cuff Repair

    Directory of Open Access Journals (Sweden)

    Xu Tao

    2015-01-01

    Full Text Available Background/Aims: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1 in the differentiation of tendon stem cells (TSCs and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Methods: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. Results: EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. Conclusion: EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries.

  7. Feasibility of a novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS expression in malignant glioma via baculovirus

    International Nuclear Information System (INIS)

    Guo Rui; Tian Lipeng; Han Bing; Xu Haoping; Zhang Miao; Li Biao

    2011-01-01

    Purpose: As intracellular iodine is released rapidly, increased expression of sodium/iodide symporter (NIS) is required for effective radioiodine treatment of tumor. As Egr1 promoter is activated by 131 I and may promote human NIS (hNIS) expression, hNIS also induces 131 I uptake and activates Egr1, so the existence of a positive feedback effect of 131 I-promoted Egr1-hNIS expression is possible. Our purpose was to investigate the possible existence of this positive feedback effect through a series of in vitro pioneer studies. Method: Recombinant baculovirus (Bac-Egr1-hNIS) encoding the hNIS gene under the control of a radiation-inducible Egrl promoter was constructed. To test 131 I-promoted hNIS expression, human malignant glioma U87 cells were transfected with Bac-Egr1-hNIS, stimulated with or without 131 I; the expression of hNIS protein was detected by immunofluorescence and flow cytometry test. In addition, the uptake and efflux of 131 I were determined after the incubation of Bac-Egr1-hNIS-transfected U87 cells with or without 131 I. Results: Immunocytochemical staining and flow cytometry test showed a higher hNIS protein expression in Bac-Egr1-hNIS-transfected U87 cells with 131 I stimulation than in cells without stimulation. Bac-Egr1-hNIS-transfected U87 cells accumulated up to about 4.05 times of 131 I after 131 I stimulation. The amount of 131 I uptake in both groups showed a baculovirus dose-dependent manner. However, rapid efflux of radioactivity was observed in both groups, with 50% lost during the first 2 min after the 131 I-containing medium had been replaced by a nonradioactive medium. Conclusion: Our results indicated that an improved transgene expression of 131 I-stimulated hNIS in U87 cells using a baculovirus vector containing the Egr1 promoter is possible, and the increased expression of hNIS is responsible for a higher 131 I uptake. It might provide a reference for the existence of a positive feedback effect in 131 I-promoted Bac-Egr1-h

  8. Egr-1 activation by cancer-derived extracellular vesicles promotes endothelial cell migration via ERK1/2 and JNK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yae Jin Yoon

    Full Text Available Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs, also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1 activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.

  9. Function of the EGR-1/TIS8 radiation inducible promoter in a minimal HSV-1 amplicon system

    International Nuclear Information System (INIS)

    Spear, M.A.; Sakamoto, K.M.; Herrlinger, U.; Pechan, P.; Breakefield, X.O.

    1997-01-01

    Purpose: To evaluate function of the EGR-1/TIS8 promoter region in minimal HSV-1 amplicon system in order to determine the feasibility of using the system to regulate vector replication with radiation. Materials and Methods: A 600-base pair 5' upstream region of the EGR-1 promoter linked to chloramphenicol acetyltransferase (CAT) was recombined into a minimal HSV-1 amplicon vector system (pONEC). pONEC or a control plasmid was transfected into U87 glioma cells using the Lipofectamine method. Thirty-six hours later one aliquot of cells from each transfection was irradiated to a dose of 20 Gy and another identical aliquot served as a control. CAT activity was assayed 8 hours after irradiation. Results: pONEC transfected cells irradiated with 20 Gy demonstrated 2.0 fold increase in CAT activity compared to non-irradiated cells. Cells transfected with control plasmid showed no change in CAT activity. Unirradiated pONEC cells had CAT activity 1.3 times those transfected with control plasmid. Conclusion: We have previously created HSV-1 gene therapy amplicon vector systems which allow virus-amplicon interdependent replication, with the intent of regulating replication. The above data demonstrates that a minimal amplicon system will allow radiation dependent regulation by the EGR-1 promoter, thus indicating the possibility of using this system to regulate onsite, spatially and temporally regulated vector production. Baseline CAT activity was higher and relative induction lower than other reported expression constructs, which raises concern for the ability of the system to produce a differential in transcription levels sufficient for this purpose. This is possibly the result of residual promoter/enhancer elements remaining in the HSV-1 sequences. We are attempting to create constructs lacking these elements. Addition of secondary promoter sequences may also be of use. We are also currently evaluating the efficacy of the putative IEX-1 radiation inducible promoter region in

  10. Radioprotective effect of hematopoietic growth factor gene therapy regulated by Egr-1 promoter on radiation injury of SCID mice

    International Nuclear Information System (INIS)

    Du Nan; Pei Xuetao; Luo Chengji; Su Yongping; Cheng Tianmin

    2002-01-01

    Objective: To explore the radioprotective effect of the expression of hematopoietic growth factors regulated by radio-inducible promoter on radiation injury. Methods: The human FL cDNA and EGFP cDNA were linked together with an internal ribosome entry site (IRES) and then inserted into the eukaryotic expression vector pCI-neo with the Egr-1 promoter (Egr-EF), and further transduced into bone marrow stromal cell lines HFCL (HFCL/EF). The HFCL/EF and CD34 + cells from human umbilical cord blood were transplanted i.v. one after the other into sublethally irradiated severe combined immunodeficient (SCID) mice. The number of peripheral blood WBC and human cells engrafted in recipient mice were detected by flow cytometry and CFU-GM assay. Results: In contrast to two control groups (HFCL and HFCL/F), HFCL/EF (the Egr-1 regulatory element-driven expression of FL gene therapy) resulted in a proportionally obvious increase in the number of the WBC at early stage after irradiation. Significant differences were found for CD45 + , CD34 + , CFU-GM, and nucleated cells in the bone marrow. Conclusion: Hematopoietic growth factor gene therapy regulated by radio-inducible promoter has radioprotective effect on radiation hematopoietic injury

  11. Basic calcium phosphate crystal-induced Egr-1 expression stimulates mitogenesis in human fibroblasts

    International Nuclear Information System (INIS)

    Zeng, Xiao R.; Sun Yubo; Wenger, Leonor; Cheung, Herman S.

    2005-01-01

    Previously, we have reported that basic calcium phosphate (BCP) crystals stimulate mitogenesis and synthesis of matrix metalloproteinases in cultured human foreskin and synovial fibroblasts. However, the detailed mechanisms involved are still unclear. In the present study, using RT-PCR and Egr-1 promoter analysis we showed that BCP crystals could stimulate early growth response gene Egr-1 transcription through a PKCα-dependent p44/p42 MAPK pathway. Using a retrovirus gene expression system (Clontech) to overexpress Egr-1 in human fibroblast BJ-1 cells resulted in promotion of mitogenesis measured either by MTT cell proliferation analysis or by direct cell counting. The results demonstrate that Egr-1 may play a key role in mediating BCP crystal-induced synovial fibroblast mitogenesis

  12. Expression and prognostic value of EGR1 and EGR3 in gliomas

    DEFF Research Database (Denmark)

    Møldrup Knudsen, Arnon

    Introduction Gliomas are the most frequent primary brain tumors. For the most malignant glioma – the glioblastoma - the median survival is below 15 months. Since only few prognostic biomarkers are of benefit in daily practice, new markers are urgently needed. EGR1 and EGR3 are transcription factors...... involved in the regulation of cell-cycle, but they have also been associated with the migration of cancer cells. Studies have shown prognostic potential of EGR1 and EGR3 in breast-, gastric-, colorectal-, and prostate cancer. The purpose of this study was to investigate the expression and potential....... Cox proportional hazards regression showed that a high EGR1 fraction remained a significant prognostic variable when adjusted for confounders, both in all gliomas as one group (P=0.048) and glioblastomas exclusively (P=0.011). The combination of EGR1 high/EGR3 low in glioblastomas also remained...

  13. Transcriptional regulation of the p73 gene, a member of the p53 family, by early growth response-1 (Egr-1)

    International Nuclear Information System (INIS)

    Lee, Sang-Wang; Kim, Eun-Joo; Um, Soo-Jong

    2007-01-01

    To elucidate the regulatory mechanism of p73 gene expression, we analyzed the human p73 promoter and found three putative Egr-1-binding sites located upstream of exon 1 (-1728, -321, and -38). The Egr-1 responsiveness of these sites was analyzed by transient transfection assays using 5'- and 3'-serial truncations of the p73 promoter, subcloned in a CAT reporter vector. The functional significance of the region was further confirmed by an electrophoretic mobility shift assay using the Egr-1 protein synthesized in vitro and a [ 32 P]-labeled middle site sequence, followed by competition with unlabeled wild-type or mutant oligonucleotides and supershift assays using an anti-Egr-1 antibody. When induced by either the nitric oxide donor NOC-18 or the PPARγ agonist troglitazone, Egr-1 bound to the p73 promoter, as assessed by chromatin immunoprecipitation assays, accompanied by increased expression of p73. MTT assays revealed that cell growth was significantly inhibited on treating the cells with troglitazone. Overall, our results provide direct evidence that Egr-1 positively regulated p73 expression by binding to its promoter in vivo, consistent with Egr-1 and p73 being involved in p53-independent tumor suppression

  14. Analysis list: Egr1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Egr1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr1.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Eg...r1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr1.Blood.tsv,http://dbarch...ive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr1.Liver.tsv http://dbarchive.bioscience

  15. Regulation of the voltage-gated Ca2+ channel CaVα2δ-1 subunit expression by the transcription factor Egr-1.

    Science.gov (United States)

    González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Gómez-Mora, Kimberly; Felix, Ricardo

    2018-04-23

    It is well known that the Ca V α 2 δ auxiliary subunit regulates the density of high voltage-activated Ca 2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of Ca V α 2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of Ca V α 2 δ. Overexpression and knockdown analysis of Egr-1 showed significant changes in the transcriptional activity of the Ca V α 2 δ promoter. Egr-1 also regulated the expression of Ca V α 2 δ at the level of protein. Also, functional studies showed that Egr-1 knockdown significantly decreases Ca 2+ currents in dorsal root ganglion (DRG) neurons, while overexpression of the transcription factor increased Ca 2+ currents in the F11 cell line, a hybrid of DRG and N18TG2 neuroblastoma cells. Studying the effects of Egr-1 on the transcriptional expression of Ca V α 2 δ could help to understand the regulatory mechanisms of this protein in both health and disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

    Science.gov (United States)

    Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

    2014-12-01

    EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

  17. Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Chen

    2008-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7. Cigarette smoke extract (CSE is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1 and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

  18. EGR-1 regulates Ho-1 expression induced by cigarette smoke

    International Nuclear Information System (INIS)

    Chen, Huaqun; Wang, Lijuan; Gong, Tao; Yu, Yang; Zhu, Chunhua; Li, Fen; Wang, Li; Li, Chaojun

    2010-01-01

    As an anti-oxidant molecule, heme oxygenase-1 (HO-1) has been implicated in the protection of lung injury by cigarette smoke (CS). The mechanisms regulating its expression have not been defined. In this report, the role of early growth response 1 (EGR-1) in the regulation of Ho-1 expression was investigated. In C57BL/6 mice with CS exposure, HO-1 was greatly increased in bronchial epithelial cells and alveolar inflammatory cells. In primary cultured mouse lung fibroblasts and RAW264.7 cells exposed to cigarette smoke water extract (CSE), an increase in HO-1 protein level was detected. In addition, CSE induced HO-1 expression was decreased in Egr-1 deficient mouse embryo fibroblasts (Egr-1 -/- MEFs). Nuclear localization of EGR-1 was examined in mouse lung fibroblasts after exposure to CSE. Luciferase reporter activity assays showed that the enhancer region of the Ho-1 gene containing a proposed EGR-1 binding site was responsible for the induction of HO-1. A higher increase of alveolar mean linear intercept (Lm) was observed in lung tissues, and a larger increase in the number of total cells and monocytes/macrophages from bronchial alveolar lavage fluid was found in CS-exposed mice by loss of function of EGR-1 treatment. In summary, the present data demonstrate that EGR-1 plays a critical role in HO-1 production induced by CS.

  19. Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis

    Directory of Open Access Journals (Sweden)

    Karin Zins

    2014-01-01

    Full Text Available The early growth response transcription factor Egr-1 controls cell specific responses to proliferation, differentiation and apoptosis. Expression of Egr-1 and downstream transcription is closely controlled and cell specific upregulation induced by processes such as hypoxia and ischemia has been previously linked to multiple aspects of cardiovascular injury. In this study, we showed constitutive expression of Egr-1 in cultured human ventricular cardiac fibroblasts, used adenoviral mediated gene transfer to study the effects of continuous Egr-1 overexpression and studied downstream transcription by Western blotting, immunohistochemistry and siRNA transfection. Apoptosis was assessed by fluorescence microscopy and flow cytometry in the presence of caspase inhibitors. Overexpression of Egr-1 directly induced apoptosis associated with caspase activation in human cardiac fibroblast cultures in vitro assessed by fluorescence microscopy and flow cytometry. Apoptotic induction was associated with a caspase activation associated loss of mitochondrial membrane potential and transient downstream transcriptional up-regulation of the pro-apoptotic gene product Siva-1. Suppression of Siva-1 induction by siRNA partially reversed Egr-1 mediated loss of cell viability. These findings suggest a previously unknown role for Egr-1 and transcriptional regulation of Siva-1 in the control of cardiac accessory cell death.

  20. The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

    Science.gov (United States)

    Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa; Bastianelli, Daniela; Maroder, Marella; Ragona, Giuseppe; Roussel, Pascal; Thiry, Marc; Mercola, Dan; Calogero, Antonella

    2014-01-01

    EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

  1. The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

    Directory of Open Access Journals (Sweden)

    Donatella Ponti

    Full Text Available EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

  2. Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

    Science.gov (United States)

    Park, Mira; Kim, Hye-Ryun; Kim, Yeon Sun; Yang, Seung Chel; Yoon, Jung Ah; Lyu, Sang Woo; Lim, Hyunjung Jade; Hong, Seok-Ho; Song, Haengseok

    2018-07-15

    Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E 2 ) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E 2 induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions. Spatiotemporal expression of c-Kit followed that of EGR1 in uteri of ovariectomized mice at various time points after E 2 treatment. E 2 activated ERK1/2 and p38 to induce EGR1, which then activated c-Kit expression in the uterus. EGR1 transfection produced rapid and transient induction of c-KIT in a time- and dose-dependent manner. Furthermore, luciferase assays to measure c-Kit promoter activity confirmed that a functional EGR1 binding site(s) (EBS) was located within -1 kb of the c-Kit promoter. Site-directed mutagenesis and chromatin immunoprecipitation-PCR for three putative EBS within -1 kb demonstrated that the EBS at -818/-805 was critical for EGR1-dependent c-Kit transcription. c-Kit expression was significantly increased in the uterus on day 4 and administration of Masitinib, a c-Kit inhibitor, effectively interfered with embryo implantation. Collectively, our results showed that estrogen induces transcription factor EGR1 to regulate c-Kit transcription for uterine receptivity for embryo implantation in the mouse uterus. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Construction of pEgr.p-TNFα and its expression in NIH3T3 cells induced by ionizing irradiation

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: To isolate and amplify Egr-1 promoter, construct pEgr.p-TNFα and study its response to different doses of ionizing radiation. Methods: Egr-1 promote was isolated from genomic DNA by PCR to construct pEgr.p-TNFα expression plasmid. Plasmids were transfected into NIH3T3 cells with liposome and the expression level of TNFα was detected by ELISA after irradiation with different doses of X-ray. Results: The sequence of Egr-1 promoter obtained was essentially same as reported. Egr-1 promoter and TNF α cDNA were inserted into expression vector correctly. Eight hours after irradiation with different doses of X-rays, the expression level of TNFα was higher than that of nonirradiated group (P< 0.05-0.001). Conclusion: Egr-1 promoter obtained can be activated by ionizing irradiation and regulate the expression of downstream gene. Low dose irradiation is for the first time found to be able to induce the expression of the downstream gene. the observation may be of potential significance in tumor therapy

  4. TRAIL overexpression co-regulated by Egr1 and HRE enhances radiosensitivity of hypoxic A549 cells depending on its apoptosis inducing role.

    Science.gov (United States)

    Yang, Yan-Ming; Fang, Fang; Li, Xin; Yu, Lei; Wang, Zhi-Cheng

    2017-01-01

    Ionizing radiation can upregulate the expression levels of TRAIL and enhance tumor cell apoptosis. While Early growth response 1 (Egr1) gene promoter has radiation inducible characteristics, the expression for exogenous gene controlled by Egr1 promoter could be enhanced by ionizing radiation, but its efficiency is limited by tissue hypoxia. Hypoxia response elements (HREs) are important hypoxic response regulatory sequences and sensitivity enhancers. Therefore, we chose TRAIL as the gene radiotherapy to observe whether it is regulated by Egr1 and HER and its effects on A549 cells and its mechanism. The pcDNA3.1-Egr1-TRAIL (pc-E-hsT) and pcDNA3.1-HRE/Egr1-TRAIL (pc-H/E-hsT) plasmids containing Egr1-hsTRAIL and HRE/Egr1-hsTRAIL were transfected into A549 cells, the cells were treated by hypoxia and radiation. The TRAIL mRNA in the cells and protein concentration in the culture supernatants were measured by RT-PCR and ELISA, respectively. Mean lethal dose D0 value was evaluated with colony forming assay. The cell apoptotic rates were analyzed by FCM and TUNEL assay. Expression of DR4, DR5 and cleaved caspase-3 proteins were analyzed by western blotting. It showed that TRAIL mRNA expression and TRAIL concentration all significantly increased under hypoxia and/or radiation. D0 value of pc-H/E‑hsT transfected cells under hypoxia was lowest, indicating more high radiosensitivity. Hypoxia could not cause the pc-E-hsT transfected cell apoptotic rate increase, but there were promoting effects in pc-H/E-hsT transfected cells. DR4 had not obvious change in pc-E-hsT and pc-H/E-hsT transfected cells under normoxic and hypoxic condition, otherwise, DR5 and cleaved caspase-3 increased mostly in pc-H/E-hsT transfected cells under hypoxic condition. TRAIL overexpression was co-regulated by Egr1 and HRE. TRAIL might promote hypoxic A549 cell radiosensitivity and induce apoptosis depending on DR5 to caspase-3 pathways.

  5. Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

    Directory of Open Access Journals (Sweden)

    Margot Martinez-Moreno

    2017-08-01

    Full Text Available Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA. During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS biology.

  6. Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1 in Colorectal Cancer Cells

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    Cyril Sobolewski

    2015-08-01

    Full Text Available The RNA-binding protein tristetraprolin (TTP promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE. In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC inhibitors (Trichostatin A, SAHA and sodium butyrate promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells and cervix carcinoma cells (HeLa. We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1. Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

  7. Mice Lacking EGR1 Have Impaired Clock Gene (BMAL1) Oscillation, Locomotor Activity, and Body Temperature.

    Science.gov (United States)

    Riedel, Casper Schwartz; Georg, Birgitte; Jørgensen, Henrik L; Hannibal, Jens; Fahrenkrug, Jan

    2018-01-01

    Early growth response transcription factor 1 (EGR1) is expressed in the suprachiasmatic nucleus (SCN) after light stimulation. We used EGR1-deficient mice to address the role of EGR1 in the clock function and light-induced resetting of the clock. The diurnal rhythms of expression of the clock genes BMAL1 and PER1 in the SCN were evaluated by semi-quantitative in situ hybridization. We found no difference in the expression of PER1 mRNA between wildtype and EGR1-deficient mice; however, the daily rhythm of BMAL1 mRNA was completely abolished in the EGR1-deficient mice. In addition, we evaluated the circadian running wheel activity, telemetric locomotor activity, and core body temperature of the mice. Loss of EGR1 neither altered light-induced phase shifts at subjective night nor affected negative masking. Overall, circadian light entrainment was found in EGR1-deficient mice but they displayed a reduced locomotor activity and an altered temperature regulation compared to wild type mice. When placed in running wheels, a subpopulation of EGR1-deficient mice displayed a more disrupted activity rhythm with no measurable endogenous period length (tau). In conclusion, the present study provides the first evidence that the circadian clock in the SCN is disturbed in mice deficient of EGR1.

  8. An Evaluation on Transfection Efficiency of pHRE-Egr1-EGFP in Hepatocellular Carcinoma Cells Bel-7402 Mediated by PEI-MZF-NPs

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    Mei Lin

    2011-01-01

    Full Text Available To improve transfection and expression efficiency of target gene, especially under cancer anoxic microenvironment, we have developed pHRE-Egr1-EGFP/PEI-MZF-NPs nanosystem, in which pHRE-Egr1-EGFP, eukaryotic gene expression plasmid, is constructed by combining radiation promoter Egr1 with anoxia induction components (HRE, forming anoxic radiation double sensitive HRE/Egr1 promoter to activate reporter gene EGFP expression. MZF-NPs (Mn0.5 Zn0.5 Fe2O4 magnetic nanoparticles, obtained by coprecipitation method, are coated with cation poly(ethylenimine (PEI. We transferred pHRE-Egr1-EGFP into hepatocellular carcinoma Bel-7402 cells, using PEI-MZF-NPs as the carrier and tested some relevant efficacy. The results show that PEI-MZF-NPs have good DNA-binding ability, protection ability, release ability, little toxicity, and high transfection efficiency, obviously superior to those of the liposome method and electricity perforation method. Moreover, the expression level of EGFP gene induced by anoxia and radiation was significantly higher than that of single radiation activation. It is therefore concluded that HRE/Egr1 can induce and improve target gene expression efficiency in cancer anoxic microenvironment, and that PEI-MZF-NPs can be used as a novel nonviral gene vector which offers a viable approach to the mediated radiation gene therapy of cancer.

  9. File list: Oth.Bld.10.Egr1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.Egr1.AllCell mm9 TFs and others Egr1 Blood SRX122513,SRX122511,SRX122510...,SRX122512 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.Egr1.AllCell.bed ...

  10. File list: Oth.Bld.05.Egr1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.Egr1.AllCell mm9 TFs and others Egr1 Blood SRX122511,SRX122510,SRX122512...,SRX122513 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.Egr1.AllCell.bed ...

  11. Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway.

    Science.gov (United States)

    Lim, Jung Hwa; Jung, Cho-Rok; Lee, Chan-Hee; Im, Dong-Soo

    2008-11-01

    E2-EPF ubiquitin carrier protein (UCP) has been shown to be highly expressed in common human cancers and target von Hippel-Lindau (VHL) for proteosomal degradation in cells, thereby stabilizing hypoxia-inducible factor (HIF)-1alpha. Here, we investigated cellular factors that regulate the expression of UCP gene. Promoter deletion assay identified binding sites for early growth response-1 (Egr-1) and serum response factor (SRF) in the UCP promoter. Hepatocyte or epidermal growth factor (EGF), or phorbol 12-myristate 13-acetate induced UCP expression following early induction of Egr-1 expression in HeLa cells. Serum increased mRNA and protein levels of SRF and UCP in the cell. By electrophoretic mobility shift and chromatin immunoprecipitation assays, sequence-specific DNA-binding of Egr-1 and SRF to the UCP promoter was detected in nuclear extracts from HeLa cells treated with EGF and serum, respectively. Overexpression of Egr-1 or SRF increased UCP expression. RNA interference-mediated depletion of endogenous Egr-1 or SRF impaired EGF- or serum-mediated induction of UCP expression, which was required for cancer cell proliferation. Systemic delivery of EGF into mice also increased UCP expression following early induction of Egr-1 expression in mouse liver. The induced UCP expression by the growth factors or serum increased HIF-1alpha protein level under non-hypoxic conditions, suggesting that the Egr-1/SRF-UCP-VHL pathway is in part responsible for the increased HIF-1alpha protein level in vitro and in vivo. Thus, growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces UCP expression that positively regulates cancer cell growth.

  12. Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model.

    Science.gov (United States)

    Pawlinski, Rafal; Pedersen, Brian; Kehrle, Bettina; Aird, William C; Frank, Rolf D; Guha, Mausumee; Mackman, Nigel

    2003-05-15

    In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1(+/+) mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1(-/-) mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1(+/+) mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1(-/-) mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor alpha in endotoxemic mice. Moreover, Egr-1(+/+) and Egr-1(-/-) mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs.

  13. File list: Oth.ALL.50.Egr1.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Egr1.AllCell mm9 TFs and others Egr1 All cell types SRX204724,SRX122513,...SRX122511,SRX122510,SRX122512 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.50.Egr1.AllCell.bed ...

  14. The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

    Science.gov (United States)

    Shen, Ning; Jiang, Shan; Lu, Jia-Ming; Yu, Xiao; Lai, Shan-Shan; Zhang, Jing-Zi; Zhang, Jin-Long; Tao, Wei-Wei; Wang, Xiu-Xing; Xu, Na; Xue, Bin; Li, Chao-Jun

    2015-02-01

    The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. γ-Oryzanol suppresses COX-2 expression by inhibiting reactive oxygen species-mediated Erk1/2 and Egr-1 signaling in LPS-stimulated RAW264.7 macrophages.

    Science.gov (United States)

    Shin, Soon Young; Kim, Heon-Woong; Jang, Hwan-Hee; Hwang, Yu-Jin; Choe, Jeong-Sook; Kim, Jung-Bong; Lim, Yoongho; Lee, Young Han

    2017-09-16

    Cyclooxygenase (COX)-2 produces prostanoids, which contribute to inflammatory responses. Nuclear factor (NF)-κB is a key transcription factor mediating COX-2 expression. γ-Oryzanol is an active component in rice bran oil, which inhibits lipopolysaccharide (LPS)-mediated COX-2 expression by inhibiting NF-κB. However, the inhibition of COX-2 expression by γ-oryzanol independently of NF-κB is poorly understood. We found that LPS upregulated Egr-1 expression at the transcriptional level. Forced expression of Egr-1 trans-activated the Cox-2 promoter independently of NF-κB. In contrast, silencing of Egr-1 abrogated LPS-mediated COX-2 expression. LPS produced reactive oxygen species (ROS), which, in turn, induced Egr-1 expression via the Erk1/2 MAPK pathway. ROS scavenging activity of γ-oryzanol suppressed Egr-1 expression by inhibiting the Erk1/2 MAPK pathway. Our results suggest that γ-oryzanol inhibits LPS-mediated COX-2 expression by suppressing Erk1/2-mediated Egr-1 expression. This study supports that γ-oryzanol may be useful for ameliorating LPS-mediated inflammatory responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Valsartan independent of AT1 receptor inhibits tissue factor, TLR-2 and-4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions

    Science.gov (United States)

    Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

    2014-01-01

    Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and-4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and-4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2,-4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. PMID:25109475

  17. IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM.

    Directory of Open Access Journals (Sweden)

    Estella Sanchez-Guerrero

    Full Text Available The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP and a disintegrin and a metalloproteinase (ADAM. Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR. This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.

  18. 转录因子Egr-1参与长期性恐惧记忆和焦虑%Transcription factor Egr-1 is required for long-term fear memory and anxiety

    Institute of Scientific and Technical Information of China (English)

    Shanelle; W.Ko; 敖虎山; Amelia; Gallitano-Mendel; 邱长申; 魏峰; Jeffrey; Milbrandt; 卓敏

    2005-01-01

    The zinc finger transcription factor Egr-1 is critical for coupling extracellular signals to changes in cellular gene expression.In the hippocampus and amygdala, two major central regions for memory formation and storage, Egr-1 is up-regulated by long-term potentiation (LTP) and learning paradigms. Using Egr-1 knockout mice, we showed that Egr-1 was selectively required for late auditory fear memory while short term, trace and contextual memory were not affected. Additionally, synaptic potentiation induced by theta burst stimulation in the amygdala and auditory cortex was significantly reduced or blocked in Egr-1 knockout mice. Our study suggests that the transcription factor Egr-1 plays a selective role in late auditory fear memory.%锌指转录因子Egr-1在将细胞外信号和胞内基因表达的变化相耦联过程中发挥重要的作用.海马和杏仁体是记忆形成和储存的两个主要的脑区.在海马和杏仁体中,Egr-1可被长时程增强(long-term potentiation,LTP)和学习过程上调.在Egr-1敲除小鼠上观察到晚时相声音恐惧记忆受损,而短时的痕迹和场景记忆却不受影响;另外,在Egr-1敲除小鼠上,用thetaburst刺激杏仁体和听觉皮层所引起的突触增强被明显减弱或完全阻断.因此,我们的研究表明,转录因子Egr-1选择性地在晚时相听觉恐惧记忆中发挥作用.

  19. Dual‑sensitive HRE/Egr1 promoter regulates Smac overexpression and enhances radiation‑induced A549 human lung adenocarcinoma cell death under hypoxia.

    Science.gov (United States)

    Li, Chang-Feng; Chen, Li-Bo; Li, Dan-Dan; Yang, Lei; Zhang, Bao-Gang; Jin, Jing-Peng; Zhang, Ying; Zhang, Bin

    2014-08-01

    The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual‑sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr‑1) promoter in order to overexpress the therapeutic second mitochondria‑derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy‑induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1Egr1‑Smac (pE‑Smac) and pcDNA3.1‑HRE/Egr-1‑Smac (pH/E‑Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X‑ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V‑fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE‑Smac and pH/E‑Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase‑9/caspase‑3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X‑ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual‑sensitive chimeric HRE/Egr‑1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.

  20. Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1.

    Directory of Open Access Journals (Sweden)

    Karine Z Oben

    Full Text Available An understanding of how each individual 5q chromosome critical deleted region (CDR gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs. Early Growth Response 1 (EGR1 is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell quiescence as well as the master regulator of apoptosis-p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.

  1. pH Modulates the Binding of EGR1 Transcription Factor to DNA

    Science.gov (United States)

    Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

    2013-01-01

    EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

  2. Valsartan independent of AT₁ receptor inhibits tissue factor, TLR-2 and -4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions.

    Science.gov (United States)

    Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

    2014-10-01

    Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and -4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and -4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2, -4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory

    Directory of Open Access Journals (Sweden)

    Roseline Poirier

    2007-12-01

    Full Text Available It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.

  4. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    Energy Technology Data Exchange (ETDEWEB)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

    2015-03-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.

  5. Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

    International Nuclear Information System (INIS)

    Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald

    2015-01-01

    Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interrupts the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified

  6. Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma

    Directory of Open Access Journals (Sweden)

    Gagliardi Franco

    2004-01-01

    Full Text Available Abstract Background The aim of this work was to investigate in vitro the putative role of EGR-1 in the growth of glioma cells. EGR-1 expression was examined during the early passages in vitro of 17 primary cell lines grown from 3 grade III and from 14 grade IV malignant astrocytoma explants. The explanted tumors were genetically characterized at the p53, MDM2 and INK4a/ARF loci, and fibronectin expression and growth characteristics were examined. A recombinant adenovirus overexpressing EGR-1 was tested in the primary cell lines. Results Low levels of EGR-1 protein were found in all primary cultures examined, with lower values present in grade IV tumors and in cultures carrying wild-type copies of p53 gene. The levels of EGR-1 protein were significantly correlated to the amount of intracellular fibronectin, but only in tumors carrying wild-type copies of the p53 gene (R = 0,78, p = 0.0082. Duplication time, plating efficiency, colony formation in agarose, and contact inhibition were also altered in the p53 mutated tumor cultures compared to those carrying wild-type p53. Growth arrest was achieved in both types of tumor within 1–2 weeks following infection with a recombinant adenovirus overexpressing EGR-1 but not with the control adenovirus. Conclusions Suppression of EGR-1 is a common event in gliomas and in most cases this is achieved through down-regulation of gene expression. Expression of EGR-1 by recombinant adenovirus infection almost completely abolishes the growth of tumor cells in vitro, regardless of the mutational status of the p53 gene.

  7. Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

    Energy Technology Data Exchange (ETDEWEB)

    Phookphan, Preeyaphan; Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Post-graduate Program in Environmental Toxicology, Chulabhorn Graduate Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand); Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Ruchirawat, Mathuros, E-mail: mathuros@cri.or.th [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health, Toxicology (EHT), Office of the Higher Education Commission, Ministry of Education (Thailand)

    2017-02-01

    Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

  8. Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

    International Nuclear Information System (INIS)

    Phookphan, Preeyaphan; Navasumrit, Panida; Waraprasit, Somchamai; Promvijit, Jeerawan; Chaisatra, Krittinee; Ngaotepprutaram, Thitirat; Ruchirawat, Mathuros

    2017-01-01

    Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is

  9. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

    Science.gov (United States)

    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium.

    Science.gov (United States)

    Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J; Roschmann, Kristina I L; Fokkens, Wytske J; van Drunen, Cornelis M

    2015-05-01

    Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state. We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA. The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%. Deregulation of EGR-1 and/or DUSP-1 in nasal epithelium could be responsible for the prolonged activated transcriptional state observed in vivo in allergic disease. This could have clinical consequences as cytokine levels after the steroid treatment in EGR-1 or DUSP-1 knock-down remained higher than in the control cell line. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Egr-1 induction provides a genetic response to food aversion in zebrafish

    Directory of Open Access Journals (Sweden)

    Brigitte eBoyer

    2013-05-01

    Full Text Available As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labelling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labelled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labelling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

  12. Egr-1 induction provides a genetic response to food aversion in zebrafish.

    Science.gov (United States)

    Boyer, Brigitte; Ernest, Sylvain; Rosa, Frédéric

    2013-01-01

    As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labeling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labeled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labeling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

  13. Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China); Cai, Zhifeng; Liu, Mengmeng [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Zhao, Cuifen, E-mail: zhaocuifen@sdu.edu.cn [Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012 (China); Li, Dong [Research Room of Hypothermia Medicine, Qilu Hospital, Shandong University, Jinan 250012 (China); Lv, Chenguang; Wang, Yuping; Xu, Tengfei [Biomedical Engineering Institute, School of Control Science and Engineering, Shandong University, Jinan 250061 (China)

    2015-11-27

    Aim: The objective of this study was to investigate the effects of urotensin II (UII) treatment on the proliferation and collagen synthesis of cultured rat pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these effects are mediated by mitogen-activated protein kinase (MAPK) signaling pathways and early growth response 1 (Egr-1). Methods: The proliferation of cultured PASMCs stimulated with different doses of UII was detected by BrdU incorporation. The mRNA expression levels of procollagen I (procol I), procollagen III (procol III), extracellular regulated protein kinase 1/2 (ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA in cultured PASMCs after treatment with UII, the UII-specific antagonist urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase chain reaction (PCR), and the protein expression levels of procol I, procol III, phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western blotting. Results: Treatment with UII increased the proliferation of cultured PASMCs in a dose-dependent manner (P < 0.05). However, treatment with urantide and PD98059 inhibited the promoting effect of UII on PASMC proliferation (P < 0.05). Real-time PCR analysis showed that UII up-regulated the expression of procol I, procol III, ERK1/2, Sapk, and Egr-1 mRNA (P < 0.05), but not p38 mRNA. However, the up-regulating effect of UII was inhibited by PD98059 and urantide. Western blotting analysis showed that UII increased the synthesis of collagen I, collagen III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by PD98059 and urantide (P < 0.05). Conclusions: Egr-1 participates in the UII-mediated proliferation and collagen synthesis of cultured rat PASMCs via activation of the ERK1/2 signaling pathway.

  14. Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells

    International Nuclear Information System (INIS)

    Li, Yang; Hu, Fang; Xue, Meng; Jia, Yi-Jie; Zheng, Zong-Ji; Wang, Ling; Guan, Mei-Ping; Xue, Yao-Ming

    2017-01-01

    Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear. In the present study, we assessed human MCs that were incubated under high-glucose conditions to mimic diabetes. Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN), collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and protein expression levels were determined by RT-qPCR and western blotting respectively. High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p-Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up-regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover, the effects of si-Klotho on Egr-1 expression were abolished by the TGF-β1 inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production in high-glucose-treated human MCs, an effect that has been partially attributed to Egr-1 down-regulation facilitated by TGF-β1/Smad3 signaling inhibition. - Highlights: • High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. • Klotho overexpression down-regulated Egr-1 and prevented mesangial ECM production in high-glucose-treated human MCs. • Klotho down-regulated Egr-1 by inhibiting

  15. Analysis list: Egr2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Egr2 Blood + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr2.1.tsv h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Egr2.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Eg...r2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Egr2.Blood.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Blood.gml ...

  16. Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7-oxysterol or p53.

    Science.gov (United States)

    Miah, Sayem; Zadeh, Shahram Nour Mohammad; Yuan, Xi-Ming; Li, Wei

    2013-07-01

    Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer. However, it is unknown whether p53 and Egr1 are interactively involved in apoptosis in atherosclerosis. We found that in human carotid plaques, the expression of p53 was inversely correlated with Egr1. In U937 cells, 7β-hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen species (ROS), transient up-regulation of Egr1 followed by late induction of p53 and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53 showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS induced by 7-oxysterols may function as an early initiator of Egr1 expression. The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is linked to the reduction of Egr1 levels, which resembles the differential expression of p53 and Egr1 in human atheroma progression. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

    Science.gov (United States)

    Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

    2009-01-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

  18. Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

    Science.gov (United States)

    Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

    2009-12-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

  19. Propranolol decreases retention of fear memory by modulating the stability of surface glutamate receptor GluA1 subunits in the lateral amygdala.

    Science.gov (United States)

    Zhou, Jun; Luo, Yi; Zhang, Jie-Ting; Li, Ming-Xing; Wang, Can-Ming; Guan, Xin-Lei; Wu, Peng-Fei; Hu, Zhuang-Li; Jin, You; Ni, Lan; Wang, Fang; Chen, Jian-Guo

    2015-11-01

    Posttraumatic stress disorder (PTSD) is a mental disorder with enhanced retention of fear memory and has profound impact on quality of life for millions of people worldwide. The β-adrenoceptor antagonist propranolol has been used in preclinical and clinical studies for the treatment of PTSD, but the mechanisms underlying its potential efficacy on fear memory retention remain to be elucidated. We investigated the action of propranolol on the retention of conditioned fear memory, the surface expression of glutamate receptor GluA1 subunits of AMPA receptors and synaptic adaptation in the lateral amygdala (LA) of rats. Propranolol attenuated reactivation-induced strengthening of fear retention while reducing enhanced surface expression of GluA1 subunits and restoring the impaired long-term depression in LA. These effects of propranolol were mediated by antagonizing reactivation-induced enhancement of adrenergic signalling, which activates PKA and calcium/calmodulin-dependent protein kinase II and then regulates the trafficking of AMPA receptors via phosphorylation of GluA1 subunits at the C-terminus. Both i.p. injection and intra-amygdala infusion of propranolol attenuated reactivation-induced enhancement of fear retention. Reactivation strengthens fear retention by increasing the level of noradrenaline and promotes the surface expression of GluA1 subunits and the excitatory synaptic transmission in LA. These findings uncover one mechanism underlying the efficiency of propranolol on retention of fear memories and suggest that β-adrenoceptor antagonists, which act centrally, may be more suitable for the treatment of PTSD. © 2015 The British Pharmacological Society.

  20. Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

    Directory of Open Access Journals (Sweden)

    Jia Fei

    2011-01-01

    Full Text Available Atherogenic ω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if ω-6 lipids modulated the early growth response-1 (Egr-1/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs were exposed to ω-6 lipids, linoleic acid (LA, or its oxidized form, 13-HPODE (OxLA in the presence or absence of a PPARα antagonist (MK886 or PPARγ antagonist (GW9662 or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1 mRNA and protein levels at the acute phase (1–4 hrs when PPARα was downregulated and at subacute phase (4–12 hrs by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.

  1. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

    2009-01-01

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  2. Obtain and characterization of chitosan / propranolol microparticles by spray drying; Obtencao e caracterizacao de microparticulas de quitosana / propranolol por spray drying

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Ednaldo G. do; Silva Junior, Arnobio A. da, E-mail: ednaldogn@yahoo.com.br [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Santos, Katia S.C.R. dos [Universidade Federal do Amazonas (UFAM), Manaus, AM (brazil)

    2015-07-01

    The study investigated the application of chitosan microparticles as carriers into hard gelatin capsule containing propranolol, evaluating the variability of the molecular weight and the chitosan particles by spray drying. The formulations were characterized by average weight, dosing unit dose uniformity and dissolution profile according to the pharmacopoeia. While the microparticles were characterized by Fourier transformed infrared spectroscopy, scanning electron microscopy and X-ray diffraction. The results showed that chitosan microparticles obtained without the drug and then physically mixed with propranolol promoted a modified release 85% of the drug after 5 hours. While, chitosan microparticles sprayed with propranolol released only 55% at 5 hours is presented both as a modified release system. Samples of dried chitosan showed up amorphous and homogeneous and spherical morphology. (author)

  3. The immediate early gene product EGR1 and polycomb group proteins interact in epigenetic programming during chondrogenesis.

    Directory of Open Access Journals (Sweden)

    Frank Spaapen

    Full Text Available Initiation of and progression through chondrogenesis is driven by changes in the cellular microenvironment. At the onset of chondrogenesis, resting mesenchymal stem cells are mobilized in vivo and a complex, step-wise chondrogenic differentiation program is initiated. Differentiation requires coordinated transcriptomic reprogramming and increased progenitor proliferation; both processes require chromatin remodeling. The nature of early molecular responses that relay differentiation signals to chromatin is poorly understood. We here show that immediate early genes are rapidly and transiently induced in response to differentiation stimuli in vitro. Functional ablation of the immediate early factor EGR1 severely deregulates expression of key chondrogenic control genes at the onset of differentiation. In addition, differentiating cells accumulate DNA damage, activate a DNA damage response and undergo a cell cycle arrest and prevent differentiation associated hyper-proliferation. Failed differentiation in the absence of EGR1 affects global acetylation and terminates in overall histone hypermethylation. We report novel molecular connections between EGR1 and Polycomb Group function: Polycomb associated histone H3 lysine27 trimethylation (H3K27me3 blocks chromatin access of EGR1. In addition, EGR1 ablation results in abnormal Ezh2 and Bmi1 expression. Consistent with this functional interaction, we identify a number of co-regulated targets genes in a chondrogenic gene network. We here describe an important role for EGR1 in early chondrogenic epigenetic programming to accommodate early gene-environment interactions in chondrogenesis.

  4. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    DEFF Research Database (Denmark)

    Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels

    2009-01-01

    bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

  5. Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Susilowati, Heni [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Okamura, Hirohiko [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Hirota, Katsuhiko, E-mail: hirota@dent.tokushima-u.ac.jp [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Shono, Masayuki [Support Center for Advanced Medical Sciences, The University of Tokushima, Tokushima 770-8504 (Japan); Yoshida, Kaya [Department of Fundamental Oral Health Science, School of Oral Health and Welfare, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Murakami, Keiji [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Tabata, Atsushi; Nagamune, Hideaki [Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506 (Japan); Haneji, Tatsuji [Department of Histology and Oral Histology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan); Miyake, Yoichiro [Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504 (Japan)

    2011-01-07

    Research highlights: {yields} ILY leads to the accumulation of [Ca{sup 2+}]i in the nucleus in HuCCT1 cells. {yields} ILY induced activation of NFAT1 through a calcineurin-dependent pathway. {yields} Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca{sup 2+}]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-{kappa}B translocation in human hepatic HepG2 cells, ILY did not affect NF-{kappa}B localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca{sup 2+}]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

  6. Intermedilysin induces EGR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells

    International Nuclear Information System (INIS)

    Susilowati, Heni; Okamura, Hirohiko; Hirota, Katsuhiko; Shono, Masayuki; Yoshida, Kaya; Murakami, Keiji; Tabata, Atsushi; Nagamune, Hideaki; Haneji, Tatsuji; Miyake, Yoichiro

    2011-01-01

    Research highlights: → ILY leads to the accumulation of [Ca 2+ ]i in the nucleus in HuCCT1 cells. → ILY induced activation of NFAT1 through a calcineurin-dependent pathway. → Calcineuri/NFAT pathway is involved in EGR-1 expression in response to ILY treatment. -- Abstract: Intermedilysin (ILY) is a cholesterol-dependent cytolysin produced by Streptococcus intermedius, which is associated with human brain and liver abscesses. Although intrahepatic bile duct cells play a valuable role in the pathogenesis of liver abscess, the molecular mechanism of ILY-treated intrahepatic bile duct cells remains unknown. In this study, we report that ILY induced a nuclear accumulation of intracellular calcium ([Ca 2+ ]i) in human cholangiocellular cells HuCCT1. We also demonstrate that 10 ng/ml ILY induced NFAT1 dephosphorylation and its nuclear translocation in HuCCT1 cells. In contrast to the result that ILY induced NF-κB translocation in human hepatic HepG2 cells, ILY did not affect NF-κB localization in HuCCT1 cells. Dephosphorylation and nuclear translocation of NFAT1 caused by ILY were prevented by [Ca 2+ ]i calcium chelator, BAPTA/AM, and calcineurin inhibitors, cyclosporine A and tacrolimus. ILY induced early growth response-1 (EGR-1) expression and it was inhibited by the pre-treatment with cyclosporine A, indicating that the calcineurin/NFAT pathway was involved in EGR-1 expression in response to ILY. ILY-induced calcineurin/NFAT1 activation and sequential EGR-1 expression might be related to the pathogenesis of S. intermedius in human bile duct cells.

  7. Androgen Modulates Functions of Endothelial Progenitor Cells through Activated Egr1 Signaling

    Directory of Open Access Journals (Sweden)

    Yizhou Ye

    2016-01-01

    Full Text Available Researches show that androgens have important effects on migration of endothelial cells and endothelial protection in coronary heart disease. Endothelial progenitor cells (EPCs as a progenitor cell type that can differentiate into endothelial cells, have a critical role in angiogenesis and endothelial protection. The relationship between androgen and the functions of EPCs has animated much interest and controversy. In this study, we investigated the angiogenic and migratory functions of EPCs after treatment by dihydrotestosterone (DHT and the molecular mechanisms as well. We found that DHT treatment enhanced the incorporation of EPCs into tubular structures formed by HUVECs and the migratory activity of EPCs in the transwell assay dose dependently. Moreover, microarray analysis was performed to explore how DHT changes the gene expression profiles of EPCs. We found 346 differentially expressed genes in androgen-treated EPCs. Angiogenesis-related genes like Egr-1, Vcan, Efnb2, and Cdk2ap1 were identified to be regulated upon DHT treatment. Furthermore, the enhanced angiogenic and migratory abilities of EPCs after DHT treatment were inhibited by Egr1-siRNA transfection. In conclusion, our findings suggest that DHT markedly enhances the vessel forming ability and migration capacity of EPCs. Egr1 signaling may be a possible pathway in this process.

  8. Propranolol as an adjunct therapy for hyperthyroid tremor.

    Science.gov (United States)

    Henderson, J M; Portmann, L; Van Melle, G; Haller, E; Ghika, J A

    1997-01-01

    We evaluated the use of propranolol as an adjunct to carbimazole in the treatment of hyperthyroid tremor and tachycardia in a double-blind, cross-over and placebo-controlled study. Seven patients were given carbimazole plus either placebo or propranolol (40 mg) for 1 month and then switched to the alternative adjunct treatment for a further month. All patients showed significant improvements (p tremor amplitude after 1 or 2 months from baseline. One month after the baseline, the mean improvements of heart rate were 23% for the carbimazole + placebo group and 38% for carbimazole + propranolol group. Tremor also improved during the 1st month of the study by 31% in the carbimazole + placebo group versus 59% in the carbimazole + propranolol group. Whereas further improvements were observed in both variables in those receiving propranolol as the second adjunct treatment, this was not the case in those who received placebo during the same period. These findings confirm that the beta-blocker propranolol is a useful adjunct in the early treatment of both the tremor and tachycardia of hyperthyroidism.

  9. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice.

    Science.gov (United States)

    Kwon, Wookbong; Kim, Hyeng-Soo; Jeong, Jain; Sung, Yonghun; Choi, Minjee; Park, Song; Lee, Jinhee; Jang, Soyoung; Kim, Sung Hyun; Lee, Sanggyu; Kim, Myoung Ok; Ryoo, Zae Young

    2018-01-01

    Ten-eleven translocation methylcytosine dioxygenase 1 ( Tet1 ) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories. We confirmed that Tet1 overexpression affected adult neurogenesis with oligodendrocyte differentiation in the hippocampal dentate gyrus of Tet1-TG mice. In addition, Tet1 overexpression induced the elevated expression of immediate early genes, such as Egr1 , c-fos , Arc , and Bdnf , followed by the activation of intracellular calcium signals ( i.e. , CamKII, ERK, and CREB) in prefrontal and hippocampal neurons. The expression of GABA receptor subunits ( Gabra2 and Gabra4 ) fluctuated in the prefrontal cortex and hippocampus. We evaluated the effects of Tet1 overexpression on intracellular calcium-dependent cascades by activating the Egr1 promoter in vitro Tet1 enhanced Egr1 expression, which may have led to alterations in Gabra2 and Gabra4 expression in neurons. Taken together, we suggest that the Tet1 overexpression in our Tet1-TG mice can be applied as an effective model for studying various stress-related diseases that show hyperactivation of intracellular calcium-dependent cascades in the brain.-Kwon, W., Kim, H.-S., Jeong, J., Sung, Y., Choi, M., Park, S., Lee, J., Jang, S., Kim, S. H., Lee, S., Kim, M. O., Ryoo, Z. Y. Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice. © FASEB.

  10. The Immediate Early Gene Egr3 Is Required for Hippocampal Induction of Bdnf by Electroconvulsive Stimulation

    Directory of Open Access Journals (Sweden)

    Kimberly T. Meyers

    2018-05-01

    Full Text Available Early growth response 3 (Egr3 is an immediate early gene (IEG that is regulated downstream of a cascade of genes associated with risk for psychiatric disorders, and dysfunction of Egr3 itself has been implicated in schizophrenia, bipolar disorder, and depression. As an activity-dependent transcription factor, EGR3 is poised to regulate the neuronal expression of target genes in response to environmental events. In the current study, we sought to identify a downstream target of EGR3 with the goal of further elucidating genes in this biological pathway relevant for psychiatric illness risk. We used electroconvulsive stimulation (ECS to induce high-level expression of IEGs in the brain, and conducted expression microarray to identify genes differentially regulated in the hippocampus of Egr3-deficient (-/- mice compared to their wildtype (WT littermates. Our results replicated previous work showing that ECS induces high-level expression of the brain-derived neurotrophic factor (Bdnf in the hippocampus of WT mice. However, we found that this induction is absent in Egr3-/- mice. Quantitative real-time PCR (qRT-PCR validated the microarray results (performed in males and replicated the findings in two separate cohorts of female mice. Follow-up studies of activity-dependent Bdnf exons demonstrated that ECS-induced expression of both exons IV and VI requires Egr3. In situ hybridization demonstrated high-level cellular expression of Bdnf in the hippocampal dentate gyrus following ECS in WT, but not Egr3-/-, mice. Bdnf promoter analysis revealed eight putative EGR3 binding sites in the Bdnf promoter, suggesting a mechanism through which EGR3 may directly regulate Bdnf gene expression. These findings do not appear to result from a defect in the development of hippocampal neurons in Egr3-/- mice, as cell counts in tissue sections stained with anti-NeuN antibodies, a neuron-specific marker, did not differ between Egr3-/- and WT mice. In addition, Sholl

  11. Fast spatially resolved exhaust gas recirculation (EGR) distribution measurements in an internal combustion engine using absorption spectroscopy.

    Science.gov (United States)

    Yoo, Jihyung; Prikhodko, Vitaly; Parks, James E; Perfetto, Anthony; Geckler, Sam; Partridge, William P

    2015-09-01

    Exhaust gas recirculation (EGR) in internal combustion engines is an effective method of reducing NOx emissions while improving efficiency. However, insufficient mixing between fresh air and exhaust gas can lead to cycle-to-cycle and cylinder-to-cylinder non-uniform charge gas mixtures of a multi-cylinder engine, which can in turn reduce engine performance and efficiency. A sensor packaged into a compact probe was designed, built and applied to measure spatiotemporal EGR distributions in the intake manifold of an operating engine. The probe promotes the development of more efficient and higher-performance engines by resolving high-speed in situ CO2 concentration at various locations in the intake manifold. The study employed mid-infrared light sources tuned to an absorption band of CO2 near 4.3 μm, an industry standard species for determining EGR fraction. The calibrated probe was used to map spatial EGR distributions in an intake manifold with high accuracy and monitor cycle-resolved cylinder-specific EGR fluctuations at a rate of up to 1 kHz.

  12. Carvedilol or propranolol in portal hypertension?

    DEFF Research Database (Denmark)

    Hobolth, Lise; Møller, Søren; Grønbæk, Henning

    2012-01-01

    Abstract Objectives. Carvedilol is a non-selective ß-blocker with intrinsic anti-a(1)-adrenergic activity, potentially more effective than propranolol in reducing hepatic venous pressure gradient (HVPG). We compared the long-term effect of carvedilol and propranolol on HVPG and assessed whether t...

  13. Egr2 enhances insulin resistance via JAK2/STAT3/SOCS-1 pathway in HepG2 cells treated with palmitate.

    Science.gov (United States)

    Lu, Lin; Ye, Xinhua; Yao, Qing; Lu, Aijiao; Zhao, Zhen; Ding, Yang; Meng, Chuchen; Yu, Wenlong; Du, Yunfeng; Cheng, JinLuo

    2018-05-01

    Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Obtain and characterization of chitosan / propranolol microparticles by spray drying

    International Nuclear Information System (INIS)

    Nascimento, Ednaldo G. do; Silva Junior, Arnobio A. da; Santos, Katia S.C.R. dos

    2015-01-01

    The study investigated the application of chitosan microparticles as carriers into hard gelatin capsule containing propranolol, evaluating the variability of the molecular weight and the chitosan particles by spray drying. The formulations were characterized by average weight, dosing unit dose uniformity and dissolution profile according to the pharmacopoeia. While the microparticles were characterized by Fourier transformed infrared spectroscopy, scanning electron microscopy and X-ray diffraction. The results showed that chitosan microparticles obtained without the drug and then physically mixed with propranolol promoted a modified release 85% of the drug after 5 hours. While, chitosan microparticles sprayed with propranolol released only 55% at 5 hours is presented both as a modified release system. Samples of dried chitosan showed up amorphous and homogeneous and spherical morphology. (author)

  15. Cycle-by-cycle variations in a spark ignition engine fueled with natural gas-hydrogen blends combined with EGR

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Bin; Hu, Erjiang; Huang, Zuohua; Zheng, Jianjun; Liu, Bing; Jiang, Deming [State Key Laboratory of Multiphase Flow in Power Engineering, Xi' an Jiaotong University, 710049 Xi' an (China)

    2009-10-15

    Study of cycle-by-cycle variations in a spark ignition engine fueled with natural gas-hydrogen blends combined with exhaust gas recirculation (EGR) was conducted. The effects of EGR ratio and hydrogen fraction on engine cycle-by-cycle variations are analyzed. The results show that the cylinder peak pressure, the maximum rate of pressure rise and the indicated mean effective pressure decrease and cycle-by-cycle variations increase with the increase of EGR ratio. Interdependency between the above parameters and their corresponding crank angles of cylinder peak pressure is decreased with the increase of EGR ratio. For a given EGR ratio, combustion stability is promoted and cycle-by-cycle variations are decreased with the increase of hydrogen fraction in the fuel blends. Non-linear relationship is presented between the indicated mean effective pressure and EGR ratio. Slight influence of EGR ratio on indicated mean effective pressure is observed at low EGR ratios while large influence of EGR ratio on indicated mean effective pressure is demonstrated at high EGR ratios. The high test engine speed has lower cycle-by-cycle variations due to the enhancement of air flow turbulence and swirls in the cylinder. Increasing hydrogen fraction can maintain low cycle-by-cycle variations at high EGR ratios. (author)

  16. Appliance of high EGR rates with a short and long route EGR system on a heavy duty diesel engine

    NARCIS (Netherlands)

    Aken, van M.; Willems, F.P.T.; Jong, de D.J.

    2007-01-01

    The goal of this work was to investigate the possibilities of applying high EGR rates with low NOx and PM emission levels on a two-stage turbocharged 12 liter heavy duty diesel engine. The EGR is applied by using a long and short route EGR system. For the ESC operating points A25 and C100 EGR is

  17. Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi-Feng [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Yu, Hong-Wei [Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001 (China); Sun, Li-Li [Department of Ophthalmology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); You, Lu; Tao, Gui-Zhou [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China); Qu, Bao-Ze, E-mail: qubaoze1971@hotmail.com [Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001 (China)

    2015-12-25

    Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. - Highlights: • Apelin-13 mediates Egr-1 upregulation in vascular smooth muscle cells via ERK1/2. • The underlying mechanisms are unknown, but exclude Jnk or p38 pathway activation. • Apelin-13 binds to Gi, activating the PI3K/Akt and PKC signaling cascades. • Consequent ERK phosphorylation results in increased Egr-1

  18. Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways

    International Nuclear Information System (INIS)

    Liu, Qi-Feng; Yu, Hong-Wei; Sun, Li-Li; You, Lu; Tao, Gui-Zhou; Qu, Bao-Ze

    2015-01-01

    Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling. - Highlights: • Apelin-13 mediates Egr-1 upregulation in vascular smooth muscle cells via ERK1/2. • The underlying mechanisms are unknown, but exclude Jnk or p38 pathway activation. • Apelin-13 binds to Gi, activating the PI3K/Akt and PKC signaling cascades. • Consequent ERK phosphorylation results in increased Egr-1

  19. Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

    Science.gov (United States)

    Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

    2012-08-30

    Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. pEgr-sTRAIL transfer in combination with 60Co γ ray irradiation to induce the apoptosis on HeLa cells and activation of Caspase-3

    International Nuclear Information System (INIS)

    Tian Mei; Guo Zhiying; Zhao Baofeng; Ruan Jianlei; Su Xu

    2009-01-01

    In order to approach the radiosensitivity of TRAIL expression controlled by Egr-1 promotor, the recombinant vector pEgr-sTRAIL was tranfected into HeLa cells, the early apoptosis and Caspase-3 activity were detected after different doses of 60 Co γ-ray irradiation. The results showed that pEgr-sTRAIL transfected in combination with γ-ray irradiation could significantly induce the apoptosis of HeLa cells in a dose-dependent manner. The higher activity of Capase-3 was also found in pEgr-sTRAIL irradiated group by using western blotting and spectrophotometry. Our result demonstrated that the activity of Caspase-3, as the apoptosis executor, play an important role in TRAIL-induced apoptosis and the enhanced TRAIL-induced apoptosis in transfected cells after irradiation can be controlled by radio-sensitive promoter Egr-1. (authors)

  1. EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium

    NARCIS (Netherlands)

    Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J.; Roschmann, Kristina I. L.; Fokkens, Wytske J.; van Drunen, Cornelis M.

    2015-01-01

    Background: Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. Objective: To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could

  2. the effect of ascorbic acid and propranolol on normal sleep

    African Journals Online (AJOL)

    sleep promoting effects in the wistar rats in doses of propranolol. Conclusion: It is possible ... motor activities as swimming, flying, walking, running, rearing and hopping etc. ..... The Homotypical Cortex - The ssociation Areas. Physiological and ...

  3. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Science.gov (United States)

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  4. Comparison of propranolol and metoprolol in the management of hyperthyroidism.

    Science.gov (United States)

    Murchison, L E; How, J; Bewsher, P D

    1979-01-01

    1 Propranolol and metoprolol were both effective in controlling the symptoms and signs of hyperthyroidism. 2 Propranolol caused a highly significant increase in serum reverse T3 concentrations with lesser changes in other serum thyroid hormone levels, whereas metoprolol did not have this effect. 3 Steady-state plasma propranolol and metoprolol levels showed marked inter-individual variation. Metoprolol concentrations showed relatively little intra-individual variability, and could be related to the clinical efficacy of the drug, whereas no such relationship was demonstrated for propranolol. PMID:391258

  5. Construction of Egr1-mediated human truncated apoptosis inducing factor expression vector and its expression regularity induced by radiation in breast cancer MCF-7 cells

    International Nuclear Information System (INIS)

    Wang Jianfeng; Gong Shouliang; Wang Zhicheng; Fang Fang; Liu Yang; Wu Jiahui

    2012-01-01

    Objective: To clone human truncated apoptosis inducing factor (AIF) cDNA sequence, and to construct early growth response 1 (Egr1)-mediated recombinant expression vector pcDNA 3.1-Egr1-AIF Δ1-480 (pEgr1-AIFΔ 1-480 ), and to observe its regularity induced by radiation in human breast cancer MCF-7 cells. Methods: The total mRNA extracted from human leukemia Jurkat cells used as template, and the human AIFΔ 1-480 was acquired by RT-PCR, and it was linked to pMD18T vector for sequencing. Egr1 fragment was digested from pMD19T-Egr1 by restrictive enzyme, and the Egr1-mediated expression plasmid pEgr1-AIFΔ 1-480 was constructed by gene recombination. There were control group, pcDNA3.1 group, pAIFΔ 1-480 group and pEgr1-AIFΔ 1-480 group in the experiment. After the plasmids in various groups were transfected into human breast cancer MCF-7 cells, the AIF and AIFΔ 1-480 protein expression time-effect (0, 2, 4, 12, 24 and 48 h after 2.0 Gy irradiation) and dose-effect (24 h after 0, 0.2, 0.5, 1.0, 2.0 and 5.0 Gy irradiation) regularity were measured by Western blotting method. Results: The sequencing results showed that the AIFΔ 1-480 acquired by RT-PCR was consistent with the sequence expected, the pEgr-AIFΔ 1-480 was confirmed by PCR and restrictive enzyme digestion. After 0-48 h the MCF-7 cells were irradiated by 2.0 Gy, and the AIF protein expressed in the cells in each group, and it increased significantly from 4 h and the AIF expressions in 4, 12, 24 and 48 h groups were higher than that in 0 h group (P<0.05), and it reached to maximum value at 48 h. But the AIFΔ 1-480 protein expressed in the cells in pAIFΔ 1-480 and pEgr1-AIFΔ 1-480 groups from 2 h (P<0.05), and it reached to peak value at 24 h. The AIFΔ 1-480 expressions in pEgr1-AIFΔ 1-480 group were higher than those in pAIFΔ 1-480 group at and 48 h (P<0.05). After the MCF-7 cells were irradiated by 0-5 Gy for 24 h, the AIF protein expressed in the cells in each group, but the AIFΔ 1-480 protein

  6. Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.

    Science.gov (United States)

    Dollery, C T; Junod, A F

    1976-01-01

    1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation. PMID:1276542

  7. Emission behavior of OH radical in internal EGR using a 2-cycle engine; 2 cycle engine wo mochiita naibu EGR no OH radical no hakko kyodo

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, S; Amino, Y; Yoshida, K; Shoji, H; Saima, A [Nihon University, Tokyo (Japan)

    1997-10-01

    The purpose of this study was to examine and consider the influence, which the remained gas exercised on combustion. 2-cycle engine was Used as the test engine. Internal EGR was run. The means was that the test engine was fitted the back pressure control plate on the exhaust port. The conditions, which were run with internal EGR and without internal EGR, were compared. The OH radical, which plays important role in combustion of hydrocarbon fuels, was measured with emission spectroscopy. In internal EGR, the unburned end gas on exhaust port side was susceptible to the remained gas. 6 refs., 8 figs., 1 tab.

  8. Context-Dependent Egr1 Expression in the Avian Hippocampus.

    Science.gov (United States)

    Grella, Stephanie L; Guigueno, Mélanie F; White, David J; Sherry, David F; Marrone, Diano F

    2016-01-01

    In mammals, episodic memory and spatial cognition involve context-specific recruitment of unique ensembles in the hippocampal formation (HF). Despite their capacity for sophisticated spatial (e.g., for migration) and episodic-like (e.g., for food-caching) memory, the mechanisms underlying contextual representation in birds is not well understood. Here we demonstrate environment-specific Egr1 expression as male brown-headed cowbirds (Molothrus ater) navigate environments for food reward, showing that the avian HF, like its mammalian counterpart, recruits distinct neuronal ensembles to represent different contexts.

  9. Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?

    Science.gov (United States)

    Bührer, Christoph; Bassler, Dirk

    2015-01-01

    Oral propranolol has improved the treatment of infantile hemangiomas, and a pediatric oral solution of propranolol has recently been licensed in the USA and Europe. In very preterm infants, infantile hemangiomas are associated with the occurrence of retinopathy of prematurity (ROP), and both diseases share a peculiar time course, featuring a lag phase after birth followed by rapid growth and then gradual regression. To identify clinical studies evaluating the use of oral propranolol in preterm infants with ROP. Two small bicentric, pilot, randomized controlled trials found a nonsignificant reduction of ROP requiring intervention by laser treatment or bevacizumab injection of similar magnitude. Together, 6 of 35 (17%) infants who had been receiving oral propranolol underwent ROP intervention, as opposed to 14 of 36 (39%) controls (relative risk 0.42, 95% CI: 0.15-1.16). Randomized controlled trials are ongoing that investigate early preventive oral propranolol starting at 1 week of age and propranolol eye drops in preterm infants with stage 2 ROP. Further, large interventional studies are required to determine the clinical benefit-risk ratio of oral propranolol to prevent vision-threatening ROP in very preterm infants. © 2015 S. Karger AG, Basel.

  10. Egr2 induced during DC development acts as an intrinsic negative regulator of DC immunogenicity.

    Science.gov (United States)

    Miah, Mohammad Alam; Byeon, Se Eun; Ahmed, Md Selim; Yoon, Cheol-Hee; Ha, Sang-Jun; Bae, Yong-Soo

    2013-09-01

    Early growth response gene 2 (Egr2), which encodes a zinc finger transcription factor, is rapidly and transiently induced in various cell types independently of de novo protein synthesis. Although a role for Egr2 is well established in T-cell development, Egr2 expression and its biological function in dendritic cells (DCs) have not yet been described. Here, we demonstrate Egr2 expression during DC development, and its role in DC-mediated immune responses. Egr2 is expressed in the later stage of DC development from BM precursor cells. Even at steady state, Egr2 is highly expressed in mouse splenic DCs. Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities. Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine. DC-mediated cytotoxic T lymphocyte (CTL) activation and antitumor immunity were significantly enhanced by Egr2-KD, and impaired by Egr2 overexpression in antigen-pulsed DC vaccines. These data suggest that Egr2 acts as an intrinsic negative regulator of DC immunogenicity and can be an attractive molecular target for DC vaccine development. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A randomized, controlled trial of oral propranolol in infantile hemangioma.

    Science.gov (United States)

    Léauté-Labrèze, Christine; Hoeger, Peter; Mazereeuw-Hautier, Juliette; Guibaud, Laurent; Baselga, Eulalia; Posiunas, Gintas; Phillips, Roderic J; Caceres, Hector; Lopez Gutierrez, Juan Carlos; Ballona, Rosalia; Friedlander, Sheila Fallon; Powell, Julie; Perek, Danuta; Metz, Brandie; Barbarot, Sebastien; Maruani, Annabel; Szalai, Zsuzsanna Zsofia; Krol, Alfons; Boccara, Olivia; Foelster-Holst, Regina; Febrer Bosch, Maria Isabel; Su, John; Buckova, Hana; Torrelo, Antonio; Cambazard, Frederic; Grantzow, Rainer; Wargon, Orli; Wyrzykowski, Dariusz; Roessler, Jochen; Bernabeu-Wittel, Jose; Valencia, Adriana M; Przewratil, Przemyslaw; Glick, Sharon; Pope, Elena; Birchall, Nicholas; Benjamin, Latanya; Mancini, Anthony J; Vabres, Pierre; Souteyrand, Pierre; Frieden, Ilona J; Berul, Charles I; Mehta, Cyrus R; Prey, Sorilla; Boralevi, Franck; Morgan, Caroline C; Heritier, Stephane; Delarue, Alain; Voisard, Jean-Jacques

    2015-02-19

    Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by

  12. Postmarketing comparison of labetalol and propranolol in hypertensive patients.

    Science.gov (United States)

    Due, D L; Giguere, G C; Plachetka, J R

    1986-01-01

    A survey was conducted to compare the safety and effectiveness of labetalol and propranolol under routine conditions of clinical use. Patients received either labetalol (n = 805) or propranolol (n = 135) twice daily, according to package insert instructions, for six weeks. Every two weeks the patients were evaluated and weight, heart rate, blood pressure, dose, and adverse symptoms were recorded. Both treatment groups experienced a significant decline in blood pressure at six weeks; blood pressure decreased by 24/15 mmHg in the labetalol patients and by 20/14 mmHg in the propranolol patients. Heart rate decreased significantly in both groups, but the drop in the propranolol group was greater than in the labetalol group. Significantly more propranolol-treated patients reported fatigue (15.2% versus 6.3%), impotence (9.0% versus 3.2%), bad dreams (2.3% versus 0.3%), and cold extremities (2.3% versus 0%). Dizziness was reported more frequently by the labetalol group (9.1% versus 3.8%). Overall, both drugs were safe and effective in treating hypertension, but complaints of beta-blocker-associated side effects were more frequent with propranolol.

  13. Comparison of propranolol and practolol in the management of hyperthyroidism.

    Science.gov (United States)

    Murchison, L E; Bewsher, P D; Chesters, M I; Ferrier, W R

    1976-04-01

    Twenty-one hyperthyroid patients participated in an 8-week double-blind crossover trial of propranolol and practolol, and the effecte of these drugs on the clinical and metabolic features of the disease were studied. Propranolol was marginally more effective than practolol, as measured by the hyperthyroid diagnostic index and anxiety scale. Propranolol produced a significant reduction in the serum concentration ratio of tri-iodothyronine to thyroxine, compatible with partial inhibition of peripheral deiodination of thyroxine. Adverse reactions occurred more frequently with propranolol than with practolol. In veiw of the efficacy of practoloo, further trials in hyperthyroid patients of newer beta1-adrenoceptor antagonists, preferably without partial agonist activity, are indicated.

  14. Propranolol and survival from breast cancer

    DEFF Research Database (Denmark)

    Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

    2016-01-01

    BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

  15. PPARa and PPAR¿ coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats

    DEFF Research Database (Denmark)

    Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer

    2009-01-01

    in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological...... activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active....

  16. One and three doses of propranolol a day in hypertension.

    Science.gov (United States)

    van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

    1980-01-01

    In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

  17. Inhibitory effects of recombinant plasmid pshuttle-Egr1-shTRAIL transfection in combination with X-irradiation on growth of liver cancer cells SMMC7721

    International Nuclear Information System (INIS)

    Chen Zhiyong; Liu Min; Dong Lihua; Gong Shouliang

    2011-01-01

    Objective: To investigate the effect of recombinant plasmid pshuttle-Egr1-shTRAIL stable transfection in combination with X-ray irradiation on the TRAIL protein expression and the apoptosis in human SMMC7721 hepatoma cells. Methods: The pshuttle-Egr1-shTRAIL packaged with liposome was stably transfected into SMMC7721 cells in vitro. The shTRAIL protein expression were measured with ELISA assay, Annexin V-FITC kit was adopted to measure the apoptosis of pshuttle-Egr1-shTRAIL cells, and the changes in survival rate of SMMC7721 cells measured with cell cloning assay. Results: The TRAIL protein expressions in pshuttle-Egr1-shTRAIL plus different doses of irradiation groups were significantly increased compared with 0 Gy group (P<0.001). The percentage of apoptotic cells was significantly higher than that in 0 Gy group (P<0.05 or P<0.001), and the survival rate of SMMC7721 cells was decreased significantly (P<0.05 or P<0.001). Conclusion: The pshuttle-Egr1-shTRAIL stable transfection in combination with irradiation can significantly induce the apoptosis of SMMC7721 tumor cells and inhibit the cell proliferation. (authors)

  18. Propranolol in treatment of huge and complicated infantile hemangiomas in egyptian children.

    Science.gov (United States)

    Hassan, Basheir A; Shreef, Khalid S

    2014-01-01

    Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed.

  19. Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

    Directory of Open Access Journals (Sweden)

    Guo XN

    2017-09-01

    Full Text Available Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs in microspheres made of poly(lactic-co-glycolic acid-b-poly(ethylene glycol-b-poly(lactic-co-glycolic acid copolymers (PLGA-PEG-PLGA. The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs. Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm and drug encapsulation efficiency (~23.9% and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF] in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001. The mean microvessel density of

  20. Propranolol in Treatment of Huge and Complicated Infantile Hemangiomas in Egyptian Children

    Directory of Open Access Journals (Sweden)

    Basheir A. Hassan

    2014-01-01

    Full Text Available Background. Infantile hemangiomas (IHs are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were clinically evaluated. Results. Superficial cutaneous hemangiomas began to respond to propranolol therapy within one to two weeks after the onset of treatment. The mean treatment period that was needed for the occurrence of complete resolution was 9.4 months. Treatment with propranolol was well tolerated and had few side effects. No rebound growth of the tumors was noted when propranolol dosing stopped except in one case. Conclusion. Propranolol is a promising treatment for IHs without obvious side effects. However, further studies with longer follow-up periods are needed.

  1. LC-MS/MS Estimation of Propranolol level in Exhaled Breath Condensate

    Directory of Open Access Journals (Sweden)

    Samin Hamidi 1, Maryam Amini 2, Maryam Khoubnasabjafari 3, Vahid Jouyban-Gharamaleki 4,5, Hossein Sate 6, Abolghasem Jouyban 5,7 *

    2017-12-01

    Full Text Available Background: Exhaled breath condensate (EBC could be used as a non-invasive and alternative specimen to urine and blood for monitoring propranolol levels. A simple, sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS method is employed for the determination of propranolol in EBC samples. Methods: Samples directly injected to a C18 analytical column and isocratically separated using a mobile phase composed of methanol + acetic acid (99:1 v/v. Detection was performed by positive electrospray ionization in multiple reaction monitoring and selected ion recording modes. Results: The chromatographic separation was obtained within 6.0 min and was linear over the concentration range of 5.6–224.0 ng/mL (R2 = 0.999. The accuracy and precision of the method were within 15% according to FDA guideline. The found concentrations of propranolol in EBC of two patients receiving 80 mg/day were 30 and 40 ng/mL. Conclusion: Developed method was applied to determine propranolol levels in three patients receiving propranolol in their medication. The obtained propranolol levels in EBC could be used to develop simpler, cheaper and more feasible analytical methods to be used in routine analysis of propranolol in biomedical analytical laboratories.

  2. Successful Treatment of Mild Pediatric Kasabach-Merritt Phenomenon with Propranolol Monotherapy

    Directory of Open Access Journals (Sweden)

    Worawut Choeyprasert

    2014-01-01

    Full Text Available Kasabach-Merritt phenomenon (KMP is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, a β-adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

  3. Numerical investigation of a dual-loop EGR split strategy using a split index and multi-objective Pareto optimization

    International Nuclear Information System (INIS)

    Park, Jungsoo; Song, Soonho; Lee, Kyo Seung

    2015-01-01

    Highlights: • Model-based control of dual-loop EGR system is performed. • EGR split index is developed to provide non-dimensional index for optimization. • EGR rates are calibrated using EGR split index at specific operating conditions. • Multi-objective Pareto optimization is performed to minimize NO X and BSFC. • Optimum split strategies are suggested with LP-rich dual-loop EGR at high load. - Abstract: A proposed dual-loop exhaust-gas recirculation (EGR) system that combines the features of high-pressure (HP) and low-pressure (LP) systems is considered a key technology for improving the combustion behavior of diesel engines. The fraction of HP and LP flows, known as the EGR split, for a given dual-loop EGR rate play an important role in determining the engine performance and emission characteristics. Therefore, identifying the proper EGR split is important for the engine optimization and calibration processes, which affect the EGR response and deNO X efficiencies. The objective of this research was to develop a dual-loop EGR split strategy using numerical analysis and one-dimensional (1D) cycle simulation. A control system was modeled by coupling the 1D cycle simulation and the control logic. An EGR split index was developed to investigate the HP/LP split effects on the engine performance and emissions. Using the model-based control system, a multi-objective Pareto (MOP) analysis was used to minimize the NO X formation and fuel consumption through optimized engine operating parameters. The MOP analysis was performed using a response surface model extracted from Latin hypercube sampling as a fractional factorial design of experiment. By using an LP rich dual-loop EGR, a high EGR rate was attained at low, medium, and high engine speeds, increasing the applicable load ranges compared to base conditions

  4. Regulation of radiation-induced apoptosis by early growth response-1 gene in solid tumors

    International Nuclear Information System (INIS)

    Ahmed, M.

    2003-01-01

    Ionizing radiation exposure is associated with activation of certain immediate-early genes that function as transcription factors. These include members of jun or fos and early growth response (EGR) gene families. In particular, the functional role of EGR-1 in radiation-induced signaling is pivotal since the promoter of EGR-1 contains radiation-inducible CArG DNA sequences. The Egr-1 gene belongs to a family of Egr genes that includes EGR-2, EGR-3, EGR-4, EGR-α and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene product, EGR-1, is a nuclear protein that contains three zinc fingers of the C 2 H 2 subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3' or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of transcription factors, growth factors, receptors, cell cycle regulators and pro-apoptotic genes. The gene targets mediated by Egr-1 in response to ionizing radiation include TNF-α , p53, Rb and Bax, all these are effectors of apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early signal transduction events in response to ionizing radiation leading to either growth arrest or cell death in tumor cells. There are two potential application of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains information for appropriate spatial and temporal expression in-vivo that can be regulated by ionizing radiation to control transcription of genes that have pro-apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate 'induced-radiation resistance' by inhibiting the functions of radiation-induced pro-survival genes (NFκB activity and bcl-2 expression) and activate pro-apoptotic genes (such as bax) to confer a significant radio-sensitizing effect. Together, the reported findings from my laboratory demonstrate clearly that EGR-1 is an early central gene that confers radiation sensitivity and its pro-apoptotic functions are synergized by abrogation of induced radiation

  5. Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

    Science.gov (United States)

    Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

    2016-01-01

    Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

  6. Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.

    Science.gov (United States)

    Huang, Chin-Wei; Lai, Ming-Liang; Lin, Min-Shung; Lee, Hwei-Ling; Huang, Jin-Ding

    2003-01-01

    For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the beta-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the beta-blockade effect of propranolol in Chinese subjects.

  7. Propranolol in Treatment of Huge and Complicated Infantile Hemangiomas in Egyptian Children

    OpenAIRE

    Hassan, Basheir A.; Shreef, Khalid S.

    2014-01-01

    Background. Infantile hemangiomas (IHs) are the most common benign tumours of infancy. Propranolol has recently been reported to be a highly effective treatment for IHs. This study aimed to evaluate the efficacy and side effects of propranolol for treatment of complicated cases of IHs. Patients and Methods. This prospective clinical study included 30 children with huge or complicated IHs; their ages ranged from 2 months to 1 year. They were treated by oral propranolol. Treatment outcomes were...

  8. Construction and expression of secreting type human TRAIL gene vector mediated by hypoxia/radiation double sensitive promoter

    International Nuclear Information System (INIS)

    Yang Yanming; Jia Xiaojing; Qu Yaqin; Li Yanbo

    2009-01-01

    Objective: To construct secreting type human TRAIL (shTRAIL) gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter, and observe the effect of hypoxia and radiation on shTRAIL. Methods: HRE upper and lower strands were gotten by chemical synthesis, double strands HRE was gotten by PCR; pMD19T-Egr1 was digested by Sac I and Hind III, then Egr1 was obtained, pshuttle-shTRAIL was digested by Kpn I and BamH I, then shTRAIL was obtained; HRE/Egr1 double sensitive promoter mediated shTRAIL expression vector pcDNA3.1-HRE/Egr1-shTRAIL was constructed by gene recombination technique, it was identified correctly by enzyme digestion, PCR and sequencing. A549 cells were divided into normal, hypoxia (0.1%), irradiation (6 Gy) and hypoxia + irradiation groups. Results: After enzyme digestion by BamH I and Sma I, the fragments which lengths were 1284 bp and 4 998 bp, 2 292 bp and 3 990 bp were obtained; the vector was amplified by PCR with Egr1 and shTRAIL primer, the products which lengthens were 469 bp and 820 bp were obtained; pcDNA3.1-HRE/Egr1-shTRAIL was sequenced, the result was same to designed, this demonstrated that the construction was right. The vectors were transfected into A549 cells of adenocarcinoma of lung, the expression levels of shTRAIL mRNA and protein were increased after treated with hypoxia and radiation, it had statistically significant differences compared with normal group (P<0.05), and when they were combinated, the effect was more obvious. Conclusion: Secreting type human TRAIL gene vector pcDNA3.1-HRE/Egr1-shTRAIL mediated by hypoxia/radiation double sensitive promoter is constructed successfully, and hypoxia and radiation could increase the expression of TRAIL, and they have synergetic effect. (authors)

  9. Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.

    Directory of Open Access Journals (Sweden)

    Kai Weng

    Full Text Available Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1 as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.

  10. Successful management of airway hemangioma with propranolol.

    Science.gov (United States)

    Mendiratta, Vibhu; Varghese, Bincy; Chander, Ram; Parakh, Ankit; Solanki, Ravi S

    2013-06-01

    Airway hemangiomas can be difficult to manage and cause anxiety in both the parents and the treating physician. Propranolol, a nonselective beta-blocker, has recently been used for treating proliferating infantile hemangiomas. We report successful management of a proliferating, large, mixed infantile hemangioma with subglottic extension in an Indian infant using oral propranolol in a dose of 2mg/kg/day without any side effects. Induction of early involution and freedom from the side effects of steroid therapy seem encouraging for using propranolol as a first line treatment modality in the management of troublesome hemangiomas. © 2013 The International Society of Dermatology.

  11. Early growth response gene-2 (Egr-2 regulates the development of B and T cells.

    Directory of Open Access Journals (Sweden)

    Suling Li

    2011-04-01

    Full Text Available Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development.The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2(+ lymphocytes resulted in a severe reduction of CD4(+CD8(+ (DP cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow.Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.

  12. Study on the Combustion Process and Emissions of a Turbocharged Diesel Engine with EGR

    Directory of Open Access Journals (Sweden)

    Mei Deqing

    2012-01-01

    Full Text Available A high pressure EGR system was adopted to a turbocharged inter-cooled diesel engine, to analyze its combustion and emission characteristics under the condition of different loads and constant speed. Under the same steady operating mode, with the increase of EGR rate, the temperature of compressed gas ascended, the ignition delay was shortened, the pressure and temperature of the burned gas descended, and the combustion process was prolonged. According to the experimental data, it was found that, at the same EGR rate, lower the load of engine was, lower the temperature in cylinder, and higher the increase rate of CO was. However, the increase rate of HC present a falling trend. The decrease rate of the specific emission of NOx linearly varied with EGR rate with a slope of 1.651. The increase rate of smoke opacity behaved a second-order polynomial uprising trend, and the higher the load was, the sharpener the smoke opacity deteriorated, with the increase of EGR rate. From the point of emission view, the engine with EGR system can achieve the lesser exhaust emissions in some operations by adjusting the engine parameters.

  13. Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults.

    Science.gov (United States)

    Ali, Arham; Herndon, David N; Mamachen, Ashish; Hasan, Samir; Andersen, Clark R; Grogans, Ro-Jon; Brewer, Jordan L; Lee, Jong O; Heffernan, Jamie; Suman, Oscar E; Finnerty, Celeste C

    2015-05-04

    Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge. Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P operative intervention is optimal.

  14. Mean Value Modelling of an SI Engine with EGR

    DEFF Research Database (Denmark)

    Føns, Michael; Muller, Martin; Chevalier, Alain

    1999-01-01

    Mean Value Engine Models (MVEMs) are simplified, dynamic engine models which are physically based. Such models are useful for control studies, for engine control system analysis and for model based control systems. Very few published MVEMs have included the effects of Exhaust Gas Recirculation (EGR......). The purpose of this paper is to present a modified MVEM which includes EGR in a physical way. It has been tested using newly developed, ver fast manifold pressure, manifold temperature, port and EGR mass flow sensores. Reasonable agreement has been obtained on an experimental engine, mounted on a dynamometer....

  15. Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    M.J.C. Carmona

    2005-05-01

    Full Text Available The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB, resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m², receiving propranolol before surgery (80-240 mg a day and postoperatively (10 mg a day. Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9 to 10.6 h (95% CI = 8.2-14.7; P < 0.01 and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3 to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05, while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6 vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

  16. Beta-Defensin 2 and 3 Promote Bacterial Clearance of Pseudomonas aeruginosa by Inhibiting Macrophage Autophagy through Downregulation of Early Growth Response Gene-1 and c-FOS

    Directory of Open Access Journals (Sweden)

    Yongjian Wu

    2018-02-01

    Full Text Available Beta-defensins 2 and 3 (BD2 and BD3 are inducible peptides present at the sites of infection, and they are well characterized for their antimicrobial activities and immune-regulatory functions. However, no study has thoroughly investigated their immunomodulatory effects on macrophage-mediated immune responses against Pseudomonas aeruginosa (PA. Here, we use THP-1 and RAW264.7 cell lines and demonstrate that BD2 and BD3 suppressed macrophage autophagy but enhanced the engulfment of PA and Zymosan bioparticles as well as the formation of phagolysosomes, using immunofluorescence staining and confocal microscopy. Plate count assay showed that macrophage-mediated phagocytosis and intracellular killing of PA were promoted by BD2 and BD3. Furthermore, microarray and real-time PCR showed that the expression of two genes, early growth response gene-1 (EGR1 and c-FOS, was attenuated by BD2 and BD3. Western blot revealed that BD2 and BD3 inhibited the expression and nuclear translocation of EGR1 and c-FOS. Knockdown of EGR1 and c-FOS by siRNA transfection suppressed macrophage autophagy before and after PA infection; while overexpression of these two transcription factors enhanced autophagy but reversed the role of BD2 and BD3 on macrophage-mediated PA eradication. Together, these results demonstrate a novel immune defense activity of BD2 and BD3, which promotes clearance of PA by inhibiting macrophage autophagy through downregulation of EGR1 and c-FOS.

  17. Oral versus topical propranolol for management of superficial ...

    African Journals Online (AJOL)

    was treated with oral propranolol and group B (n = 24) was treated with propranolol .... months during treatment, or if any undesirable drawbacks .... dosage and the serum concentration of the drug in this route [29]. However, McMahon et al.

  18. System and method for regulating EGR cooling using a rankine cycle

    Science.gov (United States)

    Ernst, Timothy C.; Morris, Dave

    2015-12-22

    This disclosure relates to a waste heat recovery (WHR) system and method for regulating exhaust gas recirculation (EGR) cooling, and more particularly, to a Rankine cycle WHR system and method, including a recuperator bypass arrangement to regulate EGR exhaust gas cooling for engine efficiency improvement and thermal management. This disclosure describes other unique bypass arrangements for increased flexibility in the ability to regulate EGR exhaust gas cooling.

  19. Mean Value Engine Modelling of an SI Engine with EGR

    DEFF Research Database (Denmark)

    Føns, Michael; Müller, Martin; Chevalier, Alain

    1999-01-01

    Mean Value Engine Models (MVEMs) are simplified, dynamic engine models what are physically based. Such models are useful for control studies, for engine control system analysis and for model based engine control systems. Very few published MVEMs have included the effects of Exhaust Gas...... Recirculation (EGR). The purpose of this paper is to present a modified MVEM which includes EGR in a physical way. It has been tested using newly developed, very fast manifold pressure, manifold temperature, port and EGR mass flow sensors. Reasonable agreement has been obtained on an experimental engine...

  20. File list: Oth.Bld.50.Egr2.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.Egr2.AllCell mm9 TFs and others Egr2 Blood SRX270570,SRX270569,SRX329255...,SRX110637,SRX110636,SRX329257,SRX329256,SRX122432,SRX122435,SRX122433,SRX122434 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.Egr2.AllCell.bed ...

  1. File list: Oth.ALL.20.Egr2.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Egr2.AllCell mm9 TFs and others Egr2 All cell types SRX270570,SRX270569,...SRX329255,SRX110637,SRX110636,SRX329257,SRX329256,SRX122432,SRX122435,SRX122433,SRX122434 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.20.Egr2.AllCell.bed ...

  2. File list: Oth.ALL.10.Egr2.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.10.Egr2.AllCell mm9 TFs and others Egr2 All cell types SRX270570,SRX270569,...SRX110637,SRX329255,SRX110636,SRX329257,SRX329256,SRX122434,SRX122432,SRX122435,SRX122433 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.10.Egr2.AllCell.bed ...

  3. Egr3 dependent sympathetic target tissue innervation in the absence of neuron death.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available Nerve Growth Factor (NGF is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax-deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appears to effect target tissue innervation heterogeneously. In some tissues, such as heart, spleen, bowel, kidney, pineal gland and the eye, Egr3 is essential for normal innervation, whereas in other tissues such as lung, stomach, pancreas and liver, Egr3 appears to have little role in innervation. Moreover, in salivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that abnormal target tissue innervation is not due to deregulation of these neurotrophins in target tissues. Taken together, these results clearly demonstrate a role for Egr3 in mediating sympathetic target tissue innervation that is independent of neuron survival or neurotrophin deregulation.

  4. Computation and Analysis of EGR Mixing in Internal Combustion Engine Manifolds

    OpenAIRE

    Sakowitz, Alexander

    2013-01-01

    This thesis deals with turbulent mixing processes occurring in internal combustion engines, when applying exhaust gas recirculation (EGR). EGR is a very efficient way to reduce emissions of nitrogen oxides (NOx) in internal combustion engines. Exhaust gases are recirculated and mixed with the fresh intake air, reducing the oxygen con- centration of the combustion gas and thus the peak combustion temperatures. This temperature decrease results in a reduction of NOx emissions. When applying EGR...

  5. Atenolol vs. propranolol in essential tremor. A controlled, quantitative study.

    Science.gov (United States)

    Larsen, T A; Teräväinen, H; Calne, D B

    1982-11-01

    The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo. These drugs did not affect tremor frequency. Twelve of the patients preferred propranolol subjectively, one preferred atenolol and none preferred placebo. No marked side-effects were observed. It was concluded that atenolol and other cardio-selective blockers offer an alternative for patients unable to tolerate the non-selective drugs. The site of action and receptor sub-type involved have still to be determined.

  6. Amitriptyline induces early growth response-1 gene expression via ERK and JNK mitogen-activated protein kinase pathways in rat C6 glial cells.

    Science.gov (United States)

    Chung, Eun Young; Shin, Soon Young; Lee, Young Han

    2007-07-05

    Astrocytes play important roles in guiding the construction of the nervous system, controlling extracellular ions and neurotransmitters, and regulating CNS synaptogenesis. Egr-1 is a transcription factor involved in neuronal differentiation and astrocyte cell proliferation. In this study, we investigated whether the tricyclic antidepressant (TCA) amitriptyline induces Egr-1 expression in astrocytes using rat C6 glioma cells as a model. We found that amitriptyline increased the expression of Egr-1 in a dose- and time-dependent manner. The amitriptyline-induced Egr-1 expression was mediated through serum response elements (SREs) in the Egr-1 promoter. SREs were activated by the Ets-domain transcription factor Elk-1 through the ERK and JNK mitogen-activated protein (MAP) kinase pathways. The inhibition of the ERK and JNK MAP kinase signals attenuated amitriptyline-induced transactivation of Gal4-Elk-1 and Egr-1 promoter activity. Our findings suggest that the induction of Egr-1 expression in astrocytes may be required to attain the therapeutic effects of antidepressant drugs.

  7. Systemic propranolol acts centrally to reduce conditioned fear in rats without impairing extinction.

    Science.gov (United States)

    Rodriguez-Romaguera, Jose; Sotres-Bayon, Francisco; Mueller, Devin; Quirk, Gregory J

    2009-05-15

    Previous work has implicated noradrenergic beta-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The beta-receptor blocker propranolol has been used clinically to reduce anxiety. With an auditory fear conditioning task in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar-pressing. One day after receiving auditory fear conditioning, rats were injected with saline, propranolol, or peripheral beta-receptor blocker sotalol (both 10 mg/kg, IP). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed. Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons. Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

  8. Effects of Propranolol on the Left Ventricular Volume of Normal Subjects During CT Coronary Angiography

    International Nuclear Information System (INIS)

    Mo, Yuan Heng; Jaw, Fu Shan; Wang, Yung Cheng; Jeng, Chin Ming; Peng, Shinn Forng

    2011-01-01

    The purpose of this study is to determine the effects of propranolol on the left ventricular (LV) volume during CT coronary angiography. The LV volume of 252 normal Chinese subjects (126 subjects with propranolol medication and 126 age- and gender-matched Chinese subjects without medication) was estimated using 64 slices multi-detector CT (MDCT). The heart rate difference was analyzed by the logistic linear regression model with variables that included gender, age, body height, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the dosage of propranolol. The following global LV functional parameters were calculated: the real-end diastolic volume (EDV), the real-end systolic volume (ESV) and the real-ejection fraction (EF). The female subjects had a greater decrease of heart rate after taking propranolol. The difference of heart rate was negatively correlated with the dosage of propranolol. The real-EDV, the real-ESV and the real-EF ranged from 48.1 to 109 mL/m2, 6.1 to 57.1 mL/m2 and 41% to 88%, respectively. There was no significant difference in the SBP and DBP between the groups without and with propranolol medication (123 ± 17 and 80 ± 10 mmHg; 120 ± 14 and 80 ± 11 mmHg, respectively). The real-EDV showed no significant difference between these two groups, but the real-ESV and real-EF showed significant differences between these two groups (69.4 ± 9.3 and 70.6 ± 8.9 mL/m2; 23.5 ± 5.7 and 25.6 ± 3.7 mL/m2, 66.5 ± 5.1% and 63.5 ± 4.6%, respectively). The difference of heart rate is significantly influenced by gender and the dosage of propranolol. Propranolol will also increase the ESV, which contributes to a decreased EF, while the SBP, DBP and EDV are not statistically changed.

  9. Thermodynamic analysis of EGR effects on the first and second law efficiencies of a boosted spark-ignited direct-injection gasoline engine

    International Nuclear Information System (INIS)

    Li, Tie; Wu, Da; Xu, Min

    2013-01-01

    Highlights: • We clarified the mechanism of EGR improving fuel economy of gasoline engines. • At constant air–fuel ratio, reduction of heat transfer loss is most significant. • At full load, elimination of fuel enrichment is dominant. • Combustion irreversibility increases with EGR. • Availability in the exhaust and heat transfer losses is smaller than energy losses. - Abstract: Exhaust gas recirculation (EGR) is effective to improve fuel economy of spark-ignition gasoline engines, but the detailed mechanism needs to be further investigated. In this paper, an in-depth analysis of the effects of cooled EGR on the fuel conversion efficiency of a boosted, spark-ignited, direct-injection, gasoline engines operated at the full, medium and low loads is conducted with the engine experiment and 1-D cycle simulation based on the first and second laws of thermodynamics. For all the operating loads, EGR increases the ratio of specific heat of working gas, reduces the fraction of heat transfer through the combustion chamber walls, and improves the pumping work during the gas exchanging stroke. Besides, EGR may replace the fuel enrichment at high load, advance the combustion phasing and increase the degree of constant volume heat release at the medium and high loads. As a result, about 1.1–4.1% improvements in the brake thermal efficiency are obtained by the 12–17% EGR at different loads. Despite the increased fraction of combustion-generated irreversibility (destruction in availability or exergy), the fraction of indicated work in the total availability increases with EGR for all the operating loads. Among the influencing factors, the effect of reduction in the heat transfer loss owing to EGR is dominant in improvement of the fuel conversion efficiency at constant air–fuel ratio, while replacement of the fuel enrichment with EGR is most effective at full load

  10. Comparison of betaxolol, a new beta 1-adrenergic antagonist, to propranolol in the treatment of mild to moderate hypertension.

    Science.gov (United States)

    Davidov, M E; Glazer, N; Wollam, G; Zager, P G; Cangiano, J

    1988-07-01

    A double-blind, multicenter study compared the safety and efficacy of oral betaxolol 10 to 40 mg once daily (n = 68) with propranolol 40 to 160 mg twice daily (n = 73) in the treatment of mild to moderate essential hypertension. Both agents produced significant (P less than 0.01) and comparable reductions in mean supine systolic and diastolic blood pressures (7/11 mm Hg on betaxolol and 9/10 mm Hg on propranolol). Both betaxolol and propranolol significantly (P less than 0.01) reduced mean supine heart rate by 9 beats per minute. Patients achieved a more significant (P less than 0.01) reduction in blood pressure earlier (weeks 2 and 4 of the titration period) with betaxolol. By the end of treatment there was no significant difference in response between treatment groups. A higher incidence of central nervous system side effects (insomnia, bizarre dreams, depression, hallucinations, dizziness), however, was seen with propranolol than with betaxolol. Overall, the data show that in patients with mild to moderate essential hypertension, betaxolol 10 to 40 mg administered once daily is as effective as and better tolerated than propranolol 40 to 160 mg administered twice daily.

  11. Cyproheptadine versus propranolol in the prevention of migraine headaches in children

    International Nuclear Information System (INIS)

    Asadi, B.; Khorvash, F.

    2012-01-01

    Objective: There are conflicting results on the efficacy of propranolol and cyproheptadine in the prevention of migraine headaches in children. Therefore, in this study, we evaluated the efficacy of propranolol versus cyproheptadine in the prevention of migraine headaches. Methodology: This was a randomized, double-blind trial. Sixty children aged 8-15 yrs with migraine headaches were randomized to be treated with either propranolol (40-80 mg per day) or cyproheptadine (8-12 mg per day) for 4 weeks. The patients were requested to record the Severity and duration of their headaches during a 2-week period before starting the intervention. The patients were followed at 2-week intervals for a period of 1 month after starting treatment. The headache diary was analyzed for each patient and was compared with baseline using SPSS software and statistical tests including the student's t-test. Results: Out of 60 patients at baseline, nine patients in the cyproheptadine group and six patients in the propranolol group did not appear at the appropriate time for follow-up visits and therefore were excluded from the study. The mean age in the cyproheptadine group was 11.9+-2.23 years and in the propranolol group was 0.7 +- 2.33 years. Based on the diaries, the results Showed that propranolol and cyproheptadine decreased headaches by 54.61% and 70.53% (p < 0.05), respectively, at the end of four weeks of treatment. Conclusion: Overall, the results of our study suggest that cyproheptadine is a good choice for prevention of migraine headache in pediatric group although more prolonged study with higher number of the patient is recommended. (author)

  12. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems

    Directory of Open Access Journals (Sweden)

    Elham A. Afify

    2017-11-01

    Full Text Available Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate, (visceral, acetic acid, and (inflammatory, formalin test in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively. The study revealed that propranolol (0.25–20 mg/Kg, IP administration did not produce analgesia in mice. However, 10 mg/Kg propranolol, enhanced the antinociceptive effect of sub-analgesic doses of morphine (0.2, 1, and 2 mg/Kg, IP in the three nociceptive tests. It also shifted the dose response curve of morphine to the left. The combined effect of propranolol and morphine was attenuated by haloperidol (D2 receptor antagonist, 1.5 mg/Kg, IP, and bicuculline (GABAA receptor antagonist, 2 mg/Kg, IP. Repeated daily administration of propranolol (10 mg/Kg, IP did not alter the nociceptive responses in the three pain tests, but it significantly potentiated morphine-induced antinociception in the hot plate, acetic acid-evoked writhing, and in the second phase of formalin tests. Together, the data suggest that a cross-talk exists between the opioidergic and adrenergic systems and implicate dopamine and GABA systems in this synergistic effect of morphine-propranolol combination. Propranolol may serve as an adjuvant therapy to potentiate the effect of opioid analgesics.

  13. Propranolol reduces the anxiety associated with day case surgery.

    Science.gov (United States)

    Mealy, K; Ngeh, N; Gillen, P; Fitzpatrick, G; Keane, F B; Tanner, A

    1996-01-01

    To find out if propranolol, a non-cardioselective beta-blocker, can reduce the anxiety associated with day case surgery. Prospective randomized double blind trial. University hospital, Ireland. An unselected group of 53 patients undergoing day case surgery. Subjects randomised to receive either propranolol (10 mg) or placebo on the morning of operation. Blood pressure; pulse, anxiety, pain score and patient satisfaction. Mean (SD) Hospital Anxiety and Depression score was significantly lower in the propranolol group than in the control group (2.5 (0.7) compared with 4.6 (0.7), p anxiety.

  14. Effect of external hot EGR dilution on combustion, performance and particulate emissions of a GDI engine

    International Nuclear Information System (INIS)

    Xie, Fangxi; Hong, Wei; Su, Yan; Zhang, Miaomiao; Jiang, Beiping

    2017-01-01

    Highlights: • Effect of hot EGR on combustion and PN emission is investigated on a GDI engine. • Appropriate addition of hot EGR can reduce fuel consumption, NO_x and PN emission. • Relationship between BSFC and emissions of hot EGR is better than cooled EGR. • Condition with low-medium speeds and medium loads are more suitable for hot EGR. - Abstract: In this paper, an experimental investigation about the influence of hot EGR addition on the engine combustion, performance and particulate number emission was conducted at a spark-ignition gasoline direct injection (GDI) engine. Meanwhile, the different effects between cooled and hot EGR addition methods were compared and the variations of fuel consumption and particle number emissions under six engine operating conditions with different speeds and loads were analyzed. The research result indicated that increasing hot EGR ratio properly with adjustment of ignition timing could effectively improve the relationship among brake-specific fuel consumption (BSFC), NO_x and particle number emissions. When hot EGR ratio increased to 20%, not only BSFC but also the NO_x and particle number emissions were reduced, which were about 7%, 87% and 36% respectively. Compared with cooled EGR, the flame development and propagation speeds were accelerated, and cycle-by-cycle combustion variation decreased with hot EGR. Meanwhile, using hot EGR made the engine realize a better relationship among fuel consumption, NO_x and particle number emissions. The biggest improvements of BSFC, NO_x and particle number emissions were obtained at low-medium speed and medium load engine conditions by hot EGR addition method. While engine speed increased and load decreased, the improvement of engine fuel consumption and emission reduced with hot EGR method.

  15. Selection of Suitable Microorganism for Biocatalytic Oxidation Reaction of Racemic Propranolol

    Directory of Open Access Journals (Sweden)

    Rahime SONGÜR

    2017-12-01

    Full Text Available Propranolol is one of the β-blockers which are pharmaceutically important, especially used for treatment of cardiovasculer disease. In this study, the production of enantiomerically pure propranolol was aimed via biocatalytic deracemization including tandem oxidation-reduction reactions of racemic propranolol. Within this content, firstly suitable microorganism for the oxidation of racemic propranolol was investigated. Alcohol dehydrogenase (ADH enzyme for oxidation of propranolol and NADH oxidase enzyme for cofactor regeneration were necessary for the oxidation reactions. For this reason, ADH and NADH oxidase enzymes activities of different microorganisms were measured to select the microorganism for using as enzyme source. These microorganisms are Lactobacillus kefir NRRL B-1839, Rhodotorula glutunis DSM 70398, Rhizopus oryzae CBS 111718, Rhizopus arhizus. The highest ADH and NADH oxidase activities were obtained for L. kefir.

  16. Control of lithium tremor with propranolol.

    Science.gov (United States)

    Lapierre, Y D

    1976-04-03

    Lithium tremor is an irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency. It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of perpheral origin. Five patients were successfully treated with propranolol. In general, the dosage of propranolol must be individually adjusted and is usually from 30 to 40 mg daily in divided doses. This blocker of beta-adrenergic receptors remains effective with long-term administration and increases in dosage are not required.

  17. A predictive model for knock onset in spark-ignition engines with cooled EGR

    International Nuclear Information System (INIS)

    Chen, Longhua; Li, Tie; Yin, Tao; Zheng, Bin

    2014-01-01

    Highlights: • Ratio of specific heats should be used as variable in development of knock model. • Increases in EGR or excess air ratio lead to increases in the ratio of specific heats. • The widely-used Douaud–Eyzat correlation fails to predict the knock onset when increasing EGR. • The newly developed model including p, T, EGR and λ as variables predicts the knock onset accurately. • Effect of temperature at intake valve closure on the predicted knock onset is relatively small. - Abstract: A predictive knock model is crucial for one dimensional (1-D) engine cycle simulation that has been proven to be a powerful tool in both optimization of the conceptual design and reduction of calibration efforts in development of spark-ignition (SI) engines. With application of advanced technologies such as exhaust gas recirculation (EGR) in modern SI engines, update of knock model is needed to give an acceptable prediction of knock onset. In this study, bench tests of a turbocharged gasoline SI engine with cooled EGR system operated under knocking conditions were conducted, the cylinder pressure traces were analyzed by the band-pass filtering technique, and the crank angle of knock onset was determined by the signal energy ratio (SER) and image processing method. A knock model considering multi-variable effects including pressure, temperature, EGR ratio and excess air ratio (λ) is formulated and calibrated with the experimental data using the multi-island genetic algorithm (GA). The calculation method of the end gas temperature, the impacts of the ratio of specific heats as well as the temperature at the intake valve closure on the end gas temperature are discussed. The performance of the new model is compared with the widely-used phenomenological knock models such as Douaud–Eyzat model and Hoepke model. While the widely-used knock models fail to give acceptable predictions when increasing EGR with fuel enrichment operations, the new model predicts the knock

  18. Energy efficiency impact of EGR on organizing clean combustion in diesel engines

    International Nuclear Information System (INIS)

    Divekar, Prasad S.; Chen, Xiang; Tjong, Jimi; Zheng, Ming

    2016-01-01

    Highlights: • Studied EGR impact on efficiency and emissions of diesel and dual-fuel combustion. • Quantified effectiveness of intake dilution for NOx reduction using EGR. • Identified suitable EGR ranges for mitigating emissions–efficiency trade-off. • Developed careful control of intake dilution and in-cylinder excess ratio. • Enabled ultra-low NOx in both diesel and dual-fuel combustion via EGR control. - Abstract: Exhaust gas recirculation (EGR) is a commonly recognized primary technique for reducing NOx emissions in IC engines. However, depending on the extent of its use, the application of EGR in diesel engines is associated with an increase in smoke emissions and a reduction in thermal efficiency. In this work, empirical investigations and parametric analyses are carried out to assess the impact of EGR in attaining ultra-low NOx emissions while minimizing the smoke and efficiency penalties. Two fuelling strategies are studied, namely diesel-only injection and dual-fuel injection. In the dual-fuel strategy, a high volatility liquid fuel is injected into the intake ports, and a diesel fuel is injected directly into the cylinder. The results suggest that the reduction in NOx can be directly correlated with the intake dilution caused by EGR and the correlation is largely independent of the fuelling strategy, the intake boost, and the engine load level. Simultaneously ultra-low NOx and smoke emissions can be achieved at high intake boost and intake dilution levels in the diesel-only combustion strategy and at high ethanol fractions in the dual-fuel strategy. The efficiency penalty associated with EGR is attributed to two primary factors; the combustion off-phasing and the reduction in combustion efficiency. The combustion off-phasing can be minimized by the closed loop control of the diesel injection timing in both the fuelling strategies, whereas the combustion efficiency can be improved by limiting the intake dilution to moderate levels. The

  19. Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Sørensen, T I

    1991-01-01

    1 year of treatment with propranolol, whereas a decrease in azygos blood flow was observed only in the propranolol group. The beneficial effect of propranolol on the risk of bleeding from oesophageal varices may, therefore, mostly be due to a selective decrease in collateral blood flow and thereby...

  20. Labetalol compared with propranolol in the treatment of black hypertensive patients.

    Science.gov (United States)

    Saunders, E; Curry, C; Hinds, J; Kong, B W; Medakovic, M; Poland, M; Roper, K

    1987-09-01

    A double-blind parallel group study was conducted to examine the effects of oral labetalol, in doses from 100 to 800 mg BID, and propranolol, 40 to 320 mg, in patients with mild to moderate hypertension. The doses of labetalol (n = 74) and propranolol (n = 79) were titrated weekly to achieve a sitting diastolic blood pressure (DBP) of less than 90 mmHg or at least a 10-mmHg decrease from placebo baseline on two consecutive visits. A 2-month fixed-dose maintenance phase followed in which a diuretic could be added if the sitting DBP was greater than or equal to 100 mmHg on maximum doses of either drug. BP and heart rate were measured 8-12 hours after a dose in the sitting and standing positions. Labetalol was significantly more effective at the end of monotherapy than propranolol was in lowering both the sitting (p less than .05) and standing (p less than .04) DBP. The reduction in the systolic, although more pronounced for those on labetalol, was not significantly different; 53% of patients had a "good" response to labetalol compared with 30% of the propranolol group. Propranolol significantly (p less than 0.01) lowered heart rate compared with labetalol. Nine patients in the labetalol group and 10 in the propranolol group required a diuretic. The decrease in BP after the addition of a diuretic was comparable. Changes in plasma lipids were not significant, but HDL increased 9% with labetalol and decreased 2% with propranolol. Triglycerides increased 25% with labetalol and 31% with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Propranolol modulates the collateral vascular responsiveness to vasopressin via a G(α)-mediated pathway in portal hypertensive rats.

    Science.gov (United States)

    Lee, Jing-Yi; Huo, Teh-Ia; Huang, Hui-Chun; Lee, Fa-Yauh; Lin, Han-Chieh; Chuang, Chiao-Lin; Chang, Ching-Chih; Wang, Sun-Sang; Lee, Shou-Dong

    2011-12-01

    Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague-Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a G(α) inhibitor) or suramin pre-incubation. G(α) mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg x kg(-1) of body weight x day(-1)) for 9 days. Then the concentration-response relationship of AVP and G(α) mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt G(αq) and G(α11) mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of G(α11) as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. G(αs) expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to G(αq) and G(α11) up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to G(αs) up-regulation. The G(α) signalling

  2. Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

    Science.gov (United States)

    Forbes, Angela S; Regis, David P; Hall, Aaron A; Mahon, Richard T; Cronin, William A

    2017-04-01

    Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

  3. The pathogenesis of propranolol-withdrawal syndrome in essential hypertension.

    Science.gov (United States)

    Kristensen, B O; Steiness, E; Weeke, J

    1979-12-01

    1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.

  4. Influence of ethanol and EGR on laminar burning behaviors of FACE-C gasoline and its surrogate

    KAUST Repository

    Mannaa, Ossama Abde El Hamid; Mansour, Morkous; Roberts, William L.; Chung, Suk-Ho

    2017-01-01

    Laminar burning velocities of FACE-C gasoline and a surrogate comprised of toluene primary reference fuels (TPRFs) were investigated under the effects of EGR dilution and ethanol blending. Measurements were conducted in a spherical constant volume combustion chamber for a range of equivalence ratios from 0.8 to 1.6 at initial temperatures and pressures up to 383 K and 0.6 MPa, respectively. These measurements highlighted the effects of real combustion residuals at mole fractions up to 0.3 and various volumetric percentages of ethanol blending. For both studied fuels, significant reductions in stretched and un-stretched flame speeds were observed for mixtures laden with real combustion residuals. Blends with less than 50% ethanol showed a minimal enhancement in the flame speed. By combining both EGR and ethanol blending, the flame speed reduction by EGR can be compensated for with ethanol addition. For example, up to 10% of EGR requires 60% ethanol blending to maintain the same flame speed. Flame stability enhancement by EGR addition was also quantified through the determination of the Markstein length.

  5. Influence of ethanol and EGR on laminar burning behaviors of FACE-C gasoline and its surrogate

    KAUST Repository

    Mannaa, Ossama Abde El Hamid

    2017-10-31

    Laminar burning velocities of FACE-C gasoline and a surrogate comprised of toluene primary reference fuels (TPRFs) were investigated under the effects of EGR dilution and ethanol blending. Measurements were conducted in a spherical constant volume combustion chamber for a range of equivalence ratios from 0.8 to 1.6 at initial temperatures and pressures up to 383 K and 0.6 MPa, respectively. These measurements highlighted the effects of real combustion residuals at mole fractions up to 0.3 and various volumetric percentages of ethanol blending. For both studied fuels, significant reductions in stretched and un-stretched flame speeds were observed for mixtures laden with real combustion residuals. Blends with less than 50% ethanol showed a minimal enhancement in the flame speed. By combining both EGR and ethanol blending, the flame speed reduction by EGR can be compensated for with ethanol addition. For example, up to 10% of EGR requires 60% ethanol blending to maintain the same flame speed. Flame stability enhancement by EGR addition was also quantified through the determination of the Markstein length.

  6. The role of propranolol as a radiosensitizer in gastric cancer treatment

    Directory of Open Access Journals (Sweden)

    Liao XH

    2018-03-01

    Full Text Available Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy 

  7. Effect of exhaust gas recirculation (EGR) and multiple injections on diesel soot nano-structure and reactivity

    International Nuclear Information System (INIS)

    Rohani, Behzad; Bae, Choongsik

    2017-01-01

    Highlights: • EGR reduced the nano-structural order, regardless of injection strategy. • EGR reduces both VOF and reactivity, regardless of injection strategy. • Longer dwell time between pilot and main injection increases VOF and reactivity. • With EGR, VOF and reactivity are both reduced and un-affected by injection strategy. • VOF-reactivity correlation (without causality) suggests role of surface roughness. - Abstract: The physio-chemical characteristics of soot particles are of importance with regard to performance of diesel after-treatment systems. In this study, the soot particles generated in a single-cylinder heavy-duty diesel engine are examined in terms of nanostructure, oxidative reactivity and volatile organic fraction (VOF), using thermogravimetric analysis (TGA), X-ray diffraction (XRD), Raman micro-spectroscopy, and high resolution transmission electron microscopy (HRTEM). Five different injection strategies including single injection and multiple injections with various pilot injection amounts and dwell times were tested with and without exhaust gas recirculation (EGR), while combustion phasing, engine speed, and fuel injection quantity was matched for all cases. Results indicate that for the soot produced under EGR condition, nano-structural order (indicated by crystallite size obtained from XRD and AD1/AG resulted from the Raman Analysis) can explain the soot reactivity. However, in the absence of EGR, the reactivity trend cannot be explained by the structural order. It is discussed that a possible reason can be a higher level of in-cylinder oxidation in non-EGR cases (indicated by higher level of surface functional groups) which roughens the soot surface, and enhances the oxidation by increasing the specific soot surface area. It is also found that in the absence of EGR, different injection strategies impact the soot reactivity and VOF content, which can be explained mainly through the level of charge premixed-ness and the in

  8. Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

  9. Corticosterone and propranolol's role on taste recognition memory.

    Science.gov (United States)

    Ruetti, E; Justel, N; Mustaca, A; Boccia, M

    2014-12-01

    Taste recognition is a robust procedure to study learning and memory processes, as well as the different stages involved in them, i.e. encoding, storage and recall. Considerable evidence indicates that adrenal hormones and the noradrenergic system play an important role in aversive and appetitive memory formation in rats and humans. The present experiments were designed to characterize the effects of immediate post training corticosterone (Experiment 1) and propranolol administration (Experiment 2 and 3) on taste recognition memory. Administration of a high dose of corticosterone (5mg/kg, sc) impairs consolidation of taste memory, but the low and moderate doses (1 and 3mg/kg, sc) didn't affect it. On the other hand, immediate post-training administration of propranolol (1 and 2mg/kg, ip) impaired taste recognition memory. These effects were time-dependent since no effects were seen when drug administration was delayed 3h after training. These findings support the importance of stress hormones and noradrenergic system on the modulation of taste memory consolidation. Copyright © 2014. Published by Elsevier Inc.

  10. Induction of the early response protein EGR-1 in human tumour cells after ionizing radiation is correlated with a reduction of repair of lethal lesions and an increase of repair of sublethal lesions

    NARCIS (Netherlands)

    Franken, Nicolaas A. P.; ten Cate, Rosemarie; van Bree, Chris; Haveman, Jaap

    2004-01-01

    The role of EGR-1 in potentially lethal damage repair (PLDR) was studied. Induction of the early response protein EGR-1 and survival after ionizing radiation of two human tumour cell lines after culturing for 48 h in serum-deprived medium was investigated. The glioblastoma cell line (Gli-6) and a

  11. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory.

    Science.gov (United States)

    Penke, Zsuzsa; Morice, Elise; Veyrac, Alexandra; Gros, Alexandra; Chagneau, Carine; LeBlanc, Pascale; Samson, Nathalie; Baumgärtel, Karsten; Mansuy, Isabelle M; Davis, Sabrina; Laroche, Serge

    2014-01-05

    It is well established that Zif268/Egr1, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of Zif268 in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce Zif268 overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that Zif268 overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging Zif268 contribute to determining the strength of newly encoded memories.

  12. Numerical Investigation on Effects of Assigned EGR Stratification on a Heavy Duty Diesel Engine with Two-Stage Fuel Injection

    Directory of Open Access Journals (Sweden)

    Zhaojie Shen

    2018-02-01

    Full Text Available External exhaust gas recirculation (EGR stratification in diesel engines contributes to reduction of toxic emissions. Weak EGR stratification lies in that strong turbulence and mixing between EGR and intake air by current introduction strategies of EGR. For understanding of ideal EGR stratification combustion, EGR was assigned radically at −30 °CA after top dead center (ATDC to organize strong EGR stratification using computational fluid dynamics (CFD. The effects of assigned EGR stratification on diesel performance and emissions are discussed in this paper. Although nitric oxides (NOx and soot emissions are both reduced by means of EGR stratification compared to uniform EGR, the trade-off between NOx and soot still exists under the condition of arranged EGR stratification with different fuel injection strategies. A deterioration of soot emissions was observed when the interval between main and post fuel injection increased, while NO emissions increased first then reduced. The case with a 4 °CA interval between main and post fuel injection is suitable for acceptable NO and soot emissions. Starting the main fuel injection too early and too late is not acceptable, which results in high NO emissions and high soot emissions respectively. The start of the main fuel injection −10 °CA ATDC is suitable.

  13. Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study.

    Science.gov (United States)

    Bayart, Cheryl B; Tamburro, Joan E; Vidimos, Allison T; Wang, Lu; Golden, Alex B

    2017-07-01

    The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial. Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS). The mean change in HAS was -2.94 ± 1.20 for patients treated with atenolol and -2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol. Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters. © 2017 Wiley Periodicals, Inc.

  14. Regulation of glucose transport and c-fos and egr-1 expression in cells with mutated or endogenous growth hormone receptors

    DEFF Research Database (Denmark)

    Gong, T W; Meyer, D J; Liao, J

    1998-01-01

    To identify mechanisms by which GH receptors (GHR) mediate downstream events representative of growth and metabolic responses to GH, stimulation by GH of c-fos and egr-1 expression and glucose transport activity were examined in Chinese hamster ovary (CHO) cells expressing mutated GHR. In CHO cel...

  15. EGR technology for lowest emissions

    NARCIS (Netherlands)

    Baert, R.S.G.; Beckman, D.E.; Veen, A.

    1996-01-01

    An EGR system for turbocharged and aftercooled HD diesel engines has been demonstrated on a 12 litre 315 kW engine with 4 valves per cylinder and a high pressure injection system. In this system exhaust gas is tapped off before the turbine, run through a cooler and mixed with the intake air after

  16. Combustion and emission characteristics of a natural gas-fueled diesel engine with EGR

    International Nuclear Information System (INIS)

    Abdelaal, M.M.; Hegab, A.H.

    2012-01-01

    Highlights: ► An existed DI diesel engine has been modified to suit dual fuel operation with EGR. ► Comparative study has been conducted between different operating modes. ► Dual fuel mode exhibits better performance at high loads than diesel. ► Dual fuel mode exhibits lower NOx and higher HC emissions than diesel. ► EGR improves performance at part loads and emissions of dual fuel mode. - Abstract: The use of natural gas as a partial supplement for liquid diesel fuel is a very promising solution for reducing pollutant emissions, particularly nitrogen oxides (NOx) and particulate matters (PM), from conventional diesel engines. In most applications of this technique, natural gas is inducted or injected in the intake manifold to mix uniformly with air, and the homogenous natural gas–air mixture is then introduced to the cylinder as a result of the engine suction. This type of engines, referred to as dual-fuel engines, suffers from lower thermal efficiency and higher carbon monoxide (CO) and unburned hydrocarbon (HC) emissions; particularly at part load. The use of exhaust gas recirculation (EGR) is expected to partially resolve these problems and to provide further reduction in NOx emission as well. In the present experimental study, a single-cylinder direct injection (DI) diesel engine has been properly modified to run on dual-fuel mode with natural gas as a main fuel and diesel fuel as a pilot, with the ability to employ variable amounts of EGR. Comparative results are given for various operating modes; conventional diesel mode, dual-fuel mode without EGR, and dual-fuel mode with variable amounts of EGR, at different operating conditions; revealing the effect of utilization of EGR on combustion process and exhaust emission characteristics of a pilot ignited natural gas diesel engine.

  17. A clinical trial of the beta blocker propranolol in premature ejaculation.

    Science.gov (United States)

    Cooper, A J; Magnus, R V

    1984-01-01

    Twelve male patients, with a primary complaint of premature ejaculation in a setting of chronic anxiety with prominent somatic manifestations, participated in a double-blind trial: propranolol against placebo. The study consisted of 5 X 4 week phases: run-in, propranolol or placebo--120 mg/day allocated randomly, wash-out; placebo or propranolol and run-out, in a balanced design. Anxiety was rated initially, and every 2 weeks, throughout the trial using the Hamilton Rating Scale. Sitting blood pressure and pulse were also noted. The time to coital ejaculation (every 3 days) was recorded using a stopwatch, and subjects were also required to rate "overall coital satisfaction" and "quality of erection". Neither prematurity nor other signs/symptoms of anxiety improved on the preparations, which were statistically equivalent. Moderate beta-blockade was achieved with propranolol as evidenced by a median reduction in pulse rate of 5 beats/min.

  18. Odor discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

    Science.gov (United States)

    Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2018-04-19

    Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odor. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odor (PO) and aversive odor (AO) memory in C. sphinx We used preferred (0.8% wt/wt of cinnamon powder) and aversive (0.4% wt/vol of citral) odor substances, with freshly-prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of Egr-1 and C-fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but different for AO. The response to AO elevated the level of C-fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism entailing protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that the C-fos expression is possibly controlled by an odor-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

  19. Long-term recognition memory of individual conspecifics is associated with telencephalic expression of Egr-1 in the electric fish Apteronotus leptorhynchus.

    Science.gov (United States)

    Harvey-Girard, Erik; Tweedle, Jessica; Ironstone, Joel; Cuddy, Martin; Ellis, William; Maler, Leonard

    2010-07-15

    Primates and songbirds can learn to recognize individual conspecifics based on complex sensory cues; this requires a large, highly differentiated dorsal telencephalon. Here we show that the electric fish Apteronotus leptorhynchus can learn to recognize individual conspecifics based on a simple cue, the beat frequency of their summed sinusoidal electric organ discharges (EOD). Male fish produce transient communication signals (chirps) in response to mimic EODs. The chirp response habituates over repeated stimulus presentations within one experimental session, continues to habituate over successive daily sessions and is nearly extinguished after 5-7 days. Habituation of the chirp response was specific to the presented beat frequency. The conversion of short- to long-term habituation could be disrupted by cooling the head 30 minutes after the daily habituation trials. Consolidation of long-term memory in mammals is thought to involve induced expression of an immediate early gene, Egr-1. We cloned the Apteronotid homolog of the Egr-1 gene and found that chirp-evoking stimuli induced strong expression of its mRNA within the dorsal (Dd), central (DC), and lateral (DL) subdivisions of the dorsal telencephalon. Interestingly, the dorsolateral region is hypothesized to be homologous to the amniote hippocampal formation. We conclude that A. leptorhynchus can learn to identify individual conspecifics based on their EOD frequency and can remember these frequencies for several days. We hypothesize that this form of learning, as in primates and songbirds, requires a subset of dorsal telencephalic areas and involves a consolidation-like process that includes the expression of the transcription factor AptEgr-1.

  20. Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Hansen, Morten Bagge

    2018-01-01

    clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16......), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal.......555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. CONCLUSION: This study does not provide any support for unselective...

  1. Combustion and emissions characteristics of high n-butanol/diesel ratio blend in a heavy-duty diesel engine and EGR impact

    International Nuclear Information System (INIS)

    Chen, Zheng; Wu, Zhenkuo; Liu, Jingping; Lee, Chiafon

    2014-01-01

    Highlights: • Effects of EGR on high n-butanol/diesel ratio blend (Bu40) were investigated and compared with neat diesel (Bu00). • Bu40 has higher NOx due to wider combustion high-temperature region. • Bu40 has lower soot due to local lower equivalence ratio distribution. • Bu40 has higher CO due to lower gas temperature in the late expansion process. • For Bu40, EGR reduces NOx emissions dramatically with no obvious influence on soot. - Abstract: In this work, the combustion and emission fundamentals of high n-butanol/diesel ratio blend with 40% butanol (i.e., Bu40) in a heavy-duty diesel engine were investigated by experiment and simulation at constant engine speed of 1400 rpm and an IMEP of 1.0 MPa. Additionally, the impact of EGR was evaluated experimentally and compared with neat diesel fuel (i.e., Bu00). The results show that Bu40 has higher cylinder pressure, longer ignition delay, and faster burning rate than Bu00. Compared with Bu00, moreover, Bu40 has higher NOx due to wider combustion high-temperature region, lower soot due to local lower equivalence ratio distribution, and higher CO due to lower gas temperature in the late expansion process. For Bu40, EGR reduces NOx emissions dramatically with no obvious influence on soot. Meanwhile, there is no significant change in HC and CO emissions and indicated thermal efficiency (ITE) with EGR until EGR threshold is reached. When EGR rate exceeds the threshold level, HC and CO emissions increase dramatically, and ITE decreases markedly. Compared with Bu00, the threshold of Bu40 appears at lower EGR rate. Consequently, combining high butanol/diesel ratio blend with medium EGR has the potential to achieve ultra-low NOx and soot emissions simultaneously while maintaining high thermal efficiency level

  2. A comparative study of propranolol versus silver nitrate cautery in the treatment of recurrent primary epistaxis in children

    Science.gov (United States)

    Ahmed, Ahmed E; Abo El-Magd, Essam A; Hasan, Gamal M; El-Asheer, Osama M

    2015-01-01

    Background Epistaxis is a common medical problem in pediatric population. Although in most cases it is mild and self-limiting, a proportion of childhood epistaxis is massive, recurrent, or resistant to conventional management. Objective To compare effectiveness of propranolol as a treatment option for childhood epistaxis versus conventional silver nitrate cautery. Study design and methodology This is a prospective interventional comparative study that was carried out during a period of 1 year (January 1, 2013 to December 31, 2013) at Qena University Hospital and Assiut University Children’s Hospital. One hundred children aged 6–12 years who presented with epistaxis to Qena University Hospital and Assiut University Children’s Hospital during the study period and fulfilling the inclusion criteria were included in the study. They were randomly assigned into one of two interventional groups, where 50 children were treated with oral propranolol (propranolol treatment group) and another 50 children were treated with conventional silver nitrate cautery (cauterization treatment group) for their epistaxis. Propranolol was given at a dose of 1.5–2 mg/kg/day (divided into three doses). Patients were followed for 6 months after their discharge for recurrence of epistaxis. Results Both groups of patients showed minimal recurrent epistaxis with rates of 14% for propranolol treated group and 12% for cauterization group, with no statistically significant difference between both groups. Local pain was found to be more in patients treated with silver nitrate cauterization. Conclusion Treatment of primary epistaxis with propranolol or silver nitrate cautery showed equal rates of recurrence, and local nasal pain was slightly more among silver nitrate cauterization treated group. Propranolol could be a favorable treatment option for patients with primary epistaxis. Further studies that include multiple centers and larger number of patients are recommended for more clarification

  3. Effects of carvedilol and propranolol on circulatory regulation and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Hobolth, Lise; Bendtsen, Flemming; Hansen, Erik F

    2014-01-01

    =16) or propranolol (n=13). Cardiac, systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months. RESULTS: Arterial blood pressure, heart rate, and cardiac output decreased equally, central circulation time and systemic vascular...... oxygen gradient remained constant in both groups. Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups (-17% and -20%, non significant). CONCLUSIONS: Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could...

  4. A numerical investigation on the influence of EGR in a supercharged SI engine fueled with gasoline and alternative fuels

    International Nuclear Information System (INIS)

    Mardi K, Mohsen; Khalilarya, Shahram; Nemati, Arash

    2014-01-01

    Highlights: • CFD modeling the combustion of different alternative fuels in SI engine. • 10% of EGR is the most desirable amount from the viewpoint of emissions and power. • EGR affects on methane fuel more than others. • Supercharging has the most noticeable effect on gasoline fuel and the least on hydrogen fuel. - Abstract: Alternative fuels are mostly extracted from renewable resources, and their emission levels can be lower than those of traditional fossil-based fuels. A computational fluid dynamics (CFD) method is utilized to investigate the effects of exhaust gas recirculation (EGR) and initial charge pressure on the emissions and performance of a SI engine. The engine is fueled separately by gasoline and some of potential alternative fuels including hydrogen, propane, methane, ethanol and methanol. The results of simulation are compared to the experimental data. In all validation cases, experimental and numerical results were observed to have good agreement with each other. The calculations are carried out for EGR ratios between 0% and 20% and four cases of initial pressure have been mentioned: P in = 1, 1.2, 1.4, 1.6 bar. The effect of EGR on NO x emission of methane is more than other fuels and its effect on IMEP of hydrogen is less than other fuels. From the viewpoints of emission and power, 10% of EGR seems to be the most desirable amount. The most noticeable effect of supercharging is on gasoline unlike hydrogen, which seems to be affected the least. The comparison of results shows that hydrogen due to its high heating value and burning without producing any carbon-based compounds such as HC, CO and CO 2 is an ideal alternative fuel compared to the other fuels

  5. The therapeutic efficacy of propranolol in children with recurrent primary epistaxis

    Science.gov (United States)

    Bjelakovic, Bojko; Bojanovic, Mila; Lukic, Stevo; Saranac, Ljiljana; Vukomanovic, Vladislav; Prijic, Sergej; Zivkovic, Nikola; Randjelovic, Dusica

    2013-01-01

    We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5–2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis. PMID:23467483

  6. New EGR technology retains HD diesel economy with 21st century emissions

    NARCIS (Netherlands)

    Baert, R.S.G.; Beckman, D.E.; Verbeek, R.P.

    1996-01-01

    An EGR system for turbocharged (and aftercooled) heavy-duty diesel engines have been demonstrated on a 12 litre 315 kW engine with 4 valves per cyclinder head and high pressure injection system. In the EGR system exhaust gas is tapped of before the turbine, run through a cooler and mixed with the

  7. Propranolol for extensive hemangiomas of infancy: two case reports Hemangiomas extensos da infância tratados com propranolol: relato de dois caso

    Directory of Open Access Journals (Sweden)

    Luíza Helena dos Santos Cavaleiro

    2011-06-01

    Full Text Available Hemangiomas are the most common benign tumors of childhood. They show rapid growth, followed by a regression phase that culminates in the partial or total disappearance of the lesion. Therapeutic options should be evaluated for extensive cases. Systemic glucocorticoids are the therapy of choice; however, there are reports that propranolol offers better and faster results. We report two cases of large volume infantile hemangioma associated with functional limitation and aesthetic disfigurement, treated successfully with propranolol, a drug that comes as a therapeutic option providing satisfactory and maintained results, with few side effects.Hemangiomas são os tumores benignos mais frequentes da infância, apresentando como história natural crescimento rápido, seguido de uma fase de regressão que culmina com o desaparecimento parcial ou total da lesão. Opções terapêuticas devem ser avaliadas para casos extensos. Os glicocorticoides sistêmicos são a terapia de escolha; contudo, há relatos de que o propranolol oferece resultados melhores e mais rápidos. Este trabalho descreve dois casos de hemangioma infantil de grande volume associados à limitação funcional e desfiguração estética com significativa resposta ao propranolol, droga esta que surge como uma proposta terapêutica oferecendo resultados satisfatórios e mantidos, com poucos efeitos colaterais.

  8. The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

    Science.gov (United States)

    Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-07-28

    Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Usefulness and safety of propranolol injection into vein for acquisition of coronary multidetector-row computed tomography

    International Nuclear Information System (INIS)

    Sekine, Takako; Kodama, Takahide; Kondo, Takeshi

    2010-01-01

    A low heart rate (HR), associated with a prolonged slow filling phase (SF), is necessary to obtain a high quality coronary CT at a low radiation dose with conventional 64 multidetector-row computed tomography (MDCT). The purpose of our study was to confirm the safety of injecting propranolol (2-10 mg) into the vein for lowering heart rate in patients requiring MDCT and to document the effect of the drug on HR, PQ and SF. Of 1290 consecutive patients who were initially considered for enrollment in the coronary MDCT study, 40 patients with atrial fibrillations, 3 with atrial flutters, and 13 with artificial pacemakers were excluded. Of the remaining 1234 patients (M/F=714/520), 331 had already taken an oral beta-blocker before the CT examination, and were included in the study. In patients with no contraindications, propranolol was aggressively injected (2-10 mg) into the vein to reduce the HR. In patients not taking an oral beta blocker, 2 mg propranolol reduced the HR by -10±5 bpm and 10 mg, by -20±7 bpm. However, in patients taking an oral beta-blocker, the decrease in HR by propranolol was minimal (2 mg, -6±4 bpm; 10 mg, -10±6 bpm). Propranolol significantly prolonged the PQ interval (from 169±27 to 179±29 ms, P<0.0001), and SF (from 125±69 to 264±79 ms, P<0.0001). Adverse effects of propranolol injection were observed in only 3 [2 mild hypotension and 1 paroxysmal atrial fibrillation (recovered to sinus rhythm by DC counter shock)] of 3212 patients. All 3 patients became stable after 1 or 2 hours of rest and could return home. Propranolol injection was a relatively safe and useful method to reduce HR and prolong SF, necessary for obtaining high quality coronary MDCT with a low radiation dose. (author)

  10. Real-time CO2 sensor for the optimal control of electronic EGR system

    Science.gov (United States)

    Kim, Gwang-jung; Choi, Byungchul; Choi, Inchul

    2013-12-01

    In modern diesel engines, EGR (Exhaust Gas Recirculation) is an important technique used in nitrogen oxide (NOx) emission reduction. This paper describes the development and experimental results of a fiber-optical sensor using a 2.7 μm wavelength absorption to quantify the simultaneous CO2 concentration which is the primary variable of EGR rate (CO2 in the exhaust gas versus CO2 in the intake gas, %). A real-time laser absorption method was developed using a DFB (distributed feedback) diode laser and waveguide to make optimal design and control of electronic EGR system required for `Euro-6' and `Tier 4 Final' NOx emission regulations. While EGR is effective to reduce NOx significantly, the amount of HC and CO is increased in the exhaust gas if EGR rate is not controlled based on driving conditions. Therefore, it is important to recirculate an appropriate amount of exhaust gas in the operation condition generating high volume of NOx. In this study, we evaluated basic characteristics and functions of our optical sensor and studied basically in order to find out optimal design condition. We demonstrated CO2 measurement speed, accuracy and linearity as making a condition similar to real engine through the bench-scale experiment.

  11. Study on construction of pEgr-hPTEN expression vector induced by irradiation and its anti-tumor effect in vitro

    International Nuclear Information System (INIS)

    Tian Mei; Jin Guanghui; Piao Chunji; Li Xiuyi; Liu Linlin

    2003-01-01

    Objective: To clone the cDNA of human tumor suppressor gene-PTEN, construct pEgr-hPTEN expression vector induced by irradiation and study its inhibitory effect on proliferation of malignant glioma cell line SHG-44 transfected steadily with pEgr-hPTEN after different doses of X-ray irradiation. Methods: A DNA fragment about 1200 bp, PTEN, was amplified from human placenta tissues by using RT-nested PCR and was cloned into pUCm-T vector after automatic sequencing, then the fragment was inserted into a vector pcD-NA3.1-Egr to construct an expression vector pEgr-hPTEN. pEgr-hPTEN was transfected into SHG-44 cells in vitro. Stably transfected cell line SHG-44-sPTEN was selected through G418. The inhibitor effect on SHG-44-sPTEN was observed after different doses of X-ray irradiation in vitro. Results: The PTEN cDNA has been cloned correctly and its expression vector pEgr-hPTEN was also constructed. Growth of SHG-44 cells was inhibited significantly by stable pEgr-hPTEN transfection combined with X-ray irradiation. With the increase of dose, the inhibitory effect was enhanced within 5 Gy. Conclusion: Human tumor suppressor gene-PTEN cDNA has been cloned and its expression vector has been constructed. The tumor was inhibited significantly by gene-radiotherapy in vitro. The result provides the theoretical and experimental basis for improvement of clinical radiotherapeutic effect on tumors

  12. Comparison of alterations in c-fos and Egr-1 (zif268) expression throughout the rat brain following acute administration of different classes of antidepressant compounds.

    Science.gov (United States)

    Slattery, David A; Morrow, John A; Hudson, Alan L; Hill, David R; Nutt, David J; Henry, Brian

    2005-07-01

    The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.

  13. [Absence of effect of propranolol on urinary excretion of 3-methylhistidine in hyperthyroidism].

    Science.gov (United States)

    Beylot, M; Riou, J P; Sautot, G; Mornex, R

    Lean body mass and muscle protein breakdown were evaluated in euthyroid and hyperthyroid subjects by measuring the urinary excretion of creatinine and 3-methylhistidine. Since catecholamines probably have an inhibitory effect on muscle protein catabolism through a beta-receptor mechanism, the effects of propranolol on 3-methylhistidine excretion were also evaluated in hyperthyroid subjects. Hyperthyroid subjects had a lower lean body mass (34.9 +/- 6.3 kg versus 47.7 +/- 8.9 kg, p less than 0.001) and a greater 3-methylhistidine excretion (25.1 +/- 7.4 versus 19.0 +/- 4.8 mumol/mmol creatinine, p less than 0.05) than euthyroid subjects. Propranolol administered orally to hyperthyroid subjects decreased pulse rate (p less than 0.01) and plasma triiodothyronine concentrations (from 5.40 +/- 2.28 to 3.61 +/- 1.61 nmol/l, p less than 0.01), but did not modify urinary 3-methylhistidine excretion (24.8 +/- 8.7 versus 25.1 +/- 7.4 mumol/mmol creatinine). These results suggest that muscle wasting in hyperthyroidism is related to increased protein catabolism. This increased protein breakdown is not modified by short term administration of propranolol, a beta-blocking agent widely used in the management of hyperthyroidism.

  14. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

    Science.gov (United States)

    Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

    2018-03-15

    Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

  15. Experimental investigations of effects of EGR on performance and emissions characteristics of CNG fueled reactivity controlled compression ignition (RCCI) engine

    International Nuclear Information System (INIS)

    Singh Kalsi, Sunmeet; Subramanian, K.A.

    2016-01-01

    Highlights: • NO_x emission decreased drastically in RCCI engine with EGR. • CO and HC emissions decreased with 8% EGR. • Smoke emission increased with EGR but is still less than base diesel. • Brake thermal efficiency does not change with EGR up to 15% • 8% EGR is optimum based on less CO, HC, NO_x except smoke. - Abstract: Experimental: tests were carried out on a single cylinder diesel engine (7.4 kW rated power at 1500 rpm) under dual fuel mode (CNG-Diesel) with EGR (exhaust gas recirculation). Less reacting fuel (CNG) was injected inside the intake manifold using timed manifold gas injection system whereas high reactive diesel fuel was directly injected into the engine’s cylinder for initiation of ignition. EGR at different percentages (8%, 15% and 30%) was inducted to the engine through intake manifold and tests were conducted at alternator power output of 2 kW and 5 kW. The engine can operate under dual fuel mode with maximum CNG energy share of 85% and 92% at 5 kW and 2 kW respectively. The brake thermal efficiency of diesel engine improved marginally at 5 kW power output under conventional dual fuel mode with the CNG share up to 37% whereas the efficiency did not change with up to 15% EGR however it decreased beyond the EGR percentage. NO_x emission in diesel engine under conventional dual fuel mode decreased significantly and it further decreased drastically with EGR. The notable point emerged from this study is that CO and HC emissions, which are major problems at part load in reactivity controlled compression ignition engine (RCCI), decreased with 8% EGR along with further reduction of NO_x. However, smoke emission is marginally higher with EGR than without EGR but it is still less than conventional mode (Diesel alone). The new concept emerged from this study is that CO and HC emissions of RCCI engine at part load can be reduced using EGR.

  16. Variation in social relationships relates to song preferences and EGR1 expression in a female songbird.

    Science.gov (United States)

    Schubloom, Hannah E; Woolley, Sarah C

    2016-09-01

    Social experiences can profoundly shape social behavior and the underlying neural circuits. Across species, the formation of enduring social relationships is associated with both neural and behavioral changes. However, it remains unclear how longer-term relationships between individuals influence brain and behavior. Here, we investigated how variation in social relationships relates to variation in female preferences for and neural responses to song in a pair-bonding songbird. We assessed variation in the interactions between individuals in male-female zebra finch pairs and found that female preferences for their mate's song were correlated with the degree of affiliation and amount of socially modulated singing, but not with the frequency of aggressive interactions. Moreover, variation in measures of pair quality and preference correlated with variation in the song-induced expression of EGR1, an immediate early gene related to neural activity and plasticity, in brain regions important for auditory processing and social behavior. For example, females with weaker preferences for their mate's song had greater EGR1 expression in the nucleus Taeniae, the avian homologue of the mammalian medial amygdala, in response to playback of their mate's courtship song. Our data indicate that the quality of social interactions within pairs relates to variation in song preferences and neural responses to ethologically relevant stimuli and lend insight into neural circuits sensitive to social information. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1029-1040, 2016. © 2016 Wiley Periodicals, Inc.

  17. Consolidation and reconsolidation are impaired by oral propranolol administered before but not after memory (re)activation in humans.

    Science.gov (United States)

    Thomas, Émilie; Saumier, Daniel; Pitman, Roger K; Tremblay, Jacques; Brunet, Alain

    2017-07-01

    Propranolol administered immediately after learning or after recall has been found to impair memory consolidation or reconsolidation (respectively) in animals, but less reliably so in humans. Since reconsolidation impairment has been proposed as a treatment for mental disorders that have at their core an emotional memory, it is desirable to understand how to reliably reduce the strength of pathogenic memories in humans. We postulated that since humans (unlike experimental animals) typically receive propranolol orally, this introduces a delay before this drug can exert its memory impairment effects, which may render it less effective. As a means to test this, in two double-blind placebo-controlled experiments, we examined the capacity of propranolol to impair consolidation and reconsolidation as a function of timing of ingestion in healthy subjects. In Experiment 1, (n=36), propranolol administered immediately after learning or recall failed to impair the consolidation or reconsolidation of the memory of a standardized slideshow with an accompanying emotional story. In Experiment 2 (n=50), propranolol given 60-75min before learning or recall successfully impaired memory consolidation and reconsolidation. These results suggest that it is possible to achieve reliable memory impairment in humans if propranolol is given before learning or before recall, but not after. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis

    NARCIS (Netherlands)

    S.A. Steenen (Serge A.); A.J. van Wijk (Arjen); G.J.M.G. Van Der Heijden (Geert J.M.G.); R. van Westrhenen (Roos); J. de Lange (Jan); A. de Jongh (Ad)

    2016-01-01

    textabstractThe effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and meta-analysis of randomised controlled trials, addressing the efficacy of oral propranolol versus placebo or other medication

  19. Reversal of propranolol blockade of adrenergic receptors and related toxicity with drugs that increase cyclic AMP.

    Science.gov (United States)

    Whitehurst, V E; Vick, J A; Alleva, F R; Zhang, J; Joseph, X; Balazs, T

    1999-09-01

    An overdose of propranolol, a widely used nonselective beta-adrenergic receptor blocking agent, can result in hypotension and bradycardia leading to irreversible shock and death. In addition, the blockade of adrenergic receptors can lead to alterations in neurotransmitter receptors resulting in the interruption of the activity of other second messengers and the ultimate cellular responses. In the present experiment, three agents, aminophylline, amrinone, and forskolin were tested in an attempt to reverse the potential lethal effects of a propranolol overdose in dogs. Twenty-two anesthetized beagle dogs were given a 10-min infusion of propranolol at a dose of 1 mg/kg/min. Six of the dogs, treated only with intravenous saline, served as controls. Within 15-30 min all six control dogs exhibited profound hypotension and severe bradycardia that led to cardiogenic shock and death. Seven dogs were treated with intravenous aminophylline 20 mg/kg 5 min after the end of the propranolol infusion. Within 10-15 min heart rate and systemic arterial blood pressure returned to near control levels, and all seven dogs survived. Intravenous amrinone (2-3 mg/kg) given to five dogs, and forskolin (1-2 mg/kg) given to four dogs, also increased heart rate and systemic arterial blood pressure but the recovery of these parameters was appreciably slower than that seen with aminophylline. All of these animals also survived with no apparent adverse effects. Histopathologic evaluation of the hearts of the dogs treated with aminophylline showed less damage (vacuolization, inflammation, hemorrhage) than the hearts from animals given propranolol alone. Results of this study showed that these three drugs, all of which increase cyclic AMP, are capable of reversing the otherwise lethal effects of a propranolol overdose in dogs.

  20. Propranolol medication among coronary patients: relationship to type A behavior and cardiovascular response.

    Science.gov (United States)

    Krantz, D S; Durel, L A; Davia, J E; Shaffer, R T; Arabian, J M; Dembroski, T M; MacDougall, J M

    1982-09-01

    The present correlational study compared behavioral and psychophysiological characteristics of coronary patients who were either medicated or not medicated with the beta-adrenergic blocking drug propranolol. Eighty-eight patients were given a structured Type A interview (SI) and a history quiz while heart rate and blood pressure were monitored. Data were analyzed controlling for age, sex, extent of coronary artery disease, and history of angina. Results indicated that patients taking propranolol (n = 65) were significantly lower in intensity of Type A behavior than patients not taking propranolol (n = 23). No effects were obtained for patients medicated or not medicated with diuretics, nitrates, or other CNS active drugs. Propranolol patients also showed lesser heart rate and rate-pressure product responses to the interview, but did not differ in blood pressure responses. Components of Type A which were lower in propranolol patients included speech stylistics (loud/explosive, rapid/accelerated, potential for hostility). Content of responses to the SI and scores on the Jenkins Activity Survey did not differ between the groups. An explanation for these results is offered in terms of the effects of propranolol on peripheral sympathetic responses, and evidence for a physiological substrate for Type A behavior. A conceptualization of the Type A pattern in terms of cognitive and physiological components is advanced, and implications for clinical intervention are discussed.

  1. The use of propranolol in the treatment of anxiety disorders.

    Science.gov (United States)

    Fonte, R J; Stevenson, J M

    1985-01-01

    The authors review the available literature on the use of propranolol in the treatment of anxiety disorders. First studied in 1966, propranolol has been shown to be most effective in the control of certain somatic symptoms associated with anxiety. Despite these studies, however, it is still not certain where this beta-adrenergic blocker fits into the overall treatment of anxiety disorders. Reasons for this uncertainty and other related problems are discussed.

  2. System Properties and Control of Turbocharged Diesel Engines with High-and Low-Pressure EGR Propriétés système et contrôle de moteurs Diesel turbocompressés avec EGR haute et basse pression

    Directory of Open Access Journals (Sweden)

    Mrosek M.

    2011-09-01

    Full Text Available An extension of the air-and exhaust-system with a low-pressure EGR has the potential to significantly reduce the NOx emissions. Besides a cooled high-pressure EGR and the turbocharger with variable geometry turbine, the low-pressure EGR introduces an additional degree of freedom to control the cylinder charge. This increasing complexity of the air system can be handled with model based control structures and a model based controller calibration. Its static and dynamic properties are investigated. Besides the static couplings in the classical air path, additional couplings appear. A decentralised gain scheduled PI(D-control approach is chosen to control the variables air mass flow rate, high-pressure EGR mass flow rate and charge air pressure. An automated controller calibration, based on a semi-physical mean value model of reduced complexity, is presented. The controller maps depend on the engine operation point and are calibrated by a local linearisation of the semi-physical model. Further, a semi-physical control is capable to almost solely control the air mass flow rate via the low-pressure EGR actuators. This control implicitly accounts for couplings between charge air pressure, high-pressure EGR and the low-pressure EGR system. Finally testbed results are shown. Une extension du système d’air et d’échappement au moyen d’EGR basse pression peut potentiellement réduire significativement les émissions de NOx. À côté de l’EGR haute pression refroidi et du turbocompresseur à turbine à géométrie variable, l’EGR basse pression introduit un degré de liberté supplémentaire pour contrôler la charge du cylindre. Cette complexité croissante du système d’air peut être traitée à l’aide de structures de contrôle et d’un étalonnage de régulateur basés sur des modèles. Ses propriétés statiques et dynamiques sont étudiées. En dehors des couplages statiques dans la boucle d’air classique, des couplages

  3. EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Bianca Pfaffenseller

    2018-02-01

    Full Text Available Bipolar disorder (BD is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 (EGR3 of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients. As a central transcription factor, EGR3 regulates an array of target genes that mediate critical neurobiological processes such as synaptic plasticity, memory and cognition. Considering that EGR3 expression is induced by brain-derived neurotrophic factor (BDNF that has been consistently related to BD pathophysiology, we suggest a link between BDNF and EGR3 and their potential role in BD. A growing body of data from our group and others has shown that peripheral BDNF levels are reduced during mood episodes and also with illness progression. In this same vein, BDNF has been proposed as an important growth factor in the impaired cellular resilience related to BD. Taken together with the fact that EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also indirectly induce BDNF expression, here we propose a feed-forward gene regulatory network involving EGR3 and BDNF and its potential role in BD.

  4. Propranolol transport across the inner blood-retinal barrier: potential involvement of a novel organic cation transporter.

    Science.gov (United States)

    Kubo, Yoshiyuki; Shimizu, Yoshimi; Kusagawa, Yusuke; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

    2013-09-01

    The influx transport of propranolol across the inner blood-retinal barrier (BRB) was investigated. In the in vivo analysis of carotid artery single-injection method, [(3) H]propranolol uptake by the retina was greater than that of an internal reference compound, and was reduced by several organic cations. In the in vitro uptake study, TR-iBRB2 cells, an in vitro model of the inner BRB, showed a time-, concentration-, pH- and temperature-dependent [(3) H]propranolol uptake, suggesting the involvement of a carrier-mediated transport process in the influx of propranolol across the inner BRB. In the inhibition study, various organic cations, including drugs and candidates for the treatment of the retinal diseases, inhibited the [(3) H]propranolol uptake by TR-iBRB2 cells with no significant effects by the substrates and inhibitors of well-characterized organic cation transporters, suggesting that the influx transport of propranolol is performed by a novel transporter at the inner BRB. An analysis of the relationship between the inhibitory effect and the lipophilicity of inhibitors suggests a lipophilicity-dependent inhibitory effect of amines on the [(3) H]propranolol uptake by TR-iBRB2 cells. These results showed that influx transport of propranolol across the inner BRB is performed by a carrier-mediated transport process, suggesting the involvement of a novel organic cation transporter. Copyright © 2013 Wiley Periodicals, Inc.

  5. In vitro transdermal delivery of propranolol hydrochloride through rat skin from various niosomal formulations

    Directory of Open Access Journals (Sweden)

    Eskandar Moghimipour

    2013-09-01

    Full Text Available   Objective(s: The purpose of the present study was to prepare and to evaluate a novel niosome as transdermal drug delivery system for propranolol hydrochloride and to compare the in vitro efficiency of niosome by either thin film hydration or hand shaking method.   Materials and Methods: Niosomes were prepared by Thin Film Hydration (TFH or Hand Shaking (HS method. Propranolol niosomes were prepared using different surfactants (span20, 80 ratios and a constant cholesterol concentration. In vitro characterization of niosomes included microscopical observation, size distribution, laser light scattering evaluation, stability of propranolol niosomes and permeability of formulations in phosphate buffer (pH=7 through rat abdominal skin. Results: The percentage of entrapment efficiency (%EE increased with increase in surfactant concentration in all formulations. Among them, F3 formulation (containing span80:cholesterol ratio of 3:1 showed the highest entrapment efficiency (86.74±2.01%, Jss (6.33μg/cm2.h and permeability coefficient ( . By increasing the percentage of entrapment efficiency (resulting in increase in surfactant concentration, the drug released time is not prolonged. Among all the formulations, F4 needed more time for maximum drug release. Among these formulations, F4 was also found to have the maximum vesicle size as compared to other formulations. It was observed that niosomal suspension prepared from span 80 was more stable than span 20. Conclusion: This study demonstrates that niosomal formulations may offer a promise transdermal delivery of propranolol which improves drug efficiency and can be used for controlled delivery of propranolol

  6. A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

    Science.gov (United States)

    Dolder, Patrick C.; Grünblatt, Edna; Müller, Felix; Borgwardt, Stefan J.; Liechti, Matthias E.

    2017-01-01

    Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo. Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans. PMID:28701958

  7. EVALUATION OF PRIMARY PROPHYLAXIS WITH PROPRANOLOL AND ELASTIC BAND LIGATION IN VARICEAL BLEEDING IN CIRRHOTIC CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    Júlio Rocha PIMENTA

    Full Text Available ABSTRACT Background The efficacy of nonselective β-blocker and endoscopic procedures, such as endoscopic variceal ligation, as primary prophylaxis of variceal hemorrhage in cirrhotic adults was demonstrated by numerous controlled trials, but in pediatric population, few are the number of studies. Objective The objective of this study is to evaluate the primary prophylaxis with β-blocker in cirrhotic children and adolescents with portal hypertension. Methods This is a cohort study encompassing 26 cirrhotic patients. β-blocker prophylaxis was performed with propranolol. When contraindicated the use of β-blocker, or if side effects presents, the patients were referred to endoscopic therapy with band ligation. Patients were evaluated by endoscopy, and those who had varicose veins of medium and large caliber or reddish spots, regardless of the caliber of varices, received primary prophylaxis. Results Of the 26 patients evaluated, 9 (34.6% had contraindications to the use of propranolol and were referred for endoscopic prophylaxis. Six (35.3% of the 17 patients who received β-blocker (propranolol, had bled after a median follow-up time of 1.9 years. β-blockage dosage varied from 1 mg/kg/day to 3.1 mg/kg/day and seven (41.2% patients had the propranolol suspended due to fail of the β-blockage or adverse effects, such as drowsiness, bronchospasm and hypotension. Patients who received endoscopic prophylaxis (elastic bandage had no bleeding during the follow-up period. Conclusion All of the patients that had upper gastroinstestinal bleeding in this study were under propranolol prophylaxis. The use of propranolol showed a high number of contraindications and side effects, requiring referral to endoscopic prophylaxis. The endoscopic prophylaxis was effective in reducing episodes of bleeding.

  8. Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis.

    Science.gov (United States)

    Lonergan, Michelle H; Olivera-Figueroa, Lening A; Pitman, Roger K; Brunet, Alain

    2013-07-01

    Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the ß-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults. Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations

  9. Influence of propranolol on uptake of radioiodinated heptadecanoic acid and thallium-201 in the dog heart

    International Nuclear Information System (INIS)

    Wall, E.E. van der; Eenige, M.J. van; Scholtalbers, S.; Visser, F.C.; Roos, J.P.; Westera, G.; Hollander, W. de

    1983-01-01

    In an experimental study, the influence of propranolol on myocardial uptake of radioiodinated heptadecanoic acid ( 131 I-HDA) and thallium-201 ( 201 Tl) in the dog heart was assessed. Uptake of 131 I-HDA and 201 Tl was evaluated in ten control dogs and in ten dogs 20 min after IV administration of propranolol (0.15 mg/kg). In both groups, four healthy dogs were studied and six dogs were studied after coronary artery occlusion. It was shown that both total uptake of 131 I-HDA and 201 Tl did not alter significantly, regardless of significant changes in hemodynamic parameters and total arterial plasma FFA levels. However, distribution of both 131 I-HDA and 201 Tl was markedly affected by propranolol, since the endocardial to epicardial ratio showed significantly higher values in the ischemic myocardial regions. The results of our study indicate that propranolol (1) preserves myocardial perfusion in the normal and acutely ischemic dog heart, and (2) gives a more favorable distribution in the ischemic myocardial region towards the subendocardial layers. (orig.)

  10. Chronic effects assessment and plasma concentrations of the {beta}-blocker propranolol in fathead minnows (Pimephales promelas)

    Energy Technology Data Exchange (ETDEWEB)

    Giltrow, Emma [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Eccles, Paul D. [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Winter, Matthew J.; McCormack, Paul J. [AstraZeneca Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA (United Kingdom); Rand-Weaver, Mariann [Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Hutchinson, Thomas H. [Natural Environmental Research Council, Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH (United Kingdom); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    2009-11-27

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker ({beta}-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC{sup hatchability} and LOEC{sup female} {sup GSI} values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC{sup m}ale wet weight value of 1.0 mg/L, and the LOEC{sup r}eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human

  11. Chronic effects assessment and plasma concentrations of the β-blocker propranolol in fathead minnows (Pimephales promelas)

    International Nuclear Information System (INIS)

    Giltrow, Emma; Eccles, Paul D.; Winter, Matthew J.; McCormack, Paul J.; Rand-Weaver, Mariann; Hutchinson, Thomas H.; Sumpter, John P.

    2009-01-01

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (β-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC hatchability and LOEC female GSI values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC m ale wet weight value of 1.0 mg/L, and the LOEC r eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human therapeutic plasma concentration

  12. EGR distribution and fluctuation probe based on CO.sub.2 measurements

    Science.gov (United States)

    Parks, II, James E; Partridge, Jr., William P; Yoo, Ji Hyung

    2015-04-07

    A diagnostic system having a single-port EGR probe and a method for using the same. The system includes a light source, an EGR probe, a detector and a processor. The light source may provide a combined light beam composed of light from a mid-infrared signal source and a mid-infrared reference source. The signal source may be centered at 4.2 .mu.m and the reference source may be centered at 3.8 .mu.m. The EGR probe may be a single-port probe with internal optics and a sampling chamber with two flow cells arranged along the light path in series. The optics may include a lens for focusing the light beam and a mirror for reflecting the light beam received from a pitch optical cable to a catch optical cable. The signal and reference sources are modulated at different frequencies, thereby allowing them to be separated and the signal normalized by the processor.

  13. Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, Naoki [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); College of Life and Health Sciences, Chubu University, Kasugai (Japan); Omori, Yukari [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kawamoto, Yoshiyuki; Sobue, Sayaka; Ichihara, Masatoshi [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Suzuki, Motoshi [Division of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kyogashima, Mamoru [Department of Microbiology and Molecular Biology, Nihon Pharmaceutical University, Saitama (Japan); Nakamura, Mitsuhiro [Department of Drug Information, Gifu Pharmaceutical University, Gifu (Japan); Tamiya-Koizumi, Keiko [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Nozawa, Yoshinori [Tokai Gakuin University, Kakamigahara (Japan); Murate, Takashi, E-mail: murate@isc.chubu.ac.jp [College of Life and Health Sciences, Chubu University, Kasugai (Japan)

    2016-02-19

    Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. - Highlights: • Resveratrol inhibited cell proliferation of K562 and HCT116 cells. • Resveratrol increased cellular ceramide and decreased sphingomyelin and S1P. • ASMase mRNA and activity were increased with resveratrol. • ASMase inhibition suppressed RSV-induced ceramide accumulation. • Increased ASMase transcription was at least partially due to EGR family proteins.

  14. Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

    International Nuclear Information System (INIS)

    Mizutani, Naoki; Omori, Yukari; Kawamoto, Yoshiyuki; Sobue, Sayaka; Ichihara, Masatoshi; Suzuki, Motoshi; Kyogashima, Mamoru; Nakamura, Mitsuhiro; Tamiya-Koizumi, Keiko; Nozawa, Yoshinori; Murate, Takashi

    2016-01-01

    Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. - Highlights: • Resveratrol inhibited cell proliferation of K562 and HCT116 cells. • Resveratrol increased cellular ceramide and decreased sphingomyelin and S1P. • ASMase mRNA and activity were increased with resveratrol. • ASMase inhibition suppressed RSV-induced ceramide accumulation. • Increased ASMase transcription was at least partially due to EGR family proteins.

  15. Combined effects of cooled EGR and a higher geometric compression ratio on thermal efficiency improvement of a downsized boosted spark-ignition direct-injection engine

    International Nuclear Information System (INIS)

    Su, Jianye; Xu, Min; Li, Tie; Gao, Yi; Wang, Jiasheng

    2014-01-01

    Highlights: • Experiments for the effects of cooled EGR and two compression ratios (CR) on fuel efficiency were conducted. • The mechanism for the observed fuel efficiency behaviors by cooled EGR and high CR was clarified. • Cooled EGR offers more fuel efficiency improvement than elevating CR from 9.3 to 10.9. • Combining 18–25% cooled EGR with 10.9 CR lead to 2.1–3.5% brake thermal efficiency improvements. - Abstract: The downsized boosted spark-ignition direct-injection (SIDI) engine has proven to be one of the most promising concepts to improve vehicle fuel economy. However, the boosted engine is typically designed at a lower geometric compression ratio (CR) due to the increased knock tendency in comparison to naturally aspirated engines, limiting the potential of improving fuel economy. On the other hand, cooled exhaust gas recirculation (EGR) has drawn attention due to the potential to suppress knock and improve fuel economy. Combing the effects of boosting, increased CR and cooled EGR to further improve fuel economy within acceptable knock tolerance has been investigated using a 2.0 L downsized boosted SIDI engine over a wide range of engine operating conditions from 1000 rpm to 3000 rpm at low to high loads. To clarify the mechanism of this complicated effects, the first law of thermodynamics analysis was conducted with the inputs from GT-Power® engine simulation. Experiment results indicate that cooled EGR provides more brake thermal efficiency improvement than increasing geometric CR from 9.3 to 10.9. The benefit of brake thermal efficiency from the higher CR is limited to low load conditions. The attributes for improving brake thermal efficiency by cooled EGR include reduced heat transfer loss, reduced pumping work and increased ratio of specific heats for all the engine operating conditions, as well as higher degree of constant volume heat release only for the knock-limited high load conditions. The combined effects of 18–25% cooled EGR

  16. An EGR performance evaluation and decision-making approach based on grey theory and grey entropy analysis.

    Science.gov (United States)

    Zu, Xianghuan; Yang, Chuanlei; Wang, Hechun; Wang, Yinyan

    2018-01-01

    Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX emissions and has been widely used in marine diesel engines. This paper proposes an optimized comprehensive assessment method based on multi-objective grey situation decision theory, grey relation theory and grey entropy analysis to evaluate the performance and optimize rate determination of EGR, which currently lack clear theoretical guidance. First, multi-objective grey situation decision theory is used to establish the initial decision-making model according to the main EGR parameters. The optimal compromise between diesel engine combustion and emission performance is transformed into a decision-making target weight problem. After establishing the initial model and considering the characteristics of EGR under different conditions, an optimized target weight algorithm based on grey relation theory and grey entropy analysis is applied to generate the comprehensive evaluation and decision-making model. Finally, the proposed method is successfully applied to a TBD234V12 turbocharged diesel engine, and the results clearly illustrate the feasibility of the proposed method for providing theoretical support and a reference for further EGR optimization.

  17. Neuroanatomical heterogeneity of essential tremor according to propranolol response.

    Directory of Open Access Journals (Sweden)

    Seok Jong Chung

    Full Text Available BACKGROUND: Recent studies have suggested that essential tremor (ET is a more complex and heterogeneous clinical entity than initially thought. In the present study, we assessed the pattern of cortical thickness and diffusion tensor white matter (WM changes in patients with ET according to the response to propranolol to explore the pathogenesis underlying the clinical heterogeneity of ET. METHODS: A total of 32 patients with drug naive ET were recruited prospectively from the Movement Disorders outpatient clinic. The patients were divided into a propranolol-responder group (n = 18 and a non-responder group (n = 14. We analyzed the pattern of cortical thickness and diffusion tensor WM changes between these two groups and performed correlation analysis between imaging and clinical parameters. RESULTS: There were no significant differences in demographic characteristics, general cognition, or results of detailed neuropsychological tests between the groups. The non-responder group showed more severe cortical atrophy in the left orbitofrontal cortex and right temporal cortex relative to responders. However, the responders exhibited significantly lower fractional anisotropy values in the bilateral frontal, corpus callosal, and right parietotemporal WM compared with the non-responder group. There were no significant clusters where the cortical thickness or WM alterations were significantly correlated with initial tremor severity or disease duration. CONCLUSIONS: The present data suggest that patients with ET have heterogeneous cortical thinning and WM alteration with respect to responsiveness to propranolol, suggesting that propranolol responsiveness may be a predictive factor to determine ET subtypes in terms of neuroanatomical heterogeneity.

  18. A study of the relationship between serum bile acids and propranolol pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in healthy controls.

    Directory of Open Access Journals (Sweden)

    Anne B Taegtmeyer

    Full Text Available The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of propranolol. An open-label crossover study was performed to determine the pharmacokinetics and pharmacodynamics of propranolol after oral (40 mg and intravenous (1 mg administration as well as the concentration of total and individual fasting serum bile acids in 15 patients with liver cirrhosis and 5 healthy controls. After intravenous propranolol, patients showed a 1.8-fold increase in the area under the plasma concentration-time curve (AUC0-∞, a 1.8-fold increase in volume of distribution and a 3-fold increase in the elimination half-life (mean ± SEM: 641±100 vs. 205±43 minutes compared to controls. After oral application, AUC0-∞ and elimination half-life of propranolol were increased 6- and 4-fold, respectively, and bioavailability 3-fold (83±8 vs. 27±9.2%. Maximal effects on blood pressure and heart rate occurred during the first 4 and first 2 hours, respectively, after intravenous and oral application in both patients and controls. Total serum bile acid concentrations were higher in patients than controls (42±11 vs. 2.7±0.3 µmol/L and were linearly correlated with the serum chenodeoxycholic acid concentration. There was a linear correlation between the SBA concentration and propranolol oral AUC0-∞ in subjects not receiving interacting drugs (r2 = 0.73, n = 18. The bioavailability of and exposure to oral propranolol are increased in patients with cirrhosis. Fasting serum bile acid concentration may be helpful in predicting the exposure to oral propranolol in these patients.

  19. AAS and spectrophotometric determination of propranolol HCl and metoprolol tartrate.

    Science.gov (United States)

    El-Ries, M A; Abou Attia, F M; Ibrahim, S A

    2000-12-15

    Two simple and accurate spectrophotometric methods are described for the determination of propranolol hydrochloride (I) and metoprolol tartrate (II). The methods are based on the reaction of each drug as a secondary amine: (a) with carbon disulphide, the formed complex extracted into iso-butyl methyl ketone (IBMK) after chelation with Cu(II) ions at pH 7.5, followed by measuring the absorbance at 435.4 nm or indirectly for the drug by flame atomic absorption spectrophotometry (AAS). The calibration graph is linear up to 40 and 60 microg ml(-1) with apparent molar absorptivities of 6.89 x 10(3) and 1.08 x 104 l mol(-1) cm(-1) and correlation coefficients of 0.9994 and 0.9995 for propranolol and metoprolol, respectively; (b) with pi-acceptors, tetracyanoethylene (TCNE), or chloranilic acid (CLA) to give highly coloured complex species. The coloured products are quantitated spectrophotometrically at 415 or 510 nm for the two drugs with TCNE and CLA, respectively, and obey Beer's Law with RSD less than 2.0. The methods were applied to the determination of these drugs in pharmaceutical preparation without interferences.

  20. Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes.

    Science.gov (United States)

    Severino, Anna; Zara, Chiara; Campioni, Mara; Flego, Davide; Angelini, Giulia; Pedicino, Daniela; Giglio, Ada Francesca; Trotta, Francesco; Giubilato, Simona; Pazzano, Vincenzo; Lucci, Claudia; Iaconelli, Antonio; Ruggio, Aureliano; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna

    2017-03-14

    Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 μg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-γ-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P 3-fold changes).The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.

  1. Simulation research on the effect of cooled EGR, supercharging and compression ratio on downsized SI engine knock

    Science.gov (United States)

    Shu, Gequn; Pan, Jiaying; Wei, Haiqiao; Shi, Ning

    2013-03-01

    Knock in spark-ignition(SI) engines severely limits engine performance and thermal efficiency. The researches on knock of downsized SI engine have mainly focused on structural design, performance optimization and advanced combustion modes, however there is little for simulation study on the effect of cooled exhaust gas recirculation(EGR) combined with downsizing technologies on SI engine performance. On the basis of mean pressure and oscillating pressure during combustion process, the effect of different levels of cooled EGR ratio, supercharging and compression ratio on engine dynamic and knock characteristic is researched with three-dimensional KIVA-3V program coupled with pressure wave equation. The cylinder pressure, combustion temperature, ignition delay timing, combustion duration, maximum mean pressure, and maximum oscillating pressure at different initial conditions are discussed and analyzed to investigate potential approaches to inhibiting engine knock while improving power output. The calculation results of the effect of just cooled EGR on knock characteristic show that appropriate levels of cooled EGR ratio can effectively suppress cylinder high-frequency pressure oscillations without obvious decrease in mean pressure. Analysis of the synergistic effect of cooled EGR, supercharging and compression ratio on knock characteristic indicates that under the condition of high supercharging and compression ratio, several times more cooled EGR ratio than that under the original condition is necessarily utilized to suppress knock occurrence effectively. The proposed method of synergistic effect of cooled EGR and downsizing technologies on knock characteristic, analyzed from the aspects of mean pressure and oscillating pressure, is an effective way to study downsized SI engine knock and provides knock inhibition approaches in practical engineering.

  2. Effect of thin-film coating on wear in EGR-contaminated oil

    International Nuclear Information System (INIS)

    Ajayi, O. O.; Aldajah, S. H.; Erdemir, A.; Fenske, G. R.

    2001-01-01

    Increased use of higher-efficiency compression ignition direct injection (CIDI) diesel engines instead of today's gasoline engines will result in reduced fuel consumption and greenhouse gases emissions. However, NO(sub x) and particulate exhaust emissions from diesel engines must be significantly reduced due to their possible adverse health effects. Exhaust gas recirculation (EGR) is an effective way to reduce NO(sub x) emissions from diesel engines, but the particulates and acidic exhaust products in the recirculated gas will contaminate engine lubricant oil by increasing the soot content and total acid number (TAN). These factors will increase the wear rate in many critical engine components and seriously compromise engine durability. We have investigated the use of commercially available thin and hard coatings (TiN, TiCN, TiAlN, and CrN) to mitigate the negative effects of EGR on wear. In tests with the four-ball machine according to ASTM D4172, we found that all the four coatings deposited on M-50 steel significantly reduced wear in EGR-contaminated oils when compared with uncoated M50 steel balls

  3. A Psychophysiologic Study of Weakening Traumatic Combat Memories with Post-Reactivation Propranolol

    Science.gov (United States)

    2011-06-01

    Research Protection Office, subjects gave written informed consent. Study medication Propranolol hydrochloride is a non-selective synthetic β1...confounding substances, including opiates, barbiturates, and methadone , at the time of the script-driven imagery procedure. When the analyses were repeated

  4. Modifying intake flow to increase EGR tolerance in an Internal Combustion Engine

    Science.gov (United States)

    Rubio, Daniel; Drabo, Mebougna; Puzinauskas, Paul

    2010-11-01

    The worldwide effort to reduce vehicle emissions and increase fuel efficiencies has continuously intensified as the need to improve air quality and reduce fuel consumption becomes more acute. Exhaust gas recirculation (EGR) is a method that has long been employed to reduce combustion temperatures and therefore reduce thermal NOx formation and accommodate higher compression ratios and more optimum combustion phasing for improved efficiency. Generally the effective EGR level as a percent of trapped charge is limited by its affect on combustion stability. Inducing flow structures such as swirl, squish and tumble in the trapped charge have proven to extend this EGR limit in homogeneous charge spark-ignited engines at part load, but this enhancement has not been significantly studied at full loads in such engines. This research explored modifying the intake flow into an engine to create tumble and evaluate its effect at high loads in such engines. This exploration included characterizing the flow on a steady flow bench and quantifying the results using engine dynamometer tests.

  5. Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

    Science.gov (United States)

    Godoy, Aline A; Kummrow, Fábio; Pamplin, Paulo Augusto Z

    2015-07-01

    Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor.

  6. Role of engine age and lubricant chemistry on the characteristics of EGR soot

    Science.gov (United States)

    Adeniran, Olusanmi Adeniji

    Exhaust products of Diesel Engines serves as an environmental hazard, and to curtail this problem a Tier 3 emission standard was introduced which involves change in engine designs and introduction of EGR systems in Diesel engines. EGR systems, however has the challenge of generating soot which are abrasive and are major causes of wear in Diesel engines. This work has studied the characteristics of EGR soot formed in different range of engine age and in different lubricant chemistries of Mineral and Synthetic based diesel Oils. It is found that lubricant degradation is encouraged by less efficient combustion as engine age increases, and these are precursors to formation of crystalline and amorphous particles that are causes of wear in Diesel Engines. It is found that soot from new engine is dominated by calcium based crystals which are from calcium sulfonate detergent, which reduces formation of second phase particles that can be abrasive. Diversity and peak intensity is seen to increase in soot samples as engine age increases. This understanding of second phase particles formed in engines across age ranges can help in the durability development of engine, improvement of Oil formulation for EGR engines, and in development of chemistries for after-treatment Oil solutions that can combat formation of abrasive particles in Oils.

  7. Effects of intravenous propranolol on heat pain sensitivity in healthy men.

    Science.gov (United States)

    Schweinhardt, P; Abulhasan, Y B; Koeva, V; Balderi, T; Kim, D J; Alhujairi, M; Carli, F

    2013-05-01

    Clinical studies have shown opioid-sparing effects of β-adrenergic antagonists perioperatively and β-blockers are being investigated for chronic musculoskeletal pain. However, the direct analgesic effects of β-blockers have rarely been examined in healthy humans. In a randomized, counter-balanced, double-blind, within-subject crossover design, we tested the effect of the lipophilic β-blocker propranolol (0.035 mg/kg body weight i.v.) on heat pain sensitivity in 39 healthy males, compared with placebo. To test for peripheral versus central effects, the peripherally acting β-blocker sotalol was also examined. Experimental stimuli were brief superficial noxious heat stimuli applied to the volar forearm. Non-painful cold stimuli were included to test for specificity. Sedation, mood and anxiety were assessed to investigate potential mechanisms underlying any analgesic effect. β-blocker effects on blood pressure were incorporated into the analysis because of a known inverse relationship between pain sensitivity and systolic blood pressure. Propranolol significantly decreased perceived intensity of heat pain stimuli but only in participants with small propranolol-induced blood pressure decreases. Even in this group, the effect was small (4%). Propranolol did not influence perceived intensity of non-noxious stimuli and had no effect on sedation, anxiety or mood. Sotalol did not influence heat pain sensitivity. Propranolol decreased pain sensitivity but its analgesic effects were small and counteracted by blood pressure decreases. The analgesic effects were not mediated by peripheral β-receptor blockade, sedation, mood or anxiety. The small effect indicates that the utility of β-blockers for clinical pain must be related to factors that do not play a significant role for experimental pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

  8. Effects of recombinant plasmid pEgr-p53 transfected stably in combination with X-irradiation on cell cycle progression and proliferation in human SKOV-3 tumor cells in vitro

    International Nuclear Information System (INIS)

    Dong Lihua; Liu Feng; Li Yanbo; Fu Shibo; Gong Shouliang

    2008-01-01

    Objective: To investigate the effect of recombinant plasmid pEgr-hp53 transfected stably in combination with X-ray irradiation on the cell cycle progression and the proliferation in human SKOV-3 tumor cells. Methods: pEgr-hp53 and pcDNA3.1 packaged with liposome were stably transfected into SKOV-3 cells in vitro. SKOV-3-hp53 and SKOV-3-vect were irradiated with 0, 0.5, 2.0 and 5.0 Gy X-rays, respectively, i.e. 8 experimental groups. The SKOV-3 cell proliferation and the cell cycle progression were measured with flow cytometry and cell growth curve, respectively. Results: Compared with 0 Gy group, the cell counts in SKOV-3- hp53 plus different doses of irradiation groups 2 d after irradiation decreased significantly (P 0 /G 1 cells increased significantly (P 2 /M cells decreased in varying degrees. The cell counts in SKOV-3-hp53 plus irradiation group were significantly lower than those in corresponding SKOV-3-vect plus irradiation group, the cell counts 4-8 d after irradiation with 0.5 Gy, 2 d after 2.0 Gy irradiation and 6 d after 5.0 Gy irradiation decreased significantly (P 0 /G 1 cells increased significantly (P 2 /M cells decreased significantly (P 1 arrest in SKOV-3 cells and inhibits the cell proliferation. Ionizing radiation can activate early growth response-1 (Egr-1) gene promoter and increase the expression of p53 gene, and enhance the inhibition of tumor cell growth. (authors)

  9. New concept for low emission diesel combustion. 2nd Report. Combustion improvement by applying EGR and oxygenated fuel; Teikogai diesel engine no nensho concept. EGR, gansanso nenryo ni yoru nensho kaizen

    Energy Technology Data Exchange (ETDEWEB)

    Yokota, H.; Nakajima, H.; Kakegawa, T. [Hino Motors, Ltd., Tokyo (Japan)

    1998-05-01

    Described herein are performance of a new concept of premixed, multiple injection combustion, in which part of the fuel is injected into the combustion chamber at the early stage and the remainder is injected in the ordinary manner, and characteristics of the exhaust gases. Also described are the effects of EGR and oxygenated fuel on reduced HC emissions and fuel consumption. The ordinary premixed, multiple injection combustion system has problems related to fuel efficiency, and HC and particulate missions. When combined with an EGR system, this system reduces HC emissions to one-third. MTBE shows an effect of improving fuel efficiency, when mixed with diesel fuel. No particulate matter is exhausted and fuel efficiency is improved by 6%, when MTBE is present in the fuel at 30% by weight. The pre-mixture is less homogeneous in the absence of EGR and oxygenated fuel, producing a luminous flame observed in the fuel-rich region. No such a flame is observed, when MTBE is added to the fuel and suction air temperature is increased to the level corresponding to that associated with EGR, conceivably resulting from increased suction air temperature and lower boiling point of MTBE, which together make the pre-mixture leaner and more homogeneous. 7 refs., 9 figs., 2 tabs.

  10. Influence of preoperative propranolol on cardiac index during the anhepatic phase of liver transplantation

    Directory of Open Access Journals (Sweden)

    Emerson Seiberlich

    2015-06-01

    Full Text Available INTRODUCTION: Liver transplantation is the best therapeutic option for end-stage liver disease. Non-selective beta-blocker medications such as propranolol act directly on the cardiovascular system and are often used in the prevention of gastrointestinal bleeding resulting from HP. The effects of propranolol on cardiovascular system of cirrhotic patients during liver transplantation are not known. OBJECTIVE: Evaluate the influence of propranolol used preoperatively on cardiac index during the anhepatic phase of liver transplantation. METHOD: 101 adult patients (73 male [72.2%] who underwent cadaveric donor orthotopic liver transplantation by piggyback technique with preservation of the retrohepatic inferior vena cava performed at Hospital das Clinicas, Federal University of Minas Gerais were evaluated. There was no difference in severity between groups by the MELD system, p = 0.70. The preoperative use of propranolol and the cardiac index outcome were compared during the anhepatic phase of liver transplantation in 5 groups (I: increased cardiac index, II: cardiac index reduction lower than 16%, III: cardiac index reduction equal to or greater than 16% and less than 31%, IV: cardiac index reduction equal to or greater than 31% and less than 46%, V: cardiac index reduction equal to or greater than 46%. RESULTS: Patients in group I (46.4% who received propranolol preoperatively were statistically similar to groups II (60%, III (72.7%, IV (50% and V (30.8%, p = 0.57. CONCLUSION: The use of propranolol before transplantation as prophylaxis for gastrointestinal bleeding may be considered safe, as it was not associated with worsening of cardiac index in anhepatic phase of liver transplantation.

  11. Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome

    Directory of Open Access Journals (Sweden)

    Lu-Hang Liu

    2018-04-01

    Full Text Available Neonatal Marfan syndrome, in contrast to classical Marfan syndrome, is characterized by rapidly progressive multi-valvular cardiac disease and death from congestive heart failure, typically within the first year of life. Due to the rarity of this condition, treatment for neonatal Marfan syndrome has not been well studied. In this report, a combination of losartan and propranolol reduced the aortic root dilatation rate after three months of losartan therapy. Genetic analysis in this patient revealed a mutation in exon 25 of the FBN1 gene, which typically results in a shorter life expectancy. However, the patient's heart failure was controlled by losartan, propranolol and other anti-congestive medications, which may have prolonged his survival. Key Words: FBN1, losartan, neonatal Marfan syndrome

  12. Zumbido pulsátil: tratamento com clonazepan e propranolol Pulsatile tinnitus: treatment with clonazepam and propranolol

    Directory of Open Access Journals (Sweden)

    Sergio Albertino

    2005-02-01

    Full Text Available O zumbido pulsátil sincrônico com os batimentos cardíacos é pouco freqüente, sendo de etiologia tanto vascular arterial (malformações, fístulas artério-venosas ou venosa (anormalidades do bulbo jugular, tumor glômico jugular ou timpânico. A identificação precoce da etiologia é essencial para que a terapêutica adequada possa ser instituída. A angioressonância possibilita a identificação de alterações vasculares com maior precisão. Relatamos um caso onde, após o diagnóstico de uma alteração vascular arterial, foi instituído o tratamento com propranolol e clonazepam, com melhora da sintomatologia.Pulsatile tinnitus synchronous with heartbeat is rare and normally has vascular origin: arterial (malformation, arterial anatomical variation or venous (aberrant jugular bulb, glomus tumors, tympanic glomus tumor. Early etiology identification is essential for appropriate treatment to be established. Magnetic angioresonance makes the vascular identification possible and precise. We report a case of arterial anatomical variation in which the treatment was propranolol and clonazepam, showing tinnitus improvement.

  13. Development of High Efficiency and Low Emission Low Temperature Combustion Diesel Engine with Direct EGR Injection

    Science.gov (United States)

    Ho, R. J.; Kumaran, P.; Yusoff, M. Z.

    2016-03-01

    Focus on energy and environmental sustainability policy has put automotive research & development directed to developing high efficiency and low pollutant power train. Diffused flame controlled diesel combustion has reach its limitation and has driven R&D to explore other modes of combustions. Known effective mode of combustion to reduce emission are Low temperature combustion (LTC) and homogeneous charge combustion ignition by suppressing Nitrogen Oxide(NOx) and Particulate Matter (PM) formation. The key control to meet this requirement are chemical composition and distribution of fuel and gas during a combustion process. Most research to accomplish this goal is done by manipulating injected mass flow rate and varying indirect EGR through intake manifold. This research paper shows viable alternative direct combustion control via co-axial direct EGR injection with fuel injection process. A simulation study with OpenFOAM is conducted by varying EGR injection velocity and direct EGR injector diameter performed with under two conditions with non-combustion and combustion. n-heptane (C7H16) is used as surrogate fuel together with 57 species 290 semi-detailed chemical kinetic model developed by Chalmers University is used for combustion simulation. Simulation result indicates viability of co-axial EGR injection as a method for low temperature combustion control.

  14. Application of an EGR system in a direct injection diesel engine to reduce NOx emissions

    Science.gov (United States)

    De Serio, D.; De Oliveira, A.; Sodré, J. R.

    2016-09-01

    This work presents the application of an exhaust gas recirculation (EGR) system in a direct injection diesel engine operating with diesel oil containing 7% biodiesel (B7). EGR rates of up to 10% were applied with the primary aim to reduce oxides of nitrogen (NOx) emissions. The experiments were conducted in a 44 kW diesel power generator to evaluate engine performance and emissions for different load settings. The use of EGR caused a peak pressure reduction during the combustion process and a decrease in thermal efficiency, mainly at high engine loads. A reduction of NOx emissions of up to 26% was achieved, though penalizing carbon monoxide (CO) and total hydrocarbons (THC) emissions.

  15. Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

    Science.gov (United States)

    Imbe, Hiroki; Kimura, Akihisa

    2017-09-01

    The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics

    International Nuclear Information System (INIS)

    Van Der Heijden, J.T.M.; Krenning, E.P.; Van Toor, H.; Hennemann, G.; Docter, R.

    1988-01-01

    Tracer thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ), and 3,3',5'-triiodothyronine (rT 3 ) kinetic studies were performed in normal T 4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T 3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. No changes were observed in size of the three T 4 compartments or in fractional and mass transfer rates of T 4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T 3 , free T 3 , T 3 plasma pool, T 3 mass transfer rate to REP and SEP, and the T 3 pool masses were all significantly decreased during propranolol to a similar extent as the T 3 plasma production rate (PR). It is concluded that the D-propranolol-induced changes in thyroid hormone metabolism, resulting in a low-T 3 syndrome, are due to inhibition of thyroid hormone deiodination. This is in contrast to the low-T 3 syndrome during caloric deprivation, which results from inhibition of transport of iodothyronines into the liver

  17. Deletion of P2 promoter of GJB1 gene a cause of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Kulshrestha, R; Burton-Jones, S; Antoniadi, T; Rogers, M; Jaunmuktane, Z; Brandner, S; Kiely, N; Manuel, R; Willis, T

    2017-08-01

    X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Experimental investigation of particle emissions under different EGR ratios on a diesel engine fueled by blends of diesel/gasoline/n-butanol

    International Nuclear Information System (INIS)

    Huang, Haozhong; Liu, Qingsheng; Wang, Qingxin; Zhou, Chengzhong; Mo, Chunlan; Wang, Xueqiang

    2016-01-01

    Highlights: • The effects of EGR and blend fuels on particulate emission were studied in CI engine. • EGR ⩽ 20%, gasoline or n-butanol increases total particulate number concentration. • EGR ⩾ 30%, gasoline or n-butanol reduces total particulate number concentration. • As EGR ratio increased, the particulate mass concentrations of four fuels increased. • Gasoline or n-butanol increases the ratio of sub-25 nm particles number concentration. - Abstract: The particle emission characteristics of a high-pressure common-rail engine under different EGR conditions were investigated, using pure diesel (D100), diesel/gasoline (with a volume ratio of 70:30, D70G30), diesel/n-butanol (with a volume ratio of 70:30, D70B30) and diesel/gasoline/n-butanol (with a volume ratio of 70:15:15, D70G15B15) for combustion. Our results show that, with increasing EGR ratios, the in-cylinder pressure peak decreases and the heat release is delayed for the combustion of each fuel. At an EGR ratio of 30%, the combustion pressure peaks of D70G30, D70B30, D70G15B15 and D100 have similar values; with an EGR ratio of 40%, the combustion pressure peaks and release rate peaks of D70G30 and D70G15B15 are both lower with respect to D100. For small and medium EGR ratios (⩽20%), after the addition of gasoline and/or n-butanol to the fuel, the total particle number concentration (TPNC) increases, while both the soot emissions and the average geometric size of particles decrease. At large EGR ratios (30% and 40%), the TPNC of D70B30, D70G15B15 and D70G20 compared to D100 are reduced by a maximum amount of 74.7%, 66.7% and 28.6%, respectively. As the EGR ratio increases, the total particle mass concentration increases gradually for all four fuels. Blending gasoline or/and n-butanol into diesel induces an increase in the number concentration of sub-25 nm particles (PN25) which may be harmful in terms of health. However, the PN25 decreases with increasing the EGR ratio for all the tested fuels

  19. On the Computation of Turbulent Mixing Processes with Application to EGR in IC-engines

    OpenAIRE

    Sakowitz, Alexander

    2011-01-01

    This thesis deals with turbulent mixing processes occuring in internal combustion engines, when applying exhaust gas recirculation (EGR). EGR is a very efficient way to reduce emissions of nitrogen oxides (NOx) in internal combustion engines. Exhaust gases are recirculated and mixed with the intake air of the engine, thus reducing the oxygen concentration of the combustion gas and the maximum combustion tempera- ture. This temperature decrease results in a reduction of NOx emissions, since NO...

  20. Effects of port fuel injection (PFI) of n-butanol and EGR on combustion and emissions of a direct injection diesel engine

    International Nuclear Information System (INIS)

    Chen, Zheng; Liu, Jingping; Wu, Zhenkuo; Lee, Chiafon

    2013-01-01

    Highlights: • A DI diesel engine with PFI of n-butanol in combination with EGR is investigated. • Butanol concentration and EGR have a coupled impact on combustion process. • A combination of butanol PFI and EGR can break through tradeoff between NOx and soot. • DI diesel with butanol PFI has lower ITE than DI of diesel–butanol blends. - Abstract: An experimental investigation was conducted on a direct injection (DI) diesel engine with exhaust gas recirculation (EGR), coupled with port fuel injection (PFI) of n-butanol. Effects of butanol concentration and EGR rate on combustion, efficiency, and emissions of the tested engine were evaluated, and also compared to a DI mode of diesel–butanol blended fuel. The results show butanol concentration and EGR rate have a coupled impact on combustion process. Under low EGR rate condition, both the peak cylinder pressure and the peak heat release rate increase with increased butanol concentration, but no visible influence was found on the ignition delay. Under high EGR rate condition, however, the peak cylinder pressure and the peak heat release rate both decrease with increased butanol concentration, accompanied by longer ignition delay and longer combustion duration. As regard to the regulated emissions, HC and CO emissions increase with increased butanol concentration, causing higher indicated specific fuel consumption (ISFC) and lower indicated thermal efficiency (ITE). It is also noted that butanol PFI in combination with EGR can change the trade-off relationship between NOx and soot, and simultaneously reduce both into a very low level. Compared with the DI mode of diesel–butanol blended fuel, however, the DI diesel engine with butanol PFI has higher HC and CO emissions and lower ITE. Therefore, future research should be focused on overcoming the identified shortcomings by an improved injection strategy of butanol PFI

  1. Exhaust Aftertreatment and Low Pressure Loop EGR Applied to an Off-Highway Engine

    Energy Technology Data Exchange (ETDEWEB)

    Baumgard, Kirby; Triana, Antonio; Johnson, John; Yang, Song; Premchand, Kiran

    2006-01-30

    The goal of the project was to demonstrate that low pressure loop EGR incorporating a diesel oxidation catalyst (DOC) and a diesel particulate filter (DPF) can be applied to an off-highway engine to meet Tier 3 (Task I) and Interim Tier 4 (Task II) off-road emissions standards. Task I data was collected using a John Deere 8.1 liter engine modified with a low pressure loop EGR system. The engine and EGR system was optimized and final data over the ISO 8178 eight mode test indicated the NOx emissions were less than 4 g/kWh and the PM was less than 0.02 g/kWh which means the engine met the Tier 3 off-road standard. Considerable experimental data was collected and used by Michigan Tech University to develop and calibrate the MTU-Filter 1D DPF model. The MTU-Filter 1D DPF code predicts the particulate mass evolution (deposition and oxidation) in the diesel particulate filter (DPF) during simultaneous loading and during thermal and NO{sub 2}-assisted regeneration conditions. It also predicts the pressure drop across the DPF, the flow and temperature fields, the solid filtration efficiency and the particle number distribution downstream of the DPF. A DOC model was also used to predict the NO{sub 2} upstream of the DPF. The DPF model was calibrated to the experimental data at temperatures from 230 C to 550 C, and volumetric flow rates from 9 to 39 actual m{sup 3}/min. Model predictions of the solid particulate mass deposited in the DPF after each loading and regeneration case were in agreement within +/-10g (or +/-10%) of experimental measurements at the majority of the engine operating conditions. The activation temperatures obtained from the model calibration are in good agreement with values reported in the literature and gave good results in the model calibration by using constant pre-exponential factors throughout the entire range of conditions evaluated. The average clean filter permeability was 2.372 x 10{sup -13} m{sup 2}. Estimates of the solid particulate mass

  2. A validated RP-HPLC method for simultaneous determination of propranolol and valsartan in bulk drug and gel formulation

    Science.gov (United States)

    Imam, Syed Sarim; Ahad, Abdul; Aqil, Mohammed; Sultana, Yasmin; Ali, Asgar

    2013-01-01

    Objective: A simple, precise, and stability indicating high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of propranolol hydrochloride and valsartan in pharmaceutical dosage form. Materials and Methods: The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on Hypersil ODS C-18 column (250*4.6 mm, i.d., 5 μm particle size) with isocratic flow with UV detector. The mobile phase at a flow rate of 1.0 mL/min consisted of acetonitrile, methanol, and 0.01 M disodium hydrogen phosphate (pH 3.5) in the ratio of 50:35:15 v/v. Results: A linear response was observed over the concentration range 5-50 μg/mL of propranolol and the concentration range 4-32 μg/mL of valsartan. Limit of detection and limit of quantitation for propranolol were 0.27 μg/mL and 0.85 μg/mL, and for valsartan were 0.45 μg/mL and 1.39 μg/mL, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for linearity, accuracy, precision, specificity, robustness. Conclusion: The analysis concluded that the method was selective for simultaneous estimation of propranolol and valsartan can be potentially used for the estimation of these drugs in combined dosage form. PMID:23559826

  3. Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

    Science.gov (United States)

    Calzetti, S; Findley, L J; Gresty, M A; Perucca, E; Richens, A

    1981-01-01

    Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle. PMID:7031187

  4. Enantiomeric separation and quantitative determination of propranolol enantiomers in pharmaceutical preparations by chiral liquid chromatography Separação e determinação quantitativa dos enantiômeros do propranolol em preparações farmacêuticas por cromatografia quiral

    Directory of Open Access Journals (Sweden)

    Anil K. Singh

    2004-09-01

    Full Text Available This paper describes validated direct liquid chromatographic chiral methods for enantiomeric separation and quantitative determination of clinically significant ²-blocking agent, propranolol. A liquid chromatographic method was validated and applied for enantiomeric determination of propranolol enantiomers in pharmaceutical formulations. Separation were obtained in polar organic mode on a ±-Burke 2® chiral stationary phase (250 x 4.6 mm, 5µm with mobile phase composed of dichloromethane:methanol (90:10 v/v, along with 12 mM of ammonium acetate, at a flow rate of 0.9 mL/min. Detection was made by ultraviolet absorption at 280 nm. In all cases the run time was less than 10 min. The correlation coefficient for linear regression curves of R-propranolol and S-propranolol were 0.9995 and 0.9998 respectively. The intra-day precision, expressed as RSD was less than 2%. The accuracy determined by average recovery of R-propranolol and S-propranolol from sample matrices were 97.3% and 100.1% in commercial sample and 99.5% and 100.4% in simulated samples, respectively. Excellent levels of limit of detection (mean value = 1.34 ng and limit of quantitation (mean value = 4.47 ng, along with rapid elution time of both enantiomers, makes the method useful for routine enantiomeric quality control applications.Neste trabalho é descrito um método validado empregando a cromatografia líquida de alta eficiência com fase estacionária quiral para a separação e determinação quantitativa dos enantiômeros do propranolol em formulações farmacêuticas. A separação foi obtida em meio orgânico polar empregando a coluna ±-Burke 2® como fase estacionária quiral (250 x 4,6 mm, 5 µm e fase móvel constituída por diclorometano: metanol (90:10 v/v juntamente com 12 mM de acetato de amônio e vazão de 0,9 mL/min. A detecção foi efetuada por absorção no ultravioleta a 280 nm. Em todos casos o tempo de corrida foi menor do que 10 min. O coeficiente de

  5. Partition coefficient n-octanol/water of propranolol and atenolol at different temperatures: Experimental and theoretical studies

    International Nuclear Information System (INIS)

    Mohsen-Nia, M.; Ebrahimabadi, A.H.; Niknahad, B.

    2012-01-01

    Highlights: ► n-Octanol/water partition coefficients of propranolol and atenolol were measured. ► The effect of temperature on the partition coefficient was studied. ► The equilibrium data were correlated using the NRTL and UNIQUAC activity models. ► The binary interaction parameters of the activity models were reported. ► It is concluded that propranolol is more hydrophobic than the atenolol at 298.15 K. - Abstract: The n-octanol/water partition coefficients of propranolol and atenolol were experimentally determined by ultraviolet (UV) spectroscopy at T = (298.15, 310.15 and 314.15) K. All measurements were made at the maximum wavelength corresponding to maximum absorption. The results showed that the n-octanol/water partition coefficients of propranolol and atenolol increase with the increase of temperature. The experimental data of this work were also used to examine the phase equilibrium correlating capability of some liquid-phase models. The equilibrium experimental data were correlated using the NRTL and UNIQUAC activity coefficient models and the binary interaction parameters were reported. The average root-mea n-square deviations (RMSD) between the experimental and calculated mass fractions of the (n-octanol + propranolol + water) and (n-octanol + atenolol + water) systems were determined. From the partition coefficients obtained, it is concluded that propranolol (log P ow = 3.12 ± 0.14) is more hydrophobic than the atenolol (log P ow = 0.16 ± 0.01) at T = 298.15 K.

  6. Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

    Science.gov (United States)

    Santosh, P J; Bell, L; Lievesley, K; Singh, J; Fiori, F

    2016-11-29

    Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and

  7. Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

    Science.gov (United States)

    Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

    1976-03-31

    Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

  8. Comparative study in LTC Combustion between a short HP EGR loop without cooler and a variable lift and duration system

    Energy Technology Data Exchange (ETDEWEB)

    Bression, Guillaume; Pacaud, Pierre; Soleri, Dominique; Cessou, Jerome [IFP (France); Azoulay, David [Renault Powertrain Div. (France); Lawrence, David [Mechadyne (United Kingdom); Doradoux, Laurent; Guerrassi, Noureddine [Delphi Diesel Systems (France)

    2008-07-01

    In order to reach future Diesel emission standards such as Euro 6 or Tier 2 Bin 5, NO{sub x} emissions need to be dramatically reduced. Advanced technologies and engine settings such as higher EGR rates, reduced compression ratio, EGR cooler and low-pressure EGR loop - depending on vehicle application - may help to reach this target whilst maintaining low CO{sub 2} emissions and fuel consumption. However, the resulting low combustion temperatures and the low air-fuel ratios lead to a significant increase in HC and CO emissions, especially during the start-up phase prior to catalyst light-off. Moreover, high levels of EGR make transient operation even more difficult. So HC-CO emissions and EGR transient operation represent two key issues that could limit the extension of this alternative combustion mode. Consequently, an in-depth investigation of a variable lift and duration (VLD) system was performed to overcome these problems on a 4-cylinder engine, which was also equipped with a dual HP-LP EGR loop. The VLD system tested in this paper produces a variable camshaft-operated exhaust valve re-opening, which is controlled by a hydraulic rotary actuator, ensuring quick and accurate regulation of the internal gas recirculation (IGR). By increasing gas temperature in the combustion chamber, this advanced technology allows us to reduce HC-CO emissions by 50% under 3 bar BMEP. Although efficient, this technology has to be compared with other solutions from a cost-to-value point of view. The aim of this paper is firstly to compare the double lift exhaust system with a short route high-performance EGR loop without cooler by quantifying their respective gains on steady state points of the NEDC cycle, then by evaluating their potential performances during transient conditions. With the short-route EGR, the potential in HC-CO emission reduction remains significant on a large scale of engine temperatures representative of engine warm up. However, the VLD system allows us to

  9. A comparison between EGR and lean-burn strategies employed in a natural gas SI engine using a two-zone combustion model

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Amr; Bari, Saiful [Sustainable Energy Centre, School of Advanced Manufacturing and Mechanical Engineering, Univ. of South Australia, Mawson Lakes SA 5095 (Australia)

    2009-12-15

    Exhaust gas recirculation (EGR) strategy has been recently employed in natural gas SI engines as an alternative to lean burn technique in order to satisfy the increasingly stringent emission standards. However, the effect of EGR on some of engine performance parameters compared to lean burn is not yet quite certain. In the current study, the effect of both EGR and lean burn on natural gas SI engine performance was compared at similar operating conditions. This was achieved numerically by developing a computer simulation of the four-stroke spark-ignition natural gas engine. A two-zone combustion model was developed to simulate the in-cylinder conditions during combustion. A kinetic model based on the extended Zeldovich mechanism was also developed in order to predict NO emission. The combustion model was validated using experimental data and a good agreement between the results was found. It was demonstrated that adding EGR to the stoichiometric inlet charge at constant inlet pressure of 130 kPa decreased power more rapidly than excess air; however, the power loss was recovered by increasing the inlet pressure from 130 kPa at zero dilution to 150 kPa at 20% EGR dilution. The engine fuel consumption increased by 10% when 20% EGR dilution was added at inlet pressure of 150 kPa compared to using 20% air dilution at 130 kPa. However, it was found that EGR dilution strategy is capable of producing extremely lower NO emission than lean burn technique. NO emission was reduced by about 70% when the inlet charge was diluted at a rate of 20% using EGR instead of excess air. (author)

  10. A comparison between EGR and lean-burn strategies employed in a natural gas SI engine using a two-zone combustion model

    International Nuclear Information System (INIS)

    Ibrahim, Amr; Bari, Saiful

    2009-01-01

    Exhaust gas recirculation (EGR) strategy has been recently employed in natural gas SI engines as an alternative to lean burn technique in order to satisfy the increasingly stringent emission standards. However, the effect of EGR on some of engine performance parameters compared to lean burn is not yet quite certain. In the current study, the effect of both EGR and lean burn on natural gas SI engine performance was compared at similar operating conditions. This was achieved numerically by developing a computer simulation of the four-stroke spark-ignition natural gas engine. A two-zone combustion model was developed to simulate the in-cylinder conditions during combustion. A kinetic model based on the extended Zeldovich mechanism was also developed in order to predict NO emission. The combustion model was validated using experimental data and a good agreement between the results was found. It was demonstrated that adding EGR to the stoichiometric inlet charge at constant inlet pressure of 130 kPa decreased power more rapidly than excess air; however, the power loss was recovered by increasing the inlet pressure from 130 kPa at zero dilution to 150 kPa at 20% EGR dilution. The engine fuel consumption increased by 10% when 20% EGR dilution was added at inlet pressure of 150 kPa compared to using 20% air dilution at 130 kPa. However, it was found that EGR dilution strategy is capable of producing extremely lower NO emission than lean burn technique. NO emission was reduced by about 70% when the inlet charge was diluted at a rate of 20% using EGR instead of excess air.

  11. Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome.

    Science.gov (United States)

    Liu, Lu-Hang; Lin, Shan-Miao; Lin, Dar-Shong; Chen, Ming-Ren

    2018-04-01

    Neonatal Marfan syndrome, in contrast to classical Marfan syndrome, is characterized by rapidly progressive multi-valvular cardiac disease and death from congestive heart failure, typically within the first year of life. Due to the rarity of this condition, treatment for neonatal Marfan syndrome has not been well studied. In this report, a combination of losartan and propranolol reduced the aortic root dilatation rate after three months of losartan therapy. Genetic analysis in this patient revealed a mutation in exon 25 of the FBN1 gene, which typically results in a shorter life expectancy. However, the patient's heart failure was controlled by losartan, propranolol and other anti-congestive medications, which may have prolonged his survival. Copyright © 2017. Published by Elsevier B.V.

  12. Temporomandibular joint dislocation due to acute propranolol intoxication

    Directory of Open Access Journals (Sweden)

    Abbas Aghabiklooei

    2010-07-01

    Full Text Available Abbas Aghabiklooei1, Homan Elahi2, Babak Mostafazadeh31Department of Medical Toxicology and Forensic Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Firouzgar Hospital, Department of ENT, Tehran, Iran; 3Department of Medical Toxicology and Forensic Medicine, Shaheed Beheshty University of Medical Sciences, Tehran, IranAbstract: Temporomandibular joint (TMJ dislocation has not previously been reported as a complication of beta-blocker toxicity. We are reporting two cases of TMJ dislocation resulted from acute severe intoxication with pure propranolol (PPL for the first time. Bilateral TMJ dislocation happened in two patients who were admitted to intensive care unit with diagnosis of severe acute PPL toxicity. Clinical diagnosis of TMJ dislocation was obtained by physical examination. Successful reduction was performed for both patients without subsequent recurrence in two weeks following hospital discharge. Both of our subjects had no previous history of lower jaw dislocation. There was not any risk factor for dislocation such as convulsion during admission period, recent face trauma, or oral manipulation by the medical team. This study showed that TMJ dislocation may occur after severe acute PPL toxicity probably due to spastic contraction of the lateral pterygoid muscle. This is against previously mentioned hypothesis that stated masseteric muscles contraction as the main cause of a bilateral dislocated TMJ.Keywords: propranolol, toxicity, temporomandibular joint dislocation

  13. Port and EGR Mass Flow Sensors

    DEFF Research Database (Denmark)

    Hendricks, Elbert

    1998-01-01

    The note documents briefly work done on what is thought to be a new method of measurement of the pulsating flow in the intake port ot and SI engine and in the EGR returen line. The work reviewed has been carried out in close cooperation with Civ. Ing. Michael Føns, Civ. Ing. Christian Jepsen, the......, the author (IAU) and Spencer C. Sorenson (ET). The theory which decribes in detail the overall dynamic chracteristics of the sensor was developed at IAU and ET, DTU....

  14. Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.

    Science.gov (United States)

    Abd ElRahim, Ayman Yosry; Fouad, Rabab; Khairy, Marwa; Elsharkawy, Aisha; Fathalah, Waleed; Khatamish, Haytham; Khorshid, Omayma; Moussa, Mona; Seyam, Moataz

    2018-01-01

    Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.

  15. Determinants of Propranolol's Selective Effect on Loss Aversion.

    Science.gov (United States)

    Sokol-Hessner, Peter; Lackovic, Sandra F; Tobe, Russell H; Camerer, Colin F; Leventhal, Bennett L; Phelps, Elizabeth A

    2015-07-01

    Research on emotion and decision making has suggested that arousal mediates risky decisions, but several distinct and often confounded processes drive such choices. We used econometric modeling to separate and quantify the unique contributions of loss aversion, risk attitudes, and choice consistency to risky decision making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention's pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e., as a function of initial loss aversion and body mass index), and did not affect risk attitudes or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of emotion and risky decision making. © The Author(s) 2015.

  16. The Brain and Propranolol Pharmacokinetics in the Elderly

    Directory of Open Access Journals (Sweden)

    Andy R. Eugene

    2015-09-01

    Full Text Available Propranolol, a non-selective β-blocker, has been found to have a tremendous array of indications. Recent evidence has suggested that propranolol may be effective in patients suffering from post-traumatic stress disorder by suppressing activity in the amygdala and thereby inhibiting emotional memory formation. Dosage requirements have been well established in the pediatric and adult population, however, there has been no definitive geriatric dose recommended in the package inserts made available to the public. The aim of this paper is to use pharmacokinetic simulations in order to establish a pharmacokinetic profile dosage equivalent for the elderly as has been found in young patients. After completing the Monte-Carlo simulations for the elderly and young patients, a single 10mg dose in the elderly has shown comparable pharmacokinetic profiles as found in young patients administered a 40mg single dose.

  17. Parathyroid hormone inhibition of Na{sup +}/H{sup +} exchanger 3 transcription: Intracellular signaling pathways and transcription factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Neri, Elida Adalgisa; Bezerra, Camila Nogueira Alves, E-mail: camilab@icb.usp.br; Queiroz-Leite, Gabriella Duarte; Polidoro, Juliano Zequini; Rebouças, Nancy Amaral

    2015-06-12

    The main transport mechanism of reabsorption of sodium bicarbonate and fluid in the renal proximal tubules involves Na{sup +}/H{sup +} exchanger 3 (NHE3), which is acutely and chronically downregulated by parathyroid hormone (PTH). Although PTH is known to exert an inhibitory effect on NHE3 expression and transcription, the molecular mechanisms involved remain unclear. Here, we demonstrated that, in opossum kidney proximal tubule (OKP) cells, PTH-induced inhibition of Nhe3 gene promoter occurs even in the core promoter that controls expression of the reporter gene. We found that inhibition of the protein kinase A (PKA) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways transformed PTH from an inhibitor of promoter activity into an activator of that same activity, as did point mutations in the EGR1, Sp1, and Sp3 binding consensus elements in the promoter. In nuclear extracts of PTH-treated OKP cells, we also observed increased expression of EGR1 mRNA and of some Sp3 isoforms. Electrophoretic mobility shift assay showed a supershift of the −61 to −42-bp probe with an anti-EGR1 antibody in PTH-treated cells, suggesting that EGR1 binding is relevant for the inhibitory activity of PTH. We conclude that PTH-induced inhibition of NHE3 transcription is related to higher EGR1 expression; to EGR1 binding to the proximal and core promoters; and to PKA and JAK/STAT pathway activation. This mechanism might be responsible, at least in part, for lower NHE3 expression and sodium reabsorption in renal proximal tubules in the presence of high PTH levels. - Highlights: • PTH regulation of Nhe3 promoter depends on EGR1 binding. • EGR1, PKA and JAK/STAT are involved in PTH inhibition of the Nhe3 promoter. • PTH alters expression of EGR1 and Sp3. • PTH inhibits the Nhe3 promoter by regulating PKA and JAK/STAT signaling.

  18. Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

    Energy Technology Data Exchange (ETDEWEB)

    Skorokhod, Alexander [Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg (Germany); Institute of Molecular Biology and Genetics, Ukrainian Academy of Sciences, Zabolotnogo str. 150, 03143, Kiev (Ukraine); Bachmann, Jeannine [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich (Germany); Giese, Nathalia A [Department of General Surgery, University of Heidelberg, ImNeuenheimer Feld, 110 69120, Heidelberg (Germany); Martignoni, Marc E [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich (Germany); Krakowski-Roosen, Holger [Division of Preventive Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg (Germany)

    2012-06-21

    Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.

  19. Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

    International Nuclear Information System (INIS)

    Skorokhod, Alexander; Bachmann, Jeannine; Giese, Nathalia A; Martignoni, Marc E; Krakowski-Roosen, Holger

    2012-01-01

    Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia

  20. The IAV active High-EGR concept; Das aktive Hoch-AGR-Konzept der IAV

    Energy Technology Data Exchange (ETDEWEB)

    Rohrssen, Karsten; Hoeffeler, Gerd [IAV GmbH, Gifhorn (Germany). Geschaeftsbereich Powertrain Mechatronik

    2011-01-15

    Exhaust gas recirculation (EGR) is a proven method of emissions reduction in diesel engines. The higher the exhaust gas rates in the combustion air, the more nitrogen oxide emissions are reduced. To meet always higher demands, IAV has developed the active High-EGR concept where a twin screw compressor with a newly developed rotary slide control has been placed between the exhaust-gas turbocharger and the motor. Driven by a pulley drive planetary gear with power split, the charger is able to actively compress fresh air and exhaust gas and to to mix the two elements to the desired ratio. (orig.)

  1. Controlling the heat release in HCCI combustion of DME with methanol and EGR

    DEFF Research Database (Denmark)

    Pedersen, Troels Dyhr; Schramm, Jesper; Yanai, Tadanori

    2010-01-01

    quantity required was determined. The added methanol increased the BMEP by increasing the total heat release and retarding the combustion to after TDC. Engine knock was reduced with increasing quantities of methanol. The highest BMEP was achieved when the equivalence ratio of methanol was around 0.......12 at 1000 RPM, and around 0.76 at 1800 RPM. EGR was also used to retarding the timing. With a moderate amount of EGR the effect on the combustion was not notable, but as the equivalence ratio approached unity the combustion was increasingly delayed and the rate of reaction reduced. Engine knock seized...

  2. The Effect of Exhaust Gas Recirculation (EGR on the Emission of a Single Cylinder Spark Ignition Engine

    Directory of Open Access Journals (Sweden)

    Limyaa Mahdi Asaad

    2016-07-01

    Full Text Available A single cylinder variable compression ratio spark ignition engine type PRODIT was used in this study. The  experiments  were  conducted  with  gasoline  fuel  (80  octane  No.at  equivalence  ratio  (Ø  =1.  This study examined the effects of exhaust gas recirculation on emission. It was conducted at engine speeds (1500, 1900, 2300 and 2700 r.p.m..The  exhaust  gases  were  added  in  volumetric  ratios  of  10%,  20%  and  30%  of  the  entering  air/fuel charge. The results showed that the EGR addition decreases the CO2 concentrations, in the same time CO and HC concentrations increase remarkably.  NOx concentration decreased highly with the increase of EGR percentage at variable engine speeds and constant torque. Also, it decreased when the engine run  at  constant  speed  and  variable  engine  torque.  The  exhaust  gas  temperature  decreased  with increasing EGR ratio.

  3. Study of gas (CNG) SI engine with pre-chamber. Improvement of the indicated thermal efficiency on lean mixture with EGR and supercharging; Fukushitsushiki hibana tenka asshuku tennen gas (CNG) engine ni kansuru kenkyu. Kakyu to EGR ni yoru kihakuiki no netsukoritsu kaizen

    Energy Technology Data Exchange (ETDEWEB)

    Yonetani, H.; Fukutani, I. [Polytechnic University, Kanagawa (Japan)

    1998-10-15

    As lean burn of compressed natural gas (CNG) is applied to conventional gasoline engines, a combustion period largely increases, resulting in large combustion fluctuation and low thermal efficiency. Heterogeneous spacial air/fuel ratios also have an effect on combustion in lean burn area. By preparing a pre-chamber for a combustion chamber of high- compression ratio CNG pre-mixing SI engines to utilize premixture turbulence, rapid flame propagation is obtained in lean burn area, resulting high combustion performance. Furthermore, study was made on improvement of combustion performance in lean burn area under various compression ratios, intake pressures, pre-chamber shapes and EGR ratios. As a result, lean burn operation at high intake pressure by supercharging showed possible improvement of a thermal efficiency and expansion of inflammable limits. Higher thermal efficiency in lean burn area was also obtained by using higher compression ratios considering heat loss. Although EGR was effective in controlling NOx formed in lean burn area, strict control of both air excess rate and EGR rate was required to prevent lower thermal efficiency. 2 refs., 8 figs., 1 tab.

  4. Multi-generational effects of propranolol on Daphnia magna at different environmental concentrations

    International Nuclear Information System (INIS)

    Jeong, Tae-Yong; Kim, Hyun Young; Kim, Sang Don

    2015-01-01

    To evaluate the effects of propranolol on Daphnia magna (D. magna), we employed a multi-generational exposure period for eight generations and an environmentally relevant low concentration with 1.5 ng/L, 0.2 μg/L and 26 μg/L to reflect a realistic exposure scenario. Physiological endpoints were checked, including growth, number of neonates, heart rate, frequency of abdominal appendage movement and malformation rate of neonates. In the results, growth and abdominal appendage movement were affected by environmental concentration during several generations, and the responses showed consistent tendencies of response increase with concentration increase. Heart rate was the only endpoint affected throughout all exposure generations. Inhibitory and acceleratory effects on heart rate, growth and abdominal appendage movement suggest that it is necessary to cover sub-lethal endpoints of non-targeted organisms in eco-toxicity study because the physiological responses were detected at much lower concentrations than the results of traditional toxicity tests, including environmental concentration. - Highlights: • Multi-generational exposure was conducted to evaluate the effect of propranolol on Daphnia magna. • Heart rate was the only endpoint affected throughout all exposure generations. • Growth and abdominal appendage movement were affected at environmental concentrations. • Time series fluctuations in responses appeared with no tendencies throughout all generations. • It is necessary to cover sub-organismal endpoints and long-term exposure in ecotoxicity test. - Heart rate, growth and abdominal appendage movement of D. magna were affected by the multigenerational exposure of propranolol at environmental levels.

  5. Effect of EGR on the exhaust gas temperature and exhaust opacity ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    injection, turbo-charging, air-to-air inter-cooling, combustion optimization with and .... (iii) Partly cooled EGR: To avoid water condensation, the temperature of the ... A two-cylinder constant speed diesel engine generator set is used in present ...

  6. Tissue specific promoters improve the localization of radiation-inducible gene expression

    International Nuclear Information System (INIS)

    Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

    1996-01-01

    Purpose: Site-specific activation of gene expression can be achieved by the use of a promoter that is induced by physical agents such as x-rays. The purpose of the present study was to determine whether site-specific activation of gene therapy can also be achieved within the vascular endothelium by use of radiation-inducible promoters. We studied induction of promoter-reporter gene constructs using previously identified radiation-promoters from c-jun, c-fos, Egr-1, ICAM-1, ELAM-1 after transfection into in the vascular endothelium. Methods: The following radiation-inducible genetic constructs were created: The ELAM-1 promoter fragment was cloned into pOGH to obtain the pE-sel(-587 +35)GH reporter construct. The ICAM-1 promoter fragment (-1162/+1) was cloned upstream of the CAT coding region of the pCAT-plasmid (Promega) after removal of the SV40 promoter by Bgl2/Stu1 digestion to create the pBS-CAT plasmid. The 132 to +170 bp segment of the 5' untranslated region of the c-jun promoter was cloned to the CAT reporter gene to create the -132/+170 cjun-CAT. The Egr-1 promoter fragment (-425/+75) was cloned upstream of the CAT coding region to create the pE425-CAT plasmid. Tandem repeats of the AP-1 binding site were cloned upstream of the CAT coding region (3 xTRE-CAT). Tandem repeats of the Egr binding site (EBS) were cloned upstream of the CAT coding region (EBS-CAT). Human vascular endothelial cells from both large vessel and small vessel origin (HUVEC and HMEC), as well as human tumor cell lines were transfected with plasmids -132/+170 cjun-CAT, pE425-CAT, 3 xTRE-CAT, EBS-CAT, pE-sel-GH and pBS-CAT by use of liposomes. Humor tumor cell lines included SQ20B (squamous), RIT3 (sarcoma), and HL525 (leukemia). Each plasmid was cotransfected with a plasmid containing a CMV promoter linked to the LacZ gene (1 μg). Transfected cells were treated with mock irradiation or x-rays. Cell extracts were assayed for reporter gene expression. Results: Radiation-induced gene

  7. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  8. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.

  9. Studi Experimental Penggunaan Venturi Scrubber Dan Cyclonic Separator Untuk Meningkatkan Kinerja Pada Sistem Exhaust Gas Recirculation (EGR) Dalam Menurunkan NOX Pada Motor Diesel

    OpenAIRE

    N, Samsu Dlukha; Ariana, I Made; Fathallah, Aguk Z. M

    2012-01-01

    Salah satu cara yang efektif untuk mengurangi NOX adalah dengan menggunakan metode Exhaust Gas Recirculation (EGR). Dengan metode EGR, oksigen yang masuk ke ruang bakar akan berkurang sehingga NOX dapat diturunkan dengan signifikan, akan tetapi power dari mesin tersebut juga akan berkurang dan Particulate Matter (PM) akan naik secara signifikan. Dalam penelitian ini dibahas penggunaan EGR yang telah di optimalkan dengan penambahan venturi scrubber dan cyclonic separator, tujuannya mengurangi ...

  10. Efficient EGR technology for future HD diesel engine emission targets

    NARCIS (Netherlands)

    Baert, R.S.G.; Beckman, D.E.; Veen, A.

    1999-01-01

    Different systems for achieving short-route cooled EGR on turbocharged and aftercooled heavy-duty diesel engines have been tested on a 12 litre 315 kW engine with 4 valves per cylinder and an electronically controlled unit pump fuel injection system. In all of these systems the exhaust gas was

  11. Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

    Science.gov (United States)

    Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

    1992-12-01

    The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

  12. Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry

    Energy Technology Data Exchange (ETDEWEB)

    Owen, Stewart F. [Institute for the Environment, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom); Global Safety Health and Environment, AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon, TQ5 8BA (United Kingdom); Huggett, Duane B. [Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340 (United States); Hutchinson, Thomas H.; Hetheridge, Malcolm J. [Global Safety Health and Environment, AstraZeneca, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon, TQ5 8BA (United Kingdom); Kinter, Lewis B. [AstraZeneca Pharmaceuticals US, 1800 Concord Pike, Wilmington, DE 19850 (United States); Ericson, Jon. F. [Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340 (United States); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom)

    2009-07-26

    Pharmaceuticals in the environment (PIE) are of importance since these compounds are designed to affect biological receptors/enzymes that are often conserved across vertebrate families. Across-species extrapolation of these therapeutic targets suggests potential for impacting amphibia and fish in the aquatic environment. Due to the scarcity of relevant ecotoxicological data, the long-tem impact of PIE remains a research question. Efficient use of mammalian data has been proposed to better understand and predict the potential for a given pharmaceutical to impact the environment. Using a model cardiovascular pharmaceutical (propranolol, a non-specific {beta}{sub 1}/{beta}{sub 2}-adrenergic antagonist), the hypothesis that mammalian data can be used to predict toxicity in fish was tested. Rainbow trout (Oncorhynchus mykiss (Walbaum)) have {beta}-adrenergic signalling mechanisms analogous to human cardiovascular receptors that respond to pharmacological doses of agonists and antagonists. Trout absorbed propranolol from water such that after 40 days of exposure, the linear relationship was [plasma] = 0.59[water] (n = 31, r = 0.96). Growth rate was affected only at very high aqueous concentrations (10-day {sup growth}NOEC = 1.0 and {sup growth}LOEC = 10 mg/l). Growth recovered with time (40-day {sup growth}NOEC = 10 mg/l), suggesting possible adaptation to the pharmaceutical, although the internal plasma concentration in trout exposed to 10 mg propranolol/l of water was higher than the mammalian therapeutic plasma concentration. Additional endpoints suggested subtle changes of liver and heart size at much lower concentrations may have occurred, although these were not concentration-related. There was, however, a dose-dependent effect upon overall body condition. The trout plasma concentrations at these effective aqueous concentrations fell within the range of mammalian effective plasma concentrations, supporting the potential for developing 'read-across' from

  13. Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry

    International Nuclear Information System (INIS)

    Owen, Stewart F.; Huggett, Duane B.; Hutchinson, Thomas H.; Hetheridge, Malcolm J.; Kinter, Lewis B.; Ericson, Jon. F.; Sumpter, John P.

    2009-01-01

    Pharmaceuticals in the environment (PIE) are of importance since these compounds are designed to affect biological receptors/enzymes that are often conserved across vertebrate families. Across-species extrapolation of these therapeutic targets suggests potential for impacting amphibia and fish in the aquatic environment. Due to the scarcity of relevant ecotoxicological data, the long-tem impact of PIE remains a research question. Efficient use of mammalian data has been proposed to better understand and predict the potential for a given pharmaceutical to impact the environment. Using a model cardiovascular pharmaceutical (propranolol, a non-specific β 1 /β 2 -adrenergic antagonist), the hypothesis that mammalian data can be used to predict toxicity in fish was tested. Rainbow trout (Oncorhynchus mykiss (Walbaum)) have β-adrenergic signalling mechanisms analogous to human cardiovascular receptors that respond to pharmacological doses of agonists and antagonists. Trout absorbed propranolol from water such that after 40 days of exposure, the linear relationship was [plasma] = 0.59[water] (n = 31, r = 0.96). Growth rate was affected only at very high aqueous concentrations (10-day growth NOEC = 1.0 and growth LOEC = 10 mg/l). Growth recovered with time (40-day growth NOEC = 10 mg/l), suggesting possible adaptation to the pharmaceutical, although the internal plasma concentration in trout exposed to 10 mg propranolol/l of water was higher than the mammalian therapeutic plasma concentration. Additional endpoints suggested subtle changes of liver and heart size at much lower concentrations may have occurred, although these were not concentration-related. There was, however, a dose-dependent effect upon overall body condition. The trout plasma concentrations at these effective aqueous concentrations fell within the range of mammalian effective plasma concentrations, supporting the potential for developing 'read-across' from mammalian pharmacology safety data to fish

  14. A rapid liquid chromatography tandem mass spectrometry-based method for measuring propranolol on dried blood spots.

    Science.gov (United States)

    Della Bona, Maria Luisa; Malvagia, Sabrina; Villanelli, Fabio; Giocaliere, Elisa; Ombrone, Daniela; Funghini, Silvia; Filippi, Luca; Cavallaro, Giacomo; Bagnoli, Paola; Guerrini, Renzo; la Marca, Giancarlo

    2013-05-05

    Propranolol, a non-selective beta blocker drug, is used in young infants and newborns for treating several heart diseases; its pharmacokinetics has been extensively evaluated in adult patients using extrapolation to treat pediatric population. The purpose of the present study was to develop and validate a method to measure propranolol levels in dried blood spots. The analysis was performed by using liquid chromatography/tandem mass spectrometry operating in multiple reaction monitoring mode. The calibration curve in matrix was linear in the concentration range of 2.5-200 μg/L with correlation coefficient r=0.9996. Intra-day and inter-day precisions and biases were less than 8.0% (n=10) and 11.5% (n=10) respectively. The recoveries ranged from 94 to 100% and the matrix effect did not result in a severe signal suppression. Propranolol on dried blood spot showed a good stability at three different temperatures for one month. This paper describes a micromethod for measuring propranolol levels on dried blood spot, which determines a great advantage in neonates or young infants during pharmacokinetic studies because of less invasive sampling and small blood volume required. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Construction and expression of pEgr-sHemopexin recombinant plasmid induced by ionizing radiation in vitro

    International Nuclear Information System (INIS)

    Wang Guiquan; Jilin Univ., Changchun; Xu Chuanjie; Yang Wen; Piao Chunji; Dong Zhen

    2005-01-01

    Objective: To clone mouse secretable Hemopexin (sPEX) cDNA, construct pEgr-sPEX recombinant plasmid and detect the expression of recombinant plasmid in B16F10 cells. Methods: Hemopexin cDNA was amplified from the NIH3T3 cells by RT-PCR. After the cDNA identified by sequencing, the pEgr-sPEX recombinant plasmid was constructed and the plasmid was transfected into B16F10 cells with liposome and the expression of PEX induced by ionizing radiation in B16F10 cells was detected by Western blotting. Results: The sequencing results proved the cloned sPEX cDNA to be completely identical with that reported in the GenBank. The mouse sPEX cDNA was inserted correctly into expression vector and expressed successfully. Conclusion: The mouse sPEX cDNA is cloned successfully and it is confirmed that pEgr-sPEX possesses the radiation inducing expression characteristics in vitro. (authors)

  16. Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

    Science.gov (United States)

    Zhai, Qing-Zhou

    2013-01-01

    This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

  17. Dependence on the mobile phase pH of the adsorption behavior of propranolol enantiomers on a cellulase protein used as the chiral selector

    Energy Technology Data Exchange (ETDEWEB)

    Fornstedt, T.; Goetmar, G.; Andersson, M.; Guiochon, G.

    1999-02-17

    The authors reported previously on the unusual thermodynamic characteristics of the enantioselective interactions between the enantiomers of the {beta}-blocker propranolol and the protein cellobiohydrolase I immobilized on silica. The adsorption of the more retained enantiomer, (S)-propranolol, is endothermic while that of the (R)-propranolol is exothermic. This causes a rapid increase of the selectivity factor with increasing temperature. In this work, the complex dependence of the selectivity factor on the pH of the solvent is studied. They determined the equilibrium isotherms of (R)- and (S)-propranolol in a wide concentration range (0.25 {micro}M to 1.1 mM) at six different mobile-phase pHs (4.7, 5.0, 5.2, 5.5, 5.7, and 6.0) and fitted the data obtained to the bi-Langmuir model. This gave the saturation capacity and the binding constant of the nonselective contribution for the two enantiomers. It also gave these parameters for the enantioselective contributions of each of them. The dependence of these parameters on the pH is discussed and interpreted in terms of the retention mechanism. Conclusions are in excellent agreement with recent, independent results on the structure of the protein obtained by X-ray crystallography.

  18. Removal of toxicity the pharmaceutical propranolol and your mixture with fluoxetine hydrochloride in aqueous solution using radiation with electron beam; Remocao da toxicidade do farmaco propranolol e de sua mistura com cloridrato de fluoxetina em solucao aquosa empregando irradiacao com feixe de eletrons

    Energy Technology Data Exchange (ETDEWEB)

    Boiani, Nathalia Fonseca

    2016-07-01

    Environmental health has been damage due to incorrect disposal of products and by-products. Among emerging pollutants it is possible to account with several pharmaceuticals, causing those problems when disposed in the environment by effluents. Conventional processing techniques are insufficient in removal of the pharmaceuticals, for having resistant waste and low biodegradability. Thus the advanced oxidation processes have been studied as an alternative for the treatment of different types of effluents. The objective of this study was to apply the process of irradiation with electron beam in order to reduce the toxic effects of propranolol, and the mixture with fluoxetine hydrochloride in aqueous solution. Ecotoxicological tests conducted with propranolol, and the mixture with fluoxetine hydrochloride, for Daphnia similis microcrustacean, and the Vibrio fischeri bacterium. It was observed that D. similis was more sensitive to propranolol drug and to the mixture, when compared to bacterium V.fischeri. After being subjected to the treatment with ionizing radiation, all applied doses to the propranolol and the mixture, showed significant reduction of toxicity, for D. similis. Different were the results for V. fischeri, when only 5.0 kGy reduced toxicity to propranolol. The mixture of pharmaceuticals required 2.5 and 5.0 kGy for reducing toxicity. 5.0 kGy showed the best removal efficiency for toxicity: 79.94 % for D. similis and 15.64 % for V. fischeri, when exposed to propranolol. The mixture reduction efficacy were 81.59% and 26.93 % for D.similis and V.fischeri, respectively. (author)

  19. Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

    International Nuclear Information System (INIS)

    Liao, Xinhua; Che, Xiangming; Zhao, Wei; Zhang, Danjie; Long, Houlong; Chaudhary, Prakash; Li, Haijun

    2010-01-01

    The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells. Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR). Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression. Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway

  20. Effect of propranolol on survival in patients with decompensated cirrhosis

    DEFF Research Database (Denmark)

    Bang, Ulrich C; Benfield, Thomas; Hyldstrup, Lars

    2016-01-01

    BACKGROUND & AIMS: We assessed the impact of propranolol on death, risk of hepatorenal syndrome and peritonitis in patients with cirrhosis. METHODS: This study was a retrospective observational study and data were retrieved from Danish databases. We used our own criteria to stratify the patients...

  1. A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

    National Research Council Canada - National Science Library

    Pitman, Roger K

    2008-01-01

    The objective of this project is to test whether the beta-adrenergic blocker propranolol, given following combat memory reactivation, results in a significantly greater weakening of traumatic memories...

  2. Effect of meal and propranolol on whole body and splanchnic oxygen consumption in patients with cirrhosis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Simonsen, Lene; Henriksen, Jens H

    2006-01-01

    Our aim was to measure whole body energy expenditure after a mixed liquid meal, with and without simultaneous propranolol infusion, in patients with cirrhosis. We also wanted to investigate the effect of propranolol on substrate fluxes and oxygen uptake in the tissues drained by the hepatic vein ...... as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole body oxygen consumption....

  3. Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Martyn Harvey

    2011-01-01

    Full Text Available Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING, and more recently intravenous lipid emulsion (ILE, have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity. Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group, or 10 mL/kg 20% Intralipid (ILE group. Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure was greatest in the ING group at 60 minutes (P<.05. A trend toward greater heart rate was observed in the ING group (P=.06. No difference was observed in survival between groups (4/5 ING versus 2/5 ILE; P=.524. Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

  4. The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index.

    Science.gov (United States)

    Korkmaz, Levent; Baştuğ, Osman; Ozdemir, Ahmet; Korkut, Sabriye; Karaca, Cagatay; Akin, Mustafa Ali; Gunes, Tamer; Kurtoglu, Selim; Ozturk, Mehmet Adnan

    2017-01-01

    Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values.

  5. A Psychophysiologic Study of Weakening Traumatic Combat Memories With Post-Reactivation Propranolol

    National Research Council Canada - National Science Library

    Pitman, Roger K

    2008-01-01

    ...) propranolol, will show significantly smaller psychophysiologic responses during script-driven imagery testing a week later, indicative of weakening of the emotional memory, compared to those who receive (non-reactivation...

  6. The influence of the flavonoid quercetin on the interaction of propranolol with human serum albumin: Experimental and theoretical approaches

    Energy Technology Data Exchange (ETDEWEB)

    Mohseni-Shahri, Fatemeh S., E-mail: fmohsenishahri@gmail.com [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Housaindokht, Mohammad R. [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Bozorgmehr, Mohammad R. [Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Moosavi-Movahedi, Ali A. [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of)

    2014-10-15

    The binding of propranolol (PROP) to human serum albumin (HSA) in the absence and presence of quercetin (QUER) in aqueous solution was investigated by multiple techniques. The presence of quercetin (QUER) increased binding constant of propranolol (PROP) with HSA. Fluorescence spectroscopy showed that quercetin (QUER) could quench the HSA fluorescence spectra. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that propranolol (PROP) and quercetin (QUER) would alter the micro-environment around tryptophan (Trp) and tyrosine (Tyr) residues. According molecular dynamics (MD) simulation results suggested that these ligands can interact with the protein, with affecting the secondary structure of HSA and with a modification of its tertiary structure. Molecular docking studies showed that the affinity and binding site of each of the ligands to HSA altered in the presence of the other. All above results may have related consequence in rationalizing the interferences of ordinary food to cardiac dysrhythmias treatments. - Highlights: • The presence of quercetin increased binding constant of propranolol with HSA. • Quercetin quenched the fluorescence of HSA through a static quenching mechanism. • The binding of propranolol and quercetin with HSA induced partial unfolding. • The tertiary structure of HSA changed after ligand binding. • After the binding of quercetin, the helix content of HSA declined.

  7. Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

    Science.gov (United States)

    Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

    2015-09-01

    Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol

  8. Enhancement of exposure therapy in participants with specific phobia: A randomized controlled trial comparing yohimbine, propranolol and placebo.

    Science.gov (United States)

    Meyerbröker, K; Morina, N; Emmelkamp, P M G

    2018-05-04

    Recent research indicates that pharmacological agents may enhance psychotherapeutic outcome. Yet, empirical results have not been conclusive with respect to two pharmacological agents, yohimbine hydrochloride (YOH) and propranolol. YOH is suggested to enhance emotional memory by elevating norepinephrine, whereas the β-adrenergic receptor antagonist propranolol might help better cope with feared situations by reducing accompanying bodily sensations. In this controlled trial, fifty-six participants with specific phobia were randomly assigned to either 1) virtual reality exposure therapy (VRET) plus YOH, 2) VRET plus Propranolol, or 3) VRET plus placebo. Participants in all conditions received three sessions of VRET over a period of two weeks. We conducted 2 × 3 repeated measures MANOVA's. Results showed a significant effect for time, with partial eta squared ranging from ηp2 = 0.647 to ηp2 = 0.692, for specific phobia, yet no significant interaction effects were found. No significant differences were found when VRET with YOH or a beta-blocker was compared to VRET with a non-active placebo. Implications for clinical practice and future research are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Dedicated EGR engine with dynamic load control

    Science.gov (United States)

    Hayman, Alan W.; McAlpine, Robert S.; Keating, Edward J.

    2016-09-06

    An internal combustion engine comprises a first engine bank and a second engine bank. A first intake valve is disposed in an intake port of a cylinder of the first engine bank, and is configured for metering the first flow of combustion air by periodically opening and closing according to a first intake valve lift and duration characteristic. A variable valve train control mechanism is configured for affecting the first intake valve lift and duration characteristic. Either a lift or duration of the first intake valve is modulated so as to satisfy an EGR control criterion.

  10. Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.

    Science.gov (United States)

    Bhatt, Parloop; Makwana, Dharmesh; Santani, Devdas; Goyal, Ramesh

    2007-05-01

    The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce

  11. Using Propranolol to Block Memory Reconsolidation in Female Veterans with PTSD

    Science.gov (United States)

    2015-11-01

    half-time support for an undergraduate student to process de- identified data and help with dissemination of recruitment materials. REPORTABLE...experience with Male Veterans and presents an important limitation to the consideration of propranolol as a PTSD treatment. Further, patient dropout

  12. Studi Experimental Penggunaan Venturi Scrubber dan Cyclonic Separator Untuk Meningkatkan Kinerja pada Sistem Exhaust Gas Recirculation (EGR dalam Menurunkan NOX pada Motor Diesel

    Directory of Open Access Journals (Sweden)

    Samsu Dlukha N

    2012-09-01

    Full Text Available Salah satu cara yang efektif untuk mengurangi NOX adalah dengan menggunakan metode Exhaust Gas Recirculation (EGR. Dengan metode EGR, oksigen yang masuk ke ruang bakar akan berkurang sehingga NOX dapat diturunkan dengan signifikan, akan tetapi power dari mesin tersebut juga akan berkurang dan Particulate Matter (PM akan naik secara signifikan. Dalam penelitian ini dibahas penggunaan EGR yang telah di optimalkan dengan penambahan venturi scrubber dan cyclonic separator, tujuannya mengurangi NOX tanpa meningkatkan PM. Hasil pengujian menunjukkan NOX turun sebesar 48.89% dan PM turun dari 69,87%  menjadi 9.87%.

  13. Removal of toxicity the pharmaceutical propranolol and your mixture with fluoxetine hydrochloride in aqueous solution using radiation with electron beam

    International Nuclear Information System (INIS)

    Boiani, Nathalia Fonseca

    2016-01-01

    Environmental health has been damage due to incorrect disposal of products and by-products. Among emerging pollutants it is possible to account with several pharmaceuticals, causing those problems when disposed in the environment by effluents. Conventional processing techniques are insufficient in removal of the pharmaceuticals, for having resistant waste and low biodegradability. Thus the advanced oxidation processes have been studied as an alternative for the treatment of different types of effluents. The objective of this study was to apply the process of irradiation with electron beam in order to reduce the toxic effects of propranolol, and the mixture with fluoxetine hydrochloride in aqueous solution. Ecotoxicological tests conducted with propranolol, and the mixture with fluoxetine hydrochloride, for Daphnia similis microcrustacean, and the Vibrio fischeri bacterium. It was observed that D. similis was more sensitive to propranolol drug and to the mixture, when compared to bacterium V.fischeri. After being subjected to the treatment with ionizing radiation, all applied doses to the propranolol and the mixture, showed significant reduction of toxicity, for D. similis. Different were the results for V. fischeri, when only 5.0 kGy reduced toxicity to propranolol. The mixture of pharmaceuticals required 2.5 and 5.0 kGy for reducing toxicity. 5.0 kGy showed the best removal efficiency for toxicity: 79.94 % for D. similis and 15.64 % for V. fischeri, when exposed to propranolol. The mixture reduction efficacy were 81.59% and 26.93 % for D.similis and V.fischeri, respectively. (author)

  14. Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study.

    Science.gov (United States)

    Zamzow, Rachel M; Ferguson, Bradley J; Stichter, Janine P; Porges, Eric C; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

    2016-04-01

    Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug's effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

  15. Potentials of cooled EGR and water injection for knock resistance and fuel consumption improvements of gasoline engines

    International Nuclear Information System (INIS)

    Bozza, Fabio; De Bellis, Vincenzo; Teodosio, Luigi

    2016-01-01

    Highlights: • 1D simulation of a turbocharged VVA engine under knock limited operation. • Description of turbulence, combustion and knock by phenomenological models. • Comparison of EGR and ported water injection at high load for knock mitigation and fuel economy. • Virtual calibration of engine control parameters by a 1D model. - Abstract: It is well known that the downsizing philosophy allows the improvement of the brake specific fuel consumption (BSFC) at part load operation for spark ignition (SI) engines. On the other hand, the BSFC is penalized at high load because of the knock occurrence and of further limitations on the turbine inlet temperature (TIT). Knock control forces the adoption of a late combustion phasing, causing a deterioration of the thermodynamic efficiency, while the TIT control requires the enrichment of the air-to-fuel ratio (A/F), with additional BSFC drawbacks. In this work, two promising techniques are investigated by a 1D approach with the aim of improving the fuel economy of a turbocharged SI engine at full load knock-limited operation. The first technique is the recirculation of low-pressure cooled exhaust gas (EGR), while the second is the injection of liquid water at the intake ports. Proper “in-house developed” sub-models are used to describe the turbulence, combustion and knock phenomena. The effects of the above techniques are studied in six operating points at full load and different speeds for various A/F levels and inert content, by varying the EGR rate and water-to-fuel ratio. The presented results highlight that both the solutions involve significant BSFC improvements, especially in the operating conditions at medium engine speeds. In fact, the introduction of inert gas in the cylinder contributes to reduce the knock tendency, resulting in the possibility to advance the combustion phasing and reduce, or even avoid, the mixture over-fuelling. The heat subtracted by the water evaporation enhances the above effects

  16. Multidimensional modeling of the effect of Exhaust Gas Recirculation (EGR) on exergy terms in an HCCI engine fueled with a mixture of natural gas and diesel

    International Nuclear Information System (INIS)

    Jafarmadar, Samad; Nemati, Peyman; Khodaie, Rana

    2015-01-01

    Highlights: • The exergy efficiency decreases by 41.3%. • The irreversibility increases by 46.80%. • The cumulative heat loss exergy decreases by 68.10%. • The cumulative work exergy decreases by 63.4%. • The exhaust losses exergy increases by 28.79%. - Abstract: One of the most important issues in HCCI engines is auto-ignition timing control. EGR introduction into intake charge can be a method to control combustion phasing and its duration. In the current study, a FORTRAN-based code which includes 10 species (O_2, N_2, H_2O, CO_2, CO, H_2, OH, O, N, NO) associated with combustion products was employed to study the exergy analysis in a dual fuel (natural gas + diesel) HCCI engine at four EGR (exhaust gas recirculation) mass fractions (0%, 10%, 20%, and 30%) while the diesel fuel amount was held constant. In order to achieve this task, a 3-D CFD code was employed to model the energy balance during a closed cycle of running engine simulation. Moreover, an efficient Extend Coherent Flame Model-Three Zone model (ECFM-3Z) method was employed to analyze the combustion process. With crank positions at different EGR mass fractions, the exergy terms were identified and calculated separately. It was found that as EGR mass fraction increased from 0% to 30% (in 10% increment steps), exergy efficiency decreased from 48.9% to 28.7%. Furthermore, with the change in EGR mass fraction, the cumulative heat loss exergy decreased from 10.1% to 5.64% of mixture fuels chemical exergy.

  17. The combined propranolol/TSST paradigm--a new method for psychoneuroendocrinology.

    Directory of Open Access Journals (Sweden)

    Julie Andrews

    Full Text Available Upon perception of a stimulus as stressful, the human brain reacts with the activation of the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system (SNS, to mobilize energy resources to better cope with the stressor. Since the perception of the stressor is the initial stimulus, a synchronicity between the subjective perception of stress and the physiological stress reactivity should be expected. However, according to a recent meta-analysis, these associations are weak and inconsistent. The goal of the current study was to investigate the interaction between the SNS, HPA and subjective stress perceptions, by introducing an experimental manipulation of this interaction. For this purpose, we combined the SNS inhibitor propranolol with the Trier Social Stress Test, and measured endocrinological and psychological responses to the stressor. Thirty healthy male participants were recruited and randomly assigned to either a propranolol (PROP; n = 15 or placebo (PLC; n = 15 group. All subjects were administered 80 mg of propranolol 60 minutes prior to exposure to psychosocial stress. Salivary cortisol and alpha amylase (sAA, heart rate, blood pressure and subjective stress responses were assessed throughout the study. We observed significantly reduced sAA levels and heart rate increases in the PROP group in response to stress, with no effects of the drug on systolic or diastolic blood pressure changes. In line with previous studies, a significant increase in cortisol was seen in response to the stress exposure. Importantly, the cortisol increase was significantly higher in the PROP group. A typical increase in subjective stress could be seen in both groups, with no significant group differences emerging. Complementing previous work, this study further demonstrates a significant interaction between the HPA and the SNS during acute stress. The HPA activity was found to be elevated in the presence of a suppressed SNS in

  18. A model to study intestinal and hepatic metabolism of propranolol in the dog.

    Science.gov (United States)

    Mills, P C; Siebert, G A; Roberts, M S

    2004-02-01

    A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery.

  19. Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas.

    Science.gov (United States)

    Mashiah, Jacob; Kutz, Ana; Rabia, Smail Hadj; Ilan, Efrat Bar; Goldberg, Ilan; Sprecher, Eli; Harel, Avikam

    2017-02-01

    Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs. We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs. A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported. This is an uncontrolled retrospective study. Propranolol 4% gel is a safe and efficient topical therapy for IH. © 2017 The International Society of Dermatology.

  20. Synthesis of nano-sized stereoselective imprinted polymer by copolymerization of (S)-2-(acrylamido) propanoic acid and ethylene glycol dimethacrylate in the presence of racemic propranolol and copper ion

    Energy Technology Data Exchange (ETDEWEB)

    Alizadeh, Taher, E-mail: talizadeh@ut.ac.ir [Department of Analytical Chemistry, Faculty of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran (Iran, Islamic Republic of); Bagherzadeh, Azam; Shamkhali, Amir Nasser [Department of Applied Chemistry, Faculty of Science, University of Mohaghegh Ardabili, Ardabil (Iran, Islamic Republic of)

    2016-06-01

    A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was obtained by reaction of (L)-alanine with acryloyl chloride. The resulting monomer was characterized by FT-IR and HNMR and then utilized for the preparation of chiral imprinted polymer (CIP). This was carried out by copolymerization of (L)-alanine-derived chiral monomer and ethylene glycol dimethacrylate, in the presence of racemic propranolol and copper nitrate, via precipitation polymerization technique, resulting in nano-sized networked polymer particles. The polymer obtained was characterized by scanning electron microscopy and FT-IR. The non-imprinted polymer was also synthesized and used as blank polymer. Density functional theory (DFT) was also employed to optimize the structures of two diasterometric ternary complexes, suspected to be created in the pre-polymerization step, by reaction of optically active isomers of propranolol, copper ion and (S)-2-(acrylamido) propanoic acid. Relative energies and other characteristics of the described complexes, calculated by the DFT, predicted the higher stability of (S)-propranolol involved complex, compared to (R)-propranolol participated complex. Practical batch extraction test which employed CIP as solid phase adsorbent, indicated that the CIP recognized selectively (S)-propranolol in the racemic mixture of propranolol; whereas, the non-imprinted polymer (NIP) showed no differentiation capability between two optically active isomers of propranolol. - Highlights: • A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was synthesized. • (S)-propranolol-selective imprinted polymer was synthesized using the chiral monomer. • Racemic propranolol mixed with Cu(II) was used as template in the imprinting. • Density functional theory was employed to clarify the imprinting mechanism. • (S)-propranolol-Cu(II) complex was shown to conduct the imprinting process.

  1. The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism

    Directory of Open Access Journals (Sweden)

    Marco De Martino

    2017-11-01

    Full Text Available Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression.

  2. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

    Science.gov (United States)

    O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

    2015-01-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

  3. Enhanced down regulation of cortical ±-propranolol sensitive [3H]-DHA binding sites by co-administration of DMI and 5-HT1A partial agonist gepirone

    International Nuclear Information System (INIS)

    Geissler, M.A.; Yocca, F.D.

    1990-01-01

    The putative interrelationship between the noradrenergic and serotonergic systems has been supported by numerous studies. Recently, Dudley et al. (1989) demonstrated significant down regulation of cortical β-adrenergic receptors by co-administration of desipramine (DMI), a norepinephrine uptake inhibitor, and the full 5-HT 1A agonist 8-OH-DPAT. To this end, the effects of acute and chronic (4 and 14 day) administration of DMI, gepirone, a selective 5-HT 1A post-synaptic partial agonist, as well as a combination of the two, on cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites were examined in rats. Down regulation was apparent after 4 and 14 day treatment with DMI. However, this was not the case with gepirone. Of particular importance is the demonstration of a greater magnitude of down regulation with co-administration of a greater magnitude of down regulation with co-administration of DMI and gepirone. These results suggests that alteration in rat cortical (±)-propranolol sensitive [ 3 H]-DHA binding sites by noradrenergic uptake inhibitors can be further modulated by selective partial agonist activity at central 5-HT 1A postsynaptic receptors. Further data on the co-administration of DMI and BMY 7378 (7,9-dioxo-8-[2-(4-o-methoxyphenylpiperazinyl)ethyl]-8-azaspiro[4,5]decane dihydrochloride), a weak partial agonist at postsynaptic 5-HT 1A receptors, are also presented

  4. Simulation and control of a HD diesel engine equipped with new EGR technology

    NARCIS (Netherlands)

    Dekker, H.J.; Sturm, W.L.

    1996-01-01

    A dynamic model of a Heavy Duty (HD) turbocharged and aftercooled diesel engine was developed. The engine was equipped with high pressure diesel injection, a Variable Geometry Turbine (VGT) and an Exhaust Gas Recirculation (EGR) system. This engine was targeted at meeting EURO4 emission

  5. A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans.

    Science.gov (United States)

    Saladin, Michael E; Gray, Kevin M; McRae-Clark, Aimee L; Larowe, Steven D; Yeatts, Sharon D; Baker, Nathaniel L; Hartwell, Karen J; Brady, Kathleen T

    2013-04-01

    This study examined the effects of propranolol vs. placebo, administered immediately after a "retrieval" session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent "test" session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up. CD participants received either 40 mg propranolol or placebo immediately following a "retrieval" CCE session. The next day, participants received a "test" session of CCE that was identical to the "retrieval" session except no medication was administered. Participants underwent a "follow-up" CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions. Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use. This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.

  6. Comparative influence of propranolol and verapamil on glycemic control and histamine sensitivity associated with L-thyroxine-induced hyperthyroidism - an experimental study.

    Science.gov (United States)

    Bhatt, Parloop A; Makwana, Dharmesh

    2008-02-01

    The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

  7. Emission characteristics of multiple stage diesel combustion. Effect of exhaust gas recirculation; Nidan nensho diesel kikan no haishutsubutsu tokusei. EGR no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Hashizume, T.; Miyamoto, T.; Akagawa, H.; Tsujimura, K. [New A.C.E. Institute Co. Ltd., Tokyo (Japan)

    1998-05-01

    For an aim to reduce NOx emission from diesel engines, it has become possible to realize it with smoke emission maintained at low levels by taking the following steps: initial combustion is carried out as lean pre-mixed combustion by adopting early fuel injection; the fuel is injected again after completion of this combustion; and EGR is combined with two-stage combustion which performs diffusion combustion under high temperature atmosphere. When a large quantity of EGR is used, cylinder temperature drops to have ignition timing delayed in the first stage, serving for improving fuel consumption. The problem of increase in smoke generation is solved by optimizing the injection timing at the second stage to suppress smoke generation increase, resulting in realization of lower NOx emission. By completing the second-stage fuel injection before ignition of the first-stage injection, it was possible to realize further lower NOx emission. Smoke increase due to higher EGR ratio was suppressed by pre-mixing both fuels injected in the first and second stages, although this is a high load operation. In addition, oxygen concentration and cylinder temperature were reduced, the gas pre-mixture was homogenized, and combustion velocity was suppressed by delaying the angle of ignition timing. This made low smoke combustion at {lambda} = 1 possible even in compressed ignition combustion. 8 refs., 12 figs., 1 tab.

  8. Analysis of Oxygenated Component (butyl Ether) and Egr Effect on a Diesel Engine

    Science.gov (United States)

    Choi, Seung-Hun; Oh, Young-Taig

    Potential possibility of the butyl ether (BE, oxygenates of di-ether group) was analyzed as an additives for a naturally aspirated direct injection diesel engine fuel. Engine performance and exhaust emission characteristics were analyzed by applying the commercial diesel fuel and oxygenates additives blended diesel fuels. Smoke emission decreased approximately 26% by applying the blended fuel (diesel fuel 80 vol-% + BE 20vol-%) at the engine speed of 25,000 rpm and with full engine load compared to the diesel fuel. There was none significant difference between the blended fuel and the diesel fuel on the power, torque, and brake specific energy consumption rate of the diesel engine. But, NOx emission from the blended fuel was higher than the commercial diesel fuel. As a counter plan, the EGR method was employed to reduce the NOx. Simultaneous reduction of the smoke and the NOx emission from the diesel engine was achieved by applying the BE blended fuel and the cooled EGR method.

  9. Effect of long-term propranolol administration on specific binding of 3H-WB-4101 with rat mesenteric vascular membranes

    International Nuclear Information System (INIS)

    Ismailov, S.I.; Rozhanets, V.V.; Val'dman, A.V.

    1985-01-01

    The aim of this investigation was, first, to study the affinity of certain beta-adrenoblockers for specific binding sites of 3 H-WB-4101 (identifiable as alpha-adrenoreceptors) of brain membranes and, second, to study the characteristics of these same receptors in membranes of mesenteric vessels of rats during long-term administration of propranolol. Isotherms of specific binding, because of the limited quantity of vascular membranes, were determined by the use of three concentrations of 3 H-WB-4101: 0.1, 0.5, and 1.0 nM. It is shown that some beta-adrenoblockers have weak affinity for alpha-adrenoreceptors of brain synaptic membranes exhibited only when these compounds are present in relatively high concentrations. It is also shown that administration of propranolol for 15 days led to a significant decrease in affinity of the alpha-adrenorecptors for their specific antagonist WB-4101

  10. The effect of ascorbic acid and propranolol on normal sleep and ...

    African Journals Online (AJOL)

    This study was designed to investigate the possible effects of ascorbic acid on open field locomotor activity and normal sleep in healthy adult rats and evaluate how these correlate with those of propranolol. MethodS: Eighty healthy adult Wistar rats of both sexes were divided into two groups of 40 animals each group.

  11. Effect of ethanol, cimetidine and propranolol on toluene metabolism in man

    DEFF Research Database (Denmark)

    Døssing, M; Bælum, Jesper; Hansen, S H

    1984-01-01

    In a climatic exposure chamber four healthy volunteers were exposed to 100ppm toluene, 100ppm toluene + ethanol, 100ppm toluene + cimetidine, and 100ppm toluene + propranolol for 7h each at random over four consecutive days. A control experiment and 3.5h of exposure to 200ppm toluene were also...

  12. Effect of Exhaust Gas Recirculation (EGR on the Performance Characteristics of a Direct Injection Multi Cylinders Diesel Engine

    Directory of Open Access Journals (Sweden)

    Khalil Ibrahim Abaas

    2016-07-01

    Full Text Available Owing  to  the  energy  crisis  and  pollution  problems  of  today  investigations  have  concentrated  on decreasing  fuel  consumption  and  on  lowering  the  concentration  of  toxic  components  in  combustion products by using exhaust gas after treatments methods like PM filters and EGR for NOx reduction. In this study, the combustion characteristics of diesel fuel were compared with that pr oduced from adding EGR at several percentages to air manifold. The tests were performed in a four-cylinder direct injection (DI diesel engine at constant engine speed (1500 rpm and variable loads (from no load to 86 kN/m2, the tests were repeated with constant load (77 kN/m2 and variable engine speeds (from 1250 to 3000 rpm.The experimental results showed that adding EGR to diesel engine provided significant reductions in brake power (bp, brake thermal efficiency and exhaust gas temperatures, while high increments in brake specific  fuel  consumption  (bsfc.  High  EGR  percentage  (as  30%  in  this  article  caused  an  11.7% reduction  in  brake  thermal  efficiency,  26.38%  reduction  in  exhaust  gas  temperatures  and  12.28%  in volumetric efficiency at full load conditions.

  13. Effect of Exhaust Gas Recirculation (EGR) on the Performance Characteristics of a Direct Injection Multi Cylinders Diesel Engine

    OpenAIRE

    Khalil Ibrahim Abaas

    2016-01-01

    Owing  to  the  energy  crisis  and  pollution  problems  of  today  investigations  have  concentrated  on decreasing  fuel  consumption  and  on  lowering  the  concentration  of  toxic  components  in  combustion products by using exhaust gas after treatments methods like PM filters and EGR for NOx reduction. In this study, the combustion characteristics of diesel fuel were compared with that pr oduced from adding EGR at several percentages to air manifold. The tests were performed in a fo...

  14. Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

    Science.gov (United States)

    O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

    2015-12-01

    NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Terazosin and propranolol as blockers to the deleterious effect of nicotine in a random skin flap, in the rat Terazosina e propanolol como bloqueadores do efeito deletério da nicotina em um retalho cutâneo randômico, no rato

    Directory of Open Access Journals (Sweden)

    Andre V. Fonseca

    2004-06-01

    Full Text Available PURPOSE: To evaluate the effect of Terazosin and Propranolol on the prevention of necrosis induced by nicotine, in a random skin flap. METHODS: This study utilized 32 adult male Wistar-EPM rats divided, at random, into four groups of eight animals each. All the 32 animals received nicotine (2 mg/kg/day subcutaneously, for one week before and one week after flap elevation. CG (Control group received distilled water (0.2 ml/day by gavage and saline (0.5 ml intraperitoneally, for seven days in the postoperative period. TG (Terazosin group received terazosin hydrochloride (3 mg/day by gavage and saline, intraperitoneally, for seven days in the postoperative period. PG (Propranolol group received propranolol (1.5 mg/day intraperitoneally and distilled water, by gavage, following the stablished pattern. TPG (Terazosin + Propranolol group received both drugs. On the seventh postoperative day, the distal necrotic area of the flaps was determined via the paper template method. Blood and skin samples were collected in order to allow determination of Malondialdehyde (MDA levels RESULTS: The control group had a mean value of 39.5 % of necrosis; the Terazosin group 25.1 %; the Propranolol group 34.5 % and the Terazosin + Propranolol group 26.2 % of necrosis. MDA levels in the serum and in the skin samples behave similarly, with an exception regarding Propranolol group in this case. CONCLUSION: Terazosin is effective in the prevention of necrosis in this animal model and Propranolol is not effective in this case.OBJETIVO: O objetivo deste estudo experimental foi avaliar o efeito da Terazosina e do Propranolol na prevenção da necrose induzida pela nicotina, em um retalho cutâneo randômico. MÉTODOS: Este estudo utilizou 32 ratos machos adultos Wistar-EPM divididos, ao acaso, em quatro grupos de oito animais. Todos os 32 animais receberam nicotina (2 mg/kg/dia, por via subcutânea, por uma semana antes e uma semana após a elevação do retalho. O grupo CG

  16. Disinhibition by propranolol and chlordiazepoxide of nonrewarded lever-pressing in the rat is unaffected by dorsal noradrenergic bundle lesion.

    Science.gov (United States)

    Salmon, P; Tsaltas, E; Gray, J A

    1989-03-01

    Ten male Sprague-Dawley rats received 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle and 10 others underwent control operations. The lesion depleted levels of noradrenaline in the hippocampus to 2% of those in the controls. All rats were then trained for 16 sessions to lever-press in a Skinner box on a variable interval 18 sec schedule of food-reinforcement, then for 42 days on a successive discrimination between periods of variable interval (VI 18 sec) food-reinforcement and periods of extinction. This report describes the effects of chlordiazepoxide (CDP; 5 mg/kg) and propranolol (5 and 10 mg/kg) injected intraperitoneally in both groups on modified ABBA designs after this training. Both drugs increased the response rates in extinction periods. The effect of propranolol was similar at each dose and smaller than that of CDP. Although CDP and propranolol (5 mg/kg) increased variable interval response rates also, this could not account for the effect on extinction response rates. Responding did not differ between the lesioned and control animals and the effects of drugs were similar in each group. It is unlikely that CDP or propranolol release nonrewarded responding by disrupting transmission in the dorsal noradrenergic bundle.

  17. Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo.

    Science.gov (United States)

    Pagel, Judith-Irina; Ziegelhoeffer, Tibor; Heil, Matthias; Fischer, Silvia; Fernández, Borja; Schaper, Wolfgang; Preissner, Klaus T; Deindl, Elisabeth

    2012-03-01

    Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. αSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis.

  18. Comparison of EGR-VTG control schemes for an EPA2010 heavy-duty diesel engine

    NARCIS (Netherlands)

    Criens, C.H.A.; Willems, F.P.T.; Steinbuch, M.

    2011-01-01

    Next generation heavy-duty diesel engines require tight air path control to meet upcoming emission legislation with minimal fuel consumption. This study concentrates on the emission control of a 13l, 360 kW EGR diesel engine, which is compliant with EPA2010 emission targets. Currently, an

  19. Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

  20. Comparison of thermal, radical and chemical effects of EGR gases using availability analysis in dual-fuel engines at part loads

    International Nuclear Information System (INIS)

    Hosseinzadeh, A.; Khoshbakhti Saray, R.; Seyed Mahmoudi, S.M.

    2010-01-01

    Dual-fuel engines at part load inevitably suffer from lower thermal efficiency and higher emission of carbon monoxide and unburned fuel. A quasi-two-zone combustion model has been developed for studying the second-law analysis of a dual-fuel (diesel-gas) engine operating under part-load conditions. The model is composed of two divisions: a single-zone combustion model with chemical kinetics for combustion of natural gas fuel and a subsidiary zone for combustion of pilot fuel. In the latter zone, the pilot fuel is considered as a heat source derived from two superposed Wiebe's combustion functions to account for contribution of pilot fuel in ignition of gaseous fuel and the rest of the total released energy. This quasi-two-zone combustion model is able to establish the development of combustion process with time and associated important operating parameters, such as pressure, temperature, heat release rate (HRR) and species concentration. The present work is an attempt to investigate the combustion phenomenon from second-law point of view at part load and using exhaust gas recirculation (EGR) to improve the aforementioned problems. Therefore, the availability analysis is applied to the engine from inlet valve closing (IVC) until exhaust valve opening (EVO). Various availability components are identified and calculated separately with crank position. In this paper, the various availability components are identified and calculated separately with crank position. Then the different cases of EGR (chemical, radical and thermal cases) are applied to the availability analysis in dual-fuel engines at part loads. It is found that the chemical case of EGR has negative effect and in this case the unburned chemical availability is increased and the work availability decreases in comparison with baseline engine (without EGR). While the thermal and radical cases have positive effects on the availability terms especially on the unburned chemical availability and work availability

  1. Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

    Science.gov (United States)

    Bouissou, P; Galen, F X; Richalet, J P; Lartigue, M; Devaux, F; Dubray, C; Atlan, G

    1989-08-01

    In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial.

    Science.gov (United States)

    Caccia, M R; Osio, M; Galimberti, V; Cataldi, G; Mangoni, A

    1989-05-01

    Accelerometric tremorgrams were recorded from 25 subjects affected by essential tremor and analysed by a Berg-Fourier frequency analyser before and during venous infusion of the following drugs: propranolol (beta-blocker), clonidine (alpha-presynaptic adrenergic agonist), urapidil (alpha-postsynaptic blocker), trazodone (adrenolytic agent) and placebo. The washout interval between infusions was 3 days. Recordings and data analyses were performed in a double-blind crossover trial. Tremor was classified as: at rest; postural (arms hyperextended); and intention (finger-nose test). Analysis of the results showed that propranolol and clonidine reduced significantly (P = 0.01 and P = 0.009, respectively) the power spectrum of postural tremor, but left at rest and intention tremors unchanged. No significant effects on the tremor power spectrum were observed after placebo, urapidil or trazodone administration. None of the drugs had any effect on tremor frequency.

  3. Combined effect of nanoemulsion and EGR on combustion and emission characteristics of neat lemongrass oil (LGO)-DEE-diesel blend fuelled diesel engine

    International Nuclear Information System (INIS)

    Sathiyamoorthi, R.; Sankaranarayanan, G.; Pitchandi, K.

    2017-01-01

    Highlights: • Neat lemongrass oil can be used as an alternate fuel in diesel engine. • The combined effect of nano emulsion and EGR using LGO25-DEE-Diesel is investigated. • The BTE is improved for nano emulsion fuel blend. • The NO_x and smoke emissions decrease significantly. • Cylinder pressure and Heat release rate increase with longer ignition delay. - Abstract: In the present experimental study, the combined effects of nanoemulsion and exhaust gas recirculation (EGR) on the performance, combustion and emission characteristics of a single cylinder, four stroke, variable compression ratio diesel engine fueled with neat lemongrass oil (LGO)-diesel-DEE (diethyl ether) blend are investigated. The Neat Lemongrass oil could be used as a new alternate fuel in compression ignition engines without any engine modifications. The entire investigation was conducted in the diesel engine using the following test fuels: emulsified LGO25, cerium oxide blended emulsified LGO25 and DEE added emulsified LGO25 with EGR respectively and compared with standard diesel and LGO25 (75% by volume of diesel and 25% by volume of lemongrass oil) fuels. The combined effect of DEE added nano-emulsified LGO25 with EGR yielded a significant reduction in NO_x and smoke emission by 30.72% and 11.2% respectively compared to LGO25. Furthermore, the HC and CO emissions were reduced by 18.18% and 33.31% respectively than with LGO25. The brake thermal efficiency and brake specific fuel consumption increased by 2.4% and 10.8% respectively than LGO25. The combustion characteristics such as cylinder pressure and heat release rate increased by 4.46% and 3.29% respectively than with LGO25. The combustion duration and ignition delay increase at nano-emulsified LGO25 with DEE and EGR mode but decrease for nano-emulsified LGO25 fuel.

  4. Effect of cooled EGR on performance and exhaust gas emissions in EFI spark ignition engine fueled by gasoline and wet methanol blends

    Science.gov (United States)

    Rohadi, Heru; Syaiful, Bae, Myung-Whan

    2016-06-01

    Fuel needs, especially the transport sector is still dominated by fossil fuels which are non-renewable. However, oil reserves are very limited. Furthermore, the hazardous components produced by internal combustion engine forces many researchers to consider with alternative fuel which is environmental friendly and renewable sources. Therefore, this study intends to investigate the impact of cooled EGR on the performance and exhaust gas emissions in the gasoline engine fueled by gasoline and wet methanol blends. The percentage of wet methanol blended with gasoline is in the range of 5 to 15% in a volume base. The experiment was performed at the variation of engine speeds from 2500 to 4000 rpm with 500 intervals. The re-circulated exhaust gasses into combustion chamber was 5%. The experiment was performed at the constant engine speed. The results show that the use of cooled EGR with wet methanol of 10% increases the brake torque up to 21.3%. The brake thermal efficiency increases approximately 39.6% using cooled EGR in the case of the engine fueled by 15% wet methanol. Brake specific fuel consumption for the engine using EGR fueled by 10% wet methanol decreases up to 23% at the engine speed of 2500 rpm. The reduction of CO, O2 and HC emissions was found, while CO2 increases.

  5. An analysis of the thermodynamic efficiency for exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB)

    International Nuclear Information System (INIS)

    Lee, Chang-Eon; Yu, Byeonghun; Lee, Seungro

    2015-01-01

    This study presents fundamental research on the development of a new boiler that is expected to have a higher efficiency and lower emissions than existing boilers. The thermodynamic efficiency of exhaust gas recirculation-condensed water recirculation-waste heat recovery condensing boilers (EGR-CWR-WHR CB) was calculated using thermodynamic analysis and was compared with other boilers. The results show the possibility of obtaining a high efficiency when the temperature of the exhaust gas is controlled within 50–60 °C because water in the exhaust gas is condensed within this temperature range. In addition, the enthalpy emitted by the exhaust gas for the new boiler is smaller because the amount of condensed water is increased by the high dew-point temperature and the low exhaust gas temperature. Thus, the new boiler can obtain a higher efficiency than can older boilers. The efficiency of the EGR-CWR-WHR CB proposed in this study is 93.91%, which is 7.04% higher than that of existing CB that is currently used frequently. - Highlights: • The study presents the development of a new boiler expected to have a high efficiency. • Thermodynamic efficiency of EGR-CWR-WHR condensing boiler was calculated. • Efficiency of EGR-CWR-WHR CB is 93.91%, which is 7.04% higher than existing CB

  6. Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

    NARCIS (Netherlands)

    Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P.; Everaerd, W.

    2009-01-01

    Rationale: Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also

  7. Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration

    NARCIS (Netherlands)

    Tollenaar, M.S.; Elzinga, B.M.; Spinhoven, P.; Everaerd, W.T.A.M.

    2009-01-01

    Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also reduces

  8. Experimental characterization of cooled EGR in a gasoline direct injection engine for reducing fuel consumption and nitrogen oxide emission

    Science.gov (United States)

    Park, Sang-Ki; Lee, Jungkoo; Kim, Kyungcheol; Park, Seongho; Kim, Hyung-Man

    2015-11-01

    The emphasis on increasing fuel economy and reducing emissions is increasing. Attention has turned to how the performance of a gasoline direct injection (GDI) engine can be improved to achieve lower fuel consumption and NOx emission. Therefore, positive effects can reduce fuel consumption and NOx emission as well as knock suppression. The cooled exhaust gas recirculation (EGR) ranges within the characteristic map are characterized from the experimental results at various speeds and brake mean effective pressures in a GDI engine. The results show that the application of cooled EGR system brought in 3.63 % reduction as for the fuel consumption and 4.34 % as for NOx emission.

  9. Model-Based State Feedback Controller Design for a Turbocharged Diesel Engine with an EGR System

    Directory of Open Access Journals (Sweden)

    Tianpu Dong

    2015-05-01

    Full Text Available This paper describes a method for the control of transient exhaust gas recirculation (EGR systems. Firstly, a state space model of the air system is developed by simplifying a mean value model. The state space model is linearized by using linearization theory and validated by the GT-Power data with an operating point of the diesel engine. Secondly, a state feedback controller based on the intake oxygen mass fraction is designed for EGR control. Since direct measurement of the intake oxygen mass fraction is unavailable on the engine, the estimation method for intake oxygen mass fraction has been proposed in this paper. The control strategy is analyzed by using co-simulation with the Matlab/Simulink and GT-Powers software. Finally, the whole control system is experimentally validated against experimental data of a turbocharged diesel engine. The control effect of the state feedback controller compared with PID controller proved to be further verify the feasibility and advantages of the proposed state feedback controller.

  10. Experimental investigation of the influence of internal and external EGR on the combustion characteristics of a controlled auto-ignition two-stroke cycle engine

    International Nuclear Information System (INIS)

    Andwari, Amin Mahmoudzadeh; Aziz, Azhar Abdul; Said, Mohd Farid Muhamad; Latiff, Zulkarnain Abdul

    2014-01-01

    Highlights: • Investigate the effect of In-EGR, Ex-EGR and octane number on a CAI 2-stroke engine. • Effect of In-EGR, Ex-EGR and octane number on combustion phasing of the engine. • Effect of In-EGR, Ex-EGR and octane number on cyclic variability of the engine. • Identify the CAI combustion upper and lower boundary for operating regions. - Abstract: A two-stroke cycle engine incorporated with a controlled auto-ignition combustion approach presents a high thermodynamic efficiency, ultra-low exhaust emissions and high power-to-weight ratio features for future demand of prime movers. The start of auto-ignition, control of the auto-ignition and its cyclic variability, are major concerns that should be addressed in the combustion timing control of controlled auto-ignition engines. Several studies have been performed to examine the effect of internal exhaust gas recirculation utilization on auto-ignited two-stroke cycle engines. However, far too little attention has been devoted to study on the influence of external exhaust gas recirculation on the cyclic variation and the combustion characteristics of controlled auto-ignition two-stroke cycle engines. The purpose of this study is to examine the influence of external exhaust gas recirculation in combination with internal exhaust gas recirculation on the combustion characteristics and the cyclic variability of a controlled auto-ignition two-stroke engine using fuel with different octane numbers. In a detailed experimental investigation, the combustion-related and pressure-related parameters of the engine are examined and statistically associated with the coefficient of variation and the standard deviation. The outcomes of the investigation indicates that the most influential controlled auto-ignition combustion phasing parameters can be managed appropriately via regulating the internal and external exhaust gas recirculation and fuel octane number. In general, start of auto-ignition and its cyclic variability are

  11. Myocardial scintigraphy with 16 123I hexadecene-9 oic acid. Study of the influence of isoproterenol, propranolol, dipyridamole and isoptine

    International Nuclear Information System (INIS)

    Comet, M.; Wolf, J.E.; Pilichowski, P.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F.; Vidal, M.

    1983-01-01

    After I.V. injection of 123 I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Tacking the anesthetized dogs as his own reference, we study the influence of isoproterenol, propranolol, dipyridamole and isoptine on value of the period. None of the drugs modify significatively the period. Nevertheless, propranolol and isoptine and to a lesser extent dipyridamole have a tendancy to increase the value of the period [fr

  12. Experimental Study of Effect of EGR Rates on NOx and Smoke Emission of LHR Diesel Engine Fueled with Blends of Diesel and Neem Biodiesel

    Science.gov (United States)

    Modi, Ashishkumar Jashvantlal; Gosai, Dipak Chimangiri; Solanki, Chandresh Maheshchandra

    2018-04-01

    Energy conservation and efficiency have been the quest of engineers concerned with internal combustion engine. Theoretically, if the heat rejected could be reduced, then the thermal efficiency would be improved, at least up to the limit set by the second law of thermodynamics. For current work a ceramic coated twin cylinder water-cooled diesel engine using blends of diesel and Neem biodiesel as fuel was evaluated for its performance and exhaust emissions. Multi cylinder vertical water cooled self-governed diesel engine, piston, top surface of cylinder head and liners were fully coated with partially stabilized zirconia as ceramic material attaining an adiabatic condition. Previous studies have reported that combustion of Neem biodiesel emitted higher NOx, while hydrocarbon and smoke emissions were lower than conventional diesel fuel. Exhaust gas recirculation (EGR) is one of the techniques being used to reduce NOx emission from diesel engines; because it decreases both flame temperature and oxygen concentration in the combustion chamber. The stationary diesel engine was run in laboratory at a high load condition (85% of maximum load), fixed speed (2000 rpm) and various EGR rates of 5-40% (with 5% increment). Various measurements like fuel flow, exhaust temperature, exhaust emission measurement and exhaust smoke test were carried out. The results indicate improved fuel economy and reduced pollution levels for the low heat rejection (LHR) engine. The results showed that, at 5% EGR with TB10, both NOx and smoke opacity were reduced by 26 and 15%, respectively. Furthermore, TB20 along with 10% EGR was also able to reduce both NOx and smoke emission by 34 and 30%, respectively compared to diesel fuel without EGR.

  13. Comparison of thermal and radical effects of EGR gases on combustion process in dual fuel engines at part loads

    International Nuclear Information System (INIS)

    Pirouzpanah, V.; Khoshbakhti Saray, R.; Sohrabi, A.; Niaei, A.

    2007-01-01

    Dual fuel engines at part load inevitably suffer from lower thermal efficiency and higher emission of carbon monoxide and unburned fuel. This work is conducted to investigate the combustion characteristics of a dual fuel (Diesel-gas) engine at part loads using a single zone combustion model with detailed chemical kinetics for combustion of natural gas fuel. In this home made software, the presence of the pilot fuel is considered as a heat source that is deriving form two superposed Wiebe's combustion functions to account for its contribution to ignition of the gaseous fuel and the rest of the total released energy. The chemical kinetics mechanism consists of 112 reactions with 34 species. This combustion model is able to establish the development of the combustion process with time and the associated important operating parameters, such as pressure, temperature, heat release rate (HRR) and species concentration. Therefore, this work is an attempt to investigate the combustion phenomenon at part load and using exhaust gas recirculation (EGR) to improve the above mentioned problems. Also, the results of this work show that each of the different cases of EGR (thermal, chemical and radical cases) has an important role on the combustion process in dual fuel engines at part loads. It is found that all the different cases of EGR have positive effects on the performance and emission parameters of dual fuel engines at part loads despite the negative effect of some diluent gases in the chemical case, which moderates too much the positive effects of the thermal and radical cases of EGR. Predicted values show good agreement with corresponding experimental values over the whole range of engine operating conditions. Implications will be discussed in detail

  14. The D. melanogaster capa-1 neuropeptide activates renal NF-kB signaling.

    Science.gov (United States)

    Terhzaz, Selim; Overend, Gayle; Sebastian, Sujith; Dow, Julian A T; Davies, Shireen-A

    2014-03-01

    The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is critical for fluid homeostasis and has been associated with desiccation tolerance in the fly, Drosophila melanogaster. The mode of capa signaling is highly complex, affecting calcium, nitric oxide and cyclic GMP pathways. Such complex physiological regulation by cell signaling pathways may occur ultimately for optimal organismal stress tolerance to multiple stressors. Here we show that D. melanogaster capa-1 (Drome-capa-1) acts via the Nuclear Factor kappa B (NF-kB) stress signaling network. Human PCR gene arrays of capaR-transfected Human Embryonic Kidney (HEK) 293 cells showed that Drome-capa-1 increases expression of NF-kB, NF-kB regulated genes including IL8, TNF and PTGS2, and NF-kB pathway-associated transcription factors i.e. EGR1, FOS, cJUN. Furthermore, desiccated HEK293 cells show increased EGR1, EGR3 and PTGS2 - but not IL8, expression. CapaR-transfected NF-kB reporter cells showed that Drome-capa-1 increased NF-kB promoter activity via increased calcium. In Malpighian tubules, both Drome-capa-1 stimulation and desiccation result in increased gene expression of the D. melanogaster NF-kB orthologue, Relish; as well as EGR-like stripe and klumpfuss. Drome-capa-1 also induces Relish translocation in tubule principal cells. Targeted knockdown of Relish in only tubule principal cells reduces desiccation stress tolerance of adult flies. Together, these data suggest that Drome-capa-1 acts in desiccation stress tolerance, by activating NF-kB signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Emission Characteristics and Egr Application of Blended Fuels with Bdf and Oxygenate (dmm) in a Diesel Engine

    Science.gov (United States)

    Choi, Seung-Hun; Oh, Young-Taig

    In this study, the possibility of biodiesel fuel and oxygenated fuel (dimethoxy methane ; DMM) was investigated as an alternative fuel for a naturally aspirated direct injection diesel engine. The smoke emission of blending fuel (biodiesel fuel 90vol-% + DMM 10vol-%) was reduced approximately 70% at 2500rpm, full load in comparison with the diesel fuel. But, engine power and brake specific energy consumption showed no significant differences. But, NOx emission of biodiesel fuel and DMM blended fuel increased compared with commercial diesel fuel due to the oxygen component in the fuel. It was needed a NOx reduction counter plan that EGR method was used as a countermeasure for NOx reduction. It was found that simultaneous reduction of smoke and NOx emission was achieved with BDF (95 vol-%) and DMM (5 vol-%) blended fuel and cooled EGR method (15%).

  16. Effect of oral propranolol on circulating catecholamines in cirrhosis: relationship to severity of liver disease and splanchnic haemodynamics

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Henriksen, Jens Henrik; Sørensen, T I

    1990-01-01

    propranolol. A borderline significant correlation was observed between the decrease in azygos blood flow and the increase in NA (r = 0.64, p = 0.06). Our results suggest that besides a relationship to liver function and severity of disease, sympathetic nervous activity, as reflected by circulating NA.......01). Azygos blood flow was increased (0.75 l/min) and positively related to plasma NA (r = 0.57, p = 0.05, n = 12). After propranolol intake, plasma NA increased from 0.52 to 0.59 ng/ml (p less than 0.01). This response was found in all Child-Turcotte classes (A: 0.37 to 0.43; B: 0.49 to 0.56; C: 0.78 to 0.......88 ng/ml), and in patients with as well as without ascites. Plasma adrenaline increased in the same way (p less than 0.01). Hepatic blood flow (from 1.10 to 0.93 l/min, p less than 0.01) and azygos blood flow (from 0.75 to 0.55 l/min, n = 9, p less than 0.05) decreased significantly after oral...

  17. Myocardial scintigraphy with 16 /sup 123/I hexadecene-9 oic acid. Study of the influence of isoproterenol, propranolol, dipyridamole and isoptine

    Energy Technology Data Exchange (ETDEWEB)

    Comet, M.; Wolf, J.E.; Pilichowski, P.; Busquet, G.; Dubois, F.; Mathieu, J.P.; Pernin, C.; Riche, F.; Vidal, M. ( Grenoble Universite, 38 - (France))

    1983-01-01

    After I.V. injection of /sup 123/I hexadecene-9 oic acid to dogs, the decreasing part of the myocardial activity curve is fitted with an exponential which period is calculated. Taking the anesthetized dog as reference, we study the influence of isoproterenol, propranolol, dipyridamole and isoptine on value of the period. None of the drugs modify significantly the period. Nevertheless, propranolol and isoptine and to a lesser extent dipyridamole have a tendancy to increase the value of the period.

  18. Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

    International Nuclear Information System (INIS)

    Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

    2005-01-01

    The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

  19. Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

    Science.gov (United States)

    Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K

    1990-03-01

    The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

  20. Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna.

    Science.gov (United States)

    Varano, Valentina; Fabbri, Elena; Pasteris, Andrea

    2017-08-01

    Pharmaceuticals are widespread emerging contaminants and, like all pollutants, are present in combination with others in the ecosystems. The aim of the present work was to evaluate the toxic response of the crustacean Daphnia magna exposed to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, and propranolol, a non-selective β-adrenergic receptor-blocking agent used to treat hypertension, were tested. Several experimental trials of an acute immobilization test and a chronic reproduction test were performed. Single chemicals were first tested separately. Toxicity of binary mixtures was then assessed using a fixed ratio experimental design. Five concentrations and 5 percentages of each substance in the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied to analyze the experimental results. This tool is a stepwise statistical procedure that evaluates if and how observed data deviate from a reference model, either concentration addition (CA) or independent action (IA), and provides significance testing for synergism, antagonism, or more complex interactions. Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1 mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a significant antagonism between chemicals in both the acute and the chronic mixture tests when CA was adopted as the reference model, while absence of interactive effects when IA was used.

  1. Enantiomers Recognition of Propranolol Based on Organic-Inorganic Hybrid Open-Tubular MIPs-CEC Column Using 3-(Trimethoxysilyl)Propyl Methacrylate as a Cross-Linking Monomer.

    Science.gov (United States)

    Chen, Guo-Ning; Li, Ning; Luo, Tian; Dong, Yu-Ming

    2017-04-01

    In this study, 3-(trimethoxysilyl)propyl methacrylate (γ-MPS), a bifunctional group compound, was used as a single cross-linking agent to prepare molecular imprinted inorganic-organic hybrid polymers by in situ polymerization for open-tubular capillary electro chromatography (CEC) column. The optimal preparation conditions were: the ratio between template molecule and functional monomer was 1:4; the volume proportion of porogen toluene and methanol was 1:1 and the volume of cross-linking agent γ-MPS was 69 μL. The optimal separation conditions were separation voltage of 15 kV; detection wavelength at 215 nm and background electrolyte composed of 70% acetonitrile/20 mmol/L boric acid salt (pH 6.9). Under the optimized conditions, the propranolol enantiomers can be separated well by CEC. The method is simple and fast, it can be a potentially useful approach for propranolol enantiomers separation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Effect of a sustainable biofuel – n-octanol – on the combustion, performance and emissions of a DI diesel engine under naturally aspirated and exhaust gas recirculation (EGR) modes

    International Nuclear Information System (INIS)

    Rajesh Kumar, B.; Saravanan, S.; Rana, D.; Anish, V.; Nagendran, A.

    2016-01-01

    Highlights: • It is possible to operate a DI diesel engine with up to 30% n-octanol/diesel blends without modifications. • Addition of n-octanol prolonged the ignition delay, generated higher peaks of pressure and heat release rates. • Simultaneous reduction of NOx and smoke is possible under both naturally-aspirated and EGR conditions. • Engine performance improved with n-octanol addition. • HC and CO emissions decreased favorably with n-octanol addition. - Abstract: Higher alcohols above n-butanol can be excellent alternative fuels for diesel engines owing to their high energy content and high cetane number. The last three years has witnessed an advent of several sustainable pathways for n-octanol bio-synthesis using engineered-microbes like Escherichia coli and Clostridium species. Therefore an investigation to evaluate the compatibility of n-octanol in diesel engines becomes essential. The influence of blending n-octanol by up to 30 vol% with fossil diesel on combustion, performance and emission characteristics of a single cylinder direct-injection (DI) diesel engine under both naturally aspirated and exhaust gas recirculation (EGR) modes was investigated with reference to diesel. Results showed that n-octanol prolonged the ignition delay generating higher peaks of in-cylinder pressure and heat release rates (HRR) during the pre-mixed combustion phase. Brake thermal efficiency (BTE) increased while brake specific fuel consumption (BSFC) decreased with an increase in n-octanol fraction. Smoke, NOx (nitrogen oxides), HC (hydro-carbons) and CO (carbon monoxide) emissions decreased with n-octanol addition. NOx and smoke emissions also remained low at all EGR rates. Both BTE and BSFC suffered at increased EGR rates. HC and CO emissions increased with escalating EGR rates. n-Octanol was found to be very promising for replacing fossil-diesel by up to 30% (subject to long term durability tests), in terms of emissions and performance at both naturally

  3. Evaluation of Plantago major L. seed mucilage as a rate controlling matrix for sustained release of propranolol hydrochloride.

    Science.gov (United States)

    Saeedi, Majid; Morteza-Semnani, Katayoun; Sagheb-Doust, Mehdi

    2013-03-01

    Polysaccharide mucilage derived from the seeds of Plantago major L. (family Plantaginaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. HPMC K4M and tragacanth were used as standards for comparison. The hardness, tensile strength, and friability of tablets increased as the concentration of mucilage increased, indicating good compactibility of mucilage powders. The rate of release of propranolol hydrochloride from P. major mucilage matrices was mainly controlled by the drug/mucilage ratio. Formulations containing P. major mucilage were found to exhibit a release rate comparable to HPMC containing matrices at a lower drug/polymer ratio (drug/HPMC 2:1). These results demonstrated that P. major mucilage is a better release retardant compared to tragacanth at an equivalent content. The results of kinetic analysis showed that in F3 (containing 1:2 drug/mucilage) the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets. The DSC and FT-IR studies showed that no formation of complex between the drug and mucilage or changes in crystallinity of the drug had occurred.

  4. Potential Fuel Economy Improvements from the Implementation of cEGR and CDA on an Atkinson Cycle Engine

    Science.gov (United States)

    Present the implementation of cEGR and CDA on an Atkinson engine and use steady state fuel consumption maps to estimate the technologies’ potential fuel economy improvements over the FTP and Highway tests. In addition to use fuel weighted modes to determine possible fuel economy...

  5. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    International Nuclear Information System (INIS)

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-01-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

  6. Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography Monitoramento do propranolol plasmático em crianças operadas da tetralogia de Fallot através de micrométodo utilizando a cromatografia líquida de alta eficiência

    Directory of Open Access Journals (Sweden)

    Cristina Sanches

    2007-01-01

    Full Text Available OBJECTIVE: To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF. Methods: Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol and 17.5 min (verapamil, internal standard from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v at flow rate 0.7 mL/min, detected at 290 nm (excitation and 358 nm (emission. Surgery was started 776 min of drug administration (8.7mg, mean; seven blood samples were collected from six patients (4M/2F; 2.1yrs;11.5kg; 0.80m; 18.9kg/m². RESULTS: Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000ng/mL, precision of 8.6% and accuracy of 3.1%. The mean duration of surgery was 283.2min, with the patients remaining under cardiopulmonary bypass (CPB for 114min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, pOBJETIVO: Avaliar o micrométodo analítico empregando a cromatografia líquida para quantificação de propranolol em crianças operadas de tetralogia de Fallot (TLF. MÉTODO: Requereu-se apenas volumes de 0,2mL de plasma para a realização do ensaio. Os picos foram eluídos em 8.4 (Propranolol e 17.5 min (verapamil, padrão interno de uma coluna C18, com fase móvel (tampão acetato 0,1 M pH 5,0 e acetonitrila, 60:40, v/v em fluxo de 0,7 mL/min, sendo detectados em 290 nm (excitação e em 358 nm (emissão. A cirurgia iniciou-se 776 min depois da dose administrada (8,7mg, média e sete amostras de sangue foram

  7. 20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice.

    Science.gov (United States)

    Lu, Cong; Dong, Liming; Lv, Jingwei; Wang, Yan; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

    2018-01-05

    20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 μmol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD). Copyright © 2017. Published by Elsevier B.V.

  8. Activation of PKCβII and PKCθ is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation

    International Nuclear Information System (INIS)

    Heo, Kyung-Sun; Kim, Dong-Uk; Kim, Lila; Nam, Miyoung; Baek, Seung-Tae; Park, Song-Kyu; Park, Youngwoo; Myung, Chang-Seon; Hwang, Sung-Ook; Hoe, Kwang-Lae

    2008-01-01

    Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCβ II and PKCθ from cytosol to plasma membrane, and inhibition of PKCβ II and PKCθ decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCβ II and PKCθ, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCβ II and PKCθ. Inhibition of PKCβ II or PKCθ, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCθ in VSMC proliferation is unique

  9. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol

    Energy Technology Data Exchange (ETDEWEB)

    Soederlund, Veli [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden)

    2007-07-15

    Uptake in brown adipose tissue (hibernating fat) is sometimes seen at FDG-PET examinations. Despite a characteristic appearance, this may hide clinically relevant uptake. Stimulation of the sympathetic nervous system increases glucose uptake of brown fat. We now re-examine patients with brown fat activity that could disguise tumour uptake after pre-treatment with propranolol (a non-selective {beta}-blocker) in order to reduce the uptake. Our first examinations of this kind are reported. Eleven patients with strong brown fat uptake were studied. There was a mean of 5 days (range 2-8) between the examinations. At the second examination, 80 mg of propranolol was given orally 2 h before FDG administration. In addition to visual evaluation of the brown fat uptake, SUV assessments of the uptake in brown fat, lung, heart, liver, spleen and bone marrow were made. All patients showed complete or almost complete disappearance of the brown fat activity at the second examination (p < 0.001) both upon visual evaluation and when comparing SUVs. In seven patients there was also uptake in a known or strongly suspected malignancy, which remained unchanged between the examinations. Beyond an insignificant decrease in the myocardial uptake, there was no redistribution to the various examined organs at the second examination. Pre-treatment with a single dose of propranolol blocks the FDG uptake in brown adipose tissue, thereby increasing the specificity of the examination. The tumour uptake seems not to be impaired. (orig.)

  10. Liquid chromatography-tandem mass spectrometry method for simultaneous quantification of bisoprolol, ramiprilat, propranolol and midazolam in rat dried blood spots.

    Science.gov (United States)

    Cvan Trobec, Katja; Trontelj, Jurij; Springer, Jochen; Lainscak, Mitja; Kerec Kos, Mojca

    2014-05-01

    Dried blood spot (DBS) sampling represents a suitable method for pharmacokinetic studies in rats, particularly if serial sampling is needed. To study the pharmacokinetics of drugs in a rat heart failure (HF) model, we developed and validated a method for the simultaneous determination of bisoprolol, ramiprilat, propranolol and midazolam in DBS samples. Bisoprolol and ramipril are widely used in the treatment of HF, and midazolam and propranolol are markers of hepatic metabolism, which can be altered in HF. A 20μL sample of rat blood was pipetted onto Whatman 903 Protein Saver Card and allowed to dry. The whole spot was excised and 300μL of solvent (methanol with 10% ultrapure water and 0.1% formic acid) was added. After mixing and incubating the sample in an ultrasonic bath, a mixture of isotopically labeled internal standards was added. After centrifugation, the extracts were cleaned on an Ostro™ plate and analyzed using liquid chromatography-tandem mass spectroscopy. The method was successfully validated. No significant interference was observed in the retention times of analytes or internal standards. The intraday and interday accuracy and precision were within a ±15% interval. The method was linear in the range 5-250μg/L and the lower limit of quantification was 5μg/L for all four analytes. The absolute matrix effect ranged from 98.7% for midazolam to 121% for ramiprilat. The recovery was lowest for ramiprilat and highest for propranolol. Samples were stable at all tested temperatures. The method has been used successfully in a real-time pharmacokinetic study in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Study on the inclusion behavior of p-sulfonatocalix[6]arene with propranolol by spectrofluorometry

    Science.gov (United States)

    Li, Hui; Song, Jin-Ping; Chao, Jian-Bin; Shuang, Shao-Min; Dong, Chuan

    2012-11-01

    The inclusion interaction between propranolol (PPL) and p-sulfonatocalix[6]arene (SCX6) was investigated by fluorescence and 1H NMR spectroscopy. Influences of pH, temperature, ionic strength and the concentration of SCX6 were examined in detail. In phosphate buffer solution with pH 7.5, the fluorescence of PPL dramatically quenched upon addition of SCX6 revealing the formation of inclusion complexes between PPL and SCX6. The stoichiometric ratio was verified to be 1:1 by the continuous variation method. The inclusion constant of PPL-SCX6 complexes was calculated as 2.2 × 104 L/mol by the nonlinear curve fitting method. 1H NMR titration spectra testified that the aliphatic chain of PPL may be partially penetrated into the hydrophobic cavity of SCX6. This was confirmed by molecular dynamics calculations.

  12. Construction and identification of double-gene co-expression vector with radiation-inducible human TRAIL and endostatin

    International Nuclear Information System (INIS)

    Li Yanbo; Guo Caixia; Gong Pingsheng; Liu Yang; Liangshuo; Wang Hongfang; Wang Jianfeng; Gong Shouliang

    2010-01-01

    Objective: To construct a recombinant plasmid pshuttle-Egr1-shTRAIL-shES containing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and endostatin double genes. Methods: The secretary endostatin gene (shES) fragment was amplified from the pMD19T-endostatin vector by PCR. The shES gene was ligated to pMD19Tand sequenced. Finally, using the gene recombinant technique, the recombinant plasmid pshuttle-Egr1- shTRAIL-shES with radiation-inducible Egr1 promoter, secretary TRAIL and endostatin double-gene was constructed. Results: The sequence of the shES gene was in concordance with that anticipated indicating shES gene was acquired successfully.Moreover, the results acquired by PCR and restrictive digestion identification of the recombinant plasmid pshuttle-Egr1-shTRAIL-shES and all the vectors refered to its construction confirmed that pshuttle-Egr1-shTRAIL-shES was constructed correctly. Conclusion: The radiation-inducible double-gene co-expression vector pshuttle-Egr1-shTRAIL-shES is constructed successfully, which would set the experimental foundation for further study on the anti-tumor effect of TRAIL and endostatin double-gene-radiotherapy and its related mechanisms. (authors)

  13. Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome

    International Nuclear Information System (INIS)

    Morel, D.R.; Dargent, F.; Bachmann, M.; Suter, P.M.; Junod, A.F.

    1985-01-01

    Because injury to the pulmonary vascular endothelium is associated with the development of the adult respiratory distress syndrome (ARDS), the authors assessed the metabolic function of pulmonary endothelial cells by the measurements of the first-pass pulmonary extraction of [ 14 C]serotonin and [ 3 H]propranolol in 15 patients with ARDS and 15 patients at risk for developing ARDS. Serotonin extraction ratio was lower in patients with ARDS (0.85 +/- 0.10, mean +/- SD) than in patients at risk (0.91 +/- 0.04) (p less than 0.025), and both values were significantly reduced (p less than 0.005) when compared with a control group value (0.97 +/- 0.01). The decrease in serotonin extraction was correlated with the severity of ARDS (r = -0.67) (p less than 0.001) and with pulmonary function changes over time. Propranolol extraction ratio was decreased in patients at risk (0.66 +/- 0.11) (p less than 0.005) but not in patients with ARDS (0.75 +/- 0.11), when compared with those in the control group (0.81 +/- 0.03). Low values in patients at risk were restored to normal by continuous positive airway pressure breathing. The authors conclude that pulmonary extraction of serotonin, an index of pulmonary endothelial cell function, correlates with the severity of ARDS

  14. Investigation on the Effects of Internal EGR by Variable Exhaust Valve Actuation with Post Injection on Auto-ignited Combustion and Emission Performance

    Directory of Open Access Journals (Sweden)

    Insu Cho

    2018-04-01

    Full Text Available Variable valve mechanisms are usually applied to a gasoline combustion engine to improve its power performance by controlling the amount of intake air according to the operating load. These mechanisms offer one possibility of resolving the conflict of objectives between a further reduction of raw emissions and an improvement in fuel efficiency. In recent years, variable valve control systems have become extremely important in the diesel combustion engine. Importantly, it has been shown that there are several potential benefits of applying variable valve timing (VVT to a compression ignition engine. Valve train variability could offer one option to achieve the reduction goals of engine-out emissions and fuel consumption. The aim of this study was to investigate the effects on part load combustion and emission performance of internal exhaust gas recirculation (EGR by variable exhaust valve lift actuation using a cam-in-cam system, which is an electronically variable valve device with a variable inside cam retarded to about 30 degrees. Numerical simulation based on GT-POWER has been performed to predict the NOx reduction strategy at the part load operating point of 1200 rpm in a four-valve diesel engine. A GT-POWER model of a common-rail direct injection engine with internal EGR was built and verified with experimental data. As a result, large potential for reducing NOx emissions through the use of exhaust valve control has been identified. Namely, it is possible to utilize heat efficiently as recompression of retarded post injection with downscaled specification of the exhaust valve rather than the intake valve, even if the CIC V1 condition with a reduction of the exhaust valve has a higher internal EGR rate of about 2% compared to that of the CIC V2 condition.

  15. Comprehensive genome-wide analysis of the Aux/IAA gene family in Eucalyptus: evidence for the role of EgrIAA4 in wood formation.

    Science.gov (United States)

    Yu, Hong; Soler, Marçal; San Clemente, Hélène; Mila, Isabelle; Paiva, Jorge A P; Myburg, Alexander A; Bouzayen, Mondher; Grima-Pettenati, Jacqueline; Cassan-Wang, Hua

    2015-04-01

    Auxin plays a pivotal role in various plant growth and development processes, including vascular differentiation. The modulation of auxin responsiveness through the auxin perception and signaling machinery is believed to be a major regulatory mechanism controlling cambium activity and wood formation. To gain more insights into the roles of key Aux/IAA gene regulators of the auxin response in these processes, we identified and characterized members of the Aux/IAA family in the genome of Eucalyptus grandis, a tree of worldwide economic importance. We found that the gene family in Eucalyptus is slightly smaller than that in Populus and Arabidopsis, but all phylogenetic groups are represented. High-throughput expression profiling of different organs and tissues highlighted several Aux/IAA genes expressed in vascular cambium and/or developing xylem, some showing differential expression in response to developmental (juvenile vs. mature) and/or to environmental (tension stress) cues. Based on the expression profiles, we selected a promising candidate gene, EgrIAA4, for functional characterization. We showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin-responsive repressor. Overexpressing a stabilized version of EgrIAA4 in Arabidopsis dramatically impeded plant growth and fertility and induced auxin-insensitive phenotypes such as inhibition of primary root elongation, lateral root emergence and agravitropism. Interestingly, the lignified secondary walls of the interfascicular fibers appeared very late, whereas those of the xylary fibers were virtually undetectable, suggesting that EgrIAA4 may play crucial roles in fiber development and secondary cell wall deposition. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Effects of prenatal cocaine exposure on social development in mice.

    Science.gov (United States)

    Kabir, Zeeba D; Kennedy, Bruce; Katzman, Aaron; Lahvis, Garet P; Kosofsky, Barry E

    2014-01-01

    Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair social development. Molecules that mediate synaptic plasticity and learning in the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic factor (BDNF) and its downstream signaling molecule, early growth response protein 1 (egr1), have been shown to affect the regulation of social interactions (SI). In this study we determined the effects of PCE on SI and the corresponding ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the PCE-induced changes in the constitutive expression of BDNF, egr1 and their transcriptional regulators in the mPFC as a possible molecular mechanism mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified increased SI and USV production at postnatal day (PD) 25, and increased SI but not USVs at PD35. By PD45 the expression of both social behaviors normalized in PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by measuring the association of acetylation of histone 3 at lysine residues 9 and 14 (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our results provide evidence of promoter-specific alterations in the mPFC of PCOC juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV promoter. These results identify a potential PCE-induced molecular alteration as the underlying neurobiological mechanism mediating the altered social development in juvenile mice. © 2014 S. Karger AG, Basel.

  17. The "3"2P applicator combined with propranolol in the treatment of large area skin capillary hemangiomain children

    International Nuclear Information System (INIS)

    Duan Yongqiang; Wu Zhenfu; Wu Min; Qiu Xuan; Fei Shinuan

    2016-01-01

    Objective: To investigate the clinical efficacy of "3"2P applicator plus propranolol in children with a large area of skin capillary hemangioma. Methods: Forty five cases of large hemangioma were divided into two groups. Control group of 20 patients recieved the conventional "3"2P application therapy. Of 20 cases in control group, there were 10 cases ≤3 years old children with hemangiomas, and 10 cases > 3 years old children with Port Wine Stain(PWS). Observation group of 25 cases recieved "3"2P applicator plus propranolol. Of 25 cases in observation group 10 cases werer ≤3 years old children with hemangiomas, 15 cases of children with PWS. Comparison was made between two different types of vascular tumors, treatment in ≤3 years old children and > 3 years old children, and adverse reactions. Data statistical analysis used χ"2 test and zero reaction test. P 0.05). The treatment efficacy in ≤3 years old children with infant hemangioma was 90.0% in control group and 100% in observation group (P > 0.05 ). The treatment efficacy for PWS in > 3 years old children was 40.0% in control group and 80% in observation group. Here the difference is statistically significant(P 3 years old children in control group,the treatment efficacy was 90.0% and 40.0%, respectively P 3 years old children in observation group, the treatment efficacy was 100.0% and 80.0% with no significant difference(P > 0.05). Complication of moist dermatitis was 25.0% in control group and 40.0% in observation group. Occurrence of depigmentation was 75.0% and 84.0% in control and observation group with no significant difference(P > 0.05). Changing in heart rate occurs in ≤3 years old children and > 3 years old children, 50.0% and 40.0%, respectively, with no significant difference(P > 0.05). Conclusion: "3"2P applicator plus propranolol treatment of refractory large hemangioma is simple, safe, and effective. But close attention needs to be paid to both "3"2P and propranolol on adverse reactions

  18. Experimental validation of a kinetic multi-component mechanism in a wide HCCI engine operating range for mixtures of n-heptane, iso-octane and toluene: Influence of EGR parameters

    International Nuclear Information System (INIS)

    Machrafi, Hatim

    2008-01-01

    The parameters that are present in exhaust gas recirculation (EGR) are believed to provide an important contribution to control the auto-ignition process of the homogeneous charge compression ignition (HCCI) in an engine. For the investigation of the behaviour of the auto-ignition process, a kinetic multi-component mechanism has been developed in former work, containing 62 reactions and 49 species for mixtures of n-heptane, iso-octane and toluene. This paper presents an experimental validation of this mechanism, comparing the calculated pressure, heat release, ignition delays and CO 2 emissions with experimental data performed on a HCCI engine. The validation is performed in a broad range of EGR parameters by varying the dilution by N 2 and CO 2 from 0 to 46 vol.%, changing the EGR temperature from 30 to 120 deg. C, altering the addition of CO and NO from 0 to 170 ppmv and varying the addition of CH 2 O from 0 to 1400 ppmv. These validations were performed respecting the HCCI conditions for the inlet temperature and the equivalence ratio. The results showed that the mechanism is validated experimentally in dilution ranges going up to 21-30 vol.%, depending on the species of dilution and over the whole range of the EGR temperature. The mechanism is validated over the whole range of CO and CH 2 O addition. As for the addition of NO, the mechanism is validated quantitatively up to 50 ppmv and qualitatively up to 170 ppmv

  19. An oncolytic adenovirus regulated by a radiation-inducible promoter selectively mediates hSulf-1 gene expression and mutually reinforces antitumor activity of I131-metuximab in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yan; Fang, Lin; Zhang, Quan'an; Zheng, Qin; Tong, Jinlong; Fu, Xiaohui; Jiang, Xiaoqing; Su, Changqing; Zheng, Junnian

    2013-06-01

    Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells. To integrate the oncolytic adenovirus-based gene therapy and the I(131)-mab-based radioimmunotherapy, this study combined the CArG element of early growth response-l (Egr-l) gene with the survivin promoter to construct a radiation-inducible enhanced promoter, which was used to recombine a radiation-inducible oncolytic adenovirus as hSulf-1 gene vector. When I(131)-mab was incorporated into the treatment regimen, not only could the antibody produce radioimmunotherapeutic effect, but the I(131) radiation was able to further boost adenoviral proliferation. We demonstrated that the CArG-enhanced survivin promoter markedly improved the proliferative activity of the oncolytic adenovirus in HCC cells, thereby augmenting hSulf-1 expression and inducing cancer cell apoptosis. This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, was demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in HCC treatment. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Coke-free dry reforming of model diesel fuel by a pulsed spark plasma at low temperatures using an exhaust gas recirculation (EGR) system

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Yasushi; Furukawa, Naotsugu; Matsukata, Masahiko; Kikuchi, Eiichi, E-mail: ysekine@waseda.jp [Department of Applied Chemistry, Waseda University, 65-301, Okubo, Shinjuku, Tokyo 169-8555 (Japan)

    2011-07-13

    Dry reforming of diesel fuel, an endothermic reaction, is an attractive process for on-board hydrogen/syngas production to increase energy efficiency. For operating this dry reforming process in a vehicle, we can use the exhaust gas from an exhaust gas recirculation (EGR) system as a source of carbon dioxide. Catalytic dry reforming of heavy hydrocarbon is a very difficult reaction due to the high accumulation of carbon on the catalyst. Therefore, we attempted to use a non-equilibrium pulsed plasma for the dry reforming of model diesel fuel without a catalyst. We investigated dry reforming of model diesel fuel (n-dodecane) with a low-energy pulsed spark plasma, which is a kind of non-equilibrium plasma at a low temperature of 523 K. Through the reaction, we were able to obtain syngas (hydrogen and carbon monoxide) and a small amount of C{sub 2} hydrocarbon without coke formation at a ratio of CO{sub 2}/C{sub fuel} = 1.5 or higher. The reaction can be conducted at very low temperatures such as 523 K. Therefore, it is anticipated as a novel and effective process for on-board syngas production from diesel fuel using an EGR system.

  1. Comparative Study of the Clonidin and Propranolol Effect in the Prevention of Hemodynamic Changes after Electroconvulsive Therapy

    Directory of Open Access Journals (Sweden)

    A. Moradi

    2009-04-01

    Full Text Available Introduction & Objective: ECT is an inevitable therapy for many of psychiatric patients. During ECT severe hemodynamic changes occur which may cause dangerous cardiovascular complications especially in elderly patients with cardiac disease and may lead to arrhythmia,ischemia and myocardial infarction. The purpose of this study was to show the effect of clonidin and propranolol on the prevention of hemodynamic changes following the ECT.Materials & Methods: This study was a controlled double blind clinical trial which was carried out on 31 patients ASA I, II hospitalized in psychiatry ward of Hamadan Sina hospital who were in need of ECT. In order to increase the accuracy of the study the personal factors on the drug metabolism were omitted and the chosen patients were given ECT three times separately with the interval of 48 hours. Two hours before every ECT clonidin (0.2 mg, propranolol (40 mg and placebo (vitamin c were administered and after each ECT the hemodynamic parameters including systolic blood pressure, diastolic blood pressure, rate pressure product and ECG were measured at certain intervals and recorded on information forms and then analyzed by SPSS 9 soft ware. Results: The result of this study showed that the average changes of hemodynamic parameters in different times occurred in all groups significantly(p<0.001. Following ECT, arrhythmia in control group has been plentiful in comparison with the other two groups, and the changes were statistically meaningful (p=0.001.Conclusion: We concluded that the modifying hemodynamic changes and decrease of arrhythmia taking the drugs in comparison with placebo have been more effective and of the two drugs, propranolol has been more effective on the prevention of hemodynamic changes after ECT.

  2. Experimental validation of a kinetic multi-component mechanism in a wide HCCI engine operating range for mixtures of n-heptane, iso-octane and toluene: Influence of EGR parameters

    Energy Technology Data Exchange (ETDEWEB)

    Machrafi, Hatim [LGPPTS, Ecole Nationale Superieure de Chimie de Paris/ Universite Pierre et Marie Curie (Paris 6), 11, rue de Pierre et Marie Curie, 75231 Paris Cedex 05 (France)

    2008-11-15

    The parameters that are present in exhaust gas recirculation (EGR) are believed to provide an important contribution to control the auto-ignition process of the homogeneous charge compression ignition (HCCI) in an engine. For the investigation of the behaviour of the auto-ignition process, a kinetic multi-component mechanism has been developed in former work, containing 62 reactions and 49 species for mixtures of n-heptane, iso-octane and toluene. This paper presents an experimental validation of this mechanism, comparing the calculated pressure, heat release, ignition delays and CO{sub 2} emissions with experimental data performed on a HCCI engine. The validation is performed in a broad range of EGR parameters by varying the dilution by N{sub 2} and CO{sub 2} from 0 to 46 vol.%, changing the EGR temperature from 30 to 120 C, altering the addition of CO and NO from 0 to 170 ppmv and varying the addition of CH{sub 2}O from 0 to 1400 ppmv. These validations were performed respecting the HCCI conditions for the inlet temperature and the equivalence ratio. The results showed that the mechanism is validated experimentally in dilution ranges going up to 21-30 vol.%, depending on the species of dilution and over the whole range of the EGR temperature. The mechanism is validated over the whole range of CO and CH{sub 2}O addition. As for the addition of NO, the mechanism is validated quantitatively up to 50 ppmv and qualitatively up to 170 ppmv. (author)

  3. pH modulates the binding of early growth response protein 1 transcription factor to DNA.

    Science.gov (United States)

    Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

    2013-08-01

    The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

  4. Effects of Pilot Injection Timing and EGR on Combustion, Performance and Exhaust Emissions in a Common Rail Diesel Engine Fueled with a Canola Oil Biodiesel-Diesel Blend

    Directory of Open Access Journals (Sweden)

    Jun Cong Ge

    2015-07-01

    Full Text Available Biodiesel as a clean energy source could reduce environmental pollution compared to fossil fuel, so it is becoming increasingly important. In this study, we investigated the effects of different pilot injection timings from before top dead center (BTDC and exhaust gas recirculation (EGR on combustion, engine performance, and exhaust emission characteristics in a common rail diesel engine fueled with canola oil biodiesel-diesel (BD blend. The pilot injection timing and EGR rate were changed at an engine speed of 2000 rpm fueled with BD20 (20 vol % canola oil and 80 vol % diesel fuel blend. As the injection timing advanced, the combustion pressure, brake specific fuel consumption (BSFC, and peak combustion pressure (Pmax changed slightly. Carbon monoxide (CO and particulate matter (PM emissions clearly decreased at BTDC 20° compared with BTDC 5°, but nitrogen oxide (NOx emissions increased slightly. With an increasing EGR rate, the combustion pressure and indicated mean effective pressure (IMEP decreased slightly at BTDC 20° compared to other injection timings. However, the Pmax showed a remarkable decrease. The BSFC and PM emissions increased slightly, but the NOx emission decreased considerably.

  5. Honey bee foraging induces upregulation of early growth response protein 1, hormone receptor 38 and candidate downstream genes of the ecdysteroid signalling pathway.

    Science.gov (United States)

    Singh, A S; Shah, A; Brockmann, A

    2018-02-01

    In honey bees, continuous foraging at an artificial feeder induced a sustained upregulation of the immediate early genes early growth response protein 1 (Egr-1) and hormone receptor 38 (Hr38). This gene expression response was accompanied by an upregulation of several Egr-1 candidate downstream genes: ecdysone receptor (EcR), dopamine/ecdysteroid receptor (DopEcR), dopamine decarboxylase and dopamine receptor 2. Hr38, EcR and DopEcR are components of the ecdysteroid signalling pathway, which is highly probably involved in learning and memory processes in honey bees and other insects. Time-trained foragers still showed an upregulation of Egr-1 when the feeder was presented at an earlier time of the day, suggesting that the genomic response is more dependent on the food reward than training time. However, presentation of the feeder at the training time without food was still capable of inducing a transient increase in Egr-1 expression. Thus, learnt feeder cues, or even training time, probably affect Egr-1 expression. In contrast, whole brain Egr-1 expression changes did not differ between dancing and nondancing foragers. On the basis of our results we propose that food reward induced continuous foraging ultimately elicits a genomic response involving Egr-1 and Hr38 and their downstream genes. Furthermore this genomic response is highly probably involved in foraging-related learning and memory responses. © 2017 The Royal Entomological Society.

  6. Influence of the single EGR valve usability on development of the charge directed to individual cylinders of an internal combustion engine

    Directory of Open Access Journals (Sweden)

    Krakowian Konrad

    2017-01-01

    Full Text Available Exhaust gas recirculation systems (EGR, aside to a catalytic converters, are nowadays widely used in piston internal combustion engines to reduce nitrogen oxides (NOx in the exhaust gas. They are characterized in that a portion of exhaust gases from the exhaust manifold is recirculated (via a condenser, and directed to a particular valve. The valve, depending on the current engine load and speed, doses the appropriate amount of exhaust gas into the exhaust manifold. Moreover, its location has a significant impact on the diverse formation of nitrogen oxides and fumes smokiness from the individual cylinders of the engine, which is a result of uneven propagation of exhaust gas into the channels of the intake manifold. This article contains the results of numerical characterized charges formed in symmetrical intake manifold with a centrally–placed EGR valve. Simulations were performed for the original intake system derived from the two-liter, turbocharged VW diesel engine.

  7. Influence of the single EGR valve usability on development of the charge directed to individual cylinders of an internal combustion engine

    Science.gov (United States)

    Krakowian, Konrad; Kaźmierczak, Andrzej; Górniak, Aleksander; Wróbel, Radosław

    2017-11-01

    Exhaust gas recirculation systems (EGR), aside to a catalytic converters, are nowadays widely used in piston internal combustion engines to reduce nitrogen oxides (NOx) in the exhaust gas. They are characterized in that a portion of exhaust gases from the exhaust manifold is recirculated (via a condenser), and directed to a particular valve. The valve, depending on the current engine load and speed, doses the appropriate amount of exhaust gas into the exhaust manifold. Moreover, its location has a significant impact on the diverse formation of nitrogen oxides and fumes smokiness from the individual cylinders of the engine, which is a result of uneven propagation of exhaust gas into the channels of the intake manifold. This article contains the results of numerical characterized charges formed in symmetrical intake manifold with a centrally-placed EGR valve. Simulations were performed for the original intake system derived from the two-liter, turbocharged VW diesel engine.

  8. Degradation of the beta-blocker propranolol by electrochemical advanced oxidation processes based on Fenton's reaction chemistry using a boron-doped diamond anode

    Energy Technology Data Exchange (ETDEWEB)

    Isarain-Chavez, Eloy; Rodriguez, Rosa Maria; Garrido, Jose Antonio; Arias, Conchita; Centellas, Francesc; Cabot, Pere Lluis [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.ed [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

    2010-12-15

    The electro-Fenton (EF) and photoelectro-Fenton (PEF) degradation of solutions of the beta-blocker propranolol hydrochloride with 0.5 mmol dm{sup -3} Fe{sup 2+} at pH 3.0 has been studied using a single cell with a boron-doped diamond (BDD) anode and an air diffusion cathode (ADE) for H{sub 2}O{sub 2} electrogeneration and a combined cell containing the above BDD/ADE pair coupled in parallel to a Pt/carbon felt (CF) cell. This naphthalene derivative can be mineralized by both methods with a BDD anode. Almost overall mineralization is attained for the PEF treatments, more rapidly with the combined system due to the generation of higher amounts of hydroxyl radical from Fenton's reaction by the continuous Fe{sup 2+} regeneration at the CF cathode, accelerating the oxidation of organics to Fe(III)-carboxylate complexes that are more quickly photolyzed by UVA light. The homologous EF processes are less potent giving partial mineralization. The effect of current density, pH and Fe{sup 2+} and drug concentrations on the oxidation power of PEF process in combined cell is examined. Propranolol decay follows a pseudo first-order reaction in most cases. Aromatic intermediates such as 1-naphthol and phthalic acid and generated carboxylic acids such as maleic, formic, oxalic and oxamic are detected and quantified by high-performance liquid chromatography. The chloride ions present in the starting solution are slowly oxidized at the BDD anode. In PEF treatments, all initial N of propranolol is completely transformed into inorganic ions, with predominance of NH{sub 4}{sup +} over NO{sub 3}{sup -} ion.

  9. Effect of EGR on a sationary VCR diesel engine using cottonseed biodiesel (B20 fuel

    Directory of Open Access Journals (Sweden)

    Nitin M. Sakhare

    2016-09-01

    Full Text Available This paper presents a view on comparative study of use of diesel fuel with B20 biodieselblend (Diesel (80 %, by vol. and Cotton seed oil (20 %, by vol. derived from Cotton seeds. As higher NOx emission and higher brake specific fuel consumption are main challenges for effective utilization of biodiesel fuel in a diesel engine, there is alarming need to find out the long term solution to reduce NOx emission for better utilization of biodiesel fuel in a diesel engine. Exhaust gas recirculation (EGR is one of the useful technologies to reduce the NOx emission of a diesel engine. In the present research work test is conducted on 3 KW single cylinder, four stroke, water cooled, variable compression ratio (VCR computerized diesel engine using diesel and B20 cotton seed biodiesel blend to study the effect of exhaust gas recirculation on performance and emissions characteristics of a diesel engine in terms of fuel consumption, thermal efficiency and emissions such as hydrocarbon (HC, carbon monoxide (CO, oxides of nitrogen (NOx and carbon dioxide (CO2 of a diesel engine. The constant engine speed of 1500 rpm was maintained through-out the experiment test. The exhaust gas recirculation was varied as 4 % and 6 % at different loading conditions with diesel and B20 biodiesel. The results show that the significant reduction in oxides of nitrogen (NOx with 4 % and 6 % EGR for B20 whereas marginal increment in CO and HC emissions.

  10. Beta 1 versus nonselective blockade in therapy of essential tremor.

    Science.gov (United States)

    Larsen, T A; Teräväinen, H

    1983-01-01

    The beta 1-selective blocker metoprolol was compared to propranolol and a placebo in a double-blind crossover trial in 24 patients with essential tremor. Both beta blockers suppressed the essential tremor, but metoprolol, which caused a mean reduction of 32.0% in tremor intensity from the base-line value, was less effective than propranolol, which reduced mean tremor intensity by 41.3%. Subjective benefit for their tremor was found by 15 of the patients taking propranolol and by one taking metoprolol. The tremor frequency was not affected. No serious side effects were observed. Metoprolol may offer an alternative for those essential tremor patients who cannot tolerate propranolol.

  11. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways

    International Nuclear Information System (INIS)

    Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.; Yu Jun; Leung, W.K.; Cho, C.H.; Sung, J.J.Y.

    2008-01-01

    Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor (α7 nAChR) and β-adrenergic receptors. Treatment of cells with α-bungarotoxin (α-BTX, α7nAChR antagonist) or propranolol (β-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE 2 and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE 2 induction can only be suppressed by propranolol, but not α-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis

  12. A multibiomarker approach to explore interactive effects of propranolol and fluoxetine in marine mussels

    International Nuclear Information System (INIS)

    Franzellitti, Silvia; Buratti, Sara; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena

    2015-01-01

    A multi-biomarker approach, including several lysosomal parameters, activity and mRNA expression of antioxidant enzymes, and DNA damage, was employed to investigate the nominal effects of 0.3 ng/L fluoxetine (FX) and 0.3 ng/L propranolol (PROP) alone or in combination (0.3 ng/L FX + 0.3 ng/L PROP) on Mediterranean mussels after a 7 day treatment. FX co-exposure appears to facilitate PROP bioaccumulation because PROP only accumulated in digestive gland of FX + PROP treated mussels. Lysosomal parameters were significantly impaired by FX + PROP treatment, while no clear antioxidant responses at the catalytic and transcriptional levels were observed. Biomarker responses led to a “medium stress level” diagnosis in FX + PROP treated mussels, according to the Expert System, whereas 0.3 ng/L PROP or FX alone did not induce consistent stress conditions. These findings suggest vulnerability of coastal marine mussels to FX and PROP contamination at environmentally relevant levels. - Highlights: • FX and PROP combined effects were assessed in marine mussels using biomarkers. • PROP bioaccumulation was observed in digestive gland of FX + PROP treated mussels. • Lysosomal parameters were significantly impaired by FX + PROP treatment. • No clear antioxidant responses at the catalytic and mRNA levels were observed. • FX + PROP treatment increased stress levels of mussels compared with the single chemicals. - Fluoxetine and propranolol induce interactive effects on marine mussels biomarker responses and pharmaceutical bioaccumulation

  13. Effect of propranolol on myocardial imaging with radioiodinated hexadecenoic acid in the dog heart

    International Nuclear Information System (INIS)

    Comet, M.; Wolf, J.E.; Pilichowfski, P.

    1982-01-01

    After I.V. injection of 16- 123 I 9-hexadecenoic acid, the following is noted: among dogs, there are important differences in the values of the half-life of the myocardial radioactivity curves without any significant differences in the biological constants; for a given dog, the value of the half-life is reproducible when there are no modifications in the physiological condition; propranolol brings about twofold increase in the value of the half-life of the myocardial radioactivity curve. On the myocardial scintigraphy, performed after an I.V. injection of a fatty acid (F.A.) labelled with 123 I, ischaemia appears as an hypoactive area which reveals a failure in the capture of the F.A. and also an abnormal lengthening of the half-life of the myocardial activity curve. It is probable that, in some cases, on the evolution curve of myocardial activity would allow a detection of metabolism anomalies of the F.A. The cause of variation of the half-life are poorly understood. Given the influence of catecholamines on normal and pathological myocardial metabolism, the influence of a #betta# blocker Propranolol, on the curve half-life after the injection of 16 123 I 9-hexadecenoic acid (I.F.A.) was studied in the dog. In order to assess the effect of the drug, the reproducibility of the curve half-lives was tested, in the absence of marked variations in the physiological condition of the animal

  14. Prevalence of Self-prescribing Propranolol Among Medical and Dental Students in Riyadh, Saudi Arabia: A Cross-sectional Study

    Directory of Open Access Journals (Sweden)

    Omar A. Al-Mohrej

    2018-03-01

    Conclusions: The overall results showed a slightly high rate of propanol misuse among medical and dental students. The majority of users are aware of the risks and potential side effects of self-prescribing medications, however; the anxiety relieving effect of propranolol increased its use prior to oral exams and presentations. Educational activity targeting students must be implemented.

  15. Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

    Science.gov (United States)

    Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

    2018-01-15

    Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Contextualizando reações ácido-base de acordo com a teoria protônica de Brönsted-Lowry usando comprimidos de propranolol e nimesulida

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    Arlan de Assis Gonsalves

    2013-01-01

    Full Text Available This paper reports the use of alternative materials for teaching experimental chemistry. In this context, nimesulide and propranolol tablets were used to teach chemical concepts about acid-base reactions according to Brönsted-Lowry protonic Theory. Important topics of Organic, Analytical and Pharmaceutical Chemistry were discussed, such as purification by acid-base extraction, solubility of organic compounds in aqueous solutions, buffers, the dissociation constant (pKa, potentiometric titration and ionization of drugs in biological fluids. The purification of propranolol and nimesulide from tablets produced yields of 75% and 90%, respectively. The experimental values of pKa for both drugs were in agreement with those from the literature.

  17. Transplacental and mammary passage of radioactivity in rats treated vaginally and orally with [14C]propranolol

    International Nuclear Information System (INIS)

    Buttar, H.S.; Moffatt, J.H.; Bura, C.

    1988-01-01

    Single doses (10 mg/kg) of an aqueous solution of [14C]propranolol were administered either orally (po) or intravaginally (ivg) on gestational d 15, or on postpartum d 7-10. Upon ivg administration, [14C]propranolol was quickly transferred to systemic circulation and the mean blood [14C] concentrations were significantly greater during the first 0.25-2 h than in po dosed counterparts. About 98% of the ivg applied dose was absorbed after 6 h in gravid rats, and the combined 6-h excretions of radioactivity in the urine (ivg = 24.6%; po = 22.9%) and feces (ivg = 16.8%; po = 14.6%) were equivalent in both groups. At the end of 6 h, the levels of [14C] in the urinary bladder, adrenal, uterus, ovary, spleen, skeletal muscle, brain, heart, lung and fat were significantly higher in ivg treated rats than po dosed animals. Compared with the maternal plasma (ivg = 0.76; po = 0.88 microgram/ml), the mean concentrations of [14C] in the placentas were similar in both groups, while the amounts of [14C] were three to five times lower in the amniotic fluids and the fetuses of both po and ivg treated dams. In lactating rats, over 99% of the administered radioactivity was absorbed from the vagina within 6 h. The blood concentrations of [14C] were significantly elevated at 0.5 and 1 h in the per vaginam treated animals, and afterward the disappearance rate of [14C] followed a similar course in both groups. Following ivg application, the milk radioactivity peaked at 0.5 h and declined rapidly. However, the appearance of [14C] in milk was rather slow after oral dosing: the milk [14C] peaked between 2 and 3 h posttreatment and remained steady thereafter. The milk to blood (M/B) [14C] concentration ratios were markedly greater during 0.5 to 1 h in the ivg group than in their po dosed counterparts

  18. Enantioselective biotransformation of propranolol to the active metabolite 4-hydroxypropranolol by endophytic fungi

    Directory of Open Access Journals (Sweden)

    Keyller Bastos Borges

    2011-01-01

    Full Text Available The enantioselective biotransformation of propranolol (Prop by the endophytic fungi Phomopsis sp., Glomerella cingulata, Penicillium crustosum, Chaetomium globosum and Aspergillus fumigatus was investigated by studying the kinetics of the aromatic hydroxylation reaction with the formation of 4-hydroxypropranolol (4-OH-Prop. Both Prop enantiomers were consumed by the fungi in the biotransformation process, but the 4-hydroxylation reaction yielded preferentially (--(S-4-OH-Prop. The quantity of metabolites biosynthesized varied slightly among the evaluated endophytic fungi. These results show that all investigated endophytic fungi could be used as biosynthetic tools in biotransformation processes to obtain the enantiomers of 4-OH-Prop.

  19. Electro-Fenton and photoelectro-Fenton degradations of the drug beta-blocker propranolol using a Pt anode: Identification and evolution of oxidation products

    Energy Technology Data Exchange (ETDEWEB)

    Isarain-Chavez, Eloy; Cabot, Pere Lluis; Centellas, Francesc; Rodriguez, Rosa Maria; Arias, Conchita; Garrido, Jose Antonio [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.edu [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

    2011-01-30

    The beta-blocker propranolol hydrochloride has been degraded by electrochemical advanced oxidation processes like electro-Fenton (EF) and photoelectro-Fenton (PEF) using a single cell with a Pt anode and an air diffusion cathode (ADE) for H{sub 2}O{sub 2} electrogeneration and a combined system containing the above Pt/ADE pair coupled in parallel to a Pt/carbon-felt (CF) cell. Organics are mainly oxidized with hydroxyl radical ({center_dot}OH) formed from Fenton's reaction between added Fe{sup 2+} and electrogenerated H{sub 2}O{sub 2}. The PEF treatment in Pt/ADE-Pt/CF system yields almost total mineralization because {center_dot}OH production is enhanced by Fe{sup 2+} regeneration from Fe{sup 3+} reduction at the CF cathode and Fe(III) complexes with generated carboxylic acids are rapidly photodecarboxylated under UVA irradiation. Lower mineralization degree is found for PEF in Pt/ADE cell due to the little influence of UVA light on Fe{sup 2+} regeneration. The homologous EF processes are much less potent as a result of the persistence of Fe(III)-carboxylate complexes. Aromatic intermediates such as 1-naphthol, 1,4-naphthoquinone and phthalic acid and generated carboxylic acids such as pyruvic, glycolic, malonic, maleic, oxamic, oxalic and formic are identified. While chloride ion remains stable, NH{sub 4}{sup +} and NO{sub 3}{sup -} ions are released to the medium. A reaction sequence for propranolol hydrochloride mineralization is proposed.

  20. A dose–response study of the effects of pre-test administration of beta-adrenergic receptor antagonist propranolol on the learning of active place avoidance, a spatial cognition task, in rats

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Petrásek, Tomáš; Valeš, Karel

    2009-01-01

    Roč. 200, č. 1 (2009), s. 144-149 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GA309/07/0341; GA ČR(CZ) GA309/09/0286 Institutional research plan: CEZ:AV0Z50110509 Keywords : propranolol * learning * spatial memory Subject RIV: FH - Neuro logy Impact factor: 3.220, year: 2009

  1. Cleaner emissions from a DI diesel engine fueled with waste plastic oil derived from municipal solid waste under the influence of n-pentanol addition, cold EGR, and injection timing.

    Science.gov (United States)

    Damodharan, Dillikannan; Sathiyagnanam, Amudhavalli Paramasivam; Rajesh Kumar, Babu; Ganesh, Kuttalam Chidambaradhanu

    2018-05-01

    Urban planning and development is a decisive factor that increases the automobile numbers which leads to increased energy demand across the globe. In order to meet the escalating requirements of energy, it is necessary to find viable alternatives. Waste plastic oil (WPO) is one such alternative which has dual benefits as it reduces the environmental pollution caused by plastic waste and it could possibly meet the energy requirement along with fossil fuels. The study attempted to reduce emissions from a DI diesel engine fueled with WPO using 30% by volume of n-pentanol with fossil diesel (WPO70P30). EGR (10, 20, and 30%) and injection timing modifications were made with the intention to find optimum engine operating conditions. The experimental results indicated that addition of renewable component like n-pentanol had improved the combustion characteristics by igniting WPO more homogeneously producing a higher premixed combustion phase. Smoke density for WPO70P30 was found to be twice lower than that of neat WPO at standard injection timing of 23°CA bTDC at any given EGR rate, NOx emissions were slightly on the higher side about 12% for WPO70P30 blend against WPO at same operating conditions. WPO70P30 showed lowest smoke and carbon monoxide emissions than diesel and WPO while delivering BTE's higher than WPO and closer to diesel at all EGR and injection timings. However NOx and HC emissions increased with n-pentanol addition. The use of EGR reduced NOx emissions but was found to aggravate other emissions. It was concluded WPO70P30 can be favorably used in a DI diesel engine at the engines advanced injection timing for better performance than diesel with a slight penalty in NOx emissions.

  2. Development of (acrylic acid/ polyethylene glycol)-zinc oxide mucoadhesive nanocomposites for buccal administration of propranolol HCl

    Science.gov (United States)

    Mahmoud, Ghada A.; Ali, Amr El-Hag; Raafat, Amany I.; Badawy, Nagwa A.; Elshahawy, Mai. F.

    2018-06-01

    A series of mucoadhesive nanocomposites with self disinfection properties composed of acrylic acid, polyethylene glycol and ZnO nanoparticles (AAc/PEG)-ZnO were developed for localized buccal Propranolol HCl delivery. γ-irradiation as a clean tool for graft copolymerization process was used for the preparation of (AAc/PEG) hydrogels. In suite precipitation technique was used for ZnO nanoparticles immobilization within (AAc/PEG) hydrogels. The developed (AAc/PEG)-ZnO nanocomposites were characterized by X-ray diffraction (XRD), UV-Vis spectrophotometer, energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM) to confirm the success of ZnO nanoparticles formation within the (AAc/PEG) matrices. The presence of ZnO nanoparticles improves the thermal stability as indicated using thermogravimetric analysis (TGA). The mucoadhesion characteristics such as hydration degree, surface pH, and mucoadhesive strength were evaluated in artificial saliva solution. The self disinfection property of the developed (AAc/PEG)-ZnO nanocomposites was investigated by examining their resistance to pathogenic microorganisms such as Staphylococcus aureus, Bacillus subtilis, and Escherichia coli using disc diffusion method. The release of Propranolol -HCl drug in artificial saliva was found to obey a non-Fickian diffusion mechanism. The obtained results suggests that (AAc/PEG)-ZnO nanocomposites could be used as mucoadhesive carrier for buccal drug delivery with efficient antibacterial properties.

  3. Modification of piston bowl geometry and injection strategy, and investigation of EGR composition for a DME-burning direct injection engine

    Directory of Open Access Journals (Sweden)

    Kianoosh Shojae

    2017-01-01

    Full Text Available The amount of pollutant gases in the atmosphere has reached a critical state due to an increase in industrial development and the rapid growth of automobile industries that use fossil fuels. The combustion of fossil fuels produces harmful gases such as carbon dioxide, nitrogen monoxide (NO, soot, particulate matter (PM, etc. The use of Dimethyl Ether (DME biofuel in diesel engines or other combustion processes have been highly regarded by researchers. Studies show that the use of pure DME in automotive engines will be possible in the near future. The present work evaluated the environmental and performance effects of changing the injection strategy (time and temperature, piston bowl geometry, and exhaust gas recirculation (EGR composition for a DME-burning engine. The modification of piston bowl parameters and engine simulation were numerically performed by using AVL fire CFD code. For model validation, the calculated mean pressure and rate of heat released (RHR were compared to the experimental data and the results showed a good agreement (under a 70% load and 1200-rpm engine speed. It was found that retarding injection timing (reduction in in-cylinder temperature, consequently caused a reduction in NO emissions and increased soot formation, reciprocally; this occurred because of a reduction in temperature and a lower soot oxidation in the combustion chamber. It became clear that 3 deg before top dead center (BTDC was the appropriate injection timing for the DME-burning heavy duty diesel engine running under 1200 rpm. Also, the parametrical modification of the piston bowl geometry and the simultaneous decrease of Tm (piston bowl depth and R3 (bowl inner radius lengths were associated with lower exhaust NO emissions. For the perfect utilization of DME fuel in an HD diesel engine, the suggested proper lengths of Tm and R3 were 0.008 and 0.0079 m, respectively. Furthermore, various EGR compositions for the reduction of exhaust NO were investigated

  4. Ansiedade social e abuso de propranolol: relato de caso

    Directory of Open Access Journals (Sweden)

    Fontanella Bruno José Barcellos

    2003-01-01

    Full Text Available Paciente com grave ansiedade social automedicou-se com propranolol durante seis anos, em doses de até 320 mg/d. Além do tratamento psicanalítico que já havia iniciado, foi tratada com tranilcipromina, apresentando melhora parcial do quadro fóbico e do abuso do betabloqueador. Após introdução de paroxetina, houve melhora ainda mais pronunciada. Apesar da automedicação com uma substância potencialmente eficaz em alguns casos, perpetuou-se durante anos um grave padrão fóbico de comportamento. O caso exemplifica as dificuldades de procura de tratamento específico pela população de fóbicos sociais. Levanta-se a hipótese da existência de uma prática crescente de automedicação com betabloqueadores entre fóbicos sociais e pessoas com ansiedade de desempenho, problema cuja relevância para a saúde pública ainda não foi pesquisada.

  5. Effects of 2,5-dimethylfuran fuel properties coupling with EGR (exhaust gas recirculation) on combustion and emission characteristics in common-rail diesel engines

    International Nuclear Information System (INIS)

    Chen, Guisheng; Di, Lei; Zhang, Quanchang; Zheng, Zunqing; Zhang, Wei

    2015-01-01

    The effects of DMF (2,5-dimethylfuran) fuel properties combined with EGR (exhaust gas recirculation), CA50, EHN (2-Ethylhexyl nitrate) and multi-injection strategies on combustion and emission characteristics were experimentally investigated in two common-rail diesel engines including a single-cylinder engine and a multi-cylinder engine. Results demonstrate that, with DMF addition into diesel, ID (ignition delay) prolongs and smoke decreases more greatly as EGR rate increases. When DMF addition fraction increases up to 40%, the inherent trade-off between NO_x and smoke can be eliminated, but the MPRR (maximum pressure rise rate) is too high. However, the higher MPRR can be reduced efficiently without serious penalties in smoke and BTE (brake thermal efficiency) by delaying CA50 and adding EHN reasonably. Although DMF and gasoline have very similar physic-chemical properties, DMF/diesel blends are much more efficient than gasoline/diesel wide-distillation blends to reduce soot with high EGR rates due to its much longer ID and atomic oxygen. With increasing DMF addition fraction, BTE is affected less by the delay of CA50, meanwhile, multi-injection strategies have less impact on soot generation. Additionally, as compared to the delay of CA50 and the addition of EHN, the employ of pilot injection is poor to reduced MPRR for DMF/diesel blends. - Highlights: • D40 can solve the NO_x-smoke trade-off relationship, but leading to higher MPRR. • Adding EHN into D40 can reduce MPRR efficiently with a little increase in soot. • Compared to gasoline, DMF is much more efficient to reduce soot in CI engines. • With DMF addition, multi-injection strategies have less impact on MPRR and soot. • DMF may be a promising alternative for reducing soot emissions in CI engine LTC.

  6. Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl

    Directory of Open Access Journals (Sweden)

    Majid Saeedi

    2015-01-01

    Full Text Available Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios.  Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets.

  7. A study of the relationship between serum bile acids and propranolol pharmacokinetics and pharmacodynamics in patients with liver cirrhosis and in healthy controls

    NARCIS (Netherlands)

    Taegtmeyer, Anne B.; Haschke, Manuel; Tchambaz, Lydia; Buylaert, Mirabel; Tschöpl, Martin; Beuers, Ulrich; Drewe, Jürgen; Krähenbühl, Stephan

    2014-01-01

    The main objectives of the study were to determine the exposure and bioavailability of oral propranolol and to investigate their associations with serum bile acid concentration in patients with liver cirrhosis and in healthy controls. A further objective was to study the pharmacodynamics of

  8. Carbon monoxide induced PPARγ SUMOylation and UCP2 block inflammatory gene expression in macrophages.

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    Arvand Haschemi

    Full Text Available Carbon monoxide (CO dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-γ (PPARγ and p38 mitogen-activated protein kinase (MAPK dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS-induced expression of the proinflammatory early growth response-1 (Egr-1 transcription factor in macrophages via activation of PPARγ. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARγ and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARγ which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARγ-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARγ-K77R mutant did not impair the effect of CO. In addition to PPARγ SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARγ SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2. Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-, produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARγ-SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response.

  9. Analysis of combustion performance and emission of extended expansion cycle and iEGR for low heat rejection turbocharged direct injection diesel engines

    Directory of Open Access Journals (Sweden)

    Shabir Mohd F.

    2014-01-01

    Full Text Available Increasing thermal efficiency in diesel engines through low heat rejection concept is a feasible technique. In LHR engines the high heat evolution is achieved by insulating the combustion chamber surfaces and coolant side of the cylinder with partially stabilized zirconia of 0.5 mm thickness and the effective utilization of this heat depend on the engine design and operating conditions. To make the LHR engines more suitable for automobile and stationary applications, the extended expansion was introduced by modifying the inlet cam for late closing of intake valve through Miller’s cycle for extended expansion. Through the extended expansion concept the actual work done increases, exhaust blow-down loss reduced and the thermal efficiency of the LHR engine is improved. In LHR engines, the formation of nitric oxide is more, to reduce the nitric oxide emission, the internal EGR is incorporated using modified exhaust cam with secondary lobe. Modifications of gas exchange with internal EGR resulted in decrease in nitric oxide emissions. In this work, the parametric studies were carried out both theoretically and experimentally. The combustion, performance and emission parameters were studied and were found to be satisfactory.

  10. The Application of High Energy Ignition and Boosting/Mixing Technology to Increase Fuel Economy in Spark Ignition Gasoline Engines by Increasing EGR Dilution Capability

    Energy Technology Data Exchange (ETDEWEB)

    Keating, Edward [General Motors LLC, Pontiac, MI (United States); Gough, Charles [General Motors LLC, Pontiac, MI (United States)

    2015-07-07

    This report summarizes activities conducted in support of the project “The Application of High Energy Ignition and Boosting/Mixing Technology to Increase Fuel Economy in Spark Ignition Gasoline Engines by Increasing EGR Dilution Capability” under COOPERATIVE AGREEMENT NUMBER DE-EE0005654, as outlined in the STATEMENT OF PROJECT OBJECTIVES (SOPO) dated May 2012.

  11. Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Christensen, N J; Sørensen, T I

    1991-01-01

    Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80...... to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained...

  12. Effect of oral propranolol on splanchnic oxygen uptake and haemodynamics in patients with cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Henriksen, Jens Henrik; Becker, Povl Ulrik

    1987-01-01

    .01), azygos venous oxygen saturation (76 vs. 67%, P less than 0.05), ICG clearance (263 vs. 226 ml/min, P less than 0.01), wedged-to-free hepatic vein pressure (16 vs. 13.5 mm Hg, P less than 0.01), hepatic blood flow (1.18 vs. 0.78 l/min, P less than 0.01), cardiac index (3.42 vs. 2.53 l/min . min 2, P less...... mg propranolol. All patients underwent hepatic vein catheterization and had a primed continuous intravenous infusion of ICG. Azygos vein catheterization was performed in six patients. Splanchnic (hepatic-intestinal) oxygen uptake (median control 68 ml/min vs. beta-blockade 56 ml/min, P less than 0...... than 0.01), and heart rate (72 vs. 56 beats per min, P less than 0.01) decreased significantly after oral beta-blockade. The hepatic extraction ratio of ICG increased significantly (0.32 vs. 0.45, P less than 0.01), whereas estimated 'intrinsic' ICG clearance (289 vs. 300 ml/min, n.s.), arterial blood...

  13. Uso del propranolol como modulador de la memoria y el aprendizaje en modelos animales

    Directory of Open Access Journals (Sweden)

    Mariana Psyrdellis

    2016-09-01

    Full Text Available El propranolol es un antagonista β-adrenérgico no selectivo de los receptores adrenérgicos β1y β2. El rol de este sistema de neurotransmisión sobre la memoria ha sido demostrado en diversas investigaciones, ya sea tanto en la fase de codificación, consolidación y evocación como en la reconsolidación. El objetivo de este trabajo es realizar una revisión sobre los efectos de este β-bloqueante en diversos aprendizajes con paradigmas animales, entendiendo por medio de esto las implicaciones del sistema noradrenérgico en los procesos de memoria. El fármaco muestra resultados particulares dependiendo del momento de su aplicación y del diseño experimental empleado. En el trabajo se discuten los efectos de la droga sobre las distintas fases de la memoria en paradigmas animales con contenido espacial, estímulos gustativos y aversivos, con entrenamientos complejos, y con aprendizajes de un solo ensayo.

  14. Investigating the pros and cons of browns gas and varying EGR on combustion, performance, and emission characteristics of diesel engine.

    Science.gov (United States)

    Thangaraj, Suja; Govindan, Nagarajan

    2018-01-01

    The significance of mileage to the fruitful operation of a trucking organization cannot be downplayed. Fuel is one of the biggest variable expenses in a trucking wander. An attempt is made in this research to improve the combustion efficiency of a diesel engine for better fuel economy by introducing hydroxy gas which is also called browns gas or HHO gas in the suction line, without compromising performance and emission. Brown's gas facilitates the air-fuel mixture to ignite faster and efficient combustion. By considering safety and handling issues in automobiles, HHO gas generation by electrolysis of water in the presence of sodium bicarbonate electrolytes (NaHCO 3 ) and usage was explored in this research work over compressed pure hydrogen, due to generation and capacity of immaculate hydrogen as of now confines the application in diesel engine operation. Brown's gas was utilized as a supplementary fuel in a single-cylinder, four-stroke compression ignition (CI) engine. Experiments were carried out on a constant speed engine at 1500 rpm, result shows at constant HHO flow rate of 0.73 liter per minute (LPM), brake specific fuel consumption (BSFC) decreases by 7% at idle load to 16% at full load, and increases brake thermal efficiency (BTE) by 8.9% at minimum load to 19.7% at full load. In the dual fuel (diesel +HHO) operation, CO emissions decreases by 19.4, 64.3, and 34.6% at 25, 50, and 75% load, respectively, and unburned hydrocarbon (UHC) emissions decreased by 11.3% at minimum load to 33.5% at maximum load at the expense of NO x emission increases by 1.79% at 75% load and 1.76% at full load than neat diesel operation. The negative impact of an increase in NO x is reduced by adding EGR. It was evidenced in this experimental work that the use of Brown's gas with EGR in the dual fuel mode in a diesel engine improves the fuel efficiency, performance, and reduces the exhaust emissions.

  15. Physicochemical characterization and evaluation of buccal adhesive patches containing propranolol hydrochloride.

    Science.gov (United States)

    Patel, V M; Prajapati, B G; Patel, J K; Patel, M M

    2006-07-01

    Buccal adhesive patches containing 20 mg of propranolol hydrochloride were prepared using solvent casting method. Chitosan was used as a natural bioadhesive polymer. Patches were prepared at different ratios of PVP K-30 and evaluated for various physicochemical characteristics such as weight variation, drug content uniformity, folding endurance, surface pH, ex-vivo mucoadhesive strength, ex-vivo residence time, in vitro drug release and in vitro buccal permeation study. Patches exhibited sustained release over a period of 7 hours. The mechanism of drug release was found to be Non-Fickian diffusion. Addition of PVP K-30 generally enhanced the releasing rate. The ex-vivo mucoadhesive strength was performed using sheep buccal mucosa on modified physical balance. Optimized patches (batch F4) showed satisfactory bioadhesive strength (9.6 degrees 2.0 gram) and ex vivo residence time (272 degrees 0.25 minutes). Swelling index was proportional to PVP K-30. The surface pH of all batches was within satisfactory limit (7.0+/-1.5) and hence patches would not cause irritation in the buccal cavity. Good correlation was observed between in vitro drug release and in vitro drug permeation with correlation coefficient of 0.9364. Stability of optimized patches was performed in natural human saliva showed that both drug and dosage forms were stable in human saliva.

  16. Application of a colorimetric technique in quality control for printed pediatric orodispersible drug delivery systems containing propranolol hydrochloride

    DEFF Research Database (Denmark)

    Vakili, Hossein; Nyman, Johan O; Genina, Natalja

    2016-01-01

    and the excipients. The inkjet printing technique deposited precise and uniform escalating doses (0.08-3.16mg) of the active pharmaceutical ingredient onto the substrates (R(2)≥0.9934). A disintegration test with clear end-point detection confirmed that all the substrates meet the requirements of the Ph. Eur....... to disintegrate within 180s. The colorimetric technique proved to be a reliable method to distinguish the small color differences between formulations containing an escalating dose of propranolol hydrochloride....

  17. SC1 Promotes MiR124-3p Expression to Maintain the Self-Renewal of Mouse Embryonic Stem Cells by Inhibiting the MEK/ERK Pathway.

    Science.gov (United States)

    Wei, Qing; Liu, Hongliang; Ai, Zhiying; Wu, Yongyan; Liu, Yingxiang; Shi, Zhaopeng; Ren, Xuexue; Guo, Zekun

    2017-01-01

    Self-renewal is one of the most important features of embryonic stem (ES) cells. SC1 is a small molecule modulator that effectively maintains the self-renewal of mouse ES cells in the absence of leukemia inhibitory factor (LIF), serum and feeder cells. However, the mechanism by which SC1 maintains the undifferentiated state of mouse ES cells remains unclear. In this study, microarray and small RNA deep-sequencing experiments were performed on mouse ES cells treated with or without SC1 to identify the key genes and microRNAs that contributed to self-renewal. SC1 regulates the expressions of pluripotency and differentiation factors, and antagonizes the retinoic acid (RA)-induced differentiation in the presence or absence of LIF. SC1 inhibits the MEK/ERK pathway through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and pathway reporting experiments. Small RNA deep-sequencing revealed that SC1 significantly modulates the expression of multiple microRNAs with crucial functions in ES cells. The expression of miR124-3p is upregulated in SC1-treated ES cells, which significantly inhibits the MEK/ERK pathway by targeting Grb2, Sos2 and Egr1. SC1 enhances the self-renewal capacity of mouse ES cells by modulating the expression of key regulatory genes and pluripotency-associated microRNAs. SC1 significantly upregulates miR124-3p expression to further inhibit the MEK/ ERK pathway by targeting Grb2, Sos2 and Egr1. © 2017 The Author(s). Published by S. Karger AG, Basel.

  18. 40 CFR 80.60 - Test fleet requirements for exhaust emission testing.

    Science.gov (United States)

    2010-07-01

    ... Multi 3W+OX Air EGR 4 GM. 9 TBI 3W+OX Air EGR 7 Chrysler. 10 Multi 3W Air EGR 5 Toyota. 11 Multi 3W No Air EGR 1 Ford. 12 Multi 3W No Air No EGR 2 Chrysler. 13 Carb 3W+OX Air EGR 9 Toyota. 14 TBI 3W No Air EGR 3 Ford. 15 Multi 3W+OX Air EGR 4 GM. 16 Multi 3W No Air EGR 1 Toyota. 17 Multi 3W No Air No EGR 2...

  19. High-Speed Multiplexed Spatiotemporally Resolved Measurements of Exhaust Gas Recirculation Dynamics in a Multi-Cylinder Engine Using Laser Absorption Spectroscopy.

    Science.gov (United States)

    Yoo, Jihyung; Prikhodko, Vitaly; Parks, James E; Perfetto, Anthony; Geckler, Sam; Partridge, William P

    2016-04-01

    The need for more environmentally friendly and efficient energy conversion is of paramount importance in developing and designing next-generation internal combustion (IC) engines for transportation applications. One effective solution to reducing emissions of mono-nitrogen oxides (NOx) is exhaust gas recirculation (EGR), which has been widely implemented in modern vehicles. However, cylinder-to-cylinder and cycle-to-cycle variations in the charge-gas uniformity can be a major barrier to optimum EGR implementation on multi-cylinder engines, and can limit performance, stability, and efficiency. Precise knowledge and fine control over the EGR system is therefore crucial, particularly for optimizing advanced engine concepts such as reactivity controlled compression ignition (RCCI). An absorption-based laser diagnostic was developed to study spatiotemporal charge-gas distributions in an IC engine intake manifold in real-time. The laser was tuned to an absorption band of carbon dioxide (CO2), a standard exhaust-gas marker, near 2.7 µm. The sensor was capable of probing four separate measurement locations simultaneously, and independently analyzing EGR fraction at speeds of 5 kHz (1.2 crank-angle degree (CAD) at 1 k RPM) or faster with high accuracy. The probes were used to study spatiotemporal EGR non-uniformities in the intake manifold and ultimately promote the development of more efficient and higher performance engines. © The Author(s) 2016.

  20. Insulin promotes diacylglycerol kinase activation by different mechanisms in rat cerebral cortex synaptosomes.

    Science.gov (United States)

    Zulian, Sandra E; Ilincheta de Boschero, Mónica G; Giusto, Norma M

    2006-10-01

    The mechanism by which insulin increases diacylglycerol kinase (DAGK) activity has been studied in cerebral cortex (CC) synaptosomes from adult (3-4 months of age) rats. The purpose of this study was to identify the role of phospholipases C and D (PLC and PLD) in DAGK activation by insulin. Neomycin, an inhibitor of PLC phosphatidylinositol-bisphosphate (PIP2) specific; ethanol, an inhibitor of phosphatidic acid (PA) formation by the promotion of a transphosphatidyl reaction of phosphatidylcholine phospholipase D (PC-PLD); and DL propranolol, an inhibitor of phosphatidate phosphohydrolase (PAP), were used in this study. Insulin (0.1 microM) shielded an increase in PA synthesis by [32P] incorporation using [gamma-32P]ATP as substrate and endogenous diacylglycerol (DAG) as co-substrate. This activated synthesis was strongly inhibited either by ethanol or DL propranolol. Pulse chase experiments also showed a PIP2-PLC activation within 1 min exposure to insulin. When exogenous unsaturated 18:0-20:4 DAG was present, insulin increased PA synthesis significantly. However, this stimulatory effect was not observed in the presence of exogenous saturated (di-16:0). In the presence of R59022, a selective DAGK inhibitor, insulin exerted no stimulatory effect on [32P]PA formation, suggesting a strong relationship between increased PA formation by insulin and DAGK activity. These data indicate that the increased synthesis of PA by insulin could be mediated by the activation of both a PC-PLD pathway to provide DAG and a direct DAGK activation that is associated to the use of 18:0-20:4 DAG species. PIP2-PLC activation may contribute at least partly to the insulin effect on DAGK activity. Copyright 2006 Wiley-Liss, Inc.

  1. Attempt of multiple stage injection with EGR for high load operation of a premixed compression ignition engine; Tadan funsha ni yoru yokongo asshuku chakka kikan no unten ryoiki kakudai

    Energy Technology Data Exchange (ETDEWEB)

    Hashizume, T.; Miyamoto, T.; Akagawa, H. [New ACE Institute Co. Ltd., Tsukuba (Japan); Tsujimura, K. [Chiba Institute of Technology, Chiba (Japan)

    2000-01-25

    By injecting fuel at the very early stage of compression stroke and thus creating homogeneous lean mixture before ignition, (PREDIC ; PREmixed lean DIesel Combustion), simultaneous reduction of NO{sub x} and smoke was obtained. However, since increasing the mixture equivalence ratio cause knocking, it was difficult to operate at higher load conditions. In this study, in order to reduce combustion rate at high load conditions in a premixed compression ignition engine, multiple stage injection method and EGR were combined, and heterogeneous mixture was made before ignition. The engine test results showed that NO{sub x} emissions could be reduced to less than 50 ppm, without knocking even at full load conditions. In addition, smoke emissions were also maintained below invisible level. It can be understood that the premixing of fuel was advanced, smoke was reduced, and EGR rate was increased, resulting lower heat release rate and NO{sub x} emissions. (author)

  2. Low pH induces co-ordinate regulation of gene expression in oesophageal cells.

    Science.gov (United States)

    Duggan, Shane P; Gallagher, William M; Fox, Edward J P; Abdel-Latif, Mohammed M; Reynolds, John V; Kelleher, Dermot

    2006-02-01

    The development of gastro-oesophageal reflux disease (GORD) is known to be a causative risk factor in the evolution of adenocarcinoma of the oesophagus. The major component of this reflux is gastric acid. However, the impact of low pH on gene expression has not been extensively studied in oesophageal cells. This study utilizes a transcriptomic and bioinformatic approach to assess regulation of gene expression in response to low pH. In more detail, oesophageal adenocarcinoma cell lines were exposed to a range of pH environments. Affymetrix microarrays were used for gene-expression analysis and results were validated using cycle limitation and real-time RT-PCR analysis, as well as northern and western blotting. Comparative promoter transcription factor binding site (TFBS) analysis (MatInspector) of hierarchically clustered gene-expression data was employed to identify the elements which may co-ordinately regulate individual gene clusters. Initial experiments demonstrated maximal induction of EGR1 gene expression at pH 6.5. Subsequent array experimentation revealed significant induction of gene expression from such functional categories as DNA damage response (EGR1-4, ATF3) and cell-cycle control (GADD34, GADD45, p57). Changes in expression of EGR1, EGR3, ATF3, MKP-1, FOSB, CTGF and CYR61 were verified in separate experiments and in a variety of oesophageal cell lines. TFBS analysis of promoters identified transcription factors that may co-ordinately regulate gene-expression clusters, Cluster 1: Oct-1, AP4R; Cluster 2: NF-kB, EGRF; Cluster 3: IKRS, AP-1F. Low pH has the ability to induce genes and pathways which can provide an environment suitable for the progression of malignancy. Further functional analysis of the genes and clusters identified in this low pH study is likely to lead to new insights into the pathogenesis and therapeutics of GORD and oesophageal cancer.

  3. A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine Estudo controlado, randomizado e duplo cego do uso de baixas doses de propranolol, nortriptilina e a combinação destas duas drogas no tratamento preventivo da migrânea

    Directory of Open Access Journals (Sweden)

    Renan B. Domingues

    2009-12-01

    Full Text Available Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a propranolol, at a dose of 40 mg per day, (b nortriptyline, at a dose of 20 mg per day, and (c the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.Poucos ensaios clínicos têm avaliado o tratamento preventivo da migrânea através da combinação de drogas. Neste estudo, três regimes terapêuticos foram comparados: (a popranolol, na dose de 40 mg por dia, (b nortriptilina, na dose de 20 mg por dia e (c combinação destas duas drogas nestas dosagens. Os grupos foram pareados de acordo com idade, sexo e freqüência de crises previamente ao tratamento. O período de tratamento foi de dois meses e a frequência e a intensidade das crises de cefaléia do período pré-tratamento foram comparadas com as do período de tratamento. Concluíram o estudo 14 pacientes do grupo A, 14 do grupo B e 16 do grupo C. Os

  4. TOPSIS-based parametric optimization of compression ignition engine performance and emission behavior with bael oil blends for different EGR and charge inlet temperature.

    Science.gov (United States)

    Muniappan, Krishnamoorthi; Rajalingam, Malayalamurthi

    2018-05-02

    The demand for higher fuel energy and lesser exhaust emissions of diesel engines can be achieved by fuel being used and engine operating parameters. In the present work, effects of engine speed (RPM), injection timing (IT), injection pressure (IP), and compression ratio (CR) on performance and emission characteristics of a compression ignition (CI) engine were investigated. The ternary test fuel of 65% diesel + 25% bael oil + 10% diethyl ether (DEE) was used in this work and test was conducted at different charge inlet temperature (CIT) and exhaust gas recirculation (EGR). All the experiments are conducted at the tradeoff engine load that is 75% engine load. When operating the diesel engine with 320 K CIT, brake thermal efficiency (BTE) is improved to 28.6%, and carbon monoxide (CO) and hydrocarbon (HC) emissions have been reduced to 0.025% and 12.5 ppm at 18 CR. The oxide of nitrogen (NOx) has been reduced to 240 ppm at 1500 rpm for 30% EGR mode. Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is frequently used in multi-factor selection and gray correlation analysis method is used to study uncertain of the systems.

  5. Effect of Propranolol on Thyroxine-Induced Changes in Body Temperature and Metabolism During Exercise in Dogs

    Science.gov (United States)

    Kaciuba-Uscilko, Hanna; Brzezinska, Zofia; Greenleaf, John E.

    1976-01-01

    Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s. c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (T(sub re)) during exercise as early as 5 h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest T(sub re), blood FFA (free fatty acid) and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in T(sub re) and blood LA concentrations during the next 30 min of exercise.

  6. Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

    Science.gov (United States)

    Zhou, Wenhu; He, Shiying; Yang, Yijun; Jian, Dan; Chen, Xiang; Ding, Jinsong

    2015-01-01

    The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 μg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

  7. Effects of tham, isoprenaline and propranolol on blood flow and vascular resistances of the liver after in- and outflow occlusion. Relation with the splanchnic shock.

    Science.gov (United States)

    Stoitchcov, E; Kawai, T; Bleser, F; Benichoux, R

    1976-01-01

    The responsibility of the portal and the hepatic artery circulations during shock states has been established by studying the effects of a 15-min occlusion of two of the following blood vessels on 23 dogs: inferior vena cava below the diaphragm, portal vein and hepatic artery. Intrahepatic vascular resistances were computed from blood pressure records in these vessels and transhepatic blood flow studies using the 133Xe clearance method. The animals were treated with THAM, plasmagel, isoprenaline, and propranolol. The tolerance of the occlusion is significantly improved when the animals are treated with the association of the four drugs. The portal and the systemic arterial blood pressures return to normal more promptly. Sinusoid and peribiliary resistances are remarkably stable if compared to the changes occurring in the control animals. The well-known benefit of THAM is improved by the apparently paradoxical association of isoprenaline and propranolol. In fact, at the doses which have been used, they counterbalance their mutual disadvantages. Finally, the analysis of the hepatic blood flow rates and vascular resistances suggests that the splanchnic shock has two components: hepatic and visceral.

  8. High glucose increases Cdk5 activity in podocytes via transforming growth factor-β1 signaling pathway

    International Nuclear Information System (INIS)

    Zhang, Yue; Li, Hongbo; Hao, Jun; Zhou, Yi; Liu, Wei

    2014-01-01

    Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in the development and progression of diabetic nephropathy (DN). Cyclin-dependent kinase 5 (Cdk5), who is an atypical but essential member of the Cdk family of proline-directed serine/threonine kinases, has been shown as a key regulator of podocyte differentiation, proliferation and morphology. Our previous studies demonstrated that the expression of Cdk5 was significantly increased in podocytes of diabetic rats, and was closely related with podocyte injury of DN. However, the mechanisms of how expression and activity of Cdk5 are regulated under the high glucose environment have not yet been fully elucidated. In this study, we showed that high glucose up-regulated the expression of Cdk5 and its co-activator p35 with a concomitant increase in Cdk5 kinase activity in conditionally immortalized mouse podocytes in vitro. When exposed to 30 mM glucose, transforming growth factor-β1 (TGF-β1) was activated. Most importantly, we found that SB431542, the Tgfbr1 inhibitor, significantly decreased the expression of Cdk5 and p35 and Cdk5 kinase activity in high glucose-treated podocytes. Moreover, high glucose increased the expression of early growth response-1 (Egr-1) via TGF-β1-ERK1/2 pathway in podocytes and inhibition of Egr-1 by siRNA decreased p35 expression and Cdk5 kinase activity. Furthermore, inhibition of Cdk5 kinase activity effectively alleviated podocyte apoptosis induced by high glucose or TGF-β1. Thus, the TGF-β1-ERK1/2-Egr-1 signaling pathway may regulate the p35 expression and Cdk5 kinase activity in high glucose-treated podocytes, which contributes to podocyte injury of DN. - Highlights: • HG up-regulated the expression of Cdk5 and p35, and Cdk5 activity in podocytes. • HG activated TGF-β1 pathway and SB431542 inhibited Cdk5 expression and activity. • HG increased the expression of Egr-1 via TGF-β1-ERK1/2 pathway. • Inhibition of Egr-1

  9. Fatty acid elongase 1 (FAE1) promoter as a candidate for genetic ...

    African Journals Online (AJOL)

    As an important cis-regulatory element, a promoter plays a key role in plant gene expression and regulation, and has been widely used in plant genetic engineering. The fatty acid elongase 1 (FAE1) promoter was isolated from Arabidopsis thaliana. Sequence analysis showed that the FAE1 promoter contains two Skn-1 ...

  10. Review of homogeneous charge compression ignition (HCCI) combustion engines and exhaust gas recirculation (EGR) effects on HCCI

    Science.gov (United States)

    Akma Tuan Kamaruddin, Tengku Nordayana; Wahid, Mazlan Abdul; Sies, Mohsin Mohd

    2012-06-01

    This paper describes the development in ICE which leads to the new advanced combustion mode named Homogeneous Charge Compression Ignition (HCCI). It explains regarding the theory and working principle of HCCI plus the difference of the process in gasoline and diesel fuelled engines. Many of pioneer and recent research works are discussed to get the current state of art about HCCI. It gives a better indication on the potential of this method in improving the fuel efficiency and emission produced by the vehicles' engine. Apart from the advantages, the challenges and future trend of this technology are also included. HCCI is applying few types of control strategy in producing the optimum performance. This paper looks into Exhaust Gas Recirculation (EGR) as one of the control strategies.

  11. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    International Nuclear Information System (INIS)

    Zhu, Haibo; He, Jie; Ye, Liang; Lin, Fei; Hou, Jian; Zhong, Yan; Jiang, Wanglin

    2015-01-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  12. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Haibo [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); He, Jie [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Ye, Liang [School of Public Health and Management, Binzhou Medical University, Yantai (China); Institute of Toxicology, Binzhou Medical University, Yantai (China); Lin, Fei; Hou, Jian; Zhong, Yan [State Key Laboratory of Long-acting Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003 (China); Jiang, Wanglin, E-mail: jwl518@163.com [School of Pharmaceutical Sciences, Institute of Materia Medica, Binzhou Medical University, Yantai (China)

    2015-11-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood–brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. - Highlights: • Curculigoside A induces cell proliferation through Wnt5a/β-catenin pathway. • Curculigoside A induces angiogenesis via VEGF/CREB/Egr-3/VCAM-1 signaling axis. • Curculigoside A promotes blood vessel maturation via Ang1/Tie2 pathway.

  13. Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride.

    Science.gov (United States)

    Patel, Vishnu M; Prajapati, Bhupendra G; Patel, Madhabhai M

    2007-03-16

    The purpose of this research work was to establish mucoadhesive buccal devices of propranolol hydrochloride (PRH) in the forms of bilayered and multilayered tablets. The tablets were prepared using sodium carboxymethylcellulose (SCMC) and Carbopol-934 (CP) as bioadhesive polymers to impart mucoadhesion and ethyl cellulose (EC) to act as an impermeable backing layer. Buccal devices were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, surface pH, swelling index, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, and in vitro drug permeation. As compared with bilayered tablets, multilayered tablets showed slow release rate of drug with improved ex vivo bioadhesive strength and enhanced ex vivo mucoadhesion time. The mechanism of drug release was found to be non-Fickian diffusion (value of n between 0.5 and 1.0) for both the buccal devices. The stability of drug in both the optimized buccal devices was tested for 6 hours in natural human saliva; both the buccal devices were found to be stable in natural human saliva. The present study concludes that mucoadhesive buccal devices of PRH can be a good way to bypass the extensive hepatic first-pass metabolism and to improve the bioavailability of PRH.

  14. [Two news drugs (ivacaftor & bedaquiline), one biomarker (florbetapir) and a re-positioned drug (propranolol) on the market].

    Science.gov (United States)

    Monneret, C

    2014-07-01

    Among the new molecular entities approved by the EMEA and the FDA in 2012, four have caught our attention for their significant contribution to the health of patient. First of all, among the notable 2012 approvals, is ivacaftor or Kalydeco®. This is the first treatment that targets one of the gene defects that is underlying cause of cystic fibrosis. This is also an example of the promise of personalized medicine. The benefits with bedaquiline or Sirturo® are its ability to likely provide clinically relevant activity as part of multi-drug regimens against tuberculosis (TB) based on clinical data in multi-drug resistant tuberculosis (MDR TB) patients, who were defined as being at least resistant against the two major tuberculostatic medicines (isaoniazide and rifampicine). On December 2012 and then, on December 2013, the FDA and European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorization for Sirturo® (bedaquiline), respectively, for use as part of a combination therapy for pulmonary multidrug resistant tuberculosis in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. Amyvid®, which is a solution for injection that contains the active substance florbetapir (18F), is a radiopharmaceutical that emits low amounts of radiation and works by targeting and attaching to β-amyloid plaques in the brain. This enables doctors to know whether or not significant amount of plaques are present in order to know if the patient is unlikely or not, to have Alzheimer's disease. Finally, the last topics addresses the propranolol, which is a beta-blocker, used alone or together with other medicines to treat high blood pressure. Propranolol is gaining a new lease of life for treating infantile hemangioma. Copyright © 2014. Published by Elsevier Masson SAS.

  15. Genotypic differences in intruder-evoked immediate early gene activation in male, but not female, vasopressin 1b receptor knockout mice.

    Science.gov (United States)

    Witchey, Shannah K; Stevenson, Erica L; Caldwell, Heather K

    2016-11-24

    The neuropeptide arginine vasopressin (Avp) modulates social behaviors via its two centrally expressed receptors, the Avp 1a receptor and the Avp 1b receptor (Avpr1b). Recent work suggests that, at least in mice, Avp signaling through Avpr1b within the CA2 region of the hippocampus is critical for normal aggressive behaviors and social recognition memory. However, this brain area is just one part of a larger neural circuit that is likely to be impacted in Avpr1b knockout (-/-) mice. To identify other brain areas that are affected by altered Avpr1b signaling, genotypic differences in immediate early gene activation, i.e. c-FOS and early growth response factor 1 (EGR-1), were quantified using immunocytochemistry following a single exposure to an intruder. In females, no genotypic differences in intruder-evoked c-FOS or EGR-1 immunoreactivity were observed in any of the brain areas measured. In males, while there were no intruder-evoked genotypic differences in c-FOS immunoreactivity, genotypic differences were observed in EGR-1 immunoreactivity within the ventral bed nucleus of the stria terminalis and the anterior hypothalamus; with Avpr1b -/- males having less EGR-1 immunoreactivity in these regions than controls. These data are the first to identify specific brain areas that may be a part of a neural circuit that includes Avpr1b-expressing cells in the CA2 region of the hippocampus. It is thought that this circuit, when working properly, plays a role in how an animal evaluates its social context.

  16. Propranolol y sus ésteres: detección y resolución enantiomérica

    Directory of Open Access Journals (Sweden)

    Ritsie Ruiz Caballero

    1998-08-01

    Full Text Available Se realizó una revisión bibliográfica sobre el racemato del clorhidrato de propranolol y sus ésteres, con el objetivo de recopilar los métodos más actuales para su detección y la resolución de su mezcla racémica, de forma que se mantengan informados los farmacéuticos, químicos sintetizadores y otros profesionales relacionados con la temática. Se consultaron las bases de datos MEDLINE (1986-1994, Analytical Abstracts (1985-1994, Chemicals Abstracts (1990-1992 y los Current Contents (Life Science y Physical, Chemical & Earth Sciences desde 1990-1996. Se reportan como técnicas de análisis para su detección: espectrofluorometría, colorimetría, cromatografía de placa delgada y cromatografía líquida de alta resolución. Se reflejan diferentes métodos de resolución de enantiómeros, como: cromatografía de fluido supercrítico, electroforesis capilar, cromatografía de placa delgada y cromatografía líquida de alta resolución utilizando fases y/o aditivos quirales, empleados estos 2 últimos tanto para la detección como para la resolución del clorhidrato de propranolol y sus ésteres.A bibliographic review on the raceme of propanolol chlorhydrate and its esters was made aimed at compiling the latest methods for its detection and the resolution of its racemic mix in order to provide information to pharmacists, synthesizer chemistry and other professionals connected with this topic. Reference was made to the MEDLINE (1986-1994, Analytical Abstracts (1985-1994, and Chemical Abstracts (1990-1992 data bases, as well as to Current Contents (Life Science & Physical, Chemical & Earth Sciences form 1990 to 1996. The spectrofluorometry, the colorimetry, the thinlayer chromatography, and the high oressure liquid chromatography are reported as analysis techniques used for its detection. The following methods of resolution of enantiomers are considered: supercritical fluid chromatography, capillary electrophoresis, thin

  17. Early growth response 4 is involved in cell proliferation of small cell lung cancer through transcriptional activation of its downstream genes.

    Directory of Open Access Journals (Sweden)

    Taisuke Matsuo

    Full Text Available Small cell lung cancer (SCLC is aggressive, with rapid growth and frequent bone metastasis; however, its detailed molecular mechanism remains poorly understood. Here, we report the critical role of early growth factor 4 (EGR4, a DNA-binding, zinc-finger transcription factor, in cell proliferation of SCLC. EGR4 overexpression in HEK293T cells conferred significant upregulation of specific splice variants of the parathyroid hormone-related protein (PTHrP gene, resulting in enhancement of the secretion of PTHrP protein, a known mediator of osteolytic bone metastasis. More importantly, depletion of EGR4 expression by siRNA significantly suppressed growth of the SCLC cell lines, SBC-5, SBC-3 and NCI-H1048. On the other hand, introduction of EGR4 into NIH3T3 cells significantly enhanced cell growth. We identified four EGR4 target genes, SAMD5, RAB15, SYNPO and DLX5, which were the most significantly downregulated genes upon depletion of EGR4 expression in all of the SCLC cells examined, and demonstrated the direct recruitment of EGR4 to their promoters by ChIP and luciferase reporter analysis. Notably, knockdown of the expression of these genes by siRNA remarkably suppressed the growth of all the SCLC cells. Taken together, our findings suggest that EGR4 likely regulates the bone metastasis and proliferation of SCLC cells via transcriptional regulation of several target genes, and may therefore be a promising target for the development of anticancer drugs for SCLC patients.

  18. Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

    Science.gov (United States)

    Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

    2009-07-01

    We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

  19. Beta-1 vs. beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans.

    Science.gov (United States)

    Maman, Stephan R; Vargas, Alvaro F; Ahmad, Tariq Ali; Miller, Amanda J; Gao, Zhaohui; Leuenberger, Urs A; Proctor, David N; Muller, Matthew D

    2017-08-01

    During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective β-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t -tests. Esmolol (Δ = 3296 ± 1204) and propranolol (Δ = 2997 ± 699) caused similar reductions in peak RPP compared with saline (Δ = 5384 ± 1865). In support of our hypothesis, ΔCBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing ΔCBV to ΔRPP. In summary, not only does selective β1 blockade reduce myocardial oxygen demand during exercise, but it also unveils β2-receptor-mediated coronary exercise hyperemia. NEW & NOTEWORTHY In this study, we evaluated the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with esmolol compared with

  20. Radioactive iodine therapy in a case of Graves' disease with allergy to antithyroid drugs (ATD) and propranolol

    International Nuclear Information System (INIS)

    Bahri, I.M.; San Luis, T.O.L.

    2007-01-01

    Full text: This is a case of V.C., 56 year old, female, from Las Pinas City, Philippines, diagnosed as a case of Graves' disease. During the course of therapy, the patient had allergy to antithyroid drugs (ATDs) and beta blocker (Propranolol). She developed rashes all over the body, sparing the face the day after taking her ATDs as well as Propranolol, thus all medications were discontinued. Other options, such as RAI therapy and surgery, with their respective advantages and disadvantages were fully explained to the patient who then opted to undergo RAI therapy. In our institution, we usually compute the dose based on the size of the gland and radioactive Iodine-131 uptake measurements (RAIU) rather than using fixed doses. Thyroid scintigraphy and RAIU were done which revealed poorly visualized thyroid gland and markedly diminished 24-hour uptake but normal 4-hour uptake [RAIU 4 hour uptake: 26% (NV= 15-25%); 24 hour uptake: 6% (NV25-45%)]. * Note: Variations in normal uptake values compared to US are due to iodine deficiency still existing in some regions. Because of the very low 24-hour uptake, we reviewed the probable causes which can result in low uptake values. All causes were ruled out and the patient was advised to undergo two weeks of strict low-iodine diet prior to repeat thyroid scintigraphy and RAIU. Thereafter, the result of repeat study showed diffuse thyromegaly with elevated uptake values indicating rapid trapping and organification processes [RAIU 4 hour uptake: 82% (NV= 15-25%); 24 hour uptake: 68% (NV25-45%)]. The day after the study, the patient was given 10 mCi I-131 based on the estimated weight of the gland, rapid thyroid iodine turnover ('small pool') and 24-hour uptake. This was considered to be the highest allowable dose of RAI to decrease the probability of relapse and the need for re-treatment. Approximately 4 weeks after the therapy, the patient is noted to have responded satisfactorily to therapy with resolution of symptoms. (author)

  1. Anti-tumor effects of Egr-IFN γ gene therapy combined with 125I-UdR radionuclide therapy

    International Nuclear Information System (INIS)

    Zhao Jingguo; Ni Yanjun; Song Xiangfu; Li Yanyi; Yang Wei; Sun Ting; Ma Qingjie; Gao Fengtong

    2008-01-01

    Objective: To explore the anti-tumor effects of Egr-IFNγ gene therapy combined with 125 I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNγ mixed with liposome was injected into tumor. 48 h later, 370 kBq 125 I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNγ in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNγ + 125 I-UdR group were obviously lower than those of control group, 125 I-UdR group and pcDNAEgr-1 + 125 I-UdR group 6-15 d after gene-radionuclide therapy. IFNγ protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNγ + 125 I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNγ + 125 I-UdR group was significantly higher than that in the other groups (P 125 I-UdR radionuclide therapy are better than those of 125 I-UdR therapy. (authors)

  2. Contextualizando reações ácido-base de acordo com a teoria protônica de Brönsted-Lowry usando comprimidos de propranolol e nimesulida

    OpenAIRE

    Gonsalves, Arlan de Assis; Araújo, Cleônia Roberta Melo; Leite Filho, Carlos Alberto; Medeiros, Felipe Santana de

    2013-01-01

    This paper reports the use of alternative materials for teaching experimental chemistry. In this context, nimesulide and propranolol tablets were used to teach chemical concepts about acid-base reactions according to Brönsted-Lowry protonic Theory. Important topics of Organic, Analytical and Pharmaceutical Chemistry were discussed, such as purification by acid-base extraction, solubility of organic compounds in aqueous solutions, buffers, the dissociation constant (pKa), potentiometric titrat...

  3. T-cell activation and early gene response in dogs.

    Directory of Open Access Journals (Sweden)

    Sally-Anne Mortlock

    Full Text Available T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR, and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA (5μg/ml, including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2, early growth response 1 (EGR1, growth arrest and DNA damage-inducible gene (GADD45B, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS, early growth response 2 (EGR2, hemogen (HEMGN, polo-like kinase 2 (PLK2 and polo-like kinase 3 (PLK3. Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in

  4. Physiologic implications of inter-hormonal interference in fish: lessons from the interaction of adrenaline with cortisol and thyroid hormones in climbing perch (Anabas testudineus Bloch).

    Science.gov (United States)

    George, Nimta; Peter, Valsa S; Peter, M C Subhash

    2013-01-15

    Adrenaline and cortisol, the major stress hormones, are known for its direct control on stress response in fish. Likewise, as an important stress modifier hormone, thyroid hormone has also been implicated in stress response of fish. We tested whether the hypothesis on the phenomenon of inter-hormonal interference, a process that explains the hormonal interactions, operates in fish particularly between adrenaline, cortisol and thyroid hormones. To achieve this goal, indices of acid-base, osmotic and metabolic regulations were quantified after adrenaline challenge in propranolol pre-treated air-breathing fish (Anabas testudineus). Short-term adrenaline (10 ng g(-1)) injection for 30 min produced a rise in plasma cortisol without affecting plasma T(3) and T(4). On the contrary, blocking of adrenaline action with a non-selective blocker, propranolol (25 ng g(-1)) for 90 min reduced plasma cortisol along with plasma T(4) and that indicate a possible interference of these hormones in the absence of adrenaline challenge. Similarly, a reduction in plasma T(3) was found after adrenaline challenge in propranolol pre-treated fish and that suggests a functional synergistic interference of adrenaline with T(3). Adrenaline challenge in these fish, however, failed to abolish this propranolol effect. The remarkable systemic hypercapnia and acidosis by propranolol pre-treatment were reversed by adrenaline challenge, pointing to a direct action of adrenaline on acid-base indices probably by a mechanism which may not require β-adrenergic receptor systems. Interestingly, the prominent adrenaline-induced hyperglycemia, hyperlactemia and hyperuremea were not altered by propranolol treatment. Similarly, adrenaline challenge promoted and propranolol reduced the osmotic competencies of the gills, kidneys and liver of this fish as evident in the sodium and proton pump activities. The modified physiologic actions of adrenaline and its modified interaction with THs and cortisol in blocked

  5. pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and purpose of the study: Propranolol HCl, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Methods: Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15 % were added to the matrices prepared by hydroxypropyl methylcellulose (HPMC and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time (MDT as well as similarity factor (¦2 were calculated for all formulations. Results and discussion: It was found that incorporation of 5 and 10 % tartaric acid in tablet formulations with 30 % HPMC resulted in a suitable pH-independent release profiles with significant higher ¦2 values (89.9 and 87.6 respectively compared to acid free tablet (58.03. The other two acids did not show the desirable effects. It seems that lower pKa of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles.

  6. Sample-efficient Strategies for Learning in the Presence of Noise

    DEFF Research Database (Denmark)

    Cesa-Bianchi, N.; Dichterman, E.; Fischer, Paul

    1999-01-01

    In this paper, we prove various results about PAC learning in the presence of malicious noise. Our main interest is the sample size behavior of learning algorithms. We prove the first nontrivial sample complexity lower bound in this model by showing that order of &egr;/&Dgr;2 + d/&Dgr; (up...... to logarithmic factors) examples are necessary for PAC learning any target class of {#123;0,1}#125;-valued functions of VC dimension d, where &egr; is the desired accuracy and &eegr; = &egr;/(1 + &egr;) - &Dgr; the malicious noise rate (it is well known that any nontrivial target class cannot be PAC learned...... with accuracy &egr; and malicious noise rate &eegr; &egr;/(1 + &egr;), this irrespective to sample complexity). We also show that this result cannot be significantly improved in general by presenting efficient learning algorithms for the class of all subsets of d elements and the class of unions of at most d...

  7. Electroacupuncture at LI11 promotes jejunal motility via the parasympathetic pathway.

    Science.gov (United States)

    Hu, Xuanming; Yuan, Mengqian; Yin, Yin; Wang, Yidan; Li, Yuqin; Zhang, Na; Sun, Xueyi; Yu, Zhi; Xu, Bin

    2017-06-21

    Gastrointestinal motility disorder has been demonstrated to be regulated by acupuncture treatment. The mechanisms underlying the effects of acupuncture stimulation of abdominal and lower limb acupoints on gastrointestinal motility have been thoroughly studied; however, the physiology underlying the effects of acupuncture on the forelimbs to mediate gastrointestinal motility requires further exploration. The aim of this study was to determine whether electroacupuncture (EA) at LI11 promotes jejunal motility, whether the parasympathetic pathway participates in this effect, and if so, which somatic afferent nerve fibres are involved. A manometric balloon was used to observe jejunal motility. The effects and mechanisms of EA at LI11 were explored in male Sprague-Dawley rats with or without drug administration (propranolol, clenbuterol, acetylcholine, and atropine) and with or without vagotomy. Three types of male mice (β 1 β 2 receptor-knockout [β 1 β 2 -/- ] mice, M 2 M 3 receptor-knockout [M 2 M 3 -/- ] mice and wild-type [WT] mice) were also studied by using different EA intensities (1, 2, 4, 6, and 8 mA). A total of 72 rats and 56 mice were included in the study. EA at LI11 increased the contractile amplitude of jejunal motility in the majority of both rats and mice. However, EA at LI11 did not enhance jejunal motility in rats administered atropine, rats that underwent vagotomy, and M 2 M 3 -‍‍/- mice (at all intensities). In WT mice, EA at LI11 significantly increased jejunal motility at all intensities except 1 mA, and a plateau was reached at intensities greater than 4 mA. Our results suggest that EA at LI11 promotes jejunal motility primarily by exciting the parasympathetic pathway, and that Aδ-fibres and C-fibres may play important roles in the process.

  8. Porcine synapsin 1: SYN1 gene analysis and functional characterization of the promoter

    DEFF Research Database (Denmark)

    Hedegaard, Claus; Kjaer-Sorensen, Kasper; Madsen, Lone Bruhn

    2013-01-01

    of elements responsible for neuron-specific expression. Expression analysis of SYN1 demonstrated presence of transcript during embryonic development. Analysis of GFP expression in transgenic zebrafish embryos suggests that the pig SYN1 promoter directs expression in neuronal cells. Thus, the SYN1 promoter...

  9. Enantioselective analysis of propranolol and 4-hydroxypropranolol by CE with application to biotransformation studies employing endophytic fungi.

    Science.gov (United States)

    Borges, Keyller Bastos; Pupo, Mônica Tallarico; Bonato, Pierina Sueli

    2009-11-01

    A CE method is described for the enantioselective analysis of propranolol (Prop) and 4-hydroxypropranolol (4-OH-Prop) in liquid Czapek medium with application in the study of the enantioselective biotransformation of Prop by endophytic fungi. The electrophoretic conditions previously optimized were as follows: an uncoated fused-silica capillary, 4% w/v carboxymethyl-beta-CD in 25 mmol/L triethylamine/phosphoric acid (H(3)PO(4)) buffer at pH 9 as running electrolyte and 17 kV of voltage. UV detection was carried out at 208 nm. Liquid-liquid extraction using diethyl ether: ethyl acetate (1:1 v/v) as extractor solvent was employed for sample preparation. The calibration curves were linear over the concentration range of 0.25-10.0 microg/mL for each 4-OH-Prop enantiomer and 0.10-10.0 microg/mL for each Prop enantiomer (r>or=0.995). Within-day and between-day relative standard deviations and relative errors for precision and accuracy were lower than 15% for all the enantiomers. Finally, the validated method was used to evaluate Prop biotransformation in its mammalian metabolite 4-OH-Prop by some selected endophytic fungi. The screening of five strains of endophytic fungi was performed and all of them could biotransform Prop to some extent. Specifically, Glomerella cingulata (VA1) biotransformed 47.8% of (-)-(S)-Prop to (-)-(S)-4-OH-Prop with no formation of (+)-(R)-4-OH-Prop in 72 h of incubation.

  10. Reacquisition of cocaine conditioned place preference and its inhibition by previous social interaction preferentially affect D1-medium spiny neurons in the accumbens corridor.

    Science.gov (United States)

    Prast, Janine M; Schardl, Aurelia; Schwarzer, Christoph; Dechant, Georg; Saria, Alois; Zernig, Gerald

    2014-01-01

    We investigated if counterconditioning with dyadic (i.e., one-to-one) social interaction, a strong inhibitor of the subsequent reacquisition of cocaine conditioned place preference (CPP), differentially modulates the activity of the diverse brain regions oriented along a mediolateral corridor reaching from the interhemispheric sulcus to the anterior commissure, i.e., the nucleus of the vertical limb of the diagonal band, the medial septal nucleus, the major island of Calleja, the intermediate part of the lateral septal nucleus, and the medial accumbens shell and core. We also investigated the involvement of the lateral accumbens core and the dorsal caudate putamen. The anterior cingulate 1 (Cg1) region served as a negative control. Contrary to our expectations, we found that all regions of the accumbens corridor showed increased expression of the early growth response protein 1 (EGR1, Zif268) in rats 2 h after reacquisition of CPP for cocaine after a history of cocaine CPP acquisition and extinction. Previous counterconditioning with dyadic social interaction inhibited both the reacquisition of cocaine CPP and the activation of the whole accumbens corridor. EGR1 activation was predominantly found in dynorphin-labeled cells, i.e., presumably D1 receptor-expressing medium spiny neurons (D1-MSNs), with D2-MSNs (immunolabeled with an anti-DRD2 antibody) being less affected. Cholinergic interneurons or GABAergic interneurons positive for parvalbumin, neuropeptide Y or calretinin were not involved in these CPP-related EGR1 changes. Glial cells did not show any EGR1 expression either. The present findings could be of relevance for the therapy of impaired social interaction in substance use disorders, depression, psychosis, and autism spectrum disorders.

  11. Ankaferd Blood Stopper induces apoptosis and regulates PAR1 and ...

    African Journals Online (AJOL)

    Mine Mumcuoglu

    2014-12-16

    Dec 16, 2014 ... investigated for its properties. However there are no ... types of proteins and factors acting on cellular functions such as protein-2 (AP2), ... ATF1), cyclic AMP response element binding protein (CREB),. E2F1–5, E2F6, EGR, ...

  12. [18 F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18 F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors

    International Nuclear Information System (INIS)

    Mirfeizi, Leila; Rybczynska, Anna A.; Waarde, Aren van; Campbell-Verduyn, Lachlan; Feringa, Ben L.; Dierckx, Rudi A.J.O.; Elsinga, Philip H.

    2014-01-01

    Cerebral β‐adrenergic receptors (β‐ARs) play important roles in normal brain and changes of β-AR expression are associated with several neuropsychiatric illnesses. Given the high density of β‐AR in several brain regions, quantification of β‐AR levels using PET is feasible. However, there is a lack of radiotracers with suitable biological properties and meeting safety requirements for use in humans. We developed a PET tracer for β‐AR by 18 F‐fluorination of 1-((9H-carbazol-4-yl)oxy)-3-4(4-((2-(2-(fluoromethoxy)-ethoxy) methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ( 18 F-FPTC). Methods: [ 18 F] FPTC was synthesized by Cu(I)-catalyzed alkyne-azide cycloaddition. First, 18 F‐PEGylated alkyne was prepared by 18 F‐fluorination of the corresponding tosylate. Next 18 F‐PEGylated alkyne was reacted with an azidoalcohol derivative of 4‐hydroxycarbazol in the presence of the phosphoramidite Monophos as a ligand and Cu(I) as a catalyst. After purification with radio‐HPLC, the binding properties of [ 18 F FPTC were tested in β‐AR‐expressing C6‐glioma cells in vitro and in Wistar rats in vivo using microPET. Results: The radiochemical yield of 18 F‐PEGylated alkyne was 74%–89%. The click reaction to prepare [ 18 F]FPTC proceeded in 10 min with a conversion efficiency of 96%. The total synthesis time was 55 min from the end of bombardment. Specific activities were > 120 GBq/μmol. Propranolol strongly and dose-dependently inhibited the binding of both [ 125 I]-ICYP and [ 18 F]FPTC to C6 glioma cells, with IC 50 values in the 50–60 nM range. However, although both FPTC and propranolol inhibited cellular [ 125 I]ICYP binding, FPTC decreased [ 125 I]ICYP uptake by only 25%, whereas propranolol reduced it by 83%. [ 18 F]FPTC has the appropriate lipophilicity to penetrate the blood brain barrier (logP + 2.48). The brain uptake reached a maximum within 2 min after injection of 20–25 MBq [ 18 F]FPTC. SUV values ranged from 0.4 to 0.6 and were not

  13. Effects of PTEN transfer on cell cycle progression and expression of P27kipl followed by X-ray irradiation

    International Nuclear Information System (INIS)

    Tian Mei; Wu Congmei; Liu Linlin; Piao Chunji; Li Xiuyi

    2007-01-01

    Objective: To investigate the effect of pEgr-hPTEN stable transfer combined with irradiation on the cell cycle progression and the expression of cell cycle kinase inhibitor P27 kipl protein of SHG-44 human glioma cells. Methods: pEgr-hPTEN vector containing the exogenous wild type PTEN gene was transfected into SHG-44 cells under mediation of lipofectamine in vitro, the positive cell clones were selected and amplified by using G418. Western blotting was used to measure the expression of PTEN protein. Transmission electron microscope was adopted to detect the cell ultrastructural changes and flow cytometry was adopted to analysis the changes of cell cycle progression and the expression of P27 kipl in SHG-44-sPTEN cells followed by different doses of X-ray irradiation. Results: Egr-1 promoter could be induced and activated by irradiation and then enhanced the expression of downstream PTEN gene within 5 Gy. The ultrastructure of SHG-44-sPTEN cells had many degenerative changes and many early apoptotic changes including the chromosome condensate around the nuclear envelope. pEgr-hPTEN stable transfer combined with X-ray irradiation could significantly induce G 1 arrest. The expression of P27 kipl proteins increased in SHG-44-sPTEN stable transfected cells. Conclusion: PTEN stable transfer combined with irradiation can significantly induce G 1 arrest. The molecular basis may be correlated with the enhanced expression of PTEN induced by irradiation and increased expression of cell cycle kinase inhibitor P27 kipl . (authors)

  14. Associations of RASSF1A, RARβ, and CDH1 promoter hypermethylation with oral cancer risk

    Science.gov (United States)

    Wen, Guohong; Wang, Huadong; Zhong, Zhaohui

    2018-01-01

    Abstract Background: Oral tumor is a heterogeneous group of tumors, in which it has several different histopathological and molecular features. Recently, genetic and epigenetic alterations are often detected in the development of oral cancer. Gene promoter hypermethylation leads to the silencing of cancer related genes without changes of genes sequence. To clarify the effect of RAS association domain family protein 1a (RASSF1A), retinoic acid receptor beta (RARβ), and E-cadherin (CDH1) promoter hypermethylation on the risk of oral cancer, we performed this meta-analysis. Methods: PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) databases were retrieved to identify eligible articles. Stata 12.0 software was used to analyze extracted data of the included articles. Odds ratios (ORs) with the corresponding 95% confidence interval (95% CI) were calculated to evaluate the associations of RASSF1A, RARβ, and CDH1 promoter hypermethylation with oral cancer risk. Results: Around 23 literatures with 29 studies were included in the final meta-analysis, in which 12 studies were about RASSF1A promoter methylation, 4 studies were about RARβ promoter methylation, and 13 studies were about CDH1 promoter methylation. Overall, the results of this meta-analysis showed that there were significant associations between RASSF1A, RARβ, and CDH1 promoter hypermethylation and oral cancer risk (RASSF1A, OR = 11.8, 95% CI = 6.14–22.66; RARβ, OR = 20.35, 95% CI = 5.64–73.39; CDH1, OR = 13.46, 95% CI = 5.31–34.17). In addition, we found that RASSF1A promoter hypermethylation exerted higher frequency in the tongue tumor than other site tumor in mouth (RASSF1A, tongue tumor vs other site tumor in mouth, unmethylation vs methylation, OR = 0.65, 95%CI = 0.44–0.98). Conclusion: RASSF1A, RARβ, and CDH1 promoter hypermethylation might significantly increase the risk of oral cancer. PMID:29538221

  15. Oxidation of atenolol, propranolol, carbamazepine and clofibric acid by a biological Fenton-like system mediated by the white-rot fungus Trametes versicolor.

    Science.gov (United States)

    Marco-Urrea, Ernest; Radjenović, Jelena; Caminal, Gloria; Petrović, Mira; Vicent, Teresa; Barceló, Damià

    2010-01-01

    Biological advanced oxidation of the pharmaceuticals clofibric acid (CA), carbamazepine (CBZP), atenolol (ATL) and propranolol (PPL) is reported for the first time. Extracellular oxidizing species were produced through a quinone redox cycling mechanism catalyzed by an intracellular quinone reductase and any of the ligninolytic enzymes of Trametes versicolor after addition of the lignin-derived quinone 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe(3+)-oxalate in the medium. Time-course experiments with approximately 10mg L(-1) of initial pharmaceutical concentration resulted in percent degradations above 80% after 6h of incubation. Oxidation of pharmaceuticals was only observed under DBQ redox cycling conditions. A similar degradation pattern was observed when CBZP was added at the environmentally relevant concentration of 50 microg L(-1). Depletion of DBQ due to the attack of oxidizing agents was assumed to be the main limiting factor of pharmaceutical degradation. The main degradation products, that resulted to be pharmaceutical hydroxylated derivatives, were structurally elucidated. The detected 4- and 7-hydroxycarbamazepine intermediates of CBZP degradation were not reported to date. Total disappearance of intermediates was observed in all the experiments at the end of the incubation period. (c) 2009 Elsevier Ltd. All rights reserved.

  16. Influence of hydralazine on the pharmacokinetics of orally administered d-propranolol and lidocaine in conscious dogs.

    Science.gov (United States)

    Heinzow, B G; Somogyi, A; McLean, A J

    1987-03-01

    A study was conducted on the influence of oral coadministration of hydralazine (H) on the pharmacokinetics of d-propranolol (P) and lidocaine (L) in 6 conscious dogs. They were given an oral solution containing P (2 mg/kg) and L (15 mg/kg) alone or together with 25 mg H. Plasma concentrations of P and L and the metabolites monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were measured by specific HPLC methods. Concomitant administration of H caused a significant (p less than 0.05) increase in P peak concentrations (Cmax, 34 +/- 5: 73 +/- 10 ng/ml) and the area under plasma concentration time curve (AUC, 142 +/- 18: 254 +/- 56 ng/ml X hr) of P with significant (p less than 0.05) 24% reduction of the apparent oral clearance. The time to reach peak concentrations (Tmax) and the terminal half life (t1/2 beta) were not altered. In contrast to the pattern seen with P the disposition of L was not affected by H. The change in presystemic clearance of P by H cannot be explained by a general underlying mechanism such as an alteration in liver blood flow alone or portal-systemic shunting, since then the pharmacokinetics of L should parallel those of P. It is speculated that other mechanisms, most likely alteration of P metabolism, are primarily responsible for the observed interaction between P and H.

  17. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

    Science.gov (United States)

    In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

    1997-03-01

    Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

  18. Distress call-induced gene expression in the brain of the Indian short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Ganesh, Ambigapathy; Raghuram, Hanumanthan; Nathan, Parthasarathy T; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2010-02-01

    Individuals in distress emit audible vocalizations to either warn or inform conspecifics. The Indian short-nosed fruit bat, Cynopterus sphinx, emits distress calls soon after becoming entangled in mist nets, which appear to attract conspecifics. Phase I of these distress calls is longer and louder, and includes a secondary peak, compared to phase II. Activity-dependent expression of egr-1 was examined in free-ranging C. sphinx following the emissions and responses to a distress call. We found that the level of expression of egr-1 was higher in bats that emitted a distress call, in adults that responded, and in pups than in silent bats. Up-regulated cDNA was amplified to identify the target gene (TOE1) of the protein Egr-1. The observed expression pattern Toe1 was similar to that of egr-1. These findings suggest that the neuronal activity related to recognition of a distress call and an auditory feedback mechanism induces the expression of Egr-1. Co-expression of egr-1 with Toe1 may play a role in initial triggering of the genetic mechanism that could be involved in the consolidation or stabilization of distress call memories.

  19. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

    Science.gov (United States)

    Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

    2013-01-01

    The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

  20. Asymmetric aminolytic kinetic resolution of racemic epoxides using recyclable chiral polymeric Co(III)-salen complexes: a protocol for total utilization of racemic epoxide in the synthesis of (R)-Naftopidil and (S)-Propranolol.

    Science.gov (United States)

    Kumar, Manish; Kureshy, Rukhsana I; Shah, Arpan K; Das, Anjan; Khan, Noor-ul H; Abdi, Sayed H R; Bajaj, Hari C

    2013-09-20

    Chiral polymeric Co(III) salen complexes with chiral ((R)/(S)-BINOL, diethyl tartrate) and achiral (piperazine and trigol) linkers with varying stereogenic centers were synthesized for the first time and used as catalysts for aminolytic kinetic resolution (AKR) of a variety of terminal epoxides and glycidyl ethers to get enantio-pure epoxides (ee, 99%) and N-protected β-amino alcohols (ee, 99%) with quantitative yield in 16 h at RT under optimized reaction conditions. This protocol was also used for the synthesis of two enantiomerically pure drug molecules (R)-Naftopidil (α1-blocker) and (S)-Propranolol (β-blocker) as a key step via AKR of single racemic naphthylglycidyl ether with Boc-protected isoproylamine with 100% epoxide utilization at 1 g level. The catalyst 1 was successfully recycled for a number of times.

  1. The electrostatic role of the Zn-Cys2His2 complex in binding of operator DNA with transcription factors: mouse EGR-1 from the Cys2His2 family.

    Science.gov (United States)

    Chirgadze, Y N; Boshkova, E A; Polozov, R V; Sivozhelezov, V S; Dzyabchenko, A V; Kuzminsky, M B; Stepanenko, V A; Ivanov, V V

    2018-01-07

    The mouse factor Zif268, known also as early growth response protein EGR-1, is a classical representative for the Cys2His2 transcription factor family. It is required for binding the RNA polymerase with operator dsDNA to initialize the transcription process. We have shown that only in this family of total six Zn-finger protein families the Zn complex plays a significant role in the protein-DNA binding. Electrostatic feature of this complex in the binding of factor Zif268 from Mus musculus with operator DNA has been considered. The factor consists of three similar Zn-finger units which bind with triplets of coding DNA. Essential contacts of the factor with the DNA phosphates are formed by three conservative His residues, one in each finger. We describe here the results of calculations of the electrostatic potentials for the Zn-Cys2His2 complex, Zn-finger unit 1, and the whole transcription factor. The potential of Zif268 has a positive area on the factor surface, and it corresponds exactly to the binding sites of each of Zn-finger units. The main part of these areas is determined by conservative His residues, which form contacts with the DNA phosphate groups. Our result shows that the electrostatic positive potential of this histidine residue is enhanced due to the Zn complex. The other contacts of the Zn-finger with DNA are related to nucleotide bases, and they are responsible for the sequence-specific binding with DNA. This result may be extended to all other members of the Cys2His2 transcription factor family.

  2. Anti-tumor effects of Egr-IFN gamma gene therapy combined with {sup 125}I-UdR radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jingguo, Zhao [No.403 Hospital of PLA, Dalian (China); Yanjun, Ni; Xiangfu, Song; Yanyi, Li; Wei, Yang; Ting, Sun; Qingjie, Ma; Fengtong, Gao

    2008-12-15

    Objective: To explore the anti-tumor effects of Egr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNgamma mixed with liposome was injected into tumor. 48 h later, 370 kBq {sup 125}I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNgamma in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNgamma + {sup 125}I-UdR group were obviously lower than those of control group, {sup 125}I-UdR group and pcDNAEgr-1 + {sup 125}I-UdR group 6-15 d after gene-radionuclide therapy. IFNgamma protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNgamma + {sup 125}I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNgamma + {sup 125}I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions: The anti-tumor effects in vivo of pcDNAEgr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy are better than those of {sup 125}I-UdR therapy. (authors)

  3. Comparative study of excipients for propanolol hydrochloryde tablets prepared by means of diferent techniques Estudo comparativo de excipientes em diferentes técnicas de preparação de comprimidos de cloridrato de propranolol

    Directory of Open Access Journals (Sweden)

    Cinara Maistro Mamprim

    2001-11-01

    Full Text Available Systemic arterial hipertension (SAH is one of the major factors in cardiovascular risk, since it contributes to the existence of more than 500 thousand cases of cerebral vascular accidents (CVA, 150 thousand deaths by cerebral hemorrhage and approximately a million myocardium infarctions (IAM. In Brazil, it is estimated that about 15% of the adult population can be considered hypertensive. Hypertension can be prevented by changes in lifestyle, although in most cases, the treatment with drugs becomes necessary. Propranolol hydrochloride is the drug chosen for the hypertensive elderly population who has had myocardium infarctation previously. The drug is commercially available as injections, solutions, capsules and tablets. Tablets can be prepared using three different techniques. The most used technique is the granulation by moisture. With the advance of new excipients available in the market for the Pharmaceutical Industry, a more simple and economical technique became possible, improving the physical and chemical stability of the product, reaching the goal of getting more efficient and safer medicine. The purpose of this study was to develop formulations of propranolol hydrochloride tablets through the variation of excipients and manufacture techniques. The propranolol hydrochloryde tablets were stored at 37o C and 50o C with 90% UR for 90 days, and analysed in pre-established time intervals the formulations were evaluated as for the physical and physical-chemical aspects.   A hipertensão arterial sistêmica (HAS é um dos mais importantes fatores de risco cardiovascular uma vez que contribui, mundialmente, com mais de 500 mil casos de acidentes cerebrovasculares (AVC, 150 mil mortes por hemorragia cerebral e aproximadamente um milhão de infartos de miocárdio (IAM. No Brasil estima-se que cerca de15% dos indivíduos adultos possam ser rotulados como hipertensos. A hipertensão pode ser prevenida com a mudança no estilo de vida, embora na

  4. 26 CFR 1.263(b)-1 - Expenditures for advertising or promotion of good will.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Expenditures for advertising or promotion of... advertising or promotion of good will. See § 1.162-14 for the rules applicable to a corporation which has elected to capitalize expenditures for advertising or the promotion of good will under the provisions of...

  5. Far infrared promotes wound healing through activation of Notch1 signaling.

    Science.gov (United States)

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  6. Functional significance of SPINK1 promoter variants in chronic pancreatitis.

    Science.gov (United States)

    Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

    2015-05-01

    Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

  7. Decreasing the emissions of a partially premixed gasoline fueled compression ignition engine by means of injection characteristics and EGR

    Directory of Open Access Journals (Sweden)

    Nemati Arash

    2011-01-01

    Full Text Available This paper is presented in order to elucidate some numerical investigations related to a partially premixed gasoline fuelled engine by means of three dimensional CFD code. Comparing with the diesel fuel, gasoline has lower soot emission because of its higher ignition delay. The application of double injection strategy reduces the maximum heat release rate and leads to the reduction of NOx emission. For validation of the model, the results for the mean in-cylinder pressure, H.R.R., NOx and soot emissions are compared with the corresponding experimental data and show good levels of agreement. The effects of injection characteristics such as, injection duration, spray angle, nozzle hole diameter, injected fuel temperature and EGR rate on combustion process and emission formation are investigated yielding the determination of the optimal point thereafter. The results indicated that optimization of injection characteristics leads to simultaneous reduction of NOx and soot emissions with negligible change in IMEP.

  8. Propranolol, but not naloxone, enhances spinal reflex bladder activity and reduces pudendal inhibition in cats.

    Science.gov (United States)

    Rogers, Marc J; Xiao, Zhiying; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-01-01

    This study examined the role of β-adrenergic and opioid receptors in spinal reflex bladder activity and in the inhibition induced by pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS). Spinal reflex bladder contractions were induced by intravesical infusion of 0.25% acetic acid in α-chloralose-anesthetized cats after an acute spinal cord transection (SCT) at the thoracic T9/T10 level. PNS or TNS at 5 Hz was applied to inhibit these spinal reflex contractions at 2 and 4 times the threshold intensity (T) for inducing anal or toe twitch, respectively. During a cystrometrogram (CMG), PNS at 2T and 4T significantly (P reflex bladder contractions. After administering propranolol (3 mg/kg iv, a β₁/β₂-adrenergic receptor antagonist), the effects of 2T and 4T PNS on bladder capacity were significantly (P reflex bladder contractions or PNS inhibition. At the end of experiments, hexamethonium (10 mg/kg iv, a ganglionic blocker) significantly (P reflex bladder contractions. This study indicates an important role of β₁/β₂-adrenergic receptors in pudendal inhibition and spinal reflex bladder activity. Copyright © 2015 the American Physiological Society.

  9. Lack of effect of spinal anesthesia on drug metabolism

    International Nuclear Information System (INIS)

    Whelan, E.; Wood, A.J.; Shay, S.; Wood, M.

    1989-01-01

    The effect of spinal anesthesia on drug disposition was determined in six dogs with chronically implanted vascular catheters using propranolol as a model compound. On the first study day, 40 mg of unlabeled propranolol and 200 microCi of [3H]propranolol were injected into the portal and femoral veins respectively. Arterial blood samples were taken for 4 hr for measurement of plasma concentrations of labeled and unlabeled propranolol by high-pressure liquid chromatography (HPLC) and of [3H]propranolol by liquid scintillation counting of the HPLC eluant corresponding to each propranolol peak. Twenty-four hr later, spinal anesthesia was induced with tetracaine (mean dose 20.7 +/- 0.6 mg) with low sacral to midthoracic levels and the propranolol infusions and sampling were then repeated. Spinal anesthesia had no significant effect on either the intrinsic clearance of propranolol (2.01 +/- 0.75 L/min before and 1.9 +/- 0.7 L/min during spinal anesthesia), or on mean hepatic plasma flow (2.01 +/- 0.5 L/min before and 1.93 +/- 0.5 L/min during spinal anesthesia). The systemic clearance and elimination half-life of propranolol were also unchanged by spinal anesthesia (0.9 +/- 0.23 L/min on the first day, 0.7 +/- 0.1 L/min during spinal anesthesia; and 101 +/- 21 min on the first day, 115 +/- 16 min during spinal anesthesia, respectively). The volume of distribution (Vd) of propranolol was similarly unaffected by spinal anesthesia

  10. Remobilization Dynamics of Caffeine, Ciprofloxacin, and Propranolol following Evaporation-Induced Immobilization in Porous Media.

    Science.gov (United States)

    Normile, Hayley J; Papelis, Charalambos; Kibbey, Tohren C G

    2017-06-06

    Changing weather conditions can cause cycles of wetting and drying in the unsaturated zone. When porewater evaporates, any nonvolatile solutes present in the pores will be driven to adsorb and ultimately precipitate on solid surfaces. When media are subsequently resaturated through rainfall infiltration, the remobilization of solutes likely depends on both the hydraulics of resaturation and the dynamics of dissolution processes. The focus of this work was to study the dynamics of remobilization of three different emerging contaminants (caffeine, ciprofloxacin, and propranolol) and two model compounds (fluorescein and sulforhodamine B) from porous media following evaporation of porewater. Remobilization column experiments were conducted to study this phenomenon and were evaluated using a finite difference model developed to simulate the adsorption-desorption dynamics during resaturation and elution. Results indicate that dissolution dynamics become increasingly important with increasing adsorption affinity for solid surfaces. Trends in observed elution behavior are not well-predicted from chemical properties, such as solubility. One of the most significant observations of the work is the presence of spikes in elution concentrations well above initial porewater concentration, resulting from the hydraulics of the resaturation process. The effect is most significant in highly mobile compounds that exhibit low adsorption affinity for solid surfaces.

  11. The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

    Science.gov (United States)

    Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

    2016-10-01

    USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

  12. Study on the combustion characteristics of a premixed combustion system with exhaust gas recirculation

    International Nuclear Information System (INIS)

    Yu, Byeonghun; Kum, Sung-Min; Lee, Chang-Eon; Lee, Seungro

    2013-01-01

    The boiler of a premixed combustion system with EGR (exhaust gas recirculation) is investigated to explore the potential for increasing thermal efficiency and lowering pollutant emissions. To achieve this purpose, a thermodynamic analysis is performed to predict the effect of EGR on the thermodynamic efficiency for various equivalence ratios. Experiments of a preheated air condensing boiler with EGR were conducted to measure the changes in the thermal efficiency and the characteristics of the pollutant emission. Finally, a 1-D premixed code was calculated to understand the effect of the EGR method on the NO reduction mechanism. The results of the thermodynamic analysis show that the thermodynamic efficiency is not changed because the temperature and the amount of the exhaust gas are unchanged, even though the EGR method is implemented in the system. However, when the EGR method is used with an equivalence ratio near 1.00, it is experimentally verified that the thermal efficiency increases and the NO x concentration decreases. Based on the results from numerical calculations, it is shown that the NO production rates of N + O 2 ↔ NO + O and N + OH ↔ NO + H are remarkably changed due to the decrease in the flame temperature and the NO mole fraction is decreased. - Highlights: • Premixed combustion system with EGR is studied for a high efficiency and low NO x . • All research is performed with various EGR and equivalence ratios. • It verified that efficiency increases and the NO x emission decreases with EGR method. • NO production rates are remarkably changed by N + O 2 ↔ NO + O and N + OH ↔ NO + H with EGR

  13. Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

    Science.gov (United States)

    Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

    2008-02-01

    Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

  14. Interferon-α regulates glutaminase 1 promoter through STAT1 phosphorylation: relevance to HIV-1 associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Lixia Zhao

    Full Text Available HIV-1 associated neurocognitive disorders (HAND develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS, glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN α specifically activated the glutaminase 1 (GLS1 promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1 phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1 mRNA levels in HIV associated-dementia (HAD individuals correlate with STAT1 (p<0.01, IFN-α (p<0.05 and IFN-β (p<0.01. Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and

  15. The tumor vasculature is a target for genetic radiotherapy

    International Nuclear Information System (INIS)

    Mauceri, Helena J.; Heimann, Ruth; Seetharam, Saraswathy; Beckett, Michael A.; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Tumor progression and metastasis require the growth of new capillaries from existing blood vessels. Tumor cells produce both activators and inhibitors of endothelial cell proliferation and migration. Changes in the balance between these regulators appear to govern an angiogenic switch which is activated during tumor development. Tumor necrosis factor-α (TNF-α) has a biphasic role in angiogenesis. It has been demonstrated that relatively low concentrations of TNF induce angiogenesis while high doses inhibit growth of blood vessels. In our previous studies, using the SQ-20B xenograft model system, we demonstrated increased tumor control when a virus containing the radiation-inducible promoter Egr-1 ligated to a cDNa for TNF-α was combined with radiation. The dominant histopathological feature of tumors receiving combined treatment with Ad.Egr-TNF and radiation was intratumoral vascular thrombosis. The present studies examine the role of TNF in tumor progression by investigating the effects of TNF on VEGF (vascular endothelial growth factor) production in vitro and on tumor vessel count in vivo. Methods: SQ-20B tumor cells in serum-free medium were exposed to hrTNF (10 ng/ml) 4 hours prior to a single dose of x-irradiation (10 Gy). 24 hrs. after treatment, the conditioned medium was harvested, centrifuged, diluted 1:10, and assayed for VEGF using a Quantikine TNF ELISA kit. For studies in vivo, female nude mice were injected sc in the right thigh with 10 6 SQ-20B cells. Xenografts were irradiated with four 5 Gy fractions (20 Gy) and injected twice with either Ad.Egr-TNF or Ad.null. Control tumors were injected with buffer. To highlight vessels, sections from paraffin embedded tissue were stained with anti-CD31 antibody using standard immunohistochemical techniques. Areas of high vascular density were identified and five high power fields (400X) were counted. Data are shown as the mean ± S.E.M. for each treatment group. Significance was evaluated using one

  16. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    International Nuclear Information System (INIS)

    Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko

    2011-01-01

    Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  17. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsukura, Hiroshi, E-mail: hmatsukura.epi@mri.tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: nsato.epi@tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)